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Sample records for electrophilic substitution reaction

  1. Electrophilic aromatic substitution over zeolites generates Wheland-type reaction intermediates

    NARCIS (Netherlands)

    Chowdhury, Abhishek Dutta; Houben, Klaartje; Whiting, Gareth T.; Chung, Sangho; Baldus, Marc; Weckhuysen, Bert M.

    2018-01-01

    The synthesis of many industrial bulk and fine chemicals frequently involves electrophilic aromatic substitution (SEAr) reactions. The most widely practiced example of the SEAr mechanism is the zeolite-catalysed ethylation of benzene, using ethylene as an alkylating agent. However, the current

  2. Computational Methods to Predict the Regioselectivity of Electrophilic Aromatic Substitution Reactions of Heteroaromatic Systems

    DEFF Research Database (Denmark)

    Kruszyk, Monika; Jessing, Mikkel; Kristensen, Jesper L

    2016-01-01

    The validity of calculated NMR shifts to predict the outcome of electrophilic aromatic substitution reactions on different heterocyclic compounds has been examined. Based on an analysis of >130 literature examples it was found that the lowest calculated 13C and/or 1H chemical shift of a heterocycle...... correlates qualitatively with the regiochemical outcome of halogenation reactions in >80% of the investigated cases. In the remaining cases, the site of electrophilic aromatic substitution can be explained by the calculated HOMO orbitals obtained using density functional theory. Using a combination...

  3. Reaction of bromine and chlorine with phenolic compounds and natural organic matter extracts--Electrophilic aromatic substitution and oxidation.

    Science.gov (United States)

    Criquet, Justine; Rodriguez, Eva M; Allard, Sebastien; Wellauer, Sven; Salhi, Elisabeth; Joll, Cynthia A; von Gunten, Urs

    2015-11-15

    Phenolic compounds are known structural moieties of natural organic matter (NOM), and their reactivity is a key parameter for understanding the reactivity of NOM and the disinfection by-product formation during oxidative water treatment. In this study, species-specific and/or apparent second order rate constants and mechanisms for the reactions of bromine and chlorine have been determined for various phenolic compounds (phenol, resorcinol, catechol, hydroquinone, phloroglucinol, bisphenol A, p-hydroxybenzoic acid, gallic acid, hesperetin and tannic acid) and flavone. The reactivity of bromine with phenolic compounds is very high, with apparent second order rate constants at pH 7 in the range of 10(4) to 10(7) M(-1) s(-1). The highest value was recorded for the reaction between HOBr and the fully deprotonated resorcinol (k = 2.1 × 10(9) M(-1) s(-1)). The reactivity of phenolic compounds is enhanced by the activating character of the phenolic substituents, e.g. further hydroxyl groups. With the data set from this study, the ratio between the species-specific rate constants for the reactions of chlorine versus bromine with phenolic compounds was confirmed to be about 3000. Phenolic compounds react with bromine or chlorine either by oxidation (electron transfer, ET) or electrophilic aromatic substitution (EAS) processes. The dominant process mainly depends on the relative position of the hydroxyl substituents and the possibility of quinone formation. While phenol, p-hydroxybenzoic acid and bisphenol A undergo EAS, hydroquinone, catechol, gallic acid and tannic acid, with hydroxyl substituents in ortho or para positions, react with bromine by ET leading to quantitative formation of the corresponding quinones. Some compounds (e.g. phloroglucinol) show both partial oxidation and partial electrophilic aromatic substitution and the ratio observed for the pathways depends on the pH. For the reaction of six NOM extracts with bromine, electrophilic aromatic substitution

  4. Reactivity of polychlorinated biphenyls in nucleophilic and electrophilic substitutions

    Energy Technology Data Exchange (ETDEWEB)

    Gorbunova, Tatyana I., E-mail: gorbunova@ios.uran.ru [I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Kovalevskoy St., 22, Ekaterinburg 620990 (Russian Federation); Subbotina, Julia O. [Ural Federal University named after the first President of Russia B.N. Yeltsin, Mira St., 19, Ekaterinburg 620002 (Russian Federation); Saloutin, Viktor I.; Chupakhin, Oleg N. [I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Kovalevskoy St., 22, Ekaterinburg 620990 (Russian Federation)

    2014-08-15

    Graphical abstract: - Highlights: • Quantum chemical calculations were carried out for PCBs congeners. • Calculated descriptors were used to explain the PCBs reactivity in S{sub N} and S{sub E} substitutions. • Obtained data were used to estimate the PCBs reactivity in the S{sub N} reactions. • Calculated descriptors were insufficient to explain the PCBs reactivity in the S{sub E} reactions. • New neutralization methods of the large-capacity PCBs were discussed. - Abstract: To explain the chemical reactivity of polychlorinated biphenyls in nucleophilic (S{sub N}) and electrophilic (S{sub E}) substitutions, quantum chemical calculations were carried out at the B3LYP/6-31G(d) level of the Density Functional Theory in gas phase. Carbon atomic charges in biphenyl structure were calculated by the Atoms-in-Molecules method. Chemical hardness and global electrophilicity index parameters were determined for congeners. A comparison of calculated descriptors and experimental data for congener reactivity in the S{sub N} and S{sub E} reactions was made. It is shown that interactions in the S{sub N} mechanism are reactions of the hard acid–hard base type, these are the most effective in case of highly chlorinated substrates. To explain the congener reactivity in the S{sub E} reactions, correct descriptors were not established. The obtained results can be used to carry out chemical transformations of the polychlorinated biphenyls in order to prepare them for microbiological destruction or preservation.

  5. Titanocene(III)-Catalyzed Three-Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes.

    Science.gov (United States)

    Zheng, Xiao; He, Jiang; Li, Heng-Hui; Wang, Ao; Dai, Xi-Jie; Wang, Ai-E; Huang, Pei-Qiang

    2015-11-09

    An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Computational Study of Chemical Reactivity Using Information-Theoretic Quantities from Density Functional Reactivity Theory for Electrophilic Aromatic Substitution Reactions.

    Science.gov (United States)

    Wu, Wenjie; Wu, Zemin; Rong, Chunying; Lu, Tian; Huang, Ying; Liu, Shubin

    2015-07-23

    The electrophilic aromatic substitution for nitration, halogenation, sulfonation, and acylation is a vastly important category of chemical transformation. Its reactivity and regioselectivity is predominantly determined by nucleophilicity of carbon atoms on the aromatic ring, which in return is immensely influenced by the group that is attached to the aromatic ring a priori. In this work, taking advantage of recent developments in quantifying nucleophilicity (electrophilicity) with descriptors from the information-theoretic approach in density functional reactivity theory, we examine the reactivity properties of this reaction system from three perspectives. These include scaling patterns of information-theoretic quantities such as Shannon entropy, Fisher information, Ghosh-Berkowitz-Parr entropy and information gain at both molecular and atomic levels, quantitative predictions of the barrier height with both Hirshfeld charge and information gain, and energetic decomposition analyses of the barrier height for the reactions. To that end, we focused in this work on the identity reaction of the monosubstituted-benzene molecule reacting with hydrogen fluoride using boron trifluoride as the catalyst in the gas phase. We also considered 19 substituting groups, 9 of which are ortho/para directing and the other 9 meta directing, besides the case of R = -H. Similar scaling patterns for these information-theoretic quantities found for stable species elsewhere were disclosed for these reactions systems. We also unveiled novel scaling patterns for information gain at the atomic level. The barrier height of the reactions can reliably be predicted by using both the Hirshfeld charge and information gain at the regioselective carbon atom. The energy decomposition analysis ensued yields an unambiguous picture about the origin of the barrier height, where we showed that it is the electrostatic interaction that plays the dominant role, while the roles played by exchange-correlation and

  7. Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench.

    Science.gov (United States)

    Talk, Ruaa A; Duperray, Alexia; Li, Xiabing; Coldham, Iain

    2016-06-07

    Substituted N-tert-butoxycarbonyl (Boc)-1,2,3,4-tetrahydroisoquinolines were prepared and treated with n-butyllithium in THF at -50 °C to test the scope of the metallation and electrophilic quench. The lithiation was optimised by using in situ ReactIR spectroscopy and the rate of rotation of the carbamate was determined. The 1-lithiated intermediates could be trapped with a variety of electrophiles to give good yields of 1-substituted tetrahydroisoquinoline products. Treatment with acid or reduction with LiAlH4 allows conversion to the N-H or N-Me compound. The chemistry was applied to the efficient total syntheses of the alkaloids (±)-crispine A and (±)-dysoxyline.

  8. A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives

    Directory of Open Access Journals (Sweden)

    Hicham Ben El Ayouchia

    2016-10-01

    Full Text Available The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components.

  9. Effect of substituent structure on pyrimidine electrophilic substitution

    CSIR Research Space (South Africa)

    Van der Westhuyzen, CW

    2007-01-01

    Full Text Available In an investigation into the electrophilic nitrosation reactions of a series of 4,6-disubstituted pyrimidine derivatives, a subtle interplay between the electronic nature of the C-4 and C-6 substituents and reactivity was found where these were...

  10. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    CERN Document Server

    Park, Y T; Kim, M S; Kwon, J H

    2002-01-01

    Photoreaction of N-(o-halophenyl)acetamide in basic acetonitrile produces an intramolecular substituted product, 2-methylbenzoxazole in addition to reduced product, acetanilide, whereas photoreaction of N-(o-halobenzyl)acetamide affords a reduced product, N-benzylacetamide only. On the basis of preparative reaction, kinetics, and UV/vis absorption behavior, an electrophilic aromatic substitution of aryl halide with oxygen of its amide bond are proposed.

  11. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong Tae; Song, Myong Geun; Kim, Moon Sub; Kwon, Jeong Hee [Kyungpook National Univ., Daegu (Korea, Republic of)

    2002-09-01

    Photoreaction of N-(o-halophenyl)acetamide in basic acetonitrile produces an intramolecular substituted product, 2-methylbenzoxazole in addition to reduced product, acetanilide, whereas photoreaction of N-(o-halobenzyl)acetamide affords a reduced product, N-benzylacetamide only. On the basis of preparative reaction, kinetics, and UV/vis absorption behavior, an electrophilic aromatic substitution of aryl halide with oxygen of its amide bond are proposed.

  12. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    International Nuclear Information System (INIS)

    Park, Yong Tae; Song, Myong Geun; Kim, Moon Sub; Kwon, Jeong Hee

    2002-01-01

    Photoreaction of N-(o-halophenyl)acetamide in basic acetonitrile produces an intramolecular substituted product, 2-methylbenzoxazole in addition to reduced product, acetanilide, whereas photoreaction of N-(o-halobenzyl)acetamide affords a reduced product, N-benzylacetamide only. On the basis of preparative reaction, kinetics, and UV/vis absorption behavior, an electrophilic aromatic substitution of aryl halide with oxygen of its amide bond are proposed

  13. Kinetics of electrophilic substitution of neodymium(III) by ytterbium(III) in aqueous solutions of ethylenediamintetraacetate and cyclohexanediaminetetraacetate

    International Nuclear Information System (INIS)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I.

    1982-01-01

    The kinetics of electrophilic substitution in systems containing rare earth element ions (REE) and Komplexon [tetrasodium ethylenediaminetetraacetate] have been studied little. At the same time, information about the mechanism of exchange is not only of theoretical interest but is important for the optimization of processes for separating and purifying REE. Least studied of all has been the mutual exchange in Komplexonate ions of light and heavy REE, although it is precisely the kinetics of exchange of different kinds of REE ions that primarily determines the effectiveness of the separation of their mixtures. We have studied electrophilic substitution in the case of the replacement of neodymium(III) by ytterbium(III) in solutions containing NdL - and Yb 3 + , where L 4 - and D 4 -

  14. The pi Complex of the Hydronium Ion Frozen on the Pathway of Electrophilic Aromatic Substitution

    Czech Academy of Sciences Publication Activity Database

    Růžičková, Z.; Holub, Josef; Melichar, Petr; Moncol, J.; Wann, D. A.; Fanfrlík, Jindřich; Růžička, A.; Hnyk, Drahomír

    2016-01-01

    Roč. 2016, č. 26 (2016), s. 4473-4475 ISSN 1434-193X R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388980 ; RVO:61388963 Keywords : Anions * Pi complexes * Electrophilic substitution * Quantum mechanics * Structure elucidation Subject RIV: CA - Inorganic Chemistry; CF - Physical ; Theoretical Chemistry (UOCHB-X) Impact factor: 2.834, year: 2016

  15. Reactivity and selectivity of the electrophile aromatic substitution in the gas phase by positive 80Br and 125I decay ions

    International Nuclear Information System (INIS)

    Knust, E.J.

    1975-02-01

    The nuclear isomeric transition sup(80m)Br(IT) 80 Br or the electron capture decay 125 Xe(EC) 125 I in the presence of high concentrations of a noble gas such as Ar or Xe are suitable for the study of the electrophilic substitution of bromium or iodonium ions in the gas phase. By using this nuclear method, which, unlike physical methods, also allows the determination of the isomer distribution, the electrophilic aromatic bromation and iodation of mono-substituted benzene compounds through unsolvated positive bromine or iodine ions could be investigated for the first time using radio-gas chromatographic techniques. (orig./LH) [de

  16. Polar Diels-Alder reactions using electrophilic nitrobenzothiophenes. A combined experimental and DFT study

    Science.gov (United States)

    Della Rosa, Claudia D.; Mancini, Pedro M. E.; Kneeteman, Maria N.; Lopez Baena, Anna F.; Suligoy, Melisa A.; Domingo, Luis R.

    2015-01-01

    The reactions between 2- and 3-nitrobenzothiophenes with three dienes of different nucleophilicity, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene, 1-trimethylsilyloxy-1,3-butadiene and isoprene developed in anhydrous benzene and alternative under microwave irradiation with molecular solvents or in free solvent conditions, respectively, for produce dibenzothiophenes permit to conclude that both nitroheterocycles act as electrophile with the cited dienes. In the cases of the dienes 1-methoxy-3-trimethylsilyloxy-1,3-butadiene and 1-trimethylsilyloxy-1,3-butadiene which posses major nucleophilicity the observed product is the normal cycloaddition one. However when the diene is isoprene the product with both electrophiles follow the hetero Diels-Alder way. These reactions are considered polar cycloaddition reactions and the yields are reasonables. Moreover the polar Diels-Alder reactions of nitrobenzothiophenes with electron rich dienes 1-trimethylsilyloxy-1,3-butadiene have been theoretically studied using DFT methods.

  17. Rate constants for some electrophilic reactions of benzyl, benzhydryl, and trityl cations in solution

    International Nuclear Information System (INIS)

    Ujdak, R.J.; Jones, R.L.; Dorfman, L.M.

    1976-01-01

    Absolute rate constants have been determined by the pulse radiolysis technique for several electrophilic reactions of the benzyl, the benzhydryl, and the trityl cation in 1,2-dichloroethane solution. The rate constants for the reactions of these carbonium ions with chloride ion, with bromide ion, and with iodide ion are all very nearly the same, namely 6 x 10 10 M -1 s -1 at 24 0 C. The values very likely represent the diffusion controlled limit for the ion combination reactions. The rate constants for the reactions with triethylamine, tri-n-propylamine, and tri-n-butylamine range from 2.0 x 10 9 to 7 x 10 6 M -1 s -1 at 24 0 C. With increasing phenyl substitution, the decreasing trend in the magnitude of the rate constant is consistent with the combined electronic and steric effects. With increasing size of the amine, the decrease in the value of the rate constant seems to indicate that the steric effect predominates. The values of the rate constants for reactions of benzyl and benzhydryl cation with methanol, ethanol, and 2-propanol indicate the following. The rate constant is higher for reaction with the alcohol dimer in solution than with alcohol monomer. The rate constants for reaction with alcohol monomer have values of 1 x 10 8 M -1 s -1 or lower

  18. Kinetics of electrophilic substitution of neodymium(3) by ytterbium(3) in aqueous solution of ethylenediaminetetraacetate solution of ethylenediaminetetraacetate and cyclohexanediaminetetraacetate

    Energy Technology Data Exchange (ETDEWEB)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I. (Moskovskij Gosudarstvennyj Univ. (USSR))

    1981-01-01

    The process of electrophilic substitution is studied spectrophotometrically taking as an example neodymium (3) substitution for ytterbium (3) in solutions, containing NdL/sup -/ and Yb/sup 3 +/, where L/sup 4 -/ = A/sup 4 -/ and D/sup 4 -/ (ethylenediaminetetraacetate- and cyclohexanediaminetetraacetate). The study of the exchange kinetics is carried out in pH range of 4-6. For the system with L=A in pH range 4.0-4.8 the exchange is realized by the way of acidic dissociation, at pH 5.5-6.0 - by the way of the direct attack. In the system with L=D in pH range 3.5-4.0 the way of acid dissociation prevails, at the same time, the rate constant of acidic dissociation for NdD/sup -/ is two order lower the constant for NdA/sup -/. However, at pH 4.7 the machanism of spontaneous dissociation prevails in the system. Thus, the structure of the complex has considerable effect on the mechanism of electrophilic substitution in rare earth complexes.

  19. Kinetics of electrophilic substitution of neodymium(3) by ytterbium(3) in aqueous solution of ethylenediaminetetraacetate solution of ethylenediaminetetraacetate and cyclohexanediaminetetraacetate

    International Nuclear Information System (INIS)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I.

    1981-01-01

    The process of electrophilic substitution is studied spectrophotometrically taking as an example neodymium (3) substitution for ytterbium (3) in solutions, containing NdL - and Yb 3+ , where L 4- = A 4- and D 4- (ethylenediaminetetraacetate- and cyclohexanediaminetetraacetate). The study of the exchange kinetics is carried out in pH range of 4-6. For the system with L=A in pH range 4.0-4.8 the exchange is realized by the way of acidic dissociation, at pH 5.5-6.0 - by the way of the direct attack. In the system with L=D in pH range 3.5-4.0 the way of acid dissociation prevails, at the same time, the rate constant of acidic dissociation for NdD - is two order lower the constant for NdA - . However, at pH 4.7 the machanism of spontaneous dissociation prevails in the system. Thus, the structure of the complex has considerable effect on the mechanism of electrophilic substitution in rare earth complexes [ru

  20. Transformations of diaziridines and their fused analogues induced by electrophilic reagents

    International Nuclear Information System (INIS)

    Makhova, Nina N; Shevtsov, Alexander V; Petukhova, Vera Yu

    2011-01-01

    The review deals with transformations of mono- and bicyclic diaziridine derivatives with different types of substitution induced by electrophilic reagents (protic acids, Lewis acids, alkylating and acylating agents, carbonyl compounds, heterocumulenes, activated alkenes and alkynes and transition metal salts). The characteristic features of the reactions are considered as functions of the structures of the starting diaziridines and the nature of the reaction medium (organic solvents, ionic liquids). Prospects of the use of diaziridine derivatives as readily available precursors for the synthesis of various nitrogen-containing heterocyclic systems based on the diaziridine ring expansion reactions are considered. The bibliography includes 136 references.

  1. Tandem electrophilic cyclization-[3+2] cycloaddition-rearrangement reactions of 2-alkynylbenzaldoxime, DMAD, and Br2.

    Science.gov (United States)

    Ding, Qiuping; Wang, Zhiyong; Wu, Jie

    2009-01-16

    Tandem electrophilic cyclization-[3+2] cycloaddition-rearrangement reactions of 2-alkynylbenzaldoximes, DMAD, and bromine are described, which afford the unexpected isoquinoline-based azomethine ylides in good to excellent yields. The products could be further elaborated via palladium-catalyzed cross-coupling reactions to generate highly functionalized isoquinoline-based stable azomethine ylides.

  2. Chiral 2-Aminobenzimidazole as Bifunctional Catalyst in the Asymmetric Electrophilic Amination of Unprotected 3-Substituted Oxindoles

    Directory of Open Access Journals (Sweden)

    Llorenç Benavent

    2018-06-01

    Full Text Available The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5. With this catalyst under optimized conditions, different oxindoles containing a wide variety of substituents at the 3-position were aminated in good yields and with good to excellent enantioselectivities using di-tert-butylazodicarboxylate as the aminating agent. The procedure proved to be also efficient for the amination of 3-substituted benzofuranones, although with moderate results. A bifunctional role of the catalyst, acting as Brønsted base and hydrogen bond donor, is proposed according to the experimental results observed.

  3. 2-Diazo-1-phenyl-2-((trifluoromethyl)sulfonyl)ethan-1-one: Another Utility for Electrophilic Trifluoromethylthiolation Reactions.

    Science.gov (United States)

    Huang, Zhongyan; Okuyama, Kenta; Wang, Chen; Tokunaga, Etsuko; Li, Xiaorui; Shibata, Norio

    2016-06-01

    2-Diazo-1-phenyl-2-((trifluoromethyl)sulfonyl)ethan-1-one (diazo-triflone) ( 2 ) is not only a building block but also a reagent. In this study, diazo-triflone, which was originally used for the synthesis of β-lactam triflones as a trifluoromethanesulfonyl (SO 2 CF 3 ) building block under catalyst-free thermal conditions, is redisclosed as an effective electrophilic trifluoromethylthiolation reagent under copper catalysis. A broad set of enamines, indoles, β-keto esters, pyrroles, and anilines were nicely transformed into corresponding trifluoromethylthio (SCF 3 ) compounds in good to high yields by diazo-triflone under copper catalysis via an electrophilic-type reaction. A coupling-type trifluoromethylthiolation reaction of aryl iodides was also realized by diazo-triflone in acceptable yields.

  4. Hydroamination reactions of alkynes with ortho-substituted anilines in ball mills: synthesis of benzannulated N-heterocycles by a cascade reaction.

    Science.gov (United States)

    Weiße, Maik; Zille, Markus; Jacob, Katharina; Schmidt, Robert; Stolle, Achim

    2015-04-20

    It was demonstrated that ortho-substituted anilines are prone to undergo hydroamination reactions with diethyl acetylenedicarboxylate in a planetary ball mill. A sequential coupling of the intermolecular hydroamination reaction with intramolecular ring closure was utilized for the syntheses of benzooxazines, quinoxalines, and benzothiazines from readily available building blocks, that is, electrophilic alkynes and anilines with OH, NH, or SH groups in the ortho position. For the heterocycle formation, it was shown that several stress conditions were able to initiate the reaction in the solid state. Processing in a ball mill seemed to be advantageous over comminution with mortar and pestle with respect to process control. In the latter case, significant postreaction modification occurred during solid-state analysis. Cryogenic milling proved to have an adverse effect on the molecular transformation of the reagents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Evidence for an Intermediate in the Methylation of CB11H12- with Methyl Triflate: Comparison of Electrophilic Substitution in Cage Boranes and in Arenes

    Czech Academy of Sciences Publication Activity Database

    Kaleta, Jiří; Akdag, Akin; Crespo, R.; Piqueras, M. C.; Michl, Josef

    2013-01-01

    Roč. 78, č. 9 (2013), s. 1174-1183 ISSN 2192-6506 Institutional support: RVO:61388963 Keywords : alkylation * boranes * carboranes * electrophilic substitution * hydrogen scrambling Subject RIV: CC - Organic Chemistry Impact factor: 3.242, year: 2013

  6. Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

    Directory of Open Access Journals (Sweden)

    Andreas Gansäuer

    2013-08-01

    Full Text Available The intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol−1 and was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG‡ and ΔGR are found. Addition reactions leading to indanes or dihydrobenzofurans are too slow to be useful synthetically.

  7. Asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)- sparteine-mediated electrophilic substitution

    International Nuclear Information System (INIS)

    Choi, Yun Soo; Kang, Kyoung Hee; Park, Yong Sun

    2015-01-01

    Tetrahydroquinolines bearing substituents are frequently found as a substructure in a number of alkaloids and natural products. Since their individual stereoisomers displays different biological activities, it is desirable to develop a highly stereoselective synthetic method for tetrahydroquinolines. While some progress has recently been made toward the development of asymmetric synthetic methods for tetrahydroquinolines, it is still a challenging topic in organic synthesis. In order to investigate the source of diastereoselection attained in the substitution reaction with a racemic epoxide, we examined the substitution of 2 with an excess amount of racemic p-chlorophenyl-substituted oxirane. We have developed a novel method for the asymmetric synthesis of trans-3,4-diaryl-substituted tetrahy- droquinolines from ortho-substituted N-pivaloyl anilines. The enantioselective process includes (+)-sparteine-mediated stereoselective lithiati on, kinetic resolution of epoxides in substitution, and stereospecific Mitsu nobu cyclization as the key reactions. The simple protocol can provide highly functionalized tetrahydroqu inoline rings and would allow their further functionalization to access more complex target molecules

  8. Asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)- sparteine-mediated electrophilic substitution

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Soo; Kang, Kyoung Hee; Park, Yong Sun [Dept. of Chemistry, Konkuk University, Seoul (Korea, Republic of)

    2015-05-15

    Tetrahydroquinolines bearing substituents are frequently found as a substructure in a number of alkaloids and natural products. Since their individual stereoisomers displays different biological activities, it is desirable to develop a highly stereoselective synthetic method for tetrahydroquinolines. While some progress has recently been made toward the development of asymmetric synthetic methods for tetrahydroquinolines, it is still a challenging topic in organic synthesis. In order to investigate the source of diastereoselection attained in the substitution reaction with a racemic epoxide, we examined the substitution of 2 with an excess amount of racemic p-chlorophenyl-substituted oxirane. We have developed a novel method for the asymmetric synthesis of trans-3,4-diaryl-substituted tetrahy- droquinolines from ortho-substituted N-pivaloyl anilines. The enantioselective process includes (+)-sparteine-mediated stereoselective lithiati on, kinetic resolution of epoxides in substitution, and stereospecific Mitsu nobu cyclization as the key reactions. The simple protocol can provide highly functionalized tetrahydroqu inoline rings and would allow their further functionalization to access more complex target molecules.

  9. Kinetics of electrophilic substitution of erbium (3) for ytterbium (3) in aqueous solution of ethylenediaminetetraacetate

    Energy Technology Data Exchange (ETDEWEB)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I. (Moskovskij Gosudarstvennyj Univ. (USSR))

    1983-08-01

    The results obtained while studing the exchange kinetics in the ErA/sup -/ - Yb/sup 3 +/ system are compared with the kinetic regularities found for the NdA/sup -/ - Yb/sup 3 +/ system. Electrophilic substitution in ethylenediamine tetraacetates of rare earths (3) independently of the nature of a departing cation is realized through two competitive mechanisms: acid dissociation and associative mechanisms. Exchange through the acid dissociation mechanisms is catalized by protons while, depending on the medium acidity, mono- and biprotonated intermediate complexes are formed. The associative mechanism predominates in less acid media and is realized through the formation of intermediate binuclear complexes. The limiting exchange stage is a break in the metal-nitrogen bond formed by the departing cation and ligand in the intermediate binuclear complex.

  10. Kinetics of electrophilic substitution of erbium (3) for ytterbium (3) in aqueous solution of ethylenediaminetetraacetate

    International Nuclear Information System (INIS)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I.

    1983-01-01

    The results obtained while stUdying the exchange kinetics in the ErA - - Yb 3+ system are compared with the kinetic regularities found for the NdA - - Yb 3+ system. Electrophilic substitution in ethylenediamine tetraacetates of rare earths (3) independently of the nature of a departing cation is realized through two competitive mechanisms: acid dissociation and associatiVe mechanisms. Exchange through the acid dissociation mechanisms is catalized by protons while, depending on the medium acidity, mono- and biprotonated intermediate complexes are formed. The associative mechanism predominates in less acid media and is realized through the formation of intermediate binOclear compleXes. The limiting exchange stage is a break in the metal-nitrogen bond formed by the departing cation and ligand in the intermediate binUclear complex

  11. One-pot regioselective synthesis of nitrophenyloxazolinyl styrene oxides by the Darzens reaction of vicarious nucleophilic substitution-formed carbanions of 2-dichloromethyl-4,4-dimethyloxazoline.

    Science.gov (United States)

    Florio, Saverio; Lorusso, Patrizia; Granito, Catia; Luisi, Renzo; Troisi, Luigino

    2004-07-23

    The vicarious nucleophilic substitution reaction of dichloromethyloxazoline 2 with nitrobenzene has been investigated. Treatment of 2 with t-BuOK followed by the addition of nitrobenzene leads to benzylic carbanions 4 or 9 depending upon the solvent used (DMSO, DMF, or THF). Subsequent treatment of 4 or 9 with aldehydes, in a Darzens-like reaction, furnishes very good yields of nitrophenyl oxazolinyloxiranes 8 and 11. 1,2-Dioxazolinyl-1,2-dinitrophenylethene 7 forms quantitatively when carbanion 4 is allowed to warm to room temperature in the absence of external electrophiles.

  12. Effects of Bentonite on p-Methoxybenzyl Acetate: A Theoretical Model for Oligomerization via an Electrophilic-Substitution Mechanism

    Directory of Open Access Journals (Sweden)

    Manuel Salmón

    2011-02-01

    Full Text Available Tonsil Actisil FF, a commercial bentonitic clay, promotes the formation of a series of electrophilic-aromatic-substitution products from para-methoxybenzyl acetate in carbon disulfide. The molecules obtained correspond to linear isomeric dimers, trimers, tetramers and a pentamer, according to their spectroscopic data. A clear indication of the title mechanistic pathway for the oligomerization growth was obtained from the analysis of a set of computational-chemistry calculations using the density-functional-theory level B3LYP/6-311++G(d,p. The corresponding conclusions were based on the computed dipole moments, the HOMO/LUMO distributions, and a natural-populations analysis of the studied molecules.

  13. Substitution reactions of technetium complexes

    International Nuclear Information System (INIS)

    Omori, T.

    1997-01-01

    Substitution reactions of a series of technetium complexes are considered in comparison with corresponding reactions of rhenium. Rhenium and technetium complexes are rather inert in substitution reactions, the latter are characterized by greater rate constants when they proceed according to dissociative mechanism. In rare cases when k Tc /k Re id little it is assumed that the reaction proceeds according to the associative mechanism. (author)

  14. Diverse Reactions of Thiophenes, Selenophenes, and Tellurophenes with Strongly Oxidizing I(III) PhI(L)2 Reagents.

    Science.gov (United States)

    Egalahewa, Sathsara; Albayer, Mohammad; Aprile, Antonino; Dutton, Jason L

    2017-02-06

    We report the outcomes of the reactions of aromatic group 16 thiophene, selenophene, and tellurophene rings with the I(III) oxidants PhI(OAc)(OTf) and [PhI(Pyr) 2 ][OTf] 2 (Pyr = pyridine). In all reactions, oxidative processes take place, with generation of PhI as the reduction product. However, with the exception of tellurophene with PhI(OAc)(OTf), +4 oxidation state complexes are not observed, but rather a variety of other processes occur. In general, where a C-H unit is available on the 5-membered ring, an electrophilic aromatic substitution reaction of either -IPh or pyridine onto the ring occurs. When all positions are blocked, reactions with PhI(OAc)(OTf) give acetic and triflic anhydride as the identifiable oxidative byproducts, while [PhI(Pyr) 2 ][OTf] 2 gives pyridine electrophilic aromatic substitution onto the peripheral rings. Qualitative mechanistic studies indicate that the presence of the oxidizable heteroatom is required for pyridine to act as an electrophile in a substantial manner.

  15. Privileged Electrophile Sensors: A Resource for Covalent Drug Development.

    Science.gov (United States)

    Long, Marcus John Curtis; Aye, Yimon

    2017-07-20

    This Perspective delineates how redox signaling affects the activity of specific enzyme isoforms and how this property may be harnessed for rational drug design. Covalent drugs have resurged in recent years and several reports have extolled the general virtues of developing irreversible inhibitors. Indeed, many modern pharmaceuticals contain electrophilic appendages. Several invoke a warhead that hijacks active-site nucleophiles whereas others take advantage of spectator nucleophilic side chains that do not participate in enzymatic chemistry, but are poised to bind/react with electrophiles. The latest data suggest that innate electrophile sensing-which enables rapid reaction with an endogenous signaling electrophile-is a quintessential resource for the development of covalent drugs. For instance, based on recent work documenting isoform-specific electrophile sensing, isozyme non-specific drugs may be converted to isozyme-specific analogs by hijacking privileged first-responder electrophile-sensing cysteines. Because this approach targets functionally relevant cysteines, we can simultaneously harness previously untapped moonlighting roles of enzymes linked to redox sensing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. ELECTROPHILIC CYCLIZATION OF DITERPENOIDS

    Directory of Open Access Journals (Sweden)

    Veaceslav Kulciţki

    2006-06-01

    Full Text Available A review of diterpenoid cyclization initiated by electrophilic reagents is provided. Conventional protonic and Lewis acids are examined along with superacids as initiators of cyclization cascade. An emphasis is placed on the use of cyclization reactions as a tool for the synthesis of compounds with potential practical utility. The review contains 74 references.

  17. Tandem ring-closing metathesis/isomerization reactions for the total synthesis of violacein

    DEFF Research Database (Denmark)

    Petersen, Mette Terp; Nielsen, Thomas Eiland

    2013-01-01

    A series of 5-substituted 2-pyrrolidinones was synthesized through a one-pot ruthenium alkylidene-catalyzed tandem RCM/isomerization/nucleophilic addition sequence. The intermediates resulting from RCM/isomerization showed reactivity toward electrophiles in aldol condensation reactions which...

  18. Kinetics of exchange reaction between neodymium(3) transcyclohexanediaminetetraacetate and europium(3)- and holmium(3) aquo-ions in the H/sub 2/O and D/sub 2/O solutions

    Energy Technology Data Exchange (ETDEWEB)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I. (Moskovskij Gosudarstvennyj Univ. (USSR))

    1983-10-01

    The exchange reaction between central ions in the NdD/sup -/Ln'/sup 3 +/ systems, where Ln'/sup 3 +/ is a substituting cation (Eu/sup 3 +/ and Ho/sup 3 +/, D/sup 4/=cyclohexanediaminetetraacetate) is studied and the electrophilic substitution mechanism is considered. To study the kinetic isotope effects, the reagents have been solved in heavy water containing 99.9% D/sub 2/O. The electrophilic substitution in the indicated systems proceeds through the dissociative mechanism catalyzed by protons and via the spontaneous dissociation mechanism. The exchange via the acid-catalyzed mechanism is limited by the intermediate protonated complex decay. The associative mechanism of the electrophilic exchange in the studied systems is not realized.

  19. Catalytic Ketone Hydrodeoxygenation Mediated by Highly Electrophilic Phosphonium Cations.

    Science.gov (United States)

    Mehta, Meera; Holthausen, Michael H; Mallov, Ian; Pérez, Manuel; Qu, Zheng-Wang; Grimme, Stefan; Stephan, Douglas W

    2015-07-06

    Ketones are efficiently deoxygenated in the presence of silane using highly electrophilic phosphonium cation (EPC) salts as catalysts, thus affording the corresponding alkane and siloxane. The influence of distinct substitution patterns on the catalytic effectiveness of several EPCs was evaluated. The deoxygenation mechanism was probed by DFT methods. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Interaction of nitriles with electrophilic reagents

    International Nuclear Information System (INIS)

    Gridnev, I.D.; Gridneva, N.A.

    1995-01-01

    Reactions of organic nitriles with various electrophiles, Lewis acids (BF 3 , BCl 3 , RuCl 2 , NbCl 5 , ReCl 4 , etc.) in particular, were analysed. Features of nitriles coordination with transition metals (Mo, Ru, Re, Pt, etc.) were considered. It is shown that numerous processes observed in these reactions exhibit rather similar features and are mainly controlled by the nucleophilic properties of a nitrile. REfs, 99, tabs. 8

  1. Kinetics of exchange reaction between neodymium(3) transcyclohexanediaminetetraacetate and europium(3)- and holmium(3) aquo-ions in the H2O and D2O solutions

    International Nuclear Information System (INIS)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I.

    1983-01-01

    The exchange reaction between central ions in the NdD - Ln' 3+ systems, where Ln' 3+ is a substituting cation (Eu 3+ and Ho 3+ , D 4 =cyclohexanediaminetetraacetate) is studied and the electrophilic suhstitution mechanism is considered. To study the kinetic isotope effects, the reagents have been solVed in heavy water containing 99.9% D 2 O. The electrophilic substitution in the indicated systems proceeds through the dissociative mechanism catalyzed by protons and via the spontaneous dissociation mechanism. The exchange via the acid-catalyzed mechanism is limited by the intermediate protonated complex decay. The associative mechanism of the electrophilic exchange in the studied systems is not realized

  2. Synthesis of Fluoroalkoxy Substituted Arylboronic Esters by Iridium-Catalyzed Aromatic C–H Borylation

    KAUST Repository

    Batool, Farhat

    2015-08-17

    The preparation of fluoroalkoxy arylboronic esters by iridium-catalyzed aromatic C–H borylation is described. The fluoroalkoxy groups employed include trifluoromethoxy, difluoromethoxy, 1,1,2,2-tetrafluoroethoxy, and 2,2-difluoro-1,3-benzodioxole. The borylation reactions were carried out neat without the use of a glovebox or Schlenk line. The regioselectivities available through the iridium-catalyzed C–H borylation are complementary to those obtained by the electrophilic aromatic substitution reactions of fluoroalkoxy arenes. Fluoroalkoxy arylboronic esters can serve as versatile building blocks.

  3. Synthesis of Fluoroalkoxy Substituted Arylboronic Esters by Iridium-Catalyzed Aromatic C–H Borylation

    KAUST Repository

    Batool, Farhat; Parveen, Shehla; Emwas, Abdul-Hamid M.; Sioud, Salim; Gao, Xin; Munawar, Munawar A.; Chotana, Ghayoor A.

    2015-01-01

    The preparation of fluoroalkoxy arylboronic esters by iridium-catalyzed aromatic C–H borylation is described. The fluoroalkoxy groups employed include trifluoromethoxy, difluoromethoxy, 1,1,2,2-tetrafluoroethoxy, and 2,2-difluoro-1,3-benzodioxole. The borylation reactions were carried out neat without the use of a glovebox or Schlenk line. The regioselectivities available through the iridium-catalyzed C–H borylation are complementary to those obtained by the electrophilic aromatic substitution reactions of fluoroalkoxy arenes. Fluoroalkoxy arylboronic esters can serve as versatile building blocks.

  4. Modeling of Toxicity-Relevant Electrophilic Reactivity for Guanine with Epoxides: Estimating the Hard and Soft Acids and Bases (HSAB) Parameter as a Predictor.

    Science.gov (United States)

    Zhang, Jing; Wang, Chenchen; Ji, Li; Liu, Weiping

    2016-05-16

    According to the electrophilic theory in toxicology, many chemical carcinogens in the environment and/or their active metabolites are electrophiles that exert their effects by forming covalent bonds with nucleophilic DNA centers. The theory of hard and soft acids and bases (HSAB), which states that a toxic electrophile reacts preferentially with a biological macromolecule that has a similar hardness or softness, clarifies the underlying chemistry involved in this critical event. Epoxides are hard electrophiles that are produced endogenously by the enzymatic oxidation of parent chemicals (e.g., alkenes and PAHs). Epoxide ring opening proceeds through a SN2-type mechanism with hard nucleophile DNA sites as the major facilitators of toxic effects. Thus, the quantitative prediction of chemical reactivity would enable a predictive assessment of the molecular potential to exert electrophile-mediated toxicity. In this study, we calculated the activation energies for reactions between epoxides and the guanine N7 site for a diverse set of epoxides, including aliphatic epoxides, substituted styrene oxides, and PAH epoxides, using a state-of-the-art density functional theory (DFT) method. It is worth noting that these activation energies for diverse epoxides can be further predicted by quantum chemically calculated nucleophilic indices from HSAB theory, which is a less computationally demanding method than the exacting procedure for locating the transition state. More importantly, the good qualitative/quantitative correlations between the chemical reactivity of epoxides and their bioactivity suggest that the developed model based on HSAB theory may aid in the predictive hazard evaluation of epoxides, enabling the early identification of mutagenicity/carcinogenicity-relevant SN2 reactivity.

  5. Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.

    Science.gov (United States)

    Park, Yongho; Harper, Kaid C; Kuhl, Nadine; Kwan, Eugene E; Liu, Richard Y; Jacobsen, Eric N

    2017-01-13

    Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction. Copyright © 2017, American Association for the Advancement of Science.

  6. Uncatalyzed hydroamination of electrophilic organometallic alkynes: fundamental, theoretical, and applied aspects.

    Science.gov (United States)

    Wang, Yanlan; Latouche, Camille; Rapakousiou, Amalia; Lopez, Colin; Ledoux-Rak, Isabelle; Ruiz, Jaime; Saillard, Jean-Yves; Astruc, Didier

    2014-06-23

    Simple reactions of the most used functional groups allowing two molecular fragments to link under mild, sustainable conditions are among the crucial tools of molecular chemistry with multiple applications in materials science, nanomedicine, and organic synthesis as already exemplified by peptide synthesis and "click" chemistry. We are concerned with redox organometallic compounds that can potentially be used as biosensors and redox catalysts and report an uncatalyzed reaction between primary and secondary amines with organometallic electrophilic alkynes that is free of side products and fully "green". A strategy is first proposed to synthesize alkynyl organometallic precursors upon addition of electrophilic aromatic ligands of cationic complexes followed by endo hydride abstraction. Electrophilic alkynylated cyclopentadienyl or arene ligands of Fe, Ru, and Co complexes subsequently react with amines to yield trans-enamines that are conjugated with the organometallic group. The difference in reactivities of the various complexes is rationalized from the two-step reaction mechanism that was elucidated through DFT calculations. Applications are illustrated by the facile reaction of ethynylcobalticenium hexafluorophosphate with aminated silica nanoparticles. Spectroscopic, nonlinear-optical and electrochemical data, as well as DFT and TDDFT calculations, indicate a strong push-pull conjugation in these cobalticenium- and Fe- and Ru-arene-enamine complexes due to planarity or near-planarity between the organometallic and trans-enamine groups involving fulvalene iminium and cyclohexadienylidene iminium mesomeric forms. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Precision Electrophile Tagging in Caenorhabditis elegans.

    Science.gov (United States)

    Long, Marcus J C; Urul, Daniel A; Chawla, Shivansh; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Wang, Yiran; Aye, Yimon

    2018-01-16

    Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile-sensor proteins, respectively. However, precision mapping between specific redox-modified targets and specific responses has only recently begun to be addressed, and systems tractable to both genetic manipulation and on-target redox signaling in vivo remain largely limited. Here we engineer transgenic Caenorhabditis elegans expressing functional HaloTagged fusion proteins and use this system to develop a generalizable light-controlled approach to tagging a prototypical electrophile-sensor protein with native electrophiles in vivo. The method circumvents issues associated with low uptake/distribution and toxicity/promiscuity. Given the validated success of C. elegans in aging studies, this optimized platform offers a new lens with which to scrutinize how on-target electrophile signaling influences redox-dependent life span regulation.

  8. Ionic Liquids: An Environmentally Friendly Media for Nucleophilic Substitution Reactions

    International Nuclear Information System (INIS)

    Jorapur, Yogesh R.; Chi, Dae Yoon

    2006-01-01

    Ionic liquids are alternative reaction media of increasing interest and are regarded as an eco-friendly alternatives, of potential use in place of the volatile organic solvents typically used in current chemical processing methods. They are emerging as the smart and excellent solvents, which are made of positive and negative ions that they are liquids near room temperature. The nucleophilic substitution reaction is one of the important method for inserting functional groups into a carbon skeleton. Many nucleophilic substitution reactions have been found with enhanced reactivity and selectivity in ionic liquid. In this review, some recent interesting results of nucleophilic substitution reactions such as hydroxylations, ether cleavages, carbon-X (X = carbon, oxygen, nitrogen, fluorine) bond forming reactions, and ring opening of epoxides in ionic liquids are discussed

  9. Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity evaluation.

    Science.gov (United States)

    Cheng, Hanyang; Song, Dean; Chang, Yangyang; Liu, Huijuan; Qu, Jiuhui

    2015-12-01

    Tramadol (TRA) is one of the most detected analgesics in environmental matrices, and it is of high significance to study the reactivity of TRA during chlorination considering its potential toxicity to the environment. The chlorine/TRA reaction is first order with respect to the TRA concentration, and a combination of first-order and second-order with respect to chlorine concentration. The pH dependence of the observed rate constants (kobs) showed that the TRA oxidation reactivity increased with increasing pH. kobs can be quantitatively described by considering all active species including Cl2, Cl2O and HOCl, and the individual rate constants of HOCl/TRA(0), HOCl/TRAH(+), Cl2/TRA and Cl2O/TRA reactions were calculated to be (2.61±0.29)×10(3)M(-1)s(-1), 14.73±4.17M(-1)s(-1), (3.93±0.34)×10(5)M(-1)s(-1) and (5.66±1.83)×10(6)M(-1)s(-1), respectively. Eleven degradation products were detected with UPLC-Q-TOF-MS, and the corresponding structures of eight products found under various pH conditions were proposed. The amine group was proposed to be the initial attack site under alkaline pH conditions, where reaction of the deprotonated amine group with HOCl is favorable. Under acidic and neutral pH conditions, however, two possible reaction pathways were proposed. One is an electrophilic substitution on the aromatic ring, and another is an electrophilic substitution on the nitrogen, leading to an N-chlorinated intermediate, which can be further oxidized. Finally, the SOS/umu test showed that the genotoxicity of TRA chlorination products increased with increasing dosage of chlorine, which was mostly attributed to the formation of some chlorine substitution products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

    Directory of Open Access Journals (Sweden)

    Madhuri Vangala

    2015-11-01

    Full Text Available The TMSOTf-mediated synthesis of β-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a “Ritter-like” reaction in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-β-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group.

  11. Preparation and Reaction Chemistry of Novel Silicon-Substituted 1,3-Dienes

    Directory of Open Access Journals (Sweden)

    Partha P. Choudhury

    2015-09-01

    Full Text Available 2-Silicon-substituted 1,3-dienes containing non transferrable groups known to promote transmetallation were prepared by Grignard chemistry and enyne metathesis. These dienes participated in one pot metathesis/Diels-Alder reactions in regio- and diastereoselective fashions. Electron-rich alkenes showed the fastest rates in metathesis reactions, and ethylene, a commonly used metathesis promoter slowed enyne metathesis. 2-Pyridyldimethylsilyl and 2-thienyldimethylsilyl substituted Diels-Alder cycloadducts participated in cross-coupling chemistry and the 2-thienyldimethylsilyl substituted cycloadducts underwent cross-coupling under very mild reaction conditions.

  12. Electrophilic properties of patulin. Adduct structures and reaction pathways with 4-bromothiophenol and other model nucleophiles.

    Science.gov (United States)

    Fliege, R; Metzler, M

    2000-05-01

    The mycotoxin patulin (PAT) is believed to exert its cytotoxic and chromosome-damaging effects by forming covalent adducts with essential cellular thiols. Since the chemical structures of such adducts are unknown to date, we have studied the reaction of PAT and its O-acetylated derivative with the monofunctional thiol model compound 4-bromothiophenol (BTP), which was chosen due to analytical advantages. By means of analytical and preparative high-performance liquid chromatography, 16 adducts of PAT and 3 adducts of acetyl-PAT were isolated and their chemical structures elucidated by (1)H and (13)C NMR, IR, and UV spectroscopy. Time course studies and analysis of daughter product formation from isolated intermediate adducts led to a detailed scheme for the reaction of PAT with BTP. The structures of adducts of PAT formed with other model nucleophiles, e. g., the aliphatic thiol 2-mercaptoethanol and the aromatic amine 4-bromoaniline, were also elucidated and found to corroborate the reaction scheme. In addition, one further reaction pathway was observed with 2-mercaptoethanol, which appears to be independent from those found for BTP. Our study with model nucleophiles provides insights into the electrophilic reactivity of PAT and proved to be useful for the structure elucidation of PAT adducts with biological nucleophiles of toxicological relevance, as will be reported by Fliege and Metzler [(2000) Chem. Res. Toxicol. 13, 373-381].

  13. Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping.

    Science.gov (United States)

    Nie, Jing; Zhu, Hong-Wei; Cui, Han-Feng; Hua, Ming-Qing; Ma, Jun-An

    2007-08-02

    A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.

  14. Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

    International Nuclear Information System (INIS)

    Muñoz-Muñoz, Jose Luis; Berna, Jose; García-Molina, María del Mar; Garcia-Molina, Francisco; Garcia-Ruiz, Pedro Antonio; Varon, Ramon

    2012-01-01

    Highlights: ► The action the copper complexes and tyrosinase on phenols is equivalent. ► Isotope effect showed that nucleophilic attack to copper atom may be the slower step. ► The value of ρ (Hammett constant) supports an electrophilic aromatic substitution. ► Data obtained in steady state pH 7 conditions support the mechanism of Scheme 1SM. -- Abstract: A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: k cat m and the Michaelis constant, K M m . Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group (δ) and σ p + , enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form E ox (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant ρ of −1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of k cat f n /k cat f 0 against n (atom fractions of deuterium), where k cat f n is the catalytic constant for a molar fraction of deuterium (n) and k cat f 0 is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that only one of the proton transfer processes from the hydroxyl groups involved the catalytic cycle is responsible for the isotope effects. We suggest that this step is the proton transfer from the hydroxyl group

  15. Palladium-catalysed electrophilic aromatic C-H fluorination

    Science.gov (United States)

    Yamamoto, Kumiko; Li, Jiakun; Garber, Jeffrey A. O.; Rolfes, Julian D.; Boursalian, Gregory B.; Borghs, Jannik C.; Genicot, Christophe; Jacq, Jérôme; van Gastel, Maurice; Neese, Frank; Ritter, Tobias

    2018-02-01

    Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.

  16. Dramatic Influence of Ionic Liquid and Ultrasound Irradiation on the Electrophilic Sulfinylation of Aromatic Compounds by Sulfinic Esters

    DEFF Research Database (Denmark)

    Nguyen, Ngoc-Lan Thi; Vo, Hong-Thom; Duus, Fritz

    2017-01-01

    The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylim......The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3...

  17. Hydroalumination of Ketenimines and Subsequent Reactions with Heterocumulenes: Synthesis of Unsaturated Amide Derivatives and 1,3-Diimines.

    Science.gov (United States)

    Jin, Xing; Willeke, Matthias; Lucchesi, Ralph; Daniliuc, Constantin-Gabriel; Fröhlich, Roland; Wibbeling, Birgit; Uhl, Werner; Würthwein, Ernst-Ulrich

    2015-06-19

    The series of differently substituted ketenimines 1 was hydroluminated using di-iso-butyl aluminum hydride. For the sterically congested ketenimine 1a, preferred hydroalumination of the C═N-bond was proven by X-ray crystallography (compound 5a). In situ treatment of the hydroaluminated ketenimines 5 with various heterocumulenes like carbodiimides, isocycanates, isothiocyanates and ketenimines as electrophiles and subsequent hydrolytic workup resulted in novel enamine derived amide species in case of N-attack (sterically less hindered ketenimines) under formation of a new C-N-bond or in 1,3-diimines by C-C-bond-formation in case of bulky substituents at the ketenimine-nitrogen atom. Furthermore, domino reactions with more than 1 equiv of the electrophile or by subsequent addition of two different electrophiles are possible and lead to polyfunctional amide derivatives of the biuret type which are otherwise not easily accessible.

  18. Electronic forces as descriptors of nucleophilic and electrophilic regioselectivity and stereoselectivity.

    Science.gov (United States)

    Liu, Shubin; Rong, Chunying; Lu, Tian

    2017-01-04

    One of the main tasks of theoretical chemistry is to rationalize computational results with chemical insights. Key concepts of such nature include nucleophilicity, electrophilicity, regioselectivity, and stereoselectivity. While computational tools are available to predict barrier heights and other reactivity properties with acceptable accuracy, a conceptual framework to appreciate above quantities is still lacking. In this work, we introduce the electronic force as the fundamental driving force of chemical processes to understand and predict molecular reactivity. It has three components but only two are independent. These forces, electrostatic and steric, can be employed as reliable descriptors for nucleophilic and electrophilic regioselectivity and stereoselectivity. The advantages of using these forces to evaluate molecular reactivity are that electrophilic and nucleophilic attacks are featured by distinct characteristics in the electrostatic force and no knowledge of quantum effects included in the kinetic and exchange-correlation energies is required. Examples are provided to highlight the validity and general applicability of these reactivity descriptors. Possible applications in ambident reactivity, σ and π holes, frustrated Lewis pairs, and stereoselective reactions are also included in this work.

  19. Hydrogen-bond-driven electrophilic activation for selectivity control: scope and limitations of fluorous alcohol-promoted selective formation of 1,2-disubstituted benzimidazoles and mechanistic insight for rationale of selectivity.

    Science.gov (United States)

    Chebolu, Rajesh; Kommi, Damodara N; Kumar, Dinesh; Bollineni, Narendra; Chakraborti, Asit K

    2012-11-16

    Hydrogen-bond-driven electrophilic activation for selectivity control during competitive formation of 1,2-disubstituted and 2-substituted benzimidazoles from o-phenylenediamine and aldehydes is reported. The fluorous alcohols trifluoroethanol and hexafluoro-2-propanol efficiently promote the cyclocondensation of o-phenylenediamine with aldehydes to afford selectively the 1,2-disubstituted benzimidazoles at rt in short times. A mechanistic insight is invoked by NMR, mass spectrometry, and chemical studies to rationalize the selectivity. The ability of the fluorous alcohols in promoting the reaction and controlling the selectivity can be envisaged from their better hydrogen bond donor (HBD) abilities compared to that of the other organic solvents as well as of water. Due to the better HBD values, the fluorous alcohols efficiently promote the initial bisimine formation by electrophilic activation of the aldehyde carbonyl. Subsequently the hydrogen-bond-mediated activation of the in situ-formed bisimine triggers the rearrangement via 1,3-hydride shift to form the 1,2-disubstituted benzimidazoles.

  20. Development of selective colorimetric probes for hydrogen sulfide based on nucleophilic aromatic substitution.

    Science.gov (United States)

    Montoya, Leticia A; Pearce, Taylor F; Hansen, Ryan J; Zakharov, Lev N; Pluth, Michael D

    2013-07-05

    Hydrogen sulfide is an important biological signaling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated submicromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications.

  1. Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity.

    Science.gov (United States)

    Pals, Justin A; Wagner, Elizabeth D; Plewa, Michael J; Xia, Menghang; Attene-Ramos, Matias S

    2017-08-01

    Haloacetamides (HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S N 2 reaction mechanism. Toxicity of the monohalogenated HAMs (iodoacetamide, IAM; bromoacetamide, BAM; or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints. Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM>BAM>CAM for Rad51, and BAM≈IAM>CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM. Copyright © 2017. Published by Elsevier B.V.

  2. Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

    Science.gov (United States)

    Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D

    2017-04-01

    Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Munoz-Munoz, Jose Luis [GENZ - Grupo de Investigacion Enzimologia, Departamento de Bioquimica y Biologia Molecular-A, Facultad de Biologia, Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia, E-30100 Espinardo, Murcia (Spain); Berna, Jose [Grupo de Quimica Organica Sintetica, Departamento de Quimica Organica, Facultad de Quimica Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia (Spain); Garcia-Molina, Maria del Mar; Garcia-Molina, Francisco [GENZ - Grupo de Investigacion Enzimologia, Departamento de Bioquimica y Biologia Molecular-A, Facultad de Biologia, Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia, E-30100 Espinardo, Murcia (Spain); Garcia-Ruiz, Pedro Antonio [QCPAI - Grupo de Quimica de Carbohidratos, Polimeros y Aditivos Industriales, Departamento de Quimica Organica, Facultad de Quimica Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia (Spain); Varon, Ramon [Departamento de Quimica-Fisica, Escuela de Ingenieros Industriales de Albacete, Universidad de Castilla la Mancha, Avda. Espana s/n. Campus Universitario, E-02071 Albacete (Spain); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer The action the copper complexes and tyrosinase on phenols is equivalent. Black-Right-Pointing-Pointer Isotope effect showed that nucleophilic attack to copper atom may be the slower step. Black-Right-Pointing-Pointer The value of {rho} (Hammett constant) supports an electrophilic aromatic substitution. Black-Right-Pointing-Pointer Data obtained in steady state pH 7 conditions support the mechanism of Scheme 1SM. -- Abstract: A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: k{sub cat}{sup m} and the Michaelis constant, K{sub M}{sup m}. Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group ({delta}) and {sigma}{sub p}{sup +}, enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form E{sub ox} (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant {rho} of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of k{sub cat}{sup f{sub n}}/k{sub cat}{sup f{sub 0}} against n (atom fractions of deuterium), where k{sub cat}{sup f{sub n}} is the catalytic constant for a molar fraction of deuterium (n) and k{sub cat}{sup f{sub 0}} is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that

  4. Microwave-induced electrophilic addition of single-walled carbon nanotubes with alkylhalides

    Energy Technology Data Exchange (ETDEWEB)

    Xu Yang [Faculty of Materials Science and Engineering, Hubei University, Wuhan 430062 (China); Wang Xianbao [Faculty of Materials Science and Engineering, Hubei University, Wuhan 430062 (China); Ministry-of-Education, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062 (China)], E-mail: wxb@hubu.edu.cn; Tian Rong; Li Shaoqing; Wan Li; Li Mingjian; You Haijun; Li Qin [Faculty of Materials Science and Engineering, Hubei University, Wuhan 430062 (China); Wang Shimin [Faculty of Materials Science and Engineering, Hubei University, Wuhan 430062 (China); Ministry-of-Education, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062 (China)

    2008-02-15

    We report the microwave-induced electrophilic addition of single-walled carbon nanotubes (SWNTs) with alkylhalides using Lewis acid as a catalyst followed by hydrolysis. The reaction results in the attachment of alkyl and hydroxyl groups to the surface of the nanotubes. This rapid and high-energy microwave radiation is found to be highly efficient for this reaction, which only needs as low as several minutes. The resulting nanotubes were characterized with FTIR, UV-vis-NIR, Raman, TGA, TEM and AFM. It demonstrates that iodo-alkanes show higher reaction activity with SWNTs than chloro- and bromo-alkanes.

  5. Relationship between electrophilicity index, Hammett constant and ...

    Indian Academy of Sciences (India)

    Unknown

    Inter-relationships between the electrophilicity index (ω), Hammett constant (óp) and nucleus- independent chemical ... cess of DFT is that it provides simple working equa- tions to elucidate ... compasses both the ability of an electrophile to ac-.

  6. Photochemical reaction of Si-substituted ethynylsilanes with 1,2-ethanedithiol

    Energy Technology Data Exchange (ETDEWEB)

    Voronkov, M.G.; Brodskaya, E.I.; Kalabin, G.A.; Vlasova, N.N.; Yarosh, O.G.; Zhila, G.Y.

    1985-12-01

    The authors investigate the chief products of the photochemical reactions of Si-substituted ethynylsilanes with 1,2,-ethanedithiol at 60-70 C. It is found that the chief products are 2-triorganylsilyl-substituted 1,4-dithiacyclopentanes and 1,4-dithiacyclohexanes. On lowering the temperature to -30 C, formation of bis (triorganylsilyl)-substituted 1,4,7,10-tetrathiacyclododecanes occurs along with the abo ve-mentioned five- and six-membered heterocycles.

  7. Metallation of N-allenylpyrroles by superbase reagents. Synthesis of new N-substituted pyrroles

    International Nuclear Information System (INIS)

    Tarasova, O.A.; Brandsma, L.; Verkrajsse, Kh.D.; Mal'kina, A.G.; Trofimov, B.A.

    1996-01-01

    Metallation of N-allenylpyrrole by BuLi-Et 2 O (THP), BuLi-t-BuOK-THP superbases and reactions of carbanions formed with different electrophilic agents have been studied. Fundamental data on mutual influence of allene group and pyrrole ring have been obtained. Alpha-proton features the highest acidity and it is the first one to be replaced by metal. In BuLi excess (more than 3-fold) in ether or in BuLi-t-BuOK-THP system a through metallation of allene group occurs. New pyrroles functionally substituted in allene chain have been prepared. 19 refs.; 3 tabs

  8. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Avonto, Cristina; Chittiboyina, Amar G. [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Rua, Diego [The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740 (United States); Khan, Ikhlas A., E-mail: ikhan@olemiss.edu [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States)

    2015-12-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  9. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    International Nuclear Information System (INIS)

    Avonto, Cristina; Chittiboyina, Amar G.; Rua, Diego; Khan, Ikhlas A.

    2015-01-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  10. Copper-Catalyzed Electrophilic Amination of Organoaluminum Nucleophiles with O-Benzoyl Hydroxylamines.

    Science.gov (United States)

    Zhou, Shuangliu; Yang, Zhiyong; Chen, Xu; Li, Yimei; Zhang, Lijun; Fang, Hong; Wang, Wei; Zhu, Xiancui; Wang, Shaowu

    2015-06-19

    A copper-catalyzed electrophilic amination of aryl and heteroaryl aluminums with N,N-dialkyl-O-benzoyl hydroxylamines that affords the corresponding anilines in good yields has been developed. The catalytic reaction proceeds very smoothly under mild conditions and exhibits good substrate scope. Moreover, the developed catalytic system is also well suited for heteroaryl aluminum nucleophiles, providing facile access to heteroaryl amines.

  11. An atom counting and electrophilicity based QSTR approach

    Indian Academy of Sciences (India)

    WINTEC

    QSTR models with two parameters result when global electrophilicity is used as the second descriptor. In ... Atom counting; QSTR; electrophilicity; conceptual DFT; Tetrahymena pyriformis. ... theoretical background whereas the computational.

  12. Gas phase reactions of protonated 1,3-diphenylpropyne and some isomeric [C15H13]+ ions

    OpenAIRE

    Bäther, Wolfgang; Kuck, Dietmar; Grützmacher, Hans-Friedrich

    1985-01-01

    Metastable (3-phenyl-2-propynyl)benzenium ions, generated by electron impact induced fragmentation from the appropriately substituted 1,4-dihydrobenzoic acid, react by loss of ·CH3 and C6H6. The study of deuterated derivatives reveals that hydrogen/deuterium exchanges involving all hydrogen and deuterium atoms precede the fragmentations. The results suggest a skeletal rearrangement by electrophilic ring-closure reactions giving rise to protonated phenylindene and protonated 9,10-methano-9,10-...

  13. Organic Chemistry Students' Ideas about Nucleophiles and Electrophiles: The Role of Charges and Mechanisms

    Science.gov (United States)

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2015-01-01

    Organic chemistry students struggle with reaction mechanisms and the electron-pushing formalism (EPF) used by practicing organic chemists. Faculty have identified an understanding of nucleophiles and electrophiles as one conceptual prerequisite to mastery of the EPF, but little is known about organic chemistry students' knowledge of nucleophiles…

  14. Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions

    DEFF Research Database (Denmark)

    Pedersen, Torben Møller; Hansen, E. Louise; Kane, John

    2001-01-01

    A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different $alpha@-oxygen-substituted, racemic aldehydes were initially transformed by asy...... the allylic stereocenter and the alkene geometry. Thus, a single $gamma@-substituted ester was obtained as the overall product, in high isomeric purity. The method was applied to a synthesis of a subunit of the iejimalides, a group of cytotoxic macrolides.......A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different $alpha@-oxygen-substituted, racemic aldehydes were initially transformed...... by asymmetric HWE reactions into mixtures of two major $alpha@,$beta@-unsaturated esters, possessing opposite configurations at their allylic stereocenters as well as opposite alkene geometry. Subsequently, these isomeric mixtures of alkenes could be subjected to palladium-catalyzed allylic substitution...

  15. Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

    International Nuclear Information System (INIS)

    Park, Kiyoung; Li, Ning; Kwak, Yeonju; Srnec, Martin

    2017-01-01

    Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2 . Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reaction shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.

  16. Substitution reactions of carbon nanotube template

    Science.gov (United States)

    Li, Chi Pui; Chen, Ying; Gerald, John Fitz

    2006-05-01

    Substitution reactions between carbon nanotube (CNT) template and SiO with the formation of carbon rich silicon oxide nanowires (SiO-C-NWs) have been investigated using transmission electron microscopy and x-ray energy dispersive spectroscopy. The reaction was carried out by thermal annealing at 1200°C for 1h of a mixture of silicon monoxide (SiO) and iron (II) phthalocyanine, FeC32N8H16 (FePc) powders. Multiwalled CNTs were produced first via pyrolysis of FePc at a lower temperature (1000°C ). SiO vapors reacted with the CNTs at higher temperatures to produce amorphous SiO-C-NWs with a uniform diameter and a length in tens of micrometers. The special bamboolike structure of the CNTs allows the reaction to start from the external surface of the tubes and transform each CNT into a solid nanowire section by section.

  17. The kinetics of substitution reaction of oxydiacetate and ...

    Indian Academy of Sciences (India)

    molar ratio 1:1 and the ternary complex Cu(R)B were recorded to confirm that ... tion, the values of the rate constants were determined. Figure 2. .... Table 4. The free enthalpy of activation values for the substitution reaction of CuODA with bipy.

  18. Development of Copper-Catalyzed Electrophilic Trifluoromethylation and Exploiting Cu/Cu2O Nanowires with Novel Catalytic Reactivity

    KAUST Repository

    Li, Huaifeng

    2014-06-01

    This thesis is based on research in Cu-catalyzed electrophilic trifluoromethylation and exploiting Cu/Cu2O nanowires with novel catalytic reactivity for developing of catalytic and greener synthetic methods. A large number of biological active pharmaceuticals and agrochemicals contain fluorine substituents (-F) or trifluoromethyl groups (-CF3) because these moieties often result in profound changes of their physical, chemical, and biological properties, such as metabolic stability and lipophilicity. For this reason, the introduction of fluorine or trifluoromethyl groups into organic molecules has attracted intensive attention. Among them, transition metal-catalyzed trifluoromethylation reactions has proved to be an efficient and reliable strategy to construct carbon-fluorine (C-F) and carbontrifluoromethyl (C-CF3) bond. We have developed a catalytic process for the first time for trifluoromethylation of terminal alkynes with Togni’s reagent, affording trifluoromethylated acetylenes in good to excellent yields. The reaction is conducted at room temperature and exhibits tolerance to a range of functional groups. Derived from this discovery, the extension of work of copper catalyzed electrophilic trifluoromethylation were investigated which include the electrophilic trifluoromethylation of arylsulfinate salts and electrophilic trifluoromethylation of organotrifluoroborates. Because of growing environmental concern, the development of greener synthetic methods has drawn much attention. Nano-sized catalysts are environment-friendly and an attractive green alternative to the conventional homogeneous catalysts. The nano-sized catalysts can be easily separated from the reaction mixture due to their insolubility and thus they can be used recycled. Notably, because of the high reactivities of nano-sized metal catalysts, the use of ligands can be avoided and the catalysts loadings can be reduced greatly. Moreover, the nano-sized catalysts can increase the exposed surface

  19. Kinetics on the reaction of substituted quinolines and p-substituted benzoylchlorides under various pressures

    International Nuclear Information System (INIS)

    Kim, Young Cheul; Lim, Jong Wan; Choi, Sung Yong; Kim, Se Kyong

    1999-01-01

    The reaction rates of substituted quinolines(6-CH 3 C 9 H 7 N, C 9 H 7 N) with p-substituted benzoylchlorides(p-CH 3 , p-H, p-NO 2 ) have been measured by conductometry in acetonitrile, and the rate constants are determined at various temperatures (10,15, 20, 25 .deg. C) and pressures(1, 200, 500, 1000bar). From the values of rate constants, the activation parameters(Ea, ΔV ≠ , ΔS ≠ , and ΔG ≠ ) and the pressure dependence of Hammett ρ values were determined. The rate constants increase as a function of temperatures and pressures, and are further increase by introduction the electron donor substituents in nucleophile(p-CH 3 ) or electron acceptor(p-NO 2 ) substituents in substrate. The activation volume, and the activation entropy are all negative. Hammett ρ values are also negative for nucleophile (ρ X ) and positive for the substrate (ρ Y ) over the pressure range studied. The results of kinetic studies for pressure and substituent show that these reactions proceed in typical S N 2 reaction mechanism and 'associative S N 2' in which bond formation favored with increasing pressures

  20. Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

    Directory of Open Access Journals (Sweden)

    Magnus Liljenberg

    2013-04-01

    Full Text Available A computational approach using density functional theory to compute the energies of the possible σ-complex reaction intermediates, the “σ-complex approach”, has been shown to be very useful in predicting regioselectivity, in electrophilic as well as nucleophilic aromatic substitution. In this article we give a short overview of the background for these investigations and the general requirements for predictive reactivity models for the pharmaceutical industry. We also present new results regarding the reaction rates and regioselectivities in nucleophilic substitution of fluorinated aromatics. They were rationalized by investigating linear correlations between experimental rate constants (k from the literature with a theoretical quantity, which we call the sigma stability (SS. The SS is the energy change associated with formation of the intermediate σ-complex by attachment of the nucleophile to the aromatic ring. The correlations, which include both neutral (NH3 and anionic (MeO− nucleophiles are quite satisfactory (r = 0.93 to r = 0.99, and SS is thus useful for quantifying both global (substrate and local (positional reactivity in SNAr reactions of fluorinated aromatic substrates. A mechanistic analysis shows that the geometric structure of the σ-complex resembles the rate-limiting transition state and that this provides a rationale for the observed correlations between the SS and the reaction rate.

  1. Diels-Alder reactions for the rational design of benzo[b]thiophenes: DFT-based guidelines for synthetic chemists

    Science.gov (United States)

    Brasca, Romina; Kneeteman, María N.; Mancini, Pedro M. E.; Fabian, Walter M. F.

    2012-02-01

    In this work we studied the capability of several diene/dienophile pairs to undergo Diels-Alder (DA) reactions leading to benzo[b]thiophenes. A variety of synthetically and commercially available nitrothiophenes were chosen as dienophiles. Methyl 5-nitro-3-thiophenecarboxylate was selected as a potential strong electrophilic candidate based on some DFT-based properties and the substitution pattern of the expected product. The mechanistic details concerning the participation of this dienophile in polar DA reactions were investigated through a theoretical point of view. The results were compared with the experimental outcomes. This methodology should allow synthetic chemists to analyze DA reactions in detail in a stage prior to the synthetic job.

  2. 40 CFR 721.6181 - Fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acid, reaction product with... Specific Chemical Substances § 721.6181 Fatty acid, reaction product with substituted oxirane, formaldehyde... as fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...

  3. Theoretical and conceptual density functional theory (DFT) study on selectivity of 4-hydroxyquinazoline electrophilic aromatic nitration

    Science.gov (United States)

    Makhloufi, A.; Belhadad, O.; Ghemit, R.; Baitiche, M.; Merbah, M.; Benachour, DJ.

    2018-01-01

    In common with other aza-heterocycles, 4-hydroxyquinazoline and their derivatives are important pharmacophores and versatile lead molecule used in several specific biological activities. The potency of these compounds depends on the nature and/or position of their substituents. In this paper, we report a theoretical study of the most probable nitration reaction centers of 4-hydroxyquinazoline for electrophilic attack, the mono and di-nitration was also discussed. In parallel, a computational study has been performed in gas by using the B3LYP/6311 G(d) level. The stability of the four nitro isomers is rationalized by means of the global index and local reactivity indices. Their molecular electrostatic potential (MEP) and Milliken charge were explored. Molecular geometries and NMR H spectra was examined. In addition, stationary points of reactant, transition state and intermediate were optimized in water condensed phase at the same level. The relative energies of the regioisomeric δ-complexes confirm that the substitution at C6 (6-nitro σ-complexes) is favored in these conditions, what was in agreement with our others calculating results (in gas).

  4. Tissue reaction and material characteristics of four bone substitutes

    DEFF Research Database (Denmark)

    Jensen, S S; Aaboe, M; Pinholt, E M

    1996-01-01

    and Interpore 500 HA/CC) were implanted into 5-mm bur holes in rabbit tibiae. There was no difference in the amount of newly formed bone around the four biomaterials. Interpore 500 HA/CC resorbed completely, whereas the other three biomaterials did not undergo any detectable biodegradation. Bio......The aim of the present study was to qualitatively and quantitatively compare the tissue reactions around four different bone substitutes used in orthopedic and craniofacial surgery. Cylinders of two bovine bone substitutes (Endobon and Bio-Oss) and two coral-derived bone substitutes (Pro Osteon 500......-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior....

  5. Reaction of singlet-excited 2,3-diazabicyclo[2.2.2]oct-2-ene and tert-butoxyl radicals with aryl-substituted benzofuranones.

    Science.gov (United States)

    Lundgren, Cecilia Vannesjö; Koner, Apurba L; Tinkl, Michael; Pischel, Uwe; Nau, Werner M

    2006-03-03

    5,7-Di-tert-butyl-3-aryl-3H-benzofuran-2-ones are lactones with potential antioxidant activity, owing to their abstractable benzylic C-H hydrogens. The fluorescence quenching of the azoalkane 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO), an established probe for the hydrogen-donor propensity of chain-breaking antioxidants, was investigated for 16 aryl-substituted benzofuranone derivatives [m,m-(CF3)2, p-CN, m-CN, p-CF3, p-COOCH3, m-CF3, p-Cl, p-F, H, m-CH3, p-CH3, m,p-(CH3)2, p-OCH3, o-CH3, o-CF3, o,m-(CH3)2]. Analysis of the rate data in terms of a linear free energy relationship yielded a reaction constant of rho = +0.35. This implies that n,pi*-excited DBO acts as nucleophilic species. In contrast, hydrogen abstraction of tert-butoxyl radicals from the benzofuranones was accelerated by electron-donating substituents (rho = -0.23), in conformity with the electrophilic character of oxygen-centered alkoxyl radicals. Possible implications for the optimization of the hydrogen-donor propensity of antioxidants through structural variation are discussed.

  6. Self-Controlled Synthesis of Hyperbranched Polyetherketones From A3 + B2 Approach Via Different Solubilities of Monomers in the Reaction Medium (Preprint)

    Science.gov (United States)

    2006-10-01

    higher yields than 1a and 2a after the similar work-up procedure, which involved Soxhlet extraction with water for 2 days and methanol for 2 days to get...the co-monomers. One such reaction medium, optimized PPA/P2O5 mixture, has been established for the electrophilic substitution reaction to yield high... Soxhlet -extracted with water for 2 days, methanol for 2 days, and finally dried under reduced pressure (0.05 mmHg) at 100°C for 150 h to give 3.30 g (76

  7. Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liver

    International Nuclear Information System (INIS)

    Klaassen, Curtis D.; Reisman, Scott A.

    2010-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes. These gene products include proteins that catalyze reduction reactions (NAD(P)H:quinone oxidoreductase 1, Nqo1), conjugation reactions (glutathione-S-transferases, Gsts and UDP-glucuronosyltransferases, Ugts), as well as the efflux of potentially toxic xenobiotics and xenobiotic conjugates (multidrug resistance-associated proteins, Mrps). The significance of Nrf2 in the liver has been established, as livers of Nrf2-null mice are more susceptible to various oxidative/electrophilic stress-induced pathologies than wild-type mice. In contrast, both pharmacological and genetic models of hepatic Nrf2 activation are protective against oxidative/electrophilic stress. Furthermore, because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of Nrf2 on the kinetics of drugs and other xenobiotics should also be considered, with a special emphasis on metabolism and excretion. Therefore, this review highlights the research that has contributed to the understanding of the importance of Nrf2 in toxicodynamics and toxicokinetics, especially that which pertains to the liver.

  8. Force-induced chemical reactions on the metal centre in a single metalloprotein molecule

    Science.gov (United States)

    Zheng, Peng; Arantes, Guilherme M.; Field, Martin J.; Li, Hongbin

    2015-01-01

    Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of single-molecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions. PMID:26108369

  9. The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.

    Science.gov (United States)

    Donckele, Etienne J; Finke, Aaron D; Ruhlmann, Laurent; Boudon, Corinne; Trapp, Nils; Diederich, François

    2015-07-17

    The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

  10. Directed ortho metalation-based methodology. Halo-, nitroso-, and boro-induced ipso-desilylation. Link to an in situ Suzuki reaction.

    Science.gov (United States)

    Zhao, Zhongdong; Snieckus, Victor

    2005-06-23

    [reaction: see text] Treatment of DoM-derived silylated aromatics 2-4 under standard electrophilic halogenation conditions cleanly affords ipso-desilyation products 5-7, while nitration of methoxy-substituted analogues 8, 9 leads to non-ipso isomers 10, 12 and 11, 13, controlled by a silicon steric effect. Sequential ipso-borodesilylation of 2a, 3a, and 20 followed by treatment with aryl halides under Pd-catalyzed conditions constitutes an in situ Suzuki-Miyaura cross-coupling protocol to biaryls and heterobiaryls 23.

  11. Alkyne Benzannulation Reactions for the Synthesis of Novel Aromatic Architectures.

    Science.gov (United States)

    Hein, Samuel J; Lehnherr, Dan; Arslan, Hasan; J Uribe-Romo, Fernando; Dichtel, William R

    2017-11-21

    Aromatic compounds and polymers are integrated into organic field effect transistors, light-emitting diodes, photovoltaic devices, and redox-flow batteries. These compounds and materials feature increasingly complex designs, and substituents influence energy levels, bandgaps, solution conformation, and crystal packing, all of which impact performance. However, many polycyclic aromatic hydrocarbons of interest are difficult to prepare because their substitution patterns lie outside the scope of current synthetic methods, as strategies for functionalizing benzene are often unselective when applied to naphthalene or larger systems. For example, cross-coupling and nucleophilic aromatic substitution reactions rely on prefunctionalized arenes, and even directed metalation methods most often modify positions near Lewis basic sites. Similarly, electrophilic aromatic substitutions access single regioisomers under substrate control. Cycloadditions provide a convergent route to densely functionalized aromatic compounds that compliment the above methods. After surveying cycloaddition reactions that might be used to modify the conjugated backbone of poly(phenylene ethynylene)s, we discovered that the Asao-Yamamoto benzannulation reaction is notably efficient. Although this reaction had been reported a decade earlier, its scope and usefulness for synthesizing complex aromatic systems had been under-recognized. This benzannulation reaction combines substituted 2-(phenylethynyl)benzaldehydes and substituted alkynes to form 2,3-substituted naphthalenes. The reaction tolerates a variety of sterically congested alkynes, making it well-suited for accessing poly- and oligo(ortho-arylene)s and contorted hexabenzocoronenes. In many cases in which asymmetric benzaldehyde and alkyne cycloaddition partners are used, the reaction is regiospecific based on the electronic character of the alkyne substrate. Recognizing these desirable features, we broadened the substrate scope to include silyl

  12. Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products.

    Science.gov (United States)

    Tian, Caiping; Sun, Rui; Liu, Keke; Fu, Ling; Liu, Xiaoyu; Zhou, Wanqi; Yang, Yong; Yang, Jing

    2017-11-16

    Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified α,β-unsaturated γ-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sequential Au(I-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates

    Directory of Open Access Journals (Sweden)

    Jianbo Wang

    2011-05-01

    Full Text Available The gold(I-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates provides 1H-isochromene derivatives in good yields. The reaction follows a catalytic sequence of gold carbene formation/water O–H insertion/alcohol-alkyne cyclization. The gold(I complex is the only catalyst in each of these steps.

  14. Phosphite radicals and their reactions. Examples of redox, substitution, and addition reactions

    International Nuclear Information System (INIS)

    Schaefer, K.; Asmus, K.D.

    1980-01-01

    Phosphite radicals HPO 3 - and PO 3 2 -, which exist in an acid-base equilibrium with pK = 5.75, are shown to take part in various types of reactions. In the absence of scavengers, they disappear mainly by second-order disproportionation and combination; a first-order contribution to the decay is also indicated. HPO 3 - and PO 3 2 - are good reductants toward electron acceptors such as tetranitromethane. In this reaction phosphate and C(NO 2 ) 3 - are formed. Phosphite radicals can, however, also act as good oxidants, e.g., toward thiols and thiolate ions. These reactions lead to the formation of RS. radicals which were identified either directly, as in the case of penicillamine, through the optical absorption of PenS. or more indirectly through equilibration of RS. with RS- to the optically absorbing RSSR-. disulfide radical anion. A homolytic substitution reaction (S/sub H/2) occurs in the reaction of the phosphite radicals with aliphatic disulfides, yielding RS. radicals and phosphate thioester RSPO 3 2 -. Lipoic acid, as an example of a cyclic disulfide, is reduced to the corresponding RSSR-. radical anion and also undergoes the S/sub H/2 reaction with about equal probability. An addition reaction is observed between phosphite radicals and molecular oxygen. The resulting peroxo phosphate radicals establish an acid-base equilibrium HPO 5 - . reversible PO 5 2- . + H+ with a pK = 3.4. Absolute rate constants were determined for all reactions discussed

  15. Organic Chemistry Students' Fragmented Ideas about the Structure and Function of Nucleophiles and Electrophiles: A Concept Map Analysis

    Science.gov (United States)

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2016-01-01

    Organic chemistry students struggle with multiple aspects of reaction mechanisms and the curved arrow notation used by organic chemists. Many faculty believe that an understanding of nucleophiles and electrophiles, among other concepts, is required before students can develop fluency with the electronpushing formalism (EPF). An expert concept map…

  16. The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.

    Science.gov (United States)

    Long, Marcus J C; Aye, Yimon

    2016-10-02

    This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis.

  17. Olives and olive oil are sources of electrophilic fatty acid nitroalkenes.

    Directory of Open Access Journals (Sweden)

    Marco Fazzari

    Full Text Available Extra virgin olive oil (EVOO and olives, key sources of unsaturated fatty acids in the Mediterranean diet, provide health benefits to humans. Nitric oxide (•NO and nitrite (NO2 (--dependent reactions of unsaturated fatty acids yield electrophilic nitroalkene derivatives (NO2-FA that manifest salutary pleiotropic cell signaling responses in mammals. Herein, the endogenous presence of NO2-FA in both EVOO and fresh olives was demonstrated by mass spectrometry. The electrophilic nature of these species was affirmed by the detection of significant levels of protein cysteine adducts of nitro-oleic acid (NO2-OA-cysteine in fresh olives, especially in the peel. Further nitration of EVOO by NO2 (- under acidic gastric digestive conditions revealed that human consumption of olive lipids will produce additional nitro-conjugated linoleic acid (NO2-cLA and nitro-oleic acid (NO2-OA. The presence of free and protein-adducted NO2-FA in both mammalian and plant lipids further affirm a role for these species as signaling mediators. Since NO2-FA instigate adaptive anti-inflammatory gene expression and metabolic responses, these redox-derived metabolites may contribute to the cardiovascular benefits associated with the Mediterranean diet.

  18. 2?Diazo?1?phenyl?2?((trifluoromethyl)sulfonyl)ethan?1?one: Another Utility for Electrophilic Trifluoromethylthiolation Reactions

    OpenAIRE

    Huang, Zhongyan; Okuyama, Kenta; Wang, Chen; Tokunaga, Etsuko; Li, Xiaorui; Shibata, Norio

    2016-01-01

    Abstract 2?Diazo?1?phenyl?2?((trifluoromethyl)sulfonyl)ethan?1?one (diazo?triflone) (2) is not only a building block but also a reagent. In this study, diazo?triflone, which was originally used for the synthesis of ??lactam triflones as a trifluoromethanesulfonyl (SO2CF3) building block under catalyst?free thermal conditions, is redisclosed as an effective electrophilic trifluoromethylthiolation reagent under copper catalysis. A broad set of enamines, indoles, ??keto esters, pyrroles, and ani...

  19. Alkylation damage by lipid electrophiles targets functional protein systems.

    Science.gov (United States)

    Codreanu, Simona G; Ullery, Jody C; Zhu, Jing; Tallman, Keri A; Beavers, William N; Porter, Ned A; Marnett, Lawrence J; Zhang, Bing; Liebler, Daniel C

    2014-03-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions.

  20. Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

    Science.gov (United States)

    Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

    2014-01-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

  1. Synthesis of substituted Calix[6] arene and 18F labeling reaction as catalyst in preparation of 18F-FET

    International Nuclear Information System (INIS)

    Peng Cheng; Ma Yunchuan; Chen Xiaoxiao; Li Guixia; Li Shilei; Zhang Shuting; He Yong; Qi Chuanmin

    2011-01-01

    The phase transfer catalyst Substituted Calix[6] arene was prepared and it was used as catalyst to prepare the tumor diagnostic drug 18 F-FET. The results showed that para-sulfonated-calix[6] arene not only catalyzes 19 F substitution reaction, but also catalyzes 18 F labelling reaction with radiochemical yield of 11%. However, para-tert-butyl-calix[6] arene has no catalytic activity for the 19 F substitution reaction nor the 18 F labelling reaction of the precursor of FET. The catalyzing of para-sulfonated-calix[6]arene may be related to it's sulfonate groups, which participated in the coordination reaction and increased the polarity of calyx[6] arene and so on. Although radiochemical yield of the para-sulfonated-calix[6] arene catalyzed 18 F labeling of the precursor of FET was much lower than that obtained by Kryptofix 2. 2. 2, this study still has significant meaning for us to find better substituted Calix[6] arene catalysts by optimizing the reaction conditions. (authors)

  2. Selenium-mediated synthesis of biaryls through rearrangement.

    Science.gov (United States)

    Shahzad, Sohail A; Vivant, Clotilde; Wirth, Thomas

    2010-03-19

    A new cyclization of beta-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.

  3. Enabling nucleophilic substitution reactions of activated alkyl fluorides through hydrogen bonding.

    Science.gov (United States)

    Champagne, Pier Alexandre; Pomarole, Julien; Thérien, Marie-Ève; Benhassine, Yasmine; Beaulieu, Samuel; Legault, Claude Y; Paquin, Jean-François

    2013-05-03

    It was discovered that the presence of water as a cosolvent enables the reaction of activated alkyl fluorides for bimolecular nucleophilic substitution reactions. DFT calculations show that activation proceeds through stabilization of the transition structure by a stronger F···H2O interaction and diminishing C-F bond elongation, and not simple transition state electrostatic stabilization. Overall, the findings put forward a distinct strategy for C-F bond activation through H-bonding.

  4. On the electrophilic character of molecules through its relation with electronegativity and chemical hardness.

    Science.gov (United States)

    Islam, Nazmul; Ghosh, Dulal C

    2012-01-01

    Electrophilicity is an intrinsic property of atoms and molecules. It probably originates logistically with the involvement in the physical process of electrostatics of soaked charge in electronic shells and the screened nuclear charge of atoms. Motivated by the existing view of conceptual density functional theory that similar to electronegativity and hardness equalization, there should be a physical process of equalization of electrophilicity during the chemical process of formation of hetero nuclear molecules, we have developed a new theoretical scheme and formula for evaluating the electrophilicity of hetero nuclear molecules. A comparative study with available bench marking reveals that the hypothesis of electrophilicity and equalization, and the present method of evaluating equalized electrophilicity, are scientifically promising.

  5. On the Electrophilic Character of Molecules Through Its Relation with Electronegativity and Chemical Hardness

    Directory of Open Access Journals (Sweden)

    Dulal C. Ghosh

    2012-02-01

    Full Text Available Electrophilicity is an intrinsic property of atoms and molecules. It probably originates logistically with the involvement in the physical process of electrostatics of soaked charge in electronic shells and the screened nuclear charge of atoms. Motivated by the existing view of conceptual density functional theory that similar to electronegativity and hardness equalization, there should be a physical process of equalization of electrophilicity during the chemical process of formation of hetero nuclear molecules, we have developed a new theoretical scheme and formula for evaluating the electrophilicity of hetero nuclear molecules. A comparative study with available bench marking reveals that the hypothesis of electrophilicity and equalization, and the present method of evaluating equalized electrophilicity, are scientifically promising.

  6. Exact substitute processes for diffusion-reaction systems with local complete exclusion rules

    International Nuclear Information System (INIS)

    Schulz, Michael; Reineker, Peter

    2005-01-01

    Lattice systems with one species diffusion-reaction processes under local complete exclusion rules are studied analytically starting from the usual master equations with discrete variables and their corresponding representation in a Fock space. On this basis, a formulation of the transition probability as a Grassmann path integral is derived in a straightforward manner. It will be demonstrated that this Grassmann path integral is equivalent to a set of Ito stochastic differential equations. Averages of arbitrary variables and correlation functions of the underlying diffusion-reaction system can be expressed as weighted averages over all solutions of the system of stochastic differential equations. Furthermore, these differential equations are equivalent to a Fokker-Planck equation describing the probability distribution of the actual Ito solutions. This probability distribution depends on continuous variables in contrast to the original master equation, and their stochastic dynamics may be interpreted as a substitute process which is completely equivalent to the original lattice dynamics. Especially, averages and correlation functions of the continuous variables are connected to the corresponding lattice quantities by simple relations. Although the substitute process for diffusion-reaction systems with exclusion rules has some similarities to the well-known substitute process for the same system without exclusion rules, there exists a set of remarkable differences. The given approach is not only valid for the discussed single-species processes. We give sufficient arguments to show that arbitrary combinations of unimolecular and bimolecular lattice reactions under complete local exclusions may be described in terms of our approach

  7. Converting homogeneous to heterogeneous in electrophilic catalysis using monodisperse metal nanoparticles.

    Science.gov (United States)

    Witham, Cole A; Huang, Wenyu; Tsung, Chia-Kuang; Kuhn, John N; Somorjai, Gabor A; Toste, F Dean

    2010-01-01

    A continuing goal in catalysis is to unite the advantages of homogeneous and heterogeneous catalytic processes. To this end, nanoparticles represent a new frontier in heterogeneous catalysis, where this unification can also be supplemented by the ability to obtain new or divergent reactivity and selectivity. We report a novel method for applying heterogeneous catalysts to known homogeneous catalytic reactions through the design and synthesis of electrophilic platinum nanoparticles. These nanoparticles are selectively oxidized by the hypervalent iodine species PhICl(2), and catalyse a range of π-bond activation reactions previously only catalysed through homogeneous processes. Multiple experimental methods are used to unambiguously verify the heterogeneity of the catalytic process. The discovery of treatments for nanoparticles that induce the desired homogeneous catalytic activity should lead to the further development of reactions previously inaccessible in heterogeneous catalysis. Furthermore, a size and capping agent study revealed that Pt PAMAM dendrimer-capped nanoparticles demonstrate superior activity and recyclability compared with larger, polymer-capped analogues.

  8. Converting Homogeneous to Heterogeneous in Electrophilic Catalysis using Monodisperse Metal Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Witham, Cole A.; Huang, Wenyu; Tsung, Chia-Kuang; Kuhn, John N.; Somorjai, Gabor A.; Toste, F. Dean

    2009-10-15

    A continuing goal in catalysis is the transformation of processes from homogeneous to heterogeneous. To this end, nanoparticles represent a new frontier in heterogeneous catalysis, where this conversion is supplemented by the ability to obtain new or divergent reactivity and selectivity. We report a novel method for applying heterogeneous catalysts to known homogeneous catalytic reactions through the design and synthesis of electrophilic platinum nanoparticles. These nanoparticles are selectively oxidized by the hypervalent iodine species PhICl{sub 2}, and catalyze a range of {pi}-bond activation reactions previously only homogeneously catalyzed. Multiple experimental methods are utilized to unambiguously verify the heterogeneity of the catalytic process. The discovery of treatments for nanoparticles that induce the desired homogeneous catalytic activity should lead to the further development of reactions previously inaccessible in heterogeneous catalysis. Furthermore, our size and capping agent study revealed that Pt PAMAM dendrimer-capped nanoparticles demonstrate superior activity and recyclability compared to larger, polymer-capped analogues.

  9. Thermodynamics of axial substitution and kinetics of reactions with amino acids for the paddlewheel complex tetrakis(acetato)chloridodiruthenium(II,III).

    Science.gov (United States)

    Santos, Rodrigo L S R; van Eldik, Rudi; de Oliveira Silva, Denise

    2012-06-18

    The known paddlewheel, tetrakis(acetato)chloridodiruthenium(II,III), offers a versatile synthetic route to a novel class of antitumor diruthenium(II,III) metallo drugs, where the equatorial ligands are nonsteroidal anti-inflammatory carboxylates. This complex was studied here as a soluble starting prototype model for antitumor analogues to elucidate the reactivity of the [Ru(2)(CH(3)COO)(4)](+) framework. Thermodynamic studies on equilibration reactions for axial substitution of water by chloride and kinetic studies on reactions of the diaqua complexes with the amino acids glycine, cysteine, histidine, and tryptophan were performed. The standard thermodynamic reaction parameters ΔH°, ΔS°, and ΔV° were determined and showed that both of the sequential axial substitution reactions are enthalpy driven. Kinetic rate laws and rate constants were determined for the axial substitution reactions of coordinated water by the amino acids that gave the corresponding aqua(amino acid)-Ru(2) substituted species. The results revealed that the [Ru(2)(CH(3)COO)(4)](+) paddlewheel framework remained stable during the axial ligand substitution reactions and was also mostly preserved in the presence of the amino acids.

  10. Direct no-carrier-added 18F-labelling of arenes via nucleophilic substitution on aryl(2-thienyl)iodonium salts

    International Nuclear Information System (INIS)

    Ross, T.L.

    2006-01-01

    For in vivo imaging of molecular processes via positron emission tomography (PET) radiotracers of high specific activity are demanded. In case of the most commonly used positron emitter fluorine-18, this is only achievable with no-carrier-added [ 18 F]fluoride, which implies nucleophilic methods of 18 F-substitution. Whereas electron deficient aromatic groups can be labelled in one step using no-carrier-added [ 18 F]fluoride, electron rich 18 F-labelled aromatic molecules are only available by multi-step radiosyntheses or carrier-added electrophilic reactions. Here, diaryliodonium salts represent an alternative, since they have been proven as potent precursor for a direct nucleophilic 18 F-introduction into aromatic molecules. Furthermore, as known from non-radioactive studies, the highly electron rich 2-thienyliodonium leaving group leads to a high regioselectivity in nucleophilic substitution reactions. Consequently, a direct nucleophilic no-carrier-added 18 F-labelling of electron rich arenes via aryl(2-thienyl)iodonium precursors was developed in this work. The applicability of direct nucleophilic 18 F-labelling was examined in a systematic study on eighteen aryl(2-thienyl)iodonium salts. As electron rich precursors the ortho-, meta- and para-methoxyphenyl(2-thienyl)iodonium bromides, iodides, tosylates and triflates were synthesised. In addition, para-substituted (R=BnO, CH 3 , H, Cl, Br, I) aryl(2-thienyl)iodonium bromides were prepared as precursors with a systematically varying electron density. As first approach, the general reaction conditions of the nucleophilic 18 F-substitution procedure were optimised. The best conditions for direct nucleophilic no-carrier-added 18 F-labelling via aryl(2-thienyl)iodonium salts were found with dimethylformamide as solvent, a reaction temperature of 130±3 C and 25 mmol/l as concentration of the precursor. (orig.)

  11. Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

    Directory of Open Access Journals (Sweden)

    Cox Liam R

    2007-02-01

    Full Text Available Abstract Background Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid-mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric β-silyloxy-α-methyl aldehydes, which contain an allylsilane tethered through the β-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. Results Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the α-site, affording only two of the four possible allylation products. Conclusion The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.. In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity.

  12. Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

    KAUST Repository

    Ghorpade, Seema Arun; Sawant, Dinesh N; Makki, Arwa; Sekar, N; Eppinger, Jö rg

    2017-01-01

    Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.

  13. Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

    KAUST Repository

    Ghorpade, Seema Arun

    2017-11-30

    Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.

  14. Electrophilic trifluoromethyl-thiolation reaction and synthesis of radioligand for medicinal PET imaging of l'α-synuclein

    International Nuclear Information System (INIS)

    Alazet, Sebastien

    2015-01-01

    Part 1: More and more applications for fluorinated molecules are being found in various fields, from materials to life sciences. In recent years, a growing interest has emerged in the association of the trifluoromethyl group with heteroatoms such as CF3O or CF3S. The CF3S moiety is of particular interest, because of its high hydrophobicity parameter (π=1.44). Consequently compounds bearing this group are important targets for various applications, in particular in medicinal chemistry and agrochemistry. However, the majority of previous methods described in the literature use toxic reagents under harsh conditions. Trifluoromethane-sulfenamides (1. and 2. generation) have demonstrated their potential in the electrophilic trifluoromethyl-thiolations. Because of their interesting reactivity, these two generations of shelf-stable reagents are now in the toolbox of organic chemists for the trifluoromethyl-thiolation of molecules, providing a convenient method to pursue less toxic pathways. Part 2: α-synuclein aggregation is a neuro-pathological hallmark of many neuro-degenerative diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), collectively termed synucleinopathies. PET imaging can reflect the amount and distribution of alpha-synuclein aggregates in the brain and would be advantageous to use for specific diagnosis of synucleinopathies in pre-symptomatic stages of disease. We focused our interest onto benzimidazole derivatives as small, planar and π-delocalized compounds to design radiotracers of synuclein aggregates. Compounds based on the association of benzimidazole moiety, rigid linker (alkyne and triazole) and another aromatic part have been designed. The radiolabeling could be performed by nucleophilic substitution with K18F during the last step. With this convergent strategy, we could have access to a large series of molecules to be evaluated. (author)

  15. Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

    DEFF Research Database (Denmark)

    Serafimova, Iana M; Pufall, Miles A; Krishnan, Shyam

    2012-01-01

    Targeting noncatalytic cysteine residues with irreversible acrylamide-based inhibitors is a powerful approach for enhancing pharmacological potency and selectivity. Nevertheless, concerns about off-target modification motivate the development of reversible cysteine-targeting strategies. Here we...... of these electrophiles into a noncovalent kinase-recognition scaffold produced slowly dissociating, covalent inhibitors of the p90 ribosomal protein S6 kinase RSK2. A cocrystal structure revealed specific noncovalent interactions that stabilize the complex by positioning the electrophilic carbon near the targeted...

  16. Direct no-carrier-added {sup 18}F-labelling of arenes via nucleophilic substitution on aryl(2-thienyl)iodonium salts

    Energy Technology Data Exchange (ETDEWEB)

    Ross, T L

    2006-01-15

    For in vivo imaging of molecular processes via positron emission tomography (PET) radiotracers of high specific activity are demanded. In case of the most commonly used positron emitter fluorine-18, this is only achievable with no-carrier-added [{sup 18}F]fluoride, which implies nucleophilic methods of {sup 18}F-substitution. Whereas electron deficient aromatic groups can be labelled in one step using no-carrier-added [{sup 18}F]fluoride, electron rich {sup 18}F-labelled aromatic molecules are only available by multi-step radiosyntheses or carrier-added electrophilic reactions. Here, diaryliodonium salts represent an alternative, since they have been proven as potent precursor for a direct nucleophilic {sup 18}F-introduction into aromatic molecules. Furthermore, as known from non-radioactive studies, the highly electron rich 2-thienyliodonium leaving group leads to a high regioselectivity in nucleophilic substitution reactions. Consequently, a direct nucleophilic no-carrier-added {sup 18}F-labelling of electron rich arenes via aryl(2-thienyl)iodonium precursors was developed in this work. The applicability of direct nucleophilic {sup 18}F-labelling was examined in a systematic study on eighteen aryl(2-thienyl)iodonium salts. As electron rich precursors the ortho-, meta- and para-methoxyphenyl(2-thienyl)iodonium bromides, iodides, tosylates and triflates were synthesised. In addition, para-substituted (R=BnO, CH{sub 3}, H, Cl, Br, I) aryl(2-thienyl)iodonium bromides were prepared as precursors with a systematically varying electron density. As first approach, the general reaction conditions of the nucleophilic {sup 18}F-substitution procedure were optimised. The best conditions for direct nucleophilic no-carrier-added {sup 18}F-labelling via aryl(2-thienyl)iodonium salts were found with dimethylformamide as solvent, a reaction temperature of 130{+-}3 C and 25 mmol/l as concentration of the precursor. (orig.)

  17. Reactivity and Regioselectivity in the Heck Reaction - A Hammett Study of 4-Substituted Styrenes

    DEFF Research Database (Denmark)

    Fristrup, Peter; Le Quement, Sebastian; Tanner, David Ackland

    2004-01-01

    The regioselectivity in the cationic Heck reaction of 4-substituted styrenes was addressed by a Hammett study. In this branching reaction, plots based on the substrate reactivity did not give meaningful data, whereas the product distribution was variable due to differing preferences for further...

  18. The Stille Reaction (Vittorio Farina, Venkat Krishnamurthy, and William J. Scott)

    Science.gov (United States)

    Cochran, John C.

    1999-10-01

    In 1997, Volume 50 of Organic Reactions was published in a handsome and appropriate gold hard-cover edition. This was only the third volume in this prestigious series that consisted of a single chapter. The treatise, The Stille Reaction, describes a palladium-catalyzed cross-coupling between a carbon ligand on tin and a carbon with electrophilic character. This reaction has been around only since 1977, and the literature is covered here through 1994 with a few references in 1995. It is truly astounding that, in the space of about 17 years, a new reaction could generate enough literature for not only a chapter in Organic Reactions, but a complete volume of 652 pages, 864 literature citations, and more than 4300 specific reaction examples. The editorial board of Organic Reactions has graciously decided to make this extensive review available to a broader audience by authorizing a paperback edition of The Stille Reaction. While the mechanistic details of the Stille reaction are generally understood, there are many fine points that must be tuned to each case. For instance, about 15 different solvents have been used, ranging in polarity from benzene to water; at least ten different ligands for the palladium atom are available and they range from hard to soft; CuI, Ag2CO3, and LiCl are sometimes useful cocatalysts but sometimes have no effect, and in some cases LiCl is inhibitory; vinyl triflates couple with alkenyl-, alkynyl- and allylstannanes but not with arylstannanes; reaction temperatures vary from room temperature to refluxing DMF. An important consideration is that most stannanes are reasonably air and moisture stable and do not react with most common functional groups. Thus, it is not necessary to build protection-deprotection sequences into the synthetic scheme. The extensive reaction examples are arranged in 33 tables that show, for each reaction, the structures of the electrophile, the stannane, and the product and specify the catalyst, cocatalyst, solvent

  19. Carbon-14 kinetic isotope effects and mechanisms of addition of 2,4-dinitrobenzenesulfenyl chloride to substituted styrenes-1-14C and styrenes-2-14C

    International Nuclear Information System (INIS)

    Kanska, M.; Fry, A.

    1983-01-01

    As the first reported examples of carbon isotope effects in simple electrophilic addition reactions we have measured the carbon-14 kinetic isotope effects in the addition of 2,4-dinitrobenzenesulfenyl chloride to a series of para-substituted α and β-labeled styrenes in acetic acid at 30.1 0 C: for para substituents Cl, H, and CH 3 the k/ 14 K values for α labeling are 1.027, 1.022, and 1.004, and the k/ 14 k values for β labeling are 1.035, 1.032, and 1.037, all +/-approx.0.004. The kinetics of the reaction were measured for the p-CH 3 O,p-CH 3 , unsubstituted, p-Cl, and m-NO 2 styrenes; electron-donating groups strongly accelerate the reaction, and electron-withdrawing groups retard it. The Hammett plot is curved with p + values ranging from about -4.6 at the electron-donating group (EDG) end to about -1.8 at the electron-withdrawing group (EWG) end. Both the isotope effect and kinetic data, and related data from the literature, are interpreted in terms of a changing mechanism, with the activated complexes of the rate-determining steps having much open carbenium ion (ion pair) character for EDG-substituted styrenes and much cyclic thiiranium io (ion par) character for EWG-substituted styrenes. 1 figure, 2 tables

  20. Tissue reaction and material biodegradation of a calcium sulfate/apatite biphasic bone substitute in rat muscle

    Directory of Open Access Journals (Sweden)

    Jian-Sheng Wang

    2016-07-01

    Conclusion: Calcium sulfate hydroxyapatite bone substitute can be used as a carrier for antibiotics or other drugs, without adverse reaction due to the fast resorption of the calcium sulfate. No bone formation was seen despite treating the bone substitute with autologous bone marrow.

  1. Chemical and physical factors which control the substitution reactions of direct fission-produced iodine with gaseous methane and the methyl halides

    International Nuclear Information System (INIS)

    Kikuchi, M.; Church, L.B.

    1976-01-01

    The factors controlling the hydrogen and halogen substitution reactions resulting from direct fission-produced iodine isotopes (*I) with gaseous methane and methyl halides were investigated. The chemical reaction probabilities, corrected for any secondary decomposition, were compared as a function of various chemical and physical parameters. These include carbon-halogen bond strength, halogen electronegativity, volume and cross sectional area of the substituted and neighboring atoms. On the basis of this analysis, it is concluded that *I-for-X (where X = H, F, Cl, Br and I) substitution reactions are controlled by the cross sectional area of the X atom. The *I-for-H substitution probability is reduced in proportion to the volume of X, suggesting that steric interference is the dominant factor influencing the reaction probability. (orig.) [de

  2. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation.

    Science.gov (United States)

    Reddy, Aravind T; Lakshmi, Sowmya P; Muchumarri, Ramamohan R; Reddy, Raju C

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs' electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease.

  3. Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

    Science.gov (United States)

    Mendes, Desiree E.; Schoffstall, Allen M.

    2011-01-01

    This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

  4. Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic.

    Science.gov (United States)

    Kim, Samuel; Bowen, Raffick A R; Zare, Richard N

    2015-01-28

    We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.

  5. The regio- and stereospecific synthesis of diarylpropenyllithium compounds from dimethylamino- and dimethylaminomethyl-substituted diarylacetylenes viatransmetallation reactions involving diarylpropenylmagnesium and tin compounds

    NARCIS (Netherlands)

    Koten, G. van; Hoedt, R.W.M. ten; Noltes, J.G.

    1979-01-01

    Dimethylamino- and dimethylaminomethyl-substituted diarylacetylenes were prepared by the Pd(PPh{3}){4}-catalyzed coupling reaction of dimethylamino- and dimethylaminomethyl-substituted aryl halides with arylacetylenes.Reaction of the asymmetric diarylacetylenes with methylmagnesium bromide in the

  6. Homoaromatics as intermediates in the substitution reactions of 1,2,4,5-tetrazines with ammonia and hydrazine

    International Nuclear Information System (INIS)

    Counotte-Potman, A.D.

    1981-01-01

    This thesis describes some nucleophilic substitution reactions between the red 1,2,4,5-tetrazines and hydrazine-hydrate or ammonia. Special attention was paid to the occurrence of the Ssub(N) (ANRORC) mechanism in these substitution reactions. This mechanism comprises a sequence of reactions, involving the Addition of a Nucleopile to a heteroaromatic species, followed by a Ring-Opening and Ring Closure reaction to the substitution product. 3-Alkyl(aryl)-1,2,4,5-tetrazines were found to undergo a Chichibabin hydrazination into 6-hydrazino-3-alkyl(aryl)-1,2,4,5-tetrazines on treatment with hydrazine-hydrate. The first step in this reaction sequence was the formation of a homoaromatic sigma-adduct. Subsequently an open-chain intermediate was observed by NMR, on raising the temperature. Finally the hydrazino compound is formed by ring closure. This reaction sequence can be considered as an Ssub(N)(ANRORC) process. With 15 N-labelled hydrazine, only part of the label was found to be built in the 1,2,4,5-tetrazine ring of the 6-hydrazino compounds. This is the first example of a reaction in which both the hydrazino compound with the 15 N-label in the ring and with the 15 N-label in the exocyclic hydrazino group are formed according to the Ssub(N)(ANRORC) mechanism. (Auth.)

  7. Kinetics of the reaction of 5-substituted orotic acids with diazodiphenylmethane

    Directory of Open Access Journals (Sweden)

    ALEKSANDAR D. MARINKOVIC

    2004-11-01

    Full Text Available Rate konstants for the reaction of eight 5-substituted orotic acids with diazodiphenylmethane (DDM in dimethylformamide (DMF were determined at 30 ºC by the known spectrophotometric method. The determined rate constants were correlated with the equations: log k2 = as1 + bsR + h log k2 = as1 + bsR + yn + h to detect the presence and investigate the influence of both electrical and steric substituent effects. The obtained results show that the electrical effect (the localized – field and delocalized – resonance is predominant and that the steric effect, althought present, is releatively small in this reaction.

  8. Copper(II)-catalyzed electrophilic amination of quinoline N-oxides with O-benzoyl hydroxylamines.

    Science.gov (United States)

    Li, Gang; Jia, Chunqi; Sun, Kai; Lv, Yunhe; Zhao, Feng; Zhou, Kexiao; Wu, Hankui

    2015-03-21

    Copper acetate-catalyzed C-H bond functionalization amination of quinoline N-oxides was achieved using O-benzoyl hydroxylamine as an electrophilic amination reagent, thereby affording the desired products in moderate to excellent yields. Electrophilic amination can also be performed in good yield on a gram scale.

  9. Dramatic Influence of Ionic Liquid and Ultrasound Irradiation on the Electrophilic Sulfinylation of Aromatic Compounds by Sulfinic Esters

    Directory of Open Access Journals (Sweden)

    Ngoc-Lan Thi Nguyen

    2017-09-01

    Full Text Available The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylimidazolium chloride and aluminum chloride were found to be the most efficient and recyclable reaction framework. Ultrasound sonication appeared to be the most useful and green activation method to afford the sulfoxides in yields better than or equivalent to those obtained under the longer-lasting conventional stirring conditions.

  10. Identification of reaction products from reactions of free chlorine with the lipid-regulator gemfibrozil.

    Science.gov (United States)

    Krkošek, Wendy H; Koziar, Stephen A; White, Robert L; Gagnon, Graham A

    2011-01-01

    High global consumption rates have led to the occurrence of pharmaceutically active compounds (PhACs) in wastewater. The use of chlorine to disinfect wastewater prior to release into the environment may convert PhACs into uncharacterized chlorinated by-products. In this investigation, chlorination of a common pharmaceutical, the antihyperlipidemic agent gemfibrozil, was documented. Gemfibrozil (2,2-dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid) was reacted with sodium hypochlorite and product formation was monitored by gas chromatography-mass spectrometry (GC-MS). The incorporation of one, two or three chlorine atoms into the aromatic region of gemfibrozil was demonstrated using negative-ion electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS). Further analysis using (1)H nuclear magnetic resonance (NMR) spectroscopy identified the reaction products as 4'-ClGem (5-(4-chloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid) 4',6'-diClGem (5-(4,6-dichloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid), and 3',4',6'-triClGem (5-(3,4,6-trichloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid), products consistent with electrophilic aromatic substitution reactions. The rapid reaction of gemfibrozil with free chlorine at pH conditions relevant to water treatment indicates that a mixture of chlorinated gemfibrozils is likely to be found in wastewater disinfected with chlorine. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Solvent and Ligand Effects on the Tandem Addition-Lithiation-Electrophilic Substitution of Phenyllithium on α,β-Unsaturated Carbonyl Compounds

    Directory of Open Access Journals (Sweden)

    N. Sbarbati Nudelman

    2005-01-01

    Full Text Available The reaction of phenyllithium with E-cinnamaldehyde is extremely sensitive to the reaction conditions and surprising changes in the product distribution were observed upon changes in the solvent, concentrations, duration or temperature of the reaction. For these reasons the above mentioned reaction was considered an appropriate model to examine solvent and aggregation effects of PhLi. On the other hand, when two or trhee equiv of phenyllithium are used, instead of one, the reaction transforms into a surprising tandem addition-lithiation-β-alkylation sequence, that can be successfully applied to the synthesis of substituted dihydrochalcones. The observed effects upon changes in the reaction conditions, as well as the effects of additives that modify the PhLi dimer-monomer equilibrium are consistent with a reaction pathway in which dimeric phenyl lithium attacks to the E-cinnamaldehyde without previous deaggregation. Usually, monomers are found to be more reactive than dimers, but, in this reaction the opposite effect is observed, and the tandem reaction spectacularly decreases with the (PhLi2 concentration.

  12. Functionalization of Carbon Nanotubes via Electrophilic Substitution Reaction in Polyphosphoric Acid

    Science.gov (United States)

    2006-07-26

    single fiber. The resulting fiber bundles were chopped, collected, and washed with diluted ammonium hydroxide, and then Soxhlet -extracted with water...quantitative yield . Anal. Calcd. for C14.98H8O2: C, 81.78%; H, 3.67%. Found: C, 80.19%; H, 3.61%. 3. Results and Discussion 3.1 Characterization of MWNT...carbon nanomaterials. Furthermore, Soxhlet extractions of MWNT-g-mPEK and VGCNF- g-mPEK with dichloromethane, which is good solvent for mPEK, were

  13. Functionalization of Carbon Nanotubes via Electrophilic Substitution Reaction in Polyphosphoric Acid

    National Research Council Canada - National Science Library

    Baek, Jong-Beom

    2006-01-01

    .... Furthermore, on the basis of all supportive evidences, this work provides one of the most efficient methods to directly and uniformly grafting the surfaces of carbon nanotubes (CNT) and nanofibers (CNF...

  14. Formation and reactions of radical cations of substituted benzenes in aqueous media

    International Nuclear Information System (INIS)

    Holcman, J.

    1977-08-01

    Radical cations of anisole, methylated benzenes, ethylbenzene, isopropylbenzene, tert-butylbenzene and N,N-dimethylaniline were studied in aqueous media by pulse radiolytic technique. Absorption spectra and reaction kinetics of the radical cations were recorded. The radical cations are formed from the corresponding OH adducts by the elimination of OH - , either by a simple dissociation or by an acid catalyzed reaction. The rate constants of the formation of the radical cations and their reactions with water, OH - and Fe 2+ , or the reaction of a proton loss, were measured. The rate constants for the reaction with water and OH - , together with the rate constants for the dissociation of the OH adducts, are correlated with the ionization potential of the parent compound. These correlations offer a possibility of predicting the acid-base properties of radical cations of substituted benzenes, or the estimation of their ionization potential. (author)

  15. Kinetics on the reaction of 6-chloroquinoline and p-substituted benzoylchlorides under high pressures

    International Nuclear Information System (INIS)

    Kim, Eung Ryul; Lim, Jong Wan; Kim, Se Kyong; Ko, Young Shin

    2002-01-01

    The reactions rates of substituted 6-chloroquinoline, with p-substituted benzoyichlorides (p-CH 3 , p-H, p-NO 2 ) have been measured by conductometry in acetonitrile, and the rate constants are determined at various temperatures (10,15,20,25 .deg. C) and pressures (1, 200, 500, 1000 bar). From the values of rate constants, the activation parameters (Ea, ΔV ≠ , ΔH ≠ , ΔS ≠ , and ΔG ≠ ) and the pressure dependence of Hammett ρ values were determined. The rate constants increased with increasing temperatures and pressures, and are further increased to introduction to the electron donor substituents in substrate (p-NO 2 ) with 6-chloroquinoline. When, the activation volume and the activation entropy are all negative. And the Hammett ρ values are positive for the substrate over the pressure and temperature range studied. The results of kinetic studies for pressure and substituent show that thease reactions proceed in typical S N 2 reaction mechanism and 'associative S N 2' in bond formation favored with increasing pressures

  16. Dynamical barrier and isotope effects in the simplest substitution reaction via Walden inversion mechanism

    Science.gov (United States)

    Zhao, Zhiqiang; Zhang, Zhaojun; Liu, Shu; Zhang, Dong H.

    2017-02-01

    Reactions occurring at a carbon atom through the Walden inversion mechanism are one of the most important and useful classes of reactions in chemistry. Here we report an accurate theoretical study of the simplest reaction of that type: the H+CH4 substitution reaction and its isotope analogues. It is found that the reaction threshold versus collision energy is considerably higher than the barrier height. The reaction exhibits a strong normal secondary isotope effect on the cross-sections measured above the reaction threshold, and a small but reverse secondary kinetic isotope effect at room temperature. Detailed analysis reveals that the reaction proceeds along a path with a higher barrier height instead of the minimum-energy path because the umbrella angle of the non-reacting methyl group cannot change synchronously with the other reaction coordinates during the reaction due to insufficient energy transfer from the translational motion to the umbrella mode.

  17. Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

    Science.gov (United States)

    Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

    2018-04-01

    Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

  18. A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

    Science.gov (United States)

    Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

    2015-05-20

    Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

  19. Chemical properties of 2,3-dihydro-1H-1,5-benzodiazepinone-2 derivatives – a review

    Directory of Open Access Journals (Sweden)

    Aleksandr A. Gaponov

    2014-03-01

    Full Text Available Condensed heterocyclic systems with two nitrogen atoms in the seven-membered ring – benzodiazepines and their derivatives – are interesting and important objects from both theoretical and applied point of view. They attract a lot of attention due to their potent and diverse biological activities. These compounds include numerous tranquilizers, sedatives, analgesics, as well as anticonvulsant, anti-inflammatory and anti-tumor agents. The presence of several reactive centers in 1,5-benzodiazepines leads to a variety of reactions with both electrophilic and nucleophilic agents. The first part of this review covers electrophilic substitution of 2,3-dihydro-1H-1,5-benzodiazepin-2-ones (nitration, halogenation, alkylation, acylation, formylation, etc. The data shows that the reaction outcome is determined by the nature of both the substrate and the electrophilic agent, as well as by the reaction conditions: temperature, time, and solvent. 

  20. The Diels-Alder Cycloaddition Reaction of Substituted Hemifullerenes with 1,3-Butadiene: Effect of Electron-Donating and Electron-Withdrawing Substituents.

    Science.gov (United States)

    Mojica, Martha; Méndez, Francisco; Alonso, Julio A

    2016-02-12

    The Diels-Alder (DA) reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs). The density functional theory (DFT) B3LYP method has been used in this work to inquire if the substitution of H over the edge of triindenetriphenylene (pristine hemifullerene 1) and pentacyclopentacorannulene (pristine hemifullerene 2), could improve the DA cycloaddition reaction with 1,3-butadiene. The substituents tested include electron-donating (NH₂, OMe, OH, Me, i-Pr) and electron-withdrawing groups (F, COOH, CF₃, CHO, CN, NO₂). The electronic, kinetic and thermodynamic parameters of the DA reactions of the substituted hemifullerenes with 1,3-butadiene have been analyzed. The most promising results were obtained for the NO₂ substituent; the activation energy barriers for reactions using this substituent were lower than the barriers for the pristine hemifullerenes. This leads us to expect that the cycloadditions to a starting fullerene fragment will be possible.

  1. Crystal Structure, Conformational Analysis, and Charge Density Distribution for Eng-Epifisetinidol: An Explanation for Regiospecific Aromatic Substitution of 5-Deoxyflavan

    Science.gov (United States)

    Fred L. Tobiason; Frank R. Fronczek; Jan P. Steynberg; Elizabeth C. Steynberg; Richard W. Hemingway; Wayne L. Mattice

    1993-01-01

    Molecular modeling and molecular orbital analyses of ent-epifisetinidol gave &ood predictions of the approximate "reverse half-chair" conformation found for the crystal structure. MNDO and AM1 analyses of HOMO electron densities provided an explanation for the stereospecific electrophilic aromatic substitution at C(6) in 5-deoxy-flavans...

  2. Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route.

    Science.gov (United States)

    Mirabella, S; Fibbi, G; Matassini, C; Faggi, C; Goti, A; Cardona, F

    2017-11-07

    A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.

  3. Synthesis and Antibacterial Activities of Novel 2,5-Diphenylindolo[2,3-e] Pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines

    Directory of Open Access Journals (Sweden)

    Mohamed G. Marei

    2011-12-01

    Full Text Available The formation of (E-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-ylhydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1 and isatin (or isatin derivatives 2 at room temperature. The (E-products could be isomerized into corresponding the (Z-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4–7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H-thione (11. The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.

  4. Boomerang-type substitution reaction: reactivity of fullerene epoxides and a halofullerenol.

    Science.gov (United States)

    Jia, Zhenshan; Zhang, Xiang; Zhang, Gaihong; Huang, Shaohua; Fang, Hao; Hu, Xiangqing; Li, Yuliang; Gan, Liangbing; Zhang, Shiwei; Zhu, Daoben

    2007-02-05

    The C(s)-symmetric fullerene chlorohydrin C60(Cl)(OH)(OOtBu)4 reacts with 4-dimethylaminopyridine (DMAP) and 1,4-diazabicyclo[2.2.2]octane (DABCO) to yield two isomers with the formula C60(O)(OOtBu)4 in good yields. These isomers differ with respect to the location of the epoxy functionality. The one from DMAP is C(s) symmetric, whereas that from DABCO is C1 symmetric with the epoxy group on the central pentagon. Two different mechanisms are proposed to explain the chemoselectivity of these reactions. The reaction with DMAP involves single-electron transfer as the key step; DMAP acts as the electron donor. A combination of an oxygen-atom shift and S(N)2'' processes (boomerang substitution) are responsible for the formation of isomer with DACBO. Various related reactions support the proposed mechanisms. The structures of new fullerene derivatives were determined by spectroscopy, single-crystal X-ray analysis, and chemical correlation experiments.

  5. Complexes of metal chlorides with proton donors — promising polyfunctional catalysts for electrophilic processes

    Science.gov (United States)

    Minsker, Karl S.; Ivanova, S. R.; Biglova, Raisa Z.

    1995-05-01

    The Bronsted acids formed as a result of the interaction of aluminium chlorides with Group I and II metal chlorides in the presence of proton-donating compounds are promising polyfunctional catalysts for electrophilic processes (polymerisation, depolymerisation and degradation of macromolecules, alkylation, desulfurisation, and hydrogenation). The factor determing the electrophilic activity and selectivity of the action of the catalysts is their acidity. This makes it possible to predict the direction of the changes in the activity and selectivity of the catalyst in specific chemical processes in conformity with the opposite variation rule: with increase in the acidity of the electrophilic catalyst, their activity increases but the selectivity of their action diminishes. The bibliography includes 72 references.

  6. Ultrasound Promoted Synthesis of Bis(substituted pyrazol-4-ylcarbonyl-Substituted Thioureas

    Directory of Open Access Journals (Sweden)

    Li Xiao

    2009-03-01

    Full Text Available A series of novel bis(substituted pyrazol-4-ylcarbonyl-substituted thioureas have been synthesized by the reactions of substituted pyrazol-4-ylcarbonyl isothiocyanates with different diamines under ultrasound irradiation and classical heating method at 20-25 °C. In general, substantial improvement in rates and modest yields increases were observed when reactions were carried out under sonication, compared with the classical heating method. The structures of these compounds have been elucidated by elemental and spectral (IR, 1H-NMR analysis.

  7. Superoxide radical-mediated photocatalytic oxidation of phenolic compounds over Ag"+/TiO_2: Influence of electron donating and withdrawing substituents

    International Nuclear Information System (INIS)

    Xiao, Jiadong; Xie, Yongbing; Han, Qingzhen; Cao, Hongbin; Wang, Yujiao; Nawaz, Faheem; Duan, Feng

    2016-01-01

    Highlights: • A weak EWG benefited photocatalytic oxidation of phenols the most. • Phenolic compounds were dominantly oxidized by ·O_2"−, rather than ·OH, "1O_2 or h"+. • ·O_2"− preferred to nucleophilically attack EDG substituted phenols. • ·O_2"− more likely electrophilically attacked EWG substituted phenols. • ·O_2"− simultaneously nucleophilically and electrophilically assaulted p-chlorophenol. - Abstract: A comparative study was constructed to correlate the electronic property of the substituents with the degradation rates of phenolic compounds and their oxidation pathways under UV with Ag"+/TiO_2 suspensions. It was verified that a weak electron withdrawing substituent benefited photocatalytic oxidation the most, while an adverse impact appeared when a substituent was present with stronger electron donating or withdrawing ability. The addition of p-benzoquinone dramatically blocked the degradation, confirming superoxide radicals (·O_2"−) as the dominant photooxidant, rather than hydroxyl radicals, singlet oxygen or positive holes, which was also independent of the substituent. Hammett relationship was established based on pseudo-first-order reaction kinetics, and it revealed two disparate reaction patterns between ·O_2"− and phenolic compounds, which was further verified by the quantum chemical computation on the frontier molecular orbitals and Mulliken charge distributions of ·O_2"− and phenolic compounds. It was found that electron donating group (EDG) substituted phenols were more likely nucleophilically attacked by ·O_2"−, while ·O_2"− preferred to electrophilically assault electron withdrawing group (EWG) substituted phenols. Exceptionally, electrophilic and nucleophilic attack by ·O_2"− could simultaneously occur in p-chlorophenol degradation, consequently leading to its highest rate constant. Possible reactive positions on the phenolic compounds were also detailedly uncovered.

  8. Lewis acid tuned facial stereodivergent HDA reactions using beta-substituted N-vinyloxazolidinones.

    Science.gov (United States)

    Gohier, Frédéric; Bouhadjera, Keltoum; Faye, Djibril; Gaulon, Catherine; Maisonneuve, Vincent; Dujardin, Gilles; Dhal, Robert

    2007-01-18

    The [4 + 2] acido-catalyzed heterocycloaddition between new beta-substituted N-vinyl-1,3-oxazolidin-2-ones (with R' = Me, Ar, CH2 Ar) and beta,gamma-unsaturated alpha-ketoesters (R = Ar) afforded heteroadducts with high levels of endo and facial selectivities. A complete reversal of facial differentiation was achieved by varying the Lewis acid, leading to the stereoselective formation of either endo-alpha or endo-beta adducts. [reaction: see text].

  9. High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1979-February 14, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Rack, E.P.

    1980-02-01

    The program consists of six interrelated areas: (1) Reactions of iodine with alkenes and alkynes activated by radiative neutron capture and isomeric transition in low pressure gaseous systems employing additives and rare gas moderators, high pressure, and liquid systems. Special attention was given to the reactivity of excited complex formation and structural effects of electrophilic iodine attack on various pi-bond systems. (2) The gas-to-condensed phase transition in halogen high energy chemistry. Current interest involves the study of caging effects of an ice lattice on recombination reactions involving neutron-irradiated frozen aqueous solutions of halogenated organic and biochemical solutes in order to learn more about kinetic energy effects, halogen size, solute molecule size, steric effects and hydrogen bonding within an ice lattice cage. (3) Systematics of halogen hot atom reactions. The reactions of /sup 80m/Br, /sup 80/Br, /sup 82m/Br + /sup 82/Br, /sup 82/Br, /sup 82/Br, /sup 128/I, /sup 130/I, and /sup 130m/I + /sup 130/I activated by radiative neutron capture or isomeric transition in hydrocarbons and halo-substituted alkanes in low pressure and high pressure gaseous systems employing additives and rare gas moderators are currently being studied. (4) Mathematical and computer simulation studies of caging events within an ice lattice are being investigated. (5) At Brookhaven National Laboratory, cyclotron-produced chlorine and fluorine hot atoms substitution reactions with molecules possessing a single chiral center are under investigation to determine the role of hot atom kinetic energy, halogen atom, enantioner structure, steric effects and phase on the extent of substitution by retention of configuration or by Walden inversion. (6) The applications of high energy techniques and concepts to neutron activation analysis for trace element determinations in biological systems was continued.

  10. Density functional theory studies on electronic properties of thiophene s oxides as aromatic dienophiles for reactivity prediction in diels-alder reactions

    International Nuclear Information System (INIS)

    Banjo, S.

    2013-01-01

    The reactivity of thiophene S-oxides was discussed with special emphasis on the use of thiophene S-oxides as dienophiles in Diels-Alder type reactions. The omega values obtained for thiophene S-oxide (TO) with electron-donating group (-CH/sub 3/) increased the nucleophilicity power whereas substitution with electron-withdrawing groups (such as -NO/sub 2/ and -CO/sub 2/CH/sub 2/CH/sub 3/) increased the electrophilicity power, indicating an increase of reactivity towards a nucleophiles. The higher the value of delta omega the more favourable the D-A process, therefore apart from (4+2) addition reactions of these TO as diene with the typical dienophiles like 1,2-dicyanoethene and 1,2-dicyanoethene, it could be possible for TO with strong electron withdrawing substituents to serve as dienophile, e.g. heterocycles Ie and If. Also, from the value of delta omega heterocycle 1d could involve in (4+2) addition reactions with heterocyles 1e and If. (author)

  11. Molecular-weight-enlarged multiple-pincer ligands: synthesis and application in palladium-catalyzed allylic substitution reactions

    NARCIS (Netherlands)

    Ronde, N.J.; Totev, D.; Müller, Christian; Lutz, M.; Spek, A.L.; Vogt, D.

    2009-01-01

    Three different pincer ligand systems are synthesized via nucleophilic substitution reactions of polyaromatic benzyl bromides as support molecules and phenol derivatives as ligand precursors. Retention tests using a polymeric nanofiltration membrane show moderate to good retention in THF and CH2Cl2.

  12. Green Synthesis of a Fluorescent Natural Product

    Science.gov (United States)

    Young, Douglas M.; Welker, Jacob J. C.; Doxsee, Kenneth M.

    2011-01-01

    Synthesis of 4-methylumbelliferone via the acid-catalyzed Pechmann condensation introduces students to several types of organic reactions: transesterification, electrophilic aromatic substitution, and alcohol dehydration. Performed with a recyclable, solid catalyst and under solvent-free conditions, the experiment illustrates many of the…

  13. [Development of boomerang-type intramolecular cascade reactions and application to natural product synthesis].

    Science.gov (United States)

    Takasu, K

    2001-12-01

    Intramolecular cascade reaction has received much attention as a powerful methodology to construct a polycyclic framework in organic synthesis. We have been developing "boomerang-type cascade reaction" to construct a variety of polycyclic skeletons efficiently. In the above reactions, a nucleophilic function of substrates changes the character into an electrophile after the initial reaction, and the electrophilic group acts as a nucleophile in the second reaction. That is, the reaction center stepwise moves from one functional group back to the same one via other functional groups. The stream of the electron concerning the cascade reaction is like a locus of boomerang. We show here three different boomerang-type reactions via ionic species or free radicals. 1) Diastereoselective Michael-aldol reaction based on the chiral auxiliary method and enantioselective Michael-aldol reaction by the use of external chiral sources. 2) Short and efficient total syntheses of longifolane sesquiterpenes utilizing intramolecular double Michael addition as a key step. 3) Development of boomerang-type radical cascade reaction of halopolyenes to construct terpenoid skeletons and its regioselectivity.

  14. Direct catalytic trifluoromethylthiolation of boronic acids and alkynes employing electrophilic shelf-stable N-(trifluoromethylthio)phthalimide.

    Science.gov (United States)

    Pluta, Roman; Nikolaienko, Pavlo; Rueping, Magnus

    2014-02-03

    A new and safe method for the synthesis of N-(trifluoromethylthio)phthalimide, a convenient and shelf-stable reagent for the direct trifluoromethylthiolation, has been developed. N-(Trifluoromethylthio)phthalimide can be used as an electrophilic source of F3 CS(+) and reacts readily with boronic acids and alkynes under copper catalysis. The utility of CF3 S-containing molecules as biologically active agents, the mild reaction conditions employed, and the high tolerance of functional groups demonstrate the potential of this new methodology to be widely applied in organic synthesis as well as industrial pharmaceutical and agrochemical research and development. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1979-February 14, 1980

    International Nuclear Information System (INIS)

    Rack, E.P.

    1980-02-01

    The program consists of six interrelated areas: (1) Reactions of iodine with alkenes and alkynes activated by radiative neutron capture and isomeric transition in low pressure gaseous systems employing additives and rare gas moderators, high pressure, and liquid systems. Special attention was given to the reactivity of excited complex formation and structural effects of electrophilic iodine attack on various pi-bond systems. (2) The gas-to-condensed phase transition in halogen high energy chemistry. Current interest involves the study of caging effects of an ice lattice on recombination reactions involving neutron-irradiated frozen aqueous solutions of halogenated organic and biochemical solutes in order to learn more about kinetic energy effects, halogen size, solute molecule size, steric effects and hydrogen bonding within an ice lattice cage. (3) Systematics of halogen hot atom reactions. The reactions of /sup 80m/Br, 80 Br, /sup 82m/Br + 82 Br, 82 Br, 82 Br, 128 I, 130 I, and /sup 130m/I + 130 I activated by radiative neutron capture or isomeric transition in hydrocarbons and halo-substituted alkanes in low pressure and high pressure gaseous systems employing additives and rare gas moderators are currently being studied. (4) Mathematical and computer simulation studies of caging events within an ice lattice are being investigated. (5) At Brookhaven National Laboratory, cyclotron-produced chlorine and fluorine hot atoms substitution reactions with molecules possessing a single chiral center are under investigation. (6) The applications of high energy techniques and concepts to neutron activation analysis for trace elements and trace molecule determinations in biological systems was continued

  16. Correction: Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric Michael addition reactions of carboxylate-substituted enones.

    Science.gov (United States)

    Yin, Feng; Garifullina, Ainash; Tanaka, Fujie

    2018-04-25

    Correction for 'Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric Michael addition reactions of carboxylate-substituted enones' by Feng Yin et al., Org. Biomol. Chem., 2017, 15, 6089-6092.

  17. Prediction of the chemo- and regioselectivity of Diels-Alder reactions of o-benzoquinone derivatives with thiophenes by means of DFT-based reactivity indices

    Science.gov (United States)

    Ghomri, Amina; Mekelleche, Sidi Mohamed

    2014-03-01

    Global and local reactivity indices derived from density functional theory were used to elucidate the regio- and chemoselectivity of Diels-Alder reactions of masked o-benzoquinones with thiophenes acting as dienophiles. The polarity of the studied reactions is evaluated in terms of the difference of electrophilicity powers between the diene and dienophile partners. Preferential cyclisation modes of these cycloadditions are predicted using Domingo's polar model based on the local electrophilicity index, ωk, of the electrophile and the local nucleophilicity index, Nuk, of the nucleophile. The theoretical calculations, carried out at the B3LYP/6-311G(d,p) level of theory, are in good agreement with experimental findings.

  18. [Glycosilated derivatives of substituted hydroxylamine. II. Phase transfer synthesis and investigation of glycosyl transfer reaction of glucosaminides of substituted hydroxylavine].

    Science.gov (United States)

    Kur'ianov, V O; Lushchik, A A; Chupakhina, T A

    2013-01-01

    1-(2-Acetamido-3,4,6,-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyloxy)-benzotriazole reacted in boiling dichloromethane, in the presence of Luis acids as a promotors with primary and secondary aliphatic and cycloaliphatic alcohols and diisopropilidene galactose with alkyl-O-1,2-trans-glucosaminides formation. It was shown that the other glucosaminides of substituted hydroxylamine are not participated in this reaction. Structures of glucosaminides were identify by 1H-NMR-spectroscopy and comparison with known compounds.

  19. Reduced Reactivity of Amines against Nucleophilic Substitution via Reversible Reaction with Carbon Dioxide

    Directory of Open Access Journals (Sweden)

    Fiaz S. Mohammed

    2015-12-01

    Full Text Available The reversible reaction of carbon dioxide (CO2 with primary amines to form alkyl-ammonium carbamates is demonstrated in this work to reduce amine reactivity against nucleophilic substitution reactions with benzophenone and phenyl isocyanate. The reversible formation of carbamates has been recently exploited for a number of unique applications including the formation of reversible ionic liquids and surfactants. For these applications, reduced reactivity of the carbamate is imperative, particularly for applications in reactions and separations. In this work, carbamate formation resulted in a 67% reduction in yield for urea synthesis and 55% reduction for imine synthesis. Furthermore, the amine reactivity can be recovered upon reversal of the carbamate reaction, demonstrating reversibility. The strong nucleophilic properties of amines often require protection/de-protection schemes during bi-functional coupling reactions. This typically requires three separate reaction steps to achieve a single transformation, which is the motivation behind Green Chemistry Principle #8: Reduce Derivatives. Based upon the reduced reactivity, there is potential to employ the reversible carbamate reaction as an alternative method for amine protection in the presence of competing reactions. For the context of this work, CO2 is envisioned as a green protecting agent to suppress formation of n-phenyl benzophenoneimine and various n-phenyl–n-alky ureas.

  20. Sulfonate activation of the electrophilic reactivity of chlorine and alkyl hypochlorides by the insertion of sulfur trioxide at the C1-C1 and O-C1 bonds. Addition of chlorine chloro- and ethoxysulfate to olefins

    International Nuclear Information System (INIS)

    Zefirov, N.S.; Koz'min, A.S.; Sorokin, V.D.; Zhdankin, V.V.

    1986-01-01

    At low temperatures (-40 to -80 0 C) sulfur trioxide enters the chlorine molecule (with the formation of chlorine chlorosulfate) and the ethyl hypochlorite molecule (giving chlorine ethoxysulfate). Both new compounds are highly reactive electrophilic chlorinating reagents and add to ethylene, activated alkenes (1-hexene and cyclohexene), and deactivated olefins (methyl methacrylate, tri- and tetrachloroethylene) in methylene chloride solution at low temperatures. The addition of chlorine chlorosulfate leads to the formation of β-chloroalkyl chlorosulfates with yields of 24-85%, and the addition of chlorine ethoxysulfate leads to β-chloroalkyl ethylsulfates with yields of 65-85%. The reactions with unsymmetrical olefins lead to mixtures of the regioisomers with a preference for the products from addition according to the Markovnikov rule; the addition to cyclohexene is trans-stereospecific. The investigated processes represent a new simple approach to the production of sulfate-activated chlorinating reagents and extend the possibilities for functional substitution of olefins

  1. An Eco-Friendly Improved Protocol for the Synthesis of Bis(3-indolyl)methanes Using Poly(4-vinylpyridinium)hydrogen Sulfate as Efficient, Heterogeneous, and Recyclable Solid Acid Catalyst

    Science.gov (United States)

    Banothu, Janardhan; Gali, Rajitha; Velpula, Ravibabu; Bavantula, Rajitha; Crooks, Peter A.

    2013-01-01

    Highly efficient and eco-friendly protocol for the synthesis of bis(3-indolyl)methanes by the electrophilic substitution reaction of indole with aldehydes catalyzed by poly(4-vinylpyridinium)hydrogen sulfate was described. Excellent yields, shorter reaction times, simple work-up procedure, avoiding hazardous organic solvents, and reusability of the catalyst are the most obvious advantages of this method. PMID:24052864

  2. Synthesis of substituted mono- and diindole C-nucleoside analogues from sugar terminal alkynes by sequential sonogashira/heteroannulation reaction.

    Science.gov (United States)

    Zhang, Fuyi; Mu, Delong; Wang, Liming; Du, Pengfei; Han, Fen; Zhao, Yufen

    2014-10-17

    The synthesis of substituted mono- and diindole C-nucleoside analogues has been achieved in good to excellent yields by sequential Sonogashira coupling/NaAuCl4-catalyzed heteroannulation reactions of substituted 2-iodoanilines with various sugar terminal alkynes in one pot. The method is general, mild, and efficient and suitable for a wide range of sugar substrates, and 42 examples are given. The amino group of the substituted 2-iodoanilines is unprotected. The sugar terminal alkynes include furanosides, pyranosides, and acyclic glycosides with free hydroxyl groups, sensitive functional subtituents, and various protecting groups having different steric hindrance.

  3. Lewis base catalyzed 1,3-dithiane addition to carbonyl and imino compounds using 2-trimethylsilyl-1,3-dithiane.

    Science.gov (United States)

    Michida, Makoto; Mukaiyama, Teruaki

    2008-09-01

    Lewis base-catalyzed 1,3-dithiane addition to electrophiles such as carbonyl compounds and N-substituted aldimines with 2-trimethylsilyl-1,3-dithiane (TMS-dithiane) is described. By the activation of the carbon-silicon bond in the presence of a Lewis base catalyst such as tetrabutylammonium phenoxide (PhONnBu(4)), a 1,3-dithiane addition reaction proceeded smoothly to afford the corresponding adducts in good to high yields under mild conditions. This synthesis is also applied to the reactions of ketones having alpha-protons, and of N-substituted aldimines.

  4. Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2017-08-01

    Full Text Available Redox imbalance in cells induces lipid peroxidation and generates a class of highly reactive metabolites known as lipid-derived electrophiles (LDEs that can modify proteins and affects their functions. Identifying targets of LDEs is critical to understand how such modifications are functionally implicated in oxidative-stress associated diseases. Here we report a quantitative chemoproteomic method to globally profile protein targets and sites modified by LDEs. In this strategy, we designed and synthesized an alkyne-functionalized aminooxy probe to react with LDE-modified proteins for imaging and proteomic profiling. Using this probe, we successfully quantified >4000 proteins modified by 4-hydroxy-2-nonenal (HNE of high confidence in mammalian cell lysate and combined with a tandem-orthogonal proteolysis activity-based protein profiling (TOP-ABPP strategy, we identified ~400 residue sites targeted by HNE including reactive cysteines in peroxiredoxins, an important family of enzymes with anti-oxidant roles. Our method expands the toolbox to quantitatively profile protein targets of endogenous electrophiles and the enlarged inventory of LDE-modified proteins and sites will contribute to functional elucidation of cellular pathways affected by oxidative stress. Keywords: Lipid-derived electrophile, 4-hydroxy-2-nonenal, Chemoproteomics, Aminooxy probe, Activity-based protein profiling

  5. α- and α'-Lithiation-Electrophile Trapping of N-Thiopivaloyl and N-tert-Butoxythiocarbonyl α-Substituted Azetidines: Rationalization of the Regiodivergence Using NMR and Computation.

    Science.gov (United States)

    Jackson, Kelvin E; Mortimer, Claire L; Odell, Barbara; McKenna, Jeffrey M; Claridge, Timothy D W; Paton, Robert S; Hodgson, David M

    2015-10-16

    (1)H NMR and computational analyses provide insight into the regiodivergent (α- and α'-) lithiation-electrophile trapping of N-thiopivaloyl- and N-(tert-butoxythiocarbonyl)-α-alkylazetidines. The magnitudes of the rotation barriers in these azetidines indicate that rotamer interconversions do not occur at the temperature and on the time scale of the lithiations. The NMR and computational studies support the origin of regioselectivity as being thiocarbonyl-directed lithiation from the lowest energy amide-like rotameric forms (cis for N-thiopivaloyl and trans for N-tert-butoxythiocarbonyl).

  6. Irreversible endo-Selective Diels–Alder Reactions of Substituted Alkoxyfurans: A General Synthesis of endo-Cantharimides

    Science.gov (United States)

    Foster, Robert W; Benhamou, Laure; Porter, Michael J; Bučar, Dejan-Krešimir; Hailes, Helen C; Tame, Christopher J; Sheppard, Tom D

    2015-01-01

    The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels–Alder reaction. PMID:25756502

  7. Kinetics and selectivity of the oxidation of methylbenzenes in Co(III)-CH3COOH-CF3COOH solutions. Comparison with nitration and hydroxylation reactions

    International Nuclear Information System (INIS)

    Rudakov, E.S.; Lobachev, V.L.

    1989-01-01

    Data have been obtained concerning the kinetics, substrate selectivity, and kinetic isotope effect for the first stage in the oxidation of a series of arenes, from benzene to hexamethylbenzene, by Co(III) acetate in CH 3 COOH-CF 3 COOH (1.9 M) solutions at 25 degree C. A similarity was noted between substrate selectivity for reactions of alkylbenzenes with Co(III) and electrophilic nitration reactions, which occur via an electron transfer step. It was also found that substrate selectivity for these reactions differs significantly from that found for electrophilic hydroxylation reactions, which occur via an intermediate slow step involving σ-complex formation

  8. Organic chemistry experiment

    International Nuclear Information System (INIS)

    Mun, Seok Sik

    2005-02-01

    This book deals with organic chemistry experiments, it is divided five chapters, which have introduction, the way to write the experiment report and safety in the laboratory, basic experiment technic like recrystallization and extraction, a lot of organic chemistry experiments such as fischer esterification, ester hydrolysis, electrophilic aromatic substitution, aldol reaction, benzoin condensation, wittig reaction grignard reaction, epoxidation reaction and selective reduction. The last chapter introduces chemistry site on the internet and way to find out reference on chemistry.

  9. Synthesis of Bisphenol Z: An Organic Chemistry Experiment

    Science.gov (United States)

    Gregor, Richard W.

    2012-01-01

    A student achievable synthesis of bisphenol Z, 4,4'-(cyclohexane-1,1-diyl)diphenol, from the acid-catalyzed reaction of phenol with cyclohexanone is presented. The experiment exemplifies all the usual pedagogy for the standard topic of electrophilic aromatic substitution present in the undergraduate organic chemistry curriculum, while providing…

  10. Superoxide radical-mediated photocatalytic oxidation of phenolic compounds over Ag{sup +}/TiO{sub 2}: Influence of electron donating and withdrawing substituents

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Jiadong [National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Beijing Engineering Research Center of Process Pollution Control, Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xie, Yongbing, E-mail: ybxie@ipe.ac.cn [National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Beijing Engineering Research Center of Process Pollution Control, Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Han, Qingzhen [State Key Laboratory of Multi-phase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Cao, Hongbin [National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Beijing Engineering Research Center of Process Pollution Control, Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China); Wang, Yujiao [Department of Chemical and Biomedical Engineering, University of Science and Technology Beijing (China); Nawaz, Faheem; Duan, Feng [National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Beijing Engineering Research Center of Process Pollution Control, Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

    2016-03-05

    Highlights: • A weak EWG benefited photocatalytic oxidation of phenols the most. • Phenolic compounds were dominantly oxidized by ·O{sub 2}{sup −}, rather than ·OH, {sup 1}O{sub 2} or h{sup +}. • ·O{sub 2}{sup −} preferred to nucleophilically attack EDG substituted phenols. • ·O{sub 2}{sup −} more likely electrophilically attacked EWG substituted phenols. • ·O{sub 2}{sup −} simultaneously nucleophilically and electrophilically assaulted p-chlorophenol. - Abstract: A comparative study was constructed to correlate the electronic property of the substituents with the degradation rates of phenolic compounds and their oxidation pathways under UV with Ag{sup +}/TiO{sub 2} suspensions. It was verified that a weak electron withdrawing substituent benefited photocatalytic oxidation the most, while an adverse impact appeared when a substituent was present with stronger electron donating or withdrawing ability. The addition of p-benzoquinone dramatically blocked the degradation, confirming superoxide radicals (·O{sub 2}{sup −}) as the dominant photooxidant, rather than hydroxyl radicals, singlet oxygen or positive holes, which was also independent of the substituent. Hammett relationship was established based on pseudo-first-order reaction kinetics, and it revealed two disparate reaction patterns between ·O{sub 2}{sup −} and phenolic compounds, which was further verified by the quantum chemical computation on the frontier molecular orbitals and Mulliken charge distributions of ·O{sub 2}{sup −} and phenolic compounds. It was found that electron donating group (EDG) substituted phenols were more likely nucleophilically attacked by ·O{sub 2}{sup −}, while ·O{sub 2}{sup −} preferred to electrophilically assault electron withdrawing group (EWG) substituted phenols. Exceptionally, electrophilic and nucleophilic attack by ·O{sub 2}{sup −} could simultaneously occur in p-chlorophenol degradation, consequently leading to its highest rate

  11. Addition of electrophilic lipids to actin alters filament structure

    International Nuclear Information System (INIS)

    Gayarre, Javier; Sanchez, David; Sanchez-Gomez, Francisco J.; Terron, Maria C.; Llorca, Oscar; Perez-Sala, Dolores

    2006-01-01

    Pathophysiological processes associated with oxidative stress lead to the generation of reactive lipid species. Among them, lipids bearing unsaturated aldehyde or ketone moieties can form covalent adducts with cysteine residues and modulate protein function. Through proteomic techniques we have identified actin as a target for the addition of biotinylated analogs of the cyclopentenone prostaglandins 15-deoxy-Δ 12,14 -PGJ 2 (15d-PGJ 2 ) and PGA 1 in NIH-3T3 fibroblasts. This modification could take place in vitro and mapped to the protein C-terminal end. Other electrophilic lipids, like the isoprostane 8-iso-PGA 1 and 4-hydroxy-2-nonenal, also bound to actin. The C-terminal region of actin is important for monomer-monomer interactions and polymerization. Electron microscopy showed that actin treated with 15d-PGJ 2 or 4-hydroxy-2-nonenal formed filaments which were less abundant and displayed shorter length and altered structure. Streptavidin-gold staining allowed mapping of biotinylated 15d-PGJ 2 at sites of filament disruption. These results shed light on the structural implications of actin modification by lipid electrophiles

  12. Bromination of Phenol

    Science.gov (United States)

    Talbot, Christopher

    2013-01-01

    This "Science note" examines the bromination of phenol, a reaction that is commonly taught at A-level and IB (International Baccalaureate) as an example of electrophilic substitution. Phenol undergoes bromination with bromine or bromine water at room temperature. A white precipitate of 2,4,6-tribromophenol is rapidly formed. This…

  13. Noncanonical Reactions of Flavoenzymes

    Directory of Open Access Journals (Sweden)

    Pablo Sobrado

    2012-11-01

    Full Text Available Enzymes containing flavin cofactors are predominantly involved in redox reactions in numerous cellular processes where the protein environment modulates the chemical reactivity of the flavin to either transfer one or two electrons. Some flavoenzymes catalyze reactions with no net redox change. In these reactions, the protein environment modulates the reactivity of the flavin to perform novel chemistries. Recent mechanistic and structural data supporting novel flavin functionalities in reactions catalyzed by chorismate synthase, type II isopentenyl diphosphate isomerase, UDP-galactopyranose mutase, and alkyl-dihydroxyacetonephosphate synthase are presented in this review. In these enzymes, the flavin plays either a direct role in acid/base reactions or as a nucleophile or electrophile. In addition, the flavin cofactor is proposed to function as a “molecular scaffold” in the formation of UDP-galactofuranose and alkyl-dihydroxyacetonephosphate by forming a covalent adduct with reaction intermediates.

  14. The chemical foundations of nitroalkene fatty acid signaling through addition reactions with thiols.

    Science.gov (United States)

    Turell, Lucía; Steglich, Martina; Alvarez, Beatriz

    2018-03-22

    Nitroalkene fatty acids can be formed in vivo and administered exogenously. They exert pleiotropic signaling actions with cytoprotective and antiinflammatory effects. The presence of the potent electron withdrawing nitro group confers electrophilicity to the adjacent β-carbon. Thiols (precisely, thiolates) are strong nucleophiles and can react with nitroalkene fatty acids through reversible Michael addition reactions. In addition, nitroalkene fatty acids can undergo several other processes including metabolic oxidation, reduction, esterification, nitric oxide release and partition into hydrophobic compartments. The signaling actions of nitroalkenes are mainly mediated by reactions with critical thiols in regulatory proteins. Thus, the thio-Michael addition reaction provides a framework for understanding the molecular basis of the biological effects of nitroalkene fatty acids at the crossroads of thiol signaling and electrophilic lipid signaling. In this review, we describe the reactions of nitroalkene fatty acids in biological contexts. We focus on the Michael addition-elimination reaction with thiols and its mechanism, and extrapolate kinetic and thermodynamic considerations to in vivo settings. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Highly enantio- and diastereoselective reactions of γ-substituted butenolides through direct vinylogous conjugate additions

    KAUST Repository

    Zhang, Wen; Tan, Davin; Lee, Richmond; Tong, Guanghu; Chen, Wenchao; Qi, Baojian; Huang, Kuo-Wei; Tan, Choonhong; Jiang, Zhiyong

    2012-01-01

    The strength of the weak: An L-tert-leucine-derived amine-thiourea catalyst (see scheme, green box) promotes the asymmetric vinylogous conjugate addition reaction between γ-aryl- and alkyl-substituted butenolides with the butenamides and enoates shown. Computational studies show the preference for the observed stereochemistry is a result of favourable weak non-bonding interactions, which stabilize the transition state. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Highly enantio- and diastereoselective reactions of γ-substituted butenolides through direct vinylogous conjugate additions

    KAUST Repository

    Zhang, Wen

    2012-09-05

    The strength of the weak: An L-tert-leucine-derived amine-thiourea catalyst (see scheme, green box) promotes the asymmetric vinylogous conjugate addition reaction between γ-aryl- and alkyl-substituted butenolides with the butenamides and enoates shown. Computational studies show the preference for the observed stereochemistry is a result of favourable weak non-bonding interactions, which stabilize the transition state. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Effects of solvent and structure on the reactivity of 6-substituted nicotinic acids with diazodiphenylmethane in aprotic solvents

    Directory of Open Access Journals (Sweden)

    BRATISLAV Ž. JOVANOVIĆ

    2009-12-01

    Full Text Available The rate constants for the reactions of diazodiphenylmethane (DDM with 6-substituted nicotinic acids in aprotic solvents at 30 °C were determined. The obtained second order rate constants in aprotic solvents, together with literature data for benzoic and nicotinic acids in protic solvents, were used for the calculation of solvent effects, employing the Kamlet-Taft solvatochromic equation (linear solvation energy relationship – LSER in the form: log k = log k0 + s* + a + b. The correlations of the kinetic data were performed by means of multiple linear regression analysis taking appropriate solvent parameters. The sign of the equation coefficients (s, a and b were in agreement with the postulated reaction mechanism, and the mode of the solvent influences on the reaction rate is discussed based on the correlation results. A similar contribution of the non-specific solvent effect and electrophilic solvation was observed for all acids, while the highest contribution of nucleophilic solvation was influenced by their high acidity. Correlation analysis of the rate data with substituent p parameters in an appropriate solvent using the Hammett equation was also performed. The substituent effect on the acid reactivity was higher in aprotic solvents of higher dipolarity/polarizability. The mode of the transmission of the substituent effect is discussed in light of the contribution of solute–solvent interaction on the acid reactivity.

  18. Synthesis of some fenchyl-substituted alkenes and enol-ethers containing 3-oxyphenyl substituents by the Barton-Kellogg reaction

    International Nuclear Information System (INIS)

    Ciscato, Luiz Francisco M.L.; Bartoloni, Fernando H.; Baader, Wilhelm Josef; Bastos, Erick L.; Guenther, Wolfgang; Weiss, Dieter; Beckert, Rainer

    2010-01-01

    The synthesis of one fenchyl-substituted alkene and two enol-ethers, containing 3-oxyphenyl substituents by the Barton-Kellogg reaction is described. The tri-substituted aromatic fenchylalkene 1a was prepared in 53% yield from thiofenchone and a diazoanisole; whereas enol-ethers 1b and 1c were obtained (95 and 75% yield, respectively) using an inverse approach based on diazofenchone and aromatic thionoesters. A mixture of Z and E isomers was obtained in all cases; isomer attribution and quantification has been carried out by analysis of NMR spectroscopic data assisted by theoretical calculations (E/Z ratio: 1a = 0.72, 1b = 2.2, 1c = 1.8). Reaction proceeds with low stereoselectivity leading to the preferential formation of diastereoisomeric olefins and enol-ethers where the aromatic substituent resides at the side of the two fenchyl methyl groups. (author)

  19. Synthesis of some fenchyl-substituted alkenes and enol-ethers containing 3-oxyphenyl substituents by the Barton-Kellogg reaction

    Energy Technology Data Exchange (ETDEWEB)

    Ciscato, Luiz Francisco M.L.; Bartoloni, Fernando H.; Baader, Wilhelm Josef, E-mail: wjbaader@iq.usp.b [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica. Dept. de Quimica Fundamental; Bastos, Erick L. [Universidade Federal do ABC (UFABC), Santo Andre, SP (Brazil). Centro de Ciencias Naturais e Humanas; Guenther, Wolfgang; Weiss, Dieter; Beckert, Rainer [Friedrich-Schiller Universitaet Jena (Germany). Institut fuer Organische Chemie und Makromolekulare Chemie

    2010-07-01

    The synthesis of one fenchyl-substituted alkene and two enol-ethers, containing 3-oxyphenyl substituents by the Barton-Kellogg reaction is described. The tri-substituted aromatic fenchylalkene 1a was prepared in 53% yield from thiofenchone and a diazoanisole; whereas enol-ethers 1b and 1c were obtained (95 and 75% yield, respectively) using an inverse approach based on diazofenchone and aromatic thionoesters. A mixture of Z and E isomers was obtained in all cases; isomer attribution and quantification has been carried out by analysis of NMR spectroscopic data assisted by theoretical calculations (E/Z ratio: 1a = 0.72, 1b = 2.2, 1c = 1.8). Reaction proceeds with low stereoselectivity leading to the preferential formation of diastereoisomeric olefins and enol-ethers where the aromatic substituent resides at the side of the two fenchyl methyl groups. (author)

  20. Akt3 is a privileged first responder in isozyme-specific electrophile response.

    Science.gov (United States)

    Long, Marcus J C; Parvez, Saba; Zhao, Yi; Surya, Sanjna L; Wang, Yiran; Zhang, Sheng; Aye, Yimon

    2017-03-01

    Isozyme-specific post-translational regulation fine tunes signaling events. However, redundancy in sequence or activity renders links between isozyme-specific modifications and downstream functions uncertain. Methods to study this phenomenon are underdeveloped. Here we use a redox-targeting screen to reveal that Akt3 is a first-responding isozyme sensing native electrophilic lipids. Electrophile modification of Akt3 modulated downstream pathway responses in cells and Danio rerio (zebrafish) and markedly differed from Akt2-specific oxidative regulation. Digest MS sequencing identified Akt3 C119 as the privileged cysteine that senses 4-hydroxynonenal. A C119S Akt3 mutant was hypomorphic for all downstream phenotypes shown by wild-type Akt3. This study documents isozyme-specific and chemical redox signal-personalized physiological responses.

  1. Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

    Science.gov (United States)

    Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

    2016-01-18

    A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

  2. New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

    Directory of Open Access Journals (Sweden)

    Pavel Nagorny

    2016-12-01

    Full Text Available Hydrogen bond donor catalysis represents a rapidly growing subfield of organocatalysis. While traditional hydrogen bond donors containing N–H and O–H moieties have been effectively used for electrophile activation, activation based on other types of non-covalent interactions is less common. This mini review highlights recent progress in developing and exploring new organic catalysts for electrophile activation through the formation of C–H hydrogen bonds and C–X halogen bonds.

  3. Further studies of the thermal and photochemical diels-alder reactions of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with naphthalene and some substituted naphthalenes

    Science.gov (United States)

    Breton; Newton

    2000-05-19

    MeTAD thermally reacted with naphthalene (2) and methylated naphthalenes to give equilibrium mixtures of starting materials and [4 + 2] cycloadducts. Methyl substitution on the naphthalene ring generally increased both the amount of cycloadduct formed and the rate of cycloaddition relative to 2. The isolated cycloadducts were all thermally labile and quantitatively reverted to the parent naphthalene in the presence of 2,3-dimethyl-2-butene as a trap for liberated MeTAD. The rates of the cycloreversion reactions were affected by substitution patterns but not appreciably by solvent. A mechanism for the cycloaddition reaction is presented that proposes the involvement of a charge-transfer complex. Photochemically, MeTAD demonstrated lower regioselectivity in its reactions with substituted naphthalenes relative to the corresponding thermal reactions.

  4. Dechlorination of chloropicrin and 1,3-dichloropropene by hydrogen sulfide species: redox and nucleophilic substitution reactions.

    Science.gov (United States)

    Zheng, Wei; Yates, Scott R; Papiernik, Sharon K; Guo, Mingxin; Gan, Jianying

    2006-03-22

    The chlorinated fumigants chloropicrin (trichloronitromethane) and 1,3-dichloropropene (1,3-D) are extensively used in agricultural production for the control of soilborne pests. The reaction of these two fumigants with hydrogen sulfide species (H2S and HS-) was examined in well-defined anoxic aqueous solutions. Chloropicrin underwent an extremely rapid redox reaction in the hydrogen sulfide solution. Transformation products indicated reductive dechlorination of chloropicrin by hydrogen sulfide species to produce dichloro- and chloronitromethane. The transformation of chloropicrin in hydrogen sulfide solution significantly increased with increasing pH, indicating that H2S is less reactive toward chloropicrin than HS- is. For both 1,3-D isomers, kinetics and transformation products analysis revealed that the reaction between 1,3-D and hydrogen sulfide species is an S(N)2 nucleophilic substitution process, in which the chlorine at C3 of 1,3-D is substituted by the sulfur nucleophile to form corresponding mercaptans. The 50% disappearance time (DT50) of 1,3-D decreased with increasing hydrogen sulfide species concentration at a constant pH. Transformation of 1,3-D was more rapid at high pH, suggesting that the reactivity of hydrogen sulfide species in the experimental system stems primarily from HS-. Because of the relatively low smell threshold values and potential environmental persistence of organic sulfur products yielded by the reaction of 1,3-D and HS-, the effects of reduced sulfide species should be considered in the development of alternative fumigation practices, especially in the integrated application of sulfur-containing fertilizers.

  5. Transformation of cefazolin during chlorination process: Products, mechanism and genotoxicity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Li, Liping, E-mail: lisaleercees807@yahoo.cn; Wei, Dongbin, E-mail: weidb@rcees.ac.cn; Wei, Guohua, E-mail: wgh@rcees.ac.cn; Du, Yuguo, E-mail: duyuguo@rcees.ac.cn

    2013-11-15

    Highlights: • Base-catalyzed electrophilic substitution occurred in cefazolin chlorination. • Oxidation of thioether in cefazolin was found in chlorination process. • The pH conditions impacted on the occurrence of reaction types. • Genotoxicity had an elevation after chlorination of cefazolin. • Reaction pathways of cefazolin chlorination were replayed in surface water matrix. -- Abstract: Large quantities of cephalosporins have entered into aquatic environment in recent years, posing potential adverse effect to human health and ecological safety. In this study, cefazolin, one of widely used cephalosporins, was targeted to explore its transformation behaviors in chlorination disinfection process. With the help of ultra high performance liquid chromatography and high resolution mass spectroscopy, one chlorinated product and four oxidation products were detected in cefazolin chlorination system. The corresponding transformation pathways of cefazolin were proposed. Two kinds of reactions occurred in chlorination system, one was oxidation of thioether-sulfur to sulfoxide and di-sulfoxide, and the other was base-catalyzed electrophilic substitution of alpha-H of amide by chlorine atom. The pH value determined the occurrence of reaction types, and increasing chlorine dose promoted transformation of cefazolin. More importantly, genotoxicity in SOS/umu assay had an elevation after chlorination, which might be attributed to the formation of chlorinated product and sulfoxide during chlorination process.

  6. Transformation of cefazolin during chlorination process: Products, mechanism and genotoxicity assessment

    International Nuclear Information System (INIS)

    Li, Liping; Wei, Dongbin; Wei, Guohua; Du, Yuguo

    2013-01-01

    Highlights: • Base-catalyzed electrophilic substitution occurred in cefazolin chlorination. • Oxidation of thioether in cefazolin was found in chlorination process. • The pH conditions impacted on the occurrence of reaction types. • Genotoxicity had an elevation after chlorination of cefazolin. • Reaction pathways of cefazolin chlorination were replayed in surface water matrix. -- Abstract: Large quantities of cephalosporins have entered into aquatic environment in recent years, posing potential adverse effect to human health and ecological safety. In this study, cefazolin, one of widely used cephalosporins, was targeted to explore its transformation behaviors in chlorination disinfection process. With the help of ultra high performance liquid chromatography and high resolution mass spectroscopy, one chlorinated product and four oxidation products were detected in cefazolin chlorination system. The corresponding transformation pathways of cefazolin were proposed. Two kinds of reactions occurred in chlorination system, one was oxidation of thioether-sulfur to sulfoxide and di-sulfoxide, and the other was base-catalyzed electrophilic substitution of alpha-H of amide by chlorine atom. The pH value determined the occurrence of reaction types, and increasing chlorine dose promoted transformation of cefazolin. More importantly, genotoxicity in SOS/umu assay had an elevation after chlorination, which might be attributed to the formation of chlorinated product and sulfoxide during chlorination process

  7. Communication: Remarkable electrophilicity of the oxalic acid monomer: An anion photoelectron spectroscopy and theoretical study

    International Nuclear Information System (INIS)

    Buonaugurio, Angela; Graham, Jacob; Buytendyk, Allyson; Bowen, Kit H.; Ryder, Matthew R.; Gutowski, Maciej; Keolopile, Zibo G.; Haranczyk, Maciej

    2014-01-01

    Our experimental and computational results demonstrate an unusual electrophilicity of oxalic acid, the simplest dicarboxylic acid. The monomer is characterized by an adiabatic electron affinity and electron vertical detachment energy of 0.72 and 1.08 eV (±0.05 eV), respectively. The electrophilicity results primarily from the bonding carbon-carbon interaction in the singly occupied molecular orbital of the anion, but it is further enhanced by intramolecular hydrogen bonds. The well-resolved structure in the photoelectron spectrum is reproduced theoretically, based on Franck-Condon factors for the vibronic anion → neutral transitions

  8. Kinetic Study on Nucleophilic Substitution Reactions of 4-Chloro-2-nitrophenyl X-Substituted-benzoates with Cyclic Secondary Amines: Effect of Substituent X on Reactivity and Reaction Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Seong Hoon; Kim, Hyun Soo; Han, Young Joon [Sejong Science High School, Seoul (Korea, Republic of); Kim, Minyoung; Um, Ikhwan [Ewha Woman' s Univ., Seoul (Korea, Republic of)

    2013-10-15

    Second-order rate constants (k{sub N}) have been measured spectrophotometrically for the reactions of 4-chloro-2-nitrophenyl X-substituted-benzoates (1a-1h) with a series of cyclic secondary amines in 80 mol % H{sub 2}O/20 mol % DMSO at 25.0 ± 0.1 .deg. C. The Hammett plot for the reactions of 1a-1h with piperidine consists of two intersecting straight lines, while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ{sub X} = 1.25 and r = 0.58, indicating that the nonlinear Hammett plot is not due to a change in the rate-determining step (RDS) but is caused by ground-state stabilization through resonance interactions for substrates possessing an electron-withdrawing group in the benzoyl moiety. The Brφnsted-type plot for the reactions of 4-chloro-2-nitrophenyl benzoate (1d) with a series of cyclic secondary amines curves downward with β{sub 2} = 0.85, β{sub 1} = 0.24, and pK{sub a}{sup o} = 10.5, implying that a change in RDS occurs from the k{sub 2} step to the k{sub 1} process as the pK{sub a} of the conjugate acid of the amine exceeds 10.5. Dissection of k{sub N} into the microscopic rate constants k{sub 1} and k{sub 2}/k{sub -1} ratio associated with the reaction of 1d reveals that k{sub 2} is dependent on the amine basicity, which is contrary to generally held views.

  9. Synthesis of Novel Benzimidazolyl-substituted Acrylonitriles and Amidino-substituted Benzimidazo[1,2-a]Quinolines

    Directory of Open Access Journals (Sweden)

    Grace Karminski-Zamola

    2006-08-01

    Full Text Available A series of novel benzimidazole derivatives 3-10 were synthesized. Benzimidazolyl-substituted acrylonitriles 3 and 4 underwent a photochemical dehydrocyclization reaction to give the corresponding mono- and dicyano-substituted benzimidazo[1,2-a] quinolines 5 and 6. Pinner reaction of these compounds did not give the expected mono- and diamidines, but rather only compounds 7-10, with amido groups at 6-position were isolated. A mechanism for the reaction is proposed. Acyclic compounds 3 and 4, as well as cyclic benzimidazo[1,2-a]quinolines 5-8, exhibit interesting spectroscopic properties and are potential biologically active compounds.

  10. Arene-mercury complexes stabilized by gallium chloride: relative rates of H/D and arene exchange.

    Science.gov (United States)

    Branch, Catherine S; Barron, Andrew R

    2002-11-27

    We have previously proposed that the Hg(arene)(2)(GaCl(4))(2) catalyzed H/D exchange reaction of C(6)D(6) with arenes occurs via an electrophilic aromatic substitution reaction in which the coordinated arene protonates the C(6)D(6). To investigate this mechanism, the kinetics of the Hg(C(6)H(5)Me)(2)(GaCl(4))(2) catalyzed H/D exchange reaction of C(6)D(6) with naphthalene has been studied. Separate second-order rate constants were determined for the 1- and 2-positions on naphthalene; that is, the initial rate of H/D exchange = k(1i)[Hg][C-H(1)] + k(2i)[Hg][C-H(2)]. The ratio of k(1i)/k(2i) ranges from 11 to 2.5 over the temperature range studied, commensurate with the proposed electrophilic aromatic substitution reaction. Observation of the reactions over an extended time period shows that the rates change with time, until they again reach a new and constant second-order kinetics regime. The overall form of the rate equation is unchanged: final rate = k(1f)[Hg][C-H(1)] + k(2f)[Hg][C-H(2)]. This change in the H/D exchange is accompanied by ligand exchange between Hg(C(6)D(6))(2)(GaCl(4))(2) and naphthalene to give Hg(C(10)H(8))(2)(GaCl(4))(2,) that has been characterized by (13)C CPMAS NMR and UV-visible spectroscopy. The activation parameters for the ligand exchange may be determined and are indicative of a dissociative reaction and are consistent with our previously calculated bond dissociation for Hg(C(6)H(6))(2)(AlCl(4))(2). The initial Hg(arene)(2)(GaCl(4))(2) catalyzed reaction of naphthalene with C(6)D(6) involves the deuteration of naphthalene by coordinated C(6)D(6); however, as ligand exchange progresses, the pathway for H/D exchange changes to where the protonation of C(6)D(6) by coordinated naphthalene dominates. The site selectivity for the H/D exchange is initially due to the electrophilic aromatic substitution of naphthalene. As ligand exchange occurs, this selectivity is controlled by the activation of the naphthalene C-H bonds by mercury.

  11. Aggregation and Cooperative Effects in the Aldol Reactions of Lithium Enolates

    NARCIS (Netherlands)

    Larrañaga, O.; de Cózar, A.; Bickelhaupt, F.M.; Zangi, R.; Cossío, F.P.

    2013-01-01

    Density functional theory and Car-Parrinello molecular dynamics simulations have been carried out for model aldol reactions involving aggregates of lithium enolates derived from acetaldehyde and acetone. Formaldehyde and acetone have been used as electrophiles. It is found that the geometries of the

  12. Study of substitution reactions of ligands in VO2+ complexes in toluene solutions by ESR method

    International Nuclear Information System (INIS)

    Lundkvist, R.; Panfilov, A.T.; Kalinichenko, N.B.; Marov, I.N.; AN SSSR, Moscow. Inst. Geokhimii i Analiticheskoj Khimii)

    1976-01-01

    Kinetics and equilibrium of stepwise substitution of ligands have been investigated at different temperatures for the complexes of oxovanadium (4) with salicylaldoxime, 8-oxyquinoline, acetylacetone, benzoylacetone, and tenoyltrifluoroacetone. The relative complexability of these ligands in toluene has been studied. The parameters of spin-Hamiltonian of EPR spectra of the VO 2+ complexes have been determined. The equilibrium constants, the rate constants, and activation energy have been found for the substitution reactions of ligands in the complexes VOA 2 : VOA 2 +HB=VOAB+HA; VOAB+HB=VOB 2 +HA, where HA and HB are the ligands with different donor atoms. The mixed complexes have been detected of the general formula VOAB, where HA is salicylaldoxime or 8-oxyquinoline and HB is β-diketone

  13. Synthesis of deuterium-labeled analogs of the lipid hydroperoxide-derived bifunctional electrophile 4-oxo-2(E)-nonenal

    OpenAIRE

    Arora, Jasbir S.; Oe, Tomoyuki; Blair, Ian A.

    2011-01-01

    Lipid hydroperoxides undergo homolytic decomposition into the bifunctional 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal (ONE). These bifunctional electrophiles are highly reactive and can readily modify intracellular molecules including glutathione (GSH), deoxyribonucleic acid (DNA) and proteins. Lipid hydroperoxide-derived bifunctional electrophiles are thought to contribute to the pathogenesis of a number of diseases. ONE is an α,β-unsaturated aldehyde that can react in multiple ways and w...

  14. Asymmetric Diels-Alder Reaction of α-Substituted and β,β-Disubstituted α,β-Enals via Diarylprolinol Silyl Ether for the Construction of All-Carbon Quaternary Stereocenters.

    Science.gov (United States)

    Hayashi, Yujiro; Bondzic, Bojan P; Yamazaki, Tatsuya; Gupta, Yogesh; Ogasawara, Shin; Taniguchi, Tohru; Monde, Kenji

    2016-10-24

    The asymmetric Diels-Alder reaction of α-substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl-substituted diarylprolinol silyl ether to afford the exo-isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels-Alder reaction of a β,β-disubstituted α,β-unsaturated aldehyde, good exo-selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all-carbon quaternary stereocenters are constructed enantioselectively. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The Reaction of Oxy Hemoglobin with Nitrite: Mechanism, Antioxidant-Modulated Effect, and Implications for Blood Substitute Evaluation

    Directory of Open Access Journals (Sweden)

    Denisa Hathazi

    2018-02-01

    Full Text Available The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb, an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high-valent ferryl form, was demonstrated in stopped-flow experiments. Reported here are the stopped flow spectra recorded upon mixing oxy Hb (native, as well as chemically-derivatized in the form of several candidates of blood substitutes with a supraphysiological concentration of nitrite. The data may be fitted to a simple kinetic model involving a transient met-aqua form, in contrast to the ferryl detected in the case of Mb in a similar reaction sequence. These data are in line with a previous observation of a transient accumulation of ferryl Hb under auto-catalytic conditions at much lower concentrations of nitrite (Grubina, R. et al. J. Biol. Chem. 2007, 282, 12916. The simple model for fitting the stopped-flow data leaves a small part of the absorbance changes unaccounted for, unless a fourth species is invoked displaying features similar to the oxy and tentatively assigned as ferrous-peroxynitrate. Density functional theory (DFT calculations support this latter assignment. The reaction allows for differentiating between the reactivities of various chemically modified hemoglobins, including candidates for blood substitutes. Polymerization of hemoglobin slows the nitrite-induced oxidation, in sharp contrast to oxidative-stress type reactions which are generally accelerated, not inhibited. Sheep hemoglobin is found to be distinctly more resistant to reaction with nitrite compared to bovine Hb, at large nitrite concentrations (stopped-flow experiments directly observing the oxy + nitrite reaction as well as under auto-catalytic conditions. Copolymerization of Hb with bovine serum albumin (BSA using glutaraldehyde leads to a distinct increase of the lag time

  16. Fragmentation pathways of O-alkyl methylphosphonothionocyanidates in the gas phase: toward unambiguous structural characterization of chemicals in the Chemical Weapons Convention framework.

    Science.gov (United States)

    Saeidian, Hamid; Babri, Mehran; Ashrafi, Davood; Sarabadani, Mansour; Naseri, Mohammad Taghi

    2013-08-01

    The electron-impact (EI) mass spectra of a series of O-alkyl methylphosphonothionocyanidates were studied for Chemical Weapons Convention (CWC) purposes. General EI fragmentation pathways were constructed and discussed, and collision-induced dissociation studies of the major EI ions were performed to confirm proposed fragment structures by analyzing fragment ions of deuterated analogs and by use of density functional theory (DFT) calculations. Thiono-thiolo rearrangement, McLafferty-type rearrangement, and a previously unknown intramolecular electrophilic aromatic substitution reaction were observed and confirmed. The study also focused on differentiation of isomeric compounds. Retention indices for all compounds, and an electrophilicity index for several compounds, are reported and interpreted.

  17. Modeling competitive substitution in a polyelectrolyte complex

    International Nuclear Information System (INIS)

    Peng, B.; Muthukumar, M.

    2015-01-01

    We have simulated the invasion of a polyelectrolyte complex made of a polycation chain and a polyanion chain, by another longer polyanion chain, using the coarse-grained united atom model for the chains and the Langevin dynamics methodology. Our simulations reveal many intricate details of the substitution reaction in terms of conformational changes of the chains and competition between the invading chain and the chain being displaced for the common complementary chain. We show that the invading chain is required to be sufficiently longer than the chain being displaced for effecting the substitution. Yet, having the invading chain to be longer than a certain threshold value does not reduce the substitution time much further. While most of the simulations were carried out in salt-free conditions, we show that presence of salt facilitates the substitution reaction and reduces the substitution time. Analysis of our data shows that the dominant driving force for the substitution process involving polyelectrolytes lies in the release of counterions during the substitution

  18. Synthesis of 2,6-trans- and 3,3,6-trisubstituted tetrahydropyran-4-ones from Maitland-Japp derived 2H-dihydropyran-4-ones: a total synthesis of diospongin B.

    Science.gov (United States)

    Clarke, Paul A; Nasir, Nadiah Mad; Sellars, Philip B; Peter, Alejandra M; Lawson, Connor A; Burroughs, James L

    2016-07-12

    6-Substituted-2H-dihydropyran-4-one products of the Maitland-Japp reaction have been converted into tetrahydropyrans containing uncommon substitution patterns. Treatment of 6-substituted-2H-dihydropyran-4-ones with carbon nucleophiles led to the formation of tetrahydropyran rings with the 2,6-trans-stereochemical arrangement. Reaction of the same 6-substituted-2H-dihydropyran-4-ones with l-Selectride led to the formation of 3,6-disubstituted tetrahydropyran rings, while trapping of the intermediate enolate with carbon electrophiles in turn led to the formation 3,3,6-trisubstituted tetrahydropyran rings. The relative stereochemical configuration of the new substituents was controlled by the stereoelectronic preference for pseudo-axial addition of the nucleophile and trapping of the enolate from the opposite face. Application of these methods led to a synthesis of the potent anti-osteoporotic diarylheptanoid natural product diospongin B.

  19. Synthesis and Biological Activity of Some 3, 5-Diarylisoxazoline Derivatives: Reaction of Substituted Chalcones with Hydroxylamine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Vandana Sharma

    2010-01-01

    Full Text Available A series of 3-aryl-5-styrylisoxazoline/ 3,5-diarylisoxazoline derivatives were synthesized by the reaction of appropriately substituted chalcones and hydroxylamine hydrochloride in presence of alkali in ethanol. The synthesized heterocycles have been characterized on the basis of their chemical properties and spectroscopic data. These compounds were tested for biological activity against a variety of test organisms

  20. Hepatic stellate cells lack AP-1 responsiveness to electrophiles and phorbol 12-myristate-13-acetate

    International Nuclear Information System (INIS)

    Reichard, John F.; Petersen, Dennis R.

    2004-01-01

    Stellate cell profibrotic gene induction and transdifferentiation are central events in liver fibrosis. Oxidative stress has been implicated as an activator of the transcription factors Nrf2 and AP-1 through shared kinase signaling pathways that also purportedly contribute to stellate cell activation. The present study examined the role of oxidative stress in ARE- and TRE-regulated gene induction in isolated hepatic stellate cells. Using a portion of the human Nqo1 promoter consisting of an ARE imbedded TRE, it was demonstrated that while the ARE was responsible for mediating inducible gene expression in response to the electrophiles 4-HNE and tBHQ, the TRE was refractory to induction by either electrophiles or PMA. It was demonstrated that stellate cells possess nuclear TRE-binding proteins that were identified as JunB, JunD, Fra1, and Fra2, which were unaffected by either electrophiles or PMA treatment. This report demonstrates that, in contrast to the ARE, the TRE and its binding cognate AP-1 did not mediate independent gene induction in hepatic stellate cells. This observation is significant given the presumed importance attributed to AP-1 in mediating profibrogenic gene expression

  1. A green Hunsdiecker reaction of cinnamic acids

    Energy Technology Data Exchange (ETDEWEB)

    Sodre, Leonardo R.; Esteves, Pierre M.; Mattos, Marcio C. S. de, E-mail: pesteves@iq.ufrj.br, E-mail: mmattos@iq.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Quimica. Departamento de Quimica

    2013-02-15

    Tribromo- and trichloroisocyanuric acids react with cinnamic acids in NaOH/H{sub 2}O/Et{sub 2}O at room temperature to produce (E)-2-halostyrenes regioselectively in 25-95% yield. Mechanism studies using Hammett correlations and DFT (density functional theory) calculations have shown that this reaction has as rate determining step the electrophilic addition of chlorine atom to the double bond. (author)

  2. Exploring the anionic reactivity of ynimines, useful precursors of metalated ketenimines.

    Science.gov (United States)

    Laouiti, Anouar; Couty, François; Marrot, Jérome; Boubaker, Taoufik; Rammah, Mohamed M; Rammah, Mohamed B; Evano, Gwilherm

    2014-04-18

    Insights into the reactivity of ynimines under anionic conditions are reported. They were shown to be excellent precursors of metalated ketenimines, which can be generated in situ by the reaction of ynimines with organolithium reagents or strong bases. The metalated ketenimines can then be trapped with various electrophiles and, depending on their substitution pattern, afford original and divergent entries to various building blocks.

  3. Transition-Metal-Catalyzed Decarbonylative Coupling Reactions: Concepts, Classifications, and Applications

    KAUST Repository

    Guo, Lin; Rueping, Magnus

    2018-01-01

    Transition metal‐catalyzed decarbonylative coupling reactions have emerged as a powerful alternative to conventional cross‐coupling protocols due to the advantages associated with the use of carbonyl‐containing functionalities as coupling electrophiles instead of commonly used organohalides or sulfates. A wide variety of novel transformations based on this concept have been successfully achieved, including decarbonylative carbon–carbon and carbon–heteroatom bond forming reactions. In this Review, we summarize the recent progress in this field and present a comprehensive overview of metal‐catalyzed decarbonylative coupling reactions with carbonyl derivatives.

  4. Transition-Metal-Catalyzed Decarbonylative Coupling Reactions: Concepts, Classifications, and Applications

    KAUST Repository

    Guo, Lin

    2018-05-14

    Transition metal‐catalyzed decarbonylative coupling reactions have emerged as a powerful alternative to conventional cross‐coupling protocols due to the advantages associated with the use of carbonyl‐containing functionalities as coupling electrophiles instead of commonly used organohalides or sulfates. A wide variety of novel transformations based on this concept have been successfully achieved, including decarbonylative carbon–carbon and carbon–heteroatom bond forming reactions. In this Review, we summarize the recent progress in this field and present a comprehensive overview of metal‐catalyzed decarbonylative coupling reactions with carbonyl derivatives.

  5. Electrophilic dark matter with dark photon: From DAMPE to direct detection

    Science.gov (United States)

    Gu, Pei-Hong; He, Xiao-Gang

    2018-03-01

    The electron-positron excess reported by the DAMPE collaboration recently may be explained by an electrophilic dark matter (DM). A standard model singlet fermion may play the role of such a DM when it is stabilized by some symmetries, such as a dark U(1)X gauge symmetry, and dominantly annihilates into the electron-positron pairs through the exchange of a scalar mediator. The model, with appropriate Yukawa couplings, can well interpret the DAMPE excess. Naively one expects that in this type of models the DM-nucleon cross section should be small since there is no tree-level DM-quark interactions. We however find that at one-loop level, a testable DM-nucleon cross section can be induced for providing ways to test the electrophilic model. We also find that a U (1) kinetic mixing can generate a sizable DM-nucleon cross section although the U(1)X dark photon only has a negligible contribution to the DM annihilation. Depending on the signs of the mixing parameter, the dark photon can enhance/reduce the one-loop induced DM-nucleon cross section.

  6. Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

    Directory of Open Access Journals (Sweden)

    Pierre Vogel

    2016-08-01

    Full Text Available Catalysis fulfills the promise that high-yielding chemical transformations will require little energy and produce no toxic waste. This message is carried by the study of the evolution of molecular catalysis of some of the most important reactions in organic chemistry. After reviewing the conceptual underpinnings of catalysis, we discuss the applications of different catalysts according to the mechanism of the reactions that they catalyze, including acyl group transfers, nucleophilic additions and substitutions, and C–C bond forming reactions that employ umpolung by nucleophilic additions to C=O and C=C double bonds. We highlight the utility of a broad range of organocatalysts other than compounds based on proline, the cinchona alkaloids and binaphthyls, which have been abundantly reviewed elsewhere. The focus is on organocatalysts, although a few examples employing metal complexes and enzymes are also included due to their significance. Classical Brønsted acids have evolved into electrophilic hands, the fingers of which are hydrogen donors (like enzymes or other electrophilic moieties. Classical Lewis base catalysts have evolved into tridimensional, chiral nucleophiles that are N- (e.g., tertiary amines, P- (e.g., tertiary phosphines and C-nucleophiles (e.g., N-heterocyclic carbenes. Many efficient organocatalysts bear electrophilic and nucleophilic moieties that interact simultaneously or not with both the electrophilic and nucleophilic reactants. A detailed understanding of the reaction mechanisms permits the design of better catalysts. Their construction represents a molecular science in itself, suggesting that sooner or later chemists will not only imitate Nature but be able to catalyze a much wider range of reactions with high chemo-, regio-, stereo- and enantioselectivity. Man-made organocatalysts are much smaller, cheaper and more stable than enzymes.

  7. Carbolanthanation of substituted alkynes

    International Nuclear Information System (INIS)

    Kalinin, V.N.; Kazimirchuk, E.I.; Vitt, S.V.; Khandozhko, V.N.; Beletskaya, I.P.

    1993-01-01

    Using the reaction between CH 3 YbI and substituted alkynes as an example, agents can enter into carbolanthanation reaction via transfer of a methyl group to carbon atom of acetylene bond with the production of a new olefin carbanion. 5 refs.; 1 fig.; 3 tabs

  8. Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation.

    Science.gov (United States)

    Mathers, Alicia R; Carey, Cara D; Killeen, Meaghan E; Salvatore, Sonia R; Ferris, Laura K; Freeman, Bruce A; Schopfer, Francisco J; Falo, Louis D

    2018-02-01

    Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO 2 ), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the growing use of fatty acids in topical formulations, we sought to further study the effect of nitro-fatty acids on cutaneous inflammation. To accomplish this, the effect of topically applied OA-NO 2 on skin inflammation was evaluated using established murine models of contact hypersensitivity (CHS). In contrast to the effects of subcutaneously injected OA-NO 2 , topical OA-NO 2 potentiated hapten-dependent inflammation inducing a sustained neutrophil-dependent inflammatory response characterized by psoriasiform histological features, increased angiogenesis, and an inflammatory infiltrate that included neutrophils, inflammatory monocytes, and γδ T cells. Consistent with these results, HPLC-MS/MS analysis of skin from psoriasis patients displayed a 56% increase in nitro-conjugated linoleic acid (CLA-NO 2 ) levels in lesional skin compared to non-lesional skin. These results suggest that nitro-fatty acids in the skin microenvironment are products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. On the Catalytic Effect of Water in the Intramolecular Diels–Alder Reaction of Quinone Systems: A Theoretical Study

    Directory of Open Access Journals (Sweden)

    Renato Contreras

    2012-11-01

    Full Text Available The mechanism of the intramolecular Diels–Alder (IMDA reaction of benzoquinone 1, in the absence and in the presence of three water molecules, 1w, has been studied by means of density functional theory (DFT methods, using the M05-2X and B3LYP functionals for exploration of the potential energy surface (PES. The energy and geometrical results obtained are complemented with a population analysis using the NBO method, and an analysis based on the global, local and group electrophilicity and nucleophilicity indices. Both implicit and explicit solvation emphasize the increase of the polarity of the reaction and the reduction of activation free energies associated with the transition states (TSs of this IMDA process. These results are reinforced by the analysis of the reactivity indices derived from the conceptual DFT, which show that the increase of the electrophilicity of the quinone framework by the hydrogen-bond formation correctly explains the high polar character of this intramolecular process. Large polarization at the TSs promoted by hydrogen-bonds and implicit solvation by water together with a high electrophilicity-nucleophilicity difference consistently explains the catalytic effects of water molecules.

  10. The labelling of 2-oxoquazepam with electrophilic 18F

    International Nuclear Information System (INIS)

    Duelfer, T.; Johnstroem, P.; Stone-Elander, S.

    1991-01-01

    2-Oxoquazepam, 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzo-diazepine-2-one, is a benzodiazepine agonist. It has been shown to bind in vitro with a higher affinity to benzodiazepine type 1 receptors than to type 2 receptors. Here we report the synthesis of a trimethylin precursor and demonstrate the feasibility of using it for radiolabelling acid- and base-sensitive benzodiazepine structures such as 2-oxoquazepam. Conversions of the electrophilic fluorine to [ 18 F]-2-oxoquazepam on the order 20-25% were obtained. (author)

  11. Organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds

    International Nuclear Information System (INIS)

    Maltsev, O V; Beletskaya, Irina P; Zlotin, Sergei G

    2011-01-01

    Recent applications of organocatalytic Michael and Friedel–Crafts reactions in enantioselective synthesis of biologically active compounds: natural products, pharmaceutical agents and plant protection agents are reviewed. The key mechanisms of stereoinduction, types of organocatalysts and reagents used in these reactions are considered. The material is classified according to the type of newly formed bonds incorporating the asymmetric carbon atom, and the information for the most numerous C–C coupling reactions is systematized according to the natures of the electrophile and the nucleophile. The bibliography includes 433 references.

  12. N-BUTYL SUBSTITUTED N-HETEROCYCLIC CARBENE-PD(II-PYRIDINE (PEPPSI COMPLEXES: SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY IN THE SUZUKI-MIYAURA REACTION

    Directory of Open Access Journals (Sweden)

    Rukiye Fırıncı

    2016-08-01

    Full Text Available A series of N-butyl substituted imidazolium salts, (1a-c and their pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI themed palladium N-heterocyclic carbene complexes (2a-c were synthesized and characterized. Pd-NHC complexes were fully determined by elemental analysis and spectroscopic. The synthesized complexes were tested in Suzuki-Miyaura cross-coupling reaction. These complexes were found to be efficient catalysts for the Suzuki-Miyaura reaction of phenylboronic acid with aryl bromides.

  13. Finite temperature grand canonical ensemble study of the minimum electrophilicity principle.

    Science.gov (United States)

    Miranda-Quintana, Ramón Alain; Chattaraj, Pratim K; Ayers, Paul W

    2017-09-28

    We analyze the minimum electrophilicity principle of conceptual density functional theory using the framework of the finite temperature grand canonical ensemble. We provide support for this principle, both for the cases of systems evolving from a non-equilibrium to an equilibrium state and for the change from one equilibrium state to another. In doing so, we clearly delineate the cases where this principle can, or cannot, be used.

  14. Substituent and structural effects on the kinetics of the reaction of N-(substituted phenylmethylene-m- and -p-aminobenzoic acids with diazodiphenylmethane

    Directory of Open Access Journals (Sweden)

    BRATISLAV Z. JOVANOVIC

    2007-12-01

    Full Text Available The rate constants for the reaction of twenty-two N-(substituted phenyl methylene-m- and -p-aminobenzoic acids with diazodiphenylmethane were determined in absolute ethanol at 30 °C. The effects of substituents on the reactivity of the investigated compounds were interpreted by correlation of the rate constants with LFER equations. The results of quantum mechanical calculations of the mole cular structure together with experimental results gave a better insight into the effects of structure on the transmission of electronic effects of the substituents. New σ constants for substituted benzylideneamino group were calculated.

  15. Regioselective aromatic substitution reactions of cyclometalated Ir(III) complexes: synthesis and photochemical properties of substituted Ir(III) complexes that exhibit blue, green, and red color luminescence emission.

    Science.gov (United States)

    Aoki, Shin; Matsuo, Yasuki; Ogura, Shiori; Ohwada, Hiroki; Hisamatsu, Yosuke; Moromizato, Shinsuke; Shiro, Motoo; Kitamura, Masanori

    2011-02-07

    In this manuscript, the regioselective halogenation, nitration, formylation, and acylation of Ir(tpy)(3) and Ir(ppy)(3) (tpy = 2-(4'-tolyl)pyridine and ppy = 2-phenylpyridine) and the subsequent conversions are described. During attempted bromination of the three methyl groups in fac-Ir(tpy)(3) using N-bromosuccinimide (NBS) and benzoyl peroxide (BPO), three protons at the 5'-position (p-position with respect to the C-Ir bond) of phenyl rings in tpy units were substituted by Br, as confirmed by (1)H NMR spectra, mass spectra, and X-ray crystal structure analysis. It is suggested that such substitution reactions of Ir complexes proceed via an ionic mechanism rather than a radical mechanism. UV-vis and luminescence spectra of the substituted Ir(III) complexes are reported. The introduction of electron-withdrawing groups such as CN and CHO groups at the 5'-position of tpy induces a blue shift of luminescence emission to about 480 nm, and the introduction of electron-donating groups such as an amino group results in a red shift to about 600 nm. A reversible change of emission for the 5'-amino derivative of Ir(tpy)(3), Ir(atpy)(3), between red and green occurs upon protonation and deprotonation.

  16. High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1980-February 14, 1981

    International Nuclear Information System (INIS)

    1981-02-01

    The stereochemistry of high energy 18 F, /sup 34m/Cl, and 76 Br substitution reactions involving enantiomeric molecules in the gas and condensed phase is studied. The gas to condensed state transition in halogen high energy chemistry, involving chlorine, bromine, and iodine activated by the (n,γ) and (I.T.) processes in halomethanes, saturated and unsaturated hydrocarbons is being investigated in more detail. Special attention is given to defining the nature of the enhancement yields in the condensed phase. High energy halogen reactions in liquid and frozen aqueous solutions of organic and biomolecular solutes are studied in an attempt to learn more about these reactions. The applications of high energy chemistry techniques and theory to neutron activation analysis of biological systems are being continued. Special attention is given to developing procedures for trace molecular determinations in biological systems. The applications of hot halogen atoms as indicators of solute-solute interactions in liquid and frozen aqueous solutions of halogenated bases and nucleosides are being developed. Experiments are designed to explain the mechanisms of the radioprotection offered biomolecular solutes trapped within the frozen ice lattice. Reactions of bromine and iodine activated by isomeric transition with halogenated biomolecular solutes in liquid and frozen aqueous solutions are studied. The high energy reactions of iodine with the isomers of pentene have been studied in low pressure gaseous systems employing additives and rare gas moderators and liquid systems. Reactivity of excited complex formation and structural effects of electrophilic iodine attack on the pi-bond systems are studied

  17. High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1980-February 14, 1981

    Energy Technology Data Exchange (ETDEWEB)

    1981-02-01

    The stereochemistry of high energy /sup 18/F, /sup 34m/Cl, and /sup 76/Br substitution reactions involving enantiomeric molecules in the gas and condensed phase is studied. The gas to condensed state transition in halogen high energy chemistry, involving chlorine, bromine, and iodine activated by the (n,..gamma..) and (I.T.) processes in halomethanes, saturated and unsaturated hydrocarbons is being investigated in more detail. Special attention is given to defining the nature of the enhancement yields in the condensed phase. High energy halogen reactions in liquid and frozen aqueous solutions of organic and biomolecular solutes are studied in an attempt to learn more about these reactions. The applications of high energy chemistry techniques and theory to neutron activation analysis of biological systems are being continued. Special attention is given to developing procedures for trace molecular determinations in biological systems. The applications of hot halogen atoms as indicators of solute-solute interactions in liquid and frozen aqueous solutions of halogenated bases and nucleosides are being developed. Experiments are designed to explain the mechanisms of the radioprotection offered biomolecular solutes trapped within the frozen ice lattice. Reactions of bromine and iodine activated by isomeric transition with halogenated biomolecular solutes in liquid and frozen aqueous solutions are studied. The high energy reactions of iodine with the isomers of pentene have been studied in low pressure gaseous systems employing additives and rare gas moderators and liquid systems. Reactivity of excited complex formation and structural effects of electrophilic iodine attack on the pi-bond systems are studied.

  18. An efficient method for synthesis of bis(indolylmethane and di-bis(indolylmethane derivatives in environmentally benign conditions using TBAHS

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Siyadatifard

    2016-05-01

    Full Text Available An efficient procedure for the synthesis of bisindolylmethanes (BIMs from condensation of indole and aromatic aldehydes or ketones is described. The aromatic electrophilic substitution reactions of indole with aromatic aldehydes and ketones are achieved in the presence of tetrabutylammonium hydrogen sulfate (TBAHS as a mild and efficient solid acid catalyst. This methodology offers several advantages such as good yields, simple procedure, mild and environmentally benign conditions.

  19. Stereoselective synthesis of organosulfur compounds incorporating N-aromatic heterocyclic motifs and quaternary carbon centers via a sulfa-Michael triggered tandem reaction.

    Science.gov (United States)

    Qin, Tianyou; Cheng, Lu; Zhang, Sean Xiao-An; Liao, Weiwei

    2015-06-14

    A novel sulfa-Michael addition (SMA)-triggered tandem reaction was developed by combining a SMA reaction with a simultaneous rearomatization process utilizing a less reactive carbonyl group as an intramolecular electrophile partner, which provided a unique synthetic route to access various organosulfur compounds incorporating an N-aromatic heterocyclic motif and quaternary carbon centers.

  20. Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers

    Science.gov (United States)

    Chipinda, Itai; Mbiya, Wilbes; Adigun, Risikat Ajibola; Morakinyo, Moshood K.; Law, Brandon F.; Simoyi, Reuben H.; Siegel, Paul D.

    2015-01-01

    Chemical allergens bind directly, or after metabolic or abiotic activation, to endogenous proteins to become allergenic. Assessment of this initial binding has been suggested as a target for development of assays to screen chemicals for their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based method for screening thiol reactive skin sensitizers, however, amine selective sensitizers are not detected by this assay. In the present study we describe an amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for identification of amine-selective and non-selective skin sensitizers. UV-Vis spectrophotometry and fluorescence were used to measure PDA reactivity for 57 chemicals including anhydrides, aldehydes, and quinones where reaction rates ranged from 116 to 6.2 × 10−6 M−1 s−1 for extreme to weak sensitizers, respectively. No reactivity towards PDA was observed with the thiol-selective sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated significantly with their respective murine local lymph node assay (LLNA) threshold EC3 values (R2 = 0.76). The use of PDA serves as a simple, inexpensive amine based method that shows promise as a preliminary screening tool for electrophilic, amine-selective skin sensitizers. PMID:24333919

  1. (4+2) Cycloaddition reactions with inverse electron demand of nitrogen bearing, heteroaromatic cations

    International Nuclear Information System (INIS)

    Ritzberger-Baumgartner, W.

    1996-06-01

    Three cationic, heteroaromatic diene-systems (1, 2, 3, 4-tetramethoxycarbonyl-quinolizinium-tetrafluoroborate (M), 8, 9, 10, 11-tetrarnethoxycarbonylpyrido[2,1-a]-isoquinolinium-TFB and triazolo[1,5-b]isoquinolinium-TFBs) and a cationic, non-aromatic diene (2,5,5-trimethyl-3-oxo-1, 2, 4-triazolium-TFB) were synthesized. The dienes were employed successfully in cycloaddition reactions with a number ofconjugated dienophiles (including norbornene). The mechanism underlying these cycloaddition reactions was discussed in the theoretical section. At first quantumchemical calculations of the frontier orbital energies provided the proof, that the reactions followed the pattern of reactions with inverse electron demand. Calculation of the charge distribution and of the orbital coefficients led to the conclusion, that these reactions are mainly orbital controlled. Two mechanistic variants were in discussion. Either the reactions proceed in a concerted manner resembling the Diels-Alder reaction with inverse electron demand or in two distinct steps with the formation of a cationic intermediate following the attack of the heterodienes acting as weak electrophiles at the dienophiles being weak nucleophiles. Calculations of a possible transition state of these cycloaddition reactions revealed a pronounced preference for the formation of the bond between the logical reaction centers in the first step of a two-step reaction. However, experimental and theoretical findings led to the conviction, that cationic polar cycloaddition reactions proceed exactly along the crossroad between a concerted and a two-step mechanism and depending on the electrophilic strength of the diene and the nucleophilic strength of the dienophile these reactions show more characteristics of one of the two mechanistic possibilities. The high regioselectivity as well as the high stereoselectivity could be explained satisfactory with the help of the calculated orbital coefficients. (author)

  2. The substitution reaction of (CNC)Fe-2N₂ with CO.

    Science.gov (United States)

    Liu, Hongyan; Liu, Shuangshuang; Zhang, Xiang

    2013-06-01

    The substitution mechanism of two N₂ ligands in (CNC)Fe-2N₂ replaced by CO was studied theoretically at the B3LYP/LACVP* level. Both SN1 and SN₂ mechanisms were considered. The calculated results for the gas phase suggested that: 1) in SN1 mechanism, N₂ elimination, which involves S₀-T₁ PESs crossing, is the rate control step for both substitution stages. The barrier heights are 9.7 kcal mol(-1) and 13.05 kcal mol(-1), respectively. 2) In SN2 mechanism, the calculated barrier heights on LS PES are respectively 13.7 and 19.83 kcal mol(-1) for the two substitution steps, but S₀-T₁ PESs crossing lowers the two barriers to 10.7 and 15.7 kcal mol(-1), respectively. 3) Inclusion of solvation effect of THF by PCM model, the relative energies of all the key species (including minima, transition states and S₀-T₁ crossing points) do not have great difference from their gas phase relative energies. Considering that for each substitution step, SN1 barrier heights is slightly smaller than SN2 barrier, SN1 mechanism seems to be slightly preferable to SN2 mechanism.

  3. Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

    Directory of Open Access Journals (Sweden)

    Grzegorz Mlostoń

    2016-04-01

    Full Text Available Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyldiazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. −40 °C to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioketones with (trimethylsilyldiazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.

  4. Synthesis of Randomly Substituted Anionic Cyclodextrins in Ball Milling

    Directory of Open Access Journals (Sweden)

    László Jicsinszky

    2017-03-01

    Full Text Available A number of influencing factors mean that the random substitution of cyclodextrins (CD in solution is difficult to reproduce. Reaction assembly in mechanochemistry reduces the number of these factors. However, lack of water can improve the reaction outcomes by minimizing the reagent’s hydrolysis. High-energy ball milling is an efficient, green and simple method for one-step reactions and usually reduces degradation and byproduct formation. Anionic CD derivatives have successfully been synthesized in the solid state, using a planetary ball mill. Comparison with solution reactions, the solvent-free conditions strongly reduced the reagent hydrolysis and resulted in products of higher degree of substitution (DS with more homogeneous DS distribution. The synthesis of anionic CD derivatives can be effectively performed under mechanochemical activation without significant changes to the substitution pattern but the DS distributions were considerably different from the products of solution syntheses.

  5. Te(II)/Te(IV) Mediated C-N Bond Formation on 2,5-Diphenyltellurophene and a Reassignment of the Product from the Reaction of PhI(OAc)2 with 2 TMS-OTf.

    Science.gov (United States)

    Aprile, Antonino; Iversen, Kalon J; Wilson, David J D; Dutton, Jason L

    2015-05-18

    We report a novel C-H to C-N bond metathesis at the 3-position of 1,2-diphenyltellurophene via oxidation of the Te(II) center to Te(IV) using the I(III) oxidant [PhI(4-DMAP)2](2+). Spontaneous reduction of a transient Te(IV) coordination compound to Te(II) generates an electrophilic equivalent of 4-DMAP that substitutes at a C-H bond at the 3-position of the tellurophene. Theoretical and synthetic reaction pathway studies confirm that a Te(IV) coordination complex with 4-DMAP is an intermediate. In the course of these pathway studies, it was also found that the identity of the I(III) oxidant generated from PhI(OAc)2 and 2 TMS-OTf is PhI(OAc)(OTf) and not PhI(OTf)2, as had been previously thought.

  6. X-ray structure determination of new monomers to establish their polymerizability: copolymerization of two tetrasubstituted electrophilic olefins with electron-rich styrenes giving polymers with an average 1.25 functional groups per chain carbon atom

    International Nuclear Information System (INIS)

    Hall, H.K. Jr.; Reineke, K.E.; Ried, J.H.; Sentman, R.C.; Miller, D.

    1982-01-01

    X-ray crystal structure determination for two tetrasubstituted electrophilic olefins, tetramethyl ethylenetetracarboxylate TMET and dimethyl dicyanofumarate DDCF, revealed two fundamentally different molecular structures. TMET is a nonplanar molecule that possesses two opposite ester groups planar and the others above and below the molecular plane. In contrast, DDCF is a molecule for which both ester groups lie in the plane of the double bond and nitrile groups. DDCF underwent thermal spontaneous copolymerization with electron-rich styrenes to give 1:1 alternating copolymers in moderate yields and molecular weights. These copolymers, which result from the first copolymerization of a tetrasubstituted olefin, possess an average functionality of 1.25 per chain carbon atom. Polymerization is made possible by low steric hindrance and the high delocalization in the propagating radical. The yields were limited by competing cycloaddition reaction. The corresponding diethyl ester also copolymerized, but not so well. Neither electrophilic olefin homopolymerized under γ-irradiation. TMET did not copolymerize at all when treated under identical conditions

  7. Kinetic study on S_NAr reactions of 1-(Y-Substituted-phenoxy)-2,4-dinitrobenzenes with azide ion: Effect of changing nucleophile from hydroxide to zzide ion on reaction mechanism and reactivity

    International Nuclear Information System (INIS)

    Seo, Hyeon Ok; Kim, Min Young; Han, So Yeop; Um, Ik Hwan

    2015-01-01

    Second-order rate constants (k_N_3_−) for SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes (2a–2h) with math formula in 80 mol % H_2O/20 mol % DMSO at 25.0 ± 0.1 °C have been measured spectrophotometrically. The Brønsted-type plot is linear with β"l"g = −0.38. The Hammett plots correlated with math formula and math formula constants exhibit highly scattered points. In contrast, the Yukawa–Tsuno plot results in an excellent linear correlation with ρ_Y = 1.02 and r = 0.51, indicating that a negative charge develops partially on the O atom of the leaving Y-substituted-phenoxy moiety in the transition state. Accordingly, the reactions have been concluded to proceed through a stepwise mechanism, in which expulsion of the leaving group occurs in the rate-determining step. Comparison of k_N_3_− with the k_O_H_− values reported previously for the corresponding reactions with OH"− has revealed that math formula is only 6- to 26-fold less reactive than OH"− toward substrates 2a–2h, although the former is over 11 pK_a units less basic than the latter. Solvation and polarizability effects have been suggested to be responsible for the unusual reactivity shown by math formula and OH"−. Effects of changing nucleophile from OH"− to N_3"− on reaction mechanism and reactivity are discussed in detail

  8. Chlorine-38 for chlorine substitution in geometric and diastereomeric compounds: mechanism and sterochemistry

    International Nuclear Information System (INIS)

    Acciani, T.R.

    1977-01-01

    In order to determine how solvents control the stereochemial course of the hot substitution reactions, the stereohemistry of the energetic 38 Cl for Cl was studied in diastereomeric 1,2-dichloro-1,2-difluoroethane and the geometric isomers of 1,2-dichlorohexafluorocyclobutane. In each system the conformer population was determined by NMR and dipole moment techniques. A comparison was made between the changes of the stereochemical course of the substitution reaction and the concentration and nature of the solvent. The results presented in this investigation indicate that the stereohemical course of a hot atom substitution reaction is directly controlled by solvents participating in the de-excitation stabilization of excited compounds or in the relaxation process of intermediate radicals. This work also indicates that the nature of the solvent cage wall can control the progress of the hot reaction. Abstraction reactions of the Cl can occur in the cage with the compounds composing the cage wall. These reactions can effectively change the stereochemical course of the hot substitution reaction. It appears that the liquid phase hot atom substitution reactions observed in this investigation are best explained by the caged radical-radical combination model. Strong solute-solvent interactions reduce the time for relaxation of the radicals in the solvent cage thus preventing the radicals from obtaining planarity and consequently retention products. On the other hand, weak solute-solvent interactions increase the time for relaxation of the intermediate which leads to a racemization of reaction products

  9. Catalytic hydrodeoxygenation of methyl-substituted phenols: correlations of kinetic parameters with molecular properties.

    Science.gov (United States)

    Massoth, F E; Politzer, P; Concha, M C; Murray, J S; Jakowski, J; Simons, Jack

    2006-07-27

    The hydrodeoxygenation of methyl-substituted phenols was carried out in a flow microreactor at 300 degrees C and 2.85 MPa hydrogen pressure over a sulfided CoMo/Al(2)O(3) catalyst. The primary reaction products were methyl-substituted benzene, cyclohexene, cyclohexane, and H(2)O. Analysis of the results suggests that two independent reaction paths are operative, one leading to aromatics and the other to partially or completely hydrogenated cyclohexanes. The reaction data were analyzed using Langmuir-Hinshelwood kinetics to extract the values of the reactant-to-catalyst adsorption constant and of the rate constants characterizing the two reaction paths. The adsorption constant was found to be the same for both reactions, suggesting that a single catalytic site center is operative in both reactions. Ab initio electronic structure calculations were used to evaluate the electrostatic potentials and valence orbital ionization potentials for all of the substituted phenol reactants. Correlations were observed between (a) the adsorption constant and the two reaction rate constants measured for various methyl-substitutions and (b) certain moments of the electrostatic potentials and certain orbitals' ionization potentials of the isolated phenol molecules. On the basis of these correlations to intrinsic reactant-molecule properties, a reaction mechanism is proposed for each pathway, and it is suggested that the dependencies of adsorption and reaction rates upon methyl-group substitution are a result of the substituents' effects on the electrostatic potential and orbitals rather than geometric (steric) effects.

  10. The effect of varying the anion of an ionic liquid on the solvent effects on a nucleophilic aromatic substitution reaction.

    Science.gov (United States)

    Hawker, Rebecca R; Haines, Ronald S; Harper, Jason B

    2018-05-09

    A variety of ionic liquids, each containing the same cation but a different anion, were examined as solvents for a nucleophilic aromatic substitution reaction. Varying the proportion of ionic liquid was found to increase the rate constant as the mole fraction of ionic liquid increased demonstrating that the reaction outcome could be controlled through varying the ionic liquid. The solvent effects were correlated with the hydrogen bond accepting ability (β) of the ionic liquid anion allowing for qualitative prediction of the effect of changing this component of the solute. To determine the microscopic origins of the solvent effects, activation parameters were determined through temperature-dependent kinetic analyses and shown to be consistent with previous studies. With the knowledge of the microscopic interactions in solution, an ionic liquid was rationally chosen to maximise rate enhancement demonstrating that an ionic solvent can be selected to control reaction outcome for this reaction type.

  11. Reactions of Fischer carbene complexes with Electron-deficient olefins: Scope and limitations of this route to donor-acceptor-substituted cyclopropanes

    Energy Technology Data Exchange (ETDEWEB)

    Wienand, A.; Reissig, H.U. (Inst. fuer Organische Chemie der Technischen Hochschule Darmstadt (West Germany))

    1990-12-01

    The Fischer carbene complex ((CO){sub 5}Cr{double bond}C(OMe)Ph) (1) is able to transfer its carbene ligand to a variety of electron-deficient olefins and provides donor-acceptor-substituted cyclopropanes in good yields. Apt activating groups with respect to the alkene are ester, amide, nitrile, sulfone, and dialkyl phosphonate functions. Methyl vinyl ketone (19) affords products in low yield that may arise from an intermediate cyclopropane derivative. Phenyl vinyl sulfoxide (24) mainly acts as an oxidizing agent, transforming 1 into methyl benzoate. for olefin 24 and {alpha}-(N-methylanilino)acrylonitrile the authors found products that should be formed on an olefin metathesis pathway. The methyl-substituted carbene complex 48 also affords the expected donor-acceptor-substituted cyclopropanes; however, acyclic isomers are formed in higher amounts. The molybdenum and tungsten complexes 55 and 56, respectively, also furnish cyclopropane derivatives, but the yields are lower than with the chromium compound 1. Disubstituted olefins and complex 1 still give the cyclopropanes in moderate yields, while all trisubstituted and most of the difunctionalized alkenes do not react with this Fischer carbene complex. The cyclopropanes synthesized can be deprotonated and alkylated or transformed into ring-opened products. These model reactions demonstrate the synthetic potentials of donor-acceptor-substituted cyclopropanes prepared via Fischer carbene complexes.

  12. Characterisation of the ester-substituted products of the reaction of p-t-butyl calix[4]arene and ethyl bromoacetate using LC-UV-MS and LC-DAD.

    Science.gov (United States)

    McMahon, Gillian; Wall, Rachel; Nolan, Kieran; Diamond, Dermot

    2002-07-19

    A series of derivatisation reactions between p-t-butyl calix[4]arene and ethyl bromoacetate were carried out in order to prepare 1,3 diester substituted calix[4]arene. Mass spectral data, obtained from direct injection of samples, indicated that the reactions were rich in the desired product. Since the ultra violet (UV) spectra of the desired product and possible impurities are very similar, liquid chromatography (LC) chromatographic data seemed to corroborate these results. However, when on-line LC-UV-MS was carried out and each LC peak subjected to MS analysis as it eluted, a very different picture emerged. It was found that many of these reactions actually contained high levels of the monoester product which, having less affinity for sodium in the MS, is therefore seriously underestimated in any direct injection assay. LC-diode array detection (DAD) methods were also used to help successfully identify and characterise the compounds being formed in these complex reactions. The overall results obtained in this paper allowed the optimal reaction conditions to be determined for this reaction. LC-MS analysis of the chromatographic peaks also identified the presence of two isomers of the diester substituted calix[4]arene (1,3 and 1,2 diesters). The combination of LC and UV/MS detection is required for accurate analysis of the products of such reactions.

  13. Reactions of metal-substituted myoglobins with excess electrons studied by pulse radiolysis and low-temperature gamma-radiolysis

    International Nuclear Information System (INIS)

    Miki, Hideho; Nakajima, Atushi; Ogasawara, Masaaki; Tamura, Mamoru

    1990-01-01

    Reactions of metal-substituted myoglobins with excess electrons in electron-pulse-irradiated aqueous solutions at room temperature and γ-irradiated aqueous matrices at 77 K were studied for the purpose of probing the functional role of heme iron. The rate constants for the reactions of various myoglobins with hydrated electrons were not much different from each other, and were close to those of diffusion-controlled reactions. In contrast, the reduction rates of myoglobins with dithionite depended markedly on the kind of central metals in the myoglobins. The difference was interpreted in terms of Marcus' theory for electron-transfer reactions. Effects of the 6-coordinate structure of the cobalt(III) species on the reaction with dithionite was also discussed. The steady-state optical-absorption measurements of γ-irradiated matrices containing cobaltimyoglobin at 77 K demonstrated the reduction of cobalt(III) species by excess electrons produced by the action of ionizing radiation. It was shown, by electron-spin resonance spectroscopy, that a 6-coordinated cobalt(II) species produced at 77 K transformed to a 5-coordinate one at higher temperatures, as reported previously. However, structural relaxation was not observed by optical spectroscopy either in the solutions or in the low-temperature matrices. It was concluded, therefore, that the intermediate 6-coordinate cobalt(II) species gave an optical absorption spectrum which was indistinguishable from that of the relaxed 5-coordinate cobalt(II) species. (author)

  14. Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

    International Nuclear Information System (INIS)

    Mbiya, Wilbes; Chipinda, Itai; Simoyi, Reuben H.; Siegel, Paul D.

    2016-01-01

    Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking.

  15. Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

    Science.gov (United States)

    Mbiya, Wilbes; Chipinda, Itai; Simoyi, Reuben H.; Siegel, Paul D.

    2015-01-01

    Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking. PMID:26612505

  16. Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.

    Science.gov (United States)

    Punthasee, Puminan; Laciak, Adrian R; Cummings, Andrea H; Ruddraraju, Kasi Viswanatharaju; Lewis, Sarah M; Hillebrand, Roman; Singh, Harkewal; Tanner, John J; Gates, Kent S

    2017-04-11

    Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 10 2 M -1 min -1 . Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.

  17. The samarium Grignard reaction. In situ formation and reactions of primary and secondary alkylsamarium(III) reagents

    Energy Technology Data Exchange (ETDEWEB)

    Curran, D.P.; Totleben, M.J. [Univ. of Pittsburgh, PA (United States)

    1992-07-15

    This work shows that primary and secondary radicals are rapidly reduced in THF/HMPA to form primary- and secondary-alkylsamarium reagents. The primary- and secondary-radicals can be formed either by direct SmI{sup 2} reductions of primary- and secondary-halides or by a previous rapid radical cyclization. The samarium reagents have moderate stability in solution, and they react with a variety of typical electrophiles, including aldehydes and ketones. The work further shows that organosamarium intermediates can be involved in the traditional samarium Barbier reaction of aldehydes and ketones conducted in THF/HMPA. A new procedure called the {open_quotes}samarium Grignard{close_quotes} method is introduced, and it is suggested that this new procedure will have considerably more scope and generality than the samarium Barbier reaction. 37 refs., 4 tabs.

  18. Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward electrophiles based on elements different from carbon.

    Science.gov (United States)

    Alonso, María; Alvarez, M Angeles; García, M Esther; Ruiz, Miguel A; Hamidov, Hayrullo; Jeffery, John C

    2010-12-20

    The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = η(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene) displayed multisite reactivity when faced with different electrophilic reagents. The reactions with the group 14 organochloride compounds ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene-bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3), GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E' = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) Å for the MoPb compound). A particular situation was found in the reaction with SnMe(3)Cl, this giving a product existing in both tautomeric forms, with the phosphide-like complex [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in dichloromethane solution. The title anions also showed a multisite behavior when reacting with transition-metal based electrophiles. Thus, the reactions with the complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' = ZrCp(2)Cl), displaying a bridging κ(1),κ(1)-P,O- oxophosphinidene ligand connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) Å, O-Zr = 2.016(4) Å for the WZr compound]. In contrast, the reactions with the complex [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans-[MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) Å). From all the above results it was concluded that the terminal oxophosphinidene complexes are preferentially formed under conditions of orbital control, while charge-controlled reactions tend to give derivatives with the electrophilic fragment bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like, oxophosphinidene-bridged derivatives).

  19. Nitropyrroles, Diels-Alder reactions assisted by microwave irradiation and solvent effect. An experimental and theoretical study

    Science.gov (United States)

    Mancini, Pedro M. E.; Kneeteman, María N.; Cainelli, Mauro; Ormachea, Carla M.; Domingo, Luis R.

    2017-11-01

    The behaviors of N-tosylnitropyrroles acting as electrophilic dienophiles in polar Diels-Alder reactions joint to different dienes of increeased nucleophilicity are analyzed. The reactions were developed under microwave irradiation using toluene or protic ionic liquids (PILs) as solvents and in free solvent conditions. In all the cases explored we observed good yields in short reaction times. For these reactions, the free solvent condition and the use of protic ionic liquids as solvents offer similar results. However, the free solvent conditions favor environmental sustainability. The role of PILs in these polar Diels-Alder reactions has been theoretically studied within the Molecular Electron Density Theory.

  20. Elucidation of Diels-Alder Reaction Network of 2,5-Dimethylfuran and Ethylene on HY Zeolite Catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Do, Phuong T. M. [Univ. of Delaware, Newark, DE (United States); McAtee, Jesse R. [Univ. of Delaware, Newark, DE (United States); Watson, Donald A. [Univ. of Delaware, Newark, DE (United States); Lobo, Raul F. [Univ. of Delaware, Newark, DE (United States)

    2012-12-12

    The reaction of 2,5-dimethylfuran and ethylene to produce p-xylene represents a potentially important route for the conversion of biomass to high-value organic chemicals. Current preparation methods suffer from low selectivity and produce a number of byproducts. Using modern separation and analytical techniques, the structures of many of the byproducts produced in this reaction when HY zeolite is employed as a catalyst have been identified. From these data, a detailed reaction network is proposed, demonstrating that hydrolysis and electrophilic alkylation reactions compete with the desired Diels–Alder/dehydration sequence. This information will allow the rational identification of more selective catalysts and more selective reaction conditions.

  1. Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

    Directory of Open Access Journals (Sweden)

    Marco Mottinelli

    2017-09-01

    Full Text Available Background: 1,2,3,4-Tetrahydroisoquinolines (THIQs are common motifs in alkaloids and in medicinal chemistry. Synthetic access to THIQs via the Pomeranz–Fritsch–Bobbit (PFB methodology using mineral acids for deactivated, electron-poor aromatic systems, is scarcely represented in the literature. Here, the factors controlling the regiochemical outcome of cyclization are evaluated.Results: A double reductive alkylation was telescoped into a one-pot reaction delivering good to excellent yields of desired aminoacetals for cyclization. Cyclization of activated systems proceeded smoothly under standard PFB conditions, but for non-activated systems the use of HClO4 alone was effective. When cyclization was possible in both para- and ortho-positions to the substituent, 7-substituted derivatives were formed with significant amounts of 5-substituted byproduct. The formation of the 4-hydroxy-THIQs vs the 4-methoxy-THIQ products could be controlled through modification of the reaction concentration. In addition, while a highly-activated system exclusively cyclized to the indole, this seems generally highly disfavored. When competition between 6- and 7-ring formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13-methanodibenzo[c,f]azonine was exclusively obtained. Furthermore, selective ring closure in the para-position could be achieved under standard PFB conditions, while a double ring closure could be obtained utilizing HClO4.Conclusion: Reactivity differences in aminoacetal precursors can be employed to control cyclization using the PFB methodology. It is now possible to select confidently the right conditions for the synthesis of N-aryl-4-hydroxy-1,2,3,4-tetrahydroisoquinolines.

  2. Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

    Science.gov (United States)

    Mottinelli, Marco; Leese, Mathew P

    2017-01-01

    Background: 1,2,3,4-Tetrahydroisoquinolines (THIQs) are common motifs in alkaloids and in medicinal chemistry. Synthetic access to THIQs via the Pomeranz–Fritsch–Bobbit (PFB) methodology using mineral acids for deactivated, electron-poor aromatic systems, is scarcely represented in the literature. Here, the factors controlling the regiochemical outcome of cyclization are evaluated. Results: A double reductive alkylation was telescoped into a one-pot reaction delivering good to excellent yields of desired aminoacetals for cyclization. Cyclization of activated systems proceeded smoothly under standard PFB conditions, but for non-activated systems the use of HClO4 alone was effective. When cyclization was possible in both para- and ortho-positions to the substituent, 7-substituted derivatives were formed with significant amounts of 5-substituted byproduct. The formation of the 4-hydroxy-THIQs vs the 4-methoxy-THIQ products could be controlled through modification of the reaction concentration. In addition, while a highly-activated system exclusively cyclized to the indole, this seems generally highly disfavored. When competition between 6- and 7-ring formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13-methanodibenzo[c,f]azonine was exclusively obtained. Furthermore, selective ring closure in the para-position could be achieved under standard PFB conditions, while a double ring closure could be obtained utilizing HClO4. Conclusion: Reactivity differences in aminoacetal precursors can be employed to control cyclization using the PFB methodology. It is now possible to select confidently the right conditions for the synthesis of N-aryl-4-hydroxy-1,2,3,4-tetrahydroisoquinolines. PMID:29062406

  3. Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz-Fritsch-Bobbitt reaction with non-activated and moderately-activated systems.

    Science.gov (United States)

    Mottinelli, Marco; Leese, Mathew P; Potter, Barry V L

    2017-01-01

    Background: 1,2,3,4-Tetrahydroisoquinolines (THIQs) are common motifs in alkaloids and in medicinal chemistry. Synthetic access to THIQs via the Pomeranz-Fritsch-Bobbit (PFB) methodology using mineral acids for deactivated, electron-poor aromatic systems, is scarcely represented in the literature. Here, the factors controlling the regiochemical outcome of cyclization are evaluated. Results: A double reductive alkylation was telescoped into a one-pot reaction delivering good to excellent yields of desired aminoacetals for cyclization. Cyclization of activated systems proceeded smoothly under standard PFB conditions, but for non-activated systems the use of HClO 4 alone was effective. When cyclization was possible in both para - and ortho -positions to the substituent, 7-substituted derivatives were formed with significant amounts of 5-substituted byproduct. The formation of the 4-hydroxy-THIQs vs the 4-methoxy-THIQ products could be controlled through modification of the reaction concentration. In addition, while a highly-activated system exclusively cyclized to the indole, this seems generally highly disfavored. When competition between 6- and 7-ring formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13-methanodibenzo[ c , f ]azonine was exclusively obtained. Furthermore, selective ring closure in the para- position could be achieved under standard PFB conditions, while a double ring closure could be obtained utilizing HClO 4 . Conclusion: Reactivity differences in aminoacetal precursors can be employed to control cyclization using the PFB methodology. It is now possible to select confidently the right conditions for the synthesis of N- aryl-4-hydroxy-1,2,3,4-tetrahydroisoquinolines.

  4. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    Science.gov (United States)

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2012-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

  5. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    KAUST Repository

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Nová k, Zoltá n; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2011-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

  6. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    KAUST Repository

    Behenna, Douglas C.

    2011-11-14

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

  7. Reaction kinetics of chemical pollutants as a basis of risk estimates in terms of rad-equivalence

    International Nuclear Information System (INIS)

    Ehrenberg, L.; Osterman-Golkar, S.

    1977-01-01

    Most mutagenic and carcinogenic chemicals are electrophilic agents or are converted to electrophilic agents in vivo. A majority of the effective genotoxic compounds are alkylating or arylating. The dose-response curve for mutation induced by alkylating agents is indicated to contain a linear component in the region of low doses. In this region the mutagenic effectiveness per unit dose was found for several alkylating agents to be approximately proportional to the calculated rate of reaction at a certain low nucleophilic strength. This proportionality appears, by and large, to be independent on the nature of the alkyl group introduced. Hence it is possible to ascribe a genetic risk to the degree of alkylation of these centers. This risk may be expressed in rad-equivalents

  8. Chemical dynamics simulations of X- + CH3Y → XCH3 + Y- gas-phase S(N)2 nucleophilic substitution reactions. Nonstatistical dynamics and nontraditional reaction mechanisms.

    Science.gov (United States)

    Manikandan, Paranjothy; Zhang, Jiaxu; Hase, William L

    2012-03-29

    Extensive classical chemical dynamics simulations of gas-phase X(-) + CH(3)Y → XCH(3) + Y(-) S(N)2 nucleophilic substitution reactions are reviewed and discussed and compared with experimental measurements and predictions of theoretical models. The primary emphasis is on reactions for which X and Y are halogen atoms. Both reactions with the traditional potential energy surface (PES), which include pre- and postreaction potential energy minima and a central barrier, and reactions with nontraditional PESs are considered. These S(N)2 reactions exhibit important nonstatistical atomic-level dynamics. The X(-) + CH(3)Y → X(-)---CH(3)Y association rate constant is less than the capture model as a result of inefficient energy transfer from X(-)+ CH(3)Y relative translation to CH(3)Y rotation and vibration. There is weak coupling between the low-frequency intermolecular modes of the X(-)---CH(3)Y complex and higher frequency CH(3)Y intramolecular modes, resulting in non-RRKM kinetics for X(-)---CH(3)Y unimolecular decomposition. Recrossings of the [X--CH(3)--Y](-) central barrier is important. As a result of the above dynamics, the relative translational energy and temperature dependencies of the S(N)2 rate constants are not accurately given by statistical theory. The nonstatistical dynamics results in nonstatistical partitioning of the available energy to XCH(3) +Y(-) reaction products. Besides the indirect, complex forming atomic-level mechanism for the S(N)2 reaction, direct mechanisms promoted by X(-) + CH(3)Y relative translational or CH(3)Y vibrational excitation are possible, e.g., the roundabout mechanism.

  9. Two Palladium-Catalyzed Domino Reactions from One Set of Substrates/Reagents: Efficient Synthesis of Substituted Indenes and cis-Stilbenoid Hydrocarbons from the Same Internal Alkynes and Hindered Grignard Reagents

    Science.gov (United States)

    Dong, Cheng-Guo; Yeung, Pik; Hu, Qiao-Sheng

    2008-01-01

    Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction and C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides an efficient access to useful polysubstituted indenes and cis-substituted stilbenes, and may offer new means to the development of tandem/domino reactions in a more efficient way. PMID:17217305

  10. Asymmetric 1,8/13,2,x-M2C2B10 14-vertex metallacarboranes by direct electrophilic insertion reactions; the VCD and BHD methods in critical analysis of cage C atom positions.

    Science.gov (United States)

    McAnaw, Amelia; Lopez, Maria Elena; Ellis, David; Rosair, Georgina M; Welch, Alan J

    2014-04-07

    The isolation of six isomeric, low-symmetry, dicobaltacarboranes with bicapped hexagonal antiprismatic cage structures, always in low yield, is described from reactions in which 13-vertex cobaltacarborane anions and sources of cobalt-containing cations were present. The vertex-to-centroid distance (VCD) and boron-H distance (BHD) methods are used to locate the correct C atom positions in the cages, thus allowing the compounds to be identified as 1,13-Cp2-1,13,2,10-closo-Co2C2B10H12 (1), 1,8-Cp2-3-OEt-1,8,2,10-closo-Co2C2B10H11 (2), 1,13-Cp2-1,13,2,9-closo-Co2C2B10H12 (3), 1,8-Cp2-1,8,2,4-closo-Co2C2B10H12 (4), 1,13-Cp2-1,13,2,4-closo-Co2C2B10H12 (5) and 1,8-Cp2-1,8,2,5-closo-Co2C2B10H12 (6). It is shown that a common alternative method of cage C atom identification, using refined (as B) U(eq) values, does not work well, at least in these cases. Having identified the correct isomeric forms of the six dicobaltacarboranes, their syntheses are tentatively rationalised in terms of the direct electrophilic insertion of a {CpCo(+)} fragment into [CpCoC2B10](-) anions and it is demonstrated that compounds 1, 4, 5 and 6 can be successfully prepared by deliberately performing such reactions.

  11. 1-Hydroxyethyl-2-Substituted Phenoxymethyl Benzimidazoles: Synthesis and Crystal Structures

    International Nuclear Information System (INIS)

    Wu, J.; Wang, Z.; Gu, H.; Chen, W.; Zhao, L.; Zhao, C.

    2016-01-01

    Five novel 1-hydroxyethyl-2-substituted phenoxymethyl benzimidazoles c1-c5 were successfully synthesized by a three-step route. Firstly, five substituted phenoxymethyl acids a1-a5 were prepared by the O-carboxymethylation reaction of the starting substituted phenols under microwave irradiation. Then, these compounds reacted with o-phenylendiamine to get the key intermediates 2-substituted phenoxymethyl benzimidazoles b1-b5. At last, the target compounds were synthesized by the N-hydroxyethylation reaction of b1-b5 with 2-chloroethyl alcohol through the solid-liquid phase transfer catalysis method, where tetrabutyl ammonium bromide (TBAB) was used as the catalyst. The structures of the target compounds were well characterized and verified by elemental analysis, MS, IR, 1H NMR, 13C NMR and single crystal X-ray diffraction analysis. (author)

  12. Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Huiqin Zhong

    2014-01-01

    Full Text Available Emerging evidence indicates that mitochondrial cardiolipins (CL are prone to free radical oxidation and this process appears to be intimately associated with multiple biological functions of mitochondria. Our previous work demonstrated that a significant amount of potent lipid electrophiles including 4-hydroxy-nonenal (4-HNE was generated from CL oxidation through a novel chemical mechanism. Here we provide further evidence that a characteristic class of CL oxidation products, epoxyalcohol-aldehyde-CL (EAA-CL, is formed through this novel mechanism in isolated mice liver mitochondria when treated with the pro-apoptotic protein t-Bid to induce cyt c release. Generation of these oxidation products are dose-dependently attenuated by a peroxidase inhibitor acetaminophen (ApAP. Using a mouse model of atherosclerosis, we detected significant amount of these CL oxidation products in liver tissue of low density lipoprotein receptor knockout (LDLR −/− mice after Western diet feeding. Our studies highlight the importance of lipid electrophiles formation from CL oxidation in the settings of apoptosis and atherosclerosis as inhibition of CL oxidation and lipid electrophiles formation may have potential therapeutic value in diseases linked to oxidant stress and mitochondrial dysfunctions.

  13. Radioiodination and bio-evaluation of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Mohamed, H.H.

    2009-01-01

    This thesis deals with the electrophilic substitution radioiodination reaction of non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox), Meloxicam (Melox), Etodolac and Naproxen for using them as anti-inflammatory imaging agent. The factors affecting the percent of radiochemical yields such as drug concentration, ph of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied. We can divide the objective of this thesis into three parts: First part performs to compare the electrophilic substitution radioiodination reaction of Piroxicam (Pirox) and Meloxicam (Melox) with Iodine-125 where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The maximum radiochemical yield of 125 I-Piroxicam ( 125 I-Pirox) was (94%) using 3.7 MBq of Na 125 I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral ph=7 at 60 degree C within 20 min where the maximum radiochemical yield of ( 125 I-Melox) was (92%) using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral ph=7 at 25 degree C within 30 min. The radiochemical yields were determined by TLC using methylene chloride: ethyl acetate (3: 7 v/v) as a developing system and by high-pressure liquid chromatography (HPLC) using reversed phase RP-18 column and methanol: water (70: 30 v/v) as mobile phase at flow rate (1 ml/min). Tracers showed good localization in inflamed muscle either (septic or sterile). The collected data indicates that Pirox can be used as anti-inflammatory imaging agent at 24 h post injection however Melox can be used as anti-inflammatory imaging agent at 2 h due to its shorter biological half life (t 1/2 ) compared with Pirox. Second part describes a fast and efficient method for radiolabeling of etodolac with iodine-125, where both chloramine-T and iodogen were used as oxidizing agents. The labeling reaction was carried out via electrophilic

  14. New Horizons in C-F Activation by Main Group Electrophiles

    Energy Technology Data Exchange (ETDEWEB)

    Ozerov, Oleg V. [Texas A & M Univ., College Station, TX (United States). Dept. of Chemistry

    2016-02-13

    This technical report describes progress on the DOE sponsored project "New Horizons in C-F Activation by Main Group Electrophiles" during the period of 09/15/2010 – 08/31/2015. The main goal of this project was to develop improved catalysts for conversion of carbon-fluorine bonds in potentially harmful compounds. The approach involved combining of a highly reactive positively charged main-group compound with a highly unreactive negatively charged species (anions) as a way to access potent catalysts for carbon-fluorine bond activation. This report details progress made in improving synthetic pathways to a variety of new anions with improved properties and analysis of their potential in catalysis.

  15. Synthesis and substitution reactions of palladium(II) complexes with 2,2'-Bipyridine and 1,10-Phenanthroline

    International Nuclear Information System (INIS)

    Zaghal, M. H.; Al-Lawatia, S.

    1996-01-01

    The complexes cis-[Pd (Nn)CI 2 ] [Nn=2,2'-bipyridine (b py) and 1,10-phenanthroline (phen)] have been prepared via a new method by reacting the benzonitrile complex cis-[Pd(Ph CN) 2 CI 2 ] with the ligands. This method gives the products rapidly, in a pure state and in high yields. The substitution reactions of cis-[Pd(Nn)CI 2 ] (Nn=b py and phen) with Br - and I - have been attempted. The complexes cis-[Pd(Nn)X 2 ] (Nn=b py or phen; X Br, I) have been isolated. The products have been characterized by elemental analysis, conductivity measurements, and infrared, electronics absorption and 1 H NMR spectra. (authors). 26 refs., 1 tab

  16. Assessment of benzophenone-4 reactivity with free chlorine by liquid chromatography quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Negreira, N; Rodríguez, I; Rodil, R; Cela, R

    2012-09-19

    The stability of the UV filter benzophenone-4 (BP-4) in free chlorine-containing water was investigated, for the first time, by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QqTOF-MS). High mass accuracy and resolution capabilities of this hybrid mass spectrometer were used for the reliable assignation of empirical formulae and chemical structures of BP-4 derivatives. Time-course profiles of the parent compound and its by-products were simultaneously recorded by direct injection of sample aliquots, after quenching the excess of chlorine, in the LC-QqTOF-MS system. At neutral pHs, in excess of chlorine, BP-4 showed a limited stability fitting a pseudo-first-order degradation kinetics. A noticeable reduction in the half-lives of BP-4 was observed when increasing the sample pH between 6 and 8 units and also in presence of bromide traces. The reaction pathway of this UV filter involved a first electrophilic substitution of hydrogen per chlorine (or bromide) in the phenolic ring, followed by oxidation of the carbonyl moiety to an ester group, which induced a further electrophilic substitution in the same aromatic ring. Above reactions were also noticed when mixing a BP-4 containing personal care product with chlorinated tap water and in chlorinated swimming pool and sewage water, previously spiked with a BP-4 standard. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. The chemical composition of synthetic bone substitutes influences tissue reactions in vivo: histological and histomorphometrical analysis of the cellular inflammatory response to hydroxyapatite, beta-tricalcium phosphate and biphasic calcium phosphate ceramics

    International Nuclear Information System (INIS)

    Ghanaati, Shahram; Barbeck, Mike; Hilbig, Ulrike; Rausch, Vera; Unger, Ronald E; Kirkpatrick, Charles James; Detsch, Rainer; Ziegler, Guenter; Deisinger, Ulrike; Sader, Robert

    2012-01-01

    Bone substitute material properties such as granule size, macroporosity, microporosity and shape have been shown to influence the cellular inflammatory response to a bone substitute material. Keeping these parameters constant, the present study analyzed the in vivo tissue reaction to three bone substitute materials (granules) with different chemical compositions (hydroxyapatite (HA), beta-tricalcium phosphate (TCP) and a mixture of both with a HA/TCP ratio of 60/40 wt%). Using a subcutaneous implantation model in Wistar rats for up to 30 days, tissue reactions, including the induction of multinucleated giant cells and the extent of implantation bed vascularization, were assessed using histological and histomorphometrical analyses. The results showed that the chemical composition of the bone substitute material significantly influenced the cellular response. When compared to HA, TCP attracted significantly greater multinucleated giant cell formations within the implantation bed. Furthermore, the vascularization of the implantation bed of TCP was significantly higher than that of HA implantation beds. The biphasic bone substitute group combined the properties of both groups. Within the first 15 days, high giant cell formation and vascularization rates were observed, which were comparable to the TCP-group. However, after 15 days, the tissue reaction, i.e. the extent of multinucleated giant cell formation and vascularization, was comparable to the HA-group. In conclusion, the combination of both compounds HA and TCP may be a useful combination for generating a scaffold for rapid vascularization and integration during the early time points after implantation and for setting up a relatively slow degradation. Both of these factors are necessary for successful bone tissue regeneration.

  18. Rac1 modification by an electrophilic 15-deoxy Δ12,14-prostaglandin J2 analog

    Directory of Open Access Journals (Sweden)

    S.B. Wall

    2015-04-01

    Full Text Available Vascular endothelial cells (ECs are important for maintaining vascular homeostasis. Dysfunction of ECs contributes to cardiovascular diseases, including atherosclerosis, and can impair the healing process during vascular injury. An important mediator of EC response to stress is the GTPase Rac1. Rac1 responds to extracellular signals and is involved in cytoskeletal rearrangement, reactive oxygen species generation and cell cycle progression. Rac1 interacts with effector proteins to elicit EC spreading and formation of cell-to-cell junctions. Rac1 activity has recently been shown to be modulated by glutathiolation or S-nitrosation via an active site cysteine residue. However, it is not known whether other redox signaling compounds can modulate Rac1 activity. An important redox signaling mediator is the electrophilic lipid, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2. This compound is a downstream product of cyclooxygenase and forms covalent adducts with specific cysteine residues, and induces cellular signaling in a pleiotropic manner. In this study, we demonstrate that a biotin-tagged analog of 15d-PGJ2 (bt-15d-PGJ2 forms an adduct with Rac1 in vitro at the C157 residue, and an additional adduct was detected on the tryptic peptide associated with C178. Rac1 modification in addition to modulation of Rac1 activity by bt-15d-PGJ2 was observed in cultured ECs. In addition, decreased EC migration and cell spreading were observed in response to the electrophile. These results demonstrate for the first time that Rac1 is a target for 15d-PGJ2 in ECs, and suggest that Rac1 modification by electrophiles such as 15d-PGJ2 may alter redox signaling and EC function.

  19. Muon substituted free radicals

    International Nuclear Information System (INIS)

    Burkhard, P.; Fischer, H.; Roduner, E.; Strub, W.; Gygax, F.N.; Brinkman, G.A.; Louwrier, P.W.F.; McKenna, D.; Ramos, M.; Webster, B.C.

    1984-01-01

    Spin polarized energetic positive muons are injected as magnetic probes into unsaturated organic liquids. They are implemented via fast chemical processes ( -10 s) in various molecules. Of particular interest among these are muonium substituted free radicals. The technique allows determination of accurate rate coefficients for fast chemical reactions of radicals. Furthermore, radiochemical processes occuring in picoseconds after injection of the muon are studied. Of fundamental interest are also the structural and dynamical implications of substituting a proton by a muon, or in other terms, a hydrogen atom by a muonium atom. Selected examples for each of these three types of experiments are given. (Auth.)

  20. Pressure-induced polymerization in substituted acetylenes

    Energy Technology Data Exchange (ETDEWEB)

    Chellappa, Raja S.; Dattelbaum, Dana M.; Sheffield, Stephen; Robbins, David (LANL)

    2012-04-10

    A fundamental understanding of shock-induced chemical reactions in organics is still lacking and there are limited studies devoted to determining reaction mechanisms, evolution of bonding, and effect of functional group substitutions. The fast timescale of reactions occurring during shock compression create significant experimental challenges (diagnostics) to fully quantify the mechanisms involved. Static compression combined with temperature provides a complementary route to investigate the equilibrium phase space and metastable intermediates under extreme P-T conditions. In this study, we present our results from our ongoing high pressure in situ synchrotron x-ray diffraction experiments on substituted acetylenes: tert-butyl acetylene [TBA: (CH{sub 3}){sub 3}-C=CH] and ethynyl trimethylsilane [ETMS: (CH{sub 3}){sub 3}-SiC=CH]. We observed that the onset pressure of chemical reactions (at room temperature) in these compounds is higher under static compression (TBA: 12 GPa and ETMS: 17.6 GPa) when compared to shock input pressures (TBA: 6.1 GPa and ETMS: 6.6 GPa). At elevated temperatures, reactivity was observed to occur at pressures comparable to shock conditions. The products were polymeric in nature, recovered to ambient conditions with little degradation.

  1. A theoretical quantum study on the distribution of electrophilic and nucleophilic active sites on Cu(100) surfaces modeled as finite clusters

    International Nuclear Information System (INIS)

    Rios R, C.H.; Romero R, M.; Ponce R, A.; Mendoza H, L.H.

    2008-01-01

    In this work, it is shown a theoretical quantum study of the active sites distribution on a monocrystalline surface of Cu(100). The copper surface was modeled as finite clusters of 14, 23, 38 and 53 atoms. We performed Hartree-Fock and Density Functional Theory (B3LYP) ab initio calculations employing the pseudopotentials of Hay and Wadt (LANLlMB y LANL2DZ). From calculations, we found a work function value of 4.1 eV. The mapping of the HOMO and LUMO in the frozen core approximation, allowed us finding the electrophilic and nucleophilic active sites distribution, respectively. The results indicated that electrophilic sites on the Cu(100) surface were located on hollow position and its numerical density was 8.6 x 10 16 sites cm -2 . From the nucleophilic local softness study, it was found that the nucleophilic sites were formed by a group of atoms and it had a numerical density of 2.4x 10 16 sitescm -2 . Last results indicated that adsorptions with 2 x 2 and 3 x 3 distributions can be favored onto a Cu(100) surface for the electrophilic and nucleophilic cases, respectively. (Author)

  2. Substituent effects on an inverse electron demand hetero Diels-Alder reaction in aqueous solution and organic solvents : Cycloaddition of substituted styrenes to di(2-pyridyl)-1,2,4,5-tetrazine

    NARCIS (Netherlands)

    Wijnen, Jan W.; Zavarise, Silvia; Engberts, Jan B.F.N.; Charton, Marvin

    1996-01-01

    The kinetics of the Diels-Alder reactions of di(2-pyridyl)-1,2,4,5-tetrazine (1) with substituted styrenes 2 was investigated in aqueous media and in organic solvents. The second-order rate constants ofthis reaction increase dramatically in water-rich media. A decrease in pH accelerates the aqueous

  3. Substitution reactions of [Pd(bipy)(malonate)] explored with a ...

    Indian Academy of Sciences (India)

    −3. NaClO4. Table 1. Metal-Ligand ratios and structures of the product complexes. Metal:Ligand. Ligand. Structure ratio. Product complex. L1 Thioglycolic acid. HS ..... O. Scheme 1. Plausible mechanistic pathway. molecules substitute the bidentate malonate in a consec- utive fashion. Among the three sulphur donor ligands.

  4. The redox-Mannich reaction.

    Science.gov (United States)

    Chen, Weijie; Seidel, Daniel

    2014-06-06

    A complement to the classic three-component Mannich reaction, the redox-Mannich reaction, utilizes the same starting materials but incorporates an isomerization step that enables the facile preparation of ring-substituted β-amino ketones. Reactions occur under relatively mild conditions and are facilitated by benzoic acid.

  5. Alkylation of N-substituted 2-phenylacetamides

    Directory of Open Access Journals (Sweden)

    SLOBODAN D. PETROVIC

    2004-10-01

    Full Text Available Various N-substituted phenylacetamides were alkylated using different alkylating agents under neutral and basic conditions. Reactions were performed at different reaction temperatures and in various solvents. Also, a number of various catalysts were used including phase-transfer catalysts. Reactions were followed using GC or GC-MS technique and the presence as well as the yields of the alkylation products were established. Generally, the best yield and high selectivity in the studied reactions were achieved under basic conditions where in the certain cases some products, mostly N-product, were obtained solely in quantitative yields.

  6. Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid.

    Science.gov (United States)

    Isobe, Yosuke; Kawashima, Yusuke; Ishihara, Tomoaki; Watanabe, Kenji; Ohara, Osamu; Arita, Makoto

    2018-04-20

    The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE. By treating mouse peritoneal macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction. Pathway analysis revealed a dramatic enrichment of proteins involved in energy metabolism and found that glycolytic flux and mitochondrial respiration were significantly affected by the expression of 12/15-LOX. Our findings thus highlight the utility of chemoproteomics using aAA for identifying intracellular targets of enzymatically generated LDE.

  7. Kinetics modeling and reaction mechanism of ferrate(VI) oxidation of benzotriazoles.

    Science.gov (United States)

    Yang, Bin; Ying, Guang-Guo; Zhang, Li-Juan; Zhou, Li-Jun; Liu, Shan; Fang, Yi-Xiang

    2011-03-01

    Benzotriazoles (BTs) are high production volume chemicals with broad application in various industrial processes and in households, and have been found to be omnipresent in aquatic environments. We investigated oxidation of five benzotriazoles (BT: 1H-benzotriazole; 5MBT: 5-methyl-1H-benzotriazole; DMBT: 5,6-dimethyl-1H-benzotriazole hydrate; 5CBT: 5-chloro-1H-benzotriazole; HBT: 1-hydroxybenzotriazole) by aqueous ferrate (Fe(VI)) to determine reaction kinetics as a function of pH (6.0-10.0), and interpreted the reaction mechanism of Fe(VI) with BTs by using a linear free-energy relationship. The pK(a) values of BT and DMBT were also determined using UV-Visible spectroscopic method in order to calculate the species-specific rate constants, and they were 8.37 ± 0.0 and 8.98 ± 0.08 respectively. Each of BTs reacted moderately with Fe(VI) with the k(app) ranged from 7.2 to 103.8 M(-1)s(-1) at pH 7.0 and 24 ± 1 °C. When the molar ratio of Fe(VI) and BTs increased up to 30:1, the removal rate of BTs reached about >95% in buffered milli-Q water or secondary wastewater effluent. The electrophilic oxidation mechanism of the above reaction was illustrated by using a linear free-energy relationship between pH-dependence of species-specific rate constants and substituent effects (σ(p)). Fe(VI) reacts initially with BTs by electrophilic attack at the 1,2,3-triazole moiety of BT, 5MBT, DMBT and 5CBT, and at the N-OH bond of HBT. Moreover, for BT, 5MBT, DMBT and 5CBT, the reactions with the species HFeO(4)(-) predominantly controled the reaction rates. For HBT, the species H(2)FeO(4) with dissociated HBT played a major role in the reaction. The results showed that Fe(VI) has the ability to degrade benzotriazoles in water. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Synthesis of heterocycles through transition-metal-catalyzed isomerization reactions

    DEFF Research Database (Denmark)

    Ishøy, Mette; Nielsen, Thomas Eiland

    2014-01-01

    of structurally complex and diverse heterocycles. In this Concept article, we attempt to cover this area of research through a selection of recent versatile examples. A sea of opportunities! Transition-metal-catalyzed isomerization of N- and O-allylic compounds provides a mild, selective and synthetically...... versatile method to form iminium and oxocarbenium ions. Given the number of reactions involving these highly electrophilic intermediates, this concept provides a sea of opportunities for heterocycle synthesis, (see scheme; Nu=nucleophile). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim....

  9. Reaction of the antitumor antibiotic olivomycin I with aryl diazonium salts. Synthesis, cytotoxic and antiretroviral potency of 5-aryldiazenyl-6-O-deglycosyl derivatives of olivomycin I.

    Science.gov (United States)

    Tevyashova, Anna N; Olsufyeva, Eugenia N; Turchin, Konstantin F; Balzarini, Jan; Bykov, Eugenyi E; Dezhenkova, Lyubov G; Shtil, Alexander A; Preobrazhenskaya, Maria N

    2009-07-15

    The azo coupling of the antibiotic olivomycin I (1) with aryl diazonium tetrafluoroborates produced 5-aryldiazenyl-6-O-deglycosyl derivatives of 1. The structures of new compounds were confirmed by (1)H NMR and mass spectrometry analysis. A quantum-chemical study was performed to analyze the possible directions of electrophilic substitution of 1 and the easiness of 6-O-disaccharide hydrolysis in the course of azo coupling. The antiproliferative and anti-retroviral activities of novel derivatives were studied.

  10. Rhodium(I)-catalyzed cycloisomerization of benzylallene-alkynes through C-H activation.

    Science.gov (United States)

    Kawaguchi, Yasuaki; Yasuda, Shigeo; Kaneko, Akira; Oura, Yuki; Mukai, Chisato

    2014-07-14

    The efficient Rh(I)-catalyzed cycloisomerization of benzylallene-alkynes produced the tricyclo[9.4.0.0(3,8)]pentadecapentaene skeleton through a C(sp2)-H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C-H bond to Rh(I), an ene-type cyclization to the vinylidenecarbene-Rh(I) intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Pd(II)-Catalyzed Ortho- or Meta-C–H Olefination of Phenol Derivatives

    Science.gov (United States)

    Dai, Hui-Xiong; Li, Gang; Zhang, Xing-Guo; Stepan, Antonia F.

    2013-01-01

    A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C–H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C–H functionalizations when functional groups are distal to target C–H bonds. The meta-C–H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds. PMID:23614807

  12. Studies on the selectivity of the reaction of (CO){sub 5}W=C(aryl)H with enynes: transfer of the carbene ligand to the C=C Bond versus insertion of the C triple bond C into the W=C Bond

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, H.; Volkland, H.P.; Stumpf, R.

    1996-10-01

    The strongly electrophilic monophenylcarbene complex [(CO){sub 5}W=C(Ph)H] (2a) reacts with the enynes H-C triple bond C-R(R=-C(Me)=CH{sub 2})(3), -C{sub 6}H{sub 4}-CH=CH{sub 2}-p (5) and subsequently with PMe{sub 3} to form the C{sub a}lpha-PMe{sub 3} adducts of the vinylidene complexes [(CO){sub 5}W-{l_brace}C(PMe{sub 3})=CH-C{sub 3}H{sub 3}(Me)Ph{r_brace}] (4) and [(CO){sub 5}W {l_brace}C(PMe{sub 3})=CH-C{sub 6}H{sub 4}-C{sub 3}H{sub 4}Ph{r_brace}] (6). The reaction very likely proceeds by transfer of the carbene ligand to the C=C bond of the enyne to form a cyclopropyl-substituted alkyne complex which is in equilibrium with its vinylidene isomer.

  13. Kinetics of the reaction of hydroxyl radicals with ethane and a series of Cl- and F-substituted methanes at 300-400degK

    International Nuclear Information System (INIS)

    Bjarnov, E.; Munk, J.; Nielsen, O.J.; Pagsberg, P.; Sillesen, A.

    1982-04-01

    Gas phase reactions of hydroxyl radicals with ethane and a series of Cl- and F-substituted methanes were studied at atmospheric pressure and over the temperature range 300-400degK. Hydroxyl radicals were produced by pulse radiolysis of water vapour and the decay rate was studied by monitoring the transient light absorption at 3090 A. Arrhenius parameters (A,Esub(a)) for the reaction RH + OH arrow R + HOH were obtained for the reactants RH = C 2 H 6 ,CH 3 Cl,CH 2 Cl 2 ,CHFCl 2 . CF 2 Cl 2 (CFC-12) which contains no C-H bonds was found to be inert toward attack by hydroxyl radicals. Since no other tropospheric sink reactions have been reported for CFC-12 its possible impact on the stratospheric ozone remains a controversial problem. (author)

  14. Sodium-carbonate co-substituted hydroxyapatite ceramics

    Directory of Open Access Journals (Sweden)

    Zoltan Z. Zyman

    2013-12-01

    Full Text Available Powders of sodium-carbonate co-substituted hydroxyapatite, having sodium content in the range of 0.25–1.5 wt.% with a 0.25 wt.% step, were prepared by a precipitation-solid state reaction route. Compacts of the powders were sintered in a CO2 flow (4 mL/min at 1100 °C for 2 h. The sintered ceramics contained sodium and carbonate ions in the ranges of 0–1.5 wt.% and 1.3–6 wt.%, respectively, which are typical impurity concentrations in biological apatite. A relationship between sodium and carbonate contents and the type of carbonate substitution was found. The total carbonate content progressively increased with the sodium content. The obtained ceramics showed an AB-type carbonate substitution. However, the substitution became more B-type as the sodium content increased. As a result, the carbonation was almost B-type (94 % for the highest sodium content (1.5 wt.%.

  15. Kinetics and mechanism of the oxidation of substituted ...

    Indian Academy of Sciences (India)

    Unknown

    Oxidation of meta- and para-substituted benzylamines by cetyltrimethyl- ... method.12 As per this method, the aldimine is hydrolysed to the aldehyde and then ... reactions were studied at constant temperature (± 0⋅1 K) and were followed by .... electronic interaction between the substituent and the reaction centre, (σ+–σ0) is ...

  16. Electrophilic acid gas-reactive fluid, proppant, and process for enhanced fracturing and recovery of energy producing materials

    Science.gov (United States)

    Fernandez, Carlos A.; Heldebrant, David J.; Bonneville, Alain; Jung, Hun Bok; Carroll, Kenneth C.

    2018-01-23

    An electrophilic acid gas-reactive fracturing fluid, proppant, and process are detailed. The fluid expands in volume to provide rapid and controlled increases in pressure that enhances fracturing in subterranean bedrock for recovery of energy-producing materials. The proppant stabilizes fracture openings in the bedrock to enhance recovery of energy-producing materials.

  17. Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

    Science.gov (United States)

    Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

    2018-05-01

    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

  18. Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

    Directory of Open Access Journals (Sweden)

    Qing He

    2016-02-01

    Full Text Available 7-Azaisatin and 7-azaoxindole skeletons are valuable building blocks in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD, as the catalyst. This route allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee. Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized.

  19. Preparation and physical characteristics of a lithium-beryllium-substituted fluorapatite

    International Nuclear Information System (INIS)

    Lexa, D.

    1999-01-01

    A lithium-beryllium-substituted fluorapatite, Li 0.50 Be 0.25 Ca 4.50 (PO 4 ) 3 F, has been prepared by means of a high-temperature reaction between lithium beryllium fluoride, Li 2 BeF 4 , and tricalcium phosphate, Ca 3 (PO 4 ) 2 . This material has potential application as a waste form for radioactive and toxic fluoride salts. Monitoring of the reaction progress by differential scanning calorimetry indicated that the reaction was initiated by melting of the fluoride salt and that it was fast and complete. While reactive sintering of lithium beryllium fluoride with tricalcium phosphate led to a rather porous product, melting of the reactants with subsequent solidification readily produced a substituted fluorapatite with a near-theoretical bulk density

  20. General synthesis of C-glycosyl amino acids via proline-catalyzed direct electrophilic alpha-amination of C-glycosylalkyl aldehydes.

    Science.gov (United States)

    Nuzzi, Andrea; Massi, Alessandro; Dondoni, Alessandro

    2008-10-16

    Non-natural axially and equatorially linked C-glycosyl alpha-amino acids (glycines, alanines, and CH2-serine isosteres) with either S or R alpha-configuration were prepared by D- and L-proline-catalyzed (de >95%) alpha-amination of C-glycosylalkyl aldehydes using dibenzyl azodicarboxylate as the electrophilic reagent.

  1. Reactivity Of Radiolytically-Produced Nitrogen Oxide Radicals Toward Aromatic Compounds

    International Nuclear Information System (INIS)

    Elias, Gracy

    2010-01-01

    radiolysis of the modifier (Cs-7SB), which solvates both metal complexes, is responsible for this change. These reactions presumably occur due to reactions with radiolytically-produced nitrogen-centered radicals like (sm b ullet)NO, (sm b ullet)NO 2 and (sm b ullet)NO 3 . Anisole (C 6 H 5 -OCH 3 ) was used in this study as a surrogate for Cs-7SB, since both are aryl ethers. Toluene was used as a surrogate for Cs-7SB because of the alkyl group on the benzene ring in both molecules. Anisole, highly reactive in acids, is a small molecule compared to Cs-7SB and the nitration products are easier to identify compared to those for the larger Cs-7SB molecule. Toluene is less reactive than anisole. Therefore, the highly reactive anisole and the less reactive toluene were considered in this study as model compounds to compare the reaction mechanisms and the nitrated products in acidic media under irradiation. Experiments were designed to elucidate the mechanism of the nitration of aromatic rings in γ-irradiated aqueous nitric acid. Since a suite of radical and ionic reactive species are produced in this condensed-phase system, solutions of nitric acid, neutral nitrate and neutral nitrite were irradiated in separate experiments to isolate selected reactive species. Product nitration species were assessed by high performance liquid chromatography (HPLC) with a reversed phase C-18 column and photodiode array detector. The nitrated anisole product distributions were the same with and without radiation in acidic solution, although more products were formed with radiation. In the irradiated acidic condensed phase, radiation-enhanced nitrous acid-catalyzed nitrosonium ion electrophilic aromatic substitution followed by oxidation reactions dominated over radical addition reactions. In contrast, the distribution of nitrated derivatives for toluene showed nitronium ion electrophilic substitution in the unirradiated acidic medium as a result of thermal nitration only at elevated temperatures

  2. Potential radiosensitizing agents. 5. 2-Substituted benzimidazole derivatives

    International Nuclear Information System (INIS)

    Gupta, R.P.; Larroquette, C.A.; Agrawal, K.C.

    1982-01-01

    A series of 2-substituted benzimidazoles and their derivatives have been synthesized and tested for their ability to selectively sensitize hypoxic Chinese hamster cells (V-79) toward the lethal effect of ionizing radiation. These compounds were prepared by reacting the 2-substituted benzimidazoles with 1,2-epoxy-3-methoxypropane in the presence of potassium carbonate. Reaction of the 2-nitro and 2-methylfonyl analogue with the epoxide also yielded a cyclized material, which was confirmed to be a benzimidazo[2,1-b]oxazole. In an attempt to increase the electron affinity, 5- or 6-nitro-2-substituted-benzimidazoles were also synthesized and then reacted with the epoxide to yield the corresponding 1-substituted derivatives. The results of the biological tests for the radiosensitizing activity of these agents against Chinese hamster cells (V-79) in culture indicated that the 2-nitro-substituted analogues were the most effective sensitizers in this series

  3. Reaction product of pyrogallol with methyl linoleate and its antioxidant potential for biodiesel

    Science.gov (United States)

    Sutanto, H.; Ainny, L.; Lukman; Susanto, B. H.; Nasikin, M.

    2018-03-01

    The demand of biodiesel as an alternative fuel is increasing due to fossil fuel depletion. Biodiesel is a renewable diesel fuel in the form of fatty acid methyl ester or FAME as a result of an esterification of plant oils in a presence of catalyst. Compared to the conventional diesel fuel, biodiesel is more biodegradable, has higher lubricity, and lower toxic emissions. However, the high content of unsaturated fatty acid leads to a problem that biodiesel is prone to oxidation during storage period. This oxidation instability causes degradation of fuel quality and will affect engine performance. Pyrogallol and other phenolic derivatives have been used as the antioxidant additives to prevent biodiesel oxidation. As reported in many researches, pyrogallol is one of the best phenolic antioxidant. However, its low solubility in biodiesel needs an attention. Several reports indicate the increasing solubility of pyrogallol using molecule modification with the addition of alkyl groups to its benzene ring via electrophilic substitution. This paper discusses the idea about modification of pyrogallol molecule and methyl linoleate using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical in order to increase its solubility in biodiesel while keeping its antioxidant property. Three responses were analyzed to examine the antioxidant activity: iodine value, viscosity, and color intensity. The result shown that the addition of 0.1% reaction product exhibit antioxidant activity in biodiesel.

  4. Kinetics of electrophilic exchange of lanthanide(3) and copper(2) ions in aqueous solutions of ethylenediaminetetraacetates

    International Nuclear Information System (INIS)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I.

    1984-01-01

    Electrophilic exchange in the MA - - Cu 2+ (M 3+ =La 3+ , P 2 3+ , Nd 3+ , Eu 3+ , Gd 3+ , Tb 3+ , Er 3+ , Yb 3+ , A 4- =ethylenediaminetetraacetate) systems is studied. Copper is chosen as a constituent cation, because the stability of the CuA 2+ - complex is higher than that of the MA - complex, besides the CuA 2- , is characterized by a high extinction coefficient E 280 =3200. Electrophilic exchange in the systems is shown to be realized through the acid dissociation mechanism and through the association mechanism. Consideration of the acid dissociation mechanism assumes that the exchange is limited by a break in the metal-oxygen bond in the intermediate protonated complex. In case of the association mechanism it is limited by a break in the metal-nitrogen bond in the intermediate binuclear complex. Rate constants of the limiting stage are calculated. Dependences of the rate constants of exchange on the stability of the complexes, the order number of the element, acidity of medium, Cu 2+ concentration are given. Differences are shown to exist between the exchange mechanisms in the studied: systems for the REE of cerium and yttrium subgroups

  5. Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines.

    Science.gov (United States)

    Pronin, Sergey V; Reiher, Christopher A; Shenvi, Ryan A

    2013-09-12

    The SN2 reaction (bimolecular nucleophilic substitution) is a well-known chemical transformation that can be used to join two smaller molecules together into a larger molecule or to exchange one functional group for another. The SN2 reaction proceeds in a very predictable manner: substitution occurs with inversion of stereochemistry, resulting from the 'backside attack' of the electrophilic carbon by the nucleophile. A significant limitation of the SN2 reaction is its intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are viable precursor substrates, tertiary alcohols and their derivatives usually either fail to react or produce stereochemical mixtures of products. Here we report the stereochemical inversion of chiral tertiary alcohols with a nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The method is chemoselective against secondary and primary alcohols, thereby complementing the selectivity of the SN2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids and enables their preparation from the corresponding terrestrial terpenes. We expect that the general attributes of the methodology will allow chiral tertiary alcohols to be considered viable substrates for stereoinversion reactions.

  6. Experimental Determination of Activation Energy of Nucleophilic Aromatic Substitution on Porphyrins

    Science.gov (United States)

    Rizvi, Waqar; Khwaja, Emaad; Siddiqui, Saim; Bhupathiraju, N. V. S. Dinesh K.; Drain, Charles Michael

    2018-01-01

    A physical organic chemistry experiment is described for second-year college students. Students performed nucleophilic aromatic substitution (NAS) reactions on 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin (TPPF[subscript 20]) using three different nucleophiles. Substitution occurs preferentially at the 4-position ("para")…

  7. A novel approach for the synthesis of 5-substituted-1H-tetrazoles

    Energy Technology Data Exchange (ETDEWEB)

    Akhlaghinia, Batool; Rezazadeh, Soodabeh, E-mail: akhlaghinia@um.ac.ir [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of)

    2012-12-15

    A series of 5-substituted-1H-tetrazoles (RCN{sub 4}H) have been synthesized by cycloaddition reaction of different aryl and alkyl nitriles with sodium azide in DMSO using CuSO{sub 4}{center_dot}5H{sub 2}O as catalyst. A wide variety of aryl nitriles underwent [3+2] cycloaddition to afford tetrazoles under mild reaction conditions in good to excellent yields. The catalyst used is readily available and environmentally friendly. Short reaction times, good to excellent yields, safe process and simple workup make this method an attractive and useful contribution to present organic synthesis of 5-substituted-1H-tetrazoles. (author)

  8. Domino reactions initiated by intramolecular hydride transfers from tri(di)arylmethane fragments to ketenimine and carbodiimide functions.

    Science.gov (United States)

    Alajarin, Mateo; Bonillo, Baltasar; Ortin, Maria-Mar; Sanchez-Andrada, Pilar; Vidal, Angel; Orenes, Raul-Angel

    2010-10-21

    The ability of triarylmethane and diarylmethane fragments to behave as hydride donors participating in thermal [1,5]-H shift/6π-ERC tandem processes involving ketenimine and carbodiimide functions is disclosed. C-Alkyl-C-phenyl ketenimines N-substituted by a triarylmethane substructure convert into a variety of 3,3,4,4-tetrasubstituted-3,4-dihydroquinolines, as structurally related carbodiimides transform into 3,4,4-trisubstituted-3,4-dihydroquinazolines via transient ortho-azaxylylenes. The first step of these one-pot conversions, the [1,5]-H shift, is considered to be a hydride migration on the basis of the known hydricity of the tri(di)arylmethane fragment and the electrophilicity of the central heterocumulenic carbon atom, whereas the final electrocyclization involves the formation of a sterically congested C-C or C-N bond. In the cases of C,C-diphenyl substituted triarylmethane-ketenimines the usual 6π-ERC becomes prohibited by the presence of two phenyl rings at each end of the azatrienic system. This situation opens new reaction channels: (a) following the initial hydride shift, the tandem sequence continues with an alternative electrocyclization mode to give 9,10-dihydroacridines, (b) the full sequence is initiated by a rare 1,5 migration of an electron-rich aryl group, followed by a 6π-ERC which leads to 2-aryl-3,4-dihydroquinolines, or (c) a different [1,5]-H shift/6π-ERC sequence involving the initial migration of a hydrogen atom from a methyl group at the ortho position to the nitrogen atom of the ketenimine function. Diarylmethane-ketenimines bearing a methyl group at the benzylic carbon atom experience a tandem double [1,5]-H shift, the first one being the usual benzylic hydride transfer whereas the second one involves the methyl group at the initial benzylic carbon atom, the reaction products being 2-aminostyrenes. Diarylmethane-ketenimines lacking such a methyl group convert into 3,4-dihydroquinolines by the habitual tandem [1,5]-H shift/6

  9. A linear solvation energy relationship study for the reactivity of 2-substituted cyclohex-1-enecarboxylic and 2-substituted benzoic acids with diazodiphenylmethane in aprotic and protic solvents

    Directory of Open Access Journals (Sweden)

    JASMINA B. NIKOLIC

    2007-12-01

    Full Text Available The rate constants for the reaction of 2-substituted cyclohex-1-enylcarboxylic acids and the corresponding 2-substituted benzoic acids with diazodiphenyl methane were determined in various aprotic solvents at 30 ºC. In order to explain the kinetic results through solvent effects, the second order rate constants of the reaction of the examined acids were correlated using the Kamlet–Taft solvatechromic equation. The correlations of the kinetic data were carried out by means of multiple linear regression analysis and the solvent effects on the reaction rates were analyzed in terms of the contributions of the initial and transition state. The signs of the equation coefficients support the proposed reaction mechanism. The quantitative relationship between the molecular structure and the chemical reactivity is discussed, as well as the effect of geometry on the reactivity of the examined molecules.

  10. Studies of ruthenium complexes, 8. Kinetic studies of the thermal substitution reaction of hexaammine and cis--dihalogenotetraammineruthenium(III) complexes in the solid state

    Energy Technology Data Exchange (ETDEWEB)

    Ohyoshi, A; Hiraki, S; Odate, T; Kohata, S; Oda, J [Kumamoto Univ. (Japan). Faculty of Engineering

    1975-01-01

    The kinetics of the thermal substitution reaction of hexaamineruthenium (III) halides and cis-dihalogenotetraamineruthenium (III) halides have been studied in the solid state. The reaction rates and kinetic parameters were determined for these two reactions; (Ru(NH/sub 3/)/sub 6/)X/sub 3/..-->..(RuX(NH/sub 3/)/sub 5/)X/sub 2/+NH/sub 3/, (X=Br, I) and cis - (RuX/sub 2/(NH/sub 3/)/sub 4/)X..-->..(RuX/sub 3/(NH/sub 3/)/sub 3/)+NH/sub 3/, (X=Cl, Br). The values of the rate constant, the activation energy, and the activation entropy were 2.10x10/sup -5/ s/sup -1/ (at 161/sup 0/C), 23.2 kcal mol/sup -1/, and -29.3 e.u. for the hexaamine bromide, and 2.92x10/sup -5/ s/sup -1/ (at 162/sup 0/C), 31.3 kcal mol/sup -1/, and -10.1 e.u. for the cis-dibromotetraamine bromide. The Ssub(N)2 mechanism is more probable for the former reaction, while the Ssub(N)1 mechanism is more probable for the latter reaction.

  11. Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase

    KAUST Repository

    Bsharat, Odey; Musa, Musa M.; Vieille, Claire; Oladepo, Sulayman; Takahashi, Masateru; Hamdan, Samir

    2017-01-01

    Ketones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically enriched alcohols by using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones, in particular, were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacts their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explain how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity.

  12. Asymmetric Reduction of Substituted 2-Tetralones by Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase

    KAUST Repository

    Bsharat, Odey

    2017-01-30

    Ketones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically enriched alcohols by using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones, in particular, were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacts their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explain how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity.

  13. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Science.gov (United States)

    2010-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

  14. A new reactivity mode for the diazo group: diastereoselective 1,3-aminoalkylation reaction of β-amino-α-diazoesters to give triazolines.

    Science.gov (United States)

    Kuznetsov, Alexey; Gulevich, Anton V; Wink, Donald J; Gevorgyan, Vladimir

    2014-08-18

    A novel mode of reactivity for the diazo group, the 1,3-addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of β-amino-α-diazoesters to form tetrasubstituted 1,2,3-triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au-catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Optical properties of new 5-(4-phenylethynyl)-substituted-1,10-phenanthroline derivatives

    International Nuclear Information System (INIS)

    Guerin, Juliette; Aronica, Christophe; Boeuf, Gaelle; Chauvin, Jerome; Moreau, Juliette; Lemercier, Gilles

    2011-01-01

    The synthesis and optical properties of a novel family of 5-substituted-1,10-phenanthroline derivatives are reported herein. One carbon-carbon triple-bond function was introduced using a Sonogashira cross-coupling reaction. The effects on optical properties, of the substitution with electro-withdrawing or -donating substituents in the 5th position of the 1,10-phenanthroline are investigated. Experimental chemical structure-polarisability relationship is analyzed according to the Lippert-Mataga correlation and compared to a theoretical study carried out with DFT calculations. These compounds are promising candidates for a fine-tuning of the internal charge-transfers but also as potential nonlinear chromophores and ligands within multifunctional coordination complexes. - Highlights: → Synthesis and optical properties of new 5-substituted-1,10-phenanthroline derivatives. → Sonogashira reaction was used for the substitution. → Structure-polarisability relationship analyzed according to Lippert-Mataga correlation. → Theoretical study was carried out with DFT calculations. → Fine-tuning of the internal charge-transfers within nonlinear compounds.

  16. Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR.

    Science.gov (United States)

    Danyal, Karamatullah; de Jong, Willem; O'Brien, Edmund; Bauer, Robert A; Heppner, David E; Little, Andrew C; Hristova, Milena; Habibovic, Aida; van der Vliet, Albert

    2016-11-01

    Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is thought to contribute to increased asthma incidence associated with smoking. Here, we explored the effects of acute acrolein exposure on innate airway responses to two common airborne allergens, house dust mite and Alternaria alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 h) dramatically inhibited innate airway responses to subsequent allergen challenge, demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL-25, and IL-1α. Acrolein and other anti-inflammatory thiol-reactive electrophiles, cinnamaldehyde, curcumin, and sulforaphane, similarly inhibited allergen-induced production of these cytokines from human or murine airway epithelial cells in vitro. Based on our previous observations indicating the importance of Ca 2+ -dependent signaling, activation of the NADPH oxidase DUOX1, and Src/EGFR-dependent signaling in allergen-induced epithelial secretion of these cytokines, we explored the impact of acrolein on these pathways. Acrolein and other thiol-reactive electrophiles were found to dramatically prevent allergen-induced activation of DUOX1 as well as EGFR, and acrolein was capable of inhibiting EGFR tyrosine kinase activity via modification of C797. Biotin-labeling strategies indicated increased cysteine modification and carbonylation of Src, EGFR, as well as DUOX1, in response to acrolein exposure in vitro and in vivo, suggesting that direct alkylation of these proteins on accessible cysteine residues may be responsible for their inhibition. Collectively, our findings indicate a novel anti-inflammatory mechanism of CS-derived acrolein and other thiol-reactive electrophiles, by directly inhibiting DUOX1- and EGFR-mediated airway epithelial responses to airborne allergens. Copyright © 2016 the American Physiological Society.

  17. Reaction of Titanocene Alkyls with Pyridines; A Novel Type of Cyclometallation Reaction

    NARCIS (Netherlands)

    Klei, E.; Teuben, J.H.

    1981-01-01

    Reaction of Cp2TiR (R = alkyl) with 2-substituted-pyridines and with quinolines leads to α-metallation of these ligands with formation of triangular titanocycles containing TiIII. Proof of the metallation at the α-position comes from reactions of the complexes formed with I2 and D2O/DCl which yield

  18. Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization

    International Nuclear Information System (INIS)

    Barbeck, Mike; Sader, Robert; Ghanaati, Shahram; Najman, Stevo; Stojanović, Sanja; Živković, Jelena M; Mitić, Žarko; Choukroun, Joseph; Kovačević, Predrag; James Kirkpatrick, C

    2015-01-01

    The present study aimed to analyze the effects of the addition of blood to the phycogenic bone substitute Algipore ® on the severity of in vivo tissue reaction. Initially, Fourier-transform infrared spectroscopy (FTIR) of the bone substitute was conducted to analyze its chemical composition. The subcutaneous implantation model in Balb/c mice was then applied for up to 30 d to analyze the tissue reactions on the basis of specialized histochemical, immunohistochemical, and histomorphometrical methods. The data of the FTIR analysis showed that the phycogenic bone substitute material is mainly composed of hydroxyapatite with some carbonate content. The in vivo analyses revealed that the addition of blood to Algipore ® had a major impact on both angiogenesis and vessel maturation. The higher vascularization seemed to be based on significantly higher numbers of multinucleated TRAP-positive cells. However, mostly macrophages and a relatively low number of multinucleated giant cells were involved in the tissue reaction to Algipore ® . The presented data show that the addition of blood to a bone substitute impacts the tissue reaction to it. In particular, the immune response and the vascularization were influenced, and these are believed to have a major impact on the regenerative potential of the process of bone tissue regeneration. (paper)

  19. Synthesis of Thioethers by InI3-Catalyzed Substitution of Siloxy Group Using Thiosilanes

    Directory of Open Access Journals (Sweden)

    Yoshihiro Nishimoto

    2016-10-01

    Full Text Available The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI3 catalyst to yield the corresponding thioethers. InI3 was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF3⋅OEt2, AlCl3, and TiCl4 were ineffective. Various silyl ethers such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic types were applicable. In addition, bulky OSitBuMe2 and OSiiPr3 groups, other than the OSiMe3 group, were successfully substituted. The substitution reaction of enantiopure secondary benzylic silyl ether yielded the corresponding racemic thioether product, which suggested that the reaction of tertiary alkyl, secondary alkyl, benzylic, and propargylic silyl ethers would proceed via a SN1 mechanism.

  20. Intermolecular Dehydrative Coupling Reaction of Arylketones with Cyclic Alkenes Catalyzed by a Well-Defined Cationic Ruthenium-Hydride Complex: A Novel Ketone Olefination Method via Vinyl C–H Bond Activation

    Science.gov (United States)

    Yi, Chae S.; Lee, Do W.

    2010-01-01

    Summary The cationic ruthenium-hydride complex [(η6-C6H6)(PCy3)(CO)RuH]+BF4− was found to be a highly effective catalyst for the intermolecular olefination reaction of arylketones with cycloalkenes. The preliminary mechanistic analysis revealed that electrophilic ruthenium-vinyl complex is the key species for mediating both vinyl C–H bond activation and the dehydrative olefination steps of the coupling reaction. PMID:20567607

  1. O ensino de reações orgânicas usando química computacional: I. reações de adição eletrofílica a alquenos Teaching organic reactions using computational chemistry: I. eletrophilic addition reactions to alkenes

    Directory of Open Access Journals (Sweden)

    Arquimedes Mariano

    2008-01-01

    Full Text Available Basic concepts that play an important role in some organic reactions are revisited in this paper, which reports a pedagogical experience involving undergraduate and graduate students. A systematic procedure has been applied in order to use widespread available computational tools. This paper aims to discuss the use of computers in teaching electrophilic addition reactions to alkenes. Two classical examples have been investigated: addition to non-conjugated alkenes and addition to conjugated dienes. The results were compared with those normally discussed in organic textbooks. Several important concepts, such as conformational analysis and energy control (kinetic and thermodynamic involved in reaction mechanisms can be taught more efficiently if one connects theoretical and practical tools.

  2. Hydrozirconation of lithium alkynylselenolate anions. Generation and reactions of alpha-zirconated vinyl selenide intermediates

    Science.gov (United States)

    Dabdoub; Begnini; Guerrero; Baroni

    2000-01-14

    Lithium alkynylselenolate anions react completely with 1.0 equiv of Cp(2)Zr(H)Cl in THF at room temperature to give exclusively the alpha-zirconated vinylselenolate intermediates 23-27, which by treatment with an alkyl halide afforded the alpha-zirconated vinyl alkylselenide intermediates 29-33. Reaction of 29-33 with butyltellurenyl bromide results in the formation of ketene telluro(seleno) acetals 35-39 with total control of the regio- and stereochemistry. The synthetic utility of the ketene telluro(seleno) acetals obtained here was demonstrated by reaction of 36 with butyllithium. This promotes the exclusive and stereospecific removal of the tellurium moiety and enables formation of the corresponding selenium-containing allylic alcohol of type 44, alpha-(alkylseleno)-alpha,beta-unsaturated aldehyde 45, ester 46, or carboxylic acid 47, after reaction with different types of electrophiles.

  3. Effect of 2-methyl-substituted nitroimidazoles on the hydrolysis of 4-nitrophenyl esters. Suffield report

    Energy Technology Data Exchange (ETDEWEB)

    Clewley, R.G.; Adie, C.P.; Brouwer, B.H.

    1994-03-01

    Prior to investigating nitroimidazole surfactants for use in a new catalytic chemical agent decontaminant, the catalysis afforded by simple nitroimidazoles in hydrolysis reactions has been examined. The effect of 2-methyl-5-nitroimidazole on the hydrolysis of 4-nitrophenyl diphenylphosphinate and of 2-methyl-5-nitrobenzimidazole on the hydrolyses of both 4-nitrophenyl diphenylphosphinate and 4-nitrophenyl acetate has been determined. In all three cases there is a simple linear dependency of the reaction rate on the concentration of the anionic form of the nitroimidazole. Previous results had suggested self-inhibition by the nucleophile occurred in the 2-methyl-5-nitroimidazole catalysed hydrolysis of 4-nitrophenyl diphenylphosphinate; this hypothesis is no longer tenable. Comparison of the reactivity of 2-methyl -substituted nitroimidazolides to that of the corresponding unsubstituted species suggests that 2-alkyl-substituted nitroionidazole surfactants would not be significantly worse catalysts of the hydrolysis of organophosphorus species than their 4-substituted analogues. Decontamination, Chemical reactivity, Displacement reactions, Nucleophilic reactions, Imidazoles, Nitroimidazoles, Phenoxides, Simulants, UV Spectrophotometry, Mechanism.

  4. Antimalarial Activity of C-10 Substituted Triazolyl Artemisinin.

    Science.gov (United States)

    Park, Gab-Man; Park, Hyun; Oh, Sangtae; Lee, Seokjoon

    2017-12-01

    We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate.

  5. A microwave-catalyzed rapid, efficient and ecofriendly synthesis of substituted pyrazol-5-ones

    Directory of Open Access Journals (Sweden)

    RAHUL P. GAVANDE

    2003-10-01

    Full Text Available A series of 1-(3,4-dihydro-3-oxo-2H-1,4-benzoxazine-2-carbonyl-3-methyl-4-(substituted phenylhydrazono-2-pyrazolin-5-ones have been synthesized by the reaction of 2H-3,4-dihydro-3-oxo-1,4-benzoxazine-2-carboxylic acid hydrazide with substituted acetoacetic ester derivatives using acetic acid as solvent under microwave irradiation (MWI, as well as by conventional methods. The reaction rate is enhanced tremendously and the yields are improved under MWI as compared to conventional methods.

  6. Structure-activity relationships for novel drug precursor N-substituted-6-acylbenzothiazolon derivatives: A theoretical approach

    Science.gov (United States)

    Sıdır, Yadigar Gülseven; Sıdır, İsa

    2013-08-01

    In this study, the twelve new modeled N-substituted-6-acylbenzothiazolon derivatives having analgesic analog structure have been investigated by quantum chemical methods using a lot of electronic parameters and structure-activity properties; such as molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, q-, qH+, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (ω), heat of formation (HOF), molar refractivity (MR), octanol-water partition coefficient (log P), thermochemical properties (entropy (S), capacity of heat (Cv)); as to investigate activity relationships with molecular structure. The correlations of log P with Vm, MR, ω, EA, EHOMO - ELUMO (ΔE), HOF in aqueous phase, χ, μ, S, η parameters, respectively are obtained, while the linear relation of log P with IP, Cv, HOF in gas phase are not observed. The log P parameter is obtained to be depending on different properties of compounds due to their complexity.

  7. Selenocysteine in thiol/disulfide-like exchange reactions.

    Science.gov (United States)

    Hondal, Robert J; Marino, Stefano M; Gladyshev, Vadim N

    2013-05-01

    Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.

  8. Computational and experimental studies on stabilities, reactions and reaction rates of cations and ion-dipole complexes

    NARCIS (Netherlands)

    Ervasti, H.K.

    2008-01-01

    In this thesis, ion stability, ion-molecule reactions and reaction rates are studied using mass spectrometry and molecular modelling. In Chapter 2 the effect of functional group substitution on neutral and ionised ketene are studied. Electron-donating substituents show a stabilising positive

  9. Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

    Science.gov (United States)

    Cichocki, Joseph A; Smith, Gregory J; Morris, John B

    2014-11-01

    The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All

  10. Kinetical Analysis of the Mechanism of the Ligand Substitution Reaction between the Ethylenediamine-N,N{sup `}-bis[2-(2-hydroxyphenyl) acetato] cadmate (2) Ion and the Ethylenediaminetetraacetatoferrate (3) Ion; Echienjiami-N,N`-bisu[2-(2-hidorokishifueniru)asetato] kadomiume (2) san eion to echirenjiamintetoraasetato tetsu (3) san ion tono aida no haiishi okikae hanno no hanno sokudoron ni yoru kiko kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Katsuyama, Tetsuo.; Orihara, Katsuo.; Takahata, Yasuyuki.; Yokota, Toshiyuki. [Yamagata University, Yamagata (Japan). Department of Materials Science and Enginering

    1998-12-10

    The kinetics of the ligand substitution reaction between the ethylenediamine-N,N`- bis[2-(2-hydroxyphenyl) acetato] cadmate (2) ion and the ethylenediaminetetraacetatoferrate (3) ion were carried out at 25 degreeC and ionic strength=0.1 mol dm{sup -3}. The substitution reaction was shown to proceed by a chain reaction mechanism where the chain propageting steps are the reactions of metal complexes with metal ions. The properties of the metal chain reaction mechanism are discussed. The metal-substitution of [Fe (edta)]{sup -} with cadmium ion was studied by the use of the chain reactins. The observed rae constants of the reaction were separated into two rate constants. The mechamism of the reactions is discussed. (author)

  11. Kinetical Analysis of the Mechanism of the Ligand Substitution Reaction between the Ethylenediamine-N,N[sup ']-bis[2-(2-hydroxyphenyl) acetato] cadmate (2) Ion and the Ethylenediaminetetraacetatoferrate (3) Ion. Echienjiami-N,N'-bisu[2-(2-hidorokishifueniru)asetato] kadomiume (2) san eion to echirenjiamintetoraasetato tetsu (3) san ion tono aida no haiishi okikae hanno no hanno sokudoron ni yoru kiko kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Katsuyama, Tetsuo.; Orihara, Katsuo.; Takahata, Yasuyuki.; Yokota, Toshiyuki. (Yamagata University, Yamagata (Japan). Department of Materials Science and Enginering)

    1998-12-10

    The kinetics of the ligand substitution reaction between the ethylenediamine-N,N'- bis[2-(2-hydroxyphenyl) acetato] cadmate (2) ion and the ethylenediaminetetraacetatoferrate (3) ion were carried out at 25 degreeC and ionic strength=0.1 mol dm[sup -3]. The substitution reaction was shown to proceed by a chain reaction mechanism where the chain propageting steps are the reactions of metal complexes with metal ions. The properties of the metal chain reaction mechanism are discussed. The metal-substitution of [Fe (edta)][sup -] with cadmium ion was studied by the use of the chain reactins. The observed rae constants of the reaction were separated into two rate constants. The mechamism of the reactions is discussed. (author)

  12. New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity.

    Science.gov (United States)

    Ćoćić, Dušan; Jovanović, Snežana; Nišavić, Marija; Baskić, Dejan; Todorović, Danijela; Popović, Suzana; Bugarčić, Živadin D; Petrović, Biljana

    2017-10-01

    Six new dinuclear Pd(II) complexes, [{Pd(2,2'-bipy)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd1), [{Pd(dach)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd2), [{Pd(en)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd3), [{Pd(2,2'-bipy)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd4), [{Pd(dach)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd5) and [{Pd(en)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd6) (where 2,2'-bipy=2,2'-bipyridyl, pz=pyrazine, dach=trans-(±)-1,2-diaminocyclohexane, en=ethylenediamine, 4,4'-bipy=4,4'-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, 1 H NMR and MALDI-TOF mass spectrometry. The pK a values of corresponding diaqua complexes were determined by spectrophotometric pH titration. Substitution reactions with thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys), l-histidine (l-His) and guanosine-5'-monophosphate (5'-GMP) were studied under the pseudo-first order conditions at pH7.2. Reactions of Pd1 with Tu, l-Met and l-Cys were followed by decomposition of complexes, while structures of dinuclear complexes were preserved during the substitution with nitrogen donors. Interactions with calf-thymus DNA (CT-DNA) were followed by absorption spectroscopy and fluorescence quenching measurements. All complexes can bind to CT-DNA exhibiting high intrinsic binding constants (K b =10 4 -10 5 M -1 ). Competitive studies with ethidium bromide (EB) have shown that complexes can displace DNA-bound EB. High values of binding constants towards bovine serum albumin protein (BSA) indicate good binding affinity. Finally, all complexes showed moderate to high cytotoxic activity against HeLa (human cervical epithelial carcinoma cell lines) and MDA-MB-231 (human breast epithelial carcinoma cell lines) tumor cell lines inducing apoptotic type cell death, whereas normal fibroblasts were significantly less sensitive. The impact on cell cycle of these cells was distinctive, where Pd4, Pd5 and Pd6 showed the most prominent effect arresting MDA-MB-231 (human lung fibroblast cell lines) cell in G1/S phase of cell

  13. Organoruthenium (II) complexes produced by insertion reactions of substituted olefins into a hydrido-ruthenium bond

    Energy Technology Data Exchange (ETDEWEB)

    Hiraki, Katsuma; Sasada, Yoko; Kitamura, Tsuneyuki [Nagasaki Univ. (Japan)

    1980-04-01

    Dimethyl fumarate, 2-vinylpyridine, and acrylonitrile insert into a H-Ru bond of (RuClH(CO)(PPh/sub 3/)/sub 3/) (1) to yield new substituted alkylruthenium(II) complexes. Methyl sorbate also reacted with 1 to give a new substituted eta/sup 3/-allylruthenium(II) complex.

  14. Synthesis and Antimicrobial Activity of Some Novel Substituted Piperazinyl-quinazolin-3(4H-ones

    Directory of Open Access Journals (Sweden)

    N. M. Raghavendra

    2008-01-01

    Full Text Available Several substituted-quinazolin-3(4H-ones were synthesized by condensation of 2-chloro-N-(4-oxo-substituted-quinazolin-3(4H-yl-acetamides with various substituted piperazines through single step reaction. Elemental analysis, IR, 1HNMR and mass spectral data confirmed the structure of the newly synthesized compounds. Synthesized quinazolin-4-one derivatives were investigated for their antibacterial and antifungal activities.

  15. The synthesis of no-carrier-added DL-4-[18F]fluorodeprenyl via the nucleophilic aromatic substitution reaction

    International Nuclear Information System (INIS)

    Plenevaux, Alain; Guillaume, Marcel

    1991-01-01

    No-carrier-added DL-α-methyl-β-4-[ 18 F]fluorophenyl-N-methyl-N-propynylethylamine (DL-4-[ 18 F]fluorodeprenyl) was synthesized via a 3-step procedure. The overall yield was 11%, the synthesis time was 90 min and the specific activity >0.57 Ci/μmol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[ 18 F]fluorodeprenyl in mice at 1, 10 and 50 min was also measured and showed that metabolic defluorination was not significant. Clearance or radioactivity from brain after injection of DL-4-[ 18 F]fluorodeprenyl was more rapid than that previously observed for [ 11 C]L-deprenyl. (author)

  16. Gold-catalyzed Alkyne Hydroxylation: Synthesis of 2-Substituted Benzo[b]furan Compounds

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuan; XIN Zhi-Jun; XUE Ji-Jun; LI Ying

    2008-01-01

    A strategy concerning the synthesis of 2-substituted benzo[b]furan compounds from o-alkynyl phenols via a gold-catalyzed alkyne hydroxylation is described, which allows the rapid synthesis of various 2-substituted benzo[b]furan derivatives in excellent yields under mild conditions. The o-alkynyl phenol precursors were readily prepared with a Sonogashira coupling reaction.

  17. Substitution and protonation reactions of nitrilotriaceta tochromium(lll) ions

    CSIR Research Space (South Africa)

    Visser, HG

    1994-04-01

    Full Text Available The reaction of NH4[Cr(NTA)(H2O)2] (NTA = nitrilotriacetic acid) with H+ has been studied at different temperatures and a rate constant of 1.27(3) x 10(-2) S-1 was obtained at 25.1-degrees-C. It is proposed that the reaction involves the formation...

  18. Photocure Reactions of Photoreactive Prepolymers with Cinnamate Groups

    International Nuclear Information System (INIS)

    Kim, Whan Gun

    2011-01-01

    The photoreactive prepolymers with multifunctional cinnamate and bisphenol A type cinnamate groups that could perform photodimerization without photoinitiators were synthesized by the reaction of t-cinnamic acids (CAs) and epoxy resins. Their photocure reaction rates and the extent of reaction conversion were measured with Fourier transform infrared spectroscopy, and these increased with the intensity of UV irradiation. The experimental data of these reaction rates showed the characteristics of nth-order kinetics reaction, and all kinetic constants of each photoreactive polymer with this equation were summarized. Although the GTR-1800-HCA and KWG1-EP-HCA with hydroxyl group substituted cinnamate showed lower reaction conversion rates and rate constant than GTR-1800-CA and KWG1-EP-CA with an unsubstituted cinnamate group, GTR-1800-MCAand KWG1-EP-MCA with methoxy group substituted cinnamate showed similar and higher reaction conversion rates than the former, respectively. These results were explained in terms of segmental mobility for photopolymerization by molecular interactions

  19. Synthesis and characterization of new meso-substituted ...

    Indian Academy of Sciences (India)

    WINTEC

    tems. 10. Their ability to carry out the reactions rather unusual in organic chemistry has been the object of intensive investigations aiming to utilize them as a model compounds for biological systems and as catalysts. 11. Therefore, the synthesis of well defined meso-substituted unsymmetrical porphyrin deriva- tives (A3B) is ...

  20. γ-Alumina Nanoparticle Catalyzed Efficient Synthesis of Highly Substituted Imidazoles

    Directory of Open Access Journals (Sweden)

    Bandapalli Palakshi Reddy

    2015-10-01

    Full Text Available γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and the reusability of catalyst were the other advantages of this developed protocol.

  1. Kinetic modeling of electron transfer reactions in photosystem I complexes of various structures with substituted quinone acceptors.

    Science.gov (United States)

    Milanovsky, Georgy E; Petrova, Anastasia A; Cherepanov, Dmitry A; Semenov, Alexey Yu

    2017-09-01

    The reduction kinetics of the photo-oxidized primary electron donor P 700 in photosystem I (PS I) complexes from cyanobacteria Synechocystis sp. PCC 6803 were analyzed within the kinetic model, which considers electron transfer (ET) reactions between P 700 , secondary quinone acceptor A 1 , iron-sulfur clusters and external electron donor and acceptors - methylviologen (MV), 2,3-dichloro-naphthoquinone (Cl 2 NQ) and oxygen. PS I complexes containing various quinones in the A 1 -binding site (phylloquinone PhQ, plastoquinone-9 PQ and Cl 2 NQ) as well as F X -core complexes, depleted of terminal iron-sulfur F A /F B clusters, were studied. The acceleration of charge recombination in F X -core complexes by PhQ/PQ substitution indicates that backward ET from the iron-sulfur clusters involves quinone in the A 1 -binding site. The kinetic parameters of ET reactions were obtained by global fitting of the P 700 + reduction with the kinetic model. The free energy gap ΔG 0 between F X and F A /F B clusters was estimated as -130 meV. The driving force of ET from A 1 to F X was determined as -50 and -220 meV for PhQ in the A and B cofactor branches, respectively. For PQ in A 1A -site, this reaction was found to be endergonic (ΔG 0  = +75 meV). The interaction of PS I with external acceptors was quantitatively described in terms of Michaelis-Menten kinetics. The second-order rate constants of ET from F A /F B , F X and Cl 2 NQ in the A 1 -site of PS I to external acceptors were estimated. The side production of superoxide radical in the A 1 -site by oxygen reduction via the Mehler reaction might comprise ≥0.3% of the total electron flow in PS I.

  2. Synthesis and biological evaluation of 2-substituted benzimidazole derivatives

    Directory of Open Access Journals (Sweden)

    Gurusamy Mariappan

    2015-09-01

    Full Text Available A novel series of 2-substituted benzimidazole derivatives (3a–3j were synthesized by the reaction of 2-chloro methyl benzimidazole with substituted primary aromatic amines. All the compounds were characterized by UV, IR, 1H NMR, mass spectral data and CHN elemental analysis. The synthesized derivatives were screened for analgesic and anti-inflammatory activities. All the compounds showed significant effect at 100 mg/kg p.o. and the experimental data are statistically significant at p < 0.01 level.

  3. Synthesis and Fungicidal activity of some sulphide derivatives of O-Ethyl-N-substituted phenylcarbamates

    International Nuclear Information System (INIS)

    Imeokparia, F.A.

    2006-01-01

    Monosulphides of O-ethyl-N-substituted phenylcarbamates were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur dichloride, while the corresponding disulphides were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur monochloride. The synthesized compounds were characterized by elemental analysis, thin layer chromatography (TLC), Fourier-transform infrared, and /sup 1/H and /sup 13/C nuclear magnetic resonance spectroscopic techniques. In vitro fungicidal assay of these sulphides against Fusarium oxysporum, Aspergillus niger, Aspergillus flavus and Rhizopus stolonifer showed that they had Greater fungicidal activity than their parent carbamates. The synthesized sulphides were more active towards A. Niger and A. flavus. Unlike the parent carbamates, the type of substituents attached to the aromatic nucleus of these sulphides had little or no effect on their fungicidal activity as there was insignificant variation in the fungicidal activity of the monosulphide and the disulphide derivatives of O-ethyl-N-substituted phenylcarbamates. (author)

  4. The mechanism of the modified Ullmann reaction

    NARCIS (Netherlands)

    Sperotto, Elena; Klink, Gerard P.M. van; Koten, Gerard van; Vries, Johannes G. de

    2010-01-01

    The copper-mediated aromatic nucleophilic substitution reactions developed by Fritz Ullmann and Irma Goldberg required stoichiometric amounts of copper and very high reaction temperatures. Recently, it was found that addition of relatively cheap ligands (diamines, aminoalcohols, diketones, diols)

  5. Carbonyl-Olefin Exchange Reaction: Present State and Outlook

    Science.gov (United States)

    Kalinova, Radostina; Jossifov, Christo

    The carbonyl-olefin exchange reaction (COER) is a new reaction between carbonyl group and olefin double bond, which has a formal similarity with the olefin metathesis (OM) - one carbon atom in the latter is replaced with an oxygen atom. Till now the new reaction is performed successfully only when the two functional groups (carbonyl group and olefin double bond) are in one molecule and are conjugated. The α, β-unsaturated carbonyl compounds (substituted propenones) are the compounds with such a structure. They polymerize giving substituted polyacetylenes. The chain propagation step of this polymerization is in fact the COER. The question arises: is it possible the COER to take place when the two functional groups are not in one molecule and are not conjugated, and could this reaction became an alternative of the existing carbonyl olefination reactions?

  6. Chemistry and electrochemistry in trifluoroacetic acid. Comparison with acetic acid

    International Nuclear Information System (INIS)

    Petit, Gerard

    1972-01-01

    As the trifluoroacetic acid is, with the acetic acid, one of most often used carboxylic acids as solvent, notably in organic chemistry, this research thesis addresses some relatively simple complexing and redox reactions to highlight the peculiar feature of this acid, and to explain its very much different behaviour with respect to acetic acid. The author develops the notion of acidity level in solvents of low dielectric constant. The second part addresses a specific solvent: BF 3 (CH 3 COOH) 2 . The boron trifluoride strengthens the acidity of acetic acid and modifies its chemical and physical-chemical properties. In the third part, the author compares solvent properties of CF 3 COOH and CH 3 COOH. Noticed differences explain why the trifluoroacetic acid is a more interesting reaction environment than acetic acid for reactions such as electrophilic substitutions or protein solubilisation [fr

  7. Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.

    Science.gov (United States)

    Kellner, Stefanie; Kollar, Laura Bettina; Ochel, Antonia; Ghate, Manjunath; Helm, Mark

    2013-01-01

    Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.

  8. The Synthesis of Substituted Piperazine-cholesterol Conjugates for ...

    African Journals Online (AJOL)

    A small library of cholesterol-piperazine conjugates were synthesized by the reaction of cholesteryl chloroformate with a set of substituted piperazines in dichloromethane at room temperature. The conjugates, all obtained in good to excellent yields, were synthesized to be key components of nucleic acid transfection ...

  9. The electronic configuration of substitutional Fe in silicon

    CERN Document Server

    Weyer, G; Fanciulli, M; Fedosseev, V; Gunnlaugsson, H P; Mishin, V I; Sielemann, R

    1999-01-01

    Ion implantations of radioactive /sup 57/Mn/sup +/ into differently doped silicon single crystals held at 300-600 K have been utilized for /sup 57/Fe Mossbauer studies of interstitial and substitutional Fe. Site and charge state assignments have been made on the basis of the determined hyperfine interaction parameters and Debye temperatures. Substantial fractions of substitutional /sup 57/Mn probe atoms are proposed to occur due to annealing reactions. This site is maintained in the subsequent decay to /sup 57/Fe by

  10. KINETICS OF SUBSTITUTION OF CIS-BIS(MALONATO ...

    African Journals Online (AJOL)

    Preferred Customer

    In this process, it indicated that the substitution reaction occurs through an Ia mechanism in the ... isotopic water exchange and other anation processes. ... The potassium salt of cis-bis(malonato)diaquochromate(III) was prepared by a reported [26] ... of the synthesized metal complex showed maxima at 415 nm (ε = 41.6 M-1 ...

  11. Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

    Directory of Open Access Journals (Sweden)

    Michele Mari

    2014-08-01

    Full Text Available The reaction of 3-substituted indoles with dehydroalanine (Dha derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization.

  12. Hydrazine in the Ugi Tetrazole Reaction

    NARCIS (Netherlands)

    Patil, Pravin; Zhang, Ji; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Dömling, Alexander

    2016-01-01

    We describe the hitherto unknown use of N-Boc-protected hydrazine in the Ugi tetrazole reaction to access a library of highly substituted 5-(hydrazinomethyl)-1-methyl-1H-tetrazoles. The reaction is very versatile and good to high yielding. A one-pot, two-step procedure is given.

  13. Synthesis and antibacterial activities of N-substituted maleopimarimide

    Directory of Open Access Journals (Sweden)

    LI Hui

    2016-02-01

    Full Text Available With Macrogol 600(PEG-600 as solvent and toluene as dehydrant,eight N-Substituted maleopimarimide compounds were synthesized from maleopimaric acid and aniline or its derivatives by one-step reaction;Their structures were confirmed and the antimicrobial activities of these compounds were also preliminarily investigated.

  14. A quantitative approach to nucleophilic organocatalysis

    Directory of Open Access Journals (Sweden)

    Herbert Mayr

    2012-09-01

    Full Text Available The key steps in most organocatalytic cyclizations are the reactions of electrophiles with nucleophiles. Their rates can be calculated by the linear free-energy relationship log k(20 °C = sN(E + N, where electrophiles are characterized by one parameter (E and nucleophiles are characterized by the solvent-dependent nucleophilicity (N and sensitivity (sN parameters.Electrophilicity parameters in the range –10 E N N parameters of enamines derived from phenylacetaldehyde and MacMillan’s imidazolidinones one can rationalize why only strong electrophiles, such as stabilized carbenium ions (–8 E E = –6.75, are suitable electrophiles for enamine activated reactions with imidazolidinones. Several mechanistic controversies concerning iminium and enamine activated reactions could thus be settled by studying the reactivities of independently synthesized intermediates.Kinetic investigations of the reactions of N-heterocyclic carbenes (NHCs with benzhydrylium ions showed that they have similar nucleophilicities to common organocatalysts (e.g., PPh3, DMAP, DABCO but are much stronger (100–200 kJ mol–1 Lewis bases. While structurally analogous imidazolylidenes and imidazolidinylidenes have comparable nucleophilicities and Lewis basicities, the corresponding deoxy Breslow intermediates differ dramatically in reactivity. The thousand-fold higher nucleophilicity of 2-benzylidene-imidazoline relative to 2-benzylidene-imidazolidine is explained by the gain of aromaticity during electrophilic additions to the imidazoline derivatives. O-Methylated Breslow intermediates are a hundred-fold less nucleophilic than deoxy Breslow intermediates.

  15. Nucleophilic Substitution Reactions of N-Methyl α-Bromoacetanilides with Benzylamines in Dimethyl Sulfoxide

    International Nuclear Information System (INIS)

    Adhikary, Keshab Kumar; Lee, Hai Whang

    2011-01-01

    Kinetic studies of the reactions of N-methyl-Y-α-bromoacetanilides with substituted X-benzylamines have been carried out in dimethyl sulfoxide at 25.0 .deg. C. The Hammett plots for substituent X variations in the nucleophiles (log k N vs σ X ) are slightly biphasic concave upwards/downwards, while the Bronsted plots (log k N vs pK a ) are biphasic concave downwards with breakpoints at X = H. The Hammett plots for substituent Y variations in the substrates (log k N vs σ Y ) are biphasic concave upwards/downwards with breakpoints at Y = H. The cross-interaction constant ρ XY values are all negative: ρ XY = -0.32 for X = Y = electron-donating: -0.22 for X = electron-withdrawing and Y = electron-donating: -1.80 for X = electron-donating and Y = electronwithdrawing: -1.43 for X = Y = electron-withdrawing substituents. Deuterated kinetic isotope effects are primary normal (k H /k D > 1) for Y = electron-donating, while secondary inverse (k H /k D < 1) for Y = electronwithdrawing substituent. The proposed mechanisms of the benzylaminolyses of N-methyl-Y-α-bromoacetanilides are a concerted mechanism with a five membered ring TS involving hydrogen bonding between hydrogen (deuterium) atom in N-H(D) and oxygen atom in C = O for Y = electron-donating, while a concerted mechanism with an enolate-like TS in which the nucleophile attacks the α-carbon for Y = electronwithdrawing substituents

  16. Synthesis of deuterium-labeled analogs of the lipid hydroperoxide-derived bifunctional electrophile 4-oxo-2(E)-nonenal.

    Science.gov (United States)

    Arora, Jasbir S; Oe, Tomoyuki; Blair, Ian A

    2011-05-15

    Lipid hydroperoxides undergo homolytic decomposition into the bifunctional 4-hydroxy-2( E )-nonenal and 4-oxo-2( E )-nonenal (ONE). These bifunctional electrophiles are highly reactive and can readily modify intracellular molecules including glutathione (GSH), deoxyribonucleic acid (DNA) and proteins. Lipid hydroperoxide-derived bifunctional electrophiles are thought to contribute to the pathogenesis of a number of diseases. ONE is an α , β -unsaturated aldehyde that can react in multiple ways and with glutathione, proteins and DNA. Heavy isotope-labeled analogs of ONE are not readily available for conducting mechanistic studies or for use as internal standards in mass spectrometry (MS)-based assays. An efficient onestep cost-effective method has been developed for the preparation of C-9 deuterium-labeled ONE. In addition, a method for specific deuterium labeling of ONE at C-2, C-3 or both C-2 and C-3 has been developed. This latter method involved the selective reduction of an intermediate alkyne either by lithium aluminum hydride or lithium aluminum deuteride and quenching with water or deuterium oxide. The availability of these heavy isotope analogs will be useful as internal standards for quantitative studies employing MS and for conducting mechanistic studies of complex interactions between ONE and DNA bases as well as between ONE and proximal amino acid residues in peptides and proteins.

  17. SYNTHESIS OF SUBSTITUTED QUINOLINE-3-CARBALDEHYDES

    Directory of Open Access Journals (Sweden)

    L. G. Klad'ko

    2015-12-01

    Full Text Available Dehalogenation of а series substituted 2-chloroquinoline-3-carbaldehydes was investigated. It was found that zinc dust in alkali ethanol practically do not react with 2-chloro-3-(1,3-dioxolan-2-yl-7-methylquinolines for a 5 day at ambient temperature. Increase temperature to boiling point of reaction mixture lead to increase yield 7-methylquinoline-3-carbaldehyde to 12.5%. This reaction with 2-chloro-3-dimetoxymetyl-7-methylquinoline give 26.5 above aldehyde. Replacement of ethanol to methanol give only traces of desired aldehyde. Neither 2-chloro-7-methylquinoline-3-carbaldehyde, nor his acetals do not react with sodium dithionite. Furthermore for activation of halogen we replaced chloraldehydes to iodoaldehydes by Finkelstein reaction, then protect aldehyde function by formation of dimethylacetals and treatment his by sodium dithionite in mixture pyridine-water. Desired aldehydes was obtained with poor to moderate yields. Increasing yields of this reaction is goal our further investigations.

  18. Newly constructed stable reporter cell lines for mechanistic studies on electrophile-responsive element-mediated gene expression reveal a role for flavonoid planarity.

    NARCIS (Netherlands)

    Boerboom, A.M.A.; Vermeulen, M.; Woude, H. van der; Bremer, B.I.; Lee-Hilz, Y.Y.; Kampman, E.; Bladeren, P.J. van; Rietjens, I.M.C.M.; Aarts, J.

    2006-01-01

    The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression modulation by certain food components. Two stably transfected luciferase reporter cell lines were developed, EpRE(hNQO1)-LUX and EpRE(mGST-Ya)-LUX, based on EpRE sequences from

  19. Newly constructed stable reporter cell lines for mechanistic studies on electrophile-responsive element-mediated gene expression reveal a role for flavonoid planarity

    NARCIS (Netherlands)

    Boerboom, A.M.J.F.; Vermeulen, M.; Woude, H. van der; Bremer, B.I.; Lee-Hilz, Y.Y.; Kampman, E.; Bladeren, P.J. van; Rietjens, I.M.C.M.; Aarts, J.M.M.J.G.

    2006-01-01

    The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression modulation by certain food components. Two stably transfected luciferase reporter cell lines were developed, EpRE(hNQO1)-LUX and EpRE(mGST-Ya)-LUX, based on EpRE sequences from

  20. The Ligand Substitution Reactions of Hydrophobic Vitamin B ...

    African Journals Online (AJOL)

    NJD

    Vitamin B. 12. Derivatives. Reaction of Cobyric Acid. Heptapropyl Ester with Heterocyclic N-donor Ligands. Mohamed S.A. .... RESEARCH ARTICLE. M.S.A. Hamza ..... neutralized with NaHCO3 and treated with excess KCN to give. DCCbs-Pr.

  1. Kinetic study of the substitution of [Tc(tu)6]3+ by polyaminocarboxylic acids

    International Nuclear Information System (INIS)

    Torres, J.; Gonalez, R.; Kremer, C.; Kremer, E.; Leon, A.

    1997-01-01

    Substitution route has been traditionally proposed for the synthesis of new Tc complexes. In particular, Tc(III) coordination compounds can be successfully prepared by substitution on [Tc(tu) 6 ] 3+ (tu = thiourea). In this substitution reaction, TcO 2 is a side product that should be minimized. The success of these synthetic procedures is based on controlling the reaction conditions in order that pure substitution could be faster enough compared to decomposition. In this work, the substitution of [Tc(tu) 6 ] 3+ by polycarboxylic acids (ethylenediaminetetraacetate (edta), diethylenetriaminepentaacetate (dtpa), N-tris(2-amino-ethyl)amin N', N', N '' , N '' , N ''' , N ''' -hexaacetate (ttaha) and 3-bromo-2,4,6-trimethylacetanilideiminodiacetate (mebrofenin)) is kinetically studied in order to obtain the best conditions for preparing Tc(III) complexes. As a general conclusion, substitution constants are strongly dependent on the pH. k obs values fall in the range 0.1-13 x 10 -2 M -1 s -1 , depending on the pH value and the temperature. No strong differences are found with different incoming ligands. For the four ligands (L), a straight line is obtained when plotting log k obs /([L m- ]) vs. pH. This is consistent with a rate constant k obs = {k 0 + Σk n [H + ] n /K n }[L m- ], where n represents the charge of the incoming ligand and m is the maximum value of n. (orig.)

  2. Ion-Molecule Reaction Dynamics.

    Science.gov (United States)

    Meyer, Jennifer; Wester, Roland

    2017-05-05

    We review the recent advances in the investigation of the dynamics of ion-molecule reactions. During the past decade, the combination of single-collision experiments in crossed ion and neutral beams with the velocity map ion imaging detection technique has enabled a wealth of studies on ion-molecule reactions. These methods, in combination with chemical dynamics simulations, have uncovered new and unexpected reaction mechanisms, such as the roundabout mechanism and the subtle influence of the leaving group in anion-molecule nucleophilic substitution reactions. For this important class of reactions, as well as for many fundamental cation-molecule reactions, the information obtained with crossed-beam imaging is discussed. The first steps toward understanding micro-solvation of ion-molecule reaction dynamics are presented. We conclude with the presentation of several interesting directions for future research.

  3. Aromatic C-nitrosation of a bioactive molecule. Nitrosation of minoxidil.

    Science.gov (United States)

    González-Jiménez, Mario; Arenas-Valgañón, Jorge; Calle, Emilio; Casado, Julio

    2011-10-26

    Minoxidil (2,4-diamino-6-(piperidin-1'-yl)pyrimidine N(3)-oxide; CASRN 38304-91-5) is a bioactive molecule with several nitrosatable groups widely used as an antihypertensive and antialopecia agent. Here the nitrosation of minoxidil was investigated. The conclusions drawn are as follows: (i) In the pH = 2.3-5.0 range, the minoxidil molecule undergoes aromatic C-nitrosation by nitrite. The dominant reaction was C-5 nitrosation through a mechanism that appears to consist of an electrophilic attack on the nitrosatable substrate by H(2)NO(2)(+)/NO(+), followed by a slow proton transfer; (ii) the reactivity of minoxidil as a C-nitrosatable substrate proved to be 7-fold greater than that of phenol, this being attributed to the preferred para- and ortho-orientations of the two -NH(2) groups at positions 2 and 4 of the minoxidil molecule, which activate electrophilic substitution in the C-5 position through their mesomeric effect. The N-nitrosominoxidil resulting from the nitrosation could be potentially harmful to the minoxidil users.

  4. Stereochemistry of substitution at trico-ordinate phosphorus

    DEFF Research Database (Denmark)

    Nielsen, John; Dahl, Otto

    1984-01-01

    A series of reactions of ring-substituted 1,3,2-dioxaphospholanes, 1,3,2-oxazaphospholanes, 1,2-oxaphospholes, and phosphetanes bearing the leaving groups Cl, OR, or NR2 on phosphorus, with the nucleophiles HCl, MeO-, MeOH, PhOH, Me2NH, Et2NH, and [CH 2]5NH have been studied. N.m.r. signals (1H...

  5. Synthesis and molecular structures of 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles

    International Nuclear Information System (INIS)

    Wu, J.W.; Zhao, L.; Wang, Z.; Gu, H.; Chen, W.; Zhao, C.

    2016-01-01

    Five novel 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles were synthesized by a three-step route. Under microwave irradiation, the p-substituted phenols were firstly O-carboxymethylated to prepare the corresponding p-substituted phenoxymethyl acids, which then reacted with o-phenylendiamine to get the key intermediates 2-(p-substituted) phenoxymethyl benzimidazole. Finally, the solid-liquid phase transfer catalysis method, where tetrabutyl ammonium bromide (TBAB) was used as the catalyst, was applied to synthesize the target compounds c/sub 1/-c/sub 5/ by the N-hydroxyethylation reaction with 2-chloroethyl alcohol. The structures of the obtained compounds were well characterized and confirmed by elemental analysis, MS, IR, /sup 1/H NMR, /sup 13/C NMR and single-crystal X-ray diffraction analysis. (author)

  6. Unprecedented Spectroscopic and Computational Evidence for Allenyl and Propargyl Titanocene(IV) Complexes: Electrophilic Quenching of Their Metallotropic Equilibrium.

    Science.gov (United States)

    Ruiz-Muelle, Ana Belén; Oña-Burgos, Pascual; Ortuño, Manuel A; Oltra, J Enrique; Rodríguez-García, Ignacio; Fernández, Ignacio

    2016-02-12

    The synthesis and structural characterization of allenyl titanocene(IV) [TiClCp2 (CH=C=CH2 )] 3 and propargyl titanocene(IV) [TiClCp2 (CH2 -C≡C-(CH2 )4 CH3 )] 9 have been described for the first time. Advanced NMR methods including diffusion NMR methods (diffusion pulsed field gradient stimulated spin echo (PFG-STE) and DOSY) have been applied and established that these organometallics are monomers in THF solution with hydrodynamic radii (from the Stokes-Einstein equation) of 3.5 and 4.1 Å for 3 and 9, respectively. Full (1) H, (13) C, Δ(1) H, and Δ(13) C NMR data are given, and through the analysis of the Ramsey equation, the first electronic insights into these derivatives are provided. In solution, they are involved in their respective metallotropic allenyl-propargyl equilibria that, after quenching experiments with aromatic and aliphatic aldehydes, ketones, and protonating agents, always give the propargyl products P (when carbonyls are employed), or allenyl products A (when a proton source is added) as the major isomers. In all the cases assayed, the ratio of products suggests that the metallotropic equilibrium should be faster than the reactions of 3 and 9 with electrophiles. Indeed, DFT calculations predict lower Gibbs energy barriers for the metallotropic equilibrium, thus confirming dynamic kinetic resolution. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Radioiodination of ibuprofen with 125I and its biological behavior in mice

    International Nuclear Information System (INIS)

    Amin, A. M.; Abd El-bary, A.; Shoukry, M. and other

    2012-12-01

    A procedure for radioiodination of Ibuprofen with iodine-125 is carried out via an electrophilic substitution reaction. The reaction parameters were studied Ibuprofen concentration, pH of the reaction mixture, reaction time temperature, and different oxidizing agents to optimize the conditions for the labeling of Ibuprofen to abstain a high radiochemical yield of 1 25I -Ibuprofen (1 25I -Ib up). Using 3.7 MBq of of Na 1 25I , 100μg of ibuprofen as substrate and 100μg of iodogen as oxidizing agent in ethanol at 60 O C for 10 min, a maximum radiochemical yield of 1 25I -Ib up (78%) was obtained. The labeled compound was separated and purified from inactive Ibuprofen by means of high-pressure liquid chromatography (HPLC). The biological distribution in normal and inflamed mice indicates the suitability of radioiodinated Ibuprofen for imaging of inflammation only induced with turpentine oil. (Author)

  8. Quantum-chemical investigation of the 1,2-proton shift in protonated five-membered aromatic heterocycles

    International Nuclear Information System (INIS)

    Abronin, I.A.; Gorb, L.G.; Litvinov, V.P.

    1985-01-01

    Calculations of the energetics of the 1,2-proton shift in protonated five-membered aromatic heterocycles - pyrrole, furan, and thiophene - have been carried out by the SCF MO LCAO method in the MINDO/3 approximation and nonempirically on the OST-3GF (OST-3GF) basis. The general features of this process, and also the influence of solvation and of taking into account the vacant d-AOs of the sulfur atom in the protonated form of thiophene on the results of the calculation are considered. The results obtained have been used for a discussion of the activity and selectivity of the heterocycles considered in aromatic electrophilic substitution reactions

  9. Synthesis of geranylhydroquinone derivatives with potential cytotoxic activity

    Energy Technology Data Exchange (ETDEWEB)

    Baeza, Evelyn; Catalan, Karen; Pena-Cortes, Hugo; Espinoza, Luis, E-mail: luis.espinozac@usm.cl [Departamento de Quimica, Universidad Tecnica Federico Santa Maria, Valparaiso (Chile); Villena, Joan [Facultad de Medicina, Universidad de Valparaiso, Centro Regional de Estudios en Alimentos Saludables, Valparaiso (Chile); Carrasco, Hector [Departamento de Ciencias Quimicas, Universidad Andres Bello, Campus Vina del Mar (Chile)

    2012-07-01

    Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS) reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF{sub 3} {center_dot}Et{sub 2}O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human ibroblasts DHF. IC{sub 50} values were in the {mu}M range. (author)

  10. Quantum Dots Embedded in Graphene Nanoribbons by Chemical Substitution

    DEFF Research Database (Denmark)

    Carbonell-Sanroma, Eduard; Brandimarte, Pedro; Balog, Richard

    2017-01-01

    Bottom-up chemical reactions of selected molecular precursors on a gold surface can produce high quality graphene nanoribbons (GNRs). Here, we report on the formation of quantum dots embedded in an armchair GNR by substitutional inclusion of pairs of boron atoms into the GNR backbone. The boron...

  11. Maximum hardness and minimum polarizability principles through lattice energies of ionic compounds

    International Nuclear Information System (INIS)

    Kaya, Savaş; Kaya, Cemal; Islam, Nazmul

    2016-01-01

    The maximum hardness (MHP) and minimum polarizability (MPP) principles have been analyzed using the relationship among the lattice energies of ionic compounds with their electronegativities, chemical hardnesses and electrophilicities. Lattice energy, electronegativity, chemical hardness and electrophilicity values of ionic compounds considered in the present study have been calculated using new equations derived by some of the authors in recent years. For 4 simple reactions, the changes of the hardness (Δη), polarizability (Δα) and electrophilicity index (Δω) were calculated. It is shown that the maximum hardness principle is obeyed by all chemical reactions but minimum polarizability principles and minimum electrophilicity principle are not valid for all reactions. We also proposed simple methods to compute the percentage of ionic characters and inter nuclear distances of ionic compounds. Comparative studies with experimental sets of data reveal that the proposed methods of computation of the percentage of ionic characters and inter nuclear distances of ionic compounds are valid.

  12. Maximum hardness and minimum polarizability principles through lattice energies of ionic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Savaş, E-mail: savaskaya@cumhuriyet.edu.tr [Department of Chemistry, Faculty of Science, Cumhuriyet University, Sivas 58140 (Turkey); Kaya, Cemal, E-mail: kaya@cumhuriyet.edu.tr [Department of Chemistry, Faculty of Science, Cumhuriyet University, Sivas 58140 (Turkey); Islam, Nazmul, E-mail: nazmul.islam786@gmail.com [Theoretical and Computational Chemistry Research Laboratory, Department of Basic Science and Humanities/Chemistry Techno Global-Balurghat, Balurghat, D. Dinajpur 733103 (India)

    2016-03-15

    The maximum hardness (MHP) and minimum polarizability (MPP) principles have been analyzed using the relationship among the lattice energies of ionic compounds with their electronegativities, chemical hardnesses and electrophilicities. Lattice energy, electronegativity, chemical hardness and electrophilicity values of ionic compounds considered in the present study have been calculated using new equations derived by some of the authors in recent years. For 4 simple reactions, the changes of the hardness (Δη), polarizability (Δα) and electrophilicity index (Δω) were calculated. It is shown that the maximum hardness principle is obeyed by all chemical reactions but minimum polarizability principles and minimum electrophilicity principle are not valid for all reactions. We also proposed simple methods to compute the percentage of ionic characters and inter nuclear distances of ionic compounds. Comparative studies with experimental sets of data reveal that the proposed methods of computation of the percentage of ionic characters and inter nuclear distances of ionic compounds are valid.

  13. Synthesis and characterization of novel substituted N-benzothiazole-2-yl-acetamides

    Directory of Open Access Journals (Sweden)

    H.C. Sakarya

    2016-11-01

    Full Text Available Schiff base derivatives of benzothiazole 2a–e have been synthesized by reacting with substituted 2-aminobenzothiazole 1a–e and different substituted benzaldehydes 5a–e. The obtained Schiff bases reaction with NaBH4 has afforded the corresponding some novel amines 3a–e. The condensation of amines with chloroacetylchloride leads to novel amide derivatives 4a–e. The structures of the synthesized compounds are characterized by elemental analysis, IR, MS, 1H NMR and 13C NMR.

  14. Electrophilic Cleavage and Functionalization of Polyisobutylenes Bearing Unsaturations in the Backbone and Synthesis of Polymers for this Process

    Science.gov (United States)

    Campbell, Christopher Garrett

    Polyisobutylene is a polymer of high commercial and academic interest due to its low cost of synthesis, high gas barrier properties, and high chemical and oxidative stability. Polyisobutylene (PIB) can only be synthesized by the cationic polymerization of isobutylene (IB). Commercial processes are currently only capable of producing monofunctional PIB or copolymers thereof. The living cationic polymerization of isobutylene is capable of producing difunctional telechelic PIB, but at the expense of difficultly or expensively synthesized initiators. Thus there exists a need for new synthetic routes for multifunctional PIBs, which can be adopted on a commercial scale. In the first project, we demonstrated a new reaction, which is a subset of the Friedel Crafts alkylation reaction, in which the alkylating carbocation undergoes a cleavage reaction prior to reaction with the aromatic substrate. This reaction was discovered by the observation that when a PIB containing a large amount of coupled fraction was subjected to a mixture of protic and Lewis acids (HCl/TiCl4) in the presence of an alkoxybenzene compound, the coupled fraction was quantitatively converted to its constituent monofunctional chains, which became functionalized by the alkoxybenzene. In the second project, a commercial polymer, poly(isobutylene- co-isoprene) (butyl rubber) was used as a substrate upon which the aforementioned electrophilic cleavage and functionalization reaction was performed. The goal of this project was to degrade a high molecular weight, main-chain olefin-containing copolymer of isobutylene into low molecular weight difunctional telechelic polyisobutylenes. This general process, though not necessarily proceeding by the aforementioned novel chemical reaction, has been described in the literature as "constructive degradation." Though we were unable to synthesize truly telechelic polyisobutylenes by this method, we were able to demonstrate this method as a viable route to low molecular

  15. Catalytic Organometallic Reactions of Ammonia

    Science.gov (United States)

    Klinkenberg, Jessica L.

    2012-01-01

    Until recently, ammonia had rarely succumbed to catalytic transformations with homogeneous catalysts, and the development of such reactions that are selective for the formation of single products under mild conditions has encountered numerous challenges. However, recently developed catalysts have allowed several classes of reactions to create products with nitrogen-containing functional groups from ammonia. These reactions include hydroaminomethylation, reductive amination, alkylation, allylic substitution, hydroamination, and cross-coupling. This Minireview describes examples of these processes and the factors that control catalyst activity and selectivity. PMID:20857466

  16. 1,3- and 1,4-Substituted tetrazolium salts

    International Nuclear Information System (INIS)

    Voitekhovich, Sergei V; Gaponik, Pavel N; Ivashkevich, Oleg A

    2002-01-01

    The published data on the synthesis, physicochemical properties, structures and reactions of 1,3-(1,3,5)- and 1,4-(1,4,5)-substituted tetrazolium salts are systematised and generalised. Their applications as starting compounds in the preparative chemistry of heterocyclic derivatives and some other branches of science and technology are reviewed. The bibliography includes 122 references.

  17. Reaction Formulation: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    Reaction formation was studied by Sigmund Freud. This defense mechanism may be related to repression, substitution, reversal, and compensation (or over-compensation). Alfred Adler considered compensation a basic process in his individual psychology. Anna Freud discussed some defense mechanisms, and Bibring, Dwyer, Huntington, and Valenstein…

  18. Rh(II)-catalyzed reactions of differentially substituted bis(diazo) functionalities.

    Science.gov (United States)

    Bonderoff, Sara A; Padwa, Albert

    2013-08-16

    The chemoselective reaction of donor/acceptor (D/A) and acceptor/acceptor (A/A) diazo moieties in the same molecule was examined using 3-diazo-1-(ethyl 2-diazomalonyl)indolin-2-one under rhodium(II) catalysis. The D/A diazo group undergoes selective cyclopropanation as well as XH-insertion, leaving behind the second diazo group for a further intramolecular dipolar cycloaddition reaction.

  19. Multicomponent One-Pot Synthesis of Substituted Hantzsch Thiazole Derivatives Under Solvent Free Conditions

    Directory of Open Access Journals (Sweden)

    Bhaskar S. Dawane

    2009-01-01

    Full Text Available Thiazole derivatives were prepared by one-pot procedure by the reaction of α-haloketones, thiourea and substituted o-hydroxybenzaldehyde under environmentally solvent free conditions.

  20. Knock-Down of the IFR1 Protein Perturbs the Homeostasis of Reactive Electrophile Species and Boosts Photosynthetic Hydrogen Production in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Venkanna, Deepak; Südfeld, Christian; Baier, Thomas; Homburg, Sarah V; Patel, Anant V; Wobbe, Lutz; Kruse, Olaf

    2017-01-01

    The protein superfamily of short-chain dehydrogenases/reductases (SDR), including members of the atypical type (aSDR), covers a huge range of catalyzed reactions and in vivo substrates. This superfamily also comprises isoflavone reductase-like (IRL) proteins, which are aSDRs highly homologous to isoflavone reductases from leguminous plants. The molecular function of IRLs in non-leguminous plants and green microalgae has not been identified as yet, but several lines of evidence point at their implication in reactive oxygen species homeostasis. The Chlamydomonas reinhardtii IRL protein IFR1 was identified in a previous study, analyzing the transcriptomic changes occurring during the acclimation to sulfur deprivation and anaerobiosis, a condition that triggers photobiological hydrogen production in this microalgae. Accumulation of the cytosolic IFR1 protein is induced by sulfur limitation as well as by the exposure of C. reinhardtii cells to reactive electrophile species (RES) such as reactive carbonyls. The latter has not been described for IRL proteins before. Over-accumulation of IFR1 in the singlet oxygen response 1 ( sor1 ) mutant together with the presence of an electrophile response element, known to be required for SOR1-dependent gene activation as a response to RES, in the promoter of IFR1 , indicate that IFR1 expression is controlled by the SOR1-dependent pathway. An implication of IFR1 into RES homeostasis, is further implied by a knock-down of IFR1 , which results in a diminished tolerance toward RES. Intriguingly, IFR1 knock-down has a positive effect on photosystem II (PSII) stability under sulfur-deprived conditions used to trigger photobiological hydrogen production, by reducing PSII-dependent oxygen evolution, in C. reinhardtii . Reduced PSII photoinhibition in IFR1 knock-down strains prolongs the hydrogen production phase resulting in an almost doubled final hydrogen yield compared to the parental strain. Finally, IFR1 knock-down could be

  1. Reaction between nitracrine and glutathione: implications for hypoxic cell radiosensitization and cytotoxicity

    International Nuclear Information System (INIS)

    Wilson, W.R.; Anderson, R.F.

    1989-01-01

    Nitracrine (NC) is an electron affinic DNA intercalating agent and a potent hypoxia-selective cytotoxin and radiosensitizer in cell culture. Although NC is too cytotoxic and too rapidly metabolized to provide hypoxic cell radiosensitization in tumors, it is of mechanistic interest as an example of a DNA affinic radiosensitizer. We have observed a rapid chemical reaction between NC and reduced glutathione (GSH), which suggests that the observed potent in vitro cytotoxicity and radiosensitization might be dependent on thiol depletion by the large extracellular reservoir of drug. However, no GSH depletion was observed under conditions providing radiosensitization or rapid cell killing, and prior depletion of GSH by buthionine sulphoximine had no effect on cytotoxicity or formation of macromolecular adducts. Further, the intracellular reaction of NC with GSH is slower than predicted on the basis of the measured second order rate constant and the total intracellular concentrations of both species. The results are consistent with a role for DNA binding in protecting NC from reaction with GSH, and in improving the efficiency with which reduced electrophilic metabolites react with DNA in preference to GSH

  2. Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

    Directory of Open Access Journals (Sweden)

    Peter A. Wade

    2013-10-01

    Full Text Available The tin(IV-catalyzed reaction of β-nitrostyrene with (E-3-methyl-1,3-pentadiene in toluene afforded two major nitronic ester cycloadducts in 27% and 29% yield that arise from the reaction at the less substituted diene double bond. Also present were four cycloadducts from the reaction at the higher substituted diene double bond, two of which were the formal cycloadducts of (Z-3-methyl-1,3-pentadiene. A Friedel–Crafts alkylation product from the reaction of the diene, β-nitrostyrene, and toluene was also obtained in 10% yield. The tin(IV-catalyzed reaction of β-nitrostyrene with (Z-3-methyl-1,3-pentadiene in dichloromethane afforded four nitronic ester cycloadducts all derived from the reaction at the higher substituted double bond. One cycloadduct was isolated in 45% yield and two others are formal adducts of the E-isomer of the diene. The product formation in these reactions is consistent with a stepwise mechanism involving a zwitterionic intermediate. The initially isolated nitronic ester cycloadducts underwent tin(IV-catalyzed interconversion, presumably via zwitterion intermediates. Cycloadducts derived from the reaction at the less substituted double bond of (E-3-methyl-1,3-pentadiene underwent a [3,3]-sigmatropic rearrangement on heating to afford 4-nitrocyclohexenes. Cycloadducts derived from the reaction at the higher substituted diene double bond of either diene failed to undergo a thermal rearrangement. Rates and success of the rearrangement are consistent with a concerted mechanism possessing a dipolar transition state. An initial assessment of substituent effects on the rearrangement process is presented.

  3. Synthesis and Antimicrobial Activity of Novel Substituted Ethyl 2-(Quinolin-4-yl-propanoates

    Directory of Open Access Journals (Sweden)

    Yong Zhou

    2013-03-01

    Full Text Available Substituted 4-hydroxyquinolines were synthesized from anilines and diethyl 2-(ethoxymethylenemalonate by the Gould-Jacobs reaction via cyclization of the intermediate anilinomethylenemalonate followed by hydrolysis and decarboxylation. The 4-hydroxyquinolines reacted with phosphorous oxychloride to form 4-chloroquinolines, which reacted on heating with diethyl sodiomethylmalonate in DMF to yield moderate yields of substituted ethyl 2-(quinolin-4-ylpropanoates, many of which showed potent antimicrobial activity against Helicobacter pylori.

  4. Kinetic study on alkaline hydrolysis of Y-substituted phenyl X-substituted benzenesulfonates: Effects of changing nucleophile from azide to hydroxide ion on reactivity and transition-state structure

    International Nuclear Information System (INIS)

    Moon, Ji Hyun; Kim, Min Young; Han, So Yeop; Um, Ik Hwan

    2015-01-01

    Second-order rate constants (math formula) for alkaline hydrolysis of 2,4-dinitrophenyl X-substituted benzenesulfonates (1a–1f) and Y-substituted phenyl 4-nitrobezenesulfonates (2a–2g) have been measured spectrophotometrically. Comparison of math formula with the math formula values reported previously for the corresponding reactions with math formula has revealed that OH [BOND] is only 10"3-fold more reactive than math formula, although the former is 11 pK _a units more basic than the latter. The Yukawa–Tsuno plot for the reactions of 1a–1f results in an excellent linear correlation with ρ_X = 2.09 and r = 0.41. The Brønsted-type plot for the reactions of 2a–2g is linear with β_l_g = −0.51, which is typical for reactions reported to proceed through a concerted mechanism. The Yukawa–Tsuno plot for the reactions of 2a–2g exhibits excellent linearity with ρ_Y = 1.85 and r = 0.25, indicating that a partial negative charge develops on the O atom of the leaving group in the transition state. Thus, the alkaline hydrolysis of 1a–1f and 2a–2g has been concluded to proceed through a concerted mechanism. Comparison of the ρ_X and β_l_g values for the reactions with math formula ions suggests that the reactions with hydroxide ion proceed through a tighter transition-state structure than those with azide ion

  5. Steam Reforming of CH4 Using Ni- Substituted Pyrochlore Catalysts

    Science.gov (United States)

    Haynes, Daniel J.

    The steam reforming of methane (SMR) continues to remain an important industrial reaction for large-scale production of H2 as well as synthesis gas mixtures which can be used for the production of useful chemicals (e.g. methanol). Although SMR is a rather mature technology, traditional nickel based catalysts used industrially are subjected to severe temperatures and reaction conditions, which lead to irreversible activity loss through sintering, support collapse, and carbon formation. Pyrochlore-based mixed oxide have been identified as refractory materials that can be modified through the substitution of catalytic metals and other promoting species into the structure to mitigate these issues causing deactivation. For this study, a lanthanum zirconate pyrochlore catalyst was substituted with Ni to determine whether the oxide structure could effectively stabilize the activity of the catalytic metal during the SMR. The effect of different variables including calcination temperature, a comparison of a substituted versus supported Ni pyrochlore catalyst, Ni weight loading, and Sr promotion have been evaluated to determine the location of the Ni in the structure, and their effect on catalytic behavior. It was revealed that the effect of calcination temperature on a 6wt% Ni substituted pyrochlore produced by the Pechini method demonstrated very little Ni was soluble in the pyrochlore lattice. It was further revealed that by XRD, TEM, and atom probe tomography that, despite the metal loading, Ni exsolves from the structure upon crystallization of the pyrochlore at 700°C, and forms NiO at the surface and grain boundaries. An additional separate La2ZrNiO6 perovskite phase also began to form at higher temperatures (>800°C). Increasing calcination temperature was found to lead to slight sintering of the NiO at the surface, which made the NiO more reducible. Meanwhile decreasing the Ni weight loading was found to produce a lower reduction temperature due to the presence of

  6. Vanadium(V-Substitution Reactions of Wells–Dawson-Type Polyoxometalates: From [X2M18O62]6− (X = P, As; M = Mo, W to [X2VM17O62]7−

    Directory of Open Access Journals (Sweden)

    Tadaharu Ueda

    2015-07-01

    Full Text Available The formation processes of V(V-substituted polyoxometalates with the Wells–Dawson-type structure were studied by cyclic voltammetry and by 31P NMR and Raman spectroscopy. Generally, the vanadium-substituted heteropolytungstates, [P2VW17O62]7− and [As2VW17O62]7−, were prepared by mixing equimolar amounts of the corresponding lacunary species—[P2W17O61]10− and [As2W17O61]10−—and vanadate. According to the results of various measurements in the present study, the tungsten site in the framework of [P2W18O62]6− and [As2W18O62]6− without defect sites could be substituted with V(V to form the [P2VW17O62]7− and [As2VW17O62]7−, respectively. The order in which the reagents were mixed was observed to be the key factor for the formation of Dawson-type V(V-substituted polyoxometalates. Even when the concentration of each reagent was identical, the final products differed depending on the order of their addition to the reaction mixture. Unlike Wells–Dawson-type heteropolytungstates, the molybdenum sites in the framework of [P2Mo18O62]6− and [As2Mo18O62]6− were substituted with V(V, but formed Keggin-type [PVMo11O40]4− and [AsVMo11O40]4− instead of [P2VMo17O62]7− and [As2VMo17O62]7−, respectively, even though a variety of reaction conditions were used. The formation constant of the [PVMo11O40]4− and [AsVMo11O40]4− was hypothesized to be substantially greater than that of the [P2VMo17O62]7− and [As2VMo17O62]7−.

  7. Rh(III)-Catalyzed C-H Activation of Benzoylacetonitriles and Tandem Cyclization with Diazo Compounds to Substituted Benzo[ de]chromenes.

    Science.gov (United States)

    Fang, Feifei; Zhang, Chunmei; Zhou, Chaofan; Li, Yazhou; Zhou, Yu; Liu, Hong

    2018-04-06

    Rh (III)-catalyzed C-H activation of benzoylacetonitriles in coupling with diazo compounds was developed to synthesize diversified substituted benzo[ de]chromenes via a formal (4 + 2) cycloaddition with a diazo compound and subsequent tandem (4 + 2) cycloaddition with another diazo compound. Intriguingly, synthesis of substituted benzo[ de]chromenes and their decarboxylation products could be realized by controlling the reaction conditions. These reactions have a broad range of substrates, moderate to good yields, and high regioselectivity.

  8. Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.

    Science.gov (United States)

    Love, Kerry Routenberg; Pandya, Renuka K; Spooner, Eric; Ploegh, Hidde L

    2009-04-17

    Protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) requires the action of activating (E1), conjugating (E2), and ligating (E3) enzymes and is a key step in the specific destruction of proteins. Deubiquitinating enzymes (DUBs) deconjugate substrates modified with Ub/Ubl's and recycle Ub inside the cell. Genome mining based on sequence homology to proteins with known function has assigned many enzymes to this pathway without confirmation of either conjugating or DUB activity. Function-dependent methodologies are still the most useful for rapid identification or assessment of biological activity of expressed proteins from cells. Activity-based protein profiling uses chemical probes that are active-site-directed for the classification of protein activities in complex mixtures. Here we show that the design and use of an expanded set of Ub-based electrophilic probes allowed us to recover and identify members of each enzyme class in the ubiquitin-proteasome system, including E3 ligases and DUBs with previously unverified activity. We show that epitope-tagged Ub-electrophilic probes can be used as activity-based probes for E3 ligase identification by in vitro labeling and activity studies of purified enzymes identified from complex mixtures in cell lysate. Furthermore, the reactivity of our probe with the HECT domain of the E3 Ub ligase ARF-BP1 suggests that multiple cysteines may be in the vicinity of the E2-binding site and are capable of the transfer of Ub to self or to a substrate protein.

  9. An optimization study for radioiodination of a new synthesized benzamide derivative as an analogue tracer for malignant melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban A.; Aglan, Hany; Seddik, Usama [Atomic Energy Authority, Cairo (Egypt). Nuclear Research Center; EL-Kafrawy, Ahmed F. [Ain Shams Univ., Cairo (Egypt). Faculty of Science

    2017-03-01

    Iodobenzamides are reported to possess some affinity for melanoma. This study describes the synthesis of a new benzamide analogue, N-(2-diethylamino-ethyl)-4-(4-chloro-nicotinamido)-5-[{sup 125}I]iodo-2 -methoxybenz amide ([{sup 125}I]H4) designed to target melanoma. The synthesis was simply achieved in four steps. There were two PyCIU/DIPEA amide condensations and a transfer hydrogenation using an ammonium formate hydrogen donor. The radioiodination step was carried out with {sup 125}I via an electrophilic substitution reaction. The reaction conditions were optimized. The labeled compound was purified by HPLC. The maximum radiochemical yield was found to be 78% at a radiochemical purity of 98%. All compounds were characterized by MS and NMR techniques. The log P value for [{sup 125}I]H4 was found as 3.96±0.5.

  10. Photo-rearrangements of some 3-allyloxy-2-phenyl-chromones: Synthesis of vinyl substituted benzopyronopyranes

    Directory of Open Access Journals (Sweden)

    Rupesh Kumar

    2008-10-01

    Full Text Available Photochemical reactions of some 3-allyloxy-2-phenylchromones have been studied. Photoreactions of the compounds afforded substituted pyronopyrane derivatives through the 1,4-biradicals.

  11. The Glaser–Hay reaction

    DEFF Research Database (Denmark)

    Vilhelmsen, Mie Højer; Jensen, Jonas; Tortzen, Christian

    2013-01-01

    The oxidative Glaser–Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies...... on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found...... to be zero-order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero-order. The onset of this change was found to depend on the catalyst loading...

  12. Synthesis of substituted 1-metallyl derivatives of o- and m-carboranes and some their transformations

    International Nuclear Information System (INIS)

    Kovredov, A.I.; Shemyakin, N.F.; Zakharkin, L.I.

    1985-01-01

    Synthesis of 1-metallyl substituted o- and m- carbonates is carried out, and alkylation of benzene by them is investigated. Synthesis with 30-95% yield has been carried out by the reaction of lithium derivatives with metallylchloride in the ester-benzene solution. The reaction of benzene alkylation is studied in the presence of aluminium chloride and H 2 SO 4 . Reaction mechanisms are considered

  13. The effect of Ce ion substituted OMS-2 nanostructure in catalytic activity for benzene oxidation

    Science.gov (United States)

    Hou, Jingtao; Li, Yuanzhi; Mao, Mingyang; Zhao, Xiujian; Yue, Yuanzheng

    2014-11-01

    The nanostructure of Ce doped OMS-2 plays a very important role in its catalytic property. We demonstrate by density functional theory (DFT) calculations that the unique nanostructure of the Ce ion substituted OMS-2 with Mn vacancy in the framework is beneficial for the improvement of catalytic activity, while the nanostructure of the Ce ion substituted OMS-2 without defects are detrimental to the catalytic activity. We establish a novel and facile strategy of synthesizing these unique Ce ion substituted OMS-2 nanostructure with Mn vacancies in the framework by hydrothermal redox reaction between Ce(NO3)3 and KMnO4 with KMnO4/Ce(NO3)3 at a molar ratio of 3 : 1 at 120 °C. Compared to pure OMS-2, the produced catalyst of Ce ion substituted OMS-2 ultrathin nanorods exhibits an enormous enhancement in the catalytic activity for benzene oxidation, which is evidenced by a significant decrease (ΔT50 = 100 °C, ΔT90 = 129 °C) in the reaction temperature of T50 and T90 (corresponding to the benzene conversion = 50% and 90%), which is considerably more efficient than the expensive supported noble metal catalyst (Pt/Al2O3). We combine both theoretical and experimental evidence to provide a new physical insight into the significant effect due to the defects induced by the Ce ion substitution on the catalytic activity of OMS-2. The formation of unique Ce ion substituted OMS-2 nanostructure with Mn vacancies in the framework leads to a significant enhancement of the lattice oxygen activity, thus tremendously increasing the catalytic activity.The nanostructure of Ce doped OMS-2 plays a very important role in its catalytic property. We demonstrate by density functional theory (DFT) calculations that the unique nanostructure of the Ce ion substituted OMS-2 with Mn vacancy in the framework is beneficial for the improvement of catalytic activity, while the nanostructure of the Ce ion substituted OMS-2 without defects are detrimental to the catalytic activity. We establish a novel

  14. Rational synthesis of AB-type N-substituted core-functionalized naphthalene diimides (cNDIs).

    Science.gov (United States)

    Berezin, Andrey A; Sciutto, Andrea; Demitri, Nicola; Bonifazi, Davide

    2015-04-17

    Acid-mediated transformation of tetraethyl 2,6-diethoxynaphthalene-1,4,5,8-tetracarboxylate selectively affords the core-substituted naphthalene-anhydride-ester (cNAE) in quantitative yield. This anhydride can be selectively converted into hetero-N-substituted core-functionalized naphthalene diimides (cNDIs) through sequential condensation reactions in the presence of the precursor amine with very high isolated yields over four steps. The approach can be applied to prepare a large variety of heterocyclic, aromatic, and aliphatic heterodiimides.

  15. Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2013-10-01

    Full Text Available An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces adducts which are subjected to a cationic gold-catalyzed diastereoselective domino cyclization to furnish diversely substituted spiroindolines. All the reactions run via an exo-dig attack in the hydroarylation step followed by an intramolecular diastereoselective trapping of the imminium ion. The whole sequence is atom economic and the application of a multicomponent reaction assures diversity.

  16. Direct Alkynylation of 3H-Imidazo[4,5-b]pyridines Using gem-Dibromoalkenes as Alkynes Source.

    Science.gov (United States)

    Aziz, Jessy; Baladi, Tom; Piguel, Sandrine

    2016-05-20

    C2 direct alkynylation of 3H-imidazo[4,5-b]pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe2 or Cu(OAc)2), a phosphine ligand (DPEphos) and a base (LiOtBu) in 1,4-dioxane at 120 °C. This C-H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and gem-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3H-imidazo[4,5-b]pyridines, a valuable scaffold in drug design.

  17. Oxidative allene amination for the synthesis of azetidin-3-ones.

    Science.gov (United States)

    Burke, Eileen G; Schomaker, Jennifer M

    2015-10-05

    Regioselectivity in the aziridination of silyl-substituted homoallenic sulfamates is readily diverted to the distal double bond of the allene to yield endocyclic bicyclic methyleneaziridines with excellent stereocontrol. Subsequent reaction with electrophilic oxygen sources initiates facile rearrangement to densely functionalized, fused azetidin-3-ones in excellent d.r., effectively transferring the axial chirality of the allene to central chirality in the products. The steric nature of the silyl group dictates which of the two rings of the fused azetidin-3-one will undergo further functionalization, providing an additional element of diversity for the preparation of enantioenriched azetidine scaffolds with potential biological activity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Characterizing Chemical Similarity with Vibrational Spectroscopy: New Insights into the Substituent Effects in Monosubstituted Benzenes.

    Science.gov (United States)

    Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi

    2017-10-26

    A novel approach is presented to assess chemical similarity based the local vibrational mode analysis developed by Konkoli and Cremer. The local mode frequency shifts are introduced as similarity descriptors that are sensitive to any electronic structure change. In this work, 59 different monosubstituted benzenes are compared. For a subset of 43 compounds, for which experimental data was available, the ortho-/para- and meta-directing effect in electrophilic aromatic substitution reactions could be correctly reproduced, proving the robustness of the new similarity index. For the remaining 16 compounds, the directing effect was predicted. The new approach is broadly applicable to all compounds for which either experimental or calculated vibrational frequency information is available.

  19. Chelation-Assisted Substrate-Controlled Asymmetric Lithiation-Allylboration of Chiral Carbamate 1,2,4-Butanetriol Acetonide

    Directory of Open Access Journals (Sweden)

    Adeem Mahmood

    2015-05-01

    Full Text Available The lithiation of 2-(2,2-dimethyl-1,3-dioxolan-4-ylethyl diisopropylcarbamate (1 is achieved freely by sec-butyllithium in diethylether with high lk-diastereoselectivity: the bicyclic chelate complexes 3a and 3b are reacted with electrophiles to form optically active precursors 4a and 4b with >95% diastereoselectivity. In addition, tertiary diamines can undergo an external complexation in contest with the internal oxygen ligand, leading to improved stereoselectivities. The further reactions of lithiated carbamates with trans alkenyl-9-BBN derivatives after 1,2 metallate rearrangements, gave the key intermediate α-substituted allylic boranes 7. Subsequent allylboration of aldehydes gave (Z-anti-homoallylic alcohols 8 in good yield and excellent d.r.

  20. Oxidation Numbers, Oxidants, and Redox Reactions: Variants of the Electrophilic Bromination of Alkenes and Variants of the Application of Oxone

    Science.gov (United States)

    Eissen, Marco; Strudthoff, Merle; Backhaus, Solveig; Eismann, Carolin; Oetken, Gesa; Kaling, Soren; Lenoir, Dieter

    2011-01-01

    Oxidation-state and donor-acceptor concepts are important areas in the chemical education. Student worksheets containing problems that emphasize oxidation numbers, redox reactions of organic compounds, and stoichiometric reaction equations are presented. All of the examples are incorporated under one unifying topic: the production of vicinal…

  1. The Ligand Substitution Reactions of Hydrophobic Vitamin B12 ...

    African Journals Online (AJOL)

    South African Journal of Chemistry ... The equilibrium constants, K, for the reaction of five-membered heterocyclic nitrogenous bases (the azoles imidazole, pyrazole and 1,2,4-triazole) with displacement of ... Keywords: Hydrophobic vitamin B12, cobalt corrinoids, equilibrium constants, solvent polarity, trans influence.

  2. A simple enantioconvergent and chemoenzymatic synthesis of optically active α-substituted amides

    NARCIS (Netherlands)

    Szymanski, Wiktor; Westerbeek, Alja; Janssen, Dick B.; Feringa, Ben L.

    2011-01-01

    Simple and efficient: The combination of an enzymatic, enantioinverting reaction with simple follow-up processes allows the transformation of readily available racemic compounds into versatile chiral α-substituted amides. These important building blocks are prepared in high overall yield and

  3. Catalytic asymmetric diels-alder reaction of quinone imine ketals: a site-divergent approach.

    Science.gov (United States)

    Hashimoto, Takuya; Nakatsu, Hiroki; Maruoka, Keiji

    2015-04-07

    The catalytic asymmetric Diels-Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl-substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels-Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3-alkyl quinone imine ketals from the inherently favored unsubstituted C=C bond to the disfavored alkyl-substituted C=C bond. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Alkylation of nitriles with gaseous carbenium ions. The ritter reaction in the dilute gas state

    International Nuclear Information System (INIS)

    Cacace, F.; Ciranni, G.; Giacomello, P.

    1982-01-01

    Radiolytically formed carbenium ions, such as sec-C 3 H 7 + , sec-C 4 H 9 + , and t-C 4 H 9 + , react in the gas phase with model aliphatic and aromatic nitriles yielding the corresponding nitrilium ions. The latter undergo efficient condensation with water that eventually leads to the formation of the corresponding N-alkylamides. The mechanism is analogous to the Ritter reaction in solution. The reactivity and selectivity of the gas-phase electrophilic attack on nitriles has been deduced from competition experiments under conditions that largely exclude the effects of solvation, ion pairing, etc., which complicate the interpretation of solution-chemistry measurements. 1 table

  5. Electrochemical behavior of meso-substituted iron porphyrins in alkaline aqueous media

    Science.gov (United States)

    Berezina, N. M.; Bazanov, M. I.; Maksimova, A. A.; Semeikin, A. S.

    2017-12-01

    The effect meso-substitution in iron porphyrin complexes has on their redox behavior in alkaline aqueous solutions is studied via cyclic voltammetry. The voltammetric features of the reduction of iron pyridylporphyrins suggest that the sites of electron transfer lie at the ligand, the metal ion, and the pyridyl moieties. The electron transfer reactions between the different forms of these compounds, including the oxygen reduction reaction they mediate, are outlined to show the sequence and potential ranges in which they occur in alkaline aqueous media. Under our experimental conditions, the iron porphyrins exist as μ-oxo dimmers whose activity for the electrocatalytic reduction of oxygen displays a considerable dependence on the nature of the substitutents and nitrogen isomerization (for pyridylporphyrins) and grows in the order (Fe( ms-Ph)4P)2O, (Fe[ ms-(Py-3)Ph3]P)2O, (Fe[ ms-(Py-4)4]P)2O, and (Fe[ ms-(Py-3)4]P)2O.

  6. A computational study of pyrolysis reactions of lignin model compounds

    Science.gov (United States)

    Thomas Elder

    2010-01-01

    Enthalpies of reaction for the initial steps in the pyrolysis of lignin have been evaluated at the CBS-4m level of theory using fully substituted b-O-4 dilignols. Values for competing unimolecular decomposition reactions are consistent with results previously published for phenethyl phenyl ether models, but with lowered selectivity. Chain propagating reactions of free...

  7. Reaction mechanisms of metal complexes

    CERN Document Server

    Hay, R W

    2000-01-01

    This text provides a general background as a course module in the area of inorganic reaction mechanisms, suitable for advanced undergraduate and postgraduate study and/or research. The topic has important research applications in the metallurgical industry and is of interest in the science of biochemistry, biology, organic, inorganic and bioinorganic chemistry. In addition to coverage of substitution reactions in four-, five- and six-coordinate complexes, the book contains further chapters devoted to isomerization and racemization reactions, to the general field of redox reactions, and to the reactions of coordinated ligands. It is relevant in other fields such as organic, bioinorganic and biological chemistry, providing a bridge to organic reaction mechanisms. The book also contains a chapter on the kinetic background to the subject with many illustrative examples which should prove useful to those beginning research. Provides a general background as a course module in the area of inorganic reaction mechanis...

  8. Quinone methides tethered to naphthalene diimides as selective G-quadruplex alkylating agents.

    Science.gov (United States)

    Di Antonio, Marco; Doria, Filippo; Richter, Sara N; Bertipaglia, Carolina; Mella, Mariella; Sissi, Claudia; Palumbo, Manlio; Freccero, Mauro

    2009-09-16

    We have developed novel G-quadruplex (G-4) ligand/alkylating hybrid structures, tethering the naphthalene diimide moiety to quaternary ammonium salts of Mannich bases, as quinone-methide precursors, activatable by mild thermal digestion (40 degrees C). The bis-substituted naphthalene diimides were efficiently synthesized, and their reactivity as activatable bis-alkylating agents was investigated in the presence of thiols and amines in aqueous buffered solutions. The electrophilic intermediate, quinone-methide, involved in the alkylation process was trapped, in the presence of ethyl vinyl ether, in a hetero Diels-Alder [4 + 2] cycloaddition reaction, yielding a substituted 2-ethoxychroman. The DNA recognition and alkylation properties of these new derivatives were investigated by gel electrophoresis, circular dichroism, and enzymatic assays. The alkylation process occurred preferentially on the G-4 structure in comparison to other DNA conformations. By dissecting reversible recognition and alkylation events, we found that the reversible process is a prerequisite to DNA alkylation, which in turn reinforces the G-quadruplex structural rearrangement.

  9. Asymmetric Synthesis of P-Chiral Diphosphines. Steric Effects on the Palladium-Complex-Promoted Asymmetric Diels-Alder Reaction between a Dimethylphenylphosphole and (E/Z)-Methyl-Substituted Diphenylvinylphosphines.

    Science.gov (United States)

    Aw, Beng-Hwee; Hor, T. S. Andy; Selvaratnam, S.; Mok, K. F.; White, Andrew J. P.; Williams, David J.; Rees, Nicholas H.; McFarlane, William; Leung, Pak-Hing

    1997-05-07

    The organopalladium complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary has been used successfully to promote the asymmetric [4+2] Diels-Alder reactions between 1-phenyl-3,4-dimethylphosphole and the following coordinated dienophiles: (a) diphenylvinylphosphine; (b) (E)-diphenyl-1-propenylphosphine; (c) (Z)-diphenyl-1-propenylphosphine. Reaction a generates three carbon and one phosphorus stereogenic centers while reactions b and c each produce four carbon and one phosphorus chiral centers. In dichloromethane, all three reactions proceeded smoothly at room temperature giving the corresponding rigid diphosphines in high yields. Under similar reaction conditions, the reaction times observed for reactions a-c are 2, 3, and 50 h, respectively. Two-dimensional ROESY NMR studies confirmed that the prolonged reaction time required for reaction c is due to several major repulsive interactions between the chiral naphthylamine auxiliary and the (Z)-methyl-substituted vinylphosphine in the transition state. Nevertheless, all three reactions gave the corresponding rigid diphosphine in high yields. The absolute stereochemistries of the three bidentate phosphine ligands that were produced from the cycloaddition reactions have been assigned by 2D ROESY NMR spectroscopy. These diphosphines are powerful sequesterers of group 8 metals although they are highly air-sensitive in the free ligand form. The coordination chemistry and the absolute stereochemistry of the optically active complex [1alpha,4alpha,5alpha(S),6alpha(S),7R]-dichloro[5-(diphenylphosphino)-2,3,6-trimethy-7-phenyl-7-phosphabicyclo[2.2.1]-hept-2-ene-P(5)(),P(7)()]palladium(II) has been studied by single-crystal X-ray analysis. Crystal structure data: C(27)H(28)Cl(2)P(2)Pd, M(r) = 591.7; triclinic; space group P1; a = 8.643(3), b = 9.044(6), c = 9.058(4) Å; alpha = 102.75(4) degrees, beta = 108.59(2) degrees, gamma = 97.82(3) degrees; V = 638.0(5) Å(3); Z = 1; R(1) = 0.036.

  10. Photochemical reaction dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Moore, B.C. [Lawrence Berkeley Laboratory, Livermore, CA (United States)

    1993-12-01

    The purpose of the program is to develop a fundamental understanding of unimolecular and bimolecular reaction dynamics with application in combustion and energy systems. The energy dependence in ketene isomerization, ketene dissociation dynamics, and carbonyl substitution on organometallic rhodium complexes in liquid xenon have been studied. Future studies concerning unimolecular processes in ketene as well as energy transfer and kinetic studies of methylene radicals are discussed.

  11. Novel One-Pot Access to 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl) indolin-2-ones

    International Nuclear Information System (INIS)

    Lin, Y.; Fu, Z.; Song, Q.; Shen, T.

    2016-01-01

    Sodium bicarbonate was applied as catalyst for the synthesis of 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl)indolin-2-ones via the reaction of isatins, hydrazine hydrate and ethyl acetoacetate or ethyl benzoylacetate. This reaction was performed in ethanol at 78 degree C, giving 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl)indolin-2-one derivatives in good to excellent yields. The structure of 5-bromo-3,3-bis(3-hydroxy-5-methyl-1H-pyrazol-4-yl) indolin-2-one was unambiguously confirmed by X-ray single crystal structure analysis and a plausible reaction mechanism is also proposed. (author)

  12. Novel synthesis and characterization of an AB-type carbonate-substituted hydroxyapatite.

    Science.gov (United States)

    Gibson, Iain R; Bonfield, William

    2002-03-15

    A novel synthesis route has been developed to produce a high-purity mixed AB-type carbonate-substituted hydroxyapatite (CHA) with a carbonate content that is comparable to the type and level observed in bone mineral. This method involves the aqueous precipitation in the presence of carbonate ions in solution of a calcium phosphate apatite with a Ca/P molar ratio greater than the stoichiometric value of 1.67 for hydroxyapatite (HA). The resulting calcium-rich carbonate-apatite is sintered/heat-treated in a carbon dioxide atmosphere to produce a single-phase, crystalline carbonate-substituted hydroxyapatite. In contrast to previous methods for producing B- or AB-type carbonate-substituted hydroxyapatites, no sodium or ammonium ions, which would be present in the reaction mixture from the sodium or ammonium carbonates commonly used as a source of carbonate ions, were present in the final product. The chemical and phase compositions of the carbonate-substituted hydroxyapatite was characterized by X-ray fluorescence and X-ray diffraction, respectively, and the level and nature of the carbonate substitution were studied using C-H-N analysis and Fourier transform infrared spectroscopy, respectively. The carbonate substitution improves the densification of hydroxyapatite and reduces the sintering temperature required to achieve near-full density by approximately 200 degrees C compared to stoichiometric HA. Initial studies have shown that these carbonate-substituted hydroxyapatites have improved mechanical and biologic properties compared to stoichiometric hydroxyapatite. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 697-708, 2002

  13. The OH-initiated atmospheric chemical reactions of polyfluorinated dibenzofurans and polychlorinated dibenzofurans: A comparative theoretical study.

    Science.gov (United States)

    Zeng, Xiaolan; Chen, Jing; Qu, Ruijuan; Pan, Xiaoxue; Wang, Zunyao

    2017-02-01

    The atmospheric chemical reactions of some polyfluorinated dibenzofurans (PFDFs) and polychlorinated dibenzofurans (PCDFs), initiated by OH radical, were investigated by performing theoretical calculations using density functional theory (DFT) and B3LYP/6-311++G(2df,p) method. The obtained results indicate that OH addition reactions of PFDFs and PCDFs occurring at C 1∼4 and C A sites are thermodynamic spontaneous changes and the branching ratio of the PF(C)DF-OH adducts is decided primarily by kinetic factor. The OH addition reactions of PFDFs taking place at fluorinated C 1∼4 positions are kinetically comparable with those occurring at nonfluorinated C 1∼4 positions, while OH addition reactions of PCDFs occurring at chlorinated C 1∼4 sites are negligible. The total rate constants of the addition reactions of PFDFs or PCDFs become smaller with consecutive fluorination or chlorination, and substituting at C 1 position has more adverse effects than substitution at other sites. The succedent O 2 addition reactions of PF(C)DF-OH adducts are thermodynamic nonspontaneous processes under the atmospheric conditions, and have high Gibbs free energies of activation (Δ r G ≠ ). The substituted dibenzofuranols are the primary oxidation products for PCDFs under the atmospheric conditions. However, other oxidative products may also be available for PFDFs besides substituted dibenzofuranols. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H-ones and isoquinoline-1,3(2H,4H-diones

    Directory of Open Access Journals (Sweden)

    Ping Qian

    2016-02-01

    Full Text Available An oxidative reaction for the synthesis of 4-alkyl-substituted dihydroisoquinolin-1(2H-ones with N-allylbenzamide derivatives as starting materials has been developed. The radical alkylarylation reaction proceeds through a sequence of alkylation and intramolecular cyclization. The substituent on the C–C double bond was found to play a key role for the progress of the reaction to give the expected products with good chemical yields. Additionally, N-methacryloylbenzamides were also suitable substrates for the current reaction and provided the alkyl-substituted isoquinoline-1,3(2H,4H-diones in good yield.

  15. High stereoselectivity on low temperature Diels-Alder reactions

    Directory of Open Access Journals (Sweden)

    Invernize Paulo

    2005-12-01

    Full Text Available Abstract We have found that some of the usually poor dienophiles (2-cycloenones can undergo Diels-Alder reaction at -78°C with unusually high stereoselectivity in the presence of niobium pentachloride as a Lewis acid catalyst. A remarkable difference in reaction rates for unsubstituted and α- or β-methyl substituted 2-cycloenones was also observed.

  16. A general approach to intermolecular carbonylation of arene C-H bonds to ketones through catalytic aroyl triflate formation

    Science.gov (United States)

    Garrison Kinney, R.; Tjutrins, Jevgenijs; Torres, Gerardo M.; Liu, Nina Jiabao; Kulkarni, Omkar; Arndtsen, Bruce A.

    2018-02-01

    The development of metal-catalysed methods to functionalize inert C-H bonds has become a dominant research theme in the past decade as an approach to efficient synthesis. However, the incorporation of carbon monoxide into such reactions to form valuable ketones has to date proved a challenge, despite its potential as a straightforward and green alternative to Friedel-Crafts reactions. Here we describe a new approach to palladium-catalysed C-H bond functionalization in which carbon monoxide is used to drive the generation of high-energy electrophiles. This offers a method to couple the useful features of metal-catalysed C-H functionalization (stable and available reagents) and electrophilic acylations (broad scope and selectivity), and synthesize ketones simply from aryl iodides, CO and arenes. Notably, the reaction proceeds in an intermolecular fashion, without directing groups and at very low palladium-catalyst loadings. Mechanistic studies show that the reaction proceeds through the catalytic build-up of potent aroyl triflate electrophiles.

  17. The Brønsted Acid-Catalyzed, Enantioselective Aza-Diels-Alder Reaction for the Direct Synthesis of Chiral Piperidones.

    Science.gov (United States)

    Weilbeer, Claudia; Sickert, Marcel; Naumov, Sergei; Schneider, Christoph

    2017-01-12

    We disclose herein the first enantioselective aza-Diels-Alder reaction of β-alkyl-substituted vinylketene silyl-O,O-acetals and imines furnishing a broad range of optically highly enriched 4-alkyl-substituted 2-piperidones. As a catalyst for this one-pot reaction we employed a chiral phosphoric acid which effects a vinylogous Mannich reaction directly followed by ring-closure to the lactam. Subsequent fully diastereoselective transformations including hydrogenation, enolate alkylation, and lactam alkylation/reduction processes converted the cycloadducts into various highly substituted piperidines of great utility for the synthesis of natural products and medicinally active compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Radioiodination and biological evaluation of levalbuterol as a new selective radiotracer. A β{sub 2}-adrenoceptor agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sanad, Mahmoud Hamdi; Abelrahman, Mohamed Abdelmotelb; Marzook, Fawzy Mohamed Abdelmaged [Atomic Energy Authority, Cairo (Egypt). Radioisotopes Production and Radioactive Sources Div.

    2016-08-01

    Levalbuterol was successfully radiolabeled with iodine using chloramine-T as an oxidizing agent via an electrophilic substitution reaction. The reaction parameters that affecting the labeling yield such as levalbuterol concentration, chloramine-T concentration, pH of the reaction medium and reaction time were studied in details. The radiochemical yield was 97.5 ± 0.5% and the radioiodinated compound was separated by HPLC. In vitro studies showed that the iodinated levalbuterol was stable for up to 24 h. The biodistribution in experimental animals showed that the lung uptake was 68.18 ± 0.17% at 5 min post injection which decreased with time until reached to 18.7 ± 0.12% at 2 h which was higher than other recent developed radiopharmaceuticals for lung imaging. The clearance pathways from the mice appear to proceed via both hepatobiliary and renal pathways. Predosing the mice with cold levalbuterol reduced the lung uptake to 20 ± 1.3% and further confirms the high specificity and selectivity of {sup 125}I-levalbuterol for the lung.

  19. Mechanisms of Base Substitution Mutagenesis in Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Albino Bacolla

    2014-03-01

    Full Text Available Cancer genome sequence data provide an invaluable resource for inferring the key mechanisms by which mutations arise in cancer cells, favoring their survival, proliferation and invasiveness. Here we examine recent advances in understanding the molecular mechanisms responsible for the predominant type of genetic alteration found in cancer cells, somatic single base substitutions (SBSs. Cytosine methylation, demethylation and deamination, charge transfer reactions in DNA, DNA replication timing, chromatin status and altered DNA proofreading activities are all now known to contribute to the mechanisms leading to base substitution mutagenesis. We review current hypotheses as to the major processes that give rise to SBSs and evaluate their relative relevance in the light of knowledge acquired from cancer genome sequencing projects and the study of base modifications, DNA repair and lesion bypass. Although gene expression data on APOBEC3B enzymes provide support for a role in cancer mutagenesis through U:G mismatch intermediates, the enzyme preference for single-stranded DNA may limit its activity genome-wide. For SBSs at both CG:CG and YC:GR sites, we outline evidence for a prominent role of damage by charge transfer reactions that follow interactions of the DNA with reactive oxygen species (ROS and other endogenous or exogenous electron-abstracting molecules.

  20. Mechanisms of base substitution mutagenesis in cancer genomes.

    Science.gov (United States)

    Bacolla, Albino; Cooper, David N; Vasquez, Karen M

    2014-03-05

    Cancer genome sequence data provide an invaluable resource for inferring the key mechanisms by which mutations arise in cancer cells, favoring their survival, proliferation and invasiveness. Here we examine recent advances in understanding the molecular mechanisms responsible for the predominant type of genetic alteration found in cancer cells, somatic single base substitutions (SBSs). Cytosine methylation, demethylation and deamination, charge transfer reactions in DNA, DNA replication timing, chromatin status and altered DNA proofreading activities are all now known to contribute to the mechanisms leading to base substitution mutagenesis. We review current hypotheses as to the major processes that give rise to SBSs and evaluate their relative relevance in the light of knowledge acquired from cancer genome sequencing projects and the study of base modifications, DNA repair and lesion bypass. Although gene expression data on APOBEC3B enzymes provide support for a role in cancer mutagenesis through U:G mismatch intermediates, the enzyme preference for single-stranded DNA may limit its activity genome-wide. For SBSs at both CG:CG and YC:GR sites, we outline evidence for a prominent role of damage by charge transfer reactions that follow interactions of the DNA with reactive oxygen species (ROS) and other endogenous or exogenous electron-abstracting molecules.

  1. Regioselectivity of conjugate additions to monoalkyl-1,4-benzoquinones

    Directory of Open Access Journals (Sweden)

    SNEZANA TRIFUNOVIC

    2002-09-01

    Full Text Available The regioselectivity of the reaction of conjugate addition of thiols, amines, methanol and hydrogen chloride with the monoalkyl-1,4-benzoquinones avarone and 2-tert-butyl-1,4-benzoquinone was investigated. It was shown that the regioselectivity of the reaction is influenced by the electrophilicity of position 5 in unprotonated 2-alkylquinones, the increased electrophilicity of position 6 in acidic medium, and by the acidity of the intermediate hydroquinones.

  2. Stereospecific nickel-catalyzed cross-coupling reactions of alkyl ethers: enantioselective synthesis of diarylethanes.

    Science.gov (United States)

    Taylor, Buck L H; Swift, Elizabeth C; Waetzig, Joshua D; Jarvo, Elizabeth R

    2011-01-26

    Secondary benzylic ethers undergo stereospecific substitution reactions with Grignard reagents in the presence of nickel catalysts. Reactions proceed with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.

  3. Concerted effects in the reaction of ·OH radicals with aromatics: radiolytic oxidation of salicylic acid

    International Nuclear Information System (INIS)

    Albarran, G.; Schuler, R.H.

    2003-01-01

    Liquid chromatographic and capillary electrophoretic studies have been used to resolve the products produced in the radiolytic oxidation of salicylic acid in aqueous solution. These studies have shown that, as in the case of phenol, · OH radicals preferentially add to the positions ortho and para to the OH substituent. However, in contrast to its reaction with phenol, addition at the ortho position is favored over addition at the para position. Because · OH radical is a strong electrophile this difference suggests that the electron population at the ortho position in the salicylate anion is enhanced as a result of the hydrogen bonding in salicylic acid

  4. Synthesis and reactions of C-phosphanylated thiazol-2-thiones.

    Science.gov (United States)

    Begum, I; Schnakenburg, G; Streubel, R

    2016-02-21

    The facile regioselective synthesis of the P(iii) substituted thiazol-2-thione 2 is presented. Reaction of 2 with hydrogenperoxide-urea, elemental sulfur and selenium resulted in P(v) chalcogenide thiazol-2-thiones 3-5. All compounds were characterized using (31)P, (1)H, (13)C NMR, IR and elemental analyses and, additionally, by the single-crystal X-ray diffraction technique. Oxidative desulfurization of the 5-phosphinoylated thiazol-2-thione 3 using hydrogenperoxide led to the first C-phosphanoyl substituted thiazolium salt (6). Deprotonation of 6 and in situ reaction with the cyclooctadiene rhodium(i) chloride dimer yielded thiazol-2-ylidene rhodium(i) complex 7 which was confirmed by NMR spectroscopy and ESI-MS spectrometry.

  5. Silica-Supported Polyphosphoric Acid in the Synthesis of 4-Substituted Tetrahydroisoquinoline Derivatives

    Directory of Open Access Journals (Sweden)

    Iliyan Ivanov

    2013-02-01

    Full Text Available We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides. We compared the cyclisation step using conventional (milieu of acetic-trifluoracetic acid = 4:1 and solid supported reagents (SiO2/PPA, as recovered, regenerated and reused without loss of its activity catalyst. We found that in comparison to conventional methods, the yields of the reaction are greater and the reaction time is shorter.

  6. Simple, heart-smart substitutions

    Science.gov (United States)

    Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

  7. Ruthenium-Catalyzed Formal Dehydrative [4 + 2] Cycloaddition of Enamides and Alkynes for the Synthesis of Highly Substituted Pyridines: Reaction Development and Mechanistic Study.

    Science.gov (United States)

    Wu, Jicheng; Xu, Wenbo; Yu, Zhi-Xiang; Wang, Jian

    2015-07-29

    Reported herein is a ruthenium-catalyzed formal dehydrative [4 + 2] cycloaddition of enamides and alkynes, representing a mild and economic protocol for the construction of highly substituted pyridines. Notably, the features of broad substrate scope, high efficiency, good functional group tolerance, and excellent regioselectivities were observed for this reaction. Density functional theory (DFT) calculations and experiments have been carried out to understand the mechanism and regiochemistry. DFT calculations suggested that this formal dehydrative [4 + 2] reaction starts with a concerted metalation deprotonation of the enamide by the acetate group in the Ru catalyst, which generates a six-membered ruthenacycle intermediate. Then alkyne inserts into the Ru-C bond of the six-membered ruthenacycle, giving rise to an eight-membered ruthenacycle intermediate. The carbonyl group (which comes originally from the enamide substrate and is coordinated to the Ru center in the eight-membered ruthenacycle intermediate) then inserts into the Ru-C bond to give an intermediate, which produces the final pyridine product through further dehydration. Alkyne insertion step is a regio-determining step and prefers to have the aryl groups of the used alkynes stay away from the catalyst in order to avoid repulsion of aryl group with the enamide moiety in the six-membered ruthenacycle and to keep the conjugation between the aryl group and the triple C-C bond of the alkynes. Consequently, the aryl groups of the used alkynes are in the β-position of the final pyridines, and the present reaction has high regioselectivity.

  8. Oxidative treatment of bromide-containing waters: formation of bromine and its reactions with inorganic and organic compounds--a critical review.

    Science.gov (United States)

    Heeb, Michèle B; Criquet, Justine; Zimmermann-Steffens, Saskia G; von Gunten, Urs

    2014-01-01

    Bromide (Br(-)) is present in all water sources at concentrations ranging from ≈ 10 to >1000 μg L(-1) in fresh waters and about 67 mg L(-1) in seawater. During oxidative water treatment bromide is oxidized to hypobromous acid/hypobromite (HOBr/OBr(-)) and other bromine species. A systematic and critical literature review has been conducted on the reactivity of HOBr/OBr(-) and other bromine species with inorganic and organic compounds, including micropollutants. The speciation of bromine in the absence and presence of chloride and chlorine has been calculated and it could be shown that HOBr/OBr(-) are the dominant species in fresh waters. In ocean waters, other bromine species such as Br2, BrCl, and Br2O gain importance and may have to be considered under certain conditions. HOBr reacts fast with many inorganic compounds such as ammonia, iodide, sulfite, nitrite, cyanide and thiocyanide with apparent second-order rate constants in the order of 10(4)-10(9)M(-1)s(-1) at pH 7. No rate constants for the reactions with Fe(II) and As(III) are available. Mn(II) oxidation by bromine is controlled by a Mn(III,IV) oxide-catalyzed process involving Br2O and BrCl. Bromine shows a very high reactivity toward phenolic groups (apparent second-order rate constants kapp ≈ 10(3)-10(5)M(-1)s(-1) at pH 7), amines and sulfamides (kapp ≈ 10(5)-10(6)M(-1)s(-1) at pH 7) and S-containing compounds (kapp ≈ 10(5)-10(7)M(-1)s(-1) at pH 7). For phenolic moieties, it is possible to derive second-order rate constants with a Hammett-σ-based QSAR approach with [Formula in text]. A negative slope is typical for electrophilic substitution reactions. In general, kapp of bromine reactions at pH 7 are up to three orders of magnitude greater than for chlorine. In the case of amines, these rate constants are even higher than for ozone. Model calculations show that depending on the bromide concentration and the pH, the high reactivity of bromine may outweigh the reactions of chlorine during

  9. Heterogeneous kinetics, products, and mechanisms of ferulic acid particles in the reaction with NO3 radicals

    Science.gov (United States)

    Liu, Changgeng; Zhang, Peng; Wen, Xiaoying; Wu, Bin

    2017-03-01

    Methoxyphenols, as an important component of wood burning, are produced by lignin pyrolysis and considered to be the potential tracers for wood smoke emissions. In this work, the heterogeneous reaction between ferulic acid particles and NO3 radicals was investigated. Six products including oxalic acid, 4-vinylguaiacol, vanillin, 5-nitrovanillin, 5-nitroferulic acid, and caffeic acid were confirmed by gas chromatography-mass spectrometry (GC-MS). In addition, the reaction mechanisms were proposed and the main pathways were NO3 electrophilic addition to olefin and the meta-position to the hydroxyl group. The uptake coefficient of NO3 radicals on ferulic acid particles was 0.17 ± 0.02 and the effective rate constant under experimental conditions was (1.71 ± 0.08) × 10-12 cm3 molecule-1 s-1. The results indicate that ferulic acid degradation by NO3 can be an important sink at night.

  10. Oxygen atom transfer reactions from Mimoun complexes to sulfides and sulfoxides. A bonding evolution theory analysis.

    Science.gov (United States)

    González-Navarrete, Patricio; Sensato, Fabricio R; Andrés, Juan; Longo, Elson

    2014-08-07

    In this research, a comprehensive theoretical investigation has been conducted on oxygen atom transfer (OAT) reactions from Mimoun complexes to sulfides and sulfoxides. The joint use of the electron localization function (ELF) and Thom's catastrophe theory (CT) provides a powerful tool to analyze the evolution of chemical events along a reaction pathway. The progress of the reaction has been monitored by structural stability domains from ELF topology while the changes between them are controlled by turning points derived from CT which reveal that the reaction mechanism can be separated in several steps: first, a rupture of the peroxo O1-O2 bond, then a rearrangement of lone pairs of the sulfur atom occurs and subsequently the formation of S-O1 bond. The OAT process involving the oxidation of sulfides and sulfoxides is found to be an asynchronous process where O1-O2 bond breaking and S-O1 bond formation processes do not occur simultaneously. Nucleophilic/electrophilic characters of both dimethyl sulfide and dimethyl sulfoxide, respectively, are sufficiently described by our results, which hold the key to unprecedented insight into the mapping of electrons that compose the bonds while the bonds change.

  11. Characterization of reversible reactions of isocyanides with molybdenum dithiolate complexes

    International Nuclear Information System (INIS)

    Miller, D.J.; DuBois, M.R.

    1980-01-01

    Dimeric molybdenum complexes with bridging dithiocarbonimidate ligands of the formula [C 5 H 5 MoS 2 CNR] 2 (where R = CH 3 , CH 2 C 6 H 5 , C 6 H 11 , and n-C 4 H 9 ) have been synthesized and characterized. The syntheses involve the room-temperature reactions of excess isocyanides with solutions of the dimeric complex [C 5 H 5 MoSC 3 H 6 S] 2 . During the course of these reactions, propene is displaced from the sulfur atoms of the bridging dithiolate ligands. Addition of excess alkene reverses the above reactions. Equilibrium constants have been calculated for the following reactions by integration of NMR resonances: [CH 3 C 5 H 4 MoSC 2 H 4 S] 2 + RNC reversible (CH 3 C 5 H 4 Mo) 2 (SC 2 H 4 S)(S 2 CNR) + C == C, K 1 = 2.9 +- 0.2; (CH 3 C 5 H 4 Mo) 2 (SC 2 H 4 S)(S 2 CNR) + RNC reversible [CH 3 C 5 H 4 MoS 2 CNR] 2 + C == C, K 2 = 0.7 +- 0.1 (R = CH 2 C 6 H 5 ). The dithiocarbonimidate complexes react cleanly with the electrophiles CH 3 OSO 2 F and HOSO 2 CF 3 to form [C 5 H 5 MoS 2 CNRR'] 2 2+ where R' = H or CH 3 . These products have been characterized by spectral and conductivity methods. The reactions of the dithiocarbonimidate complexes with reducing agents and with carbon monoxide are discussed. 1 figure, 2 tables

  12. Synthesis, radioiodination and biological evaluation of a novel phthalimide derivative

    International Nuclear Information System (INIS)

    Motaleb, M.A.; Abdel-Ghaney, I.Y.; Shamsel-Din, H.A.; Abdel-Bary, H.M.

    2016-01-01

    Biologically active novel phthalimide derivative, N-(5-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phthalimide (HPZPHT), was synthesized in excellent yield and characterized by IR, mass and 1 H NMR spectroscopy. It was radiolabeled with iodine-131 by direct electrophilic substitution reaction and radiochemical yield was determined by using different chromatographic techniques (HPLRC, paper chromatography and paper electrophoresis). 131 I-HPZPHT has high radiolabeling yield (98.00 ± 2.00 %), stability, solid tumor uptake and T/NT ratio (5.17 ± 0.03 at 30 min. post-injection) compared with many new tracers which have been developed in recent years. This study encourages the possible use of this tracer as a potential imaging and/or therapeutic agent for cancer. (author)

  13. Variational Flooding Study of a SN2 Reaction.

    Science.gov (United States)

    Piccini, GiovanniMaria; McCarty, James J; Valsson, Omar; Parrinello, Michele

    2017-02-02

    We have studied the reaction dynamics of a prototypical organic reaction using a variationally optimized truncated bias to accelerate transitions between educt and product reactant states. The asymmetric S N 2 nucleophilic substitution reaction of fluoromethane and chloromethane CH 3 F + Cl - ⇌ CH 3 Cl + F - is considered, and many independent biased molecular dynamics simulations have been performed at 600, 900, and 1200 K, collecting several hundred transitions at each temperature. The transition times and relative rate constants have been obtained for both reaction directions. The activation energies extracted from an Arrhenius plot compare well with standard static calculations.

  14. Synthesis, characterization and pharmacological evaluation of substituted phenoxy acetamide derivatives

    Directory of Open Access Journals (Sweden)

    Rani Priyanka

    2015-01-01

    Full Text Available A novel series of 2-(substituted phenoxy-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylacetamide and N-(2-bromocyclohexyl-2-(substituted phenoxyacetamide derivatives having cyclohexyl nucleus as common in both types were synthesized and assessed for their anti-inflammatory activity by a carrageenan induced rat paw oedema method, analgesic activity by Eddy’s hot plate method and antipyretic activity by brewer’s yeast induced pyrexia method. All the novel derivatives have been synthesized by the reaction of camphor and similar ketone having cyclohexane nucleus (e.g. 2-bromocyclohexanone with ammonium carbonate and formic acid resulting in the formation of aromatic amines (1a-b. These amines on further chloroacetylation with chloroacetylchloride give compounds (2a-b. Compounds (2a-b are converted to 2-(substituted phenoxy-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl acetamide and N-(2-bromocyclohexyl-2-(substituted phenoxyacetamide derivatives on treatment with substituted phenol. Among the series 3a-f, 3i, 3k, 3l compounds showed significant anti-inflammatory activity as compared to the standard drug diclofenac sodium and also compound 3a-f, 3h, 3j, 3k exhibit significant analgesic activity as compared to the standard drug. Compounds 3a-f and 3k showed antipyretic activity nearly to the standard drug indomethacin. Compounds 3a-f and 3k possess anti-inflammatory, analgesic and antipyretic activities near to the standard.

  15. Intramolecular kinetic isotope effect in gas-phase proton-transfer reactions

    International Nuclear Information System (INIS)

    Wellman, K.M.; Victoriano, M.E.; Isolani, P.C.; Riveros, J.M.

    1979-01-01

    The k/sub H//k/sub D/ isotope effects were determined by ICR for the reaction of substituted toluenes with several alkoxides. The results showed a definite trend for k/sub H//k/sub D/ starting as a normal isotope effect for appreciably exothermic reaction (> 3 kcal mol -1 ) and proceeding smoothly toward an inverse isotope effect as the reaction approached thermoneutrality or becomes endothermic. These observations were explained by a reaction which involved a double minima potential with a central energy barrier

  16. Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

    Directory of Open Access Journals (Sweden)

    Sándor B. Ötvös

    2013-07-01

    Full Text Available The preparation of novel multi-substituted 1,2,3-triazole-modified β-aminocyclohexanecarboxylic acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently, the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects.

  17. Synthesis, Spectral and Antimicrobial Studies of Some N(2)-Substituted Tetrahydroindazoles

    International Nuclear Information System (INIS)

    Amirthaganesan, Shanmugasundaram; Aridoss, Gopalakrishnan; Park, Keun Soo; Lim, Kwon Taek; Jeong, Yeon Tae

    2010-01-01

    A series of N(2)-benzothiazolyl substituted tetrahydroindazoles has been synthesized via cyclic β keto esters. Optimum reaction condition was found as acidic toluene and effect of higher acidity towards substituted hydrazines in situ was described. Synthesized compounds have been achieved as single isomer and characterized by using 1D and 2D NMR spectral reports. Antimicrobial screening was carried out for the synthesized compounds along with a series of N(2)-pyridyl tetrahydroindazoles. 1 The results of the in vitro antimicrobial screening studies revealed that compounds 13, 16 against Staphylococcus aureus, 11 against Escherichia coli, 10-12, 16 against Pseudomonas aeruginosa and 12 against Klebsiella pneumoniae recorded almost two-fold better activity compared to the standard drug used

  18. Human heme oxygenase oxidation of 5- and 15-phenylhemes.

    Science.gov (United States)

    Wang, Jinling; Niemevz, Fernando; Lad, Latesh; Huang, Liusheng; Alvarez, Diego E; Buldain, Graciela; Poulos, Thomas L; de Montellano, Paul R Ortiz

    2004-10-08

    Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.

  19. Molecular controls of the oxygenation and redox reactions of hemoglobin.

    Science.gov (United States)

    Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Banerjee, Sambuddha; Crumbliss, Alvin L

    2013-06-10

    The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.

  20. Synthesis and Characterization of 5-Substituted 1 H -Tetrazoles in ...

    African Journals Online (AJOL)

    Nano-TiCl4.SiO2 was found to be an extremely efficient catalyst for the preparation of 5-substituted 1H-tetrazole derivatives. Nano-TiCl4.SiO2 is a solid Lewis-acid was synthesized by the reaction of nano-SiO2 and TiCl4. The structure characterization of this acid was achieved with X-ray diffraction, thermogravimetric ...

  1. Amino acid derived 1,4-dialkyl substituted imidazolones

    DEFF Research Database (Denmark)

    Diness, Frederik; Meldal, Morten Peter

    2010-01-01

    A general method for synthesis of 1,4-substituted imidazolones from amino acids on solid support or in solution has been developed. Amino acid derived 3-Boc-(1,3)-oxazinane (Box) protected amino aldehyde building blocks were coupled through urea bonds to the amino terminal of dipeptides or amino...... acids. Upon acidic release, the aldehyde instantaneously formed the cyclic N-carbamyliminium ion, which rearranged to the corresponding imidazolone. Under strongly acidic conditions the imidazolones acted as nuclophiles in the Pictet-Spengler reaction....

  2. Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an efficient heteropolyacid-catalyzed procedure.

    Science.gov (United States)

    Kaoua, Rachedine; Bennamane, Norah; Bakhta, Saliha; Benadji, Sihame; Rabia, Cherifa; Nedjar-Kolli, Bellara

    2010-12-28

    An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs) was developed. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines derivatives.

  3. Synthesis of Substituted 1,4-Diazepines and 1,5-Benzodiazepines Using an Efficient Heteropolyacid-Catalyzed Procedure

    Directory of Open Access Journals (Sweden)

    Sihame Benadji

    2010-12-01

    Full Text Available An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs was developed. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines derivatives.

  4. Natural derivatives of diphenolic acid as substitutes for bisphenol-A

    Science.gov (United States)

    Ertl, Johanna; Cerri, Elisa; Rizzuto, Matteo; Caretti, Daniele

    2014-05-01

    Diphenolic acid had been originally used in the first epoxy resins and was later on forgotten as it was substituted by the cheaper bisphenol A. But in the recent years major health concerns have been raised as bisphenol A has a pseudo-hormonal effect on the body, playing the role of estrogen it can cause a severe impact on the organism, especially in males. Moreover it is produced from acetone and phenol, both from fossil, and thus limited resources. On the contrary, diphenolic acid is synthesized from levulinic acid and phenol. Levulinic acid being directly produced by hydrolysis of biomass. By substituting the fossil phenol with natural phenols from lignin or plant extraction we are able to synthesize a fully renewable substitute for bisphenol A. The reactions to yield an epoxy resin have been examined and the reactivity with epichlorohydrin is satisfying. Moreover, some of the derivatives of diphenolic acid have interesting curing properties and preliminary results show excellent properties of the cured resin, including thermal stability and pencil hardness.

  5. Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant--target interactions.

    Science.gov (United States)

    Lopachin, Richard M; Gavin, Terrence; Decaprio, Anthony; Barber, David S

    2012-02-20

    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are, however, discriminatory since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acids and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  6. APPLICATION OF THE HARD AND SOFT, ACIDS AND BASES (HSAB) THEORY TO TOXICANT-TARGET INTERACTIONS

    Science.gov (United States)

    LoPachin, Richard M.; Gavin, Terrence; DeCaprio, Anthony; Barber, David S.

    2011-01-01

    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are however discriminatory, since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acid and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this Perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  7. Biotransformations of Substituted Phenylethanols and Acetophenones by Environmental Bacteria

    Directory of Open Access Journals (Sweden)

    Edna Kagohara

    2008-01-01

    Full Text Available Whole cells of hydrocarbon-degrading bacteria, isolated from polluted sediments in the Santos Estuary (Baixada Santista, São Paulo, Brazil, were able to catalyse oxidoreduction reactions with various substituted phenylethanols and acetophenones as substrates. A number of substituted phenylethanols were formed with high (>99 % enantiomeric excess. The results of microbial oxidation of phenylethanols 2, 3, 5–7 by Acinetobacter sp. 6.4T and the reduction of acetophenones 1a–6a by Serratia marcescens 5.4T showed that the bacteria used as biocatalysts in this study present significant potential for exploitation in biotechnological processes. The reduction of prochiral acetophenones by Serratia marcescens 3.5T yielded optically active alcohols with 90–99 % enantiomeric excess, and Acinetobacter sp. 6.4T is a potential biocatalyst for the oxidation of alcohols.

  8. Catalyst-free aldol reaction of N-substituted rhodanines on aqueous ...

    Indian Academy of Sciences (India)

    N S DEVI

    2018-02-07

    Feb 7, 2018 ... catalytic aldol reaction is very common in organic sol- vents and ... −1. ). 1H NMR and 13C NMR spectra were recorded at 400 and 100 MHz in CDCl3. Chemical shifts ... 2.2 General procedure for the synthesis of rhodanine.

  9. Synthesis of Ortho Substituted Arylboronic Esters by in Situ Trapping of Unstable Lithio Intermediates

    DEFF Research Database (Denmark)

    Kristensen, Jesper Langgaard; Lysén, M.; Vedsø, Per

    2001-01-01

    matrix presented Ortho lithiation-in situ boration using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in combination with triisopropylborate (B(OiPr) ) is a highly efficient and experimentally straightforward process for the preparation of ortho substituted arylboronic esters. The mild reaction c...

  10. Making Mn substitutional impurities in InAs using a scanning tunneling microscope.

    Science.gov (United States)

    Song, Young Jae; Erwin, Steven C; Rutter, Gregory M; First, Phillip N; Zhitenev, Nikolai B; Stroscio, Joseph A

    2009-12-01

    We describe in detail an atom-by-atom exchange manipulation technique using a scanning tunneling microscope probe. As-deposited Mn adatoms (Mn(ad)) are exchanged one-by-one with surface In atoms (In(su)) to create a Mn surface-substitutional (Mn(In)) and an exchanged In adatom (In(ad)) by an electron tunneling induced reaction Mn(ad) + In(su) --> Mn(In) + In(ad) on the InAs(110) surface. In combination with density-functional theory and high resolution scanning tunneling microscopy imaging, we have identified the reaction pathway for the Mn and In atom exchange.

  11. Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Kirkpatrick, Charles James [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz (Germany); Willershausen, Ines [Institute for Dental Material Sciences and Technology, University Medical Center of the Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 14, 55128 Mainz (Germany); Thimm, Benjamin W [Institute for Biomechanics, ETH Zuerich, Wolfgang-Pauli-Str.10, 8093 Zuerich (Switzerland); Booms, Patrick [Leeds Institute of Molecular Medicine, Section of Medicine, Surgery and Anaesthesia, University of Leeds (United Kingdom); Stuebinger, Stefan; Landes, Constantin; Sader, Robert Anton, E-mail: ghanaati@uni-mainz.d [Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Theodor-Stein-Kai 7, 60596 Frankfurt am Main (Germany)

    2010-06-01

    The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute. The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

  12. Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats

    International Nuclear Information System (INIS)

    Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Kirkpatrick, Charles James; Willershausen, Ines; Thimm, Benjamin W; Booms, Patrick; Stuebinger, Stefan; Landes, Constantin; Sader, Robert Anton

    2010-01-01

    The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute. The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

  13. Method for Derivatization and Detection of Chemical Weapons Convention Related Sulfur Chlorides via Electrophilic Addition with 3-Hexyne.

    Science.gov (United States)

    Goud, D Raghavender; Pardasani, Deepak; Purohit, Ajay Kumar; Tak, Vijay; Dubey, Devendra Kumar

    2015-07-07

    Sulfur monochloride (S2Cl2) and sulfur dichloride (SCl2) are important precursors of the extremely toxic chemical warfare agent sulfur mustard and classified, respectively, into schedule 3.B.12 and 3.B.13 of the Chemical Weapons Convention (CWC). Hence, their detection and identification is of vital importance for verification of CWC. These chemicals are difficult to detect directly using chromatographic techniques as they decompose and do not elute. Until now, the use of gas chromatographic approaches to follow the derivatized sulfur chlorides is not reported in the literature. The electrophilic addition reaction of sulfur monochloride and sulfur dichloride toward 3-hexyne was explored for the development of a novel derivatization protocol, and the products were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Among various unsaturated reagents like alkenes and alkynes, symmetrical alkyne 3-hexyne was optimized to be the suitable derivatizing agent for these analytes. Acetonitrile was found to be the suitable solvent for the derivatization reaction. The sample preparation protocol for the identification of these analytes from hexane spiked with petrol matrix was also optimized. Liquid-liquid extraction followed by derivatization was employed for the identification of these analytes from petrol matrix. Under the established conditions, the detection and quantification limits are 2.6 μg/mL, 8.6 μg/mL for S2Cl2 and 2.3 μg/mL, 7.7 μg/mL for SCl2, respectively, in selected ion monitoring (SIM) mode. The calibration curve had a linear relationship with y = 0.022x - 0.331 and r(2) = 0.992 for the working range of 10 to 500 μg/mL for S2Cl2 and y = 0.007x - 0.064 and r(2) = 0.991 for the working range of 10 to 100 μg/mL for SCl2, respectively. The intraday RSDs were between 4.80 to 6.41%, 2.73 to 6.44% and interday RSDs were between 2.20 to 7.25% and 2.34 to 5.95% for S2Cl2 and SCl2, respectively.

  14. An improved synthesis of 2,2−-((4-substituted phenyl methylene difurans by Ultrasound irradiation

    Directory of Open Access Journals (Sweden)

    Naween M. Yonis

    2016-09-01

    Full Text Available A new series of 2,2−((4-substituted phenyl methylene difuran was synthesized by one-pot cyclocondensation of aldehyde with excess furan at room temperature using trifluoro acetic acid as a catalyst under ultrasound irradiation in the absence of solvent. The products were compared with the classical condensation reactions. This method consistently enjoys the advantages of mild reaction conditions, excellent yields, easy work up and short time.

  15. Energy landscapes of nucleophilic substitution reactions: a comparison of density functional theory and coupled cluster methods

    NARCIS (Netherlands)

    Swart, M.; Sola, M.; Bickelhaupt, F.M.

    2007-01-01

    We have carried out a detailed evaluation of the performance of all classes of density functional theory (DFT) for describing the potential energy surface (PES) of a wide range of nucleophilic substitution (S

  16. Evaluation of new radiopharmaceuticals: synthesis, evaluation, and biodistribution of radiolabelled peptide of VCAM-1 and αvβ3

    International Nuclear Information System (INIS)

    Ardisson, V.

    2006-07-01

    The new development of nuclear medicine implies the search of new isotopes but also for new vectors specific of functions or metabolic pathways. We investigated new radiopharmaceuticals intended for new diagnostic approaches of two physiopathological mechanisms frequently met in our populations: the atherosclerosis vulnerable plaque and the tumor angio genesis. We studied and optimized the iodine and 99 m-technetium radiolabelling, of a series of peptides in order to allow the in vivo use of these tracers for imaging studies in animals and possibly in humans. The radioiodination, was carried out by electrophilic substitution, and technetium was linked by a tri-carbonyl B.F.C.A. (Isolink). The reaction parameters were defined so that the labelling reactions presents a high radiochemical purity (>95%), and a high specificity activity. The reactions are fast and reproducible. Various physicochemical properties: lipo-solubility, stability of labelling, and pharmacokinetic properties: non specific binding, metabolization and organ biodistribution of peptides in animal model, were studied. These results indicate which peptide may be a suitable candidate for targeting trials. (author)

  17. α-Selective Ni-Catalyzed Hydroalumination of Aryl- and Alkyl-Substituted Terminal Alkynes. Practical Syntheses of Internal Vinyl Aluminums, Halides or Boronates

    Science.gov (United States)

    Gao, Fang; Hoveyda, Amir H.

    2010-01-01

    Methods for Ni-catalyzed hydroalumination of terminal alkynes, leading to the formation of α-vinylaluminum isomers efficiently (>98% conv in 2–12 h) and with high selectivity (95% to >98% α), are described. Catalytic α-selective hydroalumination reactions proceed in the presence of a reagent (diisobutylaluminum hydride; dibal–H) and 3.0 mol % metal complex (Ni(dppp)Cl2) that are commercially available and inexpensive. Under the same conditions, but with Ni(PPh3)2Cl2, hydroalumination becomes highly β-selective, and, unlike uncatalyzed transformations with dibal–H, generates little or no alkynylaluminum byproducts. All hydrometallation reactions are reliable, operationally simple and practical, and afford an assortment of vinylaluminums that are otherwise not easily accessible. The derived α-vinyl halides and boronates can be synthesized through direct treatment with the appropriate electrophiles [e.g., Br2 and methoxy(pinacolato)boron, respectively]. Ni-catalyzed hydroaluminations can be performed with as little as 0.1 mol % catalyst and on gram scale with equally high efficiency and selectivity. PMID:20698643

  18. Mechanistic aspects of ionic reactions in flames

    DEFF Research Database (Denmark)

    Egsgaard, H.; Carlsen, L.

    1993-01-01

    Some fundamentals of the ion chemistry of flames are summarized. Mechanistic aspects of ionic reactions in flames have been studied using a VG PlasmaQuad, the ICP-system being substituted by a simple quartz burner. Simple hydrocarbon flames as well as sulfur-containing flames have been investigated...

  19. Stereoselective synthesis of an iodinated resveratrol analog: Preliminary bioevaluation studies of the radioiodinated species

    Energy Technology Data Exchange (ETDEWEB)

    Dhyani, Manish V.; Kameswaran, Mythili; Korde, Aruna G.; Pandey, Usha [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Chattopadhyay, Subrata [Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila, E-mail: sharmila@barc.gov.i [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2011-07-15

    Stereoselective synthesis of an E-hydroxystilbene has been carried out using the McMurry reaction. Synthesis of a monoiodinated hydroxystilbene has been carried out by a McMurry cross-coupling reaction. For the purpose of biological evaluation, the facile electrophilic substitution route has been attempted to radioiodinate it with {sup 125}I. The HPLC pattern of the radioiodinated hydroxystilbene, which could be obtained in >90% radiochemical purity, was found to be identical to that of its non-radioactive analog that has been independently prepared using the McMurry cross-coupling route. In vitro cell uptake studies were carried out in breast cancer cells MCF7, overexpressing estrogen receptors. In vivo biodistribution studies in female Swiss mice show a uterine uptake of 0.85{+-}0.4% ID/g at 3 h.p.i. with a uterus to muscle ratio of 2.83. Uptake in the thyroid was insignificant indicating good in vivo stability of the radioiodinated hydroxystilbene.

  20. A new multicomponent reaction for the synthesis of pyridines via cycloaddition of azadienes and ketenimines

    NARCIS (Netherlands)

    Coffinier, D.; El Kaim, L.; Grimaud, L.; Ruijter, E.; Orru, R.V.A.

    2011-01-01

    The ketenimines resulting from a Nef isocyanide/Perkow sequence react with 1-azadienes to form pyridines or pyrimidines depending on their substitution pattern. The reaction is most efficient with ester-substituted ketenimines which leads to pyridines after elimination of the phosphate group. © 2011

  1. Polymethylated [Fe(eta(6)-arene)(2)](2+) dications: methyl-group rearrangements and application of the EINS mechanism

    Czech Academy of Sciences Publication Activity Database

    Štíbr, Bohumil; Bakardjiev, Mario; Hájková, Zuzana; Holub, Josef; Padělková, Z.; Růžička, A.; Kennedy, J.D.

    2011-01-01

    Roč. 40, č. 22 (2011), s. 5916-5920 ISSN 1477-9226 R&D Projects: GA MŠk LC523 Institutional research plan: CEZ:AV0Z40320502 Keywords : electrophile-induced nucleophilic substitution Subject RIV: CA - Inorganic Chemistry Impact factor: 3.838, year: 2011

  2. Organic astatine compounds, their preparation and properties

    Energy Technology Data Exchange (ETDEWEB)

    Vasaros, L; Berei, K

    1985-01-01

    Aromatic astatine compounds of possible medical application were prepared by high energy substitutions, by astatine-halogen, and by electrophil astatine-hydrogen substitutions at the Joint Institute of Nuclear Researches, Dubna. Physico-chemical properties of organic astatine compounds such as boiling point and evaporation heat, and the refraction and dissociation energy of carbon-astatine bonds were determined experimentally by gas chromatography. The results are compared with extrapolated data. (V.N.). 41 refs.; 7 figs.; 5 tables.

  3. Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

    Science.gov (United States)

    Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

    2016-04-11

    Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted phenyl...

  5. Do follow-on therapeutic substitutes induce price competition between hospital medicines? Evidence from the Danish hospital sector

    DEFF Research Database (Denmark)

    Hostenkamp, Gisela

    2013-01-01

    Objective The pricing of follow-on drugs, that offer only limited health benefits over existing therapeutic alternatives, is a recurring health policy debate. This study investigates whether follow-on therapeutic substitutes create price competition between branded hospital medicines. Methods New...... pioneer products were significantly reduced as a reaction to competition from follow-on drugs. Conclusion Competition between patented therapeutic substitutes did not seem to increase price competition and containment of pharmaceutical expenditures in the Danish hospital market. Strengthening hospitals......’ incentives to consider the price of alternative treatment options paired with a more active formulary management may increase price competition between therapeutic substitutes in the Danish hospital sector in the future....

  6. N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties

    Directory of Open Access Journals (Sweden)

    Ondrej Jandourek

    2014-01-01

    Full Text Available In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R = 3,4-Cl, 9 (R = 2-Cl and 11 (R = 4-CF3 showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL. It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig’s plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R = 3-CF3, 3 (R = 3,4-Cl and 11 (R = 4-CF3. A linear dependence between lipophilicity and herbicidal activity was observed.

  7. Simple, mild, and highly efficient synthesis of 2-substituted benzimidazoles and bis-benzimidazoles

    International Nuclear Information System (INIS)

    Eren, Bilge; Bekdemir, Yunus

    2014-01-01

    A new convenient method for preparation of 2-substituted benzimidazoles and bis-benzimidazoles is presented. In this method, o-phenylenediamines were condensed with bisulfite adducts of various aldehydes and di-aldehydes under neat conditions by microwave heating. The results were also compared with results of synthesis by conventional heating under reflux. Structures of the products were confirmed by infrared, 1 H- and 13 C-NMR spectroscopy. Short reaction times, good yields, easy purification of products, and mild reaction conditions are the main advantages of this method. (author)

  8. Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

    Science.gov (United States)

    MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

    1991-01-01

    The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

  9. Iridium-Catalyzed Regioselective Borylation of Substituted Biaryls

    KAUST Repository

    Chotana, Ghayoor

    2018-03-28

    Biarylboronic esters are generally prepared by directed ortho­ -metalation or by Miyaura borylation and hence rely on the presence of a directing group or pre-functionalization. In this paper, the preparation of biarylboronic esters by direct C–H borylation of biaryl substrates is reported. Sterically governed regioselectivities were observed in the borylation of appropriately substituted biaryls by using [Ir(OMe)(COD)] precatalyst and di- tert -butylbipyridyl ligand. The resulting biarylboronic esters were isolated in 38–98% yields. The synthesized biarylboronic esters were further successfully employed in C–O, C–Br, and C–C coupling reactions.

  10. Copper-promoted oxidative coupling of enamides and alkynes for the synthesis of substituted pyrroles.

    Science.gov (United States)

    Zhao, Mi-Na; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui

    2014-02-10

    An efficient copper-promoted oxidative coupling of enamides with alkynes has been developed for the synthesis of substituted pyrroles. The reaction proceeded through C-H and N-H bond functionalization of enamides under mild conditions. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed Mahrous Hamada

    2015-06-01

    Full Text Available The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.

  12. Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

    Science.gov (United States)

    Henkens, Robert; Alayash, Abdu I.; Banerjee, Sambuddha; Crumbliss, Alvin L.

    2013-01-01

    Abstract Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313. PMID:23198874

  13. Sodium ions as substitutes for protons in the gastric H,K-ATPase

    International Nuclear Information System (INIS)

    Polvani, C.; Sachs, G.; Blostein, R.

    1989-01-01

    In view of the striking homology among various ion-translocating ATPases including Na,K-ATPase, Ca-ATPase, and H,K-ATPase, and the recent evidence that protons can replace cytoplasmic sodium as well as potassium in the reaction mechanism of the Na,K-ATPase (Polvani, C., and Blostein, R. (1988) J. Biol. Chem. 263, 16757-16763), we studied the role of sodium as a substitute for protons in the H,K-ATPase reaction. Using hog gastric H,K-ATPase-rich inside-out membrane vesicles we observed 22Na+ influx which was stimulated by intravesicular potassium ions (K+i) at pH 8.5 but not at pH 7.1. This sodium influx was observed in medium containing ATP and was inhibited by vanadate and SCH28080, a selective inhibitor of the gastric H,K-ATPase. At least 2-fold accumulation of sodium was observed at pH 8.5. Experiments aimed to determine the sidedness of the alkaline pH requirement for K+i-dependent sodium influx showed that K+i-activated sodium influx depends on pHout and is unaffected by changes in pHin. These results support the conclusion that sodium ions substitute for protons in the H,K-ATPase reaction mechanism and provide evidence for a similarity in ion selectivity and/or binding domains of the Na,K-ATPase and the gastric H,K-ATPase enzymes

  14. Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview

    Directory of Open Access Journals (Sweden)

    Donatella Giomi

    2010-03-01

    Full Text Available Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA reactions, 4,5-dicyanopyridazine (DCP showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives.

  15. On the importance of hydrogen bonding in the promotion of Diels-Alder reactions of unactivated aldehydes: a computational study

    Science.gov (United States)

    Chemouri, Hafida; Mekelleche, Sidi Mohamed

    2014-03-01

    The kinetic solvent effects on the Diels-Alder (DA) reaction of N,N-dimethylamino-3-trimethylsilyl butadiene with p-anisaldehyde are studied by density functional calculations at the B3LYP/6-31C(d) level of theory. Experimentally, it has been found that the acceleration of this reaction is not due to the increase of the polarity of the solvent but it is rather due to hydrogen bonding (HB). Intrinsic reaction coordinate calculations combined with electron localisation function analysis show that this reaction follows a one-step two-stage mechanism with a highly asynchronous sigma bond formation process. The calculations, performed using an explicit solvent model based on the coordination of the carbonyl group with one molecule of the solvent, show a considerable decrease of the activation energy when going from the gas phase (ɛ = 1) to solution phase and this diminution is found to be more important in isopropyl alcohol (ɛ = 18.3) in comparison with acetonitrile (ɛ = 37.5). Our calculations also show that the acceleration of this DA reaction is due to the increase of the electrophilicity power of the solvated carbonyl compound and consequently the increase of the polarity of the reaction in the presence of protic solvents. The obtained results put in evidence the relevance of HB in the promotion of DA reactions of unactivated ketones as experimentally expected.

  16. Diels-Alder Reaction of Isobenzofurans/Cyclopentadienones with Tetrathiafulvalene: Preparation of Naphthalene, Fluoranthene, and Fluorenone Derivatives.

    Science.gov (United States)

    Karunakaran, Jayachandran; Mohanakrishnan, Arasambattu K

    2018-02-16

    Diels-Alder reaction of 1,3-diarylbenzo[c]furan/cyclopentadienone with TTF followed by triflic acid mediated cleavage of the resulting adducts led to the formation of the respective 1,4-diaryl substituted naphthalenes, fluoranthenes, and fluorenones. The photophysical properties of representative diaryl-substituted hydrocarbons are also reported.

  17. Physio-chemical reactions in recycle aggregate concrete.

    Science.gov (United States)

    Tam, Vivian W Y; Gao, X F; Tam, C M; Ng, K M

    2009-04-30

    Concrete waste constitutes the major proportion of construction waste at about 50% of the total waste generated. An effective way to reduce concrete waste is to reuse it as recycled aggregate (RA) for the production of recycled aggregate concrete (RAC). This paper studies the physio-chemical reactions of cement paste around aggregate for normal aggregate concrete (NAC) and RAC mixed with normal mixing approach (NMA) and two-stage mixing approach (TSMA) by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Four kinds of physio-chemical reactions have been recorded from the concrete samples, including the dehydration of C(3)S(2)H(3), iron-substituted ettringite, dehydroxylation of CH and development of C(6)S(3)H at about 90 degrees C, 135 degrees C, 441 degrees C and 570 degrees C, respectively. From the DSC results, it is confirmed that the concrete samples with RA substitution have generated less amount of strength enhancement chemical products when compared to those without RA substitution. However, the results from the TSMA are found improving the RAC quality. The pre-mix procedure of the TSMA can effectively develop some strength enhancing chemical products including, C(3)S(2)H(3), ettringite, CH and C(6)S(3)H, which shows that RAC made from the TSMA can improve the hydration processes.

  18. Physio-chemical reactions in recycle aggregate concrete

    International Nuclear Information System (INIS)

    Tam, Vivian W.Y.; Gao, X.F.; Tam, C.M.; Ng, K.M.

    2009-01-01

    Concrete waste constitutes the major proportion of construction waste at about 50% of the total waste generated. An effective way to reduce concrete waste is to reuse it as recycled aggregate (RA) for the production of recycled aggregate concrete (RAC). This paper studies the physio-chemical reactions of cement paste around aggregate for normal aggregate concrete (NAC) and RAC mixed with normal mixing approach (NMA) and two-stage mixing approach (TSMA) by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Four kinds of physio-chemical reactions have been recorded from the concrete samples, including the dehydration of C 3 S 2 H 3 , iron-substituted ettringite, dehydroxylation of CH and development of C 6 S 3 H at about 90 deg. C, 135 deg. C, 441 deg. C and 570 deg. C, respectively. From the DSC results, it is confirmed that the concrete samples with RA substitution have generated less amount of strength enhancement chemical products when compared to those without RA substitution. However, the results from the TSMA are found improving the RAC quality. The pre-mix procedure of the TSMA can effectively develop some strength enhancing chemical products including, C 3 S 2 H 3 , ettringite, CH and C 6 S 3 H, which shows that RAC made from the TSMA can improve the hydration processes

  19. A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H-furanones

    Directory of Open Access Journals (Sweden)

    Jubi John

    2014-06-01

    Full Text Available A facile route towards highly functionalized 3(2H-furanones via a sequential Mannich addition–palladium catalyzed ring closing has been elaborated. The reaction of 4-chloroacetoacetate esters with imines derived from aliphatic and aromatic aldehydes under palladium catalysis afforded 4-substituted furanones in good to excellent yields. 4-Hydrazino-3(2H-furanones could also be synthesized from diazo esters in excellent yields by utilising the developed strategy. We could also efficiently transform the substituted furanones to aza-prostaglandin analogues.

  20. Simple, mild, and highly efficient synthesis of 2-substituted benzimidazoles and bis-benzimidazoles

    Energy Technology Data Exchange (ETDEWEB)

    Eren, Bilge, E-mail: bilge.eren@bilecik.edu.tr [Faculty of Science and Arts, Department of Chemistry, Bilecik Seyh Edebali University, (Turkey); Bekdemir, Yunus [Faculty of Science and Arts, Canik Basari University, Samsun (Turkey)

    2014-07-01

    A new convenient method for preparation of 2-substituted benzimidazoles and bis-benzimidazoles is presented. In this method, o-phenylenediamines were condensed with bisulfite adducts of various aldehydes and di-aldehydes under neat conditions by microwave heating. The results were also compared with results of synthesis by conventional heating under reflux. Structures of the products were confirmed by infrared, {sup 1}H- and {sup 13}C-NMR spectroscopy. Short reaction times, good yields, easy purification of products, and mild reaction conditions are the main advantages of this method. (author)

  1. Simple, mild, and highly efficient synthesis of 2-substituted benzimidazoles and bis-benzimidazoles

    Directory of Open Access Journals (Sweden)

    Bilge Eren

    2014-01-01

    Full Text Available A new convenient method for preparation of 2-substituted benzimidazoles and bis-benzimidazoles is presented. In this method, o-phenylenediamines were condensed with bisulfite adducts of various aldehydes and di-aldehydes under neat conditions by microwave heating. The results were also compared with results of synthesis by conventional heating under reflux. Structures of the products were confirmed by infrared, ¹H- and 13C-NMR spectroscopy. Short reaction times, good yields, easy purification of products, and mild reaction conditions are the main advantages of this method.

  2. Substituting Normal and Waxy-Type Whole Wheat Flour on Dough and Baking Properties

    Science.gov (United States)

    Choi, Induck; Kang, Chun-Sik; Cheong, Young-Keun; Hyun, Jong-Nae; Kim, Kee-Jong

    2012-01-01

    Normal (cv. Keumkang, KK) and waxy-type (cv. Shinmichal, SMC) whole wheat flour was substituted at 20 and 40% for white wheat flour (WF) during bread dough formulation. The flour blends were subjected to dough and baking property measurement in terms of particle size distribution, dough mixing, bread loaf volume and crumb firmness. The particle size of white wheat flour was the finest, with increasing coarseness as the level of whole wheat flour increased. Substitution of whole wheat flour decreased pasting viscosity, showing all RVA parameters were the lowest in SMC40 composite flour. Water absorption was slightly higher with 40% whole wheat flour regardless of whether the wheat was normal or waxy. An increased mixing time was observed when higher levels of KK flour were substituted, but the opposite reaction occurred when SMC flour was substituted at the same levels. Bread loaf volume was lower in breads containing a whole wheat flour substitution compared to bread containing only white wheat flour. No significant difference in bread loaf volume was observed between normal and waxy whole flour, but the bread crumb firmness was significantly lower in breads containing waxy flour. The results of these studies indicate that up to 40% whole wheat flour substitution could be considered a practical option with respect to functional qualities. Also, replacing waxy whole flour has a positive effect on bread formulation over normal whole wheat flour in terms of improving softness and glutinous texture. PMID:24471084

  3. Radical cascades using enantioenriched 7-azabenzonorbornenes and their applications in synthesis

    Directory of Open Access Journals (Sweden)

    2008-10-01

    Full Text Available Tandem deoxygenation–neophyl-type radical rearrangement–electrophile trapping using xanthates from 7-azabenzonorbornadienes gives 3-exo-substituted 2-aza-5,6-benzonorbornenes, which in some cases undergo isomerisation to (aminomethylindenes. The starting xanthates are accessible in good yields and high enantiomeric ratios via asymmetric hydroboration of (aryne/pyrrole-derived 7-azabenzonorbornadienes. Oxidation (using RuO4 and Birch reduction of the 2-aza-5,6-benzonorbornenes provide access to substituted pyrrolidines and tetrahydroindenes, respectively.

  4. Application of isotopic substitution for studing thermal decomposition of silico-12-tungstic acid

    International Nuclear Information System (INIS)

    Khakhinov, V.V.; Pinchuk, I.N.; Tumurova, L.V.; Mokhosoev, M.V.

    1987-01-01

    Using the methods of thermal analysis and isotopic substitution, the mechanism of dehydration and decomposition of silico-12-tungstic acid hydrate is studied. It is found that H-D exchange leads to elevation of temperature of heteropoly acid decomposition. The observed isotopic effect shows that proton transfer is the limiting stage of the reaction

  5. A Catalyst-Free Amination of Functional Organolithium Reagents by Flow Chemistry.

    Science.gov (United States)

    Kim, Heejin; Yonekura, Yuya; Yoshida, Jun-Ichi

    2018-04-03

    Reported is the electrophilic amination of functional organolithium intermediates with well-designed aminating reagents under mild reaction conditions using flow microreactors. The aminating reagents were optimized to achieve efficient C-N bond formation without using any catalyst. The electrophilic amination reactions of functionalized aryllithiums were successfully conducted under mild reaction conditions, within 1 minute, by using flow microreactors. The aminating reagent was also prepared by the flow method. Based on stopped-flow NMR analysis, the reaction time for the preparation of the aminating reagent was quickly optimized without the necessity of work-up. Integrated one-flow synthesis consisting of the generation of an aryllithium, the preparation of an aminating reagent, and their combined reaction was successfully achieved to give the desired amine within 5 minutes of total reaction time. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Hydronium-Ion-Catalyzed Elimination Pathways of Substituted Cyclohexanols in Zeolite H-ZSM5

    Energy Technology Data Exchange (ETDEWEB)

    Hintermeier, Peter H. [Department; Eckstein, Sebastian [Department; Mei, Donghai [Institute; Olarte, Mariefel V. [Institute; Camaioni, Donald M. [Institute; Baráth, Eszter [Department; Lercher, Johannes A. [Department; Institute

    2017-10-02

    Hydronium ions in the pores of zeolite H-ZSM5 show high catalytic activity in the elimination of water from cyclohexanol in aqueous phase. Substitution induces subtle changes in rates and reaction pathways, which are concluded to be related to steric effects. Exploring the reaction pathways of 2-, 3-, and 4-methylcyclohexanol (2-McyOH, 3-McyOH, and 4-McyOH), 2- and 4-ethylcyclohexanol (2-EcyOH and 4-EcyOH), 2-n-propylcyclohexanol (2-PcyOH), and cyclohexanol (CyOH) it is shown that the E2 character increases with closer positioning of the alkyl and hydroxyl groups. Thus, 4-McyOH dehydration proceeds via an E1-type elimination, while cis-2-McyOH preferentially reacts via an E2 pathway. The entropy of activation decreased with increasing alkyl chain length (ca. 20 J mol-1 K-1 per CH2 unit) for 2-substituted alcohols, which is concluded to result from constraints influencing the configurational entropy of the transition states.

  7. Effect of Bronsted Acids and Bases, and Lewis Acid (Sn(2+)) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-β-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisomeric 1H-Pyrrolo[3,2-b]pyridines.

    Science.gov (United States)

    De Rosa, Michael; Arnold, David; Hartline, Douglas; Truong, Linda; Verner, Roman; Wang, Tianwei; Westin, Christian

    2015-12-18

    Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-β-diketones gave γ-1H-pyrrolo[3,2-b]pyridines via reaction at the less reactive carbonyl group. The trifluoromethyl group increased the electrophilicity of the adjacent carbonyl group and decreased the basicity of the hydroxyl group of the CF3 amino alcohol formed. This amino alcohol was formed faster, but its subsequent dehydration to the β-enaminone was slow resulting in the preferential formation of the γ-regioisomer. Reaction of 4,4,4-trifluoro-1-phenyl-1,3-butadione with 3-aminopyrrole was carried out using a series of 6 amine buffers. Yields of the α-1H-pyrrolo[3,2-b]pyridine increased as the pKa of the amine buffer decreased. Surprisingly the yield went down at higher pKas. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-β-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-β-diketone) the α-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn(2+). Similar α-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-β-diketones was carried out in the presence of base and tin(II) acetate.

  8. DIELS-ALDER REACTIONS IN AQUEOUS-SOLUTIONS - ENFORCED HYDROPHOBIC INTERACTIONS BETWEEN DIENE AND DIENOPHILE

    NARCIS (Netherlands)

    BLOKZIJL, W; BLANDAMER, MJ; ENGBERTS, JBFN

    1991-01-01

    Second-order rate constants and isobaric activation parameters for the intermolecular Diels-Alder reactions of cyclopentadiene with alkyl vinyl ketones (2a,b) and 5-substituted-1,4-naphthoquinones (3a-c) as well as for the intramolecular Diels-Alder reaction of N-furfuryl-N-methylmaleamic acid (4)

  9. A Multistep Synthesis Incorporating a Green Bromination of an Aromatic Ring

    Science.gov (United States)

    Cardinal, Pascal; Greer, Brandon; Luong, Horace; Tyagunova, Yevgeniya

    2012-01-01

    Electrophilic aromatic substitution is a fundamental topic taught in the undergraduate organic chemistry curriculum. A multistep synthesis that includes a safer and greener method for the bromination of an aromatic ring than traditional bromination methods is described. This experiment is multifaceted and can be used to teach students about…

  10. Inversion of Configuration at the Phosphorus Nucleophile in the Diastereoselective and Enantioselective Synthesis of P-Stereogenic syn-Phosphiranes from Chiral Epoxides.

    Science.gov (United States)

    Muldoon, Jake A; Varga, Balázs R; Deegan, Meaghan M; Chapp, Timothy W; Eördögh, Ádám M; Hughes, Russell P; Glueck, David S; Moore, Curtis E; Rheingold, Arnold L

    2018-04-23

    Nucleophilic substitution results in inversion of configuration at the electrophilic carbon center (S N 2) or racemization (S N 1). The stereochemistry of the nucleophile is rarely considered, but phosphines, which have a high barrier to pyramidal inversion, attack electrophiles with retention of configuration at P. Surprisingly, cyclization of bifunctional secondary phosphine alkyl tosylates proceeded under mild conditions with inversion of configuration at the nucleophile to yield P-stereogenic syn-phosphiranes. DFT studies suggested that the novel stereochemistry results from acid-promoted tosylate dissociation to yield an intermediate phosphenium-bridged cation, which undergoes syn-selective cyclization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Reactions of charged and neutral recoil particles following nuclear transformations. Progress report No. 13

    International Nuclear Information System (INIS)

    Ache, H.J.

    1979-09-01

    Research is reported on: caging and solvent effects in hot 38 Cl substitution reactions in chlorinated hydrocarbons (dichlorobenzene), excitation labelling of organic compounds using 80 Br, reactions of energetic tritium with graphite and SiC surfaces, and micellar systems and microemulsions studied by positron annihilation

  12. Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

    Science.gov (United States)

    Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

    2015-01-01

    A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

  13. Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

    Science.gov (United States)

    Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

    2013-08-01

    In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  14. Theoretical study on the reaction mechanism of hydrogenation of furfural to furfuryl alcohol on Lewis acidic BEA zeolites: effects of defect structure and tetravalent metals substitution.

    Science.gov (United States)

    Injongkol, Yuwanda; Maihom, Thana; Treesukul, Piti; Sirijaraensre, Jakkapan; Boekfa, Bundet; Limtrakul, Jumras

    2017-09-13

    Furfural acquired from agricultural sources is receiving extensive attention in the petrochemical industry as it offers an alternative route to generate more valuable hydrocarbon compounds. Herein, we investigate the furfural hydrogenation to furfuryl alcohol catalyzed by Lewis acidic BEA zeolites at the molecular level by means of the M06-L density functional theory. The mechanistic pictures in the catalytic procedure are revealed. The possible reaction pathways are considered to proceed via either concerted or stepwise mechanisms. With the contribution of zeolite oxygen bridging for the H-H splitting, the rate determining step activation barrier for the stepwise mechanism is 14.7 kcal mol -1 lower than that for the concerted mechanism. The stepwise reaction therefore seems to be favored compared to the concerted one. The catalytic effect of the defect zeolite framework on the stepwise mechanism is also investigated. The activation energy for the stepwise rate-determining step over this site is significantly lower than the corresponding step over the perfect one by 14.1 kcal mol -1 . Finally, the catalytic activity of tetravalent metal centers (Sn, Ge, Zr and Hf) substituted in BEA is also preliminarily compared and it is found to follow the order of Hf > Zr > Sn > Ge based on activation energies and the reaction rate. The difference in the activation energy can be traced back to the difference in the charge transfer from the catalytic site to the adsorbed molecules.

  15. [The substitution effect of leadership substitutes for transformational leadership in nursing organization].

    Science.gov (United States)

    Kim, Jeong-Hee

    2006-04-01

    This paper was conducted to examine the effects of transformational leadership behaviors, within the substitutes for leadership model (Kerr & Jermier, 1978). Data was collected from 181 staff nurses in 3 general hospitals, with self-reporting questionnaires (MLQ developed by Bass, rd-SLS developed by Podsakoff, et al., and MSQ developed by Weiss, et al.). Descriptive statistics, factor analysis, Cronbach's alpha and moderated regression analysis were used. 1) The transformational leader behaviors and substitutes for leadership each had correlations with job satisfaction. 2) The total amount of variance accounted for by the substitutes for leadership was substantially greater than by the transformational leadership behaviors. 3) Few of the substitutes variables moderated the relationships between the transformational leader behaviors and job satisfaction in a manner consistent with that specified by Howell, Dorfman, and Kerr (1986). The finding of this study suggest that leaders need to have a better understanding of those contextual variables that influence job satisfaction. Thus future research should focus attention on the moderating effects of substitutes, as well as the things that leaders can do to influence them. In addition, it may be good to examine the effects of substitutes on other criterion variables.

  16. Rotational barriers of 1,3-substitute pyridines and benzenes as models for the NAD+/NADH coenzyme

    NARCIS (Netherlands)

    Vanhommerig, S.A.M.; Meier, R.J.; Sluyterman, L.A.A.E.; Meijer, E.M.

    1994-01-01

    The NAD+/NADH coenzyme is involved in many enzyme-catalysed oxidation-reduction reactions. In order to obtain better insight in the catalytic mechanism of NAD+/NADH dependent dehydrogenases, conformational studies of 1,3-substituted pyridines and benzenes were carried out, using ab initio,

  17. Syntheses and biological activities of 13-substituted avermectin aglycons.

    Science.gov (United States)

    Mrozik, H; Linn, B O; Eskola, P; Lusi, A; Matzuk, A; Preiser, F A; Ostlind, D A; Schaeffer, J M; Fisher, M H

    1989-02-01

    The reactions of sulfonate esters of the allylic/homoallylic 13-alcohol of 5-O-(tert-butyldimethylsilyl)-22,23-dihydroavermectin B1a aglycon (1a) were investigated. Nucleophilic substitution gave 13 beta-chloro and 13 beta-iodo derivatives, while solvolytic reaction conditions yielded 13 alpha-methoxy, 13 alpha-fluoro, and 13 alpha-chloro products. A mixture of 13 alpha- and 13 beta-fluorides was obtained upon reaction with DAST. The 13 beta-iodide gave, upon elimination with lutidine, the 8(9),10(11),12(13),14(15)-tetraene. The 13 beta-alcohol and the rearranged 15-ol 13(14)-ene and 15-amino 13(14)-ene derivatives were obtained by substitution via the allylic carbonium ion. MEM ethers 11 and 12 of the two epimeric 13-ols were prepared by alkylation with MEM chloride. In contrast, methylation of 1a with MeI and Ag2O in CH2Cl2 occurred exclusively at the tertiary 7-hydroxy group and not at the secondary 13 alpha-ol. Oxidation of the allylic alcohol 1a proceeded under Swern conditions but not with MnO2 to the 13-oxo aglycon, which was reduced by NaBH4 exclusively to the natural 13 alpha-ol, while reductive amination with NaCNBH3-NH4OAc gave the 13 alpha-amine. The methoxime derivative was obtained in the form of the two geometric isomers. Anthelmintic activities against the sheep nematode Trichostrongylus colubriformis, miticidal activities against the two-spotted spider mite (Tetranychus urticae), and insecticidal activities against the southern armyworm (Spodoptera eridania) as well as the binding constants to a free living nematode (Caenorhabditis elegans) derived receptor assay were obtained and compared to avermectin B1a, 22,23-dihydroavermectin B1a, and the 13-deoxy-22,23-dihydroavermectin B1 aglycon related to the milbemycins. None of the newly prepared derivatives exceeded the potency of the three reference compounds. Lipophilic 13-substituents such as halogen, alkoxy, and methoxime retained high biological activities in all assays, while the more polar

  18. The three transglycosylation reactions catalyzed by cyclodextrin glycosyltransferase from Bacillus circulans (strain 251) proceed via different kinetic mechanisms

    NARCIS (Netherlands)

    Veen, Bart A. van der; Alebeek, Gert-Jan W.M. van; Uitdehaag, Joost C.M.; Dijkstra, Bauke W.; Dijkhuizen, Lubbert

    Cyclodextrin glycosyltransferase (CGTase) catalyzes three transglycosylation reactions via a double displacement mechanism involving a covalent enzyme-intermediate complex (substituted-enzyme intermediate). Characterization of the three transglycosylation reactions, however, revealed that they

  19. A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines.

    Science.gov (United States)

    Schmid, Steven C; Guzei, Ilia A; Schomaker, Jennifer M

    2017-09-25

    The reaction of rhodium-bound carbenes with strained bicyclic methylene aziridines results in a formal [3+1] ring expansion to yield highly substituted methylene azetidines with excellent regio- and stereoselectivity. The reaction appears to proceed through an ylide-type mechanism, where the unique strain and structure of the methylene aziridine promotes a ring-opening/ring-closing cascade that efficiently transfers chirality from substrate to product. The resultant products can be elaborated into new azetidine scaffolds containing vicinal tertiary-quaternary and even quaternary-quaternary stereocenters. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Kinetics of electrophilic exchange of lanthanide(3) and copper(2) ions in aqueous solutions of ethylenediaminetetraacetates. [Rare earths: La,Pr,Nd,Eu,Gd,Tb,Er,Yb

    Energy Technology Data Exchange (ETDEWEB)

    Nikitenko, S.I.; Martynenko, L.I.; Pechurova, N.I.; Spitsyn, V.I. (Moskovskij Gosudarstvennyj Univ. (USSR))

    1984-05-01

    Electrophilic exchange in the MA/sup -/ - Cu/sup 2 +/ (M/sup 3 +/=La/sup 3 +/, PUPSILON/sup 3 +/, Nd/sup 3 +/, Eu/sup 3 +/, Gd/sup 3 +/, Tb/sup 3 +/, Er/sup 3 +/, Yb/sup 3 +/, A/sup 4 -/=ethylenediaminetetraacetate) systems is studied. Copper is chosen as a constituent cation, because the stability of the CuA/sup 2 +/- complex is higher than that of the MA/sup -/ complex, besides the CuA/sup 2 -/, is characterized by a high extinction coefficient E/sub 280/=3200. Electrophilic exchange in the systems is shown to be realized through the acid dissociation mechanism and through the association mechanism. Consideration of the acid dissociation mechanism assumes that the exchange is limited by a break in the metal-oxygen bond in the intermediate protonated complex. In case of the association mechanism it is limited by a break in the metal-nitrogen bond in the intermediate binuclear complex. Rate constants of the limiting stage are calculated. Dependences of the rate constants of exchange on the stability of the complexes, the order number of the element, acidity of medium, Cu/sup 2 +/ concentration are given. Differences are shown to exist between the exchange mechanisms in the studied: systems for the REE of cerium and yttrium subgroups.

  1. X-ray Absorption Spectroscopy Combined with Time-Dependent Density Functional Theory Elucidates Differential Substitution Pathways of Au(I) and Au(III) with Zinc Fingers.

    Science.gov (United States)

    Abbehausen, Camilla; de Paiva, Raphael Enoque Ferraz; Bjornsson, Ragnar; Gomes, Saulo Quintana; Du, Zhifeng; Corbi, Pedro Paulo; Lima, Frederico Alves; Farrell, Nicholas

    2018-01-02

    A combination of two elements' (Au, Zn) X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TD-DFT) allowed the elucidation of differential substitution pathways of Au(I) and Au(III) compounds reacting with biologically relevant zinc fingers (ZnFs). Gold L 3 -edge XAS probed the interaction of gold and the C-terminal Cys 2 HisCys finger of the HIV-1 nucleocapsid protein NCp7, and the Cys 2 His 2 human transcription factor Sp1. The use of model compounds helped assign oxidation states and the identity of the gold-bound ligands. The computational studies accurately reproduced the experimental XAS spectra and allowed the proposition of structural models for the interaction products at early time points. The direct electrophilic attack on the ZnF by the highly thiophilic Au(I) resulted in a linear P-Au-Cys coordination sphere after zinc ejection whereas for the Sp1, loss of PEt 3 results in linear Cys-Au-Cys or Cys-Au-His arrangements. Reactions with Au(III) compounds, on the other hand, showed multiple binding modes. Prompt reaction between [AuCl(dien)] 2+ and [Au(dien)(DMAP)] 3+ with Sp1 showed a partially reduced Au center and a final linear His-Au-His coordination. Differently, in the presence of NCp7, [AuCl(dien)] 2+ readily reduces to Au(I) and changes from square-planar to linear geometry with Cys-Au-His coordination, while [Au(dien)(DMAP)] 3+ initially maintains its Au(III) oxidation state and square-planar geometry and the same first coordination sphere. The latter is the first observation of a "noncovalent" interaction of a Au(III) complex with a zinc finger and confirms early hypotheses that stabilization of Au(III) occurs with N-donor ligands. Modification of the zinc coordination sphere, suggesting full or partial zinc ejection, is observed in all cases, and for [Au(dien)(DMAP)] 3+ this represents a novel mechanism for nucleocapsid inactivation. The combination of XAS and TD-DFT presents the first direct experimental

  2. Substitution determination of Fmoc‐substituted resins at different wavelengths

    Science.gov (United States)

    Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

    2017-01-01

    In solid‐phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc‐substituted resins, substitution determination is often performed by suspending the Fmoc‐protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene–piperidine adduct that is quantified by ultraviolet–visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene–piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert–Beer's law, together with the substance‐specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol−1 cm−1 and 8100 l mol−1 cm−1 have been reported for the dibenzofulvene–piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28635051

  3. Theoretical study on the mechanism and kinetics of the reaction of 2,2‧,4,4‧-tetrabrominated diphenyl ether (BDE-47) with OH radicals

    Science.gov (United States)

    Cao, Haijie; He, Maoxia; Han, Dandan; Sun, Yanhui; Xie, Ju

    2011-03-01

    The mechanism and kinetic properties of OH-initiated gas-phase reaction of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) have been studied at the MPWB1K/6-311 + G(3df,2p)//MPWB1K/6-31G(d) level of theory. Two types of reactions including hydroxyl addition and hydrogen abstraction have been considered. The calculation results indicate that addition reactions except for the bromo-substituted addition reaction have lower energy barriers than hydrogen abstraction reactions. Hydroxyl radical is most likely to be added to non-substituted C atoms (C(3), C(5), and C(6) atoms). Moreover, for all the reactions with OH radical, the bromo-substituted C atoms encountered the highest barrier compared to that of the rest C atoms. The rate constants and product branching ratios of each pathway have been deduced over a wide range of 200-1000 K using canonical variational transition state (CVT) theory with small curvature tunneling (SCT) contribution. This study can be regarded as an attempt to investigate the OH-initiated photochemical reaction mechanism of polybrominated diphenyl ethers (PBDEs).

  4. 1-ethyl gallate-2-substituted phenoxymethyl benzimidazoles: synthesis, molecular structure, antimicrobial activities and complex with cr(iii)

    International Nuclear Information System (INIS)

    Zhao, L.; Wu, J.; Wu, J.; Wang, Z.; Gu, H.

    2017-01-01

    The design of gallate and benzimidazole containing derivatives is expected to produce new bioactive molecules with multiple applications. Here the synthesis of eight novel benzimidazole compounds containing ethyl gallate and substituted phenoxymethyl units are reported. Firstly, the ring closure reaction between o-phenylendiamine and substituted phenoxyacetic acids resulted in 2-substituted phenoxymethyl benzimidazoles that were then modified by the N-hydroxyethylation with 2-chloroethyl alcohol under a phase transfer catalysis condition. The obtained 1-hydroxyethyl-2-substituted phenoxymethyl benzimidazoles were finally translated into the target title compounds 8a-h by an indirect esterification method in which three O-H groups of gallic acid were first protected by acetyls and deprotected after the esterification reaction by adding hydrazine hydrate. The structures of the title products 8a-h were fully characterized and confirmed by elemental analysis, MS, IR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction techniques. Antimicrobial tests by inhibition zones indicated that these compounds exhibited diverse inhibitory effects against the test bacteria and fungi, and the type and position of the substituent groups in the phenoxymethyl moieties had obvious influence on their antimicrobial activities. Furthermore, the Cr(III) complex of 8h was synthesized, and various spectral, elemental and thermal analysis results confirmed that the central Cr(III) atom coordinated with adjacent hydroxyl groups of two 8h ligands, nitrate and H2O, respectively. (author)

  5. Substituted 2,1,3-Benzothiadiazole- And Thiophene-Based Polymers for Solar Cells - Introducing a New Thermocleavable Precursor

    DEFF Research Database (Denmark)

    Petersen, Martin Helgesen; Gevorgyan, Suren; Krebs, Frederik C

    2009-01-01

    Alkoxysubstituted and unsubstituted 2,1,3-benzothiadiazoles were prepared and copolymerized with substituted and unsubstituted thiophenes using both Stille and Yamamoto cross-coupling reactions. One class of the materials bore thermally labile ester groups. The materials were all found to have...

  6. A theoretical quantum study on the distribution of electrophilic and nucleophilic active sites on Cu(100) surfaces modeled as finite clusters; Un estudio teorico cuantico sobre la distribucion de sitios activos electrofilicos y nucleofilicos sobre superficies de Cu(100) modeladas como cumulos finitos

    Energy Technology Data Exchange (ETDEWEB)

    Rios R, C.H.; Romero R, M. [Universidad Autonoma Metropolitana-Azcapotzalco, Departamento de Materiales, Av. San Pablo 180, Col. Reynosa Tamaulipas, 02200 Mexico D.F. (Mexico); Ponce R, A.; Mendoza H, L.H. [Universidad Autonoma del Estado de Hidalgo, Centro de Investigaciones Quimicas, Carretera Pachuca-Tulancingo km. 4.5, 42181 Pachuca, Hidalgo (Mexico)]. e-mail: clara_hrr@yahoo.es

    2008-07-01

    In this work, it is shown a theoretical quantum study of the active sites distribution on a monocrystalline surface of Cu(100). The copper surface was modeled as finite clusters of 14, 23, 38 and 53 atoms. We performed Hartree-Fock and Density Functional Theory (B3LYP) ab initio calculations employing the pseudopotentials of Hay and Wadt (LANLlMB y LANL2DZ). From calculations, we found a work function value of 4.1 eV. The mapping of the HOMO and LUMO in the frozen core approximation, allowed us finding the electrophilic and nucleophilic active sites distribution, respectively. The results indicated that electrophilic sites on the Cu(100) surface were located on hollow position and its numerical density was 8.6 x 10{sup 16} sites cm{sup -2}. From the nucleophilic local softness study, it was found that the nucleophilic sites were formed by a group of atoms and it had a numerical density of 2.4x 10{sup 16} sitescm{sup -2} . Last results indicated that adsorptions with 2 x 2 and 3 x 3 distributions can be favored onto a Cu(100) surface for the electrophilic and nucleophilic cases, respectively. (Author)

  7. Kinugasa Reactions in Water: From Green Chemistry to Bioorthogonal Labelling

    Directory of Open Access Journals (Sweden)

    Mariya Chigrinova

    2015-04-01

    Full Text Available The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy.

  8. Kinugasa reactions in water: from green chemistry to bioorthogonal labelling.

    Science.gov (United States)

    Chigrinova, Mariya; MacKenzie, Douglas A; Sherratt, Allison R; Cheung, Lawrence L W; Pezacki, John Paul; Pezacki, Paul

    2015-04-16

    The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy.

  9. Solvent effect on copper-catalyzed azide-alkyne cycloaddition (CuAAC): synthesis of novel triazolyl substituted quinolines as potential anticancer agents.

    Science.gov (United States)

    Ellanki, Amarender Reddy; Islam, Aminul; Rama, Veera Swamy; Pulipati, Ranga Prasad; Rambabu, D; Krishna, G Rama; Reddy, C Malla; Mukkanti, K; Vanaja, G R; Kalle, Arunasree M; Kumar, K Shiva; Pal, Manojit

    2012-05-15

    A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties when tested in vitro especially against breast cancer cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. An Efficient Solid-phase Parallel Synthesis of 2-Amino and 2-Amidobenzo[d]oxazole Derivatives via Cyclization Reactions of 2-Hydroxyphenylthiourea Resin

    International Nuclear Information System (INIS)

    Jung, Selin; Kim, Seulgi; Lee, Geehyung; Gong, Youngdae

    2012-01-01

    An efficient solid-phase methodology has been developed for the synthesis of 2-amino and 2-amidobenzo[d]-oxazole derivatives. The key step in this procedure involves the preparation of polymer-bound 2-aminobenzo-[d]oxazole resins 4 by cyclization reaction of 2-hydroxyphenylthiourea resin 3. The resin-bound 2-hydroxy-phenylthiourea 3 is produced by the addition of 2-aminophenol to the isothiocyanate-terminated resin 2 and serve as a key intermediate for the linker resin. This core skeleton 2-aminobenzo[d]oxazole resin 4 undergoes functionalization reaction with various electrophiles, such as alkylhalides and acid chlorides to generate 2-amino and 2-amidobenzo[d]oxazole resins 5 and 6 respectively. Finally, 2-amino and 2-amidobenzo[d]oxazole derivatives 7 and 8 are then generated in good yields and purities by cleavage of the respective resins 5 and 6 under trifluoroacetic acid (TFA) in dichloromethane (CH 2 Cl 2 )

  11. N-Heterocyclic Carbene-Catalysed Diastereoselective Vinylogous Michael Addition Reaction of gamma-Substituted deconjugated Butenolides

    KAUST Repository

    Guo, Hao

    2015-11-16

    An efficient N-heterocyclic carbene (NHC)-catalysed vinylogous Michael addition of deconjugated butenolides was developed. In the presence of 5 mol% of the NHC catalyst, both γ-alkyl and aryl-substituted deconjugated butenolides undergo vinylogous Michael addition with various α, β-unsaturated ketones, esters, or nitriles to afford γ,γ-disubstituted butenolides containing adjacent quaternary and tertiary carbon centers in good to excellent yields with excellent diastereoselectivities. In this process, the free carbene is assumed to act as a strong Brønsted base to promote the conjugate addition.

  12. N-Heterocyclic Carbene-Catalysed Diastereoselective Vinylogous Michael Addition Reaction of gamma-Substituted deconjugated Butenolides

    KAUST Repository

    Guo, Hao; Xing, Fen; Du, Guang-Fen; Huang, Kuo-Wei; Dai, Bin; He, Lin

    2015-01-01

    An efficient N-heterocyclic carbene (NHC)-catalysed vinylogous Michael addition of deconjugated butenolides was developed. In the presence of 5 mol% of the NHC catalyst, both γ-alkyl and aryl-substituted deconjugated butenolides undergo vinylogous Michael addition with various α, β-unsaturated ketones, esters, or nitriles to afford γ,γ-disubstituted butenolides containing adjacent quaternary and tertiary carbon centers in good to excellent yields with excellent diastereoselectivities. In this process, the free carbene is assumed to act as a strong Brønsted base to promote the conjugate addition.

  13. Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

    Directory of Open Access Journals (Sweden)

    Katrina Tait

    2016-10-01

    Full Text Available Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene derivatives using alcohol nucleophiles were investigated. The optimal conditions were found to be 10 mol % PdCl2(CH3CN2 in methanol, offering yields up to 92%. The reaction was successful using primary, secondary and tertiary alcohol nucleophiles and was compatible with a variety of substituents on cyclopropanated oxabenzonorbornadiene. With unsymmetrical C1-substituted cyclopropanated 7-oxabenzonorbornadienes, the regioselectivity of the reaction was excellent, forming only one regioisomer in all cases.

  14. Acid-base and coordination properties of Meso-substituted porphyrins in nonaqueous solutions

    Science.gov (United States)

    Pukhovskaya, S. G.; Nam, Dao Tkhe; Fien, Chan Ding; Domanina, E. N.; Ivanova, Yu. B.; Semeikin, A. S.

    2017-09-01

    Acid-base and coordination properties of alkyl and aryl meso-substituted porphyrins are studied spectrophotometrically in nonaqueous solutions. It is found that the nature of the substituent greatly affects the basicity of ligands for porphyrins characterized by a flat structure of macrocycle. The electronic effects of substituents have a much weaker influence on the kinetics of complexing. These effects could be due to the opposite orientation of some factors: an increase in the basicity and stability of the N-H bonds of porphyrin reaction centers. Dissociation constants p K b of the cationic forms of meso-substituted derivatives of porphyrin are measured. The values of p K b are in good agreement with classic concepts of the nature of substituents, particularly those indirectly included in the macrocycle through phenyl buffer rings.

  15. Study of the Kinetics of an S[subscript N]1 Reaction by Conductivity Measurement

    Science.gov (United States)

    Marzluff, Elaine M.; Crawford, Mary A.; Reynolds, Helen

    2011-01-01

    Substitution reactions, a central part of organic chemistry, provide a model system in physical chemistry to study reaction rates and mechanisms. Here, the use of inexpensive and readily available commercial conductivity probes coupled with computer data acquisition for the study of the temperature and solvent dependence of the solvolysis of…

  16. The reactions of anthronylidene carbene with some heterocyclic compounds

    International Nuclear Information System (INIS)

    Divisia, Bernadette

    1970-01-01

    The action of the anthronylidene carbene, generated by photochemical decomposition of 9-diazo 10-anthron, on four heterocyclic compounds (furan, thiophene, 1-methyl-pyrrole and 2,5-dihydrofuran) has been examined. Two classical carbene reactions have been observed: the addition on double bond (furan, thiophene, 1-methylpyrrole) and hydrogen atom abstraction of the heterocyclic compound (2,5-dihydrofuran). In the case of furan and thiophene, the cyclo-propanic compound resulting from the addition is spontaneously transformed into an ethylenic derivative by valence isomerization. The furan derivative undergoes a cis-trans isomerization, while the thiophene one undergoes an extra carbene attack. In the case of 1-methylpyrrole, the corresponding cyclo-propanic compound undergoes a ring cleavage, followed by a hydrogen atom migration leading to the formation of a substituted anthron. Only an allylic hydrogen atom selective abstraction of heterocyclic compound takes place in the reaction of anthronylidene carbene with 2,5-dihydrofuran. The asymmetrical coupling of radicals so obtained yields the corresponding substituted anthron. (author) [fr

  17. Substitution determination of Fmoc-substituted resins at different wavelengths.

    Science.gov (United States)

    Eissler, Stefan; Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

    2017-10-01

    In solid-phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc-substituted resins, substitution determination is often performed by suspending the Fmoc-protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene-piperidine adduct that is quantified by ultraviolet-visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene-piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert-Beer's law, together with the substance-specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol -1  cm -1 and 8100 l mol -1  cm -1 have been reported for the dibenzofulvene-piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

  18. Electricity/oil substitution

    International Nuclear Information System (INIS)

    Melvin, J.G.

    1980-09-01

    The extent to which electricity could substitute for imported oil in Canada is assessed and it is concluded that the bulk of projected oil imports could be displaced. This substitution of electricity for oil could be largely completed within two decades, with existing technology, using Canadian resources. The substitution of electricity for imported oil would result in relatively low energy costs and would stimulate economic growth. Energy self-sufficiency through the substitution of electricity for oil is uniquely a Canadian option; it is not open to other industrial countries. The option exists because of Canada's resources of oil sands for essential liquid fuels, hydraulic and nuclear electrical potential, and natural gas as an interim source of energy. While other countries face an energy crisis due to declining supplies of oil, Canada faces opportunities. The policies of Federal and Provincial governments, as perceived by individual decision makers, will have a major influence on Canada's ability to realize opportunities. (auth)

  19. Zinc Enolate/Sulfinate Prepared from a Single-Run Reaction Using Zinc Dust with O-Tosylated 4-Hydroxy Coumarin and Pyrone

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ueon Sang; Joo, Seong-Ryu; Kim, Seung-Hoi [Dankook University, Cheonan (Korea, Republic of)

    2016-07-15

    We demonstrated the preparation of new zinc complexes, 2-oxo-2H-chromen-4-yloxy tosylzinc (I), and 6-methyl-2-oxo-2H-pyran-4-yloxy tosylzinc (II), by the oxidative addition of readily available zinc dust into the corresponding 4-tosylated coumarin (A) and pyrone (B), respectively. Of special interest, the thus-obtained zinc complexes showed an electrophile-dependent reactivity. The subsequent coupling reactions of I and II with a variety of acid chlorides provided the O-acylation product in moderate yields. More interestingly, it should be emphasized that the thus-prepared zinc complexes (I and II) functioned both as zinc enolate and zinc sulfinate, providing C(3)-disubstituted product (b) and sulfone (c), respectively, from a single-run reaction when I or II was treated with benzyl halides. Even though somewhat low yields were achieved under the nonoptimized conditions, the novel zinc complexes present another potential application for zinc reagents. Versatile applications of this discovery are currently underway.

  20. Zinc Enolate/Sulfinate Prepared from a Single-Run Reaction Using Zinc Dust with O-Tosylated 4-Hydroxy Coumarin and Pyrone

    International Nuclear Information System (INIS)

    Shin, Ueon Sang; Joo, Seong-Ryu; Kim, Seung-Hoi

    2016-01-01

    We demonstrated the preparation of new zinc complexes, 2-oxo-2H-chromen-4-yloxy tosylzinc (I), and 6-methyl-2-oxo-2H-pyran-4-yloxy tosylzinc (II), by the oxidative addition of readily available zinc dust into the corresponding 4-tosylated coumarin (A) and pyrone (B), respectively. Of special interest, the thus-obtained zinc complexes showed an electrophile-dependent reactivity. The subsequent coupling reactions of I and II with a variety of acid chlorides provided the O-acylation product in moderate yields. More interestingly, it should be emphasized that the thus-prepared zinc complexes (I and II) functioned both as zinc enolate and zinc sulfinate, providing C(3)-disubstituted product (b) and sulfone (c), respectively, from a single-run reaction when I or II was treated with benzyl halides. Even though somewhat low yields were achieved under the nonoptimized conditions, the novel zinc complexes present another potential application for zinc reagents. Versatile applications of this discovery are currently underway