Nucleophilic substitution reaction of benzyl benzenesulfonates with anilines in methanol-acetonitrile mixtures. Part 3

Kinetic studies on the nucleophilic substitution reaction of para-nitrobenzyl benzenesulfonates with anilines in methanol-acetonitrile mixtures are reported. It was found that the reaction proceeds via a dissociative S_N2 mechanism with a more product -like transition state compared to that for substrate with a less electron attracting substituent. A stronger electron withdrawing substituent in the benzyl moiety and in the leaving group is shown to enhance both bond making and bond breaking but the enhancement of bond making was found to be greater than that of bond breaking.     

Effect of substituent on regioselectivity and reaction mechanism in aminolysis of 2,4-dinitrophenyl X-substituted benzenesulfonates

[reaction: see text] We report on a kinetic study for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzensulfonates (X = 4-MeO, 1a, and X = 4-NO(2), 1c) with a series of primary amines in 80 mol % H(2)O/20 mol % DMSO at 25.0 degrees C. The reactions proceed through S-O and C-O bond fission pathways competitively. The fraction of the S-O bond fission increases as the attaching amine becomes more basic and the substituent X changes from 4-MeO to 4-NO(2), indicating that the regioselectivity is governed by the electronic nature of the substituent X as well as the basicity of amines. The S-O bond fission has been suggested to proceed through an addition intermediate with a change in the rate-determining step (RDS) at pK(a) degrees = 8.9 +/- 0.1. The electronic nature of the substituent X influences k(N)(S-O) and k(1) values, but not the k(2)/k(-1) ratios and the pK(a) degrees value significantly. Stabilization of the ground state (GS) through resonance interaction between the electron-donating substituent and the electrophilic center has been suggested to be responsible for the decreased reactivity of 1a compared to 1c. The second-order rate constants for the C-O bond fission exhibit no correlation with the electronic nature of the substituent X. The distance effect and the nature of the reaction mechanism have been suggested to be responsible for the absence of the correlation.     

Competitive reaction pathways in the nucleophilic substitution reactions of aryl benzenesulfonates with benzylamines in acetonitrile

The reactions of aryl benzenesulfonates (YC6H4SO2OC6H4Z) with benzylamines (XC6H4CH2NH2) in acetonitrile at 65.0 degrees C have been studied. The reactions proceed competitively by S-O (kS-O) and C-O (kC-O) bond scission, but the former provides the major reaction pathway. On the basis of analyses of the Hammett and Br?nsted coefficients together with the cross-interaction constants rho(XY), rho(YZ), and rho(XZ), stepwise mechanisms are proposed in which the S-O bond cleavage proceeds by rate-limiting formation of a trigonal-bipyramidal pentacoordinate (TBP-5C) intermediate, whereas the C-O bond scission takes place by rate-limiting expulsion of the sulfonate anion (YC6H4SO3-) from a Meisenheimer-type complex.     

Effects of substituent and solvent on the structure and spectral properties of maleimide derivatives

The maximum absorption wavelength , emission wavelength (λ_em) and the related oscillator strength (f) of the maleimides in the ground and first excited states were calculated by using the DFT, CIS and the time-dependent density functional theory (TD-DFT) methods, where the molecular structures were optimized by DFT/B3LYP/6-31G^* calculation. Solvent effects on the maleimides were examined using the PCM simulation at DFT/B3LYP level with the 6-31G^* basis set. For N-substituted maleimide, the substituent gives only a slight influence on the maleimide chromophore, while planar conformation of PhMLH leads to the improvement in π-delocalization from substituent to maleimide unit. For 3,4-substituted maleimide, the steric repulsion between substituent and maleimide chromophore influences the extent of π-delocalization and the molecular conformation. The calculated and λ_em of maleimides are in good agreement with the experimental data. In the gas phase, both absorption and emission peaks are red-shift as compared to the non-substituted maleimide. Under solvent environment, the more planar conformation of PhMLH shows a blue-shift in the calculated and λ_em as compared with other N-substituted maleimides. For 3,4-substituted maleimides, the effect of substitution produces the most significant spectral red-shift as compared to other maleimides.     

Structure-reactivity cross correlations in nucleophilic substitution: Isoparametricity and transition-state structure

Data are surveyed on cross correlations for nucleophilic substitution at benzoyl, benzyl, and benzhydryl carbon atoms. The cross correlation coefficients and isoparametric points are used to interpret the reaction mechanisms. Donetsk State University, 24 Universitetskaya ul., Donetsk 340055, Ukraine. Translated from Teoreticheskaya i éksperimental'naya Khimiya, Vol. 35, No. 2, pp. 67–78, March–April, 1999.     

Effect of substituent structure on pyrimidine electrophilic substitution

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 chloro-, mono- or disubstituted amino groups. Effects such as the presence of an aryl group or two alkyl groups on the amino moiety impede the progress of the reaction despite the presence of a second activating group.     

Effect of substituent structure on pyrimidine electrophilic substitution: a rebuttal

The report about a series of unexpected and obscure effects influencing the electrophilic nitrosation of activated pyrimidines (Tetrahedron 2007, 63, 5394) was shown to be erroneous. Instead of electrophilic substitution at position 5 of the pyrimidine ring, N-nitrosation of the secondary amino group in the 4-position of the pyrimidine ring took place. Moreover it was shown that the synthetic sequence for the preparation of purines is also incorrect.     

Reactions in microemulsion media. Nucleophilic displacement reaction of benzyl chloride with bromide ion

A kinetic and synthetic study of the reaction of benzyl chloride with bromide ion has been performed in microemulsions composed of cetyltrimethylammonium bromide, 1-butanol, water, potassium bromide, and hexane; rates and yields of benzyl bromide formation decreased with increasing hexane content.     

Regioselectivity and the nature of the reaction mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with primary amines

Second-order rate constants have been measured for the reaction of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of primary amines. The nucleophilic substitution reaction proceeds through competitive S-O and C-O bond fission pathways. The S-O bond fission occurs dominantly for reactions with highly basic amines or with substrates having a strong electron-withdrawing group in the sulfonyl moiety. On the other hand, the C-O bond fission occurs considerably for the reactions with low basic amines or with substrates having a strong electron-donating group in the sulfonyl moiety, emphasizing that the regioselectivity is governed by both the amine basicity and the electronic effect of the sulfonyl substituent X. The apparent second-order rate constants for the S-O bond fission have resulted in a nonlinear Br?nsted-type plot for the reaction of 2,4-dinitrophenyl benzenesulfonate with 10 different primary amines, suggesting that a change in the rate-determining step occurs upon changing the amine basicity. The microscopic rate constants (k(1) and k(2)/k(-)(1) ratio) associated with the S-O bond fission pathway support the proposed mechanism. The second-order rate constants for the S-O bond fission result in good linear Yukawa-Tsuno plots for the aminolyses of 2,4-dinitrophenyl X-substituted benzenesulfonates. However, the second-order rate constants for the C-O bond fission show no correlation with the electronic nature of the sulfonyl substituent X, indicating that the C-O bond fission proceeds through an S(N)Ar mechanism in which the leaving group departure occurs rapidly after the rate-determining step.     

Nucleophilic substitution of hydrogen in the reaction of 1,2,4-triazin-4-oxides with cyanamide

It was shown that cyanamide can successfully be used in reactions of nucleophilic substitution of hydrogen with 1,2,4-triazin-4-oxides in the presence of a base to give 5-cyanoimino-1,2,4-triazines. It was found by¹³C NMR spectroscopy that these compounds and their alkylation products at the cyclic nitrogen atom exist in the form of 5-cyanoimino-2,5-dihydro-1,2,4-triazines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1128–1130, June, 2000.     

多氟芳烃的亲核反应I.仲胺作为亲核试剂

本文报道全氟苯、一氯五氟苯和二氯四氟苯与仲胺在DMF或HMPA中的亲核反应结果,C6F5Cl与仲胺反应生成对位产物,C6F4Cl2(m:o:p)=73:18:9)与仲胺的反应,只有m-和o-异构体能生成预期产物,而p-C6F4Cl2只与活性高的四氢吡咯反应,延长反应时间和提高反应温度,C6F6可给出对双取代产物,六个仲胺的反应活性顺序是:四氢吡咯>哌啶>吗啡啉>二乙胺>二正丙胺>二异丙胺。     

Effect of amine nature on reaction rate and mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with alicyclic secondary amines

Second-order rate constants have been measured for reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of alicyclic secondary amines. The reaction proceeds through S-O and C-O bond fission pathways competitively. The S-O bond fission occurs more dominantly as the amine basicity increases and the substituent X in the sulfonyl moiety becomes more strongly electron withdrawing, indicating that the regioselectivity is governed by the amine basicity as well as the electronic nature of the substituent X. The S-O bond fission proceeds through an addition intermediate with a change in the rate-determining step at pK(a) degrees = 9.1. The secondary amines are more reactive than primary amines of similar basicity for the S-O bond fission. The k(1) value has been determined to be larger for reactions with secondary amines than with primary amines of similar basicity, which fully accounts for their higher reactivity. The second-order rate constants for the S-O bond fission result in linear Yukawa-Tsuno plots while those for the C-O bond fission exhibit poor correlation with the electronic nature of the substituent X. The distance effect and the nature of reaction mechanism have been suggested to be responsible for the poor correlation for the C-O bond fission pathway.     

Influence of the solvent on the rate constant of the reaction of the cumylperoxy radical with benzyl alcohol

The rate constants of the reaction of stripping of a hydrogen atom from a benzyl alcohol molecule by the cumylperoxy radical were measured in various solvents. The main factor determining the change in the value of the constant with variation of the solvent is the basicity (nucleophilicity) of the medium, an increase in which promotes the occurrence of the reaction.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 21, No. 5, pp. 615–620, September–October, 1985.     

Palladium-catalyzed regio- and enantio-selective allylic substitution reaction of monosubstituted allyl substrates with benzyl alcohols

Regio- and enantio-selectivities in Pd-catalyzed allylic substitution reaction of monosubstituted allylic substrates with substituted benzyl alcohols were realized, affording the corresponding products in high regioselectivity (up to 93/7) and enantioselectivity (up to 96%).     

Aromatic nucleophilic substitution reaction of 2,4-dinitrohalogenobenzene and ethyl α-cyano-phenylacetate benzyl anion

The aromatic nucleophilic substitution reaction of 2,4-dinitrohalogenobenzene (DNHB; halogeno =F, Cl, Br) with ethyl α-cyanophenylacetate (ECPA) benzyl anion has been studied by means of UV and IR spectrophotometry as well as gas chromatography. The rates of intermediate formation and product formation were determined respectively. In contrast with common S _N Ar reactions, the formation rate constant of the intermediates, substituted cyclohexadienates, was in the order of halogen =F>Br>Cl, whereas the rate constant of product formation was in the order F>Cl>Br, which revealed that the departure of the halogen atom was the rate-limiting step for the overall reaction in the presence of a sterically hindered nucleophile. These reactions could be catalyzed by the solvated electrons. The corresponding reaction intermediates, radical species, were detected by ESR and the reactions were proved to proceed mainly by a solvated-electron induced radical chain reaction mechanism.     

Aminolysis of aryl chlorothionoformates with anilines in acetonitrile: effects of amine nature and solvent on the mechanism

The aminolysis of aryl chlorothionoformates (7, YC(6)H(4)OC(=S)Cl) with anilines (XC(6)H(4)NH(2)) in acetonitrile at 5.0 degrees C has been investigated. The rates are slower than those for the corresponding reactions of aryl chloroformates (6, YC(6)H(4)OC(=O)Cl). This rate sequence is a reverse of that for alkyl chloroformates (1-4) in water, for which rate-limiting formation of a tetrahedral intermediate, T(+/-), is predicted. On the basis of the large negative cross-interaction constant, rho(XY) = -0.77, failure of the reactivity-selectivity principle, normal k(H)/k(D) values involving deuterated nucleophiles (XC(6)H(4)ND(2)), and low DeltaH(not equal) with large negative DeltaS(not equal) values, a concerted mechanism with a four-membered hydrogen bonded cyclic transition state (11) is proposed for the title reaction series. It has been shown that the solvent change from water to acetonitrile for the aminolysis of 6 and 7 causes a mechanistic change from stepwise to concerted.     

Nucleophilic substitution in the side chain of 5-membered heterocycles—I : Reactions of furfuryl, 2-thenyl and benzyl chlorides with aniline in acetonitrile and in benzene

The reaction kinetics of furfuryl, 2-thenyl and benzyl chlorides with aniline has been studied in acetonitrile and benzene solutions, The reactions are third order overall, first order with respect to the chloromethyl compound and second order with respect to aniline. In benzene solutions the kinetics at high aniline concentrations (≥0·8 M) deviate from the third order equation. The remarkable increase in k₃, not depending on the polarity of the reaction medium, is ascribed to the association of aniline in benzene. The reactions in acetonitrile are faster than in benzene; in both solvents furfuryl chloride reacts faster than 2-thenyl and benzyl chlorides, the latter being the less reactive. The large negative activation entropies, consistent with an ordered and highly polar transition state, determine the observed rate sequence. The rate constants were correlated with the polar constants for heterocycles.     

Nucleophilic substitution reaction at an sp carbon of vinyl halides with an intramolecular thiol moiety: synthesis of thio-heterocycles

This article presents a full account of intramolecular vinylic substitution reactions of bromoalkenes having an acetylthio moiety, which give sulfur-containing heterocycles such as dihydrothiophene, tetrahydrothiopyran, and 2-alkylidenethietane derivatives. The reaction pathways of the substitution reactions were investigated by theoretical and experimental studies.