Substituent Effects on the Electrophilic Activity of Nitroarenes in Reactions with Carbanions

Abstract

The effect on electrophilic activity of substituents located para, ortho, and meta to the nitro group of nitrobenzenes was determined by using vicarious nucleophilic substitution of hydrogen (VNS) with the carbanion of chloromethyl phenyl sulfone (1) as the model process. Values for the relative activities of substituted nitroarenes are given relative to nitrobenzene, which was taken as the standard. This process was chosen as a model reaction because it meets key criteria, such as the wide range of substituents that can be present on the nitrobenzene ring, a low sensitivity to steric hindrance, and in particular the possibility of ensuring conditions in which the overall relative rates of reaction in competitive experiments are equal to the relative rates of nucleophilic addition. The values of relative rates of addition, which were taken to be a measure of electrophilic activity, were determined by competitive experiments in which pairs of nitroarenes competed for the VNS reaction with carbanion of 1. A comprehensive set of data for effects of substituents on the electrophilic activity of nitroarenes is presented for the first time.

Aerobic Transition‐Metal‐Free Synthesis of 2,3‐Diarylindoles and 5‐Aryluracils via Oxidative Nucleophilic Substitution of Hydrogen Pathway

“…Similarly, the reaction of 1a and 3‐nitropyridine ( 2c ) afforded para ‐substitution product 3h in moderate yield (43%). No reaction was observed between 1a and nitrobenzene under the same reaction conditions …”

Synthesis of enantiomerically pure [14C]‐labelled morpholine derivatives for a class of trace amine‐associate receptor 1 agonists

“…As a potential explanation for the failure of all Grignard or metal‐mediated reactions, vicarious nucleophilic substitution, described by Mąkosza and Ricci, can be proposed as a competing side reaction (Scheme ). Mąkosza reported that Grignard reagents are able to attack ortho to a nitro group.…”

Nucleophilic substitution in nitroarenes: a general corrected mechanism

“…However, the results, although practically useful, cannot be considered as a measure of electrophilicity of nitroarenes, for two main reasons: (a) the rates of the substitution were dependent on the nature of the leaving groups, and (b) the substitution is a secondary process preceded by fast and reversible addition at positions occupied by hydrogen and formation of the σ H adducts. The true effects of substituents on the electrophilic activity of nitroarenes were determined by measuring of the rates of nucleophilic addition at positions occupied by hydrogen [50,51]. The general mechanism of nucleophilic aromatic substitution in electron-deficient arenes and its specific features presented in this paper reveal a much wider scope, versatility and diversity of the reactions between nucleophiles and nitroarenes.…”