Effect of the acyl group in the reaction of imidazole with acyl-substituted 4-nitrophenyl acetates in acetonitrile and in aqueous acetonitrile with a low water content

Abstract

Reactions of imidazole with 4-nitrophenyl chloroacetate and dichloroacetate have been studied in acetonitrile and in 0.56 mol dm–3 water in acetonitrile. The second-order dependence, beside the first-order term in imidazole, is observed for all cases. The main interest was to study whether the first-order reaction in imidazole in aqueous acetonitrile is a general base-catalysed hydrolysis or a nucleophilic reaction of imidazole. The water isotope effects, steric effects by the 2-methyl substitution of imidazole, the effect of water in the reaction solution and the thermodynamic activation parameters were determined. Comparison of the results with those found previously for the reactions of imidazole with 4-nitrophenyl acetate and trifluoroacetate suggests that for 4-nitrophenyl chloroacetate and dichloroacetate the reaction first-order in imidazole represents a nucleophilic reaction and the reaction second-order in imidazole the general base-catalysed nucleophilic reaction of the amine. Accordingly, the change in the overall second-order reaction of 4-nitrophenyl acetates from a nucleophilic reaction of imidazole to the general base-catalysed hydrolysis needs a more electron-withdrawing acyl group than the dichloro substituted one.