Kinetics and mechanism of nucleophilic addition of hydroxide to aromatic isocyanides

Abstract

para- and meta-substituted aromatic isocyanides have been found to react in alkaline aqueous dioxane yielding the corresponding formamides. From a kinetic analysis of the reaction, the observed rate constants were found to be linearly dependent upon hydroxide concentration; this observation, together with the positive value of p, was taken as evidence of direct nucleophilic attack. Decreasing values of ΔH^‡ were observed as electron-withdrawing substituents were introduced, whereas ΔS^‡was fairly constant at –57 J K^–1 mol^–1; this indicates little variation in transition-state geometry across the range of isocyanides studied. The kinetic evidence is discussed in terms of two mechanisms: nucleophilic attack of hydroxide with concerted proton transfer from water to the isocyano carbon, and nucleophilic attack of hydroxide to yield a carbanion intermediate, with protonation occurring in a rapid subsequent step. The reaction rate increases with increasing water content in the solvent; this observation appears to favour the concerted mechanism. In dioxane–deuterium oxide the reaction showed a small inverse isotope effect; the apparent lack of an appreciable primary isotope effect is consistent with a concerted mechanism only if minimal proton transfer from water to carbon has occurred in the transition state.