Intramolecular general acid–base catalysis and the rate-determining steps in the nucleophilic cleavage of maleimide- with primary amines

Abstract

The kinetics of nucleophilic cleavage of maleimide have been studied at 30 °C under the buffer solutions of 13 primary amines including three diamines and carbonate. Both ionized (S^–) and non-ionized (SH) forms of maleimide have been found to exhibit significant reactivity toward amines and carbonate anion. The respective bimolecular rate constants k₁ and k₂ for the reactions of nucleophiles with non-ionized and ionized forms of maleimide display Brönsted plots with respective slopes of βnuc₁= 0.81 ± 0.15 and βnuc₂= 0.48 ± 0.19. The significantly different values of βnuc₁ and βnuc₂, reveal the involvement of different rate-determining steps in the nucleophilic cleavage of non-ionized and ionized maleimide. The high value of βnuc₁ is attributed to the expulsion of the leaving group as the rate-determining step while the value of βnuc₂ of 0.48 indicates the nucleophilic attack within the encounter complex as the rate-determining step. The values of βnuc₁ and βbnuc₂ for the nocleophilic reactivity of diamines were found to be 0.52 ± 0.02 and 0.13 ± 0.02, respectively. The value of βnuc₁ of 0.52 has been attributed to intramolecular general acid–base-catalysed expulsion of the leaving group as the rate-determining step. The low value of βnuc₂(0.13) reveals the nucleophilic attack as the rate-determining step. A pre-association stepwise mechanism is proposed for the reactions of amines with S^– while a diffusion-controlled trapping mechanism is favoured for the reactions of amines with SH. The rate constants k₁ and k₂ for TRIS, 2-amino-2-methylpropane-1,3-diol, ammonia, and carbonate have been found to show significant negative deviations while hydrazine revealed a large positive deviation from Brönsted plots.