A Mechanism Study of Hydrogen Bond Organocatalysis of Azoles in Transamidation Reaction

Density functional theory of M062X/6-31+G(d) is used to study the reaction mechanisms in transamidation of carboxamides with methylamines catalyzed by imidazole, pyrazole and benzotriazole. In the transamidation reaction, the azoles activate the substrate carboxamide through dihydrogen bonds with carbonyl oxygen and one hydrogen of amino group, which favors the subsequent nucleophilic attack of methylamine with carboxamide. Our theoretical results show that the enthalpy barriers are 123.9 kJ·mol^-1 and 92.3 kJ·mol^-1 for imidazole and pyrazole, respectively, while it decreases to 88.3 kJ·mol^-1 for benzotriazole. Clearly, the benzotriazole favors most for the transamidation. The solvent effect of toluene and water simulated by SMD (Solvation Model Density) for the transamidation reaction catalyzed by benzotriazole elevated the enthalpy barriers significantly, which coincides well with the experimental result. Our theoretical study would be useful for further understanding and future experimental investigation on such transamidation reaction.