唑类化合物双氢键催化转酰胺反应的机制研究

通过密度泛函M062X方法在6-31+G(d)基组水平上考察乙酰胺与甲胺在唑类化合物咪唑、吡唑和苯并三唑双氢键催化作用下的转酰胺反应机制。在该机制中，催化剂通过与底物乙酰胺的羰基氧以及氨基上的一个氢形成双氢键来活化其酰胺键，从而有利于亲核试剂甲胺对乙酰胺酰胺键的亲核进攻。计算结果显示，咪唑和吡唑催化的转酰胺反应焓变能垒分别是123.9 kJ·mol-1和92.3 kJ·mol-1，而苯并三唑做催化剂时焓变能垒降低为88.3 kJ·mol-1，其催化效果优于咪唑和吡唑。当运用溶质全电子密度溶剂化模型SMD (solvation model density)来考察甲苯和水作为溶剂对苯并三唑催化的转酰胺反应产生的溶剂效应时，发现溶剂的加入使反应焓变能垒明显升高，说明溶剂的加入并不利于反应的进行

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.