College of Chemistry, Key Laboratory of Green Chemistry and Technology in Ministry of Education, Sichuan University, Chengdu 610064, P. R. China, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, P. R. China, and Department of Chemistry, Inha University, Inchon 402-751, Korea.
J Chem Theory Comput. 2008 Oct 14;4(10):1643-53. doi: 10.1021/ct800099a.
The aminolysis of substituted methylformates (XC(O)OCH3, X = NH2, H, and CF3) in the gas phase and acetonitrile are investigated by the density functional theory B3LYP/6-311+G(d,p) method and Monte Carlo (MC) simulation with free energy perturbation (FEP) techniques. The direct and the ammonia-assisted aminolysis processes are considered, involving the monomeric and dimeric ammonia molecules, respectively. In each case, two different pathways, the concerted and stepwise, are explored. The calculated results show that, for the direct aminolysis, the activation barrier of the concerted path is lower than that of the rate-controlling step of the stepwise process for all three reaction systems. In contrast, for the ammonia-assisted mechanism, the stepwise process is more favorable than the concerted pathway. The substituent effects at the carboxyl C atom of methylformate are discussed. This aminolysis of substituted methylformates is more favored for X = CF3 than for X = H and NH2 in the gas phase for both the direct and the ammonia-assisted processes. Solvent effects of CH3CN on the reaction of HC(O)OCH3 + nNH3 (n = 1, 2) are determined by Monte Carlo simulation. The potential energy profiles along the minimum energy paths in the gas phase and in acetonitrile are obtained. It is shown that CH3CN lowers the energy barriers of all reactions.
取代的甲酸盐（XC(O)OCH3，X = NH2，H 和 CF3）在气相和乙腈中的氨解反应通过密度泛函理论 B3LYP/6-311+G(d,p)方法和蒙特卡罗（MC）模拟与自由能微扰（FEP）技术进行了研究。考虑了直接和氨辅助氨解过程，分别涉及单体和二聚氨分子。在每种情况下，都探索了两种不同的途径，即协同和分步途径。计算结果表明，对于直接氨解，对于所有三个反应体系，协同途径的活化势垒均低于分步过程的速控步骤。相比之下，对于氨辅助机理，分步过程比协同途径更有利。讨论了甲酸盐羧基 C 原子上取代基的影响。对于气相中的直接和氨辅助过程，对于 X = CF3 的取代的甲酸盐的氨解比对于 X = H 和 NH2 的氨解更有利。通过蒙特卡罗模拟确定了 CH3CN 对 HC(O)OCH3 + nNH3（n = 1，2）反应的溶剂效应。在气相和乙腈中沿着最小能量路径得到了势能曲线。结果表明，CH3CN 降低了所有反应的能垒。
