可乐定分子构象异构和互变异构的理论研究

采用HF/6-31G*方法, 对氨基型和亚胺型可乐定中性分子以及质子化的可乐定分子进行了构象分析. 之后采用B3LYP/6-31G**方法对处于势能面上的能量极小构象异构体进行全自由度几何优化和频率分析. Onsager反应场溶剂模型用于水相的计算. 结果表明, 在气相和水相中可乐定中性分子主要以亚胺型存在, 这同已有实验结果一致. 进一步, 寻找构象异构化过渡态和氨基型亚胺型互变异构化过渡态, 探讨质子化和水溶剂化效应对异构化过程的几何结构和能量的影响. 为了考察氯苯的共轭效应对可乐定互变异构体稳定性的影响, 在B3LYP/6-31G**水平上, 研究了2-氨基-2-咪唑啉的互变异构化反应机理.

Theoretical Investigation on Conformational Isomerization and Tautomerization of Clonidine

The conformational analysis of the various tautomers of clonidine in both neutral and protonated forms have been investigated using HF/6-31G* method. The conformers located at minima by HF/6-31G* calculation were re-optimized by B3LYP/6-31G** method without any constraints. The B3LYP/6-31G** calculations on the tautomerism of clonidine in an aqueous medium using Onsager solvation theory model have shown that the solvent does not change the relative stability of the individual tautomers of this drug and the neutral molecule of clonidine exists as the more stable imino tautomer in the gas and aqueous phases. The results are in good agreement with available experimental ones. The protonation and solvent effects were examined by analyzing the change of molecular geometric and energy parameters. The mechanism of clonidine conformational isomerization and tautomeric reaction has been studied and the geometric parame-ters of transition states have been located by B3LYP/6-31G**. In order to evaluate conjugation effects of chlorobenzene on distribution of the clonidine tautomers, we have studied the mechanism of 2-aminoimidazoline tautomeric reaction by B3LYP/6-31G** method.