应对消除:从QM/MM模拟中阐明溶剂效应
Orlando Acevedo1, William L Jorgensen
1Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, USA.
Journal of the American Chemical Society
|May 4, 2006
概括
由于反应物的溶解程度较差,在近性溶剂中,应力消除反应的速度是百万倍的. 本研究使用QM/MM计算阐明了溶解对反应速率的影响.
科学领域:
- 计算化学计算化学
- 有机反应机制 有机反应机制
- 溶解动力学是什么意思
背景情况:
- 科普消除是有机合成中的一个关键反应.
- 了解溶剂效应是控制反应速度和结果的关键.
- 之前的研究已经探讨了溶剂效应,但对近距离溶剂中的大速加速缺乏详细的机械洞察力.
研究的目的:
- 为了研究threo-和erythro-N,N-dimethyl-3-phenyl-2-butylamine氧化物的Cope消除反应.
- 为了阐明与水相比,在接近溶剂 (THF,DMSO) 中观察到的显著速度加速.
- 分析溶解对反应物的作用,过渡状态和反应动力学.
主要方法:
- 在各种溶剂中进行量子力学/分子力学 (QM/MM) 计算.
- 从蒙特卡洛模拟与自由能量扰动 (MC/FEP) 来得出的平均力 (PMF) 的二维潜力.
- 使用MP2/6-311+G-(2d,p) 的初始计算与PCM连续溶剂模型进行比较.
主要成果:
- QM/MM计算准确地复制了近距离溶剂中的百万倍速度加速,与PCM的ab initio方法不同.
- 反应剂在近性溶剂中的较差溶解被确定为增速的主要原因.
- 对辐射分布函数的分析显示,在近极介质中,氨基氧氧和溶剂分子之间的键减少.
结论:
- 使用PDDG/PM3进行QM的QM/MM/MC方法对量化预测反应速率和溶解效应非常有效.
- 溶解动力学,特别是结的减少,在加快双极近极溶剂中的Cope消除反应中发挥着关键作用.
- 这项研究提供了关于溶剂对氨基氧化物消除作用的详细机制理解.
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