New insight on the origin of the unusual acidity of Meldrum's acid from ab initio and combined QM/MM simulation study
New insight on the origin of the unusual acidity of Meldrum's acid from ab initio and combined QM/MM simulation study
复制标题
DOI：
10.1021/ja001369r
复制
发表时间：
2001-05-02
影响因子：
15
通讯作者：
Gao, JL
中科院分区：
文献类型：
--
作者：
Byun, Y;Mo, YR;Gao, JL
采用从头算分子轨道和QM/MM蒙特卡罗模拟相结合的方法研究了梅尔德鲁姆酸异常高酸度的来源。传统上，梅尔德鲁姆酸相对于丙二酸甲酯的高酸度归因于二内酯体系中存在的两种E酯的加性效应。然而，本研究表明，存在显著的非加性效应，这也是主要的贡献。这是由于异构体立体电子相互作用使烯醇酸阴离子比梅尔德姆酸具有更优的稳定性。为了研究溶剂对水溶液酸度的影响，采用从头算QM/MM联合模拟方法确定了乙酸甲酯Z和E构象的相对酸度。溶剂对中性酯及其烯醇阴离子在水中的构象平衡都有显著的影响，导致E立体异构体的稳定。然而，计算得到的溶剂效应4.4 kcal/mol对乙酸甲酯E异构体有利，很大程度上被3.4 kcal/mol对烯醇阴离子E构象有利的溶剂化所抵消。这导致了增强；(E)-乙酸甲酯在水中的酸度为3.4千卡/摩尔。在梅尔德鲁姆酸中，由于异构效应加上酯E构象本身较高的酸度，烯醇阴离子的优先稳定是其高酸度的原因。
Ab initio molecular orbital and combined QM/MM Monte Carlo simulations have been carried out to investigate the origin of the unusually high acidity of Meldrum's acid. Traditionally, the high acidity of Meldrum's acid relative to that of methyl malonate has been attributed to an additive effect due to the presence of two E esters in the dilactone system. However, the present study reveals that there is significant nonadditive effect that also makes major contributions. This results from preferential stabilization of the enolate anion over that of Meldrum's acid due to anomeric stereoelectronic interactions. To investigate solvent effects on the acidity in aqueous solution, the relative acidities of Z and E conformers of methyl acetate have been determined in combined ab initio QM/MM simulations. There is significant solvent effect on the conformational equilibria for both the neutral ester and its enolate anion in water, leading to stabilization of the E stereoisomer. However, the computed solvent effect of 4.4 kcal/mol in favor of the E isomer of methyl acetate is largely offset by the favorable solvation of 3.4 kcal/mol for the E conformer of the enolate anion. This leads to an enhance;l acidity of 3.4 kcal/mol for the (E)-methyl acetate in water over the Z conformer. In Meldrum's acid, it is the preferential stabilization of the enolate anion due to anomeric effects coupled with the intrinsically higher acidity of the E conformation of ester that is responsible for its high acidity.