Zhao Jianming, He Fen, Zhang Fan, Yang Xin, Tian Zhiyue, Xue Ying
College of Chemistry, Key Lab of Green Chemistry, and Technology in Ministry of Education, Sichuan University, Chengdu, 610064, P.R. China.
Chemphyschem. 2017 Aug 5;18(15):2123-2131. doi: 10.1002/cphc.201700423. Epub 2017 Jun 19.
The role of water in the uncatalyzed aldol reaction of N-methyl-2,4-thiazolidinedione with N-methylisatin is investigated through Monte Carlo statistical mechanics simulations that utilize free energy perturbation theory and the mixed quantum mechanics and molecular mechanics (QM/MM) model with PDDG/PM3 for the QM method in "on-water" and DMSO environments. There are several conceivable orientations between thiazolidinedione and isatin in the process of C-C bond formation. However, the formation of the C-C bond takes place between the re face of isatin and the si face of (E)-enol of the thiazolidinedione to form the preferred anti-type product, which results from enhanced hydrogen-bonding interactions between water molecules and the oxygen atoms undergoing bond breakage and bond formation during the reaction. Novel insights into the effect of water on the aldol reaction are presented herein.
通过蒙特卡罗统计力学模拟研究了水在N-甲基-2,4-噻唑烷二酮与N-甲基异吲哚酮的非催化羟醛反应中的作用，该模拟利用自由能微扰理论以及在“水相”和二甲基亚砜（DMSO）环境中采用PDDG/PM3作为量子力学方法的混合量子力学与分子力学（QM/MM）模型。在碳-碳键形成过程中，噻唑烷二酮和异吲哚酮之间存在几种可能的取向。然而，碳-碳键的形成发生在异吲哚酮的Re面与噻唑烷二酮的（E）-烯醇的Si面之间，以形成优选的反式产物，这是由于水分子与反应过程中发生键断裂和键形成的氧原子之间增强的氢键相互作用所致。本文提出了关于水对羟醛反应影响的新见解。
