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The Role of Water in the Catalyst‐Free Aldol Reaction of Water‐Insoluble N ‐Methyl‐2,4‐thiazolidinedione with N ‐Methylisatin from QM/MM Monte Carlo Simulations
Author(s) -
Zhao Jianming,
He Fen,
Zhang Fan,
Yang Xin,
Tian Zhiyue,
Xue Ying
Publication year - 2017
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201700423
Subject(s) - chemistry , aldol reaction , hydrogen bond , computational chemistry , catalysis , qm/mm , molecule , molecular dynamics , organic chemistry
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.