Issue 9, 2019, Issue in Progress

Effects of solvents on the DACBO-catalyzed vinylogous Henry reaction of isatin with 3,5-dimethyl-4-nitroisoxazole “on-water” and in solution from QM/MM MC simulations

Abstract

The mechanism of the DABCO-catalyzed vinylogous Henry reaction of isatin with 3,5-dimethyl-4-nitroisoxazole and solvent effects on it have been investigated using density functional theory (DFT) methods and QM/MM Monte Carlo (MC) simulation under “on-water” conditions as well as in methanol and THF solutions. The DFT calculations concluded that Path A, in which DABCO directly catalyzes the reaction of isatin 1a with 3,5-dimethyl-4-nitroisoxazole 2 in water, is the most favorable and the first step, the proton transfer process, is the rate-determining step for the reaction. For the roles of solvents in the reaction, QM/MM MC simulations using free energy perturbation theory and PDDG/PM3 as the QM method have been utilized to predict the free energy profiles. The results indicated that the QM/MM method reproduced well the large rate increases on-water. Solute–solvent energy pair distribution and radial distribution functions were also analyzed and illustrated that hydrogen bonding plays a significant role in stabilizing the transition structures. This work reveals the feasible reaction mechanisms and provides new insight into solvent effects for the DACBO-catalyzed vinylogous Henry reaction.

Graphical abstract: Effects of solvents on the DACBO-catalyzed vinylogous Henry reaction of isatin with 3,5-dimethyl-4-nitroisoxazole “on-water” and in solution from QM/MM MC simulations

Supplementary files

Article information

Article type
Paper
Submitted
04 Jan 2019
Accepted
30 Jan 2019
First published
08 Feb 2019
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2019,9, 4932-4941

Effects of solvents on the DACBO-catalyzed vinylogous Henry reaction of isatin with 3,5-dimethyl-4-nitroisoxazole “on-water” and in solution from QM/MM MC simulations

L. Yang, J. Zhao, X. Yang, M. Chen and Y. Xue, RSC Adv., 2019, 9, 4932 DOI: 10.1039/C9RA00082H

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