Monte Carlo Simulation Using Quantum Mechanical Calculations (QM/MC Simulation). An Application to Alkaline Hydrolysis of Methylacetate

Abstract

Although it is possible to analyze chemical reactions in detail using molecular orbital (MO) and Density Functional Theory (DFT) calculations, these results simulate reactions at 0 K in the vacuum. Usual organic reactions proceed in solvents such as water, acetnitrile, alcohol and so on. In order to simulate the reactions in solution, it is necessary to investigate the mechanisms including solvent effects. The SCRF calculations have been used for this purpose while the method regards solvents as simple dielectric constants, and then, it is impossible to analyze the role of each solvent molecule for the reactions. Molecular dynamic (MD) calculations and Monte Carlo (MC) simulations have been used for calculating difference in free energy solvation. These theories usually use classical force fields so that it is very difficult to obtain good parameters for organic solvents used in organic synthesis. We have been developing Monte Carlo simulations using quantum mechanical calculations, called the QM/MC simulations. This approach makes it possible to analyze solvent effects from the quantum chemical view point. As an example of the simulation, we adopted alkaline hydrolysis of methyl acetate. A combination of ab initio calculations at the MP2/6-31++G** level of theory for analyzing the reaction mechanisms in the vacuum and the MC simulations using the PM3 method produced results consistent with experimental results very much.