Hybrid quantum mechanical/molecular mechanics study of the S(N)2 reaction of CH3Cl+OH- in water.

The S(N)2 mechanism for the reaction of CH(3)Cl + OH(-) in aqueous solution was investigated using combined quantum mechanical and molecular mechanics methodology. We analyzed structures of reactant, transition, and product states along the reaction pathway. The free energy profile was calculated using the multilayered representation with the DFT and CCSD(T) level of theory for the quantum-mechanical description of the reactive region. Our results show that the aqueous environment has a significant impact on the reaction process. We find that solvation energy contribution raises the reaction barrier by ~18.9 kcal/mol and the reaction free energy by ~24.5 kcal/mol. The presence of the solvent also induces perturbations in the electronic structure of the solute leading to an increase of 3.5 kcal/mol for the reaction barrier and a decrease of 5.6 kcal/mol for the reaction free energy, respectively. Combining the results of two previous calculation results on CHCl(3) + OH(-) and CH(2)Cl(2) + OH(-) reactions in water, we demonstrate that increase in the chlorination of the methyl group (from CH(3)Cl to CHCl(3)) is accompanied by the decrease in the free energy reaction barrier, with the CH(3)Cl + OH(-) having the largest barrier among the three reactions.