Reaction pathways and energy barriers for alkaline hydrolysis of carboxylic acid esters in water studied by a hybrid supermolecule-polarizable continuum approach

Reaction pathways, solvent effects, and energy barriers have been determine d for the base-catalyzed hydrolysis of two representative alkyl esters in a queous solution, using a hybrid supermolecule-polarizable continuum approac h. Four solvent water molecules were explicitly included in the supermolecu lar reaction coordinate calculations; the remaining solvent water was model ed as a polarizable dielectric continuum surrounding the supermolecular rea ction system. Two competing reaction pathways were observed, sharing a comm on first step, i.e. the formation of the tetrahedral intermediate. One path way involves a direct proton transfer in the second step, i.e. the decompos ition of the tetrahedral intermediate. A second pathway involves a water-as sisted proton transfer during the decomposition of the tetrahedral intermed iate. The direct participation of the solvent water molecule in the proton- transfer process significantly drops the energy barrier for the decompositi on of the tetrahedral intermediate. Thus, the energy barrier calculated for the decomposition of the tetrahedral intermediate through the water-assist ed proton transfer becomes lower than the barrier for the formation of the tetrahedral intermediate, while that through the direct proton transfer is higher. The computations reveal the important effect of solvent hydrogen bo nding on energy barriers; without explicit consideration of the hydrogen-bo nding effects, the calculated energy barriers for the formation of the tetr ahedral intermediate become similar to 4-5 kcal/mol smaller. The favorable pathway involving water-assisted proton transfer and the energy barriers ca lculated using the hybrid supermolecule-polarizable continuum approach, inc luding both the hydrogen-bonding effects and the remaining bulk solvent eff ects, are consistent with available experimental results. The energy barrie rs calculated for the first step of the hydrolysis in aqueous solution are in excellent agreement with the reported experimental data for methyl aceta te and methyl formate.