The mechanism of ester hydrolysis is a staple of examination questions in organic chemistry. To get a good grade, one might have to reproduce something like the below. Here, I subject that answer to a reality check.
A computational strategy that reproduces the experimental rates of hydration of formaldehyde, acetaldehyde, acetone, and cyclohexanone and the rates of acetic acid and 2-hydroxypyridine-catalyzed hydration of acetone has been extended to the results of the neutral hydrolysis of methyl acetate reported in Part 1. Calculations have been performed for one-step and two-step mechanisms, with cooperative assistance from one to three additional water molecules in the presence and absence of the acetic acid product. The calculations predict that, for the neutral reaction, a one-step mechanism will be favoured if tetrahedral intermediates have a short lifetime and do not interconvert prior to breakdown (case A), and a two-step mechanism will be operative if tetrahedral intermediates are allowed to interconvert prior to breakdown (case B). The experimental results are consistent with the predictions of case A. In the presence of acetic acid, case A predicts that the acid will contribute only 1.6% to the overall rate, a negligible acceleration over the noncatalytic process, and case B predicts general acid catalysis to be an order of magnitude greater than the experimental result. It is concluded that the neutral hydrolysis of methyl acetate is mainly a cooperative one-step process, and that general acid catalysis by the acetic acid product does not occur.
Archive of work produced using the resources of the Imperial College High Performance Computing Service.
Archive of work produced using the resources of the Imperial College High Performance Computing Service.