Role of hydrogen bonds in acid-catalyzed hydrolyses of esters

Abstract

Acid-catalyzed ester hydrolyses were studied by means of DFT calculations. A model composed of ester and H₃O⁺(H₂O)₁₅ was adopted, and substrates esters are ethyl acetate, ethyl para-X-substituted benzoates (X = O₂N, Cl, H, iso-Bu, MeO, and Me₂N), and isobutyl benzoate. For the ethyl acetate, a stepwise path, precursor → TS1 → Int1 → Int2 → TS2 → product, was obtained. Here, TS is the transition state, and Int is the tetrahedral intermediate. The path is somewhat different from the established A_AC2 mechanism; the carbocation intermediate was calculated to be absent in the present model. The absence holds even for benzoates that may stabilize the cation except the X = Me₂N substituted one. At each local energy minimum, the cation character is retained in H₃O⁺. Proton relays along hydrogen bonds were found to prompt interchanges of covalent bonds. The rate-determining step is either TS1 for the electron-withdrawing X or TS2 for the electron-donating one.