Catalysis of the Methoxyaminolysis of Phenyl Acetate by a Preassociation Mechanism with a Solvent Isotope Effect Maximum

Article abstract of DOI:10.1021/ja00393a013

General-acid catalysis of the reaction of methoxyamine with phenyl acetate by the proton, carboxylic acids, and ammonium ions follows a nonlinear Broensted curve.This curve agress quantitavely with the behavior expected for the enforced preassociation mechanism of catalysis that was predicted for this reaction.The stronger acids, including the proton, follow a Broensted slope of α=0.16 that represents rate-limiting amine attack assisted by hydrogen bonding, weaker acids react with partially rate-limiting proton transfer to the addition intermediate T^+/-, and the weakest acids follow a steeper Broensted slope approaching α=1.0 that represents rate-limiting separation of the protonated intermediate T⁺.There is no decrease in the rate constant for catalysis by chloroacetic acid with increasing viscosity in water-glycerol mixtures; a decrease is observed for the reaction of methylamine with p-tolyl acetate catalyzed by acetate buffers, which is believed to proceed by a diffusion-controlled trapping mechanism.A sharp maximum in the solvent isotope effect at pK_HA = 6.8 confirms the kinetically significant proton-transfer step in the intermediate region near ΔpK = 0.The decrease with stronger acids represents a decrease in the isotope effect for this proton-transfer step, which is largely rate limiting for acids of pK_a = 4-7, but the decrease with weaker acids can be explained by the change to rate-limiting diffusional separation of T⁺ and A^-.Two explanations are offered for the decreased isotope effect with increasing acid strengh. (1) There is a sharp change to an asymmetric structure of the transition state for the very rapid proton-transfer step, as suggested by Melander and Westheimer. (2) There is a shift to a rate-limiting change in solvation that occurs immediately either before or after the proton-transfer step with stronger acids.It is possible to fit the observed Broensted curve and isotope effect maximum with calculated rate constants that are based on a rate law and estimated rate constants for the steps of the latter mechanism.