Concerted Bifunctional Proton Transfer and General-Base Catalysis in the Methoxyaminolysis of Phenyl Acetate

Article abstract of DOI:10.1021/ja00393a014

The bifunctional acid-base catalysts cacodylic acid, bicarbonate, and the monoanions of phosphate, substituted phosphonates, and methylarsonate are up to 10²-10³ more effective than monofunctional acids or bases of comparable pK for catalysis of the methoxyaminolysis of phenyl acetate.The absence of the downward break in the Broensted plot and the solvent isotope effect maximum that are observed with monofunctional acid catalysts when proton transfer becomes partially rate limiting indicates that these bifunctional catalysts avoid this stepwise proton-transfer step.It is concluded that the two proton transfers occur through a mechanism with no detectable barrier or isotope effect, which appears to be concerted and is so fast that proton transfer never becomes kinetically significant; the rate-limiting step is amine attack with hydrogen bonding by the catalyst.Glycine and water show smaller rate increases that probably represent stepwise bifunctional proton transfer through a nine-membered ring or two water molecules in a one-encounter mechanism.Pyrazole and triazole show little or no enhancement of catalytic activity, indicating that bifunctional proton transfer through a seven-membered ring is relatively unfavorable in aqueous solution.Catalysis by monofunctional bases follows a nonlinear Broensted plot and is attributed to a preassociation mechanism analogous to that for general-acid catalysis.