Concerted General Base and Bifunctional General Acid Catalysis of the Aminolysis of Phenyl Acetate by Pyrazole'

The reaction of phenyl acetate with pyrazole is catalyzed by general bases and by bifunctional general acids. The Br~lnsted plot for general base catalysis shows downward curvature. It is consistent with either a Hammond effect on proton transfer, as described by a positive coefficient p x = a/3/-apKAH, or separate lines with p = 0.65 for cacodylate and substituted acetate monoanions and /3 = 0.38 for phosphate, phosphonate, and methylarsonate dianions. Base catalysis shows a solvent deuterium isotope effect of kHOH/kDOD = 1.8 & 0.2 with no isotope effect maximum. These results are not consistent with trapping or stepwise preassociation mechanisms. It is concluded that the reaction involves concerted general base catalysis of prQton abstraction from pyrazole as it attacks the ester. An estimated rate constant of k-, > 6 X 1 0 " ~ ~ for collapse of the zwitterionic addition species, p, to reactants suggests that the concerted mechanism is enforced by the absence of a significant lifetime for T'. Catalysis is observed with buffer acids when the acid is bifunctional. The rate constants are larger than expected for catalysis by the basic site on the catalyst but decrease with increasing acidity of the catalyst; the Brmsted slope is 01 = -0.2 or p = 0.2. This catalysis is consistent with a fully concerted mechanism in which bifunctional acid-base catalysis occurs simultaneously with nucleophilic attack. W e would like to understand mechanisms of general acid-base catalysis and the reasons that a particular mechanism is followed for a reaction. Some mechanisms are determined by the lifetimes of reaction intermediates. For example, addition reactions to aldehydes occur by a predictable series of mechanisms with (1) no buffer catalysis, ( 2 ) general acid catalysis by diffusion-controlled trapping of an unstable anionic intermediate, (3) a preassociation mechanism that is required by a decrease in the lifetime of this intermediate, with stabilization of the transition state by hydrogen bonding, and (4) a fully concerted mechanism when the initially formed addition intermediate becomes too unstable to have a significant More limited studies of general acid and base catalysis of the aminolysis of phenyl esters suggest that the mechanisms of these reactions can also be determined by the lifetime of tetrahedral intermediates along the reaction path. B r ~ n s t e d plots for the acid-catalyzed partitioning of 4-methylphenyl N-methylacetimidate toward ester formation follow typical "Eigen curves'' that are expected for an addition intermediate that undergoes diffusion-controlled proton transfer; the same addition intermediate is formed in the aminolysis of 4-methylphenyl acetate by methylamine and can be trapped by diffusion-controlled proton transfer. The lifetime of the initial addition intermediate in the aminolysis reaction, Ti, was estimated to be approximately sS4 The aminolysis of phenyl acetate by methoxyamine, which gives a less stable intermediate, follows B r ~ n s t e d plots for both general acid and general base catalysis with values of a and fi = 0.1-0.2 for strong acid and base catalysts and 1.0 for weaker catalysts, for which the proton-transfer step is thermodynamically unfavorable. Furthermore, there is a maximum in the solvent isotope effect near the break in the Bronsted plot, where the proton-transfer step becomes partially ra tel imit i~~g,~ and a large /3-deuterium isotope effect6 This is the behavior that is expected for catalysis by a preassociation mechanism, in which the transition state for the addition step is stabilized by hydrogen bonding to relatively strong acids or bases and diffusion-controlled separation from the unstable intermediate after proton transfer becomes rate-limiting with weakly acidic or basic catalysts. The preassociation mechanism is enforced by the short lifetime of the addition intermediate formed from this weakly basic amine, with (1) Supported in part by grants from the National Institutes of Health (2) Gilbert, H. F.; Jencks, W. P. J . Am. Chem. Soc. 1977, 99, 7931. (3) S~rensen , P. E.; Jencks, W. P. J . Am. Chem. SOC. 1987, 109, 4675. (4) Satterthwaite, A. C.; Jencks, W. P. J . Am. Chem. Soc. 1974, 96, 7018, (5) Cox, M . M.; Jencks, W. P. J . Am. Chem. SOC. 1981, 103, 572, 580. (6) Kovach, I. M.; Belz, M.; Larson, M.; Rousy, S.; Schowen, R. L. J. Am. (GM 20888) and the National Science Foundation (PCM 81-17816).