Rate constants for the aminolysis of the N-hydroxysuccinimide (NHS) ester of ρ-methoxybenzoic acid, in aqueous buffer systems (20% dioxane), have been determined under pseudo-first-order conditions. For the amines studied (pKa = 7.60-11.1), the data fit the rate expression kobsd - KOH-⨯ [OH-] = k1[amine]free. This rate equation is in contrast to the two-term rate equation (kobsd = k1[amine] + k2[amine]2) obtained for this reaction in anhydrous dioxane (Cline, G. W.; Hanna, S. B. J. Am. Chem. Soc. 1987,109, 3087) and is suggestive of a disproportionate decrease in the catalyzed vs the uncatalyzed reaction path upon changing from a nonaqueous to an aqueous solvent system. The correlation of amine basicity with the nucleophilic rate constant, k1 yields a slope αnuc = 1.0. The magnitude of αnuc, in terms of a reaction mechanism where a tetrahedral intermediate is formed in a fast preequilibrium followed by rate-determining breakdown to products, reflects the sensitivity to changes in charge accumulation in the formation of the tetrahedral intermediate. The resultant increased rate constants, with increased basicity, are due to the effect of an increased concentration of the tetrahedral intermediate. A qualitative evaluation of the literature and current data concerning the leaving ability of N-hydroxy esters, in comparison to phenyl esters (equivalent acyl groups and nucleophiles), reveals that, with leaving groups of comparable basicity, the nucleophilic rate constants for N-hydroxy esters are about 2 orders of magnitude greater than that for phenyl esters. © 1988, American Chemical Society. All rights reserved.
G. W. Cline and S. B. Hanna, "Kinetics And Mechanisms Of The Aminolysis Of N-Hydroxysuccinimide Esters In Aqueous Buffers," Journal of Organic Chemistry, vol. 53, no. 15, pp. 3583 - 3586, American Chemical Society, Oct 1988.
The definitive version is available at https://doi.org/10.1021/jo00250a031
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01 Oct 1988