Twelve amines, which vary substantially in basicity and in steric environment around N, have been allowed to compete—in anhydrous dioxane solution—in the aminolysis of the N-hydroxysuccinimide esters of unsubstituted, p-OCH3, p-N02, and 3,5-(N02)2 benzoic acids. The amines, which encompass a basicity range of 6.5 pk units, display a 10000-fold variation in reactivity in their reaction with the p-N02ester. for the sterically unhindered amines, a Bronsted-type plot of log kobsdvs. pKa has a slope of ~0.7. The data fit a model (Satterthwait, A. C.; Jencks, W. P. J. Am. Chem. Soc. 1974, 96, 7018–7044) in which reversible formation of a tetrahedral intermediate is followed by rate-determining breakdown to products. Appreciable sensitivity to steric factors, as evidenced from the depressed rates with a-methylbenzylamine and diethylamine, substantiates reversible formation of a crowded tetrahedral intermediate prior to the rate-determining step. The Hammett p values for the competitive acylation of aniline, a-methylbenzylamine, and benzylamine, by substituted N-succinimidyl benzoates, are 1.4,1.2, and 1.1, respectively. These values reflect the selectivity expected for these amines, and the substantial accumulation of charge density at the acyl C in the formation of the tetrahedral intermediate. Individual rate constants for the aminolysis of N-succinimidyl p-methoxybenzoate by n-butylamine and by piperidine, both show First-order and second-order terms in [amine]. The general-base catalysis term is suggestive of a path involving proton transfer in the rate-determining step. © 1987, American Chemical Society. All rights reserved.
G. W. Cline and S. B. Hanna, "The Aminolysis Of N-Hydroxysuccinimide Esters. A Structure-Reactivity Study," Journal of the American Chemical Society, vol. 109, no. 10, pp. 3087 - 3091, American Chemical Society, May 1987.
The definitive version is available at https://doi.org/10.1021/ja00244a035
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01 May 1987