The Aminolysis of N-Hydroxysuccinimde Esters. A Structure-Reactivity Study

Article abstract of DOI:10.1021/ja00244a035

Twelwe amines, which vary substantially in basicity and 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-NO2, and 3,5-(NO2)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-NO2-ester.For the sterically unhindered amines, a Broensted-type plot of log k_obsd vs. pK_a has a slope of ca. 0.7.The data fit a model (Satterthwait, A.C.; Jenks, 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 α-methylbenzylamine and diethylamine, substantiates reversible formation of a crowded tetrahedral intermediate prior to the rate-determining step.The Hammett ρ values for the competitive acylation of aniline, α-methylbenzylamin, 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 .The general-base catalysis term is suggestive of a path involving proton transfer in the rate-determining step.