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The aminolysis of N-Aroyl β-Lactams occurs by a concerted mechanism

Tsang, Wing Y., Ahmed, Naveed and Page, Michael I. (2007) The aminolysis of N-Aroyl β-Lactams occurs by a concerted mechanism. Organic and Biomolecular Chemistry, 5 (3). pp. 485-493. ISSN 1477-0539

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N-Aroyl -lactams are imides with exo- and endocyclic acyl centres which react with amines in aqueous solution to give the ring opened -lactam aminolysis product. Unlike the strongly base catalysed aminolysis of -lactam antiobiotics, such as penicillins and cephaloridines, the rate law for the aminolysis of N-aroyl -lactams is dominated by a term with a first-order dependence on amine concentration in its free base form, indicative of an uncatalysed aminolysis reaction. The second-order rate constants for this uncatalysed aminolysis of N-p-methoxybenzoyl -lactam with a series of substituted amines generates a Brønsted nuc value of +0.90. This is indicative of a large development of positive effective charge on the amine nucleophile in the transition state. Similarly, the rate constants for the reaction of 2-cyanoethylamine with substituted N-aroyl -lactams gives a Brønsted lg value of –1.03 for different amide leaving groups and is indicative of considerable change in effective charge on the leaving group in the transition state. These observations are compatible with either a late transition state for the formation of the tetrahedral intermediate of a stepwise mechanism or a concerted mechanism with simultaneous bond formation and fission in which the amide leaving group is expelled as an anion. Amide anion expulsion is also indicated by an insignificant solvent kinetic isotope effect, kH2ORNH2/kD2ORNH2, of 1.01 for the aminolysis of N-benzoyl -lactam with 2-methoxyethylamine. The Brønsted lg value decreases from –1.03 to –0.71 as the amine nucleophile is changed from 2-cyanoethylamine to propylamine. The Brønsted nuc value is more invariant although it changes from +0.90 to +0.85 on changing the amide leaving group from p-methoxy to p-chloro substituted. The sensitivity of the Brønsted nuc and lg values to the nucleofugality of the amide leaving group and the nucleophilicity of the amine nucleophiles, respectively, indicate coupled bond formation and bond fission processes.

Item Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
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Depositing User: Sara Taylor
Date Deposited: 25 Jan 2008 16:24
Last Modified: 28 Aug 2021 10:38


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