Modeling the Reaction Mechanisms of the Amide Hydrolysis in an N-(o-Carboxybenzoyl)-L-amino Acid
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- 作者：Zhijian Wu ; Fuqiang Ban ; and Russell J. Boyd
- 刊名：Journal of the American Chemical Society
- 出版年：2003
- 出版时间：June 11, 2003
- 年：2003
- 卷：125
- 期：23
- 页码：6994 - 7000
- 全文大小：205K
- 年卷期：v.125,no.23(June 11, 2003)
- ISSN：1520-5126
文摘
Reaction mechanisms of the amide hydrolysis from the protonated, neutral, and deprotonatedforms of N-(o-carboxybenzoyl)-L-amino acid have been investigated by use of the B3LYP density functionalmethod. Our calculations reveal that in the amide hydrolysis the reaction barrier is significantly lower insolution than that in the gas phase, in contrast with the mechanism for imide formation in which the solventhas little influence on the reaction barrier. In the model reactions, the water molecules function both as acatalyst and as a reactant. The reaction mechanism starting from the neutral form of N-(o-carboxybenzoyl)-L-amino acid, which corresponds to pH 0-3, is concluded to be the most favored, and a concertedmechanism is more favorable than a stepwise mechanism. This conclusion is in agreement with experimentalobservations that the optimal pH range for amide hydrolysis of N-(o-carboxybenzoyl)-L-leucine is pH 0-3where N-(o-carboxybenzoyl)-L-leucine is predominantly in its neutral form. We suggest that besides theacid-catalyzed mechanism the addition-elimination mechanism is likely to be an alternative choice forcleaving an amide bond. For the reaction mechanism initiated by protonation at the amidic oxygen (hydrogenion concentration H0 < -1), the reaction of the model compound with two water molecules lowers thetransition barrier significantly compared with that involving a single water molecule.