Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event

被引:11
作者
Scorsin, Leandro [2 ]
Affeldt, Ricardo F. [2 ]
Oliveira, Bruno S. [2 ]
Silveira, Eduardo, V [2 ]
Ferraz, Matheus S. [2 ]
de Souza, Fabio P. S. [2 ]
Caramori, Giovanni F. [2 ]
Menger, Fredric M. [1 ]
Souza, Bruno S. [2 ]
Nome, Faruk [2 ]
机构
[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA
[2] Univ Fed Santa Catarina, Dept Chem, BR-88040900 Florianopolis, SC, Brazil
关键词
MOLECULAR-ORBITAL METHODS; ESTER HYDROLYSIS; BASIS-SETS; DYNAMICS; ACID; EFFICIENCY; ANHYDRIDE; MECHANISM; ENERGY; WATER;
D O I
10.1021/acs.joc.9b03383
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A density functional theory (DFT) computational analysis, using the omega B97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.
引用
收藏
页码:4663 / 4671
页数:9
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