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Acid‐Catalyzed Reactions of Twisted Amides in Water Solution: Competition between Hydration and Hydrolysis
Author(s) -
Wang Binju,
Cao Zexing
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101274
Subject(s) - chemistry , hydrolysis , protonation , amide , nucleophile , catalysis , peptide bond , leaving group , delocalized electron , medicinal chemistry , computational chemistry , ion , organic chemistry , enzyme
The acid‐catalyzed reactions of twisted amides in water solution were investigated by using cluster‐continuum model calculations. In contrast to the previous widely suggested concerted hydration of the CO group, our calculations show that the reaction proceeds in a practically stepwise manner, and that the hydration and hydrolysis channels of the CN bond compete. The Eigen ion (H 3 O + ) is the key species involved in the reaction, and it modulates the hydration and hydrolysis reaction pathways. The phenyl substitution in the twisted amide not only activates the NCO bond, but also stabilizes the hydrolysis product through n N →π phenyl delocalization, leading exclusively to the hydrolysis product of the ring‐opened carboxylic acid. Generally, the twisted amides are more active than the planar amides, and such a rate acceleration results mainly from the increase in exothermicity in the first N‐protonation step; the second step of the nucleophilic attack is less affected by the twisting of the amide bond. The present results show good agreement with the available experimental observations.