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Keywords = base-catalyed hydrolysis

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22 pages, 7508 KB  
Article
Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold
by Diego Antonio Ocampo Gutiérrez de Velasco, Aoze Su, Luhan Zhai, Satowa Kinoshita, Yuko Otani and Tomohiko Ohwada
Molecules 2018, 23(9), 2363; https://doi.org/10.3390/molecules23092363 - 15 Sep 2018
Cited by 6 | Viewed by 7588
Abstract
Non-planar amides are usually transitional structures, that are involved in amide bond rotation and inversion of the nitrogen atom, but some ground-minimum non-planar amides have been reported. Non-planar amides are generally sensitive to water or other nucleophiles, so that the amide bond is [...] Read more.
Non-planar amides are usually transitional structures, that are involved in amide bond rotation and inversion of the nitrogen atom, but some ground-minimum non-planar amides have been reported. Non-planar amides are generally sensitive to water or other nucleophiles, so that the amide bond is readily cleaved. In this article, we examine the reactivity profile of the base-catalyzed hydrolysis of 7-azabicyclo[2.2.1]heptane amides, which show pyramidalization of the amide nitrogen atom, and we compare the kinetics of the base-catalyzed hydrolysis of the benzamides of 7-azabicyclo[2.2.1]heptane and related monocyclic compounds. Unexpectedly, non-planar amides based on the 7-azabicyclo[2.2.1]heptane scaffold were found to be resistant to base-catalyzed hydrolysis. The calculated Gibbs free energies were consistent with this experimental finding. The contribution of thermal corrections (entropy term, –TΔS) was large; the entropy term (ΔS) took a large negative value, indicating significant order in the transition structure, which includes solvating water molecules. Full article
(This article belongs to the Special Issue Amide Bond Activation)
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