Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold.
Molecules
; 23(9)2018 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-30223585
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 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, â»TΔS) was large; the entropy term (ΔS) took a large negative value, indicating significant order in the transition structure, which includes solvating water molecules.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos Bicíclicos Heterocíclicos con Puentes
/
Amidas
/
Nitrógeno
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón