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Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold
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 readil...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225387/ https://www.ncbi.nlm.nih.gov/pubmed/30223585 http://dx.doi.org/10.3390/molecules23092363 |
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author | Ocampo Gutiérrez de Velasco, Diego Antonio Su, Aoze Zhai, Luhan Kinoshita, Satowa Otani, Yuko Ohwada, Tomohiko |
author_facet | Ocampo Gutiérrez de Velasco, Diego Antonio Su, Aoze Zhai, Luhan Kinoshita, Satowa Otani, Yuko Ohwada, Tomohiko |
author_sort | Ocampo Gutiérrez de Velasco, Diego Antonio |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6225387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62253872018-11-13 Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold Ocampo Gutiérrez de Velasco, Diego Antonio Su, Aoze Zhai, Luhan Kinoshita, Satowa Otani, Yuko Ohwada, Tomohiko Molecules Article 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. MDPI 2018-09-15 /pmc/articles/PMC6225387/ /pubmed/30223585 http://dx.doi.org/10.3390/molecules23092363 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ocampo Gutiérrez de Velasco, Diego Antonio Su, Aoze Zhai, Luhan Kinoshita, Satowa Otani, Yuko Ohwada, Tomohiko Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title | Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title_full | Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title_fullStr | Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title_full_unstemmed | Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title_short | Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold |
title_sort | unexpected resistance to base-catalyzed hydrolysis of nitrogen pyramidal amides based on the 7-azabicyclic[2.2.1]heptane scaffold |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225387/ https://www.ncbi.nlm.nih.gov/pubmed/30223585 http://dx.doi.org/10.3390/molecules23092363 |
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