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Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study

N-Benzhydrylformamides are pharmacologically active compounds with anticonvulsant, enzyme-inducing, antihypoxic, and other types of biological activity. The conformational behavior of benzhydrylformamides is determined to a great extent by the presence of substituents at the nitrogen atom and in the...

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Autores principales: Sadvakassova, Madina Zh., Khlebnikov, Andrei I., Bakibaev, Abdigali A., Kotelnikov, Oleg A., Erkassov, Rakhmetulla Sh., Yelubay, Madeniyet A., Issabayeva, Manar A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863877/
https://www.ncbi.nlm.nih.gov/pubmed/36677593
http://dx.doi.org/10.3390/molecules28020535
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author Sadvakassova, Madina Zh.
Khlebnikov, Andrei I.
Bakibaev, Abdigali A.
Kotelnikov, Oleg A.
Erkassov, Rakhmetulla Sh.
Yelubay, Madeniyet A.
Issabayeva, Manar A.
author_facet Sadvakassova, Madina Zh.
Khlebnikov, Andrei I.
Bakibaev, Abdigali A.
Kotelnikov, Oleg A.
Erkassov, Rakhmetulla Sh.
Yelubay, Madeniyet A.
Issabayeva, Manar A.
author_sort Sadvakassova, Madina Zh.
collection PubMed
description N-Benzhydrylformamides are pharmacologically active compounds with anticonvulsant, enzyme-inducing, antihypoxic, and other types of biological activity. The conformational behavior of benzhydrylformamides is determined to a great extent by the presence of substituents at the nitrogen atom and in the ortho-position(s) of the diphenylmethane moiety. Particularly, the NMR spectra of these compounds often contain two sets of signals originating from different orientations of the formyl group. With the use of the dynamic NMR method and DFT calculations, we investigated the internal rotations of aromatic and formyl fragments and estimated the corresponding rotational barriers in N-benzhydrylformamide (BHFA), N-methyl-N-benzhydrylformamide (BHFA-NMe), and in a series of ortho-halogen-substituted N-benzhydrylformamides. It was found that the DFT method at M06-2X/6-311+G* level of theory satisfactorily reproduces the experimental barrier [Formula: see text] (Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the ortho-halogen derivatives, the calculated [Formula: see text] (Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the ortho-substituents significantly hinder the rotation of aryl fragment with [Formula: see text] (Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in ortho-iodo-N-benzhydrylformamide.
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spelling pubmed-98638772023-01-22 Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study Sadvakassova, Madina Zh. Khlebnikov, Andrei I. Bakibaev, Abdigali A. Kotelnikov, Oleg A. Erkassov, Rakhmetulla Sh. Yelubay, Madeniyet A. Issabayeva, Manar A. Molecules Article N-Benzhydrylformamides are pharmacologically active compounds with anticonvulsant, enzyme-inducing, antihypoxic, and other types of biological activity. The conformational behavior of benzhydrylformamides is determined to a great extent by the presence of substituents at the nitrogen atom and in the ortho-position(s) of the diphenylmethane moiety. Particularly, the NMR spectra of these compounds often contain two sets of signals originating from different orientations of the formyl group. With the use of the dynamic NMR method and DFT calculations, we investigated the internal rotations of aromatic and formyl fragments and estimated the corresponding rotational barriers in N-benzhydrylformamide (BHFA), N-methyl-N-benzhydrylformamide (BHFA-NMe), and in a series of ortho-halogen-substituted N-benzhydrylformamides. It was found that the DFT method at M06-2X/6-311+G* level of theory satisfactorily reproduces the experimental barrier [Formula: see text] (Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the ortho-halogen derivatives, the calculated [Formula: see text] (Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the ortho-substituents significantly hinder the rotation of aryl fragment with [Formula: see text] (Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in ortho-iodo-N-benzhydrylformamide. MDPI 2023-01-05 /pmc/articles/PMC9863877/ /pubmed/36677593 http://dx.doi.org/10.3390/molecules28020535 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sadvakassova, Madina Zh.
Khlebnikov, Andrei I.
Bakibaev, Abdigali A.
Kotelnikov, Oleg A.
Erkassov, Rakhmetulla Sh.
Yelubay, Madeniyet A.
Issabayeva, Manar A.
Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title_full Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title_fullStr Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title_full_unstemmed Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title_short Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study
title_sort rotational barriers in n-benzhydrylformamides: an nmr and dft study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863877/
https://www.ncbi.nlm.nih.gov/pubmed/36677593
http://dx.doi.org/10.3390/molecules28020535
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