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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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/2/535 |
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| author | Madina Zh. Sadvakassova Andrei I. Khlebnikov Abdigali A. Bakibaev Oleg A. Kotelnikov Rakhmetulla Sh. Erkassov Madeniyet A. Yelubay Manar A. Issabayeva |
| author_facet | Madina Zh. Sadvakassova Andrei I. Khlebnikov Abdigali A. Bakibaev Oleg A. Kotelnikov Rakhmetulla Sh. Erkassov Madeniyet A. Yelubay Manar A. Issabayeva |
| author_sort | Madina Zh. Sadvakassova |
| collection | DOAJ |
| 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 <i>ortho</i>-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 <i>ortho</i>-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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the <i>ortho</i>-halogen derivatives, the calculated <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the <i>ortho</i>-substituents significantly hinder the rotation of aryl fragment with <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in <i>ortho</i>-iodo-N-benzhydrylformamide. |
| first_indexed | 2024-03-09T11:37:35Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T11:37:35Z |
| publishDate | 2023-01-01 |
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| series | Molecules |
| spelling | doaj.art-dc3ffbaf2af145f0a025f71a408b67602023-11-30T23:41:14ZengMDPI AGMolecules1420-30492023-01-0128253510.3390/molecules28020535Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT StudyMadina Zh. Sadvakassova0Andrei I. Khlebnikov1Abdigali A. Bakibaev2Oleg A. Kotelnikov3Rakhmetulla Sh. Erkassov4Madeniyet A. Yelubay5Manar A. Issabayeva6Department of Chemistry, L.N. Gumilyov Eurasian National University, 010008 Astana, KazakhstanKizhner Research Center, Tomsk Polytechnic University, 634050 Tomsk, RussiaFaculty of Chemistry, National Research Tomsk State University, 634050 Tomsk, RussiaFaculty of Chemistry, National Research Tomsk State University, 634050 Tomsk, RussiaDepartment of Chemistry, L.N. Gumilyov Eurasian National University, 010008 Astana, KazakhstanDepartment of Chemistry and Chemical Technology, Toraighyrov University, 140008 Pavlodar, KazakhstanDepartment of Chemistry and Chemical Technology, Toraighyrov University, 140008 Pavlodar, KazakhstanN-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 <i>ortho</i>-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 <i>ortho</i>-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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the <i>ortho</i>-halogen derivatives, the calculated <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the <i>ortho</i>-substituents significantly hinder the rotation of aryl fragment with <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msubsup><mi>G</mi><mrow><mn>298</mn></mrow><mo>≠</mo></msubsup></mrow></semantics></math></inline-formula>(Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in <i>ortho</i>-iodo-N-benzhydrylformamide.https://www.mdpi.com/1420-3049/28/2/535N-benzhydrylformamide derivativesrotational barriersdynamic NMRDFT calculations |
| spellingShingle | Madina Zh. Sadvakassova Andrei I. Khlebnikov Abdigali A. Bakibaev Oleg A. Kotelnikov Rakhmetulla Sh. Erkassov Madeniyet A. Yelubay Manar A. Issabayeva Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study Molecules N-benzhydrylformamide derivatives rotational barriers dynamic NMR DFT calculations |
| 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 | N-benzhydrylformamide derivatives rotational barriers dynamic NMR DFT calculations |
| url | https://www.mdpi.com/1420-3049/28/2/535 |
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