Conformational analysis explores the role of electrostatic non-classical CFHC hydrogen bonding interactions in selectively halogenated cyclohexanes
Date
05/03/2024Metadata
Show full item recordAbstract
The conformational equilibria of selectively halogenated cyclohexanes are explored both experimentally (VT-NMR) for 1,1,4,-trifluorocyclohexane 7 and by computational analysis (M06-2X/aug-cc-pVTZ level), with the latter approach extending to a wider range of more highly fluorinated cyclohexanes. Perhaps unexpectedly, 7ax is preferred over the 7eq conformation by ΔG = 1.06 kcal mol–1, contradicting the accepted norm for substituents on cyclohexanes. The axial preference is stronger again in 1,1,3,3,4,5,5,-heptafluorocyclohexane 9 (ΔG = 2.73 kcal mol–1) as the CF2 groups further polarize the isolated CH2 hydrogens. Theoretical decomposition of electrostatic and hyperconjugative effects by natural bond orbital analysis indicated that nonclassical hydrogen bonding (NCHB) between the C-4 fluorine and the diaxial hydrogens at C-2 and C-6 in cyclohexane 7 and 9 largely accounts for the observed bias. The study extended to changing fluorine (F) for chlorine (Cl) and bromine (Br) at the pseudoanomeric position in the cyclohexanes. Although these halogens do not become involved in NCHBs, they polarize the geminal −CHX– hydrogen at the pseudoanomeric position to a greater extent than fluorine, and consequent electrostatic interactions influence conformer stabilities.
Citation
He , M , Piscelli , B , Cormanich , R & O'Hagan , D 2024 , ' Conformational analysis explores the role of electrostatic non-classical CFHC hydrogen bonding interactions in selectively halogenated cyclohexanes ' , The Journal of Organic Chemistry , vol. 89 , no. 6 , pp. 4009–4018 . https://doi.org/10.1021/acs.joc.3c02868
Publication
The Journal of Organic Chemistry
Status
Peer reviewed
ISSN
0022-3263Type
Journal article
Description
Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo - 2018/03910-1, 2023/14064-2; China Scholarship Council; Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas - 3472/23Collections
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