Conformational Analysis Explores the Role of Electrostatic Nonclassical CFHC Hydrogen Bonding Interactions in Selectively Halogenated Cyclohexanes

Autor(es)

He, Mengfan ; Piscelli, Bruno A. ; Cormanich, Rodrigo A. ; O'Hagan, David

• Tipo de documento: Artigo Científico
• Fonte: Journal of Organic Chemistry; v. 89, n. 6, p. 10-pg., 2024-03-05.

Resumo

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, 7 ax is preferred over the 7(eq) conformation by Delta G = 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 (Delta G = 2.73 kcal mol(-1)) as the CF(2 )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. [GRAPHICS] (AU)

• Processo FAPESP: 23/14064-2 - Modelagem da interação de ciclohexanos Janus-face com dsDNA e ssDNA.
• Beneficiário: Bruno de Almeida Piscelli
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 18/03910-1 - Estudos físico-químicos de compostos orgânicos fluorados: abordagens experimental e teórica
• Beneficiário: Rodrigo Antonio Cormanich
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores