1,3-Diaxial steric effects and intramolecular hydrogen bonding in the conformational equilibria of new cis-1,3-disubstituted cyclohexanes using low temperature NMR spectra and theoretical calculations

The conformational equilibria of 3-X-cyclohexanol [X = F (1), Cl (2), Br (3), I (4), Me (5), NMe2 (6) and MeO (7)] and of 3-X-methoxycyclohexane [X = F (8), Cl (9), Br (10), I (11), Me (12), NMe2 (13) and MeO (14)] cis isomers were determined from low temperature NMR spectra and PCMODEL calculated coupling constants. The energy differences between aa and ee conformers were obtained from these data (ΔGJav and ΔGPCav, respectively) and also by the additivity principle from data for the monosubstituted cyclohexanes (ΔGAd). H-1 and H-3 hydrogen vicinal coupling constants and ΔGJav values showed that the diequatorial conformer is predominant in the conformational equilibrium of the compounds studied at low temperature. However, ΔGPCav data show that compounds 6 and 7 constitute an exception, since they are almost equally populated by ee and aa at room temperature, due to stabilization of their aa conformer by an intramolecular hydrogen bond. ΔGAd values, obtained according to the additivity principle, show a better agreement for compounds 2 and 3, since the 1,3-diaxial steric effect is counterbalanced by the formation of an intramolecular hydrogen bond (IAHB). For the remaining compounds, ΔGAd values underestimate the energy differences, since the 1,3-diaxial steric effect, between X and OH or OCH3, is absent in the monosubstituted compounds used as references. Moreover, the ΔGPCav, calculated from the coupling constants, obtained through the PCMODEL program, are rather smaller than the ΔGJav values, since the program does not have parameters for the effect, observed in this report, of a substituent at γ position on coupling constants values for the hydrogen under consideration.