Conformational analysis. Part 28. OH⋯F hydrogen bonding and the conformation of trans-2-fluorocyclohexanol

The 1H and 13C NMR spectra of trans-2-fluorocyclohexanol 1 and the methyl ether 2 have been obtained in a variety of solvents and temperatures. From the low-temperature spectra the proportions of the ax–ax and eq–eq conformers were obtained by direct integration together with the vicinal HH couplings of the 2-proton in the dominant eq–eq conformer. From these results the conformer populations and energies in a variety of solvents are given.In 1 ΔG(aa–ee) varies from 1.5 kcal mol–1(1 cal = 4.184 J) in non polar solvents (e.g. CCl4) to ca. 1.2 kcal mol–1 in very polar solvents (acetone), whereas in 2 the corresponding values are 0.4 and 1.0 kcal mol–1. The proton donor solvents CDCl3 and CD2Cl2 are exceptions due to preferential CH⋯O hydrogen bonding in the eq–eq form.These figures are explained by solvation theory, which also provides the vapour state free energy differences of 1.6 kcal mol–1 1 and 0.1 kcal mol–1 2. In 1 ΔS is zero and ΔH equals ΔG but in 2 values of ΔS of 2.0 cal mol–1 K–1 and of ΔH of 1.1 kcal mol–1 in non polar media and 0.7 kcal mol–1 for the vapour are obtained. These values may be compared with those calculated by ab initio theory at the 6-31G*(MP2) level of 1.1 kcal mol–1 1 and –0.75 kcal mol–1 2. In both cases the eq–eq conformer is more stable than predicted, by 0.5 and 1.5 kcal mol–1.Comparison of the conformer energies with those obtained from the ΔG values for the monosubstituted cyclohexanes gives the OH⋯F hydrogen bonding attraction in the eq–eq conformer as 1.6 kcal mol–1 whilst the gauche OMe⋯F interaction is neutral, neither repulsive nor attractive. These figures support previous theoretical interpretations that the gauche form of 2-fluoroethanol is predominant due to OH⋯F hydrogen bonding and show also that the previous discrepancy between experimental measurements in the condensed phase and theory is due to solvation.