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

Abstract

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.