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

The H-1 and C-13 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-ep 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 Delta G(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 Delta S is zero and Delta H equals Delta G but in 2 values of Delta S of 2.0 cal mol(-1) K-1 and of Delta H 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 Delta G 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.