Conformational analysis of 2-halocyclohexanones: an NMR, theoretical and solvation study

Abstract

The conformational equilibria of 2-fluoro-, 2-chloro- and 2-iodo-cyclohexanone have been determined in various solvents by measurement of the J_2–3 couplings. The observed couplings were analysed using theoretical and solvation calculations to give both the conformer energies in the solvents studied plus the vapour phase energies and the coupling constants in the distinct conformers. These plus previous results for the 2-bromo compound give the conformer energies and couplings of all the 2-halocyclohexanones. In the 2-fluoro compound the axial conformation is the most stable one in the vapour phase (E_eq − E_ax = 0.45 kcal mol⁻¹), while the equatorial conformer predominates in all the solvents studied. The other haloketones show similar behaviour, but the energy difference in the vapour phase is larger (E_eq − E_ax = 1.05, 1.50 and 1.90 kcal mol⁻¹, for the chloro, bromo and iodo compounds respectively) and the axial conformer is still the prevailing conformer in CCl₄ solution for the chloro and bromo ketones and is the major form in all solvents for the iodo compound. The vapour state conformer energies for the fluoro and chloro compounds are in complete agreement with the ab initio calculated energies, but those for the bromo and iodo are not in such good agreement. Both the ab initio calculations and molecular mechanics are used to discuss the origins of the conformer energies. It is shown that the interaction between the C2 halogen and the CO oxygen in the equatorial conformer is strongly attractive for fluorine, much less so for chlorine, ca. zero for bromine and repulsive for iodine. Comparison of the conformer couplings obtained here with calculated values show generally good agreement.