On the purported axial preference in 2-methylthio and 2-methoxycyclohex-anones: steric effects versus orbital interactions

Abstract

The value for the equilibrium constant representing the ratio of equatorial to axial conformers for 2-methylthio- and 2-methoxycyclohexanone has been measured in five solvents using 500 MHz ¹H nuclear magnetic resonance. In cyclohexane solvent, the methylthio group is found to have a large axial preference while that for the methoxy is negligible. For both compounds the equilibrium shows a strong solvent dependence. Comparison of these results with those known for the halo derivatives shows the amount of axial to increase in the order: fluoro, methoxy, chloro, bromo, and methylthio. With the aid of molecular mechanics calculations it is concluded that the order of conformational preference can be attributed to a variation in the van der Waals interaction between the substituent and the carbonyl group in the equatorial conformer. Keywords: α-substituted cyclohexanones, conformation, MMX calculations, steric and dipolar effects.