NMR, solvation and theoretical investigations of conformational isomerism in 2‐X‐cyclohexanones (X=NMe2, OMe, SMe and SeMe)

Abstract

AbstractThe conformational equilibria of 2‐N,N‐dimethylamino‐ (1), 2‐methoxy‐ (2), 2‐methylthio‐ (3) and 2‐methylselenocyclohexanone (4) were determined in various solvents by measurement of the 3JH‐2,H‐3 couplings. The observed couplings were analyzed using theoretical and solvation calculations to give both the conformer energies in the solvents studied plus the vapor‐phase energies and the coupling constants for the distinct conformers. These gave the conformer energies and couplings of 2–4. The intrinsic couplings for the 2‐N,N‐dimethylamino compound were determined by the molecular mechanics PCMODEL program. The axial conformation in 1 is the most polar and also more stable in DMSO solution (Eeq−Eax=0.05 kcal mol−1) and the pure liquid, while the equatorial conformer predominates in the remaining solvents studied (except in CCl4, where self‐association is observed). In the methoxy ketone (2) the equatorial conformation is more stable in the vapor (Eeq−Eax=−0.30 kcal mol−1) and in all solvents. The opposite behavior is shown by 3 and 4, where the axial conformation is the more stable one in the vapor phase (Eeq−Eax=1.60 and 2.95 kcal mol−1 for 3 and 4, respectively) and is still the prevailing conformer in solution. The axial predominance for 3 and 4 is attributed to hyperconjugation between the electron lone pair of the hetero‐substituent and the π*CO orbital. This interaction is stronger for 3 and 4 than in the case of 1 and 2, where the ‘gauche effect’ in the equatorial conformation should be more effective in stabilizing this conformation. Copyright © 2003 John Wiley & Sons, Ltd.