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

Abstract

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 'H 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.Key words: a-substituted cyclohexanones, conformation, MMX calculations, steric and dipolar effects.Resume : Utilisant la rksonance magnCtique nuclCaire du 'H a 500 MHz et opCrant dans cinq solvants, on a mesurC la valeur de la constante d'tquilibre reprksentant le rapport des conformkres Cquatorial et axial des 2-mCthylthio-et 2-mCthoxycyclohexanones. Dans le cyclohexane comme solvant, on trouve que le groupe mtthylthio a une prCfCrence axiale alors que celle du groupe mCthoxy est negligeable. Pour les deux composts, 1'Cquilibre depend fortement du solvant. Une comparaison de ces rCsultats avec ceux connus pour les dCrivCs halogCnCs montre que la quantitC de conformkre axial augrnente dans l'ordre : fluoro, mCthoxy, chloro, bromo et rntthylthio. En se basant sur des calculs de mCcanique molCculaire, on conclut que l'ordre de prCftrences conformationnelles peut Etre attribuC a une variation de l'interaction de van der Waals entre le substituant et le groupe carbonyle du conformkre Cquatorial.

Ab initio DFT calculations of the configurational and conformational preferences of 2-phenylsulfinylcyclohexanones — Evidence for "exo-anomeric" interactions

“…Analysis of the 1 H NMR data in CDCl 3 for a diastereomeric mixture of 2-phenylsulfinylcyclohexanone (A + B) had indicated the presence of two H-2 resonances at 3.31 and 3.55 ppm (12) 4 . Comparison of line widths with those of anancomeric, conformationally biased derivatives indicated that the isomer A, whose chemical shift was 3.31 ppm, existed as a 3:2 mixture of axial:equatorial conformers, whereas B, whose chemical shift was 3.55 ppm, existed as a 2:1 mixture of equatorial:axial conformers.…”

“…It had been suggested that the increased axial preference for the heavier chalcogen substituents was due to the increased nonbonded repulsion with the carbonyl group in the equatorial conformer (3,4). However, the possibility of the role of σ C-X → π C O = * and n X → π C O = * stabilizing orbital interactions as contributors to the conformational preferences was also recognized ( Fig.…”

Light-induced reactions of 2,2-bis(2,2-dimethylethyl)-6H -1,3-oxaselenin-6-one in methanol

“…This is good evidence that all these compounds adopt one preferred conformation and that these values do not correspond to mean values reflecting equilibria between two, or possibly even more, conformations. 15 Finally, it is interesting to note, that the (formal) OCH 3 -addition to lactones 1 and 2 occurs regiospecifically at C(5) whereas for ketone 9 20% of the O,S-acetal 11 is also formed. A possible reason for this could be a different degree of twisting around the C-C double bond in the excited unsaturated molecules, the bulky substituents on C(2) totally hindering the approach of methanol to C(6) in the unsaturated lactones, but only partially in the unsaturated ketone, respectively.…”

Conformational analysis of 2‐bromocyclohexanone. A combined NMR, IR, solvation and theoretical approach

“…In the vapor phase and in non-polar solvents, three factors may contribute to a preference for the axial conformation. 27 A steric effect between the lone pairs of the oxygen and the asubstituent and a repulsive dipole-dipole interaction (both in the equatorial conformer) and an interaction between the n Br and p* CO orbitals. In polar solvents, the second factor will be decreased and the equatorial conformer becomes more stable and has the larger population.…”