Conformational properties of permethylcyclohexane as compared to cyclohexane: A force field study

The conformational properties of the recently synthesized highly strained permethylcyclohexane molecule 2 have been studied by empirical force field calculations using three different potentials (CFF, MM2, MM2′) and second‐derivative optimization methods. A comparison of the results with the conformational behavior of parent cyclohexane 1 leads to the following conclusions: The best conformation of 2 is a chair minimum whose six‐membered ring is flatter than that of 1 , due to the strong H…H repulsions introduced by the methyl groups. The twist minimum of 2 is energetically less favorable than the chair by an amount similar to 1 . A potential energy barrier Δ V # for the chair inversion of 2 of 15.32 kcal/mol results with the CFF, only about three kcal/mol higher than for 1 . The free energy of activation Δ G # for this process obtained with the CFF is 16.96 kcal/mol (at 333 K) and agrees well with the experimental value of 16.7(2) kcal/mol. 1 MM2 and MM2′ give substantially lower and higher potential energy inversion barriers Δ V # of 9.03 and 20.29 kcal/mol, respectively, which is attributed to inappropriate torsional energy terms in these force fields. The characteristic difference in the conformational behavior of 2 and 1 concerns the boat forms which are substantially less favorable in the per‐methyl compound than in 1 . Expectedly, strong H…H repulsions between the 1,4 diaxial flagpole–bowsprit methyl groups in 2 are responsible for this difference. The particularly high strain of the boat forms of 2 leads to flexibility differences as compared to 1 which in turn affect the relative entropies of the various statiomers (stationary point conformations); e.g., the chair ring inversion activation entropies of 2 and 1 are predicted by the CFF calculations to have opposite signs (−4.82 and 3.41 cal/mol K, respectively, at 298 K). The twist and half‐twist statiomers of 2 are much more rigid than those of 1 , which is a consequence of the substantially larger boat barriers along their pseudorotational interconversion paths. The boat transition state separating two enantiomeric twist minima represents a barrier calculated to be more than tenfold higher for 2 than for 1 (CFF Δ V # values 11.14 and 0.92 kcal/mol, respectively); likewise the half‐boat chair inversion barrier of 2 is calculated 5.07 kcal/mol less favorable than the respective half‐twist barrier. These statiomers are practically equienergetic in the case of 1 . Except for the axial flagpole–bowsprit CH 3 substituents of the boat forms, the methyl groups of all the relevant calculated statiomers of 2 are more or less staggered. The rotational barrier of the equatorial methyl groups of the chair minimum of 2 is computationally predicted to be 5.78 kcal/mol (Δ G # ), i.e., unusually high. Interesting vibrational effects are brought about by the strong H…H repulsions in 2 ; thus the chair minimum has a largest CH stretching frequency estimated to be 3050 cm −1 and involves several particularly low frequencies which have a substantial influence on its entropy. CFF calculations for the lower homologue permethylcyclopentane 5 indicate that its pseudorotational properties are similar to those of cyclopentane 4 , in contradistinction to the pair 2/1 .