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

Abstract

AbstractThe 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 ΔG# 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 CH3 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 (ΔG#), 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 CH 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.