Conformational Studies in the Cyclohexane Series. 1. Experimental and Computational Investigation of Methyl, Ethyl, Isopropyl, and tert-Butylcyclohexanes.

The conformational enthalpy (DeltaH degrees ), entropy (DeltaS degrees ), and free energy (-DeltaG degrees ) of methyl- (1), ethyl- (2), and isopropylcyclohexane (3) have been reinvestigated both experimentally and computationally. A novel experimental approach to evaluation of highly biased conformational equilibria is described that obviates the need to measure large axial/equatorial isomer ratios directly in order to determine the equilibrium constant: the natural abundance (13)C signal for the C(2,6) resonance in the equatorial isomer of an alkylcyclohexane may be used as an internal reference, and the ratio of this band area to that of an enriched (13)C nucleus in the axial isomer gives K following correction for statistical differences and the differing (13)C-content of the signals being monitored. The experimental conformational enthalpies (DeltaH degrees ), determined at 157 K in independent studies at two laboratories, were found to be (kcal/mol) 1.76 +/- 0.10 (Me), 1.54 +/- 0.12 (Et), and 1.40 +/- 0.15 (i-Pr); the corresponding conformational entropies (DeltaS degrees, eu) were 0.2 +/- 0.2 (Me), 1.3 +/- 0.8 (Et), and 3.5 +/- 0.9 (i-Pr). Computational studies at the QCISD level gave satisfactory agreement with the experimental results, but B3LYP gave energy differences that were too large, whereas MP2 gave differences that were too small. The computed structural data indicates that an axial alkyl substituent leads to local flattening of the cyclohexane ring but there was no evidence of a 1,3-synaxial interaction with the axial hydrogens at C(3,5).