Computational determination of the enthalpic and entropic contributions to the conformational preference of monosubstituted cyclohexanes.: Molecular mechanics, semi-empirical and density functional theory methods and ab initio calculations

Several computational methods [MM2, MM3, PM3, AM1, MNDO, HF/3-21G(d), HF/6-31G(d), B3LYP/3-21G(d). B3LYP/6-31G(d), MP2/6-31G(d), etc.] were examined in their efficiency to reproduce the experimentally obtained thermodynamic data for axial reversible arrow equatorial equilibria in benzylcyclohexane (7) and sulfur-containing derivatives methylthio (8), methylsultinyl (9), and methylsulfonylcyclohexane (10). While in general, best agreement between the theoretical results and the experimental data was found when electronic correlation was included in fairly robust NIP2/6-31G(d) calculations, for the estimation of conformational parameters in larger systems the use of lower level HF and B3LYP methods is anticipated to afford reliable data at reasonable computing times. In most cases, proper estimation of DeltaS(mixing)degrees parameters requires consideration of DeltaS(mixing)degrees, which appears as rn dominant term for DeltaS(total)degrees parameters. It is appreciated that a proper comprehension of the conformational behavior of monosubstituted cyclohexanes requires of satisfactory understanding of the enthalpic and entropic contributions to the conformational free energy difference, DeltaGdegrees. Copyright (C) 2002 John Wiley Sons, Ltd.