1,3-Diaxial steric effects and intramolecular hydrogen bonding in the conformational equilibria of new cis-1,3-di substituted cyclohexanes using low temperature NMR spectra and theoretical calculations

摘要

The conformational equilibria of 3-X-cyclohexanol [X=F (1), Cl (2), Br (3), I (4), Me (5), NMe2 (6) and MeO (7)] and of 3-X-methoxycyclohexane [X = F (8), Cl (9), Br (10), I (11), Me (12), NMe2 (13) and MeO (14)] cis isomers were determined from low temperature NMR spectra and PCMODEL calculated coupling constants. The energy differences between aa and ee conformers were obtained from these data (Delta G(J)(av) and Delta G(PC)(av) respectively) and also by the additivity principle from data for the monosubstituted cyclohexanes (Delta G(Ad)). H-1 and H-3 hydrogen vicinal coupling constants and Delta G(J)(av) values showed that the diequatorial conformer is predominant in the conformational equilibrium of the compounds studied at low temperature. However, Delta G(PC)(av) data show that compounds 6 and 7 constitute an exception, since they are almost equally populated by ee and aa at room temperature, due to stabilization of their aa conformer by an intramolecular hydrogen bond. Delta G(Ad) values, obtained according to the additivity principle, show a better agreement for compounds 2 and 3, since the 1,3-diaxial steric effect is counterbalanced by the formation of an intramolecular hydrogen bond (IAHB). For the remaining compounds, Delta G(Ad) values underestimate the energy differences, since the 1,3-diaxial steric effect, between X and OH or OCH3, is absent in the monosubstituted compounds used as references. Moreover, the Delta G(PC)(av), calculated from the coupling constants, obtained through the PCMODEL program, are rather smaller than the Delta G(J)(av) values, since the program does not have parameters for the effect, observed in this report, of a substituent at gamma position on coupling constants values for the hydrogen under consideration. (c) 2004 Elsevier B.V. All rights reserved.