Solvation Effect on Steric Bulk of Ionic Substituents: Imidazolium vs Imidazole

To compare the steric bulk of a cationic substituent with that of the corresponding neutral one, the conformational equilibria of cis-N-(4-methylcyclohexyl)imidazole (1-c), cis-N-(4-phenylcyclohexyl)imidazole (2-c), and their conjugate acids were measured by low-temperature NMR. The A value of an imidazolyl group (equatorial-to-axial free-energy change of N-cyclohexylimidazole) is 2.2±0.1 kcal/mol, in both dichloromethane and methanol. The A value of an N-protonated imidazolyl group in these solvents is 2.2±0.1 kcal/mol. Within the experimental error of this method, the cationic substituent is the same size as the neutral. To measure the relative sizes more precisely, an NMR titration method, applicable to a mixture of isomers, was developed