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-m ethylcyclohexyl)imidazole (l-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 ch ange of N-cyclohexylimidazole) is 2.2 +/- 0.1 kcal/mol, in both dichlo romethane and methanol. The A value of an N-protonated imidazolyl grou p in these solvents is 2.2 +/- 0.1 kcal/mol. Within the experimental e rror of this method, the cationic substituent is the same size as the neutral. To measure the relative sizes more precisely, an NMR, titrati on method, applicable to a mixture of isomers, was developed. The rati o of acidity constants of cis- and trans-N-(4-phenylcyclohexyl)imidazo les could be determined from the variation of H1 chemical shifts as a 1:1 mixture was titrated with DC1. In aqueous acetone the cis isomer i s found to be 0.048 +/- 0.002 pK unit less basic. This corresponds to a Delta A = A(N-imidazolylH+) - A(N-imidazolyl) of 0.089 +/- 0.004 kca l/mol, with the protonated imidazolyl slightly but detectably larger. In CD2Cl2 the difference is smaller, and in DMSO-d(6) it reverses. The significance of this result for the reverse anomeric effect in N-glyc osylimidazolium ions is discussed.