Substituent effects in saturated systems. Basicity, reactivity, and stereochemistry in 3- and 6-substituted cis-hexahydrocarbazoles

Abstract

Rates of quaternisation in acetonitrile and methanol, and pK_a values in water and aqueous 2-butoxyethanol, have been measured for a series of N-methyl-cis-hexahydrocarbazoles substituted (Bu^t, Me-, and MeO-) at the 3- and 6-positions. The marked decrease in basicity caused by 6-t-butyl, syn-3-methyl, and syn-3-t-butyl substitution is probably due to steric inhibition of general solvation of the conjugate acid, whereas in the case of the 3,3-dimethyl derivative the effect is offset by inhibition of hydrogen bonding to the free base. For individual compounds differences in rates of quaternisation accompanying a change of solvent may be interpreted in terms of steric effects on hydrogen bonding involving the nitrogen lone pair and methanol.