The conformational analysis of saturated heterocycles. Part LXVI. Stereochemical orientation of the methylation of 2-methylpiperidines

Abstract

cis- and trans-Isomers of 1-methyl-, 1-ethyl-, 1-isopropyl-, and 1-t-butyl-2-methyl-4-phenylpiperidine undergo N-methylation to yield metho-salts by both axial and equatorial attack. The stereochemistries of the quaternisation products are assigned, and literature work on the assignment of products for the quaternisation of 1-alkyl-2-methyl-piperidines is discussed. The relative and absolute rates of these reactions are determined and related to the expected effects of the 2-methyl group on conformations of the molecules, and on the rate constants for equatorial and axial attack.

The relation of these results to the predominant equatorial quaternisation observed for tropanes is discussed.