The conformational analysis of saturated heterocycles. Part XXVII. The orientation of quaternisation of piperidines: further studies

Abstract

Previous work on the quaternisation of piperidines is reviewed, and the application of n.m.r. half-widths in the unambiguous determination of configuration is described. Together with the X-ray evidence this allows a reassessment of previous and new experimental evidence from reaction rates and product ratios. The effect of changing the leaving group in the alkylating agent cannot be simply explained. It is concluded that although simple piperidines generally are methylated by axial approach, equatorial methylation can occur when axial approach is subject to steric hindrance, and equatorial attack frequently occurs with quaternising groups larger than methyl. The reasons for this behaviour are considered.