Ring inversion equilibria in 4-chloro-, 4-bromo-, and 4-methoxy-1-alkylpiperidines in a non-polar solvent

Abstract

The position of ring inversion equilibrium (axial R ⇌ equatorial R) in 4-R-N-alkylpiperidines (R = Cl, Br, or OMe), dissolved in CFCl₃–CDCl₃, has been determined by ¹³C n.m.r. spectroscopy at low temperatures. In all three series, change of NH to NMe produces a marked increase in the proportion of conformation with axial R. When R is OMe, further alterations in the N-substituent from Me to Et, Prⁱ, and CH₂CF₃ do not affect the equilibrium significantly, but the significant changes observed when R is halogen can be related to the inductive effect of the N-substituent. ¹³C Chemical shifts, proportions of conformations, and conformational free energy differences are recorded for all systems studied.