PMR spectra and conformations of the cis and trans isomers of N-substituted 2,5-dimethyl-4-piperidones

The PMR spectra of mixtures of the trans and cis isomers of N-substituted 2,5-dimethyl-4-piperidones with three N-substituents (H, CH/sub 3/, and CH/sub 2/C/sub 6/H/sub 5/) and the hydrobromide of trans-2,5-dimethyl-4-piperidone were investigated at 250 and 360 MHz. The spectra of the major trans isomers were analyzed fully for the first time, and the relation between their PMR parameters and the stereochemical structure was investigated. It was shown that these isomers are predominantly represented by the 1e, 2e, and 5e conformations in the chair form of the piperidine ring. As a result of analysis of the PMR spectra of the minor cis isomers it was established that they are conformationally nonuniform and are characterized by a conformational equilibrium between the two chair forms Cl (1a, 2e, 5a) and C2 (1a, 2a, 5e), which is displaced toward C2 with increase in the size of the N-substituent. The populations and the differences in the energies were determined for these conformers.