Benzyl group conformation in 4-benzyl-4-hydroxypiperidines

Abstract

The high-resolution 1H and 13C NMR spectra of eight 4-benzyl-4-hydroxypiperidines 1–8 were recorded in CDCl3 and analyzed. In 2, the conformation of the equatorial benzyl group at C(4) was established as an equilibrium mixture of A [the phenyl group is gauche with respect to OH and C(5)] and B [the phenyl group is gauche with respect to OH and C(3)], whereas in 3-alkyl-4-benzyl-4-hydroxypiperidines 3–8, the favored conformation of the benzyl group at C(4) is A. In 1, the axial benzyl group at C(4) adopts the gauche conformations A′ [the phenyl group is gauche with respect to OH and C(3)] and B′ [the phenyl group is gauche with respect to OH and C(5)], in which the phenyl ring of the benzyl group is gauche with respect to the OH group. The HF/DFT B3LYP/6-3G* hybrid calculations of model systems 1′–3′ also support these conformations. The 13C data reveal that the equatorial methyl group at C(3) exerts a shielding influence on the methyl-bearing carbon and the magnitude of the α effect was found to be approximately −1.5 ppm. The parameters of the 13C substituent in the benzyl group show that the the α effect of the equatorial benzyl group is considerably higher in 3-ethyl tertiary alcohol 7 than in 3-methyl tertiary alcohol 3 and 4-benzyl-t(4)-hydroxypiperidine 2. This may be explained if we take into account the different conformations of the ethyl group in t(4)-hydroxy-3-ethyl-2,6-diphenylpiperidine 12 and 3-ethyl tertiary alcohol 7.