Nuclear magnetic resonance spectra of o-hydroxythiobenzamides: the intramolecular hydrogen bond as a conformational probe

Abstract

The OH and NCH2 proton signals of 1-(2′-hydroxythiobenzoyl)-2-methylpiperidine (2) are resolved into separate peaks assigned to four conformers (EA, EB, ZA, and ZB) in 220 MHz nmr spectra at −50 °C. All have a strong intramolecular [Formula: see text] hydrogen bond. The ZB and EB conformers have the lowest and highest ground state energies, respectively. Exchanges between A and B conformers have a higher energy barrier than exchanges between Z and E isomers, but by +40 °C all four conformers interchange rapidly. The nature of all possible interchange processes is considered and a potential energy surface with respect to rotation about the Ph—C(S) and C—N bonds is presented. For the 4-methyl analogue of 2 low temperature nmr spectra exhibit two sharp OH signals arising from A and B conformers. For 2,6-di-methyl-4-(2′-hydroxythiobenzoyl)morpholine the A/B OH doublet of the cis dimethyl isomer can be distinguished from that of the trans isomer. Thus it is demonstrated that the intra-molecularly hydrogen bonded OH proton is a good spectroscopic conformational probe. Nuclear magnetic resonance, ir, and uv data all indicate that in the 2,6-dimethylpiperidine analogue of 2 the CNC and Ph—C(S)N planes are perpendicular due to steric interference. Coplanarity of the phenyl ring with the thioamide group is attributed to a very strong intramolecular [Formula: see text] hydrogen bond, in equilibrium with a proton transferred [Formula: see text] form in solution. This structure resembles the transition state for rotation in the most readily achieved exchange between conformers of 2.