1H and 13C NMR study of tetrahydro-1,4-benzothiazepine conformations

Abstract

The variable temperature (298–178 K) ¹H NMR spectra of tetrahydro-1,4-benzothiazepines 1–10 are described and discussed. Compounds 2–10 exist as two puckered mirror-image (enantiomorphic) conformers, with benzothiazepine ring chair-to-chair interconversion barriers of ca. 10 kcal mol⁻¹ in CD₂Cl₂ solution. A similar interconversion was detected for compound 1, of lower symmetry. The ground state conformations of 1–10 were assigned on the basis of the magnitudes of ¹H–¹H vicinal coupling constants. The ¹H and ¹³C NMR spectral assignments were determined by ¹H–¹H COSY, HETCOR, and NOESY experiments. The stereochemistry and conformation of compound 1 was further confirmed by a single crystal X-ray structure determination.