Conformational analysis of the tropane analogue of pethidine and related compounds by 1H NMR spectroscopy

Abstract

The preferred solute conformation of ethyl 3α‐phenyltropane‐3β‐carboxylate hydrochloride, the tropane analogue of pethidine, is shown to be a piperidine chair with an axial 3‐phenyl substituent by analysis of its ¹H NMR characteristics and spectral comparisons with model compounds. Conformational studies of synthetic intermediates are also reported and favoured boat forms identified for 3α‐diphenylhydroxymethyl‐3β‐tropanol and 3α‐phenyl‐3β‐tropanyl phenyl ketone. In the hot‐plate test for analgesia performed on mice, ethyl 3α‐phenyltropane‐3β‐carboxylate is about 1·5 times as effective as pethidine.