Syntheses and Conformational Analyses of Isomeric Cocaines: A Proton and Carbon-13 Nuclear Magnetic Resonance Study

Article abstract of DOI:10.1021/jo00340a004

The 1H and 13C NMR spectra of cocaine (1), pseudococaine (2), allococaine (3), allopseudococaine (4), and the hydrochloride salts of 1, 2, and 4 have been recorded.The conformation of the piperidine ring in all four isomers, including the orientation of the N-methyl substituent, was determined from analysis of the data.Vicinal, geminal, and long-range coupling constants strongly suggest a chair conformation for the piperidine ring of all the compounds studied.Comparison of the 1H and 13C chemical shift data suggests that 2 and 4 have a larger population of axial N-methyl substituents than 1 and 3, respectively.Improved procedures for the synthesis of 2, 3, and 4 are reported.In particular, a stereoselective route to 4 is presented.