Synthesis, structural and conformational study of some amides derived from 3-methyl-3-azabicyclo[3.2.1]octan-8α(β)-amines

Some amides (1α–7α and 1β–7β) derived from 3-methyl-3-azabicyclo[3.2.1]octan-8α(β)-amines were synthesized and studied by IR, 1H and 13C NMR spectroscopies. The assignment of all carbon and protons resonances was achieved through the application of one dimensional selective NOE and two dimensional NMR techniques: homonuclear NOESY and heteronuclear 1H–13C gHSQC correlated spectroscopies. Total correlation spectroscopy (TOCSY) experiments were also carried out. l3 solution, at room temperature, all compounds adopt a chair-envelope conformation with the N–CH3 group in equatorial disposition. In the α-epimers the piperidine ring is puckered at C8 to relieve the interactions between the amido group and the H6(7)x protons. β-Epimers show a preferred trans disposition for the NH–CO group and free rotation of the NH–CO–R group around the C8–NH bond. Finally, NMR and IR data reveal that compounds 7α and 7β adopt in CDCl3 solution a preferred s-cis conformation for the OC–CC system, the proportion of this conformation increasing when the polarity of the solvent decreases.