DOI:10.1248/cpb.51.929

Fentanyl and Its Analogue N-(1-Phenylpyrazol-3-yl)-N-[1-(2-phenylethyl)-4-piperidyl] propanamide: 1H- and 13C-NMR Spectroscopy, X-Ray Crystallography, and Theoretical Calculations.

The oxalate salts and free bases of fentanyl and N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide, a new lead compound for long-acting analgesia, have been characterized by ¹H- and ¹³C-NMR spectroscopy. The crystal structure of the hydrochloride of N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide monohydrate has been determined. Two centrosymmetrically related cations, joined through C(phenyl)-H…π contacts, encapsulate a large void that contains pairs of anions and bridged water molecules into a zero-dimensional (0D) supramolecular motif. The cations are linked to this framework via N⁺H…Cl⁻ contacts. GIAO/B3LYP calculations have been carried out to compare the experimental ¹³C chemical shifts with the absolute shieldings thus calculated. The protonation of both molecules takes place on the piperidine ring (axial protonation), as has been verified both in the solid state (X-ray) and in solution (NMR).