Configuration and conformation of alfentanil hydrochloride. Conformational study by NMR and theoretical calculations

The configurational and conformational structure of alfentanil hydrochloride (1) was studied by nuclear magnetic resonance and theoretical calculations. Compound 1 is best described by equilibrium between two stereoisomeric piperidinium rings with the N-substituent always being in equatorial position. Nuclear magnetic resonance spectra demonstrate that, depending on the solvent, 1 adopts the conformation with an axial methoxymethylene group. Computations were crucial in determining the importance of the transannular attractive interaction between the positive charge at the piperidinium N-atom and the methoxymethyl group in position 4. Copyright © 2014 John Wiley & Sons, Ltd.