Carbon-13 magnetic resonance: evidence for non-chair conformations in tropane derivatives

Abstract

The assignments of the methylene carbon resonances, C-2 and -4 and C-6 and-7, in the tropanes are clarified. Carbonyl and hydroxy additivity parameters in the tropane series (carbonyl α effect, –17.2p.p.m.: equatorial hydroxy: α, +46.8; γ, –1.1 p.p.m.; axial hydroxy: α, +47.9; γ, –0.9 p.p.m.) differ from those in the analogous piperidines, carbonyl (–14.7 p.p.m.), equatorial hydroxy: α, +42.6 and γ, –2.7 p.p.m., and axial hydroxy: α, +28.1 and γ, –4.7 p.p.m., respectively. These and related data are interpreted in terms of evidence for boat contributions to the conformation of tropine. The intramolecular bonding present in the three tropanes, ecgonine methyl ester (14), 3α-hydroxydiphenylmethyltropan-3β-ol (18), and tropanyl phenyl ketone (19) have been verified by comparing the effects of protonation observed in the carbon-13 spectra. The conformational change from boat to chair conformers is exemplified in (19). It is suggested that (16) has some preference for a non-chair conformation but the nitrogen–carbonyl interaction found in (19) is not observed in this case. The hydrochloride (19a) dissolved in methanol is a ketone–alcohol equilibrium mixture as shown by the carbon-13 spectra. The hydrochloride derivatives of (14) and (18) are also in boat conformations for solutions in methanol but an equilibrating mixture is observed in less polar media with the chair conformation contributing. Evidence is presented for a zwitterionic structure for 3α-phenyltropane-3β-carboxylic acid (17).