The nuclear magnetic resonance spectra and conformations of cyclic compounds. Part X. Conformational equilibria in 5-substituted 10,11-dihydrodibenz[b,f]azepines

Abstract

The conformational equilibria in 5-substituted 10,11-dihydrodibenz[b,f]azepines have been studied by variable temperature ¹H and ¹³C n.m.r. spectroscopy. For the parent compound and its N-alkyl-substituted derivatives, including imipramine, the conformational inversion of the seven-membered ring is too fast to be observed by these techniques. However for the N-acyl derivatives hindered rotation about the N-acyl bond produces a concomitant decrease in the rate of ring inversion due to the buttressing effect of the dibenzo-groups. The ring conformation of the N-acetyl derivative is deduced from the observed ³J_HH couplings of the ethano-bridge to be ca. 50° buckled. Ring inversion barriers for the N-acetyl, N-chloroacetyl, and N-ethoxycarbonyl derivatives are estimated and discussed. The conformation of the dimethylaminopropyl side chain of imipramine and its hydrochloride has also been deduced. Remarkably the side chain appears to exist in one predominant conformation with a gauche-C_α–C_β and trans-C_α–C_β orientation in the hydrochloride in CDCI₃ solution. In D₂O solution this conformation in the hydrochloride is less favoured (though still preferred), but the free base in CDCI₃ solution shows little conformational preference.