A nuclear magnetic resonance investigation of complex formation between imipramine and related psychotropic drugs with benzyl alcohol and other aromatic solutes

Abstract

The interaction of imipramine, chlorimipramine, promazine, chlorpromazine, and protriptyline hydrochlorides with benzyl alcohol in CDCl₃ solution has been followed by n.m.r. spectroscopy. A specific complex is formed in which the aromatic ring of the benzyl alcohol interacts with the positively charged ammonium ion of the side-chain and in addition the hydroxy of the benzyl alcohol forms a hydrogen bond with the Cl counter-ion of the hydrochloride ion-pair. Comparative studies with dibenzazepines and substituted dimethylpropylammonium chlorides and different aromatic groups show that this interaction is a general one provided certain steric and electrostatic requirements are satisfied. Thus phenol (and aniline) complex as strongly as benzyl alcohol but 2-phenylethanol much less so. The requirement of the counter-ion is demonstrated by the behaviour of the quaternary salt and the tetraphenylborate neither of which show strong association. The equilibrium constants and complex shifts have been evaluated and the complex shifts shown to agree with those calculated for a specific geometry. The effect of solvent on the complex has also been evaluated.