NMR spectral study of proton transfer in amitriptyline hydrochloride--chlordiazepoxide hydrochloride combinations in...

The singlet resonance due to the two equivalent methyl groups of amitriptyline hydrochloride in dimethyl sulfoxide-d6 solution changed into a doublet with the addition of chlordiazepoxide hydrochloride. A spin decoupling experiment revealed that the double originated because of the emergence of observable spin--spin coupling between the tertiary amine proton and the methyl groups. The phenomenon was interpreted to be due to the nature of proton transfer caused by the relative magnitudes of the basicities of the amines in these compounds, which were determined by the inductive and steric effects of the substituents, leading to the formation of hydrogen-bonded ion-pairs in the aprotic diluent. The enthalpy of the exchange process was 6.4 +/- 0.5 kcal/mole.