Annelation of drotaverine by p-quinones to form hydroxyindolo- and hydroxybenzindoloisoquinoline derivatives

Abstract

1 (3,4 Diethoxybenzyl) 6,7 diethoxy 3,4 dihydroisoquinoline (drotaverine, 1a) reacts with p benzoquinone (2) and p naphthoquinone (3) in nitromethane or during fusion to give 5 (3,4 diethoxyphenyl) 7,8 diethoxy 3 hydroxy 5a,10,11,12 tetrahydroindolo[2,1 a]iso quinoline (4) and 7 (3,4 diethoxyphenyl) 9,10 diethoxy 5 hydroxy 7a,12,13,14 tetra hydrobenz[g]indolo[2,1 a]isoquinoline (5), respectively. Compounds 4 and 5 are smoothly alkylated at the oxygen atom in the presence of bases. The structure of one alkylation product, viz., 3 allyloxy 5 (3,4 diethoxyphenyl) 7,8 diethoxy 5a,10,11,12 tetrahydroindolo[2,1 a]iso quinoline, was established by X ray diffraction analysis.

The Structural Determination of Drotaverine Hydrochloride Using NMR Studies

“…Thus, NMR experimental data demonstrate the absence of intramolecular tautomerism in drotaverine hydrochloride. The obtained conclusion corresponds to the data in the scientific literature on the mechanism of tautomerism in drotaverine hydrochloride . According to the authors’ conclusion, the intramolecular isomerization of the azomethine (I) and enamine (II) structures in drotaverine hydrochloride is considered unlikely due to unfavorable steric conditions for 1,3‐proton transfer that requires overcoming a large energy barrier .…”

“…It should be noted that NMR spectroscopy and X‐ray diffraction analysis (XRD) are direct methods that establish the structure of organic compounds without using standards and are specific to double bond position isomers. The results of the study of the structure of the compound II using these methods can be found in literature . There are no published NMR or XRD data for the compound I.…”

“…For the first time drotaverine hydrochloride was assigned with the structure of the compound II also by CHINOIN . From the 80s up to now, the INN “drotaverine hydrochloride” has been attributed to the compound I and the compound II in the scientific literature …”