1,3-Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4-Dihydroisoquinoline toward Aryl Iso(thio)cyanates

Unsubstituted and 1-methyl-substituted 1,3,4,8b-tetrahydrodiazirino[3,1-a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10b-tetrahydro[1,2,4]triazolo[5,1-a]isoquinolines. The addition of a Lewis or Bronsted acid switches the reaction pathway, producing seven-membered 2,3-benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds - 2-thioxo-5,6-dihydro-2H-[1,2,4]triazolo[5,1-a]isoquinolin-1-ium-3-ides - and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3-dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1-a]isoquinolin-2(3H)-(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Bronsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.