1, 3‐Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3, 4‐Dihydroisoquinoline toward Aryl Iso(thio)cyanates. Issue 30 (10th August 2022)

• Record Type: Journal Article
• Authors: Penney, Alexander A.; Efremova, Mariia M.; Molchanov, Alexander P.; Kryukova, Mariya A.; Kudinov, Andrey Yu.; Bunev, Alexander S.; Keresten, Valentina M.; Kuznetsov, Mikhail A.
• Is Part Of: ChemistrySelect. Volume 7:Issue 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-10
• Subjects: azomethine imines -- cycloaddition -- diaziridines -- isocyanates -- isothiocyanates; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202202627
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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 Brønsted 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‐2 H ‐[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(3 H )‐(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Brønsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts. Abstract : Reactions of two diaziridines based on 3, 4‐dihydroisoquinoline with aryl iso(thio)cyanates were investigated under thermal and catalytic conditions. For the unsubstituted diaziridine, the reaction pathway was found to depend on the conditions. Efficient new methods were developed for the synthesis of polynitrogen‐containing condensed heterocycles with a tetrahydroisoquinoline moiety, as well as 2, 3‐benzodiazepines.