A novel approach to bis(1,3-azol-2-yl)acetonitriles and bis(1,3-azol-2-yl)methanes via the [3 + 2]-dipolar cycloaddition of imidazole N-oxides and 2-heteroaryl-3,3-dimethylacrylonitriles?

Organic & Biomolecular Chemistry Pub Date: 2021-09-23 DOI: 10.1039/D1OB01441B

Abstract

A new synthetic approach for obtaining previously unknown bis(1,3-azol-2-yl)acetonitriles and bis(1,3-azol-2-yl)methanes has been developed. It is based on 1,3-dipolar cycloaddition between 2-unsubstituted imidazole N-oxides and 2-(1,3-azol-2-yl)-3,3-dimethylacrylonitriles, which are easily available through the condensation of (1,3-azol-2-yl)acetonitriles with acetone. The method allows for the construction of various unsymmetric derivatives based on imidazole, oxazole, thiazole, and 1,3,4-thiadiazole cyclic molecules. Its potential has been demonstrated via the synthesis of 24 diverse derivatives with yields of 29–92%. Bis(1,3-azol-2-yl)acetonitriles can be converted to the corresponding bis(1,3-azol-2-yl)methanes via simple acid hydrolysis followed by subsequent spontaneous decarboxylation at nearly quantitative yields.

Graphical abstract: A novel approach to bis(1,3-azol-2-yl)acetonitriles and bis(1,3-azol-2-yl)methanes via the [3 + 2]-dipolar cycloaddition of imidazole N-oxides and 2-heteroaryl-3,3-dimethylacrylonitriles
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