Preparation of 4,7-Dihydro-1H-pyrazolo[3,4-b] pyridine-5-nitriles in a Multicomponent Domino Process

In this article we present the unprecedented preparation of 4,7dihydro-1H-pyrazolo[3,4-b] pyridine-5-nitriles and pyrazolo[3,4b] pyridine-5-nitrile derivatives by the reaction of mono-substituted aryl/heteroarylhydrazines with 3-aryl-3-oxopropanonitriles in ethanol in the presence of HNO3 (conc.). This multicomponent reaction requires the in situ oxidation of the ethanol (used as a solvent) to acetaldehyde, resulting in a domino assemblage of the starting materials. The resulting products were unambiguously and rigorously characterised based on IR, NMR (1D and 2D techniques), MS and X-ray crystallography studies. Based on the results obtained from a series of reactions we also propose a mechanism for this unexpected synthesis which confirmed the involvement of in situ oxidation of ethanol and intermediacy of a 5-aminopyrazole species.