Advances in the Synthesis of Heterocycles with Two and Three Heteroatoms using Hydrazonoyl Halides

The review covers the results of studies published in the literature on the use of hydrazonoyl halides in the synthesis of five- (pyrazoles, thiazoles, triazoles, oxa- and thiadiazoles), six- (oxa- and thiadiazines, indazoles, pyridazines, pyrazines, tetrazines) or seven-membered (benzotriazepine) heterocycles. In the formation of these heterocycles, the main intermediate stage of the reaction is the in situ generation of nitrilimine, which enters into a cycloaddition reaction with substituted acetylenes (including in situ generated benzynes, naphthynes), allenes, activated olefins, anthranilic acid derivatives, organosulfur compounds (mercaptoaldehydes, mercaptocarboxylic acids) or with fused heterocycles. Examples are given of the formation of heterocycles by replacing the halogen atom from a hydrazonoyl halide molecule with a nucleophilic group, followed by exhaustive intramolecular cyclization into the target compound. There are discussions of reactions in which the cycloaddition of the nitrilimine to the in situ synthesized Knoevenagel condensation product (from CH-acid compounds, such as di- and monocarbonyl compounds, dinitrile malonic acid) occurs, leading to spiro-linked or conventional pyrazoles. Some syntheses of biologically active representatives are shown.