Pellizzari reaction

PELLIZZARI REACTION. Formation of substituted 1,2,4-triazoles by die condensation of amides and acylhydrazines. When the acyl groups of the amide and acylhydrazine are different, interchange of acyl groups may occur, widi formation of a mixture of triazoles. 

An important classical synthesis of 1,2,4-triazoles is the Pellizzari reaction in which an acylhydrazide is condensed with an amide (or thioamide) at high temperature. Variations exist in which the amide component is first activated towards nucleophilic attack as a S-alkyl thioamide salt. Employing this type of approach, S-methyl isothioamide... 

The Pellizzari reaction is the chemical reaction of an amide and a hydrazide to form a 1,2,4-triazole. Dapiprazole is an alpha-blocker that is used to reverse mydriasis after eye examination. The synthesis of dapiprazole starts with construction of a hydrazide-type structure and then follows by ring opening of piperidinone and condensation with the acylhydrazide moiety to form the final product. ... 

This reaction was first reported by Pellizzari in 1894. It is the preparation of 1,2,4-triazole derivatives by baking the mixture of amide and acyl hydrazide. Therefore, it is generally known as the Pellizzari reaction. This reaction is usually carried out at temperatures > 250°C, but very reactive substrates can proceed at relatively lower temperatures, such as the coupling between diphenylformamidine and formhydrazide at 150°C. This reaction is very useful for the preparation of monosubstituted-, disubstituted-, and 1,3,5-trisubstituted-l,2,4-l/f-triazoles. However, at such a high temperature, transamination may occur between amide and acyl hydrazide, especially for the aliphatic acid hydrazides," resulting in a mixture of triazoles and a lower yield of the expected triazole. It has been found that co-heating the mixture of formamide and hydrazine hydrochloride with two equivalents of pulverized KOH can improve the yield of 1,2,4-triazole to almost 17%. ... 

A general mechanism is outlined below for the Pellizzari reaction. 

Other references related to the Pellizzari reaction are cited in the literature. 

Paal-Knorr Pyrrole Synthesis Parham Cyclization Passerini Reaction Patemo-Biichi Reaction Pauson-Khand Reaction Payne Rearrangement Pechmann Condensation Pechmann Pyrazole Synthesis Pellizzari Reaction Pelouze Synthesis Periodic Acid Oxidation Perkin Alicyclic Synthesis Perkin Reaction Perkin Rearrangement Perkow Reaction Peterson Reaction... 

Atkinson MR, Polya JB (1952) Triazoles. Part L Unsymmetrieal Einhom-Biunner and related Pellizzari reactions. J Chem Soc 3418-3422... 

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