The conversion of isothiazoles into pyrazoles using hydrazine

Abstract

The conversion of isothiazoles into pyrazoles on treatment with hydrazine is investigated. The influence of various C-3, C-4 and C-5 isothiazole substituents and some limitations of this ring transformation are examined. When the isothiazole C-3 substituent is a good nucleofuge, 3-aminopyrazoles are obtained. However, when the 3-substituent is not a leaving group it is retained in the pyrazole product. Treatment of 4-bromo-3-chloro-5-phenylisothiazole 56 or 3-chloro-4,5-diphenylisothiazole 57 with anhydrous hydrazine at ca. 200 °C for a few minutes gives the corresponding 3-hydrazinoisothiazoles 61 and 64 respectively in high yields

the stability of these new hydrazines is investigated. 5,5′-Diphenyl-3,3′-biisothiazole-4,4′-dicarbonitrile 78 reacts with hydrazine to give 5,5′-diphenyl-3,3′-bi(1H-pyrazole)-4,4′-dicarbonitrile 79. Methylhydrazine reacts with 3-chloro-5-phenylisothiazole-4-carbonitrile 1 to give 3-(1-methylhydrazino)-5-phenylisothiazole-4-carbonitrile 83 and 3-amino-1-methyl-5-phenylpyrazole-4-carbonitrile 84. All products are fully characterised and rational mechanisms for the isothiazole into pyrazole transformation are proposed. © 2009 Elsevier Ltd. All rights reserved.