Chemoselectivity of thiophene dicarboxylate towards hydrazine hydrate: Synthesis of some new bis heterocycles from thiophene monocarbohydrazide

Abstract

Chemoselectivity of C₅-carbethoxy function over that of C₃-carbethoxy function of the thiophene dicarboxylate towards the nucleophilic attack of hydrazine hydrate has been evidenced by exclusive formation of monocarbohydrazide i.e. ethyl 2-amino-5-(hydrazinocarbonyl)-4-methylthiophene-3-carboxylate and this monocarbohydrazide was reacted separately with acetylacetone, cyanogen bromide, acetonylacetone and CS₂ in ethanolic potassium hydroxide solution to furnish corresponding derivatives of 3,5-dimethylpyrazole, 5-aminooxadiazole, 2,5-dimethylpyrrole and 5-thiooxadiazole respectively. Thiophene monocarbohydrazide was converted to hydrazone derivatives by reacting with p-chlorobenzaldehyde and isatin. The monocarbohydrazide was also converted to thiosemicarbohydrazide derivatives, which was then cyclised with POCl₃ to afford corresponding thiadiazole derivatives. The structures of all the newly synthesized compounds were elucidated on the basis of their spectral and analytical data and the compounds were screened for their antituberculosis, antibacterial and antifungal activities.

Keywords:

• Chemoselectivity
• Carbohydrazide
• Bis heterocycles
• Antitubercular activity
• Antimicrobial activity

Acknowledgements

Authors are thankful to Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF, USA) for anti-tuberculosis evaluations. Thanks are due to Mr. Sanjeev Vernekar, Muenster (Germany) for Mass Spectral (ESI) data.