Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate, thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

Abstract

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reactedwith ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.