Revista de Farmacognosia e Produtos Naturais

Uses of Cyclohexane-1,4-Dione in the synthesis of heterocyclic compounds incorporating Tetrahydrobenzo[b]Thiophene: Synthesis, characterization and cytotoxicity

Abstract

Nadia Y. Megally Abdo

Tetrahydrobenzo[b]Thiophene derivatives are well known  as  pharmaceutically  active  compounds and many of them are used as anti-cancer drugs. The aim of this work is to synthesize Tetrahydrobenzo[b]Thiophene derivative as a key starting material, use it for further  heterocyclization through reaction with different reagents and then study thier cytotoxicity and kinase inhibition.  2-Amino-6-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) was prepared  from the reaction of cyclohexan-1,4-dione  with elemental sulfur and malononitrile in1,4-dioxane containing a catalytic amount of  triethylamine. The latter compound reacted with triethylorthoformate and either malononitrile or ethyl cyanoacetate in 1,4-dioxane in presence of triethylamine afforded 4H-thieno[2,3-f]chromene 10a,b. Also, the reaction of compound (3) with phenylisothiocyanate in dimethylformamide in presence of potassium hydroxide followed by addition of either α-chloroacetate or ethyl chloroacetate afforded fused thiophene and thiazole derivatives, respectively