USES OF 4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE IN THE SYNTHESIS OF PYRIDAZINE, PYRAZOLE, THIAZOLE AND PYRIMIDINE DERIVATIVES TOGETHER WITH THEIR CYTOTOXICITY

The reaction of N-phenylbutanamide derivative 1 with bromine afforded compound 2 which it was directed to reacts with activated methylene groups, malononitrile (3a) and ethylcyanoacetae (3b) to produce compounds 4a and 4b respectively, on the other hand the reaction of compound 2 with either hydrazine hydrate (8a) or phenylhydrazine (8b) afforded pyridazine derivatives 10a,b respectively,      Moreover the reaction of compound 2 with either potassium cyanide (11a) or potassium thiocyanate (11b) produced compounds 12a,b respectively. Finally the reaction of compound 2 with thiourea (13a) afforded thiazole derivative 14. Compound 4b reacted with benzenediazonium chloride (5) afforded pyridazine derivative 7. The reactivity of compound 12a was introduced through the reaction with either hydrazine derivatives 8a,b or aromatic aldehydes 16, 18 then compounds 15a,b, 17, 19 were produced respectively.As extension of compound 1 reactions, malononitrile (3a) reacted with compound 1 afforded two isomeric compounds 20 and 21, the latter product 20 was reacted with either hydrazine derivatives 8a,b or thiourea and urea (13a,b) to produce pyrazole derivatives 22a,b and pyrimidine derivatives 23a,b respectively.Their cytotoxic  activities were tested using three different cell lines.