Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Organic Chemistry

This thesis comprises five chapters. The first is the introduction, which consists of a brief literature survey on the synthesis of [1]benzothiophen -3(2H)-one, [1]benzothieno[3,2-b]pyran and [1]benzothieno[2',3':5,6] pyrano[2,3-d]pyrimidine derivatives. It also involves an account of their cytotoxic and apoptotic properties. The second chapter deals with the aim of the work. Also, it demonstrates the pathways that have been followed for the synthesis of the target compounds as following:Scheme I deals with preparation of the starting compounds 7-flouro[1] benzothiophen-3(2H)-one (II) by applying Friedel Craft condition on S-(2-flourophenyl) thioglycolic acid (I) after treating with phosphorous trichloride.Condensation of the latter with different aromatic aldehydes afforded the target compounds 2-arylidene-7-flouro[1]benzothiophen-3(2H)-one (IIIa-f). Additionally, cyclization of IIIa-f with malononitrile and ethyl cyano acetate afforded 2-amino-4-aryl-6-flouro-4H-[1]benzothieno[3,2-b]pyran-3-carbonitrile (IVa-f) and ethyl 2-amino-4-aryl-6-flouro-4H-[1]benzo thieno[3,2-b]pyran-3-carboxlate (Va-f ) respectively. In scheme II reaction of compounds IVa-f with formamide and triethyl orthoformate afforded the the newly formed compounds 5-aryl-7-flouro-5H-[1]benzothieno[2',3':5,6]pyrano[2,3-d]pyrimidin-4-amine (VIa-f) and ethyl N-(4-aryl-3-cyano-6-flouro-4H-[1]benzothieno[3,2-b] pyran-2-yl) formimidate (VIIIa-f) respectively. Selecting compound IVb and reacting it with p-chlorobenzaldehyde gave 2-((4-chloro benzylidene)amino)-4-(4-chlorophenyl)-6-flouro-4H-[1]benzothieno [3,2-b]pyran-3-carbonitrile (VIIb). Additionally, compounds VIIIa-e were cyclized to give 5-aryl-7-flouro-3-propyl-3H-[1]benzothieno[2',3':5,6]pyrano[2,3-d]pyrimidin-4(5H)-imine (IXa-e) by stirring with N-propylamine at RT in alcoholic solution.On the other hand, compounds Va-f were cyclized to give the corresponding 5-aryl-7-flouro-3H-[1]benzothieno[2',3':5,6] pyrano [2,3-d]pyrimidin-4(5H)-one (Xa-f) by heating with formamide

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