Yeni tiyofen ve selenofen türevlerinin sentezi
Synthesis of new thiophene and selenophene derivatives
Yazar: YASEMİN ERDOĞAN
Danışman: PROF. DR. ALİYE ALTUNDAŞ
Gazi Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2013
Konu: Kimya = Chemistry
Dizin: Tiyofen = Thiophene

Özet:
Bu çalışmada biyolojik etkinlik gösterebilecek polifonksiyonel grupların bağlı olduğu tiyeno[2,3-d]pirimidin ve seleno[2,3-d]pirimidin türevleri, tiyenopirimidinhidrazon türevleri ve 2-(benzilidenamino)-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril türevleri sentezlendi.Bu amaçla çalışmanın birinci aşamasında Gewald metodunu kullanarak; tetrahidro-4H-tiyopiran-4-on' un, malonitril ve elementel kükürt ile reaksiyonu sonucunda 2-amino-5,7-dihidro-4H-tiyeno[2,3-c]tiyopiran-3-karbonitril; tetrahidro-4H-tiyopir an-4-on' un, malonitril ve metalik selenyum ile reaksiyonu sonucunda 2-amino-5,7-dihidro-4H-seleno[2,3-c]tiyopiran-3-karbonitril ve tetrahidro-4H-piran-4-on' un malonitril ve elementel kükürt ile reaksiyonu sonucunda ise 2-amino-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril bileşikleri sentezlenmiştir. Elde edi- len 2-amino-5,7-dihidro-4H-tiyeno[2,3-c]tiyopiran-3-karbonitril' in formamit ile reaksiyonu sonucunda 6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4-amin ve 2-pirrolidon ve POCl3 ile reaksiyonu sonucunda 3,4,8,9-tetrahidro-1H-pirol[1,2-?]tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-5(7H)-imin bileşikleri sen- tezlendi. 2-Amino-5,7-dihidro-4H-tiyeno[2,3-c]tiyopiran-3-karbonitril ve 2-ami no-5,7-dihidro-4H-seleno[2,3-c]tiyopiran-3-karbonitril' in formik asit ile reaksiyonu sonucunda sırasıyla 5,6-dihidro-3H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4(8H)-on ve 6-dihidro-3H-tiyopiran[4?,3?:4,5]seleno[2,3-d]pirimidin -4(8H)-on bileşikleri sentezlendi. 5,6-Dihidro-3H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4(8H)-on ve 6-dihidro-3H-tiyopiran[4?,3?:4,5]seleno[2,3-d]pirimidin -4(8H)-on' un POCl3 ile etkileşiminden ise sırasıyla 4-kloro-6,8-dihidro-5H-tiyo piran[4?,3?:4,5]tiyeno[2,3-d]pirimidin ve 4-kloro-6,8-dihidro-5H-tiyopiran[4?,3?: 4,5]seleno[2,3-d]pirimidin bileşikleri elde edildi. 4-Kloro-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin' in sülfonilamit ile etkileşiminden 4-((6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-il)diazinil)benzensül- fonilamit sentezlendi. Daha sonra 4-kloro-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiye- no[2,3-d]pirimidin' in hidrazin hidrat ile reaksiyonu sonucunda 4-hidrazinil-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin elde edildi.İkinci aşamada, 4-hidrazinil-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]piri- midin' in salisilaldehit ve türevleri ile kondenzasyonu sonucunda 4-bromo-2-((2-(6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4-il)hidrazon)metil)fenol, 4-kloro-2-((2-(6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4-il)hidrazon)metil)fenol, 2-((2-(6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4-il)hidrazon)metil)-4-metilfenol, 2-((2-(6,8-dihidro-5H-tiyopiran[4?,3: 4,5]tiyeno[2,3-d]pirimidin-il)hidrazon)metil)fenol ve 3-((2-(6,8-dihidro-5H-tiyo piran[4?,3?:4,5]tiyeno[2,3-d]pirimidin-4-il)hidrazon)metil)fenol bileşikleri sentez- lenmiştir. Daha sonra 4-hidrazinil-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin' in pirol-2-karboksialdehit ile reaksiyonu sonucunda 4-(2-((1H-pirol-il-)metilen)hidrazinil)-6,8-dihidro-5H-tiyopiran[4?,3?:4,5]tiyeno[2,3-d]pirimidin bileşiği elde edilmiştir.Çalışmanın diğer bir kısmında ise 2-amino-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril' in salisilaldehit ve türevleri ile reaksiyonu sonucunda 2-(2-hidroksibenzilidenamino)-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril, 2-(5-floro-3-kloro-2-hidroksibenzilidenamino)-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril, 2-(5-floro-2-hidroksi-3-metilbenzilidenamino)-5,7-dihidro-4H-tiye no[2,3-c]piran-3-karbonitril, 2-(5-kloro-2-hidroksibenzilidenamino)-5,7-dihidro -4H-tiyeno[2,3-c]piran-3-karbonitril, 2-(5-bromo-2-hidroksibenzilidenamino)-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril ve 2-(2-hidroksi-5-metilbenzili- denamino)-5,7-dihidro-4H-tiyeno[2,3-c]piran-3-karbonitril bileşikleri elde edildi. Sentezlenen yeni bileşiklerin yapıları spektroskopik yöntemler (1H-NMR, 13C-NMR ve FTIR) ile aydınlatılmıştır.Anahtar Kelimeler : Tiyofen, Selenofen, Gewald tepkimesi, Selenopirimidin, Tiyenopirimidinhidrazon

Abstract:
In this study, derivatives of thieno[2,3-d]pyrimidine and selenopheno[2,3-d]pyrimidine, thienopyrimidinhydrazono and 2-(benzylideneamino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile having polyfunctional groups were synthesized. The synthesized compounds are thought to show biological activity.In the first phase of the study, using the method of Gewald; 2-amino-5,7-dihydro-4H-thieno[2,3-c]thiopyran-3-carbonitrile was synthesized from the reaction of malonitrile with tetrahydro-4H-thiopyran-4-on and elemental sulfur, 2-amino-5,7-dihydro-4H-selenopheno[2,3-c]thiopyran-3-carbonitrile was synthesized from the reaction of malonitrile with tetrahydro-4H-thiopyran-4-on and metallic selenium and 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile was synthesized from the reaction of malonitrile with tetrahydro-4H-pyran-4-on and elemental sulfur. The reaction of synthesized; 2-amino-5,7-dihydro-4H-thieno[2,3-c]thiopyran-3-carbonitrile with formamide gave 6,8-di hydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine and the reaction of synthesized 2-amino-5,7-dihydro-4H-thieno[2,3-c]thiopyran-3-carbonitrile with pyrrolidin-2-one and POCl3 gave 3,4,8,9-trahydro-1H-pyrrolo[1,2-a]thio pyrano[4',3':4,5]thieno[2,3-d]pyrimidin-5(7H)-imine compounds. The reaction of synthesized; 2-amino-5,7-dihydro-4H-thieno[2,3-c]thiopyran-3-carbonitrile and 2-amino-5,7-dihydro-4H-selenopheno[2,3-c]thiopyran-3-carbonitrile with formic acid gave respectively of 5,6-dihydro-3H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4(8H)-on and 5,6-dihydro-3H-thiopyrano[4',3':4,5]selenopheno[2,3 -d]pyrimidin-4(8H)-one compounds. 5,6-dihydro-3H-thiopyrano[4',3':4,5] thieno[2,3-d]pyrimidin-4(8H)-on and 5,6-dihydro-3H-thiopyrano[4',3':4,5] selenopheno[2,3-d]pyrimidin-4(8H)-one were then reacted with POCl3 to obtain, respectively of 4-chloro-6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d] pyrimidine and 4-chloro-6,8-dihydro-5H-thiopyrano[4',3':4,5]selenopheno[2,3-d]pyrimidine compounds. 4-chloro-6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno [2,3-d]pyrimidine was then reacted with 4-aminobenzenesulfonamide to obtain 4-((6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl)amino) benzenesulfonamide. Reaction of 4-chloro-6,8-dihydro-5H-thiopyrano[4',3':4,5] thieno[2,3-d]pyrimidine with hydrazine gave 4-hydrazinyl-6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidine.The second phase, as result of the condensation of synthesized 4-hydrazinyl-6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidine with salicylaldehyde and its derivatives gave 4-bromo-2-((2-(6,8-dihydro-5H-thiopyrano[4',3':4,5] thieno[2,3-d]pyrimidin-4-yl)hydrazono)methyl)phenol, 4-chloro-2-((2-(6,8-di hydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl)hydrazono)methyl) phenol, 2-((2-(6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl) hydrazono)methyl)-4-methylphenol, 2-((2-(6,8-dihydro-5H-thiopyrano[4',3':4,5] thieno[2,3-d]pyrimidin-4-yl)hydrazono)methyl)phenol and 3-((2-(6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl)hydrazono)methyl)phenol compounds. Reaction of 4-hydrazinyl-6,8-dihydro-5H-thiopyrano[4',3':4,5] thieno[2,3-d]pyrimidine with 1H-pyrrole-2-carboxyaldehyde gave 4-(2-((1H-pyrrol-2-yl)methylene)hydrazinyl)-6,8-dihydro-5H-thiopyrano[4',3':4,5]thieno [2,3-d]pyrimidine compound.The other part of the study, Reaction of synthesized 2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile with salicylaldehyde and its derivatives gave 2-((2-hydroxybenzylidene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3- carbonitrile, 2-((3-chloro-5-fluoro-2-hydroxybenzylidene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile, 2-((5-fluoro-2-hydroxy-3-methylbenzyli- dene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile, 2-((5-chloro-2-hydroxybenzylidene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile, 2-((5-bromo-2-hydroxybenzylidene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile ve 2-((2-hydroxy-5-methylbenzylidene)amino)-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carbonitrile compounds. The structures of the synthesized compounds were confirmed by spectroscopic techniques (1H-NMR, 13C-NMR ve FTIR).Key Words : Thiophene, Selenophene, Gewald Method Selenopyrimidine, Thienopyrimidinhyrazono