Hetero atom sübstitüe naftakinon ve vitamin K3 türevlerinin sentezlenmesi
The synthesis of heteroatom substitued naphthoquinone and vitamin K3 derivatives
Yazar: AYŞEGÜL İŞCAN
Danışman: DOÇ. DR. NAHİDE GÜLŞAH DENİZ
İstanbul Üniversitesi-Cerrahpaşa / Lisansüstü Eğitim Enstitüsü / Kimya Ana Bilim Dalı / Organik Kimya Bilim Dalı
Derece: Yüksek Lisans, 2022
Konu: Kimya = Chemistry
Dizin: Aminler = Amines ; Naftakinonlar = Naphthoquinones ; Spektroskopi = Spectroscopy ; Vitamin K = Vitamin K

Özet:
Bu yüksek lisans tez çalışmasında; bazı kinon bileşiklerinin amin nükleofilleri ile Michael katılma reaksiyonları sonucunda yeni, biyolojik aktivite potansiyeline sahip N- ve N-,O-sübstitüe-1,4-naftakinon ve (metilkinon) vitamin K3 türevleri bileşikler sentezlenmiştir. Deneylerde başlangıç maddeleri olarak 2-Metil-1,4-naftakinon (1) ve 2,3-Dikloro-1,4-naftakinon (2) bileşikleri kullanıldı.
2-Metil-1,4-naftakinon (1) bileşiğinin N-metilsiklohekzilamin ile reaksiyonundan bilinmeyen yeni 3-metil-2-N-metilsiklohekzil-1,4-naftakinon (3) bileşiği elde edilmiştir. 2-Metil-1,4-naftakinon (1) bileşiğinin 4-(4-klorofenoksi)anilin ile reaksiyonu sonucu bilinmeyen yeni 2-4-(4-klorofenoksi)anilin-3-metil-1,4-naftakinon (14), 2-etoksi-3-metil-4-(4-klorofenoksi)anilin-1,4-naftakinon (15) bileşikleri elde edilmiştir. 2-Metil-1,4-naftakinon (1) bileşiğinin 1-(2-piridil)piperazin ile reaksiyonundan bilinen 2-metil-3-[1-(2-piridil)piperazin-il]-1,4-naftakinon (17) ve bilinmeyen yeni 2-metil-[1-(2-piridil)piperazin-il]-3-etoksi-1,4-naftakinon (18) bileşikleri sentezlendi.
2,3-Dikloro-1,4-naftakinon (2) bileşiğinin 1-(2-piridil)piperazin ile reaksiyonundan bilinen 3-kloro-2-(1-(2-piridil)piperazin)-1,4-naftakinon (4) ve bilinmeyen yeni 3-etoksi-2-(1-(2-piridil)piperazin)-1,4-naftakinon (5) bileşikleri sentezlendi. 2,3-Dikloro-1,4-naftakinon (2) bileşiğinin 2,5-diflorobenzilamin ile reaksiyonundan bilinmeyen yeni 2,2′-[2,5-diflorobenzilamin]-3,3′-diklorobis(1,4-naftakinon) (6) ve 2,2′-[2,5-diflorobenzilamin]-3′-kloro-3-etoksi-bis(1,4-naftakinon) (7)  bileşikleri sentezlenmiştir. 2,3-Dikloro-1,4-naftakinon (2) bileşiği ile 4-floroanilin bileşiğinin reaksiyonundan bilinen 2-(4-floroanilin)-3-kloro-1,4-naftakinon (8) ve bilinmeyen yeni 3-etoksi-2-(4-floroanilin)-1,4-naftakinon (9) bileşikleri elde edilmiştir. 2,3-Dikloro-1,4-naftakinon (2) bileşiğinin dihekzilamin ile reaksiyonundan bilinen 2-dihekzilamin-3-kloro-1,4-naftakinon (10) ve bilinmeyen yeni 2-dihekzilamin-3-etoksi-1,4-naftakinon (11) ve 2,3'-dihekzilamin-1,4-naftakinon (12) bileşikleri sentezlenmiştir. 2,3-Dikloro-1,4-naftakinon (2) bileşiğinin 4-(4-klorofenoksi) anilin ile reaksiyonundan bilinmeyen yeni 2-4-(4-klorofenoksianilin)-3-kloro-1,4-naftakinon (13) bileşiği elde edilmiştir. 2,3-Dikloro-1,4-naftakinon (2) bileşiğinin 1-(tetrahidro-2-furol)-piperazin ile reaksiyonundan bilinen 3-kloro-2-1-(tetrahidro-2-furol)-piperazin-1,4-naftakinon (16) bileşiği sentezlenmiştir.
Reaksiyonlar sonucu oluşan ürünler kolon kromatografisi yöntemi ile saflaştırıldı. Ürünlerin karakterizasyonu; mikro analiz ve çeşitli spektroskopik yöntemler kullanılarak (FT-IR, 1H-NMR, 13C-NMR, MS, UV-vis) aydınlatılmıştır.

Abstract:
In this master's thesis study, novel N- and N-,O-substitued-1,4-naphthoquinone and (methylquinone) vitamin K3 derivatives which have high biological activities were synthesized by the reactions of amine nucleophiles with some quinones according to Michael addition mechanism. The new quinone compounds were synthesized starting from 2-Methyl-1,4-naphthoquinone (1) and 2,3-Dichloro-1,4-naphthoquinone (2). In the reaction of 2-methyl-1,4-naphthoquinone (1) and N-methylcyclohexylamine novel 3-methyl-2-N-methylcyclohexyl-1,4-naphthoquinone (3) compound was synthesized. Unknown, new 2-4-(4-chlorofenoxyaniline)-3-methyl-1,4-naphthoquinone (14), 2-ethoxy-3-methyl-4-(4-chlorofenoxyaniline)-1,4-naphthoquinone (15) compounds were synthesized from the reaction between 2-methyl-1,4-naphthoquinone (1) and 4-(4-chlorofenoxy)aniline. Known 2-methyl-3-(1-(2-pyridyl)piperazine)-1,4-naphthoquinone (17) and novel 2-methyl-(1-(2-pyridyl)piperazine)-3-ethoxy-1,4-naphthoquinone (18) compounds were synthesized by the reaction of 2-Methyl-1,4-naphthoquinone (1) and 1-(2-Pyridyl)piperazine. 
As a result of the reaction between 2,3-dichloro-1,4-naphthoquinone (2) and 1-(2-pyridyl)piperazine, known 3-chloro-2-(1-(2-pyridyl)piperazine)-1,4-naphthoquinone (4) and novel 3-ethoxy-2-(1-(2-pyridyl)piperazine)-1,4-naphthoquinone (5) compounds were synthesized. Novel 2,2′-[2,5-difluorobenzylamine]-3,3′-dichlorobis(1,4-naphthoquinone) (6) and 2,2′-[2,5-difluorobenzylamine]-3′-chloro-3-ethoxy-bis(1,4-naphthoquinone) (7) compounds were synthesized from the reaction between 2,3-dichloro-1,4-naphthoquinone (2) and 2,5-difluorobenzylamine. Known 2-(4-fluoroaniline)-3-chloro-1,4-naphthoquinone (8) and new 3-ethoxy-2-(4-fluoroaniline)-1,4-naphthoquinone (9) compounds were synthesized by the reaction of 2,3-dichloro-1,4-naphthoquinone (2) and 4-fluoroaniline. In the reaction of 2,3-dichloro-1,4-naphthoquinone (2) and dihexylamine known 3-chloro-2-dihexylamine-1,4-naphthoquinone (10) and novel 2-dihexylamine-3-ethoxy-1,4-naphthoquinone (11), 2,3'-dihexylamine-1,4-naphthoquinone (12) compounds were synthesized successfully. Unknown, new 2-4-(4-chlorofenoxyaniline)-3-chloro-1,4-naphthoquinone (13) was synthesized as a result of the reaction between 2,3-dichloro-1,4-naphthoquinone (2) and 4-(4-chlorofenoxy)aniline. In the final reaction, known 3-chloro-2-1-(tetrahydro-2-furoyl)-piperazine-1,4-naphthoquinone (16) was synthesized from the reaction between 2,3-dichloro-1,4-naphthoquinone (2) and 1-(tetrahydro-2-furoyl)piperazine.
The synthesized compounds are seperated and purificated by the column chromatography method. The structures of quinone compounds were characterized with microanalysis, 1H-NMR, 13C-NMR, FT-IR and MS techniques and UV-vis spectroscopy method.