Polihalodienlerden sentezlenen bazı yeni heterosiklik bileşikler
Some new heterocyclic compounds synthesized from polyhalodienes
Yazar: ELİF BULUT
Danışman: DOÇ. DR. SERDAR GÖKŞİN AYDINLI
İstanbul Üniversitesi-Cerrahpaşa / Lisansüstü Eğitim Enstitüsü / Kimya Ana Bilim Dalı / Organik Kimya Bilim Dalı
Derece: Yüksek Lisans, 2020
Konu: Kimya = Chemistry
Dizin: Alifatik aminler = Aliphatic amines ; Alkil aminler = Alkyl amines ; Ditiyoller = Dithiols ; Etanditiyol = Ethanedithiol ; Infrared spektroskopi =   ; Kütle spektroskopisi = Mass spectroscopy ; Manyetik rezonans spektroskopi = Magnetic resonance spectroscopy ; Polibütadien = Polybutadiene

Özet:
Perhalonitro-1,3-butadienler olarak bilinen organik bileşikler, önemli bir yapı taşı olarak terapötik açıdan faydalı çoğu maddenin elde edilmesinde ve türev sentezlerinin yüksek potansiyel biyolojik aktivitesinden dolayı oldukça ilgi görmektedir. Bu dienler karbon-heteroatom bağ oluşum reaksiyonlarıyla, yüksek verimli ve seçici ürünler veren "Klik kimya" tipi sentezlerde de kullanılır. Morfolin, piperazin ve piperidin gibi heterosiklik amin türevleri olarak azot atomları içeren bazı bileşikler, psikolojik ve nörolojik bozuklukların tedavisinde daha iyi biyolojik etki gösterdiği bilinen benzer yapılarının sentezlenmesinde de uygundur. Çalışmada perhalonitro-1,3-butadienler ile bazı heterosiklik amin ve tiyol bileşiklerinin reaksiyonlarından benzer biyolojik aktivite göstermesi beklenen yeni organik bileşikler elde edilmiştir.

Çalışmada öncelikle 2-Nitropentakloro-1,3-butadien (1), 1,2-Etanditiyol ve 3-Merkapto-2-butanol bileşikleri ile doğrudan, çözücüsüz ortamda reaksiyona sokuldu. Bu difonksiyonel nükleofiller kullanıldığında siklizasyon ürünleri meydana geldi. Reaksiyon sonucunda sırasıyla bilinen S,S-sübstitüe perhalonitro-1,3-butadien bileşiği 2-(2,3,3-Trikloro-1-nitroalliliden)-1,3-ditiyolan (2) ve yeni S,O-sübstitüe perhalonitro-1,3-butadien bileşiği 2-(2,3,3-Trikloro-1-nitroalliliden)-4,5-dimetil-1,3-oksatiyolan (3) elde edildi. (3) Bileşiğinin verimi düşük olduğundan çalışmaya (2) bileşiği ile devam edildi. Sentezlenen (2) bileşiği bazı heterosiklik amin ve farklı tiyol bileşikleri ile reaksiyona sokuldu. Reaksiyonun tamamlanmasıyla bilinmeyen yeni N,S,S- ve S,S,S-sübstitüe perhalonitro-1,3-butadien bileşikleri elde edildi.

(2) bileşiği heterosiklik amin bileşikleri, 2,6-Dimetilmorfolin, 4-Benzilpiperidin, 1-(4-Fluorobenzil)piperazin, 1-(2-Piridil)piperazin, 1-(2-Pirimidil)piperazin ve 1-(2-Furoyil)piperazin ile sırasıyla reaksiyona sokuldu. Reaksiyonlardan 4-(1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)-2,6-dimetilmorfolin (4), 4-Benzil-1-(1,1-dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)piperidin (5), 1-(4-Fluorobenzil)-4-(1,1-dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)piperazin (6), 1-(1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)-4-(piridin-2-il)piperazin (7), 2-(4-(1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)piperazin-1-il)pirimidin (8) ve 4-(1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)piperazin-1-il)(furan-2-il)metanon (9) bileşikleri sırasıyla sentezlendi. (2) bileşiği, alifatik, aromatik ve heterosiklik tiyol bileşikleri, 1-Oktantiyol, 1-Dekantiyol, p-Klorotiyofenol, p-Metiltiyofenol, 4-Metoksitiyofenol, 2-Merkaptopirimidin, 2-Merkapto-4-feniltiyazol ve 7-Merkapto-4-metilkumarin ile sırasıyla reaksiyona sokuldu. Reaksiyonlardan 2-(3,3-Dikloro-2-(oktiltiyo)-1-nitroalliliden)-1,3-ditiyolan (10), 2-(3,3-Dikloro-2-(desiltiyo)-1-nitroalliliden)-1,3-ditiyolan (11), 2-(2-(4-Klorofeniltiyo)-3,3-dikloro-1-nitroalliliden)-1,3-ditiyolan (12), 2-(2-(4-Toliltiyo)-3,3-dikloro-1-nitroalliliden)-1,3-ditiyolan (13), 2-(2-(4-Metoksifeniltiyo)-3,3-dikloro-1-nitroalliliden)-1,3-ditiyolan (14), 2-((1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-il)tiyo)pirimidin (15), 2-(1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-iltiyo)-4-feniltiyazol (16) ve 7-((1,1-Dikloro-3-(1,3-ditiyolan-2-iliden)-3-nitroprop-1-en-2-iltiyo)-4-metil-2H-kromen-2-on) (17) bileşikleri sırasıyla sentezlendi.

Bu çalışmada onbeş adet yeni bileşik sentezlenmiştir. Yeni elde edilen bu bileşikler kromatografik veya kristallendirme yöntemleri ile saflaştırıldı. Molekül yapıları spektroskopik yöntemler (IR, 1H- ve 13C-NMR, MS) ile aydınlatılmıştır.

Abstract:
The relatively new class of organic compounds called per-halogenatednitro-1,3-butadienes has attracted considerable attention largely owing to their importance as convenient building blocks for many therapeutically useful materials and the wide range of potential biological activity of their synthetic derivatives. These dienes also have been used in "click chemistry" type syntheses that giving high yields and selectivity products by carbon-heteroatom bond formation reactions. Some morpholine, piperazine and piperidine compounds as heterocyclic amine derivatives containing nitrogen atoms can also be explore to synthesize many of  its analogous which can be properly exploit to obtain new molecules which shows better biological response as to treat psychological and neurological disorders. In this study, new organic compounds which are expected to show similar biological activity from the reactions of perhalonitro-1,3-butadienes and some heterocyclic amine and thiol compounds were obtained.

2-Nitropentachloro-1,3-butadiene (1) compound was immediately reacted with 1,2-Ethandithiole and 3-Mercapto-2-butanol compounds without solvents, primarily. Cyclization products were formed when these difunctional nucleophiles were used. At the end of the reactions, known S,S-substituted perhalonitro-1,3-butadiene compound 2-(2,3,3-Trichloro-1-nitroallylidene)-1,3-dithiolane (2) and new compound S,O-substituted perhalonitro-1,3-butadiene compound 2-(2,3,3-Trichloro-1-nitroallylidene)-4,5-dimethyl-1,3-oxathiolane (3) were obtained respectively. Since the yield of compound (3) was low, the study was continued with compound (2). The synthesized compound (2) was reacted with certain heterocyclic amine and thiol compounds. The reaction yielded unknown new N,S,S- and S,S,S-substituted perhalonitro-1,3-butadienes.

Compound (2) was respectively reacted with heterocyclic amine compounds 2,6-Dimethylmorfoline, 4-Benzylpiperidine, 1-(4-Fluorobenzyl)piperazine, 1-(2-Pyridyl)¬piperazine, 1-(2-Pyrimidyl)piperazine and 1-(2-Furoyl)piperazine. At the end of the reaction, 4-(1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)-2,6-dimethyl¬morpholine (4), 4-Benzyl-1-(1,1-dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)piperidine (5), 1-(4-Fluorobenzyl)-4-(1,1-dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)-3-nitroprop-1-en-2-yl)piperazine (6), 1-(1,1-Dichloro-3-(1,1-dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)-4-(pyridin-2-yl)piperazine (7), 2-(4-(1,1-Dichloro-3-(1,1-dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)piperazin-1-yl)py¬rimidine (8) and 4-(1,1-dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)piperazin-1-yl)(furan-2-yl)methanone (9) compounds were synthesized, respectively. Compound (2) was also reacted with aliphatic, aromatic and heterocyclic thiole compounds 1-Octanethiol, 1-Decanethiol, p-Chlorothiophenol, p-Methylthiophenol, 4-Methoxythiophenol, 2-Mercaptopyrimidine, 2-Mercapto-4-phenylthiazole and 7-Mercapto-4-methylcoumarin, respectively. At the end of the reaction, respectively 2-(3,3-Dichloro-2-(octylthio)-1-nitroallylidene)-1,3-dithiolane (10), 2-(3,3-Dichloro-2-(decylthio)-1-nitroallylidene)-1,3-dithiolane (11), 2-(2-(4-Chlorophenylthio)-3,3-dichloro-1-nitroallylidene)-1,3-dithiolane (12), 2-(2-(4-Tolylthio)-3,3-dichloro-1-nitroallylidene)-1,3-dithiolane (13), 2-(2-(4-Methoxyphenylthio)-3,3-dichloro-1-nitroallylidene)-1,3-dithiolane (14), 2-((1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-yl)thio)pyrimidine (15), 2-(1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitroprop-1-en-2-ylthio)-4-phenylthiazole (16) and 7-((1,1-Dichloro-3-(1,3-dithiolan-2-yliden)-3-nitroprop-1-en-2-ylthio)-4-methyl-2H-cromen-2-on) (17) compounds were synthesized.

The new fifteen compounds were synthesized. The compounds obtained were purified by chromatographic or crystallographic methods. The structures of the compounds were made clear by spectroscopic methods (IR, 1H- ve 13C-NMR, MS).