Şalkon içeren yeni karbazol türevlerinin sentezi ve karakterizasyonları
Synthesis and characterization of new carbazole derivatives with chalcone
Yazar: RÜMEYSA CAN
Danışman: PROF. DR. ARİF BARAN
Sakarya Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2022
Konu: Kimya = Chemistry
Dizin: Biyolojik aktivite = Biological activity ; Kalkonlar = Chalcones ; Karbazoller = Carbazoles ; Metal iyonları = Metal ions

Özet:
Karbazoller termal kararlılıkları, gösterdikleri ilgi çekici biyolojik aktiviteleri, iyi yük taşıma ve radikal katyon oluşturma gibi birçok özelliği nedeniyle ticari ve akademik alanlarda çok sık çalışılan bir moleküldür. Karbazollere ek olarak flavonoidlerin ve izoflavonoidlerin öncülleri olarak kabul edilen şalkonlar, çay, soya bazlı gıda maddeleri, baharat, sebze ve meyvelerde yaygın olarak bulunan doğal ürünlerin temel sınıflarından biridir. Doğal bir şekilde oluşan şalkonlar ve bunların bireşimli analogları, yaygın bir biyolojik aktiviteye sahiptir. Tıbbi özellikli doğal ve
sentetik şalkonların, çeşitli moleküler amaçları modüle edilerek çok çeşitli farmakolojik etkinlikler gösterdiği birçok çalışma ile rapor edilmiştir. Heterosiklik halka sisteminde hidroksil, karbonil, fenolik oksijen ve heteroatomların bulunması molekülleri metal koordinasyonu için mükemmel şelatlayıcı ligand yapar. Bu nedenlerden dolayı, şalkonlar hem akademi hem de endüstride sürekli ilgi gören bir nesne haline gelmiştir. Bu çalışmada 3- ve 6- konumlarından fonksiyonlandırılmış karbazol türevleri sentezlenmiştir. Başlangıç bileşiği olarak kullanılan 9H karbazol ile n-heptan bromür reaksiyona tabii tutarak 9-heptil 9-H karbazol (1) eldesinden yola çıkarak, bu moleküle Vilsmeier Haack reaksiyonu uygulanarak 9-heptil-9H-karbazol-3- karbaldehit (2) nolu molekülün sentezi gerçekleştirilmiştir. (2) nolu molekülden aseton kullanılarak (3) nolu şalkon molekülü sentezlenmiştir. Ayrıca 1 nolu molekül AcCl reaktifi kullanılarak sonucunda 1-(9-heptil-9H-karbazol-3-il)etan-1-on (4) elde edilmiştir. Takip eden reaksiyonda ise benzaldehit ile claisen schmidt reaksiyonu uygulanarak (5) nolu molekül elde edilmiştir. (1) nolu molekül nitrolama reaksiyonu ile 9-heptil-3-nitro-9H-karbazol (6) ve devam eden reaksiyonla 9-heptil-9H-karbazol-3-amin (7) elde edilmiştir ve daha sonra (7) nolu molekül sinamoil klorür ile reaksiyona tabii tutularak (E)-1-((9-heptil-9H-karbazol-3-il)amino)-4-fenilbut-3- en-2-on (8) son olarak da 7 nolu molekül akriloil klorür reaktifi ile reaksiyonu sonucu (E)-4-(3,4-dihidroksifenil)-1-((9-heptil-9H-karbazol-3-il)amino)but-3-en-2- on (9) sentezlenmiştir. Elde edilen şalkon içeren karbazol türevlerinin sensör özelliği incelenmiştir. Daha sonra elde edilen şalkon içeren karbazol türevlerinin özelliklerini araştırmak için çeşitli metallere (Ni+2, Hg+2, Fe+3, Co+, Fe+2, Mg+2, Cd+2, Sr+2, K+,Cu+2, Pb+2, Zn+2, Al+3, Ca+2, Ba+2 ve Mn+2) karşı olan ilgileri floresans spektrometresi yardımı ile incelenmiştir. Sentezlenen karbazol türevlerinie her bir metal çözeltisi ayrı ayrı eklenerek floresans duyarlılık çalışması gerçekleştirilmiştir.
Elde edilen sonuçlar, 3 nolu molekülün analiz edilen diğer metal iyonlarına kıyasla Fe+2 iyonuna karşı iyi bir floresans sönümleme etkisine sahip olduğunu göstermiştir. Buna ek olarak, 5 nolu molekül incelendiğinde ise Fe+3 iyonuna karşı floresans sönümleme etkisine sahip olduğu gözlenmiştir. 9 nolu sentez bileşiğine metal çözeltileri eklendikten sonra, sadece Cu+2 metal çözeltisi varlığında yeni ortaya çıkan bir emisyon bandı elde edilmiştir. 9'un emisyon bandında floresans şiddetindeki düşme (turn–off) oranının Cu+2 iyonuna karşı olduğu tespit edilmiştir. Buna karşılık, diğer metal iyonları 8 nolu molekülün spektrumlarında önemsiz emisyon değişikliklerine neden olmuştur. Sentezlenen moleküllerin ayırma ve saflaştırma işlemleri için kristallendirme, silika jel kolon kromotografisi, TLC (ince tabaka kromtografisi) tekniklerinden yararlanılarak ve ayrıca yapı tayinleri için FT-IR (Kızılötesi), 13C-NMR ve 1H (Nükleer Manyatik Rezonans) gibi spektroskopik yöntemleri kullanılarak karakterizasyonları yapılmıştır.

Abstract:
Carbazole is an opaque white monomer obtained from 2-nitrophenyl and petroleum products. It can be crystallized from alcohol, benzene, toluene and anhydrous acetic acid. Its melting point is 245 °C. It shows intense fluorescence and long fluorescence when exposed to UV rays. Carbazoles are a highly studied body in commercial and academic contexts due to their many properties such as thermal enclosures, attractive space centers, good charge transport and radical cation formation. The conjugated triene system on carbazole has become one of the most studied counterparts with its fluorescent effect on cancer cells. In order to increase or decrease this consumption of carbazole, it has been synthesized in large numbers by heteroatom nitrogen or by attaching various groups to cycloaromatic rings. The skeletal structure of the molecule has the same skeletal structure as the drug derivatives used in the treatment of high blood pressure, angina and heart diseases in pharmacology. This structure of carbazole and its derivatives appears to be quite common in synthetic and pharmaceutical chemists. Carbazoles, which have a good photoconductivity feature, are also used in the industrial field together with electronic and photonic applications, since they have a natural electron donating structure. Considered the precursors of flavonoids and isoflavonoids in addition to carbazoles, chalcones are one of the main classes of natural resources commonly found in tea, soy-based foodstuffs, spices, vegetables and fruits. The term chalcone encompasses all the details including the 1,3-diarylprop-2-en-1-one skeleton. The peculiarities of the
properties of these houses are the presence of olefinic bond and keto group in the propane chain. Naturally occurring chalcones and their synthetic analogues have widespread biological activity. Many studies have been conducted on chalcones due to their wide range of biological activities. The fact that chalcones contain α,β-unsaturated system (unit) in their structure makes them chemically important, and they are also used as output material from many hetero-ringed hoses. These outlet chalkons have an ideal appearance to form carboncarbon, carbosulfide and carbon-nitrogen bonds. It has been reported by many studies that natural and synthetic chalcones for medical reasons exhibit various multi-pharmacological activities used in the purpose module of various effects. The heterocyclic ring structure makes it an excellent chelating ligand for metal coordination where hydroxyl, carbonyl, phenolic oxygen and heteroatoms can be found. Because of this necessity, chalcones have become an object of constant interest in both academia and industry. In addition to this information, maintaining new storages for heavy metal ions is of great interest today. At very low temperatures, transition metal ions have major biological effects on living environments. These metals have high influence to adversely affect human testing and operating operation. The widespread use of these compounds in industry
causes many disorders such as movement and central nervous system disorders, brain damage. Heavy metals, which are widely used in industry today, pose a significant risk to both the environment and human life during and after use. Aware of all this danger, many researchers have focused their work on detecting heavy metals, removing them from the system and converting them into a harmless form against nature. Especially with the clean water resources that are decreasing day by day, the natural ecosystem is now alarming, and the number of conscious people who cannot remain indifferent to this, such issues have gained vital importance. Fluorescence-based chemosensors have a mechanism that communicates with their fluorophore unit and binding part that is selective to the analyte. It is known that carbazole-based optical sensors are widely used in optical sensor design due to their superior properties such as high chemical stability, excellent optical properties, strong absorption and emission properties. One method that can be used to detect and quantify transition metal ions is the use of fluorescent organic sensors. The fluorometric technique does not require laborious sample preparation and has distinct advantages such as being relatively fast. In another interesting feature, selective binding for the determined metal ion can be achieved with this technique. In this study, functionalized carbazole derivatives from 3- and 6- positions were synthesized. 9-heptyl 9-H carbazole (1) was obtained by reacting 9H carbazole, used as the starting compound, with n-heptane bromide in DMSO and applying the necessary purification processes. The synthesis of the molecule 9-heptyl-9H- carbazole-3-carbaldehyde (2) was carried out by applying the Vilsmeier Haack reaction with dimethylformamide (DMF) and phosphorus oxychloride (POCl3) in the presence of chloroform to this synthesized molecule, followed by isolation and purification methods. The chalcone molecule no. (E)-4-(9-heptyl-9H-carbazol-3-yl)but-3-en-2-one (3) is formed by adding acetone reagent in ethanol to molecule no.
2 and then applying the necessary isolation and purification processes. synthesized. In addition, 1-(9-heptyl-9H-carbazol-3-yl)ethane-1-one (4) was obtained by applying the necessary purification processes as a result of the reaction carried out using the molecule No. 1 AcCl and ZnCl2 reagent. In the following reaction, the molecule (E)-1-(9-heptyl-9H-carbazol-3-yl)-3-phenylprop-2-en-1-one (5) was obtained by applying the Claisen Schmidt reaction with benzaldehyde in the presence of ethanol. The molecule numbered (1) was carried out in nitration reaction under suitable conditions and 9-heptyl-3-nitro-9H-carbazole (6) was synthesized. After the completed reaction, 9-heptyl-9H-carbazole-3-amine (7) was obtained with SnCl2.2H2O reagent. The molecule no. (7) is treated with pyridine and cinnamoyl chloride, and then necessary isolation and purification processes are applied, and (E)- 1-((9-heptyl-9H-carbazol-3-yl)amino)-4-phenylbut-3-en- 2-ten (8) was obtained. Finally, as a result of the reaction of molecule numbered (7) with (E)-3-(3,4-dihydroxyphenyl)acryloyl chloride reagent in pyridine, (E)-4-(3,4-dihydroxyphenyl)-1-((9-heptyl) -9H-carbazol-3-yl)amino)but-3-en-2-one (9) was synthesized. In order to investigate the properties of carbazole derivatives containing chalcone, various metals (Ni+2, Hg+2, Fe+3 , Co+2, Fe+2, Mg+2, Cd+2, Sr+2, K+, Cu+2, Pb+2, Zn+2, Al+3, Ca+2, Ba+2 and Mn+2) were investigated with the help of fluorescence spectrometry. Fluorescence susceptibility study was carried out by adding each metal solution separately to the synthesized carbazole derivatives. The obtained results showed that
molecule 3 has a good fluorescence quenching effect against Fe+2 ion compared to other metal ions analyzed. In addition, when the molecule 5 was examined, it was observed that it had a fluorescence quenching effect against the Fe+3 ion. After adding metal solutions to the synthesis compound 9, a newly emerged emission band was obtained only in the presence of Cu+2 metal solution. It has been determined that the turn-off rate of fluorescence intensity in the emission band of 9 is against the Cu+2 ion. In contrast, other metal ions caused insignificant emission changes in the spectra of molecule 8. Characterizations of the synthesized molecules were made using crystallization, silica gel column chromatography, TLC (thin layer chromatography) techniques for separation and purification processes, and also using spectroscopic methods such as FT-IR (Infrared), 13C-NMR and 1H-NMR (Nuclear Magnetic Resonance) for structure determinations.