Helisen yapılı triazol bileşiklerinin sentezi
Synthesis of helicene-structured triazole compounds
Yazar: NİLAY KASABALI
Danışman: PROF. DR. EMİNE NACİYE TALINLI
İstanbul Teknik Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2018
Konu: Kimya = Chemistry

Özet:
Organik sentezlerde, reaksiyon hızının, veriminin ve seçiciliğin kontrol edilebilmesi büyük önem taşır. Bu kontrollerin sağlanabilmesi için ligand içeren kompleks ya da katalizör bileşikler kullanılır. Optikçe aktif ya da kiralite özelliği taşıyan ligandlar kullanılarak asimetrik sentez gerçekleştirilebilir. Bu amaçla kullanılan ligand türlerinden birisi de helisenlerdir. Helisenler, düzlemsel olmayan karakteristik şekilleri ve kiral özellikleri sebebiyle bilimsel araştırmalarda ilgi çekmektedir. Son yıllarda yapılan araştırmalarda, helisenlerin kiral molekül yapısından dolayı asimetrik katalizör olarak kullanılabilirliği gözlenmiştir.  
Bu çalışmada helisen yapıda triazol ünitesi içeren bileşiklerin sentezleri ve bunların çeşitli metallerle bir kompleks oluşturarak potansiyel ligand olarak kullanılmaları amaçlanmaktadır. Triazol halkası içeren doymuş ve doymamış helisen bileşikleri olarak sentezleri iki ana grupta toplamak mümkündür. Doymuş helisen bileşikleri naftofuranofuran türevleri ile dioksozin türevlerinin sentezini kapsarken, doymamış helisen bileşikleri ise yalnızca naftofuranofuran yapısındaki furan halkalarının çift bağ içeren türevlerini kapsamaktadır.
Doymuş naftofuranofuran türevlerinin sentezinde ilk basamak olarak, asit katalizörlüğünde 2,7-dihidroksinaftalen ve glioksal bis ile naftofuranofuran sentezlenmiş ve daha sonra elde edilen bileşik propargil eter türevine dönüştürülmüştür. Son reaksiyon aşaması olarak da azid-alkin siklokatılma reaksiyonu ile triazol yapısı içeren naftofuranofuran bileşiği elde edilmiştir. Dioksozin ve türevlerinin sentezinde ise ilk basamak olarak, asit katalizörlüğünde 2,7- dihidroksinaftalen ve malondialdehit bis (dimetil asetal) ile dioksozin sentezlenmiş ve daha sonra elde edilen bileşik propargil eter türevine dönüştürülmüştür. Son reaksiyon aşaması olarak da azid-alkin siklokatılma reaksiyonu ile triazol yapısı içeren dioksozin bileşiği elde edilmiştir. Bu doymuş helisen bileşiklerinin sentezinde eterleşme reaksiyonları bis ve mono eter bileşikleri olmak üzere iki ayrı kısımda sentezlenmiştir. Mono eter bileşiklerinin sentezinden sonra, yapıdaki serbest OH gruplarının  bir sonraki azid-alkin siklokatılma reaksiyonları aşamasında CuBr ile kompleks oluşturmasını önlemek amacıyla koruma reaksiyonları yapılmaya ihtiyaç duyulmuştur. Bunun için de koruma grubu olarak yapıya uygun olan asetil seçilmiştir. Asetilasyon yapıldıktan sonra azid-alkin siklokatılma reaksiyonuna geçilmiştir.
Çalışma planında son sentezler olarak yer alan naftofuranofuranın doymamış türevlerinde de aynı reaksiyon yöntemleri izlenmekle birlikte farklı olarak, asetalleşme reaksiyonunun ardından CCl4 varlığında NBS ile çift bağ oluşturma aşaması gerçekleştirilmiş ve yukarıda bahsedilen sentez basamakları doymamış naftofuranofuran bileşikleri için de uygulanmıştır.
Sonuç olarak yapılması hedeflenen helisen yapılı doymuş dioksa[6]helisen molekülleri başarılı bir şekilde elde edilmiştir. Planara yakın yapıdaki doymamış bileşik, sübstitüe edilerek helisen özellik kazandırılmış ve iç kavite çapı değiştirilmiştir.
Bu bileşiklerin iç kaviteleri elektronca zengin olduğundan organik katyon bağlama yeteneklerinin yanında triazol-triazol ve triazol-OH etkileşimleri ile de katyon tutma kapasitesine sahip olabilecekleri ve seçici katyon tutabilecekleri düşünülmüştür.

Abstract:
Using of ligand or catalyst obtain the control for selectivity, purity, speed and yield in organic reaction. Due to the fact that the chiral information in the organic products prepared by enantioselective catalysis derives from the optically active ligands bound to the transition metal, the design of these ligands constitutes a meticulous research. One of the ligand types used for this purpose is the helicene. 
Helicenes are polycyclic aromatic compounds in which the benzene rings are connected in ortho positions leading to screw-shaped molecules. They exhibit helical chirality even though they do not contain any asymmetric carbon. Helicenes' chirality results from the fact that clockwise and counterclockwise helices are non-superimposable. Both enantiomers are stable and isolable forms. Furthermore, their intriguing semiconductivity was foreseen opening their potential applications in organic electronic devices. Recently, researchers developed a revised microwave photodehydrocyclization procedure for preparation of various substituted helicenes in multigram scale.
Coordination chemistry of helicenes and their use as chirality inductors is still strongly under-developed. Among privileged lignads exhibiting central, axial or planar chirality, use of helically chiral ligands in transition metal catalysis is still very rare. Researchers focusing on helical phosphines and their transition-metal complexes potentially usable in homogeneous asymmetric catalysis.
The main objective of this research project has been the development and exploration of novel, supramolecular catalyst systems that are formed by the assembly of several components using non-covalent interactions. The supramolecular strategy involves the multicomponent assembly of a transition metal catalyst and various building blocks into a new supramolecular catalyst system. 
For the preparation of these assembled catalysts, selective metal-ligand interactions have been used that control the coordination geometry around the catalytically active metal center and the final shape of the supramolecular catalyst system. Suitable homogeneous transition metal catalysts in combination with properly chosen molecular building blocks led to assembled catalyst systems that improve catalytic properties such as activity and selectivity.
Naphtofuranofuran and benzofuranofurans type compounds have the property of many biological activities. Therefore, these compounds are widely used in many fields, these fields could be classified as agriculture and industry in its own. Benzofuranofuran also used in industries such as dyes in laser technology and fluorescent materials for visualization of biomolecules. 
Structures of naftofuranofuran compounds have resemblance to chiral helicene ligands, and hence dibenzofuranofuran is possible to use as a catalyst like ligands in the organic chemistry. 
Although other ligand types continue to be employed in some enantioselective catalysis, optically active helicenes play a key role as chiral ligands in various transition metal catalyzed asymmetric synthesis because of their steric and electronic variability. Morever, it has been reported that sterically congested helicene ligands remarkably increase the catalytic activities of the metal complexes. 
 Modern advanced asymmetric catalysis demands both maximum efficiency in terms of yield and enantioselectivity. Reactions using helical ligand demands the same properties, too. A variety of reaction mechanisms are used for the synthesis of phosphorus ligands. These mechanism could obtain maximum yield, purity and short reaction time.  
Helicenes have been interesting for academic researcher because helicenes and helicen-like molecules show non-planar / planar characteristics and the feature of helical chirality. In the recent advances shows that helicenes and helicen-like molecules to be potential as liquid crystal molecules, sensors, and dyes. Research give information that helicenes have been applications in areas of asymmetric catalysis and chiral molecular recognation.
Our interest in compounds such as 7,8-dioxa[6]helicene is a simple model of the new horseshoe shaped molecule. There is a low inversion barrier between helical enantiomers. A low-energy barrier between the P and M forms. Interconversion of the two forms which are racemic mixture occurs readily at room temperature in solution due to the geometic features of the five membered furane rings.
It is also known that, triazoles are found in many bioactive compounds and synthetic drugs, also, plays important role in organic synthesis.
In this study, it is aimed to synthesize the compounds containing the triazole unit in the helical structure and use them as potential ligands by forming a complex with various metals.
As the saturated and unsaturated helicene compounds containing triazole ring, it is possible to collect syntheses in two main groups. Saturated helicene compounds include the synthesis of the naphthofuranofuran derivatives and of the dioxocin derivatives, while the unsaturated helicene compounds include double bond-containing derivatives of furan rings in naphthofuranofuran structure only.
As a first step in the synthesis of saturated naphthofuranofuran derivatives, in the acid media, using 2,7-dihydroxynaphthalene and the glyoxal bis were synthesized the naphthofuranofuran and then the compound obtained was converted to the propargyl ether derivative. The final reaction step was the azid-alkyne cycloaddition reaction to gain the naphthofuranofuran compound containing the triazole structure. In the synthesis of dioxocin and its derivatives, the first step was synthesized by acid catalysed 2,7-dihydroxynaphthalene and malondialdehyde bis (dimethyl acetal) and then the compound was converted to the propargyl ether derivative. As a final reaction step, the dioxocin compound containing the triazole structure was obtained by the azide-alkyne cycloaddition reaction. In the synthesis of these saturated helicene compounds, the etherification reactions were synthesized in two separate parts as bis and mono ether compounds.
After the synthesis of mono ether compounds, protection reactions were needed to prevent free OH groups in the structure from forming complexes with CuBr in the next azide-alkyne cycloaddition reaction step. For this purpose, acetyl was chosen as the protection group. After acetylation, the azide-alkyne cycloaddition reaction was started.
The same reaction methods were observed in the unsaturated derivatives of naphthofuranofuran as the final syntheses in the study plan but there is a difference that following the acetalization reaction, a double bonding step with NBS was carried out in the presence of CCl4. The synthesis steps mentioned above were also applied for unsaturated naphthofuranofuran compounds.
As a result, the targeted helical saturated dioxa[6]helicene molecules were successfully obtained. The unsaturated compound in the structure close to the planar was substituted. The helicene feature was added and the internal cavity diameter was changed.
In addition to the internal cavities of these compounds are electron- rich, it is thought that they can have cation holding capacity and hold selective cation by their interactions with triazole-triazole and triazole-OH as well as their ability to bind organic cations.