Yeni çok fonksiyonlu ferrosenil naftakinon bileşiğinin sentezi ve seçici katyon bağlama özelliklerinin incelenmesi
Synthesis of new multifunctional ferrocenyl naphthaquinone compound and selective cation binding studies
Yazar: YUSUF ALÇAY
Danışman: PROF. DR. İSMAİL YILMAZ
İstanbul Teknik Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2015
Konu: Kimya = Chemistry

Özet:
Organometalik kimya günümüzde hızla büyüyen, endüstriyel ve akademik alanda önemli yere sahip, genel anlamda metal-karbon bağlarını inceleyen bir kimya dalıdır. 18. yüzyılın ortalarında ilk organometalik bileşikler sentezlenmesine karşın en büyük gelişmeler 19. yüzyıl sonlarında Mond ve Grignard ile olmuş, 1951 yılında ferrosenin sentezi, modern organometalik kimya için bir başlangıç noktası olarak belirlenmiştir. Ferrosen, Pauson ve Miller tarafından, susuz eter içerisinde siklopentadienil ile demir(II) klorürün reaksiyonundan fulvalen sentezlemek amacıyla yapılan bu çalışma sonucu, tesadüfen turuncu renkli bir bileşik elde edilmiş, yapılan elementel analiz sonucu, Fe(C5H5)2 molekül formülüne sahip katı bir bileşik olduğu gözlenmiştir.  Yapı aydınlatılması ise Wilkinson, Fischer ve Woodward tarafından yapılmıştır. Bu iki bilim insanı bu konudaki çalışmalarıyla 1979 Nobel Kimya Ödülüne layık görülmüştür. 
Kinonlar doğada bakteri, mantar, bitki ve hayvan kökenli bulunabilen veya sentetik yollarla elde edilebilen, konjuge diketon yapılarıdır. İlk kinon sentezi, kuinik asitin yükseltgenerek p-benzokinona çevrilmesiyle gerçekleşmiştir. Basit kinonlar, tahriş edici özelliği olan, yüksek buhar basıncına sahip katılardır. Kinonlar, biyolojik ve sentetik kimya açılarından önemli yer tutan bileşiklerdir; fotosentez, kan pıhtılaşması, hücresel solunum, farmokoloji, boya, yük transfer kompleksleri, oksitleyicilik gibi  konularda kinonlar yaygın olarak kullanılır. Ayrıca antikanser ajanı nitelikli, klinik olarak test edilen binin üzerinde kinon yapısı mevcuttur. Naftakinonlar ise iki halkalı kinon yapısı olarak nitelendirilebilir. Günlük hayatta en bilinen naftakinon yapıları, pıhtılaşma ajanı olarak işlev gören, Vitamin K1 ve K2'dir. Hidroksinaftakinon türevleri olan juglon, mantar öldürücü, lavson, boyar madde, fitiyokol ise antibiyotik olarak kullanılır. Naftakinonlar, naftalendiol, aminonaftol gibi hidroksi grubu içeren naftalen türevlerinin yükseltgenmesiyle, p-benzokinonun Diels-Alder reaksiyonlarıyla veya aromatik substitüye skuarik asitin yükseltgenmesiyle sentezlenebilir.
Makrosiklik kimyada önemli yer tutan bileşiklerden olan taç eterler, 1967 yılında Pedersen tarafından sentezlenen bileşiklerdir. Taç eterler, dioksan molekülünün halkalı oligomeri olarak görülebilir; oksijen heteroatomlu türevlerinden sonra, azataç eter, tiyataç eter gibi farklı heteroatomlu türevleri sentezlenmiş ve metal katyonlarıyla ilişkisi incelenmiştir. Taç eterlerin en bilinen özelliği çözünürleştirme işlemidir. Bu sayede taç eterler  faz tranfer katalizörü olarak reaksiyonlarda etkin yer alırlar. Taç eterler sentezlendiği döneme kadar problem olarak görülen alkali ve toprak alkali kompleksleşmesine çözüm getirmiştir. Pedersen ve çağdaşları Lehn ve Cram ile birlikte sentez ve kompleksleşme çalışmalarıyla 1987 yılında Nobel Kimya ödülüne layık görülmüşlerdir. Pedersen ilk makalesinde yer verdiği dört sentetik yöntem ile, farklı türevlendirilmiş ve farklı halka boyutlarında halkaların eldesi mümkündür.
Supramoleküler kimya, moleküler tanınma ve ev sahibi-konuk etkileşimini de içine alan iki veya daha fazla türün etkileşmesini inceleyen kimya dalıdır. Supramoleküler kimyadaki atılım, "schiff" bazları ile başlarken, taç eterler, kriptanlar, siklofan, sferand ve karserandlar ile yeni bir dönem başlamıştır ve bu moleküllerin kompleksleşmeleri çeşitli gruplarca çalışılmıştır. Supramoleküler kimyada türlerin arasındaki etkileşimin ölçülebilmesi sayesinde bu alanda çalışan diğer çalışmacılara ligand dizaynı konusunda yardımcı olur. 
Endüstride sıkça kullanılan berilyum, toksik özelliklerinden ötürü hassas ve doğru miktarının tayini yapılması gerekmektedir. Berilyum oluşturduğu kompleksler sayesinde spektroskopik, elektrokimyasal, kromatografik olarak tayin edilebilmektedir. 
Bu çalışmada taç eterlerin kompleksleşme özellikleri ve yük transfer bandındaki değişimler kullanılarak, yeni sentezlenen ferrosenil naftakinon bağlı 9-taç-3 bileşiği ile UV-VIS Spektrofotometresi yardımıyla, seçici ve hassas berilyum tayini amaçlandı.
Çalışma iki aşama olarak değerlendirilebilir; ilk aşamada ligandın sentezi gerçekleştirildi. Sentezin ilk basamağında ticari olarak bulunmayan benzo-9-taç-3 (1) bileşiği sentezlendi ve bromlanarak 4'-bromo-benzo-9-taç-3 (2) bileşiği elde edildi. Sentezin diğer basamağında ise ferrosenil siklobütendion bileşiği ile 4'-bromo-benzo-9-taç-3 (2) bileşiğinin reaksiyonundan ferrosenil naftakinon bağlı 9-taç-3 (ligand; (3a) ve (3b)) molekülü iki izomer halinde sentezlendi. Sentezlenen moleküller, FT-IR, 1H-NMR, 13C-NMR, kütle spektroskopisi ve elementel analiz yöntemleri ile karakterize edildi.
Çalışmanın ikinci aşamasında ligandlar (3a) ve (3b) ile metal katyonları arasındaki kompleksleşme ilişkisi UV-VIS Spektrofotometrik titrasyon yöntemi ile yapıldı. (3a) ve (3b) bileşiklerinin, alkali (Li+, Na+, K+, Cs+), toprak alkali (Be2+, Mg2+, Ca2+, Ba2+), geçiş metal (Fe2+, Ni2+, Zn2+) katyonları ve kurşun (Pb2+) katyonu ile kompleksleşmeleri incelendi. Berilyum iyonu (Be2+) ile ligandlar, çıplak gözle bile seçilebilen bir kompleks oluşturduğu gözlendi. Ligandların diğer katyonlar varlığında Be2+ iyonunu seçici olarak bağladığı tespit edildi. Devamında kantitatif tayin için, Be2+ iyonu ile ligandın kompleksleşmesini analitik boyuta getiren tayin sınırı, kesinlik, lineer aralık gibi uygulamalar ile çalışmalar sonlandırıldı.

Abstract:
Organometallic chemistry is a branch of chemistry which examines metal-carbon bonds, and is rapidly growing in industry and academic  areas. Although the first organometallic compounds were synthesized in the middle of 18th century, the most important improvements were reached by Mond and Grignard in the last years of 19th century and in 1951.  The synthesis of ferrocene was determined as a beginning of modern organometallic chemistry. Ferrocene was obtained with the reaction of cyclopentadienyl and iron(II) chloride in the medium of anhydrous diethyl ether by Pauson and Miller. A new orange compound was obtained by coincidence during their attempt to synthesize fulvalene. The result of elemental analysis showed that this solid compound had a Fe(C5H5)2 molecule formula. However, the structure of this compound was uncovered by Wilkinson, Fischer and Woodward and their study was awarded as Nobel Prize in Chemistry in 1979.
Quinones are conjugated diketone structures which can be found in nature as bacteria, fungi, plant and animal origin or obtained by synthetic routes. The first synthesis of quinone was achieved with  the oxidation of quinic acid to form p-benzoquinone. Simple quinones are solids which have irritation feature and high vapor pressure. Quinones are significant compounds in the terms of biologic and synthetic. Generally, they are used for photosynthesis, blood coagulation, cellular respiration, pharmacology, dye, charge transfer complexes, oxidizing. In addition, there are thousands of quinone structures tested clinically as anticancer agents. Naphthaquinones can be qualified as a bicyclic quinone structures. In daily life, the most known naphthaquinone structures which are used for blood coagulation agents, are Vitamin K1 and K2. The hydroxynaphthaquinone derivatives are juglon used as anti-fungal, lauson used as dye, phthiocol used as antibiotic. Naphthaquinones can be synthesized with the oxidation of naphtalene derivatives which include naphthalenediol, aminonaphthol etc. Also it can be synthesized with the Diels-Alder reactions of p-benzoquinone or the oxidation of aromatic squaric acid. 
Crown ether compounds which hold an important place in macrocyclic chemistry was for the first time synthesized by Pedersen in 1967. Crown ethers can be viewed as cyclic oligomers of dioxane molecule. After oxygen hetero-atom derivatives, different type of hetero-atom derivatives like azacrown ethers and thiacrown ethers were synthesized and complexation specialities with metal cations were examined. The best-known feature of the crown ether is the solubilization process. Thus, crown ethers take active part in the some types of reactions as phase transfer catalyst. Crown ethers could solve the solubility problems of alkali and alkaline earth complexes in organic solvents, which was a problem until that time, the synthesis of crown ethers. Pedersen, Lehn and Cram, thanks to their first syntheses and complexation studies of crown ethers in the same period, were awarded as the Nobel Prize for Chemistry in 1987. It is possible to synthesis of new crown ethers having different substituents and different types of rings and ring sizes using the four synthetic methods given in Pedersens' the first article.
Supramolecular chemistry is the field of chemistry that includes molecular recognition and host-guest interaction or  examining the interaction of two or more species. Advance in supramolecular chemistry began with Schiff bases and crown ethers, cryptands, cyclophane, spherand and carcerand a new era began and the complexation of these molecules were studied by various groups. Thanks to the measure of the interaction between the type of supramolecular chemistry helps to design ligands to other researchers working in this field. 
Beryllium is widely used in defence, aerospace, automotive, health and electronic industries due to remarkable strength, stability and heat- absorbing specialties. On the other hand, beryllium is a very toxic element, which should be controlled in the industrial and waste disposal areas. Due to these poisonous properties,  the determination of beryllium is required precise and accurate. Beryllium can be determined by several methods, including spectrophotometric, gravimetric, spectrofluorimetric, atomic absorption spectrometric, inductively coupled plasma mass spectrometric, , inductively coupled plasma atomic emission spectrometric,ion selective electrods, optic sensors, voltammetric, high performance liquid chromatographic, gas chromatographic and modified cantilevers. Determination of beryllium was historically based on complexation of beryllium ion with sulphonyl or aza-bridged compounds, After usage of benzo-9-crown-3 as ionophore of ion selective electrod, macrocyclic compounds are used to determine beryllium ion. Crown ethers, podands, azacrown ethers were used to determine beryllium with wide concentration range and low detection limits.
In this study, we aimed to develop a new spectrophotometric method to determine beryllium ion selectively and sensitively in DMF, which was based on the  complexation of beryllium ion and newly synthesized ferrocenyl naphthaquinone fused 9-crown-3 compound. The  UV-VIS Spectrophotometric titration technique was performed following the changes of the characteristic charge transfer band of the molecule.  Experimental part can be regarded as two stages;  the ligand synthesis and the titration studies. 
The ligand was synthesized in the first stage. Benzo-9-crown-3 (1) compound as a starting compound, not commercially available, was firstly synthesized. Benzo-9-crown-3 (1) was synthesized in the presence of catechol, LiOH and 1,5-dichloro-3-oxapentane in water. The second step was the bromination of benzo-9-crown-3 (1) compound. In this reaction, NBS and benzo-9-crown-3 (1) compound were mixed in carbon tetrachloride to obtain 4'-bromo-benzo-9-crown-3 (2) compound.
In the next step of the synthesis, ferrocenyl naphthaquinone fused 9-crown-3 (3a) and  (3b) was synthesized by the reaction of 3-ferrocenyl-4-isopropoxy-3-cyclobutene-1,2-dione and lithio-benzo-18-crown-6 ether. Lithio-benzo-9-crown-3 ether was prepared from 4'-bromo-benzo-9-crown-3 (2) and n-butyllithium (n-BuLi) as a mixture in THF at low temperature (−78 °C) under a inert atmosphere. The mixture was then transferred by means of a canula into 3-ferrocenyl-4-isopropoxy-3-cyclobutene-1,2-dione solution in a different reaction vessel at low temperature (−78 °C) under a nitrogen atmosphere. The synthesis of ferrocenyl naphthaquinone fused 9-crown-3 was achieved without isolation of ferrocenyl-substituted 4-hydroxy-4-(benzoyl-9-crown-3)cyclobutenone which was dissolved in p-xylene and refluxed open to air to promote oxidation of the intermediate hydroquinone. The reaction was monitored by observing the change in color of the solution from deep purple to deep green, which was finalized when the color change persisted with disappearance of ferrocenyl-substituted 4-hydroxy-4-(benzoyl-9-crown-3)cyclobutenone. Ferrocenyl naphthaquinone fused 9-crown-3 ether was obtained as two isomers after p-xylene was evaporated at a vacuum and column chromatography was carried out. All synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis methods. 
In the second stage of the study, complexation studies between ligands (3a) and (3b) and the metal cations were examined in DMF. The complexation studies were performed by UV-VIS spectrophotometric method. In the first step of this work, alkali metal (Li+, Na+, K+, Cs+), alkaline earth metal (Be2+, Mg2+, Ca2+, Ba2+), transition metal (Fe2+, Ni2+, Zn2+) cations and lead (Pb2+) cation were studied. In DMF and at 60 °C, metal cations were examined for whether quenching charge transfer band or not. Beryllium ion (Be2+) is the only cation that quenches charge transfer band and changes green colour of the solution to yellow.  
We started the spectrophotometric titration study after we observed a strong complexation between Be2+ and ligands (3a) and (3b) in DMF. Temperature of the solution was fixed at 60 °C via the temperature controlled unit. Then 2 µL, 0,0125 M Be2+ solution was subsequently added to the solution of the ligands and their spectrum was obtained. Maximum absorptions appeared at 670 nm for (3a) and 650 nm for (3b) corresponding to the charge transfer bands of ligands decreased due to complexation with Be2+ and ligands, by this way the log function of absorption maximum were plotted versus the concentration of Be2+ to obtain linear range. 
In the next stage, temperature effect on the complexation taking place between ligands (3a) and (3b) with Be2+ were examined in the varying temperatures (25, 30, 35, 40, 45, 50, 55, 60 °C). Excess amount of Be2+ was added to the solution of the ligands and their spectra were obtained periodically. Additionally, precision, interference and limit of detection studies were done.
In conclusion, in this study we present a new selective and sensitive spectrophtometric method to determine Be2+ ion with large concentration range, short response time, non-interferenced by other cations and low detection limits.