1,2-1,8-Antrakinon substitue makro halkalı eter sentezleri

Abstract

ÖZET Son yıllarda organik kimyanın anabilim dallarından biri durumuna gelmiş olan Supramoleküller Kimyası hızla, gelişmektedir. Bu konu içinde özellikle makro halkalı eterler gerek etkin katyon bağlama özellikleri, gerekse konuya önderlik etmeleri nedeni ile supramoleküller arasında en ilginç molekül gurubunu oluşturmaktadırlar. Bu bileşikler yapısal olarak oksi-etilen veya oksi-propilen oligomerleri olup molekül konformasyonlan açısından bir katyonu çerçeveleme özelliğine sahiptirler. Ancak, yine yapıda yer alabilen yan guruplar elektron besleme yatkınlıkları oranında katyon - ligand ilişkilerini önemli oranda düzenlemektedir. Bu çalışmada, yan grup etkisi olarak aromatik yan grup etkisi ve kromofor grup etkisini incelemek üzere antrokinon-Makrohalkalı oksietilen oligomerleri üzerinde durulmuştur. Sözü geçen bu tür moleküllerin sentezleri ve davranışları üzerinde henüz çok az çalışma yayınlanmıştır. Bu maksat ile yüksek lisans çalışmamızda, 1,2-dihidroksiantrakinon ve 1,8-dihidroksiantrakinon bileşikleri Williamson sentezi ile polietilen glikollerle kondanse edilmişlerdir. Elde edilen makrohalkalı eter türevleri erime ve bozunma noktalan yüksek kararlı bileşiklerdir. Dihidroksiantrakinonlar kararlı yapı gösteren kromofor gruplar içermeleri nedeni ile yapılarından doğan bu II - ? II* ve n - ? II* optik uyarılma geçişleri makro halka üzerindeki elektron akimlan üzerinde de etki yapabilmekte ve kromofor yapılı makro halkali eterler ortaya çıkmaktadır. Bu çalışmada 1,8-dihidroksiantrakinonlar ile çalışılmasının diğer bir nedeni sterik engelli bir yapı taşıyan fakat elmas örgü konformasyonu taşımıyan bazı makrohalkalarm tanınmasına olanak vermektir. Bu neden ile 1,2-dihidroksiantrakinon (Alizarin) ve bis-kloro poliglikoller ile alkali karbonat / DMF bulunan ortamda 80 - 90 °C de 36 - 48 saat süre ile etkileştirilmişlerdir. Reaksiyon sonucu l,2-antrakinon-12-crown-4, 15-crown-5 ve 18- crown-6 bileşikleri ele geçmiştir. 1,8-dihidroksi antrakinon (Chrysazin) ve bis- kloropolglikoller ile alkali karbonat / DMF bulunan ortamda 80 - 90 °C de 24 - 36 saat süre ile etkileştirilmişlerdir. Reaksiyon sonucu uygun verimler ile dimer 1,8- antrakinon makro halkalı yeni bileşikleri ele geçmiştir. Elde edilen bu bileşiklerin tümü orjinal olup, 'H NMR, İR, ve direkt bağlantılı kütle spektrumlan gibi genel özellikleri ve katyonlu ortamda fluoresans spektroskopisi ile ligand özellikleri incelenmiştir. iv

The Synthesis of 1,2- and 1,8-Antraquinone Derivatives of Crown Ethers SUMMARY The 1987 NOBEL prize owners of Prof. J. M. Lehn, Prof, Dr. D. J. Cram and Dr. Pedersen have been working on the topic of macrocyclic ethers individually although the fact that such compounds were primarily found and recognized by Dr. Pedersen in 1967. Since than it has been published at least 1500 papers which made the topic more than a scientific area. However, what has been so far found is actually is still less than what is going to be revealed. Natural macrocyclic oligomers of nonactin of biologically active ionophores were known to bind the cations at the earliest regarding the cation-dipole type interactions explaining the complexation of alkaline and alkaline earth cations in a solution or in a solid form if complexation. Therefore the similar type of interactions with a more power and selectivity of the macrocyclic ethers so called crown ethers towards to cationic media created such an enormous interest and accordingly plenty of the reported results in the literature. However, the role of the molecules given is not only to bind the cations but also the effect of phase transfer catalyst as well as the liquid membrane and liquid- liquid extraction of the alkali and alkaline earth cations. Particular role of such cations has to be mentioned that they exist in physiological liquids like cells and the blood. They are the synthetic precursors of computing structures against the analogous expensive natural products of similar nature. Prime importance of such systems is not only the plain cation binding in liquid and solid media but also the selective interactions and preference of the hosts for particular guests. This is certainly a fitting dynamic process regarding the cation radii and macrocyclic ring size of a dynamic nature. However, as we know what the problem is actually the synthesis and the preparation of such responsive systems. This is the why those have been tried with different reaction routs to obtain even for the similar structures. Macrocyclics are naturally formed due to their template role in a Williamson reaction where the cation is chelated - at least partly - by the suitable cavities as much as the conformational route of the reacting polyoxaethylene is allowed to do. The last question but of course not the least is the nucleophilic role of the oxygen as a reaction partner to close the macrocyclic ring in an ether synthesis. Otherwise the noncyclic long chains formed in a reaction media should be an awful problem to separate which is still a question for the large scale preparations. Those are the reasons to be taken are into the consideration what type of structures to be designed and which way to follow to synthesis. This may be the reason that benzo-crown derivatives of benzo-15-crown-5 and the benzo-18-crown-6 were the first obtained simultaneously with oligocyclic crown ethers like 18-crown-6by the Dr. Pedersen. This was, however, properly obtained in a completely purified by Prof. Cram and Prof. Gokel after several years. The 1,2-dihydroxybenezene was allowed to react with 2,2-dichlorodiethyl ether in n-BuOH / NaOH to form dibenzo-18-crown-6 in a 40 % yield as we demonstrated with our under graduate students. This was followed by the other type structures, as they are exemplified with the formulas of I, II and III. Those given, I and II however, were obtained starting from non aromatic initial products therefore the Williamson synthesis was tried with glycols and their ditosylates successfully. r °` i o o o o ex I [ 1 o o o o n -O r-cT/^ o- // m However, the most trivial part of the crown ether chemistry is the nomeclature of the such molecules. The IUPAC name of the compound I is 1,4,7,10,13,16- hexaoxacyclooctadecane while it is commonly named as 18-crown-6. In fact, this way to call them is the best practically, accordingly compound II is 1,4,8,11- tetraoxacyclotetradecane wliich is named as 14-crown-4. It is nice to mention that the compound m is benzo-12-crown-4 and it has a natural IUPAC name of 2,5,8,15,18- pentaoxabicyclo[ 1 6,4,0]nonadecatriene. VIMacrocyclics are capable to bind the cations in a solution which could be converted to a solid cation ligand type of complex of high melting structure. The solution chemistry of macrocylic-cation ligand interactions were investigated with several analytical methods which are given below as the topics of also our current interest. a. Ion selective potentiometric methods, b. UV-VIS spectroscopy of chromophore side groups. c. Fluorescence emission and excitation spectra of complexes, d. Liquid-Liquid cation extraction with macrocylics in binary systems, e. NMR of the cation ligand systems. f. Effect of macrocyclics on the reaction rates. g. Phase transfer catalysis of ammonium salts. Those were the known reliable methods have been tried by potential laboratories. However, the method used for molecular recognition is also depended on the type of a macrocyclic. Regarding the cation extraction to organic nonpolar solution phases the solubility and stability is the prime role of the macrocylic ligand due to the partition in binary solvent systems for any membrane. The potentiometry is an excellent method to be tried for cation binding estimation with the ion selective electrodes although the fact that the macrocyclics have been also tried for the preparation of the membrane type of electrodes as the cation sensors in a polymer matrix NMR methods for a nonparamagnetic cation binding are the best to estimate the equilibrium constants as far our studies are concerned. The dipole-dipole relaxation time measurements of the proton and 13-C nuclei of a the macrocyclic backbones in free and cationic media revealed the binding role of the cation due to effect of complexation on the dynamic behavior of the macrocyclic backbone. Effect of a polar solvent is known to influence the ion-molecule reactions so far and this is explained with ion-pairs theory. However, the rate of nucleophilic substitutions were remarkably increased by the addition of the macrocylics even in stoichiometric amounts. The methods are also enabled one not only to examine the molecular recognition but also to determine the ionic selectivity which gives the idea for the design of a macrocyclic structure for a specific molecular recognition. On the other hand there are some rules cleared so far to justify the cation-ligand relationship and for the analogy of the binding and selectivity of an alkali or alkaline earth cation. This is primarily the relationship between the macrocyclic ligand hole size and the cation covalent or ionic radius. The rigid macrocylic lattice of proper structure limited the rate of exchange of a cation to bind. The cavities like cryptates exhibited such a role while the podands of flexible macrononcyclic structures have rather low binding power with the higher rate of ligand-cation exchange rate. This was proved and discussed in several papers with plenty of macrocyclics structures obtained in the laboratories. By this way the analytical procedures and synthetical methods were developed. Contribution of the results to almost every field of chemistry have been great so far. vııAccordingly prior to synthesize a macrocyclic host molecule we should have some idea and target for the system of a molecular recognition. The chromophores of II - * II* and n - ». II* transitions in a chrormophore-macrocyclic moiety were expected to be influenced in the vicinity of the cations. The cation-macrocyclic ligand interactions are mostly electrostatic therefore electronic interactions of photochemical nature are going to be altered by the changes on the local electric fields of the host- guest systems. The resulting effect of the red shifts or blue shifts on the optical spectra of the chromophore could be a good measure of host-guest interactions. 1,2- and 1,8-dihydroxyanthraquinones are the typical chromophores and give intensive violet to red colors in a basic aqueous media due to anionic resonance structure. They have also an interesting fluorescence spectra in a liquid and solid systems. We primarily worked on the quite well known chromophore of 1,2-dihydroxy- 9,10-anthraquinone (alizarin) which was condensed with bis-chloro or bis-tosylated polyglycols in alkali carbonates and DMF at 90-110 °C for 36- 48 hours. The corresponding macrocyclic ether derivatives of alizarin of 12-crown-4, 15-crown-5 and 1 8-crown-6 were obtained in rather moderate yields. The structural elucidation of the products were conducted with IR, NMR and Mass spectroscopy, Scheme 1. Their fluorescence spectra were altered in the presence of the alkali salts in acetonitrile solutions due to cation-ligand interactions as expected and postulated depending on our recent investigations tried with coumarin-crown ethers successfully. 0 OH U. X. XC2H4(OC2H4)mX+ ( ) OH K2C03 m 2 3 4 CI CI Tos n 0.11. ( )l ( ) -,0~ II o 2a 2b 2c 1 2 3 Scheme 1. l,8-dihydroxy-9,10-anthraquinone (Chrysazin) which was condensed with bis- bromo, bis-chloro or bis-tosylated polyglycols in alkali carbonates and DMF at 90 - 1 10 °C for 24 - 48 hours. The dimer macrocyclic ether derivatives of Chrysazin were obtained. The structural elucidation of the products were conducted with IR, NMR vmand Mass spectroscopy, Scheme 2. The cation binding properties were examined with optical UV-VIS and fluorescence spectroscopy in nonhydroxylic solvents.. XC2H4(OC2H4)mX + Na2C03 OH 0 OH 0 1 2 3a 3b 3c Scheme - 2 Such molecules exhibiting fluorescence spectra have shown show their cation binding tendency with also fluorescence spectroscopy. Their fluorescence emission and excitation spectra were altered in the presence of alkali cations in acetonitrile solutions. The fluorescence spectra of l,2-anthraquinone-18-crown-6 and its KSCN complex is given as an example in Figure 1. 10.0 7.5 - 5.0 2.5 0.0 L 450 LU tz -z. Lü // DALGA BOYU 500 550 600 650 700 Figure I. The fluorescence spectra of l,2-anthraquinone-18-crown-6 and its KSCN complex IX