1,3-Benzotaç eterlerin sentezleri ve yapısal özellikleri

Abstract

ÖZET Bu çalışmada konu olan makro halkalı eterlerim yeni bir molekül sınıfı, 1,3 konumundaki dioksi grupları üzerinden kapanan, oksietilen halkasından oluşur. Bu bileşikler bine yakın türevi yapılan makro halkalı eterler arasında son derece az tanınmaktadırlar. Bu bileşikler genelde 1,3-dihidroksibenzen yani rezorsin türevleridirler. Çalışmalarımıza esas oluşturan sentezlerin hedefi bu grubun oluşabilen en küçük yapıdaki makro halkalarını elde etmektir. Öncelikle dibrometan ve rezorsin ile bazik ortamda yapılan çalışmalarda sentetik yönden geniş bir araştırma yapılmıştır. Bu konuda halka, ürün elde edilmesi yönünde istenilen ürünler ele geçmemiştir. Dolayısıyla template etki son derece hakimdir. Buna karşılık, rezorsin ve l,2-bis(2-kloroetoksi)etan, K2C03/DMSO bulunan ortamda eleştirildiğinde l,3-dibenzo-20-crown-6 ele geçrniştir. Buna karşın 1,2-dıbrometan yine rezorsin ile aynı reaksiyon koşullarında sadece uzun zincirli podand yapısındaki ürünlere dönüşmüştür. l,3-dibenzo-20-crown-6 ise stereokimyasal olarak son derece ilginç bir yapı sergilemektedir. İki rezorsin yan gruplarının etkisi nedeni ile bu molekül düzlemsel bir yapıya ulaşamamaktadır. Buna karşın aromatik halkaların paralel olmaları halinde özellikle Na+ iyonu için seçimli bir makro halka yapısı ortaya çıkmaktadır. Bu çalışmamızda organik sentezlerin yanında yaptığımız moleküler dinamik, MM* yöntemi ile yapılan hesaplamalar sonucu konformasyon analizleri ile molekül geometrileri ortaya konmuştur. Diğer taraftan rezorsinol (1,3-dihidroksibenzen) yine aynı koşullarda bis- kloropolietilen glikoller ile etMeştirilmiş ve l,3-benzo-13-crown-4 ve 1,3-benzo- 16-crown-5 molekülleri ile dimer l,3-dibenzo-20-crown-6 ve l,3-benzo-26-crown- 8 molekullerinin sentezleri sağlanmıştır. iv

SUMMARY Macrocyclic Ethers Cyclic polyethers are consisted from the ethylene or propyleneoxy units forming a macrocycle. Such a structure behaves as a hydrophobic exterior of hydrocarbon skeleton linked with hydrophilic oxygene donors. This type of macromolecular structures could be examplified with Figure l.a,b. The founder of such compounds, Dr. Pedersen, however, obtained the series of this molecules just accidentally [1]. In fact at least 1000 type of of similar molecules have been synthesised and their molecular recognition were conducted properly since 1967 [2] Such molecules are capable to rearrange their macrocytic backbones changing o o ^-o o-7 / I Figure 1. 1a [16]crown-5 1b. [15]crown-5 their conformations during the complex formation to orient the s electrons to almost centered strong electropositive lkali or alkaline-earth cation to bind. The process of the cation binding is thermodynamically controlled and therefore could be used to estimate the binding role of a macrocycle quantitatively. Such estimations give preferential roles to macrocycles and their functional groups which is called the molecular recognition. The binding power is of course governed by the mother solvent in solution, however, in solid state there are plenty of stable cation-ligand complexes of very high melting points and such solid structures could be identified by X-ray methods exhibiting the preferred conformation of the macrocycle. Studies with novel and classical physical and chemical methods coused excellent application of the common theories and aspects of ion-ligand interactions.The Macrocyclic Benzo Crown Ethers. The plenty of macrocyclic oligo ethers have been synthesised and characterised since the discovery of such macromolecules by Pedersen designed with oxygen donors [1]. The most popular series of such compounds are known as benzocrowns which are the oligocyclic derivatives of 1,2-dihydroxybenzene so called cathecol. Because of the low solubilities of this series of macromolecules they have been extensively synthesised and recognized so far [2]. Figure 2 and Figure 3. show the typical examples of such group of macrocycles. o o o o uo cH v-o o-7 Figure 2. Benzo[12]crown-4 Benzo[15]crown-5 Such molecules could ensemble with two aromatic rings as described in Figure 2.2. However, this molecule is one of the most well known macrocycle of the crown ether family. Macrocyclis oligo ethers are the most well known alkali and alkaline earth cation recepters of the world. They mostly attract the cations with the Coulombig forces [3]. The interactions of the cations are involved among the highly electropositive alkali or alkaline-earth cation and the 2s electrons of the oxygen in a macrocycle [3]. This is simply described in Figure 4. However, such way of doing infra structures should also be depended on the macromolecular stereocmistry the studies in this field are now full of synthesis stereochemistry, spectroscopy and the molecular recognition supplied with analytical chemistry [4]. 0 0.* -^O 0`^ ^ ^o^ Figure 3, Dibenzo [18]crown-6 VIFigure.4. The wiev of K* cation complexed [18]-crown-6 molecules. The complex formation roles of the macrocyclics have been survived with differernt analytical methods. This is shown form the work Inoue and Gokel at Table. 1 for 1 : 1 ratio complexes with the complexing free energies, AG, and LnKa of cations with the macrocyclic ether and the solvent, see Equations. 1 and 2 [5]. The role of the mother solvent is also interesting. The fact that polar organics could interact with macrocyclics forming some sort of inclusion compounds, Table l.[5] nC+ + mL ^ C+nLm Ka = [C+nLm]/[L]m[C+]n (1) (2) Table 1. The thermodynamic data for the complexation of some crown ethers at 25° C. VllThe 1,3-Benzocrown Ethers Despite the fact that 1,2-benzocrowns are very well recognized the 1,3-dioxo substituted aromatics.are little known. One of the dibenzo oligomer is given in Figure 5 in all trans forrm. The most interesting study we have ever tried is the molecules of this work we have already synthesised for about 60 different type of macro cyclic ethers of original structures since 1972 [6-16]. However, such type of molecules were tried only for twice. Once by Weber etal [17]. Stoddart et al [18]. Stoddart has now given a novel nomenclature. for such compounds namely they are called dibenzo- 3n+2-crown-n crowns, Figure 2.4. The contitutionally isomeric structures of the bismeta phenylene [BMP(3n+2)] crown ethers [19]. Figure 5' Benzo[20]crown-6 The Synthesis and Characterisation of 1,3-Benzo Macrocyclics in our Work. The origin of such compounds is mostly the 1,3-dihydroxybenzene so called as resorsin which has been condensed with polyethylene glycol dihalides and afforded mono or bis-l,3-dioxophenyl attached macrocylic ring products [17-20]. However, reported studies were not satifactorily out lined we therefore had to retry the procedures to obtain the metaphenylene and bis-metaphenylene derivatives of the crown ethers as completely pure compounds for molecular recognition via IR, NMR and Fluorescence Spectroscopy. The Spectral data and yields are given in Table 2. (See Scheme 1.) The synthesis of 1,3-Benzo Macrocyclics Accordingly, we used resorsin, la, to react with 1,2-dibromoethane in DMF or DMSO in the presence of a base like NajCOj or K2C03. However, the reaction products were mostly the open chain oligomers of metaphenylen-l,2-oxyethylene segments, see Scheme 1. However, according to GC-MS studies less then 5% the 1,3- dibenzo[14]crown-4 was dedected by LC-Mass. The reaction of resorsin, la, with P,P'-dichlorodi ethyl ether in the presence of DMF or DMSO and Na2C03 or K2C03 afforded l,3-dibenzo[20]crown-6, 3a, in good Vlllyield, Scheme 1. la, reacting with l,9-dichloro-4,7-dioxononane in presence of DMF or preferably in DMSO and Na2C03 or K2C03 gave 3b and 3c as the reaction products.. However, resorsinol, la, reacting with dichlorotetraethylene glycole in the presence of DMF and NajCOj or K2C03 gave the oligo-l,3-benzocrown ethers, like 3d, (see Table 2) OH II + OH la o 2b DMF CI K2C03 OH OH la / / Br Br DMF K2C03 OH + o o OH n (0,1.2) OH OH a ci DMSO K2C03 la 2c (m=2), 2d (m=3) o* C °J *- O O-' Scheme 1. The products of synthesis of 1, 3 -benzo derivatives of some macrocyclics and podands The structures of the products were identified with the Electron impact Mass Spectroscopy from FISONS, IR spectra as KBr from PERKİN ELMER, 'H - NMR and 13C - NMR spectra as well some 2D methods like HETCO with a 400 MHz NMR spectrometer from BRUKER IXThe Stereochemistry of 1,3-Benzo Macrocyclics. The stereochemistry of the crown ethers is the most dominating factor for the molecular recognition and cation binding. The most common method is of caurse the X- ray studies conducted with single crystall probes of the macromolecules [21]. The concept of preorganized macrocycle cavity size and the molecular geometry has been valuable especially for the cation selectivity [1-5]. Excellent reviews of X-ray crystallography of coranands have benn reported recently [22,23]. B D Figure 6. The conformational isomers of l,3-dibenzo[14]crown-4 obtaimed with MM+.Goldberg has emphasized that the bond distances and bond angles are quite similar in all complexes as well as in the uncomplexed macrocycles and the the changes in torsional angles control the cavity size therefore, crystal forces only minimally affect molecular geometry [22]. Sanger has shown the role of counter ions and water on cavity size in several macromolecular ionophores [23]. Accordingly some examples are given on Figure 3 the [18]crown-6 has a complex with D3d point group while the hexa oxygen member of free macrocycle posesses the Cx conformation. In the presented work we have particularly studied the conformations of 1,3- dibenzo[14]crown-4 and l,3-dibenzo[20]crown-6 structures with molecular mechanics using MM+ metod [24]. However, conformational energies may differ depending on the methods of mathematics and parameters used for the energy minimisation program [25,26]. The conformatonal analysis of l,3-dibenzo[14]crown-4 has shown extremely interesting results. Results primarily explained why the formation of smallest size of the 1,3-dibenzocrowns is too hard as given in experimental part, (see Figure 5) We hereby tried the MM+ in Hyper ©Chem.as a subroutine from Polak-Ribiere and obtained conformational isomers of l,3-dibenzo[14]crown-4 of different steric energies are represented in Table 3. The trans,traas isomer with 22.14 kcal/mol total energy, Figure 5A is minimized to 10.69 kcal/mol of ±gauche,±gauche isomer, Figure 5D. Figure 7. The different conformational isomers of l,3-benzo[20]crown-6 obtained with MM+ calculations using Hyperchem Software. XITable 3. The total energy of conformational isomers of l,3-benzo[14]crown-4 from MM+ The conformatonal analysis of l,3-dibenzo[20]crown-6 has also shown interesting results. Results primarily explained why the formation of medium size of the 1,3- dinzocrowns is too easy ( Scheme 1.) We hereby used the MM+ in Hyper ©Chem.as a subroutine of Wiberg's seepest decent and obtained conformational isomers of 1,3- dibenzo[20]crown-6 of different energies are represented in Figure 6, Table 4. The trans,trans, trans,trans isomer with 22.09 kcal/mol total energy, Figure 6.A is minimized to 20.01 kcal/mol of ±gauche,trans,trans,trans isomer, Figure 6B then increased to 24.31 kcal/mol with the.± >gauche,trans,gauche, trans isomer which is converted to 26.28 kcal/mol with a uniform conformation sequence of ±gauche,±gauche, ±gauche, igauche as depicted Figure 6D, see Table 4 Table 4. The total energy of conformational isomers of l,3-benzo[20]crown-6 from MM+ XllThe Synthesis of 1,3-dibenzocrown Ethers. The genaral procedure for 1,3-dibenzo crowns obtained in this work is given as follows. Resorcinol (4.64 g, 0.042 mol), 2,2'-dichlorodiethyl ether ( 6.0 g, 0.021 mol) Sodium carbonate (8.48 g, 0.042 mol) and DMSO (60 ml ) are refulxed for 72 hr at 90- 100 °C during strring with a mechanical stirrer. The mixture is then acidified and diluted with water (100 ml), then extracted with CHC13 (2 x 100 ml). Collected extratcs are dried with Alumina (Basic, 5 g) and evaporated until dryness and purified with colum chromatograpy ( 40 gr alumina, 80 x 2 cm ). Yelds and the spectral data is given in Table 2 for compound 3a,3b The Synthesis of 1,3-benzocrown Ethers. The genaral procedure for 1,3-benzo crowns obtained in this work is given as follows.Resorcinol (5.0 g, 0.045 mol), bis-dichloropolyglycol ( 0.022 mol) Sodium carbonate (9.70 g, 0.045 mol) and DMF (60 ml ) are refulxed for 72 hr at 90-100 °C during strring with a mechanical stirrer. The mixture is then acidified and diluted with water (100 ml), then extracted with CHC13 (2 x 100 ml). Collected extratcs are dried with Alumina (Basic, 5 g) and evaporated until dryness and purified with coulum chromatograpy ( 40 gr alumina, 80 x 2 cm ). Yelds and the spectral data are given in Table 2 for compounds 3c,3d. xin