Bazı spiro grubu bağlı makro halkalı eterlerin sentezleri

Abstract

Bu çalışmada makrohalkalı eterlerin sentezleri ile ilgili olarak bir "spiro crown-eter" sentez yöntemi ge liştirilmiştir. Bu yöntemde pentaer itritil tetrahaloje- nurlerin pol ietilengl ikoller in sodyum tuzları ile etki- leşt ir ilmesi ve bundan yararlanarak spiro grubu taşıyan makro halkalı eter sentezinin gerçekleştirilmesi Üzerinde durulmuştur. Bu reaksiyonlarda, THF, DÎOKSAN, DMF ve DMSO gibi polar çözücüler kullanılmış ve çözücünün reaksiyon hızı Üzerine açıkça etkisi gözlenmiştir. Diğer taraftan halojenlerin etkinliği de ilginç bir şekilde ortaya çıkmıştır. Pentaeritritiltetraklörürler, yavaş etkileşmekte ve birkaç ara urun vermekte iken pentaeritritil tetra- bromürler aynı reaksiyon süreleri içinde istenilen ürünleri vermişlerdir.

The macrocycle types discussed so far tend to form very stable complexes with transition metal ions and, as mentioned previously, have properties which often resem ble those of the naturally occurring porphyrins and cor- rins. The complexation behavior of these macrocycles contrasts in a number of ways with that of the second major category of cyclic 1 igands-the 'crown' polyethers. In 1987, a seminal paper describing the syntheses of thirty-three cyclic polyethers was published CI]. All are simple monocyclic rings-a general macrocycl ic category sometimes termed the coronands. In Pedersen' s study, the first 1 igand was prepared because of the appearance of its molecular model and its ability, on coordination, to 'crown' a metal ion, this and other members of the series were referred to as crown compo unds. The trivial names consist of, in order: Ci3 the number and kind of attached hydrocarbon rings, CixD the number of atoms in the polyether ring, CxnD the class name, crown, and CivD the number of oxygens in the polyether ring. Following the original paper, reports of the syn thesis of new crowns and crown-like molecules prolifera ted. A typical property of these systems is their abi lity to form stable complexes with the alkali metal and alkaline earth ions. Prior to synthesis of the crowns, the coordination chemistry of the above ions with orga nic 1 igands had received very title attention. A fur ther impetus to the study of such complexes was the re cognition of the important role of Na, K, Mg and Ca ions in biological systems. Apart from metal ions, many of these polyether compounds also exhibit complexing ability Cand often specificity!), for arrange of other inorganic and organic cations as well as for a variety of neutral molecules. -v- Complexes such as these, which contain species incorpo rated in the macrocycl ic cavity, are usually known as 'inclusion complexes' ; the general area covering the binding of all types of substrates in molecular cavities often being referred to as * host-guest ' chemistry. General Consideration In Crown Ether Synthesis Condensation reactions, often at medium to high dilution, have usually been used to obtain new crown polyethers C23. For the majority of such crowns, two carbon atoms link consecutive ether oxygens in the res pective rings. This structure feature, in part, a ref lection of the ready availability of suitable precursors C such as catechol or ethylene oxide and their derivati ves D for synthesizing rings of this type. Further, the cycl ic products obtained from such precursors tend to form more stable metal complexes C containing f ive-mem- bered chelate rings D than species incorporating longer or shorter bridges between the oxygens. Representat ive Cycl izat ions Typically, a given cycl izat ion involves nucleophi- 1 ic displacement of a hal ide or tosylate by alkoxide or phenoxide ion C that is, a Williamson synthesis 3 even though such reactions are frequently quite slow. Pro ducts may be converted into the corresponding cyclohex- zane derivatives by hydrogenat ion, typically in butanol, over a ruthenium catalyst. A range of crowns incorporating fur an or tetrahyd- rofuran heterocyclic rings have been synthesized. The general preparation of rings of this type has involved condensation of 2,5-bisChydroxymethylDf uran with a poly- ether ditosylate in tetrahydrof uran as solvent C3,4]. Effects Of Chain Length On Cycl izat ion The effect of chain length on cycl izat ion of a series of acyclic precursors of benzo-crowns has been studied. In accordance with kinetic data, calculations -vt- of the Monte Carlo type indicate that the probability of adoption of a conformation with a small ' head-to-tail ' distance makes a signification contribution to the cyclization rate for the small to medium rings. Tempi at e Con t r i but i ons Alkali metal ions have been documented to play a template role in a number of crown syntheses. Thus, for example, the presence of K been shown to promote the formation of 18-crown-6 in syntheses £53. The ideal template metal in such procedures appears, once again, to be one that best fits the cavity of the cycl ic pro duct. The small Li has been used to aid formation of 12-crown-4 while larger Na was used for lS-crown-S. Kinetic aspects of 'the use of alkali metals as templates for the formation of other crowns have been studied in some depth. The results of such investigat ions parallel the previous observations - namely, that the catalytic efficiency of such ions in promoting cyclization shows a strong tendency to parallel their strength of binding with the crown products C this in turn often correlates with the fit of the metal ion for the macrocycl ic cavity in the product D. Metal -I on Binding Properties Pedersen* s paper marked the beginning of a new and major development in the study of the metal -ion chemis try of macrocycl ic 1 igands. The crown exhibit a number of unusual properties such as the ability to form comp lexes with alkali metal ions which, on certain cases, stable in aqueous solution. Indeed, they also yield stable complexes of a range of non - transition metal ions but tend to bind less strongly to transition metal ions. Pedersen showed that rings incorporating between five and ten oxygen atoms tended to form the most stable complexes and complexes with some or all of the following metal ions were isolated : Li,Na, K, Rb, Cs, Ag, Au, Ca2, Sr2, Ba, Cd, Hg, La, Tl, Ce, and Pb. In such compounds the ether -oxygen interactions with the metal cation were considered to be essentially electrostatic. -vii- Since this original work many new crowns have been synthesized and their complex formation has been very extensively studied. Complexes with many other ions C including weak complexes with several transition ionsD have been characterized. Crystalline 1:1 C metal : 1 igand} 1:2, and 2:3 complexes as well as species of other stoi- chiometry have all been isolated. Since 1970, when binuelear complexes of organic macrocycl ic 1 igands were first reported, this area off coordination chemistry has seen intensive growth. Stimulations proceeded from interest in metalloenzymes, homogeneous catalysis, electrical conductance, and mag netic - exchange processes. As a result, most of the research was focussed on transition-metal coordination. Multisite 1 igands which make possible a close neighbor hood of more than one alkali or alkaline earth metal ion are still rather rare. Although new practical applica tions are imaginable, mixed systems for the common comp- lexation of alkali and transit ion -metal ions are almost known. Recently a concept for the synthesis of a novel type of multisite receptors by which any number and type of macrocycl ic binding compartment was shown can be linked together via a spiro skeleton. The multiplicity and variability in ring aggregation is demonstrated by the 1 igands can be described and represented by formulas in Chapter 3, equ. 3. 2. In the presented work a novel method was developed for the synthesis of the spirobi - crown ethers starting form the pentaerythritol tetrahal ides reacting with disodio salts of polyethylene glycols in polar solvents like DMSO e.g. Some of the reactions of penterythr ityl tetrahal ides formed cyclic mono ethers as well as bi- cycl ic ethers. Primarily, it was reported that the above mentioned compounds were prepared starting from the d i hal ides or di tosylates of the polyglycols reacting with pentaerit- hritol to give spirobi - crowns. Such molecules were reported to exhibit extraordinary binding properties. They were even able to form stable Li+ complexes with the 1:1 and 2:1 stoichiometry. Accordingly, this type of derivatives have not been deeply investigated in the recent studies we therefore found this topic rather interesting to work. -viii- However, the presented comprehensive study covers the investigation of the role of the solvent in all of the substitution reactions like THF, DIOXANE, DMF and DMSO and the role of hal ides in the substrates used like pentaerythr ithyl tetrachlorides and tetrabromides. Namely, the tetra hydroxy groups of pentaerythr itol reacted with thionyl chloride or thionyl bromide to give the principal pentaerythr i t yl tetrahal ides in very good yields. This method was shown to be good at least to compare those of the preparation methods tried with the phos phor us t r i hal i des. The Williamson reactions were started with sodium and glycole in THF or Dioxane under dry nitrogen. After the complete reaction of sodium with glycole the tetra hal ide dissolved in dioxane was added into the reaction flask under nitrogen. The r act ion was continued for 36- 48 hours during stirring. The products were usually obtained as the sodium hal ide salts of the spirobi - crowns complexes as the solids. The reaction route were followed by gas chro matography. The samples withdrawn from the reaction flask analysed directly by gas chromatography on a SE - 30 column. The reaction products of each run were followed until a certain concentration was consumed. The role of the solvent was quite drastic and in general favors the formation of desired product in the order of the polarity and the dielectric ity. Likewise, THF partially gave rise to form some cyclic products while DMF let to form complete cyclization regarding the mono and bicyclic products. Consequently, the formation of the spiro groups are involved in two steps, first and then forming second rings of the molecule. It is interesting to note that the poor reagents like pentaer ithr ityl tetrahal ides or the poor solvent like THF, or even DMF give rise the formation of only the first step instead of complete formation of double loop of a spiro crown. Pure products were then isolated and purified by column chromatography on Al O and Benzene. Results were analysed by Mass spectroscopy, high resolution C-NMR spectroscopy and FT-IR spectroscopy. -ix- Structural, studies tried with above methods showed that there is a great conformational difference between the free and complexed spiro crown molecules showing the strong cation binding behaviour.