Macrocyclic ether-containing

We first confirmed the formation of these macrocycles in the polymerization of THF by using coupled gas chromatography/mass spectrometry ( 2). Macrocyclic ethers containing up to 8 THF units could be separated and identified by this method (23). The two predominant macrocyclic species found in THF polymerization mixtures are a cyclic tetramer and a cyclic pentamer. In analogy to the "crown ether" nomenclature, we proposed the name 20-crown-4 for the cyclic tetramer and 25-crown-5 for the cyclic pentamer (22). 

The principle of cyclopolymerization has been applied to the synthesis of macrocyclic ether-containing polymers which may simulate the properties of crown ethers. l,2-Bis(ethenyloxy)benzene (a 1,7-diene) and l,2-bis(2-ethenyloxyethoxy)benzene (a 1,13-diene) are typical of the monomers synthesized. Homopolymerization of the 1,7-diene via radical and cationic initiation led to cyclopolymers of different ring sizes homopolymerization of the 1,13-diene led to cyclic polymer only via cationic initiation. Both monomer types were copolymerized with maleic anhydride to yield predominantly alternating copolymers having macro-cyclic ether-containing rings in the polymer backbone. 

Macrocyclic polyethers containing the 2.2-paracyclophane unit are interesting structures and several such compounds have been prepared . Despite the diverse structural possibilities, the syntheses of these molecules have generally been accomplished by straightforward Williamson ether syntheses. The only unusual aspect of the syntheses appears to be a novel approach to certain paracyclophanes developed by Helgeson (see footnote 7a in Ref. 91). The first step of Eq. (3.28) illustrates the formation of the required tetrol, which is then treated with base (KOH or KO-t-Bu) and the appropriate diol dito-sylate to afford the macrocycle. 

Although most of the macrocycles that contain phosphorus or arsenic which have thus far been prepared, are primarily transition metals binders, two compounds have been prepared which are essentially crown ethers containing phosphorus. Kudrya, Shtepanek and Kirsanovhave prepared two compounds which are essentially polyoxygen macrocycles but which contain one or two methylphosphonic acid esters as part of the ring. These two macrocycles are shown below as 7d and 17 and are both prepared by the reaction of 2,2 [oxybis(ethyleneoxy)] bisphenolate with methylphosphonic dichloride in a mixture of acetonitrile and benzene. The crystalline monomer 16) and dimer 17) were isolated in 17% and 11% yields respectively as indicated in Eq. (6.13). 

Colquhoun at ICI first reported the synthesis of macrocyclic monomers containing ether and ketone linkages through nickel-catalyzed coupling of... 

Synthetic routes to macrocyclic ligands containing tellurium are still very limited, mainly because of the difficulties in sequentially introducing the necessary Te centres into organic fragments, the weakness of the Te C bonds and the unavailability or instability of many Te-containing analogues of the precursors for thio- and seleno-ether macrocycles. 

The most prominent application of the Ru-arene chemistry has been for the preparation of biaryl ethers in the syntheses of portions of vancomycin,467 ristocetin (Equation (127)),462,468-473 and teicoplanin (see also Section 10.14.1.2).474-476 Additional applications477-479 have included the syntheses of the macrocyclic biaryl ether-containing compounds K-13480,481 and OF4949-III,481,482 several macrocyclic depsipeptides,483,484 and poly(phenylene oxide) polymers.485... 

Anionic units have not only been attached to macrocyclic polyethers via flexible arms but have also been incorporated into the cycle itself. Alberts and Cram (1976, 1977) have studied the ion-binding properties of crown ethers containing / -diketone units, such as [72] and [73]. 

Finally, by introducing the aryl halide into the isocyanide component, as in 96, various macrocyclic peptidomimetics containing a nonsymmetrical endo biaryl ether bridge have been synthesized [89-91]. Aryl nucleophilic substitution also takes place in this case under standard base-promoted conditions. The synthesis was also carried out on solid phase. Selected examples are shown in Fig. 19, but also a... 

Cristau P, Vors JP, Zhu JP (2001) A rapid access to biaryl ether containing macrocycles by pairwise use of Ugi 4CR and intramolecular SNAr-based cycloetherification. Org Lett 3 4079 82... 

Although the majority of reports of macrocycles in analytical chromatography have involved ligand association with the stationary phase, their use as mobile phase constituents has also been investigated. Lamb and Drake [11] showed that addition of water-soluble crown ethers to the mobile phase altered the retention of alkali metal cations on an underivatized reversed phase column. Nakagawa et al. [63-66] also used crown ether-containing mobile phases in the separation of protonated amines, amino acids and peptides, and [1-lactam antibiotics. 

The template syntheses of macrocyclic ligands, containing N,P-, P,P-, S,S-, and 0,E-atoms (E = S, Se, Te) [318,358] as donor centers have been reported. The possibility of formation of binuclear structures on a metal matrix using fragments of crown-ethers is shown [318]. However, a detailed examination of these syntheses is beyond the limits of the present monograph. 

Besides the ferrocene crown ether ligands described earlier, a variety of related macrocyclic ferrocenophanes containing various sulfur, oxygen, and nitrogen heteroatoms have been reported by a number of groups (110-115) (Scheme 21). These ligands complex transition metal guest cations such as Ag(I), Cu(I), and Pd(II) (116,117). Of particular... 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

The ratio of the size of the metal ion and the radius of the internal cavity of the macrocyclic polyether determines the stoichiometry of these complexes. The stoichiometry of these complexes also depends on the coordinating ability of the anion associated with the lanthanide. For example, 12-crown-4 ether forms a bis complex with lanthanide perchlorate in acetonitrile while a 1 1 complex is formed when lanthanide nitrate is used in the synthesis [66]. Unusual stoichiometries of M L are observed when L = 12 crown-4 ether and M is lanthanide trifluoroacetate [67]. In the case of 18-crown-6 ligand and neodymium nitrate a 4 3 stoichiometry has been observed for M L. The composition of the complex [68] has been found to be two units of [Nd(18-crown-6)(N03)]2+ and [Nd(NCh)<--)]3. A similar situation is encountered [69] when L = 2.2.2 cryptand and one has [Eu(N03)5-H20]2- anions and [Eu(2.2.2)N03]+ cations. It is important to note that traces of moisture can lead to polynuclear macrocyclic complexes containing hydroxy lanthanide ions. Thus it is imperative that the synthesis of macrocyclic complexes be performed under anhydrous conditions. 

The high yields in cesium assisted crown ether syntheses may be attributed partly to a template effect of the cesium ions. In order to estimate the importance of such a template effect in cesium assisted cyclization reactions, Kello and Kruizinga [51 a] synthesized a series of macrocyclic lactones containing an oligo-methylene chain, for which a coordination of cesium ions can be excluded. 

These macrocyclic ethers assume a crown-like shape in solution with a central cavity capable of containing a small solute. They bind to small cationic species through association with the electron-rich oxygens of the ether linkage. Chiral crown ethers (Fig. 31) serve as selectors for enantiomeric amines in the protonated state. They have been used as mobile-phase... 

An example of crown ether applied in selective separation of alkali metals is dibenzo-18-crown-6 (formula 1.15). Extractive separations of metal ions are also performed with macrocyclic ligands containing nitrogen or oxygen atoms, as well as macrocycles with combinations of oxygen, nitrogen, and sulphur atoms (N-0, S-0, N-S) [45,48]. A macrocyclic compound with only nitrogen hetero-atoms (formula 1.16) is selective for copper. 

For example, dibenzo[18]crown-6 is a crown ether with an 18-membered macrocyclic ring containing six oxygen atoms with two benzo substituents. A more generalised system of nomenclature for such neutral organic ligands was developed by Vogtle and Weber, and later modified by in which... 

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