Polymer-supported crown ethers

S)-2-Aminopropyl benzyl ether, polymer-supported reagent. The polymer is prepared by reaction of the N-phthaloyl derivative of (S)-2-aminopropanol with the Merrifield polymer in the presence of KH and 18-crown-6 in THF/HMPT followed by hydrazinolysis. 

Coating of a solid support material with a crown ether polymer... 

Polymeric crown ether resins are mechanically unstable and are, therefore, operated with low flow rates between 0.05 and 0.1 mL/min resulting in long analysis times. Typical for all polymeric crown ether phases is the relatively low chromatographic efficiency, which does not meet today s requirements. However, this problem can be overcome by immobilizing crown ether polymers on the surface of a solid support. Modified and non-modified silica are predominantly used as support materials. Igawa et al., for instance, coated silica particles with the above-mentioned polyamide crown ether resin and obtained significantly better separations then with the rmcoated resin. 

Another study of polymer-supported crown ethers prepared by the reaction poly(ethylene or propylene glycols) with crosslinked chloromethylated polystyrene is presented by Warshawsky et al. [6]. In Fig. 5 the structure of these crown ether polymers is shown. 

Polymer supported xanthene derivatives have been used in the solid phase synthesis of 1-aminophosphinic acids, RCH(NH2)PH(0)0H, <%TL1647> and of C-terminal peptide amides <96JOC6326>. Xanthene units also feature in crown ethers <96JCS(P2)2091>, calixarenes <96JOC5670> and in a flexible template for a P-sheet nucleator <96JOC7408>. 

In terms of chelating systems, nitrogen and oxygen donors (bipyridine, phenanthroline, crown ethers, etc.) have also been attached to polymer supports (364), as well as chelating phosphorus donors (see Section IV,B). 

With a view to producing catalysts that can easily be removed from reaction products, typical phase-transfer catalysts such as onium salts, crown ethers, and cryptands have been immobilized on polymer supports. The use of such catalysts in liquid-liquid and liquid-solid two-phase systems has been described as triphase catalysis (Regen, 1975, 1977). Cinquini et al. (1976) have compared the activities of catalysts consisting of ligands bound to chloromethylated polystyrene cross-linked with 2 or 4% divinylbenzene and having different densities of catalytic sites ([126], [127], [ 132]—[ 135]) in the... 

In contrast, liquidiliquid phase-transfer catalysis is virtually ineffective for the conversion of a-bromoacetamides into aziridones (a-lactams). Maximum yields of only 17-23% have been reported [31, 32], using tetra-n-butylammonium hydrogen sulphate or benzyltriethylammonium bromide over a reaction time of 4-6 days. It is significant that a solidiliquid two-phase system, using solid potassium hydroxide in the presence of 18-crown-6 produces the aziridones in 50-94% yield [33], but there are no reports of the corresponding quaternary ammonium ion catalysed reaction. Under the liquidiliquid two-phase conditions, the major product of the reaction is the piperazine-2,5-dione, resulting from dimerization of the bromoacetamide [34, 38]. However, only moderate yields are isolated and a polymer-supported catalyst appears to provide the best results [34, 38], Significant side reactions result from nucleophilic displacement by the aqueous base to produce hydroxyamides and ethers. 

With soft anions crown-ethers are more efficient than quaternary salts, the reverse being observed when less polarizable nucleophiles are used. This is explained by the different extent of complexation of crown-ethers which depends not only on the complexed cation, but also on the anionic counterpart. Swelling and hydration measurements of polymer-supported crown-ethers in toluene/aqueous KY showed that the content of water in the imbibed solvent increases with the loading. This leads to a progressive polarity increase within the polymers and to a better crown-ether complexing... 

Polymer-supported crown ethers and cryptands were found to catalyze liquid-liquid phase transfer reactions in 1976 55). Several reports have been published on the synthesis and catalytic activity of polymer-supported multidentate macrocycles. However, few studies on mechanisms of catalysis by polymer-supported macrocycles have been carried out, and all of the experimental parameters that affect catalytic activity under triphase conditions are not known at this time. Polymer-supported macrocycle... 

The dependence of kobsd on stirring speed for Br-I exchange reactions with polymer-supported crown ethers 34 and 35 has been determined under the same conditions as with polymer-supported phosphonium salts 1 and 4149). Reaction conditions were 90 °C, 0.02 molar equiv of 100-200 mesh catalyst, 16-17% RS, 2% CL, 20 mmol of 1-bromooctane, 200 mmol of KI, 20 ml of toluene, and 30 ml of water. Reaction rates with 34 and 35 increased with increased stirring speed up to 400 rpm, and were constant above that value. This result resembles that with polymer-supported onium ion catalysts and indicates that mass transfer as a limiting factor can be removed in experiments carried out at stirring speeds of 500-600 rpm, whatever kind of polymer-supported phase transfer catalyst is used. 

As with polymer-supported onium ions the degree of cross-linking of the polymer support is likely to affect mainly intraparticle diffusion in reactions with polymer-supported crown ethers or cryptands. The activity of catalyst 37 decreased by a factor of about 3 as % CL with divinylbenzene changed from 1 % to 4.5 % 146). 

The activity of polymer-supported crown ethers depends upon the degree of substitution of the polymer support. Fig. 11 reports dependence of kobsd on % RS and solvent for iodide displacement reactions (Eq. (4)) with catalysts 34,35 and 41149). The rate with 6% RS 41 was smaller than that with 17 % RS 35, though the former catalyst had a 7-atom spacer. Reduced % RS makes the catalysts more lipophilic, and results in the slower intraparticle diffusion of the KL Therefore, the lowest % RS catalysts... 

The activity of polymer-supported crown ethers is a function of % RS as shown in Fig. 11 149). Rates for Br-I exchange reactions with catalysts 34, 35, and 41 decreased as % RS increased from 14-17% to 26-34%. Increased % RS increases the hydro-philitity of the catalysts, and the more hydrated active sites are less reactive. Less contribution of intraparticle diffusion to rate limitation was indicated by less particle size dependence of kohMi with the higher % RS catalysts149). 

Complexation constants of crown ethers and cryptands for alkali metal salts depend on the cavity sizes of the macrocycles 152,153). ln phase transfer nucleophilic reactions catalyzed by polymer-supported crown ethers and cryptands, rates may vary with the alkali cation. When a catalyst 41 with an 18-membered ring was used for Br-I exchange reactions, rates decreased with a change in salt from KI to Nal, whereas catalyst 40 bearing a 15-membered ring gave the opposite effect (Table 10)l49). A similar rate difference was observed for cyanide displacement reactions with polymer-supported cryptands in which the size of the cavity was varied 141). Polymer-supported phosphonium salt 4, as expected, gave no cation dependence of rates (Table 10). 

The activity of polymer-supported crown ethers depends on solvent. As shown in Fig. 11, rates for Br-I exchange reactions with catalysts 34 and 41 increased with a change in solvent from toluene to chlorobenzene. Since the reaction with catalyst 34 is limited substantially by intrinsic reactivity (Fig. 10), the rate increase must be due to an increase in intrinsic reactivity. The reaction with catalyst 41 is limited by both intrinsic reactivity and intraparticle diffusion (Fig. 10), and the rate increase from toluene to chlorobenzene corresponds with increases in both parameters. Solvent effects on rates with polymer-supported phase transfer catalysts differ from those with soluble phase transfer catalysts60. With the soluble catalysts rates increase (for a limited number of reactions) with decreased polarity of solvent60), while with the polymeric catalysts rates increase with increased polarity of solvent74). Solvents swell polymer-supported catalysts and influence the microenvironment of active sites as well as intraparticle diffusion. The microenvironment, especially hydration... 

Polymer-supported onium ions are relatively unstable under severe conditions, especially concentrated alkali154). Polymer-supported crown ethers and cryptands are stable under such conditions. In practice, they could be reused without loss of catalytic activity for the alkylation of ketones under basic conditions, whereas the activity of polymer-supported ammonium ion 7 decreased by a factor of 3 after two recycles of the catalyst147). 

Crown ethers and cryptands, either alone or fixed on a polymer support [2.89], have been used in many processes, including selective extraction of metal ions, solubilization, isotope separation [2.90], decorporation of radioactive or toxic metals [2.17, 2.49], and cation-selective analytical methods [2.89, 2.91, 2.92] (see also Sect. 8.2.2 and 8.4.5). A number of patents have been granted for such applications. 

Alexandratos, S. and Stine, C. (2004) Synthesis of Ion-selective Polymer-supported Crown Ethers A Review, React. Fund. Polymers 60, 3-16. 

Roska, A., Klavins, M., and Ziemanis, A.. High-molecular-weight catalysts in organic-synthesis. XIX. New method of synthesis of polymer supported crown ethers, iMtv. PSR Zinat. Akad Ve.sti.s Kim. Ser., 458, 1988 Chem. Ahstr., 110, 192.545, 1989. 

Polymer-supported crown ethers, cryptands, and polyethylene glycols in organic synthesis 87MI43. 

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