Polymer-supported phase transfer catalysis

Molinari, H., F. Montanari, S. Quici, and P. Tundo, Polymer-Supported Phase-Transfer Catalysis. High Catalytic Activity of Ammonium and Phosphonium Salts Bonded to a Polystyrene Matrix, /. Amer. Chem. Soc., 101, 3920(1979). 

Svec, F., What is the Real Mechanism of Polymer-Supported Phase-Transfer Catalysi , Pure Appl. Chem, 60,377 (1988). 

Telford, S., P. Schlunt, and P. C. Chau, Mechanisms of Polymer-Supported Phase Transfer Catalysis. Effect of Phase Ratios on Low Percent Ring Substitution Microporous Polystyrene Resin, Macr-mol., 19, 2455(1986). 

At one extreme diffusivity may be so low that chemical reaction takes place only at suface active sites. In that case p is equal to the fraction of active sites on the surface of the catalyst. Such a polymer-supported phase transfer catalyst would have extremely low activity. At the other extreme when diffusion is much faster than chemical reaction p = 1. In that case the observed reaction rate equals the intrinsic reaction rate. Between the extremes a combination of intraparticle diffusion rates and intrinsic rates controls the observed reaction rates as shown in Fig. 2, which profiles the reactant concentration as a function of distance from the center of a spherical catalyst particle located at the right axis, When both diffusion and intrinsic reactivity control overall reaction rates, there is a gradient of reactant concentration from CAS at the surface, to a lower concentration at the center of the particle. The reactant is consumed as it diffuses into the particle. With diffusional limitations the active sites nearest the surface have the highest turnover numbers. The overall process of simultaneous diffusion and chemical reaction in a spherical particle has been described mathematically for the cases of ion exchange catalysis,63 65) and catalysis by enzymes immobilized in gels 66-67). Many experimental parameters influence the balance between intraparticle diffusional and intrinsic reactivity control of reaction rates with polymer-supported phase transfer catalysts, as shown in Fig. 1. 

The affinity of the polymer-bound catalyst for water and for organic solvent also depends upon the structure of the polymer backbone. Polystyrene is nonpolar and attracts good organic solvents, but without ionic, polyether, or other polar sites, it is completely inactive for catalysis of nucleophilic reactions. The polar sites are necessary to attract reactive anions. If the polymer is hydrophilic, as a dextran, its surface must be made less polar by functionalization with lipophilic groups to permit catalytic activity for most nucleophilic displacement reactions. The % RS and the chemical nature of the polymer backbone affect the hydrophilic/lipophilic balance. The polymer must be able to attract both the reactive anion and the organic substrate into its matrix to catalyze reactions between the two mutually insoluble species. Most polymer-supported phase transfer catalysts are used under conditions where both intrinsic reactivity and intraparticle diffusion affect the observed rates of reaction. The structural variables in the catalyst which control the hydrophilic/lipophilic balance affect both activity and diffusion, and it is often not possible to distinguish clearly between these rate limiting phenomena by variation of active site structure, polymer backbone structure, or % RS. 

Polystyrene has been used most often as the support for phase transfer catalysts mainly because of the availability of Merrifield resins and quaternary ammonium ion exchange resins. Although other polymers have attrative features, most future applications of polymer-supported phase transfer catalysts will use polystyrene for several reasons It is readily available, inexpensive, easy to functionalize, chemically inert in all but strongly acidic media, and physically stable enough for most uses. Silica gel and alumina offer most of these same advantages. We expect that large scale applications of triphase catalysis will use polystyrene, silica gel, or alumina. 

Nevertheless, the separation of the catalyst at the end of the reaction and, if possible, its recycling is often a limiting factor for the application of PTC. The chemical nature of the catalyst makes it at least partially soluble both in polar and apolar solvents and higher catalyst loadings are often used to maximize the effects on the reaction rates. This led very soon to the development of polymer-supported phase transfer catalysts [222], When using insoluble supports, an additional phase is added to the former biphasic system and, accordingly, the term triphase catalysis was coined (Figure 10.8) [223-225],... 

Our entry into polymer-supported phase transfer catalysts was an investigation of several empirical factors that influence catalytic activity in these complex triphase mixtures. By approaching the problem from the standpoint of reaction mechanisms one can understand better the chemical and physical features of heterogeneous catalysis. Such understanding will aid in the design of new catalysts and enable rational choice of catalysts for triphase reactions, and will be particularly important in the development of industrial processes for manufacture of fine organic chemicals and pharmaceuticals. 

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. 

In the main, the original extractive alkylation procedures of the late 1960s, which used stoichiometric amounts of the quaternary ammonium salt, have now been superseded by solid-liquid phase-transfer catalytic processes [e.g. 9-13]. Combined soliddiquid phase-transfer catalysis and microwave irradiation [e.g. 14-17], or ultrasound [13], reduces reaction times while retaining the high yields. Polymer-supported catalysts have also been used [e.g. 18] and it has been noted that not only are such reactions slower but the order in which the reagents are added is important in order to promote diffusion into the polymer. 

Numerous examples of solid/solid/liquid phase transfer catalysis are now known to be useful synthetically but have not been investigated mechanistically. Poly(ethylene glycol) immobilized on alumina and silica gel is active for reaction of solid potassium acetate with 1-bromobutane 184). Some of the best synthetic results with polymer supports are shown in Table 15. Often use of other solid salts or other catalysts gave poorer yields. It would be valuable to know for the design of future syntheses how these reactions depend on the partial solubility of the inorganic salts in the organic solvents and on the presence of trace amounts of water. 

Polymer-supported multi-site phase-transfer catalysis seems to require the use of less material in order to provide activity comparable to others253 (Table 27). Quaternary phosphonium ions on polystyrene latices, the particles of which are two orders of magnitude smaller than usual, were shown to be capable of higher activity coagulation of the catalysts under reaction conditions was minimized by specific treatment904. The spacers may also contain ether linkages. 

Apart from reactions in which anionic counterparts of phosphonium cations are essentially implicated in a phase-transfer catalysis process (polymer-supported or soluble catalysts see above), some kinds of chemical transformations in which the anion s reactivity is involved have been studied. There are two major advantages, one being experimental and the other the regenerating capability of the reagent, in monomer- or polymer-supported form. The anionic counterparts of phosphonium salts can have an influence on their own stability or structure (the formation of betaines163 and allyl-phosphonium-vinylphosphonium isomerization, for example275,278). 

In the book, the section on homogeneous catalysis covers soft Pt(II) Lewis acid catalysts, methyltrioxorhenium, polyoxometallates, oxaziridinium salts, and N-hydroxyphthalimide. The section on heterogeneous catalysis describes supported silver and gold catalysts, as well as heterogenized Ti catalysts, and polymer-supported metal complexes. The section on phase-transfer catalysis describes several new approaches to the utilization of polyoxometallates. The section on biomimetic catalysis covers nonheme Fe catalysts and a theoretical description of the mechanism on porphyrins. 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

Phase transfer catalysis is a significant advance in preparative organic chemistry, but there is a practical limitation—phase transfer agents sometimes stabilize emulsions, which make product recovery difficult. A variation of the technique, called triphase catalysis, involves bonding the phase transfer agent to a support, such as a gel-form polymer (see 14.2.4.1) . If the polymer has an affinity for boA liquid phases, the phase... 

Polymer-supported carbonate ions have proved efficient in the conversion of (237 R1=H, R2=Me R C, CHMe R2=H) to (238) (95%)192. ct-Lactams eg. (239) are fomed in high yield from the corresponding a-brcma-amides under phase transfer catalysis using quaternary armionium salts and le-crown-e1. ... 

Other areas of interest include stabilization of noncommon oxidation states, solvent extraction of cations, transfer of cations through membranes, isotopic separation, detoxification of harmful and radioactive metals, metal recovery, metal trace analysis, ion chromatography on polymer-supported cryptands, and chromo- and fluoro-ionophores. More organic-chemistry-orientated applications can be mentioned, including enhancement of metal salt solubility in organic solvents, anion activation, phase-transfer catalysis, and anionic polymerization. Many of these applications are covered in other articles in this encyclopedia as well as in the literature. 

Applications to Phase-transfer Methods.—Dehmlow has published a review on advances in phase-transfer catalysis (PTC) which discusses the introduction of crown ethers into this area. The full details are now available of a study of alkyl-substituted azamacrobicyclic polyethers (78a) as PT catalysts. When the alkyl chains are C14—C20, such molecules are very efficient catalysts in both liquid-liquid and solid-liquid phase-transfer modes, which contrasts with the lower catalytic ability of the less organophilic unsubstituted cryptand (78b). Crown ethers immobilized on polymeric supports have been demonstrated to possess increased PTC activity in 5n reactions, up to that of the non-immobilized systems, when the connection to the polymer involves long spacer chains [e.g. (79)]. 

Leznoff has published further on the solid-phase synthesis of insect sex attrac-tants. The advantages and uses of enzymes attached to solid supports have been reviewed. Aspects of triphase catalysis (organic layer-water-polymer) have been discussed by Regen, while advances in phase-transfer catalysis have been reviewed. A crown ether NAD(P)H mimic has been described,bringing synthetic chemists nearer to the objective of artificial enzyme systems. 

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