Immobilized phase transfer catalyst

Immobilized phase transfer catalysts can be expected to demonstrate the same advantages as other immobilized catalysts. 

All silica immobilized phase transfer catalysts previously reported involve two or more steps for the immobilization. Problems with preparations of this type include the difficulty in obtaining maximum functionality on the substrate and residual substrate bond intermediates which may interfere in final applications. The purpose of this work was to prepare well-characterized functionalized phase transfer catalysts that could be immobilized on siliceous substrates in a single step. As will be shown the preparation of functionalized onium catalysts proceeds readily. The route to facile immobilization of crown ether was not so direct. Avenues for high yield chemistry employing accessible or economic intermediates were not available. A new class of crown ethers which are readily functionalized during synthesis was developed. We have designated than "silacrowns". This report concentrates upon the properties and characterization of these new phase transfer catalysts. 

Substrate limitations have been documented and quantitatively described ( U, 2, 17 ). Dooley et al. (11) present an excellent description of modeling a reaction in macroreticular resin under conditions where diffusion coefficients are not constant. Their study was complicated by the fact that not all the intrinsic variables could be measured independently several intrinsic parameters were found by fitting the substrate transport with reaction model to the experimental data. Roucls and Ekerdt (16) studied olefin hydrogenation in a gel-form resin. They were able to measure the intrinsic kinetic parameters and the diffusion coefficient independently and demonstrate that the substrate transport with reaction model presented earlier is applicable to polymer-immobilized catalysts. Finally, Marconi and Ford (17) employed the same formalism discussed here to an immobilized phase transfer catalyst. The reaction was first-order and their study presents a very readable application of the principles as well as presents techniques for interpreting substrate limitations in trlphase systems. 

Liquid-liquid-solid reactors are commonly used for biphasic reactions catalyzed by immobilized phase-transfer catalysts (which form the third, solid phase). Certain basic aspects of such reactors were considered in Chapter 19. Three-phase reactions of this type are also encountered in biological reactions, for example, the enzymatic synthesis of amino acid esters in polyphasic media (Vidaluc et al., 1983), and the production of L-phenylalanine utilizing enzymatic resolution in the presence of an organic solvent (Dahod and Empie, 1986). Predictably, the performance of these reactors is influenced by the usual kinetic and mass transfer aspects of heterogeneous systems (see Lilly, 1982 Chen et al., 1982 Woodley et al., 1991a,b). Additionally, performance is also influenced by the complex hydrodynamics associated with the flow of two liquids past a bed of solids (Mitarai and Kawakami, 1994 Huneke and Flaschel, 1998). It is noteworthy, for instance, that phase distribution within the reactor is different from that in the feed and is also a function of position within the reactor and within the voids of each pellet in the bed. More intensive research is needed before these reactors can be rationally designed. 

The synthesis of polymer-supported crown ethers and the use of the latter as immobilized phase transfer catalysts in the halogen exchange reaction of 1-bromo-octane with potassium iodide has been reported. ... 

Tun1978 Tundo, P, Easy and Economical Synthesis of Widely Porous Resins Veiy Efficient Supports for Immobilized Phase-Transfer Catalysts, Synthesis, (1978) 315-316. 

An ionic surfactant or phase-transfer catalyst can also be immobilized by binding it to an insoluble resin. The binding is generally covalent (Brown and Jenkins, 1976 Brown and Lynn, 1980) but it can be coulombic (Brown et al., 1980) the catalysts are re-usable and product separations are also simplified. 

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... 

A lot of convergent knowledge was rapidly acquired in these apparently different fields and an important consequence was that a huge number of structurally different phase-transfer catalysts were made available within a few years a most significant step was the immobilization of phase-transfer catalysts on a polymer matrix (12-16). 

Phase-Transfer Catalysts Immobilized into a Polymeric Matrix... 

Immobilization of phase-transfer catalysts on polymeric matrices avoids the problem of separating and recycling the catalysts. In this case the chemical stability of the immobilized catalyst becomes very important quaternary salts often decompose under drastic reaction conditions whereas polydentate ligands are always stable. However, the difficult synthesis of cryptands, despite their high catalytic efficiency, can hardly justify their use. Synthesis of crown-ethers is much easier, but catalytic efficiences are often too low. 

Kenawy 64) immobilized ammonium and phosphonium peripheral functionalized dendritic branches on a montmorillonite supported chloromethylstyrene/methyl methacrylate copolymer (74-75). These polymer/montmorillonite-supported dendrimers were used as phase transfer catalysts (PTC) for the nucleophilic substitution reaction between -butyl bromide and thiocyanate, cyanide, and nitrite anions in a toluene or a benzene/water system. These PT catalysts could be recycled by filtration of the functionalized montmorillonite from the reaction mixture. Generally,... 

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 alkylation of phthalimide has been carried out under phase-transfer conditions by Landini and Rolla,272 using soluble phosphonium salts and later by Tundo,273 using heterogenous phase transfer catalysts immobilized on silica gel. Later the preparation of N-alkylphthalimide has been carried out directly from phthalimide by Santaniello and Ponti.274... 

Two groups have developed effective immobilized Chinchona alkaloid phase transfer catalysts, with a connection to a polymer support either through the N-benzyl group or an O-benzyl group [13-15]. 

The immobilization of phase transfer catalysts on solid substrates allows a clean reaction with no contamination of the products by the catalyst. Insoluble polystyrene matrices have been used as a solid support. The polymer matrix does not affect the velocity of the reaction, apart from steric hindrance with respect to the reagents. In the case of immobilization on modified silica the active centre is linked to the support by an alkyl chain of variable length. This length strictly determines the adsorption capacity of the polar support, which then controls the rate of reaction. A three-phase catalytic system is set up. Two distinct phases, containing reagents, come into close... 

Catalytic asymmetric alkylations of 28 have also been carried out with polymer-bound glycine substrates [43], or in the presence of polymer-supported cinchona alkaloid-derived ammonium salts as immobilized chiral phase-transfer catalysts [44], both of which feature their practical advantages especially for large-scale synthesis. 

In an attempt to develop a PEG-supported version of a chiral phase-transfer catalyst the Cinchona alkaloid-derived ammonium salt 15 used by Corey and Lygo in the stereoselective alkylation of amino acid precursors was immobilized on a modified PEG similar to that used in the case of 13. The behaviour of the catalyst obtained 16, however, fell short of the expectations (Danelli et al. 2003). Indeed, while this catalyst (10 mol%) showed good catalytic activity promoting the benzy-lation of the benzophenone imine derived from tert-butyl glycinate in 92% yield (solid CsOH, DCM, -78 to 23 °C, 22 h), the observed ee was only 30%. Even if this was increased to 64% by maintaining the reac-... 

The conversion of benzyl chloride to benzyl cyanide proceeded further than the soluble silacrovm. There is insufficient data to determine whether this is a general phenomenon. It has been pointed out by other workers7 that silica provides an adsorptive surface that can provide assistance in phase transfer. The reaction of potassium cyanide with allyl bromide under liquid/liquid phase transfer conditions produced a mixture of allyl cyanide and crotononitrile. This may be compared to the cataysis exhibited by another new phase transfer catalyst, immobilized trimethoxysilyloctyltributylammonium bromide, which produced only allyl cyanide. 

A new class of compounds, macrocyclic polyethylenoxysilanes, called silacrowns have been prepared which demonstrate phase transfer catalytic properties. An alkoxy functional silacrown has been immobilized in a single-step reaction on a siliceous support. The immobilized silacrown also demonstrates phase transfer catalytic properties. A functionalized onium phase transfer catalyst was also prepared that reacts directly with a siliceous support and is catalytically active. 

Phase transfer catalysts have been grafted onto the surface of porous capsules to facilitate product purification after reaction, and many types of immobilized cells, mycelia, enzymes, and catalysts have been encapsulated in polymers such as PDMS, PVA, or cellulose. In the specific case of PVA, they are named Lenti-kats, as commercialized by Genialab and used for nitrate and nitrite reduction and in the synthesis of fine chemicals. These beads show minimized diffusion limitations caused by the swelling of the polymeric environment under the reaction conditions. To avoid catalyst leaching, enlargement can be realized by linking them to, e.g., chitosan. 

Chiral phase-transfer catalysis (PTC) is a very interesting methodology that typically requires simple experimental operations, a mild reaction conditions and inexpensive and/or environmentally benign reagents, and which is amenable to large-scale preparations [15]. The possibihty of developing recoverable and recyclable chiral catalysts has attracted the interest of many groups. Indeed, the immobilization of chiral phase-transfer catalysts has provided the first demonstrations of the feasibility of this approach. 

A few years ago Cahard reported a series of studies on the use of immobilized cinchona alkaloid derivatives in asymmetric reactions with phase-transfer catalysts [17[. Two types of polymer-supported ammonium salts of cinchona alkaloids (types A and B in Scheme 8.4) were prepared from PS, and their activity was evaluated. The enantioselectivity was found to depend heavily on the alkaloid immobilized, with the type B catalysts usually giving better results than the type A catalysts. By performing the reaction in toluene at -50 °C in the presence of an excess of solid cesium hydroxide and 0.1 mol equiv of catalyst 10, benzylation of the tert-butyl glycinate-derived benzophenone imine afforded the expected (S)-product in 67% yield with 94% ee, a value very close to that observed with the nonsupported catalyst. (Scheme 8.4, Equation b) Unfortunately-and again, inexplicably-the pseudoenantiomer of 10 proved to be much less stereoselective, affording the R)-product in only 23% ee. No mention of catalyst recycling was reported [18]. 

Covalent attachment of ligands to polymer supports retains their complexing properties156 and widens their applications. For instance, immobilized crown poly-thers and cryptands used as phase-transfer catalysts can be recycled55. Chiral ligands have been used for a chromatographical separation of D- and L-amino acids75. ... 

Tundo, P., and P. Venturello, Synthesis, Catalytic Activity and Behaviour of Phase-Transfer Catalysts Supported on Silica Gel. Strong Influence of Substrate Adsorption on the Polar Polymeric Matrix on the Efficiency of the Immobilized Phosphonium Salts, ... 

Tundo, P., P. Venturello, and E. Angeletti, Phase Transfer Catalysts Immobilized and Adsorbed on Alumina and Silica Gel, /. Amer. Chem.Soc., 104, 6551 (1982). 

The following unusual example should be applicable in many similar cases. Preparations of a silica-gel-supported TAD derivative has been developed, and this immobilized agent was used for the separation of several mixtures of natural compounds (83JOC2654). For example, ergosterol can be effectively separated from cholesterol. This silica-gel-supported TAD was also used to remove the phase transfer catalyst Af-( , )-8,10-... 

Also useful for synthetic apphcation are heterogeneous metallic catalysts, modified with chiral auxiliaries and finally chiral soluble organic bases or acids. Less easy to apply are chiral polymeric and gel-type materials, phase-transfer catalysts or immobilized complexes. 

An emerging system similar to the preceding employs what has come to be known as triphase catalysis, in which a phase-transfer catalyst is immobilized on a solid support for use in a liquid-liquid reacting system. In view of the potential importance of such a system, it is considered at greater length in Chapter 19 on phase-transfer catalysis. 

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