Phase-transfer catalysis supported catalysts

Phase-transfer catalysis is a special type of catalysis. It is based on the addition of an ionic (sometimes non-ionic like PEG400) catalyst to a two-phase system consisting of a combination of aqueous and organic phases. The ionic species bind with the reactant in one phase, forcing transfer of this reactant to the second (reactive) phase in which the reactant is only sparingly soluble without the phase-transfer catalyst (PTC). Its concentration increases because of the transfer, which results in an increased reaction rate. Quaternary amines are effective PTCs. Specialists involved in process development should pay special attention to the problem of removal of phase-transfer catalysts from effluents and the recovery of the catalysts. Solid PTCs could diminish environmental problems. The problem of using solid supported PTCs seems not to have been successfully solved so far, due to relatively small activity and/or due to poor stability. 

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procedures of the late 1960s, which used stoichiometric amounts of the quaternary ammonium salt, have now been superseded by solid-liquid phase-transfer catalytic processes [e.g. 9-13].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. 

Before the 1990s there was little in the literature on multiphasic L-L-S and L-L-L-S systems used for chemical reactions. There is, however, a relatively large volume of work done on other types of multiphasic systems related to the present topic supported liquid-phase catalysis (SL-PC), and gas liquid phase transfer Catalysis (GL-PTC). The common denominator in both cases is the presence of an interfacial liquid layer of a hydrophilic compound between the catalyst and the bulk of the reaction. 

In 2000, Benaglia and coworkers reported preparation of MeO-PEG supported quaternary ammonium salt (10) and examined the catalytic efficiency in a series of phase-transfer reactions (Fig. 5.3) [69]. The reactions occurred at lower temperatures and with shorter reaction times than with comparable insoluble 2% cross-linked polystyrene-supported quaternary ammonium salts, although yields varied with respect to classical solution phase quaternary ammonium salt catalyzed reactions. It was observed that yields dropped with a shorter linker, and that PEG alone was not responsible for the extent of phase-transfer catalysis. While the catalyst was recovered in good yield by precipitation, it contained an undetermined amount of sodium hydroxide, although the presence of this byproduct was found to have no effect on the recyclability of the catalyst... 

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). 

It is therefore not surprising that it was only when suitable methods for catalyst separation from the substrates and reaction products of homogeneous catalysis were developed that the importance of this type of process grew. The successful developments (thermal separation or chemical reaction (e. g., [26]), immobilization by means of supports and thus heterogenization (e. g., [44]), phase transfer catalysis [45], biphasic processes (e. g., [46, 47]) or separation with membrane modules [48, 49]) are described in the relevant sections of this book (cf. [50]). 

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. 

Other interesting systems have been employed, such as CO/HjO (water gas) or CO/Hj (syngas) as reducing mixtures [49, 50], phase transfer catalysis [37], and more recently, aqueous [46, 47] and non-aqueous ionic liquid [48] biphasic catalysis which offer more promise for practical uses. Some interesting examples of metal complexes grafted onto oxides [55, 56] or supported metals [38, 39] as arene hydrogenation catalysts have been provided. 

For reasons of economy and pollution, solvent-free methods are of great interest in order to modernize classical procedures making them more clean, safe and easy to perform. Reactions on solid mineral supports, reactions without any solvent/support or catalyst, and solid-liquid phase transfer catalysis can be thus employed with noticeable increases in reactivity and selectivity. A comprehensive review of these techniques is presented here. These methodologies can moreover be improved to take advantage of microwave activation as a beneficial alternative to conventional heating under safe and efficient conditions with large enhancements in yields and savings in time. 

Since the Reimer-Tiemann reaction always yields a mixture of ortho- and para-substituted phenols whenever the two positions are unsubstituted (and sometimes even when the positions are substituted, see carboxy-substituted phenols), it is not surprising that attempts have been made to increase the regioselectivity. Earlier attempts (for details, see reviews) emphasized the nature of the cation, the solvent, or used phase-transfer catalysis. Recent studies have concentrated on the use of cyclodextrins as base-stable host compounds, permitting exclusive para substitution. Attaching the cyclodextrins to a solid support has also been attempted, a natural step in view of the high cost of the cyclodextrins and the need for cheap product i.e. p-hydroxybenzaldehyde). p-Hydroxybenzaldehyde has been prepared in 59-65% yield using P-cyclodextrin that has been immobilized with epichlorohydrin. TTie catalyst is easily recovered and can be reused without appreciable loss of activity. 

While phase-transfer catalysis (PTC) is a well established method with diverse applications in organic synthesis, conventional catalysts suffer several drawbacks including hygroscopicity, low thermal stability and difficulty in separation and recovery. Ironically, the high solubilities of conventional catalysts are a drawback to recovery and a problem to product purification. The concept of triphase catalysis, whereby the catalyst is immobilised onto a support material and the resulting supported PTC is then used in a biphasic aqueous-organic solvent reaction mixture is recognised as a viable solution to many of these problems.144-146... 

Recently, two methods were published that have attracted some interest, because no metal salts are necessary as oxidation reagents. Shi and Xu (1990) found that substituted (trifluoromethyl)-diazoalkanes (CF3CRN2, R = alkyl or aryl) are obtained by refluxing trifluoromethyl ketones and 2,4,6-tri(isopropyl)benzenesulfonyl hydrazone in a methanolic solution of KOH. Kumar (1991) synthesized a-diazocar-bonyl compounds under tri-phase phase-transfer catalysis using a polystyrene-supported (tributyl)(methyl)-ammonium chloride catalyst, methanesulfonyl chloride, NaN3, and methylsulfonyl azide in 1,2-dichloroethane and a carbonyl-activated substrate (69-94% yield). 

The histories of phase transfer catalysis, Merrifield peptide synthesis, and supported enzymes suggest that synthetic processes using polymeric catalysts may be adopted in commercial production, but that methods for multistep syntheses are less likely. The reasons for this prediction follow. 

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. 

Gas-liquid phase-transfer catalysis (GL-PTC) relies on the use of thermally stable PT catalysts adsorbed onto a solid support, which can also act as a source of the desired nucleophile. Reactions are carried out at a temperature that ensures that the catalyst is in a molten state and that reagents are in the vapor phase, and that the chemical transformation occurs in the organic microphase of molten catalyst. The products are recovered after condensation outside the reaction vessel. Only catalysts having melting points lower then the process temperature <180°C are active, but despite this limitation, GL-PTC is a versatile technique that has been applied to a number of chemical transformations. 

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)]. 

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