Phase transfer catalysts onium salts

Recently in the search for new and more versatile chiral phase transfer catalysts, onium salts 14 and 15 derived from L-methionine... 

Gas-liquid phase-transfer catalysis (GL-PTC) is a new synthetic organic method that has similarities both with phase-transfer catalysis (PTC) and with gas-liquid chromatography (GLC) in that anion transfer processes and partition equilibria between gaseous and liquid phases both take place and affect the synthesis. Using GL-PTC, nucleophilic substitution reactions have been so far carried out under operative conditions and with synthetic results, making this method different from the well known liquid-liquid (LL-) and solid-liquid (SL-) phase-transfer catalysis. As regards these latter, phase-transfer catalysts (onium salts, crown ethers and cryptands) transfer the reactive anion from an aqueous liquid (LL-PTC) or a solid salt (SL-PTC) phase into the organic one in which the substitution reaction occurs. In the case of GL-PTC, where no solvent is used, the catalyst always acts as an anion transfer (between solid and liquid phases) but, as it works in the molten state it also constitutes the medium in which the reaction proceeds. 

Abstract Phase transfer catalysts including onium salts or crown ethers transfer between heterogeneous different phases and catalytically mediate desired reactions. Chiral non-racemic phase transfer catalysts are useful for reactions producing new stereogenic centers, giving chiral non-racemic products. Recent developments in this rapid expanding area will be presented. 

Onium salts, crown ethers, alkali metal salts or similar chelated salts, quaternary ammonium and phosphonium are some of the salts which have been widely used as phase transfer catalysts (PTC). The choice of phase transfer catalysts depends on a number of process factors, such as reaction system, solvent, temperature, removal and recovery of catalyst, base strength etc. 

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... 

The choice of the catalyst is an important factor in PTC. Very hydrophilic onium salts such as tetramethylammonium chloride are not particularly active phase transfer agents for nonpolar solvents, as they do not effectively partition themselves into the organic phase. Table 5.2 shows relative reaction rates for anion displacement reactions for a number of common phase transfer agents. From the table it is clear that the activities of phase transfer catalysts are reaction dependent. It is important to pick the best catalyst for the job in hand. The use of onium salts containing both long and very short alkyl chains, such as hexade-cyltrimethylammonium bromide, will promote stable emulsions in some reaction systems, and thus these are poor catalysts. 

Quaternary onium salts were the first phase-transfer catalysts used subsequently, a number of compounds (linear polyethers, polypodands, crown-ethers, cryptands, cage-compounds, etc.) were found effective for the anion activation in two-phase systems. These structurally different systems must satisfy at least two fundamental conditions in order to behave as phase-transfer catalysts i) solubility in the organic phase ii) steric hindrance around the cationic center leading to a good cation-anion separation within the ion-pair. 

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. 

In the Starks extraction mechanism, the phase-transfer catalyst moves back and forth across the organic and aqueous phases. The onium salt equilibrates with the inorganic base in the aqueous phase, and extracts hydroxide into the organic phase. 

Clearly, the area of the interface and the basicity of the inorganic salt affect the amount of available onium carbanion. It should be also noted that an excessively lipophilic phase-transfer catalyst would hardly access the interface, and consequently the use of such a catalyst would result in an insufficient reaction. 

Crown ether is the other important class of phase-transfer catalysts which critically differs from the onium salt, in that the whole inorganic salt is transferred into the organic phase. The reaction modes described above can generally be accommodated in such crown ether-catalyzed reactions, simply by replacing the onium cation by a metal cation complex of crown ether. 

Phase-transfer catalysts are used to facilitate reactions between reagents that are in two different phases (e.g., 1-bromooctane in toluene with aqueous potassium iodide to form 1-iodooctane). They are usually quaternary ammonium or phosphonium salts or crown ethers. They can complicate the workup of the reaction and may be difficult to recover for reuse. When they are insoluble polymeric ones, workup and recycle can be done by simple filtration.192 The process is called triphase catalysis. In favorable cases, their activity can be comparable with that of their lower molecular weight analogues. They are often based on cross-linked polystyrene, for which spacers between the aromatic ring and the quaternary onium salt can increase activity two- to fourfold. Copolymerization of 4-vinylben-zyl chloride with styrene or N, N- d i m e Ihy I a c ry I a m i d e, followed by treatment with tri-/ -butylphosphine produced catalysts that were used in the reaction of benzyl chloride with solid potassium acetate (5.43).193... 

The phenomena accompanying interphase transfer of chemical materials are universally observed in biological systems. A number of carriers and various transportation methods are used and the selective transportation of materials contributes to controlling the biochemical reactions in vivo. In synthetic chemistry, however, the carriers as well as the methods are very limited. Phase-transfer catalysts (PTCs cf. Section 4.6.1) such as crown ethers or onium salts are limited to the transportation of anions from an aqueous or solid phase into an organic phase nevertheless, the PTCs contributed to the development of synthetic chemistry. The most important point is that these catalysts have enabled the biphasic reactions of lipophilic molecules with inexpensive inorganic salts and at the same time facilitated the separation of products. 

While PEGS can themselves serve as phase-transfer catalysts [86], onium salts are generally more effective as catalysts. Using the chemistry shown in Eq. 18, a methoxy-PEG5ooo derivative 47 was first treated with the Cs salt of 4-hydroxybenzyl alcohol to form the alcohol 48. Conversion of the alcohol to the bromide followed by reaction with tributylamine produced a quaternary ammonium salt 49. This salt was as active as low molecular weight salts in typical phase-transfer catalyzed reactions like those of alkyl halides with KI, KCN, phenol, and pyrrole [88]. Yields were often in the >90% range. Reactions were typically carried out at <40 °C and could be performed either with water or without solvent. Control experiments showed that the ammonium group of 49 was necessary as the simple alcoholic PEG derivative 48 was much less effec-... 

Sn2 nucleophilic substitutions take place in scC02. The presence of silica-supported onium salts 42 as a phase-transfer catalyst enhances the reaction (Scheme 72). Esters formation from carboxylic acids and alcohols via dehydration also proceeds in scC02. The conversion increases as the CO2 pressure increases. A single homogeneous phase is obtained around the critical point, at which the conversion is maximized. 

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