Ammonium salts as phase transfer catalysts

The early work by CM Starks at the Continental Oil Co., Ponca City, USA showed the versatility of quaternary ammonium salts as phase-transfer catalysts in organic synthesis. 

For reviews of the asymmetric synthesis of amino acids using quaternary ammonium salts as phase-transfer catalysts, see ... 

Starks, C. M., Quaternary Ammonium Salts as Phase Transfer Catalysts, in Industrial Applications of Surfactants II, Karsa, ed., Roy. Soc. of Chemistry, Canibridge, p. 165 (1990). 

Tsanov, T., K. Vassiler, R. Stamenova, and C. Tsvetonov, Cross-linked PoljKethylene oxide) Modified with Tetraalkyl Ammonium Salts as Phase Transfer Catalyst, J.Poly. Sci, Part A Poly.Chem.,... 

The term phase-transfer catalysis was introduced in 1971 by Starks, explaining the critical role of tetraalkylammonium or phosphonium salts to promote reactions between two substances located in different immiscible phases (325). Over the years, the use of achiral quaternary ammonium salts as phase-transfer catalysts (PTCs) has attracted widespread interest not only in academia but also for industrial applications (326, 327). Some of the most important benefits of phase-transfer catalysis are simple experimental conditions, which are usually easily scalable, in addition to mild reaction conditions, and the use of inexpensive and environmentally friendly reagents and solvents. 

The s-Triazine Compounds can be advantageously prepared in industrial scale using quarternary ammonium salts as phase transfer catalysts in water-chlorinated organic solvent. 

A major achievement was the discovery that the Heck reactions are greatly accelerated in the presence of quaternary ammonium salts as phase-transfer catalysts and solid bases (the Jeffery conditions Pd(OAc)2, MHCOj (M = K, Na), nBu4NX (X = Br, Cl), DMSO, or DMF) [197j. Under these conditions, iodoarenes and iodoalkenes can be coupled to alkenes at room temperature. The major role of the tetraalkylammonium salts apparently lies in enhancing the regeneration of the zerovalent palladium catalyst [223]. 

Okawara (5) reported that the degree of chlorine substitution on PVC suspended in water was 20% using thiophenoxide as nucleophile, and quarternary ammonium salt as phase transfer catalyst. 

In conclusion, polycondenaation of BPA with DCB in aqueous alkali-toluene system, at 65 C, using a quaternary ammonium salt as phase transfer catalyst leads to polyethers having chloromethyl groups at each end, in excellent yields. Molecular weights distribution of these polyethers is surprisingly quite narrow (see Table 2), Additional studies with this and other polymer systems are in progress. 

The introduction of the concept Phase Transfer Catalysis by Starks in 1971 [1] to explain the beneficial effect of tetraalkylammonium (or phosphonium) salts for reactions between two reaction partners that are present in two immiscible phases has significantly influenced and widened the field of organic synthesis, and the use of achiral ammonium salts as phase-transfer catalysts (PTCs) has attracted the attention as catalyst of choice for many... 

Besides the use of chiral ammonium salts as phase transfer catalyst, different azacrown ethers 51a-e derived from different sugars has been proposed as an alternative [52], For all systems the influence of the length of the chain on nitrogen atom was evaluated. For compounds 51a, b (glucose derivatives) the best results were obtained when was 2-hydroxyethyl. Whereas for compounds 51c-e, the best results were obtained for the corresponding 3-hydroxypropyl derivative. In neither case the enantiomeric excess was higher than 74%. 

In contrast to the broad synthetic utility of chiral quaternary ammonium salts in PTC, the application of chiral quaternary phosphonium salts as phase-transfer catalysts remains poorly studied, and only a few special examples have been reported so far with limited success. In 1998, Manabe prepared the chiral phosphonium salt... 

Quaternary ammonium salts as we have seen are useful m synthetic organic chem istry as phase transfer catalysts In another more direct application quaternary ammo mum hydroxides are used as substrates m an elimination reaction to form alkenes... 

Quaternaiy ammonium salts, as we have seen, aie useful in synthetic organic chemistry as phase-transfer catalysts. In another, more direct application, quaternaiy ammonium hydroxides aie used as substrates in an elimination reaction to fonn alkenes. 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

Chiral crown ethers such as 13 are suitable alternatives to the ammonium salts and not decomposed under alkaline conditions. They usually have higher catalyst turnover than the chiral ammonium salts, and the design of catalysts will be much easier. However, they are, in general, costly and difficult to prepare on large scale. Polyols (eg., (RR)-TADDOL14) also serve as phase transfer catalysts. 

The following quaternary ammonium salts are used as phase transfer catalyst tetra-K-butylammonium chloride (TBAC), tetra-n-butylammonium bromide (TBAB), benzyltriethylammonium chloride (BTEAC), and benzyltriethylammo-nium bromide (BTEAB). Chlorinated hydrocarbons, such as dichloromethane (DCM), chloroform (CF), tetrachloromethane (TCM), 1,2-dichloromethane (DCE), and nitrobenzene (NB) are used as solvents. The effects of phase-transfer catalyst and solvent on the yield and reduced viscosity are summarized in Table 9.1. 

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. 

A number of organic molecules capable of efficiently operating as phase-transfer catalysts is now available. The reaction mechanism both for soluble and polymer-supported systems is completely understood and the factors ruling the reactivity are recognised. The drawback of soluble catalysts is their difficult separation from the reaction products which in the case of the expensive macropolycyclic ligands imposes severe limitations in their use on a large scale. The cheap and easy to synthesize ammonium quaternary salts, providing they are stable under the reaction conditions, represent the catalysts of choice. 

Polymer phase-transfer catalysts (also referred to as triphase catalysts) are useful in bringing about reaction between a water-soluble reactant and a water-insoluble reactant [Akelah and Sherrington, 1983 Ford and Tomoi, 1984 Regen, 1979 Tomoi and Ford, 1988], Polymer phase transfer catalysts (usually insoluble) act as the meeting place for two immiscible reactants. For example, the reaction between sodium cyanide (aqueous phase) and 1-bromooctane (organic phase) proceeds at an accelerated rate in the presence of polymeric quaternary ammonium salts such as XXXIX [Regen, 1975, 1976]. Besides the ammonium salts, polymeric phosphonium salts, crown ethers and cryptates, polyethylene oxide), and quaternized polyethylenimine have been studied as phase-transfer catalysts [Hirao et al., 1978 Ishiwatari et al., 1980 Molinari et al., 1977 Tundo, 1978]. 

Further, methods using phase transfer catalysts are suitable for the production of transparent poly(siloxane)/PC copolymers (27). As phase transfer catalyst a methyltributyl ammonium salt is used. 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

Currently, this area is not as well developed as the use of cinchona alkaloid derivatives or spiro-ammonium salts as asymmetric phase-transfer catalysts, and the key requirements for an effective catalyst are only just becoming apparent. As a result, the enantioselectivities observed using these catalysts rarely compete with those obtainable by ammonium ion-derived phase-transfer catalysts. Nevertheless, the ease with which large numbers of analogues - of Taddol, Nobin, and salen in particular- can be prepared, and the almost infinite variety for the preparation of new, chiral metal(ligand) complexes, bodes well for the future development of more enantioselective versions of these catalysts. 

Arenediazo cyanides. Arenediazonium tetrafluoroborates react with solid KCN and 18-crown-6 (0.05 equiv.) in CH2CI2 to give arenediazo cyanides in 75-95% yield. In the absence of 18-crown-6, only low yields of the arenediazo cyanides are obtained after prolonged reaction times. Quaternary ammonium salts are not useful as phase-transfer catalysts. Arenediazo cyanides undergo various reactions, including the Diels-Alder cycloaddition. ... 

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