Phase-transfer reagents quaternary ammonium salts

Phase-transfer catalysis (PTC) is one of the most important methods for the enhancement of reactivity of inorganic reagents having poor solubility in organic solvents. As such, PTC is often used for reactions involving potassium fluoride, which has very low solubility in aprotic solvents. Both types of phase-transfer catalysts, quaternary ammonium salts and 18-crown-6, have been used to accelerate... 

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procedures of the late 1960s, which used stoichiometric amounts of the quaternary ammonium salt, have now been superseded by solid-liquid phase-transfer catalytic processes [e.g. 9-13].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

A highly enantioselective synthesis of (2S)-a-(hydroxymethyl)glutamic acid, a potent metabotropic receptor ligand, has been accomplished via the catalytic Michael addition of /-butyl 2-naphthalen-l-yl-2-oxazoline-4-carboxylate to CH2=CHC02Et, using the phosphazene base (143) and the (.S )-binaphthyl quaternary ammonium salt (144) as the chiral phase-transfer reagent in CH2CI2 at — 60 °C (<97% < < ).174... 

The symmetrical quaternary ammonium salts 5-6 have also been shown to be effective reagents for the enantioselective alkylation of the Schiff base 3 under mild phase-transfer conditions [6]. Although results with the C2-symmetrical quaternary ammonium salt 5 were disappointing (entry 6, Table 1), the more rigid spiro ammonium salts 6 were much more effective catalysts. The rate and enantioselectivity of the benzylation of 3 was found to depend critically on the substituent R. With the ammonium salt 6c (R = / -Np), the reaction was complete within 30 min at 0 °C (entry 9, Table 1) and gave the amino acid derivative 4 with 95% ee, whereas the unsubstituted catalyst 6a (R = H) required a longer reaction time and gave 4 in only 79% ee (entry 7, Table 1). 

Use of a microemulsion to overcome reagent incompatibility can be seen as an alternative to the more conventional approach of carrying out the reaction in a two-phase system with the use of a phase transfer catalyst. The latter is usually either a quaternary ammonium salt or a crown ether. There are several examples in the literature of comparisons between the microemulsion concept and phase transfer catalysis. The topic has also recently been reviewed [46]. 

In classical phase-transfer catalysis (PTC), the catalyst (often a quaternary ammonium salt) transfers the reagent... 

Uses Phase transfer catalyst chemical reagent Manuf./Distrib. Acros Org. http //www.acros.be] Amyl http //www.amyi.com] Lancaster Synthesis TCI Am. http //www.tciamerica.com] Yancheng Huaue Pharm. Chem. http //www.huayepharm. com Yixing Fangqiao East Chemical http //www. eastchemicais. com Benzyltriethyl ammonium chloride CAS 56-37-1 EINECS/ELINCS 200-270-1 Synonyms Ammonium, benzyltriethyl-, chloride Benzenemethanaminium, N,N,N-triethyl-, chloride BETEC BTEAC TEBAC N,N,N-Triethylbenzenemethanaminium chloride Triethyl benzyl ammonium chloride Classification Quaternary ammonium salt Empirical C13H22N Cl Formula C6H5CH2N(CI)(C2H5)3 Properties Solid m.w. 227.8 m.p. 197-199 C (dec.)... 

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. 

Further investigation of phase transfer catalysis, a phenomenon where quaternary ammonium salts catalyse reactions in aqueous-organic two-phase systems, has confirmed that the function of the ammonium ion is to solubilize the reagent/substrate in the organic phase. The use of phase transfer catalysis in the alkylation of weak acids such as diethyl malonate has been described other examples - - of this phenomenon are cited above. 

The first catalysts utilized in phase transfer processes were quaternary onium salts. In particular, benzyltriethylammonium chloride was favored by Makosza (7 ) whereas Starks utilized the more thermally stable phosphonium salts (6,8). In either case, the catalytic process worked in the same way the ammonium or phosphonium cation exchanged for the cation associated with the nucleophilic reagent salt. The new reagent, Q+Nu , dissolved in the organic phase and effected substitution. 

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... 

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