Phase transfer catalysis quaternary ammonium catalysts

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... 

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

It is important to make the distinction between the multiphasic catalysis concept and transfer-assisted organometallic reactions or phase-transfer catalysis (PTC). In this latter approach, a catalytic amount of quaternary ammonium salt [Q] [X] is present in an aqueous phase. The catalyst s lipophilic cation [Q] transports the reactant s anion [Y] to the organic phase, as an ion-pair, and the chemical reaction occurs in the organic phase of the two-phase organic/aqueous mixture [2]. 

Phase transfer catalysis (PTC) refers to the transfer of ions or organic molecules between two liquid phases (usually water/organic) or a liquid and a solid phase using a catalyst as a transport shuttle. The most common system encountered is water/organic, hence the catalyst must have an appropriate hydrophilic/lipophilic balance to enable it to have compatibility with both phases. The most useful catalysts for these systems are quaternary ammonium salts. Commonly used catalysts for solid-liquid systems are crown ethers and poly glycol ethers. Starks (Figure 4.5) developed the mode of action of PTC in the 1970s. In its most simple... 

Reactions performed under two-phase conditions are further complicated by the partitioning of the reactants and catalyst over the two phases. In the case of quaternary ammonium phase-transfer catalysis, the mechanistic aspects have received a great deal of attention (Brandstrom, 1977 Makosza, 1975 Starks and Owens, 1973). In contrast, the mechanism of crown ether-type phase-transfer catalysis has hardly been investigated at all, despite its... 

It was a result of demand from industry in the mid-1960s for an alternative to be found for the expensive traditional synthetic procedures that led to the evolution of phase-transfer catalysis in which hydrophilic anions could be transferred into an organic medium. Several phase-transfer catalysts are available quaternary ammonium, phosphonium and arsonium salts, crown ethers, cryptands and polyethylene glycols. Of these, the quaternary ammonium salts are the most versatile and, compared with the crown ethers, which have many applications, they have the advantage of being relatively cheap, stable and non-toxic [1, 2]. Additionally, comparisons of the efficiencies of the various catalysts have shown that the ammonium salts are superior to the crown ethers and polyethylene glycols and comparable with the cryptands [e.g. 3, 4], which have fewer proven applications and require higher... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

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. 

The general concept of phase transfer catalysis applies to the transfer of any species from one phase to another (not just anions as illustrated above), provided a suitable catalyst can be chosen, and provided suitable phase compositions and reaction conditions are used. Most published work using PTC deals only with the transfer of anionic reactants using either quaternary ammonium or phosphonium salts, or with crown ethers in liquid-liquid or liquid-solid systems. Examples of the transfer and reaction of other chemical species have been reported(24) but clearly some of the most innovative work in this area has been done by Alper and his co-workers, as described in Chapter 2. He illustrates that gas-liquid-liquid transfers with complex catalyst systems provide methods for catalytic hydrogenations with gaseous hydrogen. 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

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]. 

One of the oldest techniques for overcoming these problems is the use of biphasic water/organic solvent systems using phase-transfer methods. In 1951, Jarrouse found that the reaction of water-soluble sodium cyanide with water-insoluble, but organic solvent-soluble 1-chlorooctane is dramatically enhanced by adding a catalytic amount of tetra-n-butylammonium chloride [878], This technique was further developed by Makosza et al. [879], Starks et al. [880], and others, and has become known as liquid-liquid phase-transfer catalysis (PTC) for reviews, see references [656-658, 879-882], The mechanism of this method is shown in Fig. 5-18 for the nucleophilic displacement reaction of a haloalkane with sodium cyanide in the presence of a quaternary ammonium chloride as FT catalyst. 

Phase transfer catalysis and the use of crown ethers are also of particular advantage in alkanenitrile synthesis (Table 1). Usually quaternary ammonium and phosphonium salts serve quite well as catalysts. Another modification is represented by the use of a solid catalyst, which is insoluble in the two-phase system, for instance alumina or anion-exchange resins (triphase catalysis). Crown ethers again capture the cations and generate naked cyanide ions in fairly nonpolar solvents, leading to exceptionally mild reaction conditions. 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Among the many base-solvent systems applied for this purpose, phase-transfer catalysis is the most efficient and the simplest. Concentrated aqueous solutions of sodium or potassium hydroxide and a quaternary ammonium salt or a crown ether, e.g. dicyclohexane-18-crown-6, as a catalyst have been used. 

Other methods are also available for the generation of dichlorocarbene which, in the presence of alkenes, forms 1,1-dichlorocyclopropanes, e.g. reaction of chloroform with oxirane, using a quaternary ammonium salt as the catalyst and an alkene (Houben-Weyl, Vol. 4/3, pp 374-381 and Vol. E19b, p 1530).The discovery of new, more convenient and equally efficient methods (especially phase-transfer catalysis) means that older approaches are unused at present. 

Phase-transfer catalysis is often used in the first approach. Concentrated aqueous alkali metal hydroxides and a quaternary ammonium salt or a tertiary amine as a catalyst (liquid-liquid system) are generally used. Due to the high acidity of bromoform and high reactivity of dibromocarbene, a solid-liquid variant of phase-transfer catalysis, which allows the reaction to be performed at low temperatures, is utilized relatively frequently. 

The synthesis of 1,1-diiodocyclopropane is carried out via addition of diiodocarbene (car-benoid) to alkenes the carbene, in turn, is generated from iodoform and a base. The process is realized using phase-transfer catalysis,(33% or 50%aqueous sodium hydroxide and a quaternary ammonium salt, typically benzyltriethylammonium chloride, as a catalyst) or in the presence of potassium ter/-butoxide in /ert-butyl alcohol 25,127,128 g... 

This chapter will present recent progress made in reaction-controlled phase-transfer catalysis for the epoxidation of olefins, focusing on work with hetero-pol)q5hosphotungstates and quaternary ammonium ions from our group. We have systemically investigated the influence of composition of the heteropoly anion and various quaternary ammonium ions on the catalyst activity. The epoxidation of propylene, allyl chloride, and others olefins and the stability of the catalyst in recycle will be summarized and discussed in detail. 

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