Catalysts, phase transfer type

Class (2) reactions are performed in the presence of dilute to concentrated aqueous sodium hydroxide, powdered potassium hydroxide, or, at elevated temperatures, soHd potassium carbonate, depending on the acidity of the substrate. Alkylations are possible in the presence of concentrated NaOH and a PT catalyst for substrates with conventional pX values up to - 23. This includes many C—H acidic compounds such as fiuorene, phenylacetylene, simple ketones, phenylacetonittile. Furthermore, alkylations of N—H, O—H, S—H, and P—H bonds, and ambident anions are weU known. Other basic phase-transfer reactions are hydrolyses, saponifications, isomerizations, H/D exchange, Michael-type additions, aldol, Darzens, and similar... 

It was noted early by Smid and his coworkers that open-chained polyethylene glycol type compounds bind alkali metals much as the crowns do, but with considerably lower binding constants. This suggested that such materials could be substituted for crown ethers in phase transfer catalytic reactions where a larger amount of the more economical material could effect the transformation just as effectively as more expensive cyclic ethers. Knbchel and coworkers demonstrated the application of open-chained crown ether equivalents in 1975 . Recently, a number of applications have been published in which simple polyethylene glycols are substituted for crowns . These include nucleophilic substitution reactions, as well as solubilization of arenediazonium cations . Glymes have also been bound into polymer backbones for use as catalysts " " . 

In this method, a catalyst is used to carry the nucleophile from the aqueous into the organic phase. As an example, simply heating and stirring a two-phase mixture of 1-chlorooctane for several days with aqueous NaCN gives essentially no yield of 1-cyanooctane. But if a small amount of an appropriate quaternary ammonium salt is added, the product is quantitatively formed in about 2 h." There are two principal types of phase-transfer catalyst. Though the action of the two types is somewhat different, the effects are the same. Both get the anion into the organic phase and allow it to be relatively free to react with the substrate. 

Although phase-transfer catalysis has been most often used for nucleophilic substitutions, it is not confined to these reactions. Any reaction that needs an insoluble anion dissolved in an organic solvent can be accelerated by an appropriate phase transfer catalyst. We shall see some examples in later chapters. In fact, in principle, the method is not even limited to anions, and a small amount of work has been done in transferring cations, radicals, and molecules. The reverse type of phase-transfer catalysis has also been reported transport into the aqueous phase of a reactant that is soluble in organic solvents. ... 

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. 

A different type of synthesis, which leads to a benzannulated indolo[2,3-3][l,6]naphthyridine 15, is illustrated in Scheme 3 <1999TL3797>, and the use of an azaindolone as starting material may introduce an additional heteroatom into the indole moiety of the product, as in 16 (Equation 2) <1994TL1995>. The dipyrrolo[2,3-3 2, 3 -g][l,8]naphthyridine 18 is produced by reaction of the naphthyridine 17 with ethyl glycinate in the presence of a phase-transfer catalyst (Scheme 4) <2000PS(163)29>. 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Phase transfer catalysis. As well as their use in homogeneous reactions of the type just described, polyethers (crowns and cryptands) may be used to catalyse reactions between reagents contained in two different phases (either liquid/liquid or solid/liquid). For these, the polyether is present in only catalytic amounts and the process is termed phase transfer catalysis . The efficiency of such a process depends upon a number of factors. Two important ones are the stability constant of the polyether complex being transported and the lipophilicity of the polyether catalyst used. 

In phase transfer catalysis of the solid/liquid type, the organic phase (containing dissolved organic reactant and a small amount of the crown) is mixed directly with the solid inorganic salt. Such a procedure enables the reaction to proceed under anhydrous conditions this is a distinct advantage, for example, when hydrolysis is a possible competing reaction. Because of their open structure, crown ethers are readily able to abstract cations from a crystalline solid and are often the catalysts of choice for many solid/liquid phase transfer reactions. 

A different approach is the combination of a Pt-carbonyl-cluster with a special dye, Safranine O (Saf 3,7-diamino-2,8-dimethyl-5-phenylphenazinium) in an aqueous/organic two-phase system [48]. The dye is reduced in the organic phase and subsequently, in a type of phase-transfer catalysis, it reduced the cofactor in the aqueous phase. In this example l-LDH is used as a production enzyme, reducing pyruvate to L-lactate (Scheme 43.6). Complete conversion was obtained within 48 h, the mixture containing pyruvate, NAD+ and the Pt-cluster catalyst in a 600 10 1 molar ratio. The TOF for NAD+ was 15 h-1. 

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... 

This type of reverse set-up has been expanded to catalysts with phosphines containing crown ether substituents (Figure 8.1), with the crown ether acting as a built-in phase-transfer function [5], Using a catalyst with this phosphine, the hydrogenation of Li+, Na+, K+ and Cs+ cinnamates in water-benzene solvent mixtures was considerably faster than when the analogous catalyst was used with triphenylphosphine ligands. 

Examples of the Michael-type addition of carbanions, derived from activated methylene compounds, with electron-deficient alkenes under phase-transfer catalytic conditions have been reported [e.g. 1-17] (Table 6.16). Although the basic conditions are normally provided by sodium hydroxide or potassium carbonate, fluoride and cyanide salts have also been used [e.g. 1, 12-14]. Soliddiquid two-phase systems, with or without added organic solvent [e.g. 15-18] and polymer-supported catalysts [11] have been employed, as well as normal liquiddiquid conditions. The micellar ammonium catalysts have also been used, e.g. for the condensation of p-dicarbonyl compounds with but-3-en-2-one [19], and they are reported to be superior to tetra-n-butylammonium bromide at low base concentrations. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

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. 

These observations showed that the reaction can be simplified by preformation of the indanone enolate in toluene/50% NaOH and subsequent addition of catalyst and CH3CI (Figure 12). This eliminates the "induction period and most importantly the high sensitivity of rate and ee to the catalyst/indanone ratio. Detailed kinetic measurements on this preformed enolate methylation in toluene/50% NaOH determined that the reaction is 0.55 order in catalyst. This is consistent with our finding that the catalyst goes into solution as a dimer which must dissociate prior to com-plexation with the indanone anion. If the rate has a first order dependence on the monomer, the amount of monomer is very small, and the equilibration between dimer and monomer is fast, then the order in catalyst is expected to be 0.5. The 0.5 order in catalyst is not due to the preformation of solid sodium indanone enolate but is a peculiarity of this type of chiral catalyst. Vlhen Aliquat 336 is used as catalyst in this identical system the order in catalyst is 1. Finally, in the absence of a phase transfer catalyst less than 2% methylation was observed in 95 hours. 

Phase transfer catalysis (1,2) has become in recent years a widely used, well-established synthetic technique applied with advantage to a multitude of organic transformations. In addition to a steadily increasing number of reports in the primary literature, there are several reviews (3-6), comprehensive monographs (7-10) and an ACS Audio Course (1 ) which describe the phase transfer process and which provide extensive compilations of phase transfer agents and reaction types. While the list of applications and in many cases the synthetic results are impressive, phase transfer catalysts (PTCs) suffer some of the same disadvantages as more conventional hetero-and homogeneous catalysts — separation and... 

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