Stable catalysts for phase transfer

Stable Catalysts for Phase Transfer at Elevated Temperatures... 

Brunelle, D. J., Stable Catalysts for Phase Transfer at Elevated Temperatures, in Phase-Transfer Catalysis New Chemistry, Cata-lysts, and j plications, C. M. Starks, ed., Amer. Chem. Soc. Symp. Ser.No.326,p.38 (1987). 

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

Polystyrene has been used most often as the support for phase transfer catalysts mainly because of the availability of Merrifield resins and quaternary ammonium ion exchange resins. Although other polymers have attrative features, most future applications of polymer-supported phase transfer catalysts will use polystyrene for several reasons It is readily available, inexpensive, easy to functionalize, chemically inert in all but strongly acidic media, and physically stable enough for most uses. Silica gel and alumina offer most of these same advantages. We expect that large scale applications of triphase catalysis will use polystyrene, silica gel, or alumina. 

Another reaction involving an SCF/PTC system is an esterification reaction [22] where the primary role of the SCF is to solubilize an intermediate product to prevent the overreaction to an unwanted byproduct. In this system (Scheme 4.10-3) an insoluble aromatic carboxylic acid 4 with a second reactive functional group is esterified at elevated temperature in supercritical dimethyl ether (scDME) with ethylene oxide 5, which is soluble in the fluid phase, in the presence of a thermally stable and insoluble phase-transfer catalyst. When esterification occurs, the product ester 6 is then soluble in the SCF and is pulled away from the site of reaction and trapped before the second functional group can be altered. Experimental data for this work were obtained using a modified Hewlett-Packard supercritical fluid extractor. This is an example of a PTC reaction where an intermediate product is desired, and the SCF system is designed to obtain only that intermediate. 

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. 

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 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. 

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. 

A potential way to avoid the formation of undesired side products, like in 7.2., is the use of such boron compounds that have only one transferable group. In most cases boronic acids are the compounds of choice, as they are easy to prepare, insensitive to moisture and air, and usually form crystalline solids. In certain cases, however the transmetalation of the heteroaryl group might be hindered by the formation of stable hydrogen bonded complexes. In such cases the use of a boronate ester, such as in equation 7.4., provides better yields. For example pyridine-2-boronic acid dimethylester coupled readily with a bromoquinoline derivative under conditions similar to 7.3. (potassium hydroxide was used as base and tetrabutylammonium bromide as phase transfer catalyst).6... 

Sodium or potassium ions can also participate in the phase-transfer process when they are converted to lipophilic cations by complexation or by strong specific solvation. A variety of neutral organic compounds are able to form reasonably stable complexes with K+ or Na + and can act as catalysts in typical phase-transfer processes. Such compounds include monocyclic polyethers, or crown ethers (1), and bicyclic aminopolyethers (cryptates) (2). They can solubilize inorganic salts in nonpolar solvents and are particularly recommended for reactions of naked anions. Applications of these compounds have been studied.12,21-31... 

In the example (Expt 6.79) the reaction of the diazonium salt from o-chloroaniline with benzene to yield 2-chlorobiphenyl is illustrative. It should be noted, however, that when the liquid aromatic compound in which substitution is to occur is of the type ArZ, the directive influences which are used to explain electrophilic substitution processes are not operative. Thus irrespective of the nature of the substituent Z, ortho-para substitution predominates this result supports the assumption that the substitution process is radical in type. Although the classical reaction occurs in a two-phase system, the use of the more stable diazonium fluoroborates together with the phase-transfer catalyst 18-crown-6 can sometimes be more convenient. The literature method for the preparation of 4-chlorobiphenyl in this way is given as a cognate preparation in Expt 6.19 ... 

The technology also represents a suitable strategy for the preparation of multiphase reaction systems that use phase transfer (bio)catalysts. Giorno et al. [88] reported on the use of membrane emulsification to distribute lipase from Candida rugosa at the interface of stable oil-in-water emulsions. The enzyme itself was used as a surfactant. Shirasu Porous Glassy (SPG) membranes having a nominal pore... 

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