Cryptates, phase-transfer

Phase-tiansfei catalysis (PTC) is a technique by which leactions between substances located in diffeient phases aie biought about oi accelerated. Typically, one OI more of the reactants are organic Hquids or soHds dissolved in a nonpolar organic solvent and the coreactants are salts or alkah metal hydroxides in aqueous solution. Without a catalyst such reactions are often slow or do not occur at ah the phase-transfer catalyst, however, makes such conversions fast and efficient. Catalysts used most extensively are quaternary ammonium or phosphonium salts, and crown ethers and cryptates. Although isolated examples of PTC can be found in the early Hterature, it is only since the middle of the 1960s that the method has developed extensively. 

The crown ethers and cryptates are able to complex the alkaU metals very strongly (38). AppHcations of these agents depend on the appreciable solubihty of the chelates in a wide range of solvents and the increase in activity of the co-anion in nonaqueous systems. For example, potassium hydroxide or permanganate can be solubiHzed in benzene [71 -43-2] hy dicyclohexano-[18]-crown-6 [16069-36-6]. In nonpolar solvents the anions are neither extensively solvated nor strongly paired with the complexed cation, and they behave as naked or bare anions with enhanced activity. Small amounts of the macrocycHc compounds can serve as phase-transfer agents, and they may be more effective than tetrabutylammonium ion for the purpose. The cost of these macrocycHc agents limits industrial use. 

Dietrich, Lehn and Sauvage recognized not only the possibility of enclosing a cation completely in a lipophilic shell, but they also recognized the potential for using such systems for activating associated anions. This is made particularly clear in a paper which appeared some years later One of the original motivations for our work on cryptates rested on their potential use for salt solubilization, anion activation and phase transfer catalysis . This particular application is discussed below in Sect. 8.3. 

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]. 

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... 

Crown ethers and cryptates are phase transfer catalysts but the use of these compounds in PTC reactions is limited to cases in which TAA salts are unsuitable.42... 

Crown ethers and cryptates represent new classes of heterocyclic catalysts having the ability to complex cations and thereby to promote solid-liquid phase transfer catalysis. A detailed description of their properties is found in the literature.12,21-31... 

Reviews. Gokel and Weber have reviewed the principles involved in phase-transfer catalysis and the applications to synthesis (128 references). The review includes crown ethers and cryptates as well as quaternary ammonium and phos-phonium salts. 

CONJUGATE ADDITION (3-Bromopropion-aldehyde ethylene acetal. 1-r-Butylthio-1 -trimethylsilyloxyethylene. Cryptates. l-EthylsuIfinyl-3-pentanone. HexamethyF phosphoric triamide. Ketene bis-(methylthio)ketal monoxide. Organo-lithiuni compounds. Palladium(II) chloride. Phase-transfer catalysts. 

Review. A review of cryptates (82 references) not only discusses known effects of inclusion complexes of this type but notes possible future uses. Thus a cryptate has been prepared that forms a complex with the highly toxic Cd but not with Zn and Ca +. Such cryptates should be useful in treatment of metal poisoning and in control of pollution. Some cryptates are very efficient phase-transfer catalysts (liquid to liquid). Isotope separation may be possible with cryptates. 

There are also many uses for nonenzymatic polymeric catalysts. For instance, polymer-bound crown ethers, cryptates, and channel compounds behave as polymeric phase-transfer catalysts. The catalytic activity is based on selective complex formation. An example is the use of polystyrene-attached oxygen heterocycles [18]-crown-6 or a cryptand[222] to catalyze replacements of bromine in n-octyl bromide by an iodine or by a cyanide groups... 

Alternate types of phase transfer catalysts for two-phase reactions involving salts are crown ethers, cryptates and dialkylpolyethylene oxides, which form reversible complexes with many cations. For example, crown ether 18-crown-6, also strongly catalyzes reaction (1). In this case, the crown ether transfers the entire KCN molecule into the organic phase by complexation. 

The macrocyclic polyethers were prepared by Pedersen a decade ago and shown to complex a variety of cationic substrates [39]. Among these substrates are alkali metal cations, alkaline earth cations and ammonium ions [40]. It has been shown that hindered esters could be saponified by KOH in toluene solution in the presence of dicyclo-hexyl-18-crown-6 [41] or cryptate [42]. Potassium hydroxide is both solubilized in toluene and activated by the crown ether [43]. Sam and Simmons, however, first clearly demonstrated the potential of crowns as phase transfer reagents by solubilizing potassium permanganate in benzene solution (see Eq. 1.15) and using the solubilized reagent in a variety of oxidation processes [44]. 

Although numerous substances have been utilized as phase transfer reagents in specific cases, very little comparative work is available. Such a study [48] is reported for what might almost be called the standard reaction for catalyst evaluation the displacement of chloride from benzyl chloride by acetate ion. Included in this study are yield and rate data (half lives are compared) for inter alia) several crown ethers, aminopolyethers, cryptates, an octopus molecule and nonactin [48]. Several generalizations are offered which will not be reiterated here. We note that such comparisons can be a valuable guide to catalyst selection. 

Phase transfer processes rely on the catalytic effect of quaternary onium or crown type compounds to solubilize in organic solutions otherwise insoluble anionic nucleophiles and bases. The solubility of the ion pairs depends on lipophilic solvation of the ammonium or phosphonium cations or crown ether complexes and the associated anions (except for small amounts of water) are relatively less solvated. Because the anions are remote from the cationic charge and are relatively solvation free they are quite reactive. Their increased reactivity and solubility in nonpolar media allows numerous reactions to be conducted in organic solvents at or near room temperature. Both liquid-liquid and solid-liquid phase transfer processes are known the former ordinarily utilize quaternary ion catalysts whereas the latter have ordinarily utilized crowns or cryptates. Crowns and cryptates can be used in liquid-liquid processes, but fewer successful examples of quaternary ion catalysis of solid-liquid processes are available. In most of the cases where amines are reported to catalyze phase transfer reactions, in situ quat formation has either been demonstrated or can be presumed. 

All four commonly occurring halide ions (fluoride [1-5], chloride [5—11], bromide [5, 8-10], and iodide [5, 7-9, 10, 12-15] have been phase-transferred and in the process, quaternary ions [1, 6-8, 10, 12-15], crowns [2, 4, 8, 9, 13], cryptates [3, 13] and resins [5] have all been utilized. Most of the processes reported are essentially Finkelstein reactions [16]. In a typical phase transfer of fluoride utilizing crown ether as catalyst, an acetonitrile solution of benzyl bromide is stirred with a catalytic amount of 18-crown-6 and solid potassium fluoride. The product, benzyl fluoride (see Eq. 9.1), is isolated in quantitative yield [2]. 

Carbanions have been oxidized under phase transfer conditions in the presence of both crown ethers and cryptates. The substrate which has been most studied is fluorene which undergoes phase transfer catalyzed air oxidation to yield fluorenone in high yield according to equation 11.11 [10, 18]. Crown complexed f-butoxide in... 

Quaternary onium salts, crown ethers, and cryptates have all proved effective as catalysts in the synthesis of unsymmetrical thioethers under phase transfer conditions. Both primary and secondary alkyl bromides can be used to alkylate the mercaptan or thiophenol under basic conditions [5—9]. 

Alkylthiocyanates have been prepared in higji yield by reaction of alkali metal thiocyanates with various primary and secondary alkyl halides under phase transfer conditions. Quaternary alkylammonium salts [12—14], crown ethers [15], cryptates [16], and tertiary amines [14] have all proved effective phase transfer catalysts for this reaction (Eq. 13.7 and Table 13.4). The mechanism of the thiocyanate displacement is probably similar to that of the cyanide displacement reaction (see Sect. 7.2). 

Another type of phase-transfer catalysts is synthetic macro-cyclic polyethers, so-called cro m ethers, and poly(ethylene glycol) derivatives. Since the discovery of crown ethers and their complex-ing capabilities toward metal and ammonium ions in 1967 by Pedersen, crown ethers and modified compounds such as cryptates > have been attracting ever increasing interest among scientists having different applications in their mind. Complexes formed between these compounds and cations correspond to Q" " shown in Fig. 1 and possess phase-thransfer capacity for anions. The nature of cations is known to greatly influence the complexation with a given crown either or cryptate. ... 

A new non-cyclic cryptate (109) for alkali-metal ions has been prepared whose phase-transfer activity exceeds that of dibenzo-18-crown-6. Its high selectivity for bivalent cations, particularly Ba " and Sr ", and also its marked preference for Na" over and Li have led the authors to speculate that cryptates of this type may have the greatest complexation capacity of all neutral ligands so far investigated . 

RCO , RO, BH , Mno , Cio ) which is transferred into the apolar phase (benzene, toluene, pentane, CH2CI2, CHClj, CQ ) by the help of a catalytic cation C (R4N, R P", R4As, metal cation complexed with crown ethers or cryptates) suitable for forming an ion pair, [C" A ]°, in the apolar solvent. 

Complete kinetic determinations are apparently limited to the lipophilic [2.2.2, C14] cryptand 4b which behaves as a PTC catalyst. In this case as well, reactions follow a mechanism similar to that of quaternary salts the observed pseudo-first-order rate constants are linearly correlated with the concentration of the cryptate in the organic phase. Moreover, in a water-chlorobenzene system it is found entirely in the organic phase, as cryptand and/or cryptate. Anion exchange dora not require the simultaneous transfer from the aqueous phase of the cationic partner. 

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