Phase transfer catalysts ammonium salts

Another important use of the susceptibility of phosphonium salts to undergo alkaline hydrolysis concerns their use as liquid-liquid phase-transfer catalysts. Phosphonium salts can be decomposed much more easily than ammonium salts, under alkaline conditions726-729, and they have to be used under much milder conditions [i.e. low temperature (< 25 °C) and moderate aqueous base concentration (< 15%)] in all cases reaction conditions should be used which prevent the extraction of OH - into the organic phase or minimize its reactivity730. 

Sometimes, the exchange does not work well under reflux conditions. A few alternatives are the use of phase transfer catalysts (ammonium or phosphonium salts), crown ethers, or exchange in melts or under solid-state conditions (Apparu and Madelmont, 1998). Melts are either the substrate itself at its melting point (where it has to be stable, and must have a high dielectric constant to solubilize Na I), a melt of acetamide or formamide, or ammonium sulfate below its melting point (reaction at 120—160°C). This technique is mostly used with aromatic compounds (Seevers and Counsell, 1982). 

Quaternary ammonium salts as we have seen are useful m synthetic organic chem istry as phase transfer catalysts In another more direct application quaternary ammo mum hydroxides are used as substrates m an elimination reaction to form alkenes... 

Halex rates can also be increased by phase-transfer catalysts (PTC) with widely varying stmctures quaternary ammonium salts (51—53) 18-crown-6-ether (54) pytidinium salts (55) quaternary phosphonium salts (56) and poly(ethylene glycol)s (57). Catalytic quantities of cesium duoride also enhance Halex reactions (58). 

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. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

Quaternaiy ammonium salts, as we have seen, aie useful in synthetic organic chemistry as phase-transfer catalysts. In another, more direct application, quaternaiy ammonium hydroxides aie used as substrates in an elimination reaction to fonn alkenes. 

Phase transfer catalysts were used for nucleophilic displacement reactions of activated leaving groups by hydroxyfurazanyl anions. For example, tetrachloro-pyrazine was found to react with hydroxyfurazans in benzene/Na2C03/tetraalkyl-ammonium salts giving products of mono- or disubstitution (Scheme 173) (94MI1). The course of the reaction depends on the ratio of the reactants and the nature of the ammonium salt. 

Ionic liquid synthesis in a commercial context is in many respects quite different from academic ionic liquid preparation. While, in the commercial scenario, labor-intensive steps add significantly to the price of the product (which, next to quality, is another important criterion for the customer), they can easily be justified in academia to obtain a purer material. In a commercial environment, the desire for absolute quality of the product and the need for a reasonable price have to be reconciled. This is not new, of course. If one looks into the very similar business of phase-transfer catalysts or other ionic modifiers (such as commercially available ammonium salts), one rarely finds absolutely pure materials. Sometimes the active ionic compound is only present in about 85 % purity. However, and this is a crucial point, the product is well specified, the nature of the impurities is known, and the quality of the material is absolutely reproducible from batch to batch. 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

Another catalytic system which has been successfully applied to the autoxidation of substituted toluenes involves the combination of Co/Br" with a quaternary ammonium salt as a phase transfer catalyst (ref. 20). For example, cobalt(II) chloride in combination with certain tetraalkylammonium bromides or tetraalkylphosphonium bromides afforded benzoic acid in 92 % yield from toluene at 135-160 °C and 15 bar (Fig. 19). It should be noted that this system does not require the use of acetic acid as solvent. The function of the phase transfer catalyst is presumably to solubilize the cobalt in the ArCH3 solvent via the formation of Q + [CoBr]. ... 

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. 

A method for the depolymerisation of PETP fibres using quarternary ammonium salt phase transfer catalysts in saponification processes at atmospheric pressure and temperatures as low as room temperature is reported. Terephthalic acid was produced in yields as high as 93%. Also reported are similar processes for the depolymerisation of nylon 66 and nylon 46 fibres. Nylon 46 oligomers produced were repolymerised using solid-state polymerisation to produce high molecular weight nylon 46. Nylon 66 was depolymerised to produce oligomers and adipic acid in reasonable yields. 11 refs. USA... 

Benzylic quaternary phosphonium and ammonium salts are dealky-lated by mild heating and/or nucleophilic anions, particularly iodide (9) and thiolate (10), but also hydroxide (11). Most N-benzyl-pyridinium or quaternary aryl ammonium compounds are particularly susceptible (12). Decompositions of this sort have seriously limited the usefulness of solid phase-transfer catalysts derived from (chloromethyl)polystyrene (13, 14). 

Quaternary ammonium azides will displace halogens in a synthesis of alkyl azides. Dichloromethane has been used as a solvent, although this can slowly form diazido-methane which may be concentrated by distillation dining work-up, thereafter easily exploding [1]. An accident attributed to this cause is described, and acetonitrile recommended as a preferable solvent, supported polymeric azides, excess of which can be removed by filtration are also preferred in place of the tetrabutylam-monium salt [2]. A similar explosion was previously recorded when the quaternary azide was generated in situ from sodium azide and a phase transfer catalyst in a part aqueous system [3,4],... 

In the following example, although the synthesis of the azoniaspirocycle does not involve an acyclic compound, the reaction itself is very similar to those described in this section, hence its inclusion here (Equation 34). Maruoka and co-workers have designed a C2-symmetric chiral quarternary ammonium salt, which is then employed as a phase-transfer catalyst in an enantioselective alkylation <1999JA6519, 2001JFC(112)95, 2004TA1243>. 

The 9,10-dihydrodiol of 3-MC (24a) was synthesized from 9-hy-droxy-3-MC by Method IV (86). Oxidation of this phenol with Fremy s salt in the presence of Adogen 464, a quaternary ammonium phase transfer catalyst, furnished 3-MC 9,10-dione. Reduction of the qui-none with NaBH -C gave pure 24a in good yield. Treatment of 24a with m-chloroperbenzoic acid was monitored by HPLC in order to optimize the yield of the anti diol epoxide (25 ) and minimize its decomposition. 

Hydrophobic ammonium ions which are phase transfer catalysts such as tri-n-octylalkylammonium ions (C8H17)3NR+X (R = Me, Et, CH2CH2OH X = Cl, Br, MeS03) are surface active but appear to form small nonmicellar aggregates (Okahata et al., 1977 Kunitake et al., 1980). The salts of these ions are only sparingly soluble in water, but they are very effective at speeding reactions of hydrophobic nucleophilic anions. 

Arai et al.51 reported that by using a catalytic amount of chiral quaternary ammonium salt as a phase transfer catalyst, a catalytic cycle was established in asymmetric HWE reactions in the presence of an inorganic base. Although catalytic turnover and enantiomeric excess for this reaction are not high, this is one of the first cases of an asymmetric HWE reaction proceeding in a catalytic manner (Scheme 8-20). 

Cinchona alkaloids now occupy the central position in designing the chiral non-racemic phase transfer catalysts because they have various functional groups easily derivatized and are commercially available with cheap price. The quaternary ammonium salts derived from cinchona alkaloids as well as some other phase transfer catalysts are... 

Chiral crown ethers such as 13 are suitable alternatives to the ammonium salts and not decomposed under alkaline conditions. They usually have higher catalyst turnover than the chiral ammonium salts, and the design of catalysts will be much easier. However, they are, in general, costly and difficult to prepare on large scale. Polyols (eg., (RR)-TADDOL14) also serve as phase transfer catalysts. 

The first practical and efficient asymmetric alkylation by use of chiral phase-transfer catalysts was the alkylation of the phenylindanone 15 (R1=Ph), reported by the Merck research group in 1984.114-161 By use of the quaternary ammonium salt 7 (R=4-CF3i X=Br) derived from cinchonine, the alkylated products 16 were obtained in excellent yield with high enantiomeric excess, as shown in... 

The catalytic asymmetric Horner-Wadsworth-Emmons reaction was realized by use of the quaternary ammonium salts 7 derived from cinchonine as a phase transfer catalyst.1631 Thus, tert-butylcyclo-hexanone 85 reacted with triethyl phosphonoacet-ate 86 together with RbOH-H20 in the presence of the ammonium salts 7, and then the product 87 was isolated after reesterification by treatment with acidic ethanol, as shown in Scheme 27 Among the... 

The following quaternary ammonium salts are used as phase transfer catalyst tetra-K-butylammonium chloride (TBAC), tetra-n-butylammonium bromide (TBAB), benzyltriethylammonium chloride (BTEAC), and benzyltriethylammo-nium bromide (BTEAB). Chlorinated hydrocarbons, such as dichloromethane (DCM), chloroform (CF), tetrachloromethane (TCM), 1,2-dichloromethane (DCE), and nitrobenzene (NB) are used as solvents. The effects of phase-transfer catalyst and solvent on the yield and reduced viscosity are summarized in Table 9.1. 

Onium salts, crown ethers, alkali metal salts or similar chelated salts, quaternary ammonium and phosphonium are some of the salts which have been widely used as phase transfer catalysts (PTC). The choice of phase transfer catalysts depends on a number of process factors, such as reaction system, solvent, temperature, removal and recovery of catalyst, base strength etc. 

It is worth mentioning at this point that according to Normant et al. (1975) simple polyamines such as tetramethylethylenediamine (TMEDA) are even more active than [2.2.2]-cryptand in the benzylation of acetates in acetonitrile under liquid-solid conditions. These authors suggested that the activity was due to salt solubilization by cation complexation and not to formation of a quaternary ammonium ion since the latter showed no activity. This statement, however, is not in line with the results of Cote and Bauer (1977), who were unable to detect any interaction between K+ and TMEDA in acetonitrile. Furthermore, Vander Zwan and Hartner (1978) found Aliquat 336 (tricaprylylmethylammonium chloride) to be almost as effective as TMEDA in this reaction (Table 30). It might well be, however, that in amine-catalysed benzylation reactions the quaternary salt formed in situ acts both as a reactant and as a phase-transfer catalyst, since Dou et al. (1977) have shown that the benzyltriethylammonium ion is a powerful benzylation agent. 

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