Lipophilic catalyst

The vast literature on applications of PTC in substitution reactions is mainly restricted to nucleophilic substitution reactions with an anionic reagent. However, recently the use of PTC in electrophilic reactions, like diazotization andazocou-pling C-and N-nitrosation, C-alkylation, acid hydrolysis of esters, chloromethylation, nitrite-initiated nitrations, and so on have been reported(Velichko et al., 1992 Kachurin et al., 1995). Alkylbenzene sulfonates and lipophilic sodium tetrakis[3,5-bis(trifluoromethyl)phenylboranate are typical electrophilic PT catalysts. Lipophilic dipolar molecules of the betaine type and zwitterionic compounds also function well as PT agents for both nucleophilic as well as electrophilic reactions. 

Among inorganic anions used as reducing agents, BH4 occupies a dominant position. This anion is sufficiently stable in an aqueous solution of its sodium salt and can be transferred into a nonpolar solvent by typical PT catalysts - lipophilic TAA salts. The use of PTC facilitates reduction of carbonyl compounds insoluble in hydroxylic solvents. In some cases even reduction of an ester group is possible under these conditions ... 

A comparison between literature data about performances of different catalysts in a particular reaction is not always an easy task to achieve. In fact when the reaction is not run under the same reaction conditions correct comparisons are difficult since various factors are usually simultaneously involved, often counteracting each other. Therefore, evaluation of the important requirements for a PTC process such as catalyst lipophilicity, selective anion extraction, cation-anion separation within the ion pair, and poor anion solvation may be not sufficient for useful predictions. Other factors such as the structure of the substrate or anion hydration, interaction with solvent, or ionic strength of the aqueous phase may assume great importance. 

Figure 1 shows the mechanistic picture developed by C. M. Starks (1,2) for Hquid—Hquid PTC in a graphical form. The catalyst cation extracts the more hpholilic anion Y from the aqueous to the nonpolar organic phase where it is present in the form of a poorly solvated ion pair Y ]. This then reacts rapidly with RX, and the newly formed ion pair X ] returns to the aqueous phase for another exchange process X — Y . In practice most catalyst cations used are rather lipophilic and do not extract strongly into the aqueous phase so that the anions are exchanged at the phase boundary. 

Catalyst Cation. The logarithms of extraction constants for symmetrical tetra- -alkylammonium salts (log rise by ca 0.54 per added C atom. Although absolute numerical values for extraction coefficients are vastly different in various solvents and for various anions, this relation holds as a first approximation for most solvent—water combinations tested and for many anions. It is important to note, however, that the lipophilicity of phenyl and benzyl groups carrying ammonium salts is much lower than the number of C atoms might suggest. Benzyl is extracted between / -propyl and -butyl. The extraction constants of tetra- -butylammonium salts are about 140 times larger than the constants for tetra- -propylammonium salts of the same anion in the same solvent—water system. 

For practical appHcation in mixtures of water—organic solvent, only ammonium and phosphonium salts containing 15 or more C atoms are sufficiently lipophilic. In empirical catalyst comparisons crown ethers (hexaoxacyclooctodecanes) (1)—(3) were often as effective as the best onium salts. 

Landini, Montanari and Rolla ° were able to incorporate cyclohexyl residues in the strands and thereby increase lipophilicity. As with the compounds referred to above, these were effective phase transfer catalysts. 

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]. 

As described previously, lipophilic monoimidazole ligands form 2 1 complexes with the Zn2 + ion (n = 2 in Scheme 2) as active catalysts except for some sterically hindered ligands (Table 3, 5, 7), and bisimidazole ligands form 1 1 complexes (n = 1 in Scheme 2, Table 5). In this chiral system, the latter 1 1 complex accords with kinetic analyses for both L-47 and L,L-49 ligands as shown in Fig. 12 and Table 11. These conclusions seem to be reasonable since monoimidazole derivatives have only one imidazole nitrogen, while the other bisimidazole and chiral ligands have more than two nitrogen atoms which can effectively coordinate to the Zn2 + ion. 

Experience in PTC with cationic catalysts showed that, in general, the most suitable compounds have symmetrical structures, are lipophilic, and have the active cationic charge centrally located or sterically shielded by substituents. For anionic catalysis sodium tetraphenylborate fulfills these conditions, but it is not stable under acidic conditions. However, certain derivatives of this compound, namely sodium tetra-kis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB, 12.162) and sodium tetrakis[3,5-bis-(l,l,l,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]borate (HFPB) are sufficiently stable to be used as PTC catalysts for azo coupling reactions (Iwamoto et al., 1983b 1984 Nishida et al., 1984). These fluorinated tetraphenylborates were found to catalyze strongly azo coupling reactions, some of which were carried out with the corresponding diazotization in situ. 

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... 

The formation of nitrosamines in aprotic solvents has applicability to many practical lipophilic systems including foods (particularly bacon), cigarette smoke, cosmetics, and some drugs. The very rapid kinetics of nitrosation reactions in lipid solution indicates that the lipid phase of emulsions or analogous multiphase systems can act as "catalyst" to facilitate nitrosation reactions that may be far slower in purely aqueous media (41, 53, 54). This is apparently true in some cosmetic emulsion systems and may have important applicability to nitrosation reactions in vivo, particularly in the GI tract. In these multiphase systems, the pH of the aqueous phase may be poor for nitrosation in aqueous media (e.g., neutral or alkaline pH) because of the very small concentration of HONO or that can exist at these pH ranges. 

PT catalysts are often difficult to separate from the product, while it is also desirable that the catalyst should be reusable or recyclable. Distillation and extraction are the most common separation processes. The main disadvantage of lipophilic quats is their tendency to remain in the organic phase and consequently contaminate the product. Therefore, extraction in water often is not satisfactory. Furthermore, products in the fine chemicals industry often have high boiling points and/or are heat sensitive, which makes separation of the catalyst by distillation impossible. Often the only means to remove the catalyst in these cases is to adsorb it using a high surface area sorbent such as silica, Florisil or active carbon (Sasson, 1997). After filtration, the catalyst can then be recovered by elution. 

Catalysis in Transacylation Reactions. The principal objective of the study was to evaluate 4 as an effective organic soluble lipophilic catalyst for transacylation reactions of carboxylic and phosphoric acid derivatives in aqueous and two-phase aqueous-organic solvent media. Indeed 4 catalyzes the conversion of benzoyl chloride to benzoic anhydride in well-stirred suspensions of CH2CI2 and 1.0 M aqueous NaHCC>3 (Equations 1-3). The results are summarized in Table 1 where yields of isolated acid, anhydride and recovered acid chloride are reported. The reaction is believed to involve formation of the poly(benzoyloxypyridinium) ion intermediate (5) in the organic phase (Equation 1) and 5 then quickly reacts with bicarbonate ion and/or hydroxide ion at the interphase to form benzoate ion (Equation 2 and 3). Apparently most of the benzoate ion is trapped by additional 5 in the organic layer or at the interphase to produce benzoic anhydride (Equation 4), an example of normal phase-... 

The change in selectivity is not credited to the catalyst alone In general, the bulkier the alkyl residue of the diazoacetate is, the more of the m-permethric acid ester results 77). Alternatively, cyclopropanation of 2,5-dimethyl-2,4-hexadiene instead of l,l-dichloro-4-methyl-l,3-pentadiene leads to a preference for the thermodynamically favored trans-chrysanthemic add ester for most eatalyst/alkyl diazoacetate combinations77 . The reasons for these discrepandes are not yet clear, the interplay between steric, electronic and lipophilic factors is considered to determine the stereochemical outcome of an individual reaction77 . This seems to be true also for the cyclopropanation of isoprene with different combinations of alkyl diazoacetates and rhodium catalysts77 . 

As Table 20 shows, the yields of the Rh(II)-promoted reaction are temperature-dependent. Furthermore, competitive experiments between pairs of alkanes revealed a marked dependence on the alkoxy group of the diazoester and on the perfluoroalkyl carboxylate part of the catalyst. The observed relative selectivities have been taken as evidence for the importance of lipophilic interactions between carbenoid and alkane. 

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. 

The trend was studied and verified, for instance, for reactions catalysed by transition metal, organo- and enzyme catalysts entrapped in ORMOSIL prepared by copolymerization of tetramethoxysilane (TMOS) and the modifying co-precursor methyltrimethoxysilane (MTMS). It has been correlated with the encapsulation itself but also with the structure of the sol-gel matrix, namely the hydrophobicity-lipophilicity balance (HLB) and the textural properties of the materials.9... 

Greater durability of the colloidal Pd/C catalysts was also observed in this case. The catalytic activity was found to have declined much less than a conventionally manufactured Pd/C catalyst after recycling both catalysts 25 times under similar conditions. Obviously, the lipophilic (Oct)4NCl surfactant layer prevents the colloid particles from coagulating and being poisoned in the alkaline aqueous reaction medium. Shape-selective hydrocarbon oxidation catalysts have been described, where active Pt colloid particles are present exclusively in the pores of ultramicroscopic tungsten heteropoly compounds [162], Phosphine-free Suzuki and Heck reactions involving iodo-, bromo-or activated chloroatoms were performed catalytically with ammonium salt- or poly(vinylpyrroli-done)-stabilized palladium or palladium nickel colloids (Equation 3.9) [162, 163],... 

In general, there are two immiscible phases in reaction mixture, viz. an aqueous phase which contains a salt (a base or nucleophile) and the other an organic phase containing the substrate which is expected to react with the salt. When a phase transfer catalyst (usually contains a lipophilic cation) is added to the reaction mixture, the lipophilic cation (which has solubility in both aqueous and organic phases), exchanges anions with the excess of anions in the salt solution. 

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