Examples of Biphasing

Reaction Catalyst Organic solvent Enhancement Reference 

Enzymatic oxidation of ethanol and butanol Alcohol oxidase Toluene Conversion increases with increasing volume fraction of organic phase Hidaka et al. (1995) 

Synthesis of poly(2,6-dimethyl-1,4-phenylene oxide) Cuprous chloride, also used a surface active ligand to promote the reaction Toluene and chloroform n-Hq tane and diethyl ether Chloroform slightly more effective than toluene polymer molecular weight on the order of 50,000 and yield in excess of 80% Not effective Dautenhahn and Lim (1992) 

Hydrolysis of 2-naphthyl acetate Oi o Lipase from Rhizopus delemar n-Heptane Assuming film thickness 6 = 10 cm, enhancement is 10 times that in aqueous phase alone Miyake et al. (1991) 

Hydrolysis of olive oil Candida rugosa lipase Isooctane No enhancement information available Equilibrium conversions higher than 98% obtained Tsai et al. (1991) 

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TABLE 11.3 Examples of Biphasic and Triphasic MudPIT Analyses... 

The first example of biphasic catalysis was actually described for an ionic liquid system. In 1972, one year before Manassen proposed aqueous-organic biphasic catalysis [1], Par shall reported that the hydrogenation and alkoxycarbonylation of alkenes could be catalysed by PtCh when dissolved in tetraalkylammonium chloride/tin dichloride at temperatures of less than 100 °C [2], It was even noted that the product could be separated by decantation or distillation. Since this nascent study, synthetic chemistry in ionic liquids has developed at an incredible rate. In this chapter, we explore the different types of ionic liquids available and assess the factors that give rise to their low melting points. This is followed by an evaluation of synthetic methods used to prepare ionic liquids and the problems associated with these methods. The physical properties of ionic liquids are then described and a summary of the properties of ionic liquids that are attractive to clean synthesis is then given. The techniques that have been developed to improve catalyst solubility in ionic liquids to prevent leaching into the organic phase are also covered. 

Biocatalysis in Biphasic Systems General Table 8.1 Some recent examples of biphasic systems in biocatalysis. 

Most examples describe catalyzed biphasic reactions taking the extra advantage of product isolation and catalyst recycling. De Bellefon et al. [211] published one of the first examples of biphasic reactions performed in a microreactor. The isomerization of allylic alcohols to carbonyl compounds was conducted in a liquid-liquid system using a micromixer combined with a microchannel tube. As there are limited examples of biphasic isomerization reactions, the authors were interested on... 

BIphasic Reaction Engineering 591 Table 18.3 Examples of biphasic reactions of different classes... 

Ester formation is a typical example of category 2. Although other methods such as the use of distillation column reactors (see Chapter 25) are preferred, layer separation can also be used by adding dichloromethane to remove the water. A well-known example of biphasing in organic synthesis belongs to this class, the Schotten-Baumann acylation reaction... 

As water is immiscible with most organic substrates, most reactions involving water are done with liquid-liquid biphasic systems. The use of biphasic organometallic catalysts to catalyze aqueous-phase reactions is a novel method to address this issue. The catalyst in such reactions is a water-soluble transition metal complex with substrates that are partially water-soluble. The Ruhrchemie-Rhone-Poulenc process, which involves hydrofor-mylation of propylene to n-butanol, is an example of biphasic organometallic catalysts being used on an industrial scale (Comils and Kuntz, 1995). The catalyst employed is a water-soluble Rhodium (I) complex of trisulfonated triphenylphosphine (tppts) (see Fig. 5.3). 

A very interesting example of biphasic carbonylation of chloroarenes apparently involving an implicit phase transfer was described.f In this method chloroarene itself is used as an organic phase in the system containing aqueous alkali and palladium salt in the presence of CysP without any phase transfer or solubilizing agents. 

An example of a stereoselective hydrogenation in ionic liquids was recently successfully demonstrated by Drie en-H6lscher et al. On the basis of investigations into the biphasic water/n-heptane system [51], the ruthenium-catalyzed hydrogenation of sorbic acid to cis-3-hexenoic acid in the [BMIM][PFg]/MTBE system was studied [52], as shown in Scheme 5.2-8. 

Finally, a special example of transition metal-catalyzed hydrogenation in which the ionic liquid used does not provide a permanent biphasic reaction system should be mentioned. The hydrogenation of 2-butyne-l,4-diol, reported by Dyson et al., made use of an ionic liquid/water system that underwent a reversible two-... 

Biphasic catalysis is not a new concept for oligomerization chemistry. On the contrary, the oligomerization of ethylene was the first commercialized example of a biphasic, catalytic reaction. The process is known under the name Shell Higher Olefins Process (SHOP) , and the first patents originate from as early as the late 1%0 s. 

One technically important example of an oligomerization that could not be carried out in a liquid-liquid biphasic mode with polar organic solvents or water is the... 

An example of a biphasic, Ni-catalyzed co-dimerization in ionic liquids with weakly coordinating anions has been described by the author s group in collaboration with Leitner et al. [12]. The hydrovinylation of styrene in the biphasic ionic liq-uid/compressed CO2 system with a chiral Ni-catalyst was investigated. Since it was found that this reaction benefits particularly from this unusual biphasic solvent system, more details about this specific application are given in Section 5.4. 

Flowever, information concerning the characteristics of these systems under the conditions of a continuous process is still very limited. From a practical point of view, the concept of ionic liquid multiphasic catalysis can be applicable only if the resultant catalytic lifetimes and the elution losses of catalytic components into the organic or extractant layer containing products are within commercially acceptable ranges. To illustrate these points, two examples of applications mn on continuous pilot operation are described (i) biphasic dimerization of olefins catalyzed by nickel complexes in chloroaluminates, and (ii) biphasic alkylation of aromatic hydrocarbons with olefins and light olefin alkylation with isobutane, catalyzed by acidic chloroaluminates. 

Typically the reaction was carried out as follows to a mixture of lipase in the IL were added this racemic alcohol and vinyl acetate as the acyl donor. The resulting mixture was stirred at 35°C and the reaction course was monitored by GC analysis. After the reaction, ether was added to the reaction mixture to form a biphasic layer, and product acetate and unreacted alcohol were extracted with ether quantitatively. The enzyme remained in the IL phase as expected (Fig. 2). Two months later, Kim and co-workers reported similar results and Lozano and Ibora " reported other examples of lipase-catalyzed reaction in June. Further Park and Kazlauskas reported full details of lipase-catalyzed reaction in an IL solvent... 

An example of a large scale application of the aqueous biphasic concept is the Ruhrchemie/Rhone-Poulenc process for the hydroformylation of propylene to n-butanal (Eqn. (15)), which employs a water-soluble rhodium(I) complex of trisulphonated triphenylphosphine (tppts) as the catalyst (Cornils and Wiebus, 1996). 

Ten Brink et al. (2000) have shown how biphasic systems, sometimes with the sparingly soluble alcohols as one phase and an aqueous phase as the other phase, benefit from the strategy for air oxidation to aldehydes/ketones by using water soluble Pd complex of bathophenanthroline disulphonate. This is a nice example of green technology. 

An important problem in emulsified organic-aqueous systems is that of scale-up, which is concerned with the realization of stable emulsions and the separation of phases after the reaction. The use of biphasic membrane systems that contain the enzyme and keep the two phases separated is likely to solve this problem. In the case of 5-naproxen an ee of 92% has been demonstrated without any decay in activity over a period of two weeks of continuous operation. A number of examples of biocatalytic membrane reactors have been provided by Giorno and Drioli (2000) and include the conversion of fumaric acid to L-aspartic acid, L-aspartic acid to L-alanine, and cortexolone to hydrocortisone and prednisolone. 

In both cases, the half-wave potential shifts by RT/ ziF)vaN per pH unit, and a typical example of such a behavior is given in Fig. 9 for the transfer of two acidic fi-diketones at the water-nitrobenzene interface. These results were unexpected, since a current wave is measured at a pH where the compound of interest is by a very large majority neutral, but they in fact represent the typical behavior of ionizable compounds at the ITIES and prove that the interfacial potential and the transfer of protons plays a key role for the distribution in biphasic systems. 

The use of thermomorphic systems has recently been studied as a way of achieving catalyst separation in homogeneous catalysis. For example, a biphasic hydroformylation catalyst system was developed to take advantage of the unusual solvent characteristics of perfluorocarbons combined with typical organic solvents (4). Fluorous/organic mixtures such as perfiuoromethylcyclohexane... 

Immobilization of catalysts is an important process design feature (see Chapter 9.9). A recent example of catalyst immobilization is the biphasic approach which seems superior to immobilization on solids, as successfully proven in the Ruhrchemie/Rhone Poulenc process for the hydro-formylation of olefins.286 Supported liquid phase catalysis was devised as a method for the immobilization of homogeneous catalysts on solids. When the liquid phase is water, a water-soluble catalyst may be physically bound to the solid. 

In contrast, we intend to demonstrate the principle aspects of catalyst recycling and regeneration using the ionic liquid methodology. These aspects will be explored in more detail for the example of Rh-catalysed hydroformylation (see Section 7.2). First, however, we will briefly introduce important general facts concerning transition metal catalysis in ionic liquids (see Section 7.1.2). This will be followed by a consideration of liquid-liquid biphasic reactions in these media from an engineering point of view (see Section 7.1.3). 

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