Biphasic liquid phase

The drawback of SILP strategy to heterogeneous catalysis lies in the weak interactions (physical adsorption) between the IL and the solid support which limit applications to gas-solid phase reactions, only. Indeed, in biphasic liquid phase conditions both mechanical forces and partitioning processes could slowly remove the IL film from the solid support. To circumvent this problem, stronger interactions must be created between the IL phase and the support. 

In the aqueous biphasic hydroformylation reaction, the site of the reaction has been much discussed (and contested) and is dependent on reaction conditions (temperature, partial pressure of gas, stirring, use of additives) and reaction partners (type of alkene) [35, 36]. It has been suggested that the positive effects of cosolvents indicate that the bulk of the aqueous liquid phase is the reaction site. By contrast, the addition of surfactants or other surface- or micelle-active compounds accelerates the reaction, which apparently indicates that the reaction occurs at the interfacial layer. 

The most important biphasic liquid systems are probably those that combine a conventional organic phase with another type of solvent, such as water, a fluorous organic solvent, or an ionic liquid [3]. In those cases the solvent can be considered as the support for the catalyst phase and we have therefore limited the examples in this review to those where the recycled liquid catalyst phase is recovered as a whole. 

In 1982, Lilly [21] reviewed the first two-liquid phase biocatalysis. In 1987 and 1992, Lilly s group [39,40] published reviews dealing with process engineering of biphasic bioreactors. In 1993, Van Sonsbeek et al. [41] gave an overview on biocatalysis in different biphasic... 

Several experiments using different organic solvents in different biphasic media are necessary to find the adequate distribution of the reaction components. A series of experiments are essential for the choice of a process and for scaling-up. Experiments using Lewis cells [44] may yield useful results for understanding equilibrium, kinetics, and interactions between organic solvent-substrate and/or organic solvent-biocatalyst. A study of two-liquid phase biotransformation systems is detailed below in Sections II-IX. 

Biphasic systems are composed of two continuous liquid phases the organic and the aqueous phases [13,25,27,31,36]. An interface generally separates the aqueous phase containing the biocatalyst from the organic phase containing the substrate. Moreover, the reaction product, if poorly soluble in water, can be easily separated from the biocatalyst. The use of carefully measured concentrations in hydrophobic reactants becomes facile in such systems, and substrate excess inhibition of the biocatalyst is reduced. 

The volumetric ratio of the two liquid phases (j6 = Forg/ Faq) can affect the efficiency of substrate conversion in biphasic media. The biocatalyst stability and the reaction equilibrium shift are dependent on the volume ratio of the two phases [29]. In our previous work [37], we studied the importance of the nonpolar phase in a biphasic system (octane-buffer pH 9) by varying the volume of solvent. The ratio /I = 2/10 has been the most appropriate for an improvement of the yield of the two-enzyme (lipase-lipoxygenase) system. We found that a larger volume of organic phase decreases the total yield of conversion. Nevertheless, Antonini et al. [61] affirmed that changes in the ratios of phases in water-organic two-phase system have little effect upon biotransformation rate. 

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. 

Quite new ideas for the reactor design of aqueous multiphase fluid/fluid reactions have been reported by researchers from Oxeno. In packed tubular reactors and under unconventional reaction conditions they observed very high space-time yields which increased the rate compared with conventional operation by a factor of 10 due to a combination of mass transfer area and kinetics [29]. Thus the old question of aqueous-biphase hydroformylation "Where does the reaction takes place " - i.e., at the interphase or the bulk of the liquid phase [23,56h] - is again questionable, at least under the conditions (packed tubular reactors, other hydrodynamic conditions, in mini plants, and in the unusual,and costly presence of ethylene glycol) and not in harsh industrial operation. The considerable reduction of the laminar boundary layer in highly loaded packed tubular reactors increases the mass transfer coefficients, thus Oxeno claim the successful hydroformylation of 1-octene [25a,26,29c,49a,49e,58d,58f], The search for a new reactor design may also include operation in microreactors [59]. 

Biphasic systems, in which the catalyst is designed to be dissolved in a liquid phase which is immiscible with the product (either with or without a separate solvent) potentially provide some of the most attractive solutions to the problem of product... 

The term Supported Ionic Liquid Phase (SILP) catalysis has recently been introduced into the literature to describe the heterogenisation of a homogeneous catalyst system by confining an ionic liquid solution of catalytically active complexes on a solid support [68], In comparison to the conventional liquid-liquid biphasic catalysis in organic-ionic liquid mixtures, the concept of SILP-catalysis offers very efficient use of the ionic liquid. Figure 7.10 exemplifies the concept for the Rh-catalysed hydroformylation. 

Recently, platinum nanoparticles protected by N,N-dimethyl-N-cetyl-N-(2-hydro-xyethyl)ammonium chloride salt and modified with cinchonidine were investigated in the enantiomeric hydrogenation of ethyl pyruvate in pure biphasic liquid-liquid (water/substrate) media at room temperature [139]. For the first time, the aqueous phase containing Pt(0) nanocatalysts with an average size of 2.5 nm could be reused for successive hydrogenations, and with a total conversion of activity and enantioselectivity in (R)-(+)-ethyl lactate up to 55% (Scheme 9.12). 

As with classical multiphase catalysis, the organometallic catalyst is retained here in a liquid phase that is immiscible with the second phase containing substrates and/or products. For hydrogenation, the liquid/SCF system is always biphasic, whereas conventional systems are usually triphasic (liquid-1 /liquid-2/ H2). The liquid phase must provide a stable environment for the organometallic catalyst and should be insoluble in the SCF phase. Water, ILs and PEG have been used successfully for this purpose, together with scC02 as the mobile phase. Again, the products must not be too polar in order to be effectively extracted if C02 is used as the SCF. 

Biphasic systems that contain the catalyst in the supercritical phase and the substrates/products in a second liquid phase can also be implemented. With water as the polar phase, these inverted systems are particularly attractive for the conversion of highly polar and/or low-volatile hydrophilic substrates with limited solubility in typical SCFs such as scC02. 

A rather new concept for biphasic reactions with ionic liquids is the supported ionic liquid phase (SILP) concept [115]. The SILP catalyst consists of a dissolved homogeneous catalyst in ionic liquid, which covers a highly porous support material (Fig. 41.13). Based on the surface area of the solid support and the amount of the ionic liquid medium, an average ionic liquid layer thickness of between 2 and 10 A can be estimated. This means that the mass transfer limitations in the fluid/ionic liquid system are greatly reduced. Furthermore, the amount of ionic liquid required in these systems is very small, and the reaction can be carried in classical fixed-bed reactors. 

These examples reveal the attractive features of fluorous biphasic catalysis methods for chemical processes. Reactions occur in the liquid phase and can be either homogeneous or biphasic. In either case, biphasic conditions are established at the end of the reaction so the separation is easy. Fluorous sol-... 

The most widely encountered biphasic method commences with two immiscible phases, one containing the catalyst, the other the substrate or substrates, and was first recognized by Manassen in 1973 [1], Liquid phases may be immiscible if their polarities are sufficiently different, as explained in Chapter 1. The two phases are vigorously mixed allowing reaction between the catalyst and substrates to take place. When the reaction is complete, the mixing is stopped and the two phases separate. A schematic representation of such a process is illustrated in Figure 2.1. In the ideal system, the catalyst is retained in one phase ready for reuse and the product is contained in the other phase and can be removed without being contaminated by the catalyst. In certain cases, neat substrates may be used as one phase, without additional solvents. 

Onium salts, such as tetraethylammonium bromide (TEAB) and tetra-n-butylammonium bromide (TBAB), were also tested as PTCs immobilized on clay. In particular, Montmorillonite KIO modified with TBAB efficiently catalyzed the substitution reaction of a-tosyloxyketones with azide to a-azidoketones, in a biphasic CHCI3/water system (Figure 6.13). ° The transformation is a PTC reaction, where the reagents get transferred from the hquid to the solid phase. The authors dubbed the PTC-modified catalyst system surfactant pillared clay that formed a thin membrane-hke film at the interface of the chloroform in water emulsion, that is, a third liquid phase with a high affinity for the clay. The advantages over traditional nucleophilic substitution conditions were that the product obtained was very pure under these conditions and could be easily recovered without the need for dangerous distillation steps. 

The preparation of novel phase transfer catalysts and their application in solving synthetic problems are well documented(l). Compounds such as quaternary ammonium and phosphonium salts, phosphoramides, crown ethers, cryptands, and open-chain polyethers promote a variety of anionic reactions. These include alkylations(2), carbene reactions (3), ylide reactions(4), epoxidations(S), polymerizations(6), reductions(7), oxidations(8), eliminations(9), and displacement reactions(10) to name only a few. The unique activity of a particular catalyst rests in its ability to transport the ion across a phase boundary. This boundary is normally one which separates two immiscible liquids in a biphasic liquid-liquid reaction system. 

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