Biphasic medium

Fig. 20. Homogeneous rliodium-cataly2ed oxo process in biphasic media developed by Ruhrchemie/Rhc ne-Poulenc (83).

These ligands were used in protic and biphasic media by modifying their structure using hydroxyalkyl groups [28,29]. The solubihty of the corresponding Ru(II) complexes was significantly increased in protic solvents. Hence, by performing the reaction in mixtures of toluene and water or al-... 

In 1999, Albach and Jautelat described in a patent the use of a sulfobetaine as the surfactant to stabilize Ru, Rh, Pd, Ni nanoparticles and bimetalUc mixtures [77]. Benzene, cumene and isopropylbenzene are reduced in biphasic media under various conditions 100-150 °C and 60 bar of H2. 250 TTO are... 

Figure 2.29. Pd/tppt.s-catalysed carbonylations in aqueous biphasic media.

Biocatalysis in Liquid-Liquid Biphasic Media Coupled Mass Transfer and Chemical Reactions... 

Since the beginning of the 20th century, organic solvents have been used in enzymatic reaction media [30]. Biocatalytic reactions in water-organic biphasic media were first carried out by Cremonesi et al. [31] and by Buckland et al. [32] less than 30 years ago. Their work aimed at the conversion of high concentrations of poorly water soluble components, particularly steroids. Later, biphasic systems were used for enzyme-catalyzed synthesis reactions that were unfavored in water, changing the reaction equilibrium towards the higher yield of the product, such as esters or peptides. 

The development of biphasic media requires a knowledge of general rules based on observation. The choice of the biocatalyst and the organic solvent is very important. Estimation of the biocatalyst tolerance to an organic solvent is based on various indicators, described later in this chapter. Biocatalysts are also sensitive to the process of the liquid-liquid interface. They can be used in two different forms free, soluble or immobilized. 

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 media are macroheterogenous, with a well-defined liquid-liquid interface [25,63] [Fig. 1(g), (h)], or microheterogeneous consisting of an emulsion with a very important interface area [37,38] [Fig. 1-f]. The first medium is used for kinetic studies... 

Several kinds of states in which enzymes may be used for various reactions in aqueous-organic biphasic systems have been developed in previous work (Table 2). In biphasic media, the biocatalyst is easily recovered after the reaction then it is not always necessary to be immobilized. Nevertheless, the immobilization can confer important properties, such as improved stability of biocatalyst. Furthermore, protection of the biocatalyst against a damaging turbulent environment can also play a role. 

With biphasic media, as free biocatalyst, the catalyst support material is generally immersed in the aqueous phase (Fig. 1). Most of the support materials which are already... 

TABLE 1 Effect of the Organic Solvent on Stability and/or Activity of Biocatalysts in Biphasic Media... 

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. 

The lipases demonstrated very high stability in media partially or totally composed of organic solvent. In such media, the lipases catalyze esterification, transesterification, and resolution of enantiomers [19,45,75,97-100]. Nevertheless, several biphasic systems (organic-aqueous) are used for hydrolysis of lipid and fats [7,34,101]. Kinetic studies in biphase media or in inverted micelles demonstrate that the lipase behavior is different... 

As the majority of enzyme systems in aqueous-organic biphasic media, lipase-catalyzed hydrolysis uses substrates that are insoluble in aqueous media and yield hydrophobic products (Fig. 3). Therefore, the aqueous phase serves as a biocatalyst reservoir. 

Kinetic behavior of the two-enzyme system (lipase-lipoxygenase) in biphasic media (curve c in Fig. 5) is compared with kinetics of lipoxygenase in the same biphasic medium (b) and in an aqueous medium (a). These curves demonstrated that the configuration of the media influences the production rate of HP. As previously stated, lipoxygenase in biphasic media has an apparent kinetic behavior different from that in aqueous media (see difference between curves a and b in Fig. 5). 

Yang and Russell [7] made comparison of lipase-catalyzed hydrolysis in three different systems organic, biphasic, and reversed micelles. They affirmed that water content is an important factor that distinctly affects every system. Their results demonstrated that activity of lipase in organic-aqueous biphasic media was lower than that obtained in reversed micelles. However, better productivities were obtained in biphasic media, which were the most suitable environment. 

TABLE 4 Yields of Different Enzyme-Catalyzed Reactions in Biphasic Media. 100% Conversion Yield Corresponds to the Total Conversion of Substrate to Product... 

As proven in this review and other papers, organic-aqueous biphasic media have been useful in many areas of biocatalysis applications. We summarize the potential advantages in carrying out biocatalysis in biphasic systems ... 

B. Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide homoallylic alcohol in high yields (>94%) and excellent diastereoselectivity (dr >98 2). The presence of a phase-transfer catalyst (e.g., B114NI) significantly accelerates the rate of reaction, whereas adding fluoride ion retards the reaction (Eq. 8.70).165 The method was applied to the asymmetric total synthesis of the antiobesity agent tetrahydrolipstatin (orlistat).166... 

Mevellec, V., Roucoux, A., Ramirez, E., Philippot, K. and Chaudret, B. (2004) Surfactant-stabilized aqueous iridium(O) colloidal suspension an effident reusable catalyst for hydrogenation of arenes in biphasic media. Advanced Synthesis and Catalysis, 346 (1), 72-76. 

Catalysis in biphasic media is one of the most elegant and efficient means to solve the problem of catalyst recovery. Many excellent reviews are available and industrial processes are currently running.104-107 This method is (like all others) not applicable for all situations, and is particularly... 

A series of tri- and tetra-nuclear Ru clusters previously reported by the groups of Siiss-Fink [60] and of Dyson [61] as catalysts for the hydrogenation of benzene and other simple aromatics in biphasic media have later been shown to consist predominantly of active metallic particles [9, 10, 62]. 

Diphenylacetylene and 1-phenyl-1-propyne were hydrogenated to the corresponding 1,2-disubstituted alkenes in aqueous organic biphasic media using [ RuCl2(wtppms)2 2] and an excess of wtppms (80 °C, 1 bar H2, TOFs up to 25 h-1). The stereoselectivity of the reaction depended heavily on the pH of the catalyst-containing aqueous phase (Fig. 38.1) and, under acidic conditions, Z-al-kenes could be obtained with a selectivity close to 100% [71]. 

Enantioselective hydrogenation of prochiral ketones has rarely been studied in aqueous biphasic media. In addition to the chiral bisphosphonic acid derivatives of 1,2-cyclohexanediamine [130], the protonated 4,4 -, 5,5 -, and 6,6 -amino-methyl-substituted BINAP (diamBINAP 2HBr) ligands (Scheme 38.7) served as constituents of the Ru(II)-based catalysts in the biphasic hydrogenations of ethyl acetoacetate [131, 132]. These catalysts were recovered in the aqueous phase and used in at least four cycles, with only a marginal loss of activity and enantio-selectivity. 

In order to keep the mild conditions, hydroxycarbonylation has been performed in biphasic media, maintaining the catalyst in the aqueous phase thanks to water-soluble mono- or diphosphine ligands. In the presence of the sodium salt of trisulfonated triphenylphosphine (TPPTS), palladium was shown to carbonylate efficiently acrylic ester [19], propene and light alkenes [20,21] in acidic media. For heavy alkenes the reduced activity due to the mass transfer problems between the aqueous and organic phases can be overcome by introducing an inverse phase transfer agent, and particularly dimeihyl-/-i-cyclodextrin [22,23]. Moreover, a dicationic palladium center coordinated by the bidentate diphosphine ligand 2,7-bis(sulfonato)xantphos (Fig. 2) catalyzes, in the presence of tolylsulfonic acid for stability reasons, the hydroxycarbonylation of ethylene, propene and styrene and provides a ca. 0.34 0.66 molar ratio for the two linear and branched acids [24],... 

To understand the pharmacokinetic relevance of the proxibarbal-valofan equilibrium, the kinetics and thermodynamics of the reaction were carefully examined in aqueous and biphasic media. The various pseudo-first-order rate constants shown in Fig. 11.19 were determined in the pH range of 6.7 - 8.0... 

Table 4.4.. Asymmetric hydroformylation of styrene in organic and in aqueous biphasic media ...

Table 4.6. Rhodium-catalyzed hydrofoimylation in aqueous-organic biphasic media with...

Concentrated aqueous salt solutions were used for dehydration of carbohydrates catalyzed by RuCh + Ag2S04 ( RUSO4 ) [47]. Such solvents may also help in constracting aqueous-organic biphasic media with good phase separation properties. Selective dehydroxylation of polyols and sugars was achieved in aqueous solutions with the use of anionic rathenium carbonyls, as well [48]. 

---