Aqueous - organic biphasic

A recent proposal concerns mixed organic-aqueous tunable solvents (OATS) such as dimethyl ether-water, the solubility of which for substrates can be influenced by a third component such as carbon dioxide. CO2 acts as a antisolvent and as a switch to cause a phase separation and to decant the phases from each other (preferably under pressure). This behavior makes the operation of bi- or multiphase homogeneous catalytic processes easier and more economic the preferential dissolution at modest pressure of carbon dioxide causes phase separation which results in large distribution coefEcients of target molecules in biphasic organic-aqueous systems. This extraordinary behavior lead to a sophisticated flow scheme (Figure 6) [7]. 

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. 

On the other hand, biocatalyst stability can be affected by the presence of organic-aqueous interface. In our previous work [25], we studied the effect of interface with octane on the lipoxygenase stability in an octane-buffer pH 9.6 biphasic system. This loss in activity is more pronounced than that observed in the aqueous system. During lipoxygena-tion, the active enzyme concentration [E] in the aqueous phase of our biphasic bioreactor was ... 

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... 

The present section deals with the improvement in the performance of biocatalysis when carried out in organic-aqueous biphasic systems. Such systems are very useful in equilibrium reactions and conversion yield where substrates and products can be dissolved and drawn into different phases. Subsequently the synthesis in the reactive aqueous phase is allowed to continue. 

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. 

Many interesting biocatalytic reactions involve organic components that are poorly water-soluble. When using organic-aqueous biphasic bioreactor, availability of poorly water-soluble reactants to cells and enzymes is improved, and product extraction can be coupled to the bioreaction. Many applications in two-phase media can use the existing standard-type bioreactors, such as stirred-tank, fluidized-bed, and column reactors with minor adjustments. 

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 ... 

Owing to the very reactive nature of RuO relatively few solvents are suitable for its reactions. It is soluble in water to the extent of some 2% and is stable in such solutions, but reacts violently with diethyl ether, benzene and pyridine [236]. It has often been used catalytically in a biphasic system, with the co-oxidant in the aqueous layer. Under these circumstances the RuO formed from reduction of RuO by the substrate is re-oxidised at the organic - aqueous interface, so that oxidations with such systems can be much enhanced by stirring, shaking or sonication. In some cases (e.g. oxidation of aUcenes) it may be necessary to cool the reactants below room temperature, but in most cases ambient temperatures suffice, as indeed they do for the vast majority of organic oxidations catalysed by Ru complexes. 

Organic-Aqueous Biphasic Systems General Considerations... 

The most common approach in organic-aqueous biphasic systems is to operate with a continuous aqueous phase, which prevents the occurrence of extreme pH spots, with a volume phase ratio up to 0.4 [35]. An adequate selection of the organic-aqueous volume phase ratio allows for high interfacial areas. The influence of the volume phase ratio in the interfacial area (a) can be predicted according to Equation 1. 

Figure 8.4 Reactor types used in organic-aqueous biphasic systems (a) Emulsion reactor, (b) Lewis cell, (c) passive membrane reactor, (d) active membrane reactor. E represents enzyme molecules.

A major improvement in both catalytic activity and selectivity of propene hydroformylation in the organic-aqueous biphasic system was achieved by using the newly synthesized BINAS-Na ligand 10 in combination with rhodium(III) acetate (65). 

Phase transfer catalysis involves typically an organic/aqueous biphasic system in the presence of a transfer agent such as a tetraalkylammonium salt which facilitates the exchange of the catalyst between the two phases, while the reactants and the products are usually retained in the organic layer. Almost all types of homogeneously catalyzed reactions can be carried out in this way.173... 

Biphasic solvent mixtures can also be used for chiral cyanohydrin formation. Loos et al. reported optimisation studies during the development of an industrial process for the production of (J )-mandelonitrile [167,168]. A number of crucial reaction parameters such as pH-value, temperature, type of solvent and the phase ratio (organic/aqueous) were varied and optimised to give a highly productive method. 

Aqueous biphase Organic biphase Ionic liquids sc fluids Fluorous biphase Polymer supported... 

Preparation of 26 [14] Allyl alcohol 22 (0.91 mmol) and triethylamine (1 equiv.) were dissolved in dry tetrahydrofuran (THF) (2 mL) under argon. A solution of bromo tris(2-perfluorohexylethyl)silane 23 (0.25 equiv) in THF (2 mL) was slowly added to the reaction mixture at 25 °C. The resulting mixture was stirred at 25 °C for 3 h. After removal of the solvent, the residue was purified by three-phase extraction with FC-72 (10 mL), dichloromethane (10 mL), and water (10 mL). The organic/aqueous biphase was extracted twice more wdth FC-72 (10 mL). After concentration of the combined fluorous extracts, the residue was purified by flash chromatography (hexane/diethyl ether, 50 1) to yield a colorless oil. 

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