Organic biphasic system

Stability of several enzymes like proteases from thermophilic micro-organisms can be increased in aqueous-organic biphasic systems. Owusu and Cowan [67] observed a strong positive correlation between bacterial growth temperature, the thermostability of free protein extracts, and enzyme stability in aqueous-organic biphasic systems (Table 1). Enzymes, like other cell components (membranes, DNA, (RNA ribosomes), are adapted to withstand the environmental conditions under which the organism demonstrates optimal growth. 

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. 

Rhodium catalysis in an aqueous-organic biphasic system was highly effective for intramolecular [2+2+2] cyclotrimerization. It has been shown that the use of a biphasic system could control the concentration of an organic hydrophobic substrate in the aqueous phase, thus increasing the reaction selectivity. The intramolecular cyclization for... 

DipolarCycloaddition Reactions. The 1,3-dipolar cyclization of nitrile oxide with dipolarophiles generates structurally important heterocycles. As shown by Lee,139 the reaction can be carried out in an aqueous-organic biphasic system in which the nitrile oxide substrates can be generated from oximes or hydrazones in situ. The method provides a convenient one-pot procedure for generating a variety of heterocyclic products. 

Other salts of formic acid have been used with good results. For example, sodium and preferably potassium formate salts have been used in a water/organic biphasic system [36, 52], or with the water-soluble catalysts discussed above. The aqueous system makes the pH much easier to control minimal COz is generated during the reaction as it is trapped as bicarbonate, and often better reaction rates are observed. The use of hydrazinium monoformate salts as hydrogen donors with heterogeneous catalysts has also been reported [53]. 

For the hydrogenation ofpolystyrene-fo-polybutadiene-fo-polystyrene (SBS) block co-polymer with Ru-TPPTS complex as catalyst, Jang et al. [92] applied a poly-ether-modified ammonium salt ionic liquid/organic biphasic system (Fig. 41.3). 

Optimization of a fluorous-organic biphasic system requires knowledge of the solubility of the fluorous catalysts and reagents in the fluorous solvents with... 

In most aqueous/organic biphasic systems, the catalyst resides in the aqueous phase and the substrates and products are dissolved in (or constitute) the organic phase. In a few cases a reverse setup was applied i.e. the catalyst was dissolved in the organic phase and the substrates and products in the aqueous one. This way, in one of the earliest attempts of liquid-liquid biphasic catalysis an aqueous solution of butane-diol was hydrogenated with a [RhCl(PPh3)3] catalyst dissolved in benzene [22]. 

In many cases only one of the enantiomers displays the desired biological effect, the other is ineffective or even harmful. The development of enantioselective catalysis in non-aqueous solvents has been closely followed by the studies of similar aqueous systems - logically, attempts were made in order to solubilize the ligands and catalysts in aqueous media. Using aqueous/organic biphasic systems (often water/ethyl acetate) one may have a possibility of recovery and recycle of the often elaborate and expensive catalysts. However, with a few exceptions, up till now catalyst recovery has been rather a desire than a subject of intensive studies, obviously because of the lack of large-scale synthetic processes. 

Table 4. /. Hydroformylation in aqueous/organic biphasic systems...

In 1975 Kuntz has described that the complexes formed from various rhodium-containing precursors and the sulfonated phosphines, TPPDS (2) or TPPTS (3) were active catalysts of hydroformylafion of propene and 1-hexene [15,33] in aqueous/organic biphasic systems with virtually complete retention of rhodium in the aqueous phase. The development of this fundamental discovery into a large scale industrial operation, known these days as the Ruhrchemie-Rhone Poulenc (RCH-RP) process for hydroformylation of propene, demanded intensive research efforts [21,28]. Tire final result of these is characterized by the data in Table 4.2 in comparison with cobalt- or rhodium-catalyzed processes taking place in homogeneous organic phases. 

The only other olefin feedstock which is hydroformylated in an aqueous/organic biphasic system is a mixture of butenes and butanes called raffinate-II [8,61,62]. This low-pressure hydroformylation is very much like the RCH-RP process for the production of butyraldehyde and uses the same catalyst. Since butenes have lower solubility in water than propene, satisfactory reaction rates are obtained only with increased catalyst concentrations. Otherwise the process parameters are similar (Scheme 4.3), so much that hydroformylation of raffinate-11 or propene can even be carried out in the same unit by slight adjustment of operating parameters. 

In the hydroformylation of alkenes, the major differences between the [RhH(CO)(PPh3)3], and [RhH(CO)(TPPTS)3] catalysts are the lower activity and higher selectivity of the water-soluble complex in aqueous/organic biphasic systems. Lower activity is not unexpected, since alkenes have limited solubility in water (see 4.1.1.1, Table 3). On the other hand, the higher selectivity towards formation of the linear product deserves more scrutiny. 

In general, the mechanism of alkene hydroformylation with an [RhH(CO)P3] catalyst in water or in aqueous/organic biphasic systems (P = TPPTS) is considered to be analogous [61] to that of the same reaction in homogeneous organic solutions (P = PPh3) [84], a basic version of which is shown on Scheme 4.8. 

The phosphinated ligands 135 and 136 prepared from poly(acrylic acid) and from poly(ethyleneimine), respectively, gave active hydroformylation catalysts in reaction with [Rh(acac)(CO)2]. Under the conditions of Table 4.6 low conversions were observed in aqueous/organic biphasic systems, due to the low solubility of 1-octene. Addition of a surfactant (SDS) or an organic co-solvent (MeOH) led to dramatic increases in the yield of aldehydes, revealing the high intrinsic activity of the catalyst [120]. 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

Higher olefins have negligible solubility in water therefore their hydrocarboxylation in aqueous/organic biphasic systems needs co-solvents or phase transfer agents. With the aid of various PT catalysts 1-octene and 1-dodecene were successfully carbonylated to the corresponding carboxylic acids with good yields (< 85 %) and up to 87 % selectivity towards the formation of the linear add with a [Co2(CO)g] catalyst precursor under forcing conditions (150 °C, 200 bar CO) [57],... 

The linear telomerization reaction of dienes was one of the very first processes catalyzed by water soluble phosphine complexes in aqueous media [7,8]. The reaction itself is the dimerization of a diene coupled with a simultaneous nucleophilic addition of HX (water, alcohols, amines, carboxylic acids, active methylene compounds, etc.) (Scheme 7.3). It is catalyzed by nickel- and palladium complexes of which palladium catalysts are substantially more active. In organic solutions [Pd(OAc)2] + PPhs gives the simplest catalyst combination and Ni/IPPTS and Pd/TPPTS were suggested for mnning the telomerizations in aqueous/organic biphasic systems [7]. An aqueous solvent would seem a straightforward choice for telomerization of dienes with water (the so-called hydrodimerization). In fact, the possibility of separation of the products and the catalyst without a need for distillation is a more important reason in this case, too. 

In the presence of Co(I)-catalysts alkynes and nitriles can be co-trimerized in organic solvents to yield substituted pyridines under rather harsh conditions. The reaction is biased by formation of large quantities of benzene derivatives and with acetylene gas as much as 30 % of all products may arise from homotrimerization. It has been found recently, that with cobalt(I) catalysts heterotrimerization of various nitriles and C2H2 could be achieved under ambient conditions using aqueous/organic biphasic systems and irradiating the reaction mixture with visible light (Scheme 7.12) [39,40]. 

It has been reported that the use of aqueous-organic biphasic systems may enhance the selectivity (Sect. 1.2) [12, 16, 47, 48]. In fact, sugar diethers are quasi insoluble in water and can be extracted in the organic phase. When the telomerization is carried out in the presence of Me2NCi2H25 and a large excess of 1 (15 equiv., Table 9), the conditions are already biphasic the diethers of 15 have thus been obtained in a 57% yield at 99% conversion of the telogen. 

In spite of numerous advantages of aqueous-organic biphasic systems, drawbacks also exist. The biocatalyst may be denaturated by the organic solvent, and in addition the introduction of an organic phase leads to an increasing of the reaction complexity. The selection of appropriate solvents represents an efficient way to avoid these phenomena. 

Li D, Dunlap JR, Zhao B (2008) Thermosensitive water-dispersible hairy particle-supported Pd nanoparticles for catalysis of hydrogenation in an aqueous/organic biphasic system. Langmuir 24 5911-5918... 

Yazu, K., Yamamoto, Y., Furuya, T., Miki, K., and Ukegawa, K. Oxidation of dibenzothiophenes in an organic biphasic system and its application to oxidative desulfurization of light oil. 

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