BIPHASIC SYSTEMS WATER-ORGANIC

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]. 

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. 

Figure 2.3. Water-Organic Biphasic Catalyst System...

In another example, undecanal was hydrogenated to undecanol with a water-soluble catalyst in the presence of chemically modified yS-cyclodextrins, which facilitated the mass transfer between the aqueous and the organic phase [134]. Hydrogenation of cinnamaldehyde with very high (99%) selectivity to cinnamyl alcohol was also performed in water scC02 biphasic systems [135] which al-... 

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. 

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. 

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],... 

Reactions of the same substrate with several nucleophiles were also catalyzed by the water-soluble Pd-complex of a phosphinite-oxazoline ligand which was prepared from natural D-glucosamine (Scheme 6.23) [53]. The catalyst dissolves weU both in water and in CH3CN but not in diethyl ether. Therefore the reactions could be ran either in water/toluene biphasic systems or in homogeneous water/CHaCN solutions. In the latter case, phase separation could be induced by addition of diethyl ether upon which the catalyst moved quantitatively to the aqueous phase. The product was obtained from the organic phase by evaporation of the solvent(s) and the aqueous solution of the Pd-complex was recycled. In aqueous systems the... 

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. 

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. 

DKR of thioesters (Scheme 21.2) with a chiral center at the a-carbon has been achieved in a water/acetonitrile biphasic system by racemization with mild organic bases, such as trioctylamine, coupled to enantioselective hydrolysis of the thioester with subtilisin Carlsberg.28 Such an approach can be applied to a wide variety of thioesters but not oxoesters, which have less acidic a-protons. 

Water has several attractive features as a solvent and, as we have said elsewhere, the best solvent is no solvent, but if one has to use a solvent then let it be water. Water is the most abundant molecule on the planet and is, hence, readily available and inexpensive. It is nonflammable and incombustible and odorless and colorless (making contamination easy to spot). It has a high thermal conductivity, heat capacity and heat of evaporation, which means that exothermic reactions can be controlled effectively. It readily separates from organic solvents owing to its polarity, density and because of the hydrophobic effect [12], which makes it eminently suitable for biphasic catalysis. Indeed, water forms biphasic systems with many organic solvents, with fluorous solvents, some ionic liquids and with scC02 [13]. 

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... 

One of the oldest techniques for overcoming these problems is the use of biphasic water/organic solvent systems using phase-transfer methods. In 1951, Jarrouse found that the reaction of water-soluble sodium cyanide with water-insoluble, but organic solvent-soluble 1-chlorooctane is dramatically enhanced by adding a catalytic amount of tetra-n-butylammonium chloride [878], This technique was further developed by Makosza et al. [879], Starks et al. [880], and others, and has become known as liquid-liquid phase-transfer catalysis (PTC) for reviews, see references [656-658, 879-882], The mechanism of this method is shown in Fig. 5-18 for the nucleophilic displacement reaction of a haloalkane with sodium cyanide in the presence of a quaternary ammonium chloride as FT catalyst. 

It should be emphasized that the conditions found in aqueous polymeric biphasic systems seem to simulate those in biological systems to a good approximation 33>. The properties of both phases of such systems are only slightly different as compared to those of the phases of water-organic solvent systems. Hence, the partition coefficient of a solute in an aqueous polymeric biphasic system is much more responsive not only to the modifications of the molecule structure but to the alterations in the conformation of the molecule as well. The application of the partition... 

Phospholipases are very versatile enzymes which allow the transformation of inexpensive natural products into highly valuable compounds like specific structurally defined phospholipids, organic monophosphates or diphosphates and DAG with the natural absolute configuration. Of particular synthetic utility is PLD from bacterial sources which is able to effect the phosphoryl transfer in a water-containing biphasic system. PLD shows a wide substrate specificity for both the polar head and the alcohol acceptors as well as for the lipophilic part of the molecule. The enzyme behaves like a generic phosphodiesterase with broad substrate specificity and high transphosphatidylation ability. The molecular basis of this behavior should become clear by inspection of the three-dimensional structure and comparison with other phosphoric acid ester hydrolytic enzymes. The crystal structure of this enzyme has not been elucidated. The potential of the many different PLD from plants which show peculiar substrate specificity should allow one to expand the synthetic utility to the hydrolysis-synthesis of natural and unnatural phosphatidylinositols. 

Hydridopentacyanocobaltate(II), [HCo(CN)5]3, is a catalyst of choice for selective hydrogenation of conjugated dienes and polyenes to monoenes unactivated alkenes are totally unreactive [12, 62, 63]. In general, hydrogenation proceeds with 1,4-addition of H2 (Eq. 28). Because of the insolubility of dienes in water, such reactions are carried out in aqueous/organic biphasic systems. The possibilities for modification of the catalyst by ligand alteration are very restricted but various additives, such as KCN, KOH, lanthanide salts, cyclodextrins, phase-transfer, and micellar agents, are known to influence the selectivity of [HCo(CN)r, 3 -catalyzed reactions. 

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