Aqueous-organic biphasic reactions

The ejfect of water on the conversion and selectivity of cohalt-catalyzed hydroformylations has long been noticed in industry [7,85,86], A systematic study [87] of this effect in hydroformylation of 1-octene with [Co2(CO)s] with and without P Bu3 revealed that addition of water, and especially when it formed a separate aqueous phase, significantly inaeased the hydrogenation activity of the phosphine-modified catalyst Under the same reaction conditions (190 °C, 56 bar CO H2 1 1, P Co 3 1), approximately 40 % nonanols were formed instead of 5 % observed with water-free solutions. No clear explanation could be given for this phenomenon, although the possible participation of water itself in the hydroformylation reaction through the water gas shift was mentioned. It was also established, that the [Co2(CO)g]-catalyzed hydroformylation was severly retarded in the presence of water. Under the conditions above, 95 % conversion was observed in 15 hour with no added water, while only 10 % conversion to aldehydes (no alcohols) was found in an aqueous/organic biphasic reaction. 

In an attempt to produce CMF under milder reaction conditions, Gao et al. described an aqueous-organic biphasic reaction system where a combination of concentrated HCI (37%) and H3PO4 (85%) were used in the aqueous phase with chloroform as the extracting solvent at only 45°C [125]. CMF was obtained in 47% isolated yield from fructose, although glucose and cellulose gave poor yields of CMF, 7.3% and 7.8%, respectively. Surprisingly, CMF yields up to 31% were obtained when cellulosic feedstocks (e.g., eucalyptus wood) were used. 

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. 

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]. 

Hydrogenation reactions in water have been extensively studied and many of the water-solubilizing ligands described in Chapter 5 have been tested in aqueous-organic biphasic hydrogenation reactions. One of the earliest catalysts used was the water-soluble analogue of Wilkinson s catalyst, RhCl(tppms)3 (tppms = monosulfonated triphenylphosphine), but many other catalysts have since been used including [Rh(cod)(tppts)2]+, [Rh(cod)2]+ and [Rh(acac)(CO)2]+ (cod = cyclooctadiene). 

The limitations of hydroformylation reactions in water are the same as those of hydrogenation reactions, i.e. the poor solubility of the substrates (see Section 8.2.1). While aqueous-organic biphasic hydroformylation works well for alkenes with chain lengths up to C7, the solubility of longer chain alkenes is too low for viable processes. Although simple alkenes are poorly soluble, many functional alkenes have solubilities in water that are sufficiently high to avoid mass transfer problems, but at the same time this can impede separation. 

With a water-soluble hydroformylation catalyst the overwhelming majority of the reactions take place in an aqueous/organic biphasic mixture for the simple reason of most olefins being insoluble in water. Research in aqueous organometallic hydroformylation is therefore directed to several aims ... 

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. 

Hydroformylation of higher olefins provide long chain alcohols which find use mainly as plasticizers. No aqueous/organic biphasic process is operated yet for this reaction, for several reasons. First, solubility of higher olefins is too small to achieve reasonable reaction rates without applying special additives (co-solvents, detergents, etc.) or other means (e.g. 

Veiy recently it was disclosed, that the water-soluble dinuclear complex obtained in the reaction of [ RhCl(COD) 2] and 11-mercaptoundecanoic acid catalyzed the aqueous/organic biphasic hydroformylation of styrene and various arene-substituted styrenes with good activity and useful selectivity to the branched aldehydes (Scheme 4.6) [82], Below pH 4 the acid form of the complex [ Rh(p-S(CH2)ioC02H)(COD) 2] precipitated virtually quantitatively but could be redissolved in water on addition of base. Importantly, higher olefins could also be hydroformylated by this catalyst (for 1-octene TOP = 17.5 h at 55 °C, 35 bar syngas, n/i = 1.0). 

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]. 

Benzyl halides are easily carbonylated to phenylacetic acid derivatives which are valuable intermediates for Pharmaceuticals, cosmetics and fragrances [2,3], Several papers report the aqueous/organic biphasic realization of this reaction [1,19-22] (Scheme 5.3). The main characteristics of these processes are summarized in Table 5.1. 

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. 

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]. 

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