Alcohol aqueous biphasic reaction

Other aqueous biphasic organometallic reactions include fat-chemical processes, such as the Ru-catalyzed oxidation of fatty alcohols to the corresponding aldehydes or acids [174, 175, 244 g]. Oxidation reactions of water-soluble ligands in aqueous biphasic reactions (especially TPPTS) have been investigated by Larpent, Patin and co-workers [176]. Recent examples of other aqueous biphasic reactions are compiled in Table 3. 

Scheme 9.15 Aqueous biphasic reactions via self-assembly for oxidation of alcohols with hydrogen peroxide.

The conversion of tetralin to a-tetralone may be achieved under aqueous biphasic conditions in the presence of 02, using NiCl2 as a catalyst, as shown in Scheme 9.3 [7], It is necessary to use tetraethylene pentamine (TEPA) as a surface-active ligand, as well as an emulsifier, dodecyl sodium sulfate. Some alcohol and naphthol by-products were also observed, and a radical chain mechanism has been proposed for this reaction. 

The Boots Hoechst Celanese (BHC) ibuprofen process involves palladium-catalyzed carbonylation of a benzylic alcohol (IBPE). More recently, we performed this reaction in an aqueous biphasic system using Pd/tppts as the catalyst (Figure 9.6 tppts = triphenylphosphinetrisulfonate). This process has the advantage of easy removal of the catalyst, resulting in less contamination of the product. 

Ru(II)-TPPTS to the corresponding unsaturated alcohols in biphasic mode. If one compares the reaction times until full conversion, it becomes clear that the reaction rate correlates with the solubility of the substrate in the aqueous phase, as expected. The latter decreases with increasing chain length or branching of the chain at the C3-atom. In contrast to heterogeneously catalysed hydrogenations of o , d-unsaturated aldehydes, the steric hindrance of substituents at the C3-atom only plays a minor role in the coordination mode of the substrate at the metal centre, since selectivity differences from croton-aldehyde to citral are marginal. 

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. 

The reactions can be carried out in aqueous solutions or biphasic mixtures of the substrates with no additional solvent, in the presence of NaOAc (pH s 11.5) at 100 °C. At this pH the resting state of the catalyst is probably the dinuclear species depicted on Scheme 8.1, which falls apart upon coordination of the substrate alcohol. In this respect the catalyst system as very similar to that for the oxidation of terminal olefins [10,11]. Good results were obtained with 30 bar of air, however, an 8 % O2/N2 mixture can also be used, which further improves the safety of the process. Recycling of the aqueous catalyst solution is possible and is especially easy in case of biphasic reaction mixtures. Taking all these features, this Pd-catalyzed oxidation of alcohols is a green process, indeed. 

Reactions with these compounds suffer from very low substrate concentrations due to the low solubility of hydrophobic ketone substrates in aqueous media, which leads to unsatisfactory volumetric productivities. To achieve higher substrate concentrations, a biphasic reaction medium was introduced. The system water/ n-heptane (4 1) proved to be the most suitable system with regard to stability of the examined enzymes. The large-scale available (S)-specific ADH from R. erythropolis as well as FDH from C. boidinii are stable for long periods of time in this aqueous-organic solvent system. Preparative conversions with a variety of aromatic ketone substrates were carried out with this reaction medium. For example, p-chloroacetophenone was converted into the corresponding (S )-alcohol with >99% ee and 69% conversion. The obvious increase in volumetric productivity is due to the higher substrate concentrations. The reduction of p-chloroacetophenone... 

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. 

The most important and oldest application of aqueous biphasic, homogeneous catalysis is hydroformylation (oxo process, Roelen reaction). This process is used to produce n-butyraldehyde, the desired main product of the reaction of propylene, which is converted by aldolization into 2-ethyUiexenal and this is finally hydrogenated to give 2-ethylhexanol (2-EH), the most economically important plasticizer alcohol (Scheme 1) ... 

NADP+ in a reaction with 2-propanol accompanied by formation of acetone as coproduct. Both ketone/alcohol reactions are equilibrium processes and therefore high 3delds of (f )-2-octanol are not available in a monophasic aqueous system, or in an organic-aqueous biphasic system where the partition coefficients of 2-propanol and acetone are approximately the same. It was found, however, that in a biphasic water/[bmim][(CF3S02)2N] system acetone was preferentially dissolved by the IL phase and this pulled the catalytic transfer hydrogenation of NADP+ by 2-propanol in the aqueous phase to near completion. Consequently, almost quantitative yields of (i )-2-octanol were obtained (275). 

An ingenious apphcation of an aqueous biphasic and monophasic methodology described above was suggested for the selective deprotection of primary and secondary amines and alcohols protected by aUyloxycarbonyl (AUoc) group. " Using diethy-lamine as an acceptor of allyl, the reaction proceeds very smoothly under mild conditions and is characterized by a formidable chanoselectivity, which can be seen from the example in Scheme 65. 

As a consequence of showing that alkylated polyethyleneimines can facilitate aqueous biphasic catalysis, we extended the concept by the preparation of a cross-linked polyethyleneimine assembly that encapsulated a polyoxometalate catalyst, which resulted in the Upophiloselective oxidation of secondary alcohols (Scheme 9.17) [152]. Thus, even though reactions were carried out in water, competitive oxidation of a more hydrophobic alcohol in the presence of a hydrophilic alcohol significantly favored the former. The lipophiloselectivity was proportional to the relative partition coefficient of the substrates. 

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