Monophasic reaction system

Lin and coworkers disclosed that, at room temperature, nonenzymatic chemical addition was still observed in a water-organic solvent biphasic reaction system, though the volume of aqueous phases was relative small. Lin developed a method of preparing an active enzyme meal that contained essential water to retain its power for catalysis and found a new catalytic reaction system by application of the prepared meal in a nonaqueous monophasic organic medium (Figure 5.7). There was no problem over a wide range of temperature (from 0-30 °C) when the reactions were carried out under micro-aqueous conditions [50]. 

Figure 8.4. Chemoselectivity as a function of system pressure during the hydroformylation of long chain olefins with Rh/PEt3 catalysts. The change in chemoselectivity has been correlated with the transition from biphasic to monophasic reaction conditions...

The catalytic principle of micelles as depicted in Fig. 6.2, is based on the ability to solubilize hydrophobic compounds in the miceUar interior so the micelles can act as reaction vessels on a nanometer scale, as so-called nanoreactors [14, 15]. The catalytic complex is also solubihzed in the hydrophobic part of the micellar core or even bound to it Thus, the substrate (S) and the catalyst (C) are enclosed in an appropriate environment In contrast to biphasic catalysis no transport of the organic starting material to the active catalyst species is necessary and therefore no transport limitation of the reaction wiU be observed. As a consequence, the conversion of very hydrophobic substrates in pure water is feasible and aU the advantages mentioned above, which are associated with the use of water as medium, are given. Often there is an even higher reaction rate observed in miceUar catalysis than in conventional monophasic catalytic systems because of the smaller reaction volume of the miceUar reactor and the higher reactant concentration, respectively. This enhanced reactivity of encapsulated substrates is generally described as micellar catalysis [16, 17]. Due to the similarity to enzyme catalysis, micelle and enzyme catalysis have sometimes been correlated in literature [18]. 

As an alternative to distillation, extraetion with a eo-solvent that is poorly mis-eible with the ionie liquid has often been used. There are many solvents that can be used to extract product from the ionic liquid phase, whether from a monophase reaction or from a partially miscible system. Typical solvents are alkanes and ethers (15). Supercritical CO2 (SCCO2) was recently shown to be a potential alternative solvent for extraction of organics from ionic liquids (22). CO2 has a remarkably high solubility in ionic liquids. The SCCO2 dissolves quite well in ionic liquids to facilitate extraction, but there is no appreciable ionic liquid solubilization in the CO2 phase in the supercritical state. As a result, pure products can be recovered. For example, about 0.5 mol fraction of CO2 was dissolved at 40°C and 50 bar pressure in [BMIMJPFe, but the total volume was only swelled by 10%. Therefore, supercritical CO2 may be applied to extract a wide variety of solutes from ionic liquids, without product contamination by the ionic liquid (29). 

The selectivity of the trap towards hydroxyl radicals was demonstrated by several control experiments using different radicals, showing that the formation of the respective hydroxylation product, 5-hydroxy-6-0-zso-propyl-y-tocopherol (57), was caused exclusively by hydroxyl radicals, but not by hydroperoxyl, alkylperoxyl, alkoxyl, nitroxyl, or superoxide anion radicals. These radicals caused the formation of spin adducts from standard nitrone-and pyrroline-based spin traps, whereas a chemical change of spin trap 56 was only observed in the case of hydroxyl radicals. This result was independent of the use of monophasic, biphasic, or micellar reaction systems in all OH radical generating test systems, the trapping product 57 was found. For quantitation, compound 57 was extracted with petrol ether, separated by adsorption onto basic alumina and subsequently oxidized in a quantitative reaction to a-tocored, the deeply red-colored 5,6-tocopheryldione, which was subsequently determined by UV spectrophotometry (Scheme 23). 

Mechanistic studies of this two-phase reaction system showed that the solubility properties of both ketone and alkene, as well as the reaction pH, were important factors [9]. In this context, the report by Yang in 1995 of a monophasic... 

This monophasic biotransformation system was used for the hydroxylation of 2,2 -dihydroxybiphenyl to 2,2, 3-trihydroxybiphenyI within a reaction time of 2.5 h and 2.2. 3,3 -tetrahydroxybiphenyl after 23 h. A mean volume productivity of 0.43 and 0.05 g l-1 h 1, respectively, was achieved for these biotransformations. Furthermore, HbpA and FDH were applied in 80 vol.% decanol to hydroxylate 2-hydroxybiphenyl to 2,3-dihydroxybiphenyl with a productivity of 0.46 g 1 1 h 1 and a total turnover number of 503. In 10 vol.% aqueous methanol the total turnover number of 30 and enzyme stability for at least 60 h were observed. Because of the... 

While the monophasic reaction in organic solvents is known to suffer from product inhibition, the continuous reaction in the liquid-liquid biphasic system allowed to overcome this limitation by in situ product extraction from the ionic catalyst phase. To avoid metal leaching out of the ionic liquid phase, the catalyst... 

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). 

Employing a solvent system containing the ionic liquid [BMIm][BF4] with Pi-chia membranaefaciens Hansen ZJPH07 cells afforded a higher yield and enan-tiopurity during the (R)-selective reduction of ethyl acetoacetate as compared to a monophasic system. It was also demonstrated that the addition of [BMIM] [BF4] to the reaction system markedly reduced substrate inhibition and moderately improved the enantioselectivity compared to a monophasic aqueous system [58]. 

The authors correlate the observed catalytic activity with the solubility of the 1,3-butadiene feedstock in the ionic liquid, which was found to be twice as high in the tetrafluoroborate ionic liquid as in the corresponding hexafluorophosphate system. It is noteworthy that the same reaction in a monophasic systems with toluene as the solvent was found to be significantly less active (TOF = 240 h ... 

In summary, what we have found is that the combination of a thermomorphic system and a surfactant is very effective for the hydroformylation of 1-octene and 1-dodecene. We believe that although a 90 10 ethanol/water and heptane system becomes miscible at 70°C, the additional water in a 50 50 ethanol/water and heptane system raises the miscibility temperature to >100°C. When a surfactant is added, the miscibility temperature is lowered and the biphasic solution becomes monophasic below the reaction temperature, resulting in good reaction rates. In addition, the presence of the surfactant also enhances the selectivity compared to the completely homogeneous system from 1.8 to 5.3 L/B... 

Measures for the controlled switch of the catalyst system from the two-phase system (suitable for the separation of products from the catalyst) to a monophasic system which supports the reaction itself (Figure 5.9, [27,54]). 

Another way to produce biphenyl derivates using flow was described by Leeke et al. [34] where they performed a Pd catalyzed Suzuki-Miyaura synthesis in the presence of a base. First experiments were carried out in toluene/methanol solvent. A reaction mixture was passed through the encapsulated Pd filled column bed length 14.5 cm (some cases 10 cm) x 25.4 mm id. 45 g of PdEnCat. Base concentration, temperature and flow rate were optimized and at optimum parameters (0.05 M base concentration, 100°C and 9.9 mL/min) the conversion was 74%. Then the reaction was performed under supercritical conditions using supercritical CO2 at high pressure and temperature. After optimizing the concentration of base, flow rate, pressure and temperature, the highest conversion rate (81%) was observed at 166 bar and 100°C where the reactant mixture was monophasic in the supercritical state. This system is able to produce 0.06 g/min of the desired product. 

The OATS concept was tested on the catalytic hydroformylation of 1-octene, a hydrophobic substrate. This reaction was selected because it has previously been shown to be inactive for traditional aqueous biphasic systems (18). The catalyst used was a Rh/TPPTS complex, an industrial water soluble catalyst (22). The application of the OATS concept increased catalytic efficiency by a factor of 65 (TOP increased from 5 h for biphasic to 325 h for monophasic). 

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