Solvents monophasic systems

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 ... 

Monophasic systems in which the ionic liquid acts as both the solvent and the catalyst, e.g. dialkylimidazolium chloroaluminates as Friedel-Crafts catalysts (see later). 

Biphasic systems proved to be advantageous as well in the biocatalytic synthesis of (-)-l-trimethylsilylethanol which was performed by asymmetric reduction of acetyltrimethylsilane with an isolate from Rhodotorula sp. AS2.2241 [144]. Immobilized cells were employed due to the easy separation of the product as well as the improved tolerance against unfavorable factors. In an aqueous/organic solvent biphasic system higher product yield and enantiomeric excess were achieved as compared to an aqueous monophasic system. Several organic solvents were examined, and isooctane was found to be the most suitable organic phase for the reaction. 

This need for efficient separation of product and catalyst, while maintaining the advantages of a homogeneous catalyst, has led to the concept of liquid-liquid biphasic catalysis, whereby the catalyst is dissolved in one phase and the reactants and product(s) in the second liquid phase. The catalyst is recovered and recycled by simple phase separation. Preferably, the catalyst solution remains in the reactor and is reused with a fresh batch of reactants without further treatment or, ideally, it is adapted to continuous operation. Obviously, both solvents are subject to the same restrictions as discussed above for monophasic systems. The biphasic concept comes in many forms and they have been summarized by Keim in a recent review [7] ... 

In this context it is interesting to note the recent reports of fluorous catalysis without fluorous solvents [68]. The thermomorphic fluorous phosphines, P[(CH2)m(CF2)7CF3]3 (m=2 or 3) exhibit ca. 600-fold increase in n-octane solubility between -20 and 80 °C. They catalyze the addition of alcohols to methyl propiolate in a monophasic system at 65 °C and can be recovered by precipitation on cooling (Fig. 7.20) [68]. Similarly, perfluoroheptadecan-9-one catalyzed the epoxidation of olefins with hydrogen peroxide in e.g. ethyl acetate as solvent [69]. The catalyst could be recovered by cooling the reaction mixture, which resulted in its precipitation. 

When either the organic solvent or the ionic liquid is used as a pure solvent, the control of the water content, or rather the water activity, is of crucial importance as a minimum amount is necessary to maintain the enzyme activity. For ionic liquids, the same methods can be used to operate a reaction at constant water activity as those established for organic solvents [17,70,72]. As pure solvents and in biphasic systems [BMIM][PF6] or [BMIM][(CF3S02)2N], for example, are used. Water-miscible ionic liquids can be used in monophasic systems, e.g. [BMIM][Bp4] or [MMIM][MeS04]. 

Hydrogenolysis of benzo[fc]thiophene was performed in 20 mL of solvent mixture (methanol/n-heptane or methanol-water/n-heptane) with 180 mg of NaOH present. The catalyst/substrate ratio was 1 100, at an H2 pressure of 3 MPa, and 160 °C for 5 h. After the reaction, hydrochloric acid was added to obtain 2-ethylthiophenol. Both biphasic systems gave good yields of 2-ethylthiophenol (95% for methanol/ n-heptane and 89% for mefhanol-water/n-heptane). These results were similar to those obtained in the monophasic systems of methanol (93%) and methanol-water (84%). In both biphasic systems, aU the 2-efhylthiophenol is found in the polar phase as sodium 2-ethylthiophenolate, leaving the hydrocarbon phase almost completely desulfurized. 

Table 3 gives the third-order nonlinear optical properties of bioengineered polymers prepared by enzyme-catalyzed polymerization using horseradish peroxidase in biphasic solvent systems. Water-immiscible solvents used for the biphasic media are benzene, chloroform, toluene, tetrahydrofuran, and isooctane. Third-order nonlinear optical properties of homopolymers and copolymers prepared in biphasic solvent systems are similar to those of polymers prepared in monophasic systems. The values of polyaromatic amines solutions measured at 532 nm are one to two orders higher than the x values observed with polyphenolic compounds. Third-order nonlinear optical properties of copolymers of aromatic amines with... 

In this chapter, latest advancements in solvent engineering in bioreductions and greener needs for bioreaction media have been discussed in depth with recent examples. Solvents for bioreductions may be categorized as (i) aqueous (ii) water/water-miscible (monophasic aqueous-organic system) (iii) water/ water-immiscible (biphasic aqueous-organic system) (iv) nonaqueous (mono-phasic organic system, including solvent-free system) and (v) nonconventional media (e.g., ionic liquids, supercritical fluids, gas-phase media, and reverse micelles). 

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]. 

When the phenylacetyl carbinol-generating biottansformations catalyzed by yeast whole cells were carried out in monophasic systems consisting of an aqueous phase and water-miscible organic solvents, a decrease in benzyl alcohol formation was observed [44,45]. 

To eliminate the need to recover the product by distillation, researchers are now looking at thermomorphic solvent mixtures. A thermomorphic system is characterized by solvent pairs that reversibly change from being biphasic to monophasic as a function of temperature. Many solvent pairs exhibit varying miscibility as a function of temperature. For example, methanol/cyclohexane and n-butanol/water are immiscible at ambient temperature, but have consolute temperatures (temperatures at which they become miscible) of 125°C and 49°C, respectively (3). 

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]. 

Several monophasic solvent systems are useful for the separation of carbohydrate mixtures, and in all those listed in Table 9.3 the smallest solute molecules have the fastest mobility. Thus pentoses have higher RF values than hexoses, followed by disaccharides and oligosaccharides. 

Enzyme catalysis in nonconventional media can be divided into a number of different categories depending on whether the aqueous and organic phases are miscible or immiscible and whether the biocatalyst is dissolved or not. In this section, only free enzymes will be considered. Thus, the field can be simplified to just two categories, depending on whether the solvent is water miscible or immiscible (systems employing water-immiscible solvents, where water is present in quantities that are below its solubility limit, have been considered as monophasic) ... 

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. 

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). 

Mixtures of chloroform and methanol have had wide use as lipid extractants (e.g., Bligh and Dyer, 1959). This solvent system allows for extraction of both polar and nonpolar lipids, unlike extraction with hexane (see Basic Protocol 1 and Alternate Protocol 1). Optimum extraction may be achieved when water in the tissue, or that added to the medium, y ields a monophasic solution. Subsequently, additional water and/or chloroform... 

Enzymes as different as yeast alcohol oxidase, mushroom polyphenol oxidase, and horse-liver alcohol dehydrogenase demonstrated vastly increased enzymatic activity in several different solvents upon an increase in the water content, which always remained below the solubility limit (Zaks, 1988b). While much less water was required for maximal activity in hydrophobic than in hydrophilic solvents, relative saturation seems to be most relevant to determining the level of catalytic activity. Correspondingly, miscibility of a solvent with water is not a decisive criterion upon transition from a monophasic to a biphasic solvent system, no significant change in activity level was observed (Narayan, 1993). Therefore, the level of water essential for activity depends more on the solvent than on the enzyme. 

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