Biphasic layers

Typically the reaction was carried out as follows to a mixture of lipase in the IL were added this racemic alcohol and vinyl acetate as the acyl donor. The resulting mixture was stirred at 35°C and the reaction course was monitored by GC analysis. After the reaction, ether was added to the reaction mixture to form a biphasic layer, and product acetate and unreacted alcohol were extracted with ether quantitatively. The enzyme remained in the IL phase as expected (Fig. 2). Two months later, Kim and co-workers reported similar results and Lozano and Ibora " reported other examples of lipase-catalyzed reaction in June. Further Park and Kazlauskas reported full details of lipase-catalyzed reaction in an IL solvent... 

The bromide ionie liquid was dissolved in distilled water (200 cm ), and then transferred into a conieal flask (500 em ) equipped with a stirring bar. A slight excess of lithium bistriflamide was weighed (57.56 g 0.201 mol) in a beaker, dissolved in distilled water (100 em ), and then poured into the conical flask. The mixture was left to stir for 2 h at room temperature. A biphasic layer was formed, with a clear upper layer (aqueous layer) and yellow bottom layer (bistriflamide ionic liquid) respectively. The upper layer was decanted, and the bottom yellow layer was then transferred to a separating funnel. It was then washed with water (4 x 100 cm ). The bottom yellow layer was collected from the separating funnel and was left to dry for 15 h under high vaeuum at 80 °C to remove any traces of water. The product was obtained as a yellow liquid. 

A solution of 6-bromoindole (O.lOmol) in toluene (200 ml) was treated with Pd(PPh3)4 (5mol%) and stirred for 30 min. A solution of 4-fluorophenyl-boronic acid (0.25 M, 0.15 mol) in abs. EtOH was added, followed immediately by sal aq. NaHCOj (10 eq.). The biphasic mixture was refluxed for several hours and then cooled to room temperature. The reaction mixture was poured into sat. aq. NaCl (200 ml) and the layers separated. The aq. layer was extracted with additional EtOAc (200 ml) and the combined organic layers dried (Na2S04), filtered and concentrated in vacuo. The solution was filtered through silica gel using hexane-CHjCl -hexanc for elution and evaporated. Final purification by recrystallization gave the product (19 g, 90%). 

Since no special ligand design is usually required to dissolve transition metal complexes in ionic liquids, the application of ionic ligands can be an extremely useful tool with which to immobilize the catalyst in the ionic medium. In applications in which the ionic catalyst layer is intensively extracted with a non-miscible solvent (i.e., under the conditions of biphasic catalysis or during product recovery by extraction) it is important to ensure that the amount of catalyst washed from the ionic liquid is extremely low. Full immobilization of the (often quite expensive) transition metal catalyst, combined with the possibility of recycling it, is usually a crucial criterion for the large-scale use of homogeneous catalysis (for more details see Section 5.3.5). 

Obviously, there are many good reasons to study ionic liquids as alternative solvents in transition metal-catalyzed reactions. Besides the engineering advantage of their nonvolatile natures, the investigation of new biphasic reactions with an ionic catalyst phase is of special interest. The possibility of adjusting solubility properties by different cation/anion combinations permits systematic optimization of the biphasic reaction (with regard, for example, to product selectivity). Attractive options to improve selectivity in multiphase reactions derive from the preferential solubility of only one reactant in the catalyst solvent or from the in situ extraction of reaction intermediates from the catalyst layer. Moreover, the application of an ionic liquid catalyst layer permits a biphasic reaction mode in many cases where this would not be possible with water or polar organic solvents (due to incompatibility with the catalyst or problems with substrate solubility, for example). 

In the aqueous biphasic hydroformylation reaction, the site of the reaction has been much discussed (and contested) and is dependent on reaction conditions (temperature, partial pressure of gas, stirring, use of additives) and reaction partners (type of alkene) [35, 36]. It has been suggested that the positive effects of cosolvents indicate that the bulk of the aqueous liquid phase is the reaction site. By contrast, the addition of surfactants or other surface- or micelle-active compounds accelerates the reaction, which apparently indicates that the reaction occurs at the interfacial layer. 

Flowever, information concerning the characteristics of these systems under the conditions of a continuous process is still very limited. From a practical point of view, the concept of ionic liquid multiphasic catalysis can be applicable only if the resultant catalytic lifetimes and the elution losses of catalytic components into the organic or extractant layer containing products are within commercially acceptable ranges. To illustrate these points, two examples of applications mn on continuous pilot operation are described (i) biphasic dimerization of olefins catalyzed by nickel complexes in chloroaluminates, and (ii) biphasic alkylation of aromatic hydrocarbons with olefins and light olefin alkylation with isobutane, catalyzed by acidic chloroaluminates. 

It has been found that the tris(tert-butyloxycarbonyl) protected hydantoin of 4-piperidone 2, selectively hydrolyses in alkali to yield the N-tert-butyloxycarbonylated piperidine amino acid 3. The hydrolysis, which is performed in a biphasic mixture of THF and 2.0M KOH at room temperature, cleanly partitions the deprotonated 4-amino-N -(tert-butyloxycarbonyl)piperidine-4-carboxylic acid into the aqueous phase of the reaction with minimal contamination of the hydrolysis product, di-tert-butyl iminodicarboxylate, which partitions into the THF layer. Upon neutralization of the aqueous phase with aqueous hydrochloric acid, the zwitterion of the amino acid is isolated. The Bolin procedure to introduce the 9-fluorenylmethyloxycarbonyl protecting group efficiently produces 4.8 This synthesis is a significant improvement over the previously described method9 where the final protection step was complicated by contamination of the hydrolysis side-product, di-tert-butyl iminodicarboxylate, which is very difficult to separate from 4, even by chromatographic means. 

Room temperature ionic liquids are air stable, non-flammable, nonexplosive, immiscible with many Diels-Alder components and adducts, do not evaporate easily and act as support for the catalyst. They are useful solvents, especially for moisture and oxygen-sensitive reactants and products. In addition they are easy to handle, can be used in a large thermal range (typically —40 °C to 200 °C) and can be recovered and reused. This last point is particularly important when ionic liquids are used for catalytic reactions. The reactions are carried out under biphasic conditions and the products can be isolated by decanting the organic layer. 

Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic environment. It is commonly measured by its distribution behavior in a biphasic system, either liquid-liquid (e.g. partition coefficient in 1-octanol-water) or solid-liquid (retention on reversed-phase high-performance liquid chromatography or thin-layer chromatography system). 

A delaminated zeolite with an Si/Al ratio of 29, derived from the layered zeolite Nu-6(1), was employed as catalyst for dehydration of xylose at 170 °C, using a water-toluene biphasic reactor-system.140 This material, designated del-Nu-6(l), proved to be efficient for this transformation, giving 47% selectivity to furfural at 90% xylose conversion. 

Quite new ideas for the reactor design of aqueous multiphase fluid/fluid reactions have been reported by researchers from Oxeno. In packed tubular reactors and under unconventional reaction conditions they observed very high space-time yields which increased the rate compared with conventional operation by a factor of 10 due to a combination of mass transfer area and kinetics [29]. Thus the old question of aqueous-biphase hydroformylation "Where does the reaction takes place " - i.e., at the interphase or the bulk of the liquid phase [23,56h] - is again questionable, at least under the conditions (packed tubular reactors, other hydrodynamic conditions, in mini plants, and in the unusual,and costly presence of ethylene glycol) and not in harsh industrial operation. The considerable reduction of the laminar boundary layer in highly loaded packed tubular reactors increases the mass transfer coefficients, thus Oxeno claim the successful hydroformylation of 1-octene [25a,26,29c,49a,49e,58d,58f], The search for a new reactor design may also include operation in microreactors [59]. 

Apart from these recycling aspects, liquid-liquid biphasic catalysis can also help to improve the selectivity of a given reaction. Attractive options arise from the preferential solubility of only one reactant in the catalyst solvent or from the in-situ extraction of desired reaction products out of the catalyst layer in order to avoid unfavourable consecutive reactions (see Figure 7.4) [36]. 

In the case of ionic liquids, these general aspects for all fluid-fluid reactions are of particular importance, since mass transfer into an ionic liquid layer is generally slower than into an organic or aqueous medium. This is because ionic liquids usually have much higher viscosities than organic solvents. The least viscous ionic liquids are somewhat similar to ethylene glycol as demonstrated in Table 7.2. However, many ionic liquids used in liquid-liquid biphasic catalysis are significantly more viscous. 

A rather new concept for biphasic reactions with ionic liquids is the supported ionic liquid phase (SILP) concept [115]. The SILP catalyst consists of a dissolved homogeneous catalyst in ionic liquid, which covers a highly porous support material (Fig. 41.13). Based on the surface area of the solid support and the amount of the ionic liquid medium, an average ionic liquid layer thickness of between 2 and 10 A can be estimated. This means that the mass transfer limitations in the fluid/ionic liquid system are greatly reduced. Furthermore, the amount of ionic liquid required in these systems is very small, and the reaction can be carried in classical fixed-bed reactors. 

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