Biphasic Mixture

Catalytic Conversion of COj in an Ionic Liquid/scCOj Biphasic Mixture 

Continuous Reactions in an Ionic Liquid/Compressed COj System 

During the continuous reaction, alkene, CO, H2, and CO2 were separately fed into the reactor containing the ionic liquid catalyst solution. The products and uncon- 

Slightly later, and independently of Cole-Hamilton s pioneering work, the author s group demonstrated in collaboration with Leitner et al. that the combination of a suitable ionic liquid with compressed CO2 can offer much more potential for homogeneous transition metal catalysis than only being a new procedure for easy product isolation and catalyst recychng. In the Ni-catalyzed hydrovinylation of 

At first, the reaction was investigated in batch mode, by use of different ionic liquids with weakly coordinating anions as the catalyst medium and compressed CO2 as simultaneous extraction solvent. These experiments revealed that the activation of Wilke s catalyst by the ionic liquid medium was clearly highly dependent on the nature of the ionic liquid s anion. Comparison of the results in different ionic liquids with [FMIM] as the common cation showed that the catalyst s activity drops in the order [BARF] [Al OC(CF3)2Ph 4r [(CF3S02)2N] [BFJ . This trend is consistent with the estimated nucleophilicity/coordination strength of the anions. 

Catalytic Conversion of CO2 in an Ionic Liquid/scC02 Biphasic Mixture 

4 Multiphasic Catalysis with Ionic Liquids in Combination with Compressed CO2 

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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 a biphase mixture is possible in most condensate return lines, their correct sizing becomes essential. 

Industrial environments expose individuals to a plethora of airborne chemical compounds in the form of vapors, aerosols, or biphasic mixtures of both. These atmospheric contaminants primarily interface with two body surfaces the respiratory tract and the skin. Between these two routes of systemic exposure to airborne chemicals (inhalation and transdermal absorption) the respiratory tract has the larger surface area and a much greater percentage of this surface exposed to the ambient environment. Or dinary work clothing generally restricts skin exposures to the arms, neck, and head, and special protective clothing ensembles further limit or totally eliminate skin exposures, but breathing exposes much of the airway to contaminants. 

Because of the great importance of liquid-liquid biphasic catalysis for ionic liquids, all of Section 5.3 is dedicated to specific aspects relating to this mode of reaction, with special emphasis on practical, technical, and engineering needs. Finally, Section 5.4 summarizes a very interesting recent development for biphasic catalysis with ionic liquids, in the form of the use of ionic liquid/compressed CO2 biphasic mixtures in transition metal catalysis. 

The first application involving a catalytic reaction in an ionic liquid and a subsequent extraction step with SCCO2 was reported by Jessop et al. in 2001 [9]. These authors described two different asymmetric hydrogenation reactions using [Ru(OAc)2(tolBINAP)] as catalyst dissolved in the ionic liquid [BMIM][PFg]. In the asymmetric hydrogenation of tiglic acid (Scheme 5.4-1), the reaction was carried out in a [BMIM][PF6]/water biphasic mixture with excellent yield and selectivity. When the reaction was complete, the product was isolated by SCCO2 extraction without contamination either by catalyst or by ionic liquid. 

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. 

Cyclohexanecarboxylic acid hydrazide has low solubility in water. A biphasic mixture developed during the reaction, which led to the predominant formation of the bis-acylated material. 

Hydrolysis of substrates is performed in water, buffered aqueous solutions or biphasic mixtures of water and an organic solvent. Hydrolases tolerate low levels of polar organic solvents such as DMSO, DMF, and acetone in aqueous media. These cosolvents help to dissolve hydrophobic substrates. Although most hydrolases require soluble substrates, lipases display weak activity on soluble compounds in aqueous solutions. Their activity markedly increases when the substrate reaches the critical micellar concentration where it forms a second phase. This interfacial activation at the lipid-water interface has been explained by the presence of a... 

Finally, the groups of Chaudret and Choukroun have demonstrated that PVP-protected native Rh nanoparticles synthesized by an organometallic approach are active in the hydrogenation of benzene in a biphasic mixture. 

The effect of biphasic mixtures on the productivity includes the contributions of solvent partitioning on enzyme activity and stability. An important activity does not necessarily lead to increased productivity. We must then distinguish between the effect of the environment on activity and productivity. 

An investigation of different organic solvents, buffer, surfactants, and organorhodium compounds established that the catalytic reduction of tetralin using [ Rh(l,5-hexadiene)Cl 2] proceeds with high efficiency at high substrate-to-catalyst ratios. The reaction occurs at r. t. and 1 atm. pressure in a biphasic mixture of hexane and an aqueous buffer containing a low concentration of a surfactant which stabilizes the catalysts.314... 

The various isomeric hexenoic acids are useful starting materials for the production of fine chemicals, and the stereoselective hydrogenation of sorbic acid has attracted considerable interest. It was shown recently that this reaction could be catalyzed by [Ru(CO)(Cp )(mtppts)] [CF3SO3] (Cp =//5-C5Me5) in a water -heptane biphasic mixture to yield tra s-3-hexenoic acid with up to 85% selectivity [39] (Scheme 38.3). Conversely, the use of [ RuC12(PR3)2 2] (R=CH2CH2CH2OH) as catalyst precursor led to the selective formation of 4-hexenoic acid [40]. 

Aqueous two-phase hydrogenations are dominated by platinum group metal catalysts containing water-soluble tertiary phosphine ligands. The extremely stable and versatile N-heterocyclic carbene complexes attracted only limited interest, despite the fact that such complexes were described in the literature [62-65]. Recently, it was reported that the water-soluble [RuXY(l-butyl-3-methylimi-dazol-2-ylidene) ( 76-p-cymene)]n+ (X=Ch, H20 Y = C1-, H20, pta) complexes preferentially hydrogenated cinnamaldehyde and benzylideneacetone at the C = C double bond (Scheme 38.5) with TOF values of 30 to 60 h 1 in water substrate biphasic mixtures (80 °C, lObar H2) [66]. 

Methoxy-2 -methylbiphenyl. o-Tolylboronic acid, 10.0 g (73.6 mmol) (Note 1), 16.8 g (71.8 mmol) of 4-iodoanisole (Note 2), and 200 mL of acetone (Note 3) are combined in a 1-L, three-necked flask equipped with an efficient stirbar, two stoppers, and a reflux condenser attached to a gas-flow adapter with a stopcock. Potassium carbonate, 25.0 g (0.180 mol), is dissolved in 200 mL of water (Note 4) in a separate 250-mL Schlenk flask. In a third flask (25-mL Schlenk flask) 3.30 mg (0.02 mmol, 0.2%) of palladium acetate (Note 5) is dissolved in 10 mL of acetone. All three flasks are then thoroughly degassed by four freeze-pump-thaw cycles. Under an argon back flow, one of the stoppers on the three-necked flask is replaced with a rubber septum, and the carbonate and catalyst solutions are added via cannula to form a biphasic mixture. The top layer turns brown upon addition of the catalyst. The septum is... 

Probably the most important group of phase transfer reactions, and certainly the commonest, are those in which an anion is transferred from the aqueous phase into the organic solvent, where nucleophilic substitution occurs. These would once have been performed in a dipolar aprotic solvent such as DMF. A good example is the reaction between an alkyl halide (such as 1-chlorooctane), and aqueous sodium cyanide, shown in Scheme 5.5. Without PTC, the biphasic mixture can be stirred and heated together for 2 weeks and the only observable reaction will be hydrolysis of the cyanide group. Addition of a catalytic amount of a quaternary onium salt, or a crown ether, however, will lead to the quantitative conversion to the nitrile within 2 h. 

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 ... 

There is very little information available on asymmetric hydroformylation in aqueous solutions or biphasic mixtures despite that asymmetric hydroformylation in organic solvents has long been studied very actively. This is even more surprising since enantioselective hydrogenation in aqueous media has been traditionally a focal point of aqueous organometallic catalysis and several water soluble phosphine ligands have been synthetized in enantiomerically pure form. 

Diarylethenes, 1,1-diarylallylalcohols and aryl vinyl ethers were succesfully hydroformylated in water/toluene or water/cyclohexane biphasic mixtures with a catalyst prepared in situ from[ RhCl(COD) 2] and TPPTS (Scheme 4.15). Yields of the desired linear aldehyde product were around 80%. This method was applied for the synthesis of the neuroleptics Fluspirilen and Penfluridol (Scheme 4.16) and for other pharmaceutically active compounds containing the 4,4-bis(p-fluorophenyl)butyl group [153]. 

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