Reaction with Subsequent Product Extraction

Catalytic Reaction with Subsequent Product Extraction 

25°C/ 5bar after reaction extraction with. VCCO2 

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Catalytic Reaction with Subsequent Product Extraction... 

PFs-anion. The authors attributed the difference to the stronger ionicity of the BF4 anion as compared with the PF anion and a better ability of the former to stabilize enamine transition state 39 (Scheme 22.15). After completion of the reaction and subsequent product extraction with diethyl ether, the system [emim][Pro]/[bmim]... 

C in a TH F-toluene-hexane mixture. After the mixture was cooled below —50 °C, ketone 41 was added. After 60min, the reaction was quenched with aqueous citric acid. The organic layer was then solvent switched into toluene, and the product 50 was crystallized by the addition of heptane (91-93% isolated yield, >99.5% ee). The chiral modifier 46 is easily recycled from the aqueous layer by basification with NaOH and extraction into toluene to recover 46 (>99% purity, 98% recovery yield). The modifier has been recycled up to nine times in subsequent chiral addition reactions without any problem. 

The palladium leaching to the product phase was investigated via ICP-OES measurements. In all cases about 5% of the metal catalyst is lost. This palladium loss is in the same range as in the biphasic reaction in water with subsequent extraction with cyclohexane. Therefore, one can conclude that the use of cyclodextrins has almost no influence on the palladiiun leaching. For the reaction described in this work, this makes the use of cyclodextrins as PCT catalysts more attractive than the TMS systems to overcome mass transfer limitations. 

In a typical experiment, benzaldehyde (106 mg, 1 mmol) was added to the finely powdered paraformaldehyde (60 mg, 2 mmol). To this mixture, powdered barium hydroxide octahydrate (631 mg, 2 mmol) was added in a glass test tube and the reaction mixture was placed in an alumina bath (neutral alumina 125 g, mesh 150, Aldrich bath 5.7 cm diameter) inside a household microwave oven and irradiated for the specified time at its full power of 900 W intermittently or heated in an oil bath at 100-110 °C. On completion of the reaction, as indicated by TLC (hexane-EtOAc, 4 1, v/v), the reaction mixture was neutralized with dilute HC1 and the product extracted into ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The pure benzyl alcohol (99 mg, 91%), however, is obtained by extracting the reaction mixture with ethyl acetate prior to neutralization and subsequent removal of the solvent under reduced pressure. 

It is important for the discussion below to distinguish between direct and indirect process routes. Direct carbonation is the simplest approach to carbonate production (or mineral carbonation see Section 14.4) and the principal approach is that a suitable feedstock-for example, serpentine or a Ca/Mg-rich solid residue-is carbonated in a single process step. For an aqueous process this means that both the extraction of metals from the feedstock and the subsequent reaction with the dissolved C02 to form carbonates takes place in the same reactor. 

Extension of this proline-catalyzed a-amination to the use of aldehydes as starting materials has been described independently by the Jorgensen and List groups [6, 7]. The principle of the reaction and some representative examples are shown in Scheme 7.4. The practicability is high - comparable with that of the analogous reaction with ketones described above. For example, in the presence of 5 mol% L-proline as catalyst propanal reacts with azodicarboxylate 3a at room temperature in dichloromethane with formation of the a-aminated product 5a in 87% yield and with 91% ee [7]. Good yields and high enantioselectivity can be also obtained by use of other types of solvent, e.g. toluene and acetonitrile. The products of type 5 were isolated simply by addition of water, extraction with ether, and subsequent evaporation. 

Reductive amination was also conducted using cell extracts from E. coli strain SC16496 expressing PDHmod and cloned FDH from Pichia pastoris. Cells from a 15-L tank had 133 u/g FDH, 65u/g PDH (phenylpyruvate assay), and 12.7 u/g PDH (assayed with keto acid 3). The extract was used for conversion of 30g 3 to 4 in close to 100% yield, and this material, after filtration for protein removal, was converted to 2 by BOC protection. Further experiments showed that the E. coli extract could be used at 2.5% w/v concentration instead of the 12.5% concentration used for batches with Pichia pastoris extract. In subsequent experiments, the substrate input was increased to 100 g/ L and the reaction was carried out at pH 8.0. Cell extracts of E. coli strain SC16496 after polyethyleneamine treatment, clarification and concentration was used to complete the reaction in 30hrs with >96% yield and >99.9% ee of product 4. PDHmod and FDH expressed in E. coli have now been used to prepare several hundred kg of BOC-protected amino acid 2 to support the development of Saxagliptin (Hanson et al., 2007). 

HNOj (90%) was dehydrated by distillation from 30 % oleum (2 raol equiv, excess) at reduced pressure. The dried acid (0.15 g, 2.4 mmol) was mixed with 2 TfOH -B(OTf)3 (1.8 g, 1 mL, 2.4 mmol)" under anhyd Nj in a three-necked, round-bottomed flask. The nitronium salt [NOj B(OTf)4 ] partially precipitated as a white solid. Without isolation, the calculated amount of arene was then added while the mixture was stirred vigorously. The reaction times and temperatures were dependent on the arene. After completion of the reaction, the mixture was quenched with ice water, extracted with CHCI3 (3x20niL), and the combined CHCI3 extracts were washed carefully with 5% aq NaHC03 soln. The CHCl, layer was dried (MgS04), filtered, and evaporated to give the crude nitro products these were subsequently purified further by distillation or recrystallization. 

Before being fed to Contactor III, the aqueous feed solution was treated to reduce Pu to the Pu(III) state, to prevent its extraction and ensure its recovery in the aqueous Pu product stream (3PP). The reference reductant for the flow sheet was hydroxyla-mine nitrate (HAN) at 0.3 mol/L with hydrazine nitrate (0.1 mol/L) as a holding agent or HNO2 scavenger (10). Use of HAN as Pu reductant was considered desirable because in reaction with Pu, as well as in subsequent reactions where the reductant is destroyed, only gaseous products are formed (equations 1 and 2). 

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