Solvents, acidic supercritical carbon dioxide

The reaction of a carboxylic acid with N,Af -carbonyldiimidazolellH33 (abbreviated as CDI), forming an imidazolide as the first step followed by alcoholysis or phenolysis of the imidazolide (second step), constitutes a synthesis of esters that differs from most other methods by virtue of its particularly mild reaction conditions.t41,[5] It may be conducted in two separate steps with isolation of the carboxylic acid imidazolide, but more frequently the synthesis is carried out as a one-pot reaction without isolation of the intermediate. Equimolar amounts of carboxylic acid, alcohol, and CDI are allowed to react in anhydrous tetrahydrofuran, benzene, trichloromethane, dichloromethane, dimethylformamide, or nitromethane to give the ester in high yield. The solvents should be anhydrous because of the moisture sensitivity of CDI (see Chapter 2). Even such unusual solvent as supercritical carbon dioxide at a pressure of 3000 psi and a temperature of 36-68 °C has been used for esterification with azolides.[6]... 

In general, the choice of counteranion has a minor effect on catalyst performance, with typical examples being selected from BF4, OTD, PFg, or BARF-. In one example, however, it was noted that [(R.R)-Et-DuPhos Rh CODJOTf gave superior selectivity for the reduction of / -/ disubstituted a-dehydroamino acid derivatives than the corresponding BARF complex when performed in a range of solvents, including supercritical carbon dioxide [39]. 

Lipases are the most common enzymes used in non conventional media like organic solvents and supercritical carbon dioxide. Lipases usually hydrolyse fats into fatty acids and glycerol. The special property of lipases is their ability to act at the interface between water and oil. In these experiments lipase (EC 3.1.1.34) from Rhizopus arrhizus (Boehringer Mannheim) was used to investigate the effects of lipase under hydrostatic pressure. The analysed reaction was the hydrolysis of p-Nitrophenyllaureate at different concentrations at 35 °C. The dependance of the kinetic constants between 1 bar and 3000 bar is presented in table 2. Like the thermophilic GDH at 1000 bar lipase is activated under pressure as well. The initial reaction rate increases by a factor of 1.5 at 1000 bar compared to the initial reaction rate at ambient... 

Soluble HBA or HCA derivatives are frequently extracted from fmits and vegetables with ethanol or methanol-water solutions (80 0, v/v), using low temperatures and adding an antioxidant to prevent oxidation during the extraction procedure. Chemical or enzymatic hydrolysis of the plant material is necessary when phenolic acids are linked to cell wall constituents to give insoluble forms [6]. Apolar solvents or supercritical carbon dioxide may be useful to extract phenolic lipids [7,8]. In the case of acylated flavonoids, solvents must be adapted to the characteristics of the flavonoid itself, e.g., acidic methanol for fruit anthocyanins, although some artefacts may appear under these conditions. 

Chapters are also included on yeast-mediated stereoselective biocatalysis, stereoselective synthesis of steroids, chemo-enzymatic synthesis of enantiopure arylpropionic acids, supercritical carbon dioxide as a solvent in enzyme catalysis, state-of-the-art techniques in enzyme immobilization, biocatalysis by polyethylene glycol-modified enzymes, and enzymatic deprotection techniques in organic synthesis. 

Interestingly, Qi, Smith, and co-workers reported that addition of an organic solvent such as acetone, DMSO, methanol, ethanol, ethylacetate, or supercritical carbon dioxide to BMIM Cl allowed the reaction to proceed at room temperature. For instance, in the presence of Amberlyst 15 as solid acid catalyst, authors showed that addition of 5 wt% of acetone to BMIM CF yielded, at room temperature, HMF with 86% selectivity at 90% conversion. Further investigations revealed that addition of an organic solvent to BMIM CF allowed one to overcome important mass transfer at room temperature due to the high viscosity of BMIM CD [96]. 

Extraction of 25 different binary mixtures of racemic acids (2-(4-isobutylphenyl)-propionic acid (1), and cis- and trans-chrysanthemic (2)), and various chiral bases with supercritical carbon dioxide permitted the conclusion that molecular chiral differentiation in a supercritical fluid is more efficient than in conventional solvents. In the majority of cases, however, complete separation could not be achieved. In five cases, remarkable partial resolutions were realized (30-75% ee) and resolution was possible on a preparative scale. The pair ds-chrysanthemic acid and (S)-(-i-)-2-(benzylamino)-1-butanol (3) was studied in detail. Pressure, temperature, and time, as well as the molar ratio of base and acid, had a marked influence on the quantity and quality of the products. Increasing pressure or decreasing temperature resulted in higher ee values. (-)-cw-Chrysanthemic acid in 99% ee was obtained from the raffinate in a single extraction step. Multiple extractions produced the (-i-)-cA-acid in 90% ee (see fig. 6.3) (Simandi et al., 1997). 

Esterification between oleic acid and oleyl alcohol, catalyzed by the Mucor miehei immobihzed hpase in a batch-stirred tank reactor with supercritical carbon dioxide as solvent produced higher reaction rates at supercritical conditions than in the solvent-free system (Knez et al., 1995). 

Whilst the use of supercritical carbon dioxide as a solvent has recently been reported, it should be noted that it can also be a substrate one ruthenium catalyst is reported to be capable of its conversion to formic acid at the rate of 1400 mol per mol of catalyst per hour202. 

Fluoromethylbenzoic acids, metallation, 9, 26-27 Fluoro(phenyl) complexes, with platinum(II), 8, 482 Fluorosilanes, elimination in fluorinated alkene activation, 1, 732 in fluorinated aromatic activation, 1, 731 and hydrodefluorination, 1, 748 Fluorosilicate anions, hypercoordinated anions, 3, 484 Fluorotoluenes, metallation, 9, 21 Fluorous alkylstannanes, preparation, 3, 820 Fluorous biphasic system, as green solvent, 12, 844 Fluorous ligands, with supercritical carbon dioxide, 1, 82 Fluorous media... 

Other extraction methods used in the lipid extraction include supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE). With SEE, good extraction yields have been obtained for nonpolar lipids including ester-ified fatty acids, acylglycerols, and unsaponifiable matter. However, complex polar lipids are only sparingly soluble in supercritical carbon dioxide alone and polar modifiers, such as methanol, ethanol, or even water is required to improve the extraction of polar lipids (10). SFE has been used for the extraction of lipids especially from various food matrices, such as different nuts, edible oils, and seeds (11). The recoveries of lipids in SFE were on the same levels than with conventional solvent extraction methods (12,13), no significant differences between the fatty acids extracted were observed. PLE has also been used in lipid extraction, although only in very few applications (14). The elevated temperatures used in PLE can cause alteration of the lipid composition. 

In contrast to alkamides, alternative extraction solvents such as SF carbon dioxide appear to be ineffective as an extraction solvent for CAP removal (Catchpole et al., 2002 Sun et al., 2002). Conditions evaluated by these researchers include pressures of 31 - 55 MPa and temperatures between 41 and 60°C. In both studies, ethanol was used as a solvent modifier, but the supercritical carbon dioxide was not modified sufficiently to promote the extraction of CAP. The addition of 10% methanol to the supercritical carbon dioxide at 25 MPa and 60°C was sufficient to promote the extraction of rosmarinic acid, a compound with similar structure features as cichoric acid (Bicchi et al., 2000). Thus, additional work is needed to determine if SFE can be used as a method to remove CAP. 

The recovery and purification of furfural from aqueous effluents by high-pressure extraction is of technical interest. Alternative extraction tests with supercritical carbon dioxide were carried out [1,2]. Further research [3-5] led to the conclusion that carbon dioxide is a good alternative to organic solvents with comparable and even better extraction results. For all these experiments the system furfural - water without acetic acid was used. 

Other reagents and solvents were obtained from commercial sources. The samples were prepared by mixing various chiral bases with racemic acids in 0.5 1 molar ratio. A porous supporting material (Perfilt), impregnated with these mixtures, was put into the extractor vessel and extracted with supercritical carbon dioxide. 

Finally, it should be noted that Lewis acids and bases can also be used in other non-conventional media, as described in Chapter 7, e.g. fluorous solvents, supercritical carbon dioxide and ionic liquids by designing the catalyst, e.g. for solubility in a fluorous solvent or an ionic liquid, to facilitate its recovery and reuse. For example, the use of the ionic liquid butylmethylimidazolium hydroxide, [bmim][OH], as both a catalyst and reaction medium for Michael additions (Fig. 2.45) has been recently reported [151]. 

Like supercritical carbon dioxide, supercritical water is a very interesting substance that has strikingly different properties from those of liquid water. For example, recent experiments have shown that supercritical (superfluid) water can behave simultaneously as both a polar and a nonpolar solvent. While the reasons for this unusual behavior remain unclear, the practical value of this behavior is very clear It makes superfluid water a very useful reaction medium for a wide variety of substances. One extremely important application of this idea involves the environmentally sound destruction of industrial wastes. Most hazardous organic (nonpolar) substances can be dissolved in supercritical water and oxidized by dissolved 02 in a matter of minutes. The products of these reactions are water, carbon dioxide, and possibly simple acids (which result when halogen-containing compounds are reacted). Therefore, the aqueous mixture that results from the reaction often can be disposed of with little further treatment. In contrast to the incinerators used to destroy organic waste products, a supercritical water reactor is a closed system (has no emissions). 

Recently, polymeric ultrafiltration membranes were used for degumming crude soybean oil and removing phospholipids from the crude oil/hexane miscella (168). Crude soybean oil also can be de-acidified by methanol extraction of the free fatty acids and the extract separated into fatty acids and solvent by a membrane filter (169). A surfactant-aided membrane degumming also has been applied to crude soybean oil, and the degummed oil contained 20-58 ppm of phosphorus (170). Supercritical carbon dioxide extraction was shown to be an effective means of degumming (171). In this process, soybean oil countercurrently contacted supercritical carbon dioxide at 55 MPa and 75°C. The phosphorus content of the oil was reduced from 620 ppm to less than 5 ppm. Ultrasonic degumming was also successfully used to reduce the gum content of soybean oil (172). 

With the use of solvatochromic probes, other non-specific forces (dispersion, dipole-induced dipole, and dipole-dipole) and specific acid-base forces have been explored in SCF solvents. In an effort to compare liquid and supercritical carbon dioxide, Hyatt(ll) measured UV-visible spectra of several solvatochromic probes. There was little difference between the Ex in the liquid and SCF states however, the data can not be interpreted fully since the density and the pressure were not given at the supercritical condition. The results indicated that the... 

The use of ion exchange resins combined with supercritical extraction results in an attractive isolation technique. Since the pyrrolizidine alkaloids are generally basic, the process described here could be used for the isolation of other members of this class, and for other basic alkaloids. In designing a process using ion exchange resins, it is important that the co-solvent not deactivate the resin. In our example, water and ethanol are acidic in carbon dioxide and, therefore, do not deactivate the acidic resin. An industrial process based on this concept could be quite efficient and inexpensive since pressure reduction and subsequent solvent recompression are unnecessary (Figure 11). 

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