Organic Co-solvent

Phosphate buffer is known to enhance the activity of the enzyme PGA [13]. In the present studies, the enzyme PGA displayed satisfactory activity in water without phosphate buffer. 

As the pH of the reaction medium dictates the activity of the enzyme PGA, pH plays an important role. The acylation reaction was studied at different pH values ranging from 4.5 to 7.5. The enzyme showed maximum acylation activity around pH 5.3. However, acylation activity declined sharply at pH values below 5.2. The pH range from 5.25 to 6.25 (Fig. 8) seems to be optimum for phenylacetamide formation. 

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A widely used procedure for the reduction of conjugated enones to saturated ketones is that of Bowers, Ringold and Denot, Procedure 5 (section V). Ether-dioxane (1 1) is used as the organic co-solvent and solid ammonium... 

Organic co-solvent not needed High miscibility of CO2 with gas... 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

The Meerwein reaction is a valuable method for the arylation of alkenes because of the easy availability of cheap aromatic amines and compounds containing double bonds. A disadvantage is that the yield is often low (normally 20-50%, in exceptional cases reaching 80%, see Table 10-3). The reaction can be carried out in water if the alkene derivative is sufficiently soluble otherwise an organic co-solvent is necessary. Meerwein et al. (1939) used acetone, which is still the most popular solvent used today. The mechanistic function of acetone will be discussed later in this section. 

HMF is an important versatile sugar derivative and is a key intermediate between bio-based carbohydrate chemistry and petroleum based industrial organic chemistry (1, 2). The most coimnon feedstock for HMF is fructose and reactions are carried out in water-based solvent systems using acid catalysis (3,4). HMF is unstable in water at low pH and breaks down to form levulinic acid and formic acid, resulting in an expensive HMF recovery process. In strongly polar organic co-solvents, such as dimethylsulfoxide (DMSO), levuhnic acid formation is reduced and HMF yields are improved (5). 

The nitrilase activity of Arthrobacter sp. F-73 retains substantial activity in aqueous solutions containing a significant concentration of organic co-solvent [84]. More than 10% of nitrilase activity remains at acetone concentrations up to 60%, whereas no activity... 

There are only few examples of organic reactions catalysed effectively by Lewis acids which can be carried out in pure water without any organic co-solvent. While water can be used successfully for the uncatalysed Michael addition of 1,3-diketones (Table 4, entry D)22, the corresponding reaction of /i-kctocsters does not give satisfactory results. On the other hand, the Yb(OTf)3 catalysed Michael reaction of various /i-ketoesters (Table 21, entry A)257 and a-nitroesters (Table 21, entry B)258 takes place. 

The phosphinated ligands 135 and 136 prepared from poly(acrylic acid) and from poly(ethyleneimine), respectively, gave active hydroformylation catalysts in reaction with [Rh(acac)(CO)2]. Under the conditions of Table 4.6 low conversions were observed in aqueous/organic biphasic systems, due to the low solubility of 1-octene. Addition of a surfactant (SDS) or an organic co-solvent (MeOH) led to dramatic increases in the yield of aldehydes, revealing the high intrinsic activity of the catalyst [120]. 

In order to improve the activity in the absence of co-solvent, the use of a surfactant was studied in the presence of TPPTS-based catalyst [55]. Monflier et al. reported the hydrodimerization of 1 in the presence of surfactants in order to improve butadiene mass transfer in pure water solution [56-58]. Such an additive used in very low amount avoided the presence of an organic co-solvent. It was shown in the case of hydrodimerization that neutral or cationic surfactants played a significant role in the process. Similar behaviors were reported for the telomerization of 1 with 21. While 30% conversion of 1 was achieved in pure water after 24 h reaction time at 50°C using 0.4 mol% of catalyst, the conversion reached 87% when polyether surfactant (POEA) was added to the reaction medium under similar reaction conditions (Table 12). It was found that the conversion is strongly affected by the nature of the surfactant (Table 13). 

The Ruhrchemie/Rhone-Poulenc process is performed annually on a 600,000 metric ton scale (18). In this process, propylene is hydroformylated to form butyraldehyde. While the solubility of propylene in water (200 ppm) is sufficient for catalysis, the technique cannot be extended to longer-chain olefins, such as 1-octene (<3 ppm solubility) (20). Since the reaction occurs in the aqueous phase (21), the hydrophobicity of the substrate is a paramount concern. We overcame these limitations via the addition of a polar organic co-solvent coupled with subsequent phase splitting induced by dissolution of gaseous CO2. This creates the opportunity to run homogeneous reactions with extremely hydrophobic substrates in an organic/aqueous mixture with a water-soluble catalyst. After C02-induced phase separation, the catalyst-rich aqueous phase and the product-rich organic phase can be easily decanted and the aqueous catalyst recycled. 

Lundhaug, K., Overbeeke, P., Jongejan, J. and Anthonsen, T. (1998) Organic co-solvents restore the inherently high enantiomeric ratio of lipase B from Candida antarctica in hydrolytic resolution by relieving the enatiospecrfic inhibition of product alcohol. 

Solvent effects for a series of thienopyridine derivatives, 49, have been studied. In organic solvent/water mixtures, the values, ranging from 8.75 to 10.44, are found to be dependent on both the amount and the type of organic solvent (dimethylformamide (DMF), methanol, ethanol, and acetone) used in the mixture, with pA(a values increasing as the organic co-solvent concentration increases <2003CED1495>. 

Kinetic descriptions of this type of biocatalyzed system in the presence of different amounts of water [9], substrates [10], or inorganic salts [51] have been reported. In some cases, solvents ( adjuvants ) have been used to increase mass transfer [6, 7]. However, it was found that upon addition of organic co-solvents longer process times were actually required, even though the substrate solubility increased several times [54]. 

Preparation of Human Insulin. Porcine insulin can be converted to the human insulin sequence by an enzyme-catalyzed transpeptidation reaction (10,11). Under appropriate conditions trypsin acts preferentially at LysB29 rather than ArgB22 to yield a covalent des[B30]insulin/trypsin complex (acyl—enzyme intermediate). In the presence of high concentrations of organic co-solvents and the /-butyl ester of threonine, transpeptidation predominates over hydrolysis to yield the /-butyl ester of human insulin. Following appropriate purification steps and acidolytic removal of the ester, human insulin suitable for treating patients is obtained. 

F87A5F5 Random mutations on F87A Increased resistance to organic co-solvents [130]... 

When an organic co-solvent, such as acetonitrile or f-butyl alcohol, is added the reaction rate increases. This effect has been attributed to a variation in the solvation status of the reacting complex a lower solvation of the hydroxo complex may facilitate the formation of a neutral hydroxo radical. A radical scavenging of these organic solvents has been excluded because the presence of an excess of carbonate ions assures that the rate-determining step is the homolytic cleavage of the Co-OH bond. 

A range of proline derivatives have been employed as enamine-based organocatalysts of direct aldols in water, without organic co-solvent.111 Using the reaction of cyclohexanone with benzaldehydes as a test bed, lipophilic diamine (40) in the presence of TFA proved to be an excellent bifunctional catalyst system, giving performance up to 99/90/99% in terms of conversion/r/c/ee. Alkyl chains of (40) make an organic microphase likely. 

A direct organocatalytic Michael reaction of ketones or aldehydes with /3-nitrostyrene has been reported in brine solution, using a bifunctional catalyst system proline-derived diamine (70) and TFA.203 In some cases the conversion, yield, de, and ee all exceeded 95%. Results in water were poor, mainly due to polymerization, which is catalysed by amines. It is proposed that sodium cations stabilize the anionic intermediate formed from (70) and /3-nitrostyrene, thus minimizing polymer formation. While organic co-solvent is not required, an organic-rich phase is proposed to concentrate the Michael reactants and catalysts, thus accelerating the reaction. 

Knowledge of the solubility of the compound, particularly the aqueous solubility, is required in order to design the study. If the aqueous solubility is too low, then an organic co-solvent may be utilized to achieve solutions for stressing. 

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