Reactions Using Organic Solvents

Wong, H., Pink, C., Ferreira, F., and Livingston, A. (2006) Recovery and reuse of ionic liquids and palladium catalyst for Suzuki reactions using organic solvent nanofiltration. Green Chem., 8, 373-379. 

Free or immobilized enzymes have been exploited already in a number of systems. Here, biocatalysis may take place in reversed micelles or in an aqueous phase in contact with an organic solvent. In a powdered state some enzymes are able to function in pure organic solvents. Furthermore, modified enzymes such as polymer bound enzymes or surfactant-coated enzymes have been developed so that they can solubilize in organic solvents to overcome diffusion limitation. The advantages of enzymatic reactions using organic solvents can be briefly summarized as follows ... 

It is important to note that most reactions using homogeneous catalysts are run in the liquid phase in a batch-wise mode. Especially in academic research laboratories, homogeneous catalysis is attributed to batch reactions using organic solvents. However, in large-scale industrial processes, e.g., carbonyl-ation reactions, oxidations are performed in a continuous mode. 

ILs have also been used as inert additives to stabilize transition metal catalysts during evaporative workup of reactions in organic solvent systems [35,36]. The non-... 

Instead of using organic solvents, hydrophobic resin, AmberliteTM XAD, has been used to control the substrate concentration [19]. When XAD is added to the reaction mixture, substrate and products are adsorbed to the hydrophobic resin, XAD, since... 

The scope of possible reactions using water as a solvent is quite remarkable and water is much under-utilized as a solvent in many academic and industrial research institutions, largely through lack of knowledge and a culture of using organic solvents. Several other examples... 

Elemental sulfur dissolves in boiling aqueous sodium sulfite solutions with the formation of sodium thiosulfate (Na2S203). The reaction proceeds quantitatively if sulfur and excess sodium sulfite are boiled for some time in weakly alkaline solutions. In the cold, however, practically no reaction occurs. Alternatively, thiosulfate can be produced quantitatively in solution phase by using organic solvents to first dissolve sulfur and then accomplish the reaction with aqueous sulfite. In a parallel reaction, elemental selenium dissolves in alkaline sulfite solution to produce selenosulfate, SeSO ... 

Potential for new synthetic methodologies. Compared to reactions in organic solvents, the use of water as a reaction solvent has... 

Spin trapping EPR technique and UV-Vis spectroscopy have been used (Polyakov et al. 2001b) to determine the relative rates of reaction of carotenoids with OOH radicals formed by the Fenton reaction in organic solvents. The Fe3+ species generated via the Fenton reaction... 

Kragl and coworkers investigated using organic-solvent-free systems to overcome the thermodynamic limitations in the synthesis of optically active ketone cyanohydrins. With organic-solvent-free systems under optimized reaction conditions, conversions up to 78% with > 99.0 enantiomeric excess (ee) (S) were obtained. Finally, 5 mL of (S)-acetophenone cyanohydrin with an ee of 98.5% was synthesized using MeHNL [52]. 

It should be noted that the purpose of using organic solvent is to help delivery of substrate evenly into the reaction mixture, but not to help solubilize substrate in the reaction mixture. So the amount of organic solvent should be kept to a minimum, just enough to dissolve substrate. 

Organic solvents that can be used with discrete PEG compounds include DMSO, DMF, DMAC (i 7,N -dimcthylacetamide), and methylene chloride. The compounds also are very soluble in many other commonly used organic solvents, which provide flexibility for doing reactions. DMAC is particularly convenient, because it is easily dried of contaminating water (using molecular sieves), it doesn t decompose like DMF (producing amines), and it doesn t have the odors of some of the other solvents. Methylene chloride can be used for water-insoluble molecules that are to be reacted with the PEG compounds, but don t require subsequent water miscibility. 

Aldol Reactions in Water Without Using Organic Solvents... 

The catalytic asymmetric aldol reaction has been applied to the LASC system, which uses copper bis(-dodecyl sulfate) (4b) instead of CufOTf. 1261 An example is shown in Eq. 6. In this case, a Bronsted add, such as lauric add, is necessary to obtain a good yield and enantioseledivity. This example is the first one involving Lewis acid-catalyzed asymmetric aldol reactions in water without using organic solvents. Although the yield and the selectivity are still not yet optimized, it should be noted that this appredable enantioselectivity has been attained at ambient temperature in water. 

Reaction in organic solvent can sometimes provide superior selectivity to that observed in aqueous solution. For example, Keeling et al recently produced enantioenriched a-trifluoromethyl-a-tosyloxymethyl epoxide, a key intermediate in the synthetic route to a series of nonsteroidal glucocorticoid receptor agonist drug candidates, through the enan-tioselective acylation of a prochiral triol using the hpase from Burkholderia cepacia in vinyl butyrate and TBME (Scheme 1.59). In contrast, attempts to access the opposite enantiomer by desymmetrization of the 1,3-diester by lipase-catalysed hydrolysis resulted in rapid hydrolysis to triol under a variety of conditions. 

Reductions with zinc are very effective on aromatic nitro compounds using organic solvents and an acid medium at around 50-70°, No matter what kind of metal is used, good stirring is a must. After the reaction is over, the zinc is filtered off, care being taken not to let it become dry, as it is pyrophoric. Also, be careful while disposing of zinc for the very same reasons. 

Figure 13. Preparation of immobilized enzymes with different solubilities in aqueous solutions and organic solvents. Procedure A mixture of an enzyme (3 mg) and the polymer (10 mg) was incubated at pH 7.5 for 20 min. Ammonium phosphate (0.1 M, pH 7, 1 mL) was then added to react with the remaining active ester. After 20 min, the solution was ready for use, or lyophilization to give the immobilized enzyme as a powder to be used for reaction in organic solvents. Each gram of the polymer contains approximately 0.7 mmol of the active ester.

P25 Each of these [previous methods] involves one or more of the following drawbacks uses expensive and toxic metals, demonstrates severe water sensitivity, or produces hydrazoic acid, which is highly toxic and explosive as well as volatile. The few methods that seek to avoid hydrazoic acid liberation during the reaction, by avoiding acidic conditions, require a very large excess of sodium azide. In addition, ah of the known methods use organic solvents, in particular, dipolar aprotic solvents such as DMF. This is one of the solvent classes that process chemists would rather not use. (Adapted from Demko and Sharpless, 2001)... 

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