Organic Solvents as Reaction Media

Whilst the first part of this book deals mainly with concepts and theories of alternatives to the use of organic solvents as reaction media, the later Chapters (Chapters 7-11) look at some applications of these methods and compare their strengths and limitations as illustrated by these case studies. 

Ionic liquids serve as very useful reaction media, which can facilitate easy separation of product(s) and a catalyst after the reaction. These substitutes of organic solvents as reaction media have already been successfully applied to a variety of transition metal-catalyzed organic reactions such as Heck reaction, Suzuki cross-coupling, hydroformyla-tion, and alkoxycarbonylation. ... 

Sergeeva, K. Martinek, Denaturation capacity - a new quantitative criterion for selection of organic-solvents as reaction media in biocatalysis, Eur.J. Biochem. 1991,... 

Khmelnitsky, Y. L., V. V. Mozhaev, A. B. Belova, M. V. Sergeeva, and K. Martinek. 1991. Denaturation Capacity A New Quantitative Criterion for Selection of Organic Solvents as Reaction Media in Biocatalysis. European Journal of Biochemistry 198 (1) 31-41. 

The use of organic solvents as reaction media dominate in CuAAC reactions. However, several examples have been described that proceed in mixtures of organic solvents and water (i.e., iBuOH/water [9a, 17], MeOH/water [18], dimethyl sulfoxide (DMSO)/water [8c, 19], MeCN/water [20], or tetrahydrofuran (THF)/water [13g,i]). In addition, several catalytic systems. 

The use of organic solvents as reaction media for biocatalytic reactions can not only overcome the substrate solubility issue, but also facilitate the recovery of products and biocatalysts as well. This technique has been widely employed in the case of lipases, but scarcely applied for biocatalytic reduction processes, due to the rapid inactivation and poor stability of redox enzymes in organic solvents. Furthermore, all the advantages for nonaqueous biocatalysis can take effect only if the problem of cofactor dependence is also solved. Thus, bioreductions in micro- or nonaqueous organic media are generally restricted to those with substrate-coupled cofactor regeneration. 

The use of various solvents as reaction media for diverse reactions is summarized in Reichardt (1988), and Marcus (1998). The following is a partial list of organic reactions requiring solvents. In chapters 5 through 7 we will look at green solvents and provide some examples of more environmentally benign alternatives to some of the more toxic solvents. 

A very recent addition to the already powerful range of microwave cycloaddition chemistry is the development of a general procedure applying a catalyst/ionic liquid system [19]. Several studies in this area have used ionic liquids, or mixtures of ionic liquids and other solvents, as reaction media in several important microwave-heated organic syntheses [20], including Diels-Alder reactions [21, 22] and 1,3-dipolar cycloaddition reactions [23]. 

Fluorous media and supercritical CO2 are, like water and all organic solvents, molecular reaction media. In contrast, ionic liquids are salts formed by mismatched associations of cations and anions. It is usually assumed that salts are solid under normal conditions and that they melt only at very high temperatures for example, NaCl has to be heated to 803 C before it becomes liquid. However, it has been discovered that special pairings of cations and anions can lead to salts that are liquid around room temperature. These salts, called ionic liquids, constitute very promising media as they display many interesting properties. 

The kinetics of 1,3-dipolar cycloaddition of phenyl azide to nor-bornene in aqueous solutions was studied (Eq. 12.67).145 As shown in Table 12.1, when the reaction was performed in organic solvents, the reaction showed very small effects of the solvent, while in highly aqueous media, significant accelerations were observed. 

Liquid crystals are classified into lyotropic and thermotropic crystals depending on the way in which the mesomorphic phase is generated. Lyotropic liquid-crystalline solvents are formed by addition of controlled amounts of polar solvents to certain amphiphilic compounds. Thermotropic liquid-crystalline solvents, simply obtained by temperature variations, can be further classified into nematic, smectic, and cholesteric solvents depending on the type of molecular order present. Liquid crystals are usually excellent solvents for other organic compounds. Nonmesomorphic solute molecules may be incorporated into liquid-crystalline solvents without destruction of the order prevailing in the liquid-crystalline matrix (Michl and Thulstrup, 1986). Ordered solvent phases such as liquid crystals have also been used as reaction media, particularly for photochemical reactions (Nakano and Hirata, 1982). 

The application of SCF as reaction media for enzymatic synthesis has several advantages, such as the higher initial reaction rates, higher conversion, possible separation of products from unreacted substrates, over solvent-free, or solvent systems (where either water or organic solvents are used). Owing to the lower mass-transfer limitations and mild (temperature) reaction conditions, at first the reactions which were performed in non-aqueous systems will be transposed to supercritical media. An additional benefit of using SCFs as... 

Contrary to expectations that enzymes are only active in aqueous solution, activity in almost anhydrous organic solvents was already demonstrated in the 1930s and rediscovered in 1977. It was not water-miscible hydrophilic solvents such as methanol or acetone that proved to be the best reaction media, but hydrophobic water-immiscible solvents such as toluene or cyclohexane. Supposedly, the cause is the partitioning of water between the enzyme surface and the bulk phase of the organic solvent. As comparably hydrophilic solvents such as methanol or acetone can take up basically infinite amounts of water, they strip the remaining water molecules off the enzyme surface. As a consequence, the enzyme is no longer active because it requires a small but measurable amount of water for developing its activity... 

What are the advantages of organic solvents as media for hi oca lalylic reactions ... 

Acidic chloroaluminate ionic liquids were used as reaction media for Friedel-Crafts reactions as early as 1976 [34], Systematic investigations into Friedel-Crafts alkylations of benzene with the same acidic systems followed in 1986 by Wilkes et al. [35]. The alkylation of benzene with alkenes in acidic imidazolium chloroaluminate melts was disclosed in a patent by BP Chemicals in 1994 [36]. Here, as advantages over the reaction with aluminum trichloride in organic solvents, claims are made regarding the easy isolation of the product, the practically total reusability of the liquid catalyst and the better selectivity to the desired products. 

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