Solvent for organic reactions

Section 16 7 Dialkyl ethers are useful solvents for organic reactions but must be used cautiously due to their tendency to form explosive hydroperoxides by air oxidation in opened bottles... 

Ethylammoniinn niirate, l H jf HjNH tNOj, was the first limit liquid to he discovered. Its melting point of 12°C was reported in 1914 and it has since been used as a nonpolluting solvent for organic reactions and for facilitating the folding of proteins. 

This concept meshes with another important environmental issue solvents for organic reactions. The use of chlorinated hydrocarbon solvents, traditionally the solvent of choice for a wide variety of organic reactions, has been severely curtailed. In fact, so many of the solvents favoured by organic chemists have been blacklisted that the whole question of solvents requires rethinking. The best solvent is no solvent and if a solvent (diluent) is needed then water is preferred. Water is non-toxic, non-inflammable, abundantly available, and inexpensive. Moreover, owing to its highly polar character, one can expect novel reactivities and selectivities for organometallic catalysis in water. 

Why should we consider using water as a solvent for organic reactions There are many potential advantages ... 

As an aside, benzotrifluoride is a slightly polar, non-Lewis basic solvent that has favorable properties for many kinds of organic reactions. A. Ogawa, D. P. Curran, Benzotrifluoride A useful alternative solvent for organic reactions currently conducted in dichloro-methane and related solvents , J. Org Chem. 1997, 62, 450. 

A Ogawa, DP Curran. Benzotrifluoride a useful alternative solvent for organic reactions currently conducted in dichloromethane. J Org Chem 62, 450, 1997. 

Traditionally, water is not a popular solvent for organic reactions. The limited solubility of many organic substrates and reagents as well as the fact that a variety of functional groups is reactive toward water have traditionally contributed to this lack of popularity of water as a reaction medium. Contrarily, the chemistry of all life processes occurs in aqueous media, and few people will doubt the high quality and efficiency of these transformations ... 

Ionic liquids are organic salts that are liquid at or near room temperature. It has been found recently that such liquids can be useful solvents for organic reactions. Often, the organic products can be removed from the ionic liquid by extraction with, e.g., ether, without resorting to an aqueous workup. This can be particularly useful when a precious metal catalyst is used in the reaction. The catalyst often remains in the ionic liquid, so that the catalyst solution can be directly reused. 

Supercritical CO, offers many advantages over conventional solvents for organic reactions. The challenge has been to find surfactants that will allow typical organic substrates to dissolve. Shu Kobayashi of the University of Tokyo has described (J. Org. Chem. 2004,69,680) the development of perfluoroalky) aromatics that serve well, as illustrated by the conversion of 10 to 11. Both the perfluoroalkyl aromatic and the Sc(OTf), are recovered at the end of the reaction. 

Totten, G.E. and Clinton, N.A., Polyethylene glycol) derivatives as phase-transfer catalysts and solvents for organic-reactions, /. Macromol. Sci., Rev. Macromol. Chem. Phys., 1988, C28, 293. 

For lower dialkyl isohexides (90), especially 2,5-di-O-methylisosorbide, which is used as solvent for organic reactions or for pharmaceutical dosage formulations, several manufacturing processes have been reported. The most widely applied method, consisting of the reaction of the free diols (65) with dimethyl sulfate or methyl iodide, was improved by employing special conditions (see Scheme 19). Thus, acetone in the presence of 50% aqueous... 

In recent years, ionic liquids have attracted intense interest as a possible replacement for traditional solvents for organic reactions, particularly in the area of green chemistry, due to their advantageous properties (negligible vapour pressure as well as high thermal and chemical stability). 

As with other functional groups, we will discuss how ethers are formed and how they react. Ethers (other than epoxides) are relatively unreactive, however, and they are not frequently used as synthetic intermediates. Because they are stable with many types of reagents, ethers are commonly used as solvents for organic reactions. In this chapter, we consider the properties of ethers and how these properties make ethers such valuable solvents. 

Ethers are nonhydroxylic (no hydroxyl group), and they are normally unreactive toward strong bases. For this reason, ethers are frequently used as solvents for very strong polar bases (like the Grignard reagent) that require polar solvents. The four ethers shown here are common solvents for organic reactions. DME, THF, and dioxane are miscible with water, and diethyl ether is sparingly soluble in water. 

Dioxanes Heterocyclic ethers with two oxygen atoms in a six-membered ring are called dioxanes. The most common form of dioxane is the one with the two oxygen atoms in a 1,4-relationship. 1,4-Dioxane is miscible with water, and it is widely used as a polar solvent for organic reactions. 

Esters, tertiary amides, and nitriles are frequently used as solvents for organic reactions because they provide a polar reaction medium without O—H or N—H groups that can donate protons or act as nucleophiles. Ethyl acetate is a moderately polar solvent with a boiling point of 77 °C, convenient for easy evaporation from a reaction mixture. Acetonitrile, dimethylformamide (DMF), and dimethylacetamide (DMA) are highly polar solvents that solvate ions almost as well as water, but without the reactivity of O—H or N—H groups. These three solvents are miscible with water and are often used in solvent mixtures with water. 

Esters, Amides, and Nitriles Commonly Used as Solvents for Organic Reactions... 

In this chapter we have described the mesomorphic behavior and ionic conductivities of ionic liquid-based liquid crystalline materials. These ion-active anisotropic materials have great potentials for applications not only as electrolytes that anisotropically transport ions at the nanometer scale but also as ordered solvents for reactions. Ionic liquid crystals have also been studied for uses as diverse as nonliner optoelectronic materials [61, 62], photoluminescent materials [78], structuredirecting reagents for mesoporous materials [79, 80] and ordered solvents for organic reactions [47, 81]. Approaches to self-organization of ionic liquids may open a new avenue in the field of material science and supramolecular chemistry. 

Plain water has undergone a magnificent renaissance as a solvent for organic reactions, not only because it is an environmentally safe solvent, but also due to its pronounced capacity for hydrophobic hydration of apolar solutes [178-181] cf. Sections 2.2.7 and 5.5.8 as well as Table A-14 in the Appendix. 

Ethers are relatively unreactive substances, which is why diethyl ether and tetrahydrofuran are widely used as solvents for organic reactions. However, the lone pairs on the oxygen atom are a source of reactivity. The oxygen atom may be protonated, and it reacts with Lewis acids. The increased polarity of the C-O bond then makes the neighbouring carbon atoms sensitive to nucleophilic attack. 

Because ethers are so unreactive, diethyl ether and tetrahydrofuran (THF) are often used as solvents for organic reactions. 

The three common solvents below join ether, acetone, ethyl acetate (EtOAc), toluene, and pyridine as commonly used solvents for organic reactions. One or other of these will dissolve almost any organic compound. 

Diethyl ether is a usefnl solvent for organic reactions, and was formerly used as an anesthetic. It can be prodnced by a condensation reaction (a reaction in which a small molecule such as water is split out) between two molecnles of ethanol in the presence of concentrated snlfnric acid as a dehydrating agent ... 

Ogawa, A. Curran, D.P., Benzotrifluoride A Useful Alternative Solvent for Organic Reactions Currently Conducted in Dichloromethane and Related Solvents. J. Org. Chem. 1997, 62,450. 

The use of BTF as a solvent for organic reactions has only been studied over the last three years, but its characteristics and potential are beginning to emerge. BTF is readily available in highly pure form in bulk quantities at moderate prices. Its physical properties and favorable toxicity and environmental properties may render it advantageous to substitute BTF or related solvents for chloro- or hydrocarbon solvents in a diverse range of reactions. However, BTF is not Lewis basic and there is probably only a niche role for BTF as a replacement (or additive) for ether, alcohol, amide and related solvents. 

Tetrahydrofuran (THF) and dioxane are well-known solvents for organic reactions. iV-MethylpyrroMone (NMP) and sulfolane are useful dipolar aprotic solvents, with characteristics like those of dimethylfor-mamide (DMF) and dimethyl sulfoxide (DMSO). Saturated and partially unsaturated heterocycles occur widely as components of natural products (Chapter 32). 

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