Water as the Reaction Medium

Water is the medium where all biological reactions take place, including oxidation reactions, but it is a rather unfamiliar solvent for chemists who tend to avoid it, often in an over-prudent approach. When H2O2 and O2 are used as oxidants, water is present as a by-product and this prompted the investigation of catalytic asymmetric oxidation reactions in water. The hydrophobic effect, which consists of the tendency for organic species to self-assemble in water, is the most peculiar effect of this solvent and operates both on apolar catalysts and organic substrates. This overall squeeze out effect produces, in several cases, positive effects on both the catalytic activity and the enantioselectivity of asymmetric reactions, as described in the following examples of stereoselective oxidation. 

As exemplified above, the use of water as the solvent for organometallic catalysis is hampered by the low general solubility of both substrates and catalysts in this medium. Possible approaches to solving this are based on i) the use of polar cosolvents that often decrease the green character of the catalytic system or ii) the employment of surfactants that form micelles in water as apolar nano-environments where substrates and catalyst get together and react, often with enhanced activity and selectivity. Micelles are self-assembled devices arising from neutral, anionic 

Using water as the solvent also increased the selectivity in the asymmetric Baeyer-Villiger oxidation of cychc six- and four-membered ring ketones. In particular, the use of surfactants under micellar conditions allowed i) the direct solubilization of otherwise water insoluble complexes and ii) the increase of 

Overall, the use of surfactants in water for the studied BV reactions implies the partition of all reaction partners (substrate, oxidant and catalyst) between the micelle, bulk water and the interphase between the two. As a consequence, the lipophilicity of all species is crucial to rationalize their positioning in the micellar system, and as a general observation, more hydrophilic substrates worked well in neutral surfactants while more lipophilic ones worked well in anionic micelles. 

Wacker oxidation is not an exclusive characteristic of Pd(II) complexes. In 2004, Atwood reported an example of the conversion of ethylene to acetaldehyde mediated by a water-soluble Pt(II) complex of general formula cis-Pt(Cl)2(TPPTS)2 bearing intrinsically water-soluble monophosphines (TPPTS = triphenylphosphine 

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A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

In the first example of water as the reaction medium for Fischer indole synthesis, 2,3-dimethylindole was obtained in 67% yield from phenylhydrazine and butan-2-one, at 220 °C for 30 min (Scheme 2.15). Neither a preformed hydrazone nor addition of acid was required [33]. 

Li, et al. reported ethyl-bridged PMOs with Pd(ll) complexed to 3-aminopropyl-Itrimethoxysilane grafted onto the mesoporous walls to be an efficient catalysts for Barbier reaction of benzaldehyde and allyl bromide (Figure 16) [74]. Use of water as the reaction medium combined with the presence of ethyl moiety in the framework (which increased hydrophobicity of the pores) enhanced diffusion of the organic substrates. As can be seen in Table 3 the PMO material showed superior catalytic efficiency compared to grafted SBA-15 and MCM-41 materials with values comparable to homogeneous trials. 

This definition is completely independent from water as the reaction medium and is more general than the previous ones. In terms of Lewis acidity, the Br0nsted-type acid HA is the resnlt of the interaction of the Lewis-type acid species H+ with the base A . According to the definitions given, Lewis-type acids (typically, but not only, coordinatively unsatnrated cations) do not correspond to Br0nsted-type acids (typically species with acidic hydroxyl groups). On the contrary, Lewis basic species are also Br0nsted bases. 

The desire for a sustainable development in chemistry lays the foundation for environmentally benign processes. From the view point of organic chemistry, the construction of carbon skeletons plays the pivotal role. The extraordinarily mild reaction conditions in addition to the non-toxic and non-bumable properties and ubiquitous availability of water as the reaction medium make enzyme-catalyzed C-C-bond formation the first choice even for industrial production. Thanks to subtle selectivity features of the corresponding enzymes a rather broad range in substrate specificity meets with a highly conserved stereospecificity at the newly connected carbon centers. In addition, these features and the availability of the respective biocatalysts are open to intervention by recombinant genetechnological techniques. 

The role of water in the Maillard reaction was not systematically studied until rather recently. Most of the early work was conducted with water as the reaction medium, but Ambler73 mentioned that the concentration of the reactants has an effect on the course of the reaction. The change which occurs in dried eggs on storage stimulated research into the effect of small... 

The use of water as the reaction medium for biocatalysis has long been advocated as one of the major advantages of the application of biocatalysts. This so-called... 

During the last decade there have been many new applications of water-soluble organometallic catalysts in the field of organic synthesis. Although the first aim of this new concept was the easy separation of the catalyst fi-om the reaction products for its eventual recycling, new selectivities and sometimes higher activities were found using water as the reaction medium. 

Several years later, a similar approach succeeded even in the application of deactivated bromoanisole (because it was donor-substituted) with acrylic acid in water at 100 °C, using 1 mol% palladium chloride with 3 equiv. of sodium carbonate, which demonstrates the efficient application of water as the reaction medium... 

The jS-CD inclusion complexes of aryloxyepoxides with amines afforded amino-alcohols enantioselectively in the solid state. When carried out in water as the reaction medium, nearly racemic aminoalcohols were produced. 

These reactions employ microwave heating and water as the reaction medium at 100 °C for 7-9 min. The mechanism for diastereoselectivity was confirmed by density functional theory (DFT) (B3LYP) calculations. Subsequently, new multicomponent domino reactions of Meldrum s acid 159, aromatic aldehydes 69, and electron-rich heteroaryl-amines 80 have been established for the synthesis of spiro pyrazolo[l,3]dioxanes-pyridine -4,6-diones and spirojisoxazolo [l,3]dioxanes-pyridine -4,6-diones 160 in aqueous solution under microwave irradiation (Scheme 12.64) [88]. A total of 26 examples were examined to show the broad substrate scope and high overall yields (76-93%). A new mechanism was proposed to explain the reaction process and the resulting chemo-, regio-, and stereoselectivity. 

Enzymes use water as the reaction medium, and as the disposal of organic solvents becomes progressively more difficult, this may become increasingly important. On the other hand, some enzymes (e.g. lipases) can function as catalysts in organic media, thus allowing a choice to be made regarding the preferred solvent system. 

A small library of alkyl, sulfone, and carboxamide-functionalized pyrazoles and isoxazoles has been developed via a rapid sequential condensation of various R-acylketene dithioacetals with hydrazine hydrate or hydroxylamine hydrochloride, followed by oxidation of sulfide to sulfone using water as the reaction medium [3] (Scheme 8.3). An efficient and safe oxidation of sulfides to the corresponding sul-fones using sodium per borate system in aqueous medium has also been reported. The concise and two-step synthesis of trisubstituted pyrazoles and isoxazoles was investigated under a variety of reaction conditions. The newly developed methodology has the advantage of excellent yield and chemical purity with short reaction time using water as a solvent. 

Organic reactions in water, without the use of any harmful organic solvent, are of great interest, because water is nontoxic, nonflammable, abundantly available, and inexpensive. Thus, water as the reaction medium is generally considered a cheap. 

Organic reactions in water, without the use of any harmful organic solvents, are of great interest because water is nontoxic, nonflammable, abundantly available, and inexpensive. Thus, water as the reaction medium is generally considered a cheap, safe, and environmentally benign alternative to synthetic solvents. Furthermore, because of the low solubility of common organic compounds in water, the use of water as a solvent often makes the purification of products very easy by simple filtration or extraction. 

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