Condensations in aqueous media

In modern synthetic chemistry, the advantages of zinc were rediscovered. New selective reactions illustrated below were found, together with an unexpected possibility of performing some condensations in aqueous media. 

Fringuelli, F., Piermatti, O., Pizzo, F. Base-catalyzed aldol- and Michael-type condensations in aqueous media. Organic Synthesis in Water 1998,250-261. 

On the basis of extensive work, Breslow found that the benzoin condensation in aqueous media using inorganic salts (e.g., LiCl) is about 200 times faster than in ethanol (without any salt). The addition of y-cyclodextrin also accelerates the reaction, whereas the addition of p-cyclodextrin inhibits the condensation. 

Base-catalyzed aldol- and Michael-type condensations in aqueous media... 

Treatment of the cyclometallated complexes [Au(N,N,C)Cl][PF6] [N,N,CH = 6-methylbenzyl- (a) or 6-(l,l-dimethylbenzyl)-2,2 -bipyridine (b)] [20] with KOH or Ag20 in aqueous media affords the hydroxo complexes [Au(N,N,C)(OH)][PF6] (36) in fairly good yields [45b, 101] these are air-stable white solids, quite soluble in water and in many organic solvents. When refluxed in anhydrous THF they condense to give the oxo-bridged complexes [Au2(N,N,C)2( J--0)] (37) (Equation 2.10 in Scheme 2.5) which, in turn, can be obtained by a different route [102] (see Section 3.2) the reaction can be reversed by refluxing the 0x0 complex in water. 

It is worth noting that the Ullmann-Goldberg condensation of aryl halides with phenols and anilines worked efficiently in the presence of copper in water.50 For example, the coupling of 2-chlorobenzoic acid with 4-chlorophenol (K2C03/pyridine/copper powder) gave 2-(4-chlorophenoxy)carboxylic acid (Eq. 6.23).51 The Cu(I)-catalyzed transformation of 2-bromobenzoic acid into salicylic acid has also been studied in aqueous media (Eq. 6.24).52... 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

Amines can react with various carbonyl compounds and their derivatives in aqueous media to give the corresponding imine derivatives. These reactions have been discussed in related chapters. The synthetically most useful reaction of this type is the formation of imines and imine derivatives from the condensation of amines with aldehydes and ketones. Water is an excellent solvent for such condensation reactions. For example, water was found to be an ideal solvent for a high-yield, fast preparation of easily hydrolyzable 2-pyrrolecarbaldimines.23 In the presence of Cu2+, the reaction afforded the corresponding Cu(II) chelates (Eq. 11.19). 

Although the pre-RNA world is now much more the centre of scientific attention in prebiotic chemistry, there have been several attempts in recent years to understand the synthesis of oligonucleotides from the normal nucleotides by using simulation experiments (Ferris, 1998). In condensation reactions in aqueous media, there is always competition between synthesis and hydrolysis synthesis is generally only successful when supported by catalysts. 

The main derivatization techniques used are alkylation, acylation, silylation, or condensation (Drozd, 1975 Ahuja, 1976 Perry and Feit, 1978 Coutts and Baker, 1982). One of the few fundamental additions to derivatization reagents since the 1970s is the use of chloroformates (Wells, 1999). Chloroformates are useful in aqueous media, and a reaction with them proceeds rapidly at room temperature (Husek, 1998). Some examples of derivatization techniques are shown in O Figure 1-3. 

Other nucleophilic additions conducted in aqueous media can be found in the literature (Lubineau et al., 1994 Strauss, 1999). These reactions will include the benzoin condensation, the Prins reaction, and the Wittig-Horner reaction, and the Baeyer-Villi-ger oxidation. 

A three-component reaction of aromatic aldehydes, malononitrile and phenols leads to 4-aryl-2-amino-3-cyano-4//-chromenes this reaction can be carried out in aqueous media with improvements in yield and obvious environmental advantages (Scheme 35). The aromatic aldehyde undergoes a Knoevenagel condensation with malononitrile, followed by ortho-alkylation of the phenol and cyclization to form the iminopyran intermediate 114, which isomerizes to the 4//-chrorncncs (Scheme 36) <2003SL2001>. High yields for this three-component reaction can also be achieved in aqueous media when mediated by 7-alumina <2004TL2297> or cetyltrimethylammonium chloride <2001T1395>. 

The formation of oximes and hydrazones can be used to modify proteins due to some attractive properties, that is, some stability in aqueous media and compatibility with many functionalities of proteins [134], Their synthesis can be accomplished through the nucleophilic addition-elimination (condensation) of hydrazines and alkoxyamines with aldehydes and ketones, respectively. Typically, it has been used to modify the N-terminus [135-137] of peptides and proteins. For example, oxime formation has been used to modify BSA and diphtheria toxin with Shigella sonnei O-specific oligosaccharides [138],... 

Solvation of DNA bases/base pairs is of fundamental importance to biological processes as they take place in aqueous media. The effect of hydration on neutral bases or base pairs has been addressed using quantum chemical methods [106-112] as well as molecular dynamics (MD) simulations [113, 114], It is known that unlike the gas phase, dipole bound anions do not exist in condensed environments because such diffuse states are destabilized in the aqueous phase [115]. The drastic change in the nature of excess electron binding in the presence of water molecules with uracil has been observed experimentally by Bowen and co-workers [95b] using negative electron photoelectron spectroscopy (PES). They observed that even with a single water molecule the dipole bound state of uracil anion in gas phase... 

Lignin. On acidic treatments of lignin in aqueous media, lignin condensation reactions dominate and lead to the formation of acid-insoluble residues. This principle serves as the basis for quantitative determination of lignin content in plant materials [26]. Lignin condensation reactions, however, can be minimized by using mild conditions, organic solvents, or nucleophiles. 

The results of the investigations carried out with mixtures of acetone and ace-tone- /6 in the presence of inhibitors clearly indicate the free radical character of the photolysis in the liquid phase , in inert solvents as well as in aqueous media . The available evidence supporting the formation of primary products other than CH3CO and CH3 is not convincing. Although some radicals, which could possibly be formed in the primary process, were detected by the paramagnetic resonance spectra, these studies were made under extreme conditions. Essentially, all the experimental observations on photolysis in the condensed phase can be interpreted by the mechanism derived for the reaction in the gas phase. 

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