Water synthesis solvent

The most frequendy used technique to shift the equiUbrium toward peptide synthesis is based on differences in solubiUty of starting materials and products. Introduction of suitable apolar protective groups or increase of ionic strength decreases the product solubiUty to an extent that often allows neady quantitative conversions. Another solubiUty-controUed technique is based on introduction of a water-immiscible solvent to give a two-phase system. Products preferentially partition away from the reaction medium thereby shifting the equiUbrium toward peptide synthesis. 

Chemical tests for particular types of impurities, e.g. for peroxides in aliphatic ethers (with acidified KI), or for water in solvents (quantitatively by the Karl Fischer method, see Fieser and Fieser, Reagents for Organic Synthesis J. Wiley Sons, NY, Vol 1 pp. 353, 528, 1967, Library of Congress Catalog Card No 66-27894). 

The sequence has been applied to the synthesis of 1,4-cyclohexanedione from hydroquinone 10), using W-7 Raney nickel as prepared by Billica and Adkins 6), except that the catalyst was stored under water. The use of water as solvent permitted, after hltration of the catalyst, direct oxidation of the reaction mixture with ruthenium trichloride and sodium hypochlorite via ruthenium tetroxide 78). Hydroquinone can be reduced to the diol over /o Rh-on-C at ambient conditions quantitatively (20). 

Lubineau A, Aug6 J (1999) Water as Solvent in Organic Synthesis. 206 1-39 Lundt I, Madsen R (2001) Synthetically Useful Base Induced Rearrangements of Aldonolac-tones. 215 177-191... 

In this way, the operational range of the Kolbe-Schmitt synthesis using resorcinol with water as solvent to give 2,4-dihydroxy benzoic acid was extended by about 120°C to 220°C, as compared to a standard batch protocol under reflux conditions (100°C) [18], The yields were at best close to 40% (160°C 40 bar 500 ml h 56 s) at full conversion, which approaches good practice in a laboratory-scale flask. Compared to the latter, the 120°C-higher microreactor operation results in a 130-fold decrease in reaction time and a 440-fold increase in space-time yield. The use of still higher temperatures, however, is limited by the increasing decarboxylation of the product, which was monitored at various residence times (t). 

The accelerating influence of water as a solvent on the rate of the Claisen rearrangement has also been demonstrated on a number of other substrates. These studies showed that this methodology has potential applications in organic synthesis. In Eq. 12.72, the unprotected vinyl ether in a 2.5 1 water-methanol solvent with an equivalent of sodium hydroxide underwent rearrangement to give the aldehyde in 85% yield.157... 

Dang, F., Enomoto, N., Hojo, J. and Enpuku, K. (2009) Sonochemical synthesis of monodispersed magnetite nanopartides by using an ethanol—water mixed solvent Ultrasonics Sonochemistry, 16 (5), 649-654. 

A somewhat related approach was followed by Molteni and coworkers, who have described the three-component, one-pot synthesis of fused pyrazoles by reacting cyclic 1,3-diketones with DMFDMA and a suitable bidentate nucleophile, such as a hydrazine derivative (Scheme 6.195) [357]. Again, the reaction proceeds by initial formation of an enamino ketone as the key intermediate from the 1,3-diketone and DMFDMA precursors, followed by a tandem addition-elimination/cydodehydration step. The details of this reaction, carried out in superheated water as solvent, have been described in Section 4.3.3.1. 

The team of Crooks is involved in the synthesis and the use of dendrimers and, more particularly, poly(amidoamine) dendrimers (PAMAM), for the preparation of dendrimer-encapsulated mono- or bimetallic nanoparticles of various metals (Pt, Pd, Cu, Au, Ag, Ni, etc.) [55, 56]. The dendrimers were used as nanocatalysts for the hydrogenation of allyl alcohol and N-isopropylacrylamide or other alkenes under different reaction conditions (water, organic solvents, biphasic fluorous/or-ganic solvents or supercritical COz). The hydrogenation reaction rate is dependent on dendrimer generation, as higher-generation dendrimers are more sterically... 

Synthesis. Poly(ethylene sebacamide) (A), poly(1,2-propylene sebacamide) (B), poly(2-hydroxy-l,3-propylene sebacamide) (E), poly(2-hydroxy-l,3-propylene sebacamide-co-2propylene sebacamide) (F), poly(benzylethylene sebacamide) (H), and poly(piper-azinyl sebacamide) (J) were prepared by interfacial polymerization using carbon tetrachloride and water as solvents. (4)... 

Biocatalysis has traditionally been performed in aqueous environments, but this is of limited value for the vast majority of nonpolar reactants used in chemical synthesis. For a long time it was assumed that all organic solvents act as denaturants, primarily based on the flawed extrapolation of data obtained from the exposure of aqueous solutions of enzyme to a few water-miscible solvents, such as alcohols and acetone, to that of all organic sol vents. 

Lubineau A,Aug6 J (1999) Water as Solvent in Organic Synthesis. 206 1-39 Loupy A (1999) Solvent-Free Reactions. 206 153-207 March NH (1999) Localization via Density Functionals. 203 201-230 Maul J J, Ostrowski PJ, Ublacker GA, Linclau B, Curran DP (1999) Benzotrifluoride and Derivates Useful Solvents for Organic Synthesis and Fluorous Synthesis. 206 79-105 McDonnell KA, see Imperial B (1999) 202 1-38... 

Lewis acids are quite often used as catalysts in organic synthesis. Although most Lewis acids decompose in water, it was found that rare earth triflates such as Sc(OTf)3, Yb(OTf)3, etc. can be used as Lewis acid catalysts in water or water-containing solvents (water-compatible Lewis acids) [6-9]. For example, the Mukaiyama aldol reactions of aldehydes with silyl enol ethers were catalyzed by Yb(OTf)3 in water-THF (1 4) to give the corresponding aldol adducts in high yields [10, 11]. Interestingly, when the reactions were carried out in dry THF (without water), the yield of the aldol adducts was very low (ca. 10%). Thus, this catalyst is not only compatible with water but also is activated by water, probably due to dissociation of the counteranions from the Lewis acidic metal. Furthermore, the catalyst can be easily recovered and reused. 

The use of sydnones for the synthesis of polyimides is referred to in Section 4.03.5.2.6. 3-Methylsydnone has been used as a polar, water-miscible solvent for electrolytes <84CL1477>. 

Ideally, thermodynamic activities of the reactants should be used in the equation, but since concentrations are normally easier to measure these are often used instead. The use of the activity of water (which can be measured fairly easily) and the concentrations of the other reactants has been recommended for studies of enzyme catalyzed reactions in organic media (Hailing, 1984). In order to increase the synthesis of the ester, the water concentration (or activity) should be reduced. This can be achieved by replacing part of the water with a water miscible solvent. 

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