Additions carboxylic acids

Oxidation of Aldehydes to Carboxylic Acids - Addition of Oxygen... 

The greater effect of the structure of the carboxylic acid additives appears... 

Grignard reagent reacts with CO2 to give magnesium salts of carboxylic acid. Addition of aqueous acid produces carboxylic acid. 

Aqueous TCE has also been irradiated with -y-rays by Getoff [14], who measured the same by-products. The major, stable reaction products for the irradiation of TCE in aqueous solution are nonhalogenated carboxylic acids. Additional studies are necessary to determine the relative concentration of these known reaction by-products in natural waters. 

Fig. 8.13. Arndt-Eistert homologation of carboxylic acids—addition of H20 to a ketene in part 2 of the third reaction of this three-step reaction sequence.

Because mineral acids are stronger than carboxylic acids, addition of a mineral acid converts a carboxylic acid salt back to the original carboxylic acid. 

The major limitation of the x(30) values is the fact that they cannot be measured for acidic solvents such as carboxylic acids. Addition of traces of an acid to solutions of (44) or (45) immediately changes the colour to pale yellow due to protonation at the phenolic oxygen atom of the dye. The protonated form no longer exhibits the long-wavelength solvatochromic absorption band. The excellent linear correlation between iix(30) and Kosower s Z values, which are available for acidic solvents, allows the calculation of t(30) values for such solvents [174]. A further limitation has been the fact that it has not been possible to measure the absorption maximum of the standard betaine dye (44) in the gas phase as a reference state. 

Activation of the carboxylic acid can easily be accomplished by the classical thionyl chloride method.To generate acid chlorides under mild conditions without the evolution of gaseous HCl the reaction is carried out in SOCl2/DMF or started with the dicyclohexylammonium salt of the carboxylic acid. Addition of DMF accelerates the reaction. An imide chloride is considered to be the reactive species (Scheme 2). Other methods include activation with cyanuric chloride or triphenylphosphine/ tetrachloromethane. ... 

Formal Carboxylic Acid Addition to (Alk-l-enyl)cyclopropanes... 

Acid chloride formation from carboxylic acid, see under Carboxylic acid Addition, amine to acrylonitrile, 98, 118 bromine to methyl acrylate, 202 bromine to vinyl acetate, 102 chlorine to methyl acrylate, 202 chlorine to vinyl acetate, 147 HC1 to styrene, 77 HC1 and HBr to acrylonitrile, 82. ... 

Condensation of alkynes with carboxylic acids. Addition of RC(X)H to alky-nes forms enol carboxylates. On the other hand, heterocyclization occurs with acetylenedicarboxylic esters. ... 

Scheme 4.12 Copper-catalyzed arylations of aryl boronic acids using carboxylic acid additives.

As carboxylic acid additives increased the efficiency of palladium catalysts in direct arylations through a cooperative deprotonation/metallation mechanism (see Chapter 11) [45], their application to ruthenium catalysis was tested. Thus, it was found that a ruthenium complex modified with carboxylic acid MesC02H (96) displayed a broad scope and allowed for the efficient directed arylation of triazoles, pyridines, pyrazoles or oxazolines [44, 46). With respect to the electrophile, aryl bromides, chlorides and tosylates, including ortho-substituted derivatives, were found to be viable substrates. It should be noted here that these direct arylations could be performed at a lower reaction temperatures of 80 °C (Scheme 9.34). 

Reaction conditions for C-H activation of thiophenes can be divided into three groups 1) Heck (Jeffery) conditions/ although these are used infrequently 2) with carboxylic acid additives 3) without carboxylic acid additives. The last two types of conditions have been used in polar and aprotic solvents and may be carried out with a phosphine ligand. 

Carboxylic acid additives have been shown to assist in the deprotonation process vide infra). Fagnou and coworkers have used palladium (II) acetate, a phosphine ligand, potassium carbonate and pivalic acid (PivOH) in DM Ac or toluene to prepare several small molecules through the coupling of thiophenes and 2,2 -bithiophenes with arylbromides. An example of a biscoupling of 2,2 -bithiophene with two equivalents of l-bromo-3,5-dimethylbenzene to give 7 is shown in Scheme 19.3. 

Coupling Reactions. Palladium pivalate is an effective catalyst for mild and efficient direct arylation reactions. One account described the intramolecular arylation phenolic ethers (eq 1). Initial optimization with Pd(OAc)2 in conjunction with electron-deficient phosphines led to the desired biphenyl in low yield. Upon the addition of carboxylic acid additives, the yield improved markedly with the optimal additive being pivalic acid. Indeed it was determined that the additive was not needed when Pd(OPiv)2 was errqtloyed as a catalyse although improved yields were observed when the title compound was used in conjunction with the acid additive. The role of the pivalate is believed to be that of a proton shuttle in a concerted metallation-deprotonation (CMD) sequence. A further advantage of using Pd(OPiv)2 was the rate enhancement of the arylation with most reactions complete in less than 6 h (vs. 12 or more hours with Pd(OAc)2). The catalyst was applied to a range of electron-rich and -deficient arenes with good to excellent yields. 

Direct Amination of Azoles, Decarbonylative amidation and amination of benzoxazole andbenzothiazole couldbe achieved using a Pd VAg system, promoted by carboxylic acid additives. Silver(I) fluoride performed inferiorly to Ag2C03 (30 vs. 78%). Stoichiometric amounts of silver salt were required to maximize reactivity no reaction occurred using only catalytic silver. Silver is postulated to help rearomatize the heteroarene following amination. Diversely substituted benzoxazoles and benzothiazoles afforded the C2-aminated product in moderate to excellent yield (eq 18). 

The monoarylation of aryl-triazoles with arylchlorides can be achieved with [RuCl2(p-cymene)]2 catalyst with large excess of PCya in more drastic conditions, 120-135°C for 20 h, than with carboxylic acid additive, whereas arylbromides... 

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