Carboxylic acid derivatives catalysed reactions

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Intramolecular catalyses of cleavage reactions at carboxylic acid derivatives are well known, and outside the scope of this book. However, cleavage reactions can also be catalyzed by species that bind to the substrate and carry out a selective reaction that depends on the geometry of the mixed complex. Since this is in the spirit of the rest of what has been described, it will be briefly included here. Such reactions imitate enzymatic cleavage processes, so they are biomimetic in the same sense that selective functionalizations within mixed complexes are biomimetic [1]. The work using cyclodextrin binding has been extensively reviewed recently [30]. 

In the chemistry of (3-lactam antibiotics, isolations of carboxylic acid derivatives are successfully achieved by formation of amidinium salts [56]. Lewis acid catalysed reaction of 4-substituted 1-trimethylsilyloxyfurans with 4-acetoxyazetidinone chiron leads to highly enantioselective construction of tricyclic carbapenam and penems, in which DBU (1) and Eshenmoser amidine (4) were used for the introduction of the exo double bond on the (3-lactam skeleton by demesylation (A route) and the isolation of carboxylic acids as... 

The Gewald synthesis of 2-aminothiophen-3-carboxylic acid derivatives has been extended to cyanoacetic acid hydrazides. In the base-catalysed reaction with cyclohexanone and sulphur, the hydrazides yielded the thienopyrimidone derivative (24), which could be hydrolysed to the 2-aminothiophen-3-carboxylic acid hydrazide (24a). A series of substituted 2-aminothiophen-3-carboxylic esters have been prepared by a... 

In 2007, Milstein reported an approach for the transition metal catalysed intermolecular formation of amides from alcohols and amines in the absence of a hydrogen acceptor (Scheme 12.19). In contrast with conventional amide synthesis from activated carboxylic acid derivatives which produces chemical waste, this environmentally benign approach produces hydrogen gas as the only byproduct. The catalyst used for this reaction is a dearomatised Ru(PNN)pincer complex which serves as a bifunctional catalyst. The ligands, as well as the metal centre, play a role in bond making or bond breaking steps of the catalytic cycle. 

An interesting preparation of alkyl carboxylates in high yield (Table 3.14) from the sodium salt of the carboxylic acids under mild phase-transfer catalytic conditions involves their reaction with alkyl chlorosulphate [50] and has been used with success in the preparation of alkyl esters derived from p-lactam antibiotics. The procedure is also excellent for the production of chloromethyl esters, particularly where the carboxylic acids will not withstand the classical Lewis acid-catalysed procedure using an acid chloride and formaldehyde, or where the use of iodochloromethane [51] results in the formation of the bis(acyloxy)methane. The procedure has been applied with some success to the synthesis of chloromethyl A-protected a-amino carboxylates [52],... 

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

The oxidation of aciy lic acid can be rationalized in terms of the endogenous catabolism of propionic acid, in which acrylyl coenzyme A is an intermediate. This pathway is analogous with fatty acid 3-oxidation, common to all species and, unlike the corresponding pathway in plants, does not involve vitamin 8,2. 3-Hydroxypropionic acid has been found as an intennediate in the metabolism of acrylic acid in vitro in rat liver and mitochondria (Finch Frederick, 1992). The CO2 excreted derives from the carboxyl carbon, while carbon atoms 2 and 3 are converted to acetyl coenzyme A, which participates in a variety of reactions. The oxidation of acrylic acid is catalysed by enzymes in a variety of tissues (Black Finch, 1995). In mice, the greatest activity was found in kidney, which was five times more active than liver and 50 times more active than skin (Black et al., 1993). 

The use of much-neglected bismuth derivatives for the oxidation of organic compounds has been reviewed.74 Bismuth(III) carboxylates, obtained by reaction of Bi2C>3 with pyridine mono- and di-carboxylic acids and with phthalic acid, act as catalysts for the oxidation of styrene oxide to benzoic acid in DM SO in the presence of 02.75 It is proposed that the bismuth may activate both epoxide and oxidant in a solvate, from which dimethyl sulfide evolution and elimination leads to a ketoalkoxide-bismuth complex (and hence to the initial product, 2-hydroxyacetophenone). Further oxidation to tlie ketoaldehyde and acid requires molecular oxygen, but is also found to be catalysed by bismuth. 

The addition of alkoxycarbonylcarbene derived by catalysed decomposition of methyl diazoacetate to several simple, and in particular terminal, alkynes leads to low yields S7), but the reaction with 1 -trimethylsilylalkynes proceeds reasonably efficiently subsequent removal of the silyl-group either by base or fluoride ion provides a route to l-alkyl-3-cyclopropenecarboxylic acids. In the same way 1,2-bis-trimethylsilyl-ethyne can be converted to cyclopropene-3-carboxylic acid itself58 . The use of rhodium carboxylates instead of copper catalysts also generally leads to reasonable yields of cyclopropenes, even from terminal alkynes 59). 

Toluene has been oxidized by the silver ion catalysed reaction with peroxy-disulfate. The reaction produces a mixture of bibenzyl, benzaldehyde and benzoic acids.299 Russian workers have described the conversion of 4-methoxy-toluene to the benzaldehyde by oxidation with peroxydisulfate in the presence of silver or copper ions and oxalic acid.300 The presence of copper salts in iron or copper catalysed peroxydisulfate oxidation is believed to suppress side-reactions.301 Phillips have patented a palladium(II)/tin(IV)/persulfate system for the oxidation of toluene derivatives.302 The reactions are carried out in carboxylic acid solvents (Figure 3.78). 

At a first glance it may appear eccentric to show interest in the basicities of carboxylic acids. However, this is not as curious as it seems, since protonated carboxylic acids and their derivatives play the role as important intermediates during acid-catalysed reactions of these compounds. As a matter of fact, Scheele showed as early as in 1782 that addition of sulphuric acid to a mixture of acetic acid and ethanol accelerated esterification [192]. In this respect it is a key point that carboxylic acids, esters and anhydrides possess two oxygens which are po-... 

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