Reactions of Carboxylic Acids An Overview

We commented earlier in this chapter that carboxylic acids are similar in some respects to both alcohols and ketones. Like alcohols, carboxylic acids can be depro-tonated to give anions, which are good nucleophiles in 5 2 reactions. Like ketones, 

How would you prepare phenylacetic acid (PI1CH2CO2H) from benzyl bromide (PhCH2Br) Strategy 

How might you prepare 2-phenylethanol from benzyl bromide More than one step is needed. 

Nitriles are analogous to carboxylic acids in that both have a carbon atom with three bonds to an electronegative atom and both contain a it bond. Thus, some reactions of nitriles and carboxylic acids are similar. Both kinds of 

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Preparing Carboxylic Acids Reactions of Carboxylic Acids An Overview... 

Theoretical studies have been reported for the neutral29 and alkaline30,31 hydrolysis of formamide. A theoretical study of the acid hydrolysis of iV-formylaziridine concluded that both N- and O-protonated pathways compete.32 In an historical overview of tetrahedral intermediates in the reactions of carboxylic acid derivatives with nucleophiles, several citations of amide reactions are included.33... 

For an overview of reactions of carboxylic acid derivatives, see Bender, M. L. Chem. Rev. 1960, 60,53 and references therein. 

The biocatalytic reduction of carboxylic acids to their respective aldehydes or alcohols is a relatively new biocatalytic process with the potential to replace conventional chemical processes that use toxic metal catalysts and noxious reagents. An enzyme known as carboxylic acid reductase (Car) from Nocardia sp. NRRL 5646 was cloned into Escherichia coli BL21(DE3). This E. coli based biocatalyst grows faster, expresses Car, and produces fewer side products than Nocardia. Although the enzyme itself can be used in small-scale reactions, whole E. coli cells containing Car and the natural cofactors ATP and NADPH, are easily used to reduce a wide range of carboxylic acids, conceivably at any scale. The biocatalytic reduction of vanillic acid to the commercially valuable product vanillin is used to illustrate the ease and efficiency of the recombinant Car E. coli reduction system." A comprehensive overview is given in Reference 6, and experimental details below are taken primarily from Reference 7. 

A significant amount of kinetic data exists for the decarboxylation and oxidation of carboxylic acids. However, a relatively small fraction of these results deals with n-C2 to n-C4 aliphatic mono- and dicarboxylic acids under conditions pertinent to geological interests. For example, the early studies of the decarboxylation kinetics of acetic acid utilized flow-though silica tubes in which the anhydrous gas was exposed to very high temperatures for only seconds (Bamford and Dewar 1949 Blake and Jackson 1968, 1969). Nevertheless, it is useful to consider all of these results because it reveals trends common for structural classes of carboxylic acids. In this background discussion, a brief introduction to the subject of isokinetic relationships is given, as well as an overview of the decarboxylation and oxidation of carboxylic acids in which isokinetic relationships are used to establish trends and gross variations in reaction mechanisms between structural classes of acids. 

The Minisci reaction has been used successfully for the alkylation of various heteroarenes, including lepidine, pyrazine, quinoline and quinoxaline [2e,g, 111]. Compounds such as alkanes, alkenes, carboxylic acids, esters, amides, amines, alcohols, ethers, aldehydes, ketones and halides (among others) have been used as radical precursors in the Minisci reaction [118]. An overview of the different methods that have been applied to generate alkyl radicals for these processes is provided in Ref. [11 lb]. 

This overview will concentrate exclusively on the use of dirhodium(II) complexes as these are the most active catalysts for this transformation. The preparation of rhodium(II) carboxylate complexes was first reported in 1960 by the group of Chernyaev following the reaction of rhodium(III) chloride in refluxing formic acid. Their ability to decompose diazo compounds for the formation of a metaUocarbene was then discovered by Teyssie and coworkers a decade later. This seminal study has opened the vast domain of dirhodium(II)-catalyzed carbene additions that has proved highly successful. ° Their use in catalytic nitrene addition, though less extensively investigated, has also led to significant achievements that are summarized below with an emphasis on the latest developments made in the last 5 years. 

In addition to the information given in the general literature cited above, the oxidation of aldehydes has specifically been reviewed [19, 20]. The presentation here will begin with an overview of reagents that have been used for the conversion of aldehydes into carboxylic acids and derivatives thereof Subsequently, more specific oxidation reactions such as dismutations and oxidative rearrangements will be described. In the final part, oxidations of aldehyde derivatives such as acetals, oximes and hydrazones will be presented. 

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