Synthesizing carboxylic acids

A number of methods are used in the synthesis of carboxylic acids. Most of these methods involve the oxidation of some organic molecule, but other methods can be used. In this section we take a look at a few of these methods. 

The synthesis of carboxylic acids by the oxidation of alkenes is a two-step process. In the first step, a hot basic potassium permanganate (KMnO ) solution oxidizes an alkene, and in the second step, the oxidized alkene is acidified. The process cleaves the Ccirbon backbone at the carbon-carbon double bond to produce two smaller carboxylic acid molecules. For example, oleic acid (CH3(CH2)yCH=CI-l(CI-l2)yCOOH) yields of mixture of nonanoic acid (CH3(CH2)7C00H) and nonadioic acid (HOOC(CH2)7COOH). 

The oxidation of either primary alcohols or aldehydes doesn t change the carbon backbone, so you end up with a carboxylic acid containing the same number of carbon atoms as the aldehyde or alcohol. Alcohols require considerably stronger oxidizing conditions than aldehydes do. 

The oxidation of a secondary alcohol gives a ketone, and neither ketones nor terticiry alcohols readily oxidize. 

Hot acidic potassium dichromate (K2Cr20. ) u Chromium trioxide (Cr03) in sulfuric acid (H2SO (Jones rec ent) u Hot basic permanganate followed by acidification 

An example of this type reaction is the conversion of 1-decanol (CH3(CH2)8CH2OH) to decanoic acid (CH3(CH2)8COOH). 

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Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

Another way to synthesize carboxylic acid functional hyperbranched polyesteramides is to invert the monomer ratio by using an excess of cyclic anhydride with respect to diisopropanolamine. In this case the theoretical A2B building block consisting of 2 carboxylic acid and 1 hydroxyl function can be envisioned (Fig. 14). 

Organocatalysed carbonylations of arylhalogenides are an interesting way of synthesizing carboxylic acids and their derivatives. They are usually carried out with the use of pressurized CO at elevated temperatures [27-29]. 

Show how to synthesize carboxylic acids from oxidation of alcohols and aldehydes. Problems 20-36, 39, and 44 carboxylation of Grignard reagents, oxidative cleavage of alkenes and alkynes, hydrolysis of nitriles, and oxidation of alkylbenzenes. 

Sock and co workers [31] synthesized carboxylic acids by reducing alkyl bromides at platinum, gold, stainless steel, and graphite in the presence of carbon dioxide in either DMF or a THF-hexamethylphosphoramide (HMPA) mixture. Reduction of an alkyl monobromide at nickel in DMF containing TBABr and in the presence of an arylalkene and a sacrificial aluminum anode leads to an addition product [32]. 

Problem 18.3 (a) Carbon monoxide converts a sulfuric acid solution of each of the following into 2,2-dimethyibutanoic acid 2-methyl-2-butene, ferr-pentyl alcohol, neopentyl alcohol. Suggest a likely mechanism for this method of synthesizing carboxylic acids, (b) / Butyl alcohol and rec-butyl alcohol give the same product. What would you expect it to be ... 

Scheme 12. Attempts to synthesize carboxylic acid 81 led to a roadblock.

Also other routes were prosecuted to synthesize carboxylic acids by nickel induced coupling of dienes and CO2. If piperylene is reacted with carbon dioxide and the resulting nickel complex is worked up with maleic anhydride (MSA), sorbic acid is formed in yields up to 40 % [46,47] (Equation 5). 

Carboxylic acids can be created via FGIs, including oxidations and acyl substitutions. A variety of carbon-carbon bond-forming reactions can also be used to synthesize carboxylic acids. 

Hydrolysis of nitriles provides a valuable way to synthesize carboxylic acids from primary or secondary haloalkanes. To do so, add one carbon in the form of a cyano group (Table 8.1) to the carbon chain and convert this to a carboxyl group. 

Electrochemical carboxylation of organic halides with aluminum, zinc, or magnesium anode brought about the selective formation of carboxylic acids in high yield. Carboxylation of organic halides suffered from esterification of carboxylate anion with unreacted organic halide. This method enabled us to synthesize carboxylic acids by trapping carboxylate anion with metal ion. 

Fig. 53.7 Biosynthesis of natural and unnatural flavonoids and stillxaies in E. coli. Supplementation of unnatural synthesized carboxylic acids and natural carboxylic acids in E. coli recombinants produced unnatural and natural respective chalcones, flavanones, flavones, flavonols, and stilbenes. The red circle shown in the figure is one of the structure/groups shown in the inset...

Although carboxylation reactions (which involve C-C bond formation) are not typical oxidation reactions, they are related to those we have discussed above in view of the possible use of common types of catalysts. Moreover, they are also of synthetic relevance, allowing to synthesize carboxylic acids (bearing one more carbon atom than the substrate) and then-derivatives, which have several applications in our daily life [8a]. 

Reactions that synthesize carboxylic acids (RCOOH)... 

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