Carboxylic acids preparation from direct oxidation

We noted previously that aldehydes such as benzaldehyde can be prepared by direct oxidation of the side chain in the reactant. It is also possible to go from the opposite direction and reduce a carboxylic acid to the corresponding aldehyde. In both cases, side-chain halogenation using hazardous chemicals is avoided. A one-step direct hydrogenation process has been developed by Mitsubishi using a Cr modified zirconia catalyst (Yokoyama et al., 1992), which is reported to give aldehyde selectivities of 80-97% in the hydrogenation of benzoic acid, o-methylbenzoic acid, w-phenoxybenzoic acid, dimethyl terephthalate, etc. 

Zinc carboxylates are prepared in aqueous ethanol solution by sonication of zinc carbonate in the presence of the acid.1 2 Only 5-min irradiation times are required, and the method was successfully applied to Boc-protected amino acids (p. 147). Mercuric carboxylates were prepared from yellow mercuric oxide and carboxylic acids.43 The sonochemical reaction proceeds very fast in apolar solvents, and a series of salts were prepared by this method and used in hydroxy-mercuration reactions. This reaction can be effected directly from a mixture of the olefin, mercuric oxide, and a carboxylic acid (p. 119). 

Fluorinated ether-containing dicarboxyhc acids have been prepared by direct fluorination of the corresponding hydrocarbon (17), photooxidation of tetrafluoroethylene, or by fluoride ion-cataly2ed reaction of a diacid fluoride such as oxalyl or tetrafluorosuccinyl fluorides with hexafluoropropylene oxide (46,47). Equation 8 shows the reaction of oxalyl fluoride with HEPO. A difunctional ether-containing acid fluoride derived from HEPO contains regular repeat units of perfluoroisopropoxy group and is terminated by two alpha-branched carboxylates. 

There are two approaches to the production of peptide a-oxo derivatives (1) the Dakin-West acylation directly from N-protected peptides (Section 15.1.5.1), and (2) oxidation of N-protected peptidyl a-substituted carboxylic acid derivatives (Section 15.1.5.2), which are prepared from N-protected peptides or nonpeptidyl intermediates. The oxidation approach has a synthetic advantage over the Dakin-West acylation as there can be retention of configuration in the final product, but it can be tedious to perform and, in some cases, it requires particular care. 

Lithium aluminum hydride reduction of pleiocarpinilam (CXLVI-D) and kopsinilam (CXLII-D) gave, respectively, N-methylkopsinyl alcohol (CXLVI-F) and kopsinyl alcohol (CXLII-F) and thus there was every likelihood that these alkaloids were the E-ring lactams derived from pleiocarpinine and kopsinine, respectively. The correctness of this view was shown by synthesis. Pleiocarpinilam was obtained by the direct permanganate oxidation of pleiocarpinine (CXLVI-A) in acetone, while kopsinilam could be prepared, in a similar manner, from N-acetyl-kopsinine (CXLIV-A) followed by acid hydrolysis of the acetyl group, or from pleiocarpine lactam A (CXLV-D) by hydrolysis and simultaneous decarboxylation of the X-carbomethoxyl followed by reesterification of the C-3 carboxylic acid. 

Carbonation of the sodium salt of 7-azaindole (105, R = H) gives 7-azaindole-3-carboxylic acid (106, R = OH) in low yield. Robison and Robison also prepared it from 7-azaindole-3-carboxaldehyde (105, R = CHO) either by direct oxidation (28 % yield) or through the oxime, which was dehydrated with acetic anhydride to l-acetyl-3-cyano-7-azaindole. This compound was hydrolyzed in water to give 3-cyano-7-azaindole (105, R = CN) in refluxing hydrochloric acid it... 

Polymer-bound reagents have also been used. The synthetically important Weinreb amides [RCON(Me)OMe, see 16-82] can be prepared from the carboxylic acid and MeO(Me)NH HCl in the presence of tributylphosphine and 2-pyridine-A -oxide disulfide. Di(2-pyridyl)carbonate has been used in a related reaction that generates amides directly. The reaction of a carboxylic acid and imidazole under microwave irradiation gives the amide. Microwave irradiation of a secondary amine, formic acid, 2-chloro-4,6-dimethoxy[l,3,5]tria-zine, and a catalytic amount of DMAP (4-dimethylaminopyridine) leads to the formamide. ° Ammonium bicarbonate and formamide converts acids to amides with microwave irradiation. Lactams are readily produced from y- or 8-amino acids, for example. 

Problem 18.4 What carboxylic acid can be prepared from p-bromotoluene (a) by direct oxidation (b) by free-radical chlorination followed by the nitrile synthesis ... 

Directed lithiations. Arylboronic acids containing an o-carboxyl group are prepared from the corresponding neopentyl esters via directed lithiation and boration. Chiral o-hydroxyaryl phosphine oxides which are potential chiral ligands are obtained from a... 

Let s first consider how to prepare an aldehyde from a carboxylic acid. There are no good methods for going from RCO2H to RCHO directly. Instead, we do it indirectly by first reducing the carboxylic acid to the corresponding primary alcohol, then oxidizing the primary alcohol to the aldehyde. 

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