Decarboxylation of carboxylic acids

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

A complementary method is the Kochi reaction. This reaction is especially useful for the generation of secondary and tertiary alkyl chlorides through decarboxylation of carboxylic acids, where the classical method may not work. As reagents, lead tetraacetate and lithium chloride are then employed ... 

The photo-Kolbe reaction is the decarboxylation of carboxylic acids at tow voltage under irradiation at semiconductor anodes (TiO ), that are partially doped with metals, e.g. platinum [343, 344]. On semiconductor powders the dominant product is a hydrocarbon by substitution of the carboxylate group for hydrogen (Eq. 41), whereas on an n-TiOj single crystal in the oxidation of acetic acid the formation of ethane besides methane could be observed [345, 346]. Dependent on the kind of semiconductor, the adsorbed metal, and the pH of the solution the extent of alkyl coupling versus reduction to the hydrocarbon can be controlled to some extent [346]. The intermediacy of alkyl radicals has been demonstrated by ESR-spectroscopy [347], that of the alkyl anion by deuterium incorporation [344]. With vicinal diacids the mono- or bisdecarboxylation can be controlled by the light flux [348]. Adipic acid yielded butane [349] with levulinic acid the products of decarboxylation, methyl ethyl-... 

A hydroxymethyl group can be introduced (ArH —> ArCH20H) by several variations of this method. Alkylation of these substrates can also be accomplished by generating the alkyl radicals in other ways from hydroperoxides and FeS04, from alkyl iodides and H2O2—Fe V from carboxylic acids and lead tetraacetate, or from the photochemically induced decarboxylation of carboxylic acids by iodoso-benzene diacetate. 

The decarboxylation of carboxylic acid in the presence of a nucleophile is a classical reaction known as the Hunsdiecker reaction. Such reactions can be carried out sometimes in aqueous conditions. Man-ganese(II) acetate catalyzed the reaction of a, 3-unsaturated aromatic carboxylic acids with NBS (1 and 2 equiv) in MeCN/water to afford haloalkenes and a-(dibromomethyl)benzenemethanols, respectively (Eq. 9.15).32 Decarboxylation of free carboxylic acids catalyzed by Pd/C under hydrothermal water (250° C/4 MPa) gave the corresponding hydrocarbons (Eq. 9.16).33 Under the hydrothermal conditions of deuterium oxide, decarbonylative deuteration was observed to give fully deuterated hydrocarbons from carboxylic acids or aldehydes. 

OXIDATIVE DECARBOXYLATION OF CARBOXYLIC ACIDS 8.4.1 Attack of Peroxyl Radicals on C—H Bonds... 

Carboxylic acids are thermally stable. Decarboxylation of carboxylic acids is observed at 600 K and higher in the absence of dioxygen [4], At the same time, the decarboxylation of fatty acids in oxidized cumene was observed at 350 K [71]. The study of C02 production from oxidized acetic, butanoic, isobutanoic, pentanoic, and stearic acids labeled with 14C in the... 

The unusual rate enhancement of nucleophiles in micelles is a function of two interdependent effects, the enhanced nucleophilicity of the bound anion and the concentration of the reactants. In bimolecular reactions, it is not always easy to estimate the true reactivity of the bound anion separately. Unimolecular reactions would be better probes of the environmental effect on the anionic reactivity than bimolecular reactions, since one need not take the proximity term into account. The decarboxylation of carboxylic acids would meet this requirement, for it is unimolecular, almost free from acid and base catalysis, and the rate constants are extremely solvent dependent (Straub and Bender, 1972). 

Biomass pyrolysis in the presence of a catalyst, in situ, is considered as one of the options to overcome the problem characteristics of bio-oil mentioned above. Selective removal, by decarboxylation, of carboxylic acids (formic, acetic acids)... 

Scheme 24 Reaction of radicals generated by anodic decarboxylation of carboxylic acids.

The oxidative decarboxylation of carboxylic acids is the most convenient source for the alkylation of protonated heteroaromatic bases owing to their easy availability and the high versatility of the reaction, which permits methyl, primary, secondary, and tertiary alkyl radicals to be obtained under very simple experimental conditions. The following methods have been utilized. 

The usual sources used for the homolytic aromatic arylation have been utilized also in the heterocyclic series. They are essentially azo- and diazocompounds, aroyl peroxides, and sometimes pyrolysis and photolysis of a variety of aryl derivatives. Most of these radical sources have been described in the previous review concerning this subject, and in other reviews concerning the general aspects of homolytic aromatic arylation. A new source of aryl radicals is the silver-catalyzed decarboxylation of carboxylic acids by peroxydisulfate, which allows to work in aqueous solution of protonated heteroaromatic bases, as for the alkyl radicals. 

The second important class of reducing agents is generated by means of oxidative decarboxylation of carboxylic acids. Electrochemical oxidation of oxalate ion C2042 produces, in aqueous as well as in acetonitrile solutions containing Ru... 

Oxidation of hydrazines 9-13 Oxidative decarboxylation of carboxylic acids... 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

Substituent exchange in the 1,2,4-triazine ring is an extensively studied reaction, as in other systems. As earlier mentioned, the introduction of a hydrogen atom into the 1,2,4-triazine ring can be achieved by oxidation of hydrazino-l,2,4-triazines (306), as was shown for 3-hydrazino and 5-hydrazino compounds. Another method is by the decarboxylation of carboxylic acids (307). This reaction was used by Paudler and Barton for the preparation of the parent 1,2,4-triazine (1) by decarboxylation of the 3-carboxylic acid (66JOC1720), but decarboxylation of 5- and 6-carboxylic acids are also well-documented reactions. 

The persulfate ion S2OI-, with or without various transition metal ions, is a particularly effective oxidant, especially for the decarboxylation of carboxylic acids.535 In the presence of silver(I), persulfate oxidation to silver(II) readily occurs and for aliphatic carboxylic acids the decarboxylation mechanism given in Scheme 4 has been established. The aliphatic radicals produced may then disproportionate, abstract hydrogen or be further oxidized to an alcohol. In... 

The silver(II)-catalyzed decarboxylation of carboxylic acids was noted in Section 54.2.2.2. The oxidation of amino acids is thought to occur by a similar process. 

The electrochemical oxidative decarboxylation of carboxylic acid salts that leads to radicals, which dimerize. It is best applied to the synthesis of symmetrical dimers, but in some cases can be used with a mixture of two carboxylic acids to furnish unsymmetrical dimers. 

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