Decarboxylation of carboxyl radicals

The main theme of this chapter is the cleavage of alkyK aryl- and vinyl-caiboxyl single bonds by means of the fragmentation (decarboxylation) of carboxyl radicals (equation 1). The fia entation of... 

Alkyl radicals derived by decarboxylation of carboxyl radicals may be added m carbon-carbon multiple bonds resulting in an overall homologation of the starting acid. This reaction type is not stricdy a C— bond oxidation nevertheless, one of the key steps is C- bond cleavage by decarboxylation and it is appropriate to briefly consider the scope of such reactions here. A more complete description of inter- and intra-molecular radical C—C bond-forming reactions is given in Volume 4, Chapters 4.1 and... 

The known free-radical decomposition of aryl nitrosoamides (ArN(NO)COR ) and the report that nitrosoamides of 0-alkyl-hydroxylamines decompose by a free-radical pathway indicate that free-radical processes might occur in the normal nitrosoamide decomposition. In fact, the aliphatic nitrosoamides have been used as initiators at elevated temperatures for the polymerization of styrene and other olefins At, or near, room temperature, however, it appears that free radicals are not formed in the nitrosoamide decomposition. It has been found, for example, that (1) COj (a product of the decarboxylation of carboxyl radicals) is not formed in the decomposition (2) the scavenger nitric oxide has no effect on the reaction (3) normal products and no polymer are formed in the decomposition of A -(i-butyl)-A -nitrosobenzamide ° ° and N-nitroso-7V-(l-phenylethyl)acetamide -in styrene and (4) no difference in acetate yields is observed when A -nitroso-A-(1-phenyl-ethyl) acetamide is decomposed in benzene in the presence or absence of 0-1 m Styrene and 1-phenylethyl acetate react with... 

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 classic reaction involving electron transfer and decarboxylation of acyloxy radicals is the Kolbe electrolysis, in which an electron is abstracted from a carboxylate ion at the anode of an electrolysis system. This reaction gives products derived from coupling of the decarboxylated radicals. 

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. 

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

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

This reaction resembles decarboxylation of carboxylates during electrode one-electron oxidation (Kolbe reaction). Kolbe reaction also consists of one-electron oxidation, decarboxylation, and culminates in dimerization of alkyl radicals just after their formation at the electrode surface. When the sulfate radical acts as a one-electron oxidant, the caboradical dimerization is hampered. The radicals can be used in preparative procedures. One typical example is alkylation of heterocyclic nitrogen bases (Minisci et al. 1983). This difference between Kolbe reaction and the reaction with the help of a dissolved electrode (the sulfate radical) deserves some explanation. The concentration of the one-electron oxidation products in the electrode vicinity is significantly higher than that in the bulk of the solution. Therefore, in the case of anode-impelled reactions, the dimerization of radicals produced from carboxylates proceeds easily. Noticeably, 864 secures the single electron nature of oxidation more strictly than an anode. In electrode reactions, radical intermediates can... 

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. 

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). 

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... 

Another method involves electrolysis of sodium or potassium carboxylate solutions, known as Kolbe electrolysis, in which carboxylate radicals are formed by transfer of an electron from the carboxylate ion to the anode. Decarboxylation may occur simultaneously with, or subsequent to, the formation of carboxylate radicals, leading to hydrocarbon radicals, which subsequently dimerize ... 

This reaction resembles the decarboxylation of carboxylates during electrode one-electron oxidation. The Kolbe electrochemical reaction also consists of one-electron oxidation, decarboxylation, and culminates in dimerization of alkyl radicals formed intermediately. 

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. 

Generally, potassium persulfate in the presence of Ag+ is used for the Hunsdiecker type radical decarboxylation of carboxylic acids in water. (Bu4N+)2S208 (P) is soluble in THF, and a sulfate anion radical [i] is formed under refluxing conditions. Thus, refluxing treatment of / (tetrabutylammonium) persulfate (P) in the presence of alcohol in THF provides tetrahydrofuryl-protected alcohol (4), through the abstraction of a-H from THF by sulfate anion radical [I], followed by oxidation to a tetrahydrofuryl cation, as shown in eq.12.3 [28]. 

The mechanism of the decarboxylation of carboxylic acids by lead(IV),333 manganese(III),237 cobalt(III),249 and cerium(IV)288 has been well studied. Although there are some mechanistic differences, the formation of alkyl radicals by the reaction,... 

In an approach to direct C-functionalization of triazolo[4,5-c]pyridines, shown in Scheme 3, 1-methyl (or phenyl)[l,2,3]triazolo[4,5-c]pyridines (26,33) are alkylated exclusively at C-4 by radicals generated by decarboxylation of carboxylic acids (ammonium persulfate-sulfuric acid-silver nitrate) <90ZOB683>. However, with /-butanol various products are obtained depending on the catalyst employed. For example, with ammonium persulfate-sulfuric acid-silver nitrate, exclusive C(4)-methylation (34) was observed, while ammonium persulfate-sulfuric acid gave exclusively C(4)-/ -hydroxy-/ ,/ -dimethylethylation (cf. (36)). The /-butyl analogue (35) was obtained by decarboxylation of pivalic acid. 

The decarboxylation of carboxylic acid via thiohydroxamate derivatives (often called Barton esters ) is an efficient procedure for the generation of radicals. When this reaction is performed in the presence of diphenyl diselenide, the corresponding selenides are obtained in excellent yield [Eq. (42)] [104]. For example, this reaction has been used for the preparation of AT,Se-acetals from a-aminoacids [105,106]. 

The nucleophilic radicals formed by the silver-catalyzed, oxidative decarboxylation of carboxylic acids by peroxydisulfate ions attack protonated imidazoles mainly at the 2-... 

Radical substitution reactions include alkylations and arylations in the main. Nucleophilic radicals produced by the silver-catalyzed oxidative decarboxylation of carboxylic acids (by peroxydisulfate ion) attack proton-ated azoles at the most electron-deficient sites.Thus, imidazole and 1-alkylimidazoles are methylated exclusively at C-2 in rather low yields. The use of isopropyl and t-butyl radicals gives improved yields, but benzyl and acyl radicals tend to dimerize rather than substitute the... 

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