1.3- Azole acids, decarboxylation

Azocrown ethers pyrazoles, 5, 228 Azo dyes, 1, 328-331 colour and constitution, 1, 342 heterocyclic, 1, 325-326 Azo-hydrazone tautomerism, 1, 331, 334 Azoles acetic acids decarboxylation, 5, 92 acetoxymercurio reactions, 5, 107 acetyl... 

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. 

Compound (122) is also obtained by decarboxylative ring-opening of l,2-benzisoxazole-3-carboxylic acid. It has also been concluded that the reaction involves an intermediateless, concerted loss of carbon dioxide via a transition state in which the negative charge is spread over the carboxyl group and the isox azole ring. 

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... 

N-Acylimidazoles (azolides) have continued to provide a synthetic source of acid derivatives,and the various olysis reactions of these compounds have been studied. - The reactions of acetyl-imidazolium ions with amines have been found to depend largely on amine basicity. The thermal decarboxylation of Af-alkoxycarbonylimid-azoles provides a convenient synthetic route to iV-alkylimidazoles. At low temperatures the -isomer of 1-acetylimidazole predominates. ... 

In the thermal decarboxylation of l,3-azole-5-acids, the order of ease of loss of carbon dioxide is again oxazole- > thiazole- > A-methylimidazole-5-acids, but about 10 more slowly, than decarboxylation of the... 

The bisacylation of methylene-active compounds mentioned above can be avoided by using acylimidazoles in place of acyl halides (acylimidazoles are obtained from the carboxylic acid and sulfinyldiimidazole) for example, reaction of the magnesium enolate of ethyl hydrogen malonate and an acylimid-azole, with concomitant decarboxylation, gives the corresponding / -oxo ester 430... 

The direct arylation of less electron-rich azoles via cleavage of the relatively acidic C-H bond of their C2-position with ortho-substituted benzoic acids was achieved (Scheme 4.14) [18]. Similarly, the decarboxylative arylation procedure on C-H bond was successfully applied to electron-deficient polyfluoroarenes... 

The decarboxylative arylation of thiazole- and oxazole-5-carboxylic acids with aryl halides occurs in the presence of a Pd/Ag system (Scheme 4.46) [51]. The azole-azole coupling also proceeds through decarboxylation and C-H bond cleavage (Scheme 4.47) [52]. 

A theoretical study of the protonation sites of azines and purines has been used as a probe for their susceptibility to electtophilic substitution." Calculations of the electron densities in 1,3-azoles (1) are relevant to their protonation, nitfation, hydride addition, and deprotonation it is concluded that N(3) is the most stable protonation site, while the C(5) site is preferred for electrophilic addition. It has been shown that the deutero-decarboxylation of ortfto-substituted carboxylic acids may be catalysed by silver salts it is likely that aryl-silver species, such as (2), are intermediates. ... 

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