Imidazole 4,5-dicarboxylic acid

Imidazole-4,5-dicarboxylic acid, 2-methyl-pK, 5, 384 [Pg.29]

Imidazole-4,5-dicarboxylic acid, 1-methyl-decarboxylation, 5, 435 Imidazole-4,5-dicarboxylic acid anhydride synthesis, 5, 435... 

Imidazole-4,5-dicarboxylic acids, coupling, 5, 403 decarboxylation, 5, 434 1-substituted synthesis, 5, 468 synthesis, 5, 362, 402, 484 Imidazole-4,5-dione, l-alkyl-2-phenyl-synthesis, 5, 129, 479 Imidazole-2,4-diones tautomerism, 5, 370 Imidazole-4,5-diones tautomerism, 5, 370 Imidazole-2,4-dithione, 5,5-diphenyl-tautomerism, 5, 370 Imidazole-2,4-dithiones tautomerism, 5, 370 Imidazolepropanol synthesis, 5, 486 Imidazoles accelerators epoxy resins, 1, 407... 

Cefpimizole (51) appears to be less active in vitro than cefotaxime and cefoperazone and to have a somewhat narrower activity spectrum although some strains of Pseudomonas are susceptible. It is not orally active, but its performance in vivo appears superior to what would be expected from its in vitro data. Its synthesis begins by acylation of cephaloglycin (48) with the bis acid chloride of imidazole-4,5-dicarboxylic acid (49) to give amide 50. The acetyl moiety at C-3 of this intermediate is displaced with 4-pyridineethanesulfonic acid and sodium iodide to give cef-pimazole (51) [16]. 

Vigorous oxidation (e.g., with KMn04) usually degrades fused benzene rings in preference to many azole rings, especially under acidic conditions. Thus, benzimidazoles are oxidized by chromic acid or 30% hydrogen peroxide to imidazole-4,5-dicarboxylic acid, and 2,1,3-benzothiadiazole is oxidized by ozone or potassium permanganate to the dicarboxylic acid 553. 

That imidazoles and benzimidazoles have high stability has been known for many years. Resistance to acids, bases, heat and oxidation or reduction are common traits of these compounds, which display considerable aromatic character. Thus treatment of benzimidazole with permanganate leads to imidazole-4,5-dicarboxylic acid imidazoles, in general, are not easily oxidized or reduced (Sections 4.07.1.4.11, 4.07.1.5.6, 4.07.1.7.4). Thermal stability too is evidenced by the resistance of the imidazole nucleus to ring fission... 

Benzimidazole (but not 1-methylbenzimidazole) is oxidized by permanganate, dichromate or hydrogen peroxide to imidazole-4,5-dicarboxylic acid, while napth-[l,2-d]- and -[2,3-d]-imidazoles also form products in which the heterocyclic ring remains intact, hence demonstrating its stability to these conditions. With lead peroxide benzimidazole is subject to an unusual oxidation as it forms (101), also the reaction product of lead dioxide and 2,2 -bibenzimidazolyl. In dioxane, selenium dioxide oxidizes 2-methylbenzimidazole to o-hydroxyacetanilide (66RCR122). 

Electrophilic reagents preferentially attack benzimidazoles in the fused benzene ring, while nucleophiles react at C-2 which has enhanced nucleophilic activity because of the electron-withdrawal effect of the benzene moiety. The fused aryl ring appears to exhibit less aromatic stability than the heteroring as evidenced by the ready oxidation of benzimidazole to imidazole-4,5-dicarboxylic acid, and by its catalytic reduction over platinum... 

Decarboxylation can be achieved by heating the acids above their melting points, often in the presence of a copper-chromium oxide catalyst, and it is possible to remove one group at a time from imidazole-4,5-dicarboxylic acid by heating the monoanilide. Studies of the kinetics of decarboxylation of 5-aminoimidazole-4-carboxylic acids implicate a first-order decarboxylation of both the acid and the zwitterion the anion is stable and not... 

The usual range of carboxylic acid derivatives can be prepared and interconverted. Both carboxylic acid and ester functions are capable of reduction by lithium aluminum hydride to alcohols, or by controlled potential reduction to aldehydes. Attempts to form the anhydride from imidazole-4,5-dicarboxylic acid by heating with acetic anhydride failed. Instead, compound (199) is formed. This product forms the monoester (200) when heated with methanol and the hydrazide (201) when treated similarly with hydrazine (Scheme 107) (75S162). The corresponding l-methyl-4,5-dicarboxylic acid loses the 4-carboxyl group when heated with acetic anhydride, but in boiling aniline it is transformed into the 1-methyl-4-carboxanilide (79H(12)186). 

Before the turn of the century, Maquenne had prepared imidazole-4,5-dicarboxylates from tartaric ester dinitrates with either an aliphatic aldehyde or precursor in the presence of ammonium ions at pH values 3.5-6.S. Hydrolysis, especially with bromoacetic acid, of the resulting dicarboxylate esters gives imidazole-4,5-dicarboxylic acid (Scheme 75) <70AHC(12)103). 

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