5-Imidazolecarboxylic acid

In most other reactions the azolecarboxylic acids and their derivatives behave as expected (cf. Scheme 52) (37CB2309), although some acid chlorides can be obtained only as hydrochlorides. Thus imidazolecarboxylic acids show the normal reactions they can be converted into hydrazides, acid halides, amides and esters, and reduced by lithium aluminum hydride to alcohols (70AHC(12)103). Again, thiazole- and isothiazole-carboxylic acid derivatives show the normal range of reactions. 

Imidazole-5-carboxamide, l-methyl-4-nitro-mass spectra, 5, 359 Imidazole-4-carboxanilide, 1-methyl-synthesis, 5, 435 Imidazolecarboxylic acid, vinyl-polymers, 1, 281 Imidazole-2-carboxylic acid chlorination, 5, 398 mass spectra, 5, 360 synthesis, 5, 474... 

Imidazole-4-carboxylic acid, 5-methylamino-ethyl ester thermolysis, 4, 438 Imidazolecarboxylic acids decarboxylation, 5, 434—435 reactions, 5, 92, 434—435 Imidazolediazonium fluoroborates reactions, 5, 439 Imidazolediazonium salts reactions... 

The well-known application of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine as a diene in inverse electron demand Diels-Alder cyclizations was adapted for the synthesis of purines <1999JA5833>. The unstable, electron-rich dienophile 5-amino-l-benzylimidazole was generated in situ by decarboxylation of 5-amino-l-benzyl-4-imidazolecarboxylic acid under mildly acidic conditions (Scheme 54). Collapse of the Diels-Alder adduct by retro-Diels-Alder reaction and elimination of ethyl cyanoformate, followed by aromatization by loss of ammonia, led to the purine products. The reactions proceeded at room temperature if left for sufficient periods (e.g., 25 °C, 7 days, 50% yield) but were generally more efficient at higher temperatures (80-100 °C, 2-24 h). The inverse electron demand Diels-Alder cyclization of unsubstituted 1,3,5-triazine was also successful. This synthesis had the advantage of constructing the simple purine heterocycle directly in the presence of both protected and unprotected furanose substituents (also see Volume 8). 

Crosslinked polymers of vinyl-substituted imidazolecarboxylic acids have been studied as chelating resins for heavy metal ions (78MI11101). For example, polymer (75) displays stabilities and capacities in the order Cu2+ > Ni2+ > Cd2+ > Zn2+ > Mg2+ which is similar to that observed with other amino acid chelating resins. The unusual feature of the polymer, however, is that exceptionally strong complexing abilities are maintained even in strongly acidic media. Polymer (75) also displayed potential utility for the removal of mercury(II) ions from aqueous media. 

In some cases the nitration is accompanied by oxidation of the side groups [122, 123], Thus, for example, depending on the conditions, 4(5)-hydroxym-ethylimidazole is converted by the action of the sulfuric-nitric acid mixture into the corresponding aldehyde [124-126], into 4(5)-imidazolecarboxylic acid [124, 125], or into 4(5)-nitro-5(4)-imidazolecarboxylic acid [122, 123] (Scheme 11). 

The oxidation of the hydroxymethyl group probably takes place more readily than nitration of the ring [124-127], However, the entry of a nitro group into the imidazole ring without oxidation of the hydroxymethyl group has been reported [107, 110]. Imidazolecarboxylic acids are not nitrated, and their nitro derivatives are therefore obtained by different methods. Nevertheless, the 4- and 5-mononitro-substituted compounds were isolated with the 4,5-dinitro derivative as impurity during the nitration of ethyl l-methylimidazole-2-carboxylate with a mixture of 100% nitric and sulfuric acids at 95°C [128],... 

Hydrolysis (especially with bromoacetic acid)28 of the dicarboxylic esters can be followed by decarboxylation and it is possible to remove one carboxyl group at a time to prepare the imidazole-4-carboxylic acid. The decarboxylation of imidazolecarboxylic acids has been discussed by Schipper and Day.2... 

Imidazolecarboxylic acids are stable, crystalline compounds which form salts with metals, and which may exist in zwitterionic forms such as (198 Scheme 106). Such zwitterionic forms have been implicated in the decarboxylation mechanisms of the compounds. The carboxyl functions exert a pronounced base-weakening effect on the parent molecules, but it is surprising that a 5-bromo substituent in imidazole-4-carboxylic acids is not subject to ready nucleophilic displacement by CN or SOs . 

Reaction of 5-amino-l -benzyl-4-imidazolecarboxylic acid 495 with 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine 496 at 80 °C in DMF led to 9-benzyl-2,6-bis(ethoxycarbonyl)purine 501 in 83% yield. Presumably, 5-amino-l-benzyM-imidazole 497 is generated siVu from the acid and is highly reactive for the cycloaddition. The cycloadduct 498 then spontaneously undergoes retro Diels-Alder reaction with the loss of ethyl cyanoformate 499 followed by the loss of ammonia and aromatization to produce the purine in a regioselective manner (Scheme 114) <1999JA5833, 2005JOC998>. 

Representative procedure 2-Amino-4(5)-cyano-5(4)-imidazolecarboxylic acid (0.510 g, 3 mmol), anhydrous lithium chloride (0.5 g), pyridine (2 ml,... 

These organisms convert all of the purines they attack (uric acid, hypo-xanthine, guanine, and the nucleosides inosine and guanosine) to xanthine. Xanthine is hydrolyzed to 4-ureido-5-imidazolecarboxylic acid. A second enzyme that requires divalent cations splits the ureide to leave 4-amino-5-imidazolecarboxylic acid. The second step is inhibited by metal-chelating agents these were used to permit the product of the first enzyme to be accumulated and identified. Aminoimidazolecarboxylic acid is decarboxylated by a third bacterial enzyme, leaving 4-aminoimidazole. 

Updated Entry replacing M-02077 3-Methyl-4-imidazolecarboxylic acid [41806-40-0]... 

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