Imidazole decarboxylation

Both acrylic and alkynic acids of imidazoles decarboxylate normally on heating, and bromoacrylic acids in the series are dehydrobrominated under the influence of ethanolic alkali (71 CHE 132). 

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. 

Isoxazoles (478) in the presence of base undergo ring opening to a-ketonitriles (479). When the reaction was carried out in the presence of hydrazines, 5-aminopyrazoles (480) were obtained. The reaction is also a convenient source of imidazoles, For example, when the 1,2-benzisoxazole (481) was treated with phenylhydrazine, decarboxylation initially occurred with subsequent ring closure to (482) (see Chapter 4.16). 

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

Imidazole, 2-ethyl-1 -ethoxycarbonyl-4-methyl-decarboxylation, 5, 392 Imidazole, 4-ethyl-5-methyl-tautomerism, S, 363 Imidazole, 5-ethyl-4-methyl-tautomerism, S, 363... 

Imidazole-4-carboxylic acid, 5-amino-cyclization, 5, 583 decarboxylation, 5, 434—435 ethyl ester diazotization, 5, 414 synthesis, 5, 477... 

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... 

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... 

For quantitative work, it is necessary to estimate the concentration of 5-amino-l-(P-D-ribofuranosyl)imidazole in aqueous solution. It seems that the only available method is the Bratton-Marshall assay, which was originally developed for the estimation of arylamines in biological fluids. The principle of the method is the spectrometric estimation of a salmon-pink colored dyestuff obtained by diazotation in situ, followed by coupling with /V-( 1 -naphthyl)ethyl-enediamine.65 The only remaining problem then is to know the molar extinction of this dye because pure samples of AIRs are not available. A value of 16800 at 520 nM was obtained for the dyes prepared from a model compound, 5-amino-l-cyclohexylimidazole-4-carboxylic acid (54), which is crystalline. A comparable molar extinction can be expected for the dye prepared from imidazole 55, if the carboxyl group does not exert too much influence on the chromophore. Actually, its influence is perceptible even with the naked eye, the dyestuff prepared from 53 having a somewhat different, wine-red color, with max>520 nM. The molar extinction for 55 is 17400 at 500 nM. When the decarboxylation of 54 was conducted under mild acidic conditions (pH 4.8, 50°C, 1 hour), estimation of 5-aminoimidazole 55 by the Bratton-Marshall method led to the conclusion that the reaction was almost quantitative.66 Similar conditions for the final decarboxylation were adopted in the preparation of samples of AIRs labeled with stable isotopes.58... 

Amino-5-imidazole carboxylic acid (38) has been synthesized from 4-nitro-5-imidazole carboxylic acid by catalytic hydrogenation and shown [56JBC(218)175] to spontaneously decarboxylate at low pH to give 4-aminoimidazole (39). 

Five approaches to the synthesis of 5-amino-4-unsubstituted imidazoles (96) have been described and are summarized in Scheme 9. These are (a) reduction of 5-nitroimidazoles (97), (b) hydrolysis of carbamates and amides (98), (c) decarboxylation of imidazole carboxylic acids (99), (,d) ring transformations of 5-aminothiazoles (100), and (e) cyclisation of nitrile derivatives (101). 

The only problem for the matrix-isolation of 21 consisted in the non-availability of a reasonable diazo precursor molecule suited for this technique. But since we already had experience with the preparation of 2,3-dihydrothiazol-2-ylidene46 (see below) by photofragmentation of thiazole-2-carboxylic acid we tried the same method with imidazole-2-carboxylic acid (20). Indeed, irradiation of 20 with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between carbene 21 and CO2. This is shown by the observation that the experimental IR spectrum fits only with the calculated spectrum of complex 21-CC>2 (calculated stabilization energy relative to its fragments 4.3 kcal mol-1). The type of fixation of CO2 to 21 is indicated in the formula S-21 C02. 

Barbitone (barbital, 282) was irradiated in aqueous solution at pH 10 with light of 254 nm wavelength to give the ureide (289) in 68% yield. In ethanol, the derivative (290) was formed (62%). With A-methylbarbitone (283) in buffer at pH 10, a mixture of the ureide (291) and the imidazole (292) was obtained. It was suggested that the ring-opened compounds were formed via isocyanates (288). Reaction with water would then give an acid which would spontaneously decarboxylate, but in ethanol a stable urethane (290) would form [173]. 

This group of alkaloids is an exception in the transformation process of structures, because the imidazole nucleus is already made at the stage of the precursor. The a of these alkaloids is L-histidine, and the first A is developed in a decarboxylation process by histidine decarboxylase (HDC). The histamine is a product of... 

Histamine is an imidazole compound, formed by decarboxylation of the amino acid L-histidine, a reaction catalyzed by the enzyme histidine decarboxylase. 

The oxazole (232) heated with formamide gave the imidazole (233) oxazolium cations undergo similar conversions. Primary amines convert oxazole-4-carboxylic acids (234) at 150°C into imidazoles (235) with accompanying decarboxylation (53CB88) (see CHEC 4.07 and 4.18). 

Other products from histidine include the hormonal substance histamine formed by decarboxylation, the oxidation product, imidazole acetic acid, and N5- and A/c-methylhistidines. Histamine plays a role in release of gastric secretions and allergic responses (Chapter 5). Drugs (antihistamines) that inhibit its release are in widespread use. The unusual amino acid diphthamide has an unknown function in pro-... 

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