2-Imidazole sulfonic acid

Azolesulfonic acids frequently exist as zwitterions. The usual derivatives are formed, e.g. pyrazole-3-, -4- and -5-sulfonic acids all give sulfonyl chlorides with PCI5. The sulfonic acid group can be replaced by nucleophiles under more or less vigorous conditions, e.g. by hydroxyl in imidazole-4-sulfonic acids at 170 °C, and by hydroxyl or amino in thiazole-2-sulfonic acids. 

Ester formation from polysaccharides can be achieved in several ways First by acylation of the OH groups with carboxylic or sulfonic acid azolides, second by converting the OH groups with imidazole carboxylates into carbonates, and third by reaction of an acid leash on the polysaccharide with an alcohol by means of CDI or analogous azolides. The acid leash might, for example, be a succinate attached to the polysaccharide. 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

The imidazolides required for these reactions can be prepared from sulfonyl chlor-ides[1] or sulfonic anhydrides[2] and imidazole, or by treatment of the corresponding sulfonic acid with CDI,[1] ImSOIm,[3] or ImS02Im[3] (see Section 10.1.1). However, for the synthesis of sulfonamides it is more convenient to employ a one-pot reaction starting from the free sulfonic acid, CDI or ImSOIm, and the appropriate amine [1]... 

Alkali metals and ammonium Fused silica capillary suspension of cation exchange particles (slid-phase reagent, SPR) 5 mM imidazole-10 mA/MES [2-(N-morpholino)ethane-sulfonic acid], pH 6.15 370 mm x 75 pm i.d. 305 mm effective length, ion-exchange electrochromatography 179... 

Strong oxidation (e.g., by RMnO. ) forms a sulfonic acid or betaine as, for example, in the pyrazole (750 751), imidazole, thiazole, and tetrazole series. 

Electrophilic substitution of nitro and sulfonic acid groups occurs in strongly acid media and involves attack on the conjugate acid of imidazole—a system exhibiting pronounced deactivation. Electron density calculations294,296 297 predict the experimentally found substitution at positions 4 and 5. Acylation under Friedel-Crafts conditions does not occur in imidazoles. 

Substituent effects follow the general pattern of substituted benzene derivatives in that nitro, sulfonic acid, and carboxyalkyl groups deactivate the ring to further substitution, whereas amino and methoxy groups strongly activate, and methyl and chloro groups have little effect. Ridd383 has recently reviewed electrophilic substitutions on quinoline, pyridine, and imidazole. 

Hydroxylamine-O-sulfonic acid converts an imidazole-2-aldehyde into a mixture of the carboximidamide and the 2-cyanoimidazole (79JHC871). 

Imidazole- and benzimidazole-2-thiols usually exist largely as the thione tautomers. The thiol (thione) group is susceptible to alkylation (especially in alkaline media), and can be oxidized to sulfide, disulfide and sulfonic acid. This oxidation can often be carried out quite selectively by careful choice of oxidizing agent. The sulfur function can be removed with nitric acid, iron(III) chloride, hydrogen peroxide or, most commonly, Raney nickel. Alkyl- and arylthio groups can be oxidized to sulfoxide or sulfone. 

Direct electrophilic sulfonation of imidazole and 2-substituted imidazoles has been traditionally carried out using oleum at around 160°C. Yields of the 4-sulfonic acid can be above 80%, but if a three-fold excess of sulfur trioxidc in refluxing 1,2-dichloroethane is used, the acids arc obtained under much milder conditions. Care has to be taken, for if only a 1 1 or 1 2 ratio of S03 imidazole is used, a charge transfer complex is formed instead [6]. 

In acetic acid solution 30% hydrogen peroxide converts 2-imidazolyl methyl sulfides into sulfones" " and sometimes sulfoxides. In tri-fluoracetic acid the sulfoxides are formed preferentially periodate, too, can give the sulfoxides. Oxidation of 4-mercaptoimidazoles under mild conditions gives bis(4-imidazolyl) disulfides which can be cleaved by hydrogen sulfide. With 15% alkaline hydrogen peroxide at 90°C the sulfonic acid is the major product. Imidazole-5-sulfonyl chlorides give sulfonamides... 

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