Acidity of imidazole

Values for the tt-electron densities in imidazole and two related ions are given in Figure 1, The TT-electron densities in the conjugate acid of imidazole are greater at the 2-position... 

The rate-pD profile for the 2-position could be accounted for by parallel rate-determining proton abstraction from the conjugate acid of imidazole by OD and by DgO leading to an ylide intermediate (Scheme 2). These pathways together with OD -catalyzed proton abstraction from the neutral imidazole molecule accounted for the 4(5)-... 

The aqueous acidities of imidazole (4) and pyrazole (6) are quite close ... 

The amino acid histidine contains an imidazole ring. In many enzymes this ring acts as a basic catalyst. Explain which nitrogen of the imidazole ring is more basic and show the structure of the conjugate acid of imidazole. 

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. 

Proton acids at neutral azoles basicity of imidazoles and benzimidazoles Proton acids at imidazole anions acidity of imidazoles Metal ions... 

Proton acids at imidazole anions, acidity of imidazoles... 

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). 

Proton acids Basicity and acidity of imidazoles and benzimidazoles... 

For molecular properties of complex systems, especially those in solution, ab initio quantum-chemical calculations may not be able to provide accurate results. For example, the acidity of imidazole in the gas phase can be calculated to provide equivalent or greater accuracy than that obtained experimentally however, the determination of its pK value... 

Imidazole can be protonated because the lone-pair electrons in the sp orbital are not part of the tt cloud. Since the conjugate acid of imidazole has a of 6.8, imidazole exists in both the protonated and unprotonated forms at physiological pH (7.3). This is one of the reasons that histidine, the imidazole-containing amino acid, is an important catalytic component of many enzymes (Section 24.9). 

Imidazoles are moderately strong bases. The pAT value of the conjugate acid of imidazole is 7.00. They form salts with many acids, e.g. chlorides, nitrates, oxalates and picrates ... 

Imidazole thus behaves amphoterically, i.e. like a combination of pyridine and pyrrole. Substituents can alter the basicity and acidity of imidazole within certain limits. 

As seen in Figure 21.3, the electrostatic potential map of the conjugate acid of imidazole (imidazolium ion) is consistent with the resonance description in showing both nitrogens as equivalent with respect to charge. 

Unlike other amines, imidazole catalyses the isomerisation of benzylpenicillin to benzylpenicillenic acid [38] (Bundgaard, 1971a,b, 1972, 1976a). The rate law shows that the nucleophilic reaction with imidazole to give the intermediate penicilloylimidazole [65] is general base catalysed by another molecule of imidazole and general acid catalysed by the conjugate acid of imidazole. 

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