Chapter 9 Imidazoles

Abstract

The imidazole ring is present in a number of biologically important molecules as exemplified by the amino acid histidine. It can serve as a general base or a ligand for various metals (e.g. Zn, etc.) in biological systems. Furthermore, the chemistry of imidazole is prevalent in protein and DNA biomolecules in the form of histidine or adenine/guanine, respectively. Imidazole is a π-electron-excessive heterocycle. Electrophilic substitution normally occurs at C (4) or C (5), whereas nucleophilic substitution takes place at C(2). The order of reactivity for electrophilic substitution for azoles is: imidazole > thiazole > oxazole. While dealing with imidazoles, an important characteristic is their annular tautomerism. A tautomeric equilibrium for many imidazoles is rapidly achieved at room temperature. While dealing with imidazoles, an important characteristic is their annular tautomerism. A tautomeric equilibrium for many imidazoles is rapidly achieved at room temperature. In some tautomeric pairs, though, one tautomer often predominates over the other. The imidazolylzinc and imidazolyltin reagents are easier to prepare than the corresponding imidazolylboronic acids. As a consequence, if the imidazole fragment is to serve as a nucleophile in a Pd-catalyzed cross-coupling reaction, the Negishi and Stille reactions are better choices than the Suzuki coupling.