benzimidazole

Benzimidazole is a bicyclic aromatic heterocycle formed by fusion of a benzene ring to an imidazole ring, giving the formula C7H6N2. It contains two ring nitrogens, one of which bears a hydrogen in the parent molecule. The compound is a weak base and can form salts with acids, increasing its water solubility.

Synthesis of benzimidazole typically involves cyclocondensation of o-phenylenediamine with formic acid or other carboxylic acid derivatives, followed by dehydration to close the imidazole ring. Alternative routes include condensation of o-phenylenediamine with aldehydes or other carbonyl compounds, in the presence of oxidants, to give 2-substituted benzimidazoles. Substitutions can occur on the benzimidazole nitrogens (N-alkylation or N-arylation) or on the benzene ring at various positions.

Properties and significance: The benzimidazole scaffold is a privileged structure in medicinal chemistry due to its planarity, hydrogen-bonding capability, and ability to engage in π-π interactions. The ring system also acts as a diprotic heterocycle capable of coordinating metal ions, making benzimidazole derivatives useful as ligands in coordination chemistry.

Occurrence and derivatives: Numerous benzimidazole derivatives are known and have broad applications in medicine, agriculture, and materials science. Notable drugs containing the benzimidazole core include albendazole and mebendazole (anthelmintics) and proton pump inhibitors such as omeprazole, lansoprazole, and pantoprazole. Safety considerations follow standard guidelines for organic heterocycles.