Benzimidazole

Benzimidazole was discovered during research on vitamin B₁₂. The benzimidazole nucleus was found to be a stable platform on which drugs could be developed.^[3] Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,^[4] or the equivalent trimethyl orthoformate:

C₆H₄(NH₂)₂ + HC(OCH₃)₃ → C₆H₄N(NH)CH + 3 CH₃OH

2-Substituted derivatives are obtained when the condensation is conducted with aldehydes in place of formic acid, followed by oxidation.^[5]

Benzimidazole is a base:

C₆H₄N(NH)CH + H⁺ → [C₆H₄(NH)₂CH]⁺

It can also be deprotonated with stronger bases:

C₆H₄N(NH)CH + LiH → Li [C₆H₄N₂CH] + H₂

The imine can be alkylated and also serves as a ligand in coordination chemistry. The most prominent benzimidazole complex features N-ribosyl-dimethylbenzimidazole, as found in vitamin B₁₂.^[6]

N,N'-Dialkylbenzimidazolium salts are precursors to certain N-heterocyclic carbenes.^[7][8]

Benzimidazole derivatives are among the most frequently used ring systems for small molecule drugs listed by the United States Food and Drug Administration.^[9] Many pharmaceutical agents belong to the benzimidazole class of compounds. For example:

• Angiotensin II receptor blockers such as azilsartan, candesartan, and telmisartan.
• Anthelmintic agents such as albendazole, ciclobendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, triclabendazole, and thiabendazole. These drugs work by binding tubulin, a vital part of the cytoskeleton and mitotic spindle. Benzimidazoles are selectively toxic towards parasitic nematodes, selectively binding and depolymerising their tubulins.^[10]
• Antihistamines such as astemizole, bilastine, clemizole, emedastine, mizolastine, and oxatomide.
• Benzimidazole fungicides such as benomyl, carbendazim, fuberidazole, and thiabendazole. These drugs selectively bind to and depolymerise fungal tubulin.^[10]
• Benzimidazole opioids such as bezitramide, brorphine, clonitazene, etodesnitazene, etonitazene, etonitazepipne, etonitazepyne, isotonitazene, metodesnitazene, and metonitazene.
• Proton-pump inhibitors such as dexlansoprazole, esomeprazole, ilaprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, and tenatoprazole.
• Typical antipsychotics such as benperidol, clopimozide, droperidol, neflumozide, and oxiperomide, and pimozide.
• Other notable pharmaceutical agents which contain a benzimidazole group include abemaciclib, bendamustine, dabigatran, daridorexant, and glasdegib.

In printed circuit board manufacturing, benzimidazole can be used as an organic solderability preservative.^{[citation needed]}

Several dyes are derived from benzimidazoles.^[11]

• Benzimidazoline
• Polybenzimidazole, a high performance fiber

• Grimmett, M. R. (1997). Imidazole and benzimidazole synthesis. Boston: Academic Press. ISBN 0-12-303190-7.