Benzimidazole

Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Preparation

Benzimidazole was discovered during research on vitamin B₁₂. The benzimidazole nucleus was found to be a stable platform on which drugs could be developed.<ref>Template:Cite journal</ref> Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,<ref name = wagner>Template:OrgSynth</ref> 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.<ref name=Ullmann>Template:Citation</ref>

Reactions

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.<ref>Template:Cite journal</ref>

N,N'-Dialkylbenzimidazolium salts are precursors to certain N-heterocyclic carbenes.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Applications

File:Benomyl.png

Benomyl is a fungicide with a benzimidazole core

Benzimidazole derivatives are among the most frequently used ring systems for small molecule drugs listed by the United States Food and Drug Administration.<ref>Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J Med Chem 2014, 57, 5845.></ref> 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.<ref name=":0">Template:Cite journal</ref>
• 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.<ref name=":0" />
• 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.Template:Citation needed

Several dyes are derived from benzimidazoles.<ref>Template:Citation</ref>

See also

• Benzimidazoline
• Polybenzimidazole, a high performance fiber

Further reading

• Template:Cite book