Benzimidazole

Not to be confused with Benznidazole.

For medications and other benzimidazole derivatives classified as "benzimidazoles", see § Applications, below.

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.^[2]

Benzimidazole

Names
Preferred IUPAC name 1H-1,3-Benzimidazole
Other names 1H-Benzo[d]imidazole
Identifiers
CAS Number	51-17-2 Y
3D model (JSmol)	Interactive image
Beilstein Reference	109682
ChEBI	CHEBI:41275 Y
ChEMBL	ChEMBL306226 Y
ChemSpider	5593 Y
DrugBank	DB02962
ECHA InfoCard	100.000.075
EC Number	200-081-4
Gmelin Reference	3106
KEGG	C02009 Y
PubChem CID	5798
UNII	E24GX49LD8 Y
CompTox Dashboard (EPA)	DTXSID8024573
InChI InChI=1S/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9) Y Key: HYZJCKYKOHLVJF-UHFFFAOYSA-N Y InChI=1/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9) Key: HYZJCKYKOHLVJF-UHFFFAOYAX
SMILES c1ccc2c(c1)[nH]cn2
Properties
Chemical formula	C7H6N2
Molar mass	118.139 g·mol−1
Melting point	170 to 172 °C (338 to 342 °F; 443 to 445 K)
Acidity (pKa)	12.8 (for benzimidazole) and 5.6 (for the conjugate acid)[1]
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H315, H319, H335
Precautionary statements	P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
Safety data sheet (SDS)	External MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

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.^[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]

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.^[6]

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

Applications

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.^[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]

See also

• Benzimidazoline
• Polybenzimidazole, a high performance fiber