Benzimidazole is a

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

. This bicyclic compound may be viewed as fused rings of the aromatic compounds

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...

and

imidazole Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non ...

. It is a colorless solid.

Preparation

Benzimidazole is produced by condensation of o-phenylenediamine with

formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Est ...

,. or the equivalent

trimethyl orthoformate Trimethyl orthoformate (TMOF) is the organic compound with the formula HC(OCH3)3. A colorless liquid, it is the simplest orthoester. It is a reagent used in organic synthesis for the formation of methyl ethers. The product of reaction of an ald ...

: :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.Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim.

Reactions

Benzimidazole is a base: :C₆H₄N(NH)CH + H⁺ → ₆H₄(NH)₂CHsup>+ It can also be deprotonated with stronger bases: :C₆H₄N(NH)CH + LiH → Li ₆H₄N₂CH + H₂ The imine can be alkylated and also serves as a ligand in

coordination chemistry A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Man ...

. The most prominent benzimidazole complex features ''N''-ribosyl-dimethylbenzimidazole as found in vitamin B₁₂. ''N'',''N-Dialkylbenzimidazolium salts are precursors to certain ''N''-heterocyclic carbenes.

Applications

Benzimidazole derivatives are among the most frequently used ring systems for small molecule drugs listed by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

. Many pharmaceutical agents belong to the benzimidazole class of compounds. For example: * Angiotensin II receptor blockers such as azilsartan, candesartan, and telmisartan. *

Anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may ...

agents such as

albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, ho ...

ciclobendazole Ciclobendazole is an anthelmintic, that is a pharmaceutical drug against parasitic worms. It underwent a clinical trial in the 1970s, where it was found to be as effective as mebendazole in the treatment of hookworm infection and ascariasis, but s ...

fenbendazole Fenbendazole is a broad spectrum benzimidazole anthelmintic used against gastrointestinal parasites including: giardia, roundworms, hookworms, whipworms, the tapeworm genus '' Taenia'' (but not effective against '' Dipylidium caninum'', a comm ...

flubendazole Flubendazole is an anthelmintic. Its brand name is Flutelmium which is a paste manufactured by Janssen Pharmaceutica N.V. used by veterinarians for protection against internal parasites and worms in dogs and cats. Other brand names are Flubenol, ...

mebendazole Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disea ...

oxfendazole Oxfendazole is a broad spectrum benzimidazole anthelmintic. Its main use is for protecting livestock against roundworm, strongyles and pinworms. Oxfendazole is the sulfoxide metabolite of fenbendazole. Oxfendazole is an anthelmintic (wormer) co ...

oxibendazole Oxibendazole is a benzimidazole drug that is used to protect against roundworms, strongyles, threadworms, pinworms and lungworm infestations in horses and some domestic pets. It is usually white to yellowish in appearance, and may take the form ...

triclabendazole Triclabendazole, sold under the brand name Egaten among others, is a medication used to treat fascioliasis and paragonimiasis. It is very effective for both conditions. Treatment in hospital may be required. It is taken by mouth with typically ...

, and

thiabendazole Tiabendazole (INN, BAN), also known as thiabendazole (AAN, USAN) or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a preservative, an antifungal agent, and an antiparasitic agent. Uses Preservative Tiabendazole is used primar ...

. *

Antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...

s such as astemizole,

bilastine Bilastine is an antihistamine medication used to treat hives (urticaria) and inflammation of the eye (allergic conjunctivitis) caused by an allergy. It is a second-generation antihistamine and takes effect by selectively inhibiting the histami ...

, clemizole,

emedastine upright=1, Eye drop of emedastine Emedastine (trade name Emadine) is a second generation antihistamine used in eye drops to alleviate the symptoms of allergic conjunctivitis. It acts as a H1 receptor antagonist. It works by blocking the action ...

, mizolastine, and oxatomide. *

Benzimidazole fungicide Benzimidazole fungicides are a class of fungicides including benomyl, carbendazim (MBC), thiophanate-methyl, thiabendazole and fuberidazole. They can control many ascomycetes and basidiomycetes, but not oomycetes. They are applied to cereals, fr ...

s such as benomyl,

carbendazim Carbendazim is a widely used, systemic, broad-spectrum benzimidazole fungicide and a metabolite of benomyl. It is also employed as a casting worm control agent in amenity turf situations such as golf greens, tennis courts etc. and in some countr ...

, fuberidazole, and

. * Benzimidazole opioids such as bezitramide, brorphine, clonitazene, etodesnitazene, etonitazene,

etonitazepipne Etonitazepipne (N-Piperidino Etonitazene) is a benzimidazole derivative with opioid effects around 100 times more potent than morphine, which has been sold over the internet as a designer drug A designer drug is a structural or functional ana ...

etonitazepyne Etonitazepyne (N-Pyrrolidino Etonitazene) is a benzimidazole derivative with potent opioid effects which has been sold over the internet as a designer drug and linked to numerous cases of overdose A drug overdose (overdose or OD) is the inges ...

isotonitazene Isotonitazene is a benzimidazole derived opioid analgesic drug related to etonitazene, which has been sold as a designer drug. It has only around half the potency of etonitazene in animal studies, but it is likely even less potent in humans as w ...

, metodesnitazene, and

metonitazene Metonitazene is an analgesic compound related to etonitazene, which was first reported in 1957, and has been shown to have approximately 100 times the potency of morphine by central routes of administration, but if used orally it has been shown t ...

. *

Proton-pump inhibitor Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitor ...

s such as

dexlansoprazole Dexlansoprazole, sold under the trade name Dexilant among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mou ...

esomeprazole Esomeprazole, sold under the brand name Nexium among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Effectiveness is similar to ...

, ilaprazole, lansoprazole,

omeprazole Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upp ...

pantoprazole Pantoprazole, sold under the brand name Protonix, among others, is a proton pump inhibitor used for the treatment of stomach ulcers, short-term treatment of erosive esophagitis due to gastroesophageal reflux disease (GERD), maintenance of heal ...

rabeprazole Rabeprazole, sold under the brand name Aciphex, among others, is a medication that decreases stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger–Elli ...

, and tenatoprazole. *

Typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

s such as benperidol,

clopimozide Clopimozide (R-29,764) is a typical antipsychotic drug of the diphenylbutylpiperidine class. It is very potent and has an extremely long duration of action, lasting at least one week with a single dose. It was developed by Janssen Pharmaceutica ...

, droperidol, neflumozide, and oxiperomide, and

pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis ...

. * Other notable pharmaceutical agents which contain a benzimidazole group include abemaciclib,

bendamustine Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein. Common si ...

dabigatran Dabigatran, sold under the brand name Pradaxa among others, is an anticoagulant used to treat and prevent blood clots and to prevent stroke in people with atrial fibrillation. Specifically it is used to prevent blood clots following hip or kn ...

, daridorexant, and glasdegib. In printed circuit board manufacturing, benzimidazole can be used as an organic solderability preservative. Several dyes are derived from benzimidazoles.Horst Berneth "Methine Dyes and Pigments" in ''Ullmann's Encyclopedia of Industrial Chemistry'', 2008, Wiley-VCH, Weinheim.

Preparation

Reactions

Applications

See also

References

Further reading