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 organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

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

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

and

imidazole Imidazole (ImH) is an organic compound with the formula . It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. It can be classified as a heterocycle, specifically as a diazole. Many natural products, ...

. It is a white solid that appears in form of tabular crystals.

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. Benzimidazole is produced by

condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...

of o-phenylenediamine with

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

, 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

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

s in place of formic acid, followed by

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

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 In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...

can be alkylated and also serves as a ligand in

coordination chemistry A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...

. 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 In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...

drugs listed by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

. 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 without causing significant damage to the host. They may also ...

agents such as

albendazole Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuri ...

, ciclobendazole,

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

, flubendazole, mebendazole, oxfendazole, oxibendazole,

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 typicall ...

, and

thiabendazole Tiabendazole (International Nonproprietary Name, INN, British Approved Name, BAN), also known as thiabendazole (Australian Approved Name, AAN, United States Adopted Name, USAN) or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a pr ...

. 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. *

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 provides ...

s such as astemizole, bilastine, clemizole, emedastine, mizolastine, and oxatomide. * Benzimidazole fungicides such as benomyl, carbendazim, fuberidazole, and

. These drugs selectively bind to and depolymerise fungal tubulin. * 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 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 m ...

s such as benperidol, clopimozide,

droperidol Droperidol (Inapsine, Droleptan, Dridol, Xomolix, Innovar fentanyl.html" ;"title="ombination with fentanyl">ombination with fentanyl is an antidopaminergic medication, drug used as an antiemetic (that is, to prevent or treat nausea) and as an ...

, neflumozide, and oxiperomide, and

pimozide Pimozide (sold under the brand name Orap) is a neuroleptic medication, 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 weigh ...

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

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. It is commonly 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 Juan de Guillebon, better known by his stage name DyE, is a French musician. He is known for the music video of the single "Fantasy (DyE song), Fantasy" from his first album ''Taki 183 (album), Taki 183''. This video became popular, attracting ...

are derived from benzimidazoles.

Preparation

Reactions

Applications

See also

References

Further reading