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.{{Cite journal |last1=Bennet-Jenkins |first1=E. |last2=Bryant |first2=C. |date=1996 |title=Novel sources of anthelmintics |url=https://pubmed.ncbi.nlm.nih.gov/8923141/ |journal=International Journal for Parasitology |volume=26 |issue=8–9 |pages=937–947 |doi=10.1016/s0020-7519(96)80068-3 |issn=0020-7519 |pmid=8923141}} Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,{{OrgSynth | title = Benzimidazole | doi = 10.15227/orgsyn.019.0012 | volume = 19 | pages = 12 | year = 1939 | author = E. C. Wagner, W. H. Millett}} 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.{{citation| doi = 10.1002/14356007.a19_405 | chapter = Phenylene- and Toluenediamines | title = Ullmann's Encyclopedia of Industrial Chemistry | date = 2000 | last1 = Smiley | first1 = Robert A. | isbn = 978-3-527-30385-4 }}

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.{{cite journal

| author1 = H. A. Barker

| author2 = R. D. Smyth

| author3 = H. Weissbach

| author4 = J. I. Toohey

| author5 = J. N. Ladd

| author6 = B. E. Volcani

| name-list-style = amp

| title = Isolation and Properties of Crystalline Cobamide Coenzymes Containing Benzimidazole or 5,6-Dimethylbenzimidazole

| journal = Journal of Biological Chemistry

| date = February 1, 1960

| volume = 235

| issue = 2

| pages = 480–488

| doi = 10.1016/S0021-9258(18)69550-X

| pmid = 13796809

| doi-access = free

}}

N,N'-Dialkylbenzimidazolium salts are precursors to certain N-heterocyclic carbenes.{{cite journal |author1=R. Jackstell |author2=A. Frisch |author3=M. Beller |author4=D. Rottger |author5=M. Malaun |author6=B. Bildstein | title = Efficient telomerization of 1,3-butadiene with alcohols in the presence of in situ generated palladium(0)carbene complexes | year = 2002 | journal = Journal of Molecular Catalysis A: Chemical | volume = 185 | issue = 1–2 | pages = 105–112 | doi = 10.1016/S1381-1169(02)00068-7}}{{cite journal |author1=H. V. Huynh |author2=J. H. H. Ho |author3=T. C. Neo |author4=L. L. Koh | title = Solvent-controlled selective synthesis of a trans-configured benzimidazoline-2-ylidene palladium(II) complex and investigations of its Heck-type catalytic activity | year = 2005 | journal = Journal of Organometallic Chemistry | volume = 690 | issue = 16 | pages = 3854–3860 | doi = 10.1016/j.jorganchem.2005.04.053}}

File:Benomyl.png 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.Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J Med Chem 2014, 57, 5845.> 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.{{Cite journal |last=Wang |first=C. C. |date=January 1984 |title=Parasite enzymes as potential targets for antiparasitic chemotherapy |url=https://pubmed.ncbi.nlm.nih.gov/6317859/ |journal=Journal of Medicinal Chemistry |volume=27 |issue=1 |pages=1–9 |doi=10.1021/jm00367a001 |issn=0022-2623 |pmid=6317859}}
• 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.
• 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|date=May 2020}}

Several dyes are derived from benzimidazoles.{{citation| doi = 10.1002/14356007.a16_487.pub2 | chapter = Methine Dyes and Pigments | title = Ullmann's Encyclopedia of Industrial Chemistry | date = 2008 | last1 = Berneth | first1 = Horst | isbn = 978-3-527-30385-4 }}

• Benzimidazoline
• Polybenzimidazole, a high performance fiber

{{Reflist}}

• {{cite book |author=Grimmett, M. R. |title=Imidazole and benzimidazole synthesis |publisher=Academic Press |location=Boston |year=1997 |isbn=0-12-303190-7 }}

{{Simple aromatic rings}}

{{Anthelmintics}}

{{Excavata antiparasitics}}

{{Antifungals}}

{{Chemical classes of psychoactive drugs}}

{{Authority control}}

Category:Aromatic bases

Category:Simple aromatic rings