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

Chemical compound

Not to be confused with Benznidazole.

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 colorless solid.

## Contents

* 1 Preparation
* 2 Reactions
* 3 Applications
* 4 See also
* 5 References
* 6 Further reading

## Preparation[edit]

Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,[2] 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.[3]

## Reactions[edit]

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.[4]

N,N'-Dialkylbenzimidazolium salts are precursors to certain N-heterocyclic carbenes.[5][6]

## Applications[edit]

Benzimidazoles are often bioactive. Many anthelmintic drugs (albendazole, mebendazole, triclabendazole etc.) belong to the benzimidazole class of compounds. Benzimidazole fungicides are commercialized. They act by binding to the fungal microtubules and stopping hyphal growth. It also binds to the spindle microtubules and blocks nuclear division.

Benomyl (Benlate) is a fungicide with a benzimidazole core

The proton-pump inhibitors (antacids) omeprazole, lansoprazole, pantoprazole, rabeprazole, and tenatoprazole all contain a benzimidazole group. Other pharmaceutical drugs which contain a benzimidazole group include galeterone, mavatrep, and dovitinib, as well as the benzimidazole opioids such as etonitazene. Benzimidazole derivatives are among the top frequently used ring systems for small molecule drugs listed by the US FDA. [7]

In printed circuit board manufacturing, benzimidazole can be used as an organic solderability preservative.[citation needed]

Several dyes are derived from benzimidazoles.[8]

## See also[edit]

* Benzimidazoline
* Polybenzimidazole, a high performance fiber

## References[edit]

1. ^ Walba, H. & Isensee, R. W. Acidity constants of some arylimidazoles and their cations. J. Org. Chem. 26, 2789-2791 (1961).
2. ^ E. C. Wagner and W. H. Millett (1943). "Benzimidazole". Organic Syntheses.; Collective Volume, vol. 2, p. 65.
3. ^ Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a19_405
4. ^ H. A. Barker; R. D. Smyth; H. Weissbach; J. I. Toohey; J. N. Ladd & B. E. Volcani (February 1, 1960). "Isolation and Properties of Crystalline Cobamide Coenzymes Containing Benzimidazole or 5,6-Dimethylbenzimidazole". Journal of Biological Chemistry. 235 (2): 480–488. doi:10.1016/S0021-9258(18)69550-X. PMID 13796809.
5. ^ R. Jackstell; A. Frisch; M. Beller; D. Rottger; M. Malaun; B. Bildstein (2002). "Efficient telomerization of 1,3-butadiene with alcohols in the presence of in situ generated palladium(0)carbene complexes". Journal of Molecular Catalysis A: Chemical. 185 (1–2): 105–112. doi:10.1016/S1381-1169(02)00068-7.
6. ^ H. V. Huynh; J. H. H. Ho; T. C. Neo; L. L. Koh (2005). "Solvent-controlled selective synthesis of a trans-configured benzimidazoline-2-ylidene palladium(II) complex and investigations of its Heck-type catalytic activity". Journal of Organometallic Chemistry. 690 (16): 3854–3860. doi:10.1016/j.jorganchem.2005.04.053.
7. ^ Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J Med Chem 2014, 57, 5845.>
8. ^ Horst Berneth "Methine Dyes and Pigments" in Ullmann's Encyclopedia of Industrial Chemistry, 2008, Wiley-VCH, Weinheim. doi:10.1002/14356007.a16_487.pub2

## Further reading[edit]

* Grimmett, M. R. (1997). Imidazole and benzimidazole synthesis. Boston: Academic Press. ISBN 0-12-303190-7.

* v
* t
* e

Simple aromatic rings

1 ring|

| Three-membered|

* Borirene
* Cyclopropenone

|

Five-membered|

* Furan
* Pyrrole
* Imidazole
* Thiophene
* Phosphole
* Pyrazole
* Oxazole
* Isoxazole
* Thiazole
* Triazole
* Tetrazole
* Pentazole

Six-membered|

* Benzene
* Pyridine
* Pyrazine
* Pyrimidine
* Pyridazine
* Triazine
* Tetrazine
* Pentazine
* Hexazine

Seven-membered|

* Borepin
* Tropone

Nine-membered|

* Azonine

18-membered|

* Cyclooctadecanonaene

2 rings|

| Five + Five|

* Diazapentalene
* Thienothiophene
* Trithiapentalene

|

Five + Six|

* Benzofuran
* Isobenzofuran
* Indole
* Isoindole
* Benzothiophene
* Benzo(c)thiophene
* Benzophosphole
* Benzimidazole
* Purine
* Indazole
* Benzoxazole
* Benzisoxazole
* Benzothiazole
* 5-Aza-7-deazapurine

Six + Six|

* Naphthalene
* Quinoline
* Isoquinoline
* Quinoxaline
* Quinazoline
* Cinnoline
* Phthalazine

Five + Seven|

* Azulene

* v
* t
* e

Antiparasitics – Anthelmintics (P02) and endectocides (QP54)

Antiplatyhelmintic agents|

| Antitrematodals
(schistosomicides)|

| Binds tubulin|

* benzimidazole
* Triclabendazole#

|

AChE inhibitor|

* phosphonic acid
* Metrifonate‡

Other/unknown|

* quinoline
* Praziquantel#
* Oxamniquine#
* phenol
* Bithionol
* thiazole
* Niridazole
* thioxanthone
* Hycanthone
* Lucanthone
* antimony compounds
* Stibophen
* Tartar emetic‡

Anticestodals
(taeniacides)|

| Binds tubulin|

* benzimidazole
* Albendazole#

|

Other/unknown|

* quinoline
* Praziquantel#
* salicylanilide
* Niclosamide#
* aminoacridine
* Quinacrine
* butyrophenone
* Desaspidin
* chlorophenol
* Dichlorophen

Antinematodal agents
(including
macrofilaricides)|

| Binds tubulin|

* benzimidazole
* Mebendazole#
* Albendazole#
* Tiabendazole
* Fenbendazole
* Ciclobendazole
* Flubendazole

|

Glutamate-gated chloride channel, GABA receptor|

* avermectins
* Abamectin
* Doramectin
* Emamectin
* Eprinomectin
* Ivermectin#
* Selamectin
* milbemycins
* Moxidectin
* Milbemycin oxime

NMDA|

* tetrahydropyrimidine
* Pyrantel#
* pyrantel pamoate
* Oxantel
* Morantel
* Carbantel
* Febantel (aka felsantel)

Other/unknown|

* piperazine
* Piperazine
* Diethylcarbamazine#
* thiazole
* Levamisole#
* quinolinium
* Pyrvinium
* benzylammonium
* Bephenium
* naphthalenesulfonate
* Suramin#
* Ascaridole‡
* Hexylresorcinol
* Santonin‡
* Tribendimidine
* Tetrachloroethylene‡

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
* e

Antiparasitics directed at excavata parasites (P01)

Discicristata|

| Trypanosomiasis|

| African trypanosomiasis|

* ornithine (Eflornithine#)
* arsenical (Atoxyl, Melarsoprol#, Tryparsamide)
* benzamidine (Pentamidine#)
* naphthalenesulfonate (Suramin#)

* nitroimidazole (Fexinidazole†)

|

Chagas disease|

* nitroimidazole (Benznidazole#)
* nitrofuran (Nifurtimox#)

Leishmaniasis|

* polyene (Amphotericin B#)

Pentavalent antimonials (Meglumine antimoniate#, Sodium stibogluconate)

* benzamidine (Pentamidine#)
* phosphorylcholine (Miltefosine)
* neomycin (Paromomycin)

PAM|

* polyene (Amphotericin B)

Trichozoa|

| Giardiasis|

* nitroimidazole (Metronidazole#, Tinidazole)
* benzimidazole (Albendazole)

* thiazolide (Nitazoxanide)
* nitrofuran (Furazolidone)

* aminoacridine (Quinacrine)

|

Trichomoniasis|

* nitroimidazole (Carnidazole, Metronidazole#, Tinidazole)

Dientamoebiasis|

* nitroimidazole (Metronidazole
* Secnidazole)

* oxyquinoline (Iodoquinol)
* tetracycline (Doxycycline)
* neomycin  (Paromomycin)

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
* e

Antifungals (D01 and J02)

Wall/
membrane|

| Ergosterol
inhibitors|

| Azoles (lanosterol 14α-
demethylase inhibitors)|

| Imidazoles|

* Topical: bifonazole‡
* butoconazole
* chlormidazole‡
* climbazole
* clotrimazole#
* croconazole‡
* eberconazole
* econazole
* fenticonazole‡
* flutrimazole
* isoconazole
* ketoconazole
* luliconazole
* miconazole#
* neticonazole‡
* omoconazole‡
* oxiconazole
* sertaconazole
* sulconazole
* tioconazole

* Systemic: ketoconazole

|

Triazoles|

* Topical: efinaconazole
* fluconazole#
* terconazole

* Systemic: fluconazole#
* fosfluconazole
* fosravuconazole
* hexaconazole‡
* isavuconazole
* itraconazole#
* oteseconazole
* posaconazole
* voriconazole#

* Unknown: albaconazole‡
* ravuconazole†

Thiazoles|

* Topical: abafungin‡

Polyene antimycotics
(ergosterol binding)|

* Topical: hamycin‡
* natamycin
* nystatin#
Systemic: amphotericin B#, hamycin‡

Squalene monooxygenase
inhibitors|

| Allylamines|

* Topical: naftifine
* terbinafine
Systemic: terbinafine

|

Benzylamines|

* Topical: butenafine

Others|

* Topical: amorolfine

β-glucan synthase
inhibitors|

* Systemic: echinocandins (anidulafungin
* biafungin
* caspofungin
* cilofungin
* micafungin)
* ibrexafungerp

Intracellular|

| Pyrimidine analogues/
thymidylate synthase inhibitors|

* Systemic: flucytosine#

|

Mitotic inhibitors|

* Systemic: griseofulvin#

Aminoacyl tRNA synthetase inhibitors|

* Topical: tavaborole

Others|

* bromochlorosalicylanilide
* chlorophetanol
* chlorphenesin
* ciclopirox
* crystal violet
* dimazole
* ethylparaben
* haloprogin‡
* polynoxylin
* potassium iodide#
* salicylic acid
* selenium disulfide#
* sodium thiosulfate#
* sulbentine
* taurolidine
* ticlatone
* tolciclate
* tolnaftate
* tribromometacresol
* undecylenic acid
* Whitfield's ointment#

* citronella oil
* lemon grass
* lemon myrtle
* orange oil
* patchouli
* tea tree oil
* PCP: atovaquone
* dapsone
* pentamidine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

Authority control: National libraries |

* Latvia
* Japan

|

*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[H302]: H302: Harmful if swallowed
*[H315]: H315: Causes skin irritation
*[H319]: H319: Causes serious eye irritation
*[H335]: H335: May cause respiratory irritation
*[P261]: P261: Avoid breathing dust/fume/gas/mist/vapours/spray.
*[P264]: P264: Wash ... thoroughly after handling.
*[P270]: P270: Do not eat, drink or smoke when using this product.
*[P271]: P271: Use only outdoors or in a well-ventilated area.
*[P280]: P280: Wear protective gloves/protective clothing/eye protection/face protection.
*[P301+P312]: P301+P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell.
*[P302+P352]: P302+P352: IF ON SKIN: Wash with soap and water.
*[P304+P340]: P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
*[P305+P351+P338]: P305+P351+P338: IF IN EYES: Rinse continuously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
*[P312]: P312: Call a POISON CENTER or doctor/physician if you feel unwell.
*[P321]: P321: Specific treatment (see ... on this label).
*[P330]: P330: Rinse mouth.
*[P332+P313]: P332+P313: If skin irritation occurs: Get medical advice/attention.
*[P337+P313]: P337+P313: Get medical advice/attention.
*[P362]: P362: Take off contaminated clothing.
*[P403+P233]: P403+P233: Store in a well ventilated place. Keep container tightly closed.
*[P405]: P405: Store locked up.
*[P501]: P501: Dispose of contents/container to ...
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