Benzimidazole

Benzimidazole
Skeletal formula with numbering convention
Ball-and-stick model
Space-filling model
Names
Preferred IUPAC name
1H-1,3-Benzimidazole
Other names
1H-Benzo[d]imidazole
Identifiers
3D model (JSmol)
109682
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.075
EC Number
  • 200-081-4
3106
KEGG
UNII
  • InChI=1S/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9) checkY
    Key: HYZJCKYKOHLVJF-UHFFFAOYSA-N checkY
  • InChI=1/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9)
    Key: HYZJCKYKOHLVJF-UHFFFAOYAX
  • c1ccc2c(c1)[nH]cn2
Properties
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:
GHS07: Exclamation mark
Warning
H302, H315, H319, H335
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).
checkY verify (what is checkYX markN ?)
Infobox references

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]

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:

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

Certain benzimidazoles are used as precursors to synthesize benzimidazoliums by reducing the carbon-nitrogen double bond. These have been shown to act as hydride donors.[11]

Several dyes are derived from benzimidazoles.[12]

See also

References

  1. ↑ Walba, Harold; Isensee, Robert W. (1961). "Acidity Constants of Some Arylimidazoles and Their Cations". The Journal of Organic Chemistry. 26 (8): 2789–2791. doi:10.1021/jo01066a039.
  2. ↑ "Benzimidazole | CAMEO Chemicals | NOAA". cameochemicals.noaa.gov. Retrieved 2023-01-11.
  3. ↑ Bennet-Jenkins, E.; Bryant, C. (1996). "Novel sources of anthelmintics". International Journal for Parasitology. 26 (8–9): 937–947. doi:10.1016/s0020-7519(96)80068-3. ISSN 0020-7519. PMID 8923141.
  4. ↑ E. C. Wagner, W. H. Millett (1939). "Benzimidazole". Organic Syntheses. 19: 12. doi:10.15227/orgsyn.019.0012.
  5. ↑ Smiley, Robert A. (2000), "Phenylene- and Toluenediamines", Ullmann's Encyclopedia of Industrial Chemistry, doi:10.1002/14356007.a19_405, ISBN 978-3-527-30385-4
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J Med Chem 2014, 57, 5845.>
  10. 1 2 Wang, C. C. (January 1984). "Parasite enzymes as potential targets for antiparasitic chemotherapy". Journal of Medicinal Chemistry. 27 (1): 1–9. doi:10.1021/jm00367a001. ISSN 0022-2623. PMID 6317859.
  11. ↑ Lim, Chern-Hooi; Ilic, Stefan; Alherz, Abdulaziz; Worrell, Brady T.; Bacon, Samuel S.; Hynes, James T.; Glusac, Ksenija D.; Musgrave, Charles B. (2019-01-09). "Benzimidazoles as Metal-Free and Recyclable Hydrides for CO2 Reduction to Formate". Journal of the American Chemical Society. 141 (1): 272–280. doi:10.1021/jacs.8b09653. ISSN 0002-7863.
  12. ↑ Berneth, Horst (2008), "Methine Dyes and Pigments", Ullmann's Encyclopedia of Industrial Chemistry, doi:10.1002/14356007.a16_487.pub2, ISBN 978-3-527-30385-4

Further reading

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