Benzimidazole

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Benzimidazole
Benzimidazole 2D numbered.svg
Benzimidazole-3D-balls.png
Benzimidazole-3D-spacefill.png
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 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-081-4
3106
KEGG
PubChem CID
UNII
  • InChI=1S/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9) Yes check.svgY
    Key: HYZJCKYKOHLVJF-UHFFFAOYSA-N Yes check.svgY
  • 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:
GHS-pictogram-exclam.svg
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).
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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]

Contents

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 Benomyl.png
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.[ citation needed ]

Several dyes are derived from benzimidazoles. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Phenothiazine</span> Heterocyclic compound containing a ring of four carbon, one nitrogen and one sulfur atom

Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history.

<span class="mw-page-title-main">Cumene process</span> Industrial process

The cumene process is an industrial process for synthesizing phenol and acetone from benzene and propylene. The term stems from cumene, the intermediate material during the process. It was invented by R. Ūdris and P. Sergeyev in 1942 (USSR), and independently by Heinrich Hock in 1944.

Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.

In chemistry, halogenation is a chemical reaction which introduces of one or more halogens into a chemical compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs. This kind of conversion is in fact so common that a comprehensive overview is challenging. This article mainly deals with halogenation using elemental halogens. Halides are also commonly introduced using salts of the halides and halogen acids. Many specialized reagents exist for and introducing halogens into diverse substrates, e.g. thionyl chloride.

<span class="mw-page-title-main">Imidazole</span> Chemical compound

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-adjacent nitrogen atoms in meta-substitution.

Thiazole, or 1,3-thiazole, is a 5-membered heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS. The thiazole ring is notable as a component of the vitamin thiamine (B1).

<span class="mw-page-title-main">Catechol</span> Organic compound (C6H4(OH)2); benzene with two adjacent –OH groups

Catechol, also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula C6H4(OH)2. It is the ortho isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amounts. It was first discovered by destructive distillation of the plant extract catechin. About 20,000 tonnes of catechol are now synthetically produced annually as a commodity organic chemical, mainly as a precursor to pesticides, flavors, and fragrances. Small amounts of catechol occur in fruits and vegetables.

<span class="mw-page-title-main">Benzothiazole</span> Chemical compound

Benzothiazole is an aromatic heterocyclic compound with the chemical formula C
7
H
5
NS
. It is colorless, slightly viscous liquid. Although the parent compound, benzothiazole is not widely used, many of its derivatives are found in commercial products or in nature. Firefly luciferin can be considered a derivative of benzothiazole.

<span class="mw-page-title-main">Tiabendazole</span> Chemical compound

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Thiazolidine is a heterocyclic organic compound with the formula (CH2)3(NH)S. It is a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions. It is a sulfur analog of oxazolidine. Thiazolidine is a colorless liquid. Although the parent thiazolidine is only of academic interest, some derivatives, i.e., the thiazolidines, are important, such as the antibiotic penicillin.

<span class="mw-page-title-main">Benzoxazole</span> Chemical compound

Benzoxazole is an aromatic organic compound with a molecular formula C7H5NO, a benzene-fused oxazole ring structure, and an odor similar to pyridine. Although benzoxazole itself is of little practical value, many derivatives of benzoxazoles are commercially important.

<i>o</i>-Phenylenediamine Chemical compound

o-Phenylenediamine (OPD) is an organic compound with the formula C6H4(NH2)2. This aromatic diamine is an important precursor to many heterocyclic compounds. OPD is a white compound although samples appear darker owing to oxidation by air. It is isomeric with m-phenylenediamine and p-phenylenediamine.

<span class="mw-page-title-main">Xanthene</span> Chemical compound used to make dyes

Xanthene (9H-xanthene, 10H-9-oxaanthracene) is the organic compound with the formula CH2[C6H4]2O. It is a yellow solid that is soluble in common organic solvents. Xanthene itself is an obscure compound, but many of its derivatives are useful dyes.

<span class="mw-page-title-main">Imidazolidine</span> Chemical compound

Imidazolidine is a heterocyclic compound (CH2)2(NH)2CH2. The parent imidazolidine is lightly studied, but related compounds substituted on one or both nitrogen centers are more common. Generally, they are colorless, polar, basic compounds. Imidazolidines are cyclic 5-membered examples of the general class of aminals.

<span class="mw-page-title-main">Divinylbenzene</span> Organic compound, C₆H₄(CH=CH₂)₂

Divinylbenzene (DVB) is an organic compound with the chemical formula C6H4(CH=CH2)2 and structure H2C=CH−C6H4−HC=CH2. It is related to styrene by the addition of a second vinyl group. It is a colorless liquid manufactured by the thermal dehydrogenation of isomeric diethylbenzenes. Under synthesis conditions, o-divinylbenzene converts to naphthalene and thus is not a component of the usual mixtures of DVB.

<span class="mw-page-title-main">2,6-Xylidine</span> Chemical compound

2,6-Xylidine is an organic compound with the formula C6H3(CH3)2NH2. It is one of several isomeric xylidines. It is a colorless viscous liquid. Commercially significant derivatives are the anesthetics lidocaine, bupivacaine, mepivacaine, and etidocaine.

<span class="mw-page-title-main">2,4,6-Trimethylaniline</span> Chemical compound

2,4,6-Trimethylaniline is an organic compound with formula (CH3)3C6H2NH2. It is an aromatic amine that is of commercial interest as a precursor to dyes. It is prepared by selective nitration of mesitylene, avoiding oxidation of the methyl groups, followed by reduction of the resulting nitro group to the aniline.

<span class="mw-page-title-main">1-Methylimidazole</span> Chemical compound

1-Methylimidazole or N-methylimidazole is an aromatic heterocyclic organic compound with the formula CH3C3H3N2. It is a colourless liquid that is used as a specialty solvent, a base, and as a precursor to some ionic liquids. It is a fundamental nitrogen heterocycle and as such mimics for various nucleoside bases as well as histidine and histamine.

<span class="mw-page-title-main">5,6-Dimethylbenzimidazole</span> Chemical compound

5,6-Dimethylbenzimidazole is a natural benzimidazole derivative. It is a component of vitamin B12 where it serves as a ligand for the cobalt atom.

<span class="mw-page-title-main">Transition metal imidazole complex</span>

A transition metal imidazole complex is a coordination complex that has one or more imidazole ligands. Complexes of imidazole itself are of little practical importance. In contrast, imidazole derivatives, especially histidine, are pervasive ligands in biology where they bind metal cofactors.

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. Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. doi : 10.1002/14356007.a19_405
  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. 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