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Revision as of 13:24, 9 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 17:04, 20 December 2024 edit undoSmokefoot (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers74,225 edits →Formation from other heterocycles: layout, content still needs work
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			{{Short description|Chemical compound}}
	{{chembox		{{chembox
	| Watchedfields = changed		| Watchedfields = changed
	| verifiedrevid = 409747725		| verifiedrevid = 443869434
	| Name = Imidazole		| Name = Imidazole
			| ImageFileL1 = Imidazole 2D full aromatic.svg
	| ImageFile = Imidazole_chemical_structure.png
			| ImageAltL1 = Full structural formula
	| ImageSize = 345px
			| ImageFileR1 = Imidazole 2D numbered.svg
	| ImageName = Chemical structure of imidazole
			| ImageAltR1 = Skeletal formula with numbers
	| IUPACName = 1''H''-Imidazole
			| ImageFileL2 = Imidazole-3D-balls.png
	| OtherNames = 1,3-diazole<br/>glyoxaline (archaic) <br/>1,3-diazacyclopenta-2,4-diene
			| ImageAltL2 = Ball-and-stick model
	| Section1 = {{Chembox Identifiers
			| ImageFileR2 = Imidazole-3D-spacefill.png
	| KEGG_Ref = {{keggcite|correct|kegg}}
			| ImageAltR2 = Space-filling model
	| KEGG = C01589
			| ImageFile3 = Sample of Imidazole.jpg
	| InChI = 1/C3H4N2/c1-2-5-3-4-1/h1-3H,(H,4,5)
			| PIN = 1''H''-Imidazole<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = ] | date = 2014 | location = Cambridge | page = 140 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4| chapter = Front Matter }}</ref>
	| PubChem = 795
			| SystematicName =
	| InChIKey = RAXXELZNTBOGNW-UHFFFAOYAS
			| OtherNames = 1,3-Diazole<br/>Glyoxaline (archaic)
			| Section1 = {{Chembox Identifiers
			| CASNo = 288-32-4
			| CASNo_Ref = {{cascite|correct|CAS}}
			| Beilstein = 103853
			| Gmelin = 1417
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 773
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 16069
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 540		| ChEMBL = 540
			| DrugBank = DB03366
			| EINECS = 206-019-2
			| KEGG_Ref = {{keggcite|correct|kegg}}
			| KEGG = C01589
			| InChI = 1/C3H4N2/c1-2-5-3-4-1/h1-3H,(H,4,5)
			| PubChem = 795
			| RTECS = NI3325000
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 7GBN705NH1
			| UNNumber = 3263
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C3H4N2/c1-2-5-3-4-1/h1-3H,(H,4,5)		| StdInChI = 1S/C3H4N2/c1-2-5-3-4-1/h1-3H,(H,4,5)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = RAXXELZNTBOGNW-UHFFFAOYSA-N		| StdInChIKey = RAXXELZNTBOGNW-UHFFFAOYSA-N
	| CASNo = 288-32-4
	| CASNo_Ref = {{cascite|correct|CAS}}
	| EINECS = 206-019-2
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 773
	| ChEBI = 16069
	| SMILES = c1cnc1		| SMILES = c1cnc1
			}}
	| RTECS = NI3325000
			| Section2 = {{Chembox Properties
	}}
			| Formula = C<sub>3</sub>H<sub>4</sub>N<sub>2</sub>
	| Section2 = {{Chembox Properties
			| MolarMass = 68.077 g/mol
	| Formula = C<sub>3</sub>H<sub>4</sub>N<sub>2</sub>
			| Appearance = White or pale yellow solid
	| MolarMass = 68.077 g/mol
	| Appearance = white or pale yellow solid		| Density = 1.23 g/cm<sup>3</sup>, solid
			| Solubility = 633 g/L
	| Density = 1.23 g/cm<sup>3</sup>, solid
			| LambdaMax = 206 nm
	| Solubility = miscible
	| MeltingPt = 89-91 °C (362-364 K)		| MeltingPtC = 89 to 91
			| MeltingPt_notes =
	| BoilingPt = 256 °C (529 K)
	| pKa= 14.5		| BoilingPtC = 256
			| BoilingPt_notes =
	| pKb= 6.993
			| pKa = 6.95 (for the ]) <ref>{{cite journal|last1=Walba|first1=H.|last2=Isensee|first2=R. W.|title=Acidity constants of some arylimidazoles and their cations|journal=J. Org. Chem.|volume=26|issue=8|pages=2789–2791|date=1961|doi=10.1021/jo01066a039}}</ref>
	}}
			}}
	| Section3 = {{Chembox Structure
			| Section3 = {{Chembox Structure
	| Coordination = planar 5-membered ring
			| Coordination = Planar 5-membered ring
	| CrystalStruct = ]
	| Dipole = 3.61]		| CrystalStruct = ]
			| Dipole = 3.61 ]
	}}
			}}
	| Section7 = {{Chembox Hazards
			| Section7 = {{Chembox Hazards
	| ExternalMSDS =
	| MainHazards = Corrosive		| MainHazards = Corrosive
	| FlashPt = 146 °C		| FlashPtC = 146
			| GHS_ref=<ref>{{cite web |title=Imidazole |url=https://pubchem.ncbi.nlm.nih.gov/compound/795#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |access-date=17 February 2024 |language=en |archive-date=10 May 2023 |archive-url=https://web.archive.org/web/20230510184350/https://pubchem.ncbi.nlm.nih.gov/compound/795#section=Safety-and-Hazards |url-status=live }}</ref>
	| RPhrases = {{R20}} {{R22}} {{R34}} {{R41}}
	| SPhrases = {{S26}} {{S36}} {{S37}} {{S39}} {{S45}}		| GHSPictograms = {{GHS05}}{{GHS07}}{{GHS08}}
	| RSPhrases =		| GHSSignalWord = Danger
			| HPhrases = {{H-phrases|302|314|360D}}
	}}
			| PPhrases = {{P-phrases|263|270|280|301+310|305+351+338|308+313}}<ref>{{cite web| publisher=Molekula Group| website=molekula.com| url=https://molekula.com/catalog/288-32-4/21611083-Imidazole| title=Imidazole| access-date=2018-10-19| archive-date=2018-10-19| archive-url=https://web.archive.org/web/20181019164240/https://molekula.com/catalog/288-32-4/21611083-Imidazole| url-status=live}}</ref>
			}}
	}}		}}
	'''Imidazole''' is an ] with the formula C<sub>3</sub>H<sub>4</sub>N<sub>2</sub>. This ] ] is a ] and is classified as an ]. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents. This ring system is present in important biological building blocks, such as ], and the related hormone ]. Imidazole can serve as a ] and as a weak ]. Many drugs contain an imidazole ring, such as ]s and ].<ref>]; Rees. ''Comprehensive Heterocyclic Chemistry.'' Vol. 5, p.469-498, ('''1984''').</ref><ref>Grimmett, M. Ross. ''Imidazole and Benzimidazole Synthesis.'' Academic Press, ('''1997''').</ref><ref>Brown, E.G. ''Ring Nitrogen and Key Biomolecules.'' Kluwer Academic Press, ('''1998''').</ref><ref>Pozharskii, A.F, et al. ''Heterocycles in Life and Society.'' John Wiley & Sons, ('''1997''').</ref><ref>Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2</ref>
			'''Imidazole''' (ImH) is an ] with the formula {{chem2|(CH)3(NH)N}}. It is a white or colourless solid that is soluble in water, producing a mildly ]ne solution. It can be classified as a ], specifically as a ].
	==Discovery==
	Imidazole was first synthesized in 1858, but various imidazole derivatives had been discovered as early as the 1840s. His synthesis, as shown below, used ] and ] in ] to form imidazole (or glyoxaline, as it was originally named).<ref>{{cite journal
	| title = Ueber die Einwirkung des Ammoniaks auf Glyoxal
	| author = Heinrich Debus
	| journal = ]
	| volume = 107
	| issue = 2
	| pages = 199&ndash;208
	| year = 1858
	| url =
	| doi = 10.1002/jlac.18581070209}}</ref> This synthesis, while producing relatively low yields, is still used for creating C-substituted imidazoles.
	:]
	In one ] modification, the reactants are ], ] and ] in ], forming 2,4,5-triphenylimidazole (Lophine).<ref>''Microwave-Mediated Synthesis of Lophine: Developing a Mechanism To Explain a Product'' Crouch, R. David; Howard, Jessica L.; Zile, Jennifer L.; Barker, Kathryn H. J. Chem. Educ. '''2006''' 83 1658</ref>
			Many natural products, especially ]s, contain the imidazole ring. These imidazoles share the 1,3-C<sub>3</sub>N<sub>2</sub> ring but feature varied substituents. This ring system is present in important biological building blocks, such as ] and the related hormone ]. Many drugs contain an imidazole ring, such as certain ]s, the ] series of ], and the sedative ].<ref>{{cite book|author-link=Alan R. Katritzky|last1=Karitzky|first1=A. R.|last2=Rees| first2=C.W.R.| last3=Scriven| first3=E.F.V.|title=Comprehensive Heterocyclic Chemistry|volume=5|pages=469–498|date=1984| isbn=978-0-08-042072-1}}</ref><ref>{{cite book|last=Grimmett|first=M. Ross|title=Imidazole and Benzimidazole Synthesis|publisher=Academic Press|date=1997|isbn=978-0-08-053445-9}}</ref><ref>{{cite book|last=Brown|first=E. G.|title=Ring Nitrogen and Key Biomolecules|publisher=Kluwer Academic Press|date=1998| isbn=978-94-011-4906-8}}</ref><ref>{{cite book|last=Pozharskii|first=A. F.|display-authors=etal|title=Heterocycles in Life and Society|publisher=John Wiley & Sons|date=1997| isbn=978-0-471-96033-1}}</ref><ref>{{cite book|title=Heterocyclic Chemistry|first=T. L.|last=Gilchrist|publisher=Bath Press|date=1985|isbn=978-0-582-01421-3}}</ref>
	==Structure and properties==
	Imidazole is a 5-membered planar ring, which is soluble in water and other ] solvents. It exists in two equivalent ]ic forms, 1''H''-imidazole and 3''H''-imidazole, because the ] ] can be located on either of the two ] atoms. Imidazole is a highly polar compound, as evidenced by a calculated dipole of 3.61], and is entirely soluble in water. The compound is classified as ] due to the presence of a sextet of ]s, consisting of a pair of electrons from the protonated nitrogen atom and one from each of the remaining four atoms of the ring.
			When fused to a ] ring, it forms a ], which is the most widely occurring nitrogen-containing ] in nature.<ref>{{cite journal |last= Rosemeyer |first= H. |year= 2004 |title= The Chemodiversity of Purine as a Constituent of Natural Products |journal= Chemistry & Biodiversity |volume= 1 |issue= 3 |pages= 361–401 |doi= 10.1002/cbdv.200490033|pmid= 17191854 |s2cid= 12416667 }}</ref>
	Some ] structures of imidazole are shown below:
	<center>]</center>
			The name "imidazole" was coined in 1887 by the German chemist ] (1857–1935).<ref>Hantzsch, A. and Weber, J. H. (1887) {{Webarchive|url=https://web.archive.org/web/20200530234013/https://babel.hathitrust.org/cgi/pt?id=hvd.cl1hzr&view=1up&seq=872 |date=2020-05-30 }} (On compounds of thiazole (pyridines of the thiophene series), ''Berichte der deutschen chemischen Gesellschaft'', '''20''' : 3118–3132, see p. 3119. See also: Hantzsch, A. (1888) {{Webarchive|url=https://web.archive.org/web/20200530234010/https://babel.hathitrust.org/cgi/pt?id=uiug.30112025844876&view=1up&seq=13 |date=2020-05-30 }} (General observations about azoles), ''Annalen der Chemie'', '''249''' : 1–6. Hantzsch proposed a reform of the nomenclature of azole compounds, including a proposal to call the heterocyclic ring C<sub>3</sub>H<sub>3</sub>(NH)N "imidazole"; see pp. 2 and 4.</ref>
	===Amphotericity===
	Imidazole is ]. That is, it can function as both an acid and as a base. As an acid, the p''K''<sub>a</sub> of imidazole is 14.5, making it less acidic than carboxylic acids, phenols, and imides, but slightly more acidic than alcohols. The acidic proton is located on N-1. As a base, the p''K''<sub>a</sub> of the conjugate acid (cited above as p''K''<sub>BH<sup>+</sup></sub> to avoid confusion between the two) is approximately 7, making imidazole approximately sixty times more basic than ]. The basic site is N-3.
			==Structure and properties==
	==Preparation==
			Imidazole is a planar 5-membered ring, that exists in two equivalent ]ic forms because hydrogen can be bound to one or another ] atom. Imidazole is a highly polar compound, as evidenced by its ] of 3.67&nbsp;],<ref>{{cite journal|last1=Christen|first1=Dines|last2=Griffiths|first2=John H.|last3=Sheridan|first3=John|date=1981|title=The Microwave Spectrum of Imidazole; Complete Structure and the Electron Distribution from Nuclear Quadrupole Coupling Tensors and Dipole Moment Orientation|journal=Zeitschrift für Naturforschung A|volume=36|issue=12|pages=1378–1385|doi=10.1515/zna-1981-1220|bibcode=1981ZNatA..36.1378C|s2cid=3522351|doi-access=free}}</ref> and is highly soluble in water. The compound is classified as ] due to the presence of a planar ring containing 6 ]s (a pair of electrons from the protonated nitrogen atom and one from each of the remaining four atoms of the ring). Some ] structures of imidazole are shown below:
	]
			:]
	Imidazole can be synthesized by numerous methods besides the Debus method. Many of these syntheses can also be applied to different substituted imidazoles and imidazole derivatives simply by varying the ] on the reactants. In literature, these methods are commonly categorized by which and how many bonds form to make the imidazole rings. For example, the Debus method forms the (1,2), (3,4), and (1,5) bonds in imidazole, using each reactant as a fragment of the ring, and thus this method would be a three-bond-forming synthesis. A small sampling of these methods is presented below.
			<!--crystal structure?-->
			===Amphoterism===
	;Formation of one bond
			Imidazole is ], which is to say that it can function both as an acid and as a base. As an acid, the ] of imidazole is 14.5, making it less acidic than carboxylic acids, phenols, and imides, but slightly more acidic than alcohols. The acidic proton is the one bound to nitrogen. Deprotonation gives the imidazolide anion, which is symmetrical. As a base, the p''K''<sub>a</sub> of the conjugate acid (cited as p''K''<sub>BH<sup>+</sup></sub> to avoid confusion between the two) is approximately 7, making imidazole approximately sixty times more basic than ]. The basic site is the nitrogen with the lone pair (and not bound to hydrogen). Protonation gives the imidazolium cation, which is symmetrical.
	The (1,5) or (3,4) bond can be formed by the reaction of an ] and an α-aminoaldehyde or α-aminoacetal, resulting in the cyclization of an ] to imidazole. The example below applies to imidazole when R=R<sub>1</sub>=Hydrogen.
			==Preparation==
	:]
			Imidazole was first reported in 1858 by the German chemist ], although various imidazole derivatives had been discovered as early as the 1840s. It was shown that ], ], and ] condense to form imidazole (glyoxaline, as it was originally named).<ref>{{cite journal |title= Ueber die Einwirkung des Ammoniaks auf Glyoxal |trans-title= On the reaction of ammonia upon glyoxal |first= Heinrich |last= Debus |journal= ] |volume= 107 |issue= 2 |pages= 199–208 |year= 1858 |url= https://babel.hathitrust.org/cgi/pt?id=njp.32101044011045;view=1up;seq=211 |doi= 10.1002/jlac.18581070209 |access-date= 2016-10-01 |archive-date= 2020-05-30 |archive-url= https://web.archive.org/web/20200530234014/https://babel.hathitrust.org/cgi/pt?id=njp.32101044011045&view=1up&seq=211 |url-status= live }} From p. 205: ''"Die gereinigte Substanz stellt das oxalsaure Salz einer Basis dar, die ich mit Glyoxalin bezeichenen werde."'' (The purified substance constitutes the oxalic salt of a base, which I will designate as "glyoxaline".)</ref> This synthesis, while producing relatively low yields, is still used for generating ''C''-substituted imidazoles.
			:]
			In one ] modification, the reactants are ], ] and ] in ], forming 2,4,5-triphenylimidazole ("]").<ref>{{cite journal|title=Microwave-Mediated Synthesis of Lophine: Developing a Mechanism To Explain a Product|last1=Crouch|first1=R. David|last2=Howard|first2=Jessica L.|last3=Zile|first3=Jennifer L.|last4=Barker|first4=Kathryn H.|journal=J. Chem. Educ.|date=2006|volume=83|issue=11|page=1658|doi=10.1021/ed083p1658|bibcode=2006JChEd..83.1658C}}</ref>
			Imidazole can be synthesized by numerous methods besides the ]. Many of these syntheses can also be applied to different substituted imidazoles and imidazole derivatives by varying the ] on the reactants. These methods are commonly categorized by which and how many bonds form to make the imidazole rings. For example, the Debus method forms the (1,2), (3,4), and (1,5) bonds in imidazole, using each reactant as a fragment of the ring, and thus this method would be a three-bond-forming synthesis. A small sampling of these methods is presented below.
	;Formation of two bonds
	The (1,2) and (2,3) bonds can be formed by treating a 1,2-diaminoalkane, at high temperatures, with an ], ], or ]. A dehydrogenating catalyst, such as ] on ], is required.
	:]		===Formation of one bond===
	The (1,2) and (3,4) bonds can also be formed from N-substituted α-aminoketones and ] with heat. The product will be a 1,4-disubstituted imidazole, but here since R=R<sub>1</sub>=Hydrogen, imidazole itself is the product. The yield of this reaction is moderate, but it seems to be the most effective method of making the 1,4 substitution.		The (1,5) or (3,4) bond can be formed by the reaction of an ] and an α-amino] or α-amino]. The example below applies to imidazole when R<sub>1</sub> = R<sub>2</sub> = hydrogen.]
			:
	:]		===Formation of two bonds===
			The (1,2) and (2,3) bonds can be formed by treating a 1,2-diamino], at high temperatures, with an ], ], or ]. A dehydrogenating catalyst, such as ] on ], is required.
			:]
			The (1,2) and (3,4) bonds can also be formed from ''N''-substituted α-aminoketones and ] with heat. The product will be a 1,4-disubstituted imidazole, but here since R<sub>1</sub> = R<sub>2</sub> = hydrogen, imidazole itself is the product. The yield of this reaction is moderate, but it seems to be the most effective method of making the 1,4 substitution.
			::]
	;Formation of four bonds		===Formation of four bonds===
	This is a general method that is able to give good yields for substituted imidazoles. In essence, it is an adaptation of the Debus method called the ]. The starting materials are substituted glyoxal, aldehyde, amine, and ammonia or an ammonium salt.<ref>{{US patent reference|number=6,177,575|y=2001|m=01|d=23|inventor=]|title=Process for Manufacture of Imidazoles}}		This is a general method that is able to give good yields for substituted imidazoles. In essence, it is an adaptation of the Debus method called the ]. The starting materials are substituted glyoxal, aldehyde, amine, and ammonia or an ammonium salt.<ref>{{US patent reference|number=6,177,575|y=2001|m=01|d=23|inventor=]|title=Process for Manufacture of Imidazoles}}</ref>
			:]
	</ref>
			===Formation from other heterocycles===
	:]
			Imidazole can be synthesized by the ] of ]. This reaction will give substantial yields only if the 1-vinyltetrazole is made efficiently from an ], such as 2-tributylstannyltetrazole. The reaction, shown below, produces imidazole when R<sub>1</sub> = R<sub>2</sub> = R<sub>3</sub> = hydrogen.
			:]
			Imidazole can also be formed in a vapor-phase reaction. The reaction occurs with ], ], and hydrogen over ] on ], and it must take place between 340 and 480&nbsp;°C. This forms a very pure imidazole product.
			The ] can also be employed to form imidazoles starting from ] and an ].<ref>{{cite journal|last1=Van Leusen|first1=Albert M.|last2=Wildeman|first2=Jurjen|last3=Oldenziel|first3=Otto H.|date=1977|title=Chemistry of sulfonylmethyl isocyanides. 12. Base-induced cycloaddition of sulfonylmethyl isocyanides to carbon, nitrogen double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides|journal=Journal of Organic Chemistry|volume=42|issue=7|pages=1153–1159|doi=10.1021/jo00427a012|bibcode=1977JOrgC..42.1153A}}</ref>The Van Leusen Imidazole Synthesis allows the preparation of imidazoles from aldimines by reaction with tosylmethyl isocyanide (TosMIC). The reaction has later been expanded to a two-step synthesis in which the aldimine is generated in situ: the Van Leusen Three-Component Reaction (vL-3CR).
	;Formation from other heterocycles
	Imidazole can be synthesized by the ] of ]. This reaction will give substantial yields only if the 1-vinyltetrazole is made efficiently from an ], such as 2-tributylstannyltetrazole. The reaction, shown below, produces imidazole when R=R<sub>1</sub>=R<sub>2</sub>=Hydrogen.
	]
	Imidazole can also be formed in a vapor-phase reaction. The reaction occurs with ], ], and hydrogen over ], and it must take place between 340 and 480°C. This forms a very pure imidazole product.
	==Biological significance and applications==		==Biological significance and applications==
	Imidazole is incorporated into many important biological molecules. The most pervasive is the ] ], which has an imidazole ]. Histidine is present in many ] and ] and plays a vital part in the structure and binding functions of ]. Histidine can be ] to ], which is also a common biological compound. It is a component of the ] that causes ], which is another name for ] hives. The relationship between histidine and histamine are shown below:		Imidazole is incorporated into many important biological compounds. The most pervasive is the ] ], which has an imidazole ]. Histidine is present in many ] and ], e.g. by binding metal cofactors, as seen in ].
			Imidazole-based histidine compounds play a important role in intracellular buffering.<ref>{{cite book|last1=Hochachka|first1=P. W.|first2=G. N.|last2=Somero|date=2002|title=Biochemical Adaptation: Mechanisms and Process in Physiological Evolution|location=New York|publisher=Oxford University Press}}</ref> Histidine can be ] to ]. Histamine can cause ] (hives) when it is produced during ] reaction.
	<center>]</center>
			===Pharmaceutical derivatives===
	One of the applications of imidazole is in the purification of ]ged ]s in ](IMAC). Imidazole is used to elute tagged proteins bound to ] ]s attached to the surface of beads in the chromatography column. An excess of imidazole is passed through the column, which displaces the His-tag from nickel co-ordination, freeing the His-tagged proteins.
			Imidazole substituents are found in many pharmaceuticals such as anticancer drug ]. The imidazole group is present in many ]s and ], ], and ] medications. Imidazole is part of the ] molecule, found in tea leaves and coffee beans, that stimulates the ]. It is present in the
			A number of substituted imidazoles, including ], are selective inhibitors of ].<ref>{{cite journal|last1=Castaño|first1=T.|last2=Encinas|first2=A.|last3=Pérez|first3=C.|last4=Castro|first4=A.|last5=Campillo|first5=N. E.|last6=Gil|first6=C.|date=2008|title=Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase|journal=Bioorg. Med. Chem.|volume=16|issue=11|pages=6193–6206|pmid=18477512|doi=10.1016/j.bmc.2008.04.036|url=https://digital.csic.es/bitstream/10261/87090/1/accesoRestringido.pdf|type=Submitted manuscript|hdl=10261/87090|access-date=2018-07-24|archive-date=2023-03-06|archive-url=https://web.archive.org/web/20230306094210/https://digital.csic.es/bitstream/10261/87090/1/accesoRestringido.pdf|url-status=live}}</ref><ref>{{cite journal|last1=Bogle|first1=R. G.|last2=Whitley|first2=G. S.|last3=Soo|first3=S. C.|last4=Johnstone|first4=A. P.|last5=Vallance|first5=P.|date=1994|title=Effect of anti-fungal imidazoles on mRNA levels and enzyme activity of inducible nitric oxide synthase|journal=Br. J. Pharmacol.|volume=111|issue=4 |pages=1257–1261|pmc=1910171|pmid=7518297|doi=10.1111/j.1476-5381.1994.tb14881.x}}</ref> Other biological activities of the imidazole ] relate to the downregulation of intracellular ] and ] fluxes, and interference with translation initiation.<ref>{{cite journal|last1=Khalid|first1=M. H.|last2=Tokunaga|first2=Y.|last3=Caputy|first3=A. J.|last4=Walters|first4=E.|date=2005|title=Inhibition of tumor growth and prolonged survival of rats with intracranial gliomas following administration of clotrimazole|journal=J. Neurosurg.|volume=103|issue=1 |pages=79–86|pmid=16121977|doi=10.3171/jns.2005.103.1.0079}}</ref>
	Imidazole has become an important part of many pharmaceuticals. Synthetic imidazoles are present in many ]s and ], ], and ] medications. Imidazole is part of the ] molecule, found in tea leaves and coffee beans, that stimulates the ]. It is present in the anticancer medication ], which combats ] by interfering with ] activities.
			The substituted imidazole derivatives are valuable in treatment of many systemic ] ].<ref>{{cite book |title= Comprehensive Pharmacy Review |author= Leon Shargel |year= 2007 |edition= 6th |pages= 930|publisher= Lippincott Williams & Wilkins | isbn=9780781765619}}</ref> Imidazoles belong to the class of ], which includes ], ], and ].
	===Pharmaceutical derivatives===
	The substituted imidazole derivatives are valuable in treatment of many systemic ] ].<ref>Comprehensive Pharmacy Review, Leon Shargel, 6th edition, p930.</ref> Imidazoles belong to the class of ], which includes ], ], and ].
	For comparison, another group of azoles is the triazoles, which includes ], ], and ] . The difference between the imidazoles and the triazoles involves the mechanism of inhibition of the ]. The N3 of the imidazole compound binds to the heme iron atom of ferric cytochrome P450, whereas the N4 of the triazoles bind to the heme group. The triazoles have been shown to have a higher specificity for the cytochrome P450 than imidazoles, thereby making them more potent than the imidazoles.<ref>Veterinary Pharmacology and Therapeutics, Riviere and Papich, 9th ed. p1019-1020.</ref>		For comparison, another group of azoles is the triazoles, which includes ], ], and ]. The difference between the imidazoles and the triazoles involves the mechanism of inhibition of the ]. The N3 of the imidazole compound binds to the heme iron atom of ferric cytochrome P450, whereas the N4 of the triazoles bind to the heme group. The triazoles have been shown to have a higher specificity for the cytochrome P450 than imidazoles, thereby making them more potent than the imidazoles.<ref>{{cite book |title= Veterinary Pharmacology and Therapeutics |edition= 9th |pages= 1019–1020 |last1= Davis |first1= Jennifer L. |last2= Papich |first2= Mark G. |last3= Heit |first3= Mark C. |year= 2009 |chapter= Chapter 39: Antifungal and Antiviral Drugs |editor1-last= Riviere |editor1-first= Jim E. |editor2-last= Papich |editor2-first= Mark G. |chapter-url= https://books.google.com/books?id=ievLulSqwBAC |publisher= Wiley-Blackwell |isbn= 978-0-8138-2061-3 }}</ref>
			Some imidazole derivatives show effects on insects, for example ] exhibits a strong anti-feeding effect on the ]-digesting Australian carpet beetle larvae '']'', as does ] with the common clothes moth '']''.<ref>{{cite journal|last1=Sunderland|first1=M. R.|last2=Cruickshank|first2=R. H.|last3=Leighs|first3=S. J.|date=2014|title=The efficacy of antifungal azole and antiprotozoal compounds in protection of wool from keratin-digesting insect larvae|journal=Textile Res. J.|volume=84|issue=9|pages=924–931|doi=10.1177/0040517513515312|s2cid=135799368}}</ref>
	==Industrial applications==		==Industrial applications==
			Imidazole itself has few direct applications. It is instead a precursor to a variety of agrichemicals, including ], ], ], ], and ].<ref name=Ebel>{{Ullmann|author=Ebel, K., Koehler, H., Gamer, A. O., & Jäckh, R.|title=Imidazole and Derivatives|year=2002|doi=10.1002/14356007.a13_661}}</ref>
	Imidazole has been used extensively as a corrosion inhibitor on certain transition metals, such as copper. Preventing copper corrosion is important, especially in aqueous systems, where the conductivity of the copper decreases due to corrosion.
			] is one of several imidazole-derived ]s.]]
			==Coordination chemistry==
			{{main|Transition metal imidazole complex}}
			Imidazole and its derivatives have high affinity for metal cations. One of the applications of imidazole is in the purification of ]ged ]s in ] (IMAC). Imidazole is used to elute tagged proteins bound to ] ]s attached to the surface of beads in the ] column. An excess of imidazole is passed through the column, which displaces the His-tag from nickel coordination, freeing the His-tagged proteins.
			==Use in biological research==
			Imidazole is a suitable buffer for pH 6.2 to 7.8,.<ref name="Dawson 1986 p. ">{{cite book | last=Dawson | first=R. M. C. | title=Data for biochemical research | publisher=Clarendon Press | publication-place=Oxford | year=1986 | isbn=978-0-19-855299-4 | oclc=11865673 | page=325}}</ref> Pure imidazole has essentially no absorbance at protein relevant wavelengths (280&nbsp;nm),<ref>{{cite web |title=1H-Imidazole |url=https://webbook.nist.gov/cgi/cbook.cgi?ID=C288324&Mask=400 |access-date=13 May 2021 |archive-date=25 April 2021 |archive-url=https://web.archive.org/web/20210425154408/https://webbook.nist.gov/cgi/cbook.cgi?ID=C288324&Mask=400 |url-status=live }}</ref><ref>{{cite web |title=Optimizing Purification of Histidine-Tagged Proteins |url=https://www.sigmaaldrich.com/technical-documents/protocols/biology/affinity-chromatography-tagged-proteins/optimizing-purification-of-histidine-tagged-proteins.html |access-date=13 May 2021 |archive-date=13 May 2021 |archive-url=https://web.archive.org/web/20210513212432/https://www.sigmaaldrich.com/technical-documents/protocols/biology/affinity-chromatography-tagged-proteins/optimizing-purification-of-histidine-tagged-proteins.html |url-status=live }}</ref> however lower purities of imidazole can give notable absorbance at 280&nbsp;nm. Imidazole can interfere with the ].<ref name="Molina Rueda Bosque-Sendra Megias 1996 pp. 273–280">{{cite journal | last1=Molina | first1=F | last2=Rueda | first2=A | last3=Bosque-Sendra | first3=J.M | last4=Megias | first4=L | title=Determination of proteins in the presence of imidazole buffers | journal=Journal of Pharmaceutical and Biomedical Analysis | publisher=Elsevier BV | volume=14 | issue=3 | year=1996 | issn=0731-7085 | doi=10.1016/0731-7085(95)01615-5 | pages=273–280| pmid=8851751 }}</ref>
			Imidazole is often used in protein purification, where recombinant proteins with polyhistidine tags are immobilized onto nickel resins and eluted with a high imidazole concentration.
	Many compounds of industrial and technological importance contain imidazole derivatives. The thermostable polybenzimidazole PBI contains imidazole fused to a ] ring and linked to a benzene, and acts as a fire retardant. Imidazole can also be found in various compounds that are used for photography and electronics.
	==Salts of imidazole==		==Salts of imidazole==
	]		]
	Salts of imidazole where the imidazole ring is in the ] are known as imidazolium salts (for example, imidazolium chloride). These salts are formed from the ] or substitution at ] of imidazole. These salts have been used as ] and precursors to ]s. Salts where a deprotonated imidazole is an ] are also possible; these salts are known as '''imidazolide salts''' (for example, sodium imidazolide).		Salts of imidazole where the imidazole ring is the ] are known as imidazolium salts (for example, imidazolium ] or ]).<ref>{{Cite journal|last1=Zolfigol|first1=Mohammad A.|last2=Khazaei|first2=Ardeshir|last3=Moosavi-Zare|first3=Ahmad R.|last4=Zare|first4=Abdolkarim|last5=Kruger|first5=Hendrik G.|last6=Asgari|first6=Zhila|last7=Khakyzadeh|first7=Vahid|last8=Kazem-Rostami|first8=Masoud|date=2012-04-06|title=Design of Ionic Liquid 3-Methyl-1-sulfonic Acid Imidazolium Nitrate as Reagent for the Nitration of Aromatic Compounds by in Situ Generation of NO2 in Acidic Media|journal=The Journal of Organic Chemistry|volume=77|issue=7|pages=3640–3645|doi=10.1021/jo300137w|pmid=22409592|issn=0022-3263}}</ref> These salts are formed from the ] or substitution at ] of imidazole. These salts have been used as ] and precursors to ]s. Salts where a deprotonated imidazole is an ] are also well known; these salts are known as ]s (for example, sodium imidazolate, NaC<sub>3</sub>H<sub>3</sub>N<sub>2</sub>).
	==Related heterocycles==		==Related heterocycles==
	* ], an analog with a fused ] ring		* ], an analog with a fused ] ring
	* ] or benzimidazoline, an analog where 4,5-] is saturated		* ] or imidazoline, an analog where the 4,5-] is saturated
	* ], an analog with only one ] ] in position 1		* ], an analog with only one ] ] in position 1
	* ], an analog with the nitrogen atom in position 1 replaced by ]		* ], an analog with the nitrogen atom in position 1 replaced by ]
Line 140:		Line 157:
	* ], an analog with two adjacent ] atoms		* ], an analog with two adjacent ] atoms
	* ]s, analogs with three nitrogen atoms		* ]s, analogs with three nitrogen atoms
			==Safety==
			Imidazole has low acute toxicity as indicated by the {{LD50}} of 970&nbsp;mg/kg (Rat, oral).<ref name=Ebel/>
			==See also==
			* ]
			* ]
			* ] (dihydroimidazole)
	==References==		==References==
	{{reflist}}		{{reflist|30em}}
	{{Antifungals}}		{{Antifungals}}
			{{Authority control}}
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