Imidazole
IUPAC name	1,3-diazole
Other names	Imidazole 1,3-diazacyclopenta-2,4-diene
Identifiers
CAS number	288-32-4
RTECS number	N13325 1985-86
Properties
Molecular formula	C3H4N2
Molar mass	68.08 g/mol
Appearance	white or pale yellow solid
Density	1.23 g/cm3, solid
Melting point	89-91 °C (362-364 K) Image File history File links Imidazole_chemical_structure. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... RTECS, also known as Registry of Toxic Effects of Chemical Substances, is a database of toxicity information compiled from the open scientific literature that is available for charge. ... A chemical formula is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... Molar mass is the mass of one mole of a chemical element or chemical compound. ... For other uses, see Density (disambiguation). ... The melting point of a crystalline solid is the temperature range at which it changes state from solid to liquid. ...
Boiling point	256 °C (529 K) Italic text This article is about the boiling point of liquids. ...
Solubility in water	miscible
Acidity (pKa)	pKa=6.993
Structure
Crystal structure	monoclinic
Coordination geometry	planar 5-membered ring
Dipole moment	12.8 Cm*1030
Hazards
MSDS	External MSDS
Main hazards	Corrosive
Flash point	146 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Imidazole is a heterocyclic aromatic organic compound. It is further classified as an alkaloid. Imidazole refers to the parent compound C₃H₄N₂, 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 histidine, and the related hormone histamine. Imidazole can act as a base and as a weak acid. Imidazole exists in two tautomeric forms with the hydrogen atom moving between the two nitrogens. Many drugs contain an imidazole ring, such as antifungal drugs and nitroimidazole.^{[1][2][3][4][5]} Solubility is a chemical property referring to the ability for a given substance, the solute, to dissolve in a solvent. ... Impact from a water drop causes an upward rebound jet surrounded by circular capillary waves. ... The acid dissociation constant (Ka), also known as the acidity constant or the acid-ionization constant, is a specific equilibrium constant for the reaction of an acid with its conjugate base in aqueous solution [1]. // When an acid dissolves in water, it partly dissociates forming hydronium ions and its conjugate... Enargite crystals In mineralogy and crystallography, a crystal structure is a unique arrangement of atoms in a crystal. ... In crystallography, the monoclinic crystal system is one of the 7 lattice point groups. ... The coordination geometry of an atom is the geometrical pattern formed by its neighbors in a molecule or a crystal. ... The Earths magnetic field, which is approximately a dipole. ... This page meets Wikipedias criteria for speedy deletion. ... The examples and perspective in this article or section may not represent a worldwide view. ... For other uses, see Flash point (disambiguation). ... The plimsoll symbol as used in shipping In chemistry, the standard state of a material is its state at 1 bar (100 kilopascals exactly). ... Heterocyclic compounds are substances which contain a ring structure as found in benzene and the aromatic compounds, or aromatic hydrocarbons, but in which other atoms than carbon, such as sulfur, oxygen or nitrogen are found as part of the ring. ... In chemistry, an aromatic molecule is one in which electrons are free to cycle around circular arrangements of atoms, which are alternately singly and doubly bonded to one another. ... Benzene is the simplest of the arenes, a family of organic compounds An organic compound is any member of a large class of chemical compounds whose molecules contain carbon. ... Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is, strictly speaking, a naturally occurring amine produced by a plant,[1] but amines produced by animals and fungi are also called alkaloids. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... This article or section does not cite any references or sources. ... Acids and bases: Acid-base extraction Acid-base reaction Acid dissociation constant Acidity function Buffer solutions pH Proton affinity Self-ionization of water Acids: Lewis acids Mineral acids Organic acids Strong acids Superacids Weak acids Bases: Lewis bases Organic bases Strong bases Superbases Non-nucleophilic bases Weak bases edit In... For other uses, see Acid (disambiguation). ... Tautomers are organic compounds that are interconvertible by a chemical reaction called tautomerization. ... This article is about the chemistry of hydrogen. ... Properties For other meanings of Atom, see Atom (disambiguation). ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... An antifungal drug is medication used to treat fungal infections such as athletes foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. ... Nitroimidazoles are imidazole heterocycles with a nitro group that have been used to combat anaerobic bacterial and parasitic infections. ...

Discovery

Imidazole was first synthesized by H. Debus in 1858, but various imidazole derivatives had been discovered as early as the 1840s. His synthesis, as shown below, used glyoxal and formaldehyde in ammonia to form imidazole. This synthesis, while producing relatively low yields, is still used for creating C-substituted imidazoles. Glyoxal is an organic compound with the formula OCHCHO. This yellow-coloured liquid is the smallest dialdehyde. ... R-phrases , , , S-phrases , , , , , Flash point -53 °C Related Compounds Related aldehydes acetaldehyde benzaldehyde Related compounds ketones carboxylic acids Except where noted otherwise, data are given for materials in their standard state (at 25 Â°C, 100 kPa) Infobox disclaimer and references Formaldehyde (methanal) is the chemical compound with the formula... For other uses, see Ammonia (disambiguation). ...

In one microwave modification the reactants are benzil, formaldehyde and ammonia in glacial acetic acid forming 2,4,5-triphenylimidazole (Lophine).^[6] Image File history File links Debusmethod. ... Microwave chemistry is the science of applying microwave irradiation to chemical reactions . Microwaves act as high frequency electric fields and will generally heat anything with a mobile electric charge. ... Category: ... R-phrases , , , S-phrases , , , , , Flash point -53 °C Related Compounds Related aldehydes acetaldehyde benzaldehyde Related compounds ketones carboxylic acids Except where noted otherwise, data are given for materials in their standard state (at 25 Â°C, 100 kPa) Infobox disclaimer and references Formaldehyde (methanal) is the chemical compound with the formula... For other uses, see Ammonia (disambiguation). ... The chemical compound acetic acid (from the Latin word acetum, meaning vinegar), systematically called ethanoic acid, is the acid that gives vinegar its sour taste. ...

Preparation

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 functional groups 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. In ecology functional groups are collections of organisms based on morphological, physiological, behavioral, biochemical, or environmental responses or on trophic criteria. ...

Formation of One Bond

The (1,5) or (3,4) bond can be formed by the reaction of an immediate and an α-aminoaldehyde or α-aminoacetal, resulting in the cyclization of an amidine to imidazole. The example below applies to imidazole when R=R₁=Hydrogen. An amidine is a functional group or type of chemical compound that has two amine groups attached to the same carbon atom with one carbon-nitrogen double bond,exactly its derivate of acid,when suspended the double bond is protonized: HN=CR-NH2. ...

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 alcohol, aldehyde, or carboxylic acid. A dehydrogenating agent, such as platinum with alumina, must be present in the reaction for the imidazole to form. The example below applies to imidazole when R=Hydrogen. Image File history File links Onebondmethod. ... This article does not cite any references or sources. ... An aldehyde. ... Structure of a carboxylic acid The 3D structure of the carboxyl group A space-filling model of the carboxyl group Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted... General Name, Symbol, Number platinum, Pt, 78 Chemical series transition metals Group, Period, Block 10, 6, d Appearance grayish white Standard atomic weight 195. ... Aluminium oxide (or aluminum oxide) (Al2O3) is a chemical compound of aluminium and oxygen. ...

The (1,2) and (3,4) bonds can also be formed from N-substituted α-aminoketones and formamide and heat. The product will be a 1,4-disubstituted imidazole, but here since R=R₁=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. Image File history File links Twobondmethod. ... Formamide, also known as Methanamide (IUPAC) and Carbamaldehyde, formula HCONH2 is an amide derived from formic acid. ...

Formation of Four Bonds

This is a general method which is able to give good yields for substituted imidazoles. The starting materials are substituted glyoxal, aldehyde, amine, and ammonia or an ammonium salt.^[7] Image File history File links 1,2--3,4-formation. ...

Formation from other Heterocycles

Imidazole can be synthesized by the photolysis of 1-vinyltetrazole. This reaction will only give substantial yields if the 1-vinyltetrazole is made efficiently from an organotin compound such as 2-tributylstannyltetrazole. The reaction, shown below, produces imidazole when R=R₁=R₂=Hydrogen. Image File history File links Size of this preview: 800 × 190 pixelsFull resolution‎ (2,446 × 580 pixels, file size: 12 KB, MIME type: image/png) (All user names refer to en. ... Photolysis refers to any chemical reaction in which a compound is broken down by light. ... 1H-tetrazole Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen and one carbon atom (plus hydrogens). ... Organotin compounds or stannanes are chemical compounds based on tin with hydrocarbon substituents. ...

Image File history File links Ringformation. ...

Imidazole can also be formed in a vapor phase reaction. The reaction occurs with formamide, ethylenediamine, and hydrogen over platinum on alumina, and it must take place between 340 and 480 °C. This forms a very pure imidazole product. Formamide, also known as Methanamide (IUPAC) and Carbamaldehyde, formula HCONH2 is an amide derived from formic acid. ... Ethylene diamine (EDA), or 1,2-diaminoethane, is an organic compound from the amines group. ...

Structure and properties

Imidazole is a 5-membered planar ring, which is soluble in water and polar solvents. The compound has an aromatic sextet, which consists of one π electron from the =N- atom and one from each carbon atom, and two from the NH nitrogen. Some resonance structures of imidazole are shown below. A commonly-used example of a polar compound is water (H2O). ... In chemistry, an aromatic molecule is one in which electrons are free to cycle around circular arrangements of atoms, which are alternately singly and doubly bonded to one another. ... Properties For other meanings of Atom, see Atom (disambiguation). ... This article is about resonance in physics. ... Image File history File links Imidazoleresonace. ...

Imidazole is a base and an excellent nucleophile. It reacts at the NH nitrogen, attacking alkylating and acylating compounds. It is not particularly susceptible to electrophilic attacks at the carbon atoms, and most of these reactions are substitutions that keep the aromaticity intact. One can see from the resonance structure that the carbon-2 is the carbon most likely to have a nucleophile attack it, but in general nucleophilic substitutions are difficult with imidazole. In chemistry, a nucleophile (literally nucleus lover) is a reagent which is attracted to centres of positive charge. ... In chemistry, an electrophile (literally electron-lover) is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a substance. ...

Biological significance and applications

Imidazole is incorporated into many important biological molecules. The most obvious is the amino acid histidine, which has an imidazole side chain. Histidine is present in many proteins and enzymes and plays a vital part in the structure and binding functions of hemoglobin. Histidine can be decarboxylated to histamine, which is also a common biological compound. It is a component of the toxin that causes urticaria, which is basically an allergic reaction. The structures of both histidine and histamine are: This article is about the class of chemicals. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... The term Side chain can have different meanings depending on the context: In chemistry and biochemistry a side chain is a part of a molecule attached to a core structure. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Structure of hemoglobin. ... A carboxyl or carboxylic group is a functional group consisting of a carbon atom and an oxygen atom doubly bonded to each other. ... This article or section does not cite any references or sources. ... For other uses, see Toxin (disambiguation). ... Allergy is an abnormal reaction to a substance foreign to the body that is acquired, predictable and rapid. ... Image File history File links Histidine-histamine. ...

One of the applications of imidazole is in the purification of His-tagged proteins in immobilised metal affinity chromatography(IMAC). Imidazole is used to elute tagged proteins bound to Ni ions 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. A His-tag is an amino acid motif in proteins that consists of six histidine (His) residues, often at the N- or C-terminus of the protein. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... For the Second Person album, see Chromatography (album). ... For other uses, see Nickel (disambiguation). ... This article is about the electrically charged particle. ...

Imidazole has become an important part of many pharmaceuticals. Synthetic imidazoles are present in many fungicides and antifungal, antiprotozoal, and antihypertensive medications. Imidazole is part of the theophylline molecule, found in tea leaves and coffee beans, which stimulates the central nervous system. It is present in the anticancer medication mercaptopurine, which combats leukemia by interfering with DNA activities. A Fungicide is one of three main methods of pest control- chemical control of fungi in this case. ... Something antifungal kills or inhibits the growth of fungus. ... Antiprotozoal agents (ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoal infections. ... Antihypertensives are a class of drugs that are used in medicine and pharmacology to treat hypertension (high blood pressure). ... Theophylline is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. ... A diagram showing the CNS: 1. ... Mercaptopurine: chemical structure Mercaptopurine (also called 6-MP or by its brand name Purinethol®) is an immunosuppressive drug used to treat leukemia. ... Leukemia or leukaemia(Greek leukos λευκός, “white”; aima αίμα, “blood”) (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ...

Industrial applications

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.

Many compounds of industrial and technological importance contain imidazole. The thermostable polybenzimidazole PBI contains imidazole fused to a benzene ring and linked to a benzene, and acts as a fire retardant. Imidazole can also be found in various compounds which are used for photography and electronics. For benzine, see petroleum ether. ...

Salts of imidazole

Salts of imidazole where the imidazole ring is in the cation are known as imidazolium salts (for example, imidazolium chloride). These salts are formed from the protonation or substitution at nitrogen of imidazole. These salts have been used as ionic liquids and precursors to stable carbenes. Salts where a deprotanated imidazole is an anion are also possible; these salts are known as imidazolide salts (for example, sodium imidazolide). Image File history File links Imidazolium_salt. ... A cation is an ion with positive charge. ... Protonation is the addition of a proton (H+) to an atom, molecule, or ion. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... Ionic Liquids are a class of ionic materials that are liquids at temperatures below 100°C. These ionic liquids can be made from uncountable combinations of organic and non-organic cations and anions. ... A persistent carbene (also known as a stable carbene) is a particular carbene demonstrating particular stability despite being a reactive intermediate. ... An anion is an ion with negative charge. ...

Related heterocycles

• Benzimidazole, an analog with a fused benzene ring.
• Dihydroimidazole or benzimidazoline, an analog where 4,5-double bond is saturated.
• Pyrrole, an analog with only one nitrogen atom in position 1.
• Oxazole, an analog with the nitrogen atom in position 1 replaced by oxygen.
• Thiazole, an analog with the nitrogen atom in position 1 replaced by sulfur.
• Pyrazole, an analog with two adjacent nitrogen atoms.

Benzimidazole is a heterocyclic aromatic organic compound. ... For benzine, see petroleum ether. ... Chemical structure of dihydroimidazole Dihydroimidazole is a chemical group based on an imidazole structure, wherein the 4,5-double bond (i. ... Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ... Pyrrole, or pyrrol, is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H5N. Pyrroles are components of larger aromatic rings, including the porphyrins of heme, the chlorins and bacteriochlorins of chlorophyll, and the corrin ring of vitamin B12. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... Properties For other meanings of Atom, see Atom (disambiguation). ... Oxazole is the parent compound for vast class of heteroaromatic compounds. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) pale blue (liquid) Standard atomic weight 15. ... Thiazole, or 1,3-thiazole, is a clear to pale yellow flammable liquid and pyridine-like odor with the molecular formula C3H3NS. It is a 5-membered ring, in which two of the vertices of the ring are nitrogen and sulfur, and the other three are carbons [1]. Thiazole is... This article is about the chemical element. ... Pyrazole refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ...

References

1. ^ Katritzky; Rees. Comprehensive Heterocyclic Chemistry. Vol. 5, p.469-498, (1984).
2. ^ Grimmett, M. Ross. Imidazole and Benzimidazole Synthesis. Academic Press, (1997).
3. ^ Brown, E.G. Ring Nitrogen and Key Biomolecules. Kluwer Academic Press, (1998).
4. ^ Pozharskii, A.F, et.al. Heterocycles in Life and Society. John Wiley & Sons, (1997).
5. ^ Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2
6. ^ 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
7. ^ US6,177,575 (PDF version) (2001-01-23) Anthony J. Arduengo, III Process for Manufacture of Imidazoles