Oxazole

Oxazole
Names
	Preferred IUPAC name 1,3-Oxazole
Identifiers
CAS Number	288-42-6 ;
3D model (JSmol)	Interactive image ;
Beilstein Reference	103851
ChEBI	CHEBI:35597 ;
ChEMBL	ChEMBL2171710 ;
ChemSpider	8898 ;
ECHA InfoCard	100.005.474
EC Number	206-020-8;
Gmelin Reference	485850
MeSH	D010080
PubChem CID	9255 ;
UNII	FJZ20I1LPS ;
CompTox Dashboard (EPA)	DTXSID70182983 ;
	InChI InChI=1S/C3H3NO/c1-2-5-3-4-1/h1-3H Key: ZCQWOFVYLHDMMC-UHFFFAOYSA-N ; InChI=1/C3H3NO/c1-2-5-3-4-1/h1-3H Key: ZCQWOFVYLHDMMC-UHFFFAOYAD;
	SMILES C1=COC=N1;
Properties
Chemical formula	C3H3NO
Molar mass	69.06 g/mol
Density	1.050 g/cm3
Boiling point	69.5 °C (157.1 °F; 342.6 K)
Acidity (pKa)	0.8 (of conjugate acid)
Hazards
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H225, H318
Precautionary statements	P210, P233, P240, P241, P242, P243, P264+P265, P280, P303+P361+P353, P305+P354+P338, P317, P370+P378, P403+P235, P501
Supplementary data page
	Oxazole (data page)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Last updated October 31, 2023

Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon.^[4] Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base; its conjugate acid has a pK_a of 0.8, compared to 7 for imidazole.

Preparation

The classic synthetic route the Robinson–Gabriel synthesis by dehydration of 2-acylaminoketones:

The Robinson-Gabriel synthesis Robinson-Gabriel-Synthese-Ubersichtsreaktion.svg — The Robinson–Gabriel synthesis

The Fischer oxazole synthesis from cyanohydrins and aldehydes is also widely used:

Other methods are known including the reaction of α-haloketones and formamide and the Van Leusen reaction with aldehydes and TosMIC.

Biosynthesis

In biomolecules, oxazoles result from the cyclization and oxidation of serine or threonine nonribosomal peptides:^[5]

Oxazoles are not as abundant in biomolecules as the related thiazoles with oxygen replaced by a sulfur atom.

Reactions

With a pK_a of 0.8 for the conjugate acid (oxazolium salts), oxazoles are far less basic than imidazoles (pK_a = 7). Deprotonation of oxazoles occurs at C2. Formylation with dimethylformamide gives 2-formyloxazole. The lithio compound exists in equilibrium with the ring-opened enolate-isonitrile, which can be trapped by silylation.^[4]

Electrophilic aromatic substitution takes place at C5, but requiring electron donating groups.

Nucleophilic aromatic substitution takes place with leaving groups at C2.

Diels–Alder reactions involving oxazole (as dienes) and electrophilic alkenes has been well developed as a route to pyridines. In this way, alkoxy-substituted oxazoles serve a precursors to the pyridoxyl system, as found in vitamin B6. The initial cycloaddition affords a bicyclic intermediate, with an acid-sensitive oxo bridgehead.

Use of an oxazole in the synthesis of a precursor to pyridoxine, which is converted to vitamin B6.

In the Cornforth rearrangement of 4-acyloxazoles is a thermal rearrangement reaction with the organic acyl residue and the C5 substituent changing positions.

Various oxidation reactions. One study^[7] reports on the oxidation of 4,5-diphenyloxazole with 3 equivalents of CAN to the corresponding imide and benzoic acid:

In the balanced half-reaction three equivalents of water are consumed for each equivalent of oxazoline, generating 4 protons and 4 electrons (the latter derived from Ce^IV).

Additional reading

Fully Automated Continuous Flow Synthesis of 4,5-Disubstituted Oxazoles Marcus Baumann, Ian R. Baxendale, Steven V. Ley, Christoper D. Smith, and Geoffrey K. Tranmer Org. Lett.; 2006; 8(23) pp 5231 - 5234. doi : 10.1021/ol061975c

Related Research Articles

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is a functional group with the structure R−C(=O)−R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group −C(=O)−. The simplest ketone is acetone, with the formula (CH₃)₂CO. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

Pyrimidine is an aromatic, heterocyclic, organic compound similar to pyridine. One of the three diazines, it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine and pyridazine.

Pyridine is a basic heterocyclic organic compound with the chemical formula C₅H₅N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated polymeric chains, which show significant electrical conductivity. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.

Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula C₄H₄NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C₄H₄NCH₃. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.

The following outline is provided as an overview of and topical guide to organic chemistry:

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.

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.

Oxazolidine is a five-membered heterocycle ringwith the formula (CH₂)₃(NH)O.The O atom and NH groups are not mutually bonded, in contrast to isoxazolidine. Oxazolidines are derivatives of the parent oxazolidine owing to the presence of substituents on carbon and/or nitrogen. Oxazolines are unsaturated analogues of oxazolidines.

Indazole, also called isoindazole, is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and pyrazole.

Isoxazole is an electron-rich azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring. Isoxazolyl is the univalent radical derived from isoxazole.

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.

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).

The Fischer oxazole synthesis is a chemical synthesis of an oxazole from a cyanohydrin and an aldehyde in the presence of anhydrous hydrochloric acid. This method was discovered by Emil Fischer in 1896. The cyanohydrin itself is derived from a separate aldehyde. The reactants of the oxazole synthesis itself, the cyanohydrin of an aldehyde and the other aldehyde itself, are usually present in equimolar amounts. Both reactants usually have an aromatic group, which appear at specific positions on the resulting heterocycle.

Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. The parent compounds are aromatic and have two double bonds; there are successively reduced analogs with fewer. One, and only one, lone pair of electrons from each heteroatom in the ring is part of the aromatic bonding in an azole. Names of azoles maintain the prefix upon reduction. The numbering of ring atoms in azoles starts with the heteroatom that is not part of a double bond, and then proceeds towards the other heteroatom.

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.

The Dakin oxidation (or Dakin reaction) is an organic redox reaction in which an ortho- or para-hydroxylated phenyl aldehyde (2-hydroxybenzaldehyde or 4-hydroxybenzaldehyde) or ketone reacts with hydrogen peroxide (H₂O₂) in base to form a benzenediol and a carboxylate. Overall, the carbonyl group is oxidised, whereas the H₂O₂ is reduced.

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.

Oxazoline is a five-membered heterocyclic organic compound with the formula C₃H₅NO. It is the parent of a family of compounds called oxazolines, which contain non-hydrogenic substituents on carbon and/or nitrogen. Oxazolines are the unsaturated analogues of oxazolidines, and they are isomeric with isoxazolines, where the N and O are directly bonded. Two isomers of oxazoline are known, depending on the location of the double bond.

Montréalone is a mesoionic heterocyclic chemical compound. It is named for the city of Montréal, Canada, which is the location of McGill University, where it was first discovered.

tert-Butyl peroxybenzoate (TBPB) an organic compound with the formula C₆H₅CO₃CMe₃ (Me = CH₃). It is the most widely produced perester; it is an ester of peroxybenzoic acid (C₆H₅CO₃H). It is often used as a radical initiator in polymerization reactions, such as the production of LDPE from ethylene, and for crosslinking, such as for unsaturated polyester resins.

References

↑ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 140. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
↑ Zoltewicz, J. A. & Deady, L. W. Quaternization of heteroaromatic compounds. Quantitative aspects. Adv. Heterocycl. Chem. 22, 71-121 (1978).
↑ "Oxazole". pubchem.ncbi.nlm.nih.gov.
1 2 T. L. Gilchrist (1997). Heterocyclic Chemistry (3 ed.). Longman. ISBN 0-582-01421-2.
↑ Roy, Ranabir Sinha; Gehring, Amy M.; Milne, Jill C.; Belshaw, Peter J.; Walsh, Christopher T.; Roy, Ranabir Sinha; Gehring, Amy M.; Milne, Jill C.; Belshaw, Peter J.; Walsh, Christopher T. (1999). "Thiazole and Oxazole Peptides: Biosynthesis and Molecular Machinery". Natural Product Reports. 16 (2): 249–263. doi:10.1039/A806930A. PMID 10331285.
↑ Gérard Moine; Hans-Peter Hohmann; Roland Kurth; Joachim Paust; Wolfgang Hähnlein; Horst Pauling; Bernd–Jürgen Weimann; Bruno Kaesler (2011). "Vitamins, 6. B Vitamins". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.o27_o09. ISBN 978-3-527-30673-2.
↑ "Ceric Ammonium Nitrate Promoted Oxidation of Oxazoles", David A. Evans, Pavel Nagorny, and Risheng Xu. Org. Lett. ; 2006; 8(24) pp 5669 - 5671; (Letter) doi : 10.1021/ol0624530

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[1] International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 140. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.

[2] Zoltewicz, J. A. & Deady, L. W. Quaternization of heteroaromatic compounds. Quantitative aspects. Adv. Heterocycl. Chem. 22, 71-121 (1978).

[3] "Oxazole". pubchem.ncbi.nlm.nih.gov.

[TLG-4] 1 2 T. L. Gilchrist (1997). Heterocyclic Chemistry (3 ed.). Longman. ISBN 0-582-01421-2.

[5] Roy, Ranabir Sinha; Gehring, Amy M.; Milne, Jill C.; Belshaw, Peter J.; Walsh, Christopher T.; Roy, Ranabir Sinha; Gehring, Amy M.; Milne, Jill C.; Belshaw, Peter J.; Walsh, Christopher T. (1999). "Thiazole and Oxazole Peptides: Biosynthesis and Molecular Machinery". Natural Product Reports. 16 (2): 249–263. doi:10.1039/A806930A. PMID 10331285.

[6] Gérard Moine; Hans-Peter Hohmann; Roland Kurth; Joachim Paust; Wolfgang Hähnlein; Horst Pauling; Bernd–Jürgen Weimann; Bruno Kaesler (2011). "Vitamins, 6. B Vitamins". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.o27_o09. ISBN 978-3-527-30673-2.

[7] "Ceric Ammonium Nitrate Promoted Oxidation of Oxazoles", David A. Evans, Pavel Nagorny, and Risheng Xu. Org. Lett. ; 2006; 8(24) pp 5669 - 5671; (Letter) doi : 10.1021/ol0624530

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