Oxazole

Last updated
Oxazole
Oxazole 2D aromatic full.svg
Oxazole 2D numbered.svg
Oxazole-3D-balls.png
Oxazole-3D-spacefill.png
Names
Preferred IUPAC name
1,3-Oxazole [1]
Identifiers
3D model (JSmol)
103851
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.474 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 206-020-8
485850
MeSH D010080
PubChem CID
UNII
  • InChI=1S/C3H3NO/c1-2-5-3-4-1/h1-3H X mark.svgN
    Key: ZCQWOFVYLHDMMC-UHFFFAOYSA-N X mark.svgN
  • InChI=1/C3H3NO/c1-2-5-3-4-1/h1-3H
    Key: ZCQWOFVYLHDMMC-UHFFFAOYAD
  • C1=COC=N1
Properties
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) [2]
Hazards
GHS labelling: [3]
GHS-pictogram-flamme.svg GHS-pictogram-acid.svg
Danger
H225, H318
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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 pKa of 0.8, compared to 7 for imidazole.

Contents

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:

Fischer Oxazole Synthesis Fischer Oxazole Synthesis.png
Fischer Oxazole Synthesis

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]

Where X = H, CH
3 for serine and threonine respectively, B = base.
(1) Enzymatic cyclization. (2) Elimination. (3) [O] = enzymatic oxidation. Biosynthesis of oxazole.png
Where X = H, CH
3
for serine and threonine respectively, B = base.
(1) Enzymatic cyclization. (2) Elimination. (3) [O] = enzymatic oxidation.

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

Reactions

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

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. OxazoleRouteVitaminB6.png
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.

OxazolineOxidation.png
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 CeIV).

See also

Additional reading

Related Research Articles

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

In organic chemistry, a ketone is an organic compound 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.

<span class="mw-page-title-main">Organic chemistry</span> Subdiscipline of chemistry, focusing on carbon compounds

Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms. Study of structure determines their structural formula. Study of properties includes physical and chemical properties, and evaluation of chemical reactivity to understand their behavior. The study of organic reactions includes the chemical synthesis of natural products, drugs, and polymers, and study of individual organic molecules in the laboratory and via theoretical study.

<span class="mw-page-title-main">Pyridine</span> Heterocyclic aromatic organic compound

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

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<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.

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

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.

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 functional group derived from isoxazole.

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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.

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References

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