Oxazole
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| Oxazole |
<td style="background-color: #FFFFFF;">69.06 g mol−1</td></tr><tr><td style="background-color: #FFFFFF; vertical-align: top; white-space: nowrap; width: 30%;">Systematic name</td> <td style="background-color: #FFFFFF;">1,3-oxazole</td></tr><tr><td align="center" style="background-color: #ddeeff;" colspan="2">Complete data</td></tr></table></div>
Oxazole is the parent compound for vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon <ref>Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2</ref>.
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[edit] Biochemistry
In biomolecules, oxazoles result from the cyclization and oxidation of serine or threonine nonribosomal peptides:
Oxazoles are not as abundant in biomolecules as the related thiazoles with oxygen replaced by a sulfur atom.
[edit] Properties
Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base with pKa of conjugate acid of 0.8 compared to 7 for pyrrole.
[edit] Organic synthesis
Classical oxazole synthetic methods in organic chemistry are
- the Robinson-Gabriel synthesis by dehydration of 2-acylaminoketones
- the Fischer oxazole synthesis from cyanohydrins and aldehydes
- the Bredereck reaction with α-haloketones and formamide
Other methods are reported in the literature.
- Oxazolines can also be obtained from cycloisomerization of certain propargyl amides. In one study <ref>A new consecutive three-component oxazole synthesis by an amidation–coupling–cycloisomerization (ACCI) sequence Eugen Merkul and Thomas J. J. Müller Chem. Commun., 2006, 4817 - 4819, DOI:10.1039/b610839c</ref> oxazoles are synthesized in a one-pot synthesis starting with condensation of propargyl amine and benzoyl chloride to the amide followed by Sonogashira coupling of the terminal alkyne end with another equivalent of benzoylchloride and concluded with P-toluenesulfonic acid catalyzed cycloisomerization:
- In one reported oxazole synthesis the reactants are a benzoyl chloride and an isonitrile <ref>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; (Letter) DOI:10.1021/ol061975c</ref> <ref>They react together in the first phase in a continuous flow reactor to the intermediate enol and then in the second phase in a phosphazene base (PS-BEMP) induced cyclization by solid-phase synthesis.</ref>:
[edit] Organic reactions
- Deprotonation of oxazoles at C2 is often accompanied by ring-opening to the isonitrile.
- Electrophilic aromatic substitution takes place at C5 requiring Activating groups.
- Nucleophilic aromatic substitution takes place with leaving groups at C2.
- Diels-Alder reactions with oxazole dienes can be followed by loss of oxygen to form pyridines
- The Cornforth Rearrangement of 4-acyloxazoles is a thermal rearrangement reaction with the organic acyl residue and the C5 substituent trading places.
- Various oxidation reactions. One study <ref> 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</ref>reports on the oxidation of 4,5-diphenyloxazole with 3 equivalents of CAN to the formamide and benzoic acid:
- Image: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.
[edit] See also
- Isoxazole, an analog with the nitrogen atom in position 2.
- Imidazole, an analog with the oxygen replaced by a nitrogen.
- Thiazole, an analog with the oxygen replaced by a sulfur.
- Benzoxazole, where the oxazole is fused to another aromatic ring.
- Pyrrole, an analog without the oxygen atom.
- Furan, an analog without the nitrogen atom.
- Oxazoline, which has one double bond reduced.
- Oxazolidine, which has both double bonds reduced.
- oxadiazole with two nitrogens instead of one.
- Simple aromatic rings
- Link page to external chemical sources.
