Oxazole

Oxazole
IUPAC name 1,3-oxazole
Identifiers
CAS number	288-42-6 Y
PubChem	9255
Jmol-3D images	Image 1
SMILES C1=COC=N1
Properties
Molecular formula	C3H3NO
Molar mass	69.06 g mol−1
Density	1.050 g/cm3
Boiling point	69-70 °C
Basicity (pKb)	0.8
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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.^[1] 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.

Preparation

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 literature.

• Oxazolines can also be obtained from cycloisomerization of certain propargyl amides. In one study^[2] oxazoles were prepared via a one-pot synthesis consisting of the condensation of propargyl amine and benzoyl chloride to the amide, followed by a Sonogashira coupling of the terminal alkyne end with another equivalent of benzoylchloride, and concluding with p-toluenesulfonic acid catalyzed cycloisomerization:

• In one reported oxazole synthesis the reactants are a nitro-substituted benzoyl chloride and an isonitrile:^{[3] [4]}

Biosynthesis

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

Where X = H, CH₃ 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

• 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 changing positions.
• Various oxidation reactions. One study^[5] 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).

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.
• Oxadiazoles with two nitrogens instead of one (e.g. furazan).

References

1. ^ Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2
2. ^ 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
3. ^ 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
4. ^ 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.
5. ^ 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