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. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base; its conjugate acid has a pK<sub>a</sub> of 0.8, compared to 7 for imidazole.
Preparation
The classic synthetic route the Robinson–Gabriel synthesis by dehydration of 2-acylaminoketones:
center|350px|The Robinson–Gabriel synthesis
The Fischer oxazole synthesis from cyanohydrins and aldehydes is also widely used:
center|500px|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:
:[[Image:Biosynthesis of oxazole.png|thumb|450px|left|Where X = H, for serine and threonine respectively, B = base.<br/>(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 pK<sub>a</sub> of 0.8 for the conjugate acid (oxazolium salts), oxazoles are far less basic than imidazoles (pK<sub>a</sub> = 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.]]
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 reports on the oxidation of 4,5-diphenyloxazole with 3 equivalents of CAN to the corresponding imide and benzoic acid:
:400px|Oxazoline CAN oxidation
: 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<sup>IV</sup>).
See also
- Isoxazole, an analog with the nitrogen atom in position 2.
- Thiazole, an analog with the oxygen replaced by a sulfur.
- Benzoxazole, where the oxazole is fused to a benzene ring.
- Oxazoline, which has one double bond reduced.
- Oxazolidine, which has both double bonds reduced.
- Oxazolone, an analog with a carbonyl group
Additional reading <!-- to be trashed-->
- 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.