Oxazole

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

the Van Leusen reaction with aldehydes and TosMIC

Other methods are reported in literature.

Oxazolines can also be obtained from cycloisomerization of certain propargyl amides. In one study 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:

Biosynthesis

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.

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 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).