Oxazole

Preparation

• 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

• 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

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: