The Fischer oxazole synthesis is a chemical synthesis of an oxazole from a cyanohydrin and an aldehyde in the presence of anhydrous hydrochloric acid. This method was discovered by Emil Fischer in 1896. The cyanohydrin itself is derived from a separate aldehyde. The reactants of the oxazole synthesis itself, the cyanohydrin of an aldehyde and the other aldehyde itself, are usually present in equimolar amounts. Both reactants usually have an aromatic group, which appear at specific positions on the resulting heterocycle.
center|500px|Fischer Oxazole Synthesis
A more specific example of Fischer oxazole synthesis involves reacting mandelic acid nitrile with benzaldehyde to give 2,5-diphenyl-oxazole.
History
Fischer developed the Fischer oxazole synthesis during his time at Berlin University. The Fischer oxazole synthesis was one of the first syntheses developed to produce 2,5-disubstituted oxazoles.
The Fischer oxazole synthesis has also been useful in the synthesis of 2-(4-Bromophenyl)5-phenyloxazole starting with benzaldehyde cyanohydrin and 4-bromobenzaldehyde. However, oxazole ring chlorination occurs to give 2,5-bis(4-bromophenyl)-4-chlorooxazole 7 along with 2,5-bis(4-bromophenyl)-4-oxazolidinone 8. The latter compound is in general a by-product.
center|700px|Example of a Fischer Oxazole Synthesis
Another useful example is the one pot two-step synthesis of halfordinol, a parent compound for Rutaceae alkaloids.
The initial steps follow the Fischer oxazole synthesis, although the acid-catalyzed cyclization occurs in two steps rather than one, which ensures the formation of the di-chloro intermediate, preventing formation of the regioisomer.