Fischer oxazole synthesis

The Fischer oxazole synthesis is a name reaction from the field of organic chemistry . The reaction is named after its discoverer Emil Fischer (1852–1919).

With the Fischer oxazole synthesis, a 2,5-disubstituted oxazole can be prepared from an aromatic cyanohydrin and an aromatic aldehyde . The reaction takes place with exclusion of water, which is why dry ether and gaseous hydrogen chloride are used as the solvent .

Reaction mechanism

The reaction mechanism of the Fischer oxazole synthesis is little explored.

In the first synthesis step , hydrogen chloride is added to the cyano group of cyanohydrin 1 , resulting in imino chloride 2 . In the next step, the lone pair of electrons in nitrogen attacks the carbonyl carbon of the aldehyde, whereby molecule 3 is formed. This cyclizes with separation of water and subsequent deprotonation to chloro- oxazoline 4 . The elimination of hydrogen chloride produces a diarylized oxazole 5 .

variants

In 1949 John W. Cornforth developed a variant of the Fischer oxazole synthesis in which the cyanohydrin is replaced by an α-hydroxy carboxamide . In this way, unlike Fischer, oxazoles with aliphatic substituents can be prepared .

See also

• Robinson-Gabriel synthesis

Individual evidence

1. ^ Emil Fischer: New way of formation of the oxazole . In: Reports of the German Chemical Society . 29, No. 1, pp. 205-214. doi : 10.1002 / cber.18960290143 .
2. ↑ ^{a b} , JW Cornforth, RH Cornforth Mechanism and extension of the Fischer oxazole synthesis . In: Journal of the Chemical Society . No. 0, pp. 1028-1030. doi : 10.1039 / JR9490001028 .
3. ↑ BH Ingham: The mechanism of reactions induced by hydrogen chloride between aromatic aldehydes and aldehydecyanohydrins in solution . In: Journal of the Chemical Society . No. 0, pp. 692-700. doi : 10.1039 / JR9270000692 .
4. ↑ Maklad, N. Name Reactions in Heterocyclic Chemistry II Li, JJ; Wiley & Sons; Hoboken, NJ, 2011 , pp. 225-232.