FISCHER Oxazole synthesis

Oxazoles from the condensation of equimolar amounts of aldehyde cyanohydrins and aromatic aldehydes in dry ether in the presence of dry hydrochloric acid. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 107, Springer International Publishing Switzerland 2014 

Brooks, D. A. Fisher Oxazole Synthesis, hi Name Reactions in Heterocyclic Chemistry, Li, J. J., Ed. Wiley Hoboken, NJ, 20 5, pp 234-236. (Review). 

Stereoselective oxidation of alkyl-silanes into the corresponding alkyl-alcohols using peracids. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 99, Springer-Verlag Berlin Heidelberg 2009 

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FISCHER Oxazole synthesis 122 FISCHER - BORSCHE DRECHSEL Indole synthesis 123... 

F. From Cyanohydrins and Aldehydes (Fischer Oxazole Synthesis). 120... 

Other references related to the Fischer oxazole synthesis are cited in the literature. ... 

Fischer oxazole synthesis, reported in 1896 by Emil Fischer, is one of the earliest methods reported for the synthesis of 2,5-disubstituted oxazoles. It entails the reaction of cyanohydrin with aldehyde under dry acidic conditions to form the corresponding oxazole. ... 

Fischer s name is associated with a great number of important organic transformations, such as the Fischer indole synthesis, Fischer esterification, Kiliani-Fischer synthesis, and the Fischer oxazole synthesis. The Fischer oxazole synthesis was one of his first contributions in his early years in the Berlin University (currently Humboldt University). In 1896 he published a new synthesis of 2,5-diaryloxazoles using an acid-catalyzed condensation of cyanohydrins with aldehydes. 

In 1977 Davis, Temai et al. introduced an interesting variation to the synthesis. In their efforts to form substituted 2,5-diaryl oxazoles, a simple modification of the Fischer oxazole synthesis rendered a good yielding process. Acyl cyanide replaces cyanohydrins, which reacts with aldehyde to form 2,5-diaryl-4-chloro- (or bromo-) oxazoles. An example for such variation is the synthesis of the chloro-oxazoles 14. Benzoyl cyanide (12) reacts with aldehyde 13a at 0 C in the presence of HCl, and the mixture is stirred overnight to give 14a in a 75% yield. Similarly, benzoyl cyanide reacts with aldehyde 13b to give 14b in a 65% yield. 4-Bromo-oxazoles can also be formed using such variation. An example is the synthesis of 16 by the reaction of p-nitrobenzoyl cyanide (15) with benzaldehyde in the presence of HBr the 4-bromo adduct is formed in a 68% yield. 

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