Syntheses of the Oxazole Ring System

In the following sections we have attempted to rationalize numerous methods available for the synthesis of oxazoles. It was convenient to classify the syntheses according to the starting materials used rather than adopting the specific bond formations. Occasionally the closely related starting materials have been incorporated under one heading, and scope and limitations have been pointed out. 

From o-Acylamino Carbonyl Compounds (The Robinson-Gabriel Synthesis) 

One of the classical methods of the formation of oxazoles is the cycliza-tion of a-acylamino carbonyl compounds (1). This synthesis has, in fact, been the subject of oxazole research for more than a century, since the first example of this cyclization is the synthesis of benzilam (2,4,5-triphenyloxazole) in 1845 by Laurent.16 Almost six decades later, Robinson16 and Gabriel17 in their independent but systematic investigation of this reaction employed concentrated sulfuric acid and phosphorus penta-chloride, respectively, to effect the ring closure. 

Apparently, of these two dehydrating agents, sulfuric acid has been adopted more widely18 because it affords better yields and practically no by-products. Very often this is the reagent of choice for the synthesis 

The cyclization has also been carried out successfully in the presence of other dehydrating agents35 such as phosphorus pentoxide,36 thionyl chloride,37 38 a mixture of acetic anhydride and concentrated sulfuric 

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