Robinson-Gabriel oxazole synthesis

What is Robinson-Gabriel oxazole synthesis?

The Robinson-Gabriel oxazole synthesis is a reaction that was first described by Gabriel (University of Berlin) in 1907 and later by Robinson (Nobel Prize in Chemistry 1947) in 1909. The Robinson-Gabriel oxazole synthesis involves the intramolecular condensation and dehydration of N-acyl α-aminoketones in the presence of a dehydration reagent, such as PCl5 or sulfuric acid H2SO4, to yield 2,5- and 2,4,5-substituted oxazole derivatives. This reaction is also known as the Robinson-Gabriel cyclodehydration, Robinson-Gabriel dehydration, Robinson-Gabriel cyclization, or simply the Robinson-Gabriel reaction.

Robinson-Gabriel oxazole synthesis - general reaction scheme - Robinson-Gabriel cyclodehydration - Robinson-Gabriel dehydration - Robinson-Gabriel cyclization - Robinson-Gabriel reaction
Robinson-Gabriel oxazole synthesis
  • R1, R2, R= alkyl, aryl
  • cyclodehydrating agent = POCl3/pyridine, H2SO4, PPA, PCl5, COCl2, PPh3/I2/Et3N, PPh3/Cl2/Et3N, PPh3/Br2/Et3N, SOCl2, P2O5, Tf2O, etc. (see list of acronyms)

Other cyclodehydrating reagents, such as the Burgess reagent, phosphorus oxychloride, and phosgene, have also been used, but polyphosphoric acid has been found to be superior. However, due to the harsh conditions required for the Robinson-Gabriel oxazole synthesis, it is not suitable for molecules with acid-labile functional groups.

References

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