Robinson–Gabriel synthesis

The Robinson–Gabriel synthesis is an organic reaction in which a 2-acylamino-ketone reacts intramolecularly followed by a dehydration to give an oxazole. A cyclodehydrating agent is needed to catalyze the reaction It is named after Sir Robert Robinson and Siegmund Gabriel who described the reaction in 1909 and 1910, respectively.

The 2-acylamino-ketone stating materials can be synthesized using the Dakin–West reaction.

Protonation of the keto moiety (1) is followed by cyclization (2) and dehydration (3), the oxazole ring is less basic that the starting 2-acylamidoketone and so may be readily neutralized (4). Labeling studies have determined that the amide oxygen is the most Lewis basic and therefore is the one included in the oxazole.

Recently, a solid-phase version of the Robinson–Gabriel synthesis has been described. The reaction requires trifluoroacetic anhydride to be used as the cyclodehydrating agent in etheral solvent and the 2-acylamidoketone be linked by the nitrogen atom to a benzhydrylic-type linker.

A one-pot diversity-oriented synthesis has been developed via a Friedel-Crafts/Robinson–Gabriel synthesis using a general oxazolone template. The combination of aluminum chloride as the Friedel-Craft Lewis acid and trifluoromethanesulfonic acid as the Robinson-Gabriel cyclodehydrating agent were determined to generate the desired products.

...
Wikipedia