Synthesis and unusual ring transformation of 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones

•Ferrocenyl conjugates of natural products-piperazine-2,5-diones were synthesized.•They undergo a very unusual transformation to compounds featuring two oxazole rings.•A mechanism explaining this transformation was proposed.

The reaction of 1,4-diacyl-piperazine-2,5-diones with ferrocenecarbaldehyde in the presence of tBuOK in tBuOH–DMF at room temperature afforded 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones in 69–79% yields. The attempted N(4)-acylation of these compounds with carboxylic acids (2 equiv.) in the presence of N,N′-diisopropylcarbodiimide (2 equiv.) and 4-(dimethylamino)pyridine (3 equiv.) in dichloromethane at room temperature showed that the expected 1,4-diacylated products are initially formed, but undergo further transformations leading to compounds featuring conjugated ferrocenylmethylidene, azlactone (oxazolone) and oxazole units. As shown on the basis of one example, the azlactone ring in these compounds is opened in a room-temperature reaction with hydrazine, thus yielding the corresponding acyl hydrazide. The crystal structure of the starting material and the product of this reaction were confirmed by X-ray diffraction.

Graphical abstractThe paper discloses synthesis of 1-acyl-3-ferrocenylmethylidenepiperazine-2,5-diones and their unusual transformation involving opening of the piperazine ring and formation of two oxazole rings.Figure optionsDownload full-size imageDownload as PowerPoint slide