Synthesis of 3,5,5-Trisubstituted 4-Hydroxy-4H,5H-1,2,4-oxadiazoles through the Condensation of N-Hydroxyamidoximes and Ketones or Aldehydes

An interesting class of heterocyclic compounds, 1,2,4‐oxadiazoles and their derivatives have attracted the attention of chemists because of their use in the development of new pharmaceuticals and functional materials. Herein, a catalyst‐free reaction of N‐hydroxyamidoxime with various ketones or aldehydes has been investigated. The reaction was carried out in methanol under mild conditions and gave 3,5,5‐trisubstituted 4‐hydroxy‐4H,5H‐1,2,4‐oxadiazole derivatives in excellent yields. The structure of product 3f was confirmed by single‐crystal X‐ray diffraction studies. A convenient method was developed for the synthesis of 3,5,5‐trisubstituted 4‐hydroxy‐4H,5H‐1,2,4‐oxadiazole derivatives that proceeds through the condensation reaction of N‐hydroxyamidoximes and ketones or aldehydes. These reactions were efficiently carried out at room temperature in the absence of a catalyst and afforded the corresponding products in excellent yields.