A facile preparation of various N-heterocycles using amides and olefins

We herein report a one pot approach for the synthesis of various nitrogen containing heterocycles including: oxazolines, thiazolines, and dihydro dioxazines via the addition of amides to olefins in the presence of N-iodosuccinimide (NIS) and propionitrile at high temperatures. Thus, the reaction of aryl/heteroaryl amides, thioamides, N-hydroxybenzamide, and phenylurea with various olefins in the presence of NIS and propionitrile at 45 °C afforded the N-heterocycles in good to moderate yields. Reaction of the electron deficient tri-O-acetyl-d-glucal and tri-O-acetyl-d-galactal with benzamide and thiophene-2-carboxamide afforded the N-glycooxazolines in good yields. The newly made heterocycles were tested against various enzymes. Only 3,6-diphenyl-dihydro-1,4,2-dioxazine (1c) was found to moderately inhibit hexokinase II (hHK2).