One-Pot Synthesis of 1,2,4-Oxadiazoles Mediated by Microwave Irradiation under Solvent-Free Condition

Microwave-assisted synthesis of 1,2,4-oxadiazoles of amidoximes under solvent free conditions was found to be an efficient method for one-pot synthesis of 1,2,4-oxadiazole derivatives from amidoximes and acyl chlorides.This method is an easy, rapid, and high-yielding reaction for the synthesis of 1,2,4-oxadiazoles.The oxadiazole 1 nucleus is a well-studied traditional pharmacophoric scaffold that has emerged as a core structural unit of various muscarinic agonists, 2 benzodiazepine receptor partial agonists, 3 dopamine transporters, 4 antirhinovirals, 5 growth hormone secretagogous, 6 and 5-HT agonists. 7Among the oxadiazoles, 1,2,4-oxadiazole derivatives are gaining in interest in medicinal chemistry. 80][11][12][13][14][15] In general, synthesis of 1,2,4-oxadiazoles involves first the O-acylation step of an amidoxime by an activated carboxylic acid derivatives, followed by cyclodehydration. 16It has found that cyclization could be effected by treating an O-acylamidoxime with NaH or NaOEt 17a-c at room temperature, pyridine with heating, 17d,e tetrabutylammonium fluoride as catalyst 18 and using of solid support techniques 19 for the preparation of 1,2,4-oxadiazoles.The application of microwave energy to accelerate organic reactions is of increasing interest and offers several advantages over conventional techniques. 20As a part of our efforts to explore the novel utilities of microwave-assisted and surface-mediated reactions for the synthesis of heterocyclic compounds 21,22 we describe here a new method for one-pot synthesis 1,2,4-oxadiazoles from amidoximes and acyl chlorides under solvent free condition.It is found that magnesia under solvent-free conditions was capable of producing high yields of 1,2,4-oxadiazoles by reaction from amidoximes with acyl chloride under mild reaction conditions in 67-91% yields under microwave irradiation (Scheme 1, Table 1).