Efficient synthesis of 1,3,4-oxadiazoles promoted by NH4Cl

An efficient and inexpensive approach to the synthesis of 2-substituted and 2,5-disubstituted 1,3,4-oxadiazoles from arylhydrazides and orthoesters is reported using catalytic NH4Cl. The conditions are mild, and thus, compatible with a variety of functional groups. The optimized reaction is performed using 30 mol % of NH4Cl in 100% EtOH and is generally complete within I h for non-aromatic orthoesters and 2-10 h for aromatic orthoesters. The reaction permits both electron-releasing and electron-withdrawing groups on the arylhydrazide substrate. Most products are formed in high yields and require only minimal purification. Compared with earlier reports, the current reactions proceed in shorter time and require less of the orthoester. (C) 2014 Elsevier Ltd. All rights reserved.