Microwave assisted synthesis of 1,3,4-oxadiazole/thiohydantoin hybrid derivatives via dehydrative cycliztion of semicarbazide

Abstract

A series of compounds containing both 1,3,4-oxadiazole and thiohydantoin were synthesized as a promising scaffold for application in medicinal chemistry. The key step of the synthesis is a microwave-assisted cyclization of semicarbazides possessing a thiohydantoin moiety at one of the acyl termini using POCl3 as a dehydrating reagent. A wide range of semicarbazides were prepared through the substitution of hydrazides with an N-acylated thiohydantoin derived from the cyclization of the corresponding isothiocyanate with an amino acid and subsequent N-acylation of the resultant thiohydrantion. Consequently, the 58 number of 1,3,4-oxadiazole derivatives having a thiohydantoin substituent were prepared in good overall yields. Thiohydantoin 134-Oxadiazole Semicarbazide Microwave Amino acid Acknowledgments. This research was conducted under the Industrial Infrastructure Program for Fundamental Technologies and Institute for Advancement of Technology through the Inter-ER Cooperation Projects (R0002016) which are funded by the Ministry of Trade, Industry & Energy, Korea to YDG and Open Translational Research Center for Innovative Drug (2012M3A9C1053532) which are funded by National Research Foundation of Korea.