Cyclization Synthsis Of Novel Oxadiazolines By In-situ-generated N-aroyldiazenes And Isothiocyanates With Biological Evaluation

Oxadiazole is an important class of nitrogen-and oxygen-containing heterocyclic compounds having extensive applications in agriculture,medicine,and materials.Among its derivatives 1,3,4-oxadiazole has become an important construction motif for the development of new drugs because of its biological activities including anticancer,antibacterial,anti-inflammatory.Numerous methods have developed for their preparation.However,to the best of our knowledge,reactions to construct the 2-imino-1,3,4-oxadiazoline framework have not been reported yet.N?Aroyldiazenes,One of the important azo compound,has a good use in Material optics and a intermediate to organic synthesis can building some heterocycle which including nitrogen and oxygen atoms.N-acyldiazenes have attracted considerable Nheterocyclic carbenes(NHC)-catalyzed annulation reactions including 1)[2 + 3]cyclizations with ?,?-unsaturated aldehydes;2)[4 + 2] annulations with enamines,ketenes,or ?-chloroaldehydes;3)aza-Wittig reaction of N-aryliminophosphoranes with N-aryl-N-aroyldiazenes;4)symmetric [3 + 2] cycloannulations of N-acyl azonaphthalenes with azlactones or 3-vinylindoles;However,the apply of some N?aroyldiazenes were limited because of instability,and the reaction with isothiocyanate compounds has not been reported.In this dissertation,a novel one-pot annulation reaction of hydrazides with isothiocyanates has been established for the synthesis of 2-imino-1,3,4-oxadiazolines under transition-metal-free conditions.This synthetic approach is practically simple and requires no use of NHC or other organic catalysts.It can also avoid the need to isolate the less-stable N?aroyldiazene intermediates and the use of malodorous isocyanides.In all,thirty 2-imino-1,3,4-oxadiazole products were synthesized and characterized,including twenty-seven new compounds.Interaction of these 1,3,4-oxadiazole compounds with human serum albumin(HSA)was investigated.It has been demonstrated that the compounds 1g,1o and 1u possess good binding ability to HSA and are worth for further biological studies.