Synthesis and fungicidal activity of novel 2,5-disubstituted-1,3,4- thiadiazole derivatives containing 5-phenyl-2-furan.

Zi-Ning Cui,Yuan Wang,De-Kun Hu,Jia-Zhen Jiang,Hao Tian,Xiao-Jing Yan,Ya-Sheng Li

doi:10.1038/srep20204

Abstract

A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized using Lawesson’s reagent by an efficient approach under microwave irradiation in good yields. Their structures were characterized by MS, IR, 1H NMR, 13C NMR, and elemental analysis. Their in vitro and in vivo fungicidal activities revealed that the title compounds exhibited considerable activity against five selected fungi, especially to Phytophthora infestans. In order to illustrate the mechanism of title compounds against P. infestans, scanning electron micrographs (SEM) and transmission electron micrographs (TEM) were applied. The morphological and ultrastructural studies demonstrated that compound I18 led to swelling of hyphae, thickening and proliferating multilayer cell walls, excessive septation and accumulation of dense bodies. The bioassay results indicated compound I18 might act on cell wall biosynthesis, and blocked the nutrition transportation and led to cells senescence and death. Meanwhile, compound I18 had broad fungicidal activity against other twenty different kinds of fungi. These results suggested that title compounds were eligible to be development candidates and compound I18 as a promising lead compound was worthy to be further discovery, especially against P. infestans.

Highlights

It has been reported that the compounds containing furan showed broad-spectrum bioactivities
Synthesis of the title compounds 2,5-disubstituted-1,3,4-thiadiazoles was achieved following a convenient procedure starting from commercially available 2-furoic acid and the substituted anilines as outlined in Fig. 2. 5-subsitituted phenyl-2-furoic acids 2 were prepared by the method of Meerwein arylation using copper (II)-catalyzed decomposition of diazonium salts
We synthesized a series of 2-substituted phenyl-5-(5′ -substituted phenyl-2′ -furoyl)-1,3, 4-thiadiazoles using Lawesson’s reagent by an efficient approach under microwave irradiation in good yields

Summary

Introduction

It has been reported that the compounds containing furan showed broad-spectrum bioactivities. A wide range of derivatives such as dibenzoylureas[15], diacylhydrazines[16,17,18,19,20,21], acylhydrazones[22,23,24,25], semicarbazide[26], pyrazole, 1,2,4-triazole27, 1,3,4-oxadiazole[28], and carbamic acid esters[29,30] containing 5-phenyl-2-furan moiety has been synthesized and studied in our group for the development of novel chemical entities as a lead molecule in drug and agrochemical discovery. In continuation of our research on the synthesis of biological heterocyclic compounds, a series of novel 1,3,4-thiadiazole derivatives containing 5-phenyl-2- furan moiety was synthesized by an efficient approach under microwave irradiation (Fig. 1).

Methods

Results

Conclusion