Synthesis And Fungicidal Activities Of5-subsitituted-1,3,4-oxadiazole Thiol And1,2,4-triazole Thiol Derivaties

1,2,4-Triazole and1,3,4-oxadiazole were two kinds of nitrogen containing five-member heterocycle. Their derivatives showed excellent bioactivities include fungicidal, antitumor, insecticidal and herbicidal activities. In this article,4-amine-5-substituted-4H-1,2,4-triazol-3-thiol,5-substiuted-1,3,4-oxadiazol-2-thiol and their derivatives were designed and synthesized, their fungicide activities were determined and the preliminary structure-activity relationship was analysed.Different carboxylic acids were used as starting materials to synthesize thirteen4-amine-5-substituted-4H-1,2,4-triazol-3-thiols(3and8a-1) and twenty-one5-substiuted-1,3,4-oxadiazol-2-thiols(9a-u) via a facile four-step procedure including esterification, hydrazination, salt formation and cyclization. All the compounds were characterized using IR,1H NMR, MS and elemental analysis. The preliminary bioassay results showed that these compounds exhibited certain fungicidal activities against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici at the concentration of100μg/mL for the compounds3and8a-I and50μg/mL for the compounds9a-u. The preliminary structure-activity relationship revealed that, when having the same substituent group at the5-position of the nitrogen heterocycle, he compounds9a-u always showed better fungicidal activities than the compounds3and8a-1.Espectically, the compounds9with phenyl groups at the5-position echibited better fungicidal activities than with other aromatic groups.The4-amine-5-(fluorinated substituted)-4H-1,2,4-triazole-3-thiols were used as raw materials to synthesize twelve fluorined3,5-disubstituted-4H-1,2,4-triazol-4-amines(12a-j,13and14). The structures of these compounds were well supported by spectroscopic data, elemental analysis and single crystal X-ray diffraction analysis on compounds12g and13. The antifungal bioassay results demonstrated that these title compounds showed different fungicidal activities at the concentration of100μg/mL. The structure-activity relationship analysis revealed that introducing the fluorinated phenyl, especial the4-trifluoromethyl phenyl group, at the5-position of1,2,4-triazol-4-amine, or introducing the phenyl group at the3-position while the trifluoromethyl group was connected at the5-position directly were helpful to improve the fungicidal activities.The compound9b was used as a leading compound for its good fungicidal activities to designe and synthesize405-o-tolyl-1,3,4-oxadiazole-2-thiol derivates, including ten2-alkylsulfinyl-5-o-tolyl-1,3,4-oxadiazoles(16a-j), ten2-alkylsulfonyl-5-o-tolyl-1,3,4-oxadiazoles(17a-j), five2-(substituted phenoxy)-5-o-tolyl-1,3,4-oxadiazoles(18a-e), four2-(substituted phenylthio)-5-o-tolyl-1,3,4-oxadiazoles(19a-d),4-(5-o-tolyl-1,3,4-oxadiazol-2-yl)morpholine(20), five N’-(2-methylbenzoyl) pyrrolidine-l-carbohydrazides(22a-e) and five3-alkyl-5-o-tolyl-1,3,4-oxadiazol-2(3H)-ones(23a-e). The structures of these compounds were well supported by IR,1H NMR, MS, elemental analysis and single crystal X-ray diffraction analysis on the compounds22a and23a. The preliminary bioassay was performed at the concentration of100μg/mL, the EC50values of some compounds were determined. The compounds16a-e,16h-j,17a-e,17h-j,19a-d,21and23a-d exhibited good fungicidal activities. And the compounds17a showed the highest activity with the EC50values of6.3μg/mL,5.6μg/mL,1.7μg/mL and11.5μg/mL against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici, respectively. The structure-activity relationship analysis showed that the alkyls with short chain linked to the2-position of1,3,4-oxadiazole were helpful to improve the fungicidal activities. When the same alkyls were linked to sulfur, the compounds with sulfonyl showed better activities than with sulfinyl.