Preparation And Bioactivity Of 2- (1 - Phenyl - 1, 4 - Pyrazol - 4 - Yl) -1,3,4 - Oxadiazole Derivatives

For the past several decades, heterocyclic compounds were generally viewed as a hotspot in research and development of medicine and pesticide. Among them, the pyrazoles and 1,3,4-oxadiazoles with broad spectrum of bioactivities, including insecticidal, acaricidal, herbicidal, antimicrobial and plant-virus resisting activities, play an important role in the fields of pesticides. On the basis of our preceding work, 1,3,4-oxadiazole thioether(ether, sulfone) was introduced into the 1-phenyl-5-trifluoromethyl-1H-4-pyrazole with good antimicrobial activity. In this paper, a series of 1-phenyl-5-trifluoromethyl-4-(1,3,4-oxadiazole) thioether(ether or sulfone) were designed and synthesized, and the bioassay was performed to measure the antifungal and antibacterial activities.Selecting phenylhydrazine as the starting material, 16 thioether compounds I and 12 ether compounds II were synthesized via successive cyclization and 2 steps of nucleophilic substitution; followed by oxidation of compounds I to afford another 8 sulfone compounds III. All these target compounds were characterized and confirmed by IR, 1H NMR, 13 C NMR and MS.The in vitro antibacterial activities of all the compounds were tested by the nephelometry. The results demonstrated that compounds I and III have an certain inhibitory activity against the Xanthomonas oryzae pv. Oryzae. For example, the antibacterial activities of compounds I5(93.8±0.3%, 83.2±0.3%), I11(84.3±0.8%, 66.2±3.9%), III1(98.9±0.3%, 97.8±0.9%), III2(100.0%, 100.0%) and III3(100.0%, 96.9±0.5%) against X. oryzae at 200 and 100 μg/m L were higher than those of bismerthiazol(72.1±0.7%, 53.7±1.2%). Compounds III1, III2 and III3 showed strong activity against X. oryzae, with EC50 values of 31.6±1.6 μg/m L, 65.7±3.8 μg/mL, 16.6±0.2 μg/mL, respectively, which were lower than those of bismerthiazol(92.6±2.1 μg/mL) and thiodiazole-copper(121.8±3.6 μg/mL). The preliminary structure-activity relationships indicated that alkyl, rather than benzyl, substituted sulfonyl group showed better antibacterial activities. Besides, branched chain, rather than straight chain, substituted thioether and sulfonyl group in the thioether and sulfone compounds exhibited good activities as well.The antifungal activities were screened and evaluated against six pathogenic fungi, namely, Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans, Phytophthora infestans, and Sclerotinia sclerotiorum, by the mycelial growth rate method. The results indicated that compounds II and III have moderate activities against all the 6 species of fungal. Among these compounds, the antifungal activities of compounds II1(67.6±3.5%), III1(70.2±2.8%) and III3(70.2±3.2%) against F. Oxysporum at 100 μg/m L were better than those of hymexazol(62.1±2.5%). The preliminary structure-activity relationships suggested that the antifungal activity decreased with carbon chain length for alkyl substituted compounds; branched chain showed higher activities than those of straight chain containing the same numbers of carbon atoms.