Design, Synthesis And Bioactivity Of Phenoxy - Containing 1,3,4 - Oxo (thio) Oxadiazole Derivatives

Plant diseases caused by plant fungal and bacterial pathogens, which fungal diseases account for about 70-80% of plant diseases. It can be found in several or even dozens of species of fungal diseases on a crop, which are great harm to our crops and serious loss in economy. The structures of existing aryloxy modif ication can be an effective tactic to combat highly destructive pathogens, such as, anti-tumor, anti-cancer, insecticidal, fungicidal and herbicida l activities. Since the 1940 s, the development and application of phenoxy derivatives have attracted broad attention in agriculture, especially in the field of pesticide, such as 2,4-D, 2,4-MCPA and other herbicides. Fungicides triadimefon, azoxystrobin, etc. have been developed into new varieties of pesticides. In addition, sulfone compounds containing 1,3,4-oxadiazole/thiadiazole exhibit efficient, low toxicity and wide spectrum of biological activities. They are widely used in research and design of new green pesticide, such as its highly effective anti-bacterial plant and antiviral activit ies in pesticide chemistry. In the meantime, the research of synthesis and biological activities of sulfone derivatives containing phenoxy and 1,3,4-oxadiazole/thiadiazole have been one of the focuses of medicine, pesticides and other chemical fields.Fungicides which have the novel mechanism-independent, no resistant, high efficacy, low residues and its harmony with the environment, accord with agricultural control of the sustainable development. The novel green pesticides are widely welcome in the word due to its more efficacies, lower poison, broad spectrum and favorable environmental toxicity profile. We used substituted phenol and benzoic acids as a starting material. We investigated and synthesized three series of novel compounds by making use of substructure link principle. The three series of sulfone derivatives which containing phenoxy or 1,3,4-oxadiazole/thiadiazole were synthesized through five steps: esterification(williamson), hydrazidation, cyclization(salt formation), thioether ification, oxidation reaction. Namely, 20 2-(sulfonyl)-5-(substituted benzene)-1,3,4-oxadiazole(A), 14 2-(sulfonyl)-5-(substituted phenoxymethyl)-1,3,4-oxadiazole(B) and 15 2-(sulfonyl)-5-(substituted phenoxymethyl)-1,3,4-thiadiazole(C). Target compounds were characterized by 1H NMR and 13 C NMR, IR, ESI-MS, elemental analys is and X-ray diffraction.Their antifungal activities were tested against nine important phytopathogenic fungi, namely, Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica, Phytophthora inf estans, Paralepetopsis sasakii, Sclerotinia sclerotiorum, Botrytis cinerea, Verticillium dahlia and Bipolaris sorokinianum using the mycelium growth inhibition method in vitro. The results showed that those target compounds exhibited moderate to good antifungal activities against nine kinds of fungi. At the concentration of 50 μg/m L, compounds B-1 and B-12 inhibited growth of F. oxysporum at 92% and 87%, respectively, which were better than that of flutriafol(83%); compounds C-1 inhibited growth of F. oxysporum and B. cinerea at 86% and 89%, respectively, which was equivalent to that of flutriafol(96%, 85%).Their antibacterial activities were tested against five important phytopathogenic bacteria, namely, Xanthomonas oryzae, Xanthomonas campestris, Erwinia carotovora, Corn stalk rot and Ralstonia solanacearum from tobacco bacterial by the turbid meter test in vitro. Its biology research showed that those target compounds exhibited superior antibacterial activities against five kinds of bacteria. Remarkably, at the concentration of 200 and 100 μg/mL, compounds B-1, B-3, B-6, B-8, B-10, B-12 and B-13 exhibited the most potent inhibition against X. oryzae and R. solanacearum with 50% inhibition concentration(EC50) from 0.45 to 1.86 μg/m L and 1.97 to 20.51 μg/mL, respectively. The activities of compounds were better than that of bismerthiazol(92.61 μg/mL) and Kocide 3000(45.91 μg/m L); In vivo antibacterial activities tests demonstrated that the controlling effect of compounds B-3(76.1%), B-6(90.4%) and B-12(81.9%) against rice bacterial leaf blight were better than that of bismerthiazol(49.4%) and thiodiazole-copper(44.7%).