Synthesis And Biological Activity Of Pyrazole Acylthiourea And Thiazole Imine Compounds

In the21st century, under the guidance of the concept of sustainable development, Chi-na’s divine mission with pesticides is to develop the green products of ultra-efficiency,lowtoxicity and residue,environmental compatibility and good harvest assurance. In addition,some kinds of pesticides gradually have resistance to insects because of the long time use andhigh dose use. So we need not only optimization of existing structures but also looking fornew kinds of pesticides with new mechanisms, new structures. Heterocyclic compounds havea wide application for its pharmacological activity and biological activity, so designing anddiscovering new heterocyclic compounds in drug research are of great importance.Heterocyclic pesticides are the most rapidly developing pesticides in recent years, especiallynitrogen-containing heterocyclic compounds is the subject of the development of pesticide,the pyrazole is extremely important of it.Pyrazole, acylthiourea and thiazole compounds all have a wide range of biologicalactivity and environmental compatibility by studying a large number of literature and therelevant patent; In addition, difluoromethyl and imine are active group.In order to developcompounds with high biological activity, in this thesis, a new series of difluoromethylsubstituted pyrazole compounds were designed and synthesized according to the principle ofactive group association and bioisososterism, they were41difluoromethyl substitutedperazole formyl thioureas compounds (A1-A41) and31difluoromethyl substituted thiazoleimine compounds(B1-B31). All target compounds were not reported by any literature.Thestructures of the title compounds A、B were shown in the figure below:R1=H, Me,Cl,C3F7,NO2,OH,F,CF3, In this thesis, with3-difluoromethyl-1-methyl-1H-pyrazol-4-formyl isothiocyanateintermediate synthesized from difluoro ethyl acetoacetate and triethoxy methane as startingmaterial, the intermediate reacted with various substituted aniline, the six-step process toprepare difluoromethyl substituted pyrazole acylthiourea compounds(A) was studied,whichwas nucleophilic substitution、1,4-conjugate addition、cyclization、hydrolysis、chloridereaction et al. Title compounds (A) then cyclized with bromoacetone to obtain difluoromethylsubstituted pyrazole thiazol imine compound (B).In this thesis, All72chemicals were characterized by1H NMR and MS and the meltingpoint of the compounds were measured. Bioassay for all novel compounds were carried out,the preliminary results showed that: some compounds such as A33, A35, A39, A40, A41, B7,B11and B24exhibited insecticidal activity,and A18, A24exhibited fungicidal activity at thedosage of500mg/L, lethal rate of mythimna sepatara treated with compound A33, A35, A39,A40and A41were50%,80%,80%,80%and80%. lethal rate of aphis medicaginistreated with compound B7, B11and B24were60%,70%and70%. Inhibition rate ofrhizoctonia solani treated with compound A18was37%, Inhibition rate of erysiphaceaetreated with compound A18was20%, inhibition rate of corn rust treated with compoundA18was80%, Inhibition rate of botrytis cinerea treated with compound A24was45%.In this thesis, difluoromethyl substituted pyrazole ring stitched in the acyl moiety of theacyl thioureas, difluoromethyl substituted pyrazole ring and thiazole imine structure stitchedtogether firstly.72novel compounds were not reported in the literature.it will lay a certainfoundation for the study of heterocyclic pesticides. However, the biological activity of thecompounds had a certain gap to the control, the structures were worth for further optimizing.