Synthesis And Characterization Of The Fipronil Amidation,Alkylation And Oxime Derivatives

With the continuous development of organic synthetic pesticides,agricultural insecticides play a key role in ensuring the increase of crop yields.Therefore,the development of new high efficiency,low toxicity,low residue of green insecticide has become an inevitable trend,which makes the cost and difficulty of the research and development of new pesticides is also greatly improved.In the context of China's efforts to support innovation,many scientific research institutions use the"Me-too"strategy to develop more derivative drugs.Fipronil is a highly efficient insecticidal and broad-spectrum pyrazole insecticide,which limits its use because of its high toxicity to non target organisms.This thesis chooses the Fipronil as lead compound,and made structural modification on it,designed and synthesized three kinds of derivatives based on Fipronil skeleton.The main work of this thesis is as follows:?1?Fipronil was used as the parent structure,THF as solvent,NaH provides alkaline conditions,fourteen Fipronil acrylamide derivatives A₁-A₁₄ were synthesized,the structure were characterized by IR and ¹HNMR,and the structure of compound A₁₃was confirmed by X-Ray single crystal diffraction.The application of compound A in the protection of tussah was studied,the toxicity of four instar Antheraea pernyi was investigated,results showed that the toxicity of amidation modified Fipronil is low,the median lethal concentration of compound A₂ and compound A₃ were 20 times to Fipronil,and the median lethal concentration of compound A₄,compound A₉ and compound A₁₄4 were 10 times to Fipronil.The effect of compound A on the control of tussah fly maggot was also investigated,the results showed that at 500 mg/L and 200mg/L,the compounds A all met the control effect and the screening of normalized cocoon rate.The effects of compound A concentration of 200 mg/L on the propagation performance of Antheraea pernyi were studied,the results showed that the compound A did not affect the breeding performance of tussah.The overall results indicated that Fipronil amide derivatives have good application prospects in the protection of tussah.?2?Fipronil was used as the parent structure to react with brominated alkanes DMSO is used as solvent,potassium carbonate provides basic conditions.7 kinds of fipronil substituted alkylated derivatives were obtained.Fipronil is the precursor compound to react with the bromo alkane,DMF is used as solvent,potassium carbonate provides basic conditions.8 kinds of fipronil substituted alkylated derivatives are obtained.The structure were characterized by melting point,IR and ¹HNMR,and the structure of compound S₆,D₂,D₆ and D₈ was confirmed by X-Ray single crystal diffraction.The optimum conditions for the synthesis of D₂ were as follows:Potassium carbonate is used as an alkaline reagent and the amount is 1.5 EQ,DMSO as a solvent,60?for reaction 12 hours,the D₂ yield can reach 78%.Finally,the reaction mechanism of D₅,D₆,D₇ and D₈ was proposed.?3?Fipronil was used as the parent structure to react with hydroxylamine hydrochloride,acetonitrile as solvent,three ethylamine to provide basic conditions,and the product of Amidoxime fipronil was obtained;Fourteen kinds of derivatives of fipronil oxime were synthesized from amidoxime fipronil and acyl chloride.The structure were characterized by melting point,IR and ¹HNMR,and the structure of amidoxime fipronil,compound E₁₁1 and E₁₂ was confirmed by X-Ray single crystal diffraction.Seven kinds of derivatives of the oxime etherification of fipronil were synthesized from amidoxime fipronil as raw material,acetonitrile as solvent,NaH provided basic conditions and reaction with bromo alkanes.Finally,the reaction of benzonitrile and fipronil to form triazole fipronil,which is characterized by IR,NMR and MS.The single crystal structure of triazole fipronil is also obtained.The possible reaction mechanism for the formation of three azole fipronil is proposed.