Synthesis And Characterization Of Phenylpyrazole Esterification,Alkylation,Hydrazide And Amino Oxime Ester Derivatives

With the continuous development of agricultural technology,pesticides play an irreplaceable role in the control of pests in the agricultural production process.In recent years,due to the abuse of a large number of pesticides,the resistance of target organisms has increased,and the ecological environment has been severely damaged.Therefore,it has become an inevitable trend to develop a new type of green pesticide with high efficiency,high environmental protection,non-interaction resistance and low residue.Fipronil,a representative compound of phenylpyrazole insecticides,is a broad-spectrum insecticide with high biological activity.In order to save the cost of research and development of pesticides,this paper draws on the“Me-too”strategy and the principle of pharmacologically active group splicing based on the development of derivative drugs.A series of phenylpyrazole esterification,alkylation,hydrazide and amoxime ester derivatives based on the fipronil phenylpyrazole skeleton were synthesized.The main work of this thesis is as follows:1.Eight phenylpyrazole esterification compound W were synthesized by solvothermal method.Fipronil was used as the lead compound,eight alkyl alcohols with different structures were selected as reactants and reaction solvents,FeCl₃was used as a catalyst to provide acidic conditions for the reaction.Then,phenylpyrazole esterification compound W was used as a substrate,DMF was used as a solvent,and Na H was used as a basic reagent to react with 6 kinds of bromoalkanes,and finally 20phenylpyrazole esterification and alkylation compound X were generated.All compounds were characterized by IR,¹HNMR,X-Ray single crystal diffraction.The reaction mechanism was studied and the reaction conditions were optimized,the best reaction conditions for the synthesis of compound X_1b:the basic reagent was Na H,the solvent was DMF,the reaction temperature was 50℃,and the reaction time was 5 h.The chromatographic capacity factor log K determined by reversed-phase HPLC was used to study the hydrophobic properties of some compound X,which will provide a reference for subsequent research on its biological activity and test its structure-activity relationship.2.Fipronil was used as a lead compound,it was reacted with n-propanol under the condition of FeCl₃as a catalyst to synthesize phenylpyridazole carboxylic acid ester product.The carboxylic acid ester is then reacted with hydrazine hydrate to generate hydrazide intermediate.10 compound IV were synthesized by reacting hydrazide intermediates with acid chlorides with different structure,compound IV₇and IV₁₀were selected as raw materials to react with phenylacetyl chloride and propionyl chloride to synthesize 2 compound V.The synthesized compounds were characterized by IR,¹HNMR and LC-MS.And speculate the reaction mechanism of phenylpyrazole hydrazide derivatives:under acidic conditions,cyano（—C≡N）on the fipronil structure was hydrolyzed to form a carboxylic acid ester,carboxyl esters undergo nucleophilic-elimination reaction with hydrazine to obtain hydrazide intermediates,the hydrazide intermediate was nucleophilic-eliminated with the acid chloride again to give compound IV and V.Optimizing the synthesis conditions of phenylpyrazole hydrazide derivatives,the best conditions for compound IV were obtained.3.Fipronil was used as a lead substrate,hydroxylamine was prepared by neutralizing hydroxylamine hydrochloride with triethylamine.The hydroxylamine was then reacted with the cyano group at position 3 of the fipronil pyrazole ring to synthesize the amoxime intermediate.Ammoxime intermediates was used as raw materials,THF was the solvent,Na H was the basic reagent,and it reacted with sulfonyl chloride with different structures to synthesize 9 phenylpyrazole aminooxime ester compound H.The structure was verified by characterization methods such as IR,¹HNMR,X-Ray single crystal diffraction,the single crystal structure of compound H₁was also obtained.In addition,3 phenylpyrazole aminooxime ester compound L were synthesized by using ammoxime intermediate as raw material,dichloromethane as solvent and triethylamine as basic reagent,and reacting with acryloyl chloride,and structure verification by IR,¹HNMR and X-Ray single crystal diffraction.The possible reaction mechanism for the synthesis of compound H was speculated.Optimum conditions for the synthesis of compound H were obtained through optimization experiments on the synthesis conditions of phenylpyrazole aminooxime derivatives.