Design,Synthesis And Insecticidal Activity Of Isoxazoline Derivatives

Isoxazoline and its derivatives are an important type of organic five-membered heterocyclic structure containing N and O atoms,with broad-spectrum pharmacological and biological activities,its active fragments are found in many natural products and small biological molecules and have important research and development value in the fields of chemical,pharmaceutical and pesticide.With the continuous innovation and exploration of green pesticides,isoxazoline compounds have triggered a research boom in the field of insecticides,as the latest generation of non-competitive antagonists that act onγ-aminobutyric acid receptors,it performs good insecticidal activity to pests such as Lepidoptera,Hemiptera,Thysanoptera,Acarina,etc.and the insecticides high efficiency,low toxicity and no cross resistance.In order to to further explore the application of isoxazoline compounds in terms of insecticidal activity,this paper uses Nissan Chemical’s commercial pesticides fluralaner as the lead compounds,modification and derivatization of part A in its structure,introducing piperidine ring,aminomethyl piperidine ring,pyridine ring and pyrimidine ring.First,using p-bromo-o-methyl benzoic acid and trifluoromethyl acetophenone as raw materials,the 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid intermediate was efficiently constructed through 1,3-dipole cycloaddition reaction.Subsequently,four series of 25 isoxazolines were designed and synthesized,22 of which were reported for the first time,the compounds have been characterized,analyzed and verified by~1H NMR and LC/MS.Finally,some of the target compounds were tested for insecticidal activity and isoxazoline compoundsⅢ-1,Ⅲ-5,Ⅲ-6,IV-1 andⅣ-3 showed good insecticidal activity.Among them,the lethality rates of compoundsⅢ-1 andⅣ-3 to the third instar larvae of Plutella xylostella reached 62.5%and 69.0%at a concentration of 2.5 mg/L.CompoundsⅢ-1 andⅣ-1 can be used as lead compounds for further research,isoxazoline compounds seriesⅠandⅡcan still further modify their piperidine ring and amide chain.