Design,Synthesis And Insecticidal Activity Of Isoxazoline Derivatives

The invention of green pesticides is the main direction of the development of the pesticide industry in various countries.The exploration of new green pesticides can provide efficient approach for pest resistance management.Isoxazoline insecticides are novelγ-Aminobutyric acid-gated chloride channel disruptors with great development value.In this paper,a green synthesis method for important intermediates was established by using cheap and readily available organic boron reagents to prepare 83 isoxazoline derivatives containing tetrahydroquinoline,indole and different amines.Their insecticidal activities were determined,and the structure-activity relationship was analyzed.The results obtained in this paper were as follows:（1）A series of 25 new isoxazoline derivatives containing tetrahydroquinoline（I）were designed,synthesized and characterized by ¹H NMR,¹³C NMR and HRMS.The insecticidal activity of compounds I against Mythima separate,Acyrthosiphon pisum,Tenebrio molitor,and Culex pipiens pallens larvae were evaluated.The LC₅₀ value of compound I-25 against Mythima separate was 208.220μg/m L,and the LC₅₀ value of compound I-01,I-06,and I-13against Culex pipiens pallens larvae were 24.468,14.500,and 21.203μg/m L.The structure-activity relationship study showed that the type,position,spatial structure and quantity of the benzene ring substituent affected the insecticidal activity of compounds I.When the electron donating group was introduced to the ortho and para positions of the benzene ring,the insecticidal activity of compounds with methyl substitution was better than that of methoxy substitution;when the benzene ring was substituted by halogen atoms,the insecticidal activity of meta substitution was better than that of ortho and para positions,and chlorine atom and double substitution at the same position was beneficial to insecticidal activity.The introduction of a large steric group into the benzene ring was beneficial to the insecticidal activity.（2）A series of 30 new isoxazoline derivatives containing indole（II）were designed,synthesized and characterized by ¹H NMR and ¹³C NMR.The insecticidal activity of compounds II against Mythima separate,Acyrthosiphon pisum,Tenebrio molitor,and Culex pipiens pallens larvae were evaluated.The LC₅₀ values of compounds II-06,II-10,and II-11against Culex pipiens pallens larvae were 12.870,11.386,and 18.234μg/m L,respectively.It was indicated that the type and position of the indole ring substituent were significant to the insecticidal activity of compounds II.The introduction of an electron donating group into the indole ring was beneficial to the insecticidal activity,and the insecticidal activity of compounds with the methyl group was better than that with methoxy substitution at the same position;when the 5-position of the indole ring was an electron-withdrawing group,the weaker the electron-withdrawing ability was,the better the insecticidal activity was.Theoretical calculation analysis showed that the methyl substitution had little effect on HOMO,which was beneficial to the improvement of insecticidal activity;the introduction of strong electron-withdrawing nitro group was unfavorable,which was related to the dispersion of LUMO;the introduction of weak electron-withdrawing chlorine atom was beneficial to the insecticidal activity,and was related to HOMO distribution.It can be seen from MEP and ED that the introduction of heteroatoms such as N,O,and F with strong electronegativity was beneficial to the stability of isoxazoline derivatives and insecticidal activity,which was basically consistent with the conclusion obtained from the qualitative structure-activity relationship.（3）A series of 28 isoxazoline derivatives containing different amines（III）were synthesized,in which 25 were new compounds.The structures were characterized by ¹H NMR and ¹³C NMR;The insecticidal activity of compounds III against Mythima separate,Acyrthosiphon pisum,Tenebrio molitor,and Culex pipiens pallens larvae were evaluated.The LC₅₀values of compounds III-04,III-07,III-13,and III-16 against Culex pipiens pallens larvae were 1.374,1.755,1.969,and 1.545μg/m L,respectively.The LC₅₀ values of compounds III-05,III-06,and III-13 against Mythima separate were 37.246,49.059,and126.265μg/m L,respectively.The structure-activity relationship study showed that the N-substituted methyl group on the amide bond exhibited satisfactory insecticidal activity.