Design, Synthesis And Bioactivity Study Of The Lsophthalamide Compounds

The appearance of bisamide insecticides made the pesticide industry excited.The new mechanism of action,novel chemical structure,and extraordinary insecticidal efficacy lead the insecticide market trend.However,with the long-term application and unreasonable use of such pesticide products,the cross-resistance of pests has intensified,and the sensitivity of target receptors has gradually decreased,and the problem of pest resistance has become increasingly prominent.At this time,the advent of Broflanilide has become the focus of public attention.Major universities,research institutes,and companies around the world are vying to use it as the lead compound,hoping to develop new pesticide products that are more efficient,low-toxic,green and pollution-free.In this thesis,the Japanese Mitsui Company publicly reported Broflanilide as the lead compound.The skeleton is split into three parts A,B and C for structural modification.Among them,part A uses the concept of bioelectronic isostery to replace the benzene ring structure with a pyridine ring,part B introduces a cyano structure with different carbon chain lengths or a cyclopropyl methyl group with a large steric hindrance,and different halogen elements such as bromine and iodine or trifluoromethyl groups are introduced into the 2,6positions of the benzene ring of part C.Designed and synthesized 42 novel isophthalamide compounds that have not been reported in the literature.All compounds were confirmed by ¹H NMR and LC-MS analysis.According to the biological activity test results of the compound,the structure-activity relationship is summarized as follows:For part A,the optimal substituent on the 4th position of the pyridine ring is the F atom;The optimal substituents on the N atom of the amide bond of the B part vary with the changes of the substituents at the 2,6 positions on the benzene ring of the C part.When the 2,6 positions of the benzene ring of the C part are Br,Br;Br,CF₃;Br,I At this time,the optimal substituents of part B are cyanomethyl,cyanoethyl,and cyanomethyl,and the biological activity of the compound gradually decreases with the growth of the cyano carbon chain of part B.When the 2 and 6 positions of the benzene ring of the C part are I and CF₃respectively,the optimal substituent of the B part is cyanobutyl,and the biological activity of the compound gradually increases with the growth of the cyano carbon chain of the B part.For part C,the best substituents at the 2,6 positions of the benzene ring are I,CF₃,followed by Br,I;Br,CF₃,and the least active is Br,Br.The biological activity of 23 of the 42 compounds designed and synthesized in this thesis is superior to that of the already marketed products tetrachloroandiamide and chlorantraniliprole（C1-1,C2-1,C2-2,C2-4,C2-5,C2-7,C-11,C2-12,C2-15,C3-1～C3-10,C3-14,C3-15,C4-1,C4-3）.there are 3 compound whose biological activity is better than that of tetrachlorantraniliprole and comparable to that of broflanilide（C1-6,C2-10,C4-4）.There are 4 compounds with good acaricidal activity（C2-6,C2-10,C3-6,C3-10）,and the control effect on tetranychus cinnabarinus at a very low dose of 10 mg/L is more than 80%.