Design,Synthesis,and Insecticidal-Activity Studies Of Novel 4,5-Dihydropyrazolo[1,5-A]Quinazoline Derivatives

With the unreasonable application of chemical pesticides and the increasingly stringent requirements for pesticide development,the resistance of pests has become increasingly serious,resulting in a substantial increase in the use of pesticides,but the effectiveness of pest control has been greatly reduced.On the other hand,it also faces environmental problems such as the difficulty of degradation of pesticides,high residues,and high toxicity to non-target organisms.As a result,the useful life of commercial pesticides has been greatly reduced.Under this severe situation,the research team adopted a framework transition strategy in the early stage and developed a new 5,5-disubstituted-4,5-dihydropyrazolo[1,5-a]quinazoline compounds,this scaffold compounds not only exhibits excellent insecticidal activity against Plutella xylostella larvae,but also has a more prominent toxic effect on field-resistant lines.Although such structures have good insecticidal activity,few related active compounds have been reported,based on the previous work of the research group,this research carried out further diversification of the 4,5-dihydropyrazolo[1,5-a]quinazoline scaffold,and found pesticide candidate compounds with better insecticidal activity to make it a candidate pesticide and this will speed up the pesticide research and development process,control the development of pest resistance,or mix it with commercial pesticides to extend the life of commercial pesticides.Based on the previous work of the research group,the research continued to transform the 4,5-dihydropyrazolo[1,5-a]quinazoline scaffold,at the same time,a method for efficiently synthesizing a 4,5-dihydropyrazolo[1,5-a]quinazoline scaffold using 5-amino-1H-phenylpyrazole and bromomalonate as raw materials has also been developed,and the4,5-dihydropyrazolo[1,5-a]quinazolines synthesized by this method do not rearrange the benzene ring substituents,and the backbone reduces one chiral center,and the backbone reduces one chiral center.A total of 51 4,5-dihydropyrazolo[1,5-a]quinazoline compounds were synthesized in this study and all the compounds were confirmed by ¹H NMR,¹³C NMR,and HRMS,and some compound structures were characterized by X-ray single crystal diffraction was characterized.The target compounds were screened for the indoor insecticidal activity against the 3rd instar larvae of the diamondback moth,P.xylostella by the immersion method,and some compounds showed excellent insecticidal activity.compounds 4aa,4ag,6a,8ab,11a and 4ba(LC₅₀ values ranging from 1.49 to 3.87 mg/L),which is significantly better than the insecticidal activity of indoxacarb(LC₅₀=4.82 mg/L),especially for compound 6a(LC₅₀=1.49 mg/L),which is better than fipronil(LC₅₀=1.80 mg/L).The structure-activity relationship shows that the compounds with excellent insecticidal activity all contain ester groups（monoesters or diesters）in the structure.It is speculated that ester compounds can increase the fat solubility of the compounds and make it easier to bind to targets.In this study,the insecticidal activity of some 4,5-dihydropyrazolo[1,5-a]quinazoline compounds against invasive pests of Spodoptera frugiperda and invasive Solenopsis invicta was also determined.The results showed that the scaffold have a certain insecticidal activity against S.frugiperda,and has a delayed onset effect on S.invicta.In summary,this research carried out the transformation of 4,5-dihydropyrazolo[1,5-a]quinazoline scaffold,and developed a synthetic method that does not contain chiral carbon and rearrangement of benzene ring substituents of 4,5-dihydropyrazolo[1,5-a]quinazoline scaffold.One compound with excellent insecticidal activity against P.xylostella larvae was obtained and has the potential to be developed into a new insecticide.This paper expands the structural diversity of 4,5-dihydropyrazolo[1,5-a]quinazolines,and provides a basis for the design and optimization of pesticide candidate compounds based on similar scaffolds.