Synthesis And Bioactivities Of Neonicotinoids Compounds Containing 2(5H)-furanone Active Structural Moieties

Neonicotinoid compounds,the fourth generation of pesticides,play an important role in global crop protection.However,the resistance and bee toxicity problems have become increasingly serious due to the overuse of neonicotinoid insecticides.As a result,their application and development are restricted severely.So,we choose natural product Stemofoline as a lead compound,its active pharmacophore 2（5H）-furanone was further modified and introduced into the framework structure of neonicotinoid compound.Forty-six neonicotinoid compounds containing 2（5H）-furanone were successfully synthesized,whose structures were confirmed by nuclear magnetic resonance(¹H NMR,¹³C NMR)and high-resolution mass spectrometry（HRMS）.1.3-halogen-2（5H）-furanone neonicotinoids series.Halogen-containing 2（5H）-furans intermediates were synthesized by cyclization and etherification from viscous halogen acids and alcohols.The ketone intermediates were then combined with chloropyridinylamino via a Michael addition-elimination reaction.Thirty-four target compounds containing3-halogen-2（5H）-furanone were synthesized successfully.Most of the compounds had insecticidal activitives against aphids and rice planthoppers.Compound B13 had a 100%mortality against aphids at a concentration of 100 ppm,its pesticidal activity against rice planthoppers is 93.18%which is equivalent to that of commercialized imidacloprid（92.55%）.Activity test showed that introducing fluorine atom into the active structure of 2（5H）-furanone can improve the insecticidal activity of the target compounds2.5-Alkoxy-2（5H）-furanoneneonicotinoidsseries:Halogen-free5-alkoxy-2（5H）-furanone intermediates was designed to investigate the effect of halogen atoms in the active structure of 2（5H）-furanone on the insecticidal activity of the target compounds.Twelve compounds were synthesized by cyclization and etherification from chloroacetaldehyde and glyoxylic acid.This method expanded the structural diversity of the neonicotinoids containing 2（5H）-furanones.The derived compounds had insecticidal activities against aphids and rice planthoppers.Compound C09 has a 100%mortality against aphids at a concentration of 100 ppm,its pesticidal activity against rice planthoppers is 94.33%which is close to that of commercial imidacloprid（92.55%）.The results of the activity test showed that when the halogen atom in the third active site of the target compounds 2（5H）-furanone were replaced with a hydrogen atom,their biological activities can be improved.