Synthesis, Characterization And In-vivo Evaluation Of Three Novel And Fluorinated Anticoagulant Rodenticides

Anticoagulant rodenticides have good palatability and are safe to non-target animals, which have become the leading rodenticides. However, using them, the rats die slowly. Therefore, many new rodenticides are being developed and tested in many institutes worldwide, which is important to the society.In this work, five fluorinated intermediates of drug were synthesized: 4-(2-fluoroethoxy)chalcone (M1),4-fluoroacetamidochalcone (M2),4-(2-fluoroethoxy)acetop-henone (M3),4-(2-fluoroethoxy)phenyl methyl ketone (M4),4-acetylphenyl-4-(2-fluoroethox-y)benzoate (M5). And the classic structure of three novel and fluorinated anticoagulant rodenticides was provided, which were based on 4-hydroxycoumarin or 1,3-indandione:3-[3-(4-fluo roacetamido)phenyl-3-hydroxy-1-phenylpropyl]-4-hydroxycoumarin (R1),2-[4-(2-flu-oroethoxy)benzoyl]-1,3-indandione (R2) and 2-{3-[4-(2-fluoroethoxy)Phenyl]acryloyl}-1,3-indandione (R3).Firstly, the synthesis of fluoroacetic chloride and 1-bromo-2-fluoroethane based on the raw materials of sodium fluroacetate and 2-chloroethanol, and the synthetic routines for each intermediate were compared. The optimum methods were confirmed. Secondly, making use of them, these above intermediates (M1～M5) were synthesized. Making use of M2 to react with 4-hydroxycoumarin to synthesize the drug of R1. Making use of M3 and M4 to react with 1,3-indandione respectively to synthesize the drug of R1 and R2, and these optimum reaction conditions were confirmed.The structures of (M1～M5) and (R1～R3) were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). So that we can conclude the desired products of R1, R2 and R3 were synthesized. In addition, both the acute orally toxicity and the feeding indexes of R1 and R2 were tested. The LD50 of R1 and R2 were 0.718 mg/kg and 0.693 mg/kg, the feeding indexes to R1 and R2 were 0.87 and 0.70, which reached A grade. The productions had good palatability and good control effect in the laboratory, which are good candidates of rodenticides.