Synthesis And Biological Assays Of Two Fluoride 4-hydroxycoumarin Anticoagulant Rodenticides

In this paper, we design two new anticoagulant rodenticides A and B with 4-hydroxy-coumarin. We also proposed the theory to increase the acute toxicity and resolve the resistance problem by adding fluoride to the existing second generation anticoagulant rodenticides.Firstly, we synthesized the fluoroacetic acid sodium, and fluoroacetic chloride. We also explored two different ways to synthesize the fluoroacetic chloride. One is come from the material of the fluoroacetic acid, and the other way is made from the material of the fluoroacetic acid sodium. At last, we chose the second way as the best method.Secondly, we use 4-bromoaniline and cinnamic acid as original material to synthesize 4-biphenyl bromide, cinnamoyl chloride and 4-bromine-4'-cinnamoylbiphenyl. Then, making use of these intermediates, we can synthesize M, N. Besides, the optimum methods were also confirmed.Then, the structure of all the inmediates, such as fluoroacetic chloride,4-biphenyl bromide, cinnamoyl chloride, and 4-bromine-4'-cinnamoyl biphenyl were demonstrated by IR and other means. Besides, we also test and verificate the synthesis routes of various immediates to find the opitimal reaction conditions. Finally, by the test of IR,1H NMR, melting point determination, and other pthysical and chemical methods, we conculded that the target product-novel anticoagulant rodenticides A and B were synthesized.Lastly, both the acute orally toxicity and the Palatability of the desired product A and B were tested in the no-choice and choice experiments. Our statistics demonstrate that the introduction of fluoride acetyl into the bromine position of the bromodialone leads to an enormous increase in the acute toxicity. The novel compounds A and B have both merits of acute and chronic rodenticides, and their acute toxicity increases gradually with the decrease of the group connected to fluoride acetyl.