Brodifacoum 0.005%BB 0.25%TK Anticoagulant Rodenticide

                                                                              Brodifacoum

Brodifacoum is a highly lethal 4-hydroxycoumarin vitamin K antagonist anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides. It is typically used as a rodenticide, but is also used to control larger pests such as possum.

Brodifacoum has an especially long half-life in the body, which ranges up to nine months, requiring prolonged treatment with antidotal vitamin K for both human and pet poisonings. It has one of the highest risks of secondary poisoning to both mammals and birds. Significant experience in brodifacoum poisonings has been gained in many human cases where it has been used in attempted suicides, necessitating long periods of vitamin K treatment. In March 2018, cases of severe coagulopathy and bleeding associated with synthetic cannabinoid use contaminated with brodifacoum were reported in five states of the US.

Brodifacoum is a derivative of the 4-hydroxy-coumarin group. Compound 1 is the starting ester needed to synthesize brodifacoum. To obtain this starting compound, a simple Wittig condensation of ethyl chloroacetate with 4’-bromobiphenylcarboxaldehyde is accomplished. Compound 1 is transformed into 2 by consecutive hydrolysis, halogenation to form an acid chloride, and then reacted with the required lithium anion. This is done using KOH and EtOH for hydrolysis, and then adding SOCl₂ for chlorination to form the acid chloride which reacts with the addition of lithium anion. Compound 2 is then transformed using organocopper chemistry to yield compound 3 with good stereoselectivity of about 98%. Typically, a Friedel-Crafts type cyclization would then be used to obtain the two-ring system portion of compound 4, but this results in low yield. Instead, trifluoromethanesulfonic acid in dry benzene catalyzes the cyclization with good yield. The ketone is then reduced with sodium borohydride yielding a benzyl alcohol. Condensation with 4-hydroxycoumarin under HCl yields compound 5, brodifacoum