Methods for preparing 3-substituted-6-trifluoromethyl pyridines and methods for using 6-trichloromethyl halogenated pyridines
View Patent ↗3-substituted-6-trifluoromethyl pyridines are useful synthetic intermediates in the preparation of the N-substituted (6-haloalkylpyridin-3-yl)alkyl sulfoximines, which are useful in forming potent insecticides. Methods of forming such 3-substituted-6-trifluoromethyl pyridines are disclosed. Also disclosed are methods of using 6-trichloromethyl halogenated pyridines to form 3-substituted-6-trifluoromethyl pyridines are disclosed.
1. A method of forming a 3-substituted-6-trifluoromethyl pyridine, the method comprising reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine.
2. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl-2,3-dihalo pyridine with a fluorinating agent to form a 6-trifluoromethyl-2,3-dihalo pyridine.
3. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 2,3-dichloro-6-trichloromethyl pyridine with a fluorinating agent to form a 2,3-dichloro-6-trifluoromethyl pyridine.
4. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl halogenated pyridine with antimony pentafluoride to form a 6-trifluoromethyl halogenated pyridine.
5. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl halogenated pyridine with hydrogen fluoride to form a 6-trifluoromethyl halogenated pyridine.
6. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl-(4-halo)-2,3-dichloro pyridine with a fluorinating agent to form a 6-trifluoromethyl-(4-halo)-2,3-dichloro pyridine.
7. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl-2,3-dichloro pyridine with antimony pentafluoride to form a 2,3-dichloro-6-trifluoromethyl pyridine.
8. The method of claim 1 , wherein reacting a 6-trichloromethyl halogenated pyridine with a fluorinating agent to form a 6-trifluoromethyl halogenated pyridine comprises reacting a 6-trichloromethyl-2,3-dichloro pyridine with hydrogen fluoride to form a 2,3-dichloro-6-trifluoromethyl pyridine.
9. The method of claim 1 , further comprising reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent to form a 3-halo-6-trifluoromethyl pyridine.
10. The method of claim 9 , wherein reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent to form a 3-halo-6-trifluoromethyl pyridine comprises reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent comprising hydrazine and bleach to form a 3-halo-6-trifluoromethyl pyridine.
11. The method of claim 9 , wherein reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent to form a 3-halo-6-trifluoromethyl pyridine comprises reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent comprising copper and propionic acid to form a 3-halo-6-trifluoromethyl pyridine.
12. The method of claim 9 , wherein reacting the 6-trifluoromethyl halogenated pyridine with a reducing agent to form a 3-halo-6-trifluoromethyl pyridine comprises reacting a 2,3-dichloro-6-trifluoromethyl pyridine with a reducing agent to form a 3-chloro-6-trifluoromethyl pyridine.
13. The method of claim 9 , further comprising reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent to form a 3-substituted-6-trifluoromethyl pyridine.
14. The method of claim 13 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent to form a 3-substituted-6-trifluoromethyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent comprising an alkyl magnesium bromide to form a 6-trifluoromethyl-3-alkyl pyridine.
15. The method of claim 14 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent comprising an alkyl magnesium bromide to form a 6-trifluoromethyl-3-alkyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent comprising an ethyl magnesium bromide to form a 3-ethyl-6-trifluoromethyl pyridine.
16. The method of claim 13 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent to form a 3-substituted-6-trifluoromethyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of a metal-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine.
17. The method of claim 16 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of a metal-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of a nickel-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine.
18. The method of claim 16 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of a metal-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of an iron-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine.
19. A method of forming a 3-substituted-6-trifluoromethyl pyridine, the method comprising:
fluorinating a 6-trichloromethyl halogenated pyridine to form a 6-trifluoromethyl halogenated pyridine;
reducing the 6-trifluormethyl halogenated pyridine to form a 3-halo-6-trifluoromethyl pyridine; and
reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent to form the 3-substituted-6-trifluoromethyl pyridine.
20. A method of using a 6-trichloromethyl halogenated pyridine to form a 3-substituted-6-trifluoromethyl pyridine, the method comprising reacting the 6-trichloromethyl halogenated pyridine with at least one of antimony pentafluoride and hydrogen fluoride to form a 6-trifluoromethyl halogenated pyridine.
21. The method of claim 20 , further comprising reacting the 6-trifluoromethyl halogenated pyridine with either both hydrazine and sodium hypochlorite or both copper and propionic acid to form a 3-halo-6-trifluoromethyl pyridine.
22. The method of claim 21 , further comprising reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of at least one of a nickel-based and an iron-based catalyst to form the 3-substituted-6-trifluoromethyl pyridine.
23. The method of claim 20 , wherein reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of at least one of a nickel-based and an iron-based catalyst to form the 3-substituted-6-trifluoromethyl pyridine comprises reacting the 3-halo-6-trifluoromethyl pyridine with a Grignard reagent in the presence of at least one of a nickel-based and an iron-based catalyst to form a 3-substituted-6-trifluoromethyl pyridine of formula I:
wherein
R represents hydrogen, an alkyl group, or an aryl group.