Fluoronation of alpha-haloalkyl ketones
The present invention provides methods and processes for producing α-fluoroalkyl ketones from non-fluoro α-haloalkyl ketones using a fluorohydrogenate compound. In some embodiments, the fluorohydrogenate compound is an ionic liquid. One particular method of the invention utilizes a fluorohydrogenate ionic liquid compound of the formula: Q + [F.(HF) n ], wherein Q 30 is an onium cation and n is a number from 0 to 3.
1. A method for producing an α-fluoroalkyl ketone of the formula:
said method comprising contacting a non-fluoro α-haloalkyl ketone of the formula:
with a fluorohydrogenate salt in the absence of an organic base and under reaction conditions sufficient to produce an α-fluoroalkyl ketone of the Formula I,
wherein
Ar is aryl or heteroaryl, each of which is optionally substituted;
X is a non-fluoro halide;
each of R a and R b is independently hydrogen, alkyl or halide;
provided when R a , R b or both of the non-fluoro α-haloalkyl ketone of Formula II is a non-fluoro halide, then the corresponding R a , R b or both of α-halofluoroalkyl ketone of Formula I that is produced can also be fluoride.
2. The method of claim 1 , wherein said reaction is conducted in an organic solvent.
3. The method of claim 1 , wherein Ar is optionally substituted aryl.
4. The method of claim 3 , wherein Ar is substituted with one or more substituents, each of which is independently selected from the group consisting of C 1-12 alkyl, C 1-12 alkoxy, aryloxy, halide, cyano, and nitro.
5. The method of claim 1 , wherein said fluorohydrogenate salt is of the formula: Q 30 [F.(HF) n ], wherein Q + is an onium cation and n is a number from 0 to 3.
6. The method of claim 5 , wherein 1<n<3.
7. The method of claim 5 , wherein Q + is a quaternary ammonium cation, a quaternary phosphonium cation or a quaternary thiazolium cation.
8. The method of claim 7 , wherein Q + is a quaternary ammonium cation.
9. The method of claim 8 , wherein Q + is selected from the group consisting of N-ethyl-N-methylimidazolium, N-methyl-N-propylpyrrolidinium or N-methyl-N-butylpyrrolidinium, and a combination thereof.
10. The method of claim 1 , wherein said fluorohydrogenate salt is an ionic liquid.
11. The method of claim 1 , wherein R a and R b are hydrogen.
12. The method of claim 2 , wherein the organic solvent comprises dichloromethane, chloroform, tetrahydrofuran, ether, toluene, mono-, di- or triglyme, or a combination thereof.
13. The method of claim 1 , wherein the amount of said fluorohydrogenate salt used is from about 1 to about 3 equivalents relative to the amount of said non-fluoro α-halomethyl aryl ketones.
14. The method of claim 1 further comprising the steps of contacting the reaction mixture with an acidic aqueous solution.
15. The method of claim 14 , wherein said acidic aqueous solution comprises hydrochloric acid, aqueous HF, sulfuric acid, nitric acid, or any water soluble Lewis acid.
16. The method of claim 1 , wherein said α-fluoromethyl aryl ketone is an α-perfluoromethyl aryl ketone.
17. A method for producing an α-fluoroalkyl aryl ketone, said method comprising contacting a non-fluoro α-haloalkyl aryl ketone with a fluorohydrogenate ionic liquid in the absence of an organic base and under reaction conditions sufficient to produce an α-fluoroalkyl aryl ketone.
18. The method of claim 17 , wherein said α-fluoroalkyl aryl ketone is α-fluoromethyl aryl ketone.
19. The method of claim 17 , wherein said fluorohydrogenate ionic liquid comprises N-methyl-N-propylpyrrolidinium fluorohydrogenate, N-methyl-N-butylpyrrolidinium fluorohydrogenate, N-methyl-N-ethylimidazolium fluorohydrogenate or a mixture thereof.