Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1998-02-05
2000-02-29
Reamer, James H.
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
568319, 568321, 568361, 568398, 568403, C07C 4554
Patent
active
060311398
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the preparation of .alpha.-fluoroketones.
.alpha.-Fluoroketones are valuable compounds, both as intermediates in the preparation of biologically active molecules and as biologically active molecules in their own right. There is no satisfactory direct method of replacing the .alpha.-hydrogen of a ketone by fluorine, but by first making an enol ester or a trialkylsilyl ether of the parent ketone, and then treating either of these with an electrophilic fluorinating agent, good yields of .alpha.-fluoroketone can be obtained.
Examples of published attempts to prepare .alpha.-fluoroketones include the following: Chem. 1980, 16, 19) Puy, D Nalewajek, G A Shia, W J Wagner and R L Frenett; J Org Chem, 1991, 56, 5962) and M Zupan; Tetrahedron, 1989, 45, 6003) (tetrafluoroborate) (G S Lal; J Org Chem, 1993, 58, 2791) 35 and T Tsushima, K Kawada and T Tsuji; Tetrahedron Letters, 1982, 23, 1165) 4846) 187) bis(tetrafluoroborate) (G S Lal; J Org Chem, 1993, 58, 2791) Kawada and K Tomita; J Am Chem Soc, 1990, 112, 8563).
These electrophilic fluorinating agents are often difficult to prepare and sometimes difficult to handle, or they are expensive to obtain. The use of elemental fluorine for such fluorinations would seem to afford certain advantages. When enol acetates have been treated with fluorine in the past. "no matter how mild the conditions used the reaction resulted in a very complicated mixture and no .alpha.-fluoroketones could be detected". (S Rozen and Y Menachem: J Fluorine Chem 1980, 16, 19).
The use of elemental fluorine for the fluorination of trialkylsilyl ethers has been attempted by G L Cantrell and R Filler (J Fluorine Chem, 1985, 27, 35) and by S Purrington, N V Lazaridis and C L Bumgardner (Tetrahedron Letters, 1986, 27, 2715). Cantrell et al found that when a dichloromethane solution of the trimethylsilylenol ether of cyclohexanone was treated with elemental fluorine, only cyclohexanone was obtained. Purrington et al was successful in obtaining .alpha.-fluoroketones but their reactions were carried out at -78.degree. C. and the solvent was chlorotrifluoromethane. Accordingly the reactions were carried out at a temperature which is expensive to maintain and in a solvent which has been banned under the terms of the Montreal Protocol on the use of chlorofluorocarbons.
Surprisingly we have now found that enol esters and trimethylsilyl ethers of ketones can be treated with elemental fluorine at ambient temperatures in convenient, available solvents to give .alpha.-fluoroketones in good yields. In one aspect this invention is the use of a polar organic solvent in the direct fluorination, to make an .alpha.-fluoroketone, of an enol ester or enol trialkylsilyl ether of a compound containing a tautomerisable ketone group, the solvent being relatively inert to fluorine and one in which the selected ester or ether is relatively stable to hydrolysis. Enol esters are preferred over trialkylsilyl ethers.
According to the present invention there is more particularly provided a process for the preparation of an .alpha.-fluoroketone of formula R--CHFC=O.R' which includes the steps of converting a ketone of formula R--CH.sub.2 C=O.R' into a ketone derivative which is an enol ester of formula R--CH=C(OCO.R")R' or is a trialkylsilyl ether of formula R--CH=C(OSiR".sub.3).R', followed by the reaction of that ketone derivative, dissolved in a polar organic solvent which is relatively inert towards fluorine and in which the ketone derivative is relatively stable to hydrolysis, with elemental fluorine. The essence of the substrate, however, is that it is a compound containing an enol ester or enol trialkylsilylether of a tautomerisable ketone function and, except for the double bond of the enol group, relatively resistant to fluorination.
In the above formulae, the groups R and R' are independently selected from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl and substituted aryl, said groups R and R' being optionally joined to one another to form a cyclic structure such as a ste
REFERENCES:
patent: 5243080 (1993-09-01), Van Der Puy et al.
"Preparation of .alpha.-Fluoroaldehydes and .alpha.-Fluoroketones Using Dilute Fluorine," Purrington et al., Tetrahedron Letters, vol. 27, No. 24, pp. 2715-2716, 1986.
Chambers Richard Dickinson
Hutchinson John
F2 Chemicals Limited
Reamer James H.
LandOfFree
Preparation of .alpha.-fluoroketones does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preparation of .alpha.-fluoroketones, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preparation of .alpha.-fluoroketones will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-684541