FIELD OF THE INVENTION
The present invention provides a process for fluorination of ketones to prepare a compound of formula I,

Formula I
wherein, R1 and R2 are aryl, alkylaryl, halogen substituted alkyl, or a combination thereof,
The compound of formula I produced by the process of the present invention represents a well-known class of compounds with a variety of important uses.

BACKGROUND OF THE INVENTION
The compounds of formula I are widely used as intermediates in pharmaceutical compositions and in polymer industry.
U.S. 2,859,245A discloses a process for preparation of organic fluorine compound by reacting a compound containing a carbonyl compound and sulfur tetrafluoride in anhydrous condition. The process is carried out at high temperature and high-pressure conditions. The use of sulfur tetrafluoride at high temperature is not safe.
WO 2011076687 provides a process for preparation of 1-bromo-3-(1,1-difluoroethyl)-2-fluorobenzene from 3-bromo-2-fluoroacetophenone using bis(2-methoxyethyl)aminosulfur trifluoride. The bis-(2-methoxyethyl) amino sulfur trifluoride is very expensive and is non-recyclable.
U.S. 4,143,078A describes a process for fluorination of methyl ketones using vaporized aqueous hydrogen fluoride at 190-400°C to form 2,2-difluoroalkane.
EP 01044952 describes a process for preparation of 2,3-difluoro-1-(1,1-difluorohexyl)benzene from 1-(2,3-difluorophenyl)hexanone using 1,2-ethane dithiol and borontrifluoride diethyletherate complex in presence of hydrogen fluoride and pyridine mixture. The reagents used for fluorination are highly complexed, expensive and hazardous.
The process known in the art are not economical and safe, which involves harsh reaction conditions and expensive reagents.
Therefore, there is a need to develop an economical and industrially viable process for fluorination of ketones.

OBJECT OF THE INVENTION
The object of present invention is to provide a process for fluorination of ketones to prepare compound of formula I using sulfur tetrafluoride at low temperature.

SUMMARY OF THE INVENTION
In first aspect, the present invention provides a process for preparation of a compound of formula I,

Formula I
wherein, R1 and R2 are selected from aryl, alkylaryl, halogen substituted alkyl, or a combination thereof,
comprising the steps of fluorinating a compound of formula II,

Formula II
wherein, R1 and R2 are aryl, alkylaryl, halogen substituted alkyl, alkylaryl or aryl group, provided that R1 and R2 are not same.
with sulphur tetrafluoride in presence of a Lewis acid.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, alkyl group is selected from methyl, ethyl, propyl, isopropyl, tert-butyl, n-butyl or like. The alkyl group may be substituted with a substituent selected from a group consisting of chloro, fluoro, bromo, iodo and alkoxy or the like.
As used herein, aryl group refers to a group selected from phenyl, pyridyl, naphthyl or like. The aryl group may be substituted with a substituent selected from a group consisting of alkyl, chloro, fluoro, bromo, iodo and alkoxy or the like.
As used herein, Lewis acid refers to an acid selected from a group consisting of hydrogen fluoride, boron trifluoride, arsenic trifluoride, phosphorus pentafluoride, titanium tetrafluoride and the like. The preferred Lewis acid for use in the process of the present invention is hydrogen fluoride.
As used herein, an inert solvent refers to a solvent selected from a group consisting of bromobenzene, chlorobenzene, dichlorobenzene, hexane, heptane, octane, dodecane, cyclohexane, cycloheptane, methylene chloride, ethylene dichloride, ethylidene chloride, propylene chloride, trimethtylene chloride, and the like.
As used herein, a base may be selected from a group consisting of carbonates, bicarbonates, hydroxides such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, cesium hydroxide or the like.
In an embodiment, the fluorination is carried out in anhydrous condition.
As used herein, anhydrous refers to a moisture level of less than 1000ppm and more preferably less than 500ppm.
In an embodiment of the present invention, the process is carried out in absence of solvent.
In an embodiment, fluorination is carried out in presence of anhydrous hydrogen fluoride.
In one embodiment, present invention provides a process for preparation of a compound of formula I, wherein sulfur tetrafluoride is having purity greater than 95%.
In an embodiment, the present invention provides a process for preparation of a compound of formula I having purity greater than 99%.
In one embodiment, the molar ratio of hydrogen fluoride to the compound of formula II is 1-10. Preferably, the molar ratio of sulphur tetrafluoride to the compound of formula II is 2-5.
In an embodiment, the sulphur tetrafluoride may contain sulphur hexafluoride, thionyl fluoride, sulfuryl chloride.
In another embodiment, the sulphur tetrafluoride is containing sulfuryl chloride is less than 0.5% and more preferably less than 0.1%.
In another embodiment, the sulphur tetrafluoride may be added continuously or lotwise, after all the raw materials have been added to the reactor.
In another embodiment, a mixture of hydrogen fluoride and sulphur tetrafluoride is stirred for 10 hours, preferably 6 hours, and more preferably 3 hours.
In another embodiment, the hydrogen fluoride is charged in a reactor at temperature below 10°C and the process is carried out at a temperature below 50°C and more preferably below 40°C and most preferably between 10-20°C.
In one embodiment, the process is carried out in a pressure range of 2-20 Kg/cm2 and more preferably between 2-10 Kg/cm2.
In one embodiment, unreacted sulphur tetrafluoride and/or hydrogen fluoride are recycled for further batches.
The present invention also provides a process for quenching of unreacted sulphur tetrafluoride and thionyl fluorides, thionyl chloride or like using an aqueous base.
In preferred embodiment, the base is metal hydroxide, the reaction mixture is quenched with an aqueous base after pressure venting.
In one embodiment, solvent used for extraction of product is selected from a group consisting of dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, or like.
In one embodiment, the selectivity of formation of compound of formula I is greater than 95% and the yield of formation of a compound of formula I is greater than 80%.
In one embodiment, a compound of formula I refers to 1-bromo-3-(1,1-difluoroethyl) benzene, 1-bromo-3-(1, 1-difluoroethyl)-2-fluorobenzene, 1-(1, 1-difluoroethyl)-2-fluoro benzene, 4-bromo-1-(1,1-difluoroethyl)-2-fluorobenzene, 4-bromo-2-(1,1-difluoroethyl)-1-fluorobenzene, 4-bromo-1-chloro-2-(1,1-difluoroethyl)-benzene, 4-bromo-1-(1,1-difluoropropyl)-2-fluorobenzene, 1-(1,1-difluoroethyl)-3-fluoro benzene, 2-(1,1-difluoroethyl)-1,3-fluorobenzene or like.
In one embodiment, a compound of formula II refers to 3-bromoacetophenone, 3-bromo-2-fluoroacetophenone, 2-fluoroacetophenone, 4-bromo-2-fluoroacetophenone, 5-bromo-2-fluoroacetophenone, 2-chloro-5-bromoacetophenone, 4-bromo-2-fluoroacetophenone, 3-fluoroacetophenone, 2,6-difluoroacetophenone or like.
The product may be isolated using a method selected from filtration, extraction, distillation, boil-off, crystallization or combination thereof.
The completion of the reaction may be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC), liquid chromatography (LC) and alike.
The reagents used in the above process are obtained commercially.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore, should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Preparation of 1-bromo-3-(1, 1-difluoroethyl) benzene
3-bromoacetophenone (50 g), anhydrous hydrogen fluoride (80 g) and sulphur tetrafluoride (120 g) were charged in a reactor. The reaction mass was maintained at 10°C stirred for 5 hours under pressure. After reaction, the pressure of the reactor was vented in aqueous sodium hydroxide scrubber. The reaction mass was quenched with aqueous sodium hydroxide solution and stirred. Dichloromethane was added in the quenched reaction mass and organic and aqueous layer were separated. The organic layer was concentrated to obtain crude product. The crude product was distilled under reduced pressure to isolate pure product.
Purity (GC %): 99%; Yield: 80%
Example 2: Preparation of 1-bromo-3-(1, 1-difluoroethyl)-2-fluorobenzene
3-bromo-2-fluoroacetophenone (54 g), hydrogen fluoride (80 g) and sulphur tetrafluoride (120 g) were charged in a reactor. The reaction mass was maintained at 10-15°C stirred for 4-6 hours under pressure. After reaction, pressure was vented in aqueous potassium hydroxide scrubber. The reaction mass was quenched with aqueous potassium hydroxide solution. Dichloromethane was added in the quenched reaction mass and layers were separated. The organic layer was concentrated to obtain crude product. The crude product was distilled under reduced pressure to isolate pure product.
Purity (GC %): 99%; Yield: 81%
Example 3: Preparation of 1-(1, 1-difluoroethyl)-2-fluoro benzene
2-fluoroacetophenone (34 g), anhydrous hydrogen fluoride (30 g) and sulphur tetrafluoride (120 g) were charged in a reactor. The reaction mass was maintained at 10°C stirred for 4 hours under pressure. After reaction, pressure was vented in aqueous potassium hydroxide scrubber. The reaction mass was quenched with aqueous sodium hydroxide solution. Dichloromethane was added in the reaction mass and separated organic and aqueous layer. The organic layer was concentrated to obtain crude product. The crude product was distilled under reduced pressure to isolate pure product.
Purity (GC %): 99%; Yield: 80%
Example 4: Preparation of 4-bromo-1-(1,1-difluoroethyl)-2-fluorobenzene
4-bromo-2-fluoroacetophenone (54 g), anhydrous hydrogen fluoride (40 g) and sulphur tetrafluoride (120 g) were charged in a reactor. The reaction mass was maintained at 10°C-15°C stirred for 4-6 hours under pressure. After reaction, pressure was vented in aqueous potassium hydroxide scrubber. The reaction mass was quenched with aqueous sodium hydroxide solution. Dichloromethane was added in the reaction mass and organic and aqueous layer were separated. The organic layer was concentrated to obtain crude product. Further crude product was distilled to isolate pure product.
Purity (GC %): 99%; Yield: 80%

CLAIMS:WE CLAIM:
1. A process for preparation of a compound of formula I,

Formula I
wherein, R1 and R2 are selected from aryl, alkylaryl, halogen substituted alkyl, provided that R1 and R2 are not same,
comprising the step of fluorinating a compound of formula II,

Formula II
wherein, R1 and R2 are same as defined above
with sulphur tetrafluoride in presence of a Lewis acid.
2. A process as claimed in claim 1, wherein the fluorination is carried at a temperature of 10°C to 50°C.
3. The process as claimed in claim 1, wherein the Lewis acid is selected from a group consisting of hydrogen fluoride, boron trifluoride, arsenic trifluoride, phosphorus pentafluoride and titanium tetrafluoride.
4. The process as claimed in claim 1, wherein the reaction is carried out without using any solvent.
5. The process as claimed in claim 1, wherein the reaction involves quenching in presence of a base selected from a group consisting of carbonates, bicarbonates, hydroxides such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and cesium hydroxide.
6. The process as claimed in claim 1, wherein the fluorination is carried out in anhydrous conditions by maintaining a moisture level of less than 1000ppm.
7. The process as claimed in claim 1, wherein the process is carried out in a pressure range of 2-20 Kg/cm2.
8. The process as claimed in claim 1, wherein the compound of formula I is obtained with a purity greater than 99%.