The present invention provides a process for preparation of halogen substituted benzoic acid, which prevents the formation of corresponding lower halogenated benzoic acid impurities.

BACKGROUND OF THE INVENTION
The present invention provides a process to produce halogen-containing benzoic acids. These compounds are important raw material for preparing photosensitizer, medicine and pesticides, and find applications in pharmaceuticals and agrochemical industries.
Japanese Patent No. 61036244 describes a process for preparation of 2,4,6-trifluorobenzoic acid comprising the step of hydrolysing 3,5-dichloro-2,4,6-trifluorobenzonitrile to 3,5-dichloro-2,4,6-trifluorobenzoic acid using an aqueous sulfuric acid at 160°C, followed by de-chlorinating 3,5-dichloro-2,4,6-trifluorobenzoic acid to 2,4,6-trifluorobenzoic acid using potassium hydroxide in presence of palladium catalyst and hydrogen pressure. The process involves formation of dihalobenzoic acid impurities that are very difficult to separate from 2,4,6-trifluorobenzoic acid.
Thus, there is a need to develop a process, which may overcome drawbacks of the known processes.
The present invention provides an alternate process for preparation of a compound of formula I preventing formation of dihalobenzoic acid or monohalobenzoic acid impurities.

OBJECT OF THE INVENTION
The present invention provides an alternate process for preparation of halogen substituted benzoic acid, which prevents the formation of corresponding lower halogenated benzoic acid impurities.

SUMMARY OF THE INVENTION
The present invention provides a process for preparation of a compound of formula I,

Formula I
wherein X1 is selected from chloro, fluoro and H, provided that at least one of X1 is chloro or fluoro.
comprising the steps of:
a) selective de-halogenation of a compound of formula III, with a transition metal catalyst in presence of an alkanoic acid and water to obtain a compound of formula II; and

Formula III Formula II
wherein X1 is selected from chloro, fluoro and H, provided that at least one of X1 is chloro or fluoro and X2 is selected from chloro or bromo.
b) hydrolysing a compound of formula II using an acid to obtain a compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION
Lower halogenated benzoic acid impurities refers to the impurities having less number of halogens compared to the desired halogenated benzoic acid. The lower halogenated impurities formed in case of trihalobenzoic acid are dihalobenzoic acids. The lower halogenated impurities formed in case of dihalobenzoic acid are monohalobenzoic acids
The major dihalobenzoic acid impurities are identified as 2,6-dihalobenzoic acid, 2,4-dihalobenzoic acid such as 2,6-dichlorobenzoic acid, 2,4-dichlorobenzoic acid and 2,6-difluorobenzoic acid, 2,4-difluorobenzoic acid that are likely to form during the preparation of 2,4,6-trichlorobenzoic acid and 2,4,6-trifluorobenzoic acid respectively.
The major monohalobenzoic acid impurities are identified as 2-halobenzoic acid, 4-dihalobenzoic acid such as 2-fluorobenzoic acid, 4-difluorobenzoic acid or like that are likely to form during the preparation of either 2,4,-difluorobenzoic acid and 2,6-difluorobenzoic acid respectively.
Lower halogenated benzonitrile impurities refers to the impurities having less number of halogens compared to the desired halogenated benzonitrile. The lower halogenated impurities formed in case of trihalobenzonitrile are dihalobenzonitriles. The lower halogenated impurities formed in case of dihalobenzonitrile are monohalobenzonitriles
The major dihalobenzonitrile impurities are identified as 2,6-dihalobenzonitrile, 2,4-dihalobenzonitrile such as 2,6-dichlorobenzonitrile, 2,4-dichlorobenzonitrile and 2,6-difluorobenzonitrile, 2,4-difluorobenzonitrile that are likely to form during the preparation of 2,4,6-trichlorobenzonitrile and 2,4,6-trifluorobenzonitrile respectively.
The major monohalobenzonitriles impurities are identified as 2-halobenzonitrile, 4-dihalobenzonitrile such as 2-fluorobenzonitrile, 4-difluorobenzonitrile or like that are likely to form during the preparation of either 2,4,-difluorobenzonitrile and 2,6-difluorobenzonitrile respectively.
As used herein, the term “alkanoic acid” is selected from formic acid, acetic acid, trifluoroacetic acid, or the like. The molar ratio of alkanoic acid w.r.t a compound of formula III is used in the range from 2-5.
In an embodiment, alkanoic acid is added continuously in the de-halogenation reaction. The alkanoic acid in de-halogenation reaction is added in 2-5 hours.
In another embodiment, de-halogenation of a compound of formula III is carried out using a transition metal catalyst in presence of an alkanoic acid to give a compound of formula II.
The transition metal catalyst is selected from copper, zinc, zinc/copper alloy or the like. The transition metal catalyst for de-halogenation process is used in solid or powder form. The transition metal catalyst contains metal content greater than 99%. The mesh size of metal powder used is less than 100 micron and more preferably between 2-50 and most preferably 2-20 micron.
The de-halogenation is carried out at a temperature range of 70°C to 90°C. The low temperature range prevents the degradation of product and improves yield significantly. The impurities in the de-halogenation step of a compound of formula III are formed by de-halogenation of one of X1 halogen from compound of formula III.
In an embodiment, de-halogenation of a compound of formula III to obtain a compound of formula II is additionally carried out in presence of an organic solvent selected from a group consisting of toluene, tetrahydrofuran, dioxane, acetonitrile, benzonitrile, toluene, iso-butanol, sulfolane, dimethyl formamide, xylene isomers, or like or mixture thereof.
In another embodiment, de-halogenation of a compound of formula III to obtain a compound of formula II is carried out in absence of organic solvent.
In another embodiment, de-halogenation of a compound of formula III to obtain a compound of formula II is carried out in a mixture of water and an organic solvent.
In a specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc and acetic acid to obtain 2,4,6-trifluorobenzonitrile in presence of water as solvent.
In a specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc powder of mesh size between 5-10 micron and acetic acid to obtain 2,4,6-trifluorobenzonitrile in presence of water as solvent.
In another specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc and acetic acid to obtain 2,4,6-trifluorobenzonitrile in a mixture of water and an organic solvent.
In an embodiment, de-halogenation of a compound of formula III to obtain a compound of formula II is carried out using transition metal catalyst, alkanoic acid and a salt. The salt is selected from phosphate salt such as dipotassium hydrogen phosphate, ammonium dihydrogen phosphate, ammonium hydrogen phosphate, calcium dihydrogen phosphate, calcium hydrogen phosphate, calcium phosphate, potassium dihydrogen phosphate, potassium hydrogen phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, acetates salt such as sodium acetate, potassium acetate, and ammonium /phosphonium salt such as tetramethylammonium chloride, trioctylmethylammonium chloride, tetraphenylphosphonium chloride and tetraphenylphosphonium bromide, tetrabutylammonium chloride, tetrabutylammonium bromide or hydrates thereof.
In another specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc and acetic acid in presence of phosphate salt such as potassium dihydrogen phosphate to obtain 2,4,6-trifluorobenzonitrile.
In another specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc and acetic acid in presence of an ammonium salt such as tetrabutylammonium chloride to obtain 2,4,6-trifluorobenzonitrile.
In another specific embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile is de-chlorinated using zinc and acetic acid in presence of phosphonium salt such as tetraphenylphosphonium bromide to obtain 2,4,6-trifluorobenzonitrile.
The purity of isolated halogenated benzonitrile of formula II is greater than 90% and preferably more than 95% and most preferably 99%.
In an embodiment, halogenated benzonitrile of formula II contains impurities less than 2% and more preferably between 0.1-1%.
The yield of halogenated benzonitrile of formula II is greater than 80% and preferably greater than 85%.
The present invention involve two-de-halogenation step to form a compound of formula II. In a case, where only one de-halogenation is taken, the intermediate formed refers to compound of formula IV, is isolated and recycled to de-halogenation step.

Formula IV
wherein X1 is selected from chloro, fluoro and H, provided that at least one of X1 is chloro or fluoro and X2 is chloro or bromo.
The compound of formula III are selected from 3,5-dichloro-2,4,6-trifluorobenzonitrile, 3,5-dibromo-2,4,6-trifluorobenzonitrile, 3-bromo-5-chloro-2,4,6-trifluorobenzonitrile, 3,5-dichloro-2,4-difluorobenzonitrile, 3,5-dichloro-4-fluorobenzonitrile, 3,5-dichloro-2,6-difluorobenzonitrile or like.
The compound of formula II are selected from 2,4,6-trifluorobenzonitrile, 2,4,6-trichlorobenzonitrile, 2,4-difluorobenzonitrile, 4-fluorobenzonitrile, 2,6-difluorobenzonitrile, 2-chloro-4,6-difluorobenzonitrile, 4-chloro-2,6-difluorobenzonitrile or like.
The compound of formula I may be selected from a group consisting of 2,4,6-trifluorobenzoic acid, 2,4,6-trichlorobenzoic acid, 2,4-difluorobenzoic acid, 4-fluorobenzoic acid, 2,6-difluorobenzoic acid, 2-chloro-4,6-difluorobenzoic acid, 4-chloro-2,6-difluorobenzoic acid, or like.
As used herein, hydrolysing refers to reacting halogenated benzonitrile of formula II using an acid to obtain a compound of formula I;
As used herein, “acid” is selected from sulfuric acid, hydrochloric acid or like.
In an embodiment of present invention, hydrolysis is carried out using aqueous acid. The concentration of aqueous acid may range from 30-80% by mass of acid.
In an embodiment of present invention, an aqueous acid is continuously added in a compound of formula II.
In an embodiment, hydrolysis is carried out at a temperature selected in the range of 80-160°C and preferably in the range 100-150°C. The hydrolysis reaction may take 2-7 hours for completion.
In an embodiment, reaction mixture is filtered to isolate a compound of formula I. The present invention is isolating a compound of formula I by simple filtration and eliminating multiple workup operations.
In an embodiment of the present invention, the compound of formula II is hydrolysed using an acid to obtain a reaction mixture containing product of formula I, which is filtered to obtain the compound of formula I having purity of 90% to 95%, which upon recrystallization using a solvent or mixture of solvents gives pure compound of formula I.
In another embodiment, the compound of formula I after filtration is purified by recrystallisation. The recrystallisation solvent may be selected from a group consisting of hexane, toluene, cyclohexane, ethyl acetate, ethanol, methanol, butanol, propanol, isopropanol, diethyl ether, acetone, water or a mixture thereof.
The use of nitrile compound as starting material gives nitrile impurities and acids compound gives acid impurities in hydrolysis step. The known method performs hydrolysis prior to de-halogenation. The de-halogenation of 3,5-dichloro-2,4,6-trifluorobenzoic acid, after hydrolysis step, produces lower halogenated benzoic acid impurities. These lower halogenated benzoic acid impurities are difficult to separate even after multiple crystallization.
The present invention has carried out de-halogenation prior to hydrolysis to prevent formation of lower halogenated benzoic acid impurities in hydrolysis step. The de-halogenation of present invention gives lower halogenated benzonitrile impurities that are easy to separate as compared to lower halogenated benzoic acid impurities. This is an alternate process for preparation of compound of formula I and preventing formation of lower halogenated benzoic acid impurities in present invention.
In an embodiment of present invention, firstly de-halogenation is carried out, followed by separation of dihalobenzonitrile or monohalobenzonitrile impurities from reaction mixture and secondly, hydrolysis using an acid is performed to form a compound of formula I.
The dihalobenzonitrile impurities refers to 2,6-difluorobenzonitrile, 2,4-difluorobenzonitrile or like that are likely to form during the preparation of 2,4,6-trifluorobenzonitrile.
The major monohalobenzonitrile impurities refers to 2-fluorobenzonitrile, 4-fluorobenzonitrile or like that are likely to form during the preparation of either 2,4,-difluorobenzonitrile and 2,6-difluorobenzonitrile respectively.
In an embodiment of present invention, a compound of formula II used for present invention is having purity greater than 99% and containing less than 0.05% of dihalobenzonitrile or monohalobenzonitrile impurities.
In an embodiment, the present invention provides a process for preparation of compound of formula I containing lower halogenated benzoic acid impurities less than 0.5% and preferably in the range from not detectable to 0.05%.
The major dihalobenzoic acid impurities are identified as 2,6-difluorobenzoic acid, 2,4-difluorobenzoic acid or like that are likely to form during the preparation of 2,4,6-trifluorobenzois acid.
The major monohalobenzoic acid impurities are identified as 2-fluorobenzoic acid, 4-difluorobenzoic acid or like that are likely to form during the preparation of either 2,4,-difluorobenzoic acid and 2,6-difluorobenzoic acid respectively.
As used herein, the term less than 0.05% refers to an impurity that is not detectable to 0.05%.
In another embodiment, the purity of the compound of formula I before recrystallization is in the range of 90 to 95%.
In specific embodiment, 2,4,6-trifluorobenzoic acid is prepared from 2,4,6-trifluorobenzonitrile using aqueous sulfuric acid at 150°C.
In specific embodiment, 2,4,6-trifluorobenzoic acid is prepared from 2,4,6-trifluorobenzonitrile using aqueous hydrochloric acid at refluxing.
In specific embodiment, 2,4,6-trifluorobenzoic acid contains 2,4-difluorobenzoic acid and 2,6-difluorobenzoic acid in the range of not detectable to 0.05%.
In an embodiment, the selectivity of formation of compound of formula I is greater than 99%.
In an embodiment, the yield of hydrolysis step is greater than 96%.
In preferred embodiment of present invention, de-halogenation is carried out prior to hydrolysis in the preparation of compound of formula I.
In specific embodiment, present invention provides a process for preparation of 2,4,6-trifluorobenzoic acid, comprising the steps of:
a) de-chlorinating 3,5-dichloro-2,4,6-trifluorobenzonitrile using zinc and acetic acid to obtain 2,4,6-trifluorobenzonitrile; and
b) hydrolysing 2,4,6-trifluorobenzonitrile using aqueous sulfuric acid to obtain 2,4,6-trifluorobenzoic acid.
In a specific embodiment, the present invention provides a process for preparation and purification of 2,4,6-trifluorobenzoic acid, comprising the steps of:
a) hydrolysing 2,4,6-trifluorobenzonitrile using an aqueous sulfuric acid to obtain a reaction mixture containing a compound of formula I;
b) filtering step a) reaction mixture to obtain 2,4,6-trifluorobenzoic acid having purity upto 95%; and
c) crystallizing 2,4,6-trifluorobenzoic acid obtained from step b) using a mixture of ethyl acetate and hexane to obtain pure compound of formula 1 having purity greater than 99%.
In an embodiment, the present invention provides a process for preparation of 2,4,6-trifluorobenzoic acid from 2,3,4,5,6-pentachlorobenzonitrile.
In another embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile used in the present invention is prepared by fluorinating 2,3,4,5,6-pentachlorobenzonitrile using an alkali metal fluoride. The alkali metal fluoride is selected from potassium fluoride, sodium fluoride, ammonium fluoride or the like.
In another embodiment, 3,5-dichloro-2,4,6-trifluorobenzonitrile used in the present invention is formed by fluorinating 2,3,4,5,6-pentachlorobenzonitrile using an anhydrous potassium fluoride.
In another embodiment, the present invention provides a process for preparation of 2,4,6-trifluorobenzoic acid, comprising the steps of:
a) fluorinating 2,3,4,5,6-pentachlorobenzonitrile using an anhydrous potassium fluoride to obtain 3,5-dichloro-2,4,6-trifluorobenzonitrile;
a) de-chlorinating 3,5-dichloro-2,4,6-trifluorobenzonitrile using zinc and acetic acid and water to obtain 2,4,6-trifluorobenzonitrile; and
b) hydrolysing 2,4,6-trifluorobenzonitrile using an aqueous sulfuric acid to form 2,4,6-trifluorobenzoic acid.
In an embodiment, present invention provides a process for preparation of 2,4,6-trifuorobenzoic acid comprising fluorinating 2,3,4,5,6-pentachlorobenzonitrile to form 3,5-dichloro-2,4,6-trifluorobenzonitrile, de-chlorinating 3,5-dichloro-2,4,6-trifluorobenzonitrile to 2,4,6-trifluorobenzonitrile and hydrolysing 2,4,6-trifluorobenzonitrile to form 2,4,6-trifluorobenzoic acid.
In an embodiment, fluorination of 2,3,4,5,6-pentachlorobenzonitrile is carried out using potassium fluoride to form 3,5-dichloro-2,4,6-trifluorobenzonitrile.
In an embodiment, fluorination of 2,3,4,5,6-pentachlorobenzonitrile is carried out using potassium fluoride at a pressure of 2-3kg/cm2 at a temperature of 250°C.
In an embodiment, fluorination of 2,3,4,5,6-pentachlorobenzonitrile is carried out using potassium fluoride at a pressure of 2-3kg/cm2 at a temperature of 250°C under an inert atmosphere. The inert atmosphere is maintained using nitrogen, helium or argon.
The product may be isolated by any method known in the art, for example, chemical separation, extraction, acid-base neutralization, distillation, recrystallization, evaporation, column chromatography and filtration or a mixture thereof.
The compound of Formula I is isolated by any method known in the art, for example, chemical separation, extraction, acid-base neutralization, distillation, evaporation, column chromatography and filtration or a mixture 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.
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 3,5-dichloro-2,4,6-trifluorobenzonitrile
2,3,4,5,6-pentachlorobenzonitrile (200 g), benzonitrile (1200 g) and potassium fluoride (169 g) were added in an autoclave reactor in an inert atmosphere. The reaction mass heated to 250°C. The pressure of the reactor was 2-3kg/cm2 at 250°C during the reaction. The reaction mass analysis was done on gas chromatography. After reaction completed, the reaction mass was cooled to room temperature and filtered. The filtered solid was washed with benzonitrile. The filtrate was fractionally distilled under reduced pressure and product was isolated.
Yield: 90%; Purity: 99%.

Example 2: Preparation of 2,4,6-trifluorobenzonitrile
Zinc powder (73 g), water (1000 g) and 3,5-dichloro-2,4,6-trifluorobenzonitrile (100 g) were charged in a reactor. Potassium hydrogen phosphate (2 g) were added in the reactor and reaction mass heated to 80°C under stirring. The acetic acid (80 g) was added slowly to the reaction mass in 2-3 hours at 90-95°C. The reaction mass was monitored on gas chromatography. After reaction, the reaction mass cooled to 35°C and dichloromethane (300 g) was added to the reaction mass. The reaction mass was filtered under vacuum and filtrate was separated into organic and aqueous layer. The organic layer was concentrated on rota evaporator and concentrated mass was distilled to isolate 2,4,6-trifluorobenzonitrile.
Yield: 85%; Purity: 99%.
Example 3: Preparation of 2,4,6-trifluorobenzonitrile
Zinc powder (73 g), a mixture of water and tetrahydrofuran (500 g) and 3,5-dichloro-2,4,6-trifluorobenzonitrile (100 g) were charged in a reactor. Tetrabutylammonium chloride (2 g) were added in the reactor and reaction mass heated to 80°C under stirring. The acetic acid (80 g) was added slowly to the reaction mass in 2-3 hours at 80°C. The reaction mass was monitored on gas chromatography. After reaction, the reaction mass cooled to 35°C and dichloromethane (300 g) was added to the reaction mass. The reaction mass was filtered under vacuum and filtrate was separated into organic and aqueous layer. The organic layer was concentrated on rota evaporator and concentrated mass was distilled to isolate product.
Yield: 85%; Purity: 99%.
Example 4: Preparation of 2,4,6-trifluorobenzonitrile
Zinc powder (73 g), water (400 g) and 3,5-dichloro-2,4,6-trifluorobenzonitrile (100 g) were charged in a reactor. Tetrabutylammonium chloride (2 g) were added in the reactor and reaction mass heated to 90°C under stirring. The acetic acid (80 g) was added slowly to the reaction mass in 2-3 hours at 90-95°C. The reaction mass was monitored on gas chromatography. After reaction, the reaction mass cooled to 35°C and dichloromethane (300 g) was added to the reaction mass. The reaction mass was filtered under vacuum and filtrate was separated into organic and aqueous layer. The organic layer was concentrated on rota evaporator and concentrated mass was distilled to isolate product.
Yield: 70%; Purity: 99%.
Example 5: Preparation of 2,4,6-trifluorobenzonitrile
Zinc powder (73 g), water (1000 g), toluene (60 g) and 3,5-dichloro-2,4,6-trifluorobenzonitrile (100 g) were charged in a reactor. Tetraphenylphosphonium bromide (2.5 g) was added in the reactor and reaction mass heated to 80°C under stirring. The acetic acid (80 g) was added slowly to the reaction mass in 2-3 hours at 90-95°C. The reaction mass was monitored on gas chromatography. After reaction, the reaction mass cooled to 35°C. The reaction mass was filtered under vacuum and filtrate was separated into organic and aqueous layer. The organic layer was concentrated on rota evaporator and concentrated mass was fractionally distilled to isolate 2,4,6-trifluorobenzonitrile.
Yiled-90% and purity is 99%.
Example 6: Preparation of 2,4,6-trifluorobenzoic acid
Aqueous sulfuric acid (500g, 70%) was charged in a reactor and heated to 140°C. 2,4,6-trifluorobenzonitrile (100 g) was added continuously to reactor in 3-4 hours. The reaction mixture stirred for 2 hours and cooled to room temperature. The reaction mixture was filtered and product was isolated. The product was dried under vacuum at 70°C.
Yield: 95%; Purity: 95%.
2,6-difluorobenzoic acid- not detectable (less than 0.05%)
2,4-difluorobenzoic acid- not detectable (less than 0.05%)

Example 7: Preparation of 2,4,6-trifluorobenzoic acid
Aqueous sulfuric acid (500g, 70%) was charged in a reactor and heated to 140°C. 2,4,6-trifluorobenzonitrile (100 g) was added continuously to reactor in 3-4 hours. The reaction mixture stirred for 2 hours and cooled to room temperature. The reaction mixture was filtered and washed with distilled water. The filtered solid was added in a mixture of ethyl acetate and hexane. The crystallisation mixture was stirred for 30 minutes and filtered to isolate product. The product was dried under vacuum at 70°C.
Yield: 95%; Purity: 99%.
2,6-difluorobenzoic acid- not detectable (less than 0.05%)
2,4-difluorobenzoic acid- not detectable (less than 0.05%)
Example 8: Preparation of 2,4,6-trifluorobenzoic acid
2,4,6-trifluorobenzonitrile (100g) and water (300g) were charged in a reactor and heated to reflux temperature. Hydrogen chloride (140g, 35%) was added continuously to reactor in 3-4 hours. The reaction mixture stirred for 2 hours and cooled to room temperature. The reaction mixture was filtered and product was isolated. The product was dried under vacuum at 70°C.
Yield: 90%; Purity: 90%.
2,6-difluorobenzoic acid- not detectable (less than 0.05%)
2,4-difluorobenzoic acid- not detectable (less than 0.05%)
Comparative Examples
Example A: 3,5-dichloro-2,4,6-trifluorobenzoic acid
3,5-dichloro-2,4,6-trifluorobenzonitrile (100g) and water (300g) were charged in a reactor and heated to temperature. Sulfuric acid (140g, 35%) was added continuously to reactor in 3-4 hours. The reaction mixture stirred for 2 hours and cooled to room temperature. The reaction mixture was filtered and product was isolated. The product was dried under vacuum at 70°C.
Example B: Preparation of 2,4,6-trifluorobenzoic acid
Zinc powder (73 g), water (400 g) and 3,5-dichloro-2,4,6-trifluorobenzoic acid (100 g) were charged in a reactor. Tetrabutylammonium chloride (2 g) were added in the reactor and reaction mass heated to 90°C under stirring. The acetic acid (80 g) was added slowly to the reaction mass in 2-3 hours at 90-95°C. The reaction mass was monitored on gas chromatography. After reaction, the reaction mass cooled to 35°C and dichloromethane (300 g) was added to the reaction mass. The reaction mass was filtered under vacuum and filtrate was separated into organic and aqueous layer. The organic layer was concentrated on rota evaporator and concentrated mass was distilled to isolate product. Yield: 12-15%
2,6-difluorobenzoic acid- 8-10%
2,4-difluorobenzoic acid- 8-10%
Example B: Preparation of 2,4,6-trifluorobenzoic acid
3,5-dichloro-2,4,6-trifluorobenzoic acid was hydrogenated using palladium catalyst in presence of sodium carbonate. Yield: 40%
2,6-difluorobenzoic acid- 5-8%; 2,4-difluorobenzoic acid- 5-8%

WE CLAIM:

1. A process for preparation of a compound of formula I,

Formula I
wherein X1 is selected from chloro, fluoro and H, provided that at least one of X1 is chloro or fluoro.
comprising the steps of:
a) selective de-halogenation of a compound of formula III with a transition metal catalyst in presence of an alkanoic acid and water to obtain a compound of formula II; and

Formula III Formula II
wherein X1 is selected from chloro, fluoro and H, provided that at least one of X1 is chloro or fluoro and X2 is selected from chloro or bromo.
b) hydrolysing the compound of formula II using an acid to obtain a compound of formula I.
2. The process as claimed in claim 1, wherein the compound of formula I includes the compounds selected from 2,4,6-trifluorobenzoic acid, 2,4,6-trichlorobenzoic acid, 2,4-difluorobenzoic acid, 4-fluorobenzoic acid, 2,6-difluorobenzoic acid, 2-chloro-4,6-difluorobenzoic acid and 4-chloro-2,6-difluorobenzoic acid, or the like.
3. The process as claimed in claim 1, wherein the compound of formula II includes the compounds selected from 2,4,6-trifluorobenzonitrile, 2,4,6-trichlorobenzonitrile, 2,4-difluorobenzonitrile, 4-fluorobenzonitrile, 2,6-difluorobenzonitrile, 2-chloro-4,6-difluorobenzonitrile and 4-chloro-2,6-difluorobenzonitrile or the like.
4. The process as claimed in claim 1, wherein the compound of formula III includes the compounds selected from 3,5-dichloro-2,4,6-trifluorobenzonitrile, 3,5-dibromo-2,4,6-trifluorobenzonitrile, 3-bromo-5-chloro-2,4,6-trifluorobenzonitrile, 3,5-dichloro-2,4-difluorobenzonitrile, 3,5-dichloro-4-fluorobenzonitrile and 3,5-dichloro-2,6-difluorobenzonitrile or like.
5. The process as claimed in claim 1, wherein the alkanoic acid is selected from a group consisting of formic acid, acetic acid and trifluoroacetic acid.
6. The process as claimed in claim 1, wherein the transition metal catalyst used in de-halogenation step is selected from a group consisting of copper, zinc and zinc/copper alloy.
7. The process as claimed in claim 1, wherein the de-halogenation step is carried out at a temperature selected in the range of 70°C to 90°C.
8. The process as claimed in claim 1, wherein the de-chlorination step is additionally carried out in presence of an organic solvent selected from a group consisting of hexane, toluene, cyclohexane, ethyl acetate, ethanol, methanol, butanol, propanol, isopropanol, diethyl ether, acetone and water or a mixture thereof.
9. The process as claimed in claim 1, wherein the hydrolysis of is carried out in presence of an acid selected from sulfuric acid and hydrochloric acid.
10. The process as claimed in claim 1, wherein the compound of formula I contains corresponding lower halogenated benzoic acid impurities in the range of less than 0.05%.