FIELD OF THE INVENTION
The present invention relates to a process for preparation of 2,3,6-trihalobenzyl alkyl ketones, represented as compound of Formula I and intermediates thereof. These compounds are used in a wide variety of applications in pharma and agrochemical field.

Formula I
wherein X independently represents a chloro or fluoro and R represents an alkyl group.

BACKGROUND OF THE INVENTION
The 2,3,6-trihalobenzyl alkyl ketones, especially, trifluorophenyl-propan-2-one is a valuable intermediate for synthesis of active agrochemical and pharmaceutical ingredients.
WO2013169348A1 discloses a process for preparation of l-(2,3,6-trifluorophenyl)propan-2-one by reacting N-methoxy-N-methyl-2-(2,3,6-trifluorophenyl)acetamide with methyl magnesium chloride in presence of cerium(III) chloride in tetrahydrofuran at 16°C. The reactant N-methoxy-N-methyl-2-(2,3,6-trifluorophenyl) acetamide and the reagent like cerium chloride, silver-catalyst and copper (II) oxide are expensive and not easily available therefore makes the process costlier at commercial scale.
RSC Adv., 2015, 5, 15354–15358 discloses a process for preparation of trifluorobenzene by de-boronation of arylboronic acids and esters using silver-catalyst in presence of a base.
USH992H discloses a process for preparation of 1,2,4-trifluorobenzene by decarboxylation of 2,4,5-trifluorobenzoic acid in presence of copper (II) oxide in N-methyl-2-pyrrolidone.
The present invention aims to provide preparation of 2,3,6-trihalobenzyl alkyl ketones and intermediates thereof from easily available and less expensive reagents at commercial scale.

OBJECT OF THE INVENTION
The main object of present invention is to provide an economical and industrially applicable process for preparation of 2,3,6-trihalobenzyl alkyl ketones of Formula I and intermediates thereof.

SUMMARY OF THE INVENTION
In an aspect, the present invention provides a process for preparation of a 2,3,6-trihalobenzyl alkyl ketone of Formula I,

Formula I
wherein X independently represents a chloro or fluoro and R an alkyl group,
comprising the steps of:
a) formylating a 1,2,4-trihalobenzene of Formula III,

Formula III
wherein X is as defined above,
in presence of a base to form a 2,3,6-trihalobenzaldehyde of Formula II; and

Formula II
wherein X is as defined above,
b) reacting the 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile in presence of base to obtain the compound of Formula I.
In another aspect, the present invention provides a process for preparation of 1,2,4-trihalobenzene, comprising the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzoic acid;
b) de-halogenating 2,3,5,6-tetrahalobenzoic acid with zinc in presence of a catalyst to form 2,3,5-trihalobenzoic acid;
c) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.
In yet another aspect, the present invention provides a process for preparation of a 1,2,4-trihalobenzene, comprising the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzamide;
b) de-halogenating 2,3,5,6-tetrahalobenzamide with zinc in presence of a catalyst to form 2,3,5-trihalobenzamide;
c) hydrolysing 2,3,5-trihalobenzamide with an acid to obtain 2,3,5-trihalobenzoic acid;
d) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, alkyl group is selected from a group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl and pentyl or the like.
As used herein, a halo group is either a chloro or a fluoro group.
In an embodiment, the present invention provides a process for preparation of a 2,3,6-trihalobenzyl alkyl ketone of Formula I,

Formula I
wherein X independently represents a chloro or fluoro and R an alkyl group,
comprising the steps of:
a) formylating a 1,2,4-trihalobenzene of Formula III,

Formula III
wherein X is as defined above,
in presence of a base to form a 2,3,6-trihalobenzaldehyde of Formula II; and

Formula II
wherein X is as defined above,
b) reacting the 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile in presence of base to obtain the compound of Formula I.
In another embodiment, the present invention provides a process for preparation of 1,2,4-trihalobenzene, comprising the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzoic acid;
b) de-halogenating 2,3,5,6-tetrahalobenzoic acid with zinc in presence of a catalyst to form 2,3,5-trihalobenzoic acid;
c) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.
In yet another embodiment, the present invention provides a process for preparation of a 1,2,4-trihalobenzene, comprising the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzamide;
b) de-halogenating 2,3,5,6-tetrahalobenzamide with zinc in presence of a catalyst to form 2,3,5-trihalobenzamide;
c) hydrolysing 2,3,5-trihalobenzamide with an acid to obtain 2,3,5-trihalobenzoic acid;
d) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.
In a further embodiment, the present invention provides a process for a preparation of a 2,3,6-trihalobenzyl alkyl ketone of Formula I,

Formula I
wherein X independently represents a chloro or fluoro and R represents an alkyl group,
comprising the steps of:
a) hydrolysing a 2,3,5,6-tetrahalobenzonitrile of Formula VI,

Formula VI
wherein X is as defined above,
using an acid to form a 2,3,5,6-tetrahalobenzoic acid of Formula V;

Formula V
wherein X is as defined above,
b) de-halogenating the 2,3,5,6-tetrahalobenzoic acid of Formula V with zinc in the presence of a catalyst to form a 2,3,5-trihalobenzoic acid of Formula IV;

Formula IV
wherein X is as defined above,
c) de-carboxylating the 2,3,5-trihalobenzoic acid of Formula IV to form a 1,2,4-trihalobenzene of Formula III;

Formula III
d) formylating the 1,2,4-trihalobenzene of Formula III in presence of a base to form a 2,3,6-trihalobenzaldehyde of Formula II; and

Formula II
e) reacting the 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile in presence of base to obtain the compound of Formula I.
In an embodiment of the present invention, the step of formylation is carried out by reacting 1,2,4-trihalobenzene of Formula III with a formylating agent in presence of a base, selected from a group consisting of sodium hydride, potassium hydride, sodium butoxide, potassium butoxide, lithium (hexamethylsilyl)amide, potassium (hexamethylsilyl)amide, N-butyl lithium, sodium metal, potassium metal, sodium ethoxide and sodium methoxide or the like.
The solvent for formylation is selected from a group consisting of diethyl ether diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane and acetonitrile or a mixture thereof.
In another embodiment, the step of formylation of 1,2,4-trihalobenzene of Formula III is carried out by reacting a 1,2,4-trihalobenzene of Formula III with a formylating agent selected from a group consisting of dimethylformamide, diethylformamide and paraformaldehyde.
In another embodiment, the step of formylation is carried out in presence of an organic base selected from alkylamines and pyridine or the like. Preferably, the organic base is a sterically hindered amine selected from a group consisting of triethylamine, N,N-diisopropylamine and N,N-diisopropylethylamine and ethanolamine or the like.
In another embodiment, the step of formylation of 1,2,4-trihalobenzene of Formula III is carried out at a temperature of 0 to -70°C.
In another embodiment, the molar ratio of 1,2,4-trihalobenzene of Formula III to the formylating agent is in the range of 1.0-1.5.
In an embodiment, the step of reacting a 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile is carried out in presence of base selected from a group consisting of alkali hydroxide and alkali or the like in a solvent. The alkali hydroxide is selected from a group consisting of sodium hydroxide, potassium hydroxide, cesium hydroxide and magnesium hydroxide or the like, alkali alkoxide is selected from a group consisting of sodium methoxide, sodium ethoxide, sodium propoxide, potassium methoxide, potassium ethoxide and magnesium ethoxide or magnesium methoxide or the like.
The nucleophile is selected from a group consisting of methyl chloropropionate, ethyl chloropropionate, methyl bromopropionate and ethyl bromopropionate or the like.
The step of reacting a 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile is carried out in an organic solvent selected from a group consisting of toluene, heptane, hexane, dimethylformamide, dimethylacetamide, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, diisopropyl ether and tert-butyl methyl ether or a mixture thereof.
In an embodiment, the step of reacting a 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile is carried out at a temperature range of 0 to 50°C.
In another embodiment, the molar ratio of a 2,3,6-trihalobenzaldehyde of Formula II with respect to the nucleophile is in the range of 1.0: 1.0-1.2.
In an embodiment, the step of hydrolysis is carried out using an acid selected from a group consisting of sulfuric acid, phosphoric acid, hydrochloric acid, methane sulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid and trifluoroacetic acid or the like.
In another embodiment, the step of hydrolysis of 2,3,5,6-tetrahalobenzonitrile to 2,3,5,6-tetrahalobenzoic acid is carried out at a temperature range of 120-140°C using 5 to 10 equivalents of an acid.
In another embodiment, the step of hydrolysis of 2,3,5,6-tetrahalobenzonitrile to 2,3,5,6-tetrahalobenzamide is carried out at a temperature of 110 to 120°C using 4 equivalents of an acid.
In an embodiment of the present invention, the step of de-halogenation is carried out using zinc in presence of a catalyst comprising a metal complex selected from group consisting of a nickel chloride hexahydrate with a ligand selected from a group consisting of 2,2´-bipyridine or 1,10-phenanthroline, 1,10-phenonthroline monohydrate morpholine, tetramethylethylenediamine and derivatives thereof.
The solvent for de-halogenation is selected from a group consisting of water and an organic solvent. The examples of organic solvent include ethyl acetate, methyl acetate, butyl acetate, ethyl pentonoate, propyl acetate, pentyl acetate, methyl butyrate, isobutyl acetate, methyl benzoate, ethyl benzoate, methyl tetrahydrofuran, toluene, benzonitrile or a mixture thereof.
The organic solvent also includes polar aprotic solvents selected from a group consisting of dimethylsulfoxide, N,N-dimethyl formamide, N-methylpyrrolidone, N,N-dimethyl acetamide, N-vinylpyrrolidone, hexamethyl phosphoramide, tetrahydrofuran, acetonitrile and sulfolane or a mixture thereof.
In another embodiment, the step of de-halogenation is carried out in presence of nickel salt and the ligand in the ratio of 1 to 3.
In another embodiment, the step of de-halogenation is carried out at a temperature range of 30 to 70°C.
In another embodiment, the mole equivalents of zinc used in the step of de-halogenation is in the range of 2 to 5 molar equivalents.
In an embodiment, the step of de-carboxylation is carried out using a metal salt selected from a group consisting of a metal oxide, metal hydroxide or metal carbonate. The metal salt includes copper oxides, cupric oxide, silver oxide, calcium oxide and calcium hydroxide or the like. The de-carboxylation is preferably carried out in presence of cupric oxide.
In another embodiment, the mole equivalent of metal salt used is 0.05 to 0.5 molar equivalent at a temperature in the range from 150 to 180°C.
The ‘organic solvent’ used in the step of de-carboxylation is selected from a group consisting of a polar aprotic organic solvent such as sulpholane; N-methyl-2-pyrrolidone; benzonitrile; N-vinylpyrrolidone; hexamethylphosphoramide; dimethylsulfoxide; N,N-dimethylformamide and N,N-dimethylacetamide or a mixture thereof. N-methyl-2-pyrrolidone is preferred as a solvent for the step of de-carboxylation.
In another embodiment, the step of de-halogenation and de-carboxylation involves recycling and reusing the solvent.
In an embodiment, the step of de-carboxylation is carried out at a temperature range of 120 to 140°C.
In a particular embodiment, the present invention provides a process for preparation of 1-(2,3,6-trifluorophenyl)propan-2-one, comprising the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to obtain 2,3,5,6-tetrafluorobenzoic acid;
b) de-halogenating 2,3,5,6-tetrafluorobenzoic acid using zinc powder in presence of nickel chloride complex in water and an organic solvent to obtain 2,3,5-trifluorobenzoic acid;
c) de-carboxylating 2,3,5-trifluorobenzoic acid using a metal oxide or metal hydroxide to obtain 1,2,4-trifluorobenzene;
d) formylating 1,2,4-trifluorobenzene with dimethylformamide in presence of a base to obtain 2,3,6-trifluorobenzaldehyde; and
e) reacting 2,3,6-trifluorobenzaldehyde with alkylchloropropionate to obtain 1-(2,3,6-trifluorophenyl)propan-2-one.
In another embodiment of the present invention provides a process, wherein the step of formylating 1,2,4-trifluorobenzene with dimethylformamide and the step of reacting 2,3,6-trifluorobenzaldehyde with alkylchloropropionate is carried out simultaneously without isolating 2,3,6-trifluorobenzaldehyde.
In an embodiment, the present invention provides a process for preparation of compound of Formula I, having selectivity greater than 90%, in a yield of 75%.
As used herein, the 1,2,4-trihalobenzene includes 1,2,4-trifluorobenzene and 1,2,4-trichlorobenzene or the like.
As used herein, the 2,3,5,6-tetrahalobenzonitrile includes 2,3,5,6-tetrachlorobenzonitrile and 2,3,5,6-tetrafluorobenzonitrile or the like.
In an embodiment, the present invention provides a process for preparation of 1,2,4-trihalobenzene, having selectivity greater than 80%, yield greater than 75%, purity greater than 90%.
In an embodiment, the present invention provides a process for preparation of a compound of Formula II, comprising a step of reacting 1,2,4-trihalobenzene of Formula III with dimethylformamide in presence of a base.
In an embodiment, the present invention provides a process for preparation of 2,3,6-trifluorobenzaldehyde, comprising a step of reacting 1,2,4-trifluorobenzene with dimethylformamide in presence of a base.
In an embodiment, the present invention provides a process for preparation of 1,2,4-trihalobenzene of Formula III, comprising a step of de-carboxylating a compound of Formula IV using a metal oxide or metal hydroxide.
In an embodiment, the present invention provides a process for preparation of 1,2,4-trifluorobenzene, comprising a step of de-carboxylating 2,3,5-trifluorobenzoic acid using a metal oxide or metal hydroxide.
In an embodiment, the present invention provides a process for preparation of a compound of Formula IV, comprising a step of de-halogenating a compound of Formula V using zinc powder in presence of nickel chloride complex in water and an organic solvent.
In an embodiment, the present invention provides a process for preparation of 2,3,5-trifluorobenzoic acid, comprising a step of de-halogenating 2,3,5,6-tetrafluorobenzoic acid using zinc powder in presence of nickel chloride complex in water and an organic solvent.
In an embodiment, the present invention provides a process for preparation of a compound of Formula V, comprising a step of hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid.
In an embodiment, the present invention provides a process for preparation of 2,3,5,6-tetrafluorobenzoic acid, comprising a step of hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid.
In an embodiment of the present invention, the compounds of Formula II, Formula III, Formula IV, Formula V are not isolated and used in-situ for the next step of the process.
In another embodiment of the present invention, the compounds of Formula II, Formula III, Formula IV, and Formula V are isolated by crystalizing in an organic solvent selected from a group consisting of hexane, heptane, diethylether and acetone or a mixture thereof.
The compound of formula VI used as a starting material and reagents used in the present invention are commercially available and can be easily obtained.
The isolation of compound of Formula I of the present invention may be carried out by any method selected from evaporation, distillation, column chromatography, filtration or like.
Unless stated to the contrary, any of the words “comprising”, “comprises” 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 completion of the reaction can 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) and alike.
The following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Preparation of 2,3,5,6-tetrafluorobenzoic acid.
2,3,5,6-tetrafluorobenzonitrile (200 g) was added to an aqueous solution of sulfuric acid (50%, 5 M) at a room temperature in a reactor equipped with condenser. The reaction mixture was heated to 135-145°C and maintained at the same temperature for 12-14 hours. After completion of the reaction, reaction mixture was cooled to 10-15°C, filtered, washed twice with water (150 ml X 2) and dried under reduced pressure to obtain 2,3,5,6-tetrafluorobenzoic acid (yield: 95%; purity 99%).
Example 2: Preparation of 2,3,5-trifluorobenzoic acid.
Nickel chloride hexahydrate (0.2 M), 2,2´-bipyridine (0.2 M), N,N-dimethylformamide (200 ml) and water (100 ml) were taken in a reactor equipped with condenser and stirred at 60-70°C for 2-3 hours. A solution of 2,3,5,6-tetrafluorobenzoic acid (200 g) in N,N-dimethylformamide (200 ml) was added in the reaction mixture in a duration of 30 minutes. Zinc dust (2 M) was added lot-wise in the reaction mixture and the reaction was maintained at a temperature of 60-70°C for 12-15 hours. The progress of the reaction was monitored on HPLC. After the completion of the reaction, the pH of the reaction mass was adjusted using hydrochloric acid (6 M) at 10-20°C. The reaction mixture was extracted using ethyl acetate (300 ml X 2) and washed with brine solution to obtain solid residue. The residue was crystallised using heptane at 60-70°C to obtain 2,3,5-trifluorobenzoic acid (yield: 80%; purity 90%).
Example 3: Preparation of 1,2,4-trifluorobenzene.
Copper oxide (0.1 M) was added to a solution of 2,3,5-trifluorobenzoic acid (100 g, obtained in above example) and N-methyl-2-pyrrolidone (100 gm) and heated to 150-160°C. After completion of the reaction, the reaction mass was distilled, washed twice with brine, filtered through sodium sulphate bed under reduced pressure to get pure 1,2,4-trifluorobenzene (yield: 85%; purity: 98.2%).
Example 4: Preparation of 2,3,6-trifluorobenzaldehyde.
1,2,4-Trifluorobenzene (1 MEq; Example 3) was added to a reactor containing tetrahydrofuran (15 MEq.) and N,N-diisopropylamine (1.3 MEq.) and cooled the reaction mixture to a temperature of -40 to -30°C. A solution of N-butyllithium in hexane (1.25 MEq.) was added dropwise to the reaction mixture under inert atmosphere. The reaction mass was stirred at the same temperature for an hour and dimethylformamide (2.1 MEq.) was added while maintaining the temperature. After the addition is completed, the reaction mixture was stirred at -40 to -30°C for an hour to two hours. The progress of the reaction was monitored by GC. After completion of the reaction, the reaction mixture was gradually quenched using hydrochloride solution (6M) below -5°C. Water and methyl tertiary butyl ether (MTBE) was added to the reaction mass at 20°C, stirred for 30 minutes and layers were separated. The organic layer was further washed with brine. MTBE was removed completely under reduced pressure to get crude 2,3,6-trifluorobenzaldehyde. Crude product was recrystallized using n-heptane and filtered under vacuum to get 2,3,6-trifluorobenzaldehyde (Purity: 97-99%; Yield: 85%).
Example 5: Preparation of 1-(2,3,6-trifluorophenyl)propan-2-one.
Methyl chloropropionate (1.2 M) was added to a solution of 2,3,6-trifluorobenzaldehyde (1 M) in toluene (10 ml). The reaction mixture was cooled to 0-5°C. A solution of sodium methoxide in methanol (1.15 M) was added over 20 minutes at a temperature below 10°C. The resulting suspension was stirred for an additional 30 minutes at 0-5°C, then the solution was warmed to 20-30°C and stirred for 3 to 6 hours. The reaction mixture was diluted with toluene (5 mL) and warmed to 35–40°C. An aqueous sodium hydroxide solution (30%; 1.15 MEq.) was added over 45 minutes to hydrolyse the ester and the suspension was allowed to stir for an hour. After completion of the hydrolysis, water (10 mL) was added, the mixture was cooled to 20-30°C and the two phases were separated and aqueous layer containing desired product was washed with toluene (2 × 10mL).
Additional toluene (20 mL) was added, and the resulting mixture was heated to 60°C. Concentrated hydrochloric acid (1.2 MEq.) was added over 30 minutes to adjust pH to 2.5. The mixture was stirred for an hour at 60°C and for an additional 4 hours at 95°C. The biphasic mixture was then cooled to 20-30°C and the phases were separated. The toluene layer was washed twice with water. An aqueous solution of sodium metabisulfite (40% aq. 1.5 MEq.) was added into toluene layer and raised temperature to 50-60°C and maintained for an hour. Then, gradually allowed to cool at 20-30°C and maintained for 8-10 hours at 20-30°C.
The reaction mass was filtered under reduced pressure, washed twice with dichloromethane (10mL X 2) and dried for an hour to get solid product. Heptane (10g) and an aqueous sodium hydroxide solution (20-30%; 2 MEq.) was added to the solid product and stirred for 4-5 hours at 40-50°C. The layers were separated, and the upper organic layer was washed with water (10g X 2).
Heptane was completely removed from the organic layer under reduced pressure to get 1-(2,3,6-trifluorophenyl)propan-2-one (Purity: 99%; Yield: 70%).
Example 6: Preparation of 2,3,5,6-tetrafluorobenzamide.
A solution of 2,3,5,6-tetrafluoro benzonitrile (200 g) and water (0.6 M) was added to an aqueous sulphuric acid (98%, 4 M) at room temperature. The reaction mixture was stirred 110-120°C for 2-3 hours. After completion of the reaction, the reaction mixture was cooled to 10-15°C, filtered, washed twice with water (150 ml X 2) and dried under reduced pressure to obtain titled compound (yield: 95%; purity 99.5%).
Example 7: Preparation of 2,3,5-trifluorobenzamide.
A solution of 2,3,5,6-tetrafluorobenzamide (200 g) in N, N-dimethylformamide (200 ml) was added to a mixture of nickel chloride hexahydrate (0.2 M), 2,2´-bipyridine (0.2 M) in N,N-dimethylformamide (200 ml) and water (100 ml) at 60-70°C in a duration of 30 minutes. Zinc dust (2 M) was added lot-wise in the reaction mixture and stirred at a temperature of 60-70°C for 12-15 hours. The progress of reaction progress was monitored on HPLC. After completion of the reaction, pH of the reaction mass was adjusted using hydrochloric acid (6 M) at 10-20°C and then the reaction mass was extracted using ethyl acetate (300 ml X 2) and washed with brine solution to obtain a solid residue. The residue was crystallised using heptane at 60-70°C to obtain tetrafluorobenzoic acid having titled compound (yield: 80%; purity 90%).
Example 8: Preparation of 2,3,5-trifluorobenzoic acid.
A solution of 2,3,5-trifluorobenzamide (200 g) was added to an aqueous solution of sulphuric acid (50%, 5 M) at room temperature. The reaction mixture was heated to 135-145°C and stirred at same temperature for 12-14 hours. After completion of the reaction, reaction mixture was cooled to 10-15°C, filtered, washed twice with water (150 ml X 2) and dried under reduced pressure to obtain titled compound (yield: 95%; purity 99%).

CLAIMS:

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

Formula I
wherein X independently represents a chloro or fluoro and R an alkyl group,
comprising the steps of:
a) formylating 1,2,4-trihalobenzene of Formula III,

Formula III
wherein X is as defined above,
in presence of a base to form a 2,3,6-trihalobenzaldehyde of Formula II; and

Formula II
wherein X is as defined above,
b) reacting the 2,3,6-trihalobenzaldehyde of Formula II with a nucleophile in presence of base to obtain the compound of Formula I.
2. The process as claimed in claim 1, wherein the step of formylation is carried out carried out by reacting 1,2,4-trihalobenzene of Formula III with a formylating agent selected from a group consisting of dimethylformamide, diethylformamide and paraformaldehyde.
3. The process as claimed in claim 1, wherein the nucleophile is selected from a group consisting of methyl chloropropionate, ethyl chloropropionate, methyl bromopropionate and ethyl bromopropionate.
4. A process for preparation of 1,2,4-trihalobenzene, as defined in claim 1, comprises the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzoic acid;
b) de-halogenating 2,3,5,6-tetrahalobenzoic acid with zinc in presence of a catalyst to form 2,3,5-trihalobenzoic acid;
c) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.
5. The process for preparation of 1,2,4-trihalobenzene as defined in claim 1, comprises the steps of:
a) hydrolysing 2,3,5,6-tetrahalobenzonitrile using an acid to form 2,3,5,6-tetrahalobenzamide;
b) de-halogenating 2,3,5,6-tetrahalobenzamide with zinc in presence of a catalyst to form 2,3,5-trihalobenzamide;
c) hydrolysing 2,3,5-trihalobenzamide with an acid to obtain 2,3,5-trihalobenzoic acid;
d) de-carboxylating the 2,3,5-trihalobenzoic acid to obtain 1,2,4-trihalobenzene.
6. The process as claimed in claims 4 and 5, wherein the acid selected from a group consisting of sulfuric acid, phosphoric acid, hydrochloric acid, methane sulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid and trifluoroacetic acid.
7. The process as claimed in claim 4, wherein the step of hydrolysis is carried out at a temperature range of 120-140°C using 5 to 10 equivalents of an acid.
8. The process as claimed in claim 5, wherein the step of hydrolysis of 2,3,5,6-tetrahalobenzonitrile is carried out at a temperature of 110 to 120°C using 4 equivalents of an acid.
9. The process as claimed in claims 4 and 5, wherein the step of de-halogenation is carried out using zinc in presence of a catalyst comprising a metal complex selected from a group consisting of a nickel chloride hexahydrate with a ligand selected from the group consisting of 2,2´-bipyridine or 1,10-phenanthroline, 1,10-phenonthroline monohydrate morpholine and tetramethylethylenediamine.
10. The process as claimed in claims 4 and 5, wherein the step of de-carboxylation is carried out using a metal salt selected from a group consisting of a metal oxide, metal hydroxide and metal carbonate.