FIELD OF THE INVENTION
The present invention provides a process for preparing 2,5-dichloropyridine, which is useful as an intermediate for pharmaceutical and agrochemical industries.

BACKGROUND OF THE INVENTION
The present invention relates to a process for preparation of 2,5-dichloropyridine which is a useful as an intermediate in pharmaceutical and agrochemical industry. Several methods have been disclosed in the literature for the preparation of 2,5-dichloropyridine.
CN111909080 discloses a process that involves dechlorination of chloro substituted pyridine using zinc powder and ammonium chloride in presence of methanol and water at a temperature of 72? to give a mixture of products i.e., trichloropyridine 82.25%, dichloropyridine 13.42% and tetrachloropyridine 4.33%. The process produces a mixture of multichlorinated pyridines with very less amount of dichloropyridine therefore not suitable for selective preparation of dichloropyridine at a commercial scale.
U.S. 3,947,457 discloses a process for preparing 2,5-dichloropyridine by reacting 2,3,4,5-tetrachloropyridine with hydrazine in ethanol and in the presence of triethylamine. The process involves use of hydrazine which is not industrially feasible due to its high carcinogenicity.
The process for preparation of 2,5-dichloropyridine also involves formation of several by-products such as pyridine, 2-chloropyridine, 3-chloropyridine and unreacted 2,3,6-trichloropyridine.
The present invention provides a highly selective and industrially viable process for the preparation of 2,5-dichloropyridine with high purity and yield.

OBJECT OF THE INVENTION
The main object of the present invention is to provide a simple, cost effective and environment friendly process for the preparation of 2,5-dichloropyridine.

SUMMARY OF THE INVENTION
The present invention provides a process for preparation of 2,5-dichloropyridine, comprising dehalogenating a compound of formula I,

Formula I
wherein X is chloro, fluoro or bromo,
using a transition metal catalyst in presence of a base.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, the ‘base’ is metal hydroxide selected from a group consisting of sodium hydroxide, potassium hydroxide, cesium hydroxide and magnesium hydroxide, or a mixture thereof. The molar equivalents of the base with respect to a compound of formula II is in the range of 1.2 to 2.5, preferably in range of 1.2 to 2.0.
In an embodiment, the sodium hydroxide solution is used as a base in the present invention.
The transition metal catalyst as used herein, is selected from copper, nickel, zinc, tin, palladium, and platinum. Preferably the transition metal catalyst is elemental zinc.
In an embodiment, the compound of formula I is dehalogenated using zinc powder of mesh size between 5-10 micron in presence of a base and solvent. The molar ratio of the zinc powder w.r.t compound of formula I is used in the range from 1.1 to 1.5.
In an embodiment, zinc powder is added portion wise in the dehalogenation reaction. The zinc powder in dehalogenation reaction is added in 2-3 hours.
In an embodiment, dehalogenation of compound of formula I is optionally carried out in presence of a phase transfer catalyst.
The phase transfer catalyst is selected from a group consisting of ethyltriphenyl phosphonium chloride, benzyltriethylammonium chloride, methyltricaprylammonium chloride, methyltributylammonium chloride, methyltrioctylammonium chloride, tetraethylammonium bromide, tetraethylphosphonium bromide, tetraethylammonium chloride, tetraoctylphosphonium bromide, tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetrabutylammonium hydrogen sulphate, methyltriphenylphosphonium iodide, butyltriphenylphosphonium bromide, butyltriphenylphosphonium chloride, benzyltriphenylphosphonium chloride, tetraphenylphosphonium bromide and tetrapropylammonium bromide or the like.
The phase transfer catalyst will help in mixing of compound of formula I, solvent and inorganic reagents.
The dehalogenation is carried out at a temperature range of 20°C to 50°C, preferably 35°C to 50°C. The low temperature range prevents the degradation of product and improves yield significantly.
In an embodiment, dehalogenation of compound of formula I is carried out in a non-polar organic solvent selected from a group consisting of toluene, dioxane, anisole, cyclohexane, N-methylpyrrolidone and xylene isomers, or the like or a mixture thereof.
In another embodiment, dehalogenation of a compound of formula I is carried out without using any organic solvent. The absence of organic solvent in dehalogenation step eliminates the formation of by product.
In an embodiment, the compound of formula I is multi chlorinated pyridine such as 2-bromo-3,6-dichloropyridine, 3,6-dichloro-2-fluoropyridine, 2,3,6-trichlopyridine, and 2,3,4,5-tetrachloropyridine or the like.
In a specific embodiment, 2,3,6-trichlopyridine is dechlorinated using zinc in presence of sodium hydroxide in toluene to obtain 2,5-dichloropyridine.
In a specific embodiment, 2,3,6-trichloropyridine is dechlorinated using zinc powder and basic solution to obtain 2,5-dichloropyridine in presence of a phase transfer catalyst.
In another specific embodiment, 2,3,6-trichlopyridine is dechlorinated using zinc and sodium hydroxide in presence of tetraethylammonium bromide to obtain 2,5-dichloropyridine.
In a specific embodiment, 2,3,6-trichloropyridine is dechlorinated using zinc and an aqueous sodium hydroxide and toluene to obtain 2,5-dichlorpyridine in presence of tetrabutylammonium bromide.
The present invention provides a simple and highly selective process for preparation of 2,5-dichlorpyridine in basic medium that offers following advantages over the known methods:
1. The present invention reduces the number of operations at the industrial scale thereby making it cost effective.
2. The present invention eliminates use of expensive reagents.
3. The process of present invention provides efficient recycling and recovery of solvents.
4. The process of present invention is scalable and economically viable because it is a very well-known fact that high selectivity will lead to conversion of more reactant into the product which will reduce the cost of the process at industrial scale.
In an embodiment, the present invention provides a process for preparation of 2,5-dichlorpyridine, having yield greater than 84%.
In an embodiment, the present invention provides a process for preparation of 2,5-dichloropyridine, having purity greater than 97%, preferably greater than 98%, more preferably greater than 99%.
In another embodiment of the present invention, the solvent used or generated in the reaction is recovered and recycled for subsequent reactions.
The compound of formula I used in the present invention may be prepared by any method known in the prior art or may be obtained commercially.
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 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 2,5-dichloropyridine from 2,3,6-trichlopyridine
2,3,6-Trichlopyridine (5.0 g, 27.40 mmol) was added into a solution of sodium hydroxide (25%, 35.0 g, 218.7 mmol) and toluene (12.5 mL, 117.6 mmol) to form a reaction mixture. The tetraethylammonium bromide (0.075 g, 0.36 mmol) was added to the reaction mixture and stirred the mixture for 20 minutes at room temperature. Thereafter, zinc powder (3.75 g, 57.34 mmol) was added into the reaction mixture in portion wise and heated the reaction mass at 50°C for 3 hours. After completion of the reaction, toluene was recovered. Concentrated hydrochloric acid (5.3 g) and water (15 g) were added. The organic layer was separated, filtered, washed and dried to isolate the titled compound (3.43 g).
Yield: 84.5%
Selectivity: 88.5%
Purity: 97.5%
Example 2: Preparation of 2,5-dichloropyridine from 3,6-dichloro-2-fluoropyridine
3,6-Dichloro-2-fluoropyridine (5.0 g, 30.12 mmol) was added into a solution of sodium hydroxide (25% 35.0 g, 218.7 mmol) and toluene (12.5 mL, 117.6 mmol) to form a reaction mixture. The tetraethylammonium bromide (0.075 g, 0.36 mmol) was added to the reaction mixture and stirred the mixture for 20 minutes at room temperature. Thereafter, zinc powder (3.75 g, 57.34 mmol) was added into the reaction mixture in portion wise and heated the reaction mass at 50°C for 3 hours. After completion of the reaction, toluene was recovered. Concentrated hydrochloric acid (5.3 g) and water (15 g) were added. The organic layer was separated, filtered, washed and dried to isolate the titled compound (3.43 g).
Yield: 84.5%.
Selectivity: 87.5%
Purity: 97.8%
Comparative Example: Preparation of 2,5-dichloropyridine from 2,3,6-trichlopyridine in acidic medium.
2,3,6-trichlopyridine (5.0 g, 27.40 mmol) was added into a solution of sodium hydroxide (25%, 35.0 g, 218.7 mmol) and toluene (12.5 mL, 117.6 mmol) to form a reaction mixture. The tetraethylammonium bromide (0.075 g, 0.36 mmol) was added to the reaction mixture and stirred the mixture for 20 minutes at room temperature. Thereafter, zinc powder (3.75 g, 57.34 mmol) in acetic acid was added into the reaction mixture in portion wise and heated the reaction mass at 50°C for 3 hours. After completion of the reaction, toluene was recovered. Concentrated hydrochloric acid (5.3 g) and water (15 g) were added. The organic layer was separated, filtered, washed and dried to isolate the titled compound.
Conversion: 31.70%
Selectivity 2,5-dichloropyridine: 54.64%

CLAIMS:

WE CLAIM:

1. A process for preparation of 2,5-dichloropyridine, comprising dehalogenating a compound of formula I,

Formula I
wherein X is chloro, fluoro or bromo,
using a transition metal catalyst in presence of a base.
2. The process as claimed in claim 1, wherein the base used is metal hydroxide selected from a group consisting of sodium hydroxide, potassium hydroxide, cesium hydroxide and magnesium hydroxide.
3. The process as claimed in claim 1, wherein the transition metal catalyst used is selected from a group consisting of copper, nickel, zinc, tin, palladium, and platinum.
4. The process as claimed in claim 3, wherein the dehalogenation is carried out using zinc powder of mesh having size between 5-10 micron.
5. The process as claimed in claim 1, wherein the dehalogenation is additionally carried out in presence of a phase transfer catalyst, selected from a group consisting of ethyltriphenyl phosphonium chloride, benzyltriethylammonium chloride, methyltricaprylammonium chloride, methyltributylammonium chloride, methyltrioctylammonium chloride, tetraethylammonium bromide, tetraethylphosphonium bromide, tetraethylammonium chloride, tetraoctylphosphonium bromide, tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetrabutylammonium hydrogen sulphate, methyltriphenylphosphonium iodide, butyltriphenylphosphonium bromide, butyltriphenylphosphonium chloride, benzyltriphenylphosphonium chloride, tetraphenylphosphonium bromide and tetrapropylammonium bromide.
6. The process as claimed in claim 1, wherein the dehalogenation is carried out at a temperature range of 20°C to 50°C.
7. The process as claimed in claim 1, wherein the dehalogenation is carried out in a non-polar organic solvent selected from a group consisting of toluene, dioxane, anisole, cyclohexane, N-methylpyrrolidone and xylene isomers or a mixture thereof.
8. The process as claimed in claim 1, wherein dehalogenation of a compound of formula I is carried out without using any organic solvent.
9. The process as claimed in claim 1, wherein transition metal catalyst is added portion wise in the dehalogenation reaction in 2-3 hours.
10. The process as claimed in claim 1, wherein the solvent used or generated in the reaction is recovered and recycled for subsequent batches.