DESC:Field of the Invention
The present invention relates to a novel process for the production of halopyridines from their higher substituted homologues by reductive catalytic dehalogenation. Particularly, the present invention provides a catalyst friendly, large-scale industrial process for the preparation of halopyridines with good yield, high purity and simple isolation steps.
Background of the Invention
Halopyridines are important intermediates for chemical, pharmaceutical, pesticide and agrochemical industries.
For example, 2,3-dichloropyridine is a key intermediate in the synthesis of pesticide chlorantraniliprole. 2,3-; 2,5- and 2,6-Dichloropyridines are used as intermediates for agrochemicals and pharmaceuticals. 2,3-Difluoropyridine compounds are widely used in the plant protection field and as building blocks in the synthesis of pharmaceutical precursors. 2,3,5-Trichloropyridine is used as an intermediate in the synthesis of isoxapyrifop, an agrochemical compound. Similarly, 2,3,5,6-tetrachloropyridine is used as an intermediate in the synthesis of agrochemicals such as fospirate and triclopyr.
Being industrially important compounds, several processes are reported in the literature for the preparation of halopyridines.
US patent no. 4,515,953 discloses the preparation of polychlorinated pyridines by direct liquid phase chlorination of pyridine or pyridine hydrochloride in the absence of any catalyst. The products prepared by the process are 2-chloro-, 3-chloro-, 2,6-dichloro-, 3,5-dichloro, 2,3,5-trichloro, 2,3,6-trichloro-, 3,4,5-trichloro, 2,3,4,5-tetrachloro-, 2,3,5,6-tetrachloropyridine. The process results in the formation of mixtures of products and thus a number of purification steps are required to extract the desired chlorinated product. This results in low yield of the desired compound.
Japanese patent application no. 01193246A discloses the preparation of 2,3-dichloropyridine by dehalogenation of 2,3,6-trichloropyridine with hydrogen gas in the presence of acetic acid as solvent, sodium acetate as base and Pd/C catalyst. The reaction was carried out at 50 °C for 14 h resulting in the formation of 33% of 2,3-dichloropyridine, 62% of 2,3,6-trichloropyridine and 5% other compounds.
Bay et al in J. Org. Chem. 1988, 53, 12, 2858 discloses a process for the preparation of 2,3-dichloropyridine by halogenation of 2-chloro-3-nitropyridine with phenylphosphorous tetrachloride and benzene phosphorous dichloride.
Shiao et al in Synthetic Communications, 1990, 20, 19, 2971 reported the synthesis of halogenated 2-chloropyridines under Vilsmeier-Haack reaction conditions.
US patent no. 5,498,807 discloses a process for the preparation of 2,3-difluoropyridine by catalytic elimination of chlorine from 2,3-difluoro-5-chloropyridine.
US patent no. 5,468,863 discloses a process for the preparation of substituted 2,3-difluoropyridines by halogen exchange with fluoride salt and a protic solvent in presence of phase transfer catalyst in a continuous process.
Krapcho and Haydar in Heterocyclic Communications, 1998, 4, 291 reported the preparation of 2,3-dibromopyridine via the hydrogenation reaction of 2,3,6-tribromopyridine and 1-methyl-4-nitrosobenzene on Pd/C as catalyst.
US patent no. 8,293,918 discloses a multi-step process for the preparation of 2,3-dihalopyridine from 3-aminopyridine. The process involves halogenation of 3-aminopyridine in the presence of ferric chloride to obtain 3-amino-2-halopyridine followed by its diazotization to obtain diazo salt and treatment with halo acid in presence of a copper (I) catalyst to obtain crude 2,3-dihalopyridine. This 2,3-dihalopyridine is then purified by solvent extraction process.
European patent application no. 2687510 discloses the synthesis of 2,3-dichloropyridine from 2,3,6-trichloropyridine starting with 2,6-dichloropyridine. The process involves the chlorination of 2,6-dichloropyridine to get 2,3,6-trichloropyridine followed by the hydrogenation reaction to get 2,3-dichloropyridine. The hydrogenation reaction involves reacting 2,3,6-trichloropyridine with triethylamine, hydrogen gas, Pd/C catalyst and toluene in a reaction vessel under pressure 0-1MPa at a temperature of 60-80 °C. The mole ratio of 2,3,6-trichloropyridine to triethylamine is 1:0.1-0.5. When pH of the reaction solution reached 4-8 the reaction is stopped, temperature lowered and water is added to dissolve triethylamine, hydrochloride salt followed by the addition of toluene. The toluene layer is further extracted with hydrochloric acid followed with several steps of washing, filtration to get the wet 2,3-dichloropyridine which is oven dried to get the product with 85.7 % yield and > 99.5 % purity. This process involves several isolation and extraction steps which makes it commercially unattractive.
Chinese patent no. 102432528 discloses a process for the synthesis of 2,3-dichloropyridine by dechlorination of 2,3,5-trichloropyridine in the presence of a catalyst which is a composite of palladium carbon, nickel and platinum, for 20-24 hrs. The process involves mixing uniformly 2,3,5-trichloropyridine, methyl alcohol, triethylamine. The methyl alcohol used is 10-12 times that of 2,3,5-trichloropyridine.
Chinese patent no. 103232388 discloses a process for the separation of 2,3-dichloropyridine and 2,3,6-trichloropyridine by solid-liquid extraction. The process involves dissolving 2,3-dichloropyridine crude product with hydrochloric acid or sulfuric acid to obtain a solid-liquid mixture which is then filtered to separate 2,3,6-trichloropyridine as solid matter. The acid quantity of the filtrate is lowered (10% if hydrochloric acid and 5% if sulphuric acid) and once 2,3-dichloropyridine is sufficiently precipitated as solid matter, the solid-liquid separation is carried out again to obtain the 2,3-dichloropyridine product.
The halopyridines produced by the processes disclosed in the prior arts above require either multiple reaction steps or involve the formation of a number of by-products, tedious isolation and vast amount of effluent generation.
In view of increasing demand for the halopyridines of high purity and yield, there remains a need for an efficient process for the synthesis of halopyridines. The present invention provides a large-scale industrial process for the production of halopyridines with good yield and high purity. The process is catalyst friendly and cost effective.
Summary of the invention
It is a principal object of the present invention to provide a process for the preparation of halopyridine compounds of Formula (I)

Formula (I)
from compounds of Formula (II),

Formula (II)
said process comprising, reacting the compound of Formula (II) with hydrogen in the presence of transition metal catalyst and optionally a phase transfer catalyst, in the pH range of 8.5-14,
wherein, Y represents from 0 to 4 substituents independently selected from fluorine, chlorine, bromine and iodine; Z represents from 1 to 5 substituents independently selected from fluorine, chlorine, bromine and iodine.
It is yet another object of the present invention to provide a catalyst friendly, large-scale industrial process for the preparation of halopyridines with good yield and high purity.
It is yet another object of the present invention, to provide a process for the preparation of halogenated pyridines in the presence of a transition metal catalyst at a pH range of 8.5-14 wherein the catalyst is recovered and recycled even beyond fifteen recycles.
Detailed Description of the Invention
While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.
The present invention provides a novel process for the preparation of halogenated pyridines from their higher substituted homologues. The process involves reductive catalytic dehalogenation of the higher substituted homologues at a pH in the range of 8.5-14.
Catalytic reductive dehalogenation is a process where a halogen atom is removed from a chemical moiety in the presence of a catalyst. This is a useful reaction for the preparation of halopyridines from their higher substituted homologues. However, under the typical reaction conditions, not only the desired, but certain undesired by products are also formed due to various factors, such as uncontrolled / excessive dehalogenation, presence of un-reacted starting material, etc.
The inventors of the present invention have surprisingly found that performing catalytic dehalogenation of the substituted homologues at a pH in the range of 8.5-14 provides product with high purity avoiding multiple isolation steps. The process provides good conversion rate, fewer by-product formation and also recyclability of the catalyst. The process enables reuse of the catalyst more than twice while maintaining the catalyst performance, making it commercially sustainable. The catalyst performed exceptionally well and without deviation in the activity up-to fifteen re-cycles and even beyond that. Based on the above, it is evident that the life of the catalyst as per process of the present invention is high.
The invention is described herein in detail using the terms defined below unless otherwise specified.
The term “halopyridines” as used herein refers to mono, di, tri, tetra substituted pyridines, wherein the substitution is done with one or more halogens selected from the group comprising fluorine, chlorine, bromine and iodine. Examples of halogenated pyridines include, but are not limited to 2-chloropyridine, 2-bromopyridine, 2-iodopyridine, 2-fluoropyridine, 3-chloropyridine, 3-bromopyridine, 3-iodopyridine, 3-fluoropyridine; 2,3-dichloropyridine; 2,3-dibromopyridine; 2,3-diiodopyridine; 2,3-difluoropyridine; 2,4-dichloropyridine; 2,4-dibromopyridine; 2,4-diiodopyridine; 2,4-difluoropyridine; 2,5-dichloropyridine; 2,5-dibromopyridine; 2,5-diiodopyridine; 2,5-difluoropyridine; 3,5 dichloropyridine; 3,5-dibromopyridine; 3,5-diiodopyridine; 3,5-difluoropyridine; 2,6-dichloropyridine; 2,6-dibromopyridine; 2,6-diiodopyridine, 2,6-difluoropyridine; 2,3,4-trichloropyridine; 2,3,4-tribromopyridine; 2,3,4-trifluoropyridine; 2,3,5-trichloropyridine; 2,3,5-tribromopyridine; 2,3,5-trifluoropyridine; 2,3,6–trichloropyridine; 2,3,6–tribromo-pyridine; 2,3,6-trifluoro pyridine; 2,4,6-trichloropyridine; 2,4,6-trifluoropyridine; 3,4,5-trichloropyridine; 3,4,5-tribromopyridine; 3,4,5-triiodopyridine; 2,3,4,5-tetrachloropyridine; 2,3,4,5-tetrabromo pyridine; 2,3,4,5-tetraiodopyridine; 2,3,4,5-tetrafluoropyridine; 2,3,5,6-tetrachloropyridine; 2,3,5,6-tetrabromopyridine; 2,3,5,6-tetraiodopyridine ,2,3,5,6-tetrafluoropyridine and mixtures thereof.
The term “higher substituted homologues” as used herein refers to mono, di, tri, tetra and penta substituted pyridines, wherein the substitution is done with one or more halogens selected from the group comprising fluorine, chlorine, bromine and iodine. Examples of higher substituted homologues include, but are not limited to 2-chloropyridine, 2-bromopyridine, 2-iodopyridine, 2-fluoropyridine, 3-chloropyridine, 3-bromopyridine, 3-iodopyridine, 3-fluoropyridine; 2,3-dichloropyridine; 2,3-dibromopyridine; 2,3-diiodopyridine; 2,3-difluoropyridine; 2,4-dichloro pyridine; 2,4-dibromopyridine; 2,4-diiodopyridine; 2,4-difluoropyridine; 2,5-dichloropyridine; 2,5-dibromopyridine; 2,5-diiodopyridine; 2,5-difluoropyridine; 3,5-dichloropyridine, 3,5-dibromopyridine; 3,5-diiodopyridine; 3,5-difluoropyridine; 2,6-dichloropyridine; 2,6-dibromo pyridine; 2,6-diiodopyridine; 2,6-difluoropyridine; 2,3,4-trichloropyridine; 2,3,4-tribromo pyridine; 2,3,4-trifluoropyridine; 2,3,5-trichloropyridine; 2,3,5-tribromopyridine; 2,3,5-trifluoropyridine; 2,3,6–trichloropyridine; 2,3,6–tribromo pyridine; 2,3,6-trifluoropyridine; 2,4,6-trichloropyridine; 2,4,6-trifluoropyridine; 3,4,5-trichloropyridine; 3,4,5-tribromopyridine; 3,4,5-triiodopyridine; 2,3,4,5-tetrachloropyridine; 2,3,4,5-tetrabromopyridine; 2,3,4,5-tetra iodopyridine; 2,3,4,5-tetrafluoropyridine; 2,3,5,6-tetrachloropyridine; 2,3,5,6-tetrabromo pyridine; 2,3,5,6-tetraiodopyridine, 2,3,5,6-tetrafluoropyridine, pentachloropyridine, pentabromopyridine and pentafluoropyridine.
The term “solvent” as used herein refers to polar protic solvent, polar aprotic, non polar solvent and mixtures thereof. Examples of polar protic solvent include, but are not limited to n-butanol, isopropanol, n-propanol, ethanol, methanol, water; examples of polar aprotic solvent include, but are not limited to dichloromethane, tetrahydrofuran, ethyl acetate, acetone, methyl isobutyl ketone, dimethylformamide, dimethylacetamide, acetonitrile, dimethyl sulfoxide, and the mixtures thereof; examples of non polar aprotic solvent include but are not limited to hexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, methyl tert-butyl ether.
The term “acid binding agent” as used herein refers to a basic compound capable of binding to an acidic molecule. Examples of acid binding agent include, but not limited to ammonia, pyridine, monoalkylamines, dialkylamines, trialkylamines, alkali metal hydroxides, alkali earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal bicarbonates, alkaline earth metal bicarbonates, alkali metal salts, alkali metal formate, alkaline earth metal formate, alkali metal acetate, alkaline earth metal acetate and mixtures thereof. Examples of alkali metal hydroxides include lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), caesium hydroxide (CsOH), and mixtures thereof. Examples of alkaline earth metal hydroxides include magnesium hydroxide (Mg(OH)2), calcium hydroxide (Ca(OH)2), barium hydroxide (Ba(OH)2), strontium hydroxide (Sr(OH)2) and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate (Li2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), caesium carbonate (Cs2CO3) and mixtures thereof. Examples of alkaline earth metal carbonate include magnesium carbonate (MgCO3), calcium carbonate (CaCO3), barium carbonate (BaCO3), strontium carbonate (SrCO3) and mixtures thereof. Examples of alkali metal bicarbonates include sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3) and mixtures thereof. Examples of alkaline earth metal bicarbonates magnesium bicarbonate (Mg(HCO3)2), calcium bicarbonate (Ca(HCO3)2) and mixtures thereof. Examples of alkali metal acetates include sodium acetate (CH3COONa), potassium acetate (CH3COOK), and mixtures thereof. Examples of alkaline earth metal acetates include magnesium acetate (Mg(CH3COO)2), calcium acetate Ca(CH3COO)2, and mixtures thereof. Examples of alkali metal formate include sodium formate (HCOONa), potassium formate (HCOOK), and mixtures thereof. Examples of monoalkylamines include, but are not limited to methylamine, ethylamine, propylamine and mixtures thereof. Examples of dialkylamines include, but are not limited to dimethylamine, diethylamine, and mixtures thereof. Examples of trialkylamines include, but are not limited to trimethylamine, triethylamine and mixtures thereof.
The term “recycling of catalyst” and “recycled catalyst” as used herein means that the same catalyst is used more than once.
The term “transition metal catalyst” as used herein means any transition metal of groups V, VI, VII and VIII of the Periodic Table. Examples of transition metal include, but not limited to Palladium (Pd), Ruthenium (Ru), Rhodium (Rh), Platinum (Pt), Nickel (Ni), Copper (Cu), Tin (Sn), Zinc (Zn) and mixtures thereof.
The term “catalyst support” as used herein means a material on which a catalyst can be supported but in itself has no catalytic role in the reaction. Examples of support include but not limited to finely divided charcoal, carbon, silica, alumina, zeolites and mixtures thereof.
The term “phase transfer catalyst” as used herein means a catalyst that helps in the migration of a reactant from one phase into another. Examples of phase transfer catalyst include, but are not limited to tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium chloride, tetrapropylammonium bromide, tributylbenzylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium acetate, ethyltriphenylphosphonium bromide and the likes.
The term “mineral acid” as used herein means an inorganic acid. Examples of mineral acid include, but are not limited to hydrochloric acid, nitric acid, sulphuric acid, hydrofluoric acid and mixtures thereof.
It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise.
In one embodiment, the present invention provides a novel process for the preparation of halopyridine compounds of Formula (I) from their higher substituted homologues of Formula (II) by catalytic dehalogenation at pH 8.5-14. The process is catalyst friendly and is suitable for large-scale industrial preparation of halopyridines with good yield, high purity and simple isolation steps.
In one embodiment, the present invention provides a novel process for the preparation of halopyridine compounds of Formula (I)

Formula (I)
from compounds of Formula (II),

Formula (II)
said process comprising, reacting the compound of Formula (II) with hydrogen in the presence of transition metal catalyst and optionally a phase transfer catalyst in the pH range of 8.5-14,
wherein, Y represents from 0 to 4 substituents independently selected from fluorine, chlorine, bromine and iodine; Z represents from 1 to 5 substituents independently selected from fluorine, chlorine, bromine and iodine.
In another embodiment, the present invention provides a novel process for the preparation of halopyridine compounds of Formula (I) by reacting the compound of Formula (II) with hydrogen in the presence of transition metal catalyst and optionally a phase transfer catalyst, in the pH of 8.5-14, wherein the reaction further comprises isolating the compound of Formula (I) with a mineral acid.
In one embodiment of the present invention, the reaction is carried out in the presence of an acid binding agent and a solvent.
In a preferred embodiment, the acid binding agent is selected from the group comprising of ammonia, pyridine, monoalkylamines, dialkylamines, trialkylamines, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal bicarbonates, alkaline earth metal bicarbonates, alkali metal acetate, alkaline earth metal acetate, alkali metal formate, alkaline earth metal formate, and mixtures thereof.
Examples of alkali metal hydroxides include lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH) and mixtures thereof. Examples of alkaline earth metal hydroxides magnesium hydroxide (Mg(OH)2), calcium hydroxide (Ca(OH)2), barium hydroxide (Ba(OH)2), strontium hydroxide (Sr(OH)2) and mixtures thereof. Examples of alkali metal carbonates include lithium carbonate (Li2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), cesium carbonate (Cs2CO3) and mixtures thereof. Examples of alkaline earth metal carbonate include magnesium carbonate (MgCO3), calcium carbonate (CaCO3), barium carbonate (BaCO3), strontium carbonate (SrCO3) and mixtures thereof. Examples of alkali metal bicarbonates include sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3) and mixtures thereof. Examples of alkaline earth metal bicarbonates include magnesium bicarbonate (Mg(HCO3)2), calcium bicarbonate (Ca(HCO3)2) and mixtures thereof. Examples of alkali metal acetates include sodium acetate (CH3COONa), potassium acetate (CH3COOK), and mixtures thereof. Examples of alkaline earth metal acetates include magnesium acetate Mg(CH3COO)2, calcium acetate Ca(CH3COO)2 and mixtures thereof. Examples of alkali metal formate include sodium formate (HCOONa), potassium formate (HCOOK) and mixtures thereof. Examples of monoalkylamines include, but are not limited to methylamine, ethylamine, propylamine and mixtures thereof. Examples of dialkylamines, include but are not limited to dimethylamine, diethylamine, and mixtures thereof. Examples of trialkylamines include, but are not limited to trimethylamine, triethylamine and mixtures thereof.
In one embodiment of the present invention the solvent is selected from polar protic solvent, polar aprotic, non polar solvent and mixtures thereof. Examples of polar protic solvent include, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof. Examples of polar aprotic solvent include dichloromethane, tetrahydrofuran, ethyl acetate, acetone, methyl isobutyl ketone, dimethylformamide, dimethylacetamide, acetonitrile, dimethyl sulfoxide, and the mixtures thereof. Examples of non polar aprotic solvent include, hexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, methyl tert-butyl ether and mixtures thereof.
In one embodiment of the present invention, the transition metal catalyst is selected from Palladium (Pd), Ruthenium (Ru), Rhodium (Rh), Platinum (Pt), Nickel (Ni), Copper (Cu), Tin (Sn), Zinc (Zn) and mixtures thereof.
In another embodiment of the present invention, the transition metal catalyst is selected from Palladium (Pd), Ruthenium (Ru), Rhodium (Rh), Platinum (Pt), Zinc (Zn) and mixtures thereof.
In one embodiment of the present invention the catalyst support is selected from charcoal, carbon, silica, alumina, zeolites and mixtures thereof.
In one embodiment of the present invention the phase transfer catalyst is preferably selected from tetrabutylammonium bromide, tetrabutylammonium chloride, tetrapropylammonium bromide, tributylbenzylammonium bromide, tetraoctylammonium bromide, tetrabutylammonium iodide and mixtures thereof.
In a preferred embodiment, the present invention relates to a process for preparing 2,3-di-halo substituted pyridine, said process comprising reductive dehalogenation of the higher substituted homologues with a transition metal catalyst in the pH of 8.5-14.
In another embodiment, the present invention provides a process for the preparation of halogenated pyridine of Formula (I) in the presence of a transition metal catalyst and a phase transfer catalyst at a pH range of 8.5-14, wherein the compound of Formula (I) are isolated with a mineral acid.
In one embodiment the mineral acid is selected from the group comprising hydrochloric acid, nitric acid, sulphuric acid and mixtures thereof.
In one embodiment of the present invention, the dehalogenation is performed in the temperature range of 5 to 150 °C, preferably between 20 to 70 °C.
In one embodiment of the present invention, the dehalogenation is carried out at a pressure of 0.1 to 25 kg/cm2.
In yet another embodiment of the present invention, the mole ratio between the starting halogenated compound of Formula (II) and acid binding agent is in the range of 1: 1 to 1: 2.
In another embodiment, the compound of the present invention of Formula (I) is pyridine, 2-chloropyridine, 2-bromopyridine, 3-chloropyridine, 3-bromopyridine; 2,3-dichloropyridine; 2,3-dibromopyridine; 2,4-dichloropyridine; 2,4-dibromopyridine; 2,5 dichloropyridine; 2,5 dibromopyridine; 3,5-dibromopyridine; 3,5-dicloropyridine; 2,6-dichloropyridine; 2,3,4-trichloropyridine; 2,3,5-trichloropyridine; 2,3,6–trichloropyridine; 2,3,4,5- tetrachloropyridine and 2,3,5,6-tetrachloropyridine and mixtures thereof.
In a preferred embodiment, the compounds of Formula (I) are one or more compounds selected from 2-chloropyridine; 2-bromopyridine, 3-bromopyridine, 3-chloropyridine, 2,3-dichloropyridine; 2,5-dichloropyridine; 2,6-dichloropyridine; 3,5-dibromopyridine.
In another embodiment, the present invention provide a process for the preparation of halogenated pyridine of Formula (I) in the presence of a transition metal catalyst and a phase transfer catalyst at a pH range of 8.5-14, wherein the transition metal catalyst is recycled more than twice.
In another embodiment, the present invention provide a process for the preparation of halogenated pyridine of Formula (I) in the presence of a transition metal catalyst at a pH range of 8.5-14 wherein the transition metal catalyst is recycled more than twice.
In another embodiment, the present invention provide a process for the preparation of halogenated pyridine of Formula (I) in the presence of a transition metal catalyst at a pH range of 8.5-14 wherein the transition metal catalyst is recycled for fifteen times and even beyond that without effecting yield, conversion and purity of the product.
According to the present invention, the halogenated pyridines prepared by the process of the present invention are of high purity and hence are suitable as intermediates for the synthesis of agrochemical and pharmaceutical products.
The details of the process of the invention are further described in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention in any manner.
Example -1
2,3,6-Trichloropyridine (200g), toluene (400g) and 5% Ru/Alumina (10g) were charged in an autoclave at room temperature. Ammonia gas (60-81gm) was then purged into the solution followed by hydrogen gas. The pH of the reaction mass was maintained at 8.5-9.5. The completion of reaction was monitored by gas chromatography (GC). After the completion of reaction, the reaction mass was filtered, washed and extracted with HCl. The filtered catalyst was washed and kept for reuse. The organic mass was used for further reaction by making up 2,3,6-trichloropyridine. The extracted aqueous mass was neutralized, filtered and vacuum dried to yield pure 2,3-dichloropyridine (63.7g) having 99% GC purity. The product was characterized by Mass and 1H NMR. M.P.: 63-68 °C; 1H-NMR (CDCl3; 400MHz) d 7.0202-8.323 (m,3H,Ar); 13C-NMR (CDCl3; 400 MHz) d 123.222, 130.701, 138.791, 147.304, 149.300; MS (70eV): m/e 147(M+).
Example-2
2,3,6-Trichloropyridine (200g), toluene (400g) and 5% Pd/C (10g) were charged in an autoclave at room temperature. Ammonia gas (60-81gm) was then purged into the solution followed by hydrogen gas. The pH of the reaction mass was maintained at 8.5-9.5. The completion of reaction was monitored by gas chromatography. After the completion of reaction, the reaction mass was filtered, washed and extracted with HCl. The filtered catalyst was washed and kept for reuse. The organic mass was used for further reaction by making up 2,3,6-trichloropyridine. The extracted aqueous mass was neutralized, filtered and vacuum dried to yield pure 2,3-dichloropyridine (69.53g) having 99% GC purity. The product was characterized by Mass and 1 H NMR.
Example -3
2,3,6-Trichloropyridine (200g), toluene (400g), triethylamine (58.0g) and 5% Ru/C (10g) were charged in an autoclave at room temperature. Hydrogen gas was then purged into the reaction mass, the pH of the reaction mass was maintained at 8.5-9.5. The completion of reaction was monitored by gas chromatography. After the completion of reaction, the reaction mass was filtered, washed and extracted with HCl. The filtered catalyst was washed and kept for reuse. The organic mass was used for further reaction by making up 2,3,6-trichloropyridine. The extracted aqueous mass was neutralized, filtered and vacuum dried to yield pure 2,3-dichloropyridine (64.86g) having 99% GC purity. The product was characterized by Mass and 1H NMR.

Example -4
2,3,6-Trichloropyridine (200g), sodium hydroxide (80g), sodium acetate (24g), toluene (400g), tetrabutylammonium bromide (1.0g), water (320g) and 5% Pd/C (0.5g) were charged in an autoclave at room temperature. Hydrogen gas was then purged into the solution at a pH of about 13-14. The completion of reaction was monitored by gas chromatography. After the completion of reaction, the reaction mass was filtered and extracted with HCl. The filtered catalyst was washed and separated and the extracted aqueous mass was neutralized, filtered and vacuum dried to yield pure 2,3-dichloropyridine (69.72g) having GC purity of 99%. The separated organic mass was used for further reaction by making up 2,3,6-trichloropyridine. The product was characterized by Mass and 1H NMR.
Example 5
2,3,6-Tribromopyridine (200g), potassium hydroxide (139g), potassium acetate (42g), toluene (400g), water (320g) and 5% Pd/C (0.5g) are charged into an autoclave at room temperature. Hydrogen gas is then purged into the solution at a pH of about 13-14. The completion of reaction is monitored by gas chromatography. After the completion of reaction, the reaction mass is filtered and extracted with HCl. The filtered catalyst is washed, separated and kept for re use. The extracted aqueous mass is neutralized, filtered and vacuum dried to yield pure 2,3-dibromopyridine (64.5g). The separated organic mass is used for further reaction by making up 2,3,6-tribromopyridine. The product is characterized by Mass and 1H NMR.
Example 6
Pentachloropyridine (200g), sodium carbonate (104g), toluene (400g), tetrabutylammonium bromide (1.0g), water (3 20g) and 5% Pd/C (0.5g) are charged in an autoclave at room temperature. Hydrogen gas is then purged into the solution at a pH of about 12-13. The completion of reaction is monitored by gas chromatography. After the completion of reaction, the reaction mass is filtered and extracted with HCl. The filtered catalyst is washed, separated and kept for re use. The extracted aqueous mass is neutralized, filtered and vacuum dried to yield pure 2,3,5,6-tetrachloropyridine (66.56 g). The separated organic mass is used for further reaction by making up 2,3,5,6-tetrachloropyridine. The product is characterized by Mass and 1HNMR.
The results of the recyclability of the catalyst (Pd/C) at different pH are tabulated in Table as below:
pH
Bases Cycle no Purity (%) Yield (%) Remarks
5-6 AcONa 1 98.25 38.20
2 --- ---- Reaction did not proceed after one cycle. Catalyst content reduced to 1.2%.
NaOH
HCOONa 1 98.87 36.40
2 --- --- Reaction did not proceed after one cycle.Catalyst content reduced to 0.87%.
NaOH
AcONa 1 99.12 47.30
2 --- --- Reaction did not proceed after one cycle. Catalyst content reduced to 1.35%.
7- 8 NaOH 1 99.23 52.80
2 --- --- Reaction did not proceed after one cycle.
Catalyst content reduced to 1.64%.
Triethylamine 1 98.7 53.30
2 Reaction did not proceed after one cycle.
Catalyst content reduced to 0.92%.
8.5-9.5 Ammonia 1 99.83
57.14
Reaction did not proceed after 4th recycle.
Catalyst content reduced to 2.1%.
2 99.63 56.9
3 99.46 56.6
4 99.55 54.1
5 98.9 45.6
12-14 NaOH
AcONa 1 99.67
56.80
After the 10th recycle of catalyst, catalyst content reduced to 4.2%.
2 99.83 56.78
3 99.67 57.30
4 99.88 56.89
5 99.88 57.15
6 99.81 56.92
7 98.93 56.95
8 99.71 57.32
9 99.93 57.10
10 97.29 56.8
11 99.59 57.1

The catalyst performed well even beyond fifteen cycles maintaining its conversion rate. Thereafter in the subsequent cycles also, the catalyst worked well after making up. It is evident that when the catalytic dehalogenation reaction in the present invention was performed at pH range 8.5 - 14, it resulted in increasing the life efficiency of the catalyst and thus making the process commercially viable. It was also observed that the by-products formed were suppressed and high yields of the desired halopyridines are obtained.

CLAIMS:
1.A process for the preparation of compounds of Formula (I)

Formula (I)
from compounds of Formula (II),

Formula (II)
said process comprising, reacting the compound of Formula (II) with hydrogen in the presence of transition metal catalyst and optionally a phase transfer catalyst in the pH range of 8.5-14,
wherein, Y represents from 0 to 4 substituents independently selected from fluorine, chlorine, bromine and iodine; Z represents from 1 to 5 substituents independently selected from fluorine, chlorine, bromine and iodine.
2. The process as claimed in claim 1, wherein the reaction is carried out in the presence of an acid binding agent and solvent.
3. The process as claimed in claim 2, wherein the acid binding agent is selected from the group comprising ammonia, pyridine, lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), magnesium hydroxide (Mg(OH)2), calcium hydroxide (Ca(OH)2), barium hydroxide (Ba(OH)2), strontium hydroxide (Sr(OH)2), lithium carbonate (Li2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), cesium carbonate (Cs2CO3), magnesium carbonate (MgCO3), calcium carbonate (CaCO3), barium carbonate (BaCO3), strontium carbonate (SrCO3), sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3), magnesium bicarbonate (Mg(HCO3)2), calcium bicarbonate (Ca(HCO3)2), sodium acetate (CH3COONa), potassium acetate (CH3COOK), magnesium acetate Mg(CH3COO)2, calcium acetate, Ca(CH3COO)2, sodium formate (HCOONa), potassium formate (HCOOK), methylamine, ethylamine, propylamine, dimethylamine, diethylamine, trimethylamine, triethylamine and mixtures thereof.
4. The process as claimed in claim 2, wherein the solvent is selected from the group comprising n-butanol, isopropanol, n-propanol, ethanol, methanol, water, dichloromethane, tetrahydrofuran, ethyl acetate, acetone, methyl isobutyl ketone, dimethylformamide, dimethylacetamide, acetonitrile, dimethyl sulfoxide, hexane, benzene, toluene, 1,4-dioxane, chloroform, diethyl ether, methyl tert-butyl ether and mixtures thereof.
5. The process as claimed in claim 1, wherein the transition metal catalyst is selected from the group comprising palladium, ruthenium, rhodium, nickel, copper, tin, zinc and mixtures thereof.
6. The process as claimed in claim 1, wherein the transition metal catalyst is present on a catalyst support selected from the group comprising carbon, silica, alumina, and zeolite.
7. The process as claimed in any of claims 1-6, wherein the compound of Formula (I) is pyridine; 2-chloropyridine; 2-bromopyridine; 3- chloropyridine; 3- bromopyridine; 2,3-dichloropyridine; 2,3-dibromopyridine; 2,4- dichloropyridine; 2,5-dichloropyridine; 3,5-dichloropyridine; 3,5- dibromopyridine; 2,6-dichloropyridine; 2,3,4-trichloropyridine; 2,3,5- trichloropyridine; 2,3,6– trichloropyridine; 2,3,4,5-tetrachloropyridine; 2,3,5,6- tetrachloropyridine and mixtures thereof.
8. The process as claimed in claim 1, further comprising isolating the compounds of Formula (I) with a mineral acid selected from the group comprising hydrochloric acid, nitric acid, sulphuric acid.
9. The process as claimed in any of claims 1-8, wherein the reaction is carried out at a pressure of 0.1 to 25 kg/cm2.
10. The process as claimed in any of claims 1-9, wherein the catalyst is recovered and recycled.