DESC:FIELD OF THE INVENTION
The present invention relates to an improved process for production of polyhalo pyridine carboxylic acids. More, particularly, the present invention provides an improved, cost effective and eco-friendly process for large scale industrial production of 3,6-dichloro-2-pyridinecarboxylic acid with high yield and purity.

BACKGROUND OF THE INVENTION
3,6-dichloro-2-pyridinecarboxylic acid or 3,6-dichloropicolinic acid is commonly known as Clopyralid. It is represented by the following structure:

It is a selective herbicide used for control of broadleaf weeds, especially thistles and clovers. It belongs to the picolinic acid family of herbicides, which also includes aminopyralid, picloram, triclopyr, and several less common herbicides. For control of creeping thistle, Cirsium arvense, a noxious, perennial weed, it is one of the few effective herbicides available. It is typically formulated as a salt and as red-to-brown liquid concentrates that are mixed with water and applied as a spray.
Clopyralid is first disclosed in US Patent No. 3,317,549 (1967). In this document 3,6-dichloro-2- (trichloromethyl) pyridine was used as a raw material and subjected to hydrolysis with nitric acid at reflux temperature, cooling and crystallizing the reaction material after the reaction is finished to obtain clopyralid (3,6-dichloropyridine carboxylic acid). The main synthesis steps of the method are as follows

US 4,087,431 (1977) discloses a process of preparing clopyralid from tetrachloropicolinic acid. The reaction scheme is shown below:

tetrachloropicolinic acid is treated with hydrazine in the presence of base to obtain 3,5,6-trichloro-4-hydrazinopicolinic acid which is reactedwith an alkali metal hydroxide in water and alcohol followed by acidifying the reaction mixture to give clopyralid. The yield reported in this process is 78%, and purity is 90%. This method is not environmentally friendly due to high toxicity of hydrazine along with low purity of clopyralid obtained.

US Patent no. 4,217,185 discloses the preparation of 3,6-dichloropicolinic acid (clopyralid) by electrolytic reduction of tetrachloro-2-picolinic acid in basic aqueous solution at an activated silver cathode. The reaction scheme is shown below:

The electrolytic method has the advantages that the product yield and the product purity can reach 90% or above. In addition, the reducing agent used in the method is electrons, and is very environment-friendly to the environment.

Afterwards various modifications in anode used were reported in US Patent No. viz. US 4533454; US 4592811; US4755266, US 4778576 etc. All methods or processes for electrolysis synthesis of 3,6-dichloropyridine are common non-automatic reversing direct-current power supplies. Due to the fact that in the 3, 6-dichloropicolinic acid electrolysis synthesis process, the cathode and the anode need frequent reversing and changing the current density to roughen the silver cathode, and the normal direct-current power supply is used, so that the working amount is large, and the control is difficult

CN100579964C discloses a process where 2-cyanopyridine and chlorine are used as the main raw materials. Chlorination of 2-cyanopyridine with ferric chloride in the presence of zinc chloride and cobalt chloride as a catalyst to give tetrachloropicolinic acid. The resulting product is hydrolysed and reduced with hydrazine hydrate in presence of sodium carbonate at 80? to give 3,6-dichloropicolinic acid. The said synthetic route is as follows:

In the said method, the components of zinc chloride and cobalt chloride are added as catalysts in the medium of ferric chloride and hydrochloric acid to enhance the ability of metal ions during chlorination reaction. The use of mixture of metal catalyst eventually increase in the cost.

Further, the reduction of tetrachloropicolinic acid is done at 80? which may result in formation of 6-chloropicolinic acid as an impurity and use of hydrazine may result 4-hydrazino-3,6-dicloropicolinic acid as impurity. Therefore, the said method for preparing 3,6-dichloropicolinic acid is not commercially attractive.

CN105503713A discloses a process for the preparation of 3,6-dichloropicolinic acid by selective reduction of tetrachloropicolinic acid with catalyst selected from Pd/C, Pt/C or Ri-Ni at 0.1 to 1Mpa hydrogen pressure and at 30 to 60 ? in presence of base in an autoclave. The said synthetic route is as follows:

The yield of product is 70-80% and product purity is 97-98%. The said Chinese application suffered from drawback such as use of high external pressure and autoclave are required for the reaction. Moreover, catalyst used are expensive. Further, the high temperature 30 to 60 ? is required for the said reduction step which may lead to formation of 6-chloropicolinic acid as an impurity. Thus the above method is not commercially viable.

The preparation methods of 3,6-dichloro-2-pyridinecarboxylic acid as per the literature has the following limitations:
a) Use of the hydrazine which is very toxic and environment hazard
b) In electrolytic method, frequent replacement of electrodes is required, the equipment investment is high, and the productivity is small
c) Use of autoclave and hydrogen at high external pressure;
d) High temperature which leads to the formation of impurity

In order to obviate the drawbacks in the literature, there is a need to develop commercially and economically viable process for industrial manufacturing of clopyralid with high yield and purity which can address the above mentioned problems associated with the known processes.

OBJECT OF THE INVENTION
The principal object of the present invention is to provide an improved process for preparation of 3,6-dichloro-2-pyridinecarboxylic by selective reduction of tetrachloropicolinic acid using a catalyst.
It is another object of the present invention is to provide an improved process for preparation of 3,6-dichloro-2-pyridinecarboxylic acid having high selectivity.
It is another object of the invention to provide a cost effective and commercially viable process for producing clopyralid at industrial scale where process provides product with desired purity, involving simple isolation steps, avoiding multi stage operations for purification.
It is another object of the present invention to provide an eco-friendly and carbon efficient process for producing clopyralid at industrial scale, wherein the process enables production of clopyralid at industrial scale with minimum generation of effluents.
It is another object of the present invention to provide an eco-friendly and carbon efficient process for producing clopyralid at industrial scale, wherein the process involves inexpensive and easy to handle catalyst.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a process for the preparation of 3,6-dichloro-2-pyridinecarboxylic acid (clopyralid) of formula (I),

Formula (I)
said process comprising reduction of tetrachloropicolinic acid of formula (II) in the presence of a zinc based catalyst.
,
Formula (II)

In one embodiment, the zinc based catalyst used in the present invention may be selected from but not limited to Zinc(tetrahydroborato)pyridine [Zn(BH4)(pyr)] complex, zinc powder, (N-Methylimidazole)(tetrahydroborato)zinc complex, (nicotine)(tetraborato)zinc [Zn(BH4)(nic] complex, zinc cyanoborohydride, zinc borohydride, Zinc chips or zinc dust and mixtures thereof.

The reduction reaction of the present invention may be carried out in the presence of aqueous alkaline reagent and a suitable solvent. The alkaline reagent is selected from an aqueous alkali, alkaline earth metal hydroxide, aqueous ammonium hydroxide, aqueous ammonia and the like or mixture thereof. The suitable solvent(s) is selected from but not limited to water, alcohol and/or the like or mixture thereof. The solvent may be preferably selected from water, methanol, ethanol, propanol, isopropanol and the like or mixture thereof.

In one embodiment, the reduction reaction of the present invention may be carried out at a temperature in the range 0? to 25?.

In one embodimentt, the present invention provides to a process for preparation of pure 3,6-dichloropicolinic acid said process comprises:
i) Subjecting impure tetrachloropicolinic acid to acid-base treatment to obtain pure tetrachloropicolinic acid and;
ii) converting the pure tetrachloropicolinic acid to 3,6-dichloropicolinic acid.
The pure tetrachloropicolinic acid may be defined as “tetrachloropicolinic acid having purity greater than 99 %.

In another embodiment the present invention also provides the process for the preparation of clopyralid from tetrachloropicolinic acid, wherein the tetrachloropicolinic acid is prepared by hydrolysis of 3,4,5,6-tetrachloro picolinonitrile of formula III

Formula (III)

The hydrolysis of tetrachloropicolinonitrile may be carried out in the presence of acid and water. The hydrolysis reaction of the present invention may be carried out at a temperature 20? to 130?, preferably from 40? to 125? and more preferably from 70? to 125?.

It will be understood by those skilled in the art that the summary of the invention provided herein is exemplary and explanatory of the invention are not intended to be restrictive thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. The composition, methods, and examples provided herein are only illustrative and not intended to be limiting.

Advantages of the Invention: The present invention provides one or more of the following advantages:
? Catalyst used for reduction in the present invention is not toxic as hydrazine.
? Reduction in the present invention is done at atmospheric pressure. There is no need of autoclave and external high pressure as compared to prior art catalyst such as Pd/C, Pt/C or Ri-Ni.
? Reduction reaction of the present invention is carried out at a temperature in the range 0 ? to 25? which reduces the utility cost.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope. The process of preparing clopyralid and its intermediates are illustrated in the following examples:

EXAMPLES
Example 1: Process for the preparation of tetrachloropicolinic acid
3,4,5,6-Tetrachloropicolinitrile (242g, 1 mole eq.) was added to water (90g, 5.0 mole eq.) followed by addition of conc. sulphuric acid (50g 0.5 mole eq.) slowly. The temp. of reaction mass was raised to 70-125°C and maintained for 4-5 hours. After completion of reaction, reaction mass was quenched with water (1.4L) at 5-40°C. The reaction mass was stirred at 20-30°C for 4-5hours. The reaction mass was filtered and washed with water to give 3, 4, 5, 6-Tetrachloropyridine-2-carboxylic acid [Tet Acid] with purity >96 % and yield 85 to 90% w/w.

Example 2: Process for the preparation of pure tetrachloropicolinic acid
3,4,5,6-Tetrachloropicolinitrile (242g, 1 mole eq.) was added to water (90g, 5.0 mole eq.) followed by slow addition of conc. sulphuric acid (49g 0.5 mole eq.) slowly. The temp. of reaction mass was raised to 70-125°C and maintained for 4-5 hours. After completion of reaction, reaction mass was quenched with water (1.4L) at 15-40°C. The reaction mass was stirred at 20-30°C for 4-5hours. Aqueous sodium hydroxide solution (20%) was added to the reaction mass to adjust pH 9-10 followed by addition of water to get clear solution. The aqueous solution was extracted with dichloromethane followed by acidification of the aqueous layer with conc. sulphuric acid. The solid precipitated out was filtered and washed with water to give 3,4,5,6-Tetrachloropyridine-2-carboxylic acid [Tet Acid] having purity more than 99 %.

Example 3: Process for the preparation of 3,6-dichloro-2-picolinic acid
To a solution of methanol (200mL) and aqueous 25-30% ammonia solution, zinc cyanoborohydride (2.0 mole) was added and stirred for 15 minutes. After that 3,4,5,6-Tetrachloropyridine-2-carboxylic acid [Tet Acid] was added in lots at room temp. The reaction mass was stirred at room temp. for 3-4 hours. After completion of reaction, reaction mass was filtered to remove catalyst. and pH of reaction mixture was adjusted 0.5 to 1.0 by using concentrated HCl. The reaction mixture was filtered and solid product was collected as crude clopyralid.

Example 4: Process for the preparation of 3,6-dichloro-2-picolinic acid
To a solution of methanol (200mL) and aqueous 25-30% ammonia solution, zinc borohydride (2.0 mole) was added and stirred for 15 minutes. After that 3,4,5,6-Tetrachloropyridine-2-carboxylic acid [Tet Acid] was added in lots at room temp. The reaction mass was stirred at room temp. for 3-4 hours. After completion of reaction, reaction mass was filtered to remove catalyst. and pH of reaction mixture was adjusted 0.5 to 1.0 by using concentrated HCl. The reaction mixture was filtered and solid product was collected as crude clopyralid.

Example 5: Purification of 3,6-dichloro-2-pyridinecarboxylic acid (Clopyralid)
Crude clopyralid obtained in Example 3 or Example-4 was reacted with sodium carbonate solution. The resulting mass was filtered and acidified with conc. HCl to make pH of the filtrate to 0.5-1.0. The solid starts precipitating out. The solid was filtered out and washed with water and dried. Clopyralid obtained has purity 97-98% and yield 75-78%.
,CLAIMS:We claim:
1) A process for the preparation of clopyralid of the formula (I)

Formula (I)
said process comprising reduction of compound of Formula (II) in the presence of zinc based catalyst.

Formula (II)

2)The process as claimed in claim 1, wherein zinc based catalyst is selected from Zinc(tetrahydroborato)pyridine [Zn(BH4)(pyr)] complex, zinc powder, (N-Methylimidazole)(tetrahydroborato)zinc complex, (nicotine)(tetraborato)zinc [Zn(BH4)(nic] complex, zinc cyanoborohydride, zinc borohydride, Zinc chips or zinc dust and mixtures thereof.
3) The process as claimed in claim 1, wherein reduction is carried out in the presence of aqueous alkaline reagent and solvent.
4) The process as claimed in claim 3, wherein alkaline reagent is selected from an aqueous alkali, alkaline earth metal hydroxide, aqueous ammonium hydroxide, aqueous ammonia and the like or mixture thereof.
5) The process as claimed in claim 3, wherein solvent is selected from water, methanol, ethanol, propanol, isopropanol and mixture thereof
6) The process as claimed in claim 1, wherein compound of formula (II) is obtained by hydrolysis of compound of formula (III)

Formula (III) Formula (II)

7) The process as claimed in claim 6, wherein hydrolysis of compound of Formula (III) is carried out in acidic medium.

8) The process as claimed in claim 1, further comprising purifying the compound of formula (I) is purified by acid-base treatment.

9) The process as claimed in claim 1, where the said process is performed in batch mode, continuous mode, fixed bed reactor or fluidized bed reactor or loop reactor.