DESC:FIELD:

The present disclosure relates to a process for preparing triclopyr acid and its analogues. The present disclosure particularly relates to a process for preparing triclopyr acid.

BACKGROUND:

Triclopyr acid is a valuable compound and an intermediate used for extensive applications, amongst which use as an herbicide is a significant one. Triclopyr acid is a systemic and foliar herbicide effective for controlling broadleaf weeds without affecting the grasses and conifers, especially the woody plants that are found in grasslands, uncultivated land, industrial areas, plantation crops and rice fields. Triclopyr acts by getting rapidly absorbed through the roots and foliage, trans-locating throughout the plant, accumulating in the meristematic tissues and inducing auxin type responses.

The process for the preparation of triclopyr acid suggested by WO2010/023679 includes hydrolyzing a triclopyr ester with an aqueous alkali to obtain a salt of the acid, followed by acidifying the salt to obtain the triclopyr acid. However, the suggested process is associated with certain drawbacks such as excess effluent generation, excess hydrolysis leading to product degradation and loss in the yield and time consuming, multiple step synthetic route. Further, the suggested process also uses oxidizing agents such as NaOCl and H2O2 leading to increase in effluent load and making the process expensive.

Therefore, there is felt a need for a process for the preparation of triclopyr acid and its analogues that precludes at least one drawback associated with the prior art process.

OBJECTS:

Some of the objects of the present disclosure, which at least in one embodiment is adapted to provide, are described herein below:
It is an object of the present disclosure to provide a process for the preparation of triclopyr acid and its analogues.
It is another object of the present disclosure to provide a process for the preparation of triclopyr acid and its analogues, which is rapid, economic and environment friendly.
It is still another object of the present disclosure to provide a high yielding process for the preparation of triclopyr acid and its analogues.
It is yet another object of the present disclosure to provide a process for preparing triclopyr acid and its analogues having high purity.
It is yet another object of the present disclosure to provide a process for preparing triclopyr acid and its analogues which obviates the use of organic solvents during the reaction.

Other objects and advantages of the present disclosure will be more apparent from the following description which is not intended to limit the scope of the present disclosure.

SUMMARY:

The present disclosure relates to a process for preparing a triclopyr acid and its analogues from corresponding esters by hydrolyzing reaction. The hydrolyzing reaction is carried out using an acid in a water medium. One of the advantages of the hydrolyzing the triclopyr esters and its analogues in an acidic medium over that in the basic medium is that the product yield in case of acidic medium is higher than that in the basic medium. Further, the conversion of esters into acids is not complete and therefore the unconverted reactants are oxidized by using oxidizing agents such as NaOCl and hydrogen peroxide during which the desired product is also oxidized.
DETAILED DESCRIPTION:

The present disclosure provides a process for preparing a compound represented by Formula 1 by hydrolyzing a compound of Formula 2.

Formula 1 Formula 2
The substituent X in the compound of Formula 1and Formula 2 is independently selected from the group that includes but is not limited to chloride, bromide and iodide, whereas n is an integer in the range of 1 to 4. Particularly, the substituent X is chloride and an integer is 3.

The addition substituent R in the compound of Formula 2 is an alkyl group having C1 to C5 carbon atoms. Particularly, the substituent R is an alkyl group having C1-C3 alkyl groups.

To prepare the compound of Formula 1 an acid solution is prepared by dissolving at least one acid in water. The temperature during dissolving the acid in water may rise upto 90 oC due to the dissolution exo-therm. Though any concentration of the acid in the solution can affect the hydrolysis of the compound of Formula 1, for desired yield of the compound of Formula 1, operability and safety reasons the concentration of the acid in the solution is maintained in the range of 40 to 90 wt%.

To the acid solution the compound of Formula 2 is added to obtain a reaction mixture. The reaction mixture is heated to a temperature of 30 to 120 oC during which the compound of Formula 2 is hydrolyzed to the compound of Formula 1. The amount of the compound of Formula 2 after the conversion into the compound of Formula 1 does not exceed 0.5%. The compound of Formula 1 is isolated from the reaction mass filtration. If the compound of Formula 1 is isolated by filtration technique then the cake of the compound of Formula 1 obtained after filtration is washed iteratively to remove the acidity and make the compound of Formula 1 free from traces of acid. The mother liquor can also be recycled for hydrolyzing the compound of Formula 2.

The isolation of the compound of Formula 1 can also be carried out by extracting the compound of Formula 1 by an organic solvent and then distilling out the solvent to obtain the compound of Formula 1 in pure form. The yield of the compound of Formula 1obtained by the process of the present disclosure is greater than 98%.

The advantage of this reaction is that there is no loss of the product i.e., the compound of Formula 1 due to the hydrolysis as in case of processes where alkaline hydrolysis is employed. Further advantage is that the process of the present disclosure does not employ any organic solvent thereby increasing the production rate of the compound of Formula 1. Also, no effluent is generated as the acid solution is recycled to convert the compound of Formula 2 into the compound of Formula 1.

In one particular embodiment the compound of Formula 1 is triclopyr acid and the compound of Formula 2 is triclopyr methyl ester.

In another particular embodiment the compound of Formula 1 is triclopyr acid and the compound of Formula 2 is triclopyr ethyl ester.

Examples of acids useful for the purpose of the present include but are not limited to hydrochloric acid, sulfuric acid, acetic acid, sulfonic acid, methane sulfonic acid, benzene sulfonic acid, p-chloro benzene sulfonic acid and p-toluene sulfonic acid.
Examples of the solvent for extraction of the compound of Formula 1 can be an aromatic or an aliphatic solvent and is selected from the group that includes but is not limited to xylene, benzene, ethylbenzene, hexane, cyclohexane and toluene.

The compound of Formula 1 is isolated either by extraction or filtration has the purity higher than 98% by HPLC.

The compound of Formula 1 synthesized using the process of the present disclosure may be used as such or may be converted to derivatives for different applications.

The present disclosure is further described in the light of the following non-limiting examples which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure.

Example 1
1.0 g mole of Triclopyr methyl ester solid was added in 1.0 liter of 7.5 N HCl during which the temperature raised from 30.0 oC to 80.0 oC to obtain a reaction mixture. The reaction mixture was heated under stirring to a temperature 100 oC ±5 oC for 6.0 hrs. After 6 hours the content of triclopyr methyl ester was less than 0.5 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). The reaction mixture containing triclopyr acid, triclopyr methyl ester was less than 0.5 % and acid solution mass was cooled to 28-30 oC filtered to obtain a residue of triclopyr acid. The cake was washed with water to make it free of HCl. The isolated triclopyr acid was of 0.98-0.99 moles and the purity was found to be 98.5-99.5 %. The 900.0ml of the main mother liquor obtained after filtration was recycled.

Example 2
1.0 g mole of Trichlopyr methyl ester solid was added in 1.0 liter of 5.0 N HCl at 30.0 oC to 35.0 oC. The reaction mixture was then heated under stirring to a temperature ranging between 104 oC and 107 oC for 7.5 hrs. till the unreacted ester content became less than 0.5 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). Further, the resultant mass was cooled to 70-75 oC and the Trichlopyr acid was extracted in 700 ml of toluene solvent. The Trichlopyr acid toluene solution concentrated to keep 300 ml of toluene and Triclopyr acid is crystallized and filtered. The isolated Trichlopyr acid was of 0.92 moles and the purity was found to be 99.5 %. The filtrate part containing 0.08 moles of Triclopyr acid was recycled in the example 3. The separated spent HCl is also recyclable (reused) in next experiment.

Example 3
1.0 g mole of Trichlopyr methyl ester solid was added in 1.0 liter of 5.5 N HCl (containing spent HCl from the example 2) at 30.0 oC to 35.0 oC. The reaction mixture was then heated under stirring to a temperature ranging between 104 oC and 107 oC for 8.0 hrs. till the unreacted ester content became less than 0.5 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). Further, the resultant mass was cooled to 70-75 oC and the Trichlopyr acid was extracted in 700 ml of toluene solvent (contains filtrate containing 0.08 moles of Triclopyr acid from example 2). The Trichlopyr acid toluene solution concentrated to isolate Triclopyr acid. Trichlopyr acid was of 0.99 moles and the purity was found to be 99.0 %.

Example 4
1.0 g mole of Trichlopyr methyl ester solid was added in 2.0 liter of 75.0 % W/W H2SO4 at 30.0 oC to 35.0 oC. The reaction mixture was then heated under stirring to a temperature ranging between 70-75 oC for 8.0 hrs. till the unreacted ester content became less than 0.5 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). Further, the resultant mass was cooled to 50-55oC and water was added to get H2SO4 concentration of 50.0 % W/W from 75.0 % W/W. Further cooled the mass to 30.0 oC and filtered the slurry. The filtered cake was washed iteratively with water to remove traces of H2SO4. The Triclopyr acid isolated on dry basis is 0.98 mole with 99.0 % purity.

Example 5
1.0 g mole of Trichlopyr methyl ester solid was added in 2.0 liter of 75.0 % W/W H2SO4 at 30.0 oC to 35.0 oC. The reaction mixture was then heated under stirring to a temperature ranging between 70-75 oC for 8.0 hrs. till the unreacted ester content became less than 0.5 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). Further, the resultant mass was cooled to 50-55oC and water added to get H2SO4 concentration of 30.0 % W/W from 75.0 % W/W. The triclopyr acid was extracted in 900 ml of toluene solvent. The Trichlopyr acid toluene solution concentrated to isolate Triclopyr acid. Trichlopyr acid isolated was of 0.99 moles and the purity was found to be 99.0 %.

Example 6
1.0 g mole of Trichlopyr methyl ester solid was added in 1.0 liter of 30.0 % W/W H2SO4 at 30.0 oC to 35.0 oC. The reaction mixture was then heated under stirring to a temperature ranging between 104-108oC for 18-20 hrs. till the unreacted ester content became less than 0.2 %. The progress of the reaction was monitored by high performance liquid chromatography (HPLC). Further cooled the mass to 30.0 oC and filtered the slurry. The filtered cake was washed iteratively to remove traces of H2SO4. The Triclopyr acid isolated on dry basis is 0.97 mole with 99.0 % purity.

The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.

The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.

While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other modifications in the nature of the disclosure or the preferred embodiments will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,CLAIMS:1. A process for preparing a compound of Formula 1,

Formula 1
wherein,
- X is independently selected from the group consisting of chloride, bromide and iodide; and
- n is an integer in the range of 1 to 4,
from a compound of Formula 2,

Formula 2
wherein,
- R is C1-C5 alkyl groups;
- X is independently selected from the group consisting of chloride, bromide and iodide; and
- n is an integer in the range of 1 to 4.
wherein, said process comprises a step of hydrolyzing the compound of Formula 2 in an acidic reaction medium, said reaction medium consisting at least one acid and water, at a temperature ranging from 30 oC to 120 oC to obtain a reaction mass comprising the compound of Formula 1, less than 0.5% of the compound of Formula 2 and acid solution and isolating the compound of Formula 1 and the compound of Formula 2 from said reaction mass.

2. The process as claimed in claim 1, wherein the acid is at least one selected from the group consisting of hydrochloric acid, sulfuric acid, acetic acid, sulfonic acid, methane sulfonic acid, benzene sulfonic acid, p-chloro benzene sulfonic acid and p-toluene sulfonic acid.

3. The process as claimed in claim 1, wherein the step of isolating the compound of Formula 1 is carried out by at least one technique selected from the group consisting of filtration and extraction.

4. The process as claimed in claim 3, wherein an extracting solvent for extraction of the compound of Formula 1 is at least one selected from the group consisting of xylene, benzene, ethylbenzene, hexane, cyclohexane and toluene.

5. The process as claimed in claim 1, further comprises recycling an acid solution obtained after isolating the compound of Formula 1 and the compound of Formula 2 from said reaction mass.

6. A process for preparing a compound of Formula 1,

Formula 1
wherein,
- X is chloride; and
- n is an integer 3,
from a compound of Formula 2,

Formula 2
wherein,
- R is C1-C3 alkyl groups;
- X is chloride; and
- n is an integer 3
wherein, said process comprises a step of hydrolyzing the compound of Formula 2 in an acidic reaction medium, said reaction medium consisting at least one acid and water, at a temperature ranging from 30 oC to 120 oC to obtain a reaction mass comprising the compound of Formula 1, less than 0.5% of the compound of Formula 2 and acid solution and isolating the compound of Formula 1 and the compound of Formula 2 from said reaction mass.

7. The process as claimed in claim 6, further comprises recycling an acid solution obtained after isolating the compound of Formula 1 and the compound of Formula 2 from said reaction mass.

8. The process as claimed in claim 1, wherein the compound of Formula 1 is triclopyr acid and the compound of Formula 2 is triclopyr methyl ester.

9. The process as claimed in claim 1, wherein the compound of Formula 1 is triclopyr acid and the compound of Formula 2 is triclopyr ethyl ester.
10. The process as claimed in claim 1, produces the compound of Formula 1 in a yield of at least 98 % based on the compound of Formula 2 and a purity of at least 98 % by high performance liquid chromatography.