DESC:FIELD
The present disclosure relates to a process for the preparation of Chlorantraniliprole.
BACKGROUND
The background information hereinbelow relates to the present disclosure but is not necessarily prior art.
Chlorantraniliprole is an insecticide of the ryanoid class and also belongs to a new class of selective insecticides featuring a novel mode of action to control a range of pests. Chlorantraniliprole when consumed by insects it interrupts the normal muscle contraction, thereby resulting in death. The structural representation of Chlorantraniliprole is as given below:

Chlorantraniliprole
Various methods for the preparation of Chlorantraniliprole are reported in the art. Conventionally, the preparation of Chlorantraniliprole is carried out using pyridine or picoline as a base which are expensive, toxic, and difficult to recover. Moreover, the conventional processes of preparing Chlorantraniliprole result in obtaining the product with a low yield and a less purity and thus, not suitable for commercial scale-up.
Therefore, there is felt a need to provide a process for the preparation of Chlorantraniliprole that mitigates aforestated drawbacks or at least provide a useful alternative.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole.
Yet another object of the present disclosure is to provide a process for the preparation Chlorantraniliprole with a comparatively high yield and high purity.
Still another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole that is simple, efficient, and economical.
Another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole that is environmental friendly.
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 the preparation of Chlorantraniliprole. The process comprises reacting a predetermined amount of 2-amino-5-chloro-N,3-dimethylbenzamide with a base in a first fluid medium in an inert atmosphere to obtain a reaction mixture. Separately, a predetermined amount of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride is dissolved in a second fluid medium to obtain a solution. The so obtained solution is slowly added to the reaction mixture followed by equilibrating at a predetermined temperature for a predetermined time period to obtain Chlorantraniliprole.
DETAILED DESCRIPTION
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, known processes or well-known apparatus or structures, and well known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure are not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer, or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Chlorantraniliprole is an insecticide of the ryanoid class and also belongs to a new class of selective insecticides featuring a novel mode of action to control a range of pests.
Conventionally, the preparation of Chlorantraniliprole is carried out by using pyridine or picoline as a base which are expensive, toxic, and difficult to recover. Moreover, the conventional processes of preparing Chlorantraniliprole result in obtaining the product with a low yield and a less purity and thus, not suitable for commercial scale-up.
The present disclosure provides a simple, economic, and environmental friendly process for the preparation of Chlorantraniliprole.
The process is described in detail.
Firstly, a predetermined amount of 2-amino-5-chloro-N,3-dimethylbenzamide is reacted with a base in a first fluid medium in an inert atmosphere to obtain a reaction mixture.
In accordance with an embodiment of the present disclosure, the first fluid medium is at least one selected from the group consisting of acetonitrile, methylene dichloride, methyl ethyl ketone, methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, and tert-butanol. In an exemplary embodiment, the first fluid medium is acetonitrile.
In accordance with an embodiment of the present disclosure, the base is at least one selected from an inorganic base and an organic base.
In accordance with an embodiment of the present disclosure, the inorganic base is at least one selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, cesium carbonate, and calcium carbonate. In an exemplary embodiment, the inorganic base is potassium carbonate.
In accordance with an embodiment of the present disclosure, the organic base is at least one selected from the group consisting of N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine, and N,N-diisopropyl-N-ethylamine. In an exemplary embodiment, the organic base is N,N-dimethylaniline. In another exemplary embodiment, the organic base is N,N-diethylaniline. In yet another exemplary embodiment, the organic base is 4-(N,N-dimethylamino)pyridine.
In accordance with an embodiment of the present disclosure, the ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to the first fluid medium is in the range of 1:2 to 1:7 (w/v). In an exemplary embodiment of the present disclosure, the ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to the first fluid medium is 1:2.5 (w/v). In another exemplary embodiment of the present disclosure, the ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to the first fluid medium is 1:4.3 (w/v). In yet another exemplary embodiment of the present disclosure, the ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to the first fluid medium is 1:5.7 (w/v). In still another exemplary embodiment of the present disclosure, the ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to the first fluid medium is 1:6 (w/v).
In accordance with an embodiment of the present disclosure, the weight ratio of the base to 2-amino-5-chloro-N,3-dimethylbenzamide is in the range of 1:1 to 1:3. In an exemplary embodiment, the weight ratio of the base to 2-amino-5-chloro-N,3-dimethylbenzamide is 1:1.1. In another exemplary embodiment, the weight ratio of the base to 2-amino-5-chloro-N,3-dimethylbenzamide is 1:1.2. In yet another exemplary embodiment, the weight ratio of the base to 2-amino-5-chloro-N,3-dimethylbenzamide is 1:1.3. In still another exemplary embodiment, the weight ratio of the base to 2-amino-5-chloro-N,3-dimethylbenzamide is 1:1.4.
In accordance with an embodiment of the present disclosure, the inert atmosphere is selected from nitrogen or argon. In an exemplary embodiment, the inert atmosphere is nitrogen.
Separately, a predetermined amount of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride is dissolved in a second fluid medium to obtain a solution.
The chemical names ‘5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride’ and ‘3-bromo-1-(3-chloro-2-pyridinyl)-pyrazole-5-carboxylic acid chloride’ represents the same compound (CAS No. 943982-60-3), these names are used interchangeably across the draft.
In accordance with an embodiment of the present disclosure, the second fluid medium is at least one selected from the group consisting of acetonitrile, methylene dichloride, methyl ethyl ketone, methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, and tert-butanol. In an exemplary embodiment, the second fluid medium is acetonitrile.
In accordance with an embodiment of the present disclosure, a ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is in the range of 1:1 to 1:7 (w/v). In an exemplary embodiment of the present disclosure, the ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is 1:1.9. In another exemplary embodiment of the present disclosure, the ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is 1:3.3. In yet another exemplary embodiment of the present disclosure, the ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is 1:4. In still another exemplary embodiment of the present disclosure, the ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is 1:4.1. In another exemplary embodiment of the present disclosure, the ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to the second fluid medium is 1:5.3.
The so obtained solution of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride is slowly added to the reaction mixture followed by equilibrating at a predetermined temperature for a predetermined time period to obtain Chlorantraniliprole.
In accordance with an embodiment of the present disclosure, the slow addition of the solution to the reaction mixture is done for a time period in the range of 20 minutes to 180 minutes. In an exemplary embodiment, the slow addition of the solution to the reaction mixture is done for 30 minutes. In another exemplary embodiment, the slow addition of the solution to the reaction mixture is done for 45 minutes. In yet another exemplary embodiment, the slow addition of the solution to the reaction mixture is done for 60 minutes. In still another exemplary embodiment, the slow addition of the solution to the reaction mixture is done for 120 minutes.
In accordance with an embodiment of the present disclosure, the predetermined temperature is in the range of 20°C to 50°C. In an exemplary embodiment, the predetermined temperature is 30°C. In another exemplary embodiment, the predetermined temperature is 45°C.
In accordance with an embodiment of the present disclosure, the predetermined time period is in the range of 4 hours to 20 hours. In an exemplary embodiment, the predetermined time period is 5 hours. In another exemplary embodiment, the predetermined time period is 9.5 hours. In yet another exemplary embodiment, the predetermined time period is 10 hours. In still another exemplary embodiment, the predetermined time period is 13 hours. In yet another exemplary embodiment, the predetermined time period is 15 hours.
In accordance with an embodiment of the present disclosure, the reaction is monitored by using HPLC (High-performance liquid chromatography).
The schematic representation of the process for the preparation of Chlorantraniliprole is as given below:

In accordance with an embodiment of the present disclosure, the purity of Chlorantraniliprole is in the range of 85% to 99% (purity monitored by HPLC).
The present disclosure provides a simple and efficient process for the preparation of Chlorantraniliprole by using non-toxic and cheap reagents.
The process of the present disclosure uses non-toxic, inexpensive, easily recoverable, and easily available reagents, thereby making the process of the present disclosure cost-efficient, economic, and environmental friendly.
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further illustrated hereinbelow with the help of the following experiments. The experiments used herein are intended merely to facilitate an understanding of the 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 experiments should not be construed as limiting the scope of embodiments herein. These laboratory scale experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial/commercial scale.
EXPERIMENTAL DETAILS
Preparation of Chlorantraniliprole in accordance with the present disclosure:
EXAMPLE: 1
2-amino-5-chloro-N,3-dimethylbenzamide (10 gms) was added to acetonitrile (25 ml) in a nitrogen atmosphere under stirring followed by adding potassium carbonate (8.4 gms) to obtain a reaction mixture.
Separately, 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride (16 gms) was added to acetonitrile (85 ml) to obtain a solution.
The so obtained solution was slowly added to the reaction mixture over a time period of 30 minutes followed by equilibrating at 30°C for 5 hours to obtain a product mixture comprising Chlorantraniliprole. The reaction was monitored by using HPLC. Chlorantraniliprole was isolated from the product mixture to obtain Chlorantraniliprole having HPLC purity of 95.4% and yield on purity was 47%.
EXAMPLE 2:
2-amino-5-chloro-N,3-dimethylbenzamide (31.2 gms) was added to acetonitrile (135 ml) in a nitrogen atmosphere under stirring followed by adding N,N-dimethylaniline (22 gms) to obtain a reaction mixture.
Separately, 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride (48 gms) was added to acetonitrile (190 ml) to obtain a solution.
The so obtained solution was slowly added to the reaction mixture over a time period of 45 minutes followed by equilibrating at 30°C for 13 hours and further at a temperature of 45°C for 2 hours, to obtain a product mixture comprising Chlorantraniliprole. The reaction was monitored by using HPLC. Chlorantraniliprole was isolated from the product mixture to obtain Chlorantraniliprole having HPLC purity of 98.95% and yield on purity was 73.8%.
EXAMPLE 3:
2-amino-5-chloro-N,3-dimethylbenzamide (31.3 gms) was added to acetonitrile (135 ml) in a nitrogen atmosphere under stirring followed by adding N,N-diethylaniline (27.4 gms) to obtain a reaction mixture.
Separately, 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride (48 gms) was added to acetonitrile (195 ml) to obtain a solution.
The so obtained solution was slowly added to the reaction mixture over a time period of 120 minutes followed by equilibrating at 30°C for 10 hours to obtain a product mixture comprising Chlorantraniliprole. The reaction was monitored by using HPLC. Chlorantraniliprole was isolated from the product mixture to obtain Chlorantraniliprole having HPLC purity of 98.52% and yield on purity was 84%.
EXAMPLE 4:
2-amino-5-chloro-N,3-dimethylbenzamide (31.3 gms) was added to acetonitrile (190 ml) in a nitrogen atmosphere under stirring followed by adding 4-(N,N-dimethylamino)pyridine (22 gms) to obtain a reaction mixture.
Separately, 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride (48 gms) was added to acetonitrile (160 ml) to obtain a solution.
The so obtained solution was slowly added to the reaction mixture over a time period of 60 minutes followed by equilibrating at 30°C for 13 hours to obtain a product mixture comprising Chlorantraniliprole. The reaction was monitored by using HPLC. Chlorantraniliprole was isolated from the product mixture to obtain chlorantraniliprole having HPLC purity of 85.96% and yield on purity was 35%.
EXAMPLE 5:
2-amino-5-chloro-N,3-dimethylbenzamide (35.6 gms) was added to acetonitrile (203 ml) in a nitrogen atmosphere under stirring followed by adding N,N-diisopropyl-N-ethylamine (26.4 gms) to obtain a reaction mixture.
Separately, 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride (54.6 gms) was added to acetonitrile (103 ml) to obtain a solution.
The so obtained solution was slowly added to the reaction mixture over a time period of 45 minutes followed by equilibrating at 30°C for 9.5 hours to obtain a product mixture comprising Chlorantraniliprole. The reaction was monitored by using HPLC. Chlorantraniliprole was isolated from the product mixture to obtain Chlorantraniliprole having HPLC purity of 97.4% and yield on purity was 48%.
TECHNICAL ADVANCES AND ECONOMIC SIGNIFICANCE
The present disclosure described hereinabove has several technical advantages including, but not limited to, the realization of a process for the preparation of Chlorantraniliprole, that:
• is a simple and economical process for the preparation of Chlorantraniliprole;
• provides Chlorantraniliprole having comparatively high purity and high yield;
• uses an inexpensive base; and
• is environment friendly as the solvent used in the process can be recycled and reused.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following 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 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.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or 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.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments 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 changes in the preferred embodiment as well as other embodiments of the disclosure 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:WE CLAIM
1. A process for preparing Chlorantraniliprole, said process comprising the following steps:
a) reacting a predetermined amount of 2-amino-5-chloro-N,3-dimethylbenzamide with a base in a first fluid medium in an inert atmosphere to obtain a reaction mixture;
b) separately dissolving a predetermined amount of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride in a second fluid medium to obtain a solution; and
c) adding slowly said solution to said reaction mixture followed by equilibrating at a predetermined temperature for a predetermined time period to obtain Chlorantraniliprole.
2. The process as claimed in claim 1, wherein said first fluid medium and said second fluid medium is at least one independently selected from the group consisting of acetonitrile, methylene dichloride, methyl ethyl ketone, methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, and tert-butanol.
3. The process as claimed in claim 1, wherein said base is at least one selected from an inorganic base and an organic base.
4. The process as claimed in claim 3, wherein said inorganic base is at least one selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, cesium carbonate, and calcium carbonate.
5. The process as claimed in claim 3, wherein said organic base is at least one selected from the group consisting of N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine, and N,N-diisopropyl-N-ethylamine.
6. The process as claimed in claim 1, wherein said inert atmosphere is selected from nitrogen or argon.
7. The process as claimed in claim 1, wherein said slow addition of said solution to said reaction mixture is done for a time period in the range of 20 minutes to 180 minutes.
8. The process as claimed in claim 1, wherein said predetermined temperature is in the range of 20°C to 50°C.
9. The process as claimed in claim 1, wherein said predetermined time period is in the range of 4 hours to 20 hours.
10. The process as claimed in claim 1, wherein a ratio of 2-amino-5-chloro-N,3-dimethylbenzamide to said first fluid medium is in the range of 1:2 to 1:7 (w/v).
11. The process as claimed in claim 1, wherein a weight ratio of said base to 2-amino-5-chloro-N,3-dimethylbenzamide is in the range of 1:1 to 1: 3.
12. The process as claimed in claim 1, wherein a ratio of 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl chloride to said second fluid medium is in the range of 1:1 to 1:7 (w/v).
Dated this 31st day of May, 2022

_______________________________
MOHAN RAJKUMAR DEWAN, IN/PA – 25
of R.K.DEWAN & CO.
Authorized Agent of Applicant

TO,
THE CONTROLLER OF PATENTS
THE PATENT OFFICE, AT MUMBAI