Description:FIELD
The present disclosure relates to a process for the preparation of Chlorantraniliprole.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Chlorantraniliprole is an insecticide of the ryanoid class. Further, Chlorantraniliprole belongs to a new class of selective insecticides featuring a novel mode of action to control a range of pests. 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 for Chlorantraniliprole is carried out by using pyridine or picoline as a base which are expensive, toxic and difficult to recover. Further, the conventional processes for preparing Chlorantraniliprole employ solvents from a class of ethers, ketones and nitriles which are water soluble solvents. These water soluble solvents are not convenient to use at industrial scale as salts are generated during the process for preparing Chlorantraniliprole which are required to be separated by water washing. The water soluble solvents have a coordinating atom in their structure which forms a coordinate bond with water molecules during the washing step (carried out to separate salt by-products) and thereby making the washing step troublesome. Moreover, the conventional processes for preparing Chlorantraniliprole results in obtaining the product with a low yield and having a less purity and thus, not suitable for commercial scale.
Therefore, there is felt a need for a process for the preparation of Chlorantraniliprole that mitigates the drawbacks mentioned hereinabove or at least provides a useful alternative.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to ameliorate one or more problems of the background or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole.
Still another object of the present disclosure is to provide a process for the preparation Chlorantraniliprole with a comparatively high yield and high purity.
Yet another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole that is simple, efficient and economical.
Still another object of the present disclosure is to provide a process for the preparation of Chlorantraniliprole that is environment 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 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid with a base in a first fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a first reaction mixture. A first portion of methane sulfonyl chloride is added to the first reaction mixture under stirring over a second predetermined time period to obtain a second reaction mixture followed by maintaining the second reaction mixture at a second predetermined temperature for a third predetermined time period to obtain a first slurry. Separately, 2-amino-5-chloro-3-methylbenzoic acid is added to a second fluid medium to obtain a second slurry. The second slurry is added to the first slurry in portions over a fourth predetermined time period to obtain a third reaction mixture followed by maintaining the third reaction mixture at a third predetermined temperature for a fifth predetermined time period to obtain a reaction mass. Optionally, a second portion of methane sulfonyl chloride is added to the reaction mass under stirring over a sixth predetermined time period to obtain a resultant reaction mass. The reaction mass or the resultant reaction mass is maintained at a fourth predetermined temperature for a seventh predetermined time period to obtain bezoxazinone intermediate. The bezoxazinone intermediate is reacted with a methylating agent to obtain a product mass comprising Chlorantraniliprole.
The first fluid medium and the second fluid medium are independently selected from the group consisting of monochlorobenzene, dichlorobenzene, toluene, xylene, cyclohexane, hexane and n-heptane.
The base is selected from an inorganic base and an organic base.
The inorganic base is selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, caesium carbonate and calcium carbonate.
The organic base is a tertiary amine.
The tertiary amine is selected from the group consisting of triethylamine, N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine and N,N-diisopropyl-N-ethylamine.
The first predetermined temperature is in the range of 30 °C to 80 °C.
The first predetermined time period is in the range of 40 minutes to 120 minutes.
The second predetermined time period is in the range of 40 minutes to 120 minutes.
The second predetermined temperature is in the range of 40 °C to 80 °C.
The third predetermined time period is in the range of 40 minutes to 150 minutes.
The fourth predetermined time period is in the range of 40 minutes to 150 minutes.
The third predetermined temperature is in the range of 40 °C to 80 °C.
The fifth predetermined time period is in the range of 40 minutes to 120 minutes.
The sixth predetermined time period is in the range of 40 minutes to 150 minutes.
The fourth predetermined temperature is in the range of 50 °C to 80 °C.
The seventh predetermined time period is in the range of 2 hours to 4 hours.
The methylating agent is methylamine gas.
In an embodiment of the present disclosure, Chlorantraniliprole has a yield in the range of 85% to 95% and a purity is in the range of 95% to 99%.
DETAILED DESCRIPTION
The present disclosure relates to a process for the preparation of Chlorantraniliprole.
Embodiments, of the present disclosure, will now be described with reference to the accompanying drawing.
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.
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. Ryanodine is a naturally occurring insecticide isolated from Ryania speciosa.
Various conventional methods for the preparation of Chlorantraniliprole are known in the art. However, the product obtained by using the conventional methods has comparatively low yield and low purity. Further, the conventional methods for preparing Chlorantraniliprole require highly toxic reagents such as methyl chloroformate and phosgene, resulting in operational inconveniences and unsuitability for large scale production.
Further, the conventional processes for preparing Chlorantraniliprole employ water soluble solvents such as ethers, ketones and nitriles. These water soluble solvents are not convenient to use at industrial scale as salts are generated during the process for preparing Chlorantraniliprole which are required to be separated by water washing. The water soluble solvents have a coordinating atom in their structure which forms a coordinate bond with water molecules during the washing step (carried out to separate salt by-products) and thereby making the washing step troublesome.
The present disclosure provides a simple, economic and environmental friendly process for the preparation of Chlorantraniliprole.
The process for the preparation of Chlorantraniliprole comprises the following steps:
i. reacting 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid with a base in a first fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a first reaction mixture;
ii. adding a first portion of methane sulfonyl chloride to the first reaction mixture under stirring over a second predetermined time period to obtain a second reaction mixture followed by maintaining the second reaction mixture at a second predetermined temperature for a third predetermined time period to obtain a first slurry;
iii. separately, adding 2-amino-5-chloro-3-methylbenzoic acid to a second fluid medium to obtain a second slurry;
iv. adding the second slurry to the first slurry in portions over a fourth predetermined time period to obtain a third reaction mixture followed by maintaining the third reaction mixture at a third predetermined temperature for a fifth predetermined time period to obtain a reaction mass;
v. optionally, adding a second portion of methane sulfonyl chloride to the reaction mass under stirring over a sixth predetermined time period to obtain a resultant reaction mass;
vi. maintaining the reaction mass in step (iv) or the resultant reaction mass in step (v) at a fourth predetermined temperature for a seventh predetermined time period to obtain bezoxazinone intermediate; and
vii. reacting the bezoxazinone intermediate with a methylating agent to obtain a product mass comprising Chlorantraniliprole.
The first fluid medium and the second fluid medium are idependently selected from the group consisting of monochlorobenzene, dichlorobenzene, toluene, xylene, cyclohexane, hexane and n-heptane. In an exemplery embodiment of the present disclosure, the first fluid medium and the second fluid medium is monochlorobenzene.
In accordance with the present disclosure, the fluid medium is a water insoluble fluid medium. The water insoluble, non-coordinating fluid medium provides ease of operations for manufacturing of the product on a large scale. Such a fluid medium serves not only as a medium, but also has easy recovery and reuse, easy separation of salts and monomethyl amine (MMA) reagent and ease of drying.
In accordance with the present disclosure, the base is selected from an inorganic base and an organic base.
The inorganic base is selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium carbonate, lithium carbonate, caesium carbonate and calcium carbonate. In an exemplary embodiment of the present disclosure, the inorganic base is sodium carbonate.
The organic base is a tertiary amine.
The tertiary amine is selected from the group consisting of triethylamine, N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine and N,N-diisopropyl-N-ethylamine.
In accordance with the present disclosure, the tertiary amines are preferable over the secondary amines and primary amines as the secondary amines/ primary amines can form amides with the starting materials and result into impurities.
The first predetermined temperature is in the range of 30 °C to 80 °C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 55 °C. In another exemplary embodiment of the present disclosure, the first predetermined temperature is 70 °C. In still another exemplary embodiment of the present disclosure, the first predetermined temperature is 35 °C.
The first predetermined time period is in the range of 40 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the first predetermined time period is 60 minutes.
The second predetermined time period is in the range of 40 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the second predetermined time period is 60 minutes.
The second predetermined temperature is in the range of 40 °C to 80 °C. In an exemplary embodiment of the present disclosure, the second predetermined temperature is 55 °C. In another exemplary embodiment of the present disclosure, the second predetermined temperature is 70 °C.
The third predetermined time period is in the range of 40 minutes to 150 minutes. In an exemplary embodiment of the present disclosure, the third predetermined time period is 60 minutes. In another exemplary embodiment of the present disclosure, the third predetermined time period is 120 minutes.
The fourth predetermined time period is in the range of 40 minutes to 150 minutes. In an exemplary embodiment of the present disclosure, the fourth predetermined time period is 60 minutes. In another exemplary embodiment of the present disclosure, the fourth predetermined time period is 120 minutes.
The third predetermined temperature is in the range of 40 °C to 80 °C. In an exemplary embodiment of the present disclosure, the third predetermined temperature is 55 °C. In another exemplary embodiment of the present disclosure, the third predetermined temperature is 70 °C.
The fifth predetermined time period is in the range of 40 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the fifth predetermined time period is 60 minutes.
The sixth predetermined time period is in the range of 40 minutes to 150 minutes. In an exemplary embodiment of the present disclosure, the sixth predetermined time period is 60 minutes.
The fourth predetermined temperature is in the range of 50 °C to 80 °C. In an exemplary embodiment of the present disclosure, the fourth predetermined temperature is in the range of 50 °C to 55 °C.
The seventh predetermined time period is in the range of 2 hours to 4 hours. In an exemplary embodiment of the present disclosure, the seventh predetermined time period is 3 hours.
The methylating agent is methylamine gas.
In an embodiment of the present disclosure, monomethyl amine gas (MMA) is passed at room temperature over a period of 2 hours.
In an embodiment of the present disclosure, Chlorantraniliprole is isolated from the product mixture to obtain Chlorantraniliprole having HPLC purity in the range of 95% to 99% and yield in the range of 85% to 95%.
The present disclosure provides an alternative process for the preparation of Chlorantraniliprole by using non-toxic and cheap reagents.
As a result of using non-toxic, inexpensive and easily available reagents, the process of the present disclosure is cost efficient, economic and environment friendly.
In an embodiment of the present disclosure, the product mixture comprising Chlorantraniliprole is filtered and washed with monochlorobenzene to obtain a wet cake. The wet cake is washed with water and again filtered to obtain a residue. The residue is washed with water and solids obtained are dried to obtain a purified Chlorantraniliprole.
A non-coordinating fluid medium (water insoluble fluid medium) such as monochlorobenzene would be easy to remove during drying facilitating ease of drying of the final product whereas the water soluble fluid media such as ethers, ketones and nitriles have a coordinating atom in their structure and hence, would not be convenient to remove from the product during drying.
Monochlorobenzene (MCB) used in the process remains trapped in the cake during the first filtration which is washed away by using methanol. MCB is recovered by addition water to methanol.
Further, monomethyl amine (MMA) trapped in MCB is washed with water thereby providing easy recovery of MCB. For other water soluble solvents, fractionation is inevitable. The recovery of MCB is possible due to the fact that MCB is a water insoluble solvent.
MMA has greater affinity to water due to hydrogen bonding, and becomes homogeneous solution with water and water soluble organic solvent. MMA has to be converted into its salt with bisulphite (water soluble) and recovered by fractionation / distillation and re-used. Whereas a water insoluble solvent would provide a complete recovery of MMA (MMA in water and the water insoluble solvent form two separate layers) and can be re-used . Thus the use of water insoluble solvent such as MCB makes the process of the present disclosure economic.
The use of MCB as a fluid medium in the process of the present disclosure provides the following advantages:
• Flowability of MCB is better than solvents such as acetonitrile (density = 0.786) and Toluene (density = 0.867), monoglyme (0.867) as MCB has higher density (1.11).
• MCB is less hazardous than acetonitrile.
• MCB has a higher boiling point of 135 °C and can serve as better heat sink than other low boiling solvents.
• Yield obtained for CTPR is 92 – 94 %. Purity by HPLC: 96 to 98 % and ISP (purity by internal standard): 95 to 96 %.
• MMA (monomethyl amine) has solubility in MCB and forms up to 2N solution. A combination of MCB and MMA up to 0.6 to 0.7 N provides good purity of the product after purification, avoiding further purification step.
• Methanol washing of MCB provides for better colour of the product and increases the purity by 1.0 to 1.5 %.
• The product obtained is of sufficient purity and does not need further purification.
• Base is added to the solvent from the beginning (2.6 mole / mole) providing alkalinity to the medium.
• As MCB forms an azeotrope with water, moisture formed is removed by distillation under vacuum.
• As methanol wash helps removing the last traces of MCB from the cake, and subsequent washing with water, the cake is taken for drying straight away.
• Sequential addition of reagents is facilitated to get very good yields and purity.
• A temperature of 50 °C to 55 °C helps to complete the reaction in 8 to 12 hours.
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 herein below 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
Experiment 1: Preparation of Chlorantraniliprole in accordance with the present disclosure
Example: 1
2.6 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.6 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 303 g (1 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 55°C for 1 hour to obtain a reaction mixture. 138 g (1.2 m/m) (first portion) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 55 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 55°C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 55°C. 138 g (1.2 m/m) (second portion) of methane sulfonyl chloride was added to the thick slurry for 1 hour. This slurry was maintained for 3 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d][l,3]oxazin-4one (Benzoxazinone intermediate). After 3 hours, the reaction mass was cooled to room temperature (30 °C).
4. m/m methylamine gas was passed through the reaction mass till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 99% and the yield 90%.
Example 2:
2.6 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.6 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 303 g (1 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 55°C for 1 hour to obtain a reaction mixture. 276 g (2.4 m/m) (first portion) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 55 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 55°C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 55°C. This slurry was maintained for 3 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l,3]oxazin-4one (Benzoxazinone intermediate). After 3 hours the reaction mass was cooled to room temperature (30 °C)
4 m/m Methylamine gas was passed through the reaction mass till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 99% and the yield 92%.
Example 3:
2.6 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.6 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 303 g (1 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was to the mixture under stirring and was heated to 55°C for 1 hour to obtain a reaction mixture. 276 g (2.4 m/m) (first portion) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 55 °C for 2 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 30 minutes over a period of 2 hours under stirring at 55°C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 55°C. This slurry was maintained for 3 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d][l,3]oxazin-4one(Benzoxazinone intermediate). After 3 hours, the reaction mass was cooled to room temperature (30 °C)
4 m/m Methylamine gas was passed through the reaction mass till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 99% and the yield 94%.
Example 4:
2.6 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.6 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 303 g (1 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 70°C for 1 hour to obtain a reaction mixture. 276 g (2.4 m/m) (first portion) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 70 °C for 2 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 30 minutes over a period of 2 hours under stirring at 70 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 70 °C. This slurry was maintained for 3 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d][l,3]oxazin-4one(Benzoxazinone intermediate).
4.0 m/m Methylamine gas was passed through the reaction mass till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having an HPLC purity of 99% and the yield 90%.
Example 5:
2.6 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.6 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 303 g (1 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 55°C for 1 hour to obtain a reaction mixture. 138 g (1.2 m/m) (first portion) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 55 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 55 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 55 °C. 138 g (1.2 m/m) (second portion) of methane sulfonyl chloride was added to the thick slurry for 1 hour. This slurry was maintained for 3 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l, 3] oxazin-4one (Benzoxazinone intermediate). After 3 hours, the reaction mass was cooled to room temperature (30 °C)
4.0 m/m Methylamine gas was passed through the MCB. The MMA in MCB was added into the reaction mass and heated to 55 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 99% and the yield 90%.
Example 6:
3 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.9 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 151 g (0.5 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 35°C for 0.5 hour to obtain a reaction mixture. 310 g (2.7 m/m) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 35 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 35 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 35 °C. This slurry was further maintained for 10 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l, 3] oxazin-4one (Benzoxazinone intermediate). After 3 hours, the mass was cooled to room temperature (30 °C)
4.6 m/m mono-methylamine gas (MMA) was passed through the MCB. The MMA in MCB was added into the mass and heated to 35 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 97.2 % and the yield 87.23 %.
Example 7:
4 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.9 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 151 g (0.5 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 35°C for 0.5 hour to obtain a reaction mixture. 310 g (2.7 m/m) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 35 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 35 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 35 °C. This slurry was further maintained for 15 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l, 3] oxazin-4one (Benzoxazinone intermediate). After 3 hours, the mass was cooled to room temperature (30 °C)
4.32 m/m mono-methylamine gas (MMA) was passed through the MCB. The MMA in MCB was added into the mass and heated to 35 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 96.7 % and the yield 86 %.
Example 8:
3 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.9 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 151 g (0.5 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 35°C for 0.5 hour to obtain a reaction mixture. 310 g (2.7 m/m) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 35 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 35 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 35 °C. This slurry was further maintained for 15 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l, 3] oxazin-4one (Benzoxazinone intermediate). After 3 hours, the mass was cooled to room temperature (30 °C)
4.0 m/m mono-methylamine gas (MMA) was passed through the MCB. The MMA in MCB was added into the mass and heated to 35 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 97.04 % and the yield 89.85 %.
Example 9:
4 litre/m of monochlorobenzene was added in a reactor followed by the addition 2.9 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 151 g (0.5 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 35°C for 0.5 hour to obtain a reaction mixture. 310 g (2.7 m/m) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 35 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 35 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 35 °C. This slurry was further maintained for 15 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l, 3] oxazin-4one (Benzoxazinone intermediate). After 3 hours, the mass was cooled to room temperature (30 °C)
3.57 m/m mono-methylamine gas (MMA) was passed through the MCB. The MMA in MCB was added into the mass and heated to 35 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 97.1 % and the yield 86.12 %.
Example 10:
3 litre/m of monochlorobenzene was added in a reactor followed by the addition 3.4 m/m of sodium carbonate to obtain a mixture. The mixture was stirred for 30 minutes. 75.5 g (0.25 mole) of 3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid was added to the mixture under stirring and was heated to 35°C for 0.5 hour to obtain a reaction mixture. 310 g (2.7 m/m) of methane sulfonyl chloride was slowly added to the reaction mixture for 1 hour under stirring and further maintained at 35 °C for 1 hour to obtain a greenish slurry. Separately, 195 g (1.05 m/m) of 2-amino-5-chloro-3-methylbenzoic acid was added to 1 litre/m of monochlorobenzene to obtain a slurry. The so obtained slurry was added to the so obtained greenish slurry in four lots each in an interval of 15 minutes over a period of 1 hour under stirring at 35 °C to obtain a thick slurry. The thick slurry was maintained for 1 hour at 35 °C. This slurry was further maintained for 15 hours to obtain a mass containing 2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-chloro-8-methyl-benzo[d] [l,3]oxazin-4one (Benzoxazinone intermediate). After 3 hours, the mass was cooled to room temperature (30 °C)
4.0 m/m mono-methylamine gas (MMA) was passed through the MCB. The MMA in MCB was added into the mass and heated to 35 °C till HPLC showed the absence of the benzoxazinone intermediate to obtain a product mass containing Chlorantraniliprole. The product mass was filtered and was washed with monochlorobenzene to obtain a wet cake. The wet cake was slurried with water and again filtered to obtain a residue. The residue was washed with water and solids obtained were dried to obtain a purified Chlorantraniliprole having HPLC purity of 97.7 % and the yield 87.78 %.
Comparative example 1: Preparation of Chlorantraniliprole by using acetonitrile (water soluble) as a fluid media
The same procedure of Example 1 was followed except acetonitrile was used as a fluid media to obtain Chlorantraniliprole (yield: 83% to 85 %).
From the comparative example 1, it is clear that when a water soluble fluid medium is used, the yield of the final product Chlorantraniliprole is comparatively less.
The present disclosure thus provides a simple, efficient and environment friendly process for the preparation of Chlorantraniliprole.
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of Chlorantraniliprole, wherein:
• the process provides Chlorantraniliprole with high purity and in greater yields; and
• the solvent is recycled and reused, thereby making the process is simple, efficient and environment friendly.
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.
, C , Claims:WE CLAIM:
1. A process for the preparation of Chlorantraniliprole, said process comprising the following steps:
i. reacting 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid with a base in a first fluid medium under stirring at a first predetermined temperature for a first predetermined time period to obtain a first reaction mixture;
ii. adding a first portion of methane sulfonyl chloride to said first reaction mixture under stirring over a second predetermined time period to obtain a second reaction mixture followed by maintaining the second reaction mixture at a second predetermined temperature for a third predetermined time period to obtain a first slurry;
iii. separately, adding 2-amino-5-chloro-3-methylbenzoic acid to a second fluid medium to obtain a second slurry;
iv. adding said second slurry to said first slurry in portions over a fourth predetermined time period to obtain a third reaction mixture followed by maintaining the third reaction mixture at a third predetermined temperature for a fifth predetermined time period to obtain a reaction mass;
v. optionally, adding a second portion of methane sulfonyl chloride to said reaction mass under stirring over a sixth predetermined time period to obtain a resultant reaction mass;
vi. maintaining said reaction mass in step (iv) or said resultant reaction mass in step (v) at a fourth predetermined temperature for a seventh predetermined time period to obtain bezoxazinone intermediate; and
vii. reacting said bezoxazinone intermediate with a methylating agent to obtain a product mass comprising Chlorantraniliprole.
2. The process as claimed in claim 1, wherein said first fluid medium and said second fluid medium are independently selected from the group consisting of monochlorobenzene, dichlorobenzene, toluene, xylene, cyclohexane, hexane and n-heptane.
3. The process as claimed in claim 1, wherein said base is selected from an inorganic base and an organic base.
4. The process as claimed in claim 3, wherein said inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, lithium bicarbonate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, calcium bicarbonate, beryllium carbonate and beryllium bicarbonate; and said organic base is tertiary amine selected from the group consisting of triethylamine, N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine and N,N-diisopropyl-N-ethylamine.
5. The process as claimed in claim 1, wherein said first predetermined temperature is in the range of 30 °C to 80 °C.
6. The process as claimed in claim 1, wherein said first predetermined time period is in the range of 40 minutes to 120 minutes.
7. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 40 °C to 80 °C.
8. The process as claimed in claim 1, wherein said second predetermined time period is in the range of 40 minutes to 120 minutes.
9. The process as claimed in claim 1, wherein said third predetermined time period and said fourth predetermined time period are independently in the range of 40 minutes to 150 minutes.
10. The process as claimed in claim 1, wherein said third predetermined temperature is in the range of 40 °C to 80 °C.
11. The process as claimed in claim 1, wherein said fifth predetermined time period is in the range of 40 minutes to 120 minutes.
12. The process as claimed in claim 1, wherein said sixth predetermined time period is in the range of 40 minutes to 150 minutes.
13. The process as claimed in claim 1, wherein said fourth predetermined temperature is in the range of 50 °C to 80 °C.
14. The process as claimed in claim 1, wherein said seventh predetermined time period is in the range of 2 hours to 4 hours.
15. The process as claimed in claim 1, wherein said methylating agent is monomethyl amine gas.
16. The process as claimed in claim 1, wherein Chlorantraniliprole has a purity in the range of 95% to 99% and yield in the range of 85% to 95%.
Dated this 13th Day of December, 2023

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