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, in the conventional processes for preparing Chlorantraniliprole the base and methane sulfonyl chloride are required to be added in instalments/lots as there was a formation of thick mass when the base and the methane sulfonyl chloride were added in a single portion. The so formed thick mass results in a lump formation which in turn makes the stirring problematic that leads to incomplete reaction and thus results in lower yield of Chlorantraniliprole.
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.
An 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 of Chlorantraniliprole with a comparatively high yield and high purity.
Yet another object of the present disclosure is to provide a simple, efficient and economical process for the preparation of Chlorantraniliprole.
Still another object of the present disclosure is to provide an environment friendly process for the preparation of Chlorantraniliprole.
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 charging a predetermined amount of a first fluid medium to a reactor followed by adding a predetermined amount of a base to the first fluid medium at a first predetermined temperature under stirring to obtain a first mixture. The first mixture is cooled to a second predetermined temperature followed by adding methane sulfonyl chloride over a first predetermined time period by maintaining the second predetermined temperature to obtain a second mixture. Separately, 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid are dissolved in a predetermined amount of a second fluid medium at a third predetermined temperature to obtain a third mixture. The third mixture is added in the second mixture by maintaining the second predetermined temperature over a second predetermined time period under stirring and further maintaining the reaction for a third predetermined time period to obtain a benzoxazinone intermediate. Monomethyl amine is paased to the bezoxazinone intermediate followed by reacting at a fourth predetermined temperature for a fourth predetermined time period to obtain a product mass comprising Chlorantraniliprole.
The first fluid medium and the second fluid medium are independently selected from the group consisting of monoglyme, diglyme, triglyme, cyclic ether and dioxane.
The first fluid medium and the second fluid medium are anhydrous with a moisture content less than 0.1%.
The base is selected from an inorganic base and an organic base.
The 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.
The organic base is selected from the group consisting of N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine and N,N-diisopropyl-N-ethylamine.
The predetermined amount of the first fluid medium is in the range of 150 ml to 250 ml per mole of the base.
The predetermined amount of the second fluid medium is in the range of 1 litre to 4 litres per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
The predetermined amount of the base is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
The predetermined amount of the methane sulfonyl chloride is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
In an embodiment of the present disclosure, the monomethyl amine is selected from gaseous monomethyl amine and liquid monomethyl amine.
The first predetermined temperature is in the range of 20 °C to 40 °C.
The second predetermined temperature is in the range of 0 °C to 60 °C. In an embodiment of the present disclosure, the second predetermined temperature is in the range of 10 °C to 20 °C.
The first predetermined time period is in the range of 10 minutes to 120 minutes.
The second predetermined time period is in the range of 1 hour to 10 hours.
The third predetermined time period is in the range of 4 hours to 15 hours.
The third predetermined temperature is in the range of 25 °C to 70 °C.
The fourth predetermined time period is in the range of 1 hour to 8 hours.
The fourth predetermined temperature is in the range of 10 °C to 60 °C. In an embodiment of the present disclosure, the fourth predetermined temperature is in the range of 15 °C to 35 °C.
In an embodiment of the present disclosure, the product mass is cooled to a temperature in the range of 10 °C to 25 °C; filtered to obtain solids; washing the solids with the first fluid medium to obtain a wet cake; washing the wet cake by using water till the pH of the washing is neutral and free of chloride ions to obtain washed wet cake; drying the washed wet cake at a temperature in the range of 90 °C to 100 °C till constant weight to obtain the Chlorantraniliprole.
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 98% to 99%.
The process of the present disclosure is carried out in an inert atmosphere wherein the inert atmosphere is selected from a nitrogen atmosphere and an argon atmosphere.
In an embodiment of the present disclosure, the fluid medium and water are recovered and recycled and salt of Methane Sulphonic acid formed are recovered from water washings and converted back to Methane sulphonyl chloride and reused.
In an embodiment of the present disclosure, the Chlorantraniliprole obtained is polymorph B having at least three 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING
The present disclosure will now be described with the help of the accompanying drawing, in which:
Figure 1 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 1 in accordance with the present disclosure;
Figure 2 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 2 in accordance with the present disclosure;
Figure 3 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 3 in accordance with the present disclosure;
Figure 4 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 4 in accordance with the present disclosure;
Figure 5 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 5 in accordance with the present disclosure;
Figure 6 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 6 in accordance with the present disclosure;
Figure 7 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Examples 1 to 6 in accordance with the present disclosure; and
Figure 8 illustrates FTIR spectrum of the polymorph B of Chlorantraniliprole obtained in Examples 1 to 6 in accordance with the present disclosure.
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.
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, in the conventional processes for preparing Chlorantraniliprole the base and methane sulfonyl chloride are required to be added in instalments/lots as there was a formation of thick mass when the base and the methane sulfonyl chloride were added in a single portion. The so formed thick mass results in a lump formation which in turn makes the stirring problematic that leads to incomplete reaction and thus results in lower yield of Chlorantraniliprole.
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.
The present disclosure provides a simple, economic and environmental friendly process for the preparation of Chlorantraniliprole.
In accordance with the present disclosure, the process for the preparation of Chlorantraniliprole comprises the following steps:
a. charging a predetermined amount of a first fluid medium to a reactor followed by adding a predetermined amount of a base to the first fluid medium at a first predetermined temperature under stirring to obtain a first mixture;
b. cooling the first mixture to a second predetermined temperature followed by adding methane sulfonyl chloride over a first predetermined time period by maintaining the second predetermined temperature to obtain a second mixture;
c. separately dissolving 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid in a predetermined amount of a second fluid medium at a third predetermined temperature to obtain a third mixture;
d. adding the third mixture in the second mixture by maintaining the second predetermined temperature over a second predetermined time period under stirring and further maintaining the reaction for a third predetermined time period to obtain a benzoxazinone intermediate; and
e. passing monomethyl amine to the bezoxazinone intermediate followed by reacting at a fourth predetermined temperature for a fourth predetermined time period to obtain a product mass comprising Chlorantraniliprole.
The process for preparing Chlorantraniliprole is described in detail herein below.
In a first step, a predetermined amount of a first fluid medium is charged to a reactor followed by adding a predetermined amount of a base to the first fluid medium at a first predetermined temperature under stirring to obtain a first mixture.
The first fluid medium is selected from the group consisting of monoglyme, diglyme, triglyme, cyclic ether and dioxane. In an exemplary embodiment of the present disclosure, the first fluid medium is monoglyme. In another exemplary embodiment of the present disclosure, the first fluid medium is diglyme.
In the conventional processes for preparing Chlorantraniliprole, the base, 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid and methane sulfonyl chloride are required to be added in instalments as there was a formation of thick mass when the base and carboxylic acids were added in a single portion. The so formed thick mass results in a lump formation which in turn makes the stirring problematic.
Further, the conventional processes are convenient to carryout only at lab scale where real practical difficulty cannot be reflected/studied with respect to chemical engineering aspect. This conventional processes are not feasible at commercial scale and finally end up with poor yield and quality of the final product.
The inventors of the present invention found that the use of a suitable fluid medium such as monoglyme or diglyme solves the above drawbacks of the conventional process. When monoglyme or diglyme is used as a fluid medium and sequence of addition is base, methane sulfonyl chloride and carboxylic acid mixture, there is no formation of thick slurry or lumps even if the base and methane sulfonyl chloride are added in a single portion, rather, a stirrable slurry is formed.
The predetermined amount of the first fluid medium is in the range of 150 ml to 250 ml per mole of the base. In an exemplary embodiment of the present disclosure, the predetermined amount of the first fluid medium is 192.3 ml per mole (i.e. 500 ml for 2.6 moles) of the base.
The base is selected from an inorganic base and an organic base.
The 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. In an exemplary embodiment of the present disclosure, the base is sodium carbonate.
The organic base is selected from the group consisting of N,N-dimethylaniline, N,N-diethylaniline, 4-(N,N-dimethylamino)pyridine and N,N-diisopropyl-N-ethylamine.
The predetermined amount of the base is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid. In an exemplary embodiment of the present disclosure, the predetermined amount of the base is 2.6 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
The first predetermined temperature is in the range of 20 °C to 40 °C. In an exemplary embodiment of the present disclosure, the first predetermined temperature is 30 °C.
In a second step, the first mixture is cooled to a second predetermined temperature followed by adding methane sulfonyl chloride over a first predetermined time period by maintaining the second predetermined temperature to obtain a second mixture.
The second predetermined temperature is in the range of 0 °C to 60 °C. In an embodiment of the present disclosure, the second predetermined temperature is in the range of 10 °C to 25 °C. In another embodiment of the present disclosure, the second predetermined temperature is in the range of 15 °C to 20 °C.
The predetermined amount of methane sulfonyl chloride is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid. In an exemplary embodiment of the present disclosure, the predetermined amount of methane sulfonyl chloride is 2.4 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
The first predetermined time period is in the range of 10 minutes to 120 minutes. In an exemplary embodiment of the present disclosure, the first predetermined time period is 20 minutes. In another exemplary embodiment of the present disclosure, the first predetermined time period is 30 minutes.
In a third step, 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid are dissolved in a predetermined amount of a second fluid medium at a third predetermined temperature to obtain a third mixture.
The second fluid medium is selected from the group consisting of monoglyme, diglyme, triglyme, cyclic ether and dioxane. In an exemplary embodiment of the present disclosure, the second fluid medium is monoglyme. In another exemplary embodiment of the present disclosure, the second fluid medium is diglyme.
The first fluid medium and the second fluid medium are anhydrous with a moisture content less than 0.1%.
The predetermined amount of the second fluid medium is in the range of 1 litre to 4 litres per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid. In an exemplary embodiment of the present disclosure, the predetermined amount of the second fluid medium is 2.5 litres per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid. In another exemplary embodiment of the present disclosure, the predetermined amount of the second fluid medium is 2 litres per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid. In still another exemplary embodiment of the present disclosure, the predetermined amount of the second fluid medium is 1.5 litre per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
The third predetermined temperature is in the range of 25 °C to 70 °C. In an embodiment of the present disclosure, the third predetermined temperature is in the range of 30 °C to 60 °C. In an exemplary embodiment of the present disclosure, the third predetermined temperature is 35 °C. In another exemplary embodiment of the present disclosure, the third predetermined temperature is 50 °C. In still another exemplary embodiment of the present disclosure, the third predetermined temperature is 60 °C.
In a fourth step, the third mixture is added in the second mixture by maintaining the second predetermined temperature over a second predetermined time period under stirring and further maintaining the reaction for a third predetermined time period to obtain a benzoxazinone intermediate.
The second predetermined time period is in the range of 1 hour to 10 hours. In an exemplary embodiment of the present disclosure, the second predetermined time period is 4 hours. In another exemplary embodiment of the present disclosure, the second predetermined time period is 2 hours.
The third predetermined time period is in the range of 4 hours to 15 hours. In an exemplary embodiment of the present disclosure, the third predetermined time period is 8 hours. In another exemplary embodiment of the present disclosure, the third predetermined time period is 10 hours.
In a fifth step, monomethyl amine is paased to the bezoxazinone intermediate followed by reacting at a fourth predetermined temperature for a fourth predetermined time period to obtain a product mass comprising Chlorantraniliprole.
In an embodiment of the present disclosure, monomethyl amine is selected from a gaseous monomethyl amine and a liquid monomethyl amine.
The fourth predetermined temperature is in the range of 10 °C to 60 °C. In an embodiment of the present disclosure, the fourth predetermined temperature is in the range of 15 °C to 35 °C. In another embodiment of the present disclosure, the fourth predetermined temperature is in the range of 15 °C to 20 °C.
The fourth predetermined time period is in the range of 1 hour to 8 hours. In an exemplary embodiment of the present disclosure, the fourth predetermined time period is 1.5 hours. In another exemplary embodiment of the present disclosure, the fourth predetermined time period is 2 hours.
In an embodiment of the present disclosure, the product mass is cooled to a temperature in the range of 10 °C to 25 °C; filtered to obtain solids followed by washing the solids with the first fluid medium to obtain a wet cake; washing the wet cake by using water till the pH of the washing is neutral and free of chloride ions to obtain a washed wet cake; drying the washed wet cake at a temperature in the range of 90 °C to 100 °C till constant weight to obtain the Chlorantraniliprole.
The process of the present disclosure is carried out in an inert atmosphere wherein the inert atmosphere is selected from a nitrogen atmosphere and an argon atmosphere.
In an embodiment of the present disclosure, Chlorantraniliprole has a yield in the range of 85% to 95% and purity is in the range of 98% to 99%.
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 environmental friendly.
Further, the fluid media and reagents used in the process of the present disclosure are recovered, recycled and reused and hence, the process of the present disclosure is cost efficient, economic and environmental friendly. Also the process of the present disclosure is commercially scalable and operation friendly.
In an embodiment of the present disclosure, the Chlorantraniliprole obtained is polymorph B having at least three 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
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 (at laboratory scale)
Example 1:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 500 ml of monoglyme was charged into the reactor followed by adding 275.6 g of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 15 °C followed by adding 274.8 g of methane sulphonyl chloride over a period of 20 minutes by maintaining the temperature at 15 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 2.5 litres of monoglyme was charged into a 5 litre round bottom flask followed by adding 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 197.92 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 35 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 15 °C over a period of 4 hours and the temperature was further maintained for 8 hours to obtain a reaction mass, wherein benzoxazinone conversion was > 95% by HPLC analysis and unreacted BPA+ACMBA was < 1%. To the reaction mass, monomethyl amine gas (64 g) was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone < 0.5 % and free monomethyl amine (having normality 0.1 N). Further, the product mass was heated to 60 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 25 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 92 % w/w with HPLC purity 98.5%.
Recovery and Recycle:
• Monoglyme filtrate from the above process was subjected to monoglyme recovery and the recovered monoglyme was recycled in the process of the present disclosure.
• The aqueous filtrate was subjected to monoglyme recovery and recovered monoglyme was recycled in the process of the present disclosure.
• Bottom mass was evaporated to dryness to obtain a residual mass containing sodium salt of methane sulphonic acid. The residual solid mass containing sodium salt of methane sulphonic acid was reacted with thionyl chloride in dichloroethane and was converted to methane sulphonyl chloride which was distilled and recycled in the process of the present disclosure.
Figure 1 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 1.
From Figure 1, it is observed that the Chlorantraniliprole obtained in Example 1 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Example 2:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 500 ml of monoglyme was charged into the reactor followed by adding 275.6 g of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 10 °C followed by adding 275 g of methane sulphonyl chloride over a period of 30 minutes by maintaining the temperature at 10 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 2.5 litres of monoglyme was charged into a 5 litre round bottom flask followed by adding 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 189.2 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 35 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 15 °C over a period of 4 hours and the temperature was further maintained for 8 hours to obtain a reaction mass, wherein benzoxazinone conversion was 96% by HPLC analysis and unreacted BPA+ACMBA was < 0.8%. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes an off white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone < 0.5 % and free monomethyl amine (having normality 0.06 N). Further, the product mass was heated to 60 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 25 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 93 % w/w with HPLC purity 99%.
Figure 2 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 2.
From Figure 2, it is observed that the Chlorantraniliprole obtained in Example 2 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Example 3:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 500 ml of monoglyme was charged into the reactor followed by adding 265 g of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 15 °C followed by adding 274.8 g of methane sulphonyl chloride over a period of 30 minutes by maintaining the temperature at 15 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 2 litres of monoglyme was charged into a 5 litre round bottom flask followed by adding 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 189.2 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 60 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 15 °C over a period of 4 hours and the temperature was further maintained for 8 hours to obtain a reaction mass, wherein benzoxazinone conversion was 95% by HPLC analysis and unreacted BPA+ACMBA was < 1%. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone < 0.5 % and free monomethyl amine (having normality 0.1 N). Further, the product mass was heated to 60 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 30 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 94 % w/w with HPLC purity 98.5%.
Figure 3 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 3.
From Figure 3, it is observed that the Chlorantraniliprole obtained in Example 3 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Example 4:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 500 ml of monoglyme was charged into the reactor followed by adding 275.6 g of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 15 °C followed by adding 274.8 g of methane sulphonyl chloride over a period of 20 minutes by maintaining the temperature at 15 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 1.5 litres of monoglyme was charged into a 5 litre round bottom flask followed by adding 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 189.2 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 60 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 15 °C over a period of 4 hours and the temperature was further maintained for 8 hours to obtain a reaction mass, wherein benzoxazinone conversion was > 95% by HPLC analysis and unreacted BPA+ACMBA was < 1%. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone 0.4 % and free monomethyl amine (having normality 0.05 N). Further, the product mass was heated to 60 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 30 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 95 % w/w with HPLC purity 98%.
Figure 4 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 4.
From Figure 4, it is observed that the Chlorantraniliprole obtained in Example 4 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Example 5:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 500 ml of monoglyme was charged into the reactor followed by adding 275.0 g of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 25 °C followed by adding 286.25 g of methane sulphonyl chloride over a period of 20 minutes by maintaining the temperature at 25 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 2.0 litres of monoglyme was charged into 5 litre round bottom flask followed by adding 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 189.2 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 50 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 45 °C over a period of 4 hours and the temperature of 45 °C was further maintained for 6 hours to obtain a reaction mass, wherein benzoxazinone conversion was 92.0% by HPLC analysis and unreacted BPA+ACMBA was < 1%. To the reaction mass, the monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone 0.4 % and free monomethyl amine (having normality 0.04 N). Further, the product mass was heated to 60-65 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 30 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 93.0 % w/w with HPLC purity 98%.
Figure 5 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 5.
From Figure 5, it is observed that the Chlorantraniliprole obtained in Example 5 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Example 6:
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 1500 ml of diglyme was charged into the reactor followed by adding 270 g of dry Na2CO3 powder to the reactor containing diglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 18 °C followed by adding 274.8 g of methane sulphonyl chloride over a period of 20 minutes by maintaining the temperature at 15 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride. 302.5 g of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) was added over 1 hour by maintaining temperature 15 °C to get third mixture. Further, 189 g of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) was added to the third mixture under stirring by maintaining the temperature of 15 °C over a period of 3 hours and the temperature was further maintained for 10 hours to obtain a reaction mass, wherein benzoxazinone conversion was 94% by HPLC analysis and unreacted BPA+ACMBA was 1%. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone < 0.5 % and free monomethyl amine (having normality 0.1 N). Further, the product mass was heated to 60 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of diglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 5 °C and was filtered to obtain solids followed by washing the solids with 500 ml of chilled diglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 30°C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 85 % w/w with HPLC purity 98.5%.
Figure 6 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Example 6.
From Figure 6, it is observed that the Chlorantraniliprole obtained in Example 6 is polymorph B having the 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Further, Figure 7 illustrates X-ray powder diffraction spectrum of the polymorph B of Chlorantraniliprole obtained in Examples 1 to 6. From Figure 7, it is concluded that the Chlorantraniliprole obtained in Examples 1 to 6 are all having the same crystal form i.e. polymorph B as they are showing the same XRD pattern and 2? values.
In addition, the polymorph B of Chlorantraniliprole obtained in Examples 1 to 6 were subjected to FTIR characterization. Figure 8 illustrates FTIR spectrum of the polymorph B of Chlorantraniliprole prepared in Examples 1 to 6.
Comparative Example (a):
Part A: Preparation of Benzoxazinone Intermediate
A glass reactor of 5 litre capacity with a suitable stirrer, a condenser, a thermometer, an addition funnel, and an attached cooling system was used. Methanesulfonyl chloride 150 g (1.3 g mole) was dissolved in 1000 ml acetonitrile and was charged into the reactor and cooled to -5 °C to obtain a mixture. A solution of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) 302 g (1.0 g mole) and 140 g pyridine (1.7 g mole) in 1000 ml acetonitrile was added dropwise to the mixture over 30 minutes at -5°C to obtain a slurry. The slurry was stirred for 5 minutes at -5°C and then a mixture of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) 186 g and pyridine 270 g (3.42 g mole) in 1500 ml acetonitrile was added to the slurry to obtain a mass. The mass was stirred for 15 minutes at -5 °C and then 150 g methanesulfonyl chloride (1.3 g mole) in 500 ml acetonitrile was added dropwise over 30 minutes at a temperature of -5°C to obtain a reaction mixture. The reaction mixture was stirred for 15 minutes at -5°C, then allowed to warm slowly to 30 °C and stirred for 4 hours to obtain a product mass. 2000 ml water was added dropwise to the product mass and stirred for 15 minutes to obtain a resultant mass. The resultant mass was filtered and the solids were washed with a mixture of acetonitrile-water in 2:1 ratio (300 ml X 3), then with acetonitrile (200 ml X 3), and dried under nitrogen to afford the product benzoxazinone intermediate (2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-Pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one) as a light yellow powder, 407 g ( 90.2 % yield).
Part B: Preparation of Chlorantraniliprole
In a solution of 452 g (1.0 g mole) of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-Pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one (benzoxazinone intermediate) in 3500 ml tetrahydrofuran, 93 g (3 g mole) was added to obtain a reaction mass. The reaction mass was heated to 60 °C for 90 minutes and then cooled to room temperature to obtain a product mixture. Tetrahydrofuran solvent was evaporated from the product mixture under reduced pressure and the residual solid was slurried in ether and filtered and dried to obtain Chlorantraniliprole, 324 g (67 % yield)
Overall yield of Part A and Part B together is 60%.
From the examples 1 to 6 and comparative example (a) the following are observed:
? the process of the present disclosure is one pot reaction, whereas the process of the comparative example (a) is a two stage reaction;
? there is an ease of operation in the process of the present disclosure, whereas the process of the comparative example (a) has multiple operations;
? the process of the present disclosure employs a single solvent, whereas the process of the comparative example (a) employs multiple solvents;
? the reaction in the process of the present disclosure is carried out at 10 °C to 20 °C, whereas the reaction in the process of the comparative example (a) is carried out below 0 °C; and
? the yield of chlorantraniliprole prepared in accordance with the process of the present disclosure is more than 90 %, whereas the yield of chlorantraniliprole prepared in accordance with the process of the comparative example (a) is 60 %.
Experiment 2: Preparation of Chlorantraniliprole (at Kilo scale)
Example (i): Preparation of Chlorantraniliprole in accordance with the present disclosure (at Kilo scale)
A reactor of 500 litre capacity with a suitable stirrer, a condenser, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 50 litre of monoglyme was charged into the reactor followed by adding 27.5 kg of dry Na2CO3 powder to the reactor containing monoglyme under stirring at 30 °C to obtain a first mixture. The first mixture was cooled to 25 °C followed by adding 28.6 kg of methane sulphonyl chloride over a period of 20 minutes by maintaining the temperature at 25 °C to obtain a second mixture. This addition was slightly exothermic because of the trace amount of moisture in the input raw materials which reacted with methane sulphonyl chloride.
Separately, 200 litres of monoglyme was charged into 500 litre round bottom flask followed by adding 30.25 kg of 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) and 18.92 kg of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) under stirring at 50 °C to obtain a third mixture (clear solution).
The third mixture was added to the second mixture under stirring by maintaining the temperature of 45 °C over a period of 4 hours and the temperature of 45 °C was further maintained for 6 hours to obtain a reaction mass, wherein benzoxazinone conversion was 92 % by HPLC analysis and unreacted BPA+ACMBA was < 1%. To the reaction mass, the monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a white slurry and the reaction was monitored by HPLC to get unreacted Benzoxazinone 0.4 % and free monomethyl amine (having normality 0.04 N). Further, the product mass was heated to 65 °C and excess monomethyl amine if any in the product mass, was scrubbed into a scrubber of monoglyme to recover the monomethyl amine. The recovered monomethyl amine was recycled in a next batch. The product mass was cooled to 25 °C and was filtered to obtain solids followed by washing the solids with 1000 ml of chilled monoglyme to obtain a wet cake. The wet cake is reslurried in 2000 ml of water and filtered at an ambient condition (at 30 °C). The wet cake was further washed with 2000 ml of water to make it free of inorganic salts like NaCl, NaHCO3, Na2CO3 and sodium salt of methane sulphonic acid (water washing should have a neutral pH).
The wet cake was dried at 110 °C under vacuum till moisture content was < 0.5% and residual solvent level was < 0.1 %. On dry basis Chlorantraniliprole yield was 93 % w/w with HPLC purity 98%.
Comparative Example 1:
A reactor of 500 litre capacity with a suitable stirrer, a condenser, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 350 litre of acetonitrile was charged into the reactor followed by added 30.25 kg 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) at 25°C to get a first mixture. To the reaction mass, 12.0 kg sodium carbonate first lot was added at 28 °C over a period of 30 mins to have second mixture. To the second mixture, 12.0 kg of Methane sulfonyl chloride first lot was added under stirring at 30 °C in 30 minutes to get third mixture. 20.45 kg of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) was added to the third mixture under stirring for 30 min to get fourth mixture. To the fourth mixture, 12.0 kg of sodium carbonate second lot was added at 30°C over a period of 30 minutes under stirring to have fifth mixture. To the fifth mixture, 12.0 kg of Methane sulfonyl chloride second lot was added under stirring at 30 °C in 30 minutes to get sixth mixture. The reaction mass was very thick non- homogenous slurry and it was difficult to get stir. It was further maintained at 30°C for 10 hours to obtain a mass containing benzoxazinone intermediate product. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a thick white slurry, which one was filtered and washed with acetonitrile to get solid cake. The solid cake reslurried in water and filtered. The cake further washed with water and solid cake so obtained is dried to get Chlorantraniliprole having HPLC purity of 95 % with yield of 75 % w/w.
Comparative Example 2:
A reactor of 500 litre capacity with a suitable stirrer, a condenser, an attached cooling system and a nitrogen passing system was used. To the reactor, nitrogen was passed continuously to maintain inert atmosphere and to avoid moisture entering into the reactor. 350 litre of monochlorobenzene (MCB) was charged into the reactor followed by added 30.25 kg 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (BPA) at 25°C to get a first mixture. To the reaction mass, 12.0 kg sodium carbonate first lot was added at 28 °C over a period of 30 minutes to have second mixture. To the second mixture, 12.0 kg of Methane sulfonyl chloride first lot was added under stirring at 30 °C in 30 minutes to get third mixture. 20.45 kg of 2-amino-5-chloro-3-methyl benzoic acid (ACMBA) was added to the third mixture under stirring for 30 min to get fourth mixture. To the fourth mixture, 12.0 kg of sodium carbonate second lot was added at 30°C over a period of 30 mins under stirring to have fifth mixture. To the fifth mixture, 12.0 kg of Methane sulfonyl chloride second lot was added under stirring at 30 °C in 30 minutes to get sixth mixture. The reaction mass was very thick non- homogenous slurry and it was difficult to get stir. It was further maintained at 30 °C for 6 hours to obtain a mass containing benzoxazinone intermediate product. To the reaction mass, monomethyl amine gas was passed for 2 hours by maintaining the temperature at 20 °C to obtain a product mass comprising Chlorantraniliprole.
The product mass becomes a very thick white slurry, which one was filtered and washed with acetonitrile to get solid cake. The solid cake reslurried in water and filtered. The cake further washed with water and solid cake so obtained is dried to get Chlorantraniliprole having HPLC purity of 94 % with yield of 72 % w/w.
From the comparative examples 1 and 2, it is observed that when acetonitrile or MCB was used, a very thick non-homogenous slurry was formed which was difficult to stir. Thus, the conventional processes are convenient to carryout only at lab scale where real practical difficulty cannot be reflected/studied with respect to chemical engineering aspect. This conventional processes are not feasible at commercial scale and finally end up with poor yield and quality of the final product.
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;
• the process is simple, efficient, economic and environment friendly; and
• the fluid media and reagents can be recovered, 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 the preparation of Chlorantraniliprole, said process comprising the following steps:
a. charging a predetermined amount of a first fluid medium to a reactor followed by adding a predetermined amount of a base to said first fluid medium at a first predetermined temperature under stirring to obtain a first mixture;
b. cooling said first mixture to a second predetermined temperature followed by adding methane sulfonyl chloride over a first predetermined time period by maintaining said second predetermined temperature to obtain a second mixture;
c. separately dissolving 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid in a predetermined amount of a second fluid medium at a third predetermined temperature to obtain a third mixture;
d. adding said third mixture in said second mixture by maintaining the second predetermined temperature over a second predetermined time period under stirring and further maintaining the reaction for a third predetermined time period to obtain a benzoxazinone intermediate; and
e. passing monomethyl amine gas to said bezoxazinone intermediate followed by reacting at a fourth predetermined temperature for a fourth predetermined time period 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 monoglyme, diglyme, triglyme, cyclic ether and dioxane.
3. The process as claimed in claim 1, wherein said first fluid medium and said second fluid medium are anhydrous with a moisture content less than 0.1%.
4. The process as claimed in claim 1, wherein said base is selected from an inorganic base and an organic base.
5. The process as claimed in claim 4, 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 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 predetermined amount of said first fluid medium is in the range of 150 ml to 250 ml per mole of said base and said second fluid medium is 1 litre to 4 litres per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
7. The process as claimed in claim 1, wherein said predetermined amount of said base is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
8. The process as claimed in claim 1, wherein said predetermined amount of the methane sulfonyl chloride is in the range of 2 moles to 3 moles per mole of 3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid.
9. The process as claimed in claim 1, wherein said monomethyl amine is selected from gaseous monomethyl amine and liquid monomethyl amine.
10. The process as claimed in claim 1, wherein said first predetermined temperature is in the range of 20 °C to 40 °C.
11. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 0 °C to 60 °C.
12. The process as claimed in claim 1, wherein said second predetermined temperature is in the range of 10 °C to 20 °C.
13. The process as claimed in claim 1, wherein said first predetermined time period is in the range of 10 minutes to 120 minutes.
14. The process as claimed in claim 1, wherein said second predetermined time period is in the range of 1 hour to 10 hours.
15. The process as claimed in claim 1, wherein said third predetermined time period is in the range of 4 hours to 15 hours.
16. The process as claimed in claim 1, wherein said third predetermined temperature is in the range of 25 °C to 70 °C.
17. The process as claimed in claim 1, wherein said fourth predetermined temperature is in the range of 10 °C to 60 °C.
18. The process as claimed in claim 1, wherein said fourth predetermined time period is in the range of 1 hour to 8 hours.
19. The process as claimed in claim 1 is carried out in an inert atmosphere wherein said inert atmosphere is selected from a nitrogen atmosphere and an argon atmosphere.
20. The process as claimed in claim 1, wherein said product mass is cooled to a temperature in the range of 10 °C to 25 °C; filtered to obtain solids followed by washing the solids with said first fluid medium to obtain a wet cake; washing said wet cake by using water till the pH of the washing is neutral and free of chloride ions to obtain a washed wet cake; drying the washed wet cake at a temperature in the range of 90 °C to 100 °C till constant weight to obtain a pure Chlorantraniliprole.
21. The process as claimed in claim 1, wherein Chlorantraniliprole has a yield in the range of 85% to 95% and a purity is in the range of 98% to 99%.
22. The process as claimed in claim 1, wherein said fluid medium, and water are recovered and recycled and salt of methane sulphonic acid formed are recovered from water washings and converted back to methane sulphonyl chloride and reused.
23. The process as claimed in claim 1, wherein said Chlorantraniliprole is polymorph B having at least three 2? values selected from 8.59±0.2°, 9.95±0.2°, 11.47±0.2°, 12.18±0.2°, 15,54±0.2°, 17.25±0.2°, 17.80±0.2°, 18.21±0.2°, 20.44±0.2°, 21.30±0.2°, 21.72±0.2°, 22.56±0.2°, 22.88±0.2°, 24.58±0.2°, 24.95±0.2°, 25.51±0.2°, 25.71±0.2°, 27.21±0.2°, 28.31±0.2°, 28.31±0.2°, 28.92±0.2°, 30.09±0.2°, 30.40±0.2°, 32.11±0.2° and 35.82±0.2°.
Dated this 13th day of December, 2023

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

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