Preparation process of anthranilamide

Abstract

To provide a purification process for obtaining impurity-free cyantranilamide.SOLUTION: A purification process of cyantraniliprole includes purification of cyantraniliprole from an aqueous slurry thereof, the process including the steps of: a) supplying a reaction product mixture containing cyantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) agitating the slurry at a temperature of 35°C to 60°C for one hour; d) separating solids; e) optionally repeating the steps b), c), and d); and f) drying to obtain purified cyantraniliprole, wherein the aqueous slurry contains a hydrophilic solvent mixed with a product of the reaction between reaction intermediates and methylamine.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention relates to the preparation of anthranilamide. The invention further provides impurity-free anthranilamide. Specifically, the invention provides a purification process for impurity-free anthranilamide. [Background technology]

[0002] Effective control of pests, such as arthropods, is essential for crop safety. Arthropods are a significant group of pests that cause considerable damage to crops and homes worldwide every year. Anthranilamides are a new class of compounds with extremely potent insecticidal activity. These nitrogen-containing aromatic compounds selectively act on targeted ryanodine receptors in insects. The ryanodine receptor forms calcium ion channels involved in muscle function.

[0003] Examples of insecticidal anthranilamides include cyantraniliprole, chlorantraniliprole, cyclaniliprole, tetrachlorantraniliprole, and tetraniliprole. Chlorantraniliprole is an extremely potent and selective activator of insect ryanodine receptors and exhibits exceptional activity against a wide range of lepidopteran insects. Chlorantraniliprole controls various chewing pests (primarily lepidopteran, but also some coleopteran, diptera, and isopteran) in a wide range of crops, including fruits, vegetables, grapes, cotton, sugarcane, rice, and grasses.

[0004] U.S. Patent No. 7,232,836 discloses the preparation of chlorantraniliprole represented as the compound of formula IV (Scheme I).

[0005] [ka]

[0006] The intermediate 3-bromo-1-(3-chloropyridine-2-yl)-1H-pyrazole-5-carboxylic acid is represented as the compound of formula I, and the intermediate 2-amino-5-chloro-3-methylbenzoic acid is represented as the compound of formula II. 2-[3-bromo-1-(3-chloropyridine-2-yl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one is called the compound of formula III.

[0007] U.S. Patent No. 7,247,647 discloses the preparation of cyantraniliprole represented as a compound of formula VII (Scheme II).

[0008] [ka]

[0009] The intermediate 3-bromo-1-(3-chloropyridine-2-yl)-1H-pyrazole-5-carboxylic acid is represented as the compound of formula I, and the intermediate 2-amino-5-cyano-3-methylbenzoic acid is represented as the compound of formula V. 2-[3-bromo-1-(3-chloropyridine-2-yl)-1H-pyrazole-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazine-4-one is called the compound of formula VI.

[0010] The inventors of this invention have noted that the compound of formula III is not physically stable enough to be properly purified. Furthermore, it is known that further reactions with methylamine result in impurities of the compound of formula III, which have conflicting physical and chemical properties, leading to products that are ineffective for their intended use.

[0011] Furthermore, it has been observed that the low solubility of anthranilamide in water and / or organic solvents makes it difficult to carry out proper purification processes.

[0012] Therefore, it is necessary to develop improved methods for preparing and purifying anthranilamides.

[0013] (Object of the Invention) An object of the present invention is to provide an anthranilamide free of impurities.

[0014] Another object of the present invention is to provide a process for preparing anthranilamide.

[0015] Yet another object of the present invention is to provide a process for preparing chlorantraniliprole free of impurities.

Summary of the Invention

[0016] The present invention provides a compound of formula (A) substantially free of impurities:

Chemical Formula

[0017] The present invention provides a compound of formula A:

Chemical Formula

[0018] The present invention relates to formula A:

Chemical formula

[0019] The present invention further provides chlorantraniliprole substantially free of impurities.

[0020] The present invention provides a purification process for chlorantraniliprole, which process comprises purifying chlorantraniliprole from an aqueous slurry containing chlorantraniliprole.

[0021] The present invention provides a purification process for chlorantraniliprole, which process comprises: a) feeding a reaction product mixture containing chlorantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) A step of stirring the slurry for a predetermined time, d) A step to separate the solid, e) A process in which steps b), c), and d) are optionally repeated, f) The step of drying to obtain purified chlorantraniliprole, is included.

[0022] The present invention provides a process for preparing chlorantraniliprole free from impurities, the process comprising purifying chlorantraniliprole from an aqueous slurry containing the reaction product of a compound of formula III and methylamine.

[0023] The present invention provides a process for preparing chlorantraniliprole free of impurities, and this process is a) A step of reacting the compound of formula III with methylamine in an organic solvent, b) A process for separating and recovering the solid, c) A step of preparing a slurry of the product from step b) under aqueous conditions, d) A step of stirring the slurry for a predetermined time, e) A process for separating and recovering the solid, f) A process in which steps c), d), and e) are optionally repeated, g) a step of drying to obtain chlorantraniliprole that is substantially free of impurities, and

[0024] This invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, and the purification of the compound of formula III is not required.

[0025] The present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, the process comprising purifying chlorantraniliprole from an aqueous slurry, the aqueous slurry comprising a hydrophilic solvent mixed with the reaction product of a compound of formula III and methylamine.

[0026] The present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, and the process is as follows: a) A step of preparing compound III by reacting compound I and compound II in an organic solvent, b) A step of optionally purifying the compound of formula III, c) A step of reacting the compound of formula III with methylamine in an organic solvent, d) A process for separating and recovering the solid, e) A step of preparing a slurry of the product of step d) under aqueous conditions, f) A step of stirring the slurry for a predetermined time, g) A step of separating and recovering the solid, h) A process in which steps e), f), and g) are optionally repeated, i) a step of drying to obtain chlorantraniliprole free of impurities, and

[0027] The present invention provides a process for purifying cyantraniliprole, which includes purifying cyantraniliprole from an aqueous slurry of cyantraniliprole.

[0028] The present invention provides a purification process for cyantraniliprole, and this process is a) A step of supplying a reaction product mixture containing cyantraniliprole to a reactor, b) A step of preparing a slurry of the mixture under aqueous conditions, c) A step of stirring the slurry for a predetermined time, d) A step to separate the solid, e) A process in which steps b), c), and d) are optionally repeated, f) a step of drying to obtain purified cyantraniliprole, and

[0029] The present invention further provides a process for preparing cyantraniliprole free of impurities, the process being: a) A step of reacting the compound of formula VI with methylamine in an organic solvent, b) A process for separating and recovering the solid, c) A step of preparing a slurry of the product from step b) under aqueous conditions, d) A step of stirring the slurry for a predetermined time, e) A process for separating and recovering the solid, f) A process in which steps c), d), and e) are optionally repeated, g) a step of drying to obtain cyantraniliprole that is substantially free of impurities, and

[0030] The present invention further provides a process for preparing cyantraniliprole, the process comprising purifying cyantraniliprole from an aqueous slurry, the aqueous slurry comprising a hydrophilic solvent mixed with the reaction product of a compound of formula VI and methylamine. [Modes for carrying out the invention]

[0031] Many anthranilamides represented by the general structure of formula A are known to have low solubility in water or other hydrophilic solvents, making isolation and purification of the compounds difficult. Despite this low solubility in water and other hydrophilic solvents, the inventors have surprisingly found that substantially pure (i.e., substantially impurity-free) anthranilamides can be prepared from an aqueous slurry by purifying the crude reaction product of the compound of formula III with methylamine. Based on this discovery, the inventors have made it possible to provide an impurity-free insecticidal anthranilamide and a process for preparing such substantially pure anthranilamides.

[0032] Chlorantraniliprole is an example of such anthranilic amides that are difficult to prepare, purify (resulting in various physicochemical properties), and optimize their preparation processes. The compounds of formula III are not sufficiently stable to undergo an effective purification process, and previous processes that relied on the purification of the compounds of formula III to obtain pure anthranilic amides could not provide such substantially pure anthranilic amides as enabled by the process of the present invention and were known to result in a decrease in yield. Further reaction with methylamine was found to result in chlorantraniliprole containing various impurities and having non-uniform physical properties and being ineffective for the intended use. The present invention has found that purifying anthranilic amide from an aqueous slurry is a surprisingly good strategy for preparing substantially pure anthranilic amide rather than starting from the pure compound of formula III.

[0033] The inventors of the present invention have noted that following the process of the present invention, the purification of the compounds of formula III can be avoided, that is, the purification of the compounds of formula III is not essential, and yet substantially impurity-free chlorantraniliprole can be obtained.

[0034] Therefore, the present invention provides a compound of formula (A) free of impurities.

[0035]

Chemical formula

[0036] In another embodiment, the present invention also relates to formula A: [ka] (In the formula, R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivative, hydroxyl, unsubstituted or substituted linear or branched chain (C1~C) 10 ) Alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or linear or branched (C1~C 10 The present invention provides a purification process for compounds that may be alkyl, where m, n, p, and q are 0, 1, 2, or 3 in the formula, The process involves purifying the compound of formula A from an aqueous slurry containing the compound of formula A.

[0037] In one embodiment, an aqueous slurry of the compound of formula A is provided in a reactor.

[0038] In one embodiment, the aqueous slurry of the compound of formula A contains a reaction product mixture containing the compound of formula A.

[0039] In one embodiment, the reaction product mixture is the reaction product of the compound of formula III and methylamine.

[0040] In one embodiment, the reaction product mixture is the product of a reaction between the compound of formula III and methylamine carried out in an organic solvent.

[0041] In one embodiment, the compound of formula III is reacted with methylamine without purification or isolation.

[0042] In one embodiment, the aqueous slurry includes a slurry containing a reaction product mixture in water.

[0043] In one embodiment, the purification of a compound of formula A from an aqueous slurry containing the compound of formula A includes stirring the aqueous slurry for a predetermined time before purifying the compound of formula A.

[0044] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II.

[0045] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II in an organic solvent.

[0046] In one embodiment, the compound of formula III is used without being isolated or purified from the reaction of the compound of formula I and the compound of formula II, which is carried out in an organic solvent.

[0047] In one embodiment, the purification of a compound of formula A from an aqueous slurry containing the compound of formula A comprises stirring the aqueous slurry for a predetermined time, followed by purifying the compound of formula A.

[0048] In one embodiment, the purification of a compound of formula A from an aqueous slurry containing the compound of formula A includes stirring the aqueous slurry for a predetermined time, purifying the compound of formula A, and separating the compound of formula A from the aqueous slurry.

[0049] In one embodiment, the purification of a compound of formula A from an aqueous slurry containing the compound of formula A comprises repeatedly (a) stirring the aqueous slurry for a predetermined time, (b) purifying the compound of formula A, and (c) separating the compound of formula A from the aqueous slurry.

[0050] In one embodiment, steps (a), (b), and (c) may be repeated multiple times.

[0051] In one embodiment, the purification of a compound of formula A from an aqueous slurry containing the compound of formula A includes stirring the aqueous slurry for a predetermined time, purifying the compound of formula A, separating the compound of formula A from the aqueous slurry, and drying the separated compound of formula A.

[0052] In one embodiment, the present invention also includes formula A: [ka] (In the formula, R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivative, hydroxyl, unsubstituted or substituted linear or branched chain (C1~C) 10 ) Alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or linear or branched (C1~C 10 The present invention provides a purification process for compounds that may be alkyl, where m, n, p, and q may be 0, 1, 2, or 3. The process in question is a) A step of supplying a reaction product mixture containing the compound of formula A to a reactor, b) A step of preparing a slurry of the mixture under aqueous conditions, c) A step of stirring the slurry for a predetermined time, d) A step to separate the solid, e) A process in which steps b), c), and d) are optionally repeated, f) A step of drying to obtain a purified compound of formula A, and

[0053] In one embodiment, the compound of formula A has R1, R2, R3, and R4 independently being hydrogen, halogen, cyano, amino, N-thio derivative, alkyl, halogen, cyano, or amino-substituted alkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl-substituted, or linear or branched (C1-C) 10 When it is an alkyl compound, m, n, p, and q may be 0, 1, 2, or 3.

[0054] In one embodiment, when R1 is CN and CH3, R2 is Cl, R3 is Br, R4 is H and -CH3, and m and q = 2 in the formula, the compound of formula A is represented by the following structure.

[0055] [ka]

[0056] In another embodiment, when R1 is Cl and -CH3, R2 is Cl, R3 is Br, and R4 is H and -CH3, and m and q = 2, the compound of formula A is represented by the following structure.

[0057] [ka]

[0058] In another embodiment, when R1 is Cl and Br, R2 is Cl, R3 is Br, and R4 is H and 1-cyclopropylethyl, and m and q = 2, the compound of formula A is represented by the following structure.

[0059] [ka]

[0060] In yet another embodiment, when R1 is Cl, R2 is Cl, R3 is Br, and R4 is H and -CH3, and m, n, and q = 2, the compound of formula A is represented by the following structure.

[0061] [ka]

[0062] In another embodiment, when R1 is CN and -CH3, R2 is Cl, R3 is 5-(trifluoromethyl)-2H-tetrazole-2-yl]methyl, and R4 is H and -CH3, and m and q = 2, the compound of formula A is represented by the following structure.

[0063] [ka]

[0064] In one embodiment, the term “impurity” refers to unreacted synthetic intermediates, reagents, solvents, organic and / or inorganic products of side reactions, organic and / or inorganic salts, and / or other undesirable substances.

[0065] Therefore, the compounds of the present invention that are substantially free of impurities are intended to mean compounds that are substantially free of all unreacted synthetic intermediates, reagents, solvents, organic and / or inorganic products of side reactions, organic and / or inorganic salts, and / or other undesirable substances.

[0066] In one embodiment, the aqueous condition in step b) refers to water or a mixture of water and one or more solvents.

[0067] In a preferred embodiment, the aqueous condition in step b) refers to water.

[0068] In one embodiment, the slurry in step b) is prepared by mixing the reaction product with water or a mixture of water and one or more solvents.

[0069] In one embodiment, the solvent is selected from the group comprising methanol, ethanol n-propanol, n-butanol, acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, and dimethylformamide.

[0070] In one embodiment, in step c), the reaction product is stirred at a temperature of approximately 25°C to approximately 80°C.

[0071] In a preferred embodiment, in step c), the reaction product is stirred at a temperature of about 40°C to about 60°C.

[0072] In one embodiment, in step c), the reaction product is stirred for at least 15 minutes.

[0073] In a preferred embodiment, in step c), the reaction product is stirred for at least 30 minutes.

[0074] In one embodiment, the solid separation in step d) is performed by filtration, precipitation, decantation, or solid-liquid centrifugation.

[0075] In a preferred embodiment, the solid separation in step d) is carried out by filtration.

[0076] The present invention provides chlorantraniliprole that is substantially free of impurities.

[0077] In one embodiment, the present invention provides chlorantraniliprole that is substantially free of impurities.

[0078] In another embodiment, the present invention provides cyantraniliprole that is substantially free of impurities.

[0079] In another embodiment, the present invention provides chlorantraniliprole with a purity of >95% by weight.

[0080] In another embodiment, the present invention provides chlorantraniliprole with a purity of >97% by weight.

[0081] In another embodiment, the present invention provides cyantraniliprole with a purity of >95% by weight.

[0082] In another embodiment, the present invention provides cyantraniliprole with a purity of >97% by weight.

[0083] In one embodiment, the term “impurity” refers to unreacted synthetic intermediates, reagents, solvents, organic and / or inorganic products of side reactions, organic and / or inorganic salts, and / or other undesirable substances.

[0084] In another embodiment, the synthetic intermediate includes the compound of formula I, the compound of formula II, and the compound of formula III.

[0085] In another embodiment, the synthetic intermediate includes the compound of formula I, the compound of formula V, and the compound of formula VI.

[0086] In one embodiment, the reagent comprises methanesulfonyl chloride and methylamine.

[0087] In one embodiment, the organic and / or inorganic products of the side reaction include a salt of the compound of formula I with a sulfonic acid and / or chloride.

[0088] In one embodiment, the organic and / or inorganic products of the side reaction include a salt of the compound of formula I with methanesulfonyl chloride.

[0089] In another embodiment, the organic and / or inorganic products of the side reaction include a salt of the compound of formula II with a sulfonic acid and / or chloride.

[0090] In another embodiment, the organic and / or inorganic products of the side reaction include a salt of the compound of formula V with a sulfonic acid and / or chloride.

[0091] In yet another embodiment, the present invention provides chlorantraniliprole that is substantially free of the compound of formula I, the compound of formula II, the compound of formula III, and salts of the compound of formula I with sulfonic acid and chloride.

[0092] In yet another embodiment, the present invention provides cyantraniliprole that is substantially free of the compound of formula I, the compound of formula V, the compound of formula VI, and salts of the compound of formula I with sulfonic acid and chloride.

[0093] In one embodiment, the present invention provides a purification process for chlorantraniliprole, the process comprising purifying chlorantraniliprole from an aqueous slurry containing chlorantraniliprole.

[0094] In one embodiment, an aqueous slurry of chlorantraniliprole is provided in the reactor.

[0095] In one embodiment, the aqueous slurry of chlorantraniliprole contains a reaction product mixture containing chlorantraniliprole.

[0096] In one embodiment, the reaction product mixture is the reaction product of the compound of formula III and methylamine.

[0097] In one embodiment, the reaction product mixture is the product of a reaction between the compound of formula III and methylamine carried out in an organic solvent.

[0098] In one embodiment, the compound of formula III is reacted with methylamine without purification or isolation.

[0099] In one embodiment, the aqueous slurry includes a slurry containing a reaction product mixture in water.

[0100] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time before purifying the chlorantraniliprole.

[0101] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II.

[0102] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II in an organic solvent.

[0103] In one embodiment, the compound of formula III is used without being isolated or purified from the reaction of the compound of formula I and the compound of formula II, which is carried out in an organic solvent.

[0104] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole comprises stirring the aqueous slurry for a predetermined time, followed by the purification of the chlorantraniliprole.

[0105] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time, purifying the chlorantraniliprole, and separating the chlorantraniliprole from the aqueous slurry.

[0106] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole involves repeatedly (a) stirring the aqueous slurry for a predetermined time, (b) purifying the chlorantraniliprole, and (c) separating the chlorantraniliprole from the aqueous slurry.

[0107] In one embodiment, steps (a), (b), and (c) may be repeated multiple times.

[0108] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time, purifying the chlorantraniliprole, separating the chlorantraniliprole from the aqueous slurry, and drying the separated chlorantraniliprole.

[0109] Therefore, the present invention provides a purification process for chlorantraniliprole, which is a process that a) A step of supplying a reaction product mixture containing chlorantraniliprole to a reactor, b) A step of preparing a slurry of the mixture under aqueous conditions, c) A step of stirring the slurry for a predetermined time, d) A process for separating and recovering the solid, e) A process in which steps b), c), and d) are optionally repeated, f) a step of drying to obtain chlorantraniliprole that is substantially free of impurities, is included.

[0110] In one embodiment, the chlorantraniliprole of step a) can be prepared by the reaction of a compound of formula I, a derivative thereof, or a salt with a compound of formula II, a derivative thereof, or a salt.

[0111] In one embodiment, the aqueous condition in step b) refers to water or a mixture of water and one or more solvents.

[0112] In a preferred embodiment, the aqueous condition in step b) refers to water.

[0113] In one embodiment, the slurry in step b) is prepared by mixing the reaction product with water or a mixture of water and one or more solvents.

[0114] In one embodiment, in step c), the reaction product is stirred at a temperature of approximately 25°C to approximately 80°C.

[0115] In a preferred embodiment, in step c), the reaction product is stirred at a temperature of about 40°C to about 60°C.

[0116] In one embodiment, in step c), the reaction product is stirred for at least 15 minutes.

[0117] In a preferred embodiment, in step c), the reaction product is stirred for at least 30 minutes.

[0118] In one embodiment, the solid separation in step d) is performed by filtration, precipitation, decantation, or solid-liquid centrifugation.

[0119] In a preferred embodiment, the solid separation in step d) is carried out by filtration.

[0120] In another embodiment, the present invention provides a purification process for chlorantraniliprole, the process being a) A step of supplying a reaction product mixture containing chlorantraniliprole to a reactor, b) A step of preparing a slurry of the mixture in water, c) A step of stirring the slurry at 25°C to 60°C for at least 30 minutes, d) The filtering process, e) A process in which steps b), c), and d) are optionally repeated, f) a step of drying to obtain chlorantraniliprole that is substantially free of impurities, is included.

[0121] In yet another embodiment, the present invention provides a purification process for chlorantraniliprole, the process being: a) A step of supplying a reaction product mixture containing chlorantraniliprole to a reactor, b) A step of preparing a slurry of the reaction product in water, c) A step of stirring at 25°C to 60°C for at least 30 minutes, d) The filtering process, e) A step of repeating steps b), c), and d) at least once, f) a step of drying to obtain chlorantraniliprole that is substantially free of impurities, is included.

[0122] The present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities.

[0123] The present invention also provides a process for preparing chlorantraniliprole free from impurities, the process comprising purifying chlorantraniliprole from an aqueous slurry containing the reaction product of a compound of formula III with methylamine.

[0124] In one embodiment, an aqueous slurry of chlorantraniliprole is provided in the reactor.

[0125] In one embodiment, the aqueous slurry of chlorantraniliprole contains a reaction product mixture containing chlorantraniliprole.

[0126] In one embodiment, the reaction product mixture is the reaction product of the compound of formula III and methylamine.

[0127] In one embodiment, the reaction product mixture is the product of a reaction between the compound of formula III and methylamine carried out in an organic solvent.

[0128] In one embodiment, the compound of formula III is reacted with methylamine without purification or isolation.

[0129] In one embodiment, the aqueous slurry includes a slurry containing a reaction product mixture in water.

[0130] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time before purifying the chlorantraniliprole.

[0131] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II.

[0132] In one embodiment, the compound of formula III is a reaction product produced from the reaction of the compound of formula I and the compound of formula II in an organic solvent.

[0133] In one embodiment, the compound of formula III is used without being isolated or purified from the reaction of the compound of formula I and the compound of formula II, which is carried out in an organic solvent.

[0134] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole comprises stirring the aqueous slurry for a predetermined time, followed by the purification of the chlorantraniliprole.

[0135] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time, purifying the chlorantraniliprole, and separating the chlorantraniliprole from the aqueous slurry.

[0136] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole involves repeatedly (a) stirring the aqueous slurry for a predetermined time, (b) purifying the chlorantraniliprole, and (c) separating the chlorantraniliprole from the aqueous slurry.

[0137] In one embodiment, steps (a), (b), and (c) may be repeated multiple times.

[0138] In one embodiment, the purification of chlorantraniliprole from an aqueous slurry containing chlorantraniliprole includes stirring the aqueous slurry for a predetermined time, purifying the chlorantraniliprole, separating the chlorantraniliprole from the aqueous slurry, and drying the separated chlorantraniliprole.

[0139] The present invention provides a process for purifying cyantraniliprole, which includes purifying cyantraniliprole from an aqueous slurry of cyantraniliprole.

[0140] The present invention provides a purification process for cyantraniliprole, and this process is a) A step of supplying a reaction product mixture containing cyantraniliprole to a reactor, b) A step of preparing a slurry of the mixture under aqueous conditions, c) A step of stirring the slurry for a predetermined time, d) A step to separate the solid, e) A process in which steps b), c), and d) are optionally repeated, f) a step of drying to obtain purified cyantraniliprole, and

[0141] In one embodiment, the present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, the process being: a) A step of reacting the compound of formula III with methylamine in an organic solvent, b) A process for separating and recovering the solid, c) A step of preparing a slurry of the product from step b) under aqueous conditions, d) A step of stirring for a predetermined time, e) A process for separating and recovering the solid, f) A process in which steps c), d), and e) are optionally repeated, g) a step of drying to obtain chlorantraniliprole that is substantially free of impurities, and

[0142] In one embodiment, the reaction in step a) is carried out in an organic solvent selected from the group comprising acetonitrile, tetrahydrofuran, ethyl acetate, toluene, xylene, and dioxane.

[0143] In a preferred embodiment, the reaction in step a) is carried out in ethyl acetate.

[0144] In one embodiment, methylamine is used as an aqueous solution in step a).

[0145] In one embodiment, the aqueous condition in step c) refers to water or a mixture of water and one or more solvents.

[0146] In one preferred embodiment, the aqueous condition in step c) refers to water.

[0147] In one embodiment, the slurry in step c) is prepared by mixing the reaction product with water or a mixture of water and one or more solvents.

[0148] In one embodiment, in step d), the reaction product is stirred at a temperature of approximately 25°C to approximately 80°C.

[0149] In a preferred embodiment, in step d), the reaction product is stirred at a temperature of about 40°C to about 60°C.

[0150] In one embodiment, in step d), the reaction product is stirred for at least 15 minutes.

[0151] In a preferred embodiment, in step d), the reaction product is stirred for at least 30 minutes.

[0152] In one embodiment, the solid separation in step e) is carried out by filtration, precipitation, decantation, or solid-liquid centrifugation.

[0153] In a preferred embodiment, the solid separation in step e) is carried out by filtration.

[0154] The present invention also provides a process for preparing chlorantraniliprole that is substantially free of impurities, the process comprising purifying chlorantraniliprole from an aqueous slurry, the aqueous slurry comprising a hydrophilic solvent mixed with the reaction product of the compound of formula III and methylamine.

[0155] In one embodiment, the hydrophilic solvent is selected from the group comprising methanol, ethanol n-propanol, n-butanol, acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, and dimethylformamide.

[0156] In a preferred embodiment, the present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, the process being: a) A step of reacting the compound of formula III with an aqueous solution of methylamine in an organic solvent, b) A step of filtering the reaction product, c) A step of preparing a slurry of reaction products in water, d) A step of stirring at 25°C to 60°C for at least 30 minutes, e) The filtration process, f) A process that repeats steps c), d), and e) at least once, g) The step of drying to obtain purified chlorantraniliprole, and

[0157] The present invention further provides a process for preparing chlorantraniliprole that is substantially free of impurities, and the purification of the compound of formula III is not required.

[0158] The present invention provides a process for preparing chlorantraniliprole that is substantially free of impurities, and the process is as follows: a) A step of preparing compound III by reacting compound I and compound II in an organic solvent, b) A step of optionally purifying the compound of formula III, c) A step of reacting the compound of formula III with methylamine in an organic solvent, d) A process for separating and recovering the solid, e) A step of preparing a slurry of the product of step d) under aqueous conditions, f) A step of stirring the slurry for a predetermined time, g) A step of separating and recovering the solid, h) A process in which steps e), f), and g) are optionally repeated, i) a step of drying to obtain chlorantraniliprole that is substantially free of impurities.

[0159] In one embodiment, the reaction in step a) is carried out in an organic solvent selected from the group comprising acetonitrile, tetrahydrofuran, ethyl acetate, toluene, xylene, and dioxane.

[0160] In another embodiment, the reaction in step a) is carried out in the presence of a base.

[0161] In one embodiment, the purification of the compound of formula III in step b) may be optional.

[0162] In another embodiment, the compound of formula III may be partially purified in step (b).

[0163] In yet another embodiment, according to the present invention, purification of the compound of formula III is not essential.

[0164] In one embodiment, the purification of the compound of formula III in step b) can be avoided.

[0165] In one embodiment, the process of the present invention yields chlorantraniliprole that is substantially free of impurities generated during the reaction of step a).

[0166] In another embodiment, the process of the present invention avoids the purification of the more unstable compound of formula III.

[0167] In one embodiment, the reaction in step c) is carried out in an organic solvent selected from the group comprising acetonitrile, tetrahydrofuran, ethyl acetate, toluene, xylene, and dioxane.

[0168] In a preferred embodiment, the reaction in step c) is carried out in ethyl acetate.

[0169] In one embodiment, methylamine is used as an aqueous solution in step c).

[0170] In one embodiment, the aqueous condition in step e) refers to water or a mixture of water and one or more solvents.

[0171] In one preferred embodiment, the aqueous condition in step e) refers to water.

[0172] In one embodiment, the slurry of step e) is prepared by mixing the reaction product with water or a mixture of water and one or more solvents.

[0173] In one embodiment, in step f), the reaction product is stirred at a temperature of approximately 25°C to approximately 80°C.

[0174] In a preferred embodiment, in step f), the reaction product is stirred at a temperature of about 40°C to about 60°C.

[0175] In one embodiment, in step f), the reaction product is stirred for at least 15 minutes.

[0176] In a preferred embodiment, in step f), the reaction product is stirred for at least 30 minutes.

[0177] In one embodiment, the solid separation in step g) is carried out by filtration, precipitation, decantation, or solid-liquid centrifugation.

[0178] In a preferred embodiment, the solid separation in step g) is carried out by filtration.

[0179] In one embodiment, the present invention provides chlorantraniliprole having a purity of at least about 97.0%.

[0180] In one embodiment, the present invention provides chlorantraniliprole having a purity of at least about 97.5%.

[0181] In one embodiment, the present invention provides an anthranilamide insecticide having less than 0.5% intermediates of formulas I, II, and III.

[0182] In one embodiment, the present invention provides an anthranilamide insecticide having less than 0.2% of intermediates of formulas I, II, and III.

[0183] In one embodiment, the present invention provides chlorantraniliprole having less than 0.5% intermediates of formulas I, II, and III.

[0184] In one embodiment, the present invention provides chlorantraniliprole having less than 0.2% intermediates of formulas I, II, and III.

[0185] In one embodiment, the present invention provides an anthranilamide insecticide having less than 1.0% of salts of intermediates of formulas I, II, and III.

[0186] In one embodiment, the present invention provides an anthranilamide insecticide having less than 0.5% of salts of intermediates of formulas I, II, and III.

[0187] In one embodiment, the present invention provides chlorantraniliprole having less than 1.0% of salts of intermediates of formulas I, II, and III.

[0188] In one embodiment, the present invention provides chlorantraniliprole having less than 0.5% of salts of intermediates of formulas I, II, and III.

[0189] In these embodiments, the salts of the intermediates of formula I, formula II, or formula III include salts of these intermediates of methanesulfonyl chloride.

[0190] In one embodiment, the present invention provides an anthranilamide insecticide having less than 2.0% inorganic impurities.

[0191] In one embodiment, the present invention provides an anthranilamide insecticide having less than 0.5% inorganic impurities.

[0192] In one embodiment, the present invention provides chlorantraniliprole having less than 2.0% inorganic impurities.

[0193] In one embodiment, the present invention provides chlorantraniliprole having less than 0.5% inorganic impurities.

[0194] The present invention further provides a process for preparing cyantraniliprole free of impurities, the process being: a) A step of reacting the compound of formula VI with methylamine in an organic solvent, b) A process for separating and recovering the solid, c) A step of preparing a slurry of the product from step b) under aqueous conditions, d) A step of stirring the slurry for a predetermined time, e) A process for separating and recovering the solid, f) A process in which steps c), d), and e) are optionally repeated, g) a step of drying to obtain cyantraniliprole that is substantially free of impurities, and

[0195] The present invention further provides a process for preparing cyantraniliprole, the process comprising purifying cyantraniliprole from an aqueous slurry, the aqueous slurry comprising a hydrophilic solvent mixed with the reaction product of a compound of formula VI and methylamine.

[0196] The advantages and other parameters of the present invention are illustrated by the following examples. However, the scope of the present invention is not limited in any way by these examples. Those skilled in the art will understand that the present invention includes the examples described above and can be further modified and altered within the technical scope of the invention. [Examples]

[0197] Example 1: Preparation of compound III Methanesulfonyl chloride (56 g) in acetonitrile (108 g) was added to a mixture of compound I (54 g), compound II (35 g), and pyridine (73 g) in acetonitrile (162 g), and the mixture was stirred at 5-10°C, followed by stirring at 25°C for 3 hours. The mixture was then filtered, washed with acetonitrile, and dried to obtain compound III (75 g, 93% yield).

[0198] Example 2: Preparation of chlorantraniliprole The compound of formula III (75 g) was stirred in ethyl acetate (225 g) in a reactor at 15-20°C while stirring. An aqueous solution of methylamine (43 g) was added to the reaction mixture over 2 hours at 15-25°C and stirred for 3 hours. The product was then cooled to 30°C, filtered, and washed with ethyl acetate to obtain chlorantraniliprole (98 g, purity ~93%).

[0199] Example 3: Purification of chlorantraniliprole 98 g of chlorantraniliprole (prepared in Example 2) and 200 g of water were added to the reactor. The product was stirred at 40°C to 50°C for 1 hour. Next, the product was filtered. Then, the wet product was added to the reactor and 200 g of water was added. Next, the slurry was stirred at 40°C to 50°C for 1 hour. Then, the product was filtered and washed with warm water. The wet product thus obtained was dried at 70°C. 51 g, purity 97.5%.

[0200] Example 4: Preparation of compound III 56 g of methanesulfonyl chloride in 75 g of tetrahydrofuran was added to a mixture of compound I (54 g), compound II (35 g), and pyridine (73 g) in 75 g of tetrahydrofuran, and the mixture was stirred at 5-10°C, followed by stirring at 25°C for 3 hours. The mixture was then filtered, washed with acetonitrile, and dried to obtain compound III (68 g, yield 84.3%).

[0201] Example 5: Preparation of chlorantraniliprole The compound of formula III (68 g) was stirred in ethyl acetate (175 g) in a reactor at 15-20°C while stirring. An aqueous solution of methylamine (41 g) was added to the reaction mixture at 15-25°C for 2 hours and stirred for 3 hours. The product was then cooled to 30°C, 200 g of water was added and held for 1 hour, filtered, and washed with ethyl acetate to obtain chlorantraniliprole (58 g, purity ~93%).

[0202] Example 6: Purification of chlorantraniliprole 58 g of chlorantraniliprole (prepared in Example 5), 200 g of water, and 100 g of ethyl acetate were added to the reactor. The product was stirred at 40°C to 50°C for 1 hour. The product was then filtered and washed with warm water. The resulting wet product was dried at 70°C. 49 g, purity 97.5%.

[0203] Example 7: Analysis results of chlorantraniliprole prepared and purified by the process according to the present invention The analytical results of chlorantraniliprole prepared (Example 2) and purified (Example 3) according to the present invention are shown in the following table (Table 1).

[0204] [Table 1]

[0205] The intermediates include the compound of formula I, the compound of formula II, and the compound of formula III. The salt of the intermediate includes the salt of the compound of formula I with methanesulfonyl chloride. The inorganic component includes chloride. Traces of solvent, base, and other unidentified impurities are also removed by the process of the present invention. From the above experiments, it is demonstrated that the process according to the present invention can yield high-purity chlorantraniliprole and consistent properties.

[0206] Example 8: Preparation of the compound of formula VI Methanesulfonyl chloride (60 g) in acetonitrile (115 g) was added to a mixture of compound I (55 g), compound V (38 g), and pyridine (75 g) in acetonitrile (165 g), and the mixture was stirred at 5-10°C, followed by stirring at 25°C for 4 hours. The mixture was then filtered, washed with acetonitrile, and dried to obtain compound VI (73 g, 92% yield).

[0207] Example 9: Preparation of cyantraniliprole (formula VII) The compound of formula VI (73 g) was stirred in ethyl acetate (220 g) in a reactor at 15-20°C while stirring. An aqueous solution of methylamine (43 g) was added to the reaction mixture at 15-25°C for 2 hours and stirred for 3 hours. The product was then cooled to 30°C, filtered, and washed with ethyl acetate to obtain cyantraniliprole (95 g, purity ~93%).

[0208] Example 10: Purification of cyantraniliprole (formula VII) 95g of cyantraniliprole ( Example 9The prepared product (prepared as described above) and 200 g of water were added to the reactor. The product was stirred at 35°C to 40°C for 1 hour. Next, the product was filtered. Then, the wet product was added to the reactor and 200 g of water was added. The slurry was then stirred at 35°C to 40°C for 1 hour. Next, the product was filtered and washed with warm water. The wet product thus obtained was dried at 70°C (49 g, purity 97.5%).

Claims

1. A process for purifying cyantraniliprole from an aqueous slurry containing cyantraniliprole, The aforementioned process, a) A step of supplying a reaction product mixture containing cyantraniliprole to a reactor, wherein the reaction product mixture is obtained by reacting a compound of the following formula VI with methylamine in an organic solvent selected from the group consisting of acetonitrile and ethyl acetate. b) A step of preparing an aqueous slurry containing cyantraniliprole under aqueous conditions, comprising the step of mixing the reaction product mixture with water or a mixed solvent of water and ethyl acetate in order to solubilize impurities contained in the reaction product mixture to obtain an aqueous slurry, c) A step of stirring the aqueous slurry at a temperature of 35°C to 60°C for 1 hour, d) A step of separating the solid from the aqueous slurry, f) A step of drying the separated solid to obtain purified cyantraniliprole, The purification process for cyantraniliprole, including the process described above. 【Chemistry 1】

2. The process for purifying cyantraniliprole according to Claim 1, wherein steps b), c), and d) are repeated in this order at least once more before step f), except that in the second and subsequent steps b), the solid separated in step d) is used instead of the reaction product mixture.

3. The cyantraniliprole purification process according to Claim 1, wherein the compound of formula VI is obtained by reacting the compound of formula I and the compound of formula V in an organic solvent selected from acetonitrile, tetrahydrofuran, and ethyl acetate. 【Chemistry 2】

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