Preparation process of anthranilamide

Abstract

The present invention provides a process for the preparation and purification of anthranilamide.

Description

[Technical Field]

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

[0002] Effective control of pests, such as arthropods, is essential for the safety of agricultural crops. Arthropods are an important class of pest insects that cause significant damage to crops and homes worldwide each year. Anthranilamides are a new class of compounds with highly potent insecticidal activity. These nitrogen-containing aromatic compounds selectively target ryanodine receptors in insects. Ryanodine receptors form calcium ion channels involved in muscle function.

[0003] Examples of insecticidal anthranilamides are cyantraniliprole, chlorantraniliprole, cyclaniliprole, tetrachlorantraniliprole, and tetraniliprole. Chlorantraniliprole is an extremely potent and selective activator of insect ryanodine receptors and has exceptional activity against a variety of Lepidoptera. Chlorantraniliprole controls a variety of chewing pests (mainly Lepidoptera, but also some Coleoptera, Diptera, and Isoptera) in a wide range of crops, including fruits, vegetables, grapevines, cotton, sugarcane, rice, and grasses.

[0004] US Pat. 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-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid is represented by the compound of formula I, and the intermediate 2-amino-5-chloro-3-methylbenzoic acid is represented by the compound of formula II. 2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one is referred to as the compound of formula III.

[0007] US Pat. No. 7,247,647 discloses the preparation of cyantraniliprole, represented as the compound of formula VII (Scheme II).

[0008] [ka]

[0009] The intermediate 3-bromo-1-(3-chloropyridin-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-chloropyridin-2-yl)-1H-pyrazol-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazin-4-one is referred to as the compound of formula VI.

[0010] The inventors of the present invention have noted that the compound of formula III is not physically stable enough to be adequately purified. Furthermore, it is known that further reaction of the impure compound of formula III with methylamine results in chlorantraniliprole having contradictory physical and chemical properties, which makes the product ineffective for its intended use.

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

[0012] Therefore, there is a need to develop improved methods for preparing and purifying anthranilamides.

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

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

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

[0016] The present invention provides a compound of formula (A): [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) alkyl, and m, n, p, and q can be 0, 1, 2, or 3.

[0017] The present invention relates to a compound of formula A: [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) alkyl, and m, n, p, and q can be 0, 1, 2, or 3; The process involves purifying a compound of formula A from an aqueous slurry containing the compound of formula A.

[0018] The present invention relates to a compound of formula A: [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) alkyl, and m, n, p, and q can be 0, 1, 2, or 3; The process is a) providing a reaction product mixture comprising a compound of formula A to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating the solids; e) optionally repeating steps b), c), and d); and f) drying to obtain the purified compound of formula A.

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

[0020] The present invention provides a process for purifying chlorantraniliprole, the process comprising purifying chlorantraniliprole from an aqueous slurry comprising chlorantraniliprole.

[0021] The present invention provides a process for purifying chlorantraniliprole, the process comprising: a) providing a reaction product mixture comprising chlorantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating the solids; e) optionally repeating steps b), c), and d); f) drying to obtain purified chlorantraniliprole.

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

[0023] The present invention provides a process for preparing impurity-free chlorantraniliprole, the process comprising: a) reacting a compound of formula III with methylamine in an organic solvent; b) separating and recovering the solid; c) preparing a slurry of the product of step b) under aqueous conditions; d) stirring the slurry for a predetermined period of time; e) separating and recovering the solid; f) optionally repeating steps c), d), and e); g) drying to obtain chlorantraniliprole substantially free of impurities.

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

[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, the process comprising: a) preparing a compound of formula III by reacting a compound of formula I with a compound of formula II in an organic solvent; b) optionally purifying the compound of formula III; c) reacting the compound of formula III with methylamine in an organic solvent; d) separating and recovering the solid; e) preparing a slurry of the product of step d) under aqueous conditions; f) stirring the slurry for a predetermined period of time; g) separating and recovering the solid; h) optionally repeating steps e), f), and g); i) drying to obtain impurity-free chlorantraniliprole.

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

[0028] The present invention provides a process for purifying cyantraniliprole, the process comprising: a) providing a reaction product mixture comprising cyantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating the solids; e) optionally repeating steps b), c), and d); f) drying to obtain purified cyantraniliprole.

[0029] The present invention further provides a process for preparing impurity-free cyantraniliprole, the process comprising: a) reacting a compound of formula VI with methylamine in an organic solvent; b) separating and recovering the solid; c) preparing a slurry of the product of step b) under aqueous conditions; d) stirring the slurry for a predetermined period of time; e) separating and recovering the solid; f) optionally repeating steps c), d), and e); g) drying to obtain cyantraniliprole substantially free of impurities.

[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. DETAILED DESCRIPTION OF THE INVENTION

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

[0032] Chlorantraniliprole is an example of an anthranilamide that is difficult to prepare, purify (resulting in different physicochemical properties), and optimize its preparation process. The compound of formula III is not stable enough to undergo an effective purification process, and previous processes that rely on purifying the compound of formula III to obtain pure anthranilamide are known to fail to provide such substantially pure anthranilamide, as made possible by the process of the present invention, resulting in reduced yields. Further reaction with methylamine has been found to produce chlorantraniliprole, which contains various impurities and has heterogeneous physical properties, making it ineffective for its intended use. The present inventors have discovered that purifying anthranilamide from an aqueous slurry is a surprisingly better strategy for preparing substantially pure anthranilamide than starting with the pure compound of formula III.

[0033] The inventors of the present invention have noted that following the process of the present invention, purification of the compound of formula III can be avoided, i.e. purification of the compound of formula III is not necessary, and yet chlorantraniliprole can be obtained that is substantially free of impurities.

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

[0035] [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted or straight or branched chain (C1-C 10 ) alkyl, or straight or branched chain (C1-C 10 ) alkyl, where m, n, p, and q can be 0, 1, 2, or 3.

[0036] In another aspect, the present invention also provides compounds of formula A: [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) alkyl, wherein m, n, p, and q can be 0, 1, 2, or 3; The process involves purifying a 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 comprises a reaction product mixture comprising the compound of Formula A.

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

[0040] In one embodiment, the reaction product mixture is the product of the reaction of a compound of formula III with 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 comprises a slurry comprising a reaction product mixture in water.

[0043] In one embodiment, purifying the compound of formula A from an aqueous slurry containing said compound of formula A comprises stirring the aqueous slurry for a predetermined period of time prior to purifying said compound of formula A.

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

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

[0046] In one embodiment, the compound of formula III is used without isolation or purification from the reaction of a compound of formula I with a compound of formula II, which is carried out in an organic solvent.

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

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

[0049] In one embodiment, purifying the compound of formula A from an aqueous slurry containing the compound of formula A comprises repeatedly (a) stirring the aqueous slurry for a predetermined period of 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, purifying the compound of formula A from an aqueous slurry containing the compound of formula A includes stirring the aqueous slurry for a period of 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 provides compounds of formula A: [ka] wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, hydroxyl, unsubstituted or substituted straight or branched chain (C1-C 10 ) alkyl or cycloalkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) alkyl, and m, n, p, and q can be 0, 1, 2, or 3; The process is a) providing a reaction product mixture comprising a compound of formula A to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating the solids; e) optionally repeating steps b), c), and d); and f) drying to obtain the purified compound of formula A.

[0053] In one embodiment, the compound of formula A is a compound wherein R1, R2, R3, and R4 are independently hydrogen, halogen, cyano, amino, N-thio derivatives, alkyl, halogen, cyano, or amino substituted alkyl, heterocyclic unsubstituted or halogen, cyano, amino, hydroxyl substituted, or straight or branched chain (C1-C 10 ) When the compound can be an alkyl compound, m, n, p, and q can be 0, 1, 2, or 3.

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

[0063] [ka]

[0064] In one embodiment, the term "impurities" 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] Thus, a compound of the invention that is substantially free of impurities is intended to mean the compound referred to as being 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 materials.

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

[0067] In a preferred embodiment, the aqueous conditions of step b) refer to water.

[0068] In one embodiment, the slurry of 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 about 25°C to about 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 solids separation in step d) is carried out by filtration, sedimentation, decantation, or solid-liquid centrifugation.

[0075] In a preferred embodiment, the solids 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 "impurities" 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 intermediates include a compound of formula I, a compound of formula II, and a compound of formula III.

[0085] In another embodiment, the synthetic intermediates include a compound of formula I, a compound of formula V, and a 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 reactions include salts of the compound of Formula I with sulfonic acids and / or chlorides.

[0088] In one embodiment, the organic and / or inorganic products of the side reactions include salts of the compound of Formula I with methanesulfonyl chloride.

[0089] In another embodiment, the organic and / or inorganic products of the side reactions include salts of the compound of Formula II with sulfonic acids and / or chlorides.

[0090] In another embodiment, the organic and / or inorganic products of the side reactions include salts of the compound of formula V with sulfonic acids and / or chlorides.

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

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

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

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

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

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

[0097] In one embodiment, the reaction product mixture is the product of the reaction of a compound of formula III with 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 comprises a slurry comprising a reaction product mixture in water.

[0100] In one embodiment, purifying chlorantraniliprole from an aqueous slurry comprising chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of time prior to purifying the chlorantraniliprole.

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

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

[0103] In one embodiment, the compound of formula III is used without isolation or purification from the reaction of a compound of formula I with a compound of formula II, which is carried out in an organic solvent.

[0104] In one embodiment, purifying chlorantraniliprole from an aqueous slurry comprising chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of time, and then purifying the chlorantraniliprole.

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

[0106] In one embodiment, purifying chlorantraniliprole from an aqueous slurry containing the chlorantraniliprole comprises repeatedly (a) stirring the aqueous slurry for a predetermined period of 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, purifying chlorantraniliprole from an aqueous slurry containing the chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of time, purifying the chlorantraniliprole, separating the chlorantraniliprole from the aqueous slurry, and drying the separated chlorantraniliprole.

[0109] Accordingly, the present invention provides a process for purifying chlorantraniliprole, the process comprising: a) providing a reaction product mixture comprising chlorantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating and recovering the solid; e) optionally repeating steps b), c), and d); f) drying to obtain chlorantraniliprole substantially free of impurities.

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

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

[0112] In a preferred embodiment, the aqueous conditions of step b) refer to water.

[0113] In one embodiment, the slurry of 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 about 25°C to about 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 solids separation in step d) is carried out by filtration, sedimentation, decantation, or solid-liquid centrifugation.

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

[0120] In another embodiment, the present invention provides a process for purifying chlorantraniliprole, the process comprising: a) providing a reaction product mixture comprising chlorantraniliprole to a reactor; b) preparing a slurry of the mixture in water; c) stirring the slurry at 25°C to 60°C for at least 30 minutes; d) filtering; e) optionally repeating steps b), c), and d); f) drying to obtain chlorantraniliprole substantially free of impurities.

[0121] In yet another embodiment, the present invention provides a process for purifying chlorantraniliprole, the process comprising: a) providing a reaction product mixture comprising chlorantraniliprole to a reactor; b) preparing a slurry of the reaction product in water; c) stirring at 25°C to 60°C for at least 30 minutes; d) filtering; e) repeating steps b), c), and d) at least once; f) drying to obtain chlorantraniliprole substantially free of impurities.

[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 impurity-free chlorantraniliprole, the process comprising purifying chlorantraniliprole from an aqueous slurry comprising the reaction product of a compound of formula III and methylamine.

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

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

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

[0127] In one embodiment, the reaction product mixture is the product of the reaction of a compound of formula III with 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 comprises a slurry comprising a reaction product mixture in water.

[0130] In one embodiment, purifying chlorantraniliprole from an aqueous slurry comprising chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of time prior to purifying the chlorantraniliprole.

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

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

[0133] In one embodiment, the compound of formula III is used without isolation or purification from the reaction of a compound of formula I with a compound of formula II, which is carried out in an organic solvent.

[0134] In one embodiment, purifying chlorantraniliprole from an aqueous slurry comprising chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of time, and then purifying the chlorantraniliprole.

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

[0136] In one embodiment, purifying chlorantraniliprole from an aqueous slurry containing the chlorantraniliprole comprises repeatedly (a) stirring the aqueous slurry for a predetermined period of 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, purifying chlorantraniliprole from an aqueous slurry containing the chlorantraniliprole comprises stirring the aqueous slurry for a predetermined period of 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, the process comprising purifying cyantraniliprole from an aqueous slurry of cyantraniliprole.

[0140] The present invention provides a process for purifying cyantraniliprole, the process comprising: a) providing a reaction product mixture comprising cyantraniliprole to a reactor; b) preparing a slurry of the mixture under aqueous conditions; c) stirring the slurry for a predetermined period of time; d) separating the solids; e) optionally repeating steps b), c), and d); f) drying to obtain purified cyantraniliprole.

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

[0142] In one embodiment, the reaction of 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 of step a) is carried out in ethyl acetate.

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

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

[0146] In a preferred embodiment, the aqueous conditions in step c) refer to water.

[0147] In one embodiment, the slurry of 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 about 25°C to about 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 solids separation in step e) is carried out by filtration, sedimentation, decantation, or solid-liquid centrifugation.

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

[0154] The present invention also provides a process for preparing chlorantraniliprole 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.

[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 comprising: a) reacting a compound of formula III with an aqueous solution of methylamine in an organic solvent; b) filtering the reaction product; c) preparing a slurry of the reaction product in water; d) stirring at 25°C to 60°C for at least 30 minutes; e) filtering; f) repeating steps c), d), and e) at least once; g) drying to obtain purified chlorantraniliprole.

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

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

[0159] In one embodiment, the reaction of 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 of step a) is carried out in the presence of a base.

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

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

[0163] In yet another embodiment, purification of the compound of formula III is not required in accordance with the present invention.

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

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

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

[0167] In one embodiment, the reaction of 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 of step c) is carried out in ethyl acetate.

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

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

[0171] In a preferred embodiment, the aqueous conditions of step e) refer 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 about 25°C to about 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 solids separation in step g) is carried out by filtration, sedimentation, decantation, or solid-liquid centrifugation.

[0178] In a preferred embodiment, the solids 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% of intermediates of Formula I, Formula II, and Formula III.

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

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

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

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

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

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

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

[0189] In these embodiments, salts of 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 impurity-free cyantraniliprole, the process comprising: a) reacting a compound of formula VI with methylamine in an organic solvent; b) separating and recovering the solid; c) preparing a slurry of the product of step b) under aqueous conditions; d) stirring the slurry for a predetermined period of time; e) separating and recovering the solid; f) optionally repeating steps c), d), and e); g) drying to obtain cyantraniliprole substantially free of impurities.

[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 by the examples in any way. It will be understood by those skilled in the art that the present invention includes the above-mentioned examples and can be further modified and altered within the technical scope of the present invention. [Example]

[0197] Example 1: Preparation of Compounds of Formula III Methanesulfonyl chloride (56 g) in acetonitrile (108 g) was added to a mixture of the compound of formula I (54 g), the compound of formula II (35 g), and pyridine (73 g) in acetonitrile (162 g) and 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 give the compound of formula 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 stirred reactor at 15-20° C. 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 give chlorantraniliprole (98 g, purity ∼93%).

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

[0200] Example 4: Preparation of Compounds of Formula III Methanesulfonyl chloride (56 g) in tetrahydrofuran (75 g) was added to a mixture of the compound of formula I (54 g), the compound of formula II (35 g), and pyridine (73 g) in tetrahydrofuran (75 g) and 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 give the compound of formula III (68 g, 84.3% yield).

[0201] Example 5: Preparation of chlorantraniliprole The compound of Formula III (68 g) was stirred in ethyl acetate (175 g) in a stirred reactor at 15-20° C. An aqueous solution of methylamine (41 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., 200 grams of water was added, held for 1 hour, filtered, and washed with ethyl acetate to give chlorantraniliprole (58 g, ∼93% purity).

[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 charged into a reactor. The product was stirred at 40-50°C for 1 hour. The product was then filtered and washed with warm water. The wet product thus obtained was dried at 70°C. 49 g, purity 97.5%.

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

[0204] [Table 1]

[0205] The intermediates include compounds of Formula I, II, and III. The intermediate salts include salts of the compound of Formula I with methanesulfonyl chloride. The inorganics include chloride. Traces of solvents, bases, and other unidentified impurities are also removed by the process of the present invention. The above experiments demonstrate that the process of the present invention can be used to produce chlorantraniliprole of high purity and consistent properties.

[0206] Example 8: Preparation of Compound of Formula VI Methanesulfonyl chloride (60 g) in acetonitrile (115 g) was added to a mixture of the compound of formula I (55 g), the compound of formula V (38 g), and pyridine (75 g) in acetonitrile (165 g) and 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 give the compound of formula 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 stirred reactor at 15-20° C. 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 give cyantraniliprole (95 g, purity ∼93%).

[0208] Example 10: Purification of Cyantraniliprole (Formula VII) 95 g of cyantraniliprole (prepared in Example 6) and 200 g of water were charged into a reactor. The product was stirred at 35-40°C for 1 hour. The product was then filtered. The wet product was then charged into a reactor, and 200 g of water was added. The slurry was then stirred at 35-40°C for 1 hour. The product was then filtered and washed with warm water. The wet product thus obtained was dried at 70°C (49 g, purity 97.5%).

Claims

1. 1. A process for purifying chlorantraniliprole, comprising: a) preparing an aqueous slurry of a reaction product mixture containing chlorantraniliprole under aqueous conditions, wherein the reaction product mixture is subjected to a step of treating the reaction product mixture with a compound of formula III: 【Chemical 1】 with methylamine; b) stirring the aqueous slurry at a temperature of 40°C to 50°C for 1 hour; c) separating solids from the aqueous slurry; d) optionally repeating steps a), b), and c); e) drying the solid to obtain purified chlorantraniliprole with a purity of 97% or more from the reaction product mixture; wherein the aqueous slurry comprises the reaction product mixture mixed with water or a mixture of water and ethyl acetate to solubilize impurities.

2. 2. The process for purifying chlorantraniliprole according to claim 1, wherein the compound of formula III is obtained by reacting a compound of formula I with a compound of formula II in an organic solvent selected from acetonitrile, tetrahydrofuran, and ethyl acetate: 【Chemistry 2】

Images