Method for producing production intermediate of cyclaniliprole

Abstract

To provide a method for producing a production intermediate of cyclaniliprole having high purity.SOLUTION: A production intermediate of cyclaniliprole can be produced with high purity by reacting a compound represented by formula (II) or a salt thereof with a compound represented by formula (III) or a salt thereof in the presence of a solvent, a specific condensing agent and an optional condensation reaction additive.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a process for producing an intermediate for the production of cyclaniliprole. [Background technology]

[0002] Cyclaniliprole (3-bromo-N-[2-bromo-4-chloro-6-[[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide) is a compound useful as an active ingredient in commercial agricultural insecticides. 2-Amino-5-chloro-N-(1-cyclopropylethyl)benzamide (included in the compound represented by formula (I) below, hereinafter simply referred to as compound (Ia)) is an important intermediate in the production of cyclaniliprole.

[0003] Patent Document 1 describes an efficient and inexpensive method for producing anthranilamide compounds including cyclaniliprole or their salts. It also describes a method for producing compounds (compounds (V-1) and (V-2)) including compound (Ia) as a production intermediate of anthranilamide compounds (reactions [U] and [V]), and in Example 28 (1) and (2), a method for producing compound (Ia) is specifically described as a production method corresponding to reaction [U]. That is, in Example 28(1), a production method is described in which an acid chloride is synthesized from 5-chloro-2-nitrobenzoic acid using thionyl chloride, and then the acid chloride is reacted with 1-cyclopropylethylamine in the presence of triethylamine to synthesize 5-chloro-N-(1-cyclopropylethyl)-2-nitrobenzamide, and in Example 28(2), reduced iron is used to synthesize 2-amino-5-chloro-N-(1-cyclopropylethyl)benzamide from 5-chloro-N-(1-cyclopropylethyl)-2-nitrobenzamide. However, Patent Document 1 does not discuss at all the production intermediates of anthranilamide compounds from the viewpoint of producing high-purity compound (Ia). Patent Document 2 describes an amidation reaction in step e of Reaction Scheme-1. However, there is no description of an example corresponding to step e of Reaction Scheme-1, and there is no description at all regarding a specific method for producing Compound (Ia). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2008 / 072745 [Patent Document 2] International Publication No. 2022 / 058916 Summary of the Invention [Problem to be solved by the invention]

[0005] When cyclaniliprole is industrially produced as an agricultural chemical raw material, it is necessary to produce cyclaniliprole of high purity so as to meet the specified standards. To this end, it is necessary to produce a production intermediate of cyclaniliprole of high purity, and an efficient production method is desired. [Means for solving the problem]

[0006] The present inventors have conducted various investigations to solve the above problems. Specifically, 2-amino-5-chloro-benzoic acid was selected as the starting material, and an acid chloride was synthesized from 2-amino-5-chloro-benzoic acid with reference to the reaction [U] described in Patent Document 1, and then the acid chloride was reacted with 1-cyclopropylethylamine to produce compound (Ia), but the reaction did not proceed sufficiently. Therefore, the research was continued, including the reaction conditions, and it was found that a high-purity compound (I) can be efficiently produced without going through the acid chloride by selecting a specific condensing agent and, if necessary, an additive for the condensation reaction.

[0007] That is, the present invention relates to a compound of formula (I):

[0008] [ka] A method for producing a compound represented by the formula (I) or a salt thereof (hereinafter simply referred to as compound (I)), comprising the steps of: (a) in the presence of a solvent, a carbodiimide-based condensing agent, and an additive for a condensation reaction, Formula (II):

[0009] [ka] or a salt thereof (hereinafter simply referred to as compound (II)). Formula (III):

[0010] [ka] or a salt thereof (hereinafter simply referred to as compound (III)); or (b) reacting compound (II) with compound (III) in the presence of a solvent and a uronium-based condensing agent. Effect of the Invention

[0011] The present invention makes it possible to produce compound (I), which is a useful intermediate for the production of cyclaniliprole, in high purity. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] [Method for producing compound (I)] The method for producing compound (I) of the present invention is characterized by (a) a step of reacting compound (II) with compound (III) in the presence of a solvent, a carbodiimide-based condensing agent, and an additive for a condensation reaction (hereinafter also referred to simply as step (a)), or (b) a step of reacting compound (II) with compound (III) in the presence of a solvent and a uronium-based condensing agent (hereinafter also referred to simply as step (b)).

[0013] The salts of the compounds represented by formula (I), (II) or (III) include any salts that are agriculturally acceptable, such as alkali metal salts (sodium salts, potassium salts, etc.), alkaline earth metal salts (magnesium salts, calcium salts, etc.), ammonium salts, alkylammonium salts (dimethylammonium salts, triethylammonium salts, etc.), acid addition salts (hydrochlorides, hydrobromides, perchlorates, sulfates, nitrates, acetates, methanesulfonates), etc.

[0014] In the present invention, compound (II) and compound (III) can be produced by a method known in the art (for example, compound (III) can be produced by the method described in Patent Document 1, etc.) or a method equivalent thereto, or commercially available products can be used.

[0015] The amounts of compound (II) and compound (III) used in step (a) and step (b) are not particularly limited as long as the reaction proceeds. For example, 0.5 to 20 moles, preferably 1 to 10 moles, more preferably 1 to 5 moles, and particularly preferably 1 to 1.2 moles of compound (III) can be used per mole of compound (II).

[0016] The carbodiimide condensing agent used in step (a) is not particularly limited, and for example, N,N'-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N,N'-diisopropylcarbodiimide can be used. Among these, from the viewpoint of the purity of the compound (I) obtained in step (a), N,N'-dicyclohexylcarbodiimide or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is preferred, and N,N'-dicyclohexylcarbodiimide is more preferred. The carbodiimide condensing agent used in step (a) may be one type or two or more types. The amount of the carbodiimide condensing agent used in step (a) is not particularly limited, but for example, 0.5 to 20 mol, preferably 1 to 10 mol, more preferably 1 to 5 mol, and particularly preferably 1 to 1.2 mol of the carbodiimide condensing agent can be used relative to 1 mol of compound (II).

[0017] The condensation reaction additive used in step (a) is not particularly limited, but may be a hydroxytriazole-based additive (e.g., 1-hydroxybenzotriazole monohydrate, 1-hydroxy-7-azabenzotriazole, etc.), ethyl cyano(hydroxyimino)acetate, and ethyl cyanoglyoxylate oxime. Among these, from the viewpoint of the purity of compound (I) obtained in step (a), a hydroxytriazole-based additive is preferred, 1-hydroxybenzotriazole monohydrate or 1-hydroxy-7-azabenzotriazole is more preferred, and 1-hydroxybenzotriazole monohydrate is particularly preferred. The condensation reaction additive used in step (a) may be one type or two or more types. The amount of the condensation reaction additive used in step (a) is not particularly limited, but for example, 0.01 to 5 mol, preferably 0.05 to 2 mol, and more preferably 0.1 to 1 mol of the condensation reaction additive can be used per mol of compound (II).

[0018] The uronium-based condensing agent used in step (b) is not particularly limited, and examples thereof include 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate, and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate. Among these, from the viewpoint of the purity of the compound (I) obtained in step (b), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate or 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate is preferred, and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate is more preferred. The uronium-based condensing agent used in step (b) may be one type or two or more types. The amount of the uronium-based condensing agent used in step (b) is not particularly limited, but for example, 0.5 to 20 moles, preferably 1 to 10 moles, and more preferably 1.2 to 5 moles of the uronium-based condensing agent can be used per mole of compound (II).

[0019] The solvent used in step (a) and step (b) is not particularly limited, and examples thereof include ketones (acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), nitriles (acetonitrile, propionitrile, etc.), ethers (tetrahydrofuran, diethyl ether, etc.), halogenated hydrocarbons (dichloromethane, dichloroethane, chloroform, chlorobenzene, etc.), esters (ethyl acetate, isopropyl acetate, etc.), polar solvents (dimethylformamide, dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, etc.), aromatic hydrocarbons (toluene, xylene, etc.), pyridines (pyridine, picoline, etc.), and mixed solvents thereof. Among these, from the viewpoint of the purity of each of the compounds (I) obtained in each step, ketones or esters are preferred, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, ethyl acetate or isopropyl acetate are more preferred, and acetone or ethyl acetate is particularly preferred. The amount of the solvent used is not particularly limited as long as the reaction in each step proceeds, but is, for example, 1.0 to 30 times (V / W), preferably 5.3 to 20 times (V / W), more preferably 5.3 to 10 times (V / W) relative to the amount of the compound (II).

[0020] In the step (a) and the step (b), when a salt of a compound represented by formula (II) and / or a salt of a compound represented by formula (III) is used, a base may be used in some cases. The base used in the step (a) and the step (b) is not particularly limited, but for example, triethylamine, N-methylmorpholine, diazabicycloundenes, etc. can be used. When a base is used in the step (a) and the step (b), the base may be one type or two or more types. The amount of the base used in the step (a) and the step (b) is not particularly limited, but for example, 0.5 to 20 moles, preferably 1 to 10 moles, more preferably 1 to 5 moles of the base can be used relative to 1 mole of the salt of the compound (II).

[0021] Regarding the reaction form of step (a), the order of addition of compound (II), compound (III), carbodiimide-based condensing agent, condensation reaction additive and solvent is not particularly limited, and may be added and mixed in any order. Compound (II), compound (III), carbodiimide-based condensing agent, condensation reaction additive and solvent may be added to the reaction system at once or in portions, or may be added continuously. For example, the order of addition may be such that all components are mixed at once, or some components may be added later. Specific examples of such addition include, for example, mixing compound (II) and a solvent, and then sequentially adding compound (III), a carbodiimide-based condensing agent and a condensation reaction additive thereto.

[0022] Regarding the reaction form of step (b), the order of addition of compound (II), compound (III), uronium-based condensing agent and solvent is not particularly limited, and they may be added and mixed in any order. Compound (II), compound (III), uronium-based condensing agent and solvent may be added to the reaction system at once or in portions, or may be added continuously. For example, the order of addition may be such that all components are mixed at once, or some components may be added later. Specific examples of such addition include, for example, mixing compound (II) and a solvent, and then adding compound (III) and a uronium-based condensing agent thereto in sequence.

[0023] In the case where a base is used in step (a) and step (b), the order of addition of the base is not particularly limited, and the base may be added and mixed in any order. The base may be added to the reaction system in one portion, in portions, or continuously.

[0024] The reaction temperature in step (a) and step (b) is usually about 0 to 50° C., and preferably about 20 to 40° C. The reaction time in step (a) and step (b) is usually about 10 minutes to 24 hours, preferably about 1 to 16 hours, more preferably about 1 to 5 hours, and particularly preferably about 1 to 3 hours.

[0025] In step (a) and step (b), after the reaction of each step is completed, compound (I) is obtained by carrying out post-treatment by a conventional method such as neutralization, extraction, washing, and drying. Compound (I) can be isolated by appropriately selecting one or more of these conventional post-treatments. In addition, compound (I) may be purified by a conventional method such as recrystallization and repulping, if necessary. The obtained compound (I) can be used as it is in the next reaction without isolating compound (I) or purifying the isolated compound (I).

[0026] The purity of compound (I) obtained by the production method of the present invention can be determined by analyzing the reaction solution of step (a) or step (b) and / or compound (I) obtained after purification using HPLC, and the purity of compound (I) obtained by the production method of the present invention is usually 80 area % or more, preferably 90 area % or more, more preferably 95 area % or more, as a result of HPLC analysis. By producing cyclaniliprole using such compound (I), it is possible to produce cyclaniliprole of high purity that meets the standards for agricultural chemicals.

[0027] The various components in the method of the present invention can be appropriately selected from the multiple examples and conditions described above, for example, from the examples and conditions in the normal range as well as the examples and conditions in the preferred range, and can be combined with each other.

[0028] Preferred embodiments of the present invention are listed below, but the present invention is not limited to these. [1] Formula (I):

[0029] [ka] A method for producing a compound represented by the formula: (a) in the presence of a solvent, a carbodiimide-based condensing agent, and an additive for a condensation reaction, Formula (II):

[0030] [ka] or a salt thereof Formula (III):

[0031] [ka] or a salt thereof; or (b) A production method comprising the step of reacting a compound represented by formula (II) or a salt thereof with a compound represented by formula (III) or a salt thereof in the presence of a solvent and a uronium-based condensing agent. [2] The method according to [1], wherein the carbodiimide-based condensing agent is at least one selected from the group consisting of N,N'-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N,N'-diisopropylcarbodiimide. [3] The method according to [1] or [2], wherein the condensation reaction additive is at least one selected from the group consisting of hydroxytriazole (e.g., 1-hydroxybenzotriazole monohydrate, 1-hydroxy-7-azabenzotriazole), ethyl cyano(hydroxyimino)acetate, and ethyl cyanoglyoxylate oxime. [4] The method according to [1], wherein the uronium-based condensing agent is at least one selected from the group consisting of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate, and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate. EXAMPLES

[0032] Examples of the present invention will now be described, but the present invention is not to be construed as being limited thereto. In the specification, room temperature means 15 to 30°C.

[0033] ·Compound (Ia):

[0034] [ka]

[0035] ·Compound (IIa):

[0036] [ka]

[0037] ·Compound (IIIa)

[0038] [ka] ·Compound (IIIb)

[0039] [ka]

[0040] The HPLC analysis conditions in this example are as follows. Equipment used: Shimadzu Corporation Nexera XS series Column: SunShell C18 (2.6 μm, 2.1 × 100 mm) manufactured by Chromanik Technologies Co., Ltd. Detection: UV detector (240 nm) Column temperature: 40℃ ·Flow rate: 0.5mL / min Mobile phase: Solution A: 0.1% formic acid aqueous solution, and Solution B: acetonitrile The gradient conditions are as follows:

[0041] [Table 1]

[0042] (1) Synthesis of Compound (I) [Experimental Example 1] To a mixture of 20 g of compound (IIa), 9.9 g of compound (IIIa), 1.8 g of 1-hydroxybenzotriazole monohydrate, and 100 mL of acetone, 20 mL of an acetone solution in which 24.1 g of N,N'-dicyclohexylcarbodiimide was dissolved was added. After the addition was completed, the mixture was stirred at room temperature for 2 hours to obtain a reaction solution. The reaction solution obtained was checked by HPLC, and it was found that compound (Ia) was produced at 98.3 area %. Thereafter, the temperature of the reaction solution was adjusted to 40 to 45 ° C. in a water bath, and the mixture was stirred at the same temperature for 1 hour. After filtration under reduced pressure, the mixture was washed with acetone to obtain a filtrate. The filtrate obtained was concentrated under reduced pressure to precipitate crystals. The obtained crystals were washed with a mixed solvent of acetone and water, and dried with hot air, and it was confirmed that 28.1 g of compound (Ia) was quantitatively obtained as crystals. The HPLC analysis of the reaction solution showed that a high-purity compound (Ia) was obtained in high yield.

[0043] [Experimental Example 2] 13.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added to a mixture of 10 g of compound (IIa), 6.0 g of compound (IIIa), 0.89 g of 1-hydroxybenzotriazole monohydrate, and 60 mL of acetone. After the addition, the mixture was stirred at room temperature for 3 hours to obtain a reaction solution. The reaction solution was checked by HPLC, and compound (Ia) was produced at 95.7 area %. The reaction solution was then concentrated under reduced pressure, and a mixed solvent of acetone and water was added to precipitate crystals. The obtained crystals were washed with a mixed solvent of acetone and water and dried with hot air. The dried crystals were washed with acetone and dried with hot air, and 10.5 g of compound (Ia) was obtained as crystals (yield 75.5%).

[0044] [Experimental Example 3] Compound (IIa) 15g, dimethylformamide 80mL, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate 39.9g, and N-methylmorpholine 26.5g were mixed to add compound (IIIb) 12.8g. After the addition, the mixture was stirred at room temperature for 1 hour to obtain a reaction solution. The reaction solution was checked by HPLC, and it was confirmed that compound (Ia) was produced.

[0045] [Experimental Example 4] To a mixture of 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of acetonitrile, 0.72 g of N,N'-dicyclohexylcarbodiimide was added. After the addition was completed, the mixture was stirred at room temperature for 1 hour, and then the reaction was checked by HPLC, whereupon compound (Ia) was produced at 87.8 area %.

[0046] [Experimental Example 5] To a mixture of 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of dichloromethane, 0.72 g of N,N'-dicyclohexylcarbodiimide was added. After the addition was completed, the mixture was stirred at room temperature for 16 hours, and then the reaction was checked by HPLC, whereupon compound (Ia) was produced at 97.8 area %.

[0047] [Experimental Example 6] 0.72 g of N,N'-dicyclohexylcarbodiimide was added to 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of ethyl acetate. After the addition was completed, the mixture was stirred at room temperature for 16 hours, and then the reaction was checked by HPLC, confirming that compound (Ia) was produced.

[0048] [Experimental Example 7] To a mixture of 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of tetrahydrofuran, 0.72 g of N,N'-dicyclohexylcarbodiimide was added. After the addition was completed, the mixture was stirred at room temperature for 16 hours, and then the reaction was checked by HPLC, and compound (Ia) was produced at 94.9 area %.

[0049] [Experimental Example 8] To a mixture of 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of chlorobenzene, 0.72 g of N,N'-dicyclohexylcarbodiimide was added. After the addition was completed, the mixture was stirred at room temperature for 10 minutes, and then the reaction was checked by HPLC, whereupon compound (Ia) was produced at 96.2 area %.

[0050] [Experimental Example 9] To a mixture of 0.5 g of compound (IIa), 0.3 g of compound (IIIa), 0.04 g of 1-hydroxybenzotriazole monohydrate, and 5 mL of dimethylformamide, 0.72 g of N,N'-dicyclohexylcarbodiimide was added. After the addition was completed, the mixture was stirred at room temperature for 16 hours, and then the reaction was checked by HPLC, whereupon compound (Ia) was produced at 83.9 area %.

[0051] [Experimental Example 10] To a mixture of 1 g of compound (IIa), 0.08 g of 1-hydroxybenzotriazole, 5 mL of acetone, and 0.5 g of compound (IIIa), 5 mL of an acetone solution in which 1.2 g of N,N'-dicyclohexylcarbodiimide was dissolved was added. After the addition was completed, the mixture was stirred at room temperature for 16 hours to obtain a reaction solution. The reaction solution obtained was checked by HPLC, and compound (Ia) was produced at 96.0 area %.

[0052] [Experimental Example 11] To a mixture of 1 g of compound (IIa), 0.08 g of ethyl cyano(hydroxyimino)acetate, 5 mL of acetone, and 0.5 g of compound (IIIa), 5 mL of an acetone solution in which 1.2 g of N,N'-dicyclohexylcarbodiimide was dissolved was added. After the addition was completed, the mixture was stirred at room temperature for 15 hours to obtain a reaction solution. The reaction solution obtained was checked by HPLC, and compound (Ia) was produced at 90.6 area %.

[0053] (2) Comparative Example 1.2 g of N,N'-dicyclohexylcarbodiimide was added to a mixture of 1 g of compound (IIa), 0.5 g of compound (IIIa) and 5 mL of acetone. After the addition was completed, the mixture was stirred at room temperature for 10 minutes and then the reaction was checked by HPLC. On the HPLC chart, the peak of the raw material compound (IIa) disappeared, but the peak of the target compound (Ia) was not confirmed, and the peak of the by-product was confirmed. This suggests that compound (Ia) cannot be synthesized under reaction conditions using a carbodiimide-based condensing agent in the absence of a condensation reaction additive.

Claims

1. Formula (I): 【Chemistry 1】 A method for producing a compound represented by the formula: (a) in the presence of a solvent, a carbodiimide-based condensing agent, and an additive for a condensation reaction, Formula (II): 【Chemistry 2】 or a salt thereof Formula (III): 【Chemistry 3】 or a salt thereof; or (b) reacting a compound represented by formula (II) or a salt thereof with a compound represented by formula (III) or a salt thereof in the presence of a solvent and a uronium-based condensing agent.

2. 2. The method according to claim 1, wherein the carbodiimide-based condensing agent is at least one selected from the group consisting of N,N'-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N,N'-diisopropylcarbodiimide.

3. The method according to claim 1 or 2, characterized in that the condensation reaction additive is at least one selected from the group consisting of 1-hydroxybenzotriazole monohydrate, 1-hydroxy-7-azabenzotriazole, ethyl cyano(hydroxyimino)acetate, and ethyl cyanoglyoxylate oxime.

4. The method according to claim 1, wherein the uronium-based condensing agent is at least one selected from the group consisting of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate, and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate.

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