JP7633538B2 - Method for producing intermediate for the production of cyclaniliprole - Google Patents

Description

The present invention relates to a method for producing a production intermediate of cyclaniliprole. Furthermore, the present invention also relates to a method for producing cyclaniliprole using the production intermediate of cyclaniliprole.

Cyclaniliprole (3-bromo-N-[2-bromo-4-chloro-6-[[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide; a compound represented by formula (IV) described below) is described in Patent Document 1 as Compound No. 16, and is a useful compound as an active ingredient in commercially available agricultural insecticides. Methods for producing cyclaniliprole are known, for example, in Patent Documents 2 to 4. Compounds having a structure similar to cyclaniliprole and methods for producing them are also known (for example, Patent Documents 5 to 10).

International Publication No. 2005/077934 International Publication No. 2008/072745 International Publication No. 2008/072743 WO 2008/155990 International Publication No. 2003/016283 International Publication No. 2004/011453 International Publication No. WO 2006/062978 International Publication No. 2008/070158 International Publication No. 2019/207595 Chinese Patent Publication No. 102285964

When cyclaniliprole is industrially produced as an agrochemical active ingredient, it must conform to certain standards. The problem to be solved by the present invention is to produce high-purity cyclaniliprole at high yield and low cost. More specifically, the present invention aims to produce cyclaniliprole at high yield and high purity by suppressing the inclusion of impurity (B) described below in cyclaniliprole as an agrochemical active ingredient.

Patent Document 1 describes a method that can be used to produce cyclaniliprole as reaction [A]. However, the present inventors have found that when cyclaniliprole represented by formula (IV) is produced according to reaction [A] as shown in the following scheme, an impurity compound represented by formula (B) (hereinafter also referred to as impurity (B)) is by-produced, and it is very difficult to remove this impurity (B) from the obtained cyclaniliprole, and therefore the method described in Patent Document 1 is not suitable for producing high-purity cyclaniliprole that meets the standards for an agricultural chemical raw material.

このような不純物（Ｂ）の副生に関する記述は特許文献１には無く、不純物（Ｂ）の生成に関する課題は同文献では認識されていない。

Patent Document 1 does not include any description of the by-production of such impurity (B), and does not recognize the problem of the production of impurity (B).

The inventors further investigated the above problem and found that the generation of the impurity (B) is due to the presence of Br on the benzene ring. Therefore, it was believed that the method described in Patent Document 1 could not sufficiently suppress the by-production of the impurity (B).

On the other hand, Patent Document 2 discloses a method for producing cyclaniliprole via reaction [N] as a method for producing cyclaniliprole using a raw material that does not have Br on the benzene ring. However, in the specific example corresponding to reaction [N] in Patent Document 2, for example, the yield of Example 17 (4) is very low, about 14%, and the yield of Example 19 (2) is very low, about 37%, and a significant improvement in yield was necessary to use the method as an industrial production method for cyclaniliprole. In addition, Patent Document 2 does not mention or recognize the problem of the generation of impurity (B).

The present inventors conducted various studies to solve the above problems, and found that the generation of the impurity (B) is due to the presence of Br on the benzene ring, and considered it necessary to produce cyclaniliprole via a raw material that does not have Br on the benzene ring. They then discovered a production method that can produce a production intermediate of cyclaniliprole with a high yield and a very low impurity content by selecting a specific reaction reagent, even when using a raw material that does not have Br on the benzene ring. They also found that high-purity cyclaniliprole that meets the standards for an agricultural chemical raw material can be produced from the production intermediate of cyclaniliprole produced in this way.

That is, the present invention relates to a compound represented by formula (I) or a salt thereof (hereinafter, also simply referred to as compound (I)):

The present invention relates to a method for producing a compound represented by formula (II) or a salt thereof (hereinafter, also simply referred to as compound (II)):

and a compound represented by formula (III) or a salt thereof (hereinafter also referred to simply as compound (III)):

[In formula (III), R is OH or halogen]
In addition, the present invention also provides a method for producing cyclaniliprole, which comprises reacting compound (I) thus produced with a brominating agent.

According to the present invention, compound (I), which is useful for the production of cyclaniliprole, can be produced in high yield and high purity. Furthermore, from compound (I) obtained by the present invention, it is possible to produce cyclaniliprole of high purity that meets the standards for an agricultural chemical raw material.

[Method for producing compound (I)]
The method for producing compound (I) of the present invention is characterized by reacting compound (II) with compound (III) in the presence of a condensing agent and/or a base. When R is OH, it is preferable to react compound (II) with compound (III) in the presence of a condensing agent and a base, and when R is halogen, it is preferable to react compound (II) with compound (III) in the presence of a base. This reaction may be carried out in the presence of a solvent.

The salts of compound (I), compound (II) or compound (III) include any salts that are agriculturally acceptable, such as alkali metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (magnesium salt, calcium salt, etc.), ammonium salts, alkylammonium salts (dimethylammonium salt, triethylammonium salt, etc.), acid addition salts (hydrochloride, perchlorate, sulfate, nitrate, acetate, methanesulfonate, etc.). Examples of halogens represented by R include chlorine, bromine, iodine, etc., with chlorine being preferred.

The amounts of compound (II) and compound (III) used are not particularly limited as long as the reaction proceeds, but for example, 0.8 to 1.2 moles, preferably 0.9 to 1.1 moles, and more preferably 0.95 to 1.05 moles of compound (III) can be used per mole of compound (II).

Compound (II) and compound (III) in the present invention can be produced by a method known in the art, for example, the method described in Patent Documents 2, 5, 7, etc., or a method similar thereto, or a commercially available product can be used. In addition, when compound (III) in which R is a halogen is used, compound (III) in which R is a halogen can also be obtained by reacting compound (III) in which R is OH with a halogenating agent (such as an acid halide such as thionyl chloride or oxalyl chloride) according to a method known in the art.

As the condensing agent used in this reaction, sulfonyl chlorides (e.g., methanesulfonyl chloride, p-toluenesulfonyl chloride) and acid halides (e.g., thionyl chloride, oxalyl chloride) are preferred, and among these, from the viewpoints of the yield and the purity of the obtained compound (I), sulfonyl chlorides are more preferred, and methanesulfonyl chloride is particularly preferred. The amount of the condensing agent used is not particularly limited as long as the reaction proceeds, but is, for example, 1 to 2 moles, preferably 1 to 1.8 moles, and more preferably 1 to 1.5 moles per mole of compound (II).

The base used in this reaction is preferably an organic base such as pyridine or picoline (e.g., 2-picoline, 3-picoline, 4-picoline), and an inorganic base such as an alkali metal carbonate or alkali metal hydrogencarbonate, an alkaline earth metal carbonate or alkaline earth metal hydrogencarbonate, and among these, from the viewpoint of the yield and the purity of the obtained compound (I), pyridine, picoline (e.g., 2-picoline, 3-picoline, 4-picoline), an alkali metal carbonate or an alkali metal hydrogencarbonate are more preferable, pyridine or picoline (e.g., 2-picoline, 3-picoline, 4-picoline) are further preferable, and among them, 3-picoline is particularly preferable. The above-mentioned base used in this reaction may be one kind or two or more kinds.
The amount of the base used is not particularly limited as long as the reaction proceeds, but is, for example, 0 to 10 moles, preferably 1 to 7 moles, and more preferably 1 to 4 moles, relative to 1 mole of compound (II).

The solvent that may be used in this reaction is not particularly limited as long as it does not adversely affect the reaction, but 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.), or mixed solvents thereof. Among these, from the viewpoint of yield and purity of the obtained compound (I), it is preferable to use one or more types selected from the group consisting of ketones, nitriles, ethers, halogenated hydrocarbons, polar solvents, and pyridines, and more preferably one or more types selected from the group consisting of ketones, nitriles, ethers, polar solvents, and pyridines. The amount of the solvent used is not particularly limited as long as the reaction proceeds, but is, for example, 0 to 50 times (V/W), preferably 0 to 30 times (V/W), more preferably 0 to 20 times (V/W), and even more preferably 1 to 20 times (V/W), relative to compound (II).

In this reaction, the order of addition of compound (II), compound (III), condensing agent, base, and, if necessary, solvent is not particularly limited, and may be added and mixed in any order. These components may be added to the reaction system all 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, (i) mixing compound (II), base, and solvent, and adding compound (III) and condensing agent thereto, and (ii) mixing compound (II), compound (III), base, and solvent, and adding condensing agent thereto.

The temperature of this reaction is usually about 0 to 50°C, preferably about 0 to 30°C. The reaction time is usually about 1 to 24 hours, preferably about 1 to 5 hours. In this specification, "room temperature" usually means about 0 to 40°C, more specifically, 10 to 30°C.

After completion of this reaction, compound (I) can be isolated, if necessary, by carrying out post-treatments using conventional methods such as neutralization, extraction, washing and drying. Compound (I) may then be purified, if necessary, using conventional methods such as recrystallization and repulping. Alternatively, compound (I) can be used in the next reaction as is without isolating it or without purifying the isolated compound (I).

The purity of compound (I) obtained by this reaction is usually 95% by weight or more, preferably 97% by weight or more, and more preferably 98.5% by weight or more. In addition to compound (I) obtained by this reaction, a compound represented by the following formula (A) or a salt thereof (hereinafter simply referred to as impurity (A)) is contained as an impurity.

The content of is usually 1% by weight or less, preferably 0.3% by weight or less, and more preferably substantially free of impurity (A) based on the total amount of the compound represented by formula (I) or its salt and the impurity (A). Here, substantially free of impurity (A) means that it may be mixed in in an amount equivalent to the amount of impurities, for example, the content of impurity (A) is less than 0.1% by weight. By producing cyclaniliprole using such compound (I), it is possible to produce high-purity cyclaniliprole that meets the standards for an agricultural chemical raw material.

[Method of producing cyclaniliprole]
Cyclaniliprole can be produced by reacting the compound (I) obtained as described above with a brominating agent. This reaction may be carried out in the presence of a base and a solvent.
The brominating agent used in this method includes bromine, hypobromous acid, etc., and among these, bromine is preferred.

The amount of brominating agent used is not particularly limited as long as the reaction proceeds, but for example, 0.5 to 5 moles, preferably 1 to 3 moles, and more preferably 1 to 2 moles of brominating agent can be used per mole of compound (I).

The base that may be used in this reaction is preferably a metal hydroxide (sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), a metal hydride (sodium hydride, potassium hydride, etc.), or a metal alkoxide (sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.), and among these, a metal hydroxide is more preferred, and sodium hydroxide and potassium hydroxide are even more preferred. The above-mentioned base used in this reaction may be one type or two or more types.
The amount of the base used is not particularly limited as long as the reaction proceeds, but is, for example, 1 to 10 moles, preferably 1.5 to 5 moles, and more preferably 1.5 to 3.5 moles, relative to 1 mole of compound (I).

Solvents that may be used in this reaction are not particularly limited as long as they do not adversely affect the reaction, and include ethers (diethyl ether, butyl methyl ether, tetrahydrofuran, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, trichloroethane, dichloroethylene, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), aliphatic hydrocarbons (pentane, hexane, heptane, octane, cyclohexane, etc.), esters (methyl acetate, ethyl acetate, propyl acetate (isopropyl acetate, normal propyl acetate, etc.), butyl acetate, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), nitriles (acetonitrile, propionitrile, etc.), amides (for example, N,N-dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide, dimethylacetamide, N-methylpyrrolidone, etc.), or mixed solvents thereof. Among these, from the viewpoint of the yield and the purity of the obtained cyclaniliprole, it is preferable to use one or more types selected from the group consisting of ethers, halogenated hydrocarbons and esters, and it is more preferable to use one or more types selected from the group consisting of esters. The amount of the solvent used is not particularly limited as long as the reaction proceeds, but is, for example, 0 to 50 times (V/W), preferably 1 to 30 times (V/W), more preferably 3 to 20 times (V/W) relative to compound (I).

In this reaction, the order of addition of compound (I) and the brominating agent, and optionally the base and the solvent, is not particularly limited, and they may be mixed in any order. These components may be added to the reaction system all at once or in portions, or may be added continuously. For example, the order of addition may be (i) compound (I) and the brominating agent, and optionally the solvent, and then the base is added thereto, or (ii) compound (I) and the base, and optionally the solvent, and then the brominating agent is added thereto.

The reaction temperature is usually about -20 to 120°C, preferably about 0 to 50°C. The reaction time is usually about 0.5 to 48 hours, preferably about 1 to 24 hours.

After the reaction is completed, cyclaniliprole can be isolated by performing post-treatments, such as neutralization, extraction, washing, and drying, as necessary. Depending on the reaction and/or post-treatment conditions, cyclaniliprole may be isolated as a salt or solvate. In that case, it can be converted to free cyclaniliprole by a conventional method, such as neutralization and desolvation. If necessary, cyclaniliprole can then be purified by a conventional method, such as recrystallization or repulping. The purity of cyclaniliprole obtained by this reaction is usually 90% by weight or more, preferably 95% by weight or more, and more preferably 97% by weight or more. In addition to cyclaniliprole obtained by this reaction, a compound represented by the following formula (B) or a salt thereof is contained as an impurity:

The content of is usually 1% by weight or less, preferably 0.3% by weight or less, based on the total amount of cyclaniliprole and the compound represented by formula (B), and more preferably, substantially does not contain the impurity (B). Here, substantially does not contain means that it may be mixed in in an amount equivalent to the amount of impurities, and for example, means that the content of the impurity (B) is less than 0.1% by weight.

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 described above, and can be combined with each other.

Preferred embodiments of the present invention are listed below, but the present invention is not limited to these.
[1] A compound represented by formula (I) or a salt thereof:

A method for producing
A compound represented by formula (II) or a salt thereof:

and a compound represented by formula (III) or a salt thereof:

[In formula (III), R is OH or halogen]
in the presence of a condensing agent and/or a base.
[2] When R is OH, the compound represented by formula (II) or a salt thereof is reacted with the compound represented by formula (III) or a salt thereof in the presence of a condensing agent and a base, according to [1].
[3] When R is halogen, the compound represented by formula (II) or a salt thereof is reacted with a compound represented by formula (III) or a salt thereof in the presence of a base, according to [1].
[4] The method according to [1] or [2], wherein the condensing agent is a sulfonyl chloride or an acid halide.
[5] The method according to [1] or [2], wherein the condensing agent is a sulfonyl chloride.
[6] The method according to [1] or [2], wherein the condensing agent is methanesulfonyl chloride.
[7] The method according to any one of [1] to [6], wherein the base is one or more selected from the group consisting of pyridine, picoline, an alkali metal carbonate, and an alkali metal hydrogen carbonate.
[8] The method according to any one of [1] to [6], wherein the base is pyridine or picoline.
[9] The method according to any one of [1] to [6], wherein the base is pyridine or 3-picoline.
[10] The method according to any one of [1] to [9], wherein the reaction is carried out in the presence of a solvent.
[11] The method according to [10], wherein the solvent is one or more selected from the group consisting of ketones, nitriles, ethers, halogenated hydrocarbons, polar solvents, pyridines, and aromatic hydrocarbons.
[12] The production method according to [10], wherein the solvent is one or more selected from the group consisting of ketones, nitriles, ethers, halogenated hydrocarbons, polar solvents, and pyridines.
[13] The production method according to [10], wherein the solvent is one or more selected from the group consisting of ketones, nitriles, ethers, polar solvents, and pyridines.
[14] The method according to [10], wherein the solvent is one or more selected from the group consisting of tetrahydrofuran, N-methylpyrrolidone, acetone, acetonitrile, 3-picoline and pyridine.
[15] The method according to any one of [1] to [14], wherein the purity of the obtained compound represented by formula (I) or a salt thereof is 95% by weight or more.
[16] In addition to the compound represented by formula (I) or a salt thereof obtained, a compound represented by the following formula (A) or a salt thereof is contained as an impurity:

The method according to any one of [1] to [15], wherein the content of the compound represented by formula (I) or a salt thereof and the compound represented by formula (A) or a salt thereof is 1% by weight or less based on the total amount of the compound represented by formula (I) or a salt thereof and the compound represented by formula (A) or a salt thereof.
[17] The method according to any one of [1] to [15], wherein the compound represented by formula (A) or a salt thereof is substantially not contained as an impurity other than the compound represented by formula (I) or a salt thereof obtained.

[18] A method for producing cyclaniliprole, comprising reacting the compound represented by formula (I) or a salt thereof obtained by the production method according to any one of [1] to [17] with a brominating agent.
[19] The method according to [18], wherein the brominating agent is bromine or hypobromous acid.
[20] The method according to [18] or [19], wherein the reaction is carried out in the presence of a base.
[21] The method according to [20], wherein the base is one or more selected from the group consisting of metal hydroxides, metal hydrides, and metal alkoxides.
[22] The method according to [20], wherein the base is a metal hydroxide.
[23] The method according to any one of [18] to [22], wherein the reaction is carried out in the presence of a solvent.
[24] The method according to [23], wherein the solvent is one or more selected from the group consisting of ethers, halogenated hydrocarbons, aromatic hydrocarbons, aliphatic hydrocarbons, esters, ketones, nitriles, and amides.
[25] The method according to [23], wherein the solvent is one or more selected from the group consisting of ethers, halogenated hydrocarbons, and esters.
[26] The method according to [23], wherein the solvent is one or more selected from the group consisting of esters.
[27] The method according to [23], wherein the solvent is one or more selected from the group consisting of methyl acetate, ethyl acetate, propyl acetate, and butyl acetate.
[28] The method according to [23], wherein the solvent is one or more selected from the group consisting of methyl acetate, ethyl acetate, isopropyl acetate, and butyl acetate.
[29] The method according to any one of [18] to [28], wherein the purity of the obtained cyclaniliprole is 90% by weight or more.
[30] In addition to the obtained cyclaniliprole, a compound represented by the following formula (B) or a salt thereof is contained as an impurity:

The method according to any one of [18] to [29], wherein the content of is 1% by weight or less based on the total amount of cyclaniliprole and the compound represented by formula (B).
[31] The method according to any one of [18] to [28], wherein the compound represented by formula (B) or a salt thereof is not substantially contained as an impurity other than the obtained cyclaniliprole.

Examples of the present invention will now be described, but the present invention is not to be construed as being limited thereto.
The structures of compounds (IIIa), (IIIb) and compound (V) used in this example are shown below.
・Compound (IIIa):

・Compound (IIIb):

Compound (V)

The HPLC analysis conditions in this example are as follows.
Equipment used: Nexera XS series manufactured by Shimadzu Corporation Column: SunShell C18 (2.6 μm, 2.1 × 100 mm) manufactured by Chromanik Technologies Co., Ltd.
Detection: UV detector (240 nm)
Column temperature: 40°C
・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:

The purity (content ratio) is shown as an area % value determined by high performance liquid chromatography (HPLC) and/or a weight % value converted from the area %.
The area % values are obtained by measuring the reaction products obtained from the synthesis experiments by HPLC.
The weight percent value is calculated, for example, by the conversion method described below. A measurement solvent is added to the cyclaniliprole standard to prepare a cyclaniliprole standard solution, and the standard solution is measured three times by HPLC. The average value of the area values obtained by the HPLC measurement is calculated, and the average value is divided by the weight of the cyclaniliprole standard used in the measurement to calculate the unit area value. The unit area values of the compound (I) standard, the impurity (A) standard, and the impurity (B) standard are calculated in the same manner. The unit area value of the reaction product described in the examples is also calculated in the same manner. The unit area value of the reaction product and the unit area value of the standard are compared, the ratio is calculated, and the weight percent value is calculated. It is also possible to calculate the sensitivity ratio from the unit area value of each of the above-mentioned standards, and convert the sensitivity ratio to obtain the impurity content.

Example 1 Synthesis of Compound (I) A mixture of 0.5 g of compound (II), 0.6 g of compound (IIIa), 0.59 g of 3-picoline, and 10 mL of tetrahydrofuran was cooled on ice, and 0.31 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that compound (I) was produced at 88.1 area %. No impurity (A) was detected.

Example 2 Synthesis of Compound (I) A mixture of 0.5 g of compound (II), 0.6 g of compound (IIIa), 0.59 g of 3-picoline, and 10 mL of N-methylpyrrolidone was cooled on ice, and 0.31 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that compound (I) was produced at 98.6 area %. No impurity (A) was detected.

[Example 3] Synthesis of Compound (I) 0.5 g of methanesulfonyl chloride was slowly added dropwise to a mixture of 0.83 g of compound (II), 1.0 g of compound (IIIa), 0.81 g of 3-picoline, and 10 mL of acetone at room temperature. After stirring overnight at the same temperature, the reaction was checked by HPLC, and it was found that compound (I) was produced at 89.7 area %. No impurity (A) was detected.

[Example 4] Synthesis of compound (I) 0.5 g of methanesulfonyl chloride was slowly added dropwise to a mixture of 0.83 g of compound (II), 1.0 g of compound (IIIa), 0.81 g of 3-picoline, and 10 mL of acetonitrile at room temperature. After stirring overnight at the same temperature, the reaction was checked by HPLC, and compound (I) was produced at 88.9 area %. No impurity (A) was detected.

[Example 5] Synthesis of compound (I) 1.04 g of compound (IIIb) was slowly added dropwise to a mixture of 0.83 g of compound (II), 0.78 g of 3-picoline, and 10 mL of acetone in an ice bath. After the addition was completed, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and compound (I) was produced at 89.4 area %. No impurity (A) was detected.

[Example 6] Synthesis of Compound (I) 1.04 g of Compound (IIIb) was slowly added dropwise to a mixture of 0.83 g of Compound (II), 0.78 g of 3-picoline, and 10 mL of acetonitrile in an ice bath. After the addition was completed, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that Compound (I) was produced in an amount of 91.0 area %. No impurity (A) was detected.

[Example 7] Synthesis of Compound (I) 8.9 g of methanesulfonyl chloride was slowly dropped into a mixture of 16.9 g of compound (II), 20 g of compound (IIIa), 12.3 g of pyridine and 98 mL of acetone at room temperature. After stirring overnight at the same temperature, the reaction was checked by HPLC, and compound (I) was produced at 93.3 area %. At that time, impurity (A) was not detected. After confirming the completion of the reaction, 49 g of water was slowly dropped and stirred at the same temperature for 45 minutes. The slurry was filtered, and the obtained solid was washed with acetone water and dried overnight in a hot air dryer to obtain 32.6 g of compound (I) (yield: 92%; purity: 96 wt%, 98.4 area%).
The above purity is converted from area % to weight % as follows.
15.41 mg of cyclaniliprole standard was weighed into a 25 mL volumetric flask, dissolved in 1 mL of dimethylformamide, 2 mL of water, and 20 mL of acetonitrile, and then diluted with acetonitrile to prepare a standard solution. The prepared standard solution was measured three times by HPLC. The average value of the area obtained by HPLC measurement was calculated. The calculated average value was divided by 15.41, which is the mass value of cyclaniliprole standard, to calculate a unit area value of 66069. In the same manner, the unit area values of compound (I), impurity (A), and impurity (B) were calculated as 72447, 91829, and 81242. Next, the area value obtained by HPLC measurement of compound (I) obtained by synthesis was compared with the unit area value of the standard in the same manner, and the ratio was calculated to calculate the weight percentage of the impurities.

[Example 8] Synthesis of Compound (I) 0.79 g of compound (II), 1.0 g of compound (IIIa), 0.39 g of sodium carbonate, and 10 mL of acetone were slowly dropped with 0.45 g of methanesulfonyl chloride at room temperature. After stirring at the same temperature for 1 hour, the reaction was checked by HPLC, and compound (I) was produced at 75.5 area %. At that time, impurity (A) was not detected. Next, 0.15 g of sodium carbonate and 0.15 g of methanesulfonyl chloride were added to the reaction solution, and the mixture was stirred at room temperature overnight, and compound (I) was produced at 97.2 area %. At that time, impurity (A) was not detected.

[Example 9] Synthesis of cyclaniliprole A mixture of 11.6 g of compound (I) obtained according to Example 3 and 58 mL of ethyl acetate was ice-cooled, and 5.2 g of bromine was slowly added dropwise. Next, 13.8 g of aqueous sodium hydroxide solution was slowly added dropwise, and the mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete, 12.7 g of aqueous sodium sulfite solution was added dropwise in an ice bath, and the mixture was stirred at the same temperature for 1 hour. The slurry was filtered, and the solid was washed with 11.6 g of water. 17.4 mL of methanol was added to the obtained solid, and the mixture was refluxed for 1 hour and then cooled to room temperature. The slurry was filtered, and the solid was dried overnight in a hot air dryer to obtain 12.9 g of cyclaniliprole (yield: 95%). In addition, impurities (B) were not detected in the obtained cyclaniliprole (purity: 98% by weight, 97.6% by area).
The purity was converted from area % to weight % in the same manner as in Example 7.

[Example 10] Synthesis of Compound (I) A mixture of 0.5 g of Compound (II), 0.67 g of Compound (IIIa), 0.59 g of 3-picoline, and 2 mL of 3-picoline as a solvent was cooled on ice, and 0.29 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that Compound (I) was produced at 97.8 area %. At that time, no impurity (A) was detected.

[Example 11] Synthesis of Compound (I) A mixture of 0.5 g of Compound (II), 0.63 g of Compound (IIIa), 0.39 g of 3-picoline, and 5 mL of pyridine as a solvent was cooled on ice, and 0.26 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred at the same temperature for 1 hour. The reaction was checked by HPLC, and it was found that Compound (I) was produced at 96.8 area %. At that time, no impurity (A) was detected.

[Example 12] Synthesis of Compound (I) A mixture of 0.5 g of Compound (II), 0.63 g of Compound (IIIa), 0.39 g of 3-picoline, and 5 mL of acetone was cooled on ice, and 0.26 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred at the same temperature for 66 hours. The reaction was checked by HPLC, and it was found that Compound (I) was produced at 93.0 area %. At that time, no impurity (A) was detected.

[Example 13] Synthesis of Compound (I) A mixture of 0.5 g of Compound (II), 0.63 g of Compound (IIIa), 0.39 g of 3-picoline, and 5 mL of dimethylformamide was cooled on ice, and 0.26 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the addition was completed, the mixture was warmed to room temperature and stirred at the same temperature for 2 hours. The reaction was checked by HPLC, and it was found that Compound (I) was produced at 97.6 area %. At that time, no impurity (A) was detected.

[Example 14] Synthesis of Compound (I) A mixture of 0.5 g of Compound (II), 0.63 g of Compound (IIIa), 0.39 g of 3-picoline, and 5 mL of N-methylpyrrolidone was cooled on ice, and 0.26 g of methanesulfonyl chloride was slowly added dropwise to the mixture while cooling on ice. After the completion of the dropwise addition, the mixture was warmed to room temperature and stirred at the same temperature for 2 hours. The reaction was checked by HPLC, and it was found that Compound (I) was produced at 92.4 area %. At that time, no impurity (A) was detected.

Comparative Example 1 Synthesis of Cyclaniliprole To a mixture of 1.11 g of compound (V), 1.0 g of compound (IIIa), 0.81 g of 3-picoline, and 10 mL of acetone, 0.5 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring overnight at the same temperature, the reaction was checked by HPLC, and 42.9 area % of cyclaniliprole was produced. At that time, the amount of impurity (B) produced was 0.3 area %.

Comparative Example 2: Synthesis of cyclaniliprole To a mixture of 1.11 g of compound (V), 1.0 g of compound (IIIa), 0.81 g of 3-picoline, and 10 mL of acetonitrile, 0.5 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring overnight at the same temperature, the reaction was checked by HPLC, and 79.9 area % of cyclaniliprole was produced. At that time, the amount of impurity (B) produced was 5.3 area %.

Comparative Example 3 Synthesis of Cyclaniliprole To a mixture of 1.11 g of Compound (V), 0.78 g of 3-picoline, and 13 mL of acetone, 1.09 g of Compound (IIIb) was slowly added dropwise in an ice bath. After the addition, the mixture was heated to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that 73.0% by area of Cyclaniliprole was produced. At that time, the amount of impurity (B) produced was 4.2% by area.

Comparative Example 4 Synthesis of Cyclaniliprole To a mixture of 1.11 g of compound (V), 0.78 g of 3-picoline, and 13 mL of acetonitrile, 1.09 g of compound (IIIb) was slowly added dropwise in an ice bath. After the addition, the mixture was warmed to room temperature and stirred overnight at the same temperature. The reaction was checked by HPLC, and it was found that 57.7% by area of cyclaniliprole was produced. At that time, the amount of impurity (B) produced was 6.4% by area.

Impurity (A) was not detected in Examples 1 to 14. Furthermore, unlike Comparative Examples 1 to 4, the cyclaniliprole of Example 9 obtained from compound (I) obtained by the method of the present invention did not show any generation of impurity (B), and it was possible to produce cyclaniliprole of high purity that satisfies the standard as an agricultural chemical raw material.
The entire contents of the specification, claims, and abstract of Japanese Patent Application No. 2020-054157 filed on March 25, 2020 are hereby incorporated by reference as the disclosure of the present specification.

Claims (8)

A compound represented by formula (I) or a salt thereof:

A method for producing
A compound represented by formula (II) or a salt thereof:

and a compound represented by formula (III) or a salt thereof:

[In formula (III), R is OH or halogen]
in the presence of a condensing agent and/or a base , and the purity of the compound represented by formula (I) or a salt thereof obtained is 95% by weight or more, provided that the production method does not include a continuous process . The method according to claim 1, wherein when R is OH, a compound represented by formula (II) or a salt thereof is reacted with a compound represented by formula (III) or a salt thereof in the presence of a condensing agent and a base. The method according to claim 1, wherein when R is a halogen, a compound represented by formula (II) or a salt thereof is reacted with a compound represented by formula (III) or a salt thereof in the presence of a base. The method according to claim 1 or 2, wherein the condensing agent is a sulfonyl chloride. The method according to any one of claims 1 to 4, wherein the base is one or more selected from the group consisting of pyridine, picoline, alkali metal carbonates, and alkali metal hydrogen carbonates. In addition to the compound represented by formula (I) or a salt thereof obtained, a compound represented by the following formula (A) or a salt thereof is contained as an impurity:

The method according to any one of claims 1 to 5 , wherein the content of the compound represented by formula (I) or a salt thereof and the compound represented by formula (A) or a salt thereof is 1% by weight or less based on the total amount of the compound represented by formula (I) or a salt thereof. In addition to the compound represented by formula (I) or a salt thereof obtained, a compound represented by formula (A) or a salt thereof may be present as an impurity.

The method according to any one of claims 1 to 5 , wherein the method is substantially free of A method for producing cyclaniliprole, comprising producing a compound represented by formula (I) or a salt thereof by the production method according to any one of claims 1 to 7 , and reacting the compound represented by formula (I) or a salt thereof produced by the production method with a brominating agent.