KR20220157967A - Method for producing intermediates for the production of cyclaniliprole - Google Patents

Abstract

Provided is a method for producing a high-purity intermediate for producing cyclaniliprole. Production of high-yield, high-purity cyclaniliprole by reacting the compound represented by formula (II) or a salt thereof with the compound represented by formula (III) or a salt thereof in the presence of a condensing agent and/or a base. intermediates can be prepared. By using this intermediate, high-purity cyclaniliprole can be manufactured.

Description

Method for producing intermediates for the production of cyclaniliprole

The present invention relates to a method for preparing an intermediate for the production of cyclaniliprole. Further, 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-chloropyridine -2-yl) -1H-pyrazole-5-carboxamide; a compound represented by formula (IV) described later) is described as compound No. 16 in Patent Document 1, and is an active ingredient of commercially available agricultural pesticides. It is a useful compound as As a manufacturing method of cyclaniliprole, Patent Documents 2 to 4 are known, for example. In addition, compounds having a structure similar to cyclaniliprole and methods for producing the compounds 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 International Publication No. 2008/155990 International Publication No. 2003/016283 International Publication No. 2004/011453 International Publication No. 2006/062978 International Publication No. 2008/070158 International Publication No. 2019/207595 Specification of Chinese Patent Application Publication No. 102285964

In the case of industrially producing cyclaniliprole as an agrochemical raw material, it must conform to a predetermined standard. The problem to be solved by the present invention is to produce high-purity cyclaniliprole in high yield and inexpensively. More specifically, the content of the impurity (B) described later in cyclaniliprole as an agrochemical raw material is suppressed, and cyclaniliprole is produced in high yield and high purity.

Patent Literature 1 describes a method usable for producing cyclaniliprole as reaction [A]. However, the inventors of the present invention, when producing cyclaniliprole represented by formula (IV) according to the following reaction scheme according to this reaction [A], the compound represented by formula (B) as an impurity (hereinafter also referred to as impurity (B)) ) is a by-product, and it is very difficult to remove this impurity (B) from the obtained cyclaniliprole, and the method described in Patent Document 1 is used for the production of high-purity cyclaniliprole that meets the standards as an agricultural chemical raw material. Found something unsuitable.

Patent Literature 1 does not describe such a by-product of the impurity (B), and the problem of the generation of the impurity (B) is not recognized in the same document.

The present inventors further studied to solve the above problems and found that the formation of the impurity (B) is caused by the presence of Br on the benzene ring. For this reason, it was considered that the by-production of the impurity (B) could not be sufficiently suppressed by the method described in Patent Literature 1.

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 having no Br on the benzene ring. However, in specific examples corresponding to reaction [N] in Patent Document 2, for example, the yield of Example 17(4) is about 14% and the yield of Example 19(2) is about 37%, which is very low. , In order to use it as an industrial production method for cyclaniliprole, a significant improvement in yield was required. In addition, the problem concerning the generation of the impurity (B) is neither described nor recognized in Patent Literature 2.

The present inventors conducted various investigations 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 cyclanyl was obtained via a raw material having no Br on the benzene ring. It was considered necessary to manufacture a leaf roll. And, even in the case of using a raw material having no Br on the benzene ring, by selecting a specific reaction reagent, a production method capable of producing a production intermediate of cyclaniliprole with a very low content of impurities in high yield Found. And, it was also discovered that high-purity cyclaniliprole suitable for the standard as an agricultural chemical raw material could be produced from the manufacturing intermediate of cyclaniliprole produced in this way.

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

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, simply referred to as compound (III)):

[In formula (III), R is OH or halogen]

is reacted in the presence of a condensing agent and/or a base. Furthermore, the present invention also provides a method for producing cyclaniliprole, wherein the thus-prepared compound (I) is reacted with a brominating agent.

According to the present invention, compound (I) useful for the production of cyclaniliprole can be produced in high yield and high purity. Further, from the compound (I) obtained by the present invention, high-purity cyclaniliprole that satisfies the specifications as an agrochemical raw material can be produced.

[Method for producing compound (I)]

The method for producing compound (I) of the present invention is characterized in that compound (II) and compound (III) are reacted in the presence of a condensing agent and/or a base. Here, when R is OH, compound (II) and compound (III) are preferably reacted in the presence of a condensing agent and a base, and when R is halogen, compound (II) and compound (III) are reacted with a base It is preferable to react in the presence of. This reaction may be performed in the presence of a solvent.

Salts of Compound (I), Compound (II), or Compound (III) include all salts as long as they are agrochemically acceptable, and examples thereof include alkali metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (magnesium salt, calcium salt, etc.) salts, etc.), ammonium salts, alkylammonium salts (dimethylammonium salt, triethylammonium salt, etc.), acid addition salts (hydrochloride, perchlorate, sulfate, nitrate, acetate, methanesulfonate, etc.). As the halogen represented by R, chlorine, bromine, iodine, etc. are mentioned, for example, and chlorine is preferable.

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

Compound (II) and compound (III) in the present invention can be produced by a method known in the art, for example, a method described in Patent Documents 2, 5, 7, etc. or a method similar thereto, or A commercial item can also be used. In the case of using the compound (III) in which R is halogen, the compound (III) in which R is halogen is prepared by mixing the compound (III) in which R is OH with a halogenating agent (chlorination) according to a known method in the art. It can also be obtained by reacting with acid halides, such as thionyl and oxalyl chloride, etc.).

As the condensing agent used in this reaction, sulfonyl chloride (methanesulfonyl chloride, p-toluenesulfonyl chloride, etc.) and acid halides (thionyl chloride, oxalyl chloride, etc.) are preferable. From the viewpoint of the purity of (I), sulfonyl chloride is 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, based on 1 mole of Compound (II). .

Examples of the base used in this reaction include organic bases such as pyridine and picoline (eg, 2-picoline, 3-picoline and 4-picoline), and alkali metal carbonates or alkali metal hydrogencarbonates; Inorganic bases such as carbonates of alkaline earth metals or hydrogen carbonates of alkaline earth metals are preferred, and among these, pyridine, picoline (eg, 2-picoline, 3 -picoline, 4-picoline), alkali metal carbonates or alkali metal hydrogencarbonates are more preferred, and pyridine or picoline (e.g., 2-picoline, 3-picoline, 4-picoline) is More preferred, and among them, 3-picoline is particularly preferred. 1 type may be sufficient as the said base used in this reaction, and 2 or more types may be sufficient as it.

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, based on 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. For example, 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. can Among these, one or two or more selected from the group consisting of ketones, nitriles, ethers, halogenated hydrocarbons, polar solvents, and pyridines are preferred from the viewpoint of the yield and purity of Compound (I) obtained, It is more preferable that it is 1 type(s) or 2 or more types selected from the group which consists of ketones, nitriles, ethers, polar solvents, and pyridines. The amount of 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 30 times (V/W) relative to Compound (II). is 0 to 20 times (V/W), more preferably 1 to 20 times (V/W).

In this reaction, the order of addition of compound (II), compound (III), condensing agent and base, and optionally solvent is not particularly limited, and may be added and mixed in any order. Addition of these components to the reaction system may be performed at one time or dividedly, or may be performed continuously. For example, as the order of addition, all components may be mixed at once, or some components may be added later. As a specific example of such addition, for example, (i) mixing compound (II), a base and a solvent, adding compound (III) and a condensing agent to (ii) mixing compound (II), compound (III), a base and a solvent and adding a condensing agent thereto; and the like.

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 addition, in this specification, "room temperature" means about 0-40 degreeC normally, and more specifically, 10-30 degreeC.

After completion of the present reaction, compound (I) can be isolated by post-treatment, if necessary, by a conventional method such as neutralization, extraction, washing, and drying, for example. Thereafter, if necessary, compound (I) may be purified by conventional methods such as recrystallization and repulping. Alternatively, the compound (I) may be used as it is in the next reaction without isolating or 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 contained as an impurity (hereinafter, simply referred to as impurity (A)):

The content ratio of is usually 1% by weight or less, preferably 0.3% by weight or less, more preferably the amount of the impurity (A), relative to the total amount of the compound represented by the formula (I) or salt thereof and the impurity (A). It contains practically no Here, "substantially not contained" means that an amount of the order of impurities may be mixed, and means that, for example, the content ratio of the impurity (A) is less than 0.1% by weight. By producing cyclaniliprole using this compound (I), it is possible to produce cyclaniliprole of high purity that meets the specifications as an agrochemical raw material.

[Method for producing cyclaniliprole]

Cyclaniliprole can be produced by reacting Compound (I) obtained as described above with a brominating agent. This reaction may be performed in the presence of a base and a solvent.

Bromine, hypobromic acid, etc. are mentioned as a brominating agent used in this method, Among these, bromine is preferable.

The amount of bromination agent used is not particularly limited as long as the reaction proceeds, but is, for example, 0.5 to 5 moles, preferably 1 to 3 moles, more preferably 1 to 2 moles, based on 1 mole of Compound (I). of bromination agents can be used.

As the base that may be used in this reaction, metal hydroxides (sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), metal hydrides (sodium hydride, potassium hydride, etc.), metal alkoxides (sodium methoxide, sodium ethoxide, potassium t -butoxide, etc.) are preferable, among these, metal hydroxides are more preferable, and sodium hydroxide and potassium hydroxide are still more preferable. 1 type may be sufficient as the said base used in this reaction, and 2 or more types may be sufficient as it.

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, more preferably 1.5 to 3.5 moles per mole of Compound (I).

The solvent that may be used in this reaction is not particularly limited as long as it does not adversely affect the reaction, but 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, etc.) , 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 (eg, N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphorictriamide, dimethylacetamide, N-methylpyrrolidone, etc.), or these of mixed solvents. Among these, one or two or more selected from the group consisting of ethers, halogenated hydrocarbons, and esters are preferred, from the viewpoint of the yield and purity of the obtained cyclaniliprole, and one selected from the group consisting of esters. It is more preferable that it is a species or 2 or more types. 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 1 to 30 times (V/W) relative to Compound (I). is 3 to 20 times (V/W).

In this reaction, the order of addition of Compound (I), the bromination agent, if necessary, a base and a solvent is not particularly limited, and the mixture may be mixed in any order. Addition of these components to the reaction system may be performed at one time or dividedly, or may be performed continuously. For example, as the order of addition, (i) compound (I) and a bromination agent, if necessary, a solvent are mixed and a base is added thereto, or (ii) compound (I) and a base, if necessary, a solvent mixing, adding a bromination agent thereto, and the like.

The temperature of this reaction 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 completion of this reaction, if necessary, cyclaniliprole can be isolated by conducting a post-treatment by a conventional method such as neutralization, extraction, washing and drying, for example. In addition, depending on the conditions of the reaction and/or post-treatment, cyclaniliprole may be isolated as a salt or solvate, in which case, by conventional methods such as neutralization and desolvation, the free form of cyclaniliprole. Thereafter, if necessary, cyclaniliprole may be purified by conventional methods such as recrystallization and 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 the cyclaniliprole obtained by this reaction, the compound represented by the following formula (B) or a salt thereof contained as an impurity:

The content ratio of is usually 1% by weight or less, preferably 0.3% by weight or less, with respect to the total amount of cyclaniliprole and the compound represented by the formula (B), more preferably substantially containing the impurity (B). I never do that. Here, "substantially not contained" means that an amount of the order of impurities may be mixed, and means that, for example, the content ratio of the impurity (B) is less than 0.1% by weight.

The various components in the method of the present invention are appropriately selected from among a plurality of examples and conditions described above, for example, not only the examples and conditions of the above-described typical range but also the examples and conditions of the preferred range, and can be combined with each other. can

Examples of preferred embodiments of the present invention are listed below, but the present invention is not limited thereto.

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

As a manufacturing method of

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]

A manufacturing method in which a reaction is made in the presence of a condensing agent and/or a base.

[2] In the case where 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] manufacturing method.

[3] The production method according to [1], wherein when R is halogen, 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 base.

[4] The production method according to [1] or [2], wherein the condensing agent is sulfonyl chloride or an acid halide.

[5] The production method according to [1] or [2], wherein the condensing agent is sulfonyl chloride.

[6] The production method according to [1] or [2], wherein the condensing agent is methanesulfonyl chloride.

[7] The production method according to any one of [1] to [6], wherein the base is one or two or more selected from the group consisting of pyridine, picoline, carbonates of alkali metals, and hydrogen carbonates of alkali metals.

[8] The production method according to any one of [1] to [6], wherein the base is pyridine or picoline.

[9] The production method according to any one of [1] to [6], wherein the base is pyridine or 3-picoline.

[10] The production method according to any one of [1] to [9], wherein the reaction is performed in the presence of a solvent.

[11] The production method according to [10], wherein the solvent is one or two 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 two 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 two or more selected from the group consisting of ketones, nitriles, ethers, polar solvents, and pyridines.

[14] The production method according to [10], wherein the solvent is one or two 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 obtained compound represented by formula (I) or a salt thereof has a purity of 95% by weight or more.

[16] A compound represented by the following formula (A) or a salt thereof contained as an impurity in addition to the compound represented by the obtained formula (I) or a salt thereof:

The production according to any one of [1] to [15], wherein the content ratio of is 1% by weight or less relative to 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. Way.

[17] The preparation according to any one of [1] to [15], which does not substantially contain the compound represented by the formula (A) or a salt thereof as an impurity in addition to the obtained compound of the formula (I) or a salt thereof. Way.

[18] A method for producing cyclaniliprole, wherein the compound represented by formula (I) obtained by the production method according to any one of [1] to [17] or a salt thereof is reacted with a brominating agent.

[19] The production method according to [18], wherein the bromination agent is bromine or hypobromic acid.

[20] The production method according to [18] or [19], wherein the reaction is performed in the presence of a base.

[21] The production method according to [20], wherein the base is one or two or more selected from the group consisting of metal hydroxides, metal hydrides, and metal alkoxides.

[22] The production method according to [20], wherein the base is a metal hydroxide.

[23] The production method according to any one of [18] to [22], wherein the reaction is performed in the presence of a solvent.

[24] The production method according to [23], wherein the solvent is one or two or more selected from the group consisting of ethers, halogenated hydrocarbons, aromatic hydrocarbons, aliphatic hydrocarbons, esters, ketones, nitriles, and amides. .

[25] The production method according to [23], wherein the solvent is one or two or more selected from the group consisting of ethers, halogenated hydrocarbons, and esters.

[26] The production method according to [23], wherein the solvent is one or two or more selected from the group consisting of esters.

[27] The production method according to [23], wherein the solvent is one or two or more selected from the group consisting of methyl acetate, ethyl acetate, propyl acetate, and butyl acetate.

[28] The production method according to [23], wherein the solvent is one or two 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 obtained cyclaniliprole has a purity of 90% by weight or more.

[30] A compound represented by the following formula (B) or a salt thereof contained as an impurity in addition to the obtained cyclaniliprole:

The production method according to any one of [18] to [29], wherein the content ratio of is 1% by weight or less with respect to the total amount of cyclaniliprole and the compound represented by the formula (B).

[31] The production method according to any one of [18] to [28], wherein, in addition to the obtained cyclaniliprole, the compound represented by the formula (B) or a salt thereof is not substantially contained as an impurity.

Example

Examples of the present invention will be described below, but the present invention is not construed as being limited to these.

The structures of compounds (IIIa), (IIIb) and compound (V) used in this Example are shown below.

ㆍCompound (IIIa):

ㆍCompound (IIIb):

ㆍCompound (V)

The HPLC analysis conditions in this Example are as follows.

ㆍDevice used: Shimadzu Corporation Nexera XS series

ㆍColumn: SunShell C18 (2.6㎛, 2.1×100mm) manufactured by Chromatic Technologies Co., Ltd.

ㆍDetection: UV detector (240nm)

ㆍColumn temperature: 40℃

ㆍFlow rate: 0.5mL/min

ㆍMobile phase: Liquid A: 0.1% formic acid aqueous solution and Liquid B: acetonitrile

The gradient conditions are as follows.

Purity (content ratio) is represented by the area % value by high-performance liquid chromatography (HPLC) and/or the weight % value converted from area %.

The area % value is obtained by measuring the reaction product obtained by the synthesis experiment by HPLC.

The weight% value is calculated, for example, by the conversion method described below. A measurement solvent is added to the cyclaniliprol standard to prepare a cyclaniliprol 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 cyclaniliprol standard used in the measurement to calculate the unit area value. In the same way, the unit area values of the compound (I) standard, the impurity (A) standard, or the impurity (B) standard are calculated, respectively. For the reaction product described in the examples, the unit area value is calculated in the same way. The unit area value of the reaction product and the unit area value of the standard product are compared to calculate the ratio, and the weight % value is calculated. In addition, it is also possible to obtain the impurity content by calculating the sensitivity ratio from the unit area value of each standard and converting it from the sensitivity ratio.

[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 ice-cooled, and 0.31 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 88.1 area%. At that time, impurity (A) was not 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 ice-cooled, and 0.31 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 98.6 area%. At that time, impurity (A) was not detected.

[Example 3] Synthesis of Compound (I)

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, 0.5 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 89.7 area%. At that time, impurity (A) was not detected.

[Example 4] Synthesis of Compound (I)

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, 0.5 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 88.9 area%. At that time, impurity (A) was not detected.

[Example 5] Synthesis of Compound (I)

To a mixture of 0.83 g of Compound (II), 0.78 g of 3-picoline, and 10 mL of acetone, 1.04 g of Compound (IIIb) was slowly added dropwise under an ice bath. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 89.4 area%. At that time, impurity (A) was not detected.

[Example 6] Synthesis of compound (I)

To a mixture of 0.83 g of Compound (II), 0.78 g of 3-picoline, and 10 mL of acetonitrile, 1.04 g of Compound (IIIb) was slowly added dropwise under an ice bath. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 91.0 area%. At that time, impurity (A) was not detected.

[Example 7] Synthesis of Compound (I)

To a mixture of 16.9 g of Compound (II), 20 g of Compound (IIIa), 12.3 g of pyridine, and 98 mL of acetone, 8.9 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring at the same temperature overnight, 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 completion of the reaction, 49 g of water was slowly added dropwise thereto, and the mixture was stirred at the same temperature for 45 minutes. The solid obtained by filtering the slurry was washed with acetone water and dried overnight with a warm air dryer to obtain 32.6 g of compound (I) (yield: 92%; purity: 96% by weight, 98.4 area%).

In addition, the conversion method from area % of the said purity to weight % is as follows.

15.41 mg of ciclaniliprol standard was weighed into a 25 mL volumetric flask, dissolved by adding 1 mL of dimethylformamide, 2 mL of water and 20 mL of acetonitrile, and volume-up with acetonitrile to prepare a standard solution. The prepared standard solution was measured three times by HPLC. The average value of the area values obtained by HPLC measurement was calculated. The calculated average value was divided by 15.41, which is the mass value of cyclaniliprol standard, to calculate a unit area value of 66069. Unit area values 72447, 91829, and 81242 of compound (I), impurity (A), and impurity (B) were calculated in the same manner. Next, for the compound (I) obtained by synthesis, a ratio was calculated by comparing the area value obtained by HPLC measurement with the unit area value of the standard product in the same manner, and a weight % value indicating the impurity content was calculated.

[Example 8] Synthesis of Compound (I)

To a mixture of 0.79 g of Compound (II), 1.0 g of Compound (IIIa), 0.39 g of sodium carbonate, and 10 mL of acetone, 0.45 g of methanesulfonyl chloride was slowly added dropwise at room temperature. After stirring at the same temperature for 1 hour, when the reaction was checked by HPLC, compound (I) was produced at 75.5 area%. At that time, impurity (A) was not detected. Subsequently, 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 to find that 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 in accordance with Example 3 and 58 mL of ethyl acetate was ice-cooled, and 5.2 g of bromine was added dropwise slowly. 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 completed, 12.7 g of sodium sulfite aqueous solution was added dropwise under 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 after refluxing for 1 hour, it cooled to room temperature. The slurry was filtered and the solid was dried overnight with a warm air dryer to obtain 12.9 g of cyclaniliprole (yield: 95%). In addition, the impurity (B) was not detected in the obtained cyclaniliprole (purity: 98% by weight, 97.6 area%).

In addition, the conversion method from area % of the said purity to weight % was performed by the same method as the said 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 ice-cooled, and 0.29 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC, and Compound (I) was produced at 97.8 area%. At that time, impurity (A) was not 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 ice-cooled, and 0.26 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature for 1 hour, the reaction was checked by HPLC, and Compound (I) was produced at 96.8 area%. At that time, impurity (A) was not 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 ice-cooled, and 0.26 g of methanesulfonyl chloride was slowly added dropwise while ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature for 66 hours, the reaction was checked by HPLC, and Compound (I) was produced at 93.0 area%. At that time, impurity (A) was not 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 ice-cooled, and 0.26 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature for 2 hours, the reaction was checked by HPLC, and Compound (I) was produced at 97.6 area%. At that time, impurity (A) was not 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 ice-cooled, and 0.26 g of methanesulfonyl chloride was slowly added dropwise thereto under ice-cooling. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature for 2 hours, the reaction was checked by HPLC, and Compound (I) was produced at 92.4 area%. At that time, impurity (A) was not 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, when the reaction was checked by HPLC, cyclaniliprole was produced at 42.9 area%. At that time, the production amount of the impurity (B) 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, when the reaction was checked by HPLC, cyclaniliprole was produced at 79.9 area%. At that time, the production amount of the impurity (B) 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 under an ice bath. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC. As a result, cyclaniliprole was produced at 73.0 area%. At that time, the production amount of the impurity (B) was 4.2 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 under an ice bath. After completion of the dropwise addition, the temperature was raised to room temperature, and after stirring at the same temperature overnight, the reaction was checked by HPLC. As a result, cyclaniliprole was produced at 57.7 area%. At that time, the production amount of the impurity (B) was 6.4 area%.

In Examples 1 to 14, the impurity (A) was not detected. In addition, unlike Comparative Examples 1 to 4, the generation of impurity (B) was not confirmed in the cyclaniliprole of Example 9, obtained from Compound (I) obtained by the method of the present invention, and the standard as an agrochemical raw material It was possible to produce high-purity cyclaniliprole that satisfies the above.

In addition, all the content of the JP Patent application 2020-054157, the claim, and the abstract for which it applied on March 25, 2020 is referred here, and it is used as an indication of the specification of this invention.

Claims (9)

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

As a manufacturing method of,
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]
A production method comprising reacting in the presence of a condensing agent and/or a base. The method according to claim 1, wherein 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. . The production method according to claim 1, wherein when R is halogen, the compound represented by formula (II) or a salt thereof and the compound represented by formula (III) or a salt thereof are reacted in the presence of a base. The production method according to claim 1 or 2, wherein the condensing agent is sulfonyl chloride. The production method according to any one of claims 1 to 4, wherein the base is one or two or more selected from the group consisting of pyridine, picoline, alkali metal carbonate and alkali metal hydrogencarbonate. The method according to any one of claims 1 to 5, wherein the obtained compound represented by formula (I) or a salt thereof has a purity of 95% by weight or more. The compound represented by the following formula (A) or a salt thereof according to any one of claims 1 to 6, which is contained as an impurity in addition to the obtained compound represented by the formula (I) or a salt thereof:

The content ratio of is 1% by weight or less with respect to the total amount of the compound represented by the formula (I) or a salt thereof and the compound represented by the formula (A) or a salt thereof. The compound represented by the formula (A) or a salt thereof according to any one of claims 1 to 6, as an impurity, in addition to the obtained compound represented by the formula (I) or a salt thereof:

A method that does not substantially contain. A method for producing cyclaniliprole, wherein a compound represented by formula (I) or a salt thereof obtained by the production method according to any one of claims 1 to 8 is reacted with a brominating agent.