JPH10265432A - Production of 2benzoylcyclic 1,3diketone derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make the direct benzoylation in carbon at the 2popsition of a cyclic 1,3diketone proceed and produce the subject highpurity compound in high yield without producing a byproduce by using a specific equiv. amount of anhydrous aluminum chloride in a suitable solvent. SOLUTION: A cyclic 1,3-diketone represented by formula I (R<1> to R<6> each H or a 1-4C lower alkyl) is reacted with a benzoyl halide represented by formula II (X is a halogen; R<7> is H, etc.; R<8> is H, etc., R<9> is H, etc.) in the presence of anhydrous aluminum chloride and the resultant curde product is crystallized from a mixture solution of a water-soluble organic solvent and an aqueous acidic solution of a mineral acid, isolated and purified to afford the objective compound represented by formula III. The anhydrous aluminum chloride is used in an amount of 2-4 mol eqiuiv. based on the compound represented by formula II. The compound represented by formula I is preferably the one in which R<1> and R<5> together denote ethylene group and R<2> , R<3> , R<4> and R<6> denote each H. The compound represented by formula II is preferably the one in which X and R<7> denote each Cl; R<8> denotes H and R<9> denotes methylsulfonyl group.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a 2-benzoyl-cyclic 1,3-diketone derivative useful as an agricultural chemical or an agricultural chemical intermediate.

[0002]

2. Description of the Related Art It has already been known that 2-benzoyl-cyclic 1,3-diketone compounds are useful as herbicides or herbicide intermediates, and compounds having various structures have been proposed (for example, Japanese Patent Application Laid-Open (kokai) No. 2002-157572). No.58-180451, JP-A-62-29
No. 2755, JP-A-2-222, JP-A-2-6425, JP-A-3-540
No. 8, JP-A-3-63248, JP-A-3-255047, JP-A-6-25
144, JP-A-7-500818, etc.).

[0003] Such 2-benzoyl-cyclic 1,3-
Known methods for producing a diketone compound include (a) a production method by rearrangement of an enol ester, (b) a production method via benzoyl cyanide, and (c) a production method by a dehydration condensation reaction using a condensing agent (such as DCC). Have been.

(A) In the production method by rearrangement of an enol ester, a cyclic 1,3-diketone is reacted with a benzoyl chloride compound to obtain an enol ester, which is then subjected to a rearrangement reaction by various reaction reagents and catalysts. To obtain a 2-benzoyl-cyclic 1,3-diketone compound. (In the formula, R represents a substituent.)

[0005] The rearrangement reaction is carried out using a cyano source as a catalyst in the presence of a base such as triethylamine in the enol ester (Japanese Patent Publication No. 7-10787). This method is the most common method for producing a 2-benzoyl-cyclic 1,3-diketone compound. However, when a nitro group or a halogen atom is present at the ortho position of the benzoyl group, the reaction conditions A tricyclic by-product having a chromone-like ring-closure / ether structure by an elimination / condensation reaction due to a base present below, by a substituent at the ortho position of the benzoyl group and an enol proton of one ketone on the diketone. Easily occur, the yield and purity may be reduced,
There is a problem that the applicable temperature range is narrow. Further, in this method, in the synthesis and rearrangement of the enol ester, it is necessary to use a somewhat expensive triethylamine in an amount of 2 to 3 molar equivalents or more, and furthermore, since the target product is an acidic compound, It has the disadvantage of requiring a large amount of acid, which is more than the used base equivalent.

As a rearrangement reaction, a method using 2 molar equivalents of aluminum chloride as an enol ester has been disclosed (SYNTHESIS, p. 925-927 (1978)). Since pyridine is used as the base and aluminum chloride as the Lewis acid is used for the rearrangement, continuous synthesis cannot be performed in one pot. Not only must the enol ester be isolated, but the rearrangement can be carried out with a catalytic amount of a reagent. There is a problem that it cannot be realized. With respect to the mode of substitution of the benzoyl moiety, only unsubstituted and examples having a methoxy group at the meta position are disclosed, and the reaction temperature is limited to -10 to 0 ° C, which is extremely versatile. Low response.

As the rearrangement reaction, there is disclosed a method using an acidic catalyst or a basic catalyst in the presence of a base in an enol ester (Japanese Patent Application Laid-Open No. 63-154639,
JP-A-63-203644). Aluminum chloride and iron chloride are reported as acidic catalysts, and imidazole and 4-N, N-dimethylaminopyridine are reported as basic catalysts. However, its application range is extremely limited, and the rearrangement reaction often does not proceed depending on the type of cyclohexanedione derivative and the type and mode of the substituent of the benzoyl moiety, and thus lacks generality.

(B) In the production method via benzoyl cyanide, a substituted benzoyl cyanide is synthesized and then reacted with a cyclic 1,3-diketone in the presence of zinc chloride and triethylamine to give 2-benzoyl-cyclic 1,5- It is intended to obtain a 3-diketone compound (JP-A-58-180451, JP-A-6-180451).
-211780 gazette). However, the synthesis yield of substituted benzoyl cyanide is not satisfactory, and it is necessary to use a large amount of cyanide, which is problematic in terms of safety.

(C) In the production method by a dehydration condensation reaction using a condensing agent, a benzoic acid having a substituent and a cyclic 1,3-diketone are subjected to a dehydration condensation reaction in the presence of DCC (N, N-dicyclohexylcarbodiimide) and a base. , 2-
A benzoyl-cyclic 1,3-diketone compound is obtained (JP-A-1-43851). However, DCC
Is an expensive reagent, and requires a complicated process in post-treatment, so that it cannot be said to be an industrially advantageous method.

[0010]

Accordingly, it is an object of the present invention to provide a 2-benzoyl-cyclic 1,3
-To provide a simple method for producing a diketone derivative in high yield and high purity.

[0011]

SUMMARY OF THE INVENTION Benzoyl halide is a powerful acylating reagent, but when reacted with cyclic 1,3-diketones, it does not react with the carbon at position 2 sandwiched by the carbonyl groups, but rather on the other hand. Reacts with the oxygen of the carbonyl group to form an enol ester. However, the present inventors have found that by using 2-4 molar equivalents of aluminum chloride in a suitable solvent, the benzoylation proceeds directly to the 2-position carbon of the cyclic 1,3-diketone, and that the chromone-like trichloride is used. The present inventors have found that a cyclic by-product is not generated, and a 2-benzoyl-cyclic 1,3-diketone derivative having a higher purity and a higher purity can be obtained in a higher yield than the conventional production method, and the present invention has been completed.

That is, the present invention provides: 1) a general formula (1) (Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represent a hydrogen atom or a C 1-4 lower alkyl group, or R ¹ and R ³ or R ¹ R ⁵ together C
Represents 1 to 3 alkylene groups. )
3-diketone and general formula (2) (Wherein, X represents a halogen atom, R ⁷ is a hydrogen atom,
A halogen atom, a nitro group, a C1-2 lower alkyl group which may be substituted by 1 to 3 fluorine atoms, C
R ⁸ represents a hydrogen atom, a halogen atom, a C 1-2 lower alkyl group,
Represents a lower alkoxy group of 1-4, a lower alkoxymethyl group of C2-4, or a lower alkoxycarbonyl group of C2-5, and R ⁹ may be substituted by a hydrogen atom, a halogen atom, or 1-3 fluorine atoms. It represents a preferable C1-3 lower alkoxy group, a C1-3 lower alkylthio group, a C1-3 lower alkylsulfonyl group or a lower alkylsulfonyloxy group which may be substituted by 1-6 fluorine atoms. Wherein the benzoyl halide compound of the formula (1) is reacted in the presence of anhydrous aluminum chloride. (The symbols in the formula have the same meanings as described above.) 2) A method for producing a 2-benzoyl-cyclic 1,3-diketone derivative represented by the following formula: 2) Anhydrous aluminum chloride is used in an amount of 2 to 4 molar equivalents relative to the benzoyl halide compound. 3. The production method according to the above 1, wherein 3) the cyclic 1,3-diketone is such that R ¹ and R ⁵ together represent an ethylene group, and R ² , R ³ , R ⁴ and R ⁶ represent a hydrogen atom A benzoyl halide compound,
X and R ⁷ are chlorine atoms, R ⁸ is a hydrogen atom, R ⁹ is a compound representing a methylsulfonyl group, the production method according to the above 1-2, and 4) After the reaction, the obtained crude product is Crystallizing from a mixture of a neutral organic solvent and a mineral acid aqueous acid solution and isolating and purifying the above 1
3. The method according to any one of claims 1 to 3, wherein

In the production method of the present invention, the reaction is allowed to proceed by using at least 2 molar equivalents of anhydrous aluminum chloride with respect to the benzoyl halide compound. The preferred amount of anhydrous aluminum chloride is 2 to 4 molar equivalents. Preferably it is 2.5 to 3.5 molar equivalents. If the amount of anhydrous aluminum chloride used is less than 2 molar equivalents, the reaction does not proceed. The use of zinc chloride, iron (III) chloride, tin chloride, etc. instead of anhydrous aluminum chloride only produces the enol ester and does not yield the desired compound. Does not happen.

The order of mixing the anhydrous aluminum chloride, the benzoyl halide compound and the cyclic 1,3-diketone may be determined in consideration of the operability at the time of production, but from a practical viewpoint, from the practical viewpoint, the anhydrous aluminum chloride and the benzoyl halide compound After mixing, the cyclic 1,3-diketone is preferably charged and reacted.

[0015] Solvents that can be used in the present method include:
Examples include inert solvents such as halogenated hydrocarbons,
Preferred are dichloromethane and 1,2-dichloroethane (EDC). The amount of the solvent used is 10 parts by weight to 100 parts by weight based on 1 part by weight of the cyclic 1,3-diketone.

In the production method of the present invention, the applied reaction temperature is wide, and the reaction can be carried out at an ice temperature to a solvent reflux temperature. For example, when 1,2-dichloroethane, which is a preferable solvent in this reaction, is used, the reaction can be carried out in a temperature range from ice temperature to around 83 ° C., which is the reflux temperature of the solvent. Originally, a 2-benzoyl-cyclic 1,3-diketone compound having a strongly removable substituent such as a nitro group or a halogen atom at the ortho position on a substituted benzene ring was heated or particularly heated in the presence of a base. , A substituent at the ortho position on the benzoyl group is eliminated, and a ring-closing reaction occurs with the enolic oxygen atom of one ketone on the cyclic diketone, generating a tricyclic by-product with a chromone-like structure However, under the conditions of the present invention that do not require a base, not only by-products are not generated at all when heat is applied, but also the reaction is further promoted by heating, and the reaction time is even reduced. It is possible.

The end point of the reaction can be confirmed by disappearance of the raw materials by HPLC or the like. At this time, since a certain 2-benzoyl-cyclic 1,3-diketone derivative forms a complex with aluminum in the reaction solution, the complex is dissociated after the next isolation step.

After completion of the reaction, the target compound is isolated. Isolation is performed by adding a strongly acidic aqueous solution of a mineral acid such as hydrochloric acid under ice-cooling, collecting the organic layer after the separation operation, and further extracting the aqueous layer with an extraction solvent, if necessary. At this time, an acidic aqueous solution in a range in which aluminum, which is an amphoteric metal, is dissolved in the aqueous layer by a mineral acid strong acidic aqueous solution is used. When a hydrochloric acid aqueous solution is used, a 2N or more aqueous solution is usually used. For example, when a 6N hydrochloric acid aqueous solution is used, 1,3
An aqueous solution of 5 to 50 parts by weight per 1 part by weight of diketones is used. The extraction solvent is preferably the solvent used in the reaction, but is not particularly limited as long as it can dissolve the target product with a hydrophobic organic solvent. For example, benzene, toluene, aromatic hydrocarbons such as xylene, ethyl acetate,
Esters such as butyl acetate, halogen-based hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; and ethers such as diisopropyl ether and diethyl ether. At this time, the aluminum complex is also extracted into the organic layer.

By concentrating the extraction solvent, 2
A crude product of -benzoyl-cyclic 1,3-diketone derivative and its aluminum complex can be obtained, and furthermore, after dissolution in a water-soluble solvent, a mineral acid acidic aqueous solution is gradually added to precipitate crystals of a target product. Can be. By performing this crystal precipitation operation, aluminum can be dissociated from the aluminum complex, and the desired 2-benzoyl-cyclic 1,3-
Crystals of the diketone derivative can be obtained with high purity and high yield. Examples of the water-soluble solvent that can be used include alcohols such as methanol and ethanol, ketones such as acetone and methyl ethyl ketone, ethers such as THF and dioxane, and nitriles such as acetonitrile, and inexpensive methanol and acetone are advantageous. It is. In addition, the mineral acid acidic aqueous solution is preferably a strongly acidic aqueous solution such as hydrochloric acid. When a 1-6N aqueous hydrochloric acid solution is used,
The used amount is 2 to 20 parts by weight of a water-soluble solvent and 0.5 to 20 parts by weight of a mineral acid acidic aqueous solution with respect to 1 part by weight of a target substance.

In the cyclic 1,3-diketone (1) used as a raw material in the production method of the present invention, R ¹ , R ² , R ³ ,
The R ^4, R ⁵ and C1~4 lower alkyl groups which R ⁶ represents a methyl, ethyl, propyl, butyl and isomer groups thereof. The C1-3 alkylene group represented by R ¹ and R ³ or R ¹ and R ⁵ together is methylene,
Ethylene and propylene groups. Preferred cyclic 1,3-
Examples of the diketone include cyclohexane-1,3-dione and dimedone (5,5-dimethylcyclohexane-
1,3-dione), 4,4,6,6-tetramethylcyclohexane-1,3-dione, bicyclo [3.2.1]
Octane-2,4-dione and the like.

In the present invention, in the benzoyl halide compound (2) used as another raw material, X, R ⁷ ,
The halogen atoms represented by R ⁸ and R ⁹ are a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

In the general formula (2), a C1-2 lower alkyl group which may be substituted by one to three fluorine atoms represented by R ⁷ includes a methyl group, an ethyl group, a fluoromethyl group and a difluoromethyl group. Group, trifluoromethyl group, fluoroethyl group, difluoroethyl group, trifluoroethyl group and isomers thereof, and the C1-2 lower alkylsulfonyl group is a methanesulfonyl group or an ethanesulfonyl group.

In the general formula (2), the C1-2 lower alkyl groups represented by R ⁸ are a methyl group and an ethyl group;
And the lower alkoxy groups of -4 are methoxy, ethoxy, propoxy, butoxy and isomers thereof, and C2
The lower alkoxymethyl groups of ４4 are methoxymethyl, ethoxymethyl, propyloxymethyl groups and isomers thereof, and the lower alkoxycarbonyl groups of C2-5 are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and butoxycarbonyl groups. And their isomeric groups.

In the general formula (2), the C 1-3 lower alkoxy group which may be substituted by one to three fluorine atoms represented by R ⁹ includes a methoxy group, an ethoxy group, a propoxy group and a fluoromethoxy group. , A difluoromethoxy group,
Trifluoromethoxy group, fluoroethoxy group, difluoroethoxy group, trifluoroethoxy group, fluoropropoxy group, difluoropropoxy group, trifluoropropoxy group and isomers thereof. The C1-3 lower alkylthio group represented by R ⁹ is a methylthio, ethylthio, propylthio, isopropylthio group,
C1 optionally substituted with up to 6 fluorine atoms
The lower alkylsulfonyl group or lower alkylsulfonyloxy group of (1) to (3) is a methanesulfonyl (oxy), ethanesulfonyl (oxy), propanesulfonyl (oxy) group or a group in which a hydrogen atom of these alkyl groups is substituted by a fluorine atom. is there.

Preferred benzoyl halide compounds include, for example, benzoyl chloride, 2-chloro-4-methanesulfonylbenzoyl chloride, 2,4-dichlorobenzoyl chloride, 4-chloro-2-nitrobenzoyl chloride, 2-nitro-4-methane Sulfonyloxybenzoyl chloride, 2-nitro-4-difluoromethanesulfonylbenzoyl chloride, 3-methoxycarbonyl-2-methyl-4-methanesulfonylbenzoyl chloride, 4-chloro-3-ethoxy-2-
Nitrobenzoyl chloride, 2,4-dichloro-3-
Methylbenzoyl chloride and the like can be mentioned.

[0026]

Conventionally, when a cyclic 1,3-diketone and a benzoyl chloride compound are used as starting materials, a 2-benzoyl-cyclic 1,3-diketone compound is produced by a two-step reaction via an enol ester. However, in the present invention, since the 2-position carbon of the cyclic 1,3-diketone is directly benzoylated, it can be produced by a one-step reaction. Further, in the method of the present invention, by-products are hardly generated, and the target product can be obtained in high yield. Since the present invention can also be applied to bicyclic 1,3-diketones, industrially advantageous production of the compounds disclosed in JP-A-6-25144 and JP-A-7-82240 or intermediates thereof is advantageous. Can be used as a method.

[0027]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by these Examples.

Example 1 Preparation of 3- (2-chloro-4-methanesulfonylbenzoyl) bicyclo [3.2.1] octane-2,4-dione 202.6 g of anhydrous aluminum chloride was added to 1400 ml of 1,2-dichloroethane. 1.5mol) and stirred for 30 minutes,
128.5 g (0.5 mol) of 2-chloro-4-methanesulfonylbenzoyl chloride was charged. After stirring for 30 minutes, 70 g (0.5 mol) of bicyclo [3.2.1] octane-2,4-dione was charged, the reactor was heated to raise the internal temperature to 58 ° C., and the mixture was stirred for 2 hours and 30 minutes. did. After completion of the reaction was confirmed by HPLC, the mixture was allowed to cool, cooled with ice, and then cooled.
1170 ml of normal hydrochloric acid was added dropwise to stop the reaction. The organic layer was separated, and the aqueous layer was further treated with 1,2-dichloroethane 700.
The mixture was extracted with an organic layer, and the mixture was combined with the organic layer. After 700 ml of methanol was added and dissolved by heating (inner temperature: 62 ° C.), 140 ml of 6N hydrochloric acid was added dropwise over 20 minutes, and the mixture was further stirred under heating for 1 hour and at room temperature overnight. The precipitated target product was filtered, and 3- (2-chloro-4-)
Methanesulfonylbenzoyl) bicyclo [3.2.1]
164.2 g (0.46 mol) of octane-2,4-dione was obtained. The yield was 92% and the area percentage (purity) by HPLC was 99%.

Example 2 2- (2-chloro-4-methanesulfonylbenzoyl) -5,5-dimethyl-1,3-
Production of cyclohexanedione 5.79 g (43.4 mmol) of anhydrous aluminum chloride and 3.67 g (14.4 mmol) of 2-chloro-4-methanesulfonylbenzoyl chloride in 80 ml of 1,2-dichloroethane
l) and 2.03 g (14.4 mmol) of dimetone were added, and the mixture was stirred at room temperature for 48 hours. Confirm the end of the reaction by HPLC,
After cooling in an ice bath, 30 ml of a 6N aqueous hydrochloric acid solution was added, and the mixture was stirred and the organic layer was recovered by a liquid separation operation.
The mixture was extracted with 50 ml of 2-dichloroethane, and the organic layers were combined. The organic solvent was concentrated under reduced pressure, and the resulting crude 2- (2
-Chloro-4-methanesulfonylbenzoyl) -5,5
After dissolving -dimethyl-1,3-cyclohexanedione in 20 ml of acetone, 25 ml of 2N hydrochloric acid was added. After stirring overnight to sufficiently precipitate crystals, the crystals were filtered and the filtrate was dried to give 2- (2-chloro-4-methanesulfonylbenzoyl) -5,5-dimethyl-1,3-cyclohexanedione 4.73. g (13.4 mmol) was obtained, and it was confirmed by nuclear magnetic resonance that it was the desired product. The yield was 93% and the purity was 99% by HPLC area percentage.

Example 3 Preparation of 2- (2-chloro-4-methanesulfonylbenzoyl) -1,3-cyclohexanedione 5.35 g (40 mmol) of anhydrous aluminum chloride in 70 ml of 1,2-dichloroethane, 2-chloro -4-methanesulfonylbenzoyl chloride 3.39 g (13.3 mmol
l) 1.5 g of 1,3-cyclohexanedione (13.3 mm
ol) and stirred at room temperature for 48 hours. The completion of the reaction was confirmed by HPLC, and after cooling in an ice bath, 30 ml of a 2N hydrochloric acid aqueous solution was added, and the mixture was stirred and the organic layer was recovered by a liquid separation operation.
Further, the aqueous layer was extracted with 70 ml of 1,2-dichloroethane, and the organic layers were combined. The organic layer is dried and concentrated to give 4.31 g of 2- (2-chloro-4-methanesulfonylbenzoyl) -1,3-cyclohexanedione.
(13.1 mmol) was obtained, and it was confirmed by nuclear magnetic resonance that it was the desired product. The yield was 98%, with 99% purity by HPLC area percentage.

Example 4 Method for producing 2-benzoyl-1,3-cyclohexanedione 2.38 g (17.8 mmol) of anhydrous aluminum chloride in 50 ml of 1,2-dichloroethane, benzoyl chloride 1.
25 g, 1,3-cyclohexanedione 1 g (8.9 mmo
l) was added and the mixture was stirred at room temperature for 12 days. After cooling on ice, 30 ml of 6N hydrochloric acid aqueous solution was added dropwise, and the organic layer was collected, dried,
By concentrating, liquid 2-benzoyl-1,3-
1.64 g (7.6 mmol) of cyclohexanedione was obtained, and the product was confirmed to be the target product by nuclear magnetic resonance. Yield 85
%, And the area percentage (purity) by HPLC is 92%.
Met.

Examples 5 to 13 Using the cyclic 1,3-dione and the corresponding compound as the benzoyl chloride compound, the same treatment as in Examples 1 to 4 was carried out, and the 2-benzoyl-cyclic 1,3- A diketone derivative was obtained. Physical properties are also shown in Table 1.

[0033]

[Table 1]

Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 201/12 C07C 201/12 205/45 205/45 315/04 315/04 317/24 317/24 // C07B 61/00 300 C07B 61 / 00 300 (72) Inventor Toshihiko Tabuchi 2-1-1 Midorigahara, Tsukuba-shi, Ibaraki, Japan Inside SDS Biotech Tsukuba Research Laboratories (72) Inventor Junichi Iwasawa 2-1-1 Midorigahara, Tsukuba-shi, Ibaraki, Japan (72) Inventor Hideki Kishi 2-1-1 Midorigahara, Tsukuba City, Ibaraki Pref., Ltd. Inside SDS Biotech Tsukuba Research Laboratories

Claims (4)

[Claims] 1. General formula (1) (Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represent a hydrogen atom or a C 1-4 lower alkyl group, or R ¹ and R ³ or R ¹ R ⁵ together C
Represents 1 to 3 alkylene groups. )
3-diketone and general formula (2) (Wherein, X represents a halogen atom, R ⁷ is a hydrogen atom,
A halogen atom, a nitro group, a C1-2 lower alkyl group which may be substituted by 1 to 3 fluorine atoms, C
R ⁸ represents a hydrogen atom, a halogen atom, a C 1-2 lower alkyl group,
Represents a lower alkoxy group of 1-4, a lower alkoxymethyl group of C2-4, or a lower alkoxycarbonyl group of C2-5, and R ⁹ may be substituted by a hydrogen atom, a halogen atom, or 1-3 fluorine atoms. It represents a preferable C1-3 lower alkoxy group, a C1-3 lower alkylthio group, a C1-3 lower alkylsulfonyl group or a lower alkylsulfonyloxy group which may be substituted by 1-6 fluorine atoms. Wherein the benzoyl halide compound of the formula (1) is reacted in the presence of anhydrous aluminum chloride. (The symbols in the formula represent the same meaning as described above.) A method for producing a 2-benzoyl-cyclic 1,3-diketone derivative represented by the formula: 2. The method according to claim 1, wherein the anhydrous aluminum chloride is used in an amount of 2 to 4 molar equivalents relative to the benzoyl halide compound.
The production method described in 1. 3. The cyclic 1,3-diketone wherein R ¹ and R ⁵ together represent an ethylene group, R ² , R ³ , R ⁴ and R ⁶
Is a compound representing a hydrogen atom; and the benzoyl halide compound is a compound wherein X and R ⁷ are a chlorine atom, R ⁸ is a hydrogen atom, and R ⁹ is a methylsulfonyl group. 4. The production method according to claim 1, wherein after the reaction, the obtained crude product is crystallized from a mixture of a water-soluble organic solvent and a mineral acid acidic aqueous solution, and is isolated and purified.