WO2009078475A1

WO2009078475A1 - Process for production of pyrazolinone derivative

Info

Publication number: WO2009078475A1
Application number: PCT/JP2008/073140
Authority: WO
Inventors: Fumi Yonehara; Takao Inoguchi
Original assignee: Sumitomo Chemical Company, Limited
Priority date: 2007-12-14
Filing date: 2008-12-12
Publication date: 2009-06-25
Also published as: JP2009143850A; CN101896466A; IL206085A0

Abstract

Disclosed is a process for producing a pyrazolinone derivative (3), which is characterized by: reacting a pyrazolinone compound (1) with an acid halide (2) in a mixed solution of water and an organic solvent in the presence of a base; subjecting the resulting reaction mixture to the oily-layer/aqueous-layer separation; adding an acid to the aqueous layer to neutralize the aqueous layer, thereby causing the precipitation of the pyrazolinone derivative (3); and separating the pyrazolinone derivative (3). (1) (e.g., 3-amino-4-(2-methylphenyl)-pyrazolin-5-one) (2) (e.g., allylchlorothioformate) (3) (e.g., 1-[(2-propenylthio)carbonyl]-4-(2-methylphenyl)-5- amino-1H-pyrazol-3-one)

Description

Technical description Manufacturing method of pyrazolinone derivatives Technical field

The present invention may be referred to as a compound represented by the general formula (1) [hereinafter referred to as a virazolinone compound (1). ] And a compound represented by the general formula (2) [hereinafter sometimes referred to as acid halide (2). ] In the presence of a base, and a compound represented by the general formula (3) [hereinafter sometimes referred to as a birazolinone derivative (3). ] Related to the method of manufacturing.

(Wherein R ¹ R ² , R ³ , R ⁴ and R ⁵ each represents a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom. R ⁶ represents a hydrogen atom or a carbon number:! Represents an alkyl group of ˜5.)

O

X YR ⁷

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom or a sulfur atom. R ⁷ represents an alkyl group having 1 to 5 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, or 3 to 5 carbon atoms. Represents an alkynyl group of

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and Y have the same meanings as described above.)

The virazolinone derivative (3) is useful, for example, as a raw material for agricultural chemicals. Background art

As a method for producing a pyrazolinone derivative (3), for example, Japanese Patent Application Laid-Open No. 2 00 0-2 2 6 3 74 (Patent Document 1) discloses that a bisazolinone compound (1) and an acid halide (2) are mixed with water and hydrophobic. It is disclosed that a pyrazolinone derivative (3) is produced by reacting in a mixed solution with a basic organic solvent in the presence of a base, acid-treating the obtained reaction mixture without oil-water separation, and solvent extraction. ing. Disclosure of the invention

In the above conventional method, the yield is not always satisfactory. During the reaction, in addition to the target bisazolinone derivative (3), a urea compound having a structure in which two molecules of bisazolinone compound (1) are connected by a carbonyl group is produced as a by-product. It is easy to be incorporated into the precipitate of the virazolinone derivative (3), the quality is lowered, and it is not preferable for the post-process using the virazolinone derivative (3).

Accordingly, an object of the present invention is to provide a method capable of producing the virazolinone derivative (3) with good quality by suppressing the incorporation of the above-mentioned by-product with good yield. As a result of intensive studies, the inventors of the present invention reacted the bisazolinone compound (1) and the acid halide (2) in a mixed solution of water and a hydrophobic organic solvent in the presence of a base, and obtained the reaction mixture. It was found that by separating the oil and water and neutralizing the aqueous layer by adding an acid, the virazolinone derivative (3) is precipitated and separated, thereby improving the yield and suppressing the uptake of the by-product. It came to be completed.

That is, the present invention comprises reacting a bisazolinone compound (1) and an acid halide (2) in a mixture of water and a hydrophobic organic solvent in the presence of a base, separating the resulting reaction mixture from oil to water, The present invention provides a method for producing a pyrazolinone derivative characterized in that an acid is added to neutralize to precipitate a razolinone derivative (3) and separate it. According to the present invention, the virazolinone derivative (3) can be produced in good quality with good quality. BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below. General formula (1) indicating a bisazolinone compound (1)

(Wherein RR ² , R ³ , R ⁴ and R ⁵ each represent a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom. R ⁶ is a hydrogen atom or a C 1-5 carbon atom. Represents an alkyl group.)

In this case, when at least ^one of R ¹ R ² , R ³ , R ⁴ and R ⁵ is a methyl group substituted with a halogen atom or a halogen atom, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or It can be an iodine atom. The methyl group substituted with a halogen atom may be a monohalomethyl group such as a monofluoromethyl group or a monochloromethyl group, or a dihalomethyl group such as a difluoromethyl group or a dichloromethyl group. Alternatively, it may be a trihalomethyl group such as a trifluoromethyl group or a trichloromethyl group. When R ⁶ is an alkyl group having 1 to 5 carbon atoms, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butynole group, a sec-butyl group, Examples thereof include an isobutyl group, a tert-butyl group, and an n-pentyl group.

General formula (2) indicating acid halide (2)

In this case, when R ⁷ is an alkyl group having 1 to 5 carbon atoms, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-propyl group, a sec-butyl group. Group, isobutyl group, tert-butyl group, n-pentyl group and the like. When R ⁷ is an alkenyl group having 3 to 5 carbon atoms, Examples of the alkyl group include an aryl group (2-propenyl group), a methallyl group (2-methyl-2-propenyl group), a crotyl group (2-butyr group), and the like. When R ⁷ is an alkynyl group having 3 to 5 carbon atoms, examples of the alkynyl group include a 2-probule group, a 2-petitinyl group, and a 3-petitinyl group. The reaction between the lazolinone compound (1) and the acid halide (2) is carried out in the presence of a base. Examples of the base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, and carbonic acid. Alkaline metal carbonates such as sodium and carbonated lithium, inorganic bases such as alkali metal bicarbonates such as sodium bicarbonate and hydrogen carbonate, pyridine, 4_ (dimethylamino) pyridine And organic bases such as triethylamine. When the inorganic base is used, it can also be used as an aqueous solution. Preferably, an alkali metal hydroxide aqueous solution is used.

The amount of the acid halide (2) used for the reaction is usually 0.5 to 5 mol, preferably 0.9 to 1.5 mol, relative to 1 mol of the bisazolinone compound (1). The amount of the base used in the reaction is usually 1 to 5 mol, preferably 1.5 to 2.5 mol, per 1 mol of the lazolinone compound (1).

The reaction is carried out in the presence of a base with a bisazolinone compound (1) and an acid halide (2) in a mixture of water and an organic solvent.

Examples of the hydrophobic organic solvent include aromatic hydrocarbons such as benzene, toluene, xylene, and black benzene, aliphatic hydrocarbons such as n-hexane and n-heptane, cyclopentane, and cyclohexane. Alicyclic hydrocarbons such as hexane, ketones such as methyl ethyl ketone, methyl isobutyl ketone, ethers such as jetyl ether, dibutyl ether, tetrahydrofuran, and tetrahydrobrobilan. These can be used alone or in combination of two or more.

Simultaneously with the hydrophobic organic solvent, a hydrophilic organic solvent such as alcohol such as methanol, ethanol or propanol can be used.

Water and hydrophobic organic solvent may be added to the reactor in advance, A mixture with the zolinone compound (1) or the acid halide (2) may be added. The total amount of the water, the hydrophobic organic solvent and the hydrophilic organic solvent is usually 1 to 20 parts by weight, preferably 1 to 10 parts by weight per 1 part by weight of the pyrazolinone compound (1). .

The reaction temperature is usually 0 to 100 ° C, preferably 10 to 50 ° C. In addition, the reaction is usually performed near normal pressure, but may be performed under pressure or under reduced pressure as necessary. As the reaction method, any of a continuous method, a semi-continuous method, and a batch method can be adopted.

The pH during the reaction is usually 10 or more, and is usually adjusted by adding a base or an acid such as hydrochloric acid.

The order of preparation is not particularly limited, and the acid halide (2) may be added to the mixture of the bisazolinone compound (1) and the base, and the mixture of the bisazolinone compound (1) and the base is added to the acid halide (2). May be added.

After completion of the reaction, the reaction mixture is separated into oil and water, neutralized by adding acid to the aqueous layer, and the desired general formula (3)

(In the formula, I ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and Y have the same meanings as described above.)

The violazolinone derivative (3) represented by is precipitated as a solid and separated.

Examples of the acid added to the aqueous layer include hydrogen chloride and sulfuric acid, and an aqueous solution thereof is preferably used. The amount of the acid to be used is generally 0.5 to 5 mol, preferably 0.7 to 1.5 mol, per 1 mol of the birazolinone compound (1). From the aspect of quality and operation, the pH of the aqueous layer after addition of the acid is preferably 5 or more. In order to sufficiently precipitate the pyrazolinone derivative (3), the pH of the aqueous layer after addition of the acid is The pH is preferably 9 or less. The pH can be adjusted by adjusting the amount of acid used. In addition, it is preferable that the aqueous layer before adding the acid is in a state in which the virazolinone derivative (3) is dissolved.

The time for adding the acid to the aqueous layer is 3 hours or more in order to suppress the incorporation of the by-product into the precipitated virazolinone derivative (3). On the other hand, the upper limit is not particularly limited, but is usually 20 hours or less from the viewpoint of productivity.

The acid is added to precipitate the virazolinone derivative (3), and then the virazolinone derivative (3) is separated from the aqueous layer containing the precipitate by a known separation means such as filtration. By washing the separated precipitate with water or an organic solvent, the target product, virazolinone derivative (3), can be obtained as a solid.

Thus, the virazolinone derivative (3) can be obtained in good yield and with good quality while suppressing the by-product incorporation. Furthermore, it can be purified by means such as recrystallization or column chromatography if necessary.

Example

Examples of the present invention will be described below, but the present invention is not limited thereto.

Example 1

In a glass reactor equipped with a reflux condenser, thermometer, stirrer, and dropping funnel, add 3-amino-4-one (2-methylphenyl), 1-azolazoline, 5-on [R in general formula (1) Compound in which ¹ is a methyl group, and R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are hydrogen atoms] 45.00 g (0.238 mol), methanol 45. OO g, water 1 6. 16 g, 45.00 g of xylene and 39.96 g of 25% aqueous sodium hydroxide solution were added and stirred. To this aqueous solution, 10% hydrochloric acid was added to adjust the pH to about 12.0, and then at 15 ° C, chlorochloroformate [In the general formula (2), X is a chlorine atom, Y is a sulfur atom, R Compound in which ⁷ is an aryl group] A mixed solution of 34.44 g (0.252 mol) and xylene 29.5 2 g was added dropwise over 2 hours. After completion of the addition, the mixture was further stirred at the same temperature for 2 hours. During the dropwise addition of allylchlorothioformate and subsequent incubation, 10% sodium hydroxide solution was added together to maintain the pH in the reaction system at about 10.7. Then, the reaction mixture is allowed to stand for 30 minutes to separate oil and water, and 10% hydrochloric acid 82.3 is added to the aqueous layer at 25 ° C. 4 g was added dropwise over 3 hours, 1- [(2-propenylthio) carbonyl] _4 one (2-methylphenyl) one 5-amino-1 H-pyrazol one 3 _one [in the general formula (3) R ¹ is a methyl group, RR ² , R ³ , R ⁴ , R ⁵ and R ⁶ are hydrogen atoms, Y is a sulfur atom, and R ⁷ is an aryl group]. Ρρ at this time was 6.5. The aqueous layer containing this precipitate was filtered. The filtered product was washed with η-hexane and then with methanol water. 1- [(2-Propenylthio) carbonyl] _4 1 (2_methylphenol) 1 5-Amino 1 1 H-pyrazole 1 3 — 58.6 1 g of ON was obtained. This was analyzed by high-performance liquid chromatography, and the purity was calculated by an absolute calibration curve method, and the yield relative to the starting material 3-amino-4- (2-methylphenyl) mono-biazolin-5-one was determined. As a result, the purity was 95.9% and the yield was 85.2%. The content of urea compound as a by-product was calculated by the area percentage method, and the content was 1.1%.

Comparative Example 1

In the same reactor as in Example 1, 3-amino-4- (2-methylphenyl) monovirazolin_5_one 15.00 g (0.079 mol), methanolol 15.00 g, water 7.49 g, Xylene 15.00 g and 25% aqueous sodium hydroxide solution 1 3. 3 2 g were added and stirred. To this aqueous solution, 10% hydrochloric acid was added to adjust pH to 12.0, and at 15 ° C, allylchlorothioformate [in the general formula (2), X is a chlorine atom, Y is a sulfur atom, R ⁷ Compound in which is a aryl group] A mixed solution of 10.61 g (0.078 mol) and xylene 10.10 g was added dropwise over 2 hours. After completion of the addition, the mixture was further stirred at the same temperature for 2 hours. During the dropwise addition of allylic chloroformate and subsequent incubation, the pH in the reaction system was kept at about 10.7 by co-injecting 10% sodium hydroxide solution. Thereafter, 28.57 g of 10% hydrochloric acid was added dropwise to the reaction mixture at 25 ° C over 0.5 hours, and 1 _ [(2-propenylthio) carbonyl] 1- (2-methylphenyl) 1- 5-Amino-1 H-pyrazole 1-32one was precipitated. The pH at this time was 6.5. To this was added 30.00 g of n-hexane, and the mixture was stirred for 1 hour and filtered. The filtered product was washed with n-hexane and then with methanolic water, and 1 1 [(2-propenylthio) carbonyl] 1- (2-methylphenyl) -5-amino 1 H-pyrazole 1 3- 1 9.28 g of on was obtained. When analyzed in the same manner as in Example 1, The purity was 95.3% and the yield was 85.9%. The urea compound content was 1.8%. Industrial applicability

According to the present invention, the virazolinone derivative (3) can be produced in good quality with good quality.

Claims

The scope of the claims

General formula (1)

(In the formula, R ′, R ² , R ³ , R ⁴ and R ⁵ each represents a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom. R ⁶ represents a hydrogen atom or a carbon number of 1; Represents an alkyl group of ~ 5) and a bisazolinone compound represented by the general formula (2)

(In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom or a sulfur atom. R ⁷ represents an alkyl group having 1 to 5 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, or 3 to 5 carbon atoms. The acid halide represented by) is reacted in a mixed solution of water and a hydrophobic organic solvent in the presence of a base, the resulting reaction mixture is separated into oil and water, and an acid is added to the aqueous layer. General formula (3) by neutralization

(Wherein, RR ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and Y each have the same meaning as described above.) Are precipitated and separated. A method for producing a pyrazolinone derivative.

2.

2. The production method according to claim 1, wherein the hydrophobic organic solvent is toluene and Z or xylene.

3.

The bisazolinone compound represented by the general formula (1) is 3-amino-4- (2-methylphenyl) mono-biazolin-5-one, and the acid halide represented by the general formula (2) is valylchlorothioformate. The product is a bisazolinone derivative represented by the general formula (3) 1-[(2-propenylthio) carbonyl] 1 4- (2-methylphenyl) _ 5-amino _ 1 H-pyrazole 3. The method according to claim 1 or 2, wherein the method is 3-on.