WO2009044937A1

WO2009044937A1 - Method for producing pyrazolinone derivative

Info

Publication number: WO2009044937A1
Application number: PCT/JP2008/068408
Authority: WO
Inventors: Fumi Yonehara; Taro Hirose; Yoshitomo Tohyama
Original assignee: Sumitomo Chemical Company, Limited
Priority date: 2007-10-05
Filing date: 2008-10-03
Publication date: 2009-04-09
Also published as: CN101815705A; IL204792A0; JP5181609B2; JP2009091275A; IL204792A

Abstract

Disclosed is a method for producing a compound represented by the formula (3) below by reacting a compound represented by the formula (1) below with a compound represented by the formula (2) below in water and an organic solvent in the presence of a base. This method for producing a compound represented by the formula (3) below is characterized by sequentially performing the step A, the step B and the step C described below. Step A: a step for obtaining a liquid mixture containing an aqueous liquid phase by mixing so that the pH of the aqueous liquid phase is higher than 11.5 but lower than 12.5 Step B: a step for obtaining a liquid reaction mixture by adding the compound of the formula (2) until the pH of the aqueous liquid phase reaches 11.5 or lower Step C: a step for adding the compound of the formula (2) and a base so that the pH of the aqueous liquid is maintained within the range of 10.0-11.5

Description

Method for producing pyrazolinone derivative Technical Field

The present invention provides a compound of formula (1) in water and an organic solvent.

book

(In the formula, RR 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:! 5 represents an alkenoquinole group '.)

[Hereinafter, it may be referred to as a pyrazolinone compound (1). ] And the formula (2)

0

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 is an alkyl group having 1 to 5 carbon atoms, an alkyl group having 3 to 5 carbon atoms, or 3 carbon atoms. Represents an alkynyl group of ~ 5.)

[Hereinafter referred to as acid halide (2). In the presence of a salt group, and the formula (3)

(In the formula, RR ² , R ³ , R \ R ⁵ , R ⁶ , R ⁷ and Y have the same meaning as described above.)

[Hereinafter, it may be referred to as a birazolinone derivative (3). ] Made 08068408

2 It relates to the manufacturing method. The virazolinone derivative (3) is useful, for example, as a raw material for agricultural chemicals. Background art

For example, US Pat. No. 62945677 discloses a method for producing a virazolinone derivative (3), such as a method in which an acid halide (2) is added dropwise to a mixture of an organic solvent, a bisazolinone compound (1) and a base, It describes a method in which an aqueous base solution is dropped into a mixture of an organic solvent, a birazolinone compound (1) and an acid halide (2). Disclosure of the invention

However, the above-mentioned conventional methods may reduce the selectivity and yield of the reaction, and are not always satisfactory in these respects.

Accordingly, an object of the present invention is to provide a method capable of producing a virazolinone derivative (3) with good reaction selectivity and yield.

As a result of an arbitrary study, the inventors of the present invention have made a reaction between a virazolinone compound (1) and an acid halide (2) in the presence of a base to produce a virazolinone derivative (3). An organic solvent, a birazolinone compound (1) and a base are mixed so that the pH of the aqueous liquid phase is higher than 11.5 and lower than 12.5 to obtain a mixed liquid containing an aqueous liquid phase. Next, acid halide (2) is added to this mixed solution until the pH of the aqueous liquid phase becomes 11.5 or less, and then the pH of the aqueous liquid phase is adjusted to 10.0 to 11.5. It was found that the above-mentioned object can be achieved by adding the acid halide (2) and the base so as to maintain the present invention, and the present invention has been completed.

That is, the present invention provides a compound of formula (1) in water and an organic solvent.

(Wherein RR ² , R ³ , R ⁴ and R ⁵ are each a hydrogen atom, a halogen atom or It represents a methyl group which may be substituted with a mouth atom. R ⁶ represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. )

A compound represented by 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 is an alkyl group having 1 to 5 carbon atoms, an alkyl group having 3 to 5 carbon atoms, or 3 carbon atoms. Represents an alkynole group of ~ 5.)

Is reacted with a compound represented by formula (3) in the presence of a base.

(In the formula, RR ² , R ³ , RR ⁵ , ^Re , R ⁷ and Y have the same meanings as described above.)

A process for producing a compound represented by formula (3), which comprises the following step A, step B and step C, is provided.

Step A: Water, an organic solvent, a compound represented by the formula (1) and a base are mixed so that the pH of the aqueous liquid phase is higher than 11.5 and lower than 12.5. Step of obtaining a liquid mixture containing phases

Step B: A step of adding a compound represented by the formula (2) to the mixture obtained in Step A until the pH of the aqueous liquid phase is 11.5 or less to obtain a reaction mixture

Step C: A step of adding the compound represented by the formula (2) and a base to the reaction mixture obtained in Step B so that the pH of the aqueous liquid phase is maintained at 10.0 to 11.5.

According to the present invention, the virazolinone derivative (3) can be produced with good reaction selectivity and yield. BEST MODE FOR CARRYING OUT THE INVENTION 2008/068408

In the present invention, first, water, an organic solvent, a birazolinone compound (1) and a base are mixed so that the pH of the aqueous liquid phase is higher than 11.5 and lower than 12.5. A liquid mixture containing a liquid phase is obtained [Step A]. Examples of the organic solvent used herein include methanolic alcohols such as methanolate, ethanol and prononol, aromatic hydrocarbons such as benzene, toluene, xylene and black benzene, n-hexane, and n-heptane. Aliphatic hydrocarbons such as cycloaliphatic hydrocarbons such as cyclopentane and cyclohexane, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, jetyl ether, dibutyl ether, tetrahydrofuran, Examples include ethers such as 1,4 monodioxane and tetrahydropyran. If necessary, a mixed solvent composed of two or more of them can be used. Among these, a mixed solvent of an aromatic hydrocarbon and an alcohol is preferable from the viewpoint of suppressing side reactions.

Further, when water and an organic solvent are mixed, they may be mixed uniformly or may be a non-uniform oil / water two-phase system. In addition, when water and an organic solvent are mixed uniformly, such a uniform mixed solution becomes an aqueous liquid phase, and the pH of the liquid phase should be higher than 11.5 and lower than 12.5. . In addition, when the mixed liquid of water and organic solvent is a heterogeneous oil-water two-phase system, the aqueous phase becomes an aqueous liquid phase, and the pH of the liquid phase is higher than 11.5, and from 12.5 I hope it gets lower.

In process A, the formula (1)

(In the formula, RR 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 hydrogen atom. R ⁶ represents a hydrogen atom or a carbon number of 1 to Represents an alkyl group of 5)

The compound represented by the formula [Vazolinone compound (1)] is used.

In the formula (1), when at ^{least one} of R ¹ R ² , R ³ , R ⁴ and R ⁵ is a halogen atom or a methyl group substituted with a halogen atom, the halogen atom is a fluorine atom, a chlorine atom, It can be a bromine atom or an iodine atom. Also, c The methyl group substituted with a 5 atom 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 dihalomethyl group. Further, 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-butyl group, a sec-butyl group, and an isobutyl group. Group, tert-butyl group, n-pentyl group and the like.

Examples of the base used in step A include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, Inorganic bases such as alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, and organic bases such as pyridine, 4- (dimethylamino) pyridine, and triethylamine Is mentioned. When the inorganic base is used, it can be used as an aqueous solution. Of these, alkali metal hydroxides are preferred, and sodium hydroxide is more preferred.

The amount of water used in step A is usually 0.5 to 10 parts by weight, preferably 0.5 to 5 parts by weight, based on 1 part by weight of the pyrazolinone compound (1). The amount used is usually 1 to 20 parts by weight, preferably 1 to 10 parts by weight per 1 part by weight of the bisazolinone compound (1).

The amount of base used in step A may be adjusted as appropriate so that the pH of the aqueous liquid phase is higher than 11.5 and lower than 12.5. Usually, the amount of bisazolinone compound (1) is 1 mol. 0.8 to 1.2 mol, preferably 0.9 to 1.1 mol. When the pH of the aqueous liquid phase is 11.5 or less, it is only necessary to add a base so that the pH of the liquid phase is higher than 11.5. If it is 12.5 or more, an acidic aqueous solution such as hydrochloric acid (aqueous hydrogen chloride solution) or sulfuric acid aqueous solution may be added so that the pH of the liquid phase is lower than 12.5.

The mixing temperature in step A is not particularly limited, but is usually 0 to 50 ° C, preferably 5 to 40 ° C.

Next, add the liquid mixture obtained in step A to the aqueous liquid phase pH of 11.5 or less. The acid halide (2) is added to obtain a reaction mixture [Step B]. When the acid halide (2) is added in this way to cause the reaction between the pyrazolinone compound (1) and the acid halide (2) to proceed, the pH of the aqueous liquid phase gradually decreases. Go. That is, step B is a step of adding the acid halide (2) until the pH of the aqueous liquid phase becomes 11.5 or lower.

In process B, equation (2)

O

Λ ₇ ( ² )

X 'Y-R'

(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

The compound represented by the formula [acid halide (2)] is used.

In the formula (2), when R ⁷ is an alkyl group having 1 to 5 carbon atoms, the alkyl group includes, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-ptynole group, sec -Butynol group, isobutynol group, tert-butynole group, n-pentyl group and the like. When R ⁷ is an alkenyl group having 3 to .5 carbon atoms, examples of the alkenyl group include a allyl group (2-propenyl group) and a methallyl group (2-methyl-2-propenyl group). And crotyl group (2-butur group) and the like. When R ⁷ is an alkyl group having 3 to 5 carbon atoms, examples of the alkynyl group include a 2-propyl group, a 2-pentynyl group, and a 3-ptynyl group.

The amount of acid halide (2) used in Step B may be adjusted as appropriate so that the pH of the aqueous liquid phase is 11.5 or lower, but is usually 0. 05 to 0.5 mol, preferably 0.05 to 0.3 mol. The method of adding acid halide (2) in step B is not particularly limited, and is preferably added gradually or dropwise from the viewpoint of suppressing the pH S and side reactions of the aqueous liquid phase. .

In Step B, the temperature at which the acid halide (2) is added is not particularly limited, but is usually 0 to 50 ° C, preferably 5 to 40 ° C. An acid halide (2) and a base are added to the reaction mixture thus obtained so that the pH of the aqueous liquid phase is maintained at 10.0 to 11.5 [Step C]. Thus, by adding acid halide (2) and base so that the pH of the aqueous liquid phase is maintained within the above range, by-product formation and acid halide (2) decomposition can be achieved. The amount of the acid halide (2) used in Step C can be produced with good reaction selectivity and yield, and the amount of the acid halide (2) used in Step C is usually 0. 5 to 1.5 mol, preferably 0.8 to 1 · 2 mol. In addition, it is more preferable that the total amount of the acid halide (2) used in Step IV and Step C is 0.9 to 1.2 mol.

The amount of the base used in Step C may be appropriately adjusted so that ρΗ of the aqueous liquid phase is maintained at 10.0 to 11.5, but is usually 0 per 1 mol of the pyrazolinone compound (1). 5 to 1.5 moles, preferably 0.8 to 1.2 moles.

There are no particular restrictions on the method of adding acid halide (2) and base in Step C. However, these are gradually added or dropped from the viewpoint of suppressing ρΗ and side reactions in the aqueous liquid phase. It is preferable to do this.

In step C, the temperature at which the acid halide (2) and the base are added is not particularly limited, but is usually 0 to 50 ° C, preferably 5 to 40 ° C.

Thus formula (3)

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

Can be obtained, and such a bisazolinone derivative (3) can be produced with good reaction selectivity and yield.

By adding an acid to the above reaction mixture, a virazolinone derivative (3 ) Can be deposited. Examples of the acid 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 virazolinone compound (1). From the aspect of quality and operation, the pH of the aqueous liquid phase after addition of acid is preferably 5 or more. In addition, the aqueous solution after addition of acid is used to sufficiently precipitate the virazolinone derivative (3). The pH of the liquid phase is preferably 9 or less. The pH can be adjusted by adjusting the amount of acid used. The reaction mixture before adding the acid is preferably a solution in which the pyrazolinone derivative (3) is dissolved in a solvent from the viewpoint of quality.

The time for adding acid to the reaction mixture is usually 3 hours or more in terms of quality and operation. On the other hand, the upper limit is not particularly limited, but it is usually 20 hours or less from the viewpoint of productivity. After adding the acid to the reaction mixture after completion of the reaction to precipitate the virazolinone derivative (3), the mixture containing the precipitate is added. By filtration and washing the filtered product with water or an organic solvent, the target product, bisazolinone derivative (3), can be obtained as a solid with good quality. 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

To a glass reactor equipped with a reflux condenser, thermometer, stirrer, and dropping funnel, add 3-amino 4- (2-methylphenyl) monopyrazolin 1-one (in the formula (1), R ¹ is a methyl group). , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are hydrogen atoms] 15.50 g (0.079 mol), methanol 30.00 g, water 5.39 g, xylene 4 5.00 g and 25% sodium hydroxide aqueous solution 1 3.32 g was added and stirred at 15 ° C. The aqueous phase pH at this time was 13.8. After adjusting the aqueous phase pH to 1 2.0 by adding 2.32 g of 10% hydrochloric acid to this mixed solution, at 15 ° C, the aryl chloride thioformate [in the formula (2), X is a chlorine atom, γ Is a sulfur atom and R ⁷ is an aryl group Compound] A mixed solution of 1.43 g (0.0 1 1 mol) and xylene 1.23 g was added dropwise over 15 minutes. The aqueous phase pH at this time was 1.1.3. Thereafter, the reaction mixture is mixed with 10 0.05 g (0.074 monole) and xylene so that the aqueous phase pH is maintained within the range of 10 0.0 1 1.5. 8.6 1 mixture and 10% sodium hydroxide solution 33. 88 g (0.085 mol) were added dropwise over 1 hour and 45 minutes, respectively, and the mixture was stirred at the same temperature for 2 hours. Next, after the reaction mixture was brought to about 25 ° C., 28.34 g of 10% hydrochloric acid was added dropwise over 0.5 hours, and 1-[(2-propeninoretio) carbonyl]-4-( 2—Methylphenyl) — 5—Amino 1 H—Pyrazol 1 3 —one [In the formula (3), R ¹ is a methyl group R \ R ² R ³ R ⁴ R ⁵ and R ⁶ are hydrogen atoms, Y is sulfur A compound in which R ⁷ is an aryl group] was deposited. The aqueous phase pH at this time was 6.5. To this was added 30.00 g of η-hexane, and the mixture was stirred for 1 hour and filtered. The filtered product was washed with n-xane and then with aqueous methanol, and 1-[(2-propenylthio) carbonyl]

1-9.05 g of 4- (2-methylphenol) 15-amino-1- 1 H-pyrazol-3-one was obtained. This was analyzed by high performance liquid chromatography, the content was calculated by the absolute calibration curve method, and 3-aminoamino 4_ (2-methylphenyl) monovirazoline

The yield for 5_one was determined. As a result, the yield was 84.7%. The yield of the by-product diacyl [a compound formed by reacting a biazolinone compound (1) with two molecules of acid halide (2)] was 1.39%.

Comparative Example 1

In the same reactor as in Example 1, 3-amino_4_ (2-methylphenyl) monovirazolin-5-one 1 5.00 g (0.079 mol), methanol 30.00 g water 5.39 g, xylene 45 00 g and 25% aqueous sodium hydroxide solution 1 3.3 2 g were added and stirred at 15 ° C. The aqueous phase pH at this time was 1 3.8. To this mixture was added dropwise a solution of 11.48 g (0.084 mol) of xylylchlorothioformate and 9.84 g of xylene at 15 ° C over 2 hours, and then at the same temperature. Stir for 2 hours. The aqueous phase pH at this time was 7.8. Then, after the reaction mixture was brought to about 25 ° C., 0.4 1 g of 10% hydrochloric acid was added dropwise over 0.5 hours, and 1-[(2 —propeninoreti) canoleponore] 1-4— (2 —Metino ref. 0

1 H-pyrazol-3-one was precipitated. The pH at this time was 6.5. To this, 30.00 g of n-xane was added and stirred for 1 hour, followed by filtration. The filtered product is washed with n-hexane and then with methanolic water. 1- [((2-propenylthio) force sulfonyl] 1-4-1 (2-methylphenyl) 1-5-amino-1 H-pyrazole-3— 1 7.90 g of quinone was obtained. When analyzed in the same manner as in Example 1, the yield was 78.0%. The yield of the diacyl compound is 3.0 ° /. Met. Industrial applicability

According to the present invention, the virazolinone derivative (3) can be produced with good reaction selectivity and yield.

Claims

Range of requests

In water and organic solvents (1)

(In the formula, 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 of 1; Represents an alkyl group of ˜5.)

A compound represented by formula (2)

0

Λ ₇ ( ² )

X YR ⁷

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

A method for producing a compound represented by formula (3), comprising the following step A, step B and step C:

Step A: Water, an organic solvent, a compound represented by the formula (1) and a base are mixed so that the pH of the aqueous liquid phase is higher than 11.5 and lower than 12.5. For obtaining a mixed solution containing 2 Step B: A step of adding a compound represented by the formula (2) to the mixture obtained in Step A until the pH of the aqueous liquid phase is 11.5 or less to obtain a reaction mixture

2.

The method according to claim 1, wherein the base is an alkali metal hydroxide.

3.

The method according to claim 1 or 2, wherein the organic solvent is a mixed solvent of an aromatic hydrocarbon and an alcohol.