JPH0233708B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula (In the formula, R ₁ represents a lower alkyl group, X represents a halogen atom, and n represents 0, 1 or 2.)
The present invention relates to a method for producing a 4-benzoylpyrazole derivative having the following.

In the general formula (), examples of the lower alkyl group include linear or branched lower alkyl groups having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, or isopropyl.
Further, the halogen atom refers to chlorine, bromine, fluorine or iodine.

According to the method of the present invention, the compound having the general formula () can be produced as follows. That is, the general formula It can be obtained by contacting a pyrazole derivative having the formula (wherein R ₁ , X and n have the same meanings as defined above) with a catalyst.

In carrying out the present invention, the reaction is easily carried out by heating the compound having the general formula () in the presence of equimolar or more of a catalyst. The catalyst used is selected from aluminum chloride, imidazole, alkali metal carbonates and alkali metal alkoxides. Examples of alkali metal carbonates include sodium carbonate and potassium carbonate. Examples of alkali metal alkoxides include sodium methoxide, potassium ethoxide, sodium isopropoxide or potassium tert-butoxide. Furthermore, a system in which these alkali metal alkoxides are formed in the reaction solvent may be used. For example, if metallic sodium is dissolved in isopropanol, a solution containing sodium isopropoxide can be obtained, but such an alcohol solution can also be used as it is as a reaction solvent.

The reaction proceeds once the compound having the general formula () forms a rearrangement catalyst salt, but the rearrangement reaction may be performed after isolating this intermediate salt, or the rearrangement reaction may be performed without isolation. It's good to wear.

The reaction is carried out in the presence or absence of a solvent, but in order to carry out the reaction smoothly, it is preferable to use a solvent, and the solvent used is not particularly limited as long as it does not take part in this reaction. For example, diethyl Ethers such as ether, tetrahydrofuran or dioxane; halogenated hydrocarbons such as methylene chloride or carbon tetrachloride; secondary or tertiary alcohols such as isopropanol or tert-butanol; such as methyl ethyl ketone or methyl isobutyl ketone. Ketones; aromatic hydrocarbons such as benzene or chlorobenzene, and mixed solvents of these solvents.

The rearrangement catalyst is used in an amount equal to or more than the mole of the compound of formula (), preferably about 1.0 to 6.0 times, particularly about 1.5 times the mole.
Grind ~3.0 times the mole into as fine particles as possible,
Mixed with the compound of the formula () and heated to melt and stir, or in the coexistence with the above-mentioned inert solvent,
Heat and stir at 80-200°C, preferably 100-160°C.
The reaction time usually takes 30 minutes to 5 hours.

In the absence of a solvent, it generally solidifies as the rearrangement reaction progresses, making stirring often difficult. In such cases, an appropriate amount of the inert solvent described above is added. What is important is to maintain sufficient contact between the compound of formula () and the rearrangement catalyst, and it is desirable to use as little solvent as possible. Further, the presence of a small amount of water is preferable because it accelerates the reaction, but at the same time, the by-product of free benzoic acid is unavoidable, so it is desirable to keep the water content in the solvent within 1%.

After completion of the reaction, the target compound of the method of the present invention is collected from the reaction mixture by a conventional method. For example, after the reaction is completed, the target compound is obtained as a salt of the rearrangement catalyst by distilling off the solvent from the reaction mixture.
The desired compound of the obtained salts can be isolated in a free state by adjusting the pH to 3 or less by usually adding an acid. This product can be further purified by conventional methods such as recrystallization to obtain a pure product.

In carrying out the method of the present invention, the compound having the above formula () used as a raw material compound is 1-
These compounds are new except for benzoyl-5-hydroxy-3-methylpyrazole (Japanese Patent Publication No. 48-33132).

The compound having the general formula () is produced by the following series of reactions.

(In the formula, R ₁ , X and n have the same meanings as described above, and R ₂ represents a lower alkyl group.) Each step will be explained below.

Step A-1 is a step for producing a compound having the above general formula (), and is achieved by bringing an equimolar amount of hydrazine () into contact with the ketoester (). The reaction is preferably carried out in the presence of a solvent. The solvent used is not particularly limited as long as it does not participate in this reaction, and includes, for example, alcohols such as methanol, ethanol, or isopropanol; ethers such as dioxane or tetrahydrofuran; halogenated hydrocarbons such as chloroform or methylene chloride. and mixtures of these solvents. The reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature. The time required for the reaction is 5 to 20 hours.

After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method. For example, it can be obtained by distilling off the solvent from the reaction mixture. The crude target compound can also be purified by conventional methods such as recrystallization.

Step A-2 is a step for producing a compound having the above general formula (), in which the compound having the above general formula () is brought into contact with each other in an inert solvent in the presence of an equimolar to slightly excess base catalyst. It is achieved by doing so. Base catalysts used in the reaction include, for example, alkoxides such as sodium methoxide, sodium ethoxide or potassium tert-butoxide; metal hydrides such as sodium hydride or potassium hydride; sodium carbonate or potassium carbonate. and organic lithiums such as n-butyllithium.
Inert solvents used include, for example, alcohols such as methanol or ethanol; ethers such as ethyl ether or tetrahydrofuran; ketones such as acetone or methyl isobutyl ketone; amides such as hexamethylformamide; Examples include mixed solvents of solvents. The reaction temperature is not particularly limited and is usually -
It is carried out at a temperature of about 40°C to 5°C. The time required for the reaction is 2 to 24 hours.

After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method. For example, it can be obtained by distilling off the solvent from the reaction mixture. The crude target compound can also be purified by conventional methods such as recrystallization.

Among the compounds having the general formula (), R ₁
is a methyl group can also be obtained by dehydrating and ring-closing hydrazide () obtained by reacting diketene () and hydrazine () in the presence of an acid catalyst (method B).

Step B-1 is a step for producing a compound having the general formula (), and is achieved by bringing diketene () and hydrazine () into contact in an inert solvent.

The solvent used is not particularly limited as long as it does not participate in this reaction; for example, aromatic hydrocarbons such as benzene or toluene; halogenated hydrocarbons such as chloroform or tetrachloroethane; ethyl ether or Examples include ethers such as tetrahydrofuran; nitrites such as acetonitrile or propionitrile. The reaction temperature is not particularly limited, and the reaction is usually carried out around room temperature. The time required for the reaction is 2 to 6 hours.

After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method.

Step B-2 is a step for producing a compound having the general formula (), and is achieved by contacting the compound having the general formula () in the presence of an acid catalyst in an inert solvent.

Acid catalysts used in the reaction include sulfonic acids such as p-toluenesulfonic acid; Lewis acids such as aluminum chloride or trifluoroboron; carboxylic acids such as acetic acid or propionic acid; mineral acids such as hydrochloric acid or sulfuric acid. etc., and for compounds having the above general formula ()
Add 0.5 to 10% by weight. Inert solvents used include, for example, aromatic hydrocarbons such as benzene or toluene; halogenated hydrocarbons such as chloroform or tetrachloroethane; ethers such as ethyl ether or tetrahydrofuran; Examples include mixed solvents. There is no particular restriction on the reaction temperature, and the reaction is usually
It is carried out at a temperature of about 0° to 150°C. The time required for the reaction is 2 to 12 hours.

After the reaction is completed, the target compound is collected from the reaction mixture by a conventional method. For example, it can be obtained by washing the reaction mixture with water and distilling off the solvent. The crude target compound can also be purified by conventional methods such as recrystallization.

The pyrazole derivative () obtained by the method of the present invention is a herbicide (see Japanese Patent Publication No. 54-36648).
It is a compound useful as a synthetic intermediate. For example, by reacting a compound having the general formula () with a compound having the general formula R ₃ -Y () (wherein R ₃ represents a lower alkyl group and Y represents an acid residue). general formula (wherein R ₁ , R ₃ , X and n have the same meanings as defined above) can be obtained.

Next, the method of the present invention will be explained in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Example 1 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole Dissolve 1.0 g of 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole in 50 ml of dichloroethane. After that, aluminum chloride 0.74g
was added and heated at 90-95°C for 4 hours. After cooling, the reaction solution was poured into a mixture of 50 g of ice and 2 ml of concentrated hydrochloric acid, the precipitated crystals were collected, and recrystallized from methanol to obtain 0.69 g of the target compound with a melting point of 250-253°C ( yield 69%).

In addition, in the raw material compound, 4 observed at δ5.02
The proton signal at position disappeared.

Elemental analysis value (%) Calculated value as C ₁₁ H ₈ Cl ₂ N ₂ O ₂ C, 48.73; H, 2.97; N, 10.33; Cl, 26.15 Actual value C, 48.63; H, 3.01; N, 10.24; Cl, 26.52 According to the method of Example 1 above, using aluminum chloride as a catalyst, 1-benzoyl-3-methyl-5-hydroxypyrazole was converted to 4-benzoyl-3-methyl-
5-Hydroxypyrazole [melting point 279-280°C (yield 60%)] was converted into 1-(2-chlorobenzoyl)-3-methyl-
4-(2-chlorobenzoyl)-3-methyl-5-hydroxypyrazole [melting point 232-236°C (yield 62%)] was produced from 5-hydroxypyrazole.

Example 2 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole 1.0 g of 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole was added to 50 ml of tert-butanol. After dissolving in the solution, add 1.53 g of potassium tert-butoxide and 0.35 g of imidazole and heat at 80℃.
Heated for 12 hours. After cooling, the solvent was distilled off under reduced pressure, the residue was poured into ice water, acidified with hydrochloric acid, and the precipitated crystals were collected and dried. Recrystallization from methanol gave 0.69 g of the target compound (yield 69%).

The product was identical to the compound produced in Example 1.

Example 3 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole Dissolve 1.0 g of 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole in 50 ml of isopropanol. Thereafter, 1.71 g of potassium carbonate was added and heated under reflux for 15 hours. After cooling, the solvent was distilled off under reduced pressure, the residue was poured into ice water, acidified with hydrochloric acid, and the precipitated crystals were collected and dried. Recrystallization from methanol gave 0.52 g of the target compound (yield: 52
%).

The product was identical to the compound produced in Example 1.

Example 4 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole 0.28 g of sodium metal in 50 ml of isopropanol
After dissolving 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole
1.0 g was added and heated under reflux for 12 hours. After cooling, the solvent was distilled off under reduced pressure, the residue was poured into ice water, acidified with hydrochloric acid, and the precipitated crystals were collected and dried. Recrystallization from methanol gave 0.31 g of the target compound (yield 31%).

The product was identical to the compound produced in Example 1.

Example 5 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole 1.0 g of 1-(2,4-dichlorobenzoyl)-5-hydroxy 3-methylpyrazole is added to 50 ml of tert-butanol. After dissolving, 0.42 g of imidazole was added and heated under reflux for 15 hours. After cooling, the solvent was distilled off under reduced pressure, the residue was poured into ice water, acidified with hydrochloric acid, and the precipitated crystals were collected and dried. Recrystallization from methanol gave 0.38 g of the target compound (yield 38%).

The product was identical to the compound produced in Example 1.

Example 6 4-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole Dissolve 1.0 g of 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole in 50 ml of isopropanol. Thereafter, 1.71 g of potassium carbonate and 0.39 g of imidazole were added and heated at 80° C. for 15 hours. After cooling, the solvent was distilled off under reduced pressure, the residue was poured into ice water, acidified with hydrochloric acid, and the precipitated crystals were collected. Recrystallize from methanol to obtain the target compound.
0.69g was obtained (yield 69%).

The product was identical to the compound produced in Example 1.

Reference Example 1 Methyl 2,4-dichlorobenzoylhydrazoacetoacetate 2.26 g of methyl acetoacetate and 4.0 g of 2,4-dichlorobenzoylhydrazine were added to 100 ml of methanol, and the mixture was stirred at room temperature for 17 hours. After the stirring was completed, methanol was distilled off. Methylene chloride was added to the residue, which was diluted, washed with water, dried over anhydrous sodium sulfate, and concentrated to dryness. The obtained crude crystals were recrystallized from isopropyl ether to a melting point of 149-150℃.
5.91 g of the target compound having the following were obtained (yield: 100%).

Reference example 2 N-acetoacetyl-N'-2,4-dichlorobenzoylhydrazine 3 g of 2,4-dichlorobenzoylhydrazine and 3.6 diketene in 130 ml of tetrahydrofuran
g and stirred at room temperature for 4.5 hours. The reaction solution was concentrated to dryness, and the obtained crude crystals were washed with isopropyl ether and dried to obtain 3.75 g of the target compound having a melting point of 172-173°C (yield: 88.9%).

Reference Example 3 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole After dissolving 303 mg of methyl 2,4-dichlorobenzoyl hydrazoacetoacetate in a mixture of 10 ml of methanol and 5 ml of dimethylformamide, -5
56 mg of sodium methoxide was added at a temperature below 0.degree. C., and the mixture was further stirred at the same temperature for 24 hours. After stirring, the reaction mixture was adjusted to pH=3 with 2N hydrochloric acid solution, concentrated to 1/3 volume, and poured into a large amount of water. Next, extraction was performed with methylene chloride, the extract was concentrated, and the resulting crude crystals were washed with isopropyl ether and dried to determine the melting point.
214 mg of the target compound having a temperature of 161-163°C was obtained (yield 79.0%).

Reference example 4 1-(2,4-dichlorobenzoyl)-5-hydroxy-3-methylpyrazole N-acetoacetyl-N'-dichlorobenzoylhydrazine 2.5 g and p-toluenesulfonic acid 10
mg, dichloroethane 60ml, tetrachloroethane 20ml
85-90℃ after dissolving in a mixture of ml and 55ml of benzene.
The mixture was heated for 1.5 hours. After cooling, the solvent was concentrated under reduced pressure, and the solid residue was washed with isopropyl ether and subjected to silica gel column chromatography (eluent: benzene:ethyl acetate = 5:1) to fractionate and purify the melting point. Target compound with temperature of 161-163℃
1.28g was obtained (yield 54.7%).

Claims (1)

[Claims] 1 formula (In the formula, R ₁ represents a lower alkyl group, X represents a halogen atom, and n represents 0, 1 or 2.)
a pyrazole derivative having the formula in the presence of a catalyst selected from aluminum chloride, imidazole, alkali metal carbonate and alkali metal alkoxide A method for producing a 4-benzoylpyrazole derivative having the formula (wherein R ₁ , X and n have the same meanings as defined above).