KR860001878B1 - Preparation process for pyrazide derivatives - Google Patents

Abstract

Prepn. of pyrazole derivs. of formula(I) (where R1 is lower alkyl; X is halogen atom, lower alkyl or nitro; n is 0, or integer of 1-3; when n is 2 or 3, X's may be identical) comprises heating a pyrazole deriv. of formula (II) in the presence of catalyst. (I) is valuable as intermediate in the prepn. of herbicidal compd. The reaction of (I) with R3-Y (R3 is lower alkyl; Y is acid residue) gives the herbicidal cpd..

Description

Preparation of Pyrazole Derivatives

The present invention is a general formula

(Wherein R ₁ represents a lower alkyl group and X represents a halogen atom, a lower alkyl group or a nitro group. N represents an integer of 0 or 1 to 3, and when n is 2 or 3, X may be the same or different from each other.) It relates to a method for producing a 4-benzoyl pyrazole derivative having.

In the above general formula (I), as the lower alkyl group, a linear or branched lower alkyl group having 1 to 3 carbon atoms such as methyl, ethyl, n-propyl or isopropyl can be given. And halogen atoms represent chlorine, bromine, fluorine or iodine.

According to the method of the present invention, the compound having the general formula (I) can be prepared as follows. General formula

It can be obtained by contacting a pyrazole derivative having the formula (wherein R ₁ and n have the same meaning as described above) with a catalyst.

In carrying out the present invention, the reaction is easily carried out by heating the compound having the general formula (II) in the presence of an animal or more catalyst. As a catalyst used, Lewis acids, such as aluminum chloride, titanium tetrachloride, or a ditin tin chloride; Basic alkali metal salts or basic alkaline earth metal salts and mixtures thereof. The "basic" salts herein refer to salts of alkali metals or alkaline earth metals that are alkaline when used as an aqueous solution, and refer to salts of weak acids and strong bases. Carbonates such as, for example, sodium carbonate or potassium carbonate; Hydroxides such as calcium hydroxide or magnesium hydroxide; Cyanamides such as calcium cyanamide; Alkoxides such as sodium methoxide, potassium ethoxide sodium isopropoxide or potassium tert-butoxide and the like. Moreover, you may use the system in which these "basic" salts are formed in a reaction solvent. For example, when metal sodium is dissolved in isopropanol, a solution containing sodium isopropoxide is obtained, but such an alcohol solution may be used as a reaction solvent as it is.

The reaction proceeds once the compound having the general formula (II) forms a salt of the potential catalyst, but the potential reaction may be carried out after isolating the double salt, and the potential reaction may be performed without isolation.

The reaction is carried out in the presence or absence of a solvent, but in order to perform the reaction smoothly, it is preferable to use a solvent. The solvent used is not particularly limited unless it is involved in the reaction, for example, diethyl ether, tetrahydro Ethers such as furan or dioxane; Halogenated hydrocarbons such as methylene chloride or carbon tetrachloride; Isopropane or tert-butanol and secondary or tertiary alcohols; Ketones such as methyl ethyl ketone or methyl isobutyl ketone; Aromatic hydrocarbons, such as benzene or chlorobenzene, and the mixed solvent of these solvents are mentioned.

The dislocation catalyst is pulverized or more, preferably about 1.0 to 6.0 times molar, particularly 1.5 to 3.0 times molar, with respect to the compound of the formula (II), pulverized into fine particles as much as possible, mixed with the compound of the formula (II), heated to coagulation stirring, or the foregoing. Under coexistence with one inert solvent, the mixture is heated and stirred at 80 to 200 캜, preferably at 100 to 160 캜. The reaction time usually requires 30 minutes to 5 hours.

In many solvents, it is generally solidified with advancing of a dislocation reaction and it becomes difficult to stir. In such a case, an appropriate amount of the above-mentioned inert solvent is added. It is important to maintain sufficient contact between the compound of formula (II) and the potential catalyst, and the use of the solvent is preferably as small as possible.

In addition, the presence of a small amount of water is preferable to promote the reaction, but at the same time, by-products of benzoic acid in the glass are inevitable, so it is preferable to keep the water content in the solvent within 1%.

After completion of the reaction, the target compound of the present invention is taken from the reaction mixture by a conventional method. For example, the target compound is obtained as a salt of a potential catalyst by holding a solvent from the reaction mixture after completion of the reaction. These salts obtained can be isolated in the state of glass by adjusting the pH to 3 or less by adding acid. This can be refined by commercial methods such as recrystallization again to obtain the pure product.

The compound having the formula (II) used as a starting compound in carrying out the method of the present invention is new except for 1-benzoin-5-hydroxy-3-methyl pyrazole (JP-A-48-33132). Compound.

Compounds having the general formula (II) are prepared by the following series of reactions.

(Wherein R ₁ , X and n have the same meaning as described above and R ₂ represents a lower alkyl group.)

Each process is demonstrated below.

The A-1 step is a process for producing a compound having the general formula (V), which is accomplished by contacting equimolar hydrazine (IV) with ketoester (III). The reaction is most suitably carried out in the presence of a solvent. The solvent to be used is not particularly limited as long as it is not involved in the present reaction, for example, alcohols such as methanol, ethanol or isopropanol; Ethers such as dioxane or tetrahydrofuran; And halogenated hydrocarbons such as chloroform or methylene chloride and mixed solvents of these solvents. The reaction temperature is not particularly limited, and the reaction is usually performed at room temperature. The time required for the reaction is 5 to 20 hours.

After completion of the reaction, the target compound is collected from the reaction mixture by a conventional method. For example, it is obtained by holding a solvent from a reaction mixture. The target compound of preparation can also be refine | purified by a normal method, for example, a recrystallization method.

The A-2 process is a process for preparing a compound having the general formula (II), which is accomplished by contacting the compound having the general formula (V) in an inert solvent in the presence of equimolar to slightly excess base catalyst. As a base catalyst used for reaction, For example, Alkoxides, such as sodium methoxide, sodium ethoxide, or potassium tert-butoxide; Metal hydrides such as sodium hydride or potassium hydride; Carbonates such as sodium carbonate or potassium carbonate; and organic lithium such as n-butyllithium. As an inert solvent used, For example, Alcohol, such as methanol or ethanol; Ethers such as ethyl ether or tetrahydrofuran; Ketones such as acetone or methyl isobutyl ketone; Amides such as hexamethylphosphonamide and mixed solvents of these solvents. The reaction temperature is not particularly limited and is usually performed at -40 ° C to 5 ° C. The time required for response is 2 to 24 hours.

After completion of the reaction, the target compound is taken from the reaction mixture by a conventional method. For example, it is obtained by organic solvent from a reaction mixture. The target compound of preparation can also be refine | purified by a normal method, for example, a recrystallization method.

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

The B-I process is a process for producing a compound having the general formula (VII) and is achieved by contacting diketene (VI) and hydrazine (IV) in an inert solvent.

The solvent to be used is not particularly limited as long as it is not involved in the reaction, and examples thereof include aromatic hydrocarbons such as benzene or toluene; Halogenated hydrocarbons such as chloroform or tetra chloroethane; Ethers such as ethyl ether or tetrahydrofuran; Nitriles such as acetonitrile or propionitrile and the like. The reaction temperature is not particularly limited, and the reaction is usually performed in the vicinity. The time required for the reaction is 2 to 6 hours.

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

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

As an acid catalyst used for reaction, sulfonic acids, such as p-toluenesulfonic acid; Lewis acids such as aluminum chloride or trifluoroboron; Carboxylic acids such as acetic acid or propionic acid; And mineral acids such as hydrochloric acid or sulfuric acid, and 0.5 to 10% by weight based on the compound having the general formula (갖는). As an inert solvent used, for example. Aromatic hydrocarbons such as benzene or toluene; Halogen hydrocarbons such as chloroform or tetra chloroethane; Ethers such as ethyl ether or tetrahydrofuran; And mixed solvents of these solvents. The reaction temperature is not particularly limited, and the reaction is usually carried out at about 0 ° to 150 ° C. The time required for the reaction is 2 to 12 hours.

After completion of reaction, the target compound is taken from the reaction mixture by conventional methods. For example, the reaction mixture is washed with water to obtain a solvent. The target compound of preparation is a conventional method. For example, it can also refine | purify by the recrystallization method.

The pyrazole derivative (I) obtained by the method of the present invention is a compound useful as a synthetic intermediate of herbicides (see Japanese Patent Application No. 54-36648). For example, a compound having the general formula (I)

R ₃ -Y (Ⅷ)

Wherein R ₃ represents a lower alkyl group and Y represents an acid moiety.

A herbicide having (wherein R ₁ , R ₃ , X and n have the same meaning as described above) can be obtained.

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

Example 1

4- (2,4-dichlorobenzoyl) -5-hydroxy-3-methylpyrazole

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

Elemental Analysis Value (%) C ₁₁ H ₈ Cl ₂ N ₂ O ₂

Calculated C, 48.73 h, 2.97 N.10.33 Cl, 26.15

Found C, 48.63: H.3.01: N.10.24: Cl.26.52

Example 2

4- (32,4-dichlorobenzoyl) -5-hydroxy-3-methylpyrazole

1.0 g of 1- (2,4-dichlorobenzoyl) -5-hydroxy-3-methylpyrazole was dissolved in 50 ml of tert-butanol, and then 1.53 g of potassium tert-butoxide and 0.35 g of imidazole were added thereto at 80 ° C. Heated 12 hours. After cooling, the solvent was distilled off under reduced pressure, and the residue was poured into ice water, made acidic with hydrochloric acid, and the precipitated crystals were filtered and dried.

Recrystallization from methanol gave 0.69 g of the target compound. (Yield.69%)

The following compounds were prepared according to the method of Example 1 or 2 above.

4-benzoyl-3-methyl-5-hydroxy pyrazole

Melting Point 279 ~ 280 ℃

4- (2-chlorobenzoin) -3-methyl-5-hydroxypyrazole

Melting Point 232 ~ 236 ℃

Reference Example 1

Methyl 2,4-dichlorobenzoyl hydrazoacet acetate

Acetic acetic acid in 100 ml of methanol

2.26 g of methyl ester and 4.0 g of 2,4-dichlorobenzoyl hydrazine were added and stirred at room temperature for 17 hours. Methanol was distilled off after stirring was complete. Methylene chloride was added to the residue, washed with dilution, washed with water, dried over anhydrous sodium sulfate, and concentrated to solidity. The obtained crude crystal was recrystallized from isopropyl ether to obtain 5.91 g of the target compound having a melting point of 149 to 150 DEG C. (yield 100%)

Reference Example 2

N-acetyl N, -2,4-dichlorobenzoyl hydrazine

In 130 ml of tetrahydrofuran, 3 g of 2,4-dichlorobenzoylhydrazine and 3.6 g of dikerene were added, followed by stirring at room temperature for 4,5 hours. The reaction solution was concentrated to dryness, and the obtained crude crystal was washed with isopropyl ether and dried to obtain 3.75 g of the target compound having a melting point of 172 to 173 ° C. (Yield 88.9%).

Reference Example 3

Dicle 1- (2,4-Lorobenzoyl) -5-hydroxy-3-methylpyrazole

After dissolving 303 mg of methyl 2,4-dichlorobenzoyl hydrazoacetate acetate in a mixture of 10 ml of methanol and 5 ml of dimethylformamide, 56 mg of sodium methoxide was added at -5 ° C or lower, and stirred at the same temperature for 24 hours. After completion of the stirring, the reaction mixture was prepared with 2N hydrochloric acid solution at pH = 3, and concentrated to 1/3 of the mixture, and added to stock in a large amount of water. Subsequently, the crude crystals obtained by extraction with methylene chloride and concentration of the extract were washed with isopropyl ether and dried to give 214 mg of the target compound having a melting point of 161 to 163 占 폚 (yield 79.0%).

Reference Example 4

1- (2,4-dichlorobenzoyl) -5-hydroxy-3-methylpyrazole

2.5 g of N-acetyl N'-2,4-dichlorobenzoylhydrazine and 10 mg of p-toluenesulfonic acid were dissolved in a mixture of 60 mL of dichloroethane, 20 mL of tetrachloroethane and 55 mL of benzene, and heated at 85 to 90 ° C for 1.5 hours. After cooling, the solvent is concentrated under reduced pressure, and the solid residue is washed with isopropyl ether, poured into silica gel and column chromatography (eluent; benzene: ethyl acetate = 5: 1), and fractionated to obtain a melting point of 161 to 163 占 폚. Compound 1.28 g was obtained. (Yield 54.7%)

Claims (1)

A method for producing a 4-benzoylpyrazole derivative represented by the following formula (II), characterized by reacting a pyrazole derivative having the formula (I) in the presence of a catalyst.

(Wherein R ₁ represents a lower alkyl group and X represents a halogen atom, a lower alkyl group or a nitro group. N represents an integer of 0 or 1 to 3 and X may be the same or different from each other when n is 2 or 3.).