JPH0788362B2 - Process for producing pyrazole carboxylic acid chlorides - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing pyrazolecarboxylic acid chlorides useful as a raw material for medicines, agricultural chemicals and the like.

[Conventional technology]

As a conventional method for producing pyrazolecarboxylic acid chlorides, a method using thionyl chloride (JP-A-60-
Nos. 34949, Agric.Biol.Chem., 4 8 ( 1), 45~50,1984,
Aust.J.Chem., 1983, 36, 135~147 ,) has been known.

[Problems to be Solved by the Invention]

In the method using thionyl chloride, it is difficult to control the reaction because it causes an extremely violent reaction with pyrazolecarboxylic acids, and at the same time, a large amount of corrosive sulfurous acid gas is generated with a rapid heat generation. To do. Therefore, there are problems in the industrial manufacturing method such as an apparatus for processing a large amount of by-produced sulfurous acid gas and complicated labor.

[Means and Actions for Solving the Problems] As a result of diligent studies on the above problems, the present inventors have found a production method of reacting a pyrazolecarboxylic acid with phosgene or trichloromethylchloroformate, and arrived at the present invention. .

That is, the general formula (I) (In the formula, R ₁ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a lower alkyl group substituted with a halogen atom or a lower alkoxy group, R ₂ is a lower alkyl group, a lower alkenyl group, an alkylcarbamoyl group or A pyrazolecarboxylic acid represented by a lower alkyl group substituted with a halogen atom or a lower alkenyl group substituted with a halogen atom is reacted with phosgene or trichloromethylchloroformate (II). ) (In the formula, R ₁ and R ₂ are the same as those in the general formula (I).) The method for producing a pyrazole carboxylic acid chloride.

The pyrazole carboxylic acids of general formula (I), for example, if the non-limiting illustrated wherein R _1, hydrogen, fluorine, chlorine, bromine, iodine, methyl group, ethyl group, n- propyl group, iso- Propyl group, n-butyl group, sec-butyl group,
iso-butyl group, tert-butyl group, n-pentyl group, 1
-Methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1-dimethylpropyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 2-
Methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 3,3-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 1-ethyl-2-methylpropyl group, 1-ethylbutyl group, 2-ethylbutyl group, trifluoromethyl group, chloromethyl group, trichloromethyl group, methoxymethyl group, ethoxymethyl group, propoxymethyl group, methoxy group, ethoxy Groups, propoxy groups and the like, and as R ₂ , methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, sec-butyl group, iso-butyl group, tert-butyl group, n- Pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1
-Dimethylpropyl group, 2,2-dimethylpropyl group, n
-Hexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group,
3,3-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3
-Dimethylbutyl group, 1-ethyl-2-methylpropyl group, 1-ethylbutyl group, 2-ethylbutyl group, β,
β, β-trifluoroethyl group, 2-propenyl group, 1
-Methyl-2-propenyl group, 2-methyl-2-propenyl group, 3-chloropropenyl group, 2-butenyl group, methylcarbamoyl group, ethylcarbamoyl group, propylcarbamoyl group and the like.

Since the reaction of the present invention is carried out in a solution or suspension state, it is preferably carried out in a solvent. Any solvent may be used as long as it is inert to the reaction. For example, aromatic hydrocarbons such as benzene, toluene, xylene, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, ethers such as dioxane, ethyl acetate, butyl acetate, esters such as ethyl propionate, N, N-dimethylformamide. , 1,3-dimethyl-2-
Examples include, but are not limited to, aprotic polar solvents such as imidazolidinone and dimethyl sulfoxide, halogenated hydrocarbons such as tetrachloroethylene and chlorobenzene, and courageous bases such as pyridine and picoline. It is also possible to mix these solvents and use them as a reaction solvent.

The amount of the solvent added is 1 mol of pyrazolecarboxylic acid
It is efficient to use 0.5 to 10, preferably 1 to 4.

The addition amount of phosgene or trichloromethylchloroformate to the pyrazolecarboxylic acid is 1.0 to 10.0 mol, preferably 1.0 to 1.0 mol, relative to 1 mol of the pyrazolecarboxylic acid.
5.0 mol is good.

The reaction temperature may be from room temperature to the boiling point of each solution.

The reaction time is 5 to 50 hours, preferably 8 to 20 hours under heating under reflux when phosgene is blown into the solution of pyrazolecarboxylic acids. When trichloromethyl chloroformate is added dropwise to the pyrazolecarboxylic acid solution, the heating is carried out under reflux for 2 to 40 hours, preferably 5 to 20 hours.

After completion of the reaction, the reaction solution is filtered and the filtrate is concentrated to obtain pyrazolecarboxylic acid chlorides. Purity analysis of the obtained pyrazole carboxylic acid chlorides is by gas chromatography.

The preferred embodiments of the present invention are as follows.

To a solution or suspension prepared by charging a predetermined amount of pyrazolecarboxylic acid and a predetermined solvent into a reactor equipped with a thermometer, a stirrer, and a condenser, blow phosgene or drop trichloromethyl chloroformate at a predetermined temperature. The reaction is carried out under reflux for a predetermined time.

After completion of the reaction, the desired pyrazolecarboxylic acid chlorides can be obtained by filtering the reaction solution and concentrating the filtrate.

The distillate at the time of concentration can be recovered as a solvent in the reaction system again.

〔Example〕

 Hereinafter, the present invention will be specifically described with reference to examples.

Example 1 In a 100 ml three necked flask, 1,3-dimethylpyrazole 4-
5 g (0.036 mol) of carboxylic acid was suspended in 50 ml of toluene, and phosgene was blown thereinto under reflux with heating at a flow rate of 320 ml / hour for 10 hours (phosgene, 0.144 mol). After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to obtain 5.5 g of 1,3-dimethylpyrazole-4-carboxylic acid chloride. The purity was 98.0% and the yield was 98.0%.

Example 2 A device similar to that of Example 1 was used, except that 1,3-diethylpyrazole 5
-Suspension of 6.7 g (0.04 mol) of carboxylic acid in 100 ml of dioxane and heating under reflux, trichloromethyl chloroformate
11.9 g (0.06 mol) was added dropwise over 8 hours. After the dropping was completed, stirring was continued for another 2 hours. After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to obtain 6.2 g of 1,3-diethylpyrazole 5-carboxylic acid chloride. Purity 97.5%, Yield 95.0%
Met.

Example 3 In a device similar to that of Example 1, 1-methyl-3-trifluoromethylpyrazole-4-carboxylic acid 6.7 g (0.03 mol)
Suspended in 80 ml of butyl acetate and heated under reflux to remove phosgene 14
Bubbling was carried out for 14 hours at a flow rate of 0 ml / hour (phosgene: 0.09 mol). After completion of the reaction, the reaction solution is filtered and the filtrate is concentrated to
6.7 g of methyl-3-trifluoromethylpyrazole-4-carboxylic acid chloride was obtained. Purity 97.0%, Yield 95.0%
Met.

Example 4 In the same apparatus as in Example 1, 6.2 g (0.04 mol) of 1-methyl-3-methoxypyrazole-5-carboxylic acid was dissolved in 100 ml of dimethyl sulfoxide, and phosgene was adjusted to 50 at a temperature of 140 ° C.
Bubbling was carried out for 8 hours at a flow rate of 0 ml / hour (phosgene: 0.18 mol). After completion of the reaction, the reaction solution is filtered and the filtrate is concentrated to give 1-
6.6 g of methyl-3-methoxypyrazole-5-carboxylic acid chloride was obtained. The purity was 98.0% and the yield was 97.0%. Example 5 In the same apparatus as in Example 1, 5.0 g (0.03 mol) of 1-allyl-3-methylpyrazole-4-carboxylic acid was suspended in 100 ml of chlorobenzene and heated. Under reflux, bubbling was carried out for 15 hours at a flow rate of phosgene of 180 ml / hour (phosgene: 0.12 mol). After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to give 1-allyl-
5.3 g of 3-methylpyrazole-4-carboxylic acid chloride
Got The purity was 97.0% and the yield was 98.0%.

Example 6 In a device similar to that of Example 1, 1-methylcarbamoyl-3 was used.
-Methylpyrazole-4-carboxylic acid 9.1 g (0.05 mol)
Was suspended in 130 ml of pyridine, and 13.8 g (0.07 mol) of trichloromethyl chloroformate was added dropwise over 10 hours while heating under reflux. After completion of dropping, the mixture was further stirred for 2.5 hours. After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to obtain 9.7 g of 1-methylcarbamoyl-3-methylpyrazole-4-carboxylic acid chloride. The purity was 97.0% and the yield was 93.0%.

Example 7 In the same apparatus as in Example 1, 8.4 g (0.04 mol) of 1-hexyl-3-methylpyrazole-4-carboxylic acid was suspended in 120 ml of ethylene glycol dimethyl ether, and phosgene was heated under reflux at 250 ml / hour. For 18 hours (phosgene: 0.20 mol). After the completion of blowing, the mixture was further stirred for 2.0 hours. After completion of the reaction, the reaction solution was filtered and the filtrate was condensed to obtain 8.7 g of 1-hexyl-3-methylpyrazole-4-carboxylic acid chloride. The purity was 96.0% and the yield was 91.0%.

〔The invention's effect〕

According to the method of the present invention, it is easy to control the reaction, and
The desired product can be obtained with high purity and high yield without treatment of by-products. Further, the obtained pyrazole carboxylic acid chlorides can be used in the next step as an intermediate for medicines, agricultural chemicals and the like without any purification operation, which is an industrially useful method.

Claims (1)

[Claims] 1. A general formula (I) (In the formula, R ₁ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a lower alkyl group substituted with a halogen atom or a lower alkoxy group, R ₂ is a lower alkyl group, a lower alkenyl group, an alkylcarbamoyl group or A pyrazolecarboxylic acid represented by a lower alkyl group substituted with a halogen atom or a lower alkenyl group substituted with a halogen atom is reacted with phosgene or trichloromethylchloroformate (II). ) (In the formula, R ₁ and R ₂ are the same as those in the general formula (I).) A method for producing a pyrazole carboxylic acid chloride.