JPH01290662A - Production of pyrazolecarboxylic acid chlorides - Google Patents

Abstract

PURPOSE:To obtain the title substance useful as an intermediate of drugs and agricultural chemicals in ready reaction control in high purity and in high yield without treating by-products by reacting a pyrazolecarboxylic acid with phosgene or trichloromethyl chloroformate. CONSTITUTION:1mol compound shown by formula I (R1 is H, halogen, lower alkyl, lower alkoxy, etc.: R2 is lwoer alkyl, lower alkenyl, alkylcarbamoyl, etc.) is reacted with 1.0-5.0mol phosgene of trichloromethyl chloroformate at normal temperature-the boiling point of a solvent for 5-20 hours to give a compound showhn by formula II. The reaction is preferably carried out in 1-4l solvent (e.g. benzene or THF) based on 1mol compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing pyrazolecarboxylic acid chlorides useful as raw materials for medicines, agricultural chemicals, etc.

[Conventional technology]

Conventional methods for producing pyrazole carboxylic acid chlorides include a method using thionyl chloride (Japanese Unexamined Patent Publication No. 1989-1999)
-34949, Agric, l1io1. Che-,
, AL (1).

45 ~50.1984, Au5t, J, Che
m,, 1983. n, 135-147,) are known.

(This is what the invention seeks to solve!) In the method using thionyl chloride described above, an extremely violent reaction occurs with the pyrazole carboxylic acids, so it is difficult to control the reaction. , and generates large amounts of corrosive sulfur dioxide gas. Therefore, there are problems in the industrial production process, such as the need for equipment to process large amounts of sulfur dioxide gas produced as a by-product, and the need for complicated labor.

(!!! Means and action for solving the problem) As a result of intensive study on the above problem, the present inventors discovered a production method in which pyrazole carboxylic acids are reacted with phosgene or trichloromethyl chloroformate, and the present invention has been realized. It has arrived.

That is, -More (+) (wherein R1 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, h is a lower alkyl group, a lower alkenyl , an alkylcarbamoyl group, a lower alkyl group substituted with a halogen atom, or a lower alkenyl group substituted with a halogen atom) is reacted with phosgene or trichloromethylchloroform-1-. This is a method for producing pyrazolecarboxylic acid chlorides represented by the following formula (where Rh, , Ih are the same as in general formula (1)).

Examples of the pyrazole carboxylic acids of general formula (1) include, but are not limited to, R1 in the formula: hydrogen, fluorine, chlorine, bromine, iodine, methyl group, ethyl group, topropyl group,
15o-propyl group, n-butyl group, 5ec-butyl group, 1so-butyl group, ter L-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3
-methylbutyl group, 1.1-dimethylpropyl group, 2.
2-dimethylpropyl group, n-hexyl 1&, 1-methylpentyl L, 2-methylpentyl group, 3-methylpentyl group, 1.1-dimelbutyl group, 2.2-dimethylbutyl group, 3.3-dimethyl Butyl L 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 group, propoxy group, etc., and as R□, methyl group, ethyl group, n-propyl group, 1sO-propyl group, i- butyl group, 5ee-butyl group, 1so-butyl group, tert
-butyl group, n-pentyl group, 1-methylbutyl group, 2
-Methylbutyl group, 3-methylbutyl group, 1.1-dimethylpropyl group, 2.2-dimethylpropyl Ln: hexyl group, l-methylpentyl group 5.2-methylpentyl group, 3-methylpentyl group 4-methylpentyl Base, 1.
1-dimerbutyl group, 2.2-dimethylbutyl group, 3.
3-dimethylbutyl L 1.2-dimethylbutyl group, 1
．． 3-dimethylbutyl group, l-ethyl-2-methylpropyl Ll-ethylbutyl group, 2-ethylbutyl group, β,
β, β, -trifluoroethyl group, 2-propenyl group,
1-methyl-2-propenyl 5.2-methyl-2-propenyl group, 3-chloropropenyl group, 2-butenyl group,
Methylcarbamoyl group, ethylcarbamoyl! and propylcarbamoyl group.

Since the reaction of the present invention is carried out in a solution or suspension state, it is preferably carried out in a solvent. The solvent may be anything inert to the reaction. For example, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and dioxane, and ethyl acetate and butyl acetate. , esters such as ethyl propionate, aprotic scratchy solvents such as N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone, and dimethyl sulfoxide, /S chloride of tetrachloroethylene, chlorobenzene, etc. Examples include, but are not limited to, hydrocarbons and organic 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 to be added is effectively 0.5 to 1 mol, preferably 1 to 41 mol per mol of pyrazole carboxylic acid.

The amount of phosgene or trichloromethyl chloroformate added to the pyrazole carboxylic acids is 1.0 to 10.0 mol, preferably 1.0 to 5.0 mol, per 7611 mol of pyrazole carbo.

The reaction temperature can be between room temperature and the boiling point of each solution.

When blowing phosgene into a solution of pyrazole carboxylic acids, the reaction time is 5 to 50 hours, preferably 8 to 20 hours under heating and reflux. In addition, when trichloromethyl chloroformate is added dropwise to a solution of pyrazole carboxylic acids, the solution is heated under reflux for 2 to 40 hours, preferably 5 to 2 hours.
It is 0 hours.

After the reaction is completed, the reaction solution is filtered and the filtrate is concentrated to obtain pyrazolecarboxylic acid chlorides. The purity of the obtained pyrazole carboxylic acid chloride was analyzed by gas chromatography.

Preferred embodiment B of the present invention is as follows.

Phosgene is blown into a solution or suspension containing a predetermined amount of pyrazole carboxylic acids and a predetermined solvent in a reactor equipped with a thermometer, stirrer, and condenser, and trichloromethyl chloroformate is added dropwise to the solution or suspension, and the mixture is refluxed at a predetermined temperature. Below, the reaction is carried out for a predetermined period of time.

After the reaction is completed, the desired pyrazolecarboxylic acid chloride can be obtained by filtering the reaction solution and concentrating the filtrate.

Note that the distillate during concentration can be recovered as a solvent to the reaction system again.

〔Example〕

Hereinafter, the present invention will be specifically explained with reference to Examples.

Example 1 5 g (0,036 mol) of 1,3-dimethylpyrazole-4-carboxylic acid was added to 50 mJ of toluene in a 100 sffi three-lens flask! phosgene was blown into the suspension at a flow rate of 320 l/hr for 10 hours under heating under reflux (phosgene.

After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to give 5.5 g of 1.3-dimethylpyrazole-4-
Carboxylic acid chloride was obtained. The purity was 98.0% and the yield was 98.0%.

Example 2 In the same apparatus as in Example 1, 6.7 g (0.04 mol) of 1,3-diethylpyrazole-5-carboxylic acid was suspended in 100 μl of dioxane and heated under reflux to dissolve trichloromethyl chloroformate. After 11.9 g (0.06 mol) was added dropwise for 8 hours, stirring was continued for an additional 2 hours.

After the reaction is completed, the reaction solution is filtered and the filtrate is condensed to give 1.3-
Dimethylpyrazole-5-carboxylic acid chloride 6゜2
I got g. The purity was 97.5% and the yield was 95.0%.

Example 3 Into the same apparatus as in Example 1, 6.7 g (0,0
3 mol) was suspended in 80 ml of butyl acetate, heated under reflux, and 140 ml of phosgene was added. After the completion of the reaction, which was blown for 14 hours at a flow rate of 7 hours (phosgene: 0.09 mol),
The reaction solution was filtered and the filtrate was concentrated to obtain 1-methyl-3-trifluoromethylpyrazole-4-carboxylic acid chloride 6.
．． 7g was obtained. The purity was 97.0% and the yield was 95.0%.

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 sl of dimethyl sulfoxide, and the temperature was 14.
Phosgene was blown in at a flow rate of 500*l for 7 hours at 0°C for 8 hours (phosgene: Q, 18 mol). After the reaction was completed, the reaction solution was filtered and the filtrate was concentrated to obtain 1-methyl-3-methoxypyrazole, -6.6 g of carboxylic acid chloride was obtained. Example 5 with a purity of 98.0% and a yield of 97.0% Into the same apparatus as in Example 1, 5.0 g (0.03 mol) of 1-allyl-3-methylpyrazole-4-carboxylic acid was added. Chlorobenzene 100+mj! After the reaction was completed, the reaction solution was filtered and the filtrate was concentrated to obtain 1-allyl-3-methyl. 5.3 g of pyrazole-4-carboxylic acid chloride was obtained. Purity 9
The yield was 98.0%.

Example 6 In the same apparatus as in Example 1, 1-methylcarbamoyl-3
-Methylpyrazole-4-carboxylic acid 9.1g (0,0
5 mol) was suspended in 130 m2 of pyridine, and 13.8 g (0.07 mol) of trichloromethylchloroforme was suspended in 130 m2 of pyridine, and 13.8 g (0.07 mol) of trichloromethylchloroforme was added dropwise over 10 hours.
．． Stirred for 5 hours. After the reaction was completed, 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 l-hexyl-3-methylpyrazole-4-carboxylic acid was added to 120+ej! of ethylene glycol dimethyl ether. 250 ml of phosgene was blown in for 18 hours at a flow rate of 7 hours under heating under reflux (phosgene: 0.20 mol). After the blowing was completed, the mixture was further stirred for 2.0 hours. Filter and condense the filtrate to l-hexyl
3-Methylpyrazole-4-carboxylic acid chloride8.
7g was obtained. The purity was 96.0% and the yield was 91.0%.

〔Effect of the invention〕

According to the method of the present invention, the reaction can be easily controlled, and
The desired product can be obtained with high purity and high yield without the need to treat by-products. Furthermore, the obtained pyrazolecarboxylic acid chlorides can be used in the next step as intermediates for medicines, agricultural chemicals, etc. without any purification operations, and this is an industrially useful method.

Patent applicant: Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Claims] 1. General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R_1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, or a lower A lower alkyl group substituted with an alkoxy group, R_2 represents a lower alkyl group, a lower alkenyl group, an alkylcarbamoyl group, a lower alkyl group substituted with a halogen atom, or a lower alkenyl group substituted with a halogen atom. General formula (II) characterized by reacting pyrazole carboxylic acids with phosgene or trichloromethyl chloroformate ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R_1 and R_2 are the general formula (I ). Method for producing pyrazole carboxylic acid chlorides represented by ).