JP3097193B2 - Method for producing pyrazole derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a pyrazole derivative useful as a starting compound for medicines, agricultural chemicals and the like.

[0002]

2. Description of the Related Art As a method for producing pyrazole derivatives, there is known a method for producing pyrazole derivatives by reacting pyrazolones with phosphorus oxychloride and dimethylformamide (JP-A-63-267762, Chemical Abstracts).
73 3844w (1970)).

[0003]

However, in this conventional method, a large amount of phosphoric acid and hydrochloric acid are generated during the post-treatment due to decomposition of phosphorus oxychloride and the like. Therefore, a large amount of alkali is required to neutralize these acids, and as a result, production efficiency is deteriorated. In addition, in recent years when environmental problems are becoming serious, it is necessary to remove phosphorus using wastewater containing phosphorus by using a special treatment facility. Further, there is a problem in industrial production such as phosphorus oxychloride itself which is expensive as a reactant.

The present inventors have conducted intensive studies on a method for producing a pyrazole derivative in order to solve the above-mentioned problems. As a result, the pyrazole can be easily and in high yield by reacting pyrazolones with dimethylformamide in the presence of phosgene. Have been found, and the present invention has been achieved.

[0005]

That is, the present invention provides a compound represented by the following general formula (1): Wherein R ₁ and R ₂ represent the same or different lower alkyl groups, and reacting the pyrazolones with dimethylformamide in the presence of phosgene; (Wherein R ₁ and R ₂ are the same as the groups described above).

[0006] The reaction of the present invention is carried out in a solution or suspension, and is preferably carried out using a solvent. The solvent is not limited as long as it is inert to the reaction,
For example, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as tetrachloroethylene and chlorobenzene, ethers such as tetrahydrofuran, ethylene glycol dimethyl ether and dioxane, and esters such as ethyl acetate, butyl acetate and ethyl propionate. , N, N-dimethylformamide, 1,3-
Aprotic polar solvents such as dimethyl-2-imidazolidinone, dimethyl sulfoxide, pyridine, picoline,
Organic bases such as triethylamine are exemplified. Further, these solvents can be mixed and used as a reaction solvent.

The amount of dimethylformamide to be used may be at least equimolar to 1 mol of the pyrazolone, and is preferably in the range of about 1.1 to 1.6 mol. The amount of phosgene used may be 2.0 mol or more, preferably about 2 to 3 mol, per mol of pyrazolones.

[0008] The reaction temperature is selected from room temperature to the boiling point of the respective solvent, preferably in the range of about 60 to 90 ° C.

The reaction is carried out by blowing phosgene into a solution containing dimethylformamide in which heated pyrazolones are dissolved or suspended, or by adding dimethylformamide to a solvent and / or a solution of pyrazolones and adding the solvent. There is a method in which the reaction is carried out while adding a pyrazolone solution and phosgene to the mixture while heating.

In the method in which the total amount of pyrazolones is previously charged and reacted, about 0.2% of a dimer represented by the following formula is by-produced and mixed into the product. On the other hand, a method in which the reaction is carried out while adding both the solution of pyrazolones and phosgene together is preferable because the above-mentioned dimer is not produced as a by-product and the yield is slightly improved.

The reaction time varies depending on the amount of the reactants, the reaction temperature and the like, but may be selected from the range of about 1 to 48 hours.

After completion of the reaction, a pyrazole derivative as a target compound can be obtained by performing a conventional method such as pouring water into the reaction solution and neutralizing the reaction solution with an alkali. The pyrazole derivative can be used as it is or, if necessary, further purified by a means such as distillation and recrystallization, and used as a starting compound.

[0013]

Industrial Applicability According to the method of the present invention, a pyrazole derivative useful as a starting compound for medicines, agricultural chemicals and the like can be easily produced at a high yield.

[0014]

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.

Example 1 50 g of 1,3-dimethyl-2-pyrazolin-5-one
(0.446 mol), 50 g of dimethylformamide
(0.684 mol) was added to 200 g of chlorobenzene and heated to 70 to 80 ° C. 120 g of phosgene there
(1.213 mol) was blown at 70 to 80 ° C. over 4 hours, and then kept at the same temperature for 5 hours. After the reaction solution was cooled to room temperature, 100 g of water was injected while removing heat, and 23%
The solution was neutralized with 200 g (1.15 mol) of an aqueous NaOH solution.

The organic layer was separated by liquid separation and concentrated under reduced pressure to obtain 65.2 g of pale yellow crystals of 5-chloro-1,3-dimethylpyrazole-4-carbaldehyde. The yield is 92.2% and the purity of the crystals is 99.0%.
Met.

Comparative Example 1 10 g of 1,3-dimethyl-2-pyrazolin-5-one
(0.089 mol), 8.4 g of dimethylformamide
(0.115 mol) in 10 g of dichloroethane,
27.3 g (0.178 mol) of phosphorus oxychloride was added dropwise while maintaining the internal temperature at 30 ° C. or lower. Thereafter, the temperature was raised to 90 ° C. and maintained for 6 hours. After the reaction solution was cooled to room temperature, 30 g of water was injected while 30 g of dichloroethane was added and heat was removed. Next, the reaction solution was treated with a 23% NaOH aqueous solution (114 g).
(0.656 mol), sodium phosphate crystals were precipitated, and 200 g of water was added and dissolved.

The layers were separated and the aqueous layer was extracted four times with 30 g of dichloroethane. The organic layers are combined and concentrated under reduced pressure to give 5-chloro-1,3-dimethylpyrazole-4.
-12.4 g of yellow crystals of carboaldavid were obtained. The yield was 87.7% and the purity of the crystals was 99.0%.

Example 2 1,3-Dimethyl-2-pyrazolin-5-one 50.0
g (0.446 mol) and dimethylformamide 52.2
g (0.714 mol) was added to 50 g of chlorobenzene, heated to 70 ° C. and dissolved. Separately, 150 g of chlorobenzene was heated to 70 ° C., and a solution of 1,3-dimethyl-2-pyrazolin-5-one and dimethylformamide in chlorobenzene was added dropwise and 60.0 g of phosgene was added.
(0.607 mol) at 70 ° C. for 2 hours. At the same temperature, 30.0 (0.303 mol) of phosgene was further blown in for 1 hour, and the mixture was kept at 70 ° C. for 4 hours.

Next, 2.0 g of dimethylformamide (0.
027 mol) and 12.5 g (0.126 g of phosgene)
Mol) was blown at 70 ° C. over 30 minutes, and kept at the same temperature for 4 hours. This operation of adding dimethylformamide, blowing phosgene, and holding for 4 hours was further repeated twice. 100 g of water is added to the reaction solution, and 23% at 40-50 ° C.
The solution was neutralized with 200 g (1.15 mol) of an aqueous NaOH solution.
After adding 50 g of chlorobenzene and extracting and separating the organic layer, 5-chloro-1,3-dimethylpyrazole-
4-Carboxaldehyde was obtained with a yield of 93.3%. In addition, no by-product of the dimer body was observed.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-50-49278 (JP, A) JP-A-56-97283 (JP, A) JP-A-63-267762 (JP, A) Heterocyclic Chem. , 28, p. 1837-1839 (1991) Aust. J. Chem, 36, p. 135-147 (1983) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 231/06 C07D 231/18 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. The general formula (1), Wherein R ₁ and R ₂ represent the same or different lower alkyl groups, and reacting the pyrazolones with dimethylformamide in the presence of phosgene; (Wherein R ₁ and R ₂ are the same as the groups described above). 2. The pyrazole derivative according to claim 1, wherein dimethylformamide is added to the solvent and / or the pyrazolone solution, and the reaction is carried out while adding the pyrazolone solution and phosgene together in a heated solvent. Production method.