JP3477765B2 - Method for producing 1,4-dialkylpyrazoles using nitrile solvent - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a process for producing 1,4-dialkylpyrazoles which are useful as intermediates for medicines and agricultural chemicals, especially as an intermediate for herbicides. 1,
4-Dimethylpyrazole is useful as an intermediate for a herbicide for corn fields (JP-A-60-208977).

[0002]

As a method for producing an intermediate for a herbicide, a method for producing 4-methylpyrazole (Japanese Patent Laid-Open No. 2-191258) and 1,4-methylpyrazole by N-methylation A series of methods such as a method for producing dimethylpyrazole (US Pat. No. 5,153,329) is known.

In the method of using chloroform as an extraction solvent described in [3], since chloroform forms a carbene with a strong base, N as a chloroform solution remains.
-Cannot be used as a raw material for methylation, 1,2-dichloroethane reacts with 4-methylpyrazole under basic conditions to produce N-chloroethylated product,
It cannot be used as an extraction solvent for methylpyrazole. In addition, acetonitrile has a high water solubility and thus has poor extraction power.

According to the method described in (1), when methyl chloride, which is most industrially advantageous in price, is used, methyl chloride is used in a large excess, which is not always satisfactory. Further, it is described that acetonitrile can be used as a solvent, but since acetonitrile has high water solubility, post-treatment and its recovery are complicated. A solvent that can be used from extraction of 4-methylpyrazole to N-methylation is desired, but lack of extraction power caused by high water-solubility of 4-methylpyrazole and reaction rate of N-methylation There are problems such as influence, separation from the product after N-methylation, safety, and cost.

[0005]

The present inventors have made diligent efforts to solve the above problems, and as a result, 4-alkylpyrazoles (2):

[0006]

[Chemical 5]

(In the formula, R ¹ represents a C ₁ -C ₄ alkyl group.) Is reacted with an alkali metal or an alkali metal-containing base to give an alkali metal salt of (2), followed by reaction with an alkylating agent. Then, the 1,4-dialkylpyrazoles (1):

[0008]

[Chemical 6]

(In the formula, R ¹ has the same meaning as described above, and R ²
Represents a C ₁ -C ₄ alkyl group. ), A method characterized by using C _{3 to} C ₇ nitriles as a solvent, and further 2,3-dichloro-2-
Alkyl propanals (3):

[0010]

[Chemical 7]

(In the formula, R ¹ represents a C ₁ -C ₄ alkyl group.) And 4-alkylpyrazoles (2) formed from hydrazine:

[0012]

[Chemical 8]

(In the formula, R ¹ has the same meaning as described above.)
Is extracted with C ₃ -C ₇ nitriles, and the extract is used as a starting material for the above 1,4-dialkylpyrazoles (1)
A method for producing (hereinafter referred to as the method of the present invention) was found. R ¹ and R ² are each independently methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, se
Represents c-butyl and t-butyl.

Examples of C ₃ -C ₇ nitriles include propanonitrile, butyronitrile, isobutyronitrile, valeronitrile, isovaleronitrile, and benzonitrile. As the alkylating agent, methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, propyl chloride, propyl bromide, propyl iodide,
Examples thereof include alkyl halides such as isopropyl chloride, isopropyl bromide, isopropyl iodide and butyl bromide, and dialkyl sulfuric acids such as dimethyl sulfuric acid and diethyl sulfuric acid.
Especially when using alkyl chloride such as methyl chloride, the effect of C ₃ -C ₇ nitriles as a solvent is remarkable.

The reaction temperature is usually in the range of -10 to 200 ° C. According to the method of the present invention, an efficient production process of 1,4-dialkylpyrazoles (1) can be constructed. That is, by performing N-alkylation of 4-alkylpyrazoles (2) using C _{3 to} C ₇ nitriles as a solvent, the use amount of alkyl chloride such as methyl chloride is dramatically increased to about equimolar times. Can be reduced to Furthermore, the 4-alkylpyrazoles (2) obtained by reacting 2,3-dichloro-2-alkylpropanals (3) with hydrazine are efficiently extracted with C _{3 to} C ₇ nitriles. In addition, it can be used as a solution of C ₃ -C ₇ nitriles without any special purification.
-It can be used as a raw material for alkylation.

The present invention is particularly effective as a method for producing 1,4-dimethylpyrazole. Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.

[0017]

Example 18.5 g (0.369) of hydrazine monohydrate
mol), 92 g of ethanol and 30 g of water were added with 38.6 g of 35% hydrochloric acid aqueous solution to give hydrazine hydrochloride. While stirring and maintaining the reaction temperature at 74 to 84 ° C., 48.2 g (0.308 mol) of 90.1% 2,3-dichloro-2-methylpropanal was added dropwise thereto over 2 hours. At the same time, a 40% aqueous sodium hydroxide solution was added dropwise to adjust the pH to 3-5. After completion of dropping, the mixture was further stirred at a reaction temperature of 74 to 84 ° C. and a pH of 3 to 1.5 for 1.5 hours. After ethanol was distilled off at 64 ° C./400 mmHg to 68 ° C./380 mmHg, the temperature was returned to room temperature, and 6 g of 40% sodium hydroxide aqueous solution was added to make it basic. 61 g of water and 46 g of isobutyronitrile were added, the organic layer was separated, and the aqueous layer was extracted 3 times with 15 g of isobutyronitrile. When the aqueous layer after extraction was analyzed by liquid chromatography, 4-methylpyrazole was not detected. When this extract and the above organic layer were combined and analyzed by liquid chromatography, 20.0 g of 4-methylpyrazole was contained. The yield based on 2,3-dichloro-2-methylpropanal was 79%.

This solution was azeotropically dehydrated under normal pressure, and then, at 55 ° C., 12.7 g (0.307 mol) of 97% sodium hydroxide was added.
Was added and stirred for 1 hour. Then, after depressurizing to 90 mmHg as it is, 12.9 g of methyl chloride (0.256 mol
) Was blown in for 3 hours. 5 more after blowing
The mixture was stirred at 5 ° C for 1 hour, and the temperature was returned to room temperature. After adding 54 g of water to dissolve the inorganic substance and separating the organic layer, the aqueous layer was extracted twice with 13 g of isobutyronitrile. When this extract and the above organic layer were combined and analyzed by liquid chromatography, 23.4 g of 1,4-dimethylpyrazole was contained. The yield based on 4-methylpyrazole was 99%.

─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Hideaki Shintaku 6903-1 Onoda, Onoda-shi, Yamaguchi Prefecture Onoda Plant of Nissan Chemical Industries, Ltd. (56) Reference JP-A-4-211663 (JP, A) (58) Fields surveyed (Int.Cl. ⁷ , DB name) C07D 231/12

Claims (8)

(57) [Claims] 1. A 4-alkylpyrazole (2): embedded image (In the formula, R ¹ represents a C ₁ -C ₄ alkyl group.) Is reacted with an alkali metal or an alkali metal-containing base to give an alkali metal salt of (2), followed by reaction with an alkylating agent, 1,4-Dialkylpyrazoles (1): embedded image (In the formula, R ¹ has the same meaning as described above, and R ² is C ₁ to
An alkyl group of C ₄ is shown. ) A method of producing,
Produced in the production process of the 4-alkylpyrazoles (2)
(2) is extracted with C3 to C7 nitriles and extracted.
Method characterized in that there use a bottom product as a raw material. 2. A 4-alkyl-pyrazoles (2): ## STR3 ## (In the formula, R1 represents a C1-C4 alkyl group.)
By reacting a base containing Lucari metal or alkali metal
The alkali metal salt of (2) is used, and then the alkylating agent is added.
Allowed to respond, 1,4-dialkyl pyrazoles (1): ## STR00004 ## (In the formula, R1 represents the same meaning as described above, and R2 represents C1 to
An alkyl group of C4 is shown. ) In the method of manufacturing
2, 3-dichloro-2-alkyl propanals (3): embedded image (In the formula, R ¹ represents a C ₁ -C ₄ alkyl group.) And 4-alkylpyrazoles (2) formed from hydrazine: (In the formula, ^{R 1} are as defined above.) The _C 3 -C
Extract with the nitriles of ₇ and use the extract as raw material
That way. 3. A process according to claim 2 Symbol placement methods R ² is a methyl group. 4. The method of claim 2 alkylating agent is methyl chloride
Serial mounting methods. 5. A method according to claim 2 ^{R 1} and ^{R 2} is a methyl group
Serial mounting methods. 6. C ³ -C ⁷ nitriles are propanoate, butyronitrile, isobutyronitrile, valeronitrile, No mounting Claim 2 Symbol is selected from one or more of isovaleronitrile and benzonitrile Method. 7. A C ³ -C ⁷ nitriles are propanoate, butyronitrile, isobutyronitrile, valeronitrile, No mounting Claim 2 Symbol is selected from one or more of isovaleronitrile and benzonitrile Method. 8. claims reaction temperature is -10 to 200 ° C.
2 Symbol placement methods.