JPH0569106B2 - - Google Patents

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD OF THE INVENTION The present invention relates to novel aminopyrazole derivatives and methods for their production. More specifically, the present invention relates to the general formula ():

[In the formula, R ¹ , R ² and R ³ each independently represent a lower alkyl group. ]

The present invention relates to a novel aminopyrazole derivative represented by and a novel method for producing the derivative. Aminopyrazole derivatives () are useful as intermediates for pharmaceuticals, agricultural chemicals, and the like. For example, the patent application filed in 1987-
It is useful as an intermediate for the herbicide described in JP-A No. 159177 (see JP-A-61-37782). That is,
Morotsupa Patent Publication No. 87780, Japanese Unexamined Patent Publication No. 1983-
219281, Japanese Patent Application No. 59-221093 (see JP-A-61-100570), etc., the pyrazole sulfonamide derivative () is derived,
Further, the desired herbicide can be obtained according to the specification of Japanese Patent Application No. 59-159177.

[In the formula, R ¹ , R ² and R ³ have the same meanings as above. ]

Prior Art The following methods are conventionally known as methods for producing 5-amino-4-carboxypyrazole derivatives.

[R ⁵ represents a hydrogen atom or a lower alkyl group. ]

(Chemical Abstracts)
Abstracts) Volume 53, 20068f (1959))

[Chemische Berichte] (Chemische Berichte) 95
(Refer to Volume 2881 (1962))

[R ⁴ represents a lower alkyl group. ]

(Pharmazie, Vol. 30, p. 802 (1975)
year) reference)

[Chemical Abstracts]
Abstracts) Volume 93, 95181s (1980))

[C] (Journal of Organic Chemistry) Volume 40, 2720
(1975))

[R ⁶ has the same meaning as above. ]

(Pharmazie, Vol. 31, p. 532 (1976)
From the above, known substituents at the 3-position of the pyrazole ring in 5-amino-4-carboxypyrazole derivatives include hydrogen atom, lower alkyl group, alkylthio group, mercapto group, amino group,
It can be seen that the compound () of the present invention, which is a substituted amino group, a hydroxy group, etc., and which is substituted with an alkoxy group is a new compound that has not yet been described in any literature. On the other hand, it is also difficult to synthesize the compound (1) of the present invention by referring to the conventional techniques (1) to (6) above for the reasons shown below. In the reaction formula (1) above, the synthesis of the raw materials is

[Chemical formula] However, R ⁵ is limited to a hydrogen atom or a lower alkyl group such as ethyl orthoformate having a hydrogen atom and ethyl orthoacetate having a methyl group. Therefore, it is difficult to obtain pyrazole derivatives due to raw material conditions.
R ⁵ is limited to a hydrogen atom or a lower alkyl group. In the above reaction formulas (2) and (3), the raw material

[expression] and

In the synthesis of [Formula], both compounds are produced by using carbon disulfide, and when these are used, the 3-position of the pyrazole ring is inevitably a substituent via a sulfur atom. . In the above reaction formulas (4) and (5), the raw material

[Formula] is a compound made by utilizing CCl ₃ CN, and the -CCl ₃ group is successfully utilized as a leaving group. In cyclization with hydrazine, reaction with -CN group inevitably produces -NH ₂ group, and reaction with CO ₂ C ₂ H ₃ group produces -OH group, and in these cases as well, the 3-position of the pyrazole ring Ha-
It can be seen that the synthesis method is limited to NH ₂ groups or -OH groups. The above reaction formula (6) is a reaction using a sulfur compound as a leaving group, similar to the above reaction formulas (2) and (3), and is a synthetic method limited to the above. Problems to be Solved by the Invention The purpose of the present invention is to provide a novel aminopyrazole represented by the general formula (), and to find a simple and high-yielding synthetic method for the same. The compound of the present invention is a new compound that has not been described in any literature, and it is also difficult to synthesize it with reference to conventional techniques. Therefore, it became necessary to develop a new synthetic method that does not rely on conventional techniques. Means for Solving the Problems and Aspects of the Invention The present inventors have expressed the general formula ()

[In the formula, R ³ and R ⁴ have the same meanings as above. ]

A ketene dithioacetal derivative represented by the following formula (): R ³ OM () [wherein R ³ and M have the same meanings as above. ] An alcoholate represented by the following formula (): R ¹ NHNH ₂ () [In the formula, R ¹ has the same meaning as above. ] It has been found that the compound of the present invention represented by the above general formula () can be obtained by reacting with a hydrazine derivative represented by the following. The compound represented by the above general formula () is a new compound, and by using this compound, the herbicide described in Japanese Patent Application No. 159177/1988 can be produced with high yield and high quality. They found that it can be obtained and completed the present invention. In order to react the general formulas () and (), alcohol derivatives such as methanol and ethanol, ether derivatives such as ether and tetrahydrofuran, and aromatic derivatives such as benzene and toluene are used as reaction solvents. The molar ratio between formulas () and () is about 1:1 to 1:3, preferably about 1:2. The reaction temperature is −20
It is carried out at a temperature of 80°C to 80°C, but usually proceeds below room temperature. M represents an alkali metal atom such as sodium or potassium, and sodium is usually used. Next, the reaction with the hydrazine derivative () is carried out at a reaction temperature of -20°C to 80°C, but usually proceeds below room temperature. As the reaction solvent, the above-mentioned solvents can be used as they are, but the addition of an organic acid derivative such as acetic acid, formic acid, propionic acid, etc. as an acid catalyst is effective in improving the reaction yield, so the above-mentioned acetic acid etc. are usually added. It is preferable to carry out the reaction. After the reaction, the solvent is distilled off, water is added, and the target product can be extracted by extraction with an organic solvent. In addition, as an intermediate by the reaction of the above formulas () and ()

[R ² and R ³ have the same meanings as above. ]

It is presumed that is produced, but this intermediate can be reacted with the next hydrazine derivative () without being taken out. As the hydrazine derivative () used, for example, methylhydrazine, ethylhydrazine, n-propylhydrazine, i-propylhydrazine, n-butylhydrazine, t-butylhydrazine, etc. can be used. Examples of the alcoholate () include methyl alcoholate, ethyl alcoholate, n-propyl alcoholate, i-propyl alcoholate, n-propyl alcoholate, and n-propyl alcoholate.
-Butyl alcoholate, etc. can be used.
Ketenedithioacetal derivatives () are synthesized from cyanacetate, carbon disulfide, twice the molar amount of alkylating agent, and a base, but cyanacetate can be synthesized from methyl ester, ethyl ester,
-propyl ester, i-propyl ester, n
-Butyl ester, etc., and as the alkylating agent, methyl iodide, ethyl iodide, dimethyl sulfate, diethyl sulfate, etc. are used. Effects of the Invention (1) A novel aminopyrazole derivative () useful as a pharmaceutical and agricultural intermediate is obtained. (2) Pyrazole sulfonamide derivatives () can be easily derived by using the compounds of the present invention (). (3) It can be synthesized more easily and with higher yield than the easily synthesized ketene dithioacetal derivative (). Example 1 Production of ethyl 5-amino-3-methoxy-1-methylpyrazole-4-carboxylate (when acetic acid is added) After dissolving 20 g of ethyl 2,2-bis-methylthio-1-dianoacrylate in 400 ml of methanol. , methanol solution containing 11.4 g of sodium methylate
100 ml was added at room temperature and stirred for 10 minutes. Then acetic acid 40
ml, then add 4.4 g of methylhydrazine,
Stirred at room temperature for 6 hours. After methanol was distilled off under reduced pressure, water was added and extraction was performed twice with 100 ml of chloroform. The chloroform layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product.
11.5g was obtained. Melting point: 140-141°C Yield: 63% Example 2 Production of ethyl 5-amino-3-methoxy-1-methylpyrazole-4-carboxylate (when acetic acid is not added) 2,2-bis-methylthio- in 400 ml of methanol 20 g of ethyl 1-cyanoacrylate and 11.4 g of sodium methylate were mixed in the same manner as in Example 1 above, and then 4.4 g of methylhydrazine was added, followed by stirring at room temperature for 6 hours. Post-treatment was performed in accordance with Example 1 above to obtain 3.2 g of the target product. Yield 17% Reference example 4-ethoxycarbonyl-3-methoxy-1-
Production method of methylpyrazole-5-sulfonamide (i) Production of ethyl 5-chloro-3-methoxy-1-methylpyrazole-4-carboxylate 5-amino-3-methoxy-1-methylpyrazole-4-carboxylic acid 8.1 g of ethyl was dissolved in 100 ml of 35% hydrochloric acid and cooled to 0°C. Next is purity
3.7 g of 97% sodium nitrite was dissolved in 8 ml of water and added while keeping the temperature below 5°C. 10 minutes
After stirring at 10°C, 1 g of urea was added, and the mixture was further stirred for 10 minutes. Dissolve this sulfite in 50ml of carbon tetrachloride.
It was added dropwise at 5°C to the solution that had absorbed 3.6g.
After stirring at room temperature until no nitrogen gas was generated, 100 ml of water was added and the organic layer was separated. After performing an extraction operation by adding 50 ml of chloroform to the aqueous layer, the organic layer was combined with the previous organic layer, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain an oil. When 10 ml of n-hexane was added to this and stirred, crystals of the desired product precipitated and were collected.
Yield 7.1g Melting point 60-61℃ Yield 80% (ii) Production of ethyl 3-methoxy-1-methyl-5-mercaptopyrazole-4-carboxylate Suspend 5.6g of sodium bisulfide with a purity of 70% in 20ml of dimethylformamide. cloudy, 5-chloro-
Add 6.1 g of ethyl 3-methoxy-1-methylpyrazole-4-carboxylate and heat to 1.5 g at 80-85°C.
Stir for hours. After cooling, 60 ml of water was added and acid precipitated with 35% hydrochloric acid. The crystals were collected and dried to obtain 5.1 g of the desired product. Melting point 74-75℃ Yield 85% (iii) 4-ethoxycarbonyl-3-methoxy-1
-Production of methylpyrazole-5-sulfonamide 3-methoxy-1-methyl-5-
1 g of ethyl mercaptopyrazole-4-carboxylate was dissolved, 1 ml of water was added, and the mixture was cooled to 5°C. Add chlorine while keeping the reaction temperature below 10℃.
It lasted for 0.5 minutes. Add 30ml of ice water and then add 50ml of benzene.
The extraction operation was performed using ml. The organic layer was separated, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 1.1 g of crude 4-ethoxycarbonyl-3-methoxy-1-methylpyrazole-5-sulfonyl chloride. This was dissolved in 20 ml of 1,2-dichloroethane, 0.55 g of ammonium carbonate (containing 30% as NH ₃ ) was added, and the mixture was stirred at room temperature for 4 hours. After separating the inorganic salt, the solvent was distilled off to obtain 0.9 g of the desired product. Melting point 131-133℃ Yield 75%

Claims (1)

[Claims] 1 General formula (): [In the formula, R ¹ , R ² and R ³ each independently represent a lower alkyl group. ] An aminopyrazole derivative represented by 2 General formula (): [In the formula, R ³ represents a lower alkyl group, and R ⁴ represents a lower alkyl group or a benzyl group. ] A ketene dithioacetal derivative represented by the following formula (): R ² OM () [In the formula, R ² represents a lower alkyl group and M represents an alkali metal atom. ] The following formula () R ¹ NHNH ₂ () [In the formula, R ¹ represents a lower alkyl group. ] General formula () characterized by reacting with a hydrazine derivative represented by: [In the formula, R ¹ , R ² and R ³ each independently represent a lower alkyl group. ] A method for producing an aminopyrazole derivative represented by