JPH05140113A - Production of aminopyrazole derivative - Google Patents

Abstract

PURPOSE:To obtain the title compound in an industrially advantageous way, useful as an intermediate for the fine chemical field such as photographic chemicals, medicines and pesticides, from hydrazine and an alpha-substituted-beta,gamma- unsaturated nitrile compound. CONSTITUTION:The objective compound of formula II can be obtained by reaction of hydrazine with an alpha-substituted-beta,gamma-unsaturated nitrile compound of formula I (R<1> and R<2> are each H, alkyl, aralkyl or aryl; X is halogen, alkylsulfonyloxy or arylsulfonyloxy). The compound of the formula I can be efficiently derived from a compound of formula III by reaction of the compound of the formula III (an unsaturated aldehyde) with a cyanizing agent followed by reaction of the resulting cyanohydrin compound of formula IV with a halogenating agent or sulfonating agent.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the formula [II] (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group.) The present invention relates to a method for producing a pyrazole derivative.

[0002]

BACKGROUND OF THE INVENTION Pyrazole derivative [II] is a compound well known as an intermediate in the field of fine chemicals such as photographic drugs, pharmaceuticals and agricultural chemicals.
It is also known to produce by reacting hydrazine with α, β-unsaturated nitrile.

For example, a method for producing 5-amino-3-methylpyrazole by reacting hydrazine with 3-iminobutyronitrile (J. Heterocyclic Chem., 11 , 423 (197
4)), a method for producing 5-amino-3-methylpyrazole by reacting hydrazine with 2-chloro-2-butenonitrile in the presence of an alkali such as potassium-t-butoxide (J. Heterocyclic Chem., 19 , 1265 (1982)) and the like are known. However, it is not known to react hydrazine with β, γ-unsaturated nitrile.

Under the circumstances, the inventors of the present invention have conducted extensive studies on a method for producing a pyrazole derivative [II] using an unsaturated nitrile, and as a result, have found that a halogen atom at the α-position,
Α-substituted-having a specific substituent such as sulfonyloxy
It was found that β, γ-unsaturated nitriles [I] react with hydrazine to produce the desired product [II], and α,
From β-unsaturated aldecht [III] as a starting material, α-substituted-β, γ-unsaturated nitriles [I] were found to be a novel route for the production of pyrazole derivative [II], and various studies were further conducted. And completed the present invention.

[0005]

Means for Solving the Problems That is, the present invention provides (1)
Hydrazine and formula [I] (Wherein R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group, and X represents a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group). Formula [II] characterized by reacting with nitriles (In the formula, R ¹ and R ² have the same meanings as described above.)

(2) Formula [III] (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group.) The cyanohydrins represented by the formula [I] are reacted with a halogenating agent and a sulfonating agent. And a method for producing a pyrazole derivative represented by the above formula [II], which comprises reacting with α-substituted-β, γ-unsaturated nitriles and then reacting with hydrazine.

(3) Formula [IV] (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group.) An unsaturated aldehyde represented by the formula [III] is reacted with a cyanating agent. And then reacting with a halogenating agent or a sulfonating agent to obtain β, γ-unsaturated nitriles represented by the above formula [I], and then reacting with hydrazine. ] The industrially excellent manufacturing method of the pyrazole derivative shown by these is provided.

The present invention will be described in detail below. The present invention is characterized by reacting hydrazine with α-substituted-β, γ-unsaturated nitriles [I], but α-substituted-β, γ-unsaturated nitriles [I] As the substituents R ¹ and R ² of, for example, a hydrogen atom, a lower alkyl group such as methyl, ethyl, propyl and butyl, benzyl,
Aralkyl groups such as O-, m-, P-tolylmethyl, O-, m-, P-ethylphenylmethyl, phenyl, O-, m-, P-tolyl, O-, m-,
Examples thereof include aryl groups such as P-ethylphenyl. Examples of X include halogen atoms such as chlorine, bromine and iodine, alkylsulfonyloxy groups such as methanesulfonyloxy, ethanesulfonyloxy and propanesulfonyloxy, arylsulfonyloxy groups such as benzenesulfonyloxy and p-toluenesulfonyloxy. Is mentioned.

Specific compounds include, for example, α-chloro-β, γ-butenonitrile, α-chloro-β, γ-pentenonitrile, α-bromo-chloro-β, γ-butenonitrile and α-iodo-β. , Γ-butenonitrile, α-
Methanesulfonyloxy-β, γ-butenonitrile, α
-P-toluenesulfonyloxy-β, γ-butenonitrile, and the like.

Examples of hydrazine include hydrazine hydrate and anhydrous hydrazine. Usually, hydrazine hydrate is used, but it is also possible to use hydrazine produced by reacting an alkali with a salt of hydrazine and an acid, for example, hydrochloride, sulfate or acetate.

Hydrazine is usually used in an amount of 2 to 5 equivalents based on β, γ-unsaturated nitriles [I]. The coexistence of a base can reduce the amount used to about 1 equivalent. Examples of such a base include metal alcoholates such as sodium methylate, sodium ethylate and potassium butyrate, and inorganic bases such as caustic soda, caustic potash and sodium carbonate. The amount used is 0.1 to 5 equivalents relative to the β, γ-unsaturated nitrile [I].

The reaction is usually carried out in the presence of a solvent, and examples of such a solvent include hydrocarbons such as benzene and toluene, alcohols such as methanol, ethanol and butanol, and ethers such as diethyl ether and tetrahydrofuran. Is mentioned. The amount of the solvent used is usually 1 to 50 times by weight that of the β, γ-unsaturated nitrile [I].

The reaction is usually carried out at a temperature of room temperature to about 120 ° C. and is usually completed in 1 to 50 hours, though it depends on the kind of β, γ-unsaturated nitrile [I]. After the reaction,
The desired β, γ-unsaturated nitriles [I] can be taken out by means such as distillation and extraction. This one is
Further, it can be further purified by purification means such as recrystallization and various kinds of chromatography.

Next, the method for producing the α-substituted-β, γ-unsaturated nitriles [I] will be described. α-Substitution-β, γ-
Unsaturated nitriles [I] are unsaturated aldehydes [IV]
Can be produced by reacting this with a cyanating agent to obtain a cyanohydrin [III] and then reacting it with a halogenating agent or a sulfonating agent.

Substituents R ₁ and R of unsaturated aldehydes [IV]
_Examples of ₂ include the same substituents as described above. Specific compounds include, for example, acrolein, crotonaldehyde, cinnamic aldehyde, 3-methyl-2-butenal, green leaf aldehyde, citral and the like.

Cyanation is a known method, for example, a method of reacting hydrogen cyanide in the presence of a catalytic amount of a base (J. Am. Ch.
em.Soc., 57 , 1405 (1935)), metal cyanide in the presence of acid,
Method of reacting trialkylsilyl cyanide (J. Org.
Chem., 45 , 401 (1980)) and the like.

The cyanohydrins [III] thus obtained may be further purified by a purification means such as distillation, recrystallization, various chromatographs or the like, or sulfuric acid, P-toluenesulfonic acid or the like may be added as a stabilizer. You may lead to the next process as it is.

The halogenation of cyanohydrins [III] can be carried out by a known method, for example, a method of reacting thionyl chloride in the presence of pyridine, trimethylamine, etc., a method of reacting phosgene with dimethylformamide, and a phosphine salt. In the presence of carbon tetrachloride, bromine, etc., phosphorus trichloride, phosphorus tribromide, phosphorous halide such as phosphorus pentachloride, a method using Vilsmeier salt (J.Org.Chem., 55 , 575 (1990)) and the like.

Sulfonation of cyanohydrins [III] can be carried out by a known method, for example, methanesulfonic acid chloride in the presence of amines such as pyridine and triethylamine.
It can be carried out in accordance with a method of reacting a sulfonic acid halide such as p-toluenesulfonic acid chloride or a sulfonic acid anhydride such as anhydrous methanesulfonic acid.

Halogenation and sulfonation are usually carried out in the presence of a solvent, but can also be carried out in the absence thereof.
Examples of the solvent include aromatic solvents such as benzene and toluene, ether solvents such as diethyl ether, halogenated hydrocarbon solvents such as dichloromethane, chloroform and dichloromethane, and nitrile solvents such as acetonitrile. The reaction temperature is usually selected from the range of −10 ° C. to the boiling point of the solvent, and the reaction time is usually about 1 to 50 hours, depending on the reaction temperature.

The obtained α-substituted-β, γ-unsaturated nitriles [I] may be further purified by distillation, recrystallization, various chromatographies or the like, or may be directly reacted with hydrazine.

[0022]

According to the present invention, the desired pyrazole derivative [II] can be produced by reacting hydrazine with α-substituted-β, γ-unsaturated nitriles [I]. Further, since the α-substituted-β, γ-unsaturated nitriles [I] can be efficiently derived from the unsaturated aldehydes [IV], the method of the present invention is industrially advantageous.

[0023]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to the following examples.

Example 1 A 2 l flask was charged with 140 g of acrolein and 1.2 l of methylene chloride and cooled to -5 ° C. Hydrogen cyanide under stirring
A solution consisting of 119 ml, triethylamine 0.7 ml and methylene chloride 50 ml was added dropwise so that the reaction temperature did not exceed 5 ° C. After the dropping, the temperature was raised to 20 ° C. over 30 minutes, and stirring was continued at the same temperature for another 30 minutes. After the reaction, sulfuric acid was added until the pH became about 3. Then, the solvent was distilled off under reduced pressure to obtain 218 g of crude acrolein cyanhydrin. purity
The yield was 88.4% and the yield was 92%.

Example 2 Crude acrolein cyanhydrin 19.6 was added to a 200 ml flask.
g (purity 88.4%) and 80 ml of methylene chloride were charged, the mixture was cooled to -10 ° C with stirring, and 19.8 g of pyridine was added thereto. Then, 31.5 g of thionyl chloride was added dropwise so that the reaction temperature did not exceed -15 ° C, and the mixture was further added at -15 ° C for 0.5 hour.
Stirring was continued at 4 ° C for 3.5 hours. After the reaction, add 10
After adding to 0 ml and stirring for 30 minutes, the mixed solution was filtered using Celite to separate the organic layer. The aqueous layer was extracted with methylene chloride. The organic layers were combined, dried over magnesium sulfate, evaporated under reduced pressure and distilled to give 2-chloro-3-
19.8 g of butenenitrile was obtained. Boiling point 61 ℃ / 30mmHg
, The purity was 92% and the yield was 86%.

Example 3 A 50 ml flask was charged with 0.39 g (purity 92%) of 2-chloro-3-butenenitrile and 2 ml of ethanol, and the mixture was stirred at 80%.
Add 0.5 ml (8 mmol) of hydrazine hydrate and raise the temperature to 80 ° C.
Stirring was continued for 2 hours at the same temperature. Next, after distilling off low-boiling components under reduced pressure, purification by silica gel column chromatography (developing solvent: ethyl acetate / ethanol) gave 311 mg of 5-amino-3-methylpyrazole. The yield was 90.6%.

Example 4 0.47 g of crude acrolein cyanhydrin in 50 ml of slasco
(Purity of 88.4%) and methylene chloride (5 ml) were charged, and the mixture was cooled to 5 ° C with stirring. Then 0.75 ml (7
slowly added dropwise, and stirred for 5 minutes at the same temperature, then 0.47 ml (6 mmol) of methanesulfonic acid chloride was added dropwise.
Stirring was continued at 6 ° C for 6 hours. Then, the reaction solution was added to 10 ml of ice water, stirred for 30 minutes, and then separated. The aqueous layer was extracted with methylene chloride. The organic layers were combined, washed with 1N hydrochloric acid, washed with aqueous sodium bicarbonate solution, dried over magnesium sulfate,
The solvent was distilled off under reduced pressure to obtain 1.0 g of crude 2-methanesulfonyloxy-3-butenenitrile.

Example 5 In Example 3, instead of 2-chloro-3-butenenitrile, the crude 2-methanesulfonyloxy-3 obtained in Example 4 was used.
-Using butenenitrile 1.0 g, ethanol 3 ml :, 80
% Hydrazine hydrate (0.5 ml, 8 mmol) was used, and the procedure of Example 3 was repeated to obtain 445 mg of 5-amino-3-methylpyrazole. The yield was 89% based on acrolein cyanhydrin.

Example 6 The procedure of Example 1 was repeated except that 6.3 ml (50 mmol) of cinnamaldehyde was used in place of acrolein to obtain 9.6 g of crude cinnamaldehyde cyanohydrin. It was

Example 7 In Example 2, instead of acrolein cyanohydrin, 3.84 g (20 mmol) of the crude cinnamaldehyde cyanohydrin obtained in Example 6 was used, and 15 ml of methylene chloride, 2 ml of pyridine and thionyl chloride were used. Using 1.7 ml, the reaction is 5-10 ℃
The same procedure as in Example 2 was carried out except that the above was carried out to obtain 3.6 g of crude 2-chloro-4-phenyl-3-butenenitrile.

Example 8 In Example 3, 0.9 g (5 mmol) of crude 2-chloro-4-phenyl-3-butenenitrile obtained in Example 7 was used instead of 2-chloro-3-butenenitrile. 5 ml of ethanol :,
By carrying out according to Example 3 except that 0.69 ml (11 mmol) of 80% hydrazine hydrate was used, 5-amino was obtained.
3-230 mg of benzylpyrazole was obtained.

Comparative Example 1 3.1 ml (44 mmol) of acrolein and 8.6 ml of benzene were charged in 50 ml of slasco, cooled to -10 ° C, and 4.5 g (44 mmol) of acetic anhydride was added thereto. Then sodium cyanide
A solution consisting of 3.14 g and water (16 ml) was added dropwise at the same temperature for 15 minutes, and then stirring was continued at the same temperature for 2 hours. After the reaction was completed, the temperature was raised to 0 ° C., the mixture was extracted twice with diethyl ether, and the extracted ether layer was washed with 10% sodium bicarbonate, dried over magnesium sulfate, evaporated to remove 2-acetoxy-3.
-Butenenitrile (4.02 g) was obtained. Boiling point 63-65 ℃ / 10mmH
g, purity 100%. Next, add 130 ml of 2-acetoxy-3-butenenitrile, 3 ml of t-butanol and 148 mg of potassium t-butoxy, and then add 162 mg of hydrazine hydrate (2.6 mg
mol) was added and reacted at 40 ° C. for 4 hours, and the reaction solution was analyzed by gas chromatography, but 5-amino-3-methylpyrazole could not be detected. Further, the temperature was raised to 80 ° C. and the reaction was carried out for 3 hours, but the target product could not be detected.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masato Sekiguchi 3-1,98 Kasugade, Konohana-ku, Osaka City, Osaka Prefecture Sumitomo Chemical Co., Ltd.

Claims (3)

[Claims] 1. Hydrazine and formula [I] (Wherein R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group, and X represents a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group). Formula [II] characterized by reacting with γ-unsaturated nitriles (In the formula, R ¹ and R ² have the same meanings as described above.) A method for producing a pyrazole derivative. 2. A formula [III] (In the formula, R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group.) The cyanohydrin represented by the formula [I] is reacted with a halogenating agent and a sulfonating agent. (In the formula, R ¹ and R ² have the same meanings as described above, and X represents a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group.), And α-substituted-β, γ-
Formula [II] characterized by obtaining unsaturated nitriles and then reacting with hydrazine (In the formula, R ¹ and R ² have the same meanings as described above.) A method for producing a pyrazole derivative. 3. A formula [IV] (Wherein R ¹ and R ² represent a hydrogen atom, an alkyl group, an aralkyl group or an aryl group) and an unsaturated aldehyde represented by the formula [III] (In the formula, R ¹ and R ² have the same meanings as described above.) A cyanohydrin represented by the formula [I] is obtained by reacting with a halogenating agent or a sulfonating agent. (In the formula, R ¹ and R ² have the same meanings as described above, and X represents a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group.), And α-substituted-β, γ-
Formula [II] characterized by obtaining unsaturated nitriles and then reacting with hydrazine (In the formula, R ₁ and R ₂ have the same meanings as described above.) A method for producing a pyrazole derivative.