JP2000143602A - Production of hydrazone derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a hydrazone derivative useful as an intermediate of an agrochemical without using a drying process advantageously on an industrial scale by reacting a hydrazine derivative with a trifluoropyruvic aldehyde in the presence of a hydrophobic organic solvent and water. SOLUTION: 3,3,3-Trifluoropyruvic aldehyde or its hydrate, or their mixture is added to a hydrazine derivative (e.g. 4-fluoro-5-hydroxyphenylhydrazine) of formula I (X is H or a halogen; Y is a halogen) or its salt of a mineral acid in the presence of a hydrophobio organic solvent (e.g. aliphatic or aromatic hydrocarbon) and water, and they are subjected to a reaction to obtain the objective compound [e.g. 3,3,3-trifluoro-2-oxopropanal 1-(4-fluoro-5- hydroxyphenylhydrazone)] of formula II. The above-mentioned trifluoropyruvic aldehyde is used preferably in an amount of about 1-5 times the hydrazine derivative by mol, and they are made to react with each other preferably at about -20 deg.C to 150 deg.C for several minutes to about 30 hours.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a hydrazone derivative useful as an agricultural chemical intermediate or the like.

[0002]

2. Description of the Related Art Japanese Patent Application Laid-Open No. 9-323977 discloses sodium acetate and 1,1.
-Dibromo-3,3,3-trifluoroacetone was dissolved in water and heated to a solution of 4-chloro-2-fluoro-5.
-Reacting crystals of hydroxyphenylhydrazine hydrochloride to give 3,3,3-trifluoro-2-oxopropana-
A process for obtaining 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) is described.
However, in the above production method, the hydrazone derivative produced reacts with an unreacted hydrazine derivative in the general formula (3) It has been found that by-products indicated by may sometimes occur.

[0003]

Means for Solving the Problems The present inventors have made intensive studies to develop a method for producing a hydrazone derivative which produces less of the above-mentioned by-products, and as a result, have reached the present invention. That is, the present invention relates to general formula (1) (Wherein X represents a hydrogen atom or a halogen atom;
Represents a halogen atom. A) a hydrazine derivative or a salt thereof with a mineral acid, in the presence of a hydrophobic organic solvent and water, in the presence of 3,3,3-trifluoropyruvic aldehyde or a hydrate thereof or a mixture thereof General formula (2) characterized by reacting by adding (Wherein X and Y have the same meanings as described above).
The production method of the present invention is industrially extremely advantageous because there is no need to dry the hydrazine derivative (1) as a raw material, so that the drying step can be omitted and equipment for dust control is not required.

[0004]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The 3,3,3-trifluoropyruvic aldehyde or a hydrate thereof used in the present invention is represented by the following formula (4) And any of the above formulas (4) or a mixture thereof can be used. 3,3,3-Trifluoropyruvicaldehyde and hydrates thereof are described in J. Am. Org. Che. 53, 5088 (198
8 years).

In the present invention, the hydrazine derivative (1)
As the halogen atom represented by X and Y, a fluorine atom,
Examples include a chlorine atom, a bromine atom or an iodine atom.

Specific examples of the hydrazine derivative (1) include 4-fluoro-5-hydroxyphenylhydrazine, 4-chloro-5-hydroxyphenylhydrazine, 4-bromo-5-hydroxyphenylhydrazine,
4-iodo-5-hydroxyphenylhydrazine, 2,
4-difluoro-5-hydroxyphenylhydrazine,
4-chloro-2-fluoro-5-hydroxyphenylhydrazine, 4-bromo-2-fluoro-5-hydroxyphenylhydrazine, 4-iodo-2-fluoro-5-
Hydroxyphenylhydrazine, 2-chloro-4-fluoro-5-hydroxyphenylhydrazine, 2,4-dichloro-5-hydroxyphenylhydrazine, 4-bromo-2-chloro-5-hydroxyphenylhydrazine,
4-iodo-2-chloro-5-hydroxyphenylhydrazine, 2-bromo-4-fluoro-5-hydroxyphenylhydrazine, 2-bromo-4-chloro-5-hydroxyphenylhydrazine, 2,4-dibromo-5- Hydroxyphenylhydrazine, 4-iodo-2-bromo-5-hydroxyphenylhydrazine, 2-iodo-4
-Fluoro-5-hydroxyphenylhydrazine, 2-
Examples thereof include iodo-4-chloro-5-hydroxyphenylhydrazine, 2-iodo-4-bromo-5-hydroxyphenylhydrazine, and 2,4-diiodo-5-hydroxyphenylhydrazine.

These hydrazine derivatives can be used as salts with mineral acids. Such mineral acids include hydrochloric acid,
Sulfuric acid and the like.

Specific examples of the product, hydrazone derivative (2), include 3,3,3-trifluoro-2-oxopropanal 1- (4-fluoro-5-hydroxyphenylhydrazone), 3,3 3-trifluoro-2-
Oxopropanal 1- (4-chloro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-
2-oxopropanal 1- (4-bromo-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (4-iodo-5
Hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (2,4-difluoro-5-hydroxyphenylhydrazone), 3,
3,3-trifluoro-2-oxopropanal 1-
(4-chloro-2-fluoro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (4-bromo-2-fluoro-5-
Hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (4-iodo-
2-fluoro-5-hydroxyphenylhydrazone),
3,3,3-trifluoro-2-oxopropanal
1- (2-chloro-4-fluoro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (2,4-dichloro-5-hydroxyphenylhydrazone), 3, 3,3-trifluoro-2-oxopropanal 1- (4-bromo-2-
Chloro-5-hydroxyphenylhydrazone), 3,
3,3-trifluoro-2-oxopropanal 1-
(4-iodo-2-chloro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (2-bromo-4-fluoro-5-hydroxyphenylhydrazone), 3, 3,3-trifluoro-2-oxopropanal 1- (2-bromo-4
-Chloro-5-hydroxyphenylhydrazone), 3,
3,3-trifluoro-2-oxopropanal 1-
(2,4-dibromo-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (4-iodo-2-bromo-5-hydroxyphenylhydrazone), 3,3 3-trifluoro-2
-Oxopropanal-1- (2-iodo-4-fluoro-5-hydroxyphenylhydrazone), 3,3
3-trifluoro-2-oxopropanal 1- (2
-Iodo-4-chloro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1- (2-iodo-4-bromo-5-hydroxyphenylhydrazone), 3,3 3-trifluoro-
2-oxopropanal 1- (2,4-diiodo-5
-Hydroxyphenylhydrazone), and the like.

The hydrazine derivative (1) and its salt with a mineral acid can be obtained by the production method described in JP-A-09-323977.

The reaction of the hydrazine derivative (1) of the present invention or a salt thereof with a mineral acid, and 3,3,3-trifluoropyruvic aldehyde or a hydrate thereof is carried out in two layers of a hydrophobic organic solvent and water. The reaction is carried out in a system solvent and the reaction temperature is usually -2
It is in the range of about 0 ° C. to 150 ° C., and the reaction time is usually
It is about several minutes to 30 hours.

The amount of the reagent used for the reaction is 3,3,3-
Trifluoropyruvic aldehyde or a hydrate thereof is generally used in an amount of about 1 to 5 mol, preferably about 1 to 2 mol, based on the hydrazine derivative (1) or a salt thereof with a mineral acid. In order to suppress the generation of the by-product (3), it is preferable to use 3,3,3-trifluoropyruvicaldehyde or a hydrate thereof in an excessive amount.

Examples of the hydrophobic organic solvent used include aliphatic hydrocarbons such as hexane, heptane, cyclohexane and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, dichloromethane, dichloroethane, chlorobenzene and dichlorobenzene. Halogenated hydrocarbons such as chlorobenzene, ethers such as diethyl ether, t-butylmethyl ether and diisopropyl ether; esters such as ethyl formate, ethyl acetate and butyl acetate; nitromethane;
Examples thereof include nitro compounds such as nitrobenzene, and mixtures thereof. Here, without using a hydrophobic organic solvent,
When the reaction is carried out only with water or when a hydrophilic organic solvent is used, a by-product (3) is generated, which causes a decrease in the yield and quality of the hydrazone derivative (2), which is not preferable.

The amount of the hydrophobic organic solvent used is usually about 0.5 to 50 times, preferably about 1 to 20 times the weight of the hydrazine derivative (1) or a salt thereof with a mineral acid. Can be

This reaction is carried out by reacting water with a hydrophobic organic solvent.
The reaction is carried out in a layer solvent, and the amount of water used is usually about 1 to 100 times by weight, preferably 2 to 50 times by weight, based on the hydrazine derivative (1) or a salt thereof with a mineral acid. Used to a degree. The amount of use also includes water and the like contained in the raw materials.

After completion of the reaction, the reaction solution is separated if the product is dissolved, or if necessary, heated to a temperature at which the product is dissolved, or separated by adding a solvent in which the product is dissolved. After separation by liquefaction, post-treatment such as concentration is performed, and if necessary, purification by an operation such as chromatography can obtain the hydrazone derivative (2).

[0016]

According to the present invention, the hydrazone derivative (2) can be produced industrially advantageously.

[0017]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. [Production Example 1] (1,1,1-trifluoro-2,2,2)
Preparation of 3,3-propanetetraol aqueous solution) 1139.9 g of water was charged into a 2 liter glass reactor equipped with a thermometer, a stirrer, and a cooler.
6.9 g (98% product, 2.711 mol) were dissolved. Here, 178.3 g of 1,1-dichloro-3,3,3-trifluoro-2,2-propanediol (0.89
222.8 g of an aqueous solution containing
After stirring at ~ 90 ° C for 4 hours, the mixture was cooled to room temperature,
-Trifluoro-2,2,3,3-propanetetrao-
1584.5 g of an aqueous solution of toluene was obtained.

Example 1 Water was placed in a 500 milliliter glass reactor equipped with a thermometer, a stirrer, and a cooler.
2 g, monochlorobenzene 78.3 g, 4-chloro-2
Dry crude crystal 3 containing 12.8 g (60.2 mmol) of -fluoro-5-hydroxyphenylhydrazine hydrochloride
0.0 g was charged. After adjusting the internal temperature to 30 ° C., Production Example 1
1,1,1-trifluoro-2,2,3 obtained in
118.0 g of an aqueous solution of 3-propanetetraol (1,1
66.7 mmol in terms of 1-dichloro-3,3,3-trifluoro-2,2-propanediol))
The mixture was stirred at 5-35 ° C for 2 hours. The reaction mass was heated to 60 ° C., and after confirming dissolution of the crystal of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone), an oil layer was formed. Was analyzed by high performance liquid chromatography to find that the starting material, 4-chloro-2-fluoro-5-hydroxyphenylhydrazine, and the desired product, 3,3,3-trifluoro-2-oxopropanal 1- (4 -Chloro-2-
Fluoro-5-hydroxyphenylhydrazone), 3,3,3-trifluoro-2-oxopropanal 1,2-bis (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) obtained by reacting a raw material with a target substance Was 0: 99.8: 0.2. The reaction mass was cooled to room temperature, 100 g of t-butyl methyl ether was added, and the mixture was stirred and then separated. Further, the aqueous layer was extracted twice with 50 g of t-butyl methyl ether, the oil layers were combined, the solvent was removed under reduced pressure, and further dried at 50 ° C. under reduced pressure to obtain 17.0 g of yellow crystals. . The content of these crystals was determined by an internal standard method using high performance liquid chromatography, and the target product, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro- 5
-Hydroxyphenylhydrazone) 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-
2-fluoro-5-hydroxyphenylhydrazone) was 98.3%. This is 4-chloro-2-
This corresponds to a yield of 97.4% based on fluoro-5-hydroxyphenylhydrazine hydrochloride.

Example 2 Thermometer, stirrer, cooler, p
Water 2 into a 2 liter glass reactor equipped with an H meter
91.3 g, 63.7 g of 4-chloro-2-fluoro-5-hydroxyphenylhydrazine hydrochloride (0.299 m
ol). 200.0 g of crude crystals were charged.
In addition, when some crystals were separately dried, Wet. The dry matter in 100 g of the crude crystals was 68.5 g. At this time, the pH of the suspension was -0.5. While cooling the suspension with ice water, a 30% aqueous sodium hydroxide solution was added at an internal temperature of 3%.
The pH was adjusted to 1.1 by dropwise addition not to exceed 0 ° C. Add 420.2 g of monochlorobenzene and bring the internal temperature to 3
After the temperature was adjusted to 0 ° C., 617.4 g (1,1-dichloro-3,3,3,1) of the aqueous solution of 1,1,1-trifluoro-2,2,3,3-propanetetraol obtained in Production Example 1 was used. 0.34 in terms of trifluoro-2,2-propanediol
(Containing 9 mol), and the mixture was stirred at 25 to 35 ° C for 2 hours.
The pH at this time was 3.4. After adding 291.9 g of water, a 30% aqueous sodium hydroxide solution was added dropwise, and the pH was lowered.
Was adjusted to 4.0. Raise the reaction mass to 60 ° C,
3,3,3-trifluoro-2-oxopropanal
After confirming the dissolution of the crystals of 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone), Celite 10
g was filtered through a glass filter on which g had been spread in advance. The filtered material was washed with 50 g of monochlorobenzene warmed to 60 ° C. Combine the filtrates, 60 ° C
To perform liquid separation. The oil layer was analyzed by high performance liquid chromatography to find that the starting material was 4-chloro-2-fluoro-5-hydroxyphenylhydrazine and the desired product was 3,3,3-trifluoro-2-oxopropanal.
1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone), 3,3,3 obtained by reacting a raw material with an intended product
The area ratio of -trifluoro-2-oxopropanal 1,2-bis (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) was 0: 99.8: 0.2. After concentrating and drying the oil layer, the content was determined, and the content of the desired product was 99.2%. In addition, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) is used for 4-chloro-2-fluoro-5-hydroxyphenylhydrazine hydrochloride. The yield was 97.3%.

Example 3 Production Example 1 in a 500 ml glass reactor equipped with a thermometer, stirrer and cooler
1,1,1-trifluoro-2,2,3,3 obtained in
128.7 g of an aqueous solution of propanetetraol (1,1
-Dichloro-3,3,3-trifluoro-2,2-propanediol, containing 72.8 mmol) and 120 g of t-butyl methyl ether, followed by stirring.
At 25-27 ° C., 10.6 g (60.2 mmol) of 4-chloro-2-fluoro-5-hydroxyphenylhydrazine
11.6 g of dry crude crystals containing 1) were added. 25-3
After stirring at 0 ° C. for 6 hours, the mixture was allowed to stand and liquid separation was performed. Further, the aqueous layer was extracted twice with 50 g of t-butyl methyl ether. The oil layers were combined, the solvent was removed under reduced pressure, and dried. The content was determined by an internal standard method. , 3-
The yield of trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) based on 4-chloro-2-fluoro-5-hydroxyphenylhydrazine was 98.0%. . When the crystals were analyzed by high performance liquid chromatography,
3,3,3-trifluoro-2-oxopropanal
1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) and 3,3,3-trifluoro-2-
Oxopropanal 1,2-bis (4-chloro-2-
Fluoro-5-hydroxyphenylhydrazone) was 99.6: 0.4.

Comparative Example 1 Production Example 1 in a 500 ml glass reactor equipped with a thermometer, stirrer, and cooler
1,1,1-trifluoro-2,2,3,3 obtained in
-118.0 g of an aqueous solution of propanetetraol (1,1
-Dichloro-3,3,3-trifluoro-2,2-propanediol-containing 66.7 mmol), water 120
After adding 25 ml at 25-27 ° C. with stirring,
30.0 g of dry crude crystals containing 12.8 g (60.2 mmol) of chloro-2-fluoro-5-hydroxyphenylhydrazine hydrochloride were added. After stirring at 25-30 ° C. for 12 hours, the reaction mass was filtered under reduced pressure and washed with 40 g of water. The filtered product was dried at 50 ° C. under reduced pressure to obtain 17.2 g of yellow crystals. The content of these crystals was determined by an internal standard method using high performance liquid chromatography, and the target compound, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro- 5-hydroxyphenylhydrazone) was 94.2%. This corresponds to a yield of 94.7% based on 4-chloro-2-fluoro-5-hydroxyphenylhydrazine hydrochloride. When the crystals were analyzed by high performance liquid chromatography, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) and 3,3,3 -Trifluoro-2-oxopropanal 1,2-bis (4-
Chloro-2-fluoro-5-hydroxyphenylhydrazone) was 98.2: 1.8.

Comparative Example 2 Production Example 1 in a 500 ml glass reactor equipped with a thermometer, stirrer and cooler
1,1,1-trifluoro-2,2,3,3 obtained in
-118.0 g of an aqueous solution of propanetetraol (1,1
-Dichloro-3,3,3-trifluoro-2,2-propanediol-containing 66.7 mmol), water 45 m
After adding 120 g of methanol and stirring, 2
At 5-27 ° C., 10.6 g (60.2 mmol) of 4-chloro-2-fluoro-5-hydroxyphenylhydrazine
11.6 g of dry crude crystals containing 1) were charged. 25-3
After stirring at 0 ° C. for 6 hours, t-butyl methyl ether 100
g was added, and the mixture was stirred and then subjected to stationary liquid separation. Further, the aqueous layer is t-
The mixture was extracted twice with 100 g of butyl methyl ether, the oil layers were combined, the solvent was removed under reduced pressure, and the residue was dried at 50 ° C. under reduced pressure. The content was determined by an internal standard method. 3,3-trifluoro-2-oxopropana
4-chloro-2-fluoro-5 of 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone)
The yield based on -hydroxyphenylhydrazine is 90.
2%. Met. When the crystals were analyzed by high performance liquid chromatography, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-
5-hydroxyphenylhydrazone) and 3,3,3-
The area ratio of trifluoro-2-oxopropanal 1,2-bis (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) was 88.5: 11.5.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Mitsuhiro Matsumoto 2-10-1, Tsukahara, Takatsuki-shi, Osaka Sumitomo Chemical Co., Ltd. F-term (reference) 4H006 AA02 AC59 BB31 BB46 BC15

Claims (1)

[Claims] 1. The general formula (1) (Wherein X represents a hydrogen atom or a halogen atom;
Represents a halogen atom. A) a hydrazine derivative or a salt thereof with a mineral acid, in the presence of a hydrophobic organic solvent and water, in the presence of 3,3,3-trifluoropyruvic aldehyde or a hydrate thereof or a mixture thereof General formula (2) characterized by reacting by adding (Wherein X and Y have the same meanings as described above).