JP3063061B2 - Method for producing optically active 2- (4-hydroxyphenoxy) propionic acid - 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 optically active 2- (4-hydroxyphenoxy) propionic acid. Optically active 2- (4-hydroxyphenoxy)
Propionic acid is disclosed in JP-A-53-40767, JP-A-54-22371 and JP-A-56-16475.
It is a compound useful as an intermediate of an excellent herbicide disclosed in, for example, Japanese Patent Application Laid-Open Publication No. H10-15095.

A herbicide having 2- (4-hydroxyphenoxy) propionic acid as an intermediate has an asymmetric carbon atom in its structure, and thus has two types of optically active isomers. It is known that the herbicidal activity is stronger than that of JP-A-55-55372. Therefore, if a herbicide is used using an optically active substance having strong herbicidal activity, the required dosage can be significantly reduced as compared with the racemic form, and not only environmental protection and resource saving but also production and application of the herbicide This is meaningful, for example, the cost can be reduced.

[0003]

2. Description of the Related Art As a method for producing optically active 2- (4-hydroxyphenoxy) propionic acid, optically active 2-halopropionic acid and an alkali metal salt of hydroquinone are used.
A method of condensing in an aqueous solvent in the presence of an alkali metal hydroxide (JP-A-61-15894);
A method of condensing a halopropionic acid or an alkali salt with an alkali metal salt of hydroquinone in a ketone or ether solvent in the presence of an alkali metal hydroxide (JP-A-2-268134) is known. .

[0004]

Problems to be Solved by the Invention JP-A-61-1589
According to the production method of JP-A No. 4 (1994), the smaller the amount of water used as a solvent, the better the yield of optically active 2- (4-hydroxyphenoxy) propionic acid. It becomes difficult to stir, and a special stirrer is required industrially.

When the amount of water used is increased until stirring is possible, the yield of optically active 2- (4-hydroxyphenoxy) propionic acid decreases. In the production method of JP-A-2-268134, a large amount of ketones or ethers is used in order to facilitate the stirring of the slurry reaction, but it may be difficult to stir the aqueous layer. Also, a recovery and purification step of a large amount of solvent is required.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to further improve the problems of the manufacturing method disclosed in Japanese Patent Laid-Open No. 61-15894, and as a result, completed the present invention. The present invention is a soft crystal formed by reacting up to about half the amount of hydroquinone with optically active sodium 2-chloropropionate at a low slurry concentration while preventing precipitation of sodium salt of hydroquinone, which is a hard crystal, by salting out. Optically active 2- (4-hydroxyphenoxy)
After precipitation of sodium propionate by salting out,
Further, the remaining sodium salt of hydroquinone is optically active 2
-A method for obtaining optically active 2- (4-hydroxyphenoxy) propionic acid in high optical purity and high yield by reacting with chloropropionic acid sodium salt.

That is, according to the present invention, hydroquinone in an aqueous solvent and 1.5 to 2 moles of sodium hydroxide relative to hydroquinone are added, and then 0.2 to 0.5 moles of optically active 2-chloroamine are added. Propionic acid sodium salt or 0.2 to
0.5-fold molar amount of optically active 2-chloropropionic acid and 0.1.
After the first-stage reaction with 2- to 0.5-fold molar sodium hydroxide, 0.5 to 1.0 with respect to the charged hydroquinone.
The sodium salt of optically active 2- (4-hydroxyphenoxy) propionic acid formed by adding twice the molar amount of sodium hydroxide or 0.1 to 1 part by weight of sodium chloride and / or lithium chloride is subjected to salting out. 5 to 0.8 times mol of optically active 2-chloropropionic acid sodium salt or 0.5 to 0.8 times mol of optically active 2-chloropropionic acid and 0.5 to 0.8 times mol of sodium hydroxide The present invention relates to a method for producing optically active 2- (4-hydroxyphenoxy) propionic acid, which is characterized by performing a second-stage reaction.

Hereinafter, the present invention will be described in detail. 1.5 to 2 times mol of sodium hydroxide is added to hydroquinone in the presence of a small amount of water to prepare a hydroquinone sodium salt aqueous solution. The amount of water used is generally 0.8 to 2.5 parts by weight, preferably 1.0 to 1.5 parts by weight, per 1 part by weight of the charged hydroquinone.

[0009] Sodium hydroxide may be added as a solid or an aqueous solution. Sodium hydroxide aqueous solution is usually 3
A concentration of 0 to 60% by weight, preferably 30 to 60% by weight is used. The reaction temperature is usually 20 to 80
C, preferably 30 to 50C. Next, sodium salt of hydroquinone and 0.2 to 0.5-fold molar amount of optically active sodium 2-chloropropionate or 0.2 to 0.5 times
0.5-fold molar amount of optically active 2-chloropropionic acid and 0.1.
The first stage reaction is carried out with 2 to 0.5 times mol of sodium hydroxide.

It is desirable that the optically active 2-chloropropionic acid and sodium hydroxide be added simultaneously to carry out the first-stage reaction. At this time, it is more preferable that the addition rate is the same and the addition is performed continuously or intermittently without excess or shortage. The optically active 2-chloropropionic acid can be used after hydrolyzing the optically active 2-chloropropionic acid acid or alkaline and distilling off the produced alcohol.

The optically active sodium 2-chloropropionate may be added as a solid or an aqueous solution. The optically active sodium 2-chloropropionate aqueous solution usually has a concentration of 30 to 70% by weight. If the concentration exceeds 70% by weight, crystals of optically active sodium 2-chloropropionate may be precipitated.

The sodium hydroxide may be added as a solid or an aqueous solution, but an aqueous solution is preferred. The aqueous sodium hydroxide solution is usually 30 to 60% by weight, preferably 40% by weight.
A concentration of ５０50% by weight is used. The reaction temperature is usually from 20 to 80C, preferably from 30 to 50C.

After the first-stage reaction, an aqueous solution of 0.5 to 1.0 mole of sodium hydroxide or 0.1 to 1 part by weight of an aqueous solution of sodium chloride and / or lithium chloride is added to the charged hydroquinone. Optical activity 2-
The sodium salt of (4-hydroxyphenoxy) propionic acid is precipitated by salting out. The crystals mainly composed of optically active sodium 2- (4-hydroxyphenoxy) propionate precipitated by salting out are mainly different from the disodium hydroquino salt precipitated when an excessive amount of sodium hydroxide is added during the production of the sodium salt of hydroquinone. It is softer and easier to stir than the resulting crystals.

For complete salting out of the resulting optically active sodium 2- (4-hydroxyphenoxy) propionate, the total amount of water added to the charged hydroquinone is 1.5 to 2.5 parts by weight, preferably 1.5 to 2.5 parts by weight. Is preferably 1.5 to 2.0 parts by weight. As the amount of water added increases, the selectivity of optically active 2- (4-hydroxyphenoxy) propionic acid decreases.

The aqueous sodium hydroxide solution is usually 30 to 6
A concentration of 0% by weight, preferably 40-50% by weight is used. Sodium chloride may be added as a solid or an aqueous solution. The aqueous sodium chloride solution is usually 20 to
A concentration of 40% by weight is used. The salting-out temperature is usually from 20 to 80C, preferably from 30 to 50C.

The salting-out time is usually 30 minutes to 10 hours. After salting out, the remaining sodium salt of hydroquinone and 0.5 to 0.8 moles of sodium optically active 2-chloropropionate or 0.5 to 0.8 moles of optically active 2-chloropropionic acid and 0% Was reacted in the second stage with 0.5 to 0.8 times the molar amount of sodium hydroxide to give an optically active 2-
(4-Hydroxyphenoxy) propionic acid sodium salt.

It is desirable to add the optically active 2-chloropropionic acid and sodium hydroxide at the same time to cause a second stage reaction. At this time, it is more preferable that the addition rate is the same and the addition is performed continuously or intermittently without excess or shortage. The optically active sodium 2-chloropropionate may be added as a solid or an aqueous solution.

The aqueous solution of the sodium salt of optically active 2-chloropropionic acid is usually used at a concentration of 30 to 70% by weight. The optically active 2-chloropropionic acid can be used after hydrolyzing the optically active 2-chloropropionic acid acid or alkaline and distilling off the produced alcohol.

The sodium hydroxide may be added as a solid or an aqueous solution, but an aqueous solution is preferred. The aqueous sodium hydroxide solution is usually 30 to 60% by weight, preferably 40% by weight.
A concentration of ５０50% by weight is used. The reaction temperature is usually from 20 to 80C, preferably from 30 to 50C.

The reaction time is usually 1 to 10 hours, preferably 1 to 3 hours. Optical activity 2- (4
-Hydroxyphenoxy) propionic acid sodium salt can be converted to optically active 2- (4-hydroxyphenoxy) propionic acid by a known method.

[0021]

According to the method of the present invention, optical activity 2- (4
-Hydroxyphenoxy) propionic acid is obtained with high optical purity and high yield. In addition, the stirring in the slurry reaction, which is a feature of the method of the present invention, is greatly facilitated.

[0022]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. Example 1 55 g of hydroquinone and 66 g of water were charged, and after replacement with nitrogen, 38 g of sodium hydroxide was added. The temperature rises to become a homogeneous solution, but is cooled to 40 ° C.

Next, 24 g of sodium hydroxide was added to 30 g of water.
And 13.5 g of a solution in which was dissolved optically active 2-chloropropionic acid (purity 95%, optical purity 94% ee).
3 g were added simultaneously in one hour. After stirring for 1 hour, water 30
18 g of a solution in which 24 g of sodium hydroxide was dissolved was added to the resulting mixture, and the mixture was stirred for 1 hour.

During this time, the concentration of the slurry increases and crystals precipitate, but there is no problem in stirring. Further, 27.1 g of optically active 2-chloropropionic acid and 30 g of water were added to sodium hydroxide 2
22.5 g of a solution in which 4 g are dissolved is continuously and continuously 40 ° C.
For 1.5 hours, and further reacted at 40 ° C. for 1 hour, 50 ° C. for 1 hour, and 60 ° C. for 2 hours. After the reaction, 3
140 ml of a 5% by weight aqueous hydrochloric acid solution was added to make it acidic,
300 ml of water were added.

After extraction with 400 ml of methyl isobutyl ketone, an aqueous layer was further extracted with 100 ml of methyl isobutyl ketone. When the methyl isobutyl ketone layers were combined and analyzed by high performance liquid chromatography, the optically active 2-
58.2 g of (4-hydroxyphenoxy) propionic acid
I got Optical purity is 92% e. e. Met.

Analysis conditions Column Inertosyl ODS-2 4.6 × 250 mm Eluent Acetonitrile / water / acetic acid (1/2 /
0.05%) Flow rate 1.3 ml / min Detection 280 nm Internal standard substance 2-nitro-4-chloroaniline Example 2 55 g of hydroquinone and 66 g of water are charged, and after purging with nitrogen, 38 g of sodium hydroxide is added. The temperature rises to become a homogeneous solution, but is cooled to 40 ° C.

Next, 24 g of sodium hydroxide was added to 30 g of water.
Is divided into 12 portions of 4.5 g each (solution A)
Then, 43.4 g of optically active 2-chloropropionic acid (purity: 95%, optical purity: 94% ee) is divided into eight (solution B). One portion of solution A and one portion of solution B are added every 20 minutes, and a total of three portions are added.

Next, after stirring for 1 hour, 4 parts of solution A was added and stirred for 1 hour. During this time, the concentration of the slurry increases and crystals precipitate, but there is no problem in stirring. Further, one portion of solution A and one portion of solution B were added at 40 ° C. every 20 minutes, and a total of five portions were added. The reaction was further performed at 40 ° C. for 1 hour, 50 ° C. for 1 hour, and 60 ° C. for 2 hours.

After completion of the reaction, a 35% by weight aqueous solution of hydrochloric acid 14
0 ml was added to make it acidic, and 300 ml of water was added.
After extraction with 400 ml of methyl isobutyl ketone, the aqueous layer was further extracted with 100 ml of methyl isobutyl ketone. When the methyl isobutyl ketone layers were combined and analyzed by high performance liquid chromatography under the conditions of Example 1, optically active 2- (4-hydroxyphenoxy) propionic acid was obtained.
3 g were obtained. Example 3 55 g of hydroquinone and 66 g of water were charged, and after purging with nitrogen, 40 g of sodium hydroxide was added. The temperature rises to become a homogeneous solution, but is cooled to 40 ° C.

Next, 16 g of sodium hydroxide was added to 30 g of water.
Divided into 8 solutions of 5.75 g each (solution D)
Then, 43.4 g of optically active 2-chloropropionic acid (purity: 95%, optical purity: 94% ee) is divided into eight (solution B). One portion of solution D and one portion of solution B are added every 20 minutes, and a total of three portions are added.

Next, after stirring for 1 hour, sodium chloride 10
g was added and stirred for 1 hour. During this time, the concentration of the slurry increases and crystals precipitate, but there is no problem in stirring. Further, one portion of solution D and one portion of solution B were added at 40 ° C. every 20 minutes, and a total of five portions were added. 1 hour at 40 ° C, 50
The reaction was further performed at 1 hour at 60 ° C and 2 hours at 60 ° C.

After completion of the reaction, a 35% by weight aqueous solution of hydrochloric acid 14
0 ml was added to make it acidic, and 300 ml of water was added.
After extraction with 400 ml of methyl isobutyl ketone, the aqueous layer was further extracted with 100 ml of methyl isobutyl ketone. When the methyl isobutyl ketone layers were combined and analyzed by high performance liquid chromatography under the conditions of Example 1, optically active 2- (4-hydroxyphenoxy) propionic acid was obtained.
3 g were obtained. Example 4 55 g of hydroquinone and 66 g of water were charged, and after replacement with nitrogen, 38 g of sodium hydroxide was added. The temperature rises to become a homogeneous solution, but is cooled to 40 ° C.

Separately, 16 g of sodium hydroxide was added to 50 g of water.
Was added to the solution in which was dissolved at 40 ° C., and the resulting methanol and water were added at 40 ° C.
The solution was distilled at a temperature of not more than ℃ to obtain 84 g of an optically active sodium 2-chloropropionate aqueous solution, which was divided into eight portions (referred to as solution E). One division of solution E is added at 40 ° C. every 20 minutes, for a total of three divisions.

Next, after stirring for 1 hour, a solution prepared by dissolving 8 g of sodium hydroxide in 10 g of water was added and stirred for 1 hour. During this time, the concentration of the slurry increases and crystals precipitate, but there is no problem in stirring. Further, one division of Solution E is added every 4 minutes for 4 minutes.
It was added at 0 ° C., for a total of 5 portions.

1 hour at 40 ° C., 1 hour at 50 ° C., 60 ° C.
For 2 hours. After completion of the reaction, 140 ml of a 35% by weight aqueous hydrochloric acid solution was added to make the mixture acidic, and 300 m of water was added.
1 was added. After extraction with 400 ml of methyl isobutyl ketone, the aqueous layer was further extracted with 100 ml of methyl isobutyl ketone.

When the methyl isobutyl ketone layers were combined and analyzed by high performance liquid chromatography under the same conditions as in Example 1, 59.2 g of optically active 2- (4-hydroxyphenoxy) propionic acid was obtained.

Claims (2)

(57) [Claims] (1) Hydroquinone and optically active 2-chloropro
Reacting with pionic acid in the presence of sodium hydroxide
Active 2- (4-hydroxyphenoxy) pro by
In the method for producing pionic acid, hydroquinone 2 sodium
In order to prevent the salting of salt-free, to the Ha Idorokinon, 1.
Add 5 to 2 moles of sodium hydroxide, then add 0.2
0.5 to 0.5 mole of optically active sodium 2-chloropropionate or 0.2 to 0.5 mole of optically active 2-chloropropionic acid and 0.2 to 0.5 mole of sodium hydroxide. After a one-step reaction, the optical activity produced by adding 0.5 to 1.0 times mol of sodium hydroxide or 0.1 to 1 part by weight of sodium chloride and / or lithium chloride to the charged hydroquinone. The sodium salt of 2- (4-hydroxyphenoxy) propionic acid is salted out, and the optically active sodium 2-chloropropionate is 0.5 to 0.8 times mol or 0.5 to 0.8 times the optical activity. A process for producing optically active 2- (4-hydroxyphenoxy) propionic acid, which comprises reacting 2-chloropropionic acid with sodium hydroxide in a 0.5 to 0.8-fold molar amount in a second step. 2. A first stage and / or the second reaction, process according to claim 1 for reaction by addition to the same <br/> when the sodium hydroxide and optically active 2-chloropropionic acid. "