JPH02311444A - Production of optically active d-2-(4-hydroxy-phenoxy) propionic acid ester - Google Patents

Abstract

PURPOSE:To produce the subject compound having high chemical purity and optical purity independent of the optical purity of the raw material or the amount and temperature of water in reaction by reacting an l-2-halopropionic acid with hydroquinone (alkali metal salt) and subjecting the reaction product to a specific treating process. CONSTITUTION:An l-halopropionic acid is made to react with hydroquinone (alkali metal salt) in aqueous solvent in the presence of an alkali metal hydrox ide, the obtained aqueous solution is acidified, and extracted with an organic solvent and fractionated. The 1st aqueous layer is decomposed and the inorganic salt is removed. The 1st organic layer obtained by the above process is neutral ized and fractionated to obtain the 2nd aqueous layer containing d-2-(4- hydroxyphenoxy)propionic acid alkali metal salt. The aqueous layer is acidified and concentrated and the obtained concentrated aqueous solution is cooled to 10 to 40 deg.C (preferably 20 to 30 deg.C) to effect the selective crystallization of an optically active d-2-(4-hydroxyphenoxy)propionic acid. The objective com pound can be produced by esterifying the crystal in the presence of an acid catalyst.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides d-2-(4
The present invention relates to a method for industrially producing -hydroxyphenoxy)propionic acid ester.

2-(4-Hydroxyphenoxy)propionic acid ester is an important intermediate of 2-(phenoxy)propionic acid herbicides, which are herbicides that selectively exhibit strong fertilizing force against grasses.

This herbicide has two types of optically active forms, and the d-form has significantly superior herbicidal activity compared to the racemic form. Since this optical activity is derived from the intermediate d-2-(4-hydroxyphenoxy)propionic acid ester, it is difficult to industrially produce this compound with high chemical purity and high optical purity. Very meaningful.

[Prior art] As a conventional technology for producing d-2-(4-hydroxyphenoxy)propionic acid ester, Japanese Patent Application Laid-Open No. 61-15
The method described in Publication No. 8947 (hereinafter referred to as "conventional method A")
).

This "conventional method A" combines an alkali metal salt of f2-2-halopropionic acid (e.g., sodium salt) and hydroquinone or an alkali metal salt thereof (e.g., sodium salt) into an alkali metal hydroxide (e.g., hydroxide). d as one reaction product.
- Obtain an aqueous solution containing a dialkali metal salt of 2-(4-hydroxyphenoxy)propionate (e.g., disodium salt), then add a mineral acid such as hydrochloric acid to this aqueous solution to adjust the pH, and then After extraction and separation with a solvent, d-2-(4-hydroxyphenoxy)propionic acid in the resulting organic layer is subjected to an esterification reaction with an alcohol suitable for the purpose by a known method to obtain the optically active desired product. d-2-(4-hydroxyphenoxy)
This is a method for producing propionic acid ester.

However, this "conventional method A" has the following problems.

In other words, if we focus on chemical purity, "conventional method A":
In the synthesis reaction of d-2-(4-hydroxyphenoxy)propionic acid, it is necessary to control the amount and temperature of water within a certain range. When reacting with an aqueous solution of sodium salt as a raw material, f2-2
- Since the aqueous solution of chloropropionate sodium salt and the aqueous solution of hydroquinone disodium salt are both highly concentrated and highly viscous slurry solutions, it is difficult to accurately measure and control the amount of water on an industrial scale.

Furthermore, in "Conventional Method A", even if the amount of water is precisely controlled within a certain range, in addition to the target products d-2-(4-hydroxyphenoxy)pro and ionic acid, (f-2-(4-hydroxyphenoxy) −
hydroxyphenoxy)propionic acid, 2,2'-(p
-Phenyledioxy)dipropionic acid and other acidic substances and non-acidic substances such as hydroquinone are contained in large quantities. -2-(4
-Hydroxyphenoxy)propionic acid ester has low chemical purity and optical purity, and in order to obtain a product with high chemical purity and high optical purity, there is a problem in that an extensive purification step is required after esterification.

Next, focusing on the optical purity, in "F conventional method A", d-
The optical purity of 2-(4-hydroxyphenoxy)propionic acid ester is one of its raw materials! Most of it depends on the optical purity of 2-2-octalopropionic acid ester, but the optical purity of industrially produced ni-2-halopropionic acid ester varies widely, and the optical purity of commercially available products is , the obtained d-2-(4- The optical purity of the hydroxyphenoxy)propionic acid ester is approximately 1 to 3% e lower than the optical purity of the starting material, the hydro-2-halopropionic acid ester.

In addition, Japanese Patent Application Laid-Open No. 174952/1983 describes crude d
-2-(4-hydroxyphenoxy)propionic acid is purified by recrystallization and then esterified,
Method C for producing high-purity d-2-(4-hydroxyphenoxy)propionic acid esters Below, "Conventional method B"
) has been disclosed.

In other words, this "conventional method B" has a
．． Crystals of crude d-2-(4-hydroxyphenoxy)propionic acid containing 2'-(p-phenylenedioxy)dipropionic acid are treated with halogen-based solvents, ester-based solvents, aromatic hydrocarbon-based solvents, and alcohol-based solvents. and at least one solvent selected from solvents such as water, and
Dissolve by heating at about 150℃, and dissolve the resulting solution for about 30 minutes.
Recrystallization was performed by slow cooling from 0°C to room temperature over several hours, and the precipitated crystals were filtered and separated to obtain highly pure d-2-(4-hydroxyphenoxy)propionic acid. to obtain high-purity d-2-(4-
This is a method for producing hydroxyphenoxy)propionate.

However, in this "Conventional Method B", d-2-(4-hydroxyphenoxy)propionic acid obtained by the reaction of hydroquinone and fl-2-halopropionic acid is -phenylenedioxy) dipropionic acid is once crystallized, and the resulting crystals are melted by heating to become a solution again and then recrystallized, which is a waste in terms of energy cost and d-2- (4
- When the recrystallization process of hydroxyphenoxy)propionic acid is viewed as one step in the production process of the same ester, it is said that the series of production processes is complicated and it is difficult to continuously produce the same ester. There's a problem.

[Problems to be Solved by the Invention] An object of the present invention is to obtain a material with high chemical purity and unaffected by the optical purity of the raw material 2-halopropionic acid ester and the amount and temperature of water during the reaction. High optical purity d-2°-(
An object of the present invention is to provide a method for industrially and continuously producing 4-hydroxyphenoxy)propionic acid ester.

[Means for Solving the Problems] The present invention provides the following steps: , an aqueous solution containing an alkali metal salt of d-2-(4-hydroxyphenoxy)propionate is obtained, (b+) An acid is added to this aqueous solution to make it acidic, and the first water group is separated and removed by extraction and separation with an organic solvent. (c) neutralizing and separating the obtained first aqueous layer with an aqueous alkali metal hydroxide solution to obtain a second aqueous layer containing an alkali metal salt of d-2-(4-hydroxyphenoxy)propionate; (dl After adding acid again to the second aqueous layer to make it acidic.

(e) concentrating the acidic third aqueous layer, cooling the resulting concentrated aqueous solution to selectively crystallize optically active d-2-(4-hydroxyphenoxy)propionic acid, and (fl A method for producing optically active d-2-(4-hydroxyphenoxy)propionic acid ester, characterized by esterifying the obtained crystals in the presence of an acid catalyst.

Hereinafter, the method of the present invention will be explained in detail in accordance with the manufacturing steps with reference to the drawings.

FIG. 1 is a block flow diagram showing the manufacturing process of the present invention.

The method for producing nystyl d-2-(4-hydroxyphenoxy)propionate according to the method of the present invention includes a synthesis step, a first acidification step, an inorganic salt removal step, a hydroquinone removal step, and a first step, as shown in FIG. It consists of 7 steps: 2 acidification steps, a crystallization separation step, and an esterification step.

Synthesis step: In this step, an optically active ε-2-halopropionic acid ester is hydrolyzed in an aqueous alkali metal hydroxide solution to form (
While f-2-halopropionic acid was produced, the corresponding by-product alcohol was distilled off and isolated (f-2-
Halopropionic acid and hydroquinone or its alkali metal salt are reacted in an aqueous solvent in the presence of an alkali metal hydroxide to form d-2-(4-hydroxyphenoquine).
This is a step of producing a dialkali metal propionate salt, and is carried out in the same manner as the conventional method AJ.

First acidification step: This step consists of the dialkali metal salt of d-2-(4-hydroxyphenoxy)propionic acid obtained in the above step [hereinafter referred to as d-2-(4-hydroxyphenoxyphenoxy ) is acidified by adding an acid to an aqueous solution of propionic acid disodium salt.

By this acidification, the d-2-(4-hydroxyphenoxy)propionate disodium salt in the aqueous solution becomes
It changes to d-2-(4-hydroxyphenoxy)propionic acid, and a mineral acid sodium salt is produced as a by-product.

the type and concentration of the acid used for adjusting the pH;
The PU value of the acidic aqueous solution after addition of the acid, the method of adding the acid, etc. are not particularly limited as long as the purpose of this step described above can be achieved (and can be carried out by a conventional method.

Inorganic salt removal step: In this step, the acidic aqueous solution from the "first acidification step" is extracted with an organic solvent, separated into a first organic layer and a first aqueous layer, and then extracted from the first organic layer. By separating the first aqueous layer and discharging it out of the system as wastewater, the unsalted salt transferred into the first aqueous layer, that is, the alkali metal halide salt produced by the reaction in the "synthesis step" mentioned in @, and a step of removing the mineral acid sodium salt produced in the "first acidification step".

The extraction of the acidic aqueous solution with the above organic solvent is preferably carried out in two steps.
Although stage extraction is performed, the extraction temperature, extraction time, standing time for separation after extraction, and other extraction and separation operating conditions and extraction methods are not particularly limited, and may be any conventional liquid extraction method. Any method employed in the extraction/liquid separation operation may be used.

Furthermore, as the organic heating medium used in this step, as long as it has high solubility in d-2-(4-hydroxyphenoxy)propionic acid contained in the acidic aqueous solution and low mutual solubility with water, Although any organic solvent can be used, methyl isobutyl ketone is particularly preferred because of its good extraction efficiency and liquid separation properties.

The amount of organic solvent used also depends on the type of organic solvent used and the extraction rate of d-2-(4-hydroxyphenoxy)propionic acid contained in the acidic aqueous solution. However, the level used in "Conventional Method A" is sufficient.

Hydroquinone removal step: This step is the d-2-(4-
In order to facilitate the crystallization separation of hydroxyphenoxy)propionic acid, the first
This is a step to remove hydroquinone contained in the organic layer.

In this step, first, an aqueous solution of an alkali metal hydroxide is added to the first organic M obtained in the "inorganic salt removal step" to neutralize the d- 2-(4
-Hydroxyphenoxy)propionic acid to its sodium salt.

Conditions for neutralizing this first organic layer (e.g., neutralization temperature, neutralization method, type of aqueous alkali metal hydroxide solution to be added,
(concentration and amount, pFI value of the neutralizing solution, aging time after addition of the aqueous solution of alkali metal hydroxide, etc.) are the same as normal neutralization operations, and no special conditions are required.

In addition, as the aqueous solution of the alkali metal hydroxide, it is preferable to use the same kind of solution as that used in the above-mentioned "synthesis step J". In view of solubility in water, it is particularly preferable to use an aqueous sodium hydroxide solution.

Next, the neutralized solution obtained as described above is allowed to stand to form a second organic layer containing mainly non-acidic impurities such as hydroquinone and mainly d-2-(4-hydroxyphenoxy)propionate sodium salt. The liquid is separated into a second aqueous layer containing the liquid.

The second aqueous layer from which non-acidic impurities such as hydroquinone have been removed in this way is supplied to the next "second acidification step".

On the other hand, the second organic layer separated from the second aqueous layer by static separation of the neutralized liquid is supplied to a solvent recovery step, concentrated,
The organic solvent is recovered by known methods such as distillation.

Second acidification step: This "second acidification step" and the following "crystallization separation step" are steps that are characteristic of the method of the present invention and are important steps of the present invention.

That is, the second aqueous layer obtained in the above [hydroquinone removal step] contains d-2-(4-hydroxyphenoxy).
Besides propionic acid sodium salt, I2-2- (4-
Hydroxyphenoxy)propionate sodium salt, 2
．． Since it contains impurities such as 2'-(p-phenylenedioxy)dipropionic acid disodium salt, it is removed from the third aqueous layer by the "second acidification step" and the following "crystallization separation step". After selectively crystallizing the target product, d-2-(4-hydroxyphenoxy)propionic acid, the resulting crystals are led to an "esterification step" to produce d with high chemical purity and high optical purity. -2-(4-hydroxyphenoxy)propionic acid ester is obtained.

In this "second acidification step," the second aqueous layer is supplied to an acidification tank and heated to a temperature of 20 to 50°C, preferably 25 to 35°C, while cooling and stirring as necessary. acid in the second aqueous layer, pl (value 1.0 to 3) of the obtained third aqueous layer
,0, preferably 1.5 to 2,5. More preferably 2
．． It is preferable to add d-2-(4-hydroxyphenoxy) in an acidic state where the pH value of the third aqueous layer exceeds 3.0.
Since the equivalence point of propionic acid has not been reached, d-2-(4-hydroxyphenoxy) in the next "crystallization separation step"
The crystallization recovery rate of propionic acid is poor, and the p of the third aqueous layer is
Under acidic conditions where the H value is less than 1.0, the equivalence point of d-2-(4-hydroxyphenoxy)propionic acid has been passed, so even if the amount of acid added is increased further, the following An improvement in the crystallization recovery rate of d-2-(4-hydroxyphenoxy)propionic acid in the "crystallization separation step" cannot be expected.

This acidification causes d- and I2 in the second aqueous layer to
-2-(4-Hydroxyphenoxy)propionate sodium salt and 2,2'-(p-phenylenedioxy)dipropionate disodium salt are converted into free acids and inorganic salts, that is, mineral acid. Sodium salt is produced as a by-product.

The acidification tank does not require any special equipment and may be an ordinary stirring tank.The cooling method may also be such that the acidification tank is equipped with an internal corrugated pipe or other internal cooling device, an external jacket or other external cooling device, etc. It is preferable that the acidification tank be made of an acid-resistant material such as a glass lining material, as in the case of the acidification tank in the "first acidification step".

As the acid used for adjusting the pH, the above-mentioned "first acid" is used.
It is preferable to use the same type of acid as used in the "acidification process," and mineral acids such as sulfuric acid, nitric acid, and hydrochloric acid are preferable, but depending on the material of the equipment used, ease of handling, economic efficiency, etc. Therefore, it is particularly preferable to use sulfuric acid.

Further, the concentration of the mineral acid is not particularly limited, and the same concentration as that used in the above-mentioned "first acidification step" may be used, but it may be easier to adjust the pH or the next "crystallization separation step. In terms of economy, ease of operation, etc., the amount is 30 to 98% by weight, preferably 50 to 70% by weight.

Furthermore, the method for adding mineral acid may be to simultaneously add concentrated mineral acid and water in an amount ratio such that the concentration of mineral acid falls within the above concentration range, or to add concentrated mineral acid and water at the same time in an amount ratio such that the concentration of mineral acid falls within the above concentration range, or 6. Crystallization separation step in which an aqueous solution may be added: This step mainly consists of a "concentration step,""cooling crystallization step," and "crystal separation step," and as described above, d- and (f- From an acidic third aqueous layer containing 2-(4-hydroxyphenoxy)propionic acid, 2,2'-(p-phenylenedioxy)dibutionic acid and an inorganic salt (eg, sodium sulfate), etc. The target object d-2-(4-
The purpose is to selectively obtain crystals of hydroxyphenoxy)propionic acid.

In the first rl condensation step, d-2-(4-
To adjust the concentration of hydroxyphenoxypropionic acid, the acidic third aqueous layer is concentrated.

The concentration of the third aqueous layer needs to be to such an extent that the inorganic salts contained in the third aqueous layer do not precipitate in the following "cooling crystallization step J," and the concentration obtained by concentrating the third aqueous layer must be The aqueous solution is concentrated to such an extent that the weight ratio of the inorganic salt to water is 0.1 to 0.5, preferably 0.2 to 0.3.

Although this concentration can be carried out under pressure, normal pressure, or reduced pressure, vacuum concentration is particularly preferable because large crystals with a small liquid content can be obtained in the crystal separation step J, which will be described later. , in the case of vacuum concentration, 50~
150Torr, preferably 70~10Torr
It is best to perform this under moderately reduced pressure.

The heating temperature varies depending on the amount and composition of the third aqueous layer, the degree of concentration, the pressure during concentration, etc., but is 50 to 150 Torr.
When concentration is carried out under reduced pressure, it is preferably carried out at a temperature of 40 to 70°C, particularly 50 to 60°C.

Next, in the "cooling crystallization step," the concentrated aqueous solution obtained above is cooled to the crystallization temperature of d-2-(4-hydroxyphenoxy)propionic acid, and the difference in solubility in water depending on temperature is utilized. Then, crystals of d-2-(4-hydroxyphenoxy)propionic acid are precipitated.

As in the case of concentrating the third aqueous layer, the cooling/crystallization temperature of the concentrated aqueous solution is set at 10% to prevent the sodium salt of the mineral acid from precipitating.
It is preferable to set the temperature to ~40°C, preferably 20 to 30°C.

In addition, cooling and crystallization of the concentrated aqueous solution can be carried out by indirect cooling using an internal coiled pipe or other internal cooling device installed in the crystallizer, an external jacket or other external cooling device, or an organic Approximately 30 minutes or more using a method in which the a-condensation operation and cooling/crystallization operation are performed simultaneously using the latent heat of vaporization of the solvent and water, or other cooling methods commonly used in industry.
It is preferable to gradually cool down to the cooling/crystallization temperature over 5 hours, preferably 1 to 3 hours.More preferably, the cooling/crystallization operation is performed while stirring. For example, the analyzer is equipped with a stirrer, and the
The mixture may be cooled while being stirred at a slow stirring speed of about 00 r, p, m, or the concentrated aqueous solution may be stirred by external circulation and a cooler may be provided in the external circulation system for cooling.

The crystallizer does not require a special structure such as a draft tube baffle type crystallizer, and may be a normal stirring tank similar to the acidification tank in the "second acidification step".
Furthermore, the material of the crystallizer is also the same as the acidification tank.
The use of acid-resistant materials, such as glass linings, is preferred.

By the way, concentration of the third aqueous phase and cooling/cooling of the concentrated aqueous solution
The reason why the crystallization temperature is set so that the sodium salt of the mineral acid does not precipitate as described above is because in the "cooling crystallization process" the sodium salt of the mineral acid is ) If it precipitates together with propionic acid crystals, it acts to weaken the activity of the acid catalyst in the subsequent "esterification process" and has a negative impact on the esterification reaction. This is because, since it contains water, it is necessary to perform azeotropic dehydration with an organic solvent such as toluene before esterification.

As described above, an aqueous solution containing crystals of d-2-(4-hydroxyphenoxy)propionic acid (hereinafter referred to as a crystal-containing aqueous solution) that has been selectively crystallized while preventing the precipitation of the mineral acid sodium salt. is supplied to the next "crystal separation step", where the crystals of d-2-(4-hydroxyphenoxy)propionic acid are filtered and separated.

For crystallization and separation from the crystal-containing aqueous solution mentioned above, a centrifugal separation column may be used, a filter may be used,
Any other method may be used as long as it can easily separate the crystals. However, depending on the cooling temperature during cooling and crystallization of the concentrated aqueous solution, f2-2-
(4-hydroxyphenoxy)propionic acid, 2.2'
Impurities such as -(p-phenylenedioxy)dipropionic acid are attached in the form of oil, and since these oily impurities can be easily removed by centrifugation, it is preferable to use a centrifuge.

Esterification step: In this step, the d obtained in the “crystallization separation step” is
The soaked crystals of -2-(4-hydroxyphenoxy)propionic acid were esterified to give optically active d-2-(4-
This is a step of producing hydroxyphenoxy)propionic acid ester.

As the above esterification method, for example, [Conventional method AJ
A method similar to 1 can be adopted, for example, d-2-
(4-hydroxyphenoxy)propionic acid crystals,
The desired product, d-2-, is esterified in a solvent such as toluene in the presence of an acid catalyst such as sulfuric acid with an alcohol suitable for the purpose while undergoing azeotropic dehydration.
(4-Hydroxyphenoxy)pro and onic acid esters are obtained. Note that this esterification reaction is preferably carried out until the azeotropic water is exhausted.

Since the above esterification reaction is carried out in the presence of excess alcohol, a solvent solution of the obtained d-2-(4-hydroxyphenoxy)propionic acid ester is mixed with the acid catalyst and an equivalent amount of alkali metal carbonate. After neutralization with a salt, preferably sodium bicarbonate, it is concentrated to remove almost all of the unreacted alcohols and the solvent.

Purification step; Although not shown in FIG. 1, this step is the final step in the method of the present invention, and is the final step in the method of the present invention. concentrated? From the 8 liquid, optically active d-
This is a method for obtaining 2-(4-hydroxyphenoxy)propionic acid ester.

In addition, in the method of the present invention, some of the various treatment tanks in each step can be used in common, and the equipment can be considerably simplified.

[Effects of the Invention] As described above, in the method of the present invention, d-2-(4-hydroxyphenoxy)propionic acid is selectively crystallized from an aqueous solution containing it together with impurities, and the resulting crystals are converted into esters. with a chemical purity of at least 95% by weight and at least 96% e,
d-2-(4-hydroxyphenoxy)propionic acid ester having an optical purity of 0.e or higher is continuously obtained.

[Example] Next, the method of the present invention will be explained in more detail with reference to Examples and Comparative Examples, but these do not limit the method of the present invention in any way.

The composition ratio of intermediates and the chemical purity of the final product d-2-(4-hydroxyphenoxy)propionic acid ester in Examples and Comparative Examples were determined by liquid chromatography. Further, the optical purity of the raw material (f-2-halobrobionic ester) and the final product d-2-(4-hydroxyphenoxy)propionic ester was determined by liquid chromatography using an optical resolution column.

Example 1 Methyl 2-2-chloropropionate (optical purity 95% e
, e, ) 5.88 kg (48 mol) and water 7.79 k
408 kg (49 mol) of a 48 wt % aqueous solution of caustic soda was warmed to the mixed solution of 100 g at 20 to 30'C under stirring and cooling to cause a hydrolysis reaction.

Thereafter, methanol and water produced from the reaction product were distilled off using an evaporator. Distillation trap amount is 6.4
It was kg. Therefore, water was added to the residual liquid in the evaporator to obtain 11.0 kg of a slurry solution of sodium I2-2-chloropropionate.

Next, this solution was separately added to a slurry solution of hydroquinone disodium salt produced by reaction with 6.60 kg (60 mol) of hydroquinone (hereinafter abbreviated as HQ) and 11.0 kg (132 mail) of a 48% by weight aqueous solution of caustic soda. The mixture was added while stirring and cooling, and after reacting at 30 to 40°C for 15 hours, it was further aged for 2 hours.

Thereafter, 3 parts of a 20% by weight aqueous sulfuric acid solution was added to this reaction solution while cooling.
After adding 5 kg (72 mol) of methyl isobutyl ketone (hereinafter abbreviated as MIBK) to this reaction solution, 10.6 kg of methyl isobutyl ketone (hereinafter abbreviated as MIBK) was added to the reaction solution to make it acidic with a pH value of 1.5.
was added, stirred and extracted, separated, and the resulting aqueous layer was again M
The mixture was extracted with stirring using 5.4 kg of IBK, and the liquid was separated.

The MI obtained in this two-stage extraction/separation operation
The total amount of BK layer is 28.0 kg, and its composition ratio is HQ
Near, 7% by weight [2.15 kg (2.0 mol) 1
, 2-(4-hydroxyphenoxy)propionic acid (
Hereinafter abbreviated as HPPA) 22.9% by weight [6,41
kg(35,2rnall], 2.2'-(p-
phenylenedioxy) dipropionic acid (hereinafter referred to as PDPA)
) 1.83% by weight [0,51kg (2,0
mol) ], and the HPPA/PDPA value (weight ratio) was 12.6.

This MIBK layer C and below is abbreviated as MIBK-A raw material liquid) 398 g ([HPPA content: 91, Ig (
0.5 mol)] was mixed with 200 g of water, and under stirring and cooling, the pH value was adjusted to 7.5 with 30% by weight aqueous solution of caustic soda, and HPPA was extracted into the aqueous layer. % by weight of sulfuric acid aqueous solution to adjust the pH value of the aqueous layer to 2.0.
was readjusted.

Therefore, this acidic aqueous layer was concentrated under reduced pressure at a temperature of 40° C. to distill off a total of 100 g of remaining MIBK and water. Furthermore, 100 g of water was added to the residual liquid to make the weight ratio of the produced sodium sulfate to water 0.2, and then 2
After cooling to 0° C., 81.6 g of wet crystals were separated by centrifugation while avoiding the formation of sodium sulfate crystals. HPPA in this crystal was 74.9g, HPPA/P
The DPA value (weight ratio) was 89.

Next, the wet crystals were mixed with 220 g of toluene and 0 g of concentrated sulfuric acid.
Prepared in a mixed solution of 8 g and 41.2 g of ethanol,
HPPA was esterified.

1.4 g of sodium bicarbonate was added to this reaction solution, concentrated, and then distilled to give a solution of 88.
4g was obtained. Its chemical purity is 96.5% by weight (D-HP
PE purity: 84.7g), optical purity 98.5%e,
It was e.

Example 2.

Using the same amount of MIBK-A raw material liquid obtained as an intermediate in Example 1 as in Example 1, the pH value was adjusted to 7.5 with a 30% by weight aqueous sodium chloride solution, and the liquid was separated. D-HPPEPP was prepared in exactly the same manner as in Example 1, except that the aqueous layer was adjusted to a pH value of 2.5 with a 70% by weight aqueous sulfuric acid solution.
Manufactured above.

The pickled crystals obtained as an intermediate were 68. og, HPPA in this crystal is 66.1g, HPPA/PDPA
The value (weight ratio) was 1153.

In addition, D-HP obtained by esterification of this crystal
It weighs 76.1 g on PEPP, its chemical purity is 99.2% by weight (D-HPPE purity near 5.3 g), and its optical purity is 99.
．． It was 6% e, e.

Comparative Example 1 The same amount of MIBK-A raw material liquid obtained as an intermediate in Example 1 was used as in Example 1, and the pH value was adjusted to 7.5 with a 30% by weight aqueous solution of caustic soda, and until liquid separation, the same amount as in Example 1 was used. 1
I did the same thing.

After that, the obtained water stone was adjusted to pH with 30% by weight sulfuric acid aqueous solution.
The mixture was made into an acidic state with a value of 1.5, and 200 g of MIBK was further added, HPPA was stirred and extracted into the MIBK layer, and the layers were separated.

This HPPA-containing organic layer (MIBK layer) was concentrated under reduced pressure to distill off MIBK, and then 330 g of toluene, 1.2 g of concentrated sulfuric acid, and 61.8 g of ethanol were added to the concentrated solution to esterify HPPA. It became.

Add 2.1 g of baking soda to this reaction solution, concentrate and distill to D
-95.2 g of a solution of HPPH was obtained. Its chemical purity is 9
It was 0.6% by weight (D-HPPE pure content: 83.3g), and the optical purity was 93.2%ee.

Example 3! Isobutyl 2-2-chloropropionate (optical purity 9
4.2% e, e, ) 7.92 kg (48 mol) and 7.79 kg of water at 30 to 35°C under stirring and cooling.
4.08 kg (49 m) of 48% by weight aqueous solution of caustic soda
ol) was warmed to cause a hydrolysis reaction.

1 total of imbutanol and water while adding the condensate.
2.0kg distilled off! 11.8 kg of a slurry solution of sodium -2-chloropropionate was obtained.

This solution was reacted with a slurry solution of hydroquinone disodium salt in the same manner as in Example 1, and then the imbutanol remaining in the reaction solution was concentrated and then MI Extraction and separation operations were performed twice with BK.

The amount of the obtained MIBK layer (hereinafter abbreviated as MIBK-B raw material liquid) was 28.5 kg, and its composition ratio was HQ near,
82% by weight [2.23kg (2.07mail), H
PPA; 22.0% by weight [6,27kg (34,4
mol)], PDPA: 2.07% by weight [0.5
9 kg (2,31 mol) ], and HPP
The A/PDPA value (weight ratio) was 10.6.

Therefore, 414g of this MI BK-B raw material liquid [HPP
A content; 91,1 g (0.5 mol)] was used, and the same treatment as in Example 1 was performed to obtain 89.3 g of a solution of D-HPPH.The chemical purity was 96.2% by weight.
(D-HPPE pure content: 85.2g), optical purity is 98.
It was 3% e, e.

Example 4 MIBK-B obtained as an intermediate in Example 3
Methyl d-2-(4-hydroxyphenoxy)propionate (hereinafter referred to as D-HPPM) was prepared in the same manner as in Example 3, except that the same amount of the raw material liquid as in Example 3 was used and HPPA was esterified with methanol. Solution 84.2 of (abbreviated)
I got g. Its chemical purity is 97.0% by weight (D-HPP
M purity: 80.9g), optical purity: 98.2%e,
It was e.

Example 5 MIBK-B obtained as an intermediate in Example 3
In the same manner as in Example 3, except that the same amount of raw material liquid was used as in Example 3, and HPPA was esterified with butanol,
d-2-(4-hydroxyphenoxy)propionic acid n
-Butyl (hereinafter abbreviated as D-f4PPB) solution 1
01.2g was obtained. Its chemical purity and optical purity are 95.8% by weight (D-HPPB pure content: 95.9g
) and 97.8% e, e.

Example 6 Same as Example 3 except that isobutyl β-2-chloropropionate with optical purity of 84.9% ee was used.
After processing up to extraction and separation using MI BK,
A K layer was obtained.

This MI BK layer plate weighs 28.0 kg, and its composition ratio is HQ Near, 75% by weight [2.17 kg (2.02 mol
)], HPPA; 21.1% by weight [5,90kg
(32.4 mol)], PDPA; 3.57% by weight
[1,00 kg (3,92 mol)], and
The HPPA/PDPA value C (weight ratio) was 5.9.

Therefore, 432 g of this MI BK layer C (hereinafter referred to as MI BK-C raw material liquid) [HPPA content: 91.
Ig (0.5 mol)] and further Example 1
The same treatment as above was performed to obtain 80.0 g of a D-HPPH solution. Its chemical purity was 96.7% by weight (D-HPPE purity: 6.4 g), and its optical purity was 97.6% e, e.

Comparative Example 2 MIBK-C obtained as an intermediate in Example 6
A D-HPPE solution was produced in the same manner as in Comparative Example 1, except that the same amount of the raw material liquid as in Example 6 was used.

The obtained D-HPPE solution weighed 98.1 g, and its chemical purity was 88.0% by weight (D-HPPE purity + 79.3 g).
), and the optical purity was 83.8% e, e.

[Brief explanation of the drawing]

Claims (1)

Scope of Claims: (a) l-2-halopropionic acid and hydroquinone or an alkali metal salt thereof are reacted in an aqueous solvent in the presence of an alkali metal hydroxide; An aqueous solution containing an alkali metal salt of -hydroxyphenoxy)propionate is obtained, (b) an acid is added to this aqueous solution to make it acidic, and the first aqueous layer is separated and removed by extraction and separation with an organic solvent; (c) The obtained first organic layer is neutralized and separated with an aqueous alkali metal hydroxide solution to obtain a second aqueous layer containing an alkali metal salt of d-2-(4-hydroxyphenoxy)propionate; After adding acid again to the second aqueous layer to make it acidic, (e) concentrating the acidic third aqueous layer and cooling the obtained concentrated aqueous solution to obtain optically active d-2-(4-hydroxy selectively crystallizing phenoxy)propionic acid, and (f) esterifying the obtained crystals in the presence of an acid catalyst. A method for producing propionic acid ester.