JPS62145050A - Recovery of serine - Google Patents

Abstract

PURPOSE:An aqueous serine solution containing inorganic salt contaminants and/or isoserine is subjected to column chromatography filled with a cation- exchanger and developed with water to recover serine economically in high efficiency. CONSTITUTION:An aqueous serine solution containing inorganic salt contaminants and/or isoserine is subjected to column chromatography filled with a cation-exchanger selected from the group consisting of metal salt type strong-acid cation exchangers, metal salt type weak acid cation exchangers and H-type weak acid cation exchangers and developed with water. The serine fractions eluted are collected. The aqueous serine solution is obtained, e.g. by reaction of aziridine-2-carboxylic acid or its derivative of the formula (Y is -CO2H, -CONH2) with an alkalic metal hydroxide and/or oxoacid followed by neutralization.

Description

DETAILED DESCRIPTION OF THE INVENTION [Background of the Invention] The present invention relates to a method for efficiently recovering serine from an aqueous solution of serine containing inorganic salt impurities and/or isoserine. From another point of view, the present invention relates to a method for producing serine that is low in inorganic salt impurities and/or isoserine.

Serine is a type of amino acid, and L is an infusion ingredient.
D is used as a cosmetic additive, etc., and D is an antibiotic.
- It is a useful compound as a raw material for cycloserine, etc.

In general, serine is an important compound as a raw material for cysteine and tryptophan, which has recently attracted attention as a feed additive, and as a raw material for physiologically active peptides.

and No. 11 As a method for recovering serine from an aqueous serine solution containing inorganic salt impurities, the following method is known, for example.

(1) Add sulfuric acid to an aqueous solution of lithium ajibazine 2-carboxylate, heat it to generate serine, add barium chloride to precipitate the dissolved sulfate ions in the form of barium sulfate, separate it in a furnace, A method of recovering serine by treating the solution with a cation exchange resin and separating rB with dilute ammonia water [Chew, Berchte,
) flJ, 1632 (1960)).

(2) Aziridine-2-carboxylic acid or its alkali salt is reacted with sulfuric acid to produce serine, and the reaction solution is adjusted to pH 10 or higher by adding caustic soda, and cooled to below 10°C to remove the precipitated sodium sulfate. After adjusting the PL+ of the solution to 5 to 6, the solution is cooled to 25°C or below for 11 L to collect the precipitated serine crystals (Japanese Patent Laid-Open No. 58-17
Publication No. 2352).

(3) Glycolaldehye or its analogs
e After reacting with potassium cyanide, ammonium chloride and ammonia in an OH/water mixed liquid medium, the reaction solution obtained by reacting with hydrochloric acid is evaporated to dryness, the solvent is removed, m-hydrochloric acid is added to the residue, and the mixture is heated and refluxed. , Absolute ethanol was added to the residue obtained by evaporation and dryness again to remove insoluble solids, and triethylamine was added to the liquid to adjust the pH to 6.
Method for collecting serine crystals precipitated by cooling (Chew, Ber,) ±11
．． 148 (1979)).

(4) After neutralizing α-riO-β-aminopropionic hydrochloride in an aqueous solution with hatrium hydroxide, aqueous sodium hydroxide solution was gradually added dropwise and heated while keeping the pH at 5.0. Dilute hydrochloric acid was added to the solution, and the residue containing DL-serine hydrochloride obtained by evaporating to dryness in a vacuum was dissolved in anhydrous ethanol, and the solution obtained by separating the common salt in a furnace was evaporated to dryness again, then dissolved in water and subjected to ion exchange. A method for obtaining chromatographically pure OL-serine by recrystallizing crude serine obtained by resin treatment twice from a water/ethanol mixed solvent.

However, although these methods have provided some solutions, as far as the present inventors know, they still have some problems as described below.

Method (1) requires expensive barium chloride and a large amount of aqueous ammonia, and the cation exchange resin needs to be regenerated with a large amount of hydrochloric acid after use, making the recovery of serine expensive. Since the crude DL-serine produced by the above method contains less than 8% S of isorine, it is difficult to obtain high-purity serine because by-product isoserine cannot be removed by this method.

Method (2) involves many steps such as pH adjustment and filtration, making the operation complicated, and the recovery rate of serine is low (approximately 70%
%), and the purity of the obtained serine is also low (95%). Although DL-serine can be recovered by such a crystallization method, it is difficult to recover optically active serine, which has a high solubility.

Method (3) requires the reaction solution to be evaporated twice to dryness, resulting in high energy costs, the need to use expensive reagents such as anhydrous ethanol and triethylamine, and moreover, it is complicated due to the large number of steps. Therefore, it is difficult to recover serine at low cost.

Method (4) requires evaporation to dryness twice, resulting in high energy costs, does not require the use of high 1i11i anhydrous ethanol, and does not require the use of pure L-serine.
7, recrystallization must be performed twice, and this is not an industrially inexpensive method for recovering serine.

According to the experiments of the present inventors, isoserine-containing D L −
Serine (DL-serine/isoserine-3,010,21
), in order to completely remove isoserine by recrystallization, the recovery rate of DL-serine must be 80% or less, and even in this case, it is difficult to completely remove the inorganic salt (see Comparative Example 4). It must be said that industrial purification of OL-serine by recrystallization is difficult.

Thus, it cannot be said that a method for easily and inexpensively recovering high-purity serine on an industrial scale has been completed.

[Summary of the development]

□ Under these circumstances, the present invention was developed as a result of extensive research into a method for efficiently recovering serine by separating it from impurities such as inorganic salts and/or isoserine, and is an industrially significant achievement. This was made based on the new discovery that inorganic salt impurities, serine, and isoserine can be separated and eluted by using a specific ion exchanger that is inexpensively and stably available.

That is, the serine recovery method according to the present invention removes serine from an aqueous serine solution containing inorganic salt impurities and/or isoserine using a metal salt-type strongly acidic cation exchanger, a metal salt-type weakly acidic cation exchanger, and a metal salt-type weakly acidic cation exchanger. chromatography using a cation exchanger selected from the group consisting of weakly acidic cation exchangers of the type as a packing material and water as a developing agent, and separating a fraction of serine eluted; It is characterized by:

Effects The method of the present invention provides a method for recovering highly pure serine in the form of an aqueous solution by separating not only ionic salts and/or isoserine, but also impurities such as other side reaction products. The cation exchanger can be operated repeatedly without regeneration after passing the sample solution and water through the packed bed of the cation exchanger. This method has many industrial advantages, such as being extremely economical as the cost of the regenerant can be ignored.

Since the serine aqueous solution recovered by the method of the present invention has high purity, it can be used as it is or after being concentrated for desired purposes, and solid serine can be precipitated by concentration and/or addition of a precipitating agent. It can also be used as

Furthermore, the method of the present invention can be applied not only to DL-serine but also to optically active serine.

In addition, as a cation exchanger, for example, industrially
Average particle size is 100-500 and can be obtained cheaply and stably.
It must be said that the purpose of purifying and recovering phosphorus was achieved using the μ cation exchange resin.

[Detailed description of the invention]

Serine aqueous solution The serine that can be recovered by the present invention is chemically synthesized by various methods, or by racemizing optically active serine (DL-serine, biochemical method, asymmetric synthesis method, or DL-serine). L- or D-serine obtained by an optical resolution method of serine may also be used.

The serine aqueous solution targeted by the present invention is at least 1ff-free.
This is an aqueous solution of serine containing ijWs and/or isoserine as impurities. That is, it means an aqueous solution of serine containing an inorganic salt, a solution containing isoserine, or a solution containing both an inorganic salt and isoserine. The present invention is particularly effective for those containing isoserine, and those containing inorganic salts and isoserine. Furthermore, in the present invention, "containing at least inorganic salt impurities and/or isoserine" does not mean containing only these impurities. In addition to these impurities, there may be other impurities that can be removed by the method of the present invention (serine 'tIi 3 degrees will be described later).

Inorganic salts as impurities include inorganic salts that are unavoidably produced as by-products when serine is chemically synthesized, inorganic salts derived from inorganic substances that are added for pH adjustment, etc. when serine is biochemically synthesized, etc. There may be inorganic salts derived from inorganic substances added to the purified aqueous serine solution for a specific purpose, for example, for the purpose of preventing precipitation. Examples of i-free salts include:
Ammonium salts such as ammonium chloride, ammonium bromide, ammonium iodide, sulfuric acid/ammonium, etc.
cum, sodium, potassium, magnesium, calcium and other alkali or alkaline earth metal halides, sulfates, phosphates, lil! Examples include (but are not limited to) monoacid salts and the like.

Isoserine as an impurity is a compound contained as a side reaction product in serine synthesized from aziridine-2-carboxylic acid or its derivatives.

Other impurities include side reaction products other than isoserine during the serine synthesis reaction, such as β-chloralanine,
There are compounds presumed to be 2.3-diaminopropionic acid, oligomers of aziridine-2-carboxylic acid, di(1-carboxy-2-hydroxyethyl)amine, pyruvic acid, etc., but there are specific compounds in purified serine. Purpose, e.g.
It may also be a compound added for purposes such as sterilization and antifungal purposes. Moreover, the excess reaction reagent used during the serine synthesis reaction can also be included in this range.

When recovering serine according to the present invention, insoluble impurities are separated from the serine production reaction solution etc. as necessary, and then pl.
+ Can be used as is without adjustment. However, it is preferable to adjust the pH to 4 to 15, particularly preferably 5 to 10.

One of the preferred examples of the serine production solution containing impurities such as inorganic salts and/or isoserine is aziridine-2-
Examples include an aqueous solution obtained by reacting a carboxylic acid or a derivative thereof with an oxyacid, or an aqueous solution obtained by reacting with an alkali metal or alkaline earth metal hydroxide and then reacting with an oxyacid.

Here, Y represents a group selected from a carboxyl group or an ammonium salt thereof, a salt of an alkali metal or alkaline earth metal, a carbamoyl group, an alkoxycarbonyl group, (the alkoxy group has 1 to 10 carbon atoms), and a cyano group. .

Another example of a preferable serine-generating liquid is a water-soluble eZ obtained by reacting glycolaldehyde or a glycolaldehyde analog represented by formulas (IF) to (VI) with a hydrocyanic acid source and then hydrolyzing it. be able to. [Glycolaldehyde yi'i conjugate J is hydrolyzed ji'l! means a compound that can be converted to glycolaldehyde through simple operations such as

(Shi) 11 (Car)” (R’) O.

Here, Z represents a group or atom selected from an amino group, a halogen atom selected from chlorine, bromine, and iodine, and an alkoxycarbonyl group (the number of carbon atoms in the alkoxy group is 1 to 10), and R represents a carbon Represents number 1 to 10 hydrocarbon residues.

Other examples of the serine production liquid include an aqueous solution obtained by hydrolyzing 2-oxooxazolidine-4-carboxylic acid represented by formula (■) or a derivative thereof.

\. / Here, Y is the group described in the previous formula (I).

General Diseases - Knee Balls In the Present Invention J: Recovery of phosphorus is carried out by subjecting the aqueous serine solution as described above to a specific chromagraph method.

Cation Exchanger Packed Bed The packing used in the packed bed constituting the purification means in the present invention is a specific cation exchanger, a metal salt type strongly acidic cation exchanger, a metal salt type weakly acidic cation exchanger, etc. This is a cation exchanger selected from type 1-1 weakly acidic cation exchangers. Among these, metal salt type strongly acidic cation exchangers are particularly preferred. Here, "strongly acidic cation exchanger" typically refers to kabuone exchanger 1! ! Eight groups are sulfonic acid groups. Therefore, the cation exchangers targeted by the present invention do not include cation exchangers having H-type sulfonic acid groups. For a specific target, a serine aqueous solution containing the inorganic salt impurity J3 and/or isorelin, the t(type) strongly acidic cation exchanger has too strong adsorption power and cannot be used as a means of purification and recovery for this specific target. However, even if it is an H-type strongly acidic cation exchanger, it can be changed from the H-type to the metal salt type by passing an aqueous solution containing metal ions, etc. , it goes without saying that it is suitable for use for the purpose of the present invention.

In the metal salt type cation exchanger, the metal ion can be arbitrarily selected. Examples of preferred metal ions include sodium, potassium, magnesium, zinc, cobalt, copper, manganese, nickel, calcium, lead, barium, chromium, aluminum, and iron, with sodium being particularly preferred. , calcium, and other ions.

Examples of ion exchange groups in cation exchangers include sulfone 1
li91, carboxyl group, phenol group, phosphoric acid group,
Examples include phosphonic acid groups and phosphonic acid groups.

Among these, sulfone gH is preferred as a strong acid type, and carboxyl group and phosphoric acid group are preferred as a weak acid type.

Particularly preferred in the present invention is a sulfonic acid group (metal salt type)
It is.

There are no particular restrictions on the substrate to which the ion exchange group of the cation exchanger is bonded, including styrene resins, 71-nol resins,
Synthetic polymers such as acrylic acid or methacrylic acid resins, polyvinyl alcohol or partially carbonized products thereof, carbon fibers, polyacrylamide, polyphenyleneether, polysulfone, polyester, fluorine resins, natural polymers such as cellulose, agarose, dextran, etc. Examples include inorganic substances such as zeolite, silica, alumina, titania, and hydroxyapatite. These substrates are crosslinked and chemically treated on the surface to improve mechanical strength, reduce swelling/shrinkage, improve bonding of ion exchange groups, and prevent loss of ion exchange groups. It is often subjected to isochemical modification.

Among the above-mentioned examples of the substrate, styrene resins, acrylic acid or methacrylic acid resins, partially carbonized polyvinyl alcohol, cellulose, etc. are preferably used, and among them, styrene resins are particularly preferably used. Particularly preferred is one based on a styrenic resin consisting essentially of a copolymer of divinylbenzene and styrene.

Here, "substantially" means that the co-tetramer is mainly composed of these two types and that the styrenic resin is mainly composed of this copolymer. be.

The shape of the cation exchanger is not particularly limited as long as it can be packed into a packed bed. For example, spherical, fibrous, pulverized products having no specific shape, fibrous or pulverized products made into granules, pellets, sheets, cloth, etc. by appropriate means can be used. Among these shapes, spherical, fibrous, granular, etc. are preferred, and spherical is particularly preferred.

Regarding the size of the cation exchanger, in the case of spherical and pulverized products, the average particle size is usually 5 to 2000μ, preferably 50 to 2000μ.
The particle size distribution is preferably 1000μ, particularly preferably 100 to 500μ, and the narrower the particle size distribution. If the average particle size is less than 5 μm, the separation performance is high, but the pressure loss is large and a high-pressure device is required, which is industrially undesirable. On the other hand, if the average particle size exceeds 2000 μm, the pressure loss is small, but the separation performance is significantly lowered, which is not preferable.

Fibrous cation exchangers usually have an average diameter of 0.
1 to 100 μ, preferably 1 to 70 μ, particularly preferably 5 to 50 μ, and the average Iff length is 50 to 20
00μ, preferably 100 to 1000μ, particularly preferably 200 to 800μ. If the average diameter is less than 0.1μ and/or the average lIN length is less than 50μ, the separation performance is high, but the pressure loss becomes large, which is not preferable. Average diameter exceeds 100 μ and/or average mN length 200
If it exceeds 0μ, the separation performance will deteriorate and the packing density will also become small, which is not preferable.

In the case of granules or pellets, the average particle size is usually 200 to 8000μ, preferably 500 to 500μ.
0μ, particularly preferably 1000 to 3000μ.

In the case of a sheet-like or cloth-like material, it can be used by cutting it into strips of about 1 to 5 mm+, for example, to facilitate filling.

Among the above-mentioned cation exchangers, one particularly preferred specific example has a degree of crosslinking (divinylbenzene content) of 1 to 1.
Examples include sodium type or calcium type spherical styrene-based strongly acidic cation exchange resins having an average particle size of 20%, an average particle size of 100 to 500μ, an ion exchange group as a sulfonic acid group, and an exchange capacity of 0.5 to 5 meq/rRI. can. Further, as a specific example of a preferable cation exchanger, a major axis of 10 to 50 μm and a short axis of 5 to 20 μm obtained by dehydrating and sulfonating a partially carbide of polyvinyl alcohol lIn
, fiber length 200~800μ, exchange capacity 0.5~5I
lleq-g (dry side 1, strongly acidic cation exchanger 1alt of the sodium or calcium type).

Although the combination of the cation exchanger and the impurity inorganic salt contained in the serine aqueous solution is arbitrary, a combination in which cations are common is preferred, and a combination in which all metal cations are calcium ions or sodium ions is particularly preferred.

! LIJJ The recovery of serine by the method of the present invention involves supplying the aqueous solution of serine to a packed bed packed with the cation exchanger, and subsequently passing water through it, whereby serine is completely or incompletely separated from other components. This is achieved by separating the fraction of serine that is eluted.

At this time, the packed bed is usually filled with water prior to supplying the serine aqueous solution. In addition, before the serine aqueous solution comes into contact with the cation exchanger, it is preferable to take care to prevent it from mixing with the water that will be passed afterwards. For this purpose, for example, before passing the water, add water equivalent to the supply m of the serine aqueous solution. There are methods such as extracting the aqueous serine solution and water from the rear end of the packed bed, and/or making the diameter of the supply pipe sufficiently small relative to the diameter of the packed bed to create a piston flow.

The filtered water for elution does not need to be a buffer solution, and ordinary water such as tap water, industrial water, ion-exchanged water, or distilled water is sufficient, and can be used depending on the use of serine. be able to. If the water passing through is a buffer solution,
The recovered serine must be roughly intermixed to remove buffer components.

There is no particular limitation on the serine Q degree in the serine aqueous solution to be purified, but it is usually 0.01 to 60%, preferably 0.1%.
-40%, particularly preferably 1-30%.

The supply layer of the aqueous serine solution to the packed bed is usually 0.01 to 150%, preferably 0.1 to 100%, based on the volume of the packed bed.
%, particularly preferably 1 to 50%. If it is less than 0.01%, the serine recovery efficiency will be poor, and if it exceeds 150%, the separation performance between serine and other components will deteriorate, which is not preferable.

The flow rate of serine aqueous solution and water is
This varies depending on the type of cation exchanger used, the length of the packed bed, etc., and there is no particular restriction as long as the present invention is achieved.
05 to 50 hr". If the time is less than o, olr-1, the serine recovery efficiency will be poor, and if it exceeds 100 hS, the separation performance will be degraded.

The diameter of the packed bed is not particularly limited and can be determined depending on the size of serine to be collected.

The length of the packed bed is about 1 (177 L) depending on the separation of the cation exchanger. It is usually about 5 cm to 20 m, preferably about 10 cm to 1077 L.

In the method of the present invention, the packed bed may be of either a vertical or horizontal type, but a vertical type is usually preferred. Furthermore, any known chromatographic separation method such as a batch method, a moving bed method, or a continuous method such as a pseudo moving bed method can be employed. For example, by connecting multiple columns in series and providing a pumping outlet, a water or gelatin aqueous solution passage port, recycling piping, etc. at the connection between each column, extraction is performed according to the component distribution within each column. By combining , liquid passage, recycling, etc., it is possible to reduce the use of filler and water, improve the serine recovery rate and the recovered serine concentration, etc.

If the separation of serine from other components is incomplete, increase the length of the packed bed, reduce the flow rate, or recycle the fraction that elutes with overlapping components to the packed bed at least once. Complete separation can be achieved in many ways.

When water is passed through for elution, salt-free impurities are eluted first, then serine is eluted, and then isoroline is eluted, so if a fraction of serine is collected, I! serine can be recovered. Other impurities include, for example, when pyruvic acid, β-chloralanine, etc. are present, oligomers of 2,3-diaminopropionic acid, aziridine-2-carboxylic acid,
When di(1-hydroxy-2-hydroxyethyl)amine and the like are present, they elute after serine.

The temperature at which the serine aqueous solution and eluate water are passed is usually 0 to 15
The temperature is 0°C, preferably 10 to 100°C. In order to hasten the elution of components such as isoserine that elute after serine, it is a 1q strategy to increase the temperature in the latter half of elution, and in that case, it is preferable to set the temperature to 40° C. or higher. 150℃
Exceeding this is not preferable because the cation exchanger tends to deteriorate and the energy cost also increases. If it is below 0°C, water will crystallize and the separation performance will deteriorate, which is not preferable.

When the cation exchanger is used repeatedly for a long time according to the method of the present invention, the separation performance may deteriorate.In such cases, if the cation exchanger is a metal salt type cation exchanger, the cation exchanger A method in which the exchanger is removed from the packed bed or not, treated with a mineral acid, and then treated with an aqueous solution containing metal ions; In the case of a calcium salt type cation exchanger, the separation performance can be restored by treatment with an aqueous solution of calcium hydroxide, calcium chloride, etc. Furthermore, when the cation exchanger is an H-type weakly acidic cation exchanger, the separation performance can be avoided by treatment with a mineral acid or the like. The cation exchanger whose separation performance has been restored by such treatment is usually used after washing with water.

Purification/Process A specific example of the process of the phosphorus recovery method of the present invention based on the above is as shown in FIG.

Two columns of the apparatus are connected in series, and each column is connected to a valve, a pump, a tank, etc. as shown in the figure, and each column and each piping are filled with water in advance.

First culm: Valve 3 is turned on, and valve 6 is turned on (at the same time, a predetermined amount of serine aqueous solution is successively passed through valve 1. At this time, all other valves are closed. Column 1 is designed so that serine and isoserine are almost completely separated.Water or aqueous solution is discharged from valve-6 according to the amount of liquid passed from valve-1.This step is performed as follows: Continue until just before isoserine is eluted from the bottom end of column 1.

2nd step: Close valve 3 and open valve 4 to allow water to pass through. In this step, a portion of components that elute earlier than serine, such as inorganic salts, is discharged from the lower end of column 2 through valve 6 until just before serine elutes.

On the other hand, at the same time as you touch valve-3, listen to valve-2 ()
, ] Continue the flow of water through the valve so that the isoserine is eluted from the column 1 and the discharge from the valve 2 is completed by the end of the fifth step, which will be described later. At the same time as the discharge of isoserine is completed, valve-1 and valve-2 are closed.

Third step: Close valve 6 and open valve 8 to discharge most of the remaining components that elute higher than serine. This step is carried out until just before serine is eluted from the bottom end of column 3.

Fourth step: Valve 8 is closed, valve 7 is opened, and a fraction (incompletely separated fraction) in which serine and components eluting earlier than serine are mixed and eluted is discharged into a tank. This step is carried out until the amount of components that elute faster than serine in serine is within an acceptable range.

Fifth step: Close valve-7 and open valve-8 to collect the serine fraction.

Sixth step: Close valves 4 and 8, open valves 1, 3, and 6, and pass and discharge the serine aqueous solution and water in the same manner as in the first step. However, in this step, when the ratio of serine in the filtrated aqueous solution passed through the inlet of column 2 to components that elute earlier than serine becomes almost the same as that of the aqueous solution discharged into the tank in the fourth step, the valve is opened. -1 and valve-3
Close the pump, open the valve 5, and pass the aqueous solution discharged in the fourth step into the tank by the pump. Continue.

Thereafter, the second to sixth steps are repeated.

In addition, the aqueous solution discharged from valve-7 in the fourth step is
It may be a stock solution storage tank for a serine aqueous solution; in this case, the pump, valve-5, and piping for them are unnecessary, and the sixth step is the same as the first step.

Furthermore, when a high concentration of recovered serine is desired, there are methods such as increasing the discharge amount in the fourth step, or cutting off a fraction with a low serine concentration of 81 degrees that is eluted at the end of the serine fraction in the fifth step. In the latter case, the cut fraction with low serine concentration is processed in the second to fourth steps.
Almost complete recovery can be achieved by passing water through an appropriate position in column 2 or column 3 instead of passing it through valve-4.

Furthermore, when discharging isoserine from column 1 through valve-2 in the second to fifth steps, instead of passing fresh water through valve-1, The amount of water used can be reduced by passing the water or aqueous solution discharged from valve 6 in the step and the aqueous solution discharged from valve 8 in the third step.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to examples, but these are merely illustrative of the present invention, and the present invention is not limited in any way by these examples.

'+'; d3, In the following examples, analysis of serine, etc. was performed using high performance liquid chroma 1-Graphie.

Example 1: 15% 'A M 262''; Add 10.6y of calcium aziridine-2-carboxylate to J, and heat at 100''C for 5
ff, 111+J reaction sabotanora, calcium hydroxide 2
54g was added to neutralize. The precipitated cake was distributed door to door,
Furthermore, wash the cake with water, add the washing liquid to the mother liquor, and serine 3.
．． 0%, sulfur M calcium 0.2%, isoserine 0.21
% and other side reaction products were obtained.

1. Add 8.6 g of aziridine-2-carboxylic acid amide to 444% 1-lium hydroxide aqueous solution 1 oog, and heat at 70°C.
After reacting for 5 hours, add 1100 g of 50% sulfur and
React at 00°C for 5 hours, neutralize by adding 130g of 25% sodium hydroxide aqueous solution, and add 2.7% serine, 0.25% isoserine, 19% sodium sulfate, 2.0% ammonium sulfate, J3 Jζ and other accessories. 339 J of the aqueous solution containing the reaction product (Wada).

Reference Example 3 40 g of distilled water and 10.7 g of ammonium chloride, 4.9 g of cyanide! J, OJ: and 2,5-diamino-1,4-dioxane 5,97 were added and reacted at room temperature for 3 hours, followed by a 20% aqueous solution of prium hydroxide 60
g was added and reacted at 100°C for 2 hours, and 20% hydrochloric acid 91
3 was added to neutralize the solution, yielding 1 q of an aqueous solution containing 4.0% serine, 7.5% ammonium chloride, 11% sodium chloride, and their secondary reaction products.

1 Serine aqueous solution 33991-1 obtained in the same manner as Reference Example 2
The eluate obtained by treatment with a strongly acidic cation exchange resin and eluting with 1N aqueous ammonia was evaporated to dryness. The obtained solid was dissolved in distilled water at 60°C to obtain 7.0% serine.
An aqueous solution containing 0.65% isoroline and other side reaction products was prepared.

Branch ■U average particle size 320μ, degree of crosslinking 4%J3 and exchange capacity 1.2
meq/d styrene/divinylbenzene spherical Na
Type Strongly Acidic Cation Exchange Resin Product Name Diaion 5K1
04S (manufactured by Hiki Isui Co., Ltd.) was ion-exchanged into Ca type and packed into a jacketed column with an inner diameter of 1a and a height of 110 cm. 55°C hot water was circulated through the jacket, while 55°C lid distilled water was filled up to the top of the column. 6 d of the aqueous solution obtained in Reference Example 1 was placed at the top of this column at 55 ml.
After heating to 55°C and passing the liquid at a space velocity of SV 1 , Ohr'', distilled water heated to 55°C was passed through SV 1 , Ohr''.
The lower end of the column was connected to differential refraction #1, and the eluted components were continuously tracked with a recorder.The elution curve at this time was as shown in Figure 1. From the bottom end, CAM calcium was eluted first, then serine was eluted, and finally isoserine was eluted. When the serine fraction was separated, the recovery rate was 97.8%.
The serine temperature in the recovered liquid was 0.9%. When this recovered liquid was analyzed by high performance liquid chromatography, it was found to contain almost no impurities (see Figure 2).

Example 1 was repeated by changing the height of the column to 15 ctn and changing the aqueous serine solution to 8 to 23 ctn obtained in Reference Example 4, respectively. The recovery rate of serine was 98.7%, the concentration of serine in the recovered liquid was 3.1%, and it contained almost no impurities.

Example 3 The cation exchanger was converted into a spherical Na-type strongly acidic cabone exchange resin (
Product name: Diaion SKI○4S (manufactured by Nippon Rensuisha),
The jacket temperature was set at 70°C, and 5d of the pirine aqueous solution obtained in Reference Example 2 was added with 0 S of the serine aqueous solution and distilled water.
．． Example 1 was repeated with each time changed to 25 hr. The recovery rate of serine was 93.5%, and the serine concentration in the recovered solution was 1.0.
%, and contained almost no impurities.

Example 3 was repeated except that 4 ml of the aqueous solution obtained in Reference Example 3 was replaced with the Yuko Yucerin aqueous solution. The recovery rate of serine was 95.7%, the concentration of serine in the recovered liquid was 1.5%, and it contained almost no impurities.

Eidan1 Instead of the C'a type spherical strongly acidic cation exchange resin, a polyvinyl alcohol fiber was partially carbonized and then sulfonated, with a major axis of 30 μ, a minor axis of 10 μ, a length of 500 μ, and a total ion exchange capacity of 23.1 meq/ When dry - q Na type! Using a strip-like strongly acidic cation exchanger (trade name: Nichibi ion exchange fiber, manufactured by Nichibi Co., Ltd.), the jacket temperature was changed to 70°C, and Sv
Example 1 was repeated except that the time was changed to 10 hr-1. The serine recovery rate was 87.1%, the serine concentration in the recovered liquid was 0.7%, and it contained almost no impurities.

Instead of the round iM ball Ca type spherical weakly acidic cation exchange resin, the average particle size is 400μ and the exchange volume is ff13.5meq/ml! Using an acrylic acid/divinylbenzene-based spherical H-type weakly acidic cation exchange resin (trade name Diaion WK20, manufactured by Nippon Rensuisha Co., Ltd.), the jacket temperature was set to 70°C, and the serine aqueous solution obtained in Reference Example 1 was mixed with 4- Example 1 was repeated by changing the passing rates of the serine aqueous solution and distilled water to Q and 3 hr-1, respectively. The serine recovery rate was 91.3%, the serine concentration in the recovered liquid was 0.8%, and it contained almost no impurities.

Example 1 was repeated except that the yucation exchanger was replaced with a spherical H-type weakly acidic cation exchange resin (trade name: Diaion 5K104S: Nippon Rensuisha! 1). Even after 12 hours had passed since distilled water was passed through the solution, serine was not eluted.

11 Mouths 12 Spherical styrene/divinylbenzene with no ion exchange group attached, used instead of cation exchangers for adsorption removal of colored components of sugar solutions, adsorption separation and purification of vitamins, antibiotics, steroids, etc. Resin (product name Sepabeads 5)
Example 1 was repeated using P-207 (manufactured by Nippon Rensuisha). One peak was observed on the recorder, but no matter which fraction of this peak was analyzed, the ratio of calcium sulfate/serine/isoserine was almost the same as that of the aqueous solution obtained in Reference Example 1, and serine was hardly separated from other components.

Comparative Example 3 50 g of the aqueous solution obtained in Reference Example 1 was concentrated (at 70°C) to 25 g using a rotary evaporator, a small amount of precipitated white solid was separated, and methanol 259 was added to the furnace liquid and the mixture was heated at 20°C.
The solution was allowed to stand for 5 hours, and the precipitated serine was collected. Recovery rate of serine is 88.7%, purity of recovered serine is only 90.5
%Met.

Note that almost no isoserine was removed from the recovered serine.

Comparison 1 Comparative Example 3 was repeated except that methanol used was changed to 12 g. Recovery rate of DL-serine is only 75.4%, recovery D
The purity of L-serine was 96.6%. This collected DL-
The impurity in serine was mostly calcium iA acid.

[Brief explanation of drawings]

Figure 1 shows 55% of the sample obtained in Reference Example 1 consisting of 0.2% calcium sulfate, 3.0% serine and 0.21% isoserine.
This is a graph showing an elution curve when an aqueous solution at 55°C is charged into a column packed with a Ca-type strongly acidic cation exchanger, and distilled water at 55°C is passed through the column.
(See Example 1). FIG. 2 is a graph showing a chromatogram obtained when the serine fraction shown in FIG. 1 was fractionated and analyzed by high performance liquid chromatography (see Example 1). FIG. 3 is a schematic diagram of a three column apparatus as an example of an embodiment of the invention. Applicant's agent Mr. Sato Figure 2 Figure 3

Claims (1)

[Claims] 1. Serine is removed from an aqueous serine solution containing inorganic salt impurities and/or isoserine by a metal salt type strongly acidic cation exchanger, a metal salt type weakly acidic cation exchanger and H
A chromatography method using a cation exchanger selected from the group consisting of weakly acidic cation exchangers of the type as a packing material and water as a developing agent is carried out, and the fraction of serine eluted is separated. Characteristic method for recovering serine. 2. An aqueous serine solution is obtained by reacting aziridine-2-carboxylic acid represented by formula (I) or a derivative thereof with an alkali metal or alkaline earth metal hydroxide and/or an oxygen acid, and then neutralizing the reaction. The method according to claim 1, wherein the method is performed by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) Here, Y is -CO_2H, -CO_2NH_4, -C
O_2M, -CONH_2, -CO_2R, and -C
At least one group selected from the groups represented by N, where M is a cation of an alkali metal or alkaline earth metal (represents 1/2 atom in the case of an alkaline earth metal)
, R represents a hydrocarbon residue having 1 to 10 carbon atoms, respectively. 3. Serine aqueous solution contains glycolaldehyde and formula (
The claimed compound is obtained by reacting a compound selected from the group consisting of glycolaldehyde analogs represented by II) to (IV) with a hydrocyanic acid source and an ammonia source, hydrolyzing it, and neutralizing it. The method described in Scope 1. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( V) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (IV) Here, Z is a group or atom selected from -NH_2, -C1, -Br, -I, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ where R represents a hydrocarbon residue having 1 to 10 carbon atoms. 4. The cation exchanger is based on a styrenic resin consisting essentially of a copolymer of divinylbenzene and styrene, has a divinylbenzene content of 1 to 20%, and has an average particle size of 1
00 to 500 μ, the ion exchange group is a sulfonic acid group, and the exchange capacity is 0.5 to 5 meq/ml. The method according to any one of items 1 to 3. 5. The method according to any one of claims 1 to 4, wherein the temperature at which the liquid is passed through the packed bed filled with the cation exchanger is 10 to 100°C.