JP3205177B2 - Glycine purification method - 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 purifying glycine, and more particularly to a method for treating a crude glycine aqueous solution with a weakly basic or neutral basic anion exchange resin and then with a weakly acidic cation exchange resin. To obtain glycine with very few impurities. Glycine is a kind of amino acid, and is a useful compound widely used as a food additive or as a raw material for agricultural chemicals and pharmaceuticals.

[0002]

2. Description of the Related Art Hitherto, as methods for producing glycine, (1) amination method of monochloroacetic acid, (2) Strecker method, (3) hydantoin method and the like have been known. The amination method of monochloroacetic acid is a method of synthesizing glycine from monochloroacetic acid and ammonia, and the raw material is expensive. The Strecker method is a method for obtaining an alkali metal salt of glycine by hydrolyzing glycinonitrile obtained by reacting glycolonitrile, which can be synthesized from hydrocyanic acid and formaldehyde, with ammonia with an alkali such as sodium hydroxide. In the hydantoin method, glycolonitrile, which can be synthesized from hydrocyanic acid and formaldehyde, and ammonia and carbon dioxide are reacted in the presence of water to produce hydantoin.
This is a method for producing glycine by hydrolysis. In the hydantoin method, a method for directly obtaining glycine without hydrolyzing the hydantoin is known as a direct hydantoin method.

[0003] Generally, the crude glycine aqueous solution thus obtained is colored yellow to brown by polycondensation of raw materials or intermediate products. As a method of purifying glycine from such a crude glycine aqueous solution, generally, a method of treating an aqueous solution of crude glycine with activated carbon or an anion exchange resin, a method of crystallization using alcohol, and the like are known.

Japanese Patent Publication No. Sho 54-1686 discloses a method for hydrolyzing oxazolidine synthesized from glycinonitrile and ketone by the Strecker method, the monochloroacetic acid method, and the like. A method for purifying glycine which is treated with a weakly basic or medium basic anion exchange resin is disclosed. Among them, it is described that the effect of purification is not sufficient only by decolorization with activated carbon. Even though the glycine crystals obtained after the activated carbon treatment are white, coloring is observed when concentrated sulfuric acid is added, and the activated carbon treatment does not completely remove organic impurities. When the crude glycine aqueous solution is treated with activated carbon, even if it is colorless and transparent immediately after the treatment, it is colored again when heated for concentration, and recrystallization must be repeated to obtain high-purity glycine. Further, it is described that when the treatment is performed with activated carbon, a large amount of activated carbon is used.

[0005] Japanese Patent Application Laid-Open No. 4-226949 discloses a method for purifying glycine in which an aqueous glycine solution is adjusted to pH 6 or less and then treated with activated carbon. According to this method, the amount of activated carbon used can be significantly reduced.

In JP-A-6-65168, glycine crystals obtained from a reaction solution obtained by the direct hydantoin method are redissolved in water, and glycine is recrystallized by adding an organic solvent soluble in water to the solution. A method for purifying glycine is disclosed.

[0007]

Conventionally known methods for purifying glycine focus on decolorization from aqueous glycine solutions, and according to such a method, glycine crystals without coloration can be obtained. However, there is no mention of the presence of trace impurities.

[0008] As in the prior art, the aqueous glycine solution treated with activated carbon or an anion exchange resin has no color, and the glycine isolated by crystallization from such an aqueous glycine solution is:
Although the appearance is white, focusing on trace impurities, such impurities are not completely removed.

As shown in JP-B-54-1686,
Decolorization with activated carbon alone is not enough for the purification effect.
Even if the glycine crystal obtained after the activated carbon treatment is white, coloring is observed when concentrated sulfuric acid is added, and the activated carbon treatment does not completely remove organic impurities. This suggests the presence of trace impurities in white glycine.

As a method for analyzing trace impurities in glycine, the present inventors have proposed phenyl isothiocyanate (hereinafter referred to as PITC).
Phenylthiocarbamyl (hereinafter abbreviated as PTC) derivatization-HPLC analysis of impurities. Since primary and secondary amines are converted to PTC by PITC, impurities having primary and secondary amines as functional groups become PTC derivatives. By performing HPLC analysis of this PTC derivative, impurities can be analyzed.

Analysis of trace impurities in glycine crystals purified by the conventional purification method using such a method revealed that trace impurities were not sufficiently removed by the conventional purification method.

As shown in JP-B-54-1686,
Even in a method for purifying glycine in which a crude glycine aqueous solution having a pH of 7 or less is treated at 50 ° C. or less with a weakly basic anion exchange resin or a mediumly basic anion exchange resin, removal of trace impurities is not complete.

[0013] The present inventors treated an aqueous solution of glycine crystals obtained by the monochloroacetic acid method with a weakly basic or medium basic anion exchange resin at 50 ° C or lower, as shown in JP-B-54-1686. As a result of the PTC analysis, it was found that the amine component was present as an impurity without being removed. This means that the amine component did not have a negative charge and was not adsorbed by the weakly basic and neutral basic anion exchange resins, but passed through the resin together with glycine. Thus, purification with only a weakly basic or neutral basic anion exchange resin,
Despite the decolorizing effect, trace impurities cannot be completely removed.

As described above, at present, it is impossible to completely remove trace impurities in glycine by the known method. It is inappropriate to use such glycine as it is as a food additive or pharmaceutical.

An object of the present invention is to provide a method for obtaining glycine having a very small amount of trace impurities.

[0016]

Means for Solving the Problems As a result of intensive studies on a method for purifying glycine, the present inventors have treated a crude glycine aqueous solution with a weakly basic or neutral basic anion exchange resin,
By further treating with a weakly acidic cation exchange resin,
The present inventors have found that glycine having very few impurities can be obtained and completed the present invention.

That is, the present invention is to obtain a glycine with very few impurities by treating a crude glycine aqueous solution with a weakly basic or neutral basic anion exchange resin and then further treating it with a weakly acidic cation exchange resin. And a method for purifying glycine.

According to the present invention, it is possible not only to decolorize an aqueous glycine solution but also to remove trace impurities that could not be removed by a conventional purification method.

The aqueous glycine solution applied to the present invention may be an aqueous solution of crude glycine obtained by any method, but the aqueous glycine solution is resin-treated at a concentration of 33% or less. The glycine concentration may be not more than the saturation concentration at the operating temperature, but in order to make the concentration more than 33%,
It is necessary to keep the temperature of the resin at 70 ° C. or higher, which is not preferable because of the heat resistance of the resin. The pH of the glycine aqueous solution is not problematic as long as it is within the stable range of the resin, but is usually 5 to 9.

In the present invention, the crude glycine aqueous solution is treated with a weakly basic or neutral basic anion exchange resin, and then treated again with a weakly acidic cation exchange resin. The treatment with these resins may be of a batch type in which a predetermined amount of resin is added to a crude glycine aqueous solution, but a resin tower type in which a resin is filled in a tower and liquid is passed is more practical. In the case of the resin tower type, two types of resin towers are connected in series, and the crude glycine aqueous solution can be passed continuously. Glycine is not adsorbed by a weakly basic, neutrally basic anion exchange resin, or a weakly acidic cation exchange resin. Therefore, in the case of a batch method, a glycine aqueous solution containing extremely few impurities can be obtained by collecting the supernatant. In the case of the resin tower type, the resin passing solution is a purified glycine aqueous solution.

Commercially available products can be used as the weakly basic or intermediately basic anion exchange resin and the weakly acidic cation exchange resin used in the present invention. There is almost no glycine adsorption loss in the weakly or neutrally basic anion exchange resin and the weakly acidic cation exchange resin. Strongly basic anion exchange resins and strongly acidic cation exchange resins cannot be used because they adsorb glycine.

Examples of the weakly basic or neutral basic anion exchange resins include trade names such as Amberlite IRA-
93 (Organo Co., Ltd.), Diaion WA20, W
A30 (Mitsubishi Kasei Co., Ltd.), Levatit MP64
(Bayer K.K.) and the like. The exchange group form is used as the free base form (OH form).

Examples of the weakly acidic cation exchange resin include Amberlite IRC-76 (Organo Co., Ltd.), Diaion WK10, WK20 (Mitsubishi Kasei Co., Ltd.) and Levatit CNP80 (Bayer Co., Ltd.) under trade names. )). In addition, Levatit TP20
7. Chelating resins such as TP208 (Bayer) can also be used as the weakly acidic cation exchange resin. The form of the exchange group is used as H-form.

When these resins are used for the first time, it is necessary to sufficiently perform pretreatment and washing of the resin in order to prevent impurities derived from the resin from being mixed into glycine. The amount of resin used varies depending on the type and amount of impurities in the crude glycine aqueous solution.
It is in the range of 50 to 2000 ml of resin, preferably 200 to 1000 ml per kg.

The resin treatment must be performed in the order of a weakly basic or medium basic anion exchange resin, and then a weakly acidic cation exchange resin. This is because the basic anion exchange resin is unstable, so that the amine as an exchange group is easily desorbed, and may be mixed into the processing solution as impurities derived from the resin. Even in such a case, the impurities are removed by a subsequent treatment with a weakly acidic cation exchange resin.

When glycine is synthesized by the Strecker method or the hydantoin method, hydrolysis with an alkali such as sodium hydroxide produces an alkali metal salt of glycine. Obtaining an aqueous solution of crude glycine is a known technique.
For such a crude glycine aqueous solution, Japanese Patent Publication No. 54-168
6 can be applied, in which case the treatment is carried out with a weakly acidic cation exchange resin and then with a weakly basic anion exchange resin, which is different from the method of the present invention.

The temperature during the resin treatment may be room temperature, but may be heated if necessary. However, heating must be performed at 70 ° C. or lower. This is due to the problem of heat resistance of the resin.

The resin treatment time is 3 to 6 in the case of a batch type.
0 minutes, preferably 6 to 30 minutes.

In the case of treating in a resin tower system, the liquid passing speed through the resin tower is in the range of 1 to 20, preferably 2 to 10 in terms of liquid hourly space velocity (l / l-resin / Hr).

When the resin's ability to adsorb impurities reaches saturation, the resin can be used repeatedly by regenerating using an appropriate regenerating agent. For example, OH-type weakly basic anion exchange resin can be regenerated by passing an aqueous solution of sodium hydroxide. Further, the regeneration of the H-type weakly acidic cation exchange resin can be performed by passing dilute hydrochloric acid through the solution.

Glycine is crystallized from the purified glycine aqueous solution obtained according to the present invention according to a conventional method.
High-purity glycine crystals with extremely small amounts of impurities can be obtained.

[0032]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to embodiments. Example 1 A crude glycine crystal produced from monochloroacetic acid and ammonia was converted into an 18 Wt% aqueous solution (pH 6.2).
000 ml of a weakly basic anion exchange resin Amberlite IRA-93 (trade name: Organo Co., Ltd.) (OH type) 5
After passing through a resin tower filled with 0 ml, the solution was passed through a resin tower filled with 50 ml of a weakly acidic cation exchange resin Diaion WK20 (trade name, Mitsubishi Kasei Corporation) (H type). The operating temperature is 25 ° C., and the liquid hourly space velocity is 4 (l / l).
/ Hr). Impurities present in the solution passing through the weakly basic anion exchange resin in the first stage of the resin treatment are converted into phenylthiocarbamyl (hereinafter abbreviated as PTC) with phenyl isothiocyanate (hereinafter abbreviated as PITC), and then subjected to HPLC.
Analysis (column; ODS A-312, YMC Corporation)
(Trade name), φ6 × 150 mm). As a result, three of the five impurities present in the crude glycine were almost removed, but one was removed at about 90% and the remaining one was removed. It had not been removed at all. When the impurities in the weakly acidic cation exchange resin passing solution in the second stage of the resin treatment were analyzed in the same manner, it was confirmed that all of the five impurities present in the crude glycine were removed. Table 1 shows the results. The method of extracting impurities in glycine and the PTC of extracted impurities
The HPLC analysis conditions for the compound and the PTC compound are as follows.

Method for extracting impurities in glycine 50 g of glycine (in the case of an aqueous solution, an aqueous solution of 50 g of glycine was dried under reduced pressure) was heated and dissolved in 100 g of pure water, allowed to cool to room temperature, and 150 ml of methanol was added. I do. After crystallization at 5 ° C. for 20 minutes with stirring, a filtrate is obtained by filtration under reduced pressure. The filtrate was evaporated to dryness under reduced pressure, and 5 ml of pure water was added to and dissolved in the dried matter.
Add 0 ml. After crystallization at 5 ° C for 20 minutes with stirring, a filtrate is obtained by filtration under reduced pressure. The filtrate obtained by drying the filtrate under reduced pressure is defined as an extracted impurity.

PTC Conversion of Extracted Impurities A dried matter of extracted impurities is dissolved in 5 ml of pure water. 27 mg of anhydrous sodium carbonate, 10 ml of pure water, and 6.7 m of acetonitrile were added to a solution containing the equivalent of 40 mg as a dry matter.
1) Add 67 μl of PITC and react at 50 ° C. for 30 minutes. After 30 minutes, the reaction solution was ice-cooled and then cooled to 65% (V /
V) Dilute 2-fold with acetonitrile.

A column for HPLC analysis of PTC -forming impurities ; ODS A-312 (trade name) manufactured by YMC Corporation φ6 × 150 mm Eluent: A CH3CN / 0.1M ammonium acetate = 1/9 (V / V) B CH3CN /0.1M ammonium acetate = 9/1
(V / V) System; Waters PICO TAG Amino acid analyzer Gradient; Linear gradient 0 → 25 min B = 1 → 50% 25 → 35 min B = 50 → 99% 35 → 60 min B = 99% Flow rate: 0.9 ml / min Temperature 30 ° C. detection; UV 254 nm (Waters 484 tunable UV / VIS detector) Injection Volume; 20 μl

Example 2 Crude glycine crystals produced from monochloroacetic acid and ammonia were used as a 33 Wt% aqueous solution (70 ° C., pH 6.2), and 1,000 ml of the aqueous solution was used as a medium-basic anion exchange resin Levatit MP64 (trade name, Bayer Corp.) ) (OH type)
After passing through a resin tower filled with 300 ml, the solution was passed through a resin tower filled with 300 ml of a weakly acidic cation exchange resin Levatit TP208 (trade name, Bayer K.K.) (H type). The resin tower was maintained at 70 ° C. by a warm water jacket, and the liquid was passed at a liquid hourly space velocity of 4 (l / l / Hr). Impurities present in the medium-basic anion-exchange resin passage liquid in the first stage of resin treatment are converted to PTC by PITC,
PLC analysis (column: YMC Corporation ODS A-3)
12 (trade name), φ6 × 150mm)
Three of the five impurities present in the crude glycine were:
Almost all of them were removed, but one component was about 85% removed,
The remaining one component was not removed at all. When the impurities in the weakly acidic cation exchange resin passing solution in the second stage of the resin treatment were analyzed in the same manner, it was confirmed that all of the five impurities present in the crude glycine were removed. Table 2 shows the results. In addition, impurity extraction operation, PTC conversion of the extracted impurities,
The conditions for HPLC analysis of the PTC compound are the same as in Example 1.

[0037]

[Table 1] The residual ratio after passing through the resin when the amount of each component of impurities present in the crude glycine is 100%. Weakly basic anion exchange resin; Amberlite IRA-9
3 (trade name: Organo Co., Ltd.) Weakly acidic cation exchange resin; Diaion WK20 (trade name: Mitsubishi Chemical Corporation)

[0038]

[Table 2] Residual rate after passing through the resin when the amount of each component of impurities present in the crude glycine is defined as 100%. Neutral basic anion exchange resin; Levatit MP64 (trade name, Bayer K.K.) Weak acidic cation exchange Resin; Levatit TP208 (trade name, Bayer Corporation)

[0039]

According to the present invention, impurities can be easily removed from a crude aqueous glycine solution containing impurities. From a purified glycine aqueous solution obtained by treating a crude glycine aqueous solution by the method of the present invention, glycine crystals with extremely few impurities can be obtained by a usual crystallization operation.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-4-226849 (JP, A) JP-A-6-65168 (JP, A) JP-A-3-190851 (JP, A) 1686 (JP, B1) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 229/08 C07C 227/08 C07C 227/40

Claims (2)

(57) [Claims] 1. A method for purifying glycine, comprising treating an aqueous glycine solution with a weakly basic or neutral basic anion exchange resin and then treating it with a weakly acidic cation exchange resin. 2. The method according to claim 1, wherein the aqueous glycine solution is an aqueous glycine solution containing glycine obtained by reacting monochloroacetic acid with ammonia.