JPS59170048A - Masking of iminodiacetic acid and/or nitrilotriacetic acid - Google Patents

Abstract

PURPOSE:To produce threonine useful as pharmaceutical, food additive, etc., without necessitating a purification process, by masking iminodiacetic acid and nitrilotriacetic acid with a metallic compound in the reaction of crude glycine with acetaldehyde. CONSTITUTION:Threonine is produced by the reaction of crude glycine containing iminodiacetic acid and nitrilotriacetic acid as impurities of glycine, with acetaldehyde in a basic medium. In the above process, the iminodiacetic acid and nitrilotriacetic acid in the crude glycine are masked with a metallic compound capable of forming glycine metal complex (e.g. element of copper-group, iron- group or platinum-group metal, i.e. Cu, Ni, Co, Pd, etc.). The amount of the metallic compound is less than the stoichiometric amount to form the glycine metal complex.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention deals with the production of threonine from glycine and acetaldehyde, and iminone l!, which is produced as a by-product during the production of glycine and as a result, is mixed in glycine! Using 111glycine containing Il' acid and nitrilotriacetic acid as a raw material, these impurities are hidden by forming a metal complex with a metal compound, and threonine is directly used as a raw material for threonine synthesis without going through purification. This invention relates to a method for concealing iminodiacetic acid and nitrilotriacetic acid in a synthetic reaction.

Threonine is an important substance as an essential amino acid as a medicine and food additive, and it is expected that it will be used in large quantities as a feed additive in the future.

Conventionally, threonine has been produced industrially by a method in which copper glycine and acetaldehyde are reacted in a basic medium (Japanese Patent Publication No. 34-2964, Japanese Patent Publication No. 36-1968). A method of using glycine nickel instead of glycine copper (Japanese Patent Publication No. 40-27732) has also been proposed.

In the conventional method, glycine copper or glycine nickel are used as raw materials, and in order to obtain good results, these complexes are important! After separation, it was considered desirable to react with an aldehyde. (Japanese Patent Publication No. 40-27732) This means that it is necessary to use a metal salt in an amount greater than the stoichiometric amount required for complex formation. Taking copper as an example, a copper salt containing at least 0.5 gram atom of Cu per 1'rCl of glycine is required. However, when attempting to industrially produce large quantities of cheap threonine, using a large amount of copper or nickel requires the cost of copper or nickel in the raw material cost, equipment and labor for nickel recovery and recycling, and In addition, the cost of equipment and equipment for recovering small metals such as copper or nickel from wastewater is high, which is also the cause of the current high filli rating for threonine.

Furthermore, according to the conventional method, it is necessary to neutralize the chrysine metal complex, and this operation is complicated, which also increases the cost of molding threonine.

In addition, as an industrial method for producing glycine, there is a method in which aminoace 1-nitrile is produced from an aqueous solution of Polmarin, hydrocyanic acid, and ammonia, and this is hydrolyzed with an alkali, and a method in which monochloroacetic acid is reacted with excess aqueous ammonia. It is being

In either method, the production of iminodiacetic acid and nitrilotriacetic acid as by-products is unavoidable, and especially iminodiacetic acid becomes the main impurity when the purpose is to produce glycine. In order to use citrus chrysin containing these impurities as a raw material for producing threonine, a purification process was required to remove the impurities. Omitting this purification step provides an industrially more advantageous method for producing threonine.

In Japanese Patent Application No. 57-105426, the present inventors used less than the stoichiometric amount of a metal compound capable of forming a metal complex with glycine, thereby eliminating the need to isolate the glycine metal complex (in one step, a small amount of The present inventors have disclosed a very advantageous method for producing threonine using a metal compound.As a result of further research, the present inventors found that the metal complexes of iminodiacetic acid and nitriacetic acid are more stable and reactive than the glycine metal complex. ) Not only does it have significantly inferior core activity and does not inhibit the threonine synthesis reaction even when coexisting with glycine metal complexes, but
It also has a negative impact on the isolation and purification process of the threonine produced.

As a result, we were able to complete the present invention.

That is, the present invention further improves the above invention and eliminates iminodiacetic acid and nitrilotriacetic acid, which were conventionally thought to have an adverse effect on the threonine production reaction! i! ! Threonine can be produced industrially more efficiently without any adverse effect on the reaction by simply adding and concealing the metal compound without removing it. According to the present invention, in producing threonine by adding glycine, iminodiacetic acid, nitrilotriacetic acid, and threonine, and a metal compound having the ability to form a miliform body in an amount smaller than the stoichiometric amount required for glycine metal iL) formation, Furthermore, a stoichiometric amount of a metal compound necessary for converting iminodiacetic acid and/or 21-lilotriacetic acid into metal spheres may be added.

Therefore, it is no longer necessary to install a J process for purifying crude glycine.

According to the present invention, if the sum of iminodiacetic acid and nitrilotriacetic acid is less than 10 mol % of glycine, it will not affect the yield of threonine at all, and if it is less than 30 mol 9-6, no glycine purification step is required.

The present invention will be explained in detail below.

The glycine used in the present invention is glycine crystals, alkali salts of glycine salts, or solutions thereof, and iminodiacetic acid and nitrilotriacetic acid are usually mixed in the glycine in a similar manner. Iminoji l! lil: The amount of acid and 21-lilotriacetic acid mixed varies depending on the glycine eye rust method and manufacturing conditions, but considering the amount of metal compounds used, it is generally better to contain fewer impurities. However, the total amount of iminodiacetic acid and nitrilotriacetic acid is 30% relative to glycine.
U7 can be used up to mol % or less, and 10 mol % or less is particularly preferable. Further, the amount of nitrilotriacetic acid is generally 1/10 or less of that of iminodiacetic acid. Other compounds that do not affect the reaction, such as salt, may be included in the mixture.

Acetaldehyde used in the present invention is not limited to acetaldehyde itself, but also includes compounds capable of producing acetaldehyde under the reaction conditions of the present invention, such as valaldehyde and vinyl acetate. Further, the higher the purity, the more preferable it is, but those containing some amount of water can also be used.

The amount of acetaldehyde to be used is not particularly limited, and it is possible to use less than equimolar amount to chrysine to increase the efficiency of acetaldehyde, but preferably 1 to 20 times molar amount to glycine, particularly preferably is 1.5 to 10 times the mole.

reaction? n degree C0~100℃, preferably 20~80℃
It is.

The solvent is not particularly limited, but water, aliphatic alcohol, hydrated aliphatic alcohol, etc. are preferred, but mixtures of tetrahydrofuran, acetone, methyl ethyl ketone, aromatic hydrocarbons, aliphatic hydrocarbons, etc., and water and aliphatic alcohol are preferred. Solvent systems are also acceptable. There are no particular restrictions on the basic substance used to carry out the reaction in a basic medium, but alkali hydroxides such as sodium hydroxide and potassium hydroxide, alkali carbonates such as potassium carbonate and sodium carbonate, water Inorganic bases such as alkaline earth metal hydroxides such as calcium oxide, alkoxides such as sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, triethylamine, hydroxyl-ethylamine, pyridine, etc. In addition to an organic base, a basic ion exchange resin having a tertiary amine or quaternary ammonium group as an exchange group can be used.

The amount of the basic substance used is 0.1 to 2 times the mole of glycine, iminodiacetic acid and nitrilotriacetic acid, preferably 5 to 1.5 times the mole of glycine, iminodiacetic acid and nitrilotriacetic acid. Also,
For basic ion exchange resins, the ion exchange capacity is
It is used in an amount of 0.1 to 2 times, preferably 0.5 to 1.5 times, based on the total amount of glycine, iminodiacetic acid and nitrilo-I-diacetic acid. Furthermore, there is no problem in using two or more basic substances in combination.

The metal that has the ability to form a metal complex with glycine used in the present invention is not particularly limited as long as it has the ability to form a complex, but copper group, iron group, and platinum group metals are preferable, and specifically copper, iron group, and platinum group metals are preferable. Nickel, cobalt, palladium, etc.

Most preferably copper is used.

The metal compounds used include inorganic compounds such as hydroxides, basic carbonates, carbonates, halides, sulfates, phosphates, perchlorates, and nitrates of the above metals, and organic acids such as acetates. Salt etc. can be used.

The amount of these metal compounds used is less than the stoichiometric amount based on the total of glycine, iminodiacetic acid, and di-lilotriacetic acid, but the stoichiometric amount varies depending on the metal used. For example, in copper, the number of coordinations to glycine is 4, and the coordination position of glycine is 2, so the stoichiometric amount of N is 0.5 gram atom of copper for 1 mole of glycine, which is 0.5 grams. It is equivalent. Similarly, for 1 mole of iminodiacetic acid, the coordination positions of iminodiacetic acid are 3,
Since the coordination number is 6, the stoichiometric H of copper is 0.5 gram equivalent, and 1.0 gram equivalent per mole of nitrotriacetic acid.

On the other hand, in the present invention, it is necessary that the amount of the metal compound used is at least 1i or more for iminodiacetic acid and nitrilotriacetic acid, and therefore the substantial amount used is the chemical m for iminodiacetic acid and nitrilotriacetic acid.
This is the amount of chemical MiiM added to the stoichiometric amount of mucoglycine.

The substantial amount of the metal compound used is 0.001 to 0.9 times the stoichiometric amount to glycine, preferably 0.01 to 0.
．． The amount is 7 times, more preferably 0.05 to 0.25 times the sum of the stoichiometric amounts for iminodiacetic acid and nitrilotriacetic acid.

As the reaction method, both hatch type and continuous type are possible. As for the preparation method, all of the logs may be charged at once, or all other raw materials may be charged beforehand and ace-1-aldehyde may be added in portions, or the basic substance may be added in several batches or continuously. It may be added separately. Alternatively, part of the metal compound and basic substance may be charged, and the remaining basic substance, glycine (which may be mixed with the basic substance), and acetaldehyde may be added in portions.

By the method described in detail above, threonine can be produced with a good yield through simple operations, and the reaction solution can be processed using conventionally known methods such as resin treatment to remove metals and further optical resolution. , L-threonine is obtained.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples. In addition, in the examples, 19% is jF amount % unless otherwise specified.

Example 1 In a 300 ml four-eye round bottom flask with Simroth condenser, thermometer, dropping funnel and stirrer, add 7.50 g of glycine.
g (0.1 mol) iminodiacetic acid 1.33 g (0
,005 mol) CuCQz ・2 H2O1,71g
5.05 g' (0.12 mol) of sodium hydroxide (containing 0.01 gram equivalent of Cu) and 100 ml of water were charged, and 14 ml (0.25 mol) of acetaldehyde was added dropwise while maintaining the temperature below 20°C. After the completion of the dropwise addition, the reaction solution was kept at 30° C. for 30 minutes, and the reaction solution was analyzed using liquid chromatography to find that 10.4 g (yield: 87%) of threonine had been produced.

This reaction solution was neutralized with hydrochloric acid, passed through a tower filled with Kir-1-4M=1 fat to remove copper, and then concentrated under reduced pressure.
When methanol was added, white crystals were precipitated. After cooling, it was filtered and dried to obtain 10.38 crystals. The rice contained 95% threonine.

Comparative Example 1 A reaction was carried out in the same manner as in Example except that iminodiacetic acid was not added and the amount of thorium hydroxide was 4.63 g (0.11 mol). It contained 10.2g (yield 86%). This reaction solution was purified in the same manner as in Example 1 to obtain 10.1 g of crystals. This contained 95% threonine.

Examples 2 to 4 In the reactor of Example 1, 0.1 mol of glycine, iminodiacetic acid, 21-lilotriacetic acid, Cu CQz 21-1
20 and the amounts shown in Table 1 of sodium hydroxide and water 100
When kept between ml and acetaldehyde, threonine was produced with the yield shown in Table 1.
It was empty.

Example 5 12g of balaldehyde instead of acetaldehyde (
The reaction was carried out in the same manner as in Example 1 except that [1.25 mol] was used, and 8.93 g of threonine (yield 75
%) was serving as a servant.

Example 6) Threonine (9.64 g) rate of 81%) is generated -
C Inoko.

Examples 7 to 10 The reaction was carried out in the same manner as in Example 1, except that a metal compound other than cupric chloride was used and the amount of thorium hydroxide was 0.16 mol. The following results were obtained.

Claims (4)

[Claims] (1) Glycine and acetaldehyde or a compound that generates acetaldehyde under reaction conditions are reacted in a basic medium with a metal compound capable of forming a Grin metal complex present in a smaller amount than the chemical N stoichiometric amount required to form a Glisson metal complex. In order to produce threonii, crude glycine is used as the raw material 4, and a stoichiometric amount of a metal compound having the ability to form a metal complex is added to iminodiacetic acid and/or nitrilo-IJ acetic acid contained in the crude glycine. 1. A method for concealing iminodiacetic acid and/or 21-helilotriacetic acid, which comprises using crude glycine as a raw material for producing threonine by concealing it with (2) The method for concealing iminodiacetic acid and/or nitrilotriacetic acid according to claim 1, wherein the metal element having the ability to form a metal complex is a copper group, iron group, or platinum group element. (3) The method for concealing iminodiacetic acid and/or nitrilotriacetic acid according to claim 1 or 2, wherein the compound that converts acetaldehyde under the reaction conditions is balaldehyde or vinyl acetate. (4) The total amount of iminodiacetic acid and 2-1-lilo-1-lyacetic acid is 30% relative to glycine. A method for shielding iminodiacetic acid and/or nitrilo-1-acetic acid according to claims 1 to 3, wherein the amount is less than or equal to mol %.