JPH03240760A - Production of dl-serine - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as a raw material for antibiotics, etc., in high yield at a low cost by carrying out Strecker reaction under specific reaction condition using inexpensive glycol aldehyde as a reaction substrate. CONSTITUTION:A reaction liquid containing unrefined glycol aldehyde and produced by the dehydrogenation or oxidative dehydrogenation of ethylene glycol is used as a reaction substrate and is subjected to Strecker reaction with cyanic acid and ammonia at molar ratios (glycol aldehyde/cyanic acid) of 1.0-1.50 (preferably 1.01-1.30) and (ammonia/cyanic acid) of 3.0-10.0 (preferably 5.0-10.0) at a reaction temperature of 20-80 deg.C for 15-120min. The unreacted ammonia and the ammonia produced by the reaction are recovered after the subsequent alkali hydrolysis. After the Strecker reaction, the reaction product is hydrolyzed (preferably in the presence of an alkali) to obtain the objective compound.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing DL-serine, and in particular to an industrial method for producing DL-serine by a Strecker reaction using glycolaldehyde as a reaction substrate. be.

Serine is a compound useful as a raw material for amino acid infusions and antibiotics. It is also a useful compound as a raw material for L-tryptophan, which is expected to expand in the future as a feed additive.

[Prior art] As a method for synthesizing serine by the Strecker reaction using glycolaldehyde as a reaction substrate, Fi
Scher and Leuchs: CheIl, Ber
,.

35, 3787. +19021, there is a report that serine was obtained using an alcoholic solution of ammonia, hydrocyanic acid, and hydrochloric acid. The yield of serine by the reported method is very low;
We simply confirmed the production of serine.

Also, Luciano Bassignani et al.
al.: Chew.

Ber, 112.148 (1979) describes the reaction of glycolaldehyde with CN- and NH, in the presence of methanol.
A method has been proposed in which serine is produced by removing methanol from the cyanoamination reaction mixture and then hydrolyzing it with hydrochloric acid.However, with this method, it is necessary to completely remove methanol before hydrolysis. Not only that, but the yield of serine decreases unless hydrolysis is carried out with a large amount of hydrochloric acid.

Furthermore, in order to carry out these methods, it is necessary to isolate and purify glycolaldehyde.

Glycolaldehyde is produced by dehydrogenation or oxidative dehydrogenation of ethylene glycol, or by reduction reaction of glycol nitrile, but glycolaldehyde is soluble in water, highly reactive, and thermally insensitive. Due to its stability, isolation and purification are difficult. Therefore, the above method, which requires isolation and purification of glycolaldehyde, is unlikely to be an industrial method.

Therefore, without subjecting glycolaldehyde itself to the reaction,
As an analogue, a method of performing Strecker has been proposed.

As a method using glycolaldehyde analogs as raw materials, Leuchs and Geiger: Chew, He
r,, 39°2644 f19061 and mouth unn
, Redes+ann and Smlth: J.

Biol, Chew, 104.511 (1934
), the Strecker reaction of ethoxyacetaldehyde obtained by dehydrogenation of ethylene glycol monoethyl ether.

The production of serine by hydrolysis with hydrogen bromide and cleavage of the ethyl group has been reported, but the yield is still low, the raw materials are expensive, and there are problems with corrosion of the reactor, etc., so it is not an industrial production method. It's hard to say.

Further, Japanese Patent Publication No. 57-11309 discloses a method for producing serine using a glycolaldehyde precursor such as monochloroethylene oxide as a raw material. The yield of serine by the method disclosed in this publication is about 50%, and the raw material synthesis is complicated, so that it is by no means satisfactory as an industrial production method.

A method of directly subjecting the reaction solution of ethylene glycol dehydrogenation or oxidative dehydrogenation to the Strecker reaction is proposed in Japanese Patent Application Laid-open No. 10542/1982 and Japanese Patent Application No. 329851/1982. These methods are precisely based on the Zelinsky Standn, which is an improved version of the Strecker reaction.
This reaction is called the jkoff reaction, and involves reacting a mixture of alkali cyanide and ammonium chloride with a carbonium compound to synthesize aminonitrile.

Furthermore, when the reaction solution of ethylene glycol dehydrogenation or oxidative dehydrogenation reaction is directly subjected to the Strecker reaction, economical recovery of ethylene glycol is an essential condition. As a method for recovering it, it is preferable to use ion exclusion chromatography as previously proposed in Japanese Patent Application No. 1-25519.
In the method using the -5 tandnikoff reaction, a large amount of inorganic salt is produced as a by-product, and the purification conditions using ion exclusion chromatography are limited. Furthermore, since CV is present in the reaction system and purification system, the materials used, reaction conditions, purification conditions, etc. are limited.

[Problem to be Solved by the Invention J] The purpose of the present invention is to synthesize glycolaldehyde using inexpensive ethylene glycol as a raw material by its dehydrogenation or oxidative dehydrogenation, and to synthesize the obtained glycolaldehyde as it is without isolation and purification. To provide a method for industrially producing L-serine at low cost by subjecting it to Strecker reaction to synthesize α-amino-β-hydroxypropionitrile and hydrolyzing the obtained reaction product. .

[Means for Solving the Problems 1] As a result of intensive research to achieve the above object, the present inventors have discovered that glycolaldehyde obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol can be reacted without isolation and production. By using it as a substrate and subjecting it to specific Strecker reaction conditions, DL-
It was discovered that serine can be produced.

That is, the present invention provides a method for synthesizing serine by the Strecker reaction using glycolaldehyde as a reaction substrate.
In the method for producing L-serine, a reaction solution containing glycolaldehyde obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol is used as one reaction substrate, and hydrocyanic acid and ammonia are added in a molar ratio.

Glycolaldehyde/cyanic acid: i, 0-1.50,
Ammonia/cyanic acid: 3.0 to 10.0, reaction temperature = 20 to 80°C, reaction time M: 15 to 120 minutes to perform the Strecker reaction and hydrolyze the obtained reaction product. This is a method for producing OL-serine characterized by the following.

The glycolaldehyde subjected to the Strecker reaction conditions of the present invention is an unpurified glycolaldehyde solution obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol.

For the dehydrogenation reaction of ethylene glycol, a commercially available metal oxide catalyst (copper chromite catalyst, etc.) or an appropriate carrier (7
Random, alumina, etc.) are used as a catalyst in a fixed catalyst bed in normal pressure or reduced pressure gas phase.The zero reaction temperature varies depending on the catalyst used, but is generally 200~200℃.
The reaction is carried out at 500"C. Especially copper and other inorganic components,
For example, when ethylene glycol and water are reacted at 180 to 400°C using a composite catalyst consisting of copper and zinc oxide, a method in which a small amount of molecular oxygen is allowed to coexist in the reaction system is effective in dehydrogenation. This method is preferable because there is no reduction in the activity of the catalyst, and there is little generation of by-products, so that a glycolaldehyde reaction solution with a constant concentration can always be obtained.

The influence of unreacted ethylene glycol on the Strecker reaction conditions of the present invention is not so significant, and it is thought that ethylene glycol is hardly involved in the Strecker reaction using glycolaldehyde as a reaction substrate.

The glycolaldehyde concentration in the Strecker reaction solution is preferably at least 2.0% by weight, and if the concentration is lower than this, the serine yield will decrease.6 In the Strecker reaction of the present invention, cyanide is used as the cyanide compound. Use.

Compared to the method using an alkali cyanide disclosed in Japanese Patent Application No. 1-25519, the Strecker reaction using hydrocyanic acid of the present invention uses hydrocyanic acid as a less expensive cyano source, does not use ammonium chloride, and uses a solid raw material. The reaction is simple and the amount of by-product inorganic salts is greatly reduced. Therefore, ion exclusion chromatography treatment for purifying serine and recovering ethylene glycol is easy, and since there is no CV contamination, there is no problem of catalyst poisoning when the recovered ethylene glycol is reused for dehydrogenation. Furthermore, since there is no generation of NaCl, there are no material problems in the reaction system or purification system.

However, since the hydrocyanic acid used in the present invention is more toxic than, for example, sodium cyanide, safety considerations must be taken regarding the process and equipment.

Hydrocyanic acid is not limited by its production method, and can be obtained by the Sohio method, the Antriuse method, the formamide method, etc.

Regarding the amount of hydrocyanic acid used in the reaction, it is preferable to use a slight excess of glycolaldehyde, and the molar ratio of glycolaldehyde/cyanic acid is 1.0 to 1.50, preferably 1.
01-1.30. In terms of yield, good results can be obtained even if an excess of hydrocyanic acid is used, but since the hydrocyanic acid does not completely react and a portion remains unreacted, removal of cyanide in the purification system becomes complicated. On the other hand, if glycolaldehyde is in large excess, the amount of ethylene glycol to be separated and recovered after hydrolysis increases, leading to an increase in the basic unit, which is not preferred from an industrial perspective.

The amount of ammonia used is 3.0 to 1O60 relative to hydrocyanic acid.
It is twice the molar amount, preferably 5.0 to 1000 times the molar amount. In the reaction solution of ethylene glycol dehydrogenation or oxidative dehydrogenation, there are acidic substances such as by-produced formic acid, and these acidic substances are neutralized and the stability of hydrocyanic acid is increased [Wangka Journal, 65.55
2 (19627), and in order to improve the yield of serine, it is preferable to use ammonia in large excess. Unreacted ammonia and ammonia produced in the reaction are recovered after the subsequent alkaline hydrolysis.

The solvent used in the reaction may be water, and there is no need to add a lower alcohol such as methanol.

The reaction temperature is 20 to 80° C. At lower temperatures, the reaction progresses more slowly, and at higher temperatures, by-products such as glycine increase.

The reaction time is preferably a relatively short time of 15 to 120 minutes; if the reaction is carried out for an unnecessarily long time, by-products such as glycine will increase, resulting in a decrease in the yield of serine.

The hydrolysis reaction of α-amino-β-hydroxypropionitrile synthesized under the above-mentioned reaction conditions proceeds almost quantitatively by heating at 40 to 100°C for 2 to 5 hours using an acid or alkali. L-serine, which is a substance, is obtained.

However, when an acid is used in the hydrolysis reaction, a large amount of acid is consumed to neutralize unreacted ammonia in the Strecker reaction, so it is necessary to recover ammonia after the Strecker reaction is completed and before hydrolysis. Ammonia recovery requires long-term heating, which partially denatures α-amino-β-hydroxypropionitrile, lowering the serine yield and increasing by-products such as glycine, which is difficult to separate. . Furthermore, it becomes difficult to separate and recover ethylene glycol and purify serine using the ion exclusion chromatography method proposed in Japanese Patent Application No. 1-25519.

Therefore, in the method of the present invention, the hydrolysis of the Strecker reaction product a-amino-β-hydroxypropionitrile is preferably carried out in the presence of an alkali. As the alkali species, sodium hydroxide, potassium hydroxide, etc. are used. These alkalis are dissolved in water and used at a concentration of 10 to 50% by weight.

According to the method of the present invention detailed above, DL-
It is possible to produce serine, and by using inexpensive ethylene glycol as a raw material, DL-serine can be produced economically.

[Example] Below, the method of the present invention will be explained in more detail with reference to Examples.

Example 1 A catalyst precursor (manufactured by JGC Chemical, N-2111) consisting of 50 parts by weight of 1 CuO and 45 parts by weight of 2N045 parts by weight of ethylene glycol and having an average particle size of 2n+m and a specific surface area of 311/g was heated in air at 1000°C for 4 hours. The time-calcined catalyst was filled into a stainless steel reaction tube with an inner diameter of 15 mm to an apparent volume of 10 ml.

First, water vapor at 200°C was added to this filling cylinder at LH5V O,
5 for 1 hour, hydrogen diluted with nitrogen was heated at 300°C,
A copper/zinc oxide catalyst was obtained by passing the mixture under GH5V 600 for 2 hours.

Next, while keeping this reaction tube at 270°C, a mixture of two ethylene glycols = 1:6 (mole ratio) was gasified through a preheater and passed through LH3V 1, and at the same time, 1 mole of ethylene glycol was Air corresponding to an amount of 0.04 mol of oxygen was passed through.

The obtained reaction solution contained 6.6% by weight of glycolaldehyde.
The composition was 33.1% by weight of ethylene glycol, 1.2% by weight of formic acid, and 59.1% by weight of water.

Production of Serine A rotor was placed in a 100 mJ glass pressure-resistant reaction vessel, and 20 g of the above ethylene glycol dehydrogenation reaction solution (glycol aldehyde 1.32 g i22 mmol), ethylene glycol 6.62 g 1 l O 6.8 mmol), formic acid 0.
24 g + 5.2 mmol), 11.82 g of water], 0.54 g (20 mmol) of blue fi, and 6.8 g (100 mmol) of 25% aqueous ammonia were charged, and the flask was tightly stoppered. Hydrocyanic acid was prepared by decomposing sodium cyanide using ferrous sulfate as a catalyst and absorbing it into 25% aqueous ammonia.

The reaction solution was heated to 45-55°C and reacted for 30 minutes.

Next, a solution of 2.2 g (55 mmol) of sodium hydroxide dissolved in 6.6 g of water was added to the Strecker reaction solution, and the mixture was reacted at 70 to 80° C. for 2 hours for hydrolysis.

After the reaction was completed, one reaction solution was analyzed by liquid chromatography, and the amount of L-serine produced was 1.73 g.
The amount of glycine as a by-product was 0.011 g. The yield calculated based on hydrocyanic acid is 82.2% of the theoretical amount of DL-serine.
The by-product glycine was 0.7% of the theoretical amount.

Example 2, Comparative Examples 1 and 2 The same procedures as in Example 1 were carried out except that the amount of hydrocyanic acid used was changed and the molar ratio of glycolaldehyde/cyanic acid was changed as shown in Table 1.

The analysis results of the obtained reaction solution are shown in Table 1.

Table 1 *Yield based on nigericolaldehyde Comparative Example 3 The same operation as in Example 1 was carried out except that the amount of 25% ammonia water used was changed to 2.72 g f40 mmol). As a result, the amount of OL-serine produced was 1.44 g, and the yield calculated based on hydrocyanic acid was 68.5% of the theoretical amount.

Comparative Example 4 The same procedure as in Example 1 was carried out except that the Strecker reaction temperature was changed to 90°C. As a result, the amount of DL-serine produced was 1.59g, and the amount of glycine as a by-product was 0.
．． It was 042g. The yield calculated based on hydrocyanic acid is O
L-serine was 75.7% of the theoretical amount, and glycine, a by-product, was 2.8% of the theoretical amount.

[Effects of the Invention] The present invention provides an inexpensive industrial method for producing DL-serine, in which glycolaldehyde obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol is not isolated and purified, and the Strecker reaction using hydrocyanic acid is carried out. By adopting specific raw material ratios and reaction conditions, OL can be achieved with high selectivity.
-Serine can be obtained.

By the method of the present invention, DL-
Integrated production of serine is possible, which makes it possible to economically produce OL-serine from inexpensive ethylene glycol.

Claims (2)

[Claims] (1) In a method for producing DL-serine in which serine is synthesized by Strecker reaction using glycolaldehyde as a reaction substrate, a reaction solution containing glycolaldehyde obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol is used as a reaction substrate, The molar ratio of hydrocyanic acid and ammonia is glycolaldehyde/cyanic acid: 1.0-1.50, ammonia/cyanic acid: 3.0-10.0, reaction temperature: 20-80°C, reaction time: 15-120 minutes. A method for producing DL-serine, which comprises carrying out a Strecker reaction under certain conditions and hydrolyzing the obtained reaction product. (2) Claim 1, wherein the hydrolysis is carried out in the presence of an alkali.
The method described in.