JP3347185B2 - Method for producing serine or a derivative thereof - 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 producing serine or a derivative thereof for aminating glyceric acid to convert the corresponding amine to serine or a derivative thereof in high yield. Or derivatives thereof are extremely important as pharmaceuticals, intermediates for amino acids, humectants, and surfactants.

[0002]

2. Description of the Related Art Methods for producing amino acids include chemical synthesis and biochemical methods (using microorganisms and enzymes). The former has high productivity and the latter has high selectivity (L-form). Only selective production). However, in recent years, research on the production of amino acids by a chemical synthesis method has been energetically advanced in order to achieve high productivity, economic efficiency, and the like.
For example, glycine, DL-alanine, DL
-Methionine, DL-tryptophan, DL-serine and the like are produced by a chemical synthesis method. Among them, serine is particularly difficult to produce by a biochemical method, and there is also a problem in purity. Therefore, active production research by a chemical synthesis method is being promoted. Serine alone is used as a pharmaceutical product as an amino acid preparation, as a cosmetic additive for moisturizing effect, and as a raw material for food and feed, but the most important use of serine is in the production of other amino acids. Is to be used as a starting material. For example, tryptophan, cystine, cysteine, tyrosine, doper and the like can all be produced by a biochemical method using serine as a raw material.

[0003] In the production of amino acids, a chemical synthesis method with high productivity is used up to the intermediate material of the target amino acid, and a biochemical method with high selectivity is used from the intermediate material to the target amino acid. It is reasonable to take a composite approach that takes full advantage of the merits. Although there are many chemical production methods for serine in the published gazettes, the starting materials for these are often special and expensive, and are not generally used as starting materials. For example, JP-A-56-83454 and JP-A-57-192346 disclose a process for producing DL-serine, which comprises using aziridine-2-carboxylic acid as a raw material and passing it through a strongly acidic cation exchange resin. However, aziridine is a special and expensive raw material as a starting material. Also, Japanese Patent Application Laid-Open No. 56-83458
JP-A-60-34936 discloses a process for producing DL-serine, which comprises using α-halogeno-β-aminopropionitrile as a raw material and passing it through a strongly acidic cation exchange resin. However, also in this case, a special and expensive starting material is used, which is not common. Also,
JP-A-60-34937 discloses a method for producing serine using β-halogenoalanine as a raw material.
Also in this case, the starting material is special, expensive and not common.

[0004] As is clear from the above, all the conventional methods for producing serine by chemical synthesis use special raw materials or expensive starting materials, and a great deal of addition is required in terms of wastewater treatment. Therefore, it is not always an economical manufacturing method. Therefore, there is a need in the art for the development of a method for producing serine from readily available and inexpensive raw materials.

[0005] Further, when a method of aminating glyceric acid to convert it to the corresponding amine serine or a derivative thereof is employed, a conventional hydrogenation / dehydrogenation catalyst comprising a copper / nickel binary alloy is used. However, there was a major problem that the reaction could not proceed efficiently. Also, when amination reaction is carried out in water, conventional copper
It is difficult to progress the reaction with a nickel two-component alloy catalyst. Furthermore, conventional copper-nickel binary alloy catalysts exhibit favorable catalytic activity at 160 to 220 ° C., but using a catalyst at a higher reaction temperature to obtain sufficient catalytic activity is not thermally stable. In the production of a novel serine or a derivative thereof, isomerization or decomposition is involved, so that it is practically difficult to effectively proceed the reaction. In addition, the reaction can proceed even if a noble metal catalyst described in Japanese Patent Application No. 4-162156 is used, but there is a problem in terms of catalyst cost, and it is desired to use an inexpensive catalyst.

[0006]

The inventors of the present invention have conducted intensive studies on nickel and cobalt based catalysts and found that glyceric acid can be converted into the corresponding amine serine or its derivative in high yield. Was completed.

That is, the gist of the present invention is to provide (1) production of serine or a derivative thereof characterized by aminating glyceric acid in the presence of a supported catalyst composition containing nickel and / or cobalt as a catalyst component. And (2) a process for producing serine or a derivative thereof, which comprises aminating glyceric acid in the presence of Raney nickel and / or Raney cobalt.

The supported catalyst composition in the present invention is a composition comprising a catalyst component and a catalyst carrier. In the catalyst composition, the catalyst component is nickel (Ni).
And / or cobalt (Co) is used. As the catalyst carrier, one or more usually used ones selected from the group consisting of activated carbon, alumina, silica and zeolite are used. Other examples include molecular sieves.

In the present invention, Ni and Co may be used alone or in combination. However, in the case of using both, Ni and Co obtained by supporting Ni and Co on a single carrier, A mixed catalyst obtained by mixing two or more kinds of supported catalysts of a catalyst element may be used. In preparing the supported catalyst composition of the present invention, the catalyst component Ni or C
Raw materials for o include chlorides, acetates, nitrates and the like. The catalyst is prepared according to a conventional method by using an aqueous solution of the above-mentioned raw materials to form a precipitate using an aqueous solution of sodium carbonate, urea, etc., washing with water, drying, calcining, pulverizing, and then reducing the hydrogen. Further, by adding a noble metal element typified by Pd, Pt or the like to the catalyst in the present invention, the catalytic activity may be improved in some cases.

The amount of the supported catalyst in the supported catalyst composition is usually 30 to 0.1% by weight, preferably 10 to 0.5% by weight. If the supported amount is more than 30% by weight, it is disadvantageous in terms of cost and there is no particular advantage in terms of catalytic activity. Also, 0.1
If the amount is less than% by weight, the reaction cannot proceed efficiently.

In the present invention, Raney nickel (Raney Ni) or Raney cobalt (Raney Co) is also effective as a catalyst. For example, catalysts (NDT-65, CDT-60) manufactured by Kawaken Fine Chemicals Co., Ltd. are effectively used. be able to. Also in this case, Raney Ni and Raney Co may be used alone or in combination.

The amount of the catalyst to be added is not particularly limited with respect to the raw material liquid containing glyceric acid.
0.2 to 50% by weight for all Raney catalysts
Is preferable, and 1 to 30% by weight is more preferable.

The supported catalyst composition used in the present invention can be used in various reactors depending on its form. That is, when the supported catalyst composition is in the form of a powder, it can be used in a stirred tank reactor, a fluidized bed reactor, an injector reactor, or the like, while a molded granular carrier or a crushed carrier is used. Can be used for a fixed bed reactor or the like. The amination reaction itself may be a batch type or a continuous type.

The reaction route from glyceric acid to serine in the present invention can be considered as in the following formula (1). In this example, ammonia is used as an aminating agent. However, when a primary amine or a secondary amine is used instead of ammonia, the reaction proceeds similarly and is converted into a corresponding serine derivative.

[0015]

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In this reaction, the secondary hydroxyl group of glyceric acid is first dehydrogenated to form hydroxypyruvic acid, and ammonia is added thereto to form 2-aminoglyceric acid as an unstable intermediate. Next, the 2-aminoglyceric acid is hydrocracked to produce serine. Generally, it is preferable to carry out the reaction in the presence of hydrogen.

The glyceric acid used in this reaction may be any of those commercially available or those produced by oxidation of glycerin. When glycerin is produced by oxidation or the like, glycerin as a raw material can be produced by hydrolysis or transesterification of fats and oils. Further, glyceric acid may be used which is derived by another method, for example, glyceraldehyde obtained by electrolytic oxidation of glycerin, oxidation by microorganisms, enzymatic oxidation or the like.

As the aminating agent used in the amination reaction, ammonia and various primary or secondary amines can be used. The primary amine or the secondary amine may be an aliphatic, alicyclic or aromatic amine, and may have a substituent. As these primary amines or secondary amines, for example, methylamine, dimethylamine, ethylamine, diethylamine, propylamine,
Dipropylamine, hexylamine, octylamine,
Decylamine, dodecylamine, tetradecylamine,
Hexadecylamine, octadecylamine, cyclohexylamine, benzylamine and the like can be mentioned. These amines are used in different forms depending on their molecular weights.In the case of gaseous ammonia, methylamine, dimethylamine, ethylamine, etc., they may be used in gaseous form or diluted with an appropriate solvent, for example, as an aqueous solution. Good. In the case of a liquid or solid amine having a long-chain alkyl group, it can be used as a liquid or diluted with a solvent.

In the present invention, the molar ratio of the aminating agent to glyceric acid [aminating agent / glyceric acid] is 0.1.
It may be in the range of 1 to 50, preferably 0.3 to 1
0, and more preferably 0.5 to 3. When the molar ratio of the aminating agent is less than 0.1, the reaction rate is too low to be practical. On the other hand, when the molar ratio of the aminating agent exceeds 50, side reactions are likely to occur simultaneously, which is not practical.

In carrying out the amination reaction of glyceric acid using the supported catalyst composition of the present invention, glyceric acid may be used in a solvent-free system, but from the viewpoint of improving the reaction rate, the amination reaction is carried out. It may be used by diluting it with a suitable solvent which does not undergo the above. Water is particularly effective as a solvent. The reason for this is that glyceric acid is produced by catalytic oxidation of its starting material glycerin in water. In this case, the fact that glyceric acid supplied as an aqueous solution can be used as it is in the amination reaction is a great advantage in the process. The concentration of the aqueous solution of glyceric acid may be in the range of about 99.9 to 0.1% by weight, preferably 70 to 1% by weight, more preferably 50 to 2% by weight. Dilutions below 0.1% by weight are not practical. As the solvent, other usual polar solvents such as methyl alcohol, ethyl alcohol, dimethylformamide, dimethylacetamide and the like can be used.

In the amination reaction according to the present invention, the hydrogen pressure may be generally in the range of 200 atm or less, preferably 60 atm or less. The reaction can be sufficiently advanced by setting the reaction conditions even at normal pressure.
When the hydrogen pressure is higher than 200 atm, the decomposition reaction of the product is accelerated, and the yield of the product is greatly reduced. If the hydrogen pressure is lower than normal pressure, the reaction rate is reduced, and this is not always effective. Although the amination reaction in the present invention proceeds even in the absence of hydrogen as described above, it is preferably carried out in the coexistence of hydrogen from the viewpoint of improving the amination yield. In this case, a compound such as sodium borohydride or hydrazine may be used as a hydrogen generator instead of hydrogen.

In the amination of glyceric acid using the supported catalyst composition of the present invention in the presence of an aminating agent and hydrogen, the molar ratio of hydrogen to glyceric acid [hydrogen / glyceric acid] is 0.1 to 400. It is sufficient if it is in the range, preferably 0.5 to 100, more preferably 1 to 100.
50. If the hydrogen molar ratio is less than 0.1, the reaction rate is extremely slow, and if it exceeds 400, a decomposition reaction is likely to occur.

In the amination reaction of the present invention, the reaction temperature is usually in the range of 0 to 200 ° C., preferably 0 to 200 ° C.
About 120 ° C, more preferably about 0-60 ° C. When the reaction temperature exceeds 200 ° C., the decomposition reaction of the product is accelerated, and the yield of the product is greatly reduced. On the other hand, if the reaction temperature is lower than 0 ° C., the reaction rate is remarkably reduced, which is not practical. Therefore, Ni or C used in the production method of the present invention
The supported catalyst composition containing o as a catalyst component, and Raney Ni and Raney Co are optimal catalyst systems for the synthesis of thermally unstable serine and its derivatives. The reaction time varies depending on the reaction temperature, but is usually 1 to 20 hours, preferably 1 to 10 hours. When serine is produced in this reaction, a small amount of glycine is by-produced in addition to the target serine. After completion of the reaction, the target serine can be easily separated from these amino acid mixtures by appropriately using a method such as a chromatographic separation method, a crystallization separation method, or an ion exchange method.

As described above, when aminated glyceric acid is aminated in the presence of ammonia and hydrogen using the supported catalyst composition of the present invention and Raney Ni or Raney Co, for example, A 10 wt% aqueous solution and a catalyst may be added, and ammonia may be bubbled into the reactor together with hydrogen gas through a gas introduction pipe. Alternatively, when ammonia is used as ammonia water, it may be dropped into the reactor or charged at once at the start of the reaction. The reaction temperature is set at 0 to 200 ° C., and the hydrogen pressure is set to 200 atm or less. The reaction conditions are preferably set so that the reaction time is 1 to 20 hours, and preferably the amination reaction is completed within 10 hours.
If the reaction time is too long, the product may decompose. As a result of performing the amination reaction under the above conditions, serine is produced in high yield as the produced amine. When the reaction is carried out in a fixed bed continuous system, the reaction can be allowed to proceed by charging the granular catalyst in the reaction tower and supplying glyceric acid and ammonia and hydrogen in a downward cocurrent, or an upward cocurrent, or in a countercurrent. .

As described above, by carrying out the amination reaction of glyceric acid by the production method of the present invention, the carbon atom at the α-position of the carboxyl group of glyceric acid is selectively aminated, and the corresponding amine, serine or The derivative can be selectively produced. This fact is unexpected with conventional catalysts. What is particularly noteworthy is that the amination reaction of glyceric acid can efficiently proceed in water. This is a great advantage in terms of process because glyceric acid is produced by oxidizing glycerin in water. That is, since the aqueous glyceric acid solution obtained by oxidizing glycerin in water can be used as a raw material for the amination reaction, glyceric acid is directly subjected to the amination reaction according to the production method of the present invention without particular isolation. be able to.

[0026]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. Incidentally,% in the examples indicates% by weight. Example 1 500 cc of 200 g of a 10% aqueous solution of glyceric acid, 64 g of 5% aqueous ammonia, and 5 g of Raney Ni (based on a dry product)
In an autoclave. After the replacement with hydrogen, serine was synthesized by setting the gauge pressure to a hydrogen pressure of 5 kg / cm ² , heating to 60 ° C., and reacting for 4 hours. After completion of the reaction, the product obtained by separating the catalyst from the reaction mixture was subjected to amino acid analysis using an amino acid analyzer to determine the yield (mol%) of serine based on the charged glyceric acid (Table 1). The measurement conditions of the amino acid analyzer are as follows. Analyzer: Hitachi High Speed Amino Acid Analyzer L-8500
Type column: 4.6 mmI. D × 60 mmL ammonia trap column: 4.6 mmI. D × 40
mmL eluent: L8500 PF-KIT, 0.35 mL
/ Min detector: UV absorption, 570 nm

[0027]

[Table 1]

Example 2 200 g of a 10% aqueous solution of glyceric acid, 64 g of 5% aqueous ammonia and 20 g of Raney Co (based on dry product)
It was charged in a 00 cc autoclave and the catalytic activities were compared. The amination reaction was performed at 60 ° C. under a hydrogen pressure of 5 kg / cm ² G for 4 hours. After the reaction was completed, the product obtained by separating the catalyst from the reaction mixture was subjected to amino acid analysis using an amino acid analyzer. The yield (mol%) of serine based on glyceric acid charged was as shown in Table 1.

Example 3 An amination reaction was carried out in the same manner as in Example 1 except that 20 g of a 50% Ni-supported γ-alumina catalyst was used and the reaction temperature was 80 ° C. The serine yield is shown in Table 1.

Example 4 An amination reaction was carried out in the same manner as in Example 1 except that the reaction temperature was 80 ° C. using 40 g of 50% Co-supported γ-alumina as a catalyst. The serine yield is shown in Table 1.

Example 5 An amination reaction was carried out in the same manner as in Example 1, except that 64 g of a 10% aqueous solution of monomethylamine was used instead of 5% aqueous ammonia. Table 1 shows the yield of N-methylserine.

[0032]

Industrial Applicability According to the production method of the present invention, an amination reaction using glyceric acid as a raw material can be efficiently carried out at low temperature and in water to produce the corresponding amine serine or a derivative thereof in high yield. It became possible to obtain.

Continuation of the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 229/22 C07C 227/04 CA (STN) CASREACT (STN)

Claims (2)

(57) [Claims] 1. A method for producing serine or a derivative thereof, comprising aminating glyceric acid in the presence of a supported catalyst composition containing nickel and / or cobalt as a catalyst component. 2. A method for producing serine or a derivative thereof, comprising aminating glyceric acid in the presence of Raney nickel and / or Raney cobalt.