JP3814969B2 - Process for producing amino acid-N-carboxylic acid anhydride - Google Patents

Description

【００１４】
（実施例２）
実施例１において、反応容器内の温度を３０℃に維持して、１２時間反応を継続した以外は、実施例１と同様に操作した。反応容器内の最高圧力は、６８気圧であった。
得られた生成物は、実施例１の場合と同じように精製し、分析を行い上記式（１）で示されるアミノ酸−Ｎ−カルボン酸無水物であることが確認された。
【００１５】
【発明の効果】
本発明の製造方法によれば、ホスゲンを使用せずに、安全にアミノ酸−Ｎ−カルボン酸無水物を製造できる。従って、特殊な設備を用いる必要がないので、低コストでアミノ酸−Ｎ−カルボン酸無水物を提供することができる。
【００１６】
以下、本発明の製造方法の好ましい態様を記載する。
（１）アミノ酸が炭素数２〜２０のα−アミノ酸であること。
（２）アミノ酸と二酸化炭素との反応が、反応温度３０〜１００℃、反応圧力１０〜４００気圧の条件下で行われること。
（３）上記反応が吸湿剤および／または触媒の存在下で行われること。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing an amino acid-N-carboxylic acid anhydride, and more particularly to a method for producing an amino acid-N-carboxylic acid anhydride from an amino acid and carbon dioxide.
[0002]
[Prior art]
An amino acid-N-carboxylic acid anhydride, for example, an α-amino acid N-carboxylic acid anhydride, undergoes ring-opening and decarboxylation in the presence of a catalyst to produce a high molecular weight polyamide, and industrially obtains a polyamide from the amino acid. Is used as an intermediate raw material.
Conventionally, the amino acid-N-carboxylic acid anhydride is produced by reacting phosgene with an amino acid. However, since phosgene is a very dangerous compound, it must be fully equipped for industrial production, which causes safety problems and production cost problems in the production of amino acid-N-carboxylic acid anhydrides. It was.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for producing an amino acid-N-carboxylic acid anhydride from an amino acid at low cost without using phosgene.
[0004]
[Means for Solving the Problems]
According to the present invention, there is provided a method for producing an amino acid-N-carboxylic acid anhydride, which comprises reacting an amino acid with carbon dioxide in a supercritical state or a liquefied state, thereby achieving the object of the present invention. The
Hereafter, the manufacturing method of the amino acid-N-carboxylic acid anhydride of this invention is explained in full detail, By this, the other objective, structure, advantage, and effect of this invention will become clear.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
As typical examples of amino acids used in the production method of the present invention, α-amino acids can be mentioned. The α-amino acid preferably has 2 to 20 carbon atoms, specifically glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cysteine. Cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline, oxyproline and the like.
Other examples of amino acids are β-amino acids, γ-amino acids, aromatic amino acids and other amino acids other than the α-amino acids. Such amino acids are preferably those having 3 to 20 carbon atoms, and specific examples include β-alanine, γ-aminobutyric acid, anthranilic acid and the like.
As amino acids, there are optically active isomers such as D-form and L-form, and racemic isomers which are a mixture of these equivalents, any of which can be used. The amino acid is preferably an α-amino acid in which an amino group and a carboxyl group are bonded to the same carbon atom.
[0006]
When the amino acid has a plurality of amino groups and / or carboxyl groups, the amino group and / or carboxyl group other than those involved in the reaction may be converted into amino acids protected so as not to react with carbon dioxide. preferable.
As a protecting method, in the case of an amino group, the hydrogen atom of the amino group is converted into a carbobenzoxy group, a p-chlorocarbobenzoxy group, a p-bromocarbobenzoxy group, a p-methoxycarbobenzoxy group, a tert-butyloxy group. Examples of the substitution method include a carbonyl group and a p-nitrophenylthio group. In the case of a carboxyl group, a method of substituting a hydrogen atom of the carboxyl group with a methyl group, a benzyl group, a tertiary butyl group or the like can be exemplified.
Similarly, when an amino acid has a group capable of reacting with carbon dioxide other than an amino group and a carboxyl group, it is preferably converted in advance to an amino acid in which the group is protected by an appropriate method.
[0007]
Among the amino acids exemplified above, glutamic acid and those obtained by protecting the carboxyl group bonded to the γ-position of glutamic acid by the above method are preferably used as a raw material for the production method of the present invention because they can be obtained at low cost.
[0008]
In the production method of the present invention, carbon dioxide is in a supercritical state or a liquefied state, and particularly preferably in a supercritical state.
In order to bring carbon dioxide into a supercritical state or a liquefied state, it is preferable to perform the reaction under conditions of a temperature of 0 to 100 ° C. and a pressure of 30 to 400 atm, particularly a temperature of 30 to 100 ° C. and a pressure of 100 to 300 atm.
By carrying out the reaction under such temperature conditions and pressure conditions, a sufficient reaction rate can be obtained, side reactions are substantially suppressed, and expensive reaction equipment that causes high costs is not required.
[0009]
In carrying out the above reaction, carbon dioxide is preferably used in an amount of 5 mol or more, more preferably 10 to 100 mol, per mol of amino acid.
Moreover, in order to accelerate | stimulate reaction or to improve a yield, hygroscopic agents and / or catalysts, such as a silica gel, a molecular sieve, and anhydrous sodium sulfate, can be used.
[0010]
The reaction time is appropriately selected depending on the type of amino acid, the molar ratio of amino acid to carbon dioxide, the reaction temperature, the reaction pressure, the type and amount of the adsorbent and / or catalyst used as desired.
The reactor used for the reaction is a reactor that can sufficiently withstand the reaction pressure. Further, since the reaction is carried out with stirring, it is preferable that the reactor is equipped with a stirring device equipped with, for example, a stirring blade. Of course, the reactor is provided with a heating device such as a jacket, a raw material supply port, a gas discharge port, a product outlet, and the like as necessary.
[0011]
The reaction can be carried out batchwise or continuously. When the reaction is carried out batchwise, a predetermined amount of amino acid and liquefied carbon dioxide, as well as a hygroscopic agent and / or catalyst used as desired are supplied into the reactor, and then the reaction is allowed to proceed by maintaining the predetermined temperature. After completion of the reaction, carbon dioxide is discharged from the reactor, the pressure in the reactor is set to atmospheric pressure, and the reaction product remaining in the reactor is purified in the reactor or by removing it from the reactor for purification. -N-carboxylic acid anhydride can be obtained.
The purification method is appropriately selected depending on the type of amino acid-N-carboxylic acid anhydride, and can be performed by a method such as a recrystallization method or a reprecipitation method.
[0012]
【Example】
EXAMPLES Hereinafter, the present invention will be specifically described by way of examples. However, the scope of the present invention is not limited by the examples.
Example 1
γ-Benzyl-L-glutamate 10.0 g (0.042 mol), liquefied carbon dioxide 40.0 g (0.9 mol), and silica gel 5.0 g were charged into a 100 mL pressure-resistant reaction vessel and sealed. The temperature in the reaction vessel was raised to 50 ° C. with an oil bath while stirring with an electromagnetic induction stirrer, and the reaction was continued for 5 hours while maintaining the temperature at 50 ° C. The maximum pressure in the reaction vessel was 145 atmospheres. Thereafter, the heat source was turned off, and the carbon dioxide in the reactor was gradually released from the pressure reducing valve to lower the pressure to atmospheric pressure.
The reaction product remaining in the reactor was taken out and subjected to the following treatment.
That is, first, it was dissolved in 50 mL of ethyl acetate, the insoluble matter was removed by filtration, the filtrate was poured into normal hexane, the resulting precipitate was collected by filtration, and further purified by recrystallization from n-hexane. The crystals were dried at room temperature under vacuum.
The product thus obtained was confirmed to be an amino acid-N-carboxylic acid anhydride represented by the following formula (1) by NMR, infrared spectroscopy analysis, elemental analysis and the like.
[0013]
[Chemical 1]

[0014]
(Example 2)
In Example 1, the same operation as in Example 1 was carried out except that the temperature in the reaction vessel was maintained at 30 ° C. and the reaction was continued for 12 hours. The maximum pressure in the reaction vessel was 68 atm.
The obtained product was purified and analyzed in the same manner as in Example 1, and it was confirmed that it was an amino acid-N-carboxylic acid anhydride represented by the above formula (1).
[0015]
【The invention's effect】
According to the production method of the present invention, an amino acid-N-carboxylic acid anhydride can be produced safely without using phosgene. Therefore, since it is not necessary to use special equipment, an amino acid-N-carboxylic acid anhydride can be provided at low cost.
[0016]
Hereinafter, the preferable aspect of the manufacturing method of this invention is described.
(1) The amino acid is an α-amino acid having 2 to 20 carbon atoms.
(2) The reaction between an amino acid and carbon dioxide is performed under conditions of a reaction temperature of 30 to 100 ° C. and a reaction pressure of 10 to 400 atmospheres.
(3) The above reaction is performed in the presence of a hygroscopic agent and / or a catalyst.

Claims (1)

A method for producing an amino acid-N-carboxylic acid anhydride, comprising reacting an amino acid with carbon dioxide in a supercritical state or a liquefied state.