JP6639224B2 - Method for producing L-cysteine mineral salt - Google Patents

Description

  The present invention relates to a method for producing L-cysteine mineral acid salt from L-cystine by electrolytic reduction.

  L-cysteine mineral salts are used for applications such as pharmaceuticals, food additives, and cosmetics. Examples of a method for producing L-cysteine mineral acid salt include a method for producing L-cysteine mineral acid salt by reducing L-cystine using a reducing agent, and a method of treating an aqueous solution of L-cystine mineral acid with an ion exchange resin. A method of producing L-cysteine mineral acid salt by adding a caustic alkali to an aqueous solution of L-cystine mineral acid to produce L-cysteine mineral acid salt; Examples of the catholyte include a method for producing L-cysteine mineral acid salt by electrolytic reduction.

Among these, a method of producing L-cysteine mineral acid salt by electrolytic reduction using a mineral acid aqueous solution of L-cystine as a catholyte is preferably cited for the following reasons.
In the chemical reaction from L-cystine to L-cysteine, a reducing agent such as sodium borohydride is used, but it is necessary to remove the reducing agent after the reaction.
On the other hand, in the case of electrolytic reduction, the above-mentioned reducing agent is not required, and further, a purification step after the reaction is not required, so that the cost can be reduced.
In addition, the control of the amount of current can be easily managed as compared with the control of the chemical reaction (temperature, amount of catalyst, and the like), and has an advantage that selective reduction is possible.

  Next, the reaction mechanism of electrolytic reduction of L-cysteine will be described. First, a mineral acid aqueous solution of L-cystine is introduced into the electrolytic cell, an electric current is applied, L-cystine comes into contact with the electrode surface, and electrons are transferred, whereby the reaction proceeds. Therefore, although the current efficiency is high at the beginning of the reaction, the cystine concentration becomes extremely low near the end of the reaction, so that the probability of the cystine hitting the electrode surface decreases, and the progress of the reaction is slowed. Finally, water is electrolyzed more than cystine, and the desired product cannot be obtained. Therefore, there is a problem that an equilibrium state is established during the electrolytic reaction, and L-cystine, which is an unreacted raw material, remains.

For example, Patent Document 1 discloses a method for producing L-cysteine mineral acid salt by reducing L-cystine to L-cysteine by an electrolytic reaction. In order to use L-cysteine mineral salts for pharmaceuticals, food additives, and cosmetics, high purity is required, and specifically, the purity needs to be 99.8% or more.
In this method, although a higher purity can be obtained than in the method of reducing by containing a reducing agent, sufficient purity cannot be obtained by electrolytic reduction alone, and a purification step is required after electrolytic reduction.

Further, in Patent Document 2, a cation exchange resin is used as a diaphragm, and a cysteine mineral salt aqueous solution is continuously supplied and circulated into each of the cathode chambers of a closed type diaphragm electrolytic cell provided with a plurality of cathode chambers and anode chambers alternately. In addition, there is disclosed a method for producing a high-purity cysteine mineral acid salt in which a rare mineral acid is continuously supplied and circulated to each anode chamber while electrolytic reduction is performed. This is a method for producing a high-purity cysteine mineral acid salt by circulating an aqueous solution of cysteine mineral acid at an appropriate flow rate in the cathode chamber and promoting electrolytic reduction in a stepwise manner.
However, it is difficult to obtain a cysteine mineral salt having a purity of 99.8% even by using this method, and a purification step is required to obtain a cysteine mineral salt having a purity of 99.8%.

  As described above, the purity of L-cysteine mineral acid salt needs to be 99.8% or more, but until now, it was impossible to reach the purity without a purification step after the electrolytic reaction. There is a need for a method for producing L-cysteine mineral acid salt having a purity of 99.8% or more by only an electrolytic reaction without a complicated purification step.

JP-B-37-2022 JP-A-51-136620

  The present invention relates to a method for producing L-cysteine mineral acid salt by reducing L-cystine, which can obtain a cysteine mineral acid salt having a purity of 99.8% or more only by an electrolytic reaction without requiring a purification step. Providing is an issue.

  As a result of intensive studies by the present inventors, the present invention having the following contents has been completed.

  A first invention uses an electrolytic cell in which an anode chamber and a cathode chamber are separated by a separator, introduces a mineral acid aqueous solution of L-cystine into the cathode chamber, and electrolytically reduces the method to produce L-cysteine mineral acid salt. Wherein the reaction is carried out by adding a zinc salt to the aqueous solution of mineral acid.

  A second invention provides the method for producing L-cysteine mineral acid salt according to the first invention, wherein the content of the zinc salt in the aqueous mineral acid solution is 0.1 to 5.0% by mass. It is.

  A third invention is the method for producing L-cysteine mineral acid salt according to the first or second invention, wherein the aqueous mineral acid solution is an aqueous hydrochloric acid solution.

  A fourth invention is the method for producing L-cysteine mineral salt according to any one of the first to third inventions, wherein the cathode used in the cathode chamber is a carbon electrode.

  According to the present invention, a method for producing L-cysteine mineral acid salt by using an electrolytic cell in which an anode chamber and a cathode chamber are separated by a separator, introducing an aqueous solution of a mineral acid of L-cystine into the cathode chamber, and performing electrolytic reduction. In the above, the current efficiency is improved by allowing the zinc salt to be contained in the aqueous mineral acid solution to cause a reaction, and the L-cysteine mineral salt having a purity of 99.8% or more can be obtained only by an electrolytic reaction without a purification step. That's the way you can get.

In the present invention, L-cysteine is one of amino acids and refers to 2-amino-3-sulfanylpropionic acid. The mineral acid is an inorganic acid, for example, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, boric acid and the like.
L-cysteine mineral salt refers to a salt of L-cysteine and a mineral acid. In the production method of the present invention, L-cysteine mineral salt can be produced by using L-cystine as a raw material.

  The method for producing L-cysteine mineral salt of the present invention will be described.

  The present invention uses an electrolytic cell in which an anode chamber and a cathode chamber are separated by a separator, and introduces a mineral acid aqueous solution of L-cystine into the cathode chamber and electrolytically reduces the method to produce L-cysteine mineral acid salt. A method for producing a mineral salt of L-cysteine, which comprises reacting a mineral acid aqueous solution containing a zinc salt.

A mineral acid aqueous solution is introduced into the anode chamber, and the anode is immersed for use. The inorganic or organic acid used in the anode compartment need not be the same type as the aqueous mineral acid solution used in the cathode compartment.
In general, the concentration of the mineral acid in the aqueous solution of the mineral acid introduced into the anode chamber is preferably 1 to 30%.

  Examples of the inorganic acid include hydrochloric acid, sulfuric acid, phosphoric acid, boric acid and the like. Examples of the organic acid include formic acid, acetic acid, and oxalic acid.

  Examples of the material of the anode include iridium oxide, gold, platinum, palladium, silver, and lead. Of these, iridium oxide is particularly preferred because of its low oxygen overvoltage and excellent corrosion resistance.

  Into the cathode chamber, an aqueous solution of L-cystine in a mineral acid is introduced, and the cathode is immersed for use.

Examples of the material of the cathode include zinc, tin, carbon, and titanium. It is preferable to use carbon or titanium having a high hydrogen overvoltage, and it is particularly preferable to use carbon. Examples of the carbon material include graphite, carbon paper, glassy carbon, diamond-like carbon, and isotropic carbon.
Since the carbon electrode using a carbon material has a particularly high hydrogen overvoltage, water electrolysis is unlikely to occur, and electric power can be used efficiently for electrolytic reduction. Thus, L-cystine is reduced in a short time to produce L-cysteine. Can be manufactured.

When a zinc salt is contained in a mineral acid aqueous solution of L-cystine and subjected to electrolytic reduction, zinc ions receive electrons, become zinc metal, and precipitate on the electrode surface.
Zn 2 ⁺⁺ 2e ⁻ → Zn
The deposited zinc metal is dissolved by emitting electrons, and the electrons at that time are used to reduce L-cystine to L-cysteine.
^{Zn + CyCy + 2H + → Zn} 2+ + 2CyH
(In the formula, CyCy represents L-cystine, and CyH represents L-cysteine.)
As described above, when zinc acts as an electron transfer medium (mediator), the current efficiency increases, and the reaction progresses to 100% at the end of the reaction because the reaction probability to L-cystine increases. Further, after the reaction is completed, zinc as an impurity precipitates on the electrode surface, so that it is not mixed into the reaction solution, and no post-treatment is required.

The concentration of the mineral acid in the aqueous mineral acid solution used for the cathode compartment is preferably from 1 to 30% by mass, more preferably from 5 to 20% by mass. It is preferable to include 0.1 to 5 times mol based on the content of L-cystine used.
Since L-cystine itself has low solubility in water, it is necessary to increase the solubility in order to increase the reaction efficiency. L-cystine mineral salt has high solubility and can increase the reaction efficiency.
In addition, L-cysteine itself is oxidized by air and easily returns to L-cystine. Since L-cysteine mineral salt is stabilized, the addition of a mineral acid can prevent a decrease in purity.

The content of L-cystine in the mineral acid aqueous solution of L-cystine is preferably 1 to 30% by mass, and particularly preferably 5 to 20% by mass.
When the concentration of L-cystine is increased, crystals precipitate, and unreacted remains due to the precipitation of crystals in dead space, which adversely affects the purity of L-cysteine mineral acid salt. Although it is possible to prevent this crystal precipitation by a production facility having a complicated heating function, it is not realistic in production on an industrial scale. Therefore, the above-mentioned concentration range is particularly preferably mentioned as the concentration range in which L-cystine mineral salt and L-cysteine mineral salt dissolve.
However, L-cystine in the aqueous solution of L-cystine does not need to be completely dissolved in the aqueous solution of mineral acid, but may be dissolved during the electrolytic reaction.

  Examples of the zinc salt contained in the mineral acid aqueous solution include zinc chloride, zinc sulfate, and zinc phosphate.

The content of the zinc salt in the aqueous mineral acid solution is preferably from 0.1 to 5.0% by mass, more preferably from 0.5 to 4.0% by mass.
In the middle stage of the reaction, zinc plays a role of transporting electrons (mediator), so a certain amount of addition is required for the purpose of increasing the reaction efficiency, but it causes contamination, so it is not advisable to add a large amount.
Since zinc is necessary for overtaking at the end of the reaction, the present invention can be expected to be effective even in a small amount. In addition, since it is necessary to deposit zinc on the surface of the electrode and remove it from the reaction solution, it is necessary to set the amount of zinc salt to be added in consideration of the area of the electrode.

  Since the current efficiency is improved by performing the reduction reaction by including the zinc salt, it is possible to completely reduce L-cystine to L-cysteine. As a result, the cysteine ore is purified at a purity of 99.8% or more. Acid salts can be produced.

  In addition, even if a metal salt such as a lead salt, a titanium salt, a copper salt, a tin salt, and a chromium salt is used, the role of the mediator as described above hardly functions, and therefore, almost no improvement in the current efficiency is observed. There is a problem that L-cystine cannot be reduced to L-cysteine.

As the separator, a diaphragm made of polyvinyl chloride or polytetrafluoroethylene (PTFE), a diaphragm made of sucrose fatty acid ester, or a cation exchange membrane can be used. It is preferable to use a cation exchange membrane, and among the cation exchange membranes, a perfluorocarbon material composed of a hydrophobic Teflon (registered trademark) skeleton composed of carbon-fluorine and a perfluoro side chain having a sulfonic acid group is used. A membrane (for example, Nafion (registered trademark) membrane, manufactured by DuPont) is preferably exemplified.
By providing the separator, it is possible to prevent the electrolytically reduced L-cysteine from returning to L-cystine again by oxidation at the anode.

Examples of L-cysteine mineral salts include L-cysteine hydrochloride, L-cysteine sulfate, and L-cysteine phosphate, and can be produced by the production method of the present invention.
The L-cysteine mineral salt is determined by the aqueous solution of the mineral acid used in the cathode chamber. For example, by using an aqueous solution of hydrochloric acid, L-cysteine hydrochloride can be obtained.

  Among these L-cysteine mineral salts, L-cysteine hydrochloride has a higher melting point than other L-cysteine sulfates, L-cysteine phosphates, etc., and is therefore solid at room temperature and easy to handle. Therefore, it is preferably mentioned.

Next, the electrolytic reduction method will be described. Current amount at the time of electrolytic reduction, it is preferable to electrolytic reaction at a current amount of 0.1~20A / dm ^2, and the like and more preferably is an electrolytic reaction at 1 to 10 A / dm ^2. Increasing the current value increases the reaction speed. However, increasing the current value increases the voltage, which causes electrolysis of water as a side reaction, which is undesirable because it lowers the reaction efficiency. Therefore, it is possible to efficiently reduce L-cystine to L-cysteine by electrolytic reduction with the above current amount.

Next, a method for calculating the current efficiency will be described. From the following reaction formula, 1 mol of L-cystine consumes 2 electrons and 2 mol of L-cysteine is generated, so that 1 mol of 1 electron is reacted.
^{CyCy + 2H + + 2e - →} 2CyH
(In the formula, CyCy represents L-cystine, and CyH represents L-cysteine.)
Therefore, the current efficiency (%) can be calculated by the following formula based on Faraday's law.

  In the production method of the present invention, since it is not necessary to contain any other additives besides the aqueous solution of L-cystine and the zinc salt introduced into the cathode chamber, a high-purity L-cysteine mineral acid salt is obtained. At the same time, since there is no unnecessary substance deposition, the target product can be obtained with high yield and high purity by an easy operation.

  L-cysteine mineral acid salt is stable in the air, and has a characteristic that it does not oxidize in the air and return to L-cystine like L-cysteine.

  If necessary, the L-cysteine mineral acid salt obtained by the present invention can be deoxidized to L-cysteine.

  Hereinafter, the present invention will be described in more detail by way of examples. The present invention is not limited to these examples.

(Example 1)
Oxidation as an anode in a diaphragm electrolyzer (anode chamber and cathode chamber each having a capacity of 100 mL) using Nafion (registered trademark) 424 (manufactured by DuPont) having a hydrophobic Teflon (registered trademark) skeleton and a sulfonic acid group as a separator. An iridium electrode (area: 0.025 dm ² ), a carbon electrode (area: 0.025 dm ² ) as a cathode chamber, 50 ml of 10 wt% sulfuric acid as an anolyte, 5 g of L-cystine as a catholyte, and 0.1 g of zinc chloride are added. 50 ml of a 5.3 wt% hydrochloric acid solution was used. Teflon (registered trademark) stirrers were introduced into both the anode and the cathode, and electrolysis was performed while circulating. Electrolysis was performed at a cathode current density of 5 A / dm ² and an electrolysis temperature of 20 ° C., and after applying electricity for 23 hours and 30 hours, the catholyte was analyzed by high performance liquid chromatography to determine the purity of L-cysteine. The current efficiency (%) was calculated from the purity of L-cysteine after 30 hours and the amount of electricity passed.

The measurement conditions of the high performance liquid chromatograph are shown below, and a calibration curve was prepared to calculate the purity (%). Table 1 shows the results.
Equipment used: SHISEIDO NANOSPACE Sl-1
Column: TOSOH ODS-100V 5 μm 4.6 mm ID 25 cm Temperature: 40 ° C.
Eluent: A) acetonitrile _{B) 50mMNaH 2 PO 4, 5mMKH} 2 PO 4 (pH2.2; H 3 PO 4)
A / B = 2.5 / 97.5 (w / w)
Flow rate: 0.4 mL / min
Injection volume: 10 μL
Detection wavelength: 210 nm
Calibration curves were prepared by adjusting cystine and cysteine to 100, 200, and 300 ppm, respectively, and measured by high performance liquid chromatography to prepare calibration curves for wt of cystine and cysteine and AREA.

(Example 2)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of zinc sulfate was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

(Example 3)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of zinc phosphate was added instead of zinc chloride described in Example 1, and the current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 1)
Electrolysis was performed in the same manner as in Example 1 except that zinc chloride described in Example 1 was not added, and current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 2)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of copper chloride was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 3)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of copper sulfate was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 4)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of tin chloride was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 5)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of titanium chloride was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

(Comparative Example 6)
Electrolysis was performed in the same manner as in Example 1 except that 0.1 g of lead chloride was added instead of zinc chloride described in Example 1, and current efficiency and purity were determined. The results are shown in Table 1.

It can be seen that the current efficiency of Examples 1 to 3 is higher than that of Examples 1 to 6, and that L-cysteine mineral salt having a purity of 100% can be obtained after 30 hours. In particular, it was confirmed that zinc chloride used in Example 1 was more easily dissociated than other zinc salts and turned into zinc ions, and the effect of the mediator was high, so that the reaction proceeded quickly in a short time. .
According to the results of Comparative Examples 2 and 3, copper having a lower ionization tendency than hydrogen cannot repeat the deposition and dissolution of metal, so that the effect of an electron mediator was not obtained, and the improvement of current efficiency and purity was not observed. I can't.
As in Comparative Examples 4 to 6, a metal salt having a higher ionization tendency than hydrogen and capable of repeatedly depositing and dissolving a metal has a slight electron mediator effect, but is inferior to a zinc salt. Was.

  Since L-cysteine mineral acid salt obtained by the method for producing L-cysteine mineral acid salt of the present invention has a purity of 99.8% or more, it can be used in various applications such as pharmaceuticals, food additives, and cosmetics. Can be.

Claims (3)

A method for producing L-cysteine mineral acid salt by using an electrolytic cell in which an anode chamber and a cathode chamber are separated by a separator, and introducing an aqueous solution of a mineral acid of L-cystine into the cathode chamber and subjecting the same to electrolytic reduction.
Including a zinc salt in the aqueous solution of mineral acid , utilizing zinc as a mediator to reduce L-cystine to L-cysteine, and that a cathode used in the cathode chamber uses a carbon electrode. A method for producing a L-cysteine mineral salt, which is characterized in that:   The method for producing L-cysteine mineral acid salt according to claim 1, wherein the content of the zinc salt in the aqueous mineral acid solution is 0.1 to 5.0% by mass.   The method for producing L-cysteine mineral acid salt according to claim 1 or 2, wherein the aqueous mineral acid solution is an aqueous hydrochloric acid solution.