JP6183860B2 - Oxidation catalyst and organic oxide production method - Google Patents

Description

  The present invention relates to an oxidation catalyst and a method for producing an organic oxide. More specifically, the present invention relates to an oxidation catalyst capable of producing an organic oxide under low-cost reaction conditions with high reaction efficiency and close to normal temperature and pressure. The present invention relates to a method for producing an organic oxide.

Synthetic techniques for organic compounds have been applied in various fields including pharmaceuticals, chemistry, foods, and materials, and various techniques have been proposed so far. As a result, the number of organic compounds that can be artificially synthesized has increased dramatically. Nevertheless, organic compounds that are difficult to artificially synthesize or organic compounds that are inefficient even if synthesized There are also many reaction systems.
As such an organic compound, there is an organic oxide, and as one of methods for synthesizing such an organic oxide, a reaction using an enzyme with high reaction selectivity, a reaction using a metal catalyst, and the like have been proposed.
For example, in the production of gluconic acid, in Patent Document 1, glucose oxidase and catalase are used as catalysts under specific conditions without using microorganisms as a method instead of the conventional fermentation method using microorganisms. A method has been proposed in which the time required for production is shorter than that of the method and the yield is increased.
Patent Document 2 proposes a reaction system that efficiently oxidizes gluconic acid using a gold nanocatalyst in which gold nanoparticles are supported on the surface of a carbon material. Patent Document 3 proposes a method for producing an organic oxide that increases the reaction efficiency by using an enzyme in combination with a metal such as ruthenium or palladium.
Patent Document 4 proposes a production method for producing gluconic acid using a gel bead catalyst obtained by immobilizing glucosoxidase and noble metal fine particles on a polymer gel beads.

Japanese National Patent Publication No. 10-502825

JP 2009-220017 A

JP 2001-161388 A

Japanese Patent Laid-Open No. 06-70785

However, the oxidation catalyst and the method for producing an organic oxide according to the above proposal are still insufficient and not at the required level.
That is, in the proposal described in Patent Document 1, the reaction proceeds even under a somewhat low temperature condition, but is still insufficient in terms of reaction efficiency.
The proposal described in Patent Document 2 is inefficient because it is necessary to set the reaction conditions to be stricter than usual, for example, the reaction temperature must be set high.
In the proposal described in Patent Document 3, although it became possible to further improve the efficiency of the system using the enzyme by eliminating the negative factor of generation of hydrogen peroxide in the system using the enzyme, However, the reaction was not sufficient because the reaction was not progressing under low-cost reaction conditions.
The proposal described in Patent Document 4 is to promote the decomposition of H ₂ O ₂ and maintain the enzyme activity simply by using a noble metal (Pd, Pt, etc.) catalyst in combination. The reaction rate was slow, and it was still insufficient, not the production under low-cost reaction conditions close to normal temperature and pressure.
For this reason, an oxidation catalyst capable of producing an organic oxide under a low-cost reaction condition having a higher reaction efficiency than that of a conventionally proposed method and close to normal temperature and pressure, and an organic oxide production method Currently, there is a demand for development.

  Accordingly, an object of the present invention is to provide an oxidation catalyst capable of producing an organic oxide under a low-cost reaction condition having high reaction efficiency and close to normal temperature and pressure, and an organic oxide production method. is there.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors inhibit the activity of an enzyme with a normal metal when a compound capable of removing a peroxide as a by-product in an enzyme reaction is used in combination with the enzyme. As a result of further study on metal catalysts that have good compatibility with enzymes and can exhibit a synergistic effect, the present invention has been completed.

That is, the present invention provides the following inventions.
1. An oxidation catalyst used in an oxidation reaction system that generates peroxide when a predetermined enzyme is used as a catalyst in an oxidation reaction of an organic compound,
Including the enzyme and gold-containing particles,
An oxidation catalyst, wherein the gold-containing particles are particles formed by supporting gold nanoparticles on a carrier.
2. The oxidation catalyst according to 1, wherein a mixing ratio of the enzyme and the gold-containing particles is 1: 0.1 to 10 by weight.
3 The oxidation catalyst according to 1 or 2, wherein the support is a metal oxide, and the metal oxide is ZrO ₂ , Al ₂ O ₃ , CeO _2, or SiO ₂ .
4 The oxidation catalyst according to any one of 1 to 3, wherein the organic compound is glucose, the predetermined enzyme is glucose oxidase, and the peroxide is hydrogen peroxide.
5. A method for producing an organic oxide using the oxidation catalyst according to 1.
An organic compound is reacted in the presence of the oxidation catalyst at a temperature of 50 ° C. or lower and in a neutral region of pH 6-8.

The oxidation catalyst of the present invention has high reaction efficiency and can produce an organic oxide under low-cost reaction conditions close to normal temperature and pressure.
Moreover, according to the method for producing an organic oxide of the present invention, the organic oxide can be produced under low-cost reaction conditions having high reaction efficiency and close to normal temperature and pressure.

FIG. 1 is a graph showing the conversion rate of glucose to gluconic acid over time in the glucose oxidation reactions performed in Examples 1 and 2 and Comparative Examples 1 to 3. FIG. 2 is a chart showing the results of H-NMR analysis of the product of the glucose oxidation reaction of Example 1, (a) shows the entire chart, and (b) shows the gluconic acid moiety. It is an enlarged view. FIG. 3 is a graph showing the conversion rate of glucose to gluconic acid over time in the glucose oxidation reaction performed in Example 1 and Comparative Examples 1, 4 and 5. FIG. 4 is a graph showing the conversion rate of glucose to gluconic acid in the glucose oxidation reaction performed in Examples 1 and 3 over time. FIG. 5 is a graph showing the conversion rate of glucose to gluconic acid in the glucose oxidation reaction performed in Example 1 and Comparative Example 6 over time.

Hereinafter, the present invention will be described in more detail.
The oxidation catalyst of the present invention is an oxidation catalyst used in an oxidation reaction system that generates peroxide when a predetermined enzyme is used as a catalyst in the oxidation reaction of an organic compound, and includes the enzyme and gold-containing particles. The gold-containing particles are oxidation catalysts, which are particles formed by supporting gold nanoparticles on a metal oxide.

<Predetermined enzyme>
The predetermined enzyme used in the present invention is not particularly limited as long as it is used for an oxidation reaction of an organic compound, and examples thereof include oxidase that generates hydrogen peroxide. Specifically, glucose oxidase, alcohol Preferred examples include oxidase, ascorbate oxidase, sarcosine oxidase and the like.

<Gold-containing particles>
The gold-containing particles used in the present invention are particles obtained by supporting gold nanoparticles on a carrier such as a metal oxide.
The average particle size of the gold-containing particles is preferably 10 nm to 1 μm, and the composition ratio between the gold nanoparticles and the carrier is a weight ratio of the carrier 10 to 500 with respect to the gold nanoparticle 1. Is preferred.
(Gold nanoparticles)
The gold nanoparticles are particles formed by preferably collecting 10 to 50,000 gold atoms, and more preferably particles formed by collecting 200 to 10,000 gold atoms.
The particle diameter of the gold nanoparticles is preferably 2 to 10 nm as an average particle diameter, and more preferably 2 to 5 nm.

(Carrier)
Examples of the carrier used in the present invention include a metal oxide, carbon, or cellulose, and a metal oxide is particularly preferable.
The metal oxide can be used without particular limitation as long as it can support the gold nanoparticles, and examples of the metal oxide include ZrO ₂ , Al ₂ O ₃ , CeO ₂ , and SiO _2. ZrO ₂ or Al ₂ O ₃ can be preferably mentioned.
The shape of the metal oxide can be various forms such as a spherical shape, a plate shape, a flower shape, and a rod shape.
The size of the metal oxide is preferably 10 nm to 1 μm in terms of average particle diameter.
The size of the metal oxide is preferably 4 to 20 times the particle diameter of the gold nanoparticles.
Further, when the shape of the upper metal oxide is a plate shape, a flower shape, or a rod (rod) shape, the thickness is preferably 5 nm to 100 nm.
Moreover, as said carbon, the nano diamond which is a nano size diamond which has a diamond crystal structure can be mentioned preferably. As said cellulose, it can use regardless of a natural product and an artificial thing, and derivatives, such as nitrocellulose and acetylcellulose, can also be used. The shape and size of these carbon and cellulose can be the same as those of the above metal oxide.

(Production method)
The gold-containing particles can be obtained by mixing a gold compound and the metal oxide as the carrier, and firing and / or reducing the obtained mixture.
Examples of the gold compound include gold complexes of dimethyl gold β-diketone derivatives such as ethylenediamine gold complexes such as Au [C ₂ H ₄ (NH ₂ ) ₂ ] ₂ Cl ₃ and dimethyl (acetylacetonato) gold (III). Is mentioned.
In the mixing, a mixing method such as a solid phase mixing method or a wet mixing method can be used.
The solid phase mixing method is a method in which the gold compound and the metal oxide are mixed in a solid state using a mixer such as a mortar.
The wet mixing method is a method of using a mixing device such as a ball mill in a system in which the gold compound and the metal oxide are dissolved or dispersed in a solvent such as acetone or methanol.
The firing can be performed by air firing the mixture obtained by the above mixing in an electric furnace at a temperature of 100 to 400 ° C. for 1 to 10 hours.
The mixing ratio of the metal oxide and the gold compound is preferably 0.1 to 5 parts by weight with respect to 100 parts by weight of the metal oxide.
In addition, for gold-containing particles in which gold nanoparticles obtained after loading are supported on a metal oxide, a treatment such as a reduction treatment, a firing treatment, a plasma treatment, or the like is performed according to a conventional method as a post-treatment or a treatment performed simultaneously with firing. By carrying out, impurities and by-products attached to the gold-containing particles obtained can be removed.
In addition, when the carbon or cellulose is used as the carrier, it can be produced according to the case where the metal oxide is used.

(Oxidation catalyst form, blending ratio)
The use form of the oxidation catalyst of the present invention is not particularly limited as long as it contains the gold-containing particles and the enzyme. Good.
Further, the oxidation catalyst of the present invention may contain additives such as a buffer solution, various salts, and a coenzyme that are usually used in combination with this type of oxidation catalyst as long as the desired effects of the present invention are not impaired.
Moreover, the mixing method in the case where the gold-containing particles are mixed with the enzyme is not particularly limited as long as it does not deactivate the enzyme activity.
The blending ratio of the enzyme and the gold-containing particles is preferably enzyme: gold-containing particles = 1: 0.1 to 10 and more preferably 1: 0.2 to 5 by weight ratio.

<How to use>
The oxidation catalyst of the present invention is an oxidation catalyst used in an oxidation reaction system that generates peroxide when a predetermined enzyme is used as a catalyst in the oxidation reaction of an organic compound, and is used as a catalyst for the oxidation reaction of the organic compound. It is preferred that
Below, the manufacturing method of the organic oxide of this invention which uses the oxidation catalyst of this invention is demonstrated in detail.
The method for producing an organic oxide of the present invention is a method for producing an organic oxide in which the organic compound is reacted at a predetermined temperature and a predetermined pH using the oxidation catalyst.
The said temperature is a temperature of 60 degrees C or less, and it is preferable that it is 50 degrees C or less. If the temperature exceeds 50 ° C., the operation at the time of carrying out the reaction becomes complicated, and costs such as the need for special equipment are increased. Therefore, it is necessary to keep the temperature within the above range.
The pH is a neutral region of pH 6-8. If it is not a neutral region, for example, when a large amount of alkali is required, neutralization work is required after the reaction, and the reaction operation becomes complicated due to an increase in the number of steps and the accompanying cost increases. There is a need to.
In other words, the oxidation catalyst of the present invention can perform an oxidation reaction at a temperature of 50 ° C. or lower and in a neutral region of pH 6-8.
The pH is adjusted by a method such as a method of neutralizing gluconic acid produced by adding an alkaline solution such as a sodium hydroxide solution during the reaction, a method using a buffer solution having a buffering action at pH 6 to 8 in the reaction solution, or the like. Can be used. When the method of neutralization is adopted, the obtained gluconic acid can be obtained by converting the obtained sodium gluconate into gluconic acid according to a conventional method.
The oxidation catalyst of the present invention can be used in the oxidation reaction of various organic compounds. At that time, the target compound can be obtained with high reactivity in a reaction temperature close to normal temperature, a pressure condition close to normal pressure, and a neutral region. However, among these, it can be preferably used as an oxidation reaction catalyst in the organic compound synthesis reaction system described below.

(Oxidation reaction of glucose)
This is an oxidation reaction for producing gluconic acid by oxidizing glucose by the reaction shown in the following formula (Formula 1).
As the oxidation catalyst in this case, a catalyst comprising glucose oxidase as an enzyme and gold-containing particles obtained by supporting gold nanoparticles on ZrO ₂ as a metal oxide can be preferably used.
The reaction conditions are in the above-described preferable range, but the pH of the reaction solution can be kept neutral by adding an alkaline solution. In addition, the reaction temperature and pressure can be set to normal pressure under relatively low temperature conditions as described in the column of the above usage.

The oxidation catalyst of the present invention can be applied in various oxidation reaction systems other than the oxidation reaction for producing gluconic acid.
For example, the following reaction system is mentioned.
Reaction system for converting hydroxyl group to carbonyl group R ₂ C—OH → R ₂ C═O
Reaction system for converting formyl group to carboxyl group R-CHO → R-COOH
Reaction system for oxidative deamination of amino group R-CH ₂ NH ₃ ⁺ → R-CHO
NH—CH reaction system R—NH ₂ ⁺ —CH ₃ → R—NH ₃ ⁺
Nitrogen compound reaction system R-CH ₂ NO ₂ → R-CHO
Sulfur compound reaction system RSO ₃ ²⁻ → RSO ₄ ²⁻
In the above-described formulas, all Rs represent aliphatic groups such as alkyl groups, aromatic groups such as phenyl groups, and other monovalent substituents.

<Application>
The oxidation catalyst of the present invention can be used for oxidation reactions of various organic compounds, and is highly efficient under conditions close to normal temperature and normal pressure and in a neutral region, for example, pH = 7.0, temperature 30 ° C., and 1 atmosphere. It is possible to carry out the reaction.
In addition, since the enzyme is not immobilized and can be used simply by dissolving it in a solution, various reactions can be performed by simple operations.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated more concretely, this invention is not restrict | limited to these at all.

Example 1 Glucose Oxidation Reaction Using Oxidation Catalyst (Oxidation Catalyst Containing Au / ZrO ₂ and Glucose Oxidase) Dimethyl (acetylacetonate) gold (III) as a gold compound (trade name, manufactured by Trichemical Co., Ltd.) 4.2 mg of “dimethylgold acetylacetonate complex”) and ZrO ₂ as a metal oxide (made by Daiichi Rare Element Co., Ltd., trade name “ZrO2”)
RC-100 ") 0.5 g was mixed in an agate mortar for 20 minutes and subjected to a reduction treatment under conditions of 120 ° C for 2 hours under the flow of H ₂ / N ₂ (20% / 80%, volume ratio). Gold-containing particles in which Au was supported on ZrO ₂ were obtained. Details of the gold-containing particles obtained are shown below.
Average particle size of gold-containing particles: 5 to 10 nm (average particle size measured by HR-TEM (high resolution transmission electron microscope))
Average particle diameter of gold nanoparticles: 4.2 nm (average particle diameter is measured by HAADF-STEM (high angle scattering annular dark field scanning transmission electron microscope))
Composition ratio (weight ratio) of gold nanoparticles and metal oxide = 5: 1000
Next, D-glucose was dissolved in distilled water in a beaker so as to have a concentration of 0.1 mol / L, and the resulting solution was heated to 30 ° C. in a water bath and stirred at 60 mL / min. Bubbling at a flow rate of O ₂ for 30 minutes.
To the solution after bubbling, the gold-containing particles as an oxidation catalyst and glucose oxidase (trade name “20000U”, manufactured by Wako Pure Chemical Industries, Ltd.) are added at respective concentrations of 0.26 g / L and 0.13 g / L. Then, the glucose oxidation reaction was started by adding and mixing.
The glucose oxidation reaction is a condition in which O ₂ bubbling is continued at a flow rate of 60 mL / min, heated to 30 ° C. in a water bath, and 1 mol / L sodium hydroxide solution is continuously added dropwise so that the pH becomes 7.0. Went under.
The conversion rate (%) of glucose to gluconic acid was calculated by the following formula (formula) by the amount of 1M sodium hydroxide solution dropped every 5 minutes from the start of the reaction.

The result is shown in FIG.
In addition, the initial conversion rate of glucose to gluconic acid was calculated by calculating the slope of the conversion rate 10 minutes after the start of the conversion data with time. The results are shown in Table 1.
In addition, in order to examine the product of the glucose oxidation reaction, the reaction solution after completion of the reaction was analyzed by H-NMR (manufactured by JEOL Ltd., apparatus name “JMN-ECS300”) according to a conventional method.
The result is shown in FIG.

Example 2 except using Al ₂ O ₃ as a glucose oxidation metal oxide used (oxidation catalyst containing a Au / Al ₂ O ₃ and glucose oxidase) oxidation catalyst in the same manner as in Example 1 To prepare gold-containing particles.
Average particle size of gold-containing particles: 20 to 50 nm (average particle size is measured by HR-TEM)
Average particle diameter of gold nanoparticles: 11.1 nm (average particle diameter measured by HAADF-STEM)
Composition ratio (weight ratio) of gold nanoparticles and metal oxide = 5: 1000
Except for this, an oxidation catalyst was prepared in the same manner as in Example 1, a glucose oxidation reaction was performed in the same manner as in Example 1, and the conversion rate was calculated.
The result is shown in FIG.
Further, the initial conversion speed was calculated in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 1 Glucose Oxidation Reaction Using Only Enzyme A glucose oxidation reaction was performed in the same manner as in Example 1 except that only the enzyme (glucose oxidase) was added without using gold-containing particles, and the conversion rate was calculated.
The result is shown in FIG.
Further, the initial conversion speed was calculated in the same manner as in Example 1. The results are shown in Table 1.

[Comparative Example 2] Glucose oxidation reaction using only Au / ZrO ₂ A glucose oxidation reaction was carried out in the same manner as in Example 1 except that only the gold-containing particles used in Example 1 were used as the oxidation catalyst without using glucose oxidase. The conversion was calculated.
The result is shown in FIG.

Except that Comparative Example 3 Au / Al ₂ O ₃ only the glucose oxidation reaction of glucose oxidase with gold-containing particles without using (Au / Al 2 _{O 3)} was used as an oxidation catalyst in the same manner as in Example 2 A glucose oxidation reaction was performed and the conversion rate was calculated.
The result is shown in FIG.

[Comparative Example 4] Glucose oxidation reaction using an oxidation catalyst containing Pt / ZrO ₂ and glucose oxidase, except that dimethyl (acetylacetonate) gold (III) as a gold compound was replaced with bisacetylacetonatoplatinum, The particles were synthesized in the same manner as in Example 1 to obtain Pt-containing particles, and a glucose oxidation reaction was performed in the same manner as in Example 1 except that Pt-containing particles obtained instead of gold-containing particles were used. Calculated.
The result is shown in FIG.
Further, the initial conversion speed was calculated in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 5 Glucose Oxidation Reaction Using an Oxidation Catalyst Containing Au / Ketjen Black and Glucose Oxidase Instead of ZrO ₂ as a metal oxide, Ketjen Black (hereinafter sometimes referred to as “KB”) In the same manner as in Example 1 except that the gold-containing ketjen black particles were synthesized, and the oxidation of glucose was performed except that the gold-containing KB particles and glucose oxidase obtained instead of the gold-containing particles were used as the oxidation catalyst. Reaction was performed and the conversion was calculated.
The result is shown in FIG.
Further, the initial conversion speed was calculated in the same manner as in Example 1. The results are shown in Table 1.

[Example 3] Glucose oxidation reaction (40 ° C) using an oxidation catalyst containing Au / ZrO ₂ and glucose oxidase
A glucose oxidation reaction was performed in the same manner as in Example 1 except that the temperature of the reaction solution during the glucose oxidation reaction was changed to 40 ° C., and the conversion rate was calculated.
The results are shown in FIG. 4 together with the results of Example 1.

[Comparative Example 6] Glucose oxidation reaction (pH 9.5) using an oxidation catalyst containing Au / ZrO ₂ and glucose oxidase
A glucose oxidation reaction was performed in the same manner as in Example 1 except that the pH of the reaction solution during the glucose oxidation reaction was adjusted to 9.5, and the conversion rate was calculated.
The results are shown in FIG. 5 together with the results of Example 1.

The results are discussed below.
From the results shown in FIG. 1, the oxidation catalyst of the present invention has a remarkably high conversion rate and conversion rate of gluconic acid as compared with an oxidation catalyst consisting of only an enzyme (Comparative Example 1), and is useful as an oxidation catalyst. Recognize.
On the other hand, in Comparative Examples 2 and 3 using only the gold-containing metal oxide, almost no conversion to gluconic acid was observed, and these oxidation catalysts did not proceed under reaction conditions close to room temperature neutrality. It can also be seen that the reaction cannot proceed unless special reaction conditions such as basicity are prepared. From this result, it can be seen that the oxidation catalyst of the present invention can perform an oxidation reaction at a lower cost.

  The results shown in FIG. 2 show that gluconic acid can be obtained with high selectivity when the glucose oxidation reaction is carried out using the oxidation catalyst of the present invention (Example 1).

  From the results shown in FIG. 3, it can be seen that the oxidation catalyst using the platinum-containing particles (Comparative Example 4) has lower activity than the oxidation catalyst of the present invention. Moreover, the oxidation catalyst (Comparative Example 5) using the gold-containing particles prepared by using ketjen black instead of the metal oxide has lower activity than the oxidation catalyst (Comparative Example 1) consisting only of the enzyme, and the present invention. It can be seen that the activity is significantly lower than that of the oxidation catalyst.

Table 1 is data showing the initial conversion rate of glucose to gluconic acid in the glucose oxidation reaction carried out in Examples 1 and 2 and Comparative Examples 1, 4 and 5.
From the results shown in Table 1, it can be seen that the oxidation catalyst of each comparative example has a low initial addition rate and is inferior in activity as compared with the system using the oxidation catalyst of the present invention.

  From the results shown in FIG. 4, it can be seen that in the oxidation catalyst of the present invention, the reaction proceeds satisfactorily under a temperature condition close to room temperature such as 30 ° C. to 40 ° C.

  From the results shown in FIG. 5, in the reaction under basic conditions (pH 9.5, Comparative Example 6), when a certain amount of time has elapsed from the start of the reaction, the reaction efficiency activity suddenly decreases and the final conversion rate is low, It can be seen that the reaction does not proceed to high activity in the range where the pH is in the basic condition.

From the above results, it can be seen that the oxidation catalyst of the present invention is close to normal temperature and has a pH in a neutral region, which is low in production cost and can be reacted with high activity.
Moreover, according to the manufacturing method of the organic oxide of this invention, it turns out that an oxidation reaction can be performed with high efficiency, without adding an alkali etc. specially at pH of a neutral region.

The oxidation catalyst of the present invention can be used in the oxidation reaction of various organic compounds. In this case, since the target compound can be obtained with high reaction selectivity with high yield, pharmaceutical, chemical, food, material, bio, etc. It can be applied in all fields including the beginning.

Claims (4)

An oxidation catalyst used in an oxidation reaction system that generates peroxide when a predetermined enzyme is used as a catalyst in an oxidation reaction of an organic compound,
Including the enzyme and gold-containing particles,
The gold-containing particles, Ri Oh gold nanoparticles with particles made by supporting on a carrier,
The carrier is a metal oxide, an oxidation catalyst in which the metal oxide _is to _{ZrO 2, Al 2 O 3,} CeO 2 or SiO ₂ der wherein Rukoto. 2. The oxidation catalyst according to claim 1, wherein a mixing ratio of the enzyme and the gold-containing particles is 1: 0.1 to 10 by weight. The oxidation catalyst according to any one of claims 1 to 3, wherein the organic compound is glucose, the predetermined enzyme is glucose oxidase, and the peroxide is hydrogen peroxide. A method for producing an organic oxide using the oxidation catalyst according to claim 1,
An organic compound is subjected to an oxidation reaction at a temperature of 60 ° C. or lower and in a neutral region of pH 6 to 8 in the presence of the oxidation catalyst.

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