KR102487704B1 - Preparation method of ruthenium compound and ruthenium compound thereby - Google Patents

Abstract

The present invention relates to a method for preparing a ruthenium compound having improved water solubility and a ruthenium compound prepared therefrom.

Description

Manufacturing method of ruthenium compound and ruthenium compound prepared therefrom

The present invention relates to a method for preparing a ruthenium compound having improved water solubility and a ruthenium compound prepared therefrom.

Due to the recent increase in diabetic patients, a self-glucose meter capable of conveniently measuring the concentration of glucose in the blood has been widely used. Self-monitoring blood glucose consists of a test strip that reacts with blood and a reader that measures blood glucose concentration. The strip is coated with an enzyme that reacts with glucose present in the blood and an electron transfer medium that mediates the movement of electrons generated by the glucose-enzyme reaction. The reader quantifies the glucose concentration by measuring the current caused by the movement of electrons in the strip. In order to rapidly and accurately measure blood glucose using such an autologous blood glucose meter, a ruthenium compound is used as an electron transfer medium. Since the ruthenium compound is included in the coating solution and coated on the strip, the solubility in distilled water used as a solvent for the coating solution must be high, and the purity must be high to accurately measure the movement of electrons. For this reason, the ruthenium compound coated on the strip is required to have high solubility and purity.

When synthesizing and manufacturing a ruthenium compound, ruthenium chloride is generally used as a raw material. Korean Patent Publication No. 1999-014261 discloses a method for producing ruthenium chloride (RuOCl ₃ ) by injecting ozone gas while dissolving ruthenium in sodium hypochlorite to generate ruthenium tetroxide (RuO ₄ ), collecting it with hydrochloric acid and drying it. This is listed. However, in this manufacturing method, it may be difficult to obtain high-purity ruthenium chloride because there is no process for removing impurities, and when the ruthenium compound is prepared from impurity-containing ruthenium chloride, the purity of the ruthenium compound may also be reduced.

As such, in order to manufacture a ruthenium compound applicable to the self-monitoring blood glucose level, not only high purity ruthenium chloride must be used, but also impurities included in the manufacturing process must be removed while minimizing the loss of expensive ruthenium chloride. In particular, when silver (Ag) used as an oxidizing agent remains during the manufacturing process of the ruthenium compound, the activity of the enzyme coated with the ruthenium compound is inhibited by the silver, and thus the accuracy and reliability of the self-monitoring blood glucose level may deteriorate. In addition, since the purity of the ruthenium compound containing impurities such as silver (Ag) is lowered, it may not be completely dissolved in the solvent of the coating solution used for strip coating. Therefore, in order to prepare a ruthenium compound having high solubility and purity using ruthenium chloride, many studies still need to be conducted.

Patent Publication No. 1999-014261

In order to solve the above problems, an object of the present invention is to provide a method for preparing a high-purity ruthenium compound having improved solubility in water using ruthenium chloride (RuCl ₃ ) and a ruthenium compound prepared therefrom.

In order to achieve the above object, the present invention is (a) preparing a first solution by adding a reducing agent after dissolving ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl) in a solvent; (b) injecting a precipitating agent into a solution obtained by filtering the first solution, and then precipitating and recovering an intermediate of the ruthenium compound; (c) preparing a second solution by adding an oxidizing agent to the solution containing the recovered intermediate of the ruthenium compound; (d) preparing a third solution by first filtering and second filtering after adding an impurity removing agent to the second solution; (e) injecting a co-solvent into the third solution to precipitate a ruthenium compound; and (f) vacuum-freezing and drying the precipitated ruthenium compound.

In addition, the present invention provides a ruthenium compound prepared by the above production method and having improved solubility in water.

The method for producing a ruthenium compound according to the present invention is hexaamineruthenium (III) chloride having high water solubility through reduction and oxidation reactions using ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl). Ru(NH ₃ ) ₆ Cl ₃ ) can be prepared. At this time, the purity of the ruthenium compound can be increased to 99.99% or more by repeating the filtration process and using an impurity removing agent, and the loss of the ruthenium compound can be minimized by repeating the precipitation process and freeze-drying. When the conditions of the precipitation process are controlled, the crystallization of the ruthenium compound can be controlled to improve the solubility in water.

Therefore, the method for producing a ruthenium compound according to the present invention can efficiently prepare a high-purity ruthenium compound having improved solubility in water.

1 is a process chart showing a method for producing a ruthenium compound step by step according to an embodiment of the present invention.
Figure 2 is a SEM image of measuring the pore size (pore size) of the filter cloth used in the secondary filtration of step (d) of the method for producing a ruthenium compound according to an embodiment of the present invention.
3 is an SEM image of measuring the particle size of a ruthenium compound prepared according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail.

1. Manufacturing method of ruthenium compound

According to the method for producing a ruthenium compound according to an embodiment of the present invention, a ruthenium compound having high solubility in water (Ru(NH ₃ ) ₆ Cl ) is obtained by using ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl). ₃ ) can be produced. Referring to Figure 1, the manufacturing method of such a ruthenium compound will be described by dividing each step. At this time, the method for producing a ruthenium compound according to an embodiment of the present invention is not limited to the following method, and each process step may be modified or optionally mixed as necessary.

(a) preparing a first solution by dissolving ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl) in a solvent and then adding a reducing agent

In order to manufacture a ruthenium compound (Ru(NH ₃ ) ₆ Cl ₃ ), ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl) are used as raw materials. The use ratio of ruthenium chloride and ammonium chloride is not particularly limited, but may be an equivalent ratio of ruthenium chloride:ammonium chloride = 1:2 to 1:3. In order to sufficiently dissolve these ruthenium chloride and ammonium chloride, a conventional solvent known in the art may be used, and for example, distilled water or alkaline ammonia water (NH ₃ ) may be used. At this time, when using ammonia water, it is preferable that the concentration of ammonia water is 2 to 20 mM and the hydrogen ion concentration is pH 9 to 13 in order to increase the solubility of ammonium chloride (NH ₄ Cl).

A first solution is prepared by adding a reducing agent to the solution in which the ruthenium chloride and ammonium chloride are dissolved. As the reducing agent, a conventional reducing agent known in the art may be used, and for example, zinc (Zn) or hydrogen peroxide (H ₂ O ₂ ) may be used. This reducing agent may be used in a nitrogen atmosphere to prevent the reduction of the efficiency of the reduction reaction by oxygen, and the reducing agent may be used in a content of 30 to 80% by weight based on 100% by weight of the ruthenium chloride at 60 to 95 ℃ 12 to 25g / It can be injected at a rate of min. After the reducing agent is added, it may be maintained for 0.5 to 2 hours so that the reduction reaction can occur sufficiently. The first solution thus prepared includes an intermediate (Ru(NH ₃ ) ₆ Cl ₂ ) of a ruthenium compound produced by reacting ruthenium chloride with ammonium chloride.

(b) adding a precipitating agent to the solution obtained by filtering the first solution to precipitate and recover the intermediate of the ruthenium compound

Since a reducing agent not used in the reduction reaction remains in the first solution in addition to the intermediate of the ruthenium compound (Ru(NH ₃ ) ₆ Cl ₂ ), the unreacted reducing agent may be removed through filtration. At this time, as the filtration method, a conventional filtration method known in the art may be used without limitation.

Thereafter, a precipitating agent is added to the solution obtained by filtering the first solution. As the precipitating agent, a conventional precipitating agent known in the art may be used, and for example, ammonium chloride (NH ₄ Cl) may be used. At this time, since the input amount of the precipitant may affect the yield of the intermediate of the reduced ruthenium compound, it is preferable to add the first solution up to just before the supersaturation level for the filtered solution. When the precipitating agent is added, the temperature of the solution obtained by filtering the first solution is preferably 40 to 60° C. in order to improve the yield of the intermediate of the ruthenium compound to be precipitated by adjusting the supersaturation of the solution in a state where the temperature is higher than room temperature. Accordingly, the intermediate of the ruthenium compound (Ru(NH ₃ ) ₆ Cl ₂ ) contained in the first solution is precipitated, and may be recovered as a solid by filtering. At this time, as the filtration method, a conventional filtration method known in the art may be used without limitation.

(c) preparing a second solution by adding an oxidizing agent to the solution containing the intermediate of the precipitated ruthenium compound

The intermediate of the ruthenium compound recovered in a solid state is dissolved in a solvent to become a solution state. As the solvent, a conventional solvent known in the art may be used, and distilled water may be used as an example.

Thereafter, an oxidizing agent is added to the solution in which the intermediate of the ruthenium compound is sufficiently dissolved. As the oxidizing agent, a conventional oxidizing agent known in the art may be used, and for example, a compound containing silver (Ag) may be used. As such an oxidizing agent, silver chloride (AgCl) having an average particle size of 100 to 500 μm may be used to increase the oxidation efficiency of the intermediate of the ruthenium compound, and the oxidation reaction is maintained at 15 to 35 ° C. for 0.5 to 2 hours. The second solution thus prepared contains a ruthenium compound (Ru(NH ₃ ) ₆ Cl ₃ ).

(d) preparing a third solution by first filtering and second filtering after adding an impurity remover to the second solution

The second solution contains impurities such as zinc (Zn ²⁺ ) ^{and silver (Ag + )} in addition to the ruthenium compound. In order to remove these impurities, a conventional impurity removal agent known in the art may be used, and for example, sodium carbonate (Na ₂ CO ₃ ) may be used. When sodium carbonate is used as an impurity removal agent, it reacts with ZnCl ₂ dissolved in the second solution to precipitate and remove zinc ions as a solid content. At this time, sodium carbonate is preferably used in an amount of 0.05 to 1% by weight based on 100% by weight of the second solution. The impurity removing agent may be reacted at 15 to 35° C. for 0.5 to 2 hours to form impurities in the form of fine particles.

Thereafter, in order to remove impurity fine particles, a two-step filtration process is performed. As the primary filtration method, a conventional filtration method known in the art may be used, and for example, a vacuum filtration device may be used. Secondary filtration is performed to remove impurities remaining after the first filtration, and the same method as the first filtration may be used. At this time, in order to minimize impurities contained in the first filtered solution, it is preferable to use a filter having a pore size of 0.001 to 4.0 μm.

Through the use of such an impurity removing agent and a two-step filtration process, a third solution in which impurities and insoluble matters are removed from the second solution may be prepared.

(e) precipitating a ruthenium compound by adding a co-solvent to the third solution

In order to recover the ruthenium compound (Ru(NH ₃ ) ₆ Cl ₃ ) contained in the third solution, a co-solvent is introduced into the third solution and the difference in solubility is used. As the co-solvent, a conventional solvent known in the art may be used, and hydrochloric acid (HCl) may be used as an example. At this time, ethanol may be additionally used to increase the yield of the precipitated ruthenium compound. For example, after adding 1 to 3 times hydrochloric acid (HCl) to the third solution at a rate of 10 to 200 ml/min, ethanol (EtOH) is added in an amount of 0.1 to 1% by weight based on the amount of hydrochloric acid added. can do. When hydrochloric acid is added at the above rate, the crystals of the ruthenium compound can be controlled to have an average particle size of 50 to 200 μm, and solubility in water can be improved.

(f) drying the precipitated ruthenium compound by vacuum freezing

The precipitated ruthenium compound is recovered as a solid by removing the solution through a filtration process. As the filtration method, a conventional filtration method known in the art may be used without limitation. The ruthenium compound recovered as a solid content can be washed with ethanol to increase the drying efficiency, and the washing can be repeated.

Thereafter, in order to prevent the chemical structure from being deformed by heat, the ruthenium compound is dried in a vacuum-freezing state. At this time, vacuum freezing conditions are not particularly limited, but may be performed at -120 to -10 ° C for 1 to 5 hours.

Through this drying process, a high purity ruthenium compound having a water solubility of 300 to 500 mM according to the present invention can be prepared in high yield.

As such, high-purity ruthenium compounds with improved water solubility, that is, hexaamineruthenium chloride (Ru(NH ₃ ) ₆ Cl ₃ ) can be efficiently produced by using an impurity removing agent through repeated filtration and precipitation processes. there is.

2. Ruthenium compounds

The ruthenium compound prepared according to the above method is hexaamineruthenium chloride (Ru(NH ₃ ) ₆ Cl ₃ ). The ruthenium compound has a structure containing chemically stable trivalent ruthenium, and has an average particle size of 50 to 200 μm. This ruthenium compound has a solubility in water of 300 to 500 mM, which is higher than that of conventional ruthenium compounds (solubility 200 mM).

Hereinafter, the present invention will be described in detail through examples, but the following examples are merely exemplifying one form of the present invention, and the scope of the present invention is not limited by the following examples.

[ Example 1] Preparation of ruthenium compound

First, 200 g of ruthenium chloride (RuCl ₃ ) was put into a 5L beaker containing 400 ml of distilled water and completely dissolved to prepare an aqueous solution of ruthenium chloride. 50 g of ammonium chloride (NH ₄ Cl) was added to 1.8 L of ammonia water (NH ₃ ) while maintaining 80° C. by heating a closed 5L reactor capable of constant temperature, and dissolved. Thereafter, the prepared ruthenium chloride aqueous solution was introduced into a sealed reactor in which aqueous ammonia and ammonium chloride were dissolved, and nitrogen gas was introduced into the reactor at a rate of 10 L/min or less to maintain a nitrogen atmosphere. When the internal temperature reached 50° C. or more, 100 g of zinc powder was added as a reducing agent and the reduction reaction was maintained for 1 hour to prepare a first solution. Residual reducing agent contained in the first solution was removed by filtration. 600 g of ammonium chloride (NH ₄ Cl) as a precipitating agent was added to the filtered solution of the first solution, and stirred at 200 rpm for 1 hour at 30° C. to precipitate an intermediate of a ruthenium compound (Ru(NH ₃ ) ₆ Cl ₂ ). Thereafter, the precipitate was filtered to recover solid content. After completely dissolving the recovered intermediate of the ruthenium compound in 1.8 L of distilled water, 200 g of silver chloride (AgCl) having an average particle size of 150 μm was added as an oxidizing agent and stirred at 30 ° C. for 1 hour at 200 rpm to prepare a second solution. 10 g of sodium carbonate (Na ₂ CO ₃ ) was added to the second solution as an impurity removal agent, and the mixture was stirred at 30° C. for 1 hour at 200 rpm. Thereafter, as a primary filtration, impurities in the fine particles generated by the impurity removing agent and remaining oxidizing agent were removed using a vacuum filtration device. The firstly filtered solution was secondarily filtered using a filter cloth having a pore size of 2.5 μm, and finally, a third solution from which insoluble matters were removed was prepared. While stirring the third solution at 200 rpm, a hydrochloric acid (HCl) solution was added for 30 minutes at a rate of 150 ml/min using a metering pump, and then 300 ml of absolute ethanol was added to precipitate the ruthenium compound. The precipitated ruthenium compound was separated into solids by filtration and washed three times with ethanol. The separated solid content was dried in a vacuum freeze dryer at -80 °C for 3 hours to prepare a final ruthenium compound (Ru(NH ₃ ) ₆ Cl ₃ ).

[ Example 2] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that nitrogen was not supplied into the reactor.

[ Example 3] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that 450 g of ammonium chloride was added as a precipitant instead of 600 g.

[ comparative example 1] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that the first filtered solution was not second filtered.

[ comparative example 2] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that the impurity removing agent was not used in the second solution.

[ comparative example 3] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that the separated solid content was used in a forced circulation dryer instead of a vacuum freeze dryer.

[ comparative example 4] Preparation of ruthenium compound

A ruthenium compound was prepared in the same manner as in Example 1, except that the hydrochloric acid (HCl) solution was simultaneously added at a high speed within 1 minute using a metering pump while stirring the third solution at 200 rpm.

[ Experimental example 1] Purity measurement

The purity of the ruthenium compounds prepared in Examples 1 to 3 and Comparative Examples 1 to 4 was measured.

At this time, the purity of the ruthenium compound was measured by preparing an analysis sample by dissolving 0.5 g of Ru(NH ₃ ) ₆ Cl ₃ in 50 ml of 5% hydrochloric acid solution (HCl), and then using ICP-AES XDL (Thermo Co.).

[ Experimental example 2] Solubility measurement

The solubility of the ruthenium compounds prepared in Examples 1 to 3 and Comparative Examples 1 to 4 was measured.

At this time, the solubility of the ruthenium compound was confirmed by dissolving 50 mg of Ru(NH ₃ ) ₆ Cl ₃ in 1 ml of a mixed solvent (volume ratio of distilled water: 2-isopropanol = 9: 1) (dissolution temperature is 40 ° C or less, The dissolution time is 30 minutes or more, and the stirring speed is dissolved at 50 rpm or more).

[ Experimental example 3] Particle size measurement

The particle size of the ruthenium compounds prepared in Examples 1 to 3 and Comparative Examples 1 to 4 was measured.

At this time, the particle size of the ruthenium compound was measured 5 times using a Mastersizer 2000 (Malvern Company) and then described as an average value (the dispersant solution was prepared by dissolving 1 g of NaPO ₃ in 1000 g of pure water, and the mobile solvent was ethanol).

The purity, solubility, and particle size measurements of the ruthenium compounds measured in Experimental Examples 1 to 3 are shown in Table 1 below.

Ag (ppm) Zn (ppm) water(%) Solubility (mM) Particle size (㎛) transference number(%) Example 1 0.2 1.3 99.99 450 96 77 Example 2 0.2 1.5 99.99 432 90 72 Example 3 0.5 2.1 99.99 380 95 45 Comparative Example 1 120 40 99.85 220 87 75 Comparative Example 2 5 4500 99.50 185 92 72 Comparative Example 3 2 3 98.00 160 98 65 Comparative Example 4 0.2 2.3 99.99 280 10 65

As shown in Table 1, it was confirmed that the methods according to Examples 1 to 3 can produce ruthenium compounds with improved solubility with high purity and high efficiency compared to the methods according to Comparative Examples 1 to 3.

In addition, SEM images of the ruthenium compounds of Example 1 and Comparative Example 4 measured in Experimental Example 3 are shown in FIG. 3 .

Referring to FIG. 3 , it was confirmed that the method according to Example 1 can produce a ruthenium compound having a uniform particle size with high efficiency compared to the method according to Comparative Example 4.

Claims (12)

(a) preparing a first solution by dissolving ruthenium chloride (RuCl ₃ ) and ammonium chloride (NH ₄ Cl) in a solvent and then adding a reducing agent;
(b) injecting a precipitating agent into a solution obtained by filtering the first solution, and then precipitating and recovering an intermediate of the ruthenium compound;
(c) preparing a second solution by adding an oxidizing agent to the solution containing the recovered intermediate of the ruthenium compound;
(d) preparing a third solution by first filtering and second filtering after adding an impurity removing agent to the second solution;
(e) injecting a co-solvent into the third solution to precipitate a ruthenium compound; and
(f) drying the precipitated ruthenium compound by vacuum freezing at -120 to -10 ° C for 1 to 5 hours
Method for producing a ruthenium compound comprising a. According to claim 1,
Method for producing a ruthenium compound using ammonia water (NH ₃ ) having a concentration of 2 to 20 mM and a hydrogen ion concentration of pH 9 to 13 as a solvent in step (a). According to claim 1,
In step (a), ruthenium chloride and ammonium chloride are used in an equivalent ratio of ruthenium chloride: ammonium chloride = 1: 2 to 1: 3. According to claim 1,
In step (a), zinc (Zn) or hydrogen peroxide (H ₂ O ₂ ) is used as a reducing agent in an amount of 30 to 80% by weight based on 100% by weight of ruthenium chloride, and at a temperature of 60 to 95 ° C. in a nitrogen atmosphere. Method for producing a ruthenium compound that is introduced at a rate of 12 to 25 g / min. According to claim 1,
Method for producing a ruthenium compound using ammonium chloride (NH ₄ Cl) as a precipitant in step (b). According to claim 1,
In step (c), silver chloride (AgCl) having an average particle size of 100 to 500 is added as an oxidizing agent, and the reaction is performed at 15 to 35 ° C. for 0.5 to 2 hours. According to claim 1,
In the step (d), sodium carbonate (Na ₂ CO ₃ ) is added as an impurity removing agent in an amount of 0.05 to 1% by weight based on 100% by weight of the second solution. According to claim 1,
The method for producing a ruthenium compound wherein the secondary filtration in step (d) is performed using a filter having a pore size of 0.001 to 4.0 μm. According to claim 1,
In the step (e), hydrochloric acid (HCl) 1 to 3 times greater than the third solution was added as a co-solvent at a rate of 10 to 200 ml/min, and ethanol (EtOH) was added in an amount of 0.1 to 1 weight relative to the amount of hydrochloric acid added. Method for producing a ruthenium compound that is added in % content. delete A ruthenium compound prepared by the method of any one of claims 1 to 9. According to claim 11,
A ruthenium compound having a water solubility of 300 to 500 mM.

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