Efficient preparation method of ruthenium red

Abstract

The invention relates to an efficient preparation method of ruthenium red, and belongs to the technical field of synthesis of precious metal compounds. The method comprises the following steps: adding trichloro hexammine ruthenium into an ammonia water solution, stirring and dissolving to obtain a ruthenium solution; oxygen or air is introduced into the ruthenium solution, stirring reflux reaction is carried out for 6-8 hours at the temperature of 50-80 DEG C, and a ruthenium red solution is obtained; the ruthenium red solution is subjected to negative pressure concentration at the temperature of 60-80 DEG C until the volume is 25-35% of the original volume, cooling crystallization and solid-liquid separation are conducted, solids are washed with deionized water, ethyl alcohol and diethyl ether in sequence, vacuum drying is conducted, and the high-purity ruthenium red crystals are obtained. Trichloro hexammine ruthenium (Ru (III) (NH3) 6Cl3) is used as a raw material, the valence state of ruthenium is + 3, and a reducing agent is not needed, so that not only is the use of reagents reduced, but also side reactions caused by ruthenium in other valence states can be avoided, and the product purity is improved.

Description

Technical Field

[0001] The invention relates to a high-efficiency preparation method of ruthenium red, belonging to the technical field of precious metal compound synthesis. Background Art

[0002] Ruthenium Red is a mixed valence ruthenium complex with a trinuclear linear structure. Its molecular formula is [(NH3)5RuORu(NH3)4ORu(NH3)5]Cl6. The structure of its cation part is [(NH3)5Ru III -O-(NH3)4Ru IV -O-Ru III (NH3)5(NH3)5] 6+ . Ruthenium red solution is deep red and has unique polycationic properties. In electron microscopy, ruthenium red can specifically bind to high-charge-density polyanions such as cell wall pectin and acidic mucopolysaccharides, making it a key reagent for observing cell ultrastructure. In the biomedical field, nanomolar concentrations of ruthenium red can inhibit Ca²⁺ uptake driven by mitochondrial respiration and block Ca²⁺ transport in the sarcoplasmic reticulum, endoplasmic reticulum and voltage-dependent calcium channels, making it a calcium ion (Ca²⁺) channel blocker. In the field of catalysis, ruthenium red, as a redox catalyst, has shown potential in water oxidation to produce oxygen, chloride ion oxidation and organic substrate conversion.

[0003] However, the current synthesis of ruthenium red primarily relies on the reduction of ruthenium trichloride (RuCl3) and the coordination rearrangement reaction of the central ruthenium ion with ammonia, oxygen, or chlorine. The steps include: 1) Reduction: Using ethanol as a reducing agent, ruthenium of varying valence states in RuCl3 is reduced; 2) Coordination: Reaction with excess ammonia in an air environment at 90°C to form a complex compound of ruthenium coordinated with ammonia, chlorine, and oxygen; 3) Post-treatment: The product is obtained through multiple recrystallizations and chromatographic column separation and purification. This method is a classic process for the synthesis of ruthenium red, but it suffers from uncontrollable valence states of ruthenium in the raw materials, leading to uncontrollable side reactions and reduced purity of the target product. Extensive research and practical applications have confirmed that ruthenium in commercially available RuCl3 coexists in various valence states, including +2, +3, +4, and +6. During the ethanol reduction process, the +4 valent ruthenium in the RuCl3 solution is difficult to exist stably, and some +3 valent ruthenium is excessively reduced to +2 valent, causing the valence distribution of ruthenium species in the reaction system to deviate from the valence distribution required for the synthesis of ruthenium red, triggering a variety of side reactions. Among them, the oxygen-bridged ruthenium dimer generated by the side reaction has a negative effect on mitochondrial Ca 2+The inhibitory activity of uptake is even higher than that of ruthenium red itself. In addition, due to the large variety of by-products and similar chemical properties, the existing process needs to rely on multiple recrystallization, chromatographic column purification and other steps for purification, and the final yield is only 10%-20%, resulting in high cost and difficulty in scalability of the ruthenium red synthesis process. The impurities remaining in the current commercial ruthenium red not only reduce its optical properties as a dye, but also cause non-specific effects in biomedical applications. For example, the by-product oxygen-bridged ruthenium dimer has an inhibitory strength on calcium ion uniporter receptor protein that is several times that of ruthenium red, which may interfere with the accuracy of experimental results.

[0004] The low efficiency (yield <20%), high impurity content and high purification cost of existing preparation technologies have seriously hindered its transformation from laboratory to industrial production. Summary of the Invention

[0005] In view of the problems in existing ruthenium red synthesis methods, such as low ruthenium red yield, difficulty in purification and unstable product purity due to the variable ruthenium valence state in the raw material ruthenium trichloride, the present invention proposes an efficient preparation method of ruthenium red, using trichlorohexaammineruthenium (Ru(III)(NH3)6Cl3) as the raw material. The ruthenium valence state is +3 and no reducing agent is required. This not only reduces the use of reagents, but also avoids side reactions caused by ruthenium in other valence states, thereby improving product purity.

[0006] An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding trichlorohexammineruthenium to an aqueous ammonia solution and stirring to dissolve the mixture to obtain a ruthenium solution; (2) Oxygen or air is introduced into the ruthenium solution, and the mixture is stirred and refluxed at a temperature of 50-80°C for 6-8 hours (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution is concentrated under negative pressure at a temperature of 60-80°C to 25-35% of the original volume, cooled for crystallization, and solid-liquid separation is performed. The solid is washed with deionized water, ethanol, and ether in sequence, and vacuum dried to obtain high-purity ruthenium red crystals.

[0007] Preferably, the mass concentration of the ammonia solution in step (1) is 10-25%, and the liquid-to-solid ratio of the ammonia solution to trichlorohexammineruthenium (mL:g) is 20-60:1.

[0008] Preferably, the gas flow rate of oxygen or air in step (2) is 3 to 4 bubbles per second. If the gas flow rate is too large, ammonia may be lost and hydroxides that are insoluble in water may be generated.

[0009] Preferably, the negative pressure concentration method in step (3) is rotary evaporation concentration.

[0010] Preferably, the vacuum drying temperature in step (3) is 90-120°C so that the ruthenium red crystals are anhydrates. When the temperature is lower than 90°C, the ruthenium red crystals contain 1-4 crystalline waters.

[0011] The beneficial effects of the present invention are: (1) The present invention uses trichlorohexammineruthenium (Ru(III)(NH3)6Cl3) as a raw material. The valence state of ruthenium is +3, and no reducing agent is required. This not only reduces the use of reagents, but also avoids side reactions caused by ruthenium in other valence states, thereby improving product purity. (2) The yield of high-purity ruthenium red crystals of the present invention can reach 60-80%, and the purity is ≥98%; (3) The method of the present invention has simple process, strong operability, high yield, low preparation cost, and is easy to industrialize. It can solve the technical problems in the existing preparation process of ruthenium red, such as low yield of ruthenium red, difficulty in purification and unstable product purity due to the variable valence state of ruthenium in the raw material ruthenium trichloride. DETAILED DESCRIPTION

[0012] The present invention will be further described in detail below in conjunction with specific embodiments, but the protection scope of the present invention is not limited to the contents described above.

[0013] Example 1: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an aqueous ammonia solution having a mass concentration of 10%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the aqueous ammonia solution to ruthenium trichloride hexaamine is 60:1 in mL:g; (2) Oxygen is introduced into the ruthenium solution (the oxygen flow rate is controlled to be 3 bubbles per second), and the mixture is stirred and refluxed at 50°C for 6 hours (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 60°C to 35% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 90°C to obtain high-purity ruthenium red crystals. Testing showed that the yield of high-purity ruthenium red crystals in this example reached 60%. The ruthenium content in the ruthenium red crystals was analyzed to be 38.0% Ru, while the theoretical value was 38.5% Ru, with a purity of 98.7%. The solubility in water was tested to be 10 mg / ml, which was consistent with the properties of the target product, ruthenium red.

[0014] Example 2: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an aqueous ammonia solution having a mass concentration of 20%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the aqueous ammonia solution to ruthenium trichloride hexaamine is 30:1 in mL:g; (2) Air is introduced into the ruthenium solution (the air flow rate is controlled to be 4 bubbles per second), and the mixture is stirred and refluxed at 60°C for 7 h (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 60°C to 25% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 100°C to obtain high-purity ruthenium red crystals. Testing revealed that the yield of high-purity ruthenium red crystals in this example reached 60.1%. The ruthenium content in the ruthenium red crystals was analyzed to be 37.9% Ru, while the theoretical value was 38.5% Ru, resulting in a purity of 98.4%. The solubility in water was tested to be 10 mg / ml, consistent with the properties of the target product, ruthenium red.

[0015] Example 3: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an aqueous ammonia solution having a mass concentration of 15%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the aqueous ammonia solution to ruthenium trichloride hexaamine is 40:1 in mL:g; (2) Oxygen is introduced into the ruthenium solution (the oxygen flow rate is controlled to be 4 bubbles per second), and the mixture is stirred and refluxed at 80°C for 8 hours (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 70°C to 28% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 110°C to obtain high-purity ruthenium red crystals. Testing revealed that the yield of high-purity ruthenium red crystals in this example reached 72.7%. The ruthenium content in the ruthenium red crystals was analyzed to be 38.2% Ru, while the theoretical value was 38.5% Ru, resulting in a purity of 99.2%. The solubility in water was tested to be 10 mg / ml, consistent with the properties of the target product, ruthenium red.

[0016] Example 4: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an ammonia solution having a mass concentration of 25%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the ammonia solution to ruthenium trichloride hexaamine is 20:1 in mL:g; (2) Oxygen is introduced into the ruthenium solution (the oxygen flow rate is controlled to 4 bubbles per second), and the mixture is stirred and refluxed at 80°C for 6 hours (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 60°C to 30% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 100°C to obtain high-purity ruthenium red crystals. Testing showed that the yield of high-purity ruthenium red crystals in this example reached 80%. The ruthenium content in the ruthenium red crystals was analyzed to be 38.1% Ru, while the theoretical value was 38.5% Ru, with a purity of 99.0%. The solubility in water was tested to be 10 mg / ml, which was consistent with the properties of the target product, ruthenium red.

[0017] Example 5: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an aqueous ammonia solution having a mass concentration of 20%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the aqueous ammonia solution to ruthenium trichloride hexaamine is 50:1 in mL:g; (2) Oxygen is introduced into the ruthenium solution (the oxygen flow rate is controlled to be 4 bubbles per second), and the mixture is stirred and refluxed at 80°C for 8 hours (reflux reaction can prevent the loss of ammonia due to evaporation due to heat) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 80°C to 32% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 95°C to obtain high-purity ruthenium red crystals. Testing showed that the yield of high-purity ruthenium red crystals in this example reached 72%. The ruthenium content in the ruthenium red crystals was analyzed to be 37.9% Ru, while the theoretical value was 38.5% Ru, with a purity of 98.4%. The solubility in water was tested to be 10 mg / ml, which was consistent with the properties of the target product, ruthenium red.

[0018] Example 6: An efficient preparation method of ruthenium red, the specific steps are as follows: (1) adding ruthenium trichloride hexaamine to an aqueous ammonia solution having a mass concentration of 25%, stirring and dissolving the solution to obtain a ruthenium solution; wherein the liquid-to-solid ratio of the aqueous ammonia solution to ruthenium trichloride hexaamine is 45:1 in mL:g; (2) Oxygen is introduced into the ruthenium solution (the oxygen flow rate is controlled to be 3 bubbles per second), and the mixture is stirred and refluxed at 70°C for 6.5 hours (reflux reaction can prevent the loss of ammonia due to thermal evaporation) to obtain a ruthenium red solution; (3) The ruthenium red solution was concentrated under negative pressure at 65°C to 35% of the original volume, cooled for crystallization, and solid-liquid separation was performed. The solid was washed with deionized water, ethanol, and ether in sequence, and vacuum dried at 105°C to obtain high-purity ruthenium red crystals. Testing showed that the yield of high-purity ruthenium red crystals in this example reached 79.0%. The ruthenium content in the ruthenium red crystals was analyzed to be 38.1% Ru, while the theoretical value was 38.5% Ru, with a purity of 99.0%. The solubility in water was tested to be 10 mg / ml, which was consistent with the properties of the target product, ruthenium red.

[0019] The above describes the specific embodiments of the present invention in detail, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge of ordinary technicians in this field without departing from the scope of the present invention.

Claims

1. An efficient preparation method of ruthenium red, characterized in that: The specific steps are as follows: (1) adding trichlorohexammineruthenium to an aqueous ammonia solution and stirring to dissolve the mixture to obtain a ruthenium solution; (2) Oxygen or air is introduced into the ruthenium solution, and the mixture is stirred and refluxed at a temperature of 50-80°C for 6-8 hours to obtain a ruthenium red solution; (3) The ruthenium red solution is concentrated under negative pressure at a temperature of 60-80°C to 25-35% of the original volume, cooled for crystallization, and solid-liquid separation is performed. The solid is washed with deionized water, ethanol, and ether in sequence, and vacuum dried to obtain high-purity ruthenium red crystals.

2. The method for preparing ruthenium red according to claim 1, wherein: The mass concentration of the ammonia solution in step (1) is 10-25%, and the liquid-to-solid ratio of the ammonia solution to trichlorohexammineruthenium is 20-60:1 in mL:g.

3. The efficient preparation method of ruthenium red according to claim 1, characterized in that: In step (2), the flow rate of oxygen or air is 3-4 bubbles per second.

4. The efficient preparation method of ruthenium red according to claim 1, characterized in that: The method of negative pressure concentration in step (3) is rotary evaporation concentration.

5. The efficient preparation method of ruthenium red according to claim 1, characterized in that: The temperature of vacuum drying in step (3) is 90-120°C.