Improved method for preparing high-purity sodium nitroprusside dihydrate

Abstract

An improved method for preparing high-purity sodium nitroprusside dehydrate, which method comprising the following steps: 1, in a solvent, reacting potassium ferrocyanide or sodium ferrocyanide with nitric acid, then adding sodium carbonate or potassium carbonate thereto for a reaction, and then adding a water-soluble divalent copper salt or a water-soluble divalent zinc salt thereto for a reaction, so as to obtain copper nitroprusside or zinc nitroprusside; and 2, reacting the copper nitroprusside or the zinc nitroprusside with sodium bicarbonate, so as to obtain a crude sodium nitroprusside product, and purifying the crude sodium nitroprusside product, so as to obtain sodium nitroprusside dehydrate, wherein in step 2, after the reaction with sodium bicarbonate, citric acid is added to adjust the pH to 5-7. The process is high in terms of product yield and purity, simple in terms of reaction and post-treatment conditions, high in terms of operability, and very suitable for scale-up production.

Description

An improved method for preparing high-purity sodium nitrosoferricyanide dihydrate Technical Field

[0001] The invention belongs to the technical field of chemical drug synthesis, and particularly relates to a method for preparing an improved high-purity sodium nitrosoferricyanide dihydrate. Background Art

[0002] The common name of sodium nitroprusside is sodium nitroprusside, CAS number: 13755-38-9, English name: Sodium Nitroprusside, molecular formula: C5FeN6Na2O·2H2O, molecular weight: 297.95, and its structure is as follows:

[0003] Sodium nitroprusside is a fast-acting, short-acting vasodilator used clinically for emergency blood pressure reduction in hypertensive emergencies such as hypertensive crisis, hypertensive encephalopathy, malignant hypertension, and paroxysmal hypertension before and after pheochromocytoma surgery. It is also used for controlled blood pressure reduction during surgical anesthesia. It is also used for acute heart failure, including acute pulmonary edema, acute myocardial infarction, or acute heart failure associated with mitral or aortic valve regurgitation. It is widely used clinically. Sodium nitroprusside has an extremely short half-life and is administered via continuous intravenous infusion. The effect is almost immediate and can last up to 10 minutes.

[0004] To ensure the safety of clinical medication, pharmacopoeias have set limits on the content of sodium nitroprusside. The 2020 edition of the Chinese Pharmacopoeia stipulates that, calculated on a dry basis, the content of Na2Fe(CN)5NO must not be less than 99.0%. The United States Pharmacopoeia USP43 and the European Pharmacopoeia EP11.0 stipulate that the content of ferrocyanide and ferrocyanide is less than 0.02%. Because sodium nitroprusside is not very stable in aqueous solution, the purity of sodium nitroprusside prepared by existing published literature methods is difficult to meet the requirements of domestic and international pharmacopoeias. Therefore, it is necessary to develop a method for preparing high-purity sodium nitroprusside to address the problem of low purity of sodium nitroprusside prepared by existing technologies.

[0005] Early literature, such as Journal of American Chemical Society, 1897, 19(1):23-24 and Z Anorg Allg Chem., 2001(627):1663-1668 and the method commonly used in the industry is: potassium ferrocyanide and concentrated nitric acid are reacted to obtain hydrogen nitroprusside, which is then neutralized with sodium carbonate and refined with water and ethanol. The reaction formula is as follows: K4[Fe(CN)6]+6HNO3→H2[Fe(CN)5(NO)]+CO2+NH4NO3+4KNO3 H2[Fe(CN)5(NO)]+Na2CO3→Na2[Fe(CN)5(NO)]+CO2+H2O.

[0006] Since a large amount of potassium nitrate, ammonium nitrate, and sodium nitrate by-products are produced during the reaction, a cumbersome desalination process is required, resulting in a low yield (15-25%) and low purity (about 97%), making it unsuitable for industrial production. There are currently patents in China that use a method for generating water-insoluble copper nitroprusside for purification and desalination. For example, the patent application with publication number CN103159233A uses potassium nitrosoferricyanide and copper sulfate pentahydrate as reaction raw materials to react under suitable conditions to generate copper nitrosoferricyanide, which then reacts with sodium bicarbonate to generate sodium nitroprusside. The reaction formula is as follows: K2[Fe(CN)5(NO)]+CuSO4→Cu[Fe(CN)5(NO)]+K2SO4 Cu[Fe(CN)5(NO)]+2NaHCO3→Na2[Fe(CN)5(NO)]+CuCO3+CO2+H2O

[0007] The raw material potassium nitroprusside of this method is expensive and difficult to purchase, making it unsuitable for industrial production. In addition, the purity of the prepared sodium nitroprusside is only 96%, which does not meet the requirements of the Chinese Pharmacopoeia.

[0008] Patent application publication number CN110342541A describes the reaction of potassium ferrocyanide and nitric acid to produce hydrogen nitroprusside, which then reacts with copper sulfate pentahydrate to produce copper nitroprusside, which then reacts with sodium bicarbonate to produce sodium nitroprusside. The reaction equations are as follows: K4[Fe(CN)6]+6HNO3→H2[Fe(CN)5(NO)]+CO2+NH4NO3+4KNO3 H2[Fe(CN)5(NO)]+CuSO4→Cu[Fe(CN)5(NO)]+H2SO4 Cu[Fe(CN)5(NO)]+2NaHCO3→Na2[Fe(CN)5(NO)]+CuCO3+CO2+H2O

[0009] This method is simple, and the copper nitroprusside precipitate produced in the second step effectively removes the inorganic salt impurities produced in the first step. However, the second step produces a large amount of sulfuric acid as a byproduct, which is not only environmentally friendly but also potentially produces highly toxic hydrocyanic acid. The resulting sodium nitroprusside contains unreacted sodium bicarbonate, which is difficult to remove, resulting in a sodium nitroprusside content below the Chinese Pharmacopoeia requirement. The inventors conducted multiple experiments on this patented method and consistently measured sodium nitroprusside contents of less than 99.0%, which is inconsistent with the contents reported in the examples.

[0010] Patent application publication number CN114477231A also reports a similar synthesis method. However, the method differs in that glacial acetic acid is added after sodium bicarbonate is added to adjust the pH to 5-7, and then anhydrous ethanol is added to further purify and precipitate sodium nitroprusside. Although this method removes excess sodium bicarbonate by neutralization with glacial acetic acid, it produces more sodium acetate during scale-up production. Since sodium acetate is slightly soluble in ethanol at room temperature, it is difficult to remove it completely during actual operation. The inventors have conducted multiple experiments on this patented method and found that the actual yield was less than 50%, and the quality did not meet the requirements of the Chinese Pharmacopoeia (purity of about 99.0%).

[0011] The above-mentioned disclosed methods have the following problems: low sodium nitroprusside yield, low product purity, complex process, and low economic efficiency. Therefore, it is necessary to improve the current preparation method to be suitable for large-scale production to obtain high-purity sodium nitroprusside.

[0012] Summary of the Invention

[0013] The present invention aims to provide an improved method for preparing high-purity sodium nitroferricyanide dihydrate. The sodium nitroferricyanide dihydrate (sodium nitroprusside) prepared by the present invention has a purity of over 99.9%, a content that meets the requirements of the pharmacopoeia, and a simple preparation process, low pollution, and low production cost, making it suitable for industrial production.

[0014] The present invention provides a method for preparing sodium nitrosoferricyanide dihydrate, which comprises the following steps:

[0015] Step 1: In a solvent, potassium ferrocyanide or sodium ferrocyanide reacts with nitric acid, then sodium carbonate or potassium carbonate is added to react, and then a water-soluble divalent copper salt or a water-soluble divalent zinc salt is added to react to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide;

[0016] Step 2: copper nitrosoferricyanide or zinc nitrosoferricyanide reacts with sodium bicarbonate in a solvent to obtain a crude sodium nitrosoferricyanide product, and the crude sodium nitrosoferricyanide product is purified to obtain sodium nitrosoferricyanide dihydrate;

[0017] In step 2, after the reaction with sodium bicarbonate, citric acid is added to adjust the pH to 5-7.

[0018] Furthermore, step 1 includes the following steps:

[0019] (1) Potassium ferrocyanide or sodium ferrocyanide is dissolved in a solvent and nitric acid is added to react;

[0020] (2) adding sodium carbonate or potassium carbonate to the reaction product of step (1), adjusting the pH to 5.5-7.5, stirring for 1-2 hours, and filtering;

[0021] (3) adding a water-soluble divalent copper salt or a water-soluble divalent zinc salt to the filtrate obtained in step (2), mixing the mixture, and reacting to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide.

[0022] Furthermore, in step (1), the mass ratio of the potassium ferrocyanide or sodium ferrocyanide to the solvent is 1:1 to 10;

[0023] And / or, in step (1), the molar ratio of potassium ferrocyanide or sodium ferrocyanide to nitric acid is 1:5-10;

[0024] And / or, in step (3), the molar ratio of the water-soluble divalent copper salt or water-soluble divalent zinc salt to potassium ferrocyanide or sodium ferrocyanide is 1:1-5.

[0025] Furthermore, in step (1), the mass ratio of the potassium ferrocyanide or sodium ferrocyanide to the solvent is 1:1.5-3.0;

[0026] And / or, in step (1), the molar ratio of potassium ferrocyanide or sodium ferrocyanide to nitric acid is 1:6-8;

[0027] And / or, in step (3), the molar ratio of the water-soluble divalent copper salt or water-soluble divalent zinc salt to potassium ferrocyanide is 1:1 to 1.1.

[0028] Furthermore, in step (1), the solvent is water;

[0029] And / or, in step (1), the temperature when adding nitric acid is 60-80°C;

[0030] And / or, in step (1), the nitric acid is concentrated nitric acid;

[0031] And / or, in step (1), the reaction temperature is 60-80° C., and the reaction time is 1-10 h;

[0032] And / or, in step (3), the water-soluble divalent copper salt or water-soluble divalent zinc salt is anhydrous or crystalline water-containing copper sulfate, copper chloride, zinc sulfate, zinc chloride, copper acetate, or zinc acetate;

[0033] And / or, in step (3), the reaction is carried out at 20-80° C. for 1-5 hours;

[0034] And / or, in step (3), the reaction is followed by centrifugation, water washing, and drying to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide.

[0035] Furthermore, in step (3), the water-soluble divalent copper salt or water-soluble divalent zinc salt is anhydrous copper sulfate, copper chloride, or zinc sulfate with crystal water;

[0036] And / or, in step (3), the reaction is carried out at 10-30° C. for 1-5 hours.

[0037] Furthermore, step 2 includes the following steps:

[0038] 1) Dissolve copper nitrosoferrocyanide or zinc nitrosoferrocyanide in a solvent, add sodium bicarbonate to a pH of 6.5-7.5, add citric acid after the reaction to adjust the pH to 5-7, distill to dryness under reduced pressure in the dark, dissolve the residue in an alcohol solution, and evaporate the filtrate to dryness under reduced pressure to obtain crude sodium nitrosoferrocyanide;

[0039] 2) Dissolve the crude sodium nitrosoferricyanide in a solvent, add anhydrous ethanol to the filtrate, cool and crystallize, wash the resulting crystals, and dry to obtain purified sodium nitrosoferricyanide dihydrate.

[0040] Furthermore, in step 1), the mass ratio of the copper nitrosoferrocyanide or zinc nitrosoferrocyanide to the solvent is 1:2 to 10;

[0041] And / or, in step 2), the mass ratio of the crude sodium nitroferricyanide to the solvent is 1:2 to 10;

[0042] And / or, in step 2), the mass ratio of the crude sodium nitroferricyanide to anhydrous ethanol is 1:2-10.

[0043] Further, in step 1), the solvent is water;

[0044] And / or, in step 1), the temperature of adding sodium bicarbonate is 30-50°C;

[0045] And / or, in step 1), the sodium bicarbonate is a saturated sodium bicarbonate solution;

[0046] And / or, in step 1), the reaction temperature is 30-50° C., and the reaction time is 1-4 h;

[0047] And / or, in step 1), the alcohol solution is a methanol solution, an ethanol solution, or an isopropanol solution;

[0048] And / or, in step 2), the solvent is water;

[0049] And / or, in step 2), the temperature of the cooling and crystallization is lowered to 0-10° C., and the crystallization is stirred for 0.5-10 hours.

[0050] Furthermore, in step 1), the concentration of the alcohol solution is 95% to 100% when it is a methanol solution, 60% to 80% when it is an ethanol solution, and 40% to 60% when it is an isopropanol solution;

[0051] And / or, in step 2), the temperature of the cooling and crystallization is lowered to 0-10° C., and the crystallization is stirred for 3-5 hours.

[0052] Compared with the prior art, the advantages of the present invention are:

[0053] (1) The inorganic salts produced in the first step of the reaction can be effectively removed by obtaining zinc nitroprusside or copper nitroprusside; in comparison, zinc nitroprusside centrifugation is easier than copper nitroprusside and easier to operate;

[0054] (2) Citric acid is used instead of glacial acetic acid to neutralize sodium bicarbonate. Since citric acid is insoluble in alcohol, the crude sodium nitroprusside can be dissolved in an alcohol solution and then filtered to remove the citrate to achieve product desalination and purification.

[0055] (3) After adjusting the pH value with citric acid, vacuum distillation was performed in the dark. No significant changes were found in the detection of related substances in the solution before and after distillation. This operation can effectively avoid the risk of high-temperature degradation of the product during the distillation process, which is a key measure for the preparation of high-purity sodium nitroprusside.

[0056] The present invention provides an improved method for preparing high-purity sodium nitrosoferricyanide dihydrate. The sodium nitrosoferricyanide dihydrate obtained by the preparation method has a purity greater than 99.9% and a content greater than 99.0% (based on the dry product). Other indicators meet the requirements of the relevant pharmacopoeias and can be used as a raw material drug. The process product of the present invention has a high yield and high purity, and the reaction and post-treatment conditions are simple and highly operable, making it very suitable for process scale-up production.

[0057] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0058] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. DETAILED DESCRIPTION

[0059] The raw materials and equipment used in the specific embodiments of the present invention are all known products and are obtained by purchasing commercial products.

[0060] In the present invention, unless otherwise specified, a solution is an aqueous solution.

[0061] In the present invention, room temperature refers to 10 to 30°C.

[0062] The reaction principle of the present invention is as follows:

[0063] Example 1: Preparation method of high-purity sodium nitrosoferricyanide dihydrate of the present invention

[0064] Step 1: Add 8 kg (18.94 mol) of potassium ferrocyanide trihydrate and 8 kg of distilled water to a 50 L glass reactor, heat to dissolve, slowly add 12 kg (113.64 mol) of concentrated nitric acid at 70°C with stirring, and react at 70°C for 6 hours. Monitor the reaction progress with ferrous sulfate test solution (the reaction is complete when a gray-green precipitate is formed but no blue precipitate is formed). After the reaction is complete, cool to room temperature, add 4 kg of anhydrous sodium carbonate, adjust the pH to 6.5-7.5, continue stirring for 1-2 hours, and filter. The filtrate is placed in a 50 L glass reactor, and a pre-prepared copper sulfate solution (19 mol of copper sulfate) is added dropwise at room temperature. After the addition is complete, incubate for 2 hours, centrifuge, rinse with water, and air-dry at 60°C for 6 hours to obtain copper nitrosoferrocyanide in a yield of 86%.

[0065] Step 2: Copper nitrosoferrocyanide and 2 times its weight of water were added to a 50-liter glass reactor and heated to 40°C. Saturated sodium bicarbonate solution was added dropwise with stirring until the pH was 6.5-7.5. The mixture was kept warm for 2 hours, washed with water by centrifugation, and the pH was adjusted to 6.0 by adding citric acid. The mixture was distilled to dryness under reduced pressure at 65°C in the dark. 60-80% (v / v) ethanol aqueous solution was added to the residue for dissolution. Insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure to obtain crude sodium nitrosoferrocyanide in a yield of 70%. The crude product was mixed with 2 times its weight of water, heated to dissolve, and a small amount of insoluble matter was removed by filtration. Then, 2 times its weight of anhydrous ethanol was added to the filtrate, and the temperature was lowered to 0-10°C, stirred and crystallized for 4 hours, centrifuged, rinsed with anhydrous ethanol, and vacuum dried at 45°C for 4 hours to obtain sodium nitrosoferricyanide dihydrate (sodium nitroprusside) with a yield of 75%, a purity of 99.97%, a content of 99.7%, and a drying loss of 11.86%. HPLC analysis of related substances showed that ferricyanide was not detected and ferrocyanide was 0.012%.

[0066] Example 2: Preparation method of high-purity sodium nitrosoferricyanide dihydrate of the present invention

[0067] Step 1: Add 8 kg (18.94 mol) of potassium ferrocyanide trihydrate and 8 kg of distilled water to a 50 L glass reactor, heat to dissolve, slowly add 12 kg (113.64 mol) of concentrated nitric acid at 70°C with stirring, and allow to react at 70°C for 6 hours. Monitor the reaction progress with ferrous sulfate test solution (the reaction is complete when a gray-green precipitate is formed but no blue precipitate is formed). After the reaction is complete, cool to room temperature, add 4 kg of anhydrous sodium carbonate, adjust the pH to 6.5-7.5, continue stirring for 1-2 hours, and filter. Place the filtrate in a 50 L glass reactor, and add the pre-prepared zinc sulfate solution (19 mol of zinc sulfate) dropwise at room temperature. Incubate for 2 hours, centrifuge, rinse with water, and air-dry at 60°C for 6 hours to obtain zinc nitrosoferrocyanide in an 80% yield.

[0068] Step 2: Zinc nitrosoferricyanide and 2 times its weight of water were added to a 50-liter glass reactor and heated to 40°C. Saturated sodium bicarbonate solution was added dropwise with stirring until the pH was 6.5-7.5. The mixture was kept warm for 2 hours, washed with water by centrifugation, and the pH was adjusted to 6.0 by adding citric acid. The mixture was distilled to dryness under reduced pressure at 65°C in the dark. A 40-60% (v / v) isopropanol aqueous solution was added to the residue to dissolve it. The insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure to obtain crude sodium nitrosoferricyanide in a yield of 81%. The crude product was mixed with 2 times its weight of water, heated to dissolve, and a small amount of insoluble matter was removed by filtration. Then, 4 times its weight of anhydrous ethanol was added to the filtrate, and the temperature was lowered to 0-10°C, stirred and crystallized for 4 hours, centrifuged, rinsed with anhydrous ethanol, and vacuum dried at 45°C for 4 hours to obtain sodium nitrosoferricyanide dihydrate (sodium nitroprusside) with a yield of 84%, a purity of 99.97%, a content of 99.8%, and a drying loss of 11.88%. Related substances determined by HPLC were: 0.003% ferrocyanide and 0.013% ferrocyanide.

[0069] Example 3: Preparation method of high-purity sodium nitrosoferricyanide dihydrate of the present invention

[0070] Step 1: Add 8 kg (18.94 mol) of potassium ferrocyanide trihydrate and 8 kg of distilled water to a 50 L glass reactor, heat to dissolve, slowly add 12 kg (113.64 mol) of concentrated nitric acid at 70°C with stirring, and react at 70°C for 6 hours. Monitor the reaction progress with ferrous sulfate test solution (the reaction is complete when a gray-green precipitate is formed but no blue precipitate is formed). After the reaction is complete, cool to room temperature, add 4 kg of anhydrous sodium carbonate, adjust the pH to 6.5-7.5, continue stirring for 1-2 hours, and filter. Place the filtrate in a 50 L glass reactor, and add the pre-prepared copper chloride solution (19 mol of copper chloride) dropwise at room temperature. After the addition is complete, incubate for 2 hours, centrifuge, rinse with water, and air-dry at 60°C for 6 hours to obtain copper nitrosoferrocyanide in a yield of 83%.

[0071] Step 2: Copper nitrosoferrocyanide and 2 times its weight of water were added to a 50-liter glass reactor and heated to 40°C. Saturated sodium bicarbonate solution was added dropwise with stirring until the pH was 6.5-7.5. The mixture was kept warm for 2 hours, washed with water by centrifugation, and the pH was adjusted to 6.0 by adding citric acid. The mixture was distilled to dryness under reduced pressure at 65°C in the dark. Anhydrous methanol or 95% methanol solution was added to the residue for dissolution. Insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure to obtain crude sodium nitrosoferrocyanide in a yield of 76%. The crude product was mixed with 2 times its weight of water, heated to dissolve, and a small amount of insoluble matter was removed by filtration. Then, 6 times its weight of anhydrous ethanol was added to the filtrate, and the temperature was lowered to 0-10°C, stirred and crystallized for 4 hours, centrifuged, rinsed with anhydrous ethanol, and vacuum dried at 45°C for 4 hours to obtain sodium nitrosoferricyanide dihydrate (sodium nitroprusside) with a yield of 87%, a purity of 99.96%, a content of 99.6%, and a drying loss of 12.0%. Related substances determined by HPLC were: 0.008% ferrocyanide and 0.018% ferrocyanide.

[0072] Example 4: Adjusting pH with acetic acid

[0073] Step 1: Add 8 kg (18.94 mol) of potassium ferrocyanide trihydrate and 8 kg of distilled water to a 50 L glass reactor, heat to dissolve, slowly add 12 kg (113.64 mol) of concentrated nitric acid at 70°C with stirring, and react at 70°C for 6 hours. Monitor the reaction progress with ferrous sulfate test solution (the reaction is complete when a gray-green precipitate is formed but no blue precipitate is formed). After the reaction is complete, cool to room temperature, add 4 kg of anhydrous sodium carbonate, adjust the pH to 6.5-7.5, continue stirring for 1-2 hours, and filter. The filtrate is placed in a 50 L glass reactor, and a pre-prepared copper sulfate solution (19 mol of copper sulfate) is added dropwise at room temperature. After the addition is complete, heat to 70°C and react for 3 hours. After centrifugation, rinse with water, and air-dry at 60°C for 6 hours to obtain copper nitrosoferrocyanide in a yield of 87%.

[0074] Step 2: Copper nitrosoferrocyanide and 2 times its weight of water were added to a 50-liter glass reactor and heated to 40°C. Saturated sodium bicarbonate solution was added dropwise with stirring until the pH was 6.5-7.5. The mixture was kept warm for 2 hours, washed with water by centrifugation, and the pH was adjusted to 6.0 by adding glacial acetic acid. The mixture was distilled to dryness under reduced pressure at 65°C in the dark. Anhydrous methanol or 95% methanol solution was added to the residue to dissolve it. The insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure to obtain crude sodium nitrosoferrocyanide. The crude product is mixed with 2 times its weight of water, heated to dissolve, filtered to remove a small amount of insoluble matter, and then 6 times its weight of anhydrous ethanol is added to the filtrate. The mixture is cooled to 0-10°C, stirred and crystallized for 4 hours, centrifuged, rinsed with anhydrous ethanol, and vacuum dried at 45°C for 4 hours to obtain sodium nitroprusside dihydrate (sodium nitroprusside). The product is lighter in color and contains obvious white salt. The yield is 71%, the purity is 99.45%, the content is 97.8%, the drying loss is 11.67%, and the related substances measured by HPLC are: 0.12% ferricyanide and 0.34% ferrocyanide. The sodium nitroprusside prepared by this method has a low yield, low purity, and high content of related substances, which does not meet the requirements of the pharmacopoeia.

[0075] In summary, the present invention provides an improved method for preparing high-purity sodium nitrosoferricyanide dihydrate. The sodium nitrosoferricyanide dihydrate obtained by the preparation method of the present invention has a purity greater than 99.9% and a content greater than 99.0% (on a dry basis). Other indicators meet the requirements of the relevant pharmacopoeias and can be used as a bulk drug. The process product of the present invention has high yield and purity, simple reaction and post-treatment conditions, and strong operability, making it very suitable for process scale-up production.

Claims

1. A method for preparing sodium nitrosoferricyanide dihydrate, characterized in that: It includes the following steps: Step 1: In a solvent, potassium ferrocyanide or sodium ferrocyanide reacts with nitric acid, then sodium carbonate or potassium carbonate is added to react, and then a water-soluble divalent copper salt or a water-soluble divalent zinc salt is added to react to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide; Step 2: In a solvent, copper nitrosoferrocyanide or zinc nitrosoferrocyanide reacts with sodium bicarbonate to obtain a crude sodium nitrosoferrocyanide product, and the crude sodium nitrosoferrocyanide product is purified to obtain sodium nitrosoferrocyanide dihydrate; In step 2, after the reaction with sodium bicarbonate, citric acid is added to adjust the pH to 5-7.

2. The preparation method according to claim 1, characterized in that: Step 1 includes the following steps: (1) Potassium ferrocyanide or sodium ferrocyanide is dissolved in a solvent and nitric acid is added to react; (2) adding sodium carbonate or potassium carbonate to the reaction product of step (1), adjusting the pH value to 5.5 to 7.5, stirring for 1 to 2 hours, and filtering; (3) adding a water-soluble divalent copper salt or a water-soluble divalent zinc salt to the filtrate obtained in step (2), and mixing the mixture to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide.

3. The preparation method according to claim 2, characterized in that: In step (1), the mass ratio of the potassium ferrocyanide or sodium ferrocyanide to the solvent is 1:1 to 10; And / or, in step (1), the molar ratio of potassium ferrocyanide or sodium ferrocyanide to nitric acid is 1:5-10; And / or, in step (3), the molar ratio of the water-soluble divalent copper salt or water-soluble divalent zinc salt to potassium ferrocyanide or sodium ferrocyanide is 1:1-5.

4. The preparation method according to claim 3, characterized in that: In step (1), the mass ratio of the potassium ferrocyanide or sodium ferrocyanide to the solvent is 1:1.5-3.0; And / or, in step (1), the molar ratio of potassium ferrocyanide or sodium ferrocyanide to nitric acid is 1:6-8; And / or, in step (3), the molar ratio of the water-soluble divalent copper salt or the water-soluble divalent zinc salt to potassium ferrocyanide is 1:1 to 1.

1.

5. The preparation method according to any one of claims 2 to 4, characterized in that: In step (1), the solvent is water; And / or, in step (1), the temperature when adding nitric acid is 60-80° C.; And / or, in step (1), the nitric acid is concentrated nitric acid; And / or, in step (1), the reaction temperature is 60-80° C., and the reaction time is 1-10 h; And / or, in step (3), the water-soluble divalent copper salt or water-soluble divalent zinc salt is anhydrous Or copper sulfate, copper chloride, zinc sulfate, zinc chloride, copper acetate, zinc acetate with crystal water; And / or, in step (3), the reaction is carried out at 20-80° C. for 1-5 hours; And / or, in step (3), the reaction is followed by centrifugation, water washing and drying to obtain copper nitrosoferrocyanide or zinc nitrosoferrocyanide.

6. The preparation method according to claim 5, characterized in that: In step (3), the water-soluble divalent copper salt or water-soluble divalent zinc salt is anhydrous copper sulfate, copper chloride or zinc sulfate with crystal water; And / or, in step (3), the reaction is carried out at 10-30° C. for 1-5 hours.

7. The preparation method according to claim 1, characterized in that: Step 2 includes the following steps: 1) Dissolve copper nitrosoferrocyanide or zinc nitrosoferrocyanide in a solvent, add sodium bicarbonate to a pH of 6.5 to 7.5, add citric acid to adjust the pH to 5 to 7 after the reaction, distill to dryness under reduced pressure in the dark, dissolve the residue in an alcohol solution, and evaporate the filtrate to dryness under reduced pressure to obtain crude sodium nitrosoferrocyanide; 2) Dissolve the crude sodium nitrosoferrocyanide in a solvent, add anhydrous ethanol to the filtrate, cool and crystallize, wash the obtained crystals, and dry to obtain purified sodium nitrosoferrocyanide dihydrate.

8. The preparation method according to claim 7, characterized in that: In step 1), the mass ratio of the copper nitrosoferrocyanide or zinc nitrosoferrocyanide to the solvent is 1:2 to 10; And / or, in step 2), the mass ratio of the crude sodium nitroferrocyanide to the solvent is 1:2-10; And / or, in step 2), the mass ratio of the crude sodium nitroferrocyanide to anhydrous ethanol is 1:2-10.

9. The preparation method according to claim 7 or 8, characterized in that: In step 1), the solvent is water; And / or, in step 1), the temperature of adding sodium bicarbonate is 30-50°C; And / or, in step 1), the sodium bicarbonate is a saturated sodium bicarbonate solution; And / or, in step 1), the reaction temperature is 30-50° C., and the reaction time is 1-4 h; And / or, in step 1), the alcohol solution is a methanol solution, an ethanol solution, or an isopropanol solution; And / or, in step 2), the solvent is water; And / or, in step 2), the temperature of the cooling and crystallization is lowered to 0-10° C., and the crystallization is stirred for 0.5-10 hours.

10. The preparation method according to claim 9, characterized in that: In step 1), when the alcohol solution is a methanol solution, the concentration is 95% to 100%, when the alcohol solution is an ethanol solution, the concentration is 60% to 80%, and when the alcohol solution is an isopropanol solution, the concentration is 40% to 60%; And / or, in step 2), the temperature of the cooling and crystallization is lowered to 0-10° C., and the crystallization is stirred for 3-5 hours.

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