A kind of preparation method of sodium thiosulfate

Abstract

The invention discloses a method for preparing sodium thiosulfate, and relates to the technical field of pharmaceutical chemistry, including: using anhydrous sodium sulfite and sulfur powder, pharmaceutical excipients, as starting materials, heating reaction in water, and the reaction end point needs to meet the following conditions: 1) phenolphthalein indicator is colorless; 2) pH of the reaction solution is 5.8-7.0; the reaction solution is cooled and filtered, concentrated and crystallized to obtain a wet product of sodium thiosulfate pentahydrate, and the concentration end point is a concentrate density of 1.4 g / mL-1.5 g / mL; the wet product is dried to obtain sodium thiosulfate, and purified water is placed in a vacuum drying oven during the drying process to ensure that the ambient humidity is not less than 40%. Each step of this scheme has clear control parameters, the quality is controllable, and it is more conducive to industrial production. In the drying step, by placing an appropriate amount of purified water and maintaining a certain air humidity, the risk of crystal water volatilization caused by drying of the finished product is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical chemistry, and in particular to a method for preparing sodium thiosulfate. Background Art

[0002] Sodium thiosulfate is also known as baking soda, hyposulfite, and sodium hyposulfite. Its chemical formula is Na 2 S 2 O 3 .5H 2 O, colorless, transparent monoclinic crystal, odorless, its aqueous solution is weakly alkaline and has reducing properties, it decomposes and oxidizes into sodium sulfate and sodium sulfide after burning.

[0003] Sodium thiosulfate is an antidote and a sulfur donor. It has active sulfur atoms. Through sulfur transferase, it can combine with CN- in the body that is free or bound to methemoglobin, turning it into thiocyanate with low toxicity, which is excreted from the body with urine for detoxification. In the body tissues, sodium thiosulfate reacts chemically with cyanide with the participation of enzymes. Due to the combination of free CN- or CN- chemical groups bound to methemoglobin, it turns into thiocyanate with low toxicity, which is excreted from the body with urine for detoxification. Sodium thiosulfate reacts with arsenic and mercury compounds to form non-toxic sulfides, and reacts with iodides to form non-toxic new iodides for detoxification. Sodium thiosulfate is mainly used to rescue cyanide poisoning, and can also be used for bromine blue poisoning, as well as arsenic, mercury, lead, bismuth, iodine and other poisonings. It can also be used for anti-allergy and external treatment of tinea versicolor, scabies, pruritus, chronic urticaria, etc. In case of cyanide poisoning, nitrite compounds or methemoglobin generators such as methylene blue are used to produce enough methemoglobin in the body, and combine with free cyanide ions in the blood or cyanide ions bound to cytochrome oxidase to form cyanide methemoglobin, which restores the activity of cytochrome cyanase. However, cyanide methemoglobin can gradually release cyanide ions after a few minutes, causing the symptoms of poisoning to reappear. If sodium thiosulfate is given at the same time, it can combine with free or methemoglobin-bound cyanide ions in the body with the participation of thiotransferase to form non-toxic thiocyanate, which is excreted in the urine.

[0004] At present, many patents have been studied on the synthesis method of sodium thiosulfate, and the specific literature is as follows:

[0005] 1. CN1098805C uses alkaline wastewater reduced by sulfide alkali of aromatic nitro compounds as raw material, and obtains sodium thiosulfate by adding sulfur, oxidation, concentration, hot filtration, activated carbon decolorization, filtration, crystallization, and centrifugation. This process is complicated, the impurities in the raw materials are uncontrollable, the quality of the obtained product is unstable, and the risk of using it as a raw material is high.

[0006] 2. In CN105523525A, sodium hydroxide is used as the raw material, and sodium thiosulfate is obtained through secondary sulfur addition oxidation, crystallization, recrystallization, washing, and drying. This process uses sodium hydroxide to react at 80°C to 90°C. The strong alkali and high temperature cause great corrosion to the equipment. In addition, sulfur dioxide is used in the process, which is extremely unfriendly to personnel and the environment and is not suitable for large-scale production.

[0007] 3. CN106430114 A reported a method of adding water to a slag material containing elemental sulfur, stirring, washing, filtering and separating to obtain a filter cake A, adding sodium sulfite and water to the filter cake A, heating and stirring the mixed material for leaching; then filtering and washing to obtain a filtrate B containing precious metals; evaporating the filtrate B, cooling and crystallizing, overflowing, filtering and separating, and drying to obtain sodium thiosulfate pentahydrate. This scheme effectively recovers valuable elements and obtains two products, sodium thiosulfate pentahydrate and sodium sulfate, but the product prepared using the recycled slag as raw material has unstable quality and cannot be used as a raw material.

[0008] 4. CN116062708A reports a method for preparing sodium thiosulfate: taking each substance according to the molar ratio of sulfur, anhydrous sodium sulfite and water of 1:0.95-1.05:5-10, adding it to a stirred reactor for reaction, controlling the reaction temperature to 100°C-120°C, cooling the resulting liquid after the reaction, and obtaining sodium thiosulfate crystals. This scheme does not involve the purification of the product, the control of crystal water, etc., and is suitable for use as an industrial product, but does not involve strict quality control steps, and the quality of the raw material is uncontrollable. Summary of the invention

[0009] In order to solve the deficiencies of the prior art, the present invention provides a method for preparing sodium thiosulfate, which is suitable for industrial production and has controllable quality.

[0010] In order to achieve the purpose of the present invention, the following scheme is proposed:

[0011] A preparation method of sodium thiosulfate comprises the following steps: using anhydrous sodium sulfite and sulfur powder as starting materials, heating the reaction in water, and the reaction end point needs to meet the following conditions: 1) the phenolphthalein indicator is colorless; 2) the pH value of the reaction solution is 5.8-7.0; the reaction solution is cooled and filtered, concentrated and crystallized to obtain a wet product of sodium thiosulfate pentahydrate, and the concentration end point is a concentrate density of 1.4 g / mL-1.5 g / mL; the wet product is dried to obtain sodium thiosulfate, and purified water is placed in a vacuum drying oven during the drying process to ensure that the ambient humidity is not less than 40%.

[0012] (1) In addition to the traditional use of phenolphthalein as an indicator, the pH value of the reaction solution is used as a method to determine the end point of the reaction, making the process more controllable; (2) The density of the concentrate is controlled to control the difference in crystallization between batches caused by the inconsistency of the concentrate density; (3) During the drying process, an appropriate amount of purified water is placed in the drying oven to increase the ambient humidity, slow down the water loss rate, and prevent the moisture content during drying from falling below the standard lower limit; (4) The Chinese Pharmacopoeia 2020 stipulates that the weight loss of sodium thiosulfate should be 32.0% to 37.0%. In this scheme, the drying end point is controlled by the drying loss, and the problem of unqualified crystal water caused by easy water loss during the drying process is solved. The raw materials of this process are cheap and easy to obtain, and multiple process controls are added to make the entire production process more controllable and stable, and the quality of the finished product is also improved, making it more suitable for industrial production.

[0013] The reaction temperature is 80°C ± 2°C to 100°C ± 2°C, such as 80°C ± 2°C, 90°C ± 2°C, 100°C ± 2°C, preferably 100°C ± 2°C.

[0014] The reaction solvent is purified water, and the amount of the solvent is 2 to 5 times that of anhydrous sodium sulfite, such as 2 times, 3 times, 4 times, 5 times, preferably 3 times, so that the substrate anhydrous sodium sulfite can be completely dissolved and the reaction efficiency can be improved.

[0015] The sulfur powder equivalent is 1.0M~1.3M, such as 1.0M, 1.1M, 1.2M, 1.3M, preferably 1.1M.

[0016] The crystallization temperature is -5°C to 25°C, preferably 15°C to 25°C.

[0017] The crystal growing time is 3 hours to 21 hours, preferably 3 hours.

[0018] The drying temperature is 25°C to 40°C, preferably 30°C to 40°C.

[0019] The beneficial effects of the present invention are that each step has clear control parameters, the quality is controllable, and it is more conducive to industrial production. In the drying step, by placing an appropriate amount of purified water and maintaining a certain air humidity, the risk of volatilization of crystal water caused by drying of the finished product is reduced. DETAILED DESCRIPTION

[0020] Example 1

[0021] Add 1500g of water to a 2000ml reaction bottle, add 500g of anhydrous sodium sulfite and stir to dissolve, add 140g of sulfur powder, heat and reflux to react for about 31 hours, stop the reaction when the pH value of the reaction solution is 6.48, cool the reaction solution to 25℃~35℃, filter the reaction solution, concentrate at 50℃ under reduced pressure until the relative density of the concentrated solution is 1.48g / ml, then stop concentrating, slowly cool to 15℃~25℃ and grow crystals for 3 hours, filter the crystallization liquid, and dry at 30℃ under reduced pressure for 1.5 hours (use a tray oven, place a tray of about 100g of purified water at the bottom of the oven during drying, and measure the humidity of the drying environment to be 54%) to obtain sodium thiosulfate, with a material recovery of 716.8g, a drying loss of 36.7%, and a yield of 72.8%.

[0022] Example 2

[0023] Add 180g of water to a 500ml reaction bottle, add 60g of anhydrous sodium sulfite and stir to dissolve, add 16.8g of sulfur powder, heat and reflux to react for about 19 hours, stop the reaction when the pH value of the reaction solution is 6.8, cool the reaction solution to 25℃~35℃, filter the reaction solution, concentrate at 50℃ under reduced pressure until the relative density of the concentrated solution is 1.43g / ml, then stop concentrating, slowly cool to 15℃~25℃ and grow crystals for 3 hours, filter the crystallization solution, and dry at 30℃ under reduced pressure for 1.5 hours (use a tray oven, place a tray of about 50g of purified water at the bottom of the oven during drying, and measure the drying environment humidity to be 49%) to obtain sodium thiosulfate, 96g of material, 36.1% loss on drying, and 81.4% yield.

[0024] Example 3

[0025] Add 60g of water to a 250ml reaction bottle, add 20g of anhydrous sodium sulfite and stir to dissolve, add 5.6g of sulfur powder, heat and reflux to react for about 24 hours, stop the reaction when the pH value of the reaction solution is 5.8, cool the reaction solution to 25℃~35℃, filter the reaction solution, concentrate at 50℃ under reduced pressure until the relative density of the concentrated solution is 1.46g / ml, then stop concentrating, slowly cool to 15℃~25℃ to grow crystals for 3 hours, filter the crystallization solution, and dry at 30℃ under reduced pressure for 1.5 hours (use a tray oven, place a tray of about 50g of purified water at the bottom of the oven during drying, and measure the drying environment humidity to be 40%) to obtain sodium thiosulfate, 32g of material, 32.6% loss on drying, and 82.0% yield.

[0026] Comparative Example 1

[0027] Add 300g of water to a 1000ml reaction bottle, add 100g of anhydrous sodium sulfite and stir to dissolve, add 28g of sulfur powder, heat and reflux to react for about 30 hours, the pH value of the reaction solution is controlled to be 8.12, the reaction solution is cooled to 25℃~35℃, the reaction solution is filtered, concentrated at 50℃ under reduced pressure to a relative density of 1.44g / ml, then the concentration is stopped, the temperature is slowly lowered to 15℃~25℃, crystallization is carried out for 3 hours, the crystallization solution is filtered, and dried at 30℃ under reduced pressure for 1.5 hours (the measured drying environment humidity is 35%) to obtain sodium thiosulfate, 154g of material is collected, the drying loss is 31.6%, and the yield is 78.22%.

[0028] Comparative Example 2

[0029] Add 60g of water to a 2500ml reaction bottle, add 20g of anhydrous sodium sulfite and stir to dissolve, add 5.6g of sulfur powder, heat and reflux to react for about 32 hours, the pH value of the reaction solution is controlled to be 8.03, the reaction solution is cooled to 25℃~35℃, the reaction solution is filtered, concentrated at 50℃ under reduced pressure to a relative density of 1.48g / ml, then the concentration is stopped, the temperature is slowly lowered to 15℃~25℃, crystallization is carried out for 3 hours, the crystallization liquid is filtered, and dried at 30℃ under reduced pressure for 1.5 hours (the measured drying environment humidity is 37%) to obtain sodium thiosulfate, 27.1g of the material is collected, the drying loss is 31.4%, and the yield is 69%.

[0030] It can be seen from the data of the examples and comparative examples that the drying loss is closely related to the humidity of the drying environment. The Chinese Pharmacopoeia 2020 stipulates that the weight loss of sodium thiosulfate should be 32.0% to 37.0%. Therefore, during the drying process, the humidity in the drying box should not be less than 40%, as shown in Table 1 below:

[0031] Table 1

[0032]

[0033] The present invention also provides relevant test data of sodium thiosulfate prepared in the above embodiment, see Table 2 below:

[0034] Table 2

[0035]

[0036] The above embodiments are only used to illustrate the technical ideas and features of the present invention, and are not intended to be the only or limit the present invention. It should be understood by those skilled in the art that various changes or equivalent substitutions made to the present invention without departing from the scope of the present invention all fall within the scope of protection of the present invention.

Claims

1. A method for preparing sodium thiosulfate, characterized in that: The following steps are involved: Add water to the reaction bottle, add anhydrous sodium sulfite and stir to dissolve, add sulfur powder, and heat the water to react. The reaction endpoint must meet the following conditions: 1) the phenolphthalein indicator is colorless; 2) the pH of the reaction solution is 5.8~6.8; The reaction solution was cooled and filtered, and concentrated and crystallized to obtain a wet product of sodium thiosulfate pentahydrate. The concentration end point was a concentrate density of 1.4 g / mL to 1.5 g / mL. The wet product is dried to obtain sodium thiosulfate. During the drying process, purified water is placed in the drying oven to ensure that the ambient humidity is not less than 40%; The reaction solvent is purified water, and the amount of the solvent is 2 to 5 times that of anhydrous sodium sulfite; Sulfur powder equivalent is 1.0M~1.3M; The crystallization temperature is -5℃~25℃; The crystal growing time is 3 hours to 21 hours.

2. The method for preparing sodium thiosulfate according to claim 1, wherein The reaction temperature is 80℃±2℃~100℃±2℃.

3. The method for preparing sodium thiosulfate according to claim 1, characterized in that The reaction solvent is purified water, and the amount of solvent used is 3 times that of anhydrous sodium sulfite.

4. The method for preparing sodium thiosulfate according to claim 1, characterized in that The crystallization temperature is 15℃~25℃.

5. The method for preparing sodium thiosulfate according to claim 1, characterized in that: The crystal growth time is 3 hours.

6. The method for preparing sodium thiosulfate according to claim 1, characterized in that: The drying temperature is 25℃~40℃.

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