Pharmaceutical grade ammonium sulfate and method for its synthesis

Abstract

This invention relates to the field of ammonium sulfate synthesis and preparation technology, specifically to a method for synthesizing pharmaceutical-grade ammonium sulfate, comprising the following steps: concentrated sulfuric acid is slowly added to deionized water, ammonia water is introduced, and the reaction system temperature is maintained below 65°C by controlling the flow rate of ammonia water and circulating cooling water. After the reaction is completed, the mixture is filtered, concentrated under reduced pressure, crystallized, pH adjusted, and dehydrated to obtain the ammonium sulfate. This invention can effectively reduce pollution and energy consumption, and improve the purity and yield of ammonium sulfate.

Description

Technical Field

[0001] This invention relates to the field of ammonium sulfate synthesis and preparation technology, specifically to a method for synthesizing pharmaceutical-grade ammonium sulfate. Background Technology

[0002] Ammonium sulfate is an excellent nitrogen fertilizer, suitable for most soils and crops. It promotes vigorous foliage growth, improves fruit quality and yield, and enhances crop resistance to disasters. It can be used as a base fertilizer, top dressing, and seed fertilizer. It reacts with salts to form ammonium chloride, with aluminum sulfate to form ammonium alum, and with boric acid to produce refractory materials. Adding it to electroplating solutions increases conductivity. It is also a catalyst for coloring soy sauce, a nitrogen source for yeast culture in fresh yeast production, a dyeing auxiliary for acidic dyes, and a deliming agent for leather. Furthermore, it can be used in beer brewing, chemical reagents, and battery production. Additionally, it can be a raw material for the preparation of pharmaceuticals, such as cephalosporins and ampicillin.

[0003] In recent years, the demand for ammonium sulfate has been expanding across various market sectors, driving the further development of the ammonium sulfate industry. However, many existing methods for synthesizing ammonium sulfate suffer from various problems, such as low purity, low yield, severe pollution, high consumption, and high cost. Therefore, it is essential to invent an environmentally friendly, low-energy-consumption method for synthesizing high-purity pharmaceutical-grade ammonium sulfate. Summary of the Invention

[0004] To address the above problems, this invention provides an environmentally friendly, low-energy-consumption method for synthesizing high-purity pharmaceutical-grade ammonium sulfate, the method comprising the following steps:

[0005] Synthesis process: The synthesis reaction is carried out by sulfuric acid and ammonia water in a mass ratio of 1:(1.31~1.50). During the reaction, circulating cooling water is passed through and the flow rate of ammonia water is controlled at 40~80kg / h. The reaction yields ammonium sulfate synthesis solution.

[0006] Concentration process: The above ammonium sulfate synthesis solution is concentrated by vacuum distillation to obtain ammonium sulfate concentrate;

[0007] Crystallization process: The above ammonium sulfate concentrate is crystallized. The temperature of the crystallization system needs to be controlled during the crystallization process. After the crystallization process is completed, a crystallized solution is obtained.

[0008] pH adjustment process: Adjusting the pH value of the crystallization solution obtained in the crystallization process;

[0009] Dehydration process: The pH-adjusted crystallization solution is dehydrated using a centrifuge to obtain ammonium sulfate.

[0010] Preferably, in the synthesis process, the mass ratio of sulfuric acid to ammonia (25-28%) is 1:(1.31-1.50), the final synthesis pH is 7-7.5, circulating cooling water is circulated in the jacket of the synthesis reactor, the ammonia feed flow rate is 40-80 kg / h, and the synthesis temperature is below 65°C. By controlling the ammonia feed flow rate, the synthesis system temperature, the final synthesis pH, and reducing the contact time between ammonia and hot air during the feeding process, energy consumption can be effectively reduced, ensuring efficient production of ammonium sulfate while maintaining environmental friendliness.

[0011] Preferably, in the synthesis process, the pipe through which the ammonia solution flows should be submerged below the surface of the sulfuric acid solution to ensure a full reaction and reduce the decomposition of the ammonia solution by heat in the air.

[0012] Preferably, a filtration process is added after the synthesis process and before the concentration process. The filtration process uses filter bags made of polyester fiber filter cloth material, with a mesh size of approximately 350-400 mesh and 3-4 layers.

[0013] Preferably, in the concentration process, vacuum distillation is used for concentration, with the evaporation rate of water accounting for 2 / 3 to 4 / 5 of the total volume of the synthesis liquid, a vacuum degree ≤ -0.090 MPa, and a concentration temperature of 60–80°C. Compared with atmospheric pressure open-pit concentration, vacuum concentration effectively reduces ammonia loss, improves concentration efficiency, and facilitates the recovery of the distilled solvent (low-concentration ammonia water) during concentration, which can be used in the next ammonium sulfate synthesis. Combining the above concentration methods not only reduces ammonia loss but also improves overall production efficiency, and is safe and environmentally friendly.

[0014] Preferably, in the crystallization and pH adjustment process, the crystallization temperature is controlled to be no higher than 25°C; an appropriate amount of ammonia is added before dehydration to adjust the pH of the supernatant of the crystallization solution to 8. Combined with the above-mentioned reduced pressure concentration compared to atmospheric pressure concentration, the amount of ammonia added to adjust the pH of the supernatant of the crystallization solution is reduced by about 80%, and the addition of ammonia at low temperature saves energy and is safe and environmentally friendly.

[0015] Preferably, in the dehydration process, a centrifuge is used for dehydration, with a dehydration time of 30-50 minutes per centrifuge, which meets the standards of Part IV of the Chinese Pharmacopoeia (2015 edition). Acidity: Take 1.0g of this product, add 20ml of water to dissolve it, and determine the pH value according to the method (General Rule 0631). The pH value should be 5.0-6.0. Therefore, there is no need to carry out drying, grinding and other processes. By controlling the centrifugation time, energy consumption and labor can be effectively reduced.

[0016] Compared with the prior art, the beneficial effects of the present invention are:

[0017] By controlling the synthesis system temperature, ammonia feed flow rate, synthesis endpoint, and reducing the contact time between ammonia and air during synthesis, and by using reduced pressure concentration to control the system vacuum and concentration temperature during concentration, and by controlling the crystallization temperature and the final pH value of the crystallization solution during crystallization and pH adjustment, ammonia consumption is reduced, and overall production efficiency is improved. This results in the safe and environmentally friendly production of products that meet standards. During dehydration, high-speed centrifugation is used to quickly remove water adhering to the surface of ammonium sulfate. Extending the dehydration time yields higher purity pharmaceutical-grade ammonium sulfate, eliminating the need for further heating and drying. This avoids risks such as uneven content, unacceptable acidity, and the introduction of other impurities (mechanical impurities introduced from the drying oven) due to uneven contact temperature. Attached Figure Description

[0018] Figure 1 This is a process flow diagram for the production of pharmaceutical-grade ammonium sulfate. Detailed Implementation

[0019] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0020] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0021] Comparative Example 1

[0022] The effects of synthesis system temperature and ammonia water feed flow rate on the amount of ammonia water added. A 20L multi-functional reactor was used as the synthesis device. 8kg of deionized water was added, and 4kg of sulfuric acid was slowly added under stirring. Ammonia water was added at different flow rates, and the temperature inside the reactor and the actual amount of ammonia water added were recorded.

[0023]

[0024] The experiments above show that, as seen in 1-1 to 1-3, the ammonia feeding rate affects the synthesis temperature. Without circulating cooling water, the final synthesis temperature is between 87 and 98°C, resulting in an additional 50-84% consumption of ammonia. This indicates that excessively rapid ammonia feeding leads to excessively high reaction temperatures, affecting the thermal decomposition of ammonia and increasing ammonia consumption. Therefore, circulating cooling water is used to lower the reaction temperature. As shown in 1-4 to 1-9, under circulating cooling water conditions, a lower ammonia flow rate results in better cooling, lower reaction system temperature, and reduced ammonia consumption.

[0025] The experimental parameters 1-6 to 1-9 were fed into a 500L reactor. 125kg of deionized water was added, and 100kg of sulfuric acid was slowly added while stirring. The temperature was lowered to below 25℃ by circulating cooling water. Ammonia water was added at a flow rate of 20-80kg / h. The temperature inside the reactor, the feeding time, and the actual amount of ammonia water added were recorded.

[0026]

[0027] The above experiments show that the data from experiments 1-10 to 1-13 are largely consistent with those from experiments 1-6 to 1-9, further verifying that controlling the reaction temperature and ammonia flow rate can effectively reduce ammonia consumption. Experiments 1-9 and 1-13 revealed that although the ammonia flow rate was the lowest, ammonia consumption increased instead of decreasing. This may be because the reduced flow rate also increased the contact time between the ammonia and hot air. Therefore, inserting the ammonia pipe below the surface of the sulfuric acid solution prevents contact between the ammonia and hot air.

[0028] Comparative Example 2

[0029] Modify the ammonia water pipeline so that it can be submerged below the surface of the sulfuric acid solution. Feed the materials into a 500L reactor, add 125kg of deionized water, and slowly add 100kg of sulfuric acid while stirring. Circulate cooling water to cool the temperature down to below 25℃. Add ammonia water at a flow rate of 20-80kg / h. Record the temperature inside the synthesis reactor, the feeding time, and the actual amount of ammonia water added.

[0030]

[0031] Experiments show that submerging the ammonia water pipeline below the liquid surface can effectively reduce ammonia water consumption. Considering the reaction time and production efficiency, the optimal ammonia water flow rate is 60-80 kg / h, and the reaction temperature is <65℃.

[0032] Comparative Example 3

[0033] The pH of the synthesis endpoint was studied using a 20L multi-functional reactor. 8kg of deionized water was added, followed by 4kg of sulfuric acid under stirring. The mixture was cooled to below 25℃ by circulating cooling water. Ammonia was added at a flow rate of 60kg / h, with the ammonia feeding pipe submerged below the liquid surface. After synthesis, the mixture was filtered, concentrated under reduced pressure, cooled, and crystallized. The pH of the crystallized solution was controlled at 8, and then centrifuged for 45 minutes.

[0034]

[0035] Experiments show that when the final synthesis pH is <7.0, as evidenced by the temperature difference before and after adding ammonia to the crystallization solution, the synthesis was incomplete. When the final synthesis pH is ≥7.0, the amount of ammonia added to control the crystallization solution is significantly reduced. This prevents excessive ammonia addition during dehydration, avoiding pungent odors and operational disruptions, and allows for safe and environmentally friendly production under environmentally friendly equipment. When the synthesis pH is ≥8, the final product's content and acidity are both within acceptable limits, but ammonia consumption is higher than at pH = 7.0–7.5. Therefore, the optimal final synthesis pH is 7.0–7.5 (based on extensive test paper detection).

[0036] Comparative Example 4

[0037] The effects of atmospheric pressure concentration and vacuum concentration were studied. An experiment was conducted in a 20L multi-functional reactor. 8 kg of deionized water was added, followed by 4 kg of sulfuric acid slowly added with stirring. The mixture was cooled to below 25°C by circulating cooling water. Then, 5.5 kg of ammonia was added at a flow rate of 60 kg / h, with the ammonia feed pipe submerged below the liquid surface. After synthesis, the mixture was filtered, and the filtrate was divided into two portions for atmospheric pressure concentration and vacuum concentration, respectively, until two-thirds of the material precipitated. After cooling and crystallization, the pH of the crystallization solution was controlled to 8, and the solution was centrifuged for 45 min.

[0038]

[0039] Experiments show that both vacuum concentration and atmospheric concentration can produce qualified pharmaceutical-grade ammonium sulfate, but vacuum concentration reduces ammonia consumption and improves concentration efficiency. At the same time, the dilute ammonia solution distilled out can be used for the next production.

[0040] Comparative Example 5:

[0041] The effect of centrifugation time on material content. An experiment was conducted in a 20L multi-functional reactor. 8kg of deionized water was added, followed by 4kg of sulfuric acid slowly added with stirring. The mixture was cooled to below 25℃ by circulating cooling water. 5.5kg of ammonia was added at a flow rate of 60kg / h, with the ammonia feeding pipe submerged below the liquid surface. After synthesis, the mixture was filtered and concentrated under reduced pressure until 2 / 3 of the material precipitated. After cooling and crystallization, the pH of the crystallization solution was controlled at 8. Samples were taken after centrifugation for 10min, 20min, 30min, 40min, 50min, and 60min to detect the content and acidity.

[0042]

[0043]

[0044] Experiments show that longer centrifugation time leads to better dehydration of the material surface, but within certain limits, almost all the water adhering to the material surface can be separated, thus obtaining high-purity pharmaceutical-grade ammonium sulfate. Experimental data indicates that controlling the centrifugation time to 30–50 min / machine can both meet product quality standards and improve production efficiency.

[0045] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A method for the synthesis of ammonium sulfate, characterized in that, Includes the following processes: Synthesis: The reaction is carried out by sulfuric acid and ammonia water in a mass ratio of 1:(1.31~1.50). During the reaction, circulating cooling water is used and the flow rate of ammonia water is controlled at 40~80kg / h to obtain ammonium sulfate synthesis solution. Concentration: The above ammonium sulfate synthesis solution was concentrated by vacuum distillation to obtain ammonium sulfate concentrate; Crystallization: The above ammonium sulfate concentrate is crystallized, and the temperature of the crystallization system is controlled during the crystallization process. After the crystallization process is completed, a crystallized solution is obtained. pH adjustment: Adjusting the pH value of the crystallization solution obtained in the crystallization process; Dehydration: The pH-adjusted crystallization solution was dehydrated using a centrifuge to obtain ammonium sulfate; In the synthesis process, the ammonia concentration is 25%–28%, the final synthesis pH is 7.0–7.5, and the synthesis temperature is below 65°C; in the crystallization process, the crystallization temperature is controlled to not exceed 25°C; and in the dehydration process, the ammonium sulfate content is ≥99%. In the concentration process, the amount of water evaporated accounts for 2 / 3 to 4 / 5 of the total volume of the synthesis liquid, the vacuum degree is ≤-0.090MPa, and the concentration temperature is 60 to 80℃; In the pH adjustment process, ammonia is added to adjust the pH of the supernatant of the crystallizing solution to 7-8.

2. The method of claim 1, wherein the ammonium sulfate is synthesized by, A filtration process is added after the synthesis process and before the concentration process.

3. The method of claim 1, wherein the ammonium sulfate is synthesized by, In the synthesis process, the synthesis temperature is controlled by circulating cooling water through the jacket of the synthesis reactor.

4. The method of claim 1, wherein the ammonium sulfate is synthesized by, In the synthesis process, the pipe for ammonia water is submerged below the surface of the sulfuric acid solution.

5. The method for synthesizing ammonium sulfate according to claim 2, characterized in that, The filter bag, made of polyester fiber filter cloth, is used in the filtration process. The filter bag has a mesh size of 350-400 and has 3-4 layers.

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