A method for recovering paracetamol

Abstract

The present invention discloses a method for recovering paracetamol. When the raw material for recovery is paracetamol mother liquor, it comprises the following steps: (1) Concentrate the paracetamol mother liquor to 1 / 7 to 1 / 5 of the original volume, cool and crystallize the concentrated mother liquor, and filter to obtain the first crude paracetamol product; (2) Dissolve the first crude paracetamol product in water, add a dibasic acid and react until the reaction ends, cool and crystallize the reaction solution, and filter to obtain the second crude paracetamol product; (3) Dissolve the second crude paracetamol product, add modified biochar for treatment and filter, concentrate the filtrate to 1 / 2 of the original volume, cool and crystallize the concentrated filtrate, and filter to obtain qualified paracetamol; when the raw material for recovery is crude paracetamol, it is consistent with the above steps (2) and (3). This method has high recovery efficiency, high material utilization rate, stable and excellent product quality, does not require special equipment and reagents, is convenient to operate, and can achieve large-scale operation.

Description

Technical Field

[0001] The present invention relates to a method for recovering paracetamol, and particularly to a method for recovering high-quality paracetamol from the mother liquor of paracetamol production. Background Art

[0002] Paracetamol is the most commonly used non-anti-inflammatory antipyretic analgesic, and its main component is p-acetaminophen. It is a white, off-white crystalline or crystalline powder, and its solubility in water at 20 °C is 14 g / L. Paracetamol is obtained by heating and acylating p-aminophenol with an acetylating agent such as acetic acid in an acetic acid-water solvent, and after the reaction is completed, the solvent is evaporated to obtain a crude product. The crude product is first washed with water, and then recrystallized and decolorized with water to obtain a qualified product of paracetamol.

[0003] The recrystallization mother liquor generated in the above method contains a large amount of p-acetaminophen, resulting in a high COD in the production waste liquid, and both aerobic bacteria and anaerobic bacteria cannot completely treat it. Therefore, it is necessary to extract the residual paracetamol in it by concentration. Since a lot of impurities will be generated during the heating of paracetamol and p-aminophenol, the concentrated heat will cause the impurities to remain in the extracted crude paracetamol. Among them, the polarity of most impurities is similar to that of paracetamol, and some impurities are also very unstable. These impurities cause the extracted crude paracetamol to change color from pink to blue, or even to brownish-yellow during storage. Since the above impurities are difficult to separate from p-acetaminophen, p-acetaminophen cannot be effectively recovered from the mother liquor, and the extracted crude paracetamol is usually treated as solid waste, causing potential safety hazards and environmental pollution, and resulting in low resource utilization rate and rising production cost of paracetamol raw materials.

[0004] CN102816080 discloses a method for recovering p-acetaminophen from the mother liquor by using a simulated moving bed ion exchange system. The recovered paracetamol is off-white within 1 week, but since the impurities causing color change are not effectively removed, the extracted paracetamol gradually darkens and changes color after 1 week. Summary of the Invention

[0005] Object of the Invention: The present invention aims to provide a method for recovering paracetamol with high material utilization rate and excellent product quality stability.

[0006] Technical Solution: The method for recovering paracetamol according to the present invention is selected from any of the following methods:

[0007] Method 1: When the recovery raw material is paracetamol mother liquor, it includes the following steps:

[0008] (1) Concentrate the paracetamol mother liquor to 1 / 7 to 1 / 5 of the original volume, cool and crystallize the concentrated mother liquor, and filter to obtain the first crude paracetamol;

[0009] (2) Dissolve the first crude product of paracetamol in water, add a dibasic acid and react until the reaction is complete. Cool the reaction solution to crystallize, and filter to obtain the second crude product of paracetamol.

[0010] (3) Dissolve the second crude product of paracetamol, add modified biochar for treatment and filtration. Concentrate the filtrate to 1 / 2 of the original volume, cool the concentrated filtrate to crystallize, and filter to obtain the qualified product of paracetamol.

[0011] Method 2: When the recycled raw material is the crude product of paracetamol, it includes the following steps:

[0012] (1) Dissolve the crude product of paracetamol in water, add a dibasic acid and react until the reaction is complete. Cool the reaction solution to crystallize, and filter to obtain the second crude product of paracetamol.

[0013] (2) Dissolve the second crude product of paracetamol, add modified biochar for treatment and filtration. Concentrate the filtrate to 1 / 2 of the original volume, cool the concentrated filtrate to crystallize, and filter to obtain the qualified product of paracetamol.

[0014] The recovery method of the present invention is divided into two types. Method 1 uses the mother liquor of recrystallization of the crude product of paracetamol produced by the conventional preparation method of paracetamol as the raw material, and Method 2 uses the crude product of paracetamol recovered by the conventional recovery method of the mother liquor of recrystallization of the crude product of paracetamol as the raw material.

[0015] Preferably, the paracetamol mother liquor is concentrated to 1 / 7, 1 / 6, 1 / 5 of the original volume, and more preferably concentrated to 1 / 6 of the original volume.

[0016] Preferably, the method for cooling and crystallizing the concentrated mother liquor is to cool the concentrated mother liquor at a cooling rate of 1-5 °C / min until it is cooled to 5-15 °C and kept warm and stirred for 0.5-1.5 h.

[0017] Preferably, the dibasic acid is selected from sulfurous acid, sulfuric acid, oxalic acid, malonic acid, succinic acid, maleic acid (cis, trans), glutaric acid, adipic acid, phthalic acid, terephthalic acid, and the molar ratio of the dibasic acid to the first crude product of paracetamol or the crude product of paracetamol is 1:10-15.

[0018] Surprisingly, the present invention discovers through research that a dibasic acid with a suitable acidity can effectively remove the impurities that cause color change and enable the product to maintain a stable quality. Among them, the dibasic acid is selected from inorganic dibasic acids and organic dibasic carboxylic acids, including but not limited to inorganic dibasic acids such as sulfurous acid and sulfuric acid, C2-C6 saturated / unsaturated aliphatic organic dibasic carboxylic acids such as malonic acid, succinic acid, maleic acid, glutaric acid, adipic acid, and aromatic dibasic carboxylic acids such as phthalic acid and terephthalic acid, and more preferably organic dibasic carboxylic acids.

[0019] Preferably, the mass ratio of the first crude paracetamol or crude paracetamol to water is 1:2 to 5, more preferably 1:3 to 5, specifically 1:3, 1:4, 1:5.

[0020] Preferably, the reaction temperature of the first crude paracetamol or crude paracetamol with the dibasic acid is 50 to 90 °C, more preferably 50 to 70 °C, specifically 50 °C, 60 °C, 70 °C. Each specific temperature point can also fluctuate within the temperature control fluctuation range of the equipment, that is, the temperature is controlled within the range of the target value ± the control precision value. For example, when the temperature control precision is 0.5 °C, it can specifically be 50 ± 0.5 °C, 60 ± 0.5 °C, 70 ± 0.5 °C. The reaction time is 1 to 3 h, more preferably 1.5 to 3 h, specifically 1.5 h, 2 h, 3 h, and can be adjusted according to the reaction progress.

[0021] Preferably, the method for cooling and crystallizing the reaction solution is to cool the reaction solution at a cooling rate of 1 to 5 °C / min until it is cooled to 0 to 10 °C and kept stirring for 0.5 to 1.5 h, more preferably 0 to 10 °C and kept stirring for 0.5 h, 1 h, 1.5 h, and can be specifically adjusted according to the crystallization process.

[0022] Preferably, calculated by the mass-to-volume ratio of 1:4 to 6, more preferably 1:4, 1:5, 1:6, dissolve the second crude paracetamol in an acetic acid-aqueous solution with an acetic acid mass fraction of 25 to 40%, more preferably an acetic acid-aqueous solution with an acetic acid mass fraction of 25%, 30%, 40%.

[0023] Preferably, the modified biochar is loaded with a reducing agent, and the reducing agent is selected from Na2SO3, FeSO4, more preferably a reducing agent solution of 0.0005 to 0.0015 mol / L, and the modified biochar is specifically obtained by impregnating biochar particles with the reducing agent solution.

[0024] Preferably, the mass ratio of the modified biochar to the second crude paracetamol is 1:8 to 12, more preferably 1:8 to 11.9, specifically 1:8, 1:8.3, 1:10, 1:11.9.

[0025] Preferably, the treatment time of the modified biochar on the second crude paracetamol is 1 to 3 h, more preferably 2 to 3 h, specifically 2 h, 2.5 h, 3 h, and can be adjusted according to the treatment progress.

[0026] Preferably, the method for cooling and crystallizing the filtrate concentrate is to cool the filtrate concentrate at a cooling rate of 1 to 5 °C / min until it is cooled to room temperature and kept stirring for 0.5 to 1.5 h, more preferably 1 h, and can be specifically adjusted according to the treatment progress.

[0027] Beneficial effects: Compared with the prior art, the present invention has the following remarkable advantages:

[0028] High recycling efficiency, high material utilization rate, stable and excellent product quality (purity higher than 99%, total impurities lower than 0.2%, single impurity lower than 0.05%), no special equipment and reagents are required, the operation is convenient, and large-scale operation can be achieved. Description of the Drawings

[0029] Figure 1 Appearance of crude paracetamol recovered by the existing method after being placed for 6 months;

[0030] Figure 2 Appearance of qualified paracetamol recovered by the method of the present invention after being placed for 6 months;

[0031] Figure 3 HPLC detection spectrum of crude paracetamol recovered by the existing method after being placed for 6 months;

[0032] Figure 4 HPLC detection spectrum of the first crude paracetamol recovered by the method of the present invention;

[0033] Figure 5 HPLC detection spectrum of qualified paracetamol recovered by the method of the present invention after being placed for 6 months. Detailed Description of the Invention

[0034] The technical solution of the present invention will be further described below in conjunction with the embodiments.

[0035] Example 1: Preparation of Modified Biochar

[0036] Wash the wheat straw and dry it in the sun. After being crushed by a crusher and passing through a 40-mesh sieve, wheat straw biomass particles are obtained. Weigh 150 g of wheat straw biomass particles and place them in a 2-L conical flask. Then add 1.5 L of 0.0005 mol / L Na2SO3 solution to the flask. After impregnation for 2 h, filter by suction. Place the obtained biomass particles in an oven and dry them at 90 °C for 24 h. Then, pyrolyze and calcine at a pyrolysis temperature of 600 °C in a box-type resistance furnace for 2 h. Immerse the calcined biochar in 0.1 mol / L hydrochloric acid for 2 h, and then repeatedly wash it with distilled water until the pH value of the biochar is neutral, and dry it for standby.

[0037] Example 2: Preparation of Modified Biochar

[0038] Wash the wheat straw and dry it in the sun. After crushing it with a crusher, sieve it through a 40-mesh sieve to obtain wheat straw biomass particles. Weigh 150 g of wheat straw biomass particles and place them in 2-L conical flasks respectively. Then add 1.5 L of 0.001 mol / L Na2SO3 solution to the flasks. After impregnating for 2 h, filter by suction. Place the obtained biomass particles in an oven and bake at 90 °C for 24 h. Then, pyrolyze and calcine in a box-type resistance furnace at a pyrolysis temperature of 600 °C for 2 h. Immerse the calcined biochar in 0.1 mol / L hydrochloric acid for 2 h respectively, and then repeatedly wash it with distilled water until the pH value of the biochar is neutral, and dry it for standby.

[0039] Example 3: Preparation of modified biochar

[0040] Wash the wheat straw and dry it in the sun. After crushing it with a crusher, sieve it through a 40-mesh sieve to obtain wheat straw biomass particles. Weigh 150 g of wheat straw biomass particles and place them in 2-L conical flasks respectively. Then add 1.5 L of 0.0015 mol / L Na2SO3 solution to the flasks. After impregnating for 2 h, filter by suction. Place the obtained biomass particles in an oven and bake at 90 °C for 24 h. Then, pyrolyze and calcine in a box-type resistance furnace at a pyrolysis temperature of 600 °C for 2 h. Immerse the calcined biochar in 0.1 mol / L hydrochloric acid for 2 h respectively, and then repeatedly wash it with distilled water until the pH value of the biochar is neutral, and dry it for standby.

[0041] Example 4: Preparation of modified biochar

[0042] Wash the wheat straw and dry it in the sun. After crushing it with a crusher, sieve it through a 40-mesh sieve to obtain wheat straw biomass particles. Weigh 150 g of wheat straw biomass particles and place them in a 2-L conical flask. Then add 1.5 L of 0.0005 mol / L FeSO4 solution to the flask. After impregnating for 2 h, filter by suction. Place the obtained biomass particles in an oven and bake at 90 °C for 24 h. Then, pyrolyze and calcine in a box-type resistance furnace at a pyrolysis temperature of 600 °C for 2 h. Immerse the calcined biochar in 0.1 mol / L hydrochloric acid for 2 h respectively, and then repeatedly wash it with distilled water until the pH value of the biochar is neutral, and dry it for standby.

[0043] Example 5: Preparation of modified biochar

[0044] Wash the wheat straw and dry it in the sun. After pulverizing it with a pulverizer and passing it through a 40-mesh sieve, wheat straw biomass particles are obtained. Weigh 150 g of the wheat straw biomass particles and place them in a 2-L conical flask. Then add 1.5 L of a 0.001 mol / L FeSO4 solution to the flask. After impregnating for 2 h, carry out suction filtration, and place the obtained biomass particles in an oven and dry them at 90 °C for 24 h. Then, pyrolyze and calcine at a pyrolysis temperature of 600 °C in a box-type resistance furnace for 2 h, and impregnate the calcined biochar with 0.1 mol / L hydrochloric acid for 2 h respectively, and then repeatedly wash with distilled water until the pH value of the biochar is neutral, and dry for standby.

[0045] Example 6: Preparation of modified biochar

[0046] Wash the wheat straw and dry it in the sun. After pulverizing it with a pulverizer and passing it through a 40-mesh sieve, wheat straw biomass particles are obtained. Weigh 150 g of the wheat straw biomass particles and place them in a 2-L conical flask. Then add 1.5 L of a 0.0015 mol / L FeSO4 solution to the flask. After impregnating for 2 h, carry out suction filtration, and place the obtained biomass particles in an oven and dry them at 90 °C for 24 h. Then, pyrolyze and calcine at a pyrolysis temperature of 600 °C in a box-type resistance furnace for 2 h, and impregnate the calcined biochar with 0.1 mol / L hydrochloric acid for 2 h respectively, and then repeatedly wash with distilled water until the pH value of the biochar is neutral, and dry for standby.

[0047] Example 7: Preparation of paracetamol primary crude product

[0048] Concentrate the paracetamol mother liquor to 1 / 6 of its original volume, and the concentrated water can be reused. Then, at a cooling rate of 1 - 5 °C / min, cool the concentrated mother liquor with stirring to 5 - 15 °C, and keep stirring at this temperature. During the stirring and cooling process, solids continuously precipitate. After keeping stirring for 0.5 - 1.5 h, filter the precipitated solids, and the paracetamol primary crude product is obtained, with a content of 90.9%, total impurities of 9.1%, and the maximum single impurity of 4.7%.

[0049] Example 8: Preparation of paracetamol secondary crude product

[0050] Add 100 kg of the paracetamol primary crude product obtained in Example 7 to a dissolution kettle, then add 500 kg of distilled water, raise the temperature in the kettle to 50 °C, and the paracetamol primary crude product completely dissolves. Add 4.6 kg of malonic acid, and stir and react at 50 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, cool the reaction solution with stirring to 0 - 10 °C, and keep stirring at this temperature for 0.5 h. Filter the precipitated solids, which are light gray paracetamol secondary crude product, with a yield of 75%, a content of 97.9%, and total impurities of 2.1%.

[0051] Example 9: Preparation of paracetamol secondary crude product

[0052] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 400 kg of distilled water. Raise the temperature in the kettle to 60 °C. After the first crude paracetamol is completely dissolved, add 5.2 kg of malonic acid, and stir and react at 60 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 0.5 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 82%, a content of 98.7%, and a total impurity of 1.3%.

[0053] Example 10: Preparation of the second crude paracetamol

[0054] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 5.2 kg of malonic acid, and stir and react at 70 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 90%, a content of 98.6%, and a total impurity of 1.4%.

[0055] Example 11: Preparation of the second crude paracetamol

[0056] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 6.8 kg of malonic acid, and stir and react at 90 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 88%, a content of 98.1%, and a total impurity of 1.9%.

[0057] Example 12: Preparation of the second crude paracetamol

[0058] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 4.5 kg of oxalic acid, and stir and react at 70 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 86%, a content of 98.1%, and a total impurity of 1.9%.

[0059] Example 13: Preparation of the second crude paracetamol

[0060] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 5.9 kg of succinic acid, and stir and react at 70 °C for 2 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 80%, a content of 97.9%, and a total impurity of 2.1%.

[0061] Example 14: Preparation of the second crude paracetamol

[0062] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 5.8 kg of maleic acid, and stir and react at 70 °C for 3 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in light gray color, with a yield of 76%, a content of 97.1%, and a total impurity of 2.9%.

[0063] Example 15: Preparation of the second crude paracetamol

[0064] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 6.6 kg of glutaric acid, and stir and react at 70 °C for 2 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 75%, a content of 97.7%, and a total impurity of 2.3%.

[0065] Example 16: Preparation of the second crude paracetamol

[0066] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 7.3 kg of adipic acid, and stir and react at 70 °C for 3 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 70%, a content of 97.5%, and a total impurity of 2.5%.

[0067] Example 17: Preparation of the second crude paracetamol

[0068] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 8.3 kg of phthalic acid, and stir and react at 70 °C for 1.5 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 78%, a content of 98.2%, and a total impurity of 1.8%.

[0069] Example 18: Preparation of the second crude paracetamol

[0070] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 8.3 kg of terephthalic acid, and stir and react at 70 °C for 2 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 70%, a content of 97.4%, and a total impurity of 2.6%.

[0071] Example 19: Preparation of the second crude paracetamol

[0072] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 4.1 kg of sulfurous acid, and stir and react at 70 °C for 2 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 67%, a content of 96.9%, and a total impurity of 3.1%.

[0073] Example 20: Preparation of the second crude paracetamol

[0074] Add 100 kg of the first crude paracetamol obtained in Example 7 into a dissolution kettle, then add 300 kg of distilled water. Raise the temperature in the kettle to 70 °C. After the first crude paracetamol is completely dissolved, add 4.9 kg of sulfuric acid, and stir and react at 70 °C for 2 h. Then, at a cooling rate of 1 - 5 °C / min, stir and cool the reaction solution to 0 - 10 °C, and keep stirring at this temperature for 1 h. Filter the precipitated solid, which is the second crude paracetamol in off-white color, with a yield of 61%, a content of 96.3%, and a total impurity of 3.7%.

[0075] Example 21: Preparation of the second crude paracetamol

[0076] Will Figure 1 100 kg of crude paracetamol that has been stored for 6 months is added to a dissolving kettle, and then 300 kg of distilled water is added. The temperature in the kettle is raised to 70°C. After the crude paracetamol is completely dissolved, 6.8 kg of malonic acid is added, and the reaction is stirred at 70°C for 3 hours. The reaction solution is stirred and cooled to 0-10°C at a cooling rate of 1-5°C / min, and kept stirred at this temperature for 1 hour. The precipitated solid is filtered, which is a grayish white crude paracetamol secondary product, with a yield of 73%, a content of 98%, and a total impurity of 2%.

[0077] Example 22: Preparation of Paracetamol Qualified Products

[0078] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 250 liters of a 25% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 1 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 80%, a content of 99.81%, a total impurity of 0.19%, and all single impurities were less than 0.05%.

[0079] Example 23: Preparation of Paracetamol Qualified Products

[0080] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 250 liters of a 25% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 2 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1-5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 83%, a content of 99.83%, a total impurity of 0.17%, and all single impurities were less than 0.05%.

[0081] Example 24: Preparation of Paracetamol Qualified Products

[0082] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 250 liters of a 25% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 87%, a content of 99.85%, a total impurity of 0.15%, and all single impurities were less than 0.05%.

[0083] Example 25: Preparation of Paracetamol Qualified Products

[0084] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 91%, a content of 99.84%, a total impurity of 0.16%, and all single impurities were less than 0.05%.

[0085] Example 26: Preparation of Paracetamol Qualified Products

[0086] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 5 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1-5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 91%, a content of 99.82%, a total impurity of 0.18%, and all single impurities were less than 0.05%.

[0087] Example 27: Preparation of Paracetamol Qualified Products

[0088] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 4.2 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 88%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0089] Example 28: Preparation of Paracetamol Qualified Products

[0090] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 5 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 4 was added, and heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 80%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0091] Example 29: Preparation of Paracetamol Qualified Products

[0092] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 5 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 5 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 82%, a content of 99.81%, a total impurity of 0.19%, and all single impurities were less than 0.05%.

[0093] Example 30: Preparation of Paracetamol Qualified Products

[0094] 50 kg of the secondary crude paracetamol obtained in Example 10 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 5 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 6 was added, and heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 85%, a content of 99.81%, a total impurity of 0.19%, and all single impurities were less than 0.05%.

[0095] Example 31: Preparation of Paracetamol Qualified Products

[0096] 50 kg of the secondary crude paracetamol obtained in Example 12 was added to a reactor, and then 200 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 5 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 86%, a content of 99.83%, a total impurity of 0.17%, and all single impurities were less than 0.05%.

[0097] Example 32: Preparation of Paracetamol Qualified Products

[0098] 50 kg of the secondary crude paracetamol obtained in Example 13 was added to a reactor, and then 250 liters of a 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 84%, a content of 99.82%, a total impurity of 0.18%, and all single impurities were less than 0.05%.

[0099] Example 33: Preparation of Paracetamol Qualified Products

[0100] 50 kg of the secondary crude paracetamol obtained in Example 14 was added to a reactor, and then 300 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 3 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 2 / 5 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 79%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0101] Example 34: Preparation of Paracetamol Qualified Products

[0102] 50 kg of the secondary crude paracetamol obtained in Example 15 was added to a reactor, and then 250 liters of a 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2.5 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 81%, a content of 99.82%, a total impurity of 0.18%, and all single impurities were less than 0.05%.

[0103] Example 35: Preparation of Paracetamol Qualified Products

[0104] 50 kg of the secondary crude paracetamol obtained in Example 16 was added to a reactor, and then 300 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 3 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 2 / 5 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 78%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0105] Example 36: Preparation of Paracetamol Qualified Products

[0106] 50 kg of the secondary crude paracetamol obtained in Example 17 was added to a reactor, and then 250 liters of a 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and the mixture was heated, stirred and refluxed for 2.5 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 1 / 2 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 84%, a content of 99.82%, a total impurity of 0.18%, and all single impurities were less than 0.05%.

[0107] Example 37: Preparation of Paracetamol Qualified Products

[0108] 50 kg of the secondary crude paracetamol obtained in Example 18 was added to a reactor, and then 300 liters of 30% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 3 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 2 / 5 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 79%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0109] Example 38: Preparation of Paracetamol Qualified Products

[0110] 50 kg of the secondary crude paracetamol obtained in Example 19 was added to a reactor, and then 300 liters of 40% acetic acid aqueous solution was added, and the temperature in the reactor was raised to 70°C. After the secondary crude paracetamol was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added, and heated, stirred and refluxed for 3 hours. The wheat straw biochar was filtered out while hot, and the filtrate was concentrated to 2 / 5 of the original volume under reduced pressure. The concentrated filtrate was then stirred and cooled to room temperature at a cooling rate of 1 to 5°C / min, and stirred at this temperature for 1 hour. The precipitated solid was filtered, which was white paracetamol with a yield of 80%, a content of 99.8%, a total impurity of 0.2%, and all single impurities were less than 0.05%.

[0111] Example 39: Preparation of Paracetamol Qualified Products

[0112] 50 kg of the paracetamol secondary crude product obtained in Example 20 was added to a reaction kettle, and then 300 L of 40% aqueous acetic acid solution was added. The temperature in the kettle was raised to 70 °C. After the paracetamol secondary crude product was completely dissolved, 6.25 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added. After heating and stirring under reflux for 3 h, the wheat straw biochar was filtered off while it was hot. The filtrate was concentrated under reduced pressure to 2 / 5 of the original volume, and then the concentrated filtrate was stirred and cooled to room temperature at a cooling rate of 1 - 5 °C / min, and stirred at this temperature for 1 h. The solid precipitated by filtration was white paracetamol, with a yield of 78%, a content of 99.8%, a total impurity of 0.2%, and all single impurities less than 0.05%.

[0113] Example 40: Preparation of qualified paracetamol

[0114] 50 kg of the paracetamol secondary crude product obtained in Example 21 was added to a reaction kettle, and then 300 L of 30% aqueous acetic acid solution was added. The temperature in the kettle was raised to 70 °C. After the paracetamol secondary crude product was completely dissolved, 6 kg of the modified wheat straw biochar loaded with a reducing agent prepared in Example 3 was added. After heating and stirring under reflux for 3 h, the wheat straw biochar was filtered off while it was hot. The filtrate was concentrated under reduced pressure to 2 / 5 of the original volume, and then the concentrated filtrate was stirred and cooled to room temperature at a cooling rate of 1 - 5 °C / min, and stirred at this temperature for 1 h. The solid precipitated by filtration was white paracetamol, with a yield of 86%, a content of 99.82%, a total impurity of 0.18%, and all single impurities less than 0.05%.

[0115] Example 41: Comparative study on paracetamol recovered by different methods

[0116] Paracetamol in the paracetamol mother liquor was recovered by the existing method and the method of the present invention (Example 7) respectively, and then the products were placed for 6 months under the same conditions. The results showed that the paracetamol crude product recovered by the existing method had turned dark brown ( Figure 1 ), while the qualified paracetamol recovered by the method of the present invention remained off-white ( Figure 2 ).

[0117] Furthermore, the purity and impurity content of the samples recovered by the two methods were detected with reference to the existing detection methods. The results showed that the purity of the paracetamol crude product recovered by the existing method was only 80.9% after being placed for 6 months, the total impurity content was 19.1%, the contents of multiple single impurities exceeded 0.05%, and the maximum single impurity content exceeded 9% (Table 1, Figure 3 ). While the purity of the primary crude product recovered by the method of the present invention was 90.9%, the total impurity content was 10.1%, and the maximum single impurity content was 4.7% (Table 2, Figure 4)。According to the method of the present invention, the primary crude product is subjected to subsequent purification (Example 25). The obtained qualified product still has a purity of 99.84% after being stored for 6 months, the total impurity content is 0.16%, and the content of all single impurities is less than 0.05 (Table 3, Figure 5 )。

[0118] As can be seen from the above, the products recovered by the method of the present invention have significant advantages in terms of stability and product quality.

[0119] Table 1 Detection results of the crude product recovered by the existing method after being stored for 6 months

[0120] Detector A 245nm

[0121] Peak No. Compound Name Retention Time Area Area % Height 1 0.967 7370 0.007 129 2 2.088 40817 0.038 8705 3 2.857 11302 0.010 2071 4 3.285 71360 0.066 4473 5 Paracetamol 4.042 89949186 80.854 2268774 6 6.276 179309 0.165 18983 7 6.908 56123 0.052 4917 8 7.586 146088 0.135 9903 9 8.755 9917 0.009 583 10 9.380 38305 0.035 2618 11 10.015 29150 0.027 933 12 11.435 10010034 9.220 1751913 13 13.418 10012 0.009 494 14 15.260 76239 0.070 3491 15 16.565 25114 0.023 823 16 25.365 8123 0.007 241 17 29.240 23055 0.021 361 18 31.149 54462 0.050 982 19 32.840 7817022 7.200 198515 Total 108562988 100.000 4278910

[0122] Table 2 Detection results of the primary crude product recovered by the method of the present invention

[0123] Detector A 245nm

[0124] Peak No. Compound Name Retention Time Area Area % Height 1 0.966 6373 0.006 130 2 2.089 33857 0.032 9353 3 2.857 1312 0.001 2073 4 3.284 51380 0.049 4474 5 Paracetamol 4.043 95049185 90.940 2198890 6 6.277 89399 0.086 18993 7 6.904 46323 0.044 4935 8 7.589 96488 0.092 9930 9 8.759 8987 0.009 587 10 9.383 28365 0.027 2622 11 10.020 19350 0.019 939 12 11.440 4912834 4.700 909917 13 13.421 9047 0.009 496 14 15.267 66539 0.064 3505 15 16.571 15224 0.015 827 16 25.371 7129 0.007 241 17 29.247 13285 0.013 365 18 31.153 46562 0.045 1020 19 32.861 4017028 3.843 78199 Total 104518667 100.000 3247496

[0125] Table 3 Detection results of the qualified product recovered by the method of the present invention after being stored for 6 months

[0126] Detector A 245nm

[0127] Peak No. Compound Name Retention Time Area Area % Height 1 2.858 1558 0.002 707 2 3.283 8184 0.009 922 3 Paracetamol 4.005 90275748 99.843 1931007 4 5.439 10733 0.012 2467 5 6.254 30773 0.033 2164 6 6.856 31974 0.035 1893 7 10.980 6278 0.007 335 8 12.105 21083 0.023 1036 9 14.346 19073 0.021 926 10 15.132 4884 0.005 214 11 16.671 8036 0.009 333 Total 90417624 100.000 1942004

Claims

1. A method for recovering paracetamol, characterized in that, Selected from any of the following methods: Method 1: When the recycled raw material is paracetamol mother liquor, it includes the following steps: (1) Concentrate the paracetamol mother liquor to 1 / 7 - 1 / 5 of the original volume, cool and crystallize the concentrated mother liquor, and filter to obtain the first crude product of paracetamol; (2) Dissolve the first crude product of paracetamol in water, add a dibasic acid and react until the reaction ends, cool and crystallize the reaction solution, and filter to obtain the second crude product of paracetamol; (3) Dissolve the second crude product of paracetamol, add modified biochar for treatment and filter, concentrate the filtrate to 1 / 2 of the original volume, cool and crystallize the concentrated filtrate, and filter to obtain the qualified product of paracetamol; Method 2: When the recycled raw material is crude paracetamol, it includes the following steps: (1) Dissolve the crude paracetamol in water, add a dibasic acid and react until the reaction ends, cool and crystallize, and filter to obtain the second crude product of paracetamol; (2) Dissolve the second crude product of paracetamol, add modified biochar for treatment and filter, concentrate the filtrate to 1 / 2 of the original volume, cool and crystallize the concentrated filtrate, and filter to obtain the qualified product of paracetamol; The dibasic acid is selected from sulfurous acid, sulfuric acid, oxalic acid, malonic acid, succinic acid, fumaric acid, glutaric acid, adipic acid, phthalic acid, terephthalic acid; the modified biochar is loaded with a reducing agent, and the reducing agent is selected from Na2SO3, FeSO4.

2. The recycling method according to claim 1, characterized in that, The method for cooling and crystallizing the concentrated mother liquor is to cool the concentrated mother liquor at a cooling rate of 1 - 5 °C / min until it is cooled to 5 - 15 °C and keep stirring for 0.5 - 1.5 h.

3. The recovery method according to claim 1, characterized in that, The molar ratio of the dibasic acid to the first crude product of paracetamol or crude paracetamol is 1:10 - 15.

4. The recovery method according to claim 1, wherein The mass ratio of the first crude product of paracetamol or crude paracetamol to water is 1:2 - 5.

5. The recovery method according to claim 4, wherein The mass ratio of the first crude product of paracetamol or crude paracetamol to water is 1:3 - 5.

6. The recycling method according to claim 1, characterized in that, The reaction temperature of the first crude product of paracetamol or crude paracetamol with the dibasic acid is 50 - 90 °C, and the reaction time is 1 - 3 h.

7. The recovery method according to claim 6, characterized in that The reaction temperature of the first crude product of paracetamol or crude paracetamol with the dibasic acid is 50 - 70 °C.

8. The recovery method according to claim 1, wherein The method for cooling and crystallizing the reaction solution is to cool the reaction solution at a cooling rate of 1 - 5 °C / min until it is cooled to 0 - 10 °C and keep stirring for 0.5 - 1.5 h.

9. The recovery method according to claim 1, wherein Dissolve the second crude product of paracetamol in an acetic acid-aqueous solution with an acetic acid mass fraction of 25 - 40% at a mass-to-volume ratio of 1:4 - 6 kg / L.

10. The recovery method according to claim 1, characterized in that, The modified biochar is obtained by impregnating biochar particles with a reducing agent solution of 0.0005 - 0.0015 mol / L.

11. The recycling method according to claim 1, characterized in that, The mass ratio of the modified biochar to the second crude product of paracetamol is 1:8 - 12, and the time for adding the modified biochar to the second crude product of paracetamol for treatment is 1 - 3 h.

12. The recovery method according to claim 11, wherein, The mass ratio of the modified biochar to the second crude product of paracetamol is 1:8 - 11.

9.

13. The recovery method according to claim 1, characterized in that, The method for cooling and crystallizing the concentrated filtrate is to cool the concentrated filtrate at a cooling rate of 1 - 5 °C / min until it is cooled to room temperature and keep stirring for 0.5 - 1.5 h.

14. The recovery method according to claim 1, characterized in that, In Method 1, the paracetamol mother liquor is concentrated to 1 / 6 of the original volume.

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