High purity 2-thiopheneacetic acid and process for its preparation

Abstract

The application discloses high-purity 2-thiopheneacetic acid and a preparation method thereof. The preparation method comprises the following steps: heating 2-thiopheneacetic acid crude product; lowering the temperature of the system to 54-59 DEG C at a speed of 1-3 DEG C / h, adding 2-thiopheneacetic acid crystal seeds with a 2-thiopheneacetic acid content of 99.5-99.9 wt%, and crystallizing for a certain time; continuously lowering the temperature of the system, and crystallizing for a certain time again; discharging mother liquor, continuously raising the temperature of the system to sweating temperature at a speed of 1-5 DEG C / h, and crystallizing for a certain time again; discharging liquid, and obtaining solid; heating and melting the obtained solid; and repeating the crystallization for multiple times, so as to obtain high-purity 2-thiopheneacetic acid. The 2-thiopheneacetic acid product obtained by the application has a 2-thiopheneacetic acid content of greater than or equal to 99.5 wt%, and a yield of greater than 80%. The product has high purity and high yield, meets the requirement of high purity of a pharmaceutical intermediate, and is easy to realize industrial production.

Description

Technical Field

[0001] This invention belongs to the field of chemical separation technology, specifically relating to high-purity 2-thiopheneacetic acid and its preparation method. Background Technology

[0002] 2-Thiopheneacetic acid is a carboxylic acid derivative of thiophene, with the molecular formula C6H6O2S, a molecular weight of 142.18, and a melting point of 63℃~64℃. It is a white or slightly yellow scaly crystalline powder that is soluble in hot water, ethanol, ether, toluene, and carbon tetrachloride.

[0003] 2-Thiopheneacetic acid (2-CAT) is an intermediate in the production of the antibiotics cephalosporins I and II, and is widely used in the pharmaceutical industry. It is also an intermediate in the production of broad-spectrum antibiotics such as cefotaxime, cefotiam, and cefoxitin. Structural modification of the cephalosporin core 7-aminocephalosporanic acid (7-ACA) can enhance the antibacterial activity of these drugs. In recent years, many new cephalosporin antibiotics have been developed abroad using 2-CAT, including ceftriazole, cefenophenaterol, and furazolidone.

[0004] There are many industrial routes for preparing 2-thiopheneacetic acid, but research on methods for preparing high-purity 2-thiopheneacetic acid is limited. Chinese patent CN103992302A discloses a method for preparing 2-chloromethylthiophene using thiophene, hydrochloric acid gas, and formaldehyde, followed by a reaction with trimethylsilane to produce 2-thiopheneacetonitrile, and further hydrolysis and acidification to obtain 2-thiopheneacetic acid. However, this method, due to the selectivity of thiophene at the ortho and meta positions, easily produces byproducts such as 3-thiopheneacetic acid and 2,5-dithiopheneacetic acid, with contents ranging from 1.0% to 2.0%. Furthermore, the boiling points of 3-thiopheneacetic acid and 2-thiopheneacetic acid are close, making purification by distillation and other methods impossible, thus affecting product quality. Chinese patent CN104327040A discloses a method for synthesizing 2-thiopheneacetic acid. Based on the traditional route, it uses concentrated hydrochloric acid instead of hydrochloric acid gas, simplifying the preparation of 2-chloromethylthiophene, improving operational safety, better controlling reaction equilibrium, and reducing the production of 3-chloromethylthiophene and 2,5-dichloromethylthiophene. However, the purity of 2-thiopheneacetic acid after subsequent processing still does not meet the requirements. Chinese patent CN 208218735U discloses a high-efficiency purification device for recrystallization of synthesized 2-thiopheneacetic acid. By connecting multiple thermometers to the device, it better controls the uniform cooling of the solution, improving the separation effect and yield of recrystallization. However, this method uses a large amount of solvent for extraction during crystallization, resulting in high economic and environmental costs, and it also cannot separate 3-thiopheneacetic acid impurities, so the product purity does not meet the requirements.

[0005] Therefore, based on the existing 2-thiopheneacetic acid production routes, it is essential to develop a method for preparing high-purity 2-thiopheneacetic acid, promote technological development in related fields, and enhance the competitiveness of enterprises in the high-quality 2-thiopheneacetic acid market.

[0006] The information disclosed in this background section is intended only to enhance the understanding of the overall background of the invention and should not be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art. Summary of the Invention

[0007] The purpose of this invention is to provide high-purity 2-thiopheneacetic acid and its preparation method. The prepared product has a 2-thiopheneacetic acid content of ≥99.5wt%, a yield of greater than 80%, high purity, and high yield, and can be used for industrial production.

[0008] To achieve the above objectives, a specific embodiment of the present invention provides the following technical solution:

[0009] A method for preparing high-purity 2-thiopheneacetic acid includes the following steps:

[0010] S1. Take crude 2-thiopheneacetic acid and heat it;

[0011] S2. Cool the system temperature to 54-59℃ at a rate of 1-3℃ / h, add 2-thiopheneacetic acid seed crystals with a content of 99.5-99.9wt%, and grow crystals for a certain period of time.

[0012] S3. Continue to cool the system and allow it to grow crystals for a certain period of time.

[0013] S4. Discharge the mother liquor, continue to raise the system temperature to the sweating temperature at a rate of 1-5℃ / h, continue to grow crystals for a certain period of time, discharge the liquid, and obtain the solid.

[0014] S5. Melt the resulting solid by heating;

[0015] S6. Repeat steps S2 to S5 to obtain high-purity 2-thiopheneacetic acid.

[0016] In one or more embodiments of the present invention, in step S1, the system is heated to 65-70°C and kept at a constant temperature for 0.5-1 hour.

[0017] In one or more embodiments of the present invention, in step S2, seed crystals are added at a mass of 0.2% to 2.0% of the crude 2-thiopheneacetic acid.

[0018] In one or more embodiments of the present invention, in step S2, the crystal growth time is 0.5 to 1 hour.

[0019] In one or more embodiments of the present invention, step S3 is: cooling the system temperature to 52-58°C at a rate of 0.5-2°C / h, and continuing crystal growth for 1-3 hours.

[0020] In one or more embodiments of the present invention, in step S4, the system temperature is raised to 56-60°C to induce sweating; and / or,

[0021] In step S4, continue to nourish the crystals for 0.5 to 2 hours after sweating.

[0022] In one or more embodiments of the present invention, in step S5, the temperature at which the solid is heated to melt is 65-70°C.

[0023] In one or more embodiments of the present invention, in step S6, steps S2 to S5 are repeated at least twice.

[0024] In one or more embodiments of the present invention, the crude 2-thiopheneacetic acid contains 90.0 to 99.0 wt% 2-thiopheneacetic acid and 0.5 to 10.0 wt% individual impurities.

[0025] The technical solution provided by a specific embodiment of the present invention is as follows:

[0026] A high-purity 2-thiopheneacetic acid is prepared by the above-described method for preparing high-purity 2-thiopheneacetic acid.

[0027] Compared with existing technologies, the preparation method of this invention can be used to separate and purify crude 2-thiopheneacetic acid containing multiple impurities. By combining segmented crystal growth and repeated crystallization, while controlling the cooling and heating rates during the preparation process, and using high-purity seed crystals, a high-purity and high-yield 2-thiopheneacetic acid product is obtained. The resulting product contains ≥99.5 wt% 2-thiopheneacetic acid, ≤0.1 wt% of individual impurities (i.e., ≤0.1 wt% 3-thiopheneacetic acid, ≤0.1 wt% 2,5-thiophenediacetic acid, and ≤0.1 wt% of individual unknown impurities), and ≤0.3 wt% of total impurities. The preparation process achieves efficient separation of 2-thiopheneacetic acid from impurities without the need for additional organic solvents, making the operation simpler, and eliminating environmental pollution and the generation of other impurities and waste. It meets green environmental protection requirements and has high industrial application value. Detailed Implementation

[0028] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0029] A specific embodiment of the present invention provides a method for preparing high-purity 2-thiopheneacetic acid, comprising the following steps 1-6.

[0030] Step 1: Take crude 2-thiopheneacetic acid and heat it.

[0031] Specifically, crude 2-thiopheneacetic acid is added to the crystallizer. The crude 2-thiopheneacetic acid contains 90.0–99.0 wt% 2-thiopheneacetic acid and individual impurities ranging from 0.5–10.0 wt%. The system temperature is raised to 65–70°C and kept at this temperature for 0.5–1 hour to allow the 2-thiopheneacetic acid to fully melt.

[0032] Step 2: Cool the system temperature to 54-59℃ at a rate of 1-3℃ / h, add 2-thiopheneacetic acid seed crystals with a content of 99.5-99.9wt%, and grow crystals for a certain period of time.

[0033] Specifically, uniform cooling at a specific rate can reduce the occurrence of micro-crystals or irregularly shaped crystals, ensuring consistency in crystal morphology and size, while also reducing impurity adsorption. Seed crystals with a 2-thiopheneacetic acid content of 99.5–99.9 wt% and a single impurity content of <0.1 wt% are selected. The seed crystals are added at a mass of 0.2%–2.0% of the crude 2-thiopheneacetic acid, and the crystal growth time is 0.5–1 hour. Adding seed crystals can induce crystal nucleation and growth. Furthermore, selecting high-purity, homogeneous 2-thiopheneacetic acid seed crystals can yield a product with uniform particle size distribution, few fine crystals, and good crystal morphology.

[0034] Step 3: Continue to cool the system temperature and allow it to grow crystals for a certain period of time.

[0035] Specifically, the system temperature is lowered to 52–58°C at a rate of 0.5–2°C / h, and crystal growth continues for 1–3 hours. Crystal growth through different temperature gradients promotes crystal nucleation and growth, and ensures that the crystals have good morphology and purity.

[0036] Step 4: Drain the mother liquor, continue to raise the system temperature to the sweating temperature at a rate of 1-5℃ / h, continue to grow crystals for a certain period of time, drain the liquid, and obtain the solid.

[0037] Specifically, draining the mother liquor to remove some impurities and then raising the temperature to induce sweating can preferentially melt the crystals containing impurities. Then, continuing to grow crystals for 0.5 to 2 hours can further improve the product yield.

[0038] Step 5: Heat and melt the solid obtained in step 4.

[0039] Specifically, after draining the mother liquor, the system temperature is raised to 65-70°C to melt the solid.

[0040] Step 6: Repeat steps 2 to 5 to obtain high-purity 2-thiopheneacetic acid.

[0041] Specifically, steps 2 through 5 are repeated for repeated crystallization. Combining segmented crystal growth with repeated crystallization yields high-purity and high-yield 2-thiopheneacetic acid. To further improve the purity of the 2-thiopheneacetic acid product, steps 2 through 5 are repeated at least twice.

[0042] Another specific embodiment of the present invention provides high-purity 2-thiopheneacetic acid, which is prepared by the above-described method for preparing high-purity 2-thiopheneacetic acid.

[0043] The present invention will be further described in detail below with reference to specific embodiments. In the present invention, the yield of 2-thiopheneacetic acid product is calculated as follows: (mass of product × content of product - mass of seed crystals × content of seed crystals) / (mass of crude product × content of crude product) × 100%.

[0044] Example 1

[0045] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0046] S1. Add 50.0g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 96.0wt% 2-thiopheneacetic acid, 3.2wt% impurities, and 0.8wt% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 70℃ and let it stand at a constant temperature for 0.5h.

[0047] S2. Adjust the temperature inside the crystallizer and control the cooling rate to 2℃ / h. Cool the temperature uniformly to 58℃, add 0.5g of 99.7% 2-thiopheneacetic acid seed crystals to the crystallizer, and maintain the temperature for 1h.

[0048] S3. Adjust the temperature inside the crystallizer, control the cooling rate to 1℃ / h, and cool down to 55℃ at a uniform rate. Continue crystal growth for 3 hours.

[0049] S4. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 5℃ / h, and heat it uniformly to 60℃ to induce sweating. Continue to grow crystals at a constant temperature for 1.5h, then discharge the liquid from the crystallizer to obtain a solid.

[0050] S5. Rapidly raise the temperature inside the crystallizer to 68°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 99.3 wt%, the total impurity content is 0.4 wt%, and the water content is 0.3 wt%.

[0051] S6. After repeating steps S2 to S5 three times for crystallization, 43.0 g of 2-thiopheneacetic acid product was obtained, with a single batch yield of 88.27%. Analysis showed that the product contained 99.7 wt% 2-thiopheneacetic acid, ≤0.1 wt% single impurity, 0.2 wt% total impurities, and 0.1 wt% water.

[0052] Example 2

[0053] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0054] S1. Add 54.5g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 95.0wt% 2-thiopheneacetic acid, 4.3wt% impurities, and 0.7wt% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 68℃ and let it stand at a constant temperature for 1 hour.

[0055] S2. Adjust the temperature inside the crystallizer and control the cooling rate to 2.5℃ / h. Cool the temperature uniformly to 56℃, add 0.6g of 99.6% 2-thiopheneacetic acid seed crystals to the crystallizer, and maintain the temperature for 1 hour to grow crystals.

[0056] S3. Adjust the temperature inside the crystallizer and control the cooling rate to 2℃ / h. Cool down to 53℃ at a uniform rate and continue crystal growth for 2.5h.

[0057] S4. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 3℃ / h, and heat the temperature to 58℃ at a uniform rate to induce sweating. Continue to grow crystals at a constant temperature for 2 hours, then discharge the liquid from the crystallizer and separate the solid.

[0058] S5. Rapidly raise the temperature inside the crystallizer to 67°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 99.2 wt%, the total impurity content is 0.5 wt%, and the water content is 0.3 wt%.

[0059] S6. After repeating steps S2 to S5 four times for crystallization, 46.8 g of 2-thiopheneacetic acid product was obtained, with a single batch yield of 88.78%. Analysis showed that the product contained 99.5 wt% 2-thiopheneacetic acid, ≤0.1 wt% single impurity, 0.3 wt% total impurities, and 0.2 wt% water.

[0060] Example 3

[0061] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0062] S1. Add 55.0g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 97.5wt% 2-thiopheneacetic acid, 1.7wt% impurities, and 0.8wt% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 66℃ and let it stand at a constant temperature for 0.5h.

[0063] S2. Adjust the temperature inside the crystallizer and control the cooling rate to 3℃ / h. Cool the temperature uniformly to 54℃, add 0.7g of 99.8% 2-thiopheneacetic acid seed crystals to the crystallizer, and maintain the temperature for 0.5h.

[0064] S3. Adjust the temperature inside the crystallizer, control the cooling rate to 1℃ / h, and cool down to 52℃ at a uniform rate. Continue crystal growth for 2 hours.

[0065] S4. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 4℃ / h, and uniformly heat to 60℃ to induce sweating. Continue to grow crystals at a constant temperature for 1 hour, then discharge the liquid from the crystallizer and separate the solid.

[0066] S5. Rapidly raise the temperature inside the crystallizer to 68°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 99.4 wt%, the total impurity content is 0.4 wt%, and the water content is 0.2 wt%.

[0067] S6. After repeating steps S2 to S5 and undergoing secondary crystallization, 49.0 g of 2-thiopheneacetic acid product was obtained, with a single batch yield of 89.89%. Testing revealed that the product contained 99.8% 2-thiopheneacetic acid, with no single impurity exceeding 0.1%, total impurities at 0.1%, and a water content of 0.1%.

[0068] Example 4

[0069] The only difference between this embodiment and Example 1 is that the mass fraction of 2-thiopheneacetic acid in the 2-thiopheneacetic acid seed crystals is 99.5%.

[0070] During the preparation process, a sample was taken for testing in step S5. The sample contained 99.2 wt% 2-thiopheneacetic acid, 0.5 wt% total impurities, and 0.3 wt% water.

[0071] The final product obtained in this example was 43.0 g, with a single-batch yield of 88.19%. Testing revealed that the product contained 99.6 wt% 2-thiopheneacetic acid, ≤0.1 wt% single impurities, 0.2 wt% total impurities, and 0.2 wt% water.

[0072] Example 5

[0073] The only difference between this embodiment and Embodiment 1 is that the cooling rate in step S2 is 1℃ / h.

[0074] During the preparation process, a sample was taken for testing in step S5. The sample contained 99.3 wt% 2-thiopheneacetic acid, 0.5 wt% total impurities, and 0.2 wt% water.

[0075] The final product obtained in this example was 43.2g, with a single-batch yield of 88.78%. Testing revealed that the product contained 99.8wt% 2-thiopheneacetic acid, ≤0.1wt% of a single impurity, 0.1wt% of total impurities, and 0.1wt% of water.

[0076] Example 6

[0077] The only difference between this embodiment and Embodiment 1 is that the cooling rate in step S3 is 0.5℃ / h.

[0078] During the preparation process, a sample was taken for testing in step S5. The sample contained 99.4 wt% 2-thiopheneacetic acid, 0.4 wt% total impurities, and 0.2 wt% water.

[0079] The final product obtained in this example was 40.5g, with a single-batch yield of 83.08%. Testing revealed that the product contained 99.7wt% 2-thiopheneacetic acid, ≤0.1wt% of a single impurity, 0.2wt% of total impurities, and 0.1wt% of water.

[0080] Example 7

[0081] The only difference between this embodiment and Embodiment 1 is that the cooling rate in step S3 is 5℃ / h.

[0082] During the preparation process, a sample was taken for testing in step S5. The sample contained 99.3 wt% 2-thiopheneacetic acid, 0.4 wt% total impurities, and 0.3 wt% water.

[0083] The final product obtained in this example was 40.0 g, with a single-batch yield of 82.13%. Testing revealed that the product contained 99.8 wt% 2-thiopheneacetic acid, ≤0.1 wt% single impurities, 0.1 wt% total impurities, and 0.1 wt% water.

[0084] Example 8

[0085] The only difference between this embodiment and Embodiment 1 is that the operations of steps S2 to S5 are repeated once in step S6.

[0086] During the preparation process, a sample was taken for testing in step S5. The sample contained 99.3 wt% 2-thiopheneacetic acid, 0.3 wt% total impurities, and 0.4 wt% water.

[0087] The final product obtained in this example was 46.0 g, with a single-batch yield of 94.32%. Testing revealed that the product contained 99.5 wt% 2-thiopheneacetic acid, ≤0.2 wt% single impurities, 0.3 wt% total impurities, and 0.2 wt% water.

[0088] Comparative Example 1

[0089] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0090] S1. Add 30.0g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 96.0wt% 2-thiopheneacetic acid, 3.0wt% impurities, and 1.0wt% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 65℃ and let it stand at a constant temperature for 0.5h.

[0091] S2. Adjust the temperature inside the crystallizer and control the cooling rate to 2℃ / h. Cool the temperature uniformly to 58℃, add 0.3g of 99.8% 2-thiopheneacetic acid seed crystals to the crystallizer, and maintain the temperature for 0.5h.

[0092] S3. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 4℃ / h, and uniformly heat the temperature to 60℃ to induce sweating. Continue to grow crystals at a constant temperature for 1 hour, then discharge the liquid from the crystallizer and separate the solid.

[0093] S4. Rapidly raise the temperature inside the crystallizer to 68°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 98.0 wt%, the total impurity content is 1.8 wt%, and the water content is 0.2 wt%.

[0094] S5. After repeating steps S2 to S4 and undergoing secondary crystallization, 23.7 g of 2-thiopheneacetic acid product was obtained, with a single-batch yield of 80.43%. Analysis showed that the product contained 99.0 wt% 2-thiopheneacetic acid, ≤0.3 wt% single impurities, 0.9 wt% total impurities, and 0.1 wt% water.

[0095] Comparative Example 2

[0096] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0097] S1. Add 31.8g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 95.4% 2-thiopheneacetic acid, 3.8% impurities, and 0.8% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 68℃ and let it stand at a constant temperature for 0.5h.

[0098] S2. Adjust the temperature inside the crystallizer, control the cooling rate to 2℃ / h, cool down to 58℃ at a uniform rate, and maintain the temperature for crystal growth for 3 hours.

[0099] S3. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 3℃ / h, and uniformly heat to 60℃ to induce sweating. Continue to grow crystals at a constant temperature for 1 hour, then discharge the liquid from the crystallizer and separate the solid.

[0100] S4. Rapidly raise the temperature inside the crystallizer to 68°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 96.5 wt%, the total impurity content is 3.0 wt%, and the water content is 0.5 wt%.

[0101] S5. After repeating steps S2 to S4 and undergoing secondary crystallization, 27.0 g of 2-thiopheneacetic acid product was obtained, with a single-batch yield of 86.77%. Analysis showed that the product contained 97.5 wt% 2-thiopheneacetic acid, ≤0.5 wt% single impurities, 2.2 wt% total impurities, and 0.3 wt% water.

[0102] Comparative Example 3

[0103] The preparation method of high-purity 2-thiopheneacetic acid is as follows:

[0104] S1. Add 61.5g of crude 2-thiopheneacetic acid to the crystallizer. The crude product contains 95.8wt% 2-thiopheneacetic acid, 3.8wt% impurities, and 0.4wt% water. Use a combined heating and cooling unit to control the temperature inside the crystallizer at 69℃ and let it stand at a constant temperature for 0.5h.

[0105] S2. Adjust the temperature inside the crystallizer and control the cooling rate to 2℃ / h. Cool the temperature uniformly to 55℃, add 0.8g of 99.6% 2-thiopheneacetic acid seed crystals to the crystallizer, and maintain the temperature for 1h.

[0106] S3. Adjust the temperature inside the crystallizer, control the cooling rate to 1℃ / h, and cool down to 55℃ at a uniform rate. Continue crystal growth for 3 hours.

[0107] S4. Discharge the mother liquor from the crystallizer, adjust the temperature inside the crystallizer, control the heating rate to 5℃ / h, and heat it to 58℃ at a uniform rate to induce sweating. Discharge the liquid from the crystallizer and separate the solid.

[0108] S5. Rapidly raise the temperature inside the crystallizer to 70°C to melt the solid inside the crystallizer. Take a sample for testing. The 2-thiopheneacetic acid content in the sample is 98.8 wt%, the total impurity content is 0.8 wt%, and the water content is 0.4 wt%.

[0109] S6. After repeating steps S2 to S5 and undergoing secondary crystallization, 50.0 g of 2-thiopheneacetic acid product was obtained, with a single batch yield of 82.92%. Analysis showed that the product contained 99.3 wt% 2-thiopheneacetic acid, ≤0.3 wt% single impurities, 0.6 wt% total impurities, and 0.1 wt% water.

[0110] Comparative Example 4

[0111] The only difference between this comparative example and Example 1 is that the mass fraction of 2-thiopheneacetic acid in the 2-thiopheneacetic acid seed crystals is 98.5%.

[0112] During the preparation process, a sample was taken for testing in step S5. The sample contained 98.5 wt% 2-thiopheneacetic acid, 1.15 wt% total impurities, and 0.35 wt% water.

[0113] The final product obtained in this comparative example was 44.0 g, with a single-batch yield of 89.54%. Testing revealed that the product contained 98.8 wt% 2-thiopheneacetic acid, ≤0.5 wt% single impurities, 1.0 wt% total impurities, and 0.2 wt% water.

[0114] Comparative Example 5

[0115] The only difference between this comparative example and Example 1 is that the cooling rate in step S2 is 6°C / h.

[0116] During the preparation process, a sample was taken for testing in step S5. The sample contained 98.6 wt% 2-thiopheneacetic acid, 1.2 wt% total impurities, and 0.2 wt% water.

[0117] The final product obtained in this comparative example was 40.0 g, with a single-batch yield of 81.63%. Testing revealed that the product contained 99.2 wt% 2-thiopheneacetic acid, ≤0.3 wt% single impurities, 0.6 wt% total impurities, and 0.2 wt% water.

[0118] Comparative Example 6

[0119] The only difference between this comparative example and Example 1 is that the heating rate in step S4 is 8°C / h.

[0120] During the preparation process, a sample was taken for testing in step S5. The sample contained 98.7 wt% 2-thiopheneacetic acid, 0.9 wt% total impurities, and 0.4 wt% water.

[0121] The final product obtained in this comparative example was 41.0 g, with a single-batch yield of 83.69%. Testing revealed that the product contained 99.2% 2-thiopheneacetic acid, ≤0.3% of a single impurity, 0.7% of total impurities, and 0.1% water.

[0122] Based on Comparative Examples 1-4 and Examples 1-4, it can be seen that by using seed crystals of a certain purity for crystal growth and performing multiple crystal growths in segments, a high-purity product with a 2-thiopheneacetic acid content ≥99.5wt% can be obtained, with individual impurities ≤0.1wt% and total impurities ≤0.3wt%.

[0123] As can be seen from Examples 1, 5 and Comparative Example 5, the cooling rate in step S2 affects the purity and yield of the final product. Exceeding the cooling rate specified in this invention will reduce the purity and yield of the final product.

[0124] Based on Examples 1, 6 and 7, it can be seen that the cooling rate in step S3 has little impact on the purity of the final product, but mainly affects the yield of the final product. If the cooling rate is too fast, it is easy to reduce the yield of the final product.

[0125] Combining Examples 1 and 8, the number of repeated crystallizations affects both the purity and yield of the final product. The higher the number of repeated crystallizations, the better it is to obtain a 2-thiopheneacetic acid product with higher purity, but the yield will decrease at the same time.

[0126] In conjunction with Example 1 and Comparative Example 6, if the heating rate during sweating in step S4 is too fast, it can easily reduce the purity and yield of the final product. Adjusting the crystallizer temperature with the heating rate specified in this invention helps to obtain a high-purity and high-yield 2-thiopheneacetic acid product.

[0127] In summary, this invention combines segmented crystal growth with repeated crystallization, while simultaneously controlling the cooling rate, heating rate, and seed purity during the preparation process, to obtain a high-purity and high-yield 2-thiopheneacetic acid product with few impurities. The preparation process avoids the use of organic solvents, making it green and environmentally friendly, and possessing high industrial application value.

[0128] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No markings in the claims should be construed as limiting the scope of the claims.

[0129] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A method for preparing 2-thiopheneacetic acid, characterized in that, Includes the following steps: S1. Take crude 2-thiopheneacetic acid and heat it; S2. Cool the system temperature to 54-59℃ at a rate of 1-3℃ / h, add 2-thiopheneacetic acid seed crystals with a content of 99.5-99.9wt%, and grow crystals for a certain period of time. S3. Continue to cool the system and allow it to grow crystals for a certain period of time. S4. Discharge the mother liquor, continue to raise the system temperature to the sweating temperature at a rate of 1~5℃ / h, continue to grow crystals for a certain period of time, discharge the liquid, and obtain the solid. S5. Melt the resulting solid by heating; S6. Repeat steps S2 to S5 to obtain high-purity 2-thiopheneacetic acid; In step S1, the system is heated to 65~70℃ and kept at a constant temperature for 0.5~1h; In step S2, seed crystals are added at a mass of 0.2% to 2.0% of the crude 2-thiopheneacetic acid, and the crystal growth time is 0.5 to 1 hour. Step S3 is: cool the system temperature to 52-58℃ at a rate of 0.5-2℃ / h, and continue crystal growth for 1-3 hours; In step S4, the system temperature is raised to 56~60℃ to induce sweating; after sweating, crystal growth continues for 0.5~2 hours.

2. The method for preparing 2-thiopheneacetic acid according to claim 1, characterized in that, In step S5, the temperature for heating and melting the solid is 65~70℃.

3. The method for preparing 2-thiopheneacetic acid according to claim 1, characterized in that, In step S6, steps S2 to S5 are repeated at least twice.

4. The method for preparing 2-thiopheneacetic acid according to claim 1, characterized in that, The crude 2-thiopheneacetic acid contains 90.0–99.0 wt% 2-thiopheneacetic acid and 0.5–10.0 wt% individual impurities.