Preparation process of m-(beta-hydroxyethyl sulfone) aniline
A novel process involving thiolization condensation, oxidation, and hydrogenation reduction has solved the problems of low yield and severe pollution in the existing synthesis of m-(β-hydroxyethyl sulfone)aniline, achieving high-yield, high-purity, and environmentally friendly preparation of m-(β-hydroxyethyl sulfone)aniline.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHEJIANG KEYONG CHEM CO LTD
- Filing Date
- 2025-12-31
- Publication Date
- 2026-04-21
AI Technical Summary
The existing synthesis process of m-(β-hydroxyethyl sulfone)aniline has problems such as low product yield and environmental pollution, especially in the chlorosulfonation, condensation and reduction stages, which generate a large amount of wastewater and pollutants, and the cost is high.
A novel process involving mercaptolation condensation, oxidation, and hydrogenation reduction was employed, using 2-mercaptoethanol as the condensing agent, hydrogen peroxide as the oxidizing agent, and palladium on carbon as the hydrogenation catalyst. Starting with m-nitrochlorobenzene, this process avoids the high pollution associated with traditional processes, controls reaction conditions, and improves product yield and purity.
This method achieves high yield and high purity of m-(β-hydroxyethyl sulfone)aniline, reducing emissions of waste, environmental pollution, and production costs, and improving economic efficiency.
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Abstract
Description
Technical Field
[0001] This invention relates to a process for preparing m-(β-hydroxyethyl sulfone)aniline. Background Technology
[0002] m-(β-hydroxyethyl sulfone)aniline is an important intermediate for vinyl sulfone-type reactive dyes, mainly used in the production of reactive KN-R, reactive KN-B, and reactive turquoise blue KN-G. Compared with other types of reactive dyes, vinyl sulfone-type reactive dyes have the following advantages: Vinyl sulfone-type reactive dyes are mostly available in commercial form as β-sulfate ethyl sulfone (β-S... -C C -S -R), this group is well soluble in water; under alkaline conditions, the sulfate group is removed to form a vinyl sulfone group (-S). -C C -), at this point, the water solubility of the dye decreases sharply, and it turns into a fiber-friendly active group. Subsequently, this group will undergo a nucleophilic addition reaction with cellulose fibers to form a stable covalent bond. Even in a washing solution containing 10% sodium perborate oxidant at 95°C, the dyed fabric still shows good fastness.
[0003] Currently, m-(β-hydroxyethyl sulfone)aniline is produced from nitrobenzene as raw material through chlorosulfonation, sulfonyl chloride reduction, condensation, and iron powder reduction (hydrogenation reduction). In the chlorosulfonation stage, a large amount of chlorosulfonic acid must be used to increase the yield, generating a large amount of sulfuric acid wastewater that is difficult to recover and corrodes equipment. In the condensation stage, ethylene oxide or chloroethanol is used as the condensing agent. However, ethylene oxide or chloroethanol is easily hydrolyzed at high temperatures, resulting in low purity and low yield of the condensation product. Using excessive amounts of condensing agent increases costs. In the reduction stage, although using iron powder as the reducing agent can achieve a higher yield, a large amount of iron sludge is generated after the reaction, which is difficult to handle and causes serious environmental pollution.
[0004] In summary, the current synthesis process of m-(β-hydroxyethyl sulfone)aniline has the disadvantages of low product yield, environmental pollution, and lack of green and environmental protection.
[0005] Therefore, there is a need for a method that is low-cost, simple in process, mild in reaction conditions, clean and pollution-free, and has high yield and high purity. Summary of the Invention
[0006] To address the aforementioned problems, this invention provides a novel process for producing m-(β-hydroxyethyl sulfone)aniline that is low-cost, simple in process flow, mild in reaction conditions, clean and pollution-free, and yields and purifies high-quality products.
[0007] A method for preparing m-(β-hydroxyethyl sulfone)aniline includes the following steps: (1) Using m-nitrochlorobenzene as the starting material and 2-mercaptoethanol as the thiolation condensing agent, m-nitrophenyl-β-hydroxyethyl sulfide was obtained by thiolation condensation reaction; (2) Using hydrogen peroxide as an oxidant, the m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (1) is oxidized to obtain m-nitrophenyl-β-hydroxyethyl sulfone. (3) The m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (2) is hydrogenated to obtain m-(β-hydroxyethyl sulfone)aniline.
[0008] The thiolization condensation reaction of m-nitrochlorobenzene and mercaptoethanol described in step (1) of this invention is generally carried out in an organic solvent in the presence of a catalyst and an acid-binding agent.
[0009] In some embodiments, the catalyst in step (1) is cuprous iodide, cuprous bromide, or a mixture of both. Further, the amount of catalyst used is 0.1%-10% of m-nitrochlorobenzene, preferably 0.5%-2.0%, more preferably 1-2%.
[0010] In some embodiments, the acid-absorbing agent mentioned in step (1) is at least one of sodium carbonate, sodium bicarbonate, ammonia, and liquid alkali (sodium hydroxide with a mass concentration of 32%-100%), preferably liquid alkali (32%-48%), especially liquid alkali (48%). Further, the molar ratio of intermediate nitrochlorobenzene to acid-absorbing agent in step (1) is 1:1.0-2.0, preferably 1:1.01-1.05.
[0011] In some embodiments, the solvent mentioned in step (1) is DMF ( N , N -dimethylformamide), DMAC ( N , N At least one of dimethylacetamide (DMSO), preferably DMAC or DMF or a mixture of both. Further, the mass of the solvent used in step (1) is 2-10 times, preferably 4-6 times, the mass of m-nitrochlorobenzene.
[0012] In some embodiments, the molar ratio of intermediate nitrochlorobenzene to mercaptoethanol in step (1) is 1:1.0-2.0, preferably 1:1.05-1.25.
[0013] In some embodiments, the reaction temperature of the thiolization condensation reaction in step (1) is 0-50°C, preferably 20-30°C.
[0014] As a preferred embodiment, step (1) is specifically performed as follows: In the reaction apparatus, an organic solvent and m-nitrochlorobenzene are added and dissolved, then a catalyst is added. The temperature is then controlled at 0-50°C (more preferably 20-30°C) while simultaneously adding a ferric sulfate and 2-mercaptoethanol. The addition is completed within 1-8 hours (more preferably 2-4 hours), and the reaction is continued at this temperature for 0-6 hours (preferably 1-2 hours). After the reaction, excess ferric sulfate is neutralized to obtain a neutralized solution. The neutralized solution is then post-treated to obtain m-nitrophenyl-β-hydroxyethyl sulfide. Further, the post-treatment is performed as follows: the neutralized solution is distilled to remove a portion of wastewater, then the solvent is recovered by distillation (this solvent can be reused). Water is then added for cooling and crystallization. After filtration to separate the mother liquor, the solution is washed with water to obtain m-nitrophenyl-β-hydroxyethyl sulfide. Even further, after recovering the solvent, the crystallization temperature is controlled at 0-30°C, preferably 5-20°C. Furthermore, the washing agent is water, with the water mass being 1-10 times the mass of the crystalline solid, preferably 2-4 times. The washing water can be reused as the base water for crystallization.
[0015] In step (2) of the present invention, hydrogen peroxide is used as an oxidant, and m-nitrophenyl-β-hydroxyethyl sulfone is oxidized to obtain m-nitrophenyl-β-hydroxyethyl sulfone. The oxidation reaction is preferably carried out in an aqueous solvent under the action of a catalyst.
[0016] In some embodiments, the catalyst in step (2) is sodium tungstate. Further, the mass of the catalyst added is 0.1% to 1.0% of the mass of m-nitrophenyl-β-hydroxyethyl sulfide, preferably 0.1% to 0.6%.
[0017] In some embodiments, the molar ratio of H2O2 in the hydrogen peroxide to m-nitrophenyl-β-hydroxyethyl sulfide in step (2) is 2.0-3.0, preferably 2.05-2.25.
[0018] In some embodiments, the mass of the aqueous solvent in step (2) is 1-20 times, preferably 3-5 times, the mass of m-nitrophenyl-β-hydroxyethyl sulfide.
[0019] In some embodiments, the oxidation reaction temperature in step (2) is controlled at 50-105°C, preferably 95-100°C.
[0020] As a preferred embodiment, step (2) is specifically performed as follows: Bottom water, the m-nitrophenyl-β-hydroxyethyl sulfide obtained in step (1), and catalyst are added to the oxidation reactor. Hydrogen peroxide is added dropwise while controlling the temperature at 50-105℃ (more preferably 95-100℃). After the addition is complete, the reaction is maintained at this temperature. After sufficient reaction, the oxidation reaction material is obtained. The solid m-nitrophenyl-β-hydroxyethyl sulfone and the mother liquor are separated by cooling and crystallization. Further, the hydrogen peroxide addition time is controlled at 1-10 h, preferably 2-4 h. Further, the reaction time after the addition is maintained at this temperature is 0-6 h, preferably 1-2 h. Further, the cooling and crystallization temperature in step (3) is controlled at 0-30℃, preferably 5-30℃. Further, the mother liquor separated in step (2) is adsorbed by activated carbon, dehydrated, and then returned to step (2) as bottom water. The activated carbon used for adsorption is powdered carbon, granular carbon, etc., preferably granular carbon.
[0021] In step (3) of this invention, m-nitrophenyl-β-hydroxyethyl sulfone is hydrogenated to obtain m-(β-hydroxyethyl sulfone)aniline. This reaction is generally carried out in a reaction solvent under the action of a hydrogenation catalyst.
[0022] In some embodiments, the reaction solvent in step (3) is at least one of methanol, ethanol, propanol, water, etc., preferably methanol or ethanol.
[0023] In some embodiments, the hydrogenation catalyst in step (3) is selected from at least one of Raney nickel, nickel support, palladium on carbon, platinum on carbon, etc., preferably palladium on carbon. Further, the mass of the added hydrogenation catalyst is 0.5%-10% of the mass of m-nitrophenyl-β-hydroxyethyl sulfone, preferably 0.8%-1.5%.
[0024] In some embodiments, in step (3), the hydrogenation reduction temperature is controlled at 50-160℃, preferably 80-100℃; the hydrogen pressure is controlled at 0.5-5.0 MPa, preferably 1.5-2.5 MPa. The hydrogenation reduction reaction time is generally until the pressure inside the reactor becomes constant and no longer decreases.
[0025] As a preferred embodiment, step (3) is specifically performed as follows: a reaction solvent, the solid m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (2), and a hydrogenation catalyst are added to a reduction reaction apparatus, and hydrogen is passed through to carry out a reduction reaction to obtain a reducing solution; the hydrogenation catalyst is separated from the reducing solution by sedimentation, and after the solvent is removed, water is added to crystallize to obtain a solid, which is further washed with water and dried to obtain the m-(β-hydroxyethyl sulfone)aniline product. Furthermore, the hydrogenation catalyst in step (3) is reused after separation, the solvent can be reused in step (3) after removal, and the washing water can be returned to be used as the bottom water in step (2).
[0026] Compared with existing technologies, the novel process for preparing m-(β-hydroxyethyl sulfone)aniline described in this invention has the following advantages: (1) The heavily polluting and dangerous processes such as chlorination and sulfonation, sub-reduction and ethylene oxide condensation were eliminated. After adjusting to the thiolization condensation and re-oxidation process, the condensation conditions are mild and controllable, the oxidation process is safe, there are almost no reaction impurities, the amount of waste is effectively controlled, and there is almost no loss in yield. It is environmentally friendly and efficient.
[0027] (2) The reduction process replaces the traditional iron powder with hydrogenation reduction, which increases the product yield by at least 5%, and the reaction products do not pollute the environment. It is energy-saving and environmentally friendly, and has significant economic and social benefits. Attached Figure Description
[0028] Figure 1 This is a typical process flow diagram of the present invention. Detailed Implementation
[0029] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.
[0030] Example 1
[0031] (1) Add 250g of DMAC and 0.5g of cuprous iodide to a 500ml flask and start stirring. Then add 50g of m-nitrochlorobenzene, stir to dissolve, and cool to 25℃. At the same time, add 30.10g of mercaptoethanol and 41.20g of 32% liquid alkali. Under controlled temperature conditions, add the two groups of materials dropwise over 3 hours. After the addition is complete, continue to keep the temperature for 1 hour to end the reaction. Neutralize the excess acetic acid agent with 32% hydrochloric acid to obtain a neutralized solution.
[0032] (2) The neutralized liquid obtained in step (1) was distilled to remove a small amount of water, and then distilled again to recover 235.6g of DMAC. The remaining material was mixed with 150g of water, stirred and cooled to crystallize. After cooling to 15℃, it was filtered, rinsed with 150g of water and dried to obtain 62.17g of solid m-nitrophenyl-β-hydroxyethyl sulfide. The content was tested to be 99.60%, the purity was 99.56%, and the yield was calculated to be 98.51%.
[0033] (3) Add 240.50g of water, 60g of solid m-nitrophenyl-β-hydroxyethyl sulfide, and 0.30g of sodium tungstate to the oxidation reactor. While stirring, heat to 98℃ and start adding 83.11g of 27% hydrogen peroxide dropwise for about 2 hours. After the addition is completed, continue to keep the reaction at the temperature for 1 hour. Then cool down to 30℃ to crystallize. The mother liquor of crystallization is reused after being adsorbed by activated carbon. The crystallized solid is washed with a small amount of water and dried to obtain 68.97g of solid m-nitrophenyl-β-hydroxyethyl sulfone. The content is tested to be 99.61%, the purity is 99.76%, and the yield is 99.03%.
[0034] (4) Add 270g of methanol to the hydrogenation reduction reactor, then add 67g of solid m-nitrophenyl-β-hydroxyethyl sulfone, and add 0.54g of palladium on carbon catalyst (provided by Johnson Matthey Catalysts Ltd., 5% palladium on carbon). Introduce hydrogen gas and heat to 90℃ for reduction reaction. Control the pressure to maintain at 1.5-2.0 MPa. After the total reaction time is about 33min, the pressure becomes constant and no longer decreases. Continue to keep the reaction at the temperature for 5min, then cool down and open the reactor. After filtering and separating the catalyst, remove the solvent from the mother liquor, add water for crystallization and filter. After filtration, washing with water, and drying the solid, 57.67g of m-(β-hydroxyethyl sulfone)aniline product is obtained. The content is tested to be 99.57%, the purity is 99.67%, the yield is 98.89%, and the total yield of the three steps is 96.47%.
[0035] Example 2
[0036] (1) Add 250g of DMF and 1g of cuprous bromide to a 500ml flask, start stirring, then add 50g of m-nitrochlorobenzene, stir to dissolve, and then cool to 20℃. At the same time, add 30.10g of mercaptoethanol and 27.47g of 48% liquid alkali. Under controlled temperature conditions, add the two groups of materials dropwise over 3 hours. After the addition is complete, continue to keep the temperature for 1 hour to end the reaction. Neutralize the excess acetic acid agent with 32% hydrochloric acid to obtain a neutralized solution.
[0037] (2) The neutralized solution obtained in step (1) was distilled to remove a small amount of water, and then distilled again to recover 231.7g of DMF. The remaining material was mixed with 150g of water, stirred, and cooled to crystallize. After cooling to 15℃, it was filtered, rinsed with 100g of water, and dried to obtain 62.13g of solid m-nitrophenyl-β-hydroxyethyl sulfide. The content was tested to be 99.76%, the purity was 99.66%, and the yield was calculated to be 98.61%.
[0038] (3) Add 240.50g of water to the oxidation reactor (200g of which is the water sample after activated carbon adsorption of the mother liquor from the previous batch as the bottom water), then add 60g of solid m-nitrophenyl-β-hydroxyethyl sulfide to the reactor, add 0.08g of sodium tungstate, and then raise the temperature to 99℃ under stirring. Start adding 83.11g of 27% hydrogen peroxide dropwise for about 3 hours. After the dropwise addition is completed, continue to keep the temperature for 1 hour, and then cool down to 30℃ to crystallize. The crystallized solid is rinsed with a small amount of water and dried to obtain 68.99g of solid m-nitrophenyl-β-hydroxyethyl sulfone. The content is tested to be 99.82%, the purity is 99.79%, and the yield is 99.11%.
[0039] (4) Add 270g of methanol to the hydrogenation reduction reactor, then add 67g of solid m-nitrophenyl-β-hydroxyethyl sulfone, and add 0.54g of palladium on carbon catalyst (a small amount of catalyst recovered from the previous batch is added). Introduce hydrogen gas and heat to 85℃ for reduction reaction. Control the pressure to maintain at 1.5-2.0 MPa. After the total reaction time is about 36 min, the pressure becomes constant and no longer decreases. Continue to keep the reaction at the temperature for 5 min, then cool down and open the reactor. After filtering and separating the catalyst, remove the solvent from the mother liquor, add water for crystallization and filter. After filtration, washing with water, and drying the solid, 57.84g of m-(β-hydroxyethyl sulfone)aniline product is obtained. The content is tested to be 99.61%, the purity is 99.73%, the yield is 99.01%, and the total yield of the three steps is 96.82%.
[0040] Example 3
[0041] (1) Add 250g of solvent (a mixture of DMAC and DMF in a mass ratio of 1 / 1) and 1g of cuprous bromide to a 500ml flask, start stirring, then add 50g of m-nitrochlorobenzene, stir to dissolve, and then cool to 30℃. At the same time, add 30.10g of mercaptoethanol and 27.47g of 48% liquid alkali dropwise. Under controlled temperature conditions, add the two groups of materials dropwise simultaneously for 3h. After the addition is complete, continue to keep the temperature for 2h to end the reaction. Neutralize the excess acetic acid agent with 32% hydrochloric acid to obtain a neutralized solution.
[0042] (2) The neutralized liquid obtained in step (1) was distilled to remove a small amount of water, and then the mixed solvent was recovered by distillation. 230.9g of the mixed solvent was recovered. 150g of water was added to the remaining material and stirred and cooled to crystallize. After cooling to 15℃, the mixture was filtered, rinsed with 100g of water and dried to obtain 62.12g of solid m-nitrophenyl-β-hydroxyethyl sulfide. The content was tested to be 99.32%, the purity was 99.66%, and the yield was calculated to be 98.12%.
[0043] (3) Add 241.30g of water to the oxidation reactor (200g of which is the water sample after activated carbon adsorption of the mother liquor from the previous batch as the bottom water), then add 60g of solid m-nitrophenyl-β-hydroxyethyl sulfide to the reactor, add 0.08g of sodium tungstate, and then raise the temperature to 99℃ under stirring. Start adding 82.96g of 27% hydrogen peroxide dropwise for about 3 hours. After the dropwise addition is completed, continue to keep the temperature for 1 hour, and then cool down to 30℃ to crystallize. The crystallized solid is rinsed with a small amount of water and dried to obtain 68.70g of solid m-nitrophenyl-β-hydroxyethyl sulfone. The content is tested to be 99.68%, the purity is 99.69%, and the yield is 98.93%.
[0044] (4) Add 270g of methanol to the hydrogenation reduction reactor, then add 67g of solid m-nitrophenyl-β-hydroxyethyl sulfone, and add 0.54g of palladium on carbon catalyst (provided by Johnson Matthey Catalysts Ltd., 5% palladium on carbon) (a small amount of catalyst recovered from the previous batch is added). Introduce hydrogen gas and heat to 95℃ for reduction reaction. Control the pressure to maintain at 1.5-2.0 MPa. After the total reaction time is about 27min, the pressure becomes constant and no longer decreases. Continue to keep the reaction at the temperature for 5min, then cool down and open the reactor. After filtering and separating the catalyst, remove the solvent from the mother liquor, add water for crystallization and filter. After filtration, washing with water, and drying the solid, 57.84g of m-(β-hydroxyethyl sulfone)aniline product is obtained. The content is tested to be 99.13%, the purity is 99.68%, the yield is 99.12%, and the total yield of the three steps is 96.22%.
[0045] Example 4
[0046] (1) Add 250g of solvent (a mixture of DMAC and DMF in a mass ratio of 1 / 1) and 0.1g of cuprous bromide to a 500ml flask, start stirring, then add 50g of m-nitrochlorobenzene, stir to dissolve, and then cool to 30℃. At the same time, add 30.10g of mercaptoethanol and 27.47g of 48% liquid alkali dropwise. Under controlled temperature conditions, add the two groups of materials dropwise simultaneously for 3h. After the addition is complete, continue to keep the temperature for 2h to end the reaction. Neutralize the excess acetic acid agent with 32% hydrochloric acid to obtain a neutralized solution.
[0047] (2) The neutralized solution obtained in step (1) was distilled to remove a small amount of water, and then distilled again to recover 230.9g of the mixed solvent. The remaining material was mixed with 150g of water, stirred, and cooled to crystallize. After cooling to 15℃, it was filtered, rinsed with 100g of water, and dried to obtain 57.70g of solid m-nitrophenyl-β-hydroxyethyl sulfide. The content was tested to be 99.48%, the purity was 98.16%, and the yield was calculated to be 91.32%.
[0048] (3) Add 220.10g of water to the oxidation reactor (200g of which is the water sample after activated carbon adsorption of the mother liquor from the previous batch as the bottom water), then add 55g of solid m-nitrophenyl-β-hydroxyethyl sulfide to the reactor, add 0.08g of sodium tungstate, and then raise the temperature to 99℃ under stirring. Start adding 76.17g of 27% hydrogen peroxide dropwise for about 3 hours. After the dropwise addition is completed, continue to keep the temperature for 2 hours, and then cool down to 30℃ to crystallize. The crystallized solid is rinsed with a small amount of water and dried to obtain 68.70g of solid m-nitrophenyl-β-hydroxyethyl sulfone. The content is tested to be 99.36%, the purity is 98.91%, and the yield is 97.36%.
[0049] (4) 240g of methanol was added to the hydrogenation reduction reactor, followed by 60g of solid m-nitrophenyl-β-hydroxyethyl sulfone. 0.50g of palladium on carbon catalyst (provided by Johnson Matthey Catalysts Ltd., 5% palladium on carbon) was added (a small amount was added from the previous batch of recovered catalyst). Hydrogen gas was introduced and the temperature was raised to 95°C for the reduction reaction. The pressure was maintained at 1.5-2.0 MPa. After a total reaction time of approximately 29 minutes, the pressure stabilized and stopped decreasing. The reaction was continued at this temperature for another 5 minutes, then the reactor was cooled and the reactor was opened. After filtering to separate the catalyst, the mother liquor was desolventized, crystallized with water, and filtered. After filtration, washing with water, and drying, 51.89g of m-(β-hydroxyethyl sulfone)aniline product was obtained. The tested content was 99.13%, the purity was 99.32%, the calculated yield was 99.03%, and the total yield of the three steps was 88.05%. The product content and purity in all embodiments of this invention were determined by HPLC.
Claims
1. A method for preparing m-(β-hydroxyethyl sulfone)aniline, characterized in that: The preparation method includes the following steps: (1) Using m-nitrochlorobenzene as the starting material and 2-mercaptoethanol as the thiolation condensing agent, m-nitrophenyl-β-hydroxyethyl sulfide was obtained by thiolation condensation reaction; (2) Using hydrogen peroxide as an oxidant, the m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (1) is oxidized to obtain m-nitrophenyl-β-hydroxyethyl sulfone; (3) The m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (2) is hydrogenated to obtain m-(β-hydroxyethyl sulfone)aniline.
2. The preparation method according to claim 1, characterized in that: The thiolization condensation reaction of m-nitrochlorobenzene and 2-mercaptoethanol described in step (1) is carried out in an organic solvent in the presence of a catalyst and an acid-binding agent; The catalyst is cuprous iodide or cuprous bromide or a mixture of both; the amount of catalyst used is 0.1%-10% of m-nitrochlorobenzene, preferably 0.5%-2.0%, more preferably 1-2%; The acid-absorbing agent is at least one of sodium carbonate, sodium bicarbonate, ammonia, and liquid alkali. The solvent is at least one of DMF, DMAC, and DMSO.
3. The preparation method according to claim 1 or 2, characterized in that: The reaction temperature of the thiolization condensation reaction in step (1) is 0-50℃, preferably 20-30℃.
4. The preparation method according to claim 2, characterized in that: The specific steps (1) are as follows: In the reaction apparatus, organic solvent and m-nitrochlorobenzene are added and mixed to dissolve, then a catalyst is added, and then the temperature is controlled at 0~50℃ (preferably 20-30℃) while simultaneously adding Folic acid and 2-mercaptoethanol. After the addition is completed within 1~8h (preferably 2-4h), the reaction is continued at a constant temperature for 0~6h (preferably 1-2h). After the reaction is completed, the excess Folic acid is neutralized to obtain a neutralized solution. The neutralized solution is then post-treated to obtain m-nitrophenyl-β-hydroxyethyl sulfide. Preferably, the post-treatment is carried out as follows: the neutralized solution is distilled to remove wastewater, and then the solvent is recovered by distillation (the solvent can be reused). Water is then added to cool and crystallize. After filtering and separating the mother liquor, the solution is washed with water (the washing water is reused as the crystallization base water) to obtain m-nitrophenyl-β-hydroxyethyl sulfide.
5. The preparation method according to claim 1, characterized in that: The oxidation reaction in step (2) is carried out in an aqueous solvent under the action of a catalyst, which is sodium tungstate.
6. The preparation method according to claim 1 or 5, characterized in that: The oxidation reaction temperature in step (2) is controlled at 50-105℃, preferably 95-100℃.
7. The preparation method according to claim 5, characterized in that: Step (2) is specifically operated as follows: add bottom water, m-nitrophenyl-β-hydroxyethyl sulfide obtained in step (1), and catalyst to the oxidation reactor, control the temperature at 50-105℃ (preferably 95-100℃) and add hydrogen peroxide dropwise, control the dropwise time at 1-10h (preferably 2-4h), and keep the reaction at the temperature for 0-6h (preferably 1-2h) after the dropwise addition is completed, and obtain the oxidation reaction material. After cooling and crystallization, the m-nitrophenyl-β-hydroxyethyl sulfone solid and mother liquor are separated. Preferably, the mother liquor separated in step (2) is adsorbed by activated carbon, dehydrated, and then returned to step (2) as bottom water.
8. The preparation method according to claim 1, characterized in that: In step (3), m-nitrophenyl-β-hydroxyethyl sulfone is hydrogenated to obtain m-(β-hydroxyethyl sulfone)aniline. This reaction is carried out in a reaction solvent under the action of a hydrogenation catalyst. The reaction solvent is at least one of methanol, ethanol, propanol, and water; The hydrogenation catalyst is selected from at least one of Raney nickel, nickel support, palladium on carbon, and platinum on carbon.
9. The preparation method according to claim 8, characterized in that: In step (3), the hydrogenation reduction temperature is controlled at 50-160℃, preferably 80-100℃; the hydrogen pressure is controlled at 0.5-5.0 MPa, preferably 1.5-2.5 MPa.
10. The preparation method according to claim 9, characterized in that: The specific operation of step (3) is as follows: add reaction solvent, solid m-nitrophenyl-β-hydroxyethyl sulfone obtained in step (2) and hydrogenation catalyst to the reduction reaction device, pass hydrogen gas to carry out the reduction reaction, and obtain a reducing solution; the hydrogenation catalyst is separated by sedimentation of the reducing solution, and after the solvent is removed, water is added to crystallize to obtain a solid, and further washed and dried to obtain m-(β-hydroxyethyl sulfone)aniline product; preferably, the hydrogenation catalyst in step (3) is reused after separation, the solvent can be reused in step (3) after removal, and the washing water can be returned to be used as the bottom water in step (2).