Synthesis process of high-yield sodium benzenesulfinate

Abstract

The invention discloses a synthesis process of high-yield sodium benzenesulfinate, and belongs to the technical field of synthesis of sodium benzenesulfinate. The synthesis process of the high-yield sodium benzenesulfinate comprises the following preparation steps: S1, mixing a first catalyst, sodium hydroxide and a first solvent, then adding powdered sulfur, reacting for a first reaction time under microwave radiation, then adding chlorobenzene, continuously reacting for a second reaction time under microwave radiation, then filtering, carrying out reduced pressure distillation to remove the solvent, and recrystallizing, so as to obtain the high-yield sodium benzenesulfinate. The diphenyl disulfide is obtained; s2, mixing the diphenyl disulfide prepared in the step S1, alcohol, an oxidizing agent and a second solvent, stirring in the air at room temperature for a third reaction time, diluting with ultrapure water, extracting with ethyl acetate for multiple times, combining organic layers, drying, concentrating and purifying to obtain benzene sulfinate, and keeping in a dark place and in an oxygen-isolated manner; s3, under the dark and nitrogen conditions, benzene sulfinate prepared in the step S2 is hydrolyzed and refined under the alkaline condition, and sodium benzene sulfinate is obtained.

Description

Technical Field

[0001] This invention relates to a process for synthesizing sodium benzenesulfinate in high yield. Background Technology

[0002] Sodium benzenesulfinate is an important organic synthesis intermediate widely used in pharmaceuticals, pesticides, dyes, rubber additives, and photosensitive materials. As a highly efficient nucleophile and reducing agent, it plays a crucial role in coupling reactions such as the Suzuki and Negishi reactions, and is also an important precursor for the synthesis of sulfonyl chlorides, sulfonamides, and sulfones. With the continuous expansion of downstream applications and technological upgrades, the market demand for high-purity, high-yield sodium benzenesulfinate is increasing.

[0003] Currently, the main industrial synthesis methods for sodium benzenesulfonate include the following: First, using benzene as a raw material, a chlorosulfonation reaction is performed to generate benzenesulfonyl chloride, which is then subjected to alkaline hydrolysis and reduction to obtain sodium benzenesulfonate; second, sodium sulfite is reacted directly with benzenesulfonyl chloride in an aqueous phase; third, a salt is formed by reacting sulfur dioxide with a phenyl Grignard reagent and then neutralizing it. However, these traditional processes generally have many drawbacks:

[0004] First, the process is complex and the operation steps are cumbersome. For example, the chlorosulfonation process requires multiple reaction stages such as sulfonation, hydrolysis, and reduction, involving high temperature, high pressure, and highly corrosive media. This not only places high demands on equipment but also results in a long production cycle, high energy consumption, and increased operational risks and control difficulties.

[0005] Secondly, the raw material costs are high. Some methods rely on expensive benzenesulfonyl chloride or Grignard reagents, and the reactions often require large amounts of organic solvents for extraction and purification, resulting in high solvent recovery costs, which further increases the overall production cost.

[0006] Finally, product purity and yield are difficult to guarantee. Existing processes easily generate byproducts such as sodium benzenesulfonate and diphenyl sulfone during the reaction, leading to difficulties in separating and purifying the target product. The final product purity is low, typically requiring multiple recrystallizations or column chromatography, which are time-consuming and energy-intensive purification methods, severely impacting the final synthesis yield. Reported yields in the literature fluctuate significantly, generally between 60% and 75%, making it difficult to consistently achieve the high yield levels required for industrial-scale production.

[0007] To address the aforementioned problems, this invention presents a high-yield synthesis process for sodium benzenesulfinate. Summary of the Invention

[0008] The purpose of this invention is to provide a high-yield synthesis process for sodium benzenesulfinate to solve the technical problems mentioned in the background section.

[0009] The technical solution to achieve the objective of this invention is:

[0010] This invention provides a high-yield synthesis process for sodium benzenesulfinate, comprising the following process steps:

[0011] S1. Mix the first catalyst, sodium hydroxide, and the first solvent, then add sulfur powder, and react under microwave radiation for the first reaction time. Then add chlorobenzene and continue to react under microwave radiation for the second reaction time. Then filter, remove the solvent by vacuum distillation, and recrystallize to obtain diphenyl disulfide.

[0012] S2. Mix the diphenyl disulfide, alcohol, oxidant and second solvent obtained in step S1, stir at room temperature in air for a third reaction time, then dilute with ultrapure water and extract multiple times with an organic extractant. Combine the organic layers, dry, concentrate and purify to obtain benzene sulfinate, and store it in the dark and in the absence of oxygen.

[0013] S3. Under light-proof and nitrogen-protected conditions, the benzenesulfinate obtained in step S2 is hydrolyzed under alkaline conditions, concentrated, cooled and crystallized, filtered, vacuum dried, recrystallized, and vacuum dried to obtain sodium benzenesulfinate.

[0014] This invention provides a high-yield synthesis process for sodium benzenesulfinate. First, chlorobenzene and sulfur powder are used as raw materials to synthesize diphenyl disulfide under alkaline conditions with the aid of a catalyst and microwave radiation. Then, the obtained diphenyl disulfide is mixed with alcohol raw materials, and an oxidant is introduced to oxidize the diphenyl disulfide, which further undergoes a substitution reaction with the alcohol to generate benzenesulfinate. Finally, the benzenesulfinate is hydrolyzed with an alkaline solution to obtain the target product, sodium benzenesulfinate. Compared with existing technologies, the raw materials used in this process are lower in cost and more widely available, resulting in a significantly higher yield and more ideal purity of the obtained sodium benzenesulfinate.

[0015] The specific preparation process is as follows:

[0016]

[0017] Furthermore, the first catalyst is polyethylene glycol-400, and the first solvent is N,N-dimethylformamide.

[0018] In this invention, when synthesizing diphenyl disulfide from chlorobenzene and sulfur powder, polyethylene glycol-400 is used as a phase transfer catalyst and N,N-dimethylformamide is used as a solvent. The phase transfer catalyst not only promotes the formation of disulfide ions in the solution but also effectively catalyzes the substitution reaction on chlorinated hydrocarbons, thereby increasing the yield of diphenyl disulfide. N,N-dimethylformamide, as a high-boiling-point polar solvent, has excellent microwave absorption capabilities and can effectively promote the reaction under microwave radiation conditions, further improving the synthesis efficiency and yield of diphenyl disulfide.

[0019] Furthermore, the first reaction time is 3 minutes; the second reaction time is 3 to 4 minutes; and the microwave radiation power is 375W to 450W.

[0020] Furthermore, the molar ratio of the first catalyst, sodium hydroxide, sulfur powder, and chlorobenzene is 0.004–0.006:48–52:12–13:10; and the mass of the first solvent is 46–48 times the mass of the sulfur powder.

[0021] Furthermore, the oxidant is a selective fluorine reagent; the alcohol includes any one of methanol, ethanol, propanol, butanol, and isopropanol; and the second solvent is formonitrile.

[0022] This invention employs a selective fluorine reagent to promote the oxidation reaction of diphenyl disulfide with alcohols. This reaction can be carried out under mild conditions and has good substrate adaptability, being able to tolerate various types of alcohols, including complex-structured alcohols such as tertiary alcohols and natural alcohols. This significantly expands the application range of the reaction and effectively improves the yield of the generated benzenesulfinate.

[0023] Furthermore, the molar ratio of diphenyl disulfide to oxidant is 1:3 to 5; the mass ratio of alcohol to diphenyl disulfide is 17 to 19:1; and the volume ratio of alcohol to second solvent is 1:3 to 5.

[0024] Furthermore, the third reaction time is 3 to 5 hours.

[0025] Further, the specific steps of S3 are as follows: under light-protected and nitrogen-protected conditions, benzenesulfinate is mixed with an aqueous sodium hydroxide solution and hydrolyzed at 60-80°C for 1-4 hours. Subsequently, the mixture is concentrated, cooled and crystallized, filtered, vacuum dried, recrystallized, and vacuum dried again to obtain sodium benzenesulfinate.

[0026] Finally, sodium benzenesulfinate was obtained by alkaline hydrolysis of benzenesulfinate. The hydrolysis reaction was mild, simple to operate, and easy to control, and could efficiently and thoroughly complete the ester bond breaking and salt formation process, thereby further ensuring the high yield and high purity of sodium benzenesulfinate.

[0027] Furthermore, the concentration of the sodium hydroxide aqueous solution is 25–35 wt%.

[0028] Furthermore, the molar ratio of the benzenesulfinate to sodium hydroxide is 1 to 2:1.

[0029] By adopting the above technical solution, the present invention has the following beneficial effects:

[0030] (1) This invention provides a high-yield synthesis process for sodium benzenesulfinate. First, chlorobenzene and sulfur powder are used as raw materials. Under alkaline conditions, a catalyst is added and microwave radiation is used to synthesize diphenyl disulfide. Then, the obtained diphenyl disulfide is mixed with alcohol raw materials, an oxidant is introduced to oxidize the diphenyl disulfide, and further a substitution reaction is carried out with alcohol to generate benzenesulfinate. Finally, the benzenesulfinate is hydrolyzed with alkaline to obtain the target product sodium benzenesulfinate. The raw materials used in this process are lower in cost and more widely available than those in the prior art. The sodium benzenesulfinate produced not only has a significantly higher yield but also a more ideal purity.

[0031] (2) In the synthesis of diphenyl disulfide using chlorobenzene and sulfur powder as raw materials, polyethylene glycol-400 is used as a phase transfer catalyst and N,N-dimethylformamide is used as a solvent. The phase transfer catalyst not only participates in promoting the formation of disulfide ions in the solution, but also effectively catalyzes the substitution reaction on chlorinated hydrocarbons, thereby improving the yield of diphenyl disulfide. N,N-dimethylformamide, as a high-boiling-point polar solvent, has good microwave absorption capacity and can effectively promote the reaction under microwave radiation conditions, further improving the synthesis efficiency and yield of diphenyl disulfide.

[0032] (3) The present invention uses selective fluorine reagents to promote the oxidation reaction of diphenyl disulfide with alcohol. This reaction can be carried out under mild conditions and has good substrate adaptability. It can tolerate a variety of types of alcohols, including complex structured alcohols such as tertiary alcohols and natural alcohols, thereby significantly expanding the application range of the reaction and effectively improving the yield of the generated benzene sulfinate.

[0033] (4) Finally, sodium benzenesulfinate is obtained by alkaline hydrolysis of benzenesulfinate. The hydrolysis reaction is mild, simple to operate and easy to control. It can efficiently and thoroughly complete the ester bond breaking and salt formation process, thereby further ensuring the high yield and high purity of sodium benzenesulfinate. Detailed Implementation

[0034] To better understand the above technical solution, the following will provide a detailed explanation of the technical solution in conjunction with specific implementation methods.

[0035] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention.

[0036] The following embodiments are only used to illustrate the technical solutions of the present invention more clearly, and should not be used to limit the scope of protection of the present invention.

[0037] Example 1

[0038] A process for synthesizing sodium benzenesulfinate in high yield includes the following steps:

[0039] S1. Mix 0.004 mmol polyethylene glycol-400, 48 mmol sodium hydroxide, and 20 mL N,N-dimethylformamide, then add 12 mmol sulfur powder, and react under microwave radiation at 375 W for 3 min. Then add 10 mmol chlorobenzene and continue to react under microwave radiation for 3 min. Then filter, remove the solvent by vacuum distillation, and recrystallize with ethanol to obtain diphenyl disulfide with a yield of 92%.

[0040] S2. Mix 0.2 mmol diphenyl disulfide, 1 mL butanol, 0.6 mmol selective fluorine reagent, and 3 mL formonitrile obtained in step S1. Stir at room temperature in air for the third reaction time. Then dilute with 20 mL ultrapure water and extract three times with 20 mL ethyl acetate. Combine the organic layers, dry with anhydrous sodium sulfate, filter, concentrate under vacuum, and then purify by column chromatography using a 10:1 hexane / ethyl acetate mixture as eluent to obtain benzene sulfinate. Store in the dark and oxygen-free environment. The yield of benzene sulfinate is 97%.

[0041] S3. Under light-proof and nitrogen-filled conditions, the benzenesulfinate obtained in step S2 was mixed with a 25wt% sodium hydroxide aqueous solution and hydrolyzed at 60°C for 1 hour. After hydrolysis, the mixture was concentrated, cooled and crystallized, filtered, and vacuum dried. Then, it was dissolved in water, and ethanol was added and stirred. The resulting precipitate was vacuum-drawn into a distillation vessel, and vacuum distilled at 130°C under a vacuum degree controlled above -0.094 MPa to remove excess ethanol, yielding sodium benzenesulfinate with a yield of 88% and a purity of 99.2%.

[0042] Example 2

[0043] A process for synthesizing sodium benzenesulfinate in high yield includes the following steps:

[0044] S1. Mix 0.005 mmol polyethylene glycol-400, 50 mmol sodium hydroxide, and 20 mL N,N-dimethylformamide, then add 12.5 mmol sulfur powder and react under microwave irradiation at 375 W for 3 min. Then add 10 mmol chlorobenzene and continue to react under microwave irradiation for 4 min. Then filter, remove the solvent by vacuum distillation, and recrystallize with ethanol to obtain diphenyl disulfide with a yield of 94%.

[0045] S2. Mix 0.2 mmol diphenyl disulfide, 1 mL butanol, 0.8 mmol selective fluorine reagent, and 4 mL formonitrile obtained in step S1. Stir at room temperature in air for the third reaction time. Then dilute with 20 mL ultrapure water and extract three times with 20 mL ethyl acetate. Combine the organic layers, dry with anhydrous sodium sulfate, filter, concentrate under vacuum, and then purify by column chromatography using a 10:1 hexane / ethyl acetate mixture as eluent to obtain benzene sulfinate. Store in the dark and oxygen-free environment. The yield of benzene sulfinate is 98%.

[0046] S3. Under light-proof and nitrogen-filled conditions, the benzenesulfinate obtained in step S2 was mixed with a 30wt% sodium hydroxide aqueous solution and hydrolyzed at 70°C for 3 hours. After hydrolysis, the mixture was concentrated, cooled and crystallized, filtered, and vacuum dried. Then, it was dissolved in water, and ethanol was added and stirred. The resulting precipitate was vacuum-drawn into a distillation vessel, and vacuum distilled at 130°C under a vacuum degree controlled above -0.094 MPa to remove excess ethanol, yielding sodium benzenesulfinate with a yield of 91% and a purity of 99.5%.

[0047] Example 3

[0048] A process for synthesizing sodium benzenesulfinate in high yield includes the following steps:

[0049] S1. Mix 0.006 mmol polyethylene glycol-400, 52 mmol sodium hydroxide, and 20 mL N,N-dimethylformamide, then add 13 mmol sulfur powder, and react under microwave radiation at 450 W for 3 min. Then add 10 mmol chlorobenzene and continue to react under microwave radiation for 3 min. Then filter, remove the solvent by vacuum distillation, and recrystallize with ethanol to obtain diphenyl disulfide with a yield of 92%.

[0050] S2. Mix 0.2 mmol of diphenyl disulfide, 1 mL of butanol, 1 mmol of selective fluorine reagent, and 5 mL of formonitrile obtained in step S1. Stir at room temperature in air for the third reaction time. Then dilute with 20 mL of ultrapure water and extract three times with 20 mL of ethyl acetate. Combine the organic layers, dry with anhydrous sodium sulfate, filter, concentrate under vacuum, and then purify by column chromatography using a 10:1 hexane / ethyl acetate mixture as eluent to obtain benzene sulfinate. Store in the dark and oxygen-free environment. The yield of benzene sulfinate is 96%.

[0051] S3. Under light-proof and nitrogen-filled conditions, the benzenesulfinate obtained in step S2 was mixed with a 35wt% sodium hydroxide aqueous solution and hydrolyzed at 80°C for 4 hours. After hydrolysis, the mixture was concentrated, cooled and crystallized, filtered, and vacuum dried. Then, it was dissolved in water, and ethanol was added and stirred. The resulting precipitate was vacuum-drawn into a distillation vessel, and vacuum distilled at 130°C under a vacuum degree controlled above -0.094 MPa to remove excess ethanol, yielding sodium benzenesulfinate with a yield of 87% and a purity of 98.9%.

[0052] Blank example:

[0053] A process for synthesizing sodium benzenesulfinate, the process comprising the following steps:

[0054] S1. Mix benzenesulfonyl chloride and sodium sulfite in a low-temperature reactor at a molar ratio of 3:1, and control the temperature of the reactants at 10°C until benzenesulfonyl chloride dissolves.

[0055] S2. During the reaction, a diluted 38wt% sodium hydroxide solution is added to the low-temperature reactor to maintain the pH of the mixed reaction material at 8.5 and prevent the formation of sulfur dioxide.

[0056] S3. After the reaction is complete, filter to remove sodium bisulfate from the mixture, and acidify the filtrate with sulfuric acid at 0°C to obtain benzenesulfinic acid.

[0057] S4. Add benzenesulfinic acid to a mixer, then add 40wt% sodium hydroxide solution, stir at 30℃ for 2h, concentrate, cool to crystallize, filter, and vacuum dry to obtain crude sodium benzenesulfinate, wherein the molar ratio of benzenesulfinic acid to sodium hydroxide solution is 1.5:1.

[0058] S5. Crude sodium benzenesulfonate is dissolved in water, and after adding ethanol and mixing and stirring, sodium benzenesulfonate precipitate is obtained by precipitation.

[0059] S6. The sodium benzenesulfonate precipitate is vacuum-extracted into a distillation kettle, and vacuum distillation is carried out at 140°C under controlled vacuum conditions of -0.094 MPa or higher to remove excess ethanol, thereby obtaining pure sodium benzenesulfonate white solid powder.

[0060] The obtained sodium benzenesulfinate had a yield of 86% and a purity of 98.4%.

[0061] By comparing the yield and purity of sodium benzenesulfonate obtained in Examples 1-3 with that in the blank example, it can be seen that the blank example uses the traditional sodium benzenesulfonate preparation process, which is prepared by reacting benzenesulfonyl chloride with sodium sulfite. The experimental results show that the sodium benzenesulfonate prepared in Examples 1-3 is superior to that in the blank example in terms of yield and purity. The yield is increased by 1% to 6% and the purity is increased by 0.5% to 1.1% compared with the blank example, which fully demonstrates the significant advantages of the process of the present invention in improving product yield and quality.

[0062] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A process for synthesizing sodium benzenesulfinate with high yield, characterized in that, The process includes the following steps: S1. Mix the first catalyst, sodium hydroxide, and the first solvent, then add sulfur powder, and react under microwave radiation for the first reaction time. Then add chlorobenzene and continue to react under microwave radiation for the second reaction time. Then filter, remove the solvent by vacuum distillation, and recrystallize to obtain diphenyl disulfide. S2. Mix the diphenyl disulfide, alcohol, oxidant and second solvent obtained in step S1, stir at room temperature in air for a third reaction time, then dilute with ultrapure water and extract multiple times with an organic extractant. Combine the organic layers, dry, concentrate and purify to obtain benzene sulfinate, and store it in the dark and in the absence of oxygen. S3. Under light-proof and nitrogen-protected conditions, the benzenesulfinate obtained in step S2 is hydrolyzed under alkaline conditions, concentrated, cooled and crystallized, filtered, vacuum dried, recrystallized, and vacuum dried to obtain sodium benzenesulfinate.

2. The synthesis process for high-yield sodium benzenesulfinate according to claim 1, characterized in that, The first catalyst is polyethylene glycol-400, and the first solvent is N,N-dimethylformamide.

3. The synthesis process for high-yield sodium benzenesulfinate according to claim 2, characterized in that, The first reaction time is 3 minutes; the second reaction time is 3 to 4 minutes; and the microwave radiation power is 375W to 450W.

4. The synthesis process for high-yield sodium benzenesulfinate according to claim 2, characterized in that, The molar ratio of the first catalyst, sodium hydroxide, sulfur powder, and chlorobenzene is 0.004–0.006:48–52:12–13:10; the mass of the first solvent is 46–48 times the mass of the sulfur powder.

5. The synthesis process for high-yield sodium benzenesulfinate according to claim 1, characterized in that, The oxidant is a selective fluorine reagent; the alcohol includes any one of methanol, ethanol, propanol, butanol, and isopropanol; the second solvent is formonitrile.

6. The synthesis process for high-yield sodium benzenesulfinate according to claim 5, characterized in that, The molar ratio of diphenyl disulfide to oxidant is 1:3 to 5; the mass ratio of alcohol to diphenyl disulfide is 17 to 19:1; and the volume ratio of alcohol to second solvent is 1:3 to 5.

7. The synthesis process for high-yield sodium benzenesulfinate according to claim 1, characterized in that, The third reaction time is 3 to 5 hours.

8. The synthesis process for high-yield sodium benzenesulfinate according to claim 1, characterized in that, The specific steps of S3 are as follows: under light-protected and nitrogen-protected conditions, benzene sulfinate is mixed with sodium hydroxide aqueous solution and hydrolyzed at 60-80°C for 1-4 hours. Then, it is concentrated, cooled and crystallized, filtered, vacuum dried, recrystallized, and vacuum dried to obtain sodium benzene sulfinate.

9. The synthesis process for high-yield sodium benzenesulfinate according to claim 8, characterized in that, The concentration of the sodium hydroxide aqueous solution is 25–35 wt%.

10. The synthesis process for high-yield sodium benzenesulfinate according to claim 9, characterized in that, The molar ratio of benzenesulfinate to sodium hydroxide is 1 to 2:1.

Images