Preparation method of benzylsulfonyl chloride
By optimizing the process of benzyl sulfonyl chloride preparation using sulfonation and chlorination reactions, the problems of low yield and complex process in the existing technology have been solved, and high-purity and high-yield benzyl sulfonyl chloride preparation has been achieved, which is suitable for industrial application.
Patent Information
- Application Number
- CN202411962544.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-30
- Publication Date
- 2025-01-28
- Estimated Expiration
- 2044-12-30
AI Technical Summary
Existing methods for preparing benzyl sulfonyl chloride suffer from low yields and complex processes, making it difficult to meet industrial-scale requirements.
Benzyl chloride, sodium sulfite, and a sulfonation catalyst were used to carry out a sulfonation reaction in the first solvent. Subsequently, sodium benzyl sulfonate was reacted with a chlorinating agent and a chlorination catalyst in the second solvent. By optimizing the reaction conditions and post-processing steps, high-purity benzyl sulfonyl chloride was prepared.
The purity of benzyl sulfonyl chloride reached over 99%, and the yield reached over 90%. The process is simple, the raw materials are readily available, and it is suitable for industrial production.
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Abstract
Description
Technical Field
[0001] The invention relates to the field of organic synthesis, and in particular to a method for preparing benzylsulfonyl chloride. Background Art
[0002] Benzylsulfonyl chloride, molecular formula C7H7ClO2S, melting point 90-94°C, appears as a nearly white crystalline powder, with the characteristics of high reactivity, high solubility and low toxicity.
[0003] Benzylsulfonyl chloride has been widely used in various fields. In the pharmaceutical industry, benzylsulfonyl chloride can be used to synthesize various drugs, such as antibiotics, anti-tumor drugs, antihypertensive drugs, etc.; in the pesticide industry, benzylsulfonyl chloride can be used to synthesize various insecticides, fungicides, etc.; in the dye and fragrance industry, benzylsulfonyl chloride can be used to synthesize various dyes and fragrances. The market prospect of benzylsulfonyl chloride is very broad. With the continuous development of the pharmaceutical, pesticide, dye and fragrance industries, the demand for benzylsulfonyl chloride will continue to increase.
[0004] At present, the synthesis methods reported in domestic and foreign literature mainly include the chlorination method of benzylthiourea salt, the chlorination method of benzyl mercaptan, the one-step synthesis method of N-chlorosuccinimide, sulfonylhydrazide and acetonitrile, and the one-step synthesis method of benzyl chloride, potassium thioacetate and ethyl xanthate.
[0005] The benzylthiourea salt chlorination method mainly uses benzaldehyde as the starting material, obtains benzyl alcohol through reduction reaction, obtains chloromethylbenzene through chlorination reaction, obtains benzylcarbamoyl iminosulfate hydrochloride through substitution reaction, and finally obtains benzylsulfonyl chloride through sulfonyl chlorination reaction. This process has many operation steps, and the final yield is only 79%.
[0006] The benzyl mercaptan chlorination method is to continuously inject benzyl mercaptan and water into the reactor in proportion, while passing chlorine gas, and react to obtain benzyl sulfonyl chloride. This process requires continuous flow of materials and recycling of slightly reacted benzyl mercaptan until it is completely converted. It has high standards for equipment performance, operating skills and automatic control. In addition, benzyl mercaptan has a strong odor, which poses a great challenge to the working environment.
[0007] The one-step synthesis method of N-chlorosuccinimide with sulfonylhydrazine and acetonitrile is to add N-chlorosuccinimide to a CH3CN solution of sulfonylhydrazine at one time, keep it warm at room temperature, and obtain benzylsulfonyl chloride. The raw materials of this process are not easy to obtain and are expensive, and the final yield is only 87%.
[0008] The one-step synthesis method of benzyl chloride with potassium thioacetate and ethyl xanthate is to first keep benzyl chloride, MeCN and KSAc in an ice bath, then add concentrated HCl, and slowly add solid NaClO2 to obtain benzylsulfonyl chloride. The yield of this process is relatively low, only about 54%.
[0009] It can be seen that the benzyl sulfonyl chloride prepared by the existing method for preparing benzyl sulfonyl chloride has the problems of low yield and complicated process, so a method with high yield and simple preparation process is urgently needed. Summary of the invention
[0010] In order to overcome the problems existing in the above synthesis, the present invention provides a synthesis method suitable for industrial production of benzylsulfonyl chloride, in which the benzylsulfonyl chloride content reaches more than 99% and the yield reaches more than 90%, which has great production value.
[0011] The present invention provides a method for preparing benzylsulfonyl chloride, which comprises the following steps: Step 1, adding benzyl chloride, sodium sulfite and a sulfonation catalyst into a first solvent for sulfonation reaction, wherein the molar ratio of the added amounts of benzyl chloride, sodium sulfite and the catalyst is 1: (0.8-1.5): (0.005-0.05); Step 2: After the reaction is completed, the reaction solution is post-treated to obtain sodium benzyl sulfonate; Step 3, adding the obtained sodium benzyl sulfonate, chlorinating agent and chlorination catalyst to a second solvent for chlorination reaction, wherein the molar ratio of the added amounts of sodium benzyl sulfonate, chlorinating agent and chlorination catalyst is 1: (1-1.5): (0.01-0.03); Step 4: post-treating the obtained chlorination reaction solution to obtain benzylsulfonyl chloride.
[0012] Preferably, the sulfonation catalyst used in step 1 is potassium iodide, sodium bromide, bromine or a mixture of the two or more thereof.
[0013] Preferably, the first solvent used in step 1 is one or a mixed solvent of water, methanol, and ethanol, wherein the mass ratio of sodium sulfite to the solvent is 1:(1-5).
[0014] Preferably, the reaction temperature of the sulfonation reaction in step 1 is 100° C.-105° C., and the reaction time is 8-20 h.
[0015] Preferably, the reaction solution in step 2 is post-treated to obtain sodium benzyl sulfonate, which is then used after undergoing a desolventizing and dehydrating process, and the treatment steps are as follows: Step 2-1, the reaction solution is cooled to room temperature and then filtered; Step 2-2, washing the filtered filter cake with dichloroethane; Step 2-3: The washed filter cake is dried and dehydrated to obtain sodium benzyl sulfonate.
[0016] Preferably, the chlorinating agent used in step 3 is one of thionyl chloride, chlorosulfonic acid, chlorine, phosphorus trichloride, phosphorus oxychloride, and phosphorus pentachloride.
[0017] Preferably, the chlorination catalyst used in step 3 is one of N,N-dimethylformamide, pyridine, and triethylamine; the second solvent used in step 3 is one of dichloromethane, dichloroethane, and toluene, wherein the mass ratio of sodium benzyl sulfonate to the solvent is 1: (1-5).
[0018] Preferably, the reaction temperature of the chlorination reaction in step 3 is 70° C.-80° C., and the reaction time is 3-4 h.
[0019] Preferably, the benzylsulfonyl chloride reaction solution obtained in step 4 is subjected to hydrolysis, water washing, and desolventizing steps, and the processing steps are as follows: Step 4-1, continuing to heat the chlorination reaction solution to evaporate excess chlorinating agent; Step 4-2: After the distillation is completed, the chlorination reaction solution is placed in water for hydrolysis; Step 4-3, washing and drying the hydrolyzate; Step 4-4, concentrating the solvent to obtain the refined benzylsulfonyl chloride.
[0020] Preferably, the content of benzylsulfonyl chloride obtained in step 4 reaches more than 99%.
[0021] The preparation process route of benzylsulfonyl chloride of the present invention is: Reaction 1 Reaction 2 Compared with the prior art, the benzylsulfonyl chloride obtained by the method provided by the present invention has a purity of more than 99% and a yield of more than 90%, and the preparation method is simple, the raw materials are cheap and readily available, and it is easy to realize industrialization, and has extremely high application value. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 is the mass spectrum of benzylsulfonyl chloride obtained in Example 4; Figure 2 This is the gas phase spectrum of benzylsulfonyl chloride obtained in Example 4. DETAILED DESCRIPTION
[0023] Example 1, step 1, add 253 g of benzyl chloride, 277 g of sodium sulfite, and 500 g of water into a 2L four-necked bottle equipped with a thermometer and mechanical stirring, heat the bottle to a temperature of 100°C-105°C, and keep the temperature to react for 12 hours.
[0024] Step 2: After the reaction is completed, the temperature in the bottle is lowered to room temperature, the reaction solution is poured out and then centrifuged. The centrifuged solid is slurried with dichloroethane and then centrifuged. The solid material is transferred to an oven for drying, and the dried solid is sodium benzyl sulfonate.
[0025] Step 3: Add the obtained sodium benzyl sulfonate into a 2L four-necked glass bottle with a thermometer and mechanical stirring, add 800 g of ethylene dichloride and 357 g of thionyl chloride, raise the temperature to the reflux temperature of 80° C., and keep warm for 3 hours.
[0026] Step 4: After the insulation is completed, excess thionyl chloride is evaporated under negative pressure. The material in the bottle is added to 1000 g of water for hydrolysis. After hydrolysis, it is washed with water, dried with calcium chloride, and the solvent is concentrated. Finally, 259 g of benzylsulfonyl chloride is obtained by distillation, with a molar yield of 68% and a content of 99.18% detected by GC.
[0027] Embodiment 2, the preparation method of benzylsulfonyl chloride of this embodiment is different from that of embodiment 1 in that: Step 1: Add 253 g of benzyl chloride, 277 g of sodium sulfite, 250 g of water, and 250 g of ethanol to a 2L four-necked bottle equipped with a thermometer and mechanical stirring, heat the bottle to 100°C-105°C, and keep the reaction for 12 hours. The other steps remain unchanged. 286 g of benzylsulfonyl chloride is obtained, with a molar yield of 75% and a content of 99.11% detected by GC.
[0028] Embodiment 3, the preparation method of benzylsulfonyl chloride of this embodiment is different from that of embodiment 2 in that: Step 1: Add 253 g of benzyl chloride, 277 g of sodium sulfite, 2.5 g of potassium iodide, 250 g of water, and 250 g of ethanol to a 2L four-necked bottle with a thermometer and mechanical stirring, heat the bottle to 100°C-105°C, and keep the reaction for 12 hours. The other steps remain unchanged. 339 g of benzylsulfonyl chloride is obtained, with a molar yield of 89% and a content of 99.23% detected by GC.
[0029] Embodiment 4, the preparation method of benzylsulfonyl chloride in this embodiment is different from that in Embodiment 3 in that: Step 3: Add the obtained sodium benzyl sulfonate into a 2L four-necked glass bottle with a thermometer and mechanical stirring, add 800g of ethylene dichloride, 357g of thionyl chloride, and 3g of N,N-dimethylformamide, raise the temperature to reflux temperature of 80°C, and keep warm for 3 hours. The other steps remain unchanged. Obtain 355g of benzyl sulfonyl chloride (its mass spectrum is as shown in FIG. Figure 1 As shown, m / z=189.99), molar yield 93%, GC content 99.21% (its gas chromatogram is as shown Figure 2 as shown).
[0030] Embodiment 5, the preparation method of benzylsulfonyl chloride in this embodiment is different from that in Embodiment 3 in that: Step 1: Add 253 g of benzyl chloride, 277 g of sodium sulfite, 5.0 g of sodium bromide, 250 g of water, and 250 g of ethanol to a 2L four-necked bottle equipped with a thermometer and mechanical stirring, heat the bottle to 100°C-105°C, and keep the reaction for 12 hours. The other steps remain unchanged. 318.05 g of benzylsulfonyl chloride is obtained, with a molar yield of 83.5% and a content of 99.15% detected by GC.
[0031] Embodiment 6, the preparation method of benzylsulfonyl chloride in this embodiment is different from that in Embodiment 4 in that: Step 3: Add the obtained sodium benzyl sulfonate into a 2L four-necked glass bottle with a thermometer and mechanical stirring, add 800g of dichloromethane, 357g of thionyl chloride, and 3g of N,N-dimethylformamide, raise the temperature to reflux 40°C, and keep warm for 3 hours. The other steps remain unchanged. 248g of benzyl sulfonyl chloride is obtained, with a molar yield of 65% and a content of 99.08% detected by GC.
[0032] The above are only specific embodiments of the present disclosure, but the protection scope of the present disclosure is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present disclosure, which should be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.
Claims
1. A method for preparing benzylsulfonyl chloride, characterized in that: The following steps are involved: Step 1, adding benzyl chloride, sodium sulfite and a sulfonation catalyst into a first solvent for sulfonation reaction, wherein the molar ratio of the added amounts of benzyl chloride, sodium sulfite and the catalyst is 1: (0.8-1.5): (0.005-0.05); Step 2: After the reaction is completed, the reaction solution is post-treated to obtain sodium benzyl sulfonate; Step 3, adding the obtained sodium benzyl sulfonate, chlorinating agent and chlorination catalyst to a second solvent for chlorination reaction, wherein the molar ratio of the added amounts of sodium benzyl sulfonate, chlorinating agent and chlorination catalyst is 1: (1-1.5): (0.01-0.05); Step 4: post-treating the obtained chlorination reaction solution to obtain benzylsulfonyl chloride.
2. The method according to claim 1, characterized in that: The sulfonation catalyst used in step 1 is one or a mixture of potassium iodide, sodium bromide, sodium iodide, potassium bromide and bromine.
3. The method according to claim 1, characterized in that The first solvent used in step 1 is one or a mixed solvent of water, methanol, and ethanol, wherein the mass ratio of sodium sulfite to the solvent is 1:(1-5).
4. The method according to claim 1, characterized in that The reaction temperature of the sulfonation reaction in step 1 is 100° C.-105° C., and the reaction time is 8-20 h.
5. The method according to claim 1, characterized in that The reaction solution in step 2 is post-treated to obtain sodium benzyl sulfonate, which is then used after undergoing a desolventizing and dehydrating process. The treatment steps are as follows: Step 2-1, the reaction solution is cooled to room temperature and then filtered; Step 2-2, washing the filtered filter cake with dichloroethane; Step 2-3: The washed filter cake is dried and dehydrated to obtain sodium benzyl sulfonate.
6. The method according to claim 1, characterized in that The chlorinating agent used in step 3 is one of thionyl chloride, chlorosulfonic acid, chlorine, phosphorus trichloride, phosphorus oxychloride, and phosphorus pentachloride.
7. The method according to claim 1, characterized in that The chlorination catalyst used in step 3 is one of N,N-dimethylformamide, pyridine, and triethylamine; the second solvent used in step 3 is one of dichloromethane, dichloroethane, and toluene, wherein the mass ratio of sodium benzyl sulfonate to the solvent is 1: (1-5).
8. The method according to claim 1, characterized in that The reaction temperature of the chlorination reaction in step 3 is 70°C-80°C, and the reaction time is 3-4h.
9. The method according to claim 1, characterized in that The benzylsulfonyl chloride reaction solution obtained in step 4 is subjected to hydrolysis, water washing, and desolventizing steps, and the processing steps are as follows: Step 4-1, continuing to heat the chlorination reaction solution to evaporate excess chlorinating agent; Step 4-2: After the distillation is completed, the chlorination reaction solution is placed in water for hydrolysis; Step 4-3, washing and drying the hydrolyzate; Step 4-4, concentrating the solvent to obtain the refined benzylsulfonyl chloride.
10. The method according to any one of claims 1 to 9, characterized in that: The content of benzylsulfonyl chloride obtained in step 4 reaches more than 99%.