A method for preparing benzyl sulfonyl chloride

Abstract

This invention relates to the field of organic synthesis technology and proposes a method for preparing benzylsulfonyl chloride. Using benzyl chloride and sodium sulfite as raw materials, an intermediate, sodium benzylsulfonate, is synthesized under the action of a catalyst. Following chlorination, hydrolysis, and distillation, benzylsulfonyl chloride is obtained. This invention offers a simple preparation method, uses inexpensive and readily available raw materials, achieves high product yield, and is easily industrialized.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more particularly to a method for preparing benzylsulfonyl chloride. Background Technology

[0002] Benzylsulfonyl chloride, with the molecular formula C7H7ClO2S, has a melting point of 90-94℃ and appears as a nearly white crystalline powder. It is characterized by high reactivity, high solubility, and low toxicity.

[0003] Benzyl sulfonyl chloride has been widely used in various fields. In the pharmaceutical industry, it can be used to synthesize various drugs, such as antibiotics, antitumor drugs, and antihypertensive drugs. In the pesticide industry, it can be used to synthesize various insecticides and fungicides. In the dye and fragrance industry, it can be used to synthesize various dyes and fragrances. The market prospects for benzyl sulfonyl chloride are very broad, and with the continuous development of the pharmaceutical, pesticide, dye, and fragrance industries, the demand for benzyl sulfonyl chloride will continue to increase.

[0004] Currently, the main synthetic methods reported in domestic and international literature include the chlorination method of benzothiourea salt, the chlorination method of benzyl mercaptan, the one-step synthesis method of N-chlorosuccinimide with sulfonyl hydrazine and acetonitrile, and the one-step synthesis method of benzyl chloride with potassium thioacetate and ethyl xanthate.

[0005] The benzothiourea chlorination process primarily uses benzaldehyde as the starting material. The process involves reduction to obtain benzyl alcohol, chlorination to obtain chloromethylbenzene, and substitution to obtain benzylcarbamoyliminosulfate hydrochloride. Finally, sulfonyl chloride is used to obtain benzylsulfonyl chloride. This process involves numerous steps and has a final yield of only 79%.

[0006] The benzyl mercaptan chlorination process involves continuously injecting benzyl mercaptan and water into a reactor in a specific ratio, while simultaneously introducing chlorine gas, to react and produce benzyl sulfonyl chloride. This process requires a continuous flow of materials and the recycling of benzyl mercaptan generated during the micro-reaction until complete conversion, placing high demands on equipment performance, operational skills, and automation control. Furthermore, benzyl mercaptan has a strong odor, posing a significant challenge to the working environment.

[0007] The one-step synthesis of N-chlorosuccinimide with sulfonyl hydrazine and acetonitrile involves adding N-chlorosuccinimide to a CH3CN solution of sulfonyl hydrazine in a single step and maintaining the temperature at room temperature to obtain benzylsulfonyl chloride. This process uses readily available and expensive raw materials, resulting in a final yield of only 87%.

[0008] The one-step synthesis of benzyl chloride with potassium thioacetate and ethyl xanthate involves first incubating benzyl chloride with MeCN and KSAc in an ice bath, then adding concentrated HCl and slowly adding solid NaClO2 to obtain benzyl sulfonyl chloride. This process has a low yield, only about 54%.

[0009] It is evident that existing methods for preparing benzylsulfonyl chloride suffer from problems such as low yield and complex processes. Therefore, there is an urgent need for a method with high yield and simple preparation process. Summary of the Invention

[0010] To overcome the problems existing in the above synthesis, the present invention provides a synthesis method suitable for industrial production of benzyl sulfonyl chloride. The method achieves a benzyl sulfonyl chloride content of over 99% and a yield of over 90%, which is of great production value.

[0011] This invention provides a method for preparing benzyl sulfonyl chloride, which includes the following steps:

[0012] Step 1: Add benzyl chloride, sodium sulfite, and sulfonation catalyst to the first solvent to carry out the sulfonation reaction, wherein the molar ratio of benzyl chloride, sodium sulfite, and catalyst is 1:(0.8-1.5):(0.005-0.05).

[0013] Step 2: After the reaction is complete, the reaction solution is post-treated to obtain sodium benzyl sulfonate;

[0014] Step 3: Add the obtained sodium benzyl sulfonate, chlorinating agent, and chlorination catalyst to the second solvent to carry out the chlorination reaction, wherein the molar ratio of sodium benzyl sulfonate, chlorinating agent, and chlorination catalyst is 1:(1-1.5):(0.01-0.03).

[0015] Step 4: Post-process the obtained chlorination reaction solution to obtain benzylsulfonyl chloride.

[0016] Preferably, the sulfonation catalyst used in step 1 is one or a mixture of several of potassium iodide, sodium bromide, and bromine.

[0017] Preferably, the first solvent used in step 1 is one or a mixture of several of water, methanol, and ethanol, wherein the mass ratio of sodium sulfite to the solvent is 1:(1-5).

[0018] Preferably, the sulfonation reaction in step 1 is carried out at a temperature of 100℃-105℃ and for a reaction time of 8-20h.

[0019] Preferably, the sodium benzyl sulfonate obtained in step 2 is used after undergoing solvent removal and dehydration processes. The processing steps are as follows:

[0020] Step 2-1: After cooling the reaction solution to room temperature, filter it.

[0021] Step 2-2: Wash the filtered filter cake with dichloroethane;

[0022] Steps 2-3: After washing, the filter cake is dried and dehydrated to obtain sodium benzyl sulfonate.

[0023] Preferably, the chlorinating agent used in step 3 is one of thionyl chloride, chlorosulfonic acid, chlorine, phosphorus trichloride, phosphorus oxychloride, and phosphorus pentachloride.

[0024] 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 solvent is 1:(1-5).

[0025] Preferably, the chlorination reaction in step 3 is carried out at a temperature of 70℃-80℃ for 3-4 hours.

[0026] Preferably, the benzyl sulfonyl chloride reaction solution obtained in step 4 undergoes hydrolysis, washing, and solvent removal processes, as follows:

[0027] Step 4-1: Continue heating the chlorination reaction solution to evaporate excess chlorinating agent;

[0028] Step 4-2: After distillation, the chlorination reaction solution is placed in water for hydrolysis.

[0029] Step 4-3: Wash the hydrolysate with water and dry it;

[0030] Step 4-4: Concentrate the solvent to obtain refined benzylsulfonyl chloride.

[0031] Preferably, the benzyl sulfonyl chloride obtained in step 4 has a content of 99% or more.

[0032] The preparation process of benzyl sulfonyl chloride in this invention is as follows:

[0033] Reaction 1

[0034] Reaction 2

[0035] Compared with existing technologies, the benzyl sulfonyl chloride obtained by the method provided by this invention has a purity of over 99% and a yield of over 90%. Moreover, the preparation method is simple, the raw materials are inexpensive and readily available, and it is easy to industrialize, thus having extremely high application value. Attached Figure Description

[0036] Figure 1 The mass spectrum of benzyl sulfonyl chloride obtained in Example 4;

[0037] Figure 2 The image shows the gas phase spectrum of benzyl sulfonyl chloride obtained in Example 4. Detailed Implementation

[0038] Example 1, Step 1: Add 253g of benzyl chloride, 277g of sodium sulfite, and 500g of water to a 2L four-necked flask equipped with a thermometer and mechanical stirrer. Heat the flask to 100℃-105℃ and maintain the temperature for 12 hours.

[0039] Step 2: After the reaction is complete, lower the temperature inside the flask to room temperature, pour out the reaction solution, and centrifuge. The solid is then slurried using dichloroethane and centrifuged. The solid material is transferred to an oven for drying; the dried solid is sodium benzyl sulfonate.

[0040] Step 3: Add the obtained sodium benzyl sulfonate to a 2L four-necked glass bottle equipped with a thermometer and mechanical stirrer, add 800g of dichloroethane and 357g of thionyl chloride, heat to reflux temperature of 80°C, and keep warm for 3 hours.

[0041] Step 4: After the heat preservation is completed, excess thionyl chloride is distilled off under negative pressure. The material in the bottle is added to 1000g of water for hydrolysis. After hydrolysis, the mixture is washed with water, dried with calcium chloride, the solvent is concentrated, and finally distilled to obtain 259g of benzylsulfonyl chloride, with a molar yield of 68% and a GC content of 99.18%.

[0042] Example 2: The preparation method of benzyl sulfonyl chloride in this example differs from that in Example 1 in that:

[0043] Step 1: Add 253g of benzyl chloride, 277g of sodium sulfite, 250g of water, and 250g of ethanol to a 2L four-necked flask equipped with a thermometer and mechanical stirrer. Heat to 100℃-105℃ and maintain the reaction temperature for 12 hours. Other steps remain unchanged. 286g of benzyl sulfonyl chloride is obtained, with a molar yield of 75% and a GC content of 99.11%.

[0044] Example 3: The preparation method of benzyl sulfonyl chloride in this example differs from that in Example 2 in that:

[0045] Step 1: Add 253g of benzyl chloride, 277g of sodium sulfite, 2.5g of potassium iodide, 250g of water, and 250g of ethanol to a 2L four-necked flask equipped with a thermometer and mechanical stirrer. Heat to 100℃-105℃ and maintain the reaction temperature for 12 hours. Other steps remain unchanged. 339g of benzyl sulfonyl chloride is obtained, with a molar yield of 89% and a GC content of 99.23%.

[0046] Example 4: The preparation method of benzyl sulfonyl chloride in this example differs from that in Example 3 in that:

[0047] Step 3: Add the obtained sodium benzyl sulfonate to a 2L four-necked glass flask equipped with a thermometer and mechanical stirrer. Add 800g of dichloroethane, 357g of thionyl chloride, and 3g of N,N-dimethylformamide. Heat to reflux temperature of 80°C and maintain this temperature for 3 hours. Other steps remain unchanged. 355g of benzyl sulfonyl chloride is obtained (its mass spectrum is shown below). Figure 1 As shown, m / z=189.99), molar yield 93%, GC detection content 99.21% (its gas chromatogram is shown in Figure 1). Figure 2 (As shown).

[0048] Example 5: The preparation method of benzyl sulfonyl chloride in this example differs from that in Example 3 in that:

[0049] Step 1: Add 253g of benzyl chloride, 277g of sodium sulfite, 5.0g of sodium bromide, 250g of water, and 250g of ethanol to a 2L four-necked flask equipped with a thermometer and mechanical stirrer. Heat to 100℃-105℃ and maintain the temperature for 12 hours. Other steps remain unchanged. 318.05g of benzyl sulfonyl chloride is obtained, with a molar yield of 83.5% and a GC content of 99.15%.

[0050] Example 6: The preparation method of benzyl sulfonyl chloride in this example differs from that in Example 4 in that:

[0051] Step 3: Add the obtained sodium benzyl sulfonate to a 2L four-necked glass flask equipped with a thermometer and mechanical stirrer. Add 800g of dichloromethane, 357g of thionyl chloride, and 3g of N,N-dimethylformamide. Heat to reflux at 40°C and maintain this temperature for 3 hours. Other steps remain unchanged. 248g of benzyl sulfonyl chloride is obtained, with a molar yield of 65% and a GC content of 99.08%.

[0052] The above are merely specific embodiments of this disclosure, but the scope of protection of this disclosure is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this disclosure should be included within the scope of protection of this disclosure. Therefore, the scope of protection of this disclosure should be determined by the scope of the claims.

Claims

1. A process for the preparation of benzylsulfonyl chloride, characterized in that, Comprising the following steps: Step 1, add benzyl chloride 253 g, sodium sulfite 277 g, potassium iodide 2.5 g, water 250 g, ethanol 250 g to a 2L four-necked bottle with a thermometer and mechanical stirring, heat to a bottle temperature of 100-105°C, and keep the temperature for 12 hours; Step 2, after the reaction is completed, reduce the bottle temperature to room temperature, pour out the reaction solution and centrifuge; centrifugal solids are slurried with dichloroethane, then centrifuged; solid materials are transferred to an oven for drying, and the dried solid is sodium benzyl sulfonate; Step 3, add the obtained sodium benzyl sulfonate to a 2L four-necked glass bottle with a thermometer and mechanical stirring, add dichloroethane 800 g, thionyl chloride 357 g, N,N-dimethylformamide 3 g, heat to a reflux temperature of 80°C, and keep the temperature for 3 hours; Step 4, after the temperature is kept, excess thionyl chloride is distilled out under negative pressure; the bottle materials are added to 1000 g of water for hydrolysis; after hydrolysis, water washing, calcium chloride drying, and solvent concentration, benzyl sulfonyl chloride 355 g is obtained by final distillation, with a molar yield of 93% and a GC detection content of 99.21%.

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