Synthesis method of 4-methylsulfonyl toluene derivative

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of a 4-methylsulfonyl toluene derivative, which is technically characterized in that the synthesis process is # imgabs0 #, and the definition of a substituent group is as follows: R is one of NO2, CN, COCH3, COC2H5, COOCH3, COOC2H5, CH3CONH, CF3 and CCl3 groups. The method solves the problems of relatively long steps, large amount of waste acid and waste gas, high treatment difficulty and high treatment cost of the existing process route, the target product can be obtained by directly sulfonating, chlorinating and methylating the toluene raw material containing ortho-substituent groups, the final reaction process of R substituent groups is omitted, the production steps are reduced, and the production cost is reduced. Production equipment and technological operation are simplified, loss caused by material transfer is reduced, and the product yield is increased.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing a 4-methylsulfonyltoluene derivative. Background Art

[0002] 2-Nitro-4-methylsulfonyltoluene is the most widely used chemical product among 4-methylsulfonyltoluene derivatives. 2-Nitro-4-methylsulfonyltoluene is an important organic chemical intermediate, widely used in pesticides, dyes, medicines and other fields, especially in the field of pesticides, it is an important intermediate for the synthesis of herbicides mesotrione. Mesotrione, also known as mesotrione and mesotrione, has a chemical name of 2-(2-nitro-4-methylsulfonylbenzoyl)cyclohexane-1,3-dione, which is a triketone herbicide developed by Syngenta. As a new type of systemic herbicide for corn fields, mesotrione has the characteristics of a wide spectrum of weed control, high activity, strong miscibility, safety to crops, and strong environmental compatibility, and has great development and use prospects in my country.

[0003] At present, 2-nitro-4-methylsulfonyltoluene is usually obtained by chlorosulfonation, methylation, nitration and oxidation of toluene. The synthetic process route is as follows:

[0004] This process route has certain industrial value, but there are the following problems: the route steps are relatively long, especially in the nitration process, a large amount of high-content waste acid and waste gas is generated, which is difficult to treat and the cost of treating the three wastes is high. Summary of the invention

[0005] The purpose of the present invention is to provide a method for synthesizing 4-methylsulfonyltoluene derivatives, so as to solve the problems of long steps, large amount of waste acid and waste gas, great difficulty in treatment and high treatment cost in the existing process route. By adopting a toluene raw material containing an ortho-substituted group, the target product can be obtained by directly performing sulfonation, chlorination and methylation, the reaction process of the last R substituent is omitted, the production steps are reduced, the production equipment and process operation are simplified, the loss caused by material transfer is reduced, and the product yield is improved.

[0006] The technical solution of the present invention is: A method for synthesizing a 4-methylsulfonyltoluene derivative, the technical key points of which are that the synthesis process is:

[0007] Wherein, the substituents are defined as follows: R is for NO 2 、CN、COCH 3 、COC 2 H 5 、COOCH 3 、COOC2 H 5 , CH 3 CONH, CF 3 , CCl 3 One of the groups.

[0008] The above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives specifically comprises the following steps: Step 1, add a sulfonating agent and a chlorinating agent into a reaction bottle, start the stirrer, add ammonium chloride in batches, after the ammonium chloride is added, dissolve the ortho-derivative toluene in a solvent or without adding a solvent, slowly dropwise add it into the reaction bottle, control the temperature in the bottle to 65-70°C, and the dropwise addition time is 2-3h. After the dropwise addition is completed, the system is kept at this temperature for 2 hours to react, and the reaction is terminated; Step 2: Add process water to another reaction bottle in advance and cool it to 5-10°C, slowly drop the product in step 1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining sulfonating agent and chlorinating agent, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2 hours and then stop; after the sulfonating agent and chlorinating agent are hydrolyzed and destroyed, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 4-methylbenzenesulfonyl chloride derivative. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled; Step 3, add water to a new reaction bottle, raise the temperature to 60°C, start the stirrer, add sodium sulfite and sodium carbonate, raise the temperature to 75°C, slowly add 4-methylbenzenesulfonyl chloride derivative in batches, maintain the temperature at 80-82°C during the addition process, and keep the temperature at this temperature for 1 hour after the addition is completed; Step 4, after the heat preservation, filter while hot, the mother liquor enters the autoclave, and then replaces the air in the autoclave with nitrogen three times, and then replaces the nitrogen in the autoclave with a gaseous methylating agent three times, and starts to pass the gaseous methylating agent, and adjusts the pressure. When the pressure in the autoclave no longer decreases after the air is stopped, keep warm for 1 hour, and confirm that the pressure in the autoclave remains unchanged, then the reaction is over, and the material is transferred to a flask, and the pH value is adjusted in the flask with liquid alkali; after the pH value is adjusted, cooling water is started to cool, and the material is stirred until crystals are precipitated, and the material is filtered and washed at a set temperature, and the washed material is dried to obtain a 4-methylsulfonyltoluene derivative; Alternatively, after the heat preservation, the mixture is filtered while hot, the mother liquor enters the reactor, the air in the reactor is replaced with nitrogen three times, and the liquid methylation reagent is added dropwise. After the addition is completed, the mixture is kept warm for 1 hour. After the intermediate control reaction is completed, the material is transferred to a flask, and the pH value is adjusted in the flask with liquid alkali. After the pH value is adjusted, cooling water is passed to cool the mixture, and the mixture is stirred until crystals are precipitated. The material is filtered and washed at the set temperature, and the washed material is dried to obtain a 4-methylsulfonyltoluene derivative.

[0009] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, the sulfonating agent is one of concentrated sulfuric acid, oleum, chlorosulfonic acid, sulfonyl chloride, sulfonyl fluoride, sulfur trioxide, aminosulfonic acid, sulfite, a mixture of sulfur dioxide and chlorine, or a mixture of sulfur dioxide and oxygen.

[0010] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, the chlorinating agent is one of chlorosulfonic acid, thionyl chloride, sulfuryl chloride, phosphorus pentachloride, phosphorus oxychloride, diphosgene, triphosgene and oxalyl chloride.

[0011] The above-mentioned synthesis method of 4-methylsulfonyltoluene derivatives, wherein the methylating agent is one of methyl chloride, methyl bromide, methyl iodide, dimethyl sulfate, dimethyl carbonate, methyl p-toluenesulfonate, methyl methanesulfonate, methanol, DMF-DMA, trimethyl phosphate, trimethyl orthoformate, methyl trifluoromethanesulfonate, and sodium chloroacetate.

[0012] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, the solvent used in step 1 is one of dichloroethane, dichloromethane, chloroform, toluene, ethyl acetate, and no solvent.

[0013] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, in step 1, the molar ratio of the sulfonating agent: the chlorinating agent: the ammonium chloride: the o-methylbenzene derivative is 0-4:0-2:0-1:1.

[0014] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, the total weight ratio of process water to sulfonating agent and chlorinating agent used in step 2 is 0.5:1.

[0015] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, in step 3, the mixing ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 0.5-1.5:0.5-1.5:1 in molar ratio.

[0016] In the above-mentioned method for synthesizing 4-methylsulfonyltoluene derivatives, the pressure in step 4 is adjusted to a range of 0 to 2.0 MPa; and the pH value of the liquid alkali is adjusted to a range of 5 to 14.

[0017] The beneficial effects of the present invention are: By using toluene raw materials containing ortho-substituted groups, the target product can be directly obtained by sulfonation, chlorination and methylation, omitting the reaction process of the final R substituent, reducing the production steps, simplifying the production equipment and process operations, reducing the losses caused by material transfer, and improving the product yield, thereby solving the problems of the existing process route with long steps, large amounts of waste acid and waste gas, great difficulty in treatment and high treatment cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1is the chemical formula of the product of Example 1 and Example 2 of the present invention; Figure 2 is the product test result of Example 2 of the present invention; Figure 3 is the chemical formula of the product of Example 3 and Example 4 of the present invention; Figure 4 is the product test result of Example 4 of the present invention; Figure 5 is the chemical formula of the product of Example 5 and Example 6 of the present invention; Figure 6 This is the product test result of Example 6 of the present invention. DETAILED DESCRIPTION

[0019] Take the production of 2-nitro-4-methylsulfonyltoluene as an example.

[0020] Embodiment 1, this synthesis method specifically comprises the following steps: Step 1: In the reaction bottle, add 392.4g sulfuric acid and 233g chlorosulfonic acid, start the stirrer, add 53.5g ammonium chloride in batches, after the ammonium chloride is added, dissolve 137.1g o-nitrotoluene in 150g toluene, slowly add it dropwise into the reaction bottle, control the temperature in the bottle to 65-70°C, and the dropping time is 2-3h. After the dropping is completed, the system is kept at this temperature for 2 hours, and the reaction is completed.

[0021] Step 2: Add 312.7g of process water to another reaction bottle in advance, and cool it to 5-10°C. Slowly drop the product in step 1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining sulfuric acid and chlorosulfonic acid, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2 hours and then stop; the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-nitro-4-methylbenzenesulfonyl chloride 209.7g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0022] Step 3: Place a new reaction bottle and add 426g of water, raise the temperature to 60°C, start the stirrer, add 114.5g of sodium sulfite and 98.3g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-nitro-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep the temperature at this temperature for 1 hour.

[0023] Step 4: After the heat preservation, filter while hot, the mother liquor enters the autoclave, and then replaces the air in the autoclave with nitrogen three times, and then replaces the nitrogen in the autoclave with chloroform three times, and starts to pass chloroform, and adjusts the pressure to 1-2MPa. When the pressure in the autoclave no longer decreases after the air is stopped, keep warm for 1 hour, and confirm that the pressure in the autoclave remains unchanged, then the reaction is over, and the material is transferred to a flask. In the flask, adjust the pH to 8 with liquid alkali; after adjusting the pH value, start passing cooling water to cool, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 175.1g of 2-nitro-4-methylsulfonyltoluene.

[0024] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 4:2:1:1; the total weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.01:1.03:1.

[0025] Embodiment 2, this synthesis method specifically comprises the following steps: Step 1: In a reaction vessel, add 279.6g of chlorosulfonic acid, start the stirrer, and add 10.7g of ammonium chloride in batches. After the addition of ammonium chloride, dissolve 137.1g of o-nitrotoluene in dichloroethane and slowly add it dropwise into the reaction bottle. Control the temperature in the bottle to 65-70°C and the addition time to 2-3h. After the addition is completed, the system is kept at this temperature for 2 hours and the reaction is completed.

[0026] Step 2: Add 139.8g of process water to another reaction bottle in advance, and cool it to 5-10°C. Slowly drop the product in S1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining chlorosulfonic acid, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2 hours and stop; after the hydrolysis destroys the chlorosulfonic acid, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-nitro-4-methylbenzenesulfonyl chloride 212.9g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0027] Step 3: Place a new reaction bottle and add 420g of water, raise the temperature to 60°C, start the stirrer, add 115.5g of sodium sulfite and 99.1g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-nitro-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep warm at this temperature for 1 hour.

[0028] Step 4: After the heat preservation, filter while hot, the mother liquor enters the autoclave, and then replaces the air in the autoclave with nitrogen three times, and then replaces the nitrogen in the autoclave with chloroform three times, and starts to pass chloroform to adjust the pressure. When the air is not introduced, the pressure in the autoclave no longer decreases. Keep warm for 1 hour, confirm that the pressure in the autoclave remains unchanged, then the reaction is over, transfer the material to a flask, and adjust the pH to 8 with liquid alkali in the flask; after adjusting the pH value, start passing cooling water to cool, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 175.5g of 2-nitro-4-methylsulfonyltoluene.

[0029] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 0:2.4:0.2:1; the weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.03:1.05:1.

[0030] After testing, the product yield can reach 90%, and the HPLC purity can reach 99.85%. Figure 2 The test results.

[0031] Take the production of 2-acetyl-4-methylsulfonyltoluene as an example.

[0032] Embodiment 3, this synthesis method specifically comprises the following steps: Step 1: In a reaction container, add 148.5g of sulfonyl chloride and 184g of phosphorus oxychloride, start the stirrer, dissolve 140g of o-acetyltoluene in 150g of chloroform, and slowly add it dropwise into the reaction bottle. Control the temperature in the bottle to 65-70°C and the addition time to 2-3h. After the addition is completed, keep the system at this temperature for 2 hours and the reaction is completed.

[0033] Step 2: Add 166.2g of water to another reaction bottle in advance, and cool it to 5-10°C. Slowly drop the product in S1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining sulfonyl chloride and phosphorus oxychloride, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2h and stop; after the hydrolysis and destruction of sulfonyl chloride and phosphorus oxychloride, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-acetyl-4-methylbenzenesulfonyl chloride 215g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0034] Step 3: Place a new reaction bottle and add 430g of water, raise the temperature to 60°C, start the stirrer, add 118.6g of sodium sulfite and 155.3g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-acetyl-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep warm at this temperature for 1 hour.

[0035] Step 4: After the insulation, filter while hot, the mother liquor enters the reactor, and then replace the air in the reactor with nitrogen three times, start to add dimethyl sulfate dropwise, and after the addition is completed, keep warm for 1 hour. After the mid-control reaction is completed, transfer the material to a flask, and adjust the pH to 14 with liquid alkali in the flask; after adjusting the pH value, start to cool with cooling water, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 179.2g of 2-acetyl-4-methylsulfonyltoluene.

[0036] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 1.1:1.2:0:1; the weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.02:1.5:1.

[0037] Embodiment 4, this synthesis method specifically comprises the following steps: Step 1: In a reaction vessel, add 116.5g of aminosulfonic acid and 130.9g of thionyl chloride, start the stirrer, and add 10.7g of ammonium chloride in batches. After the ammonium chloride is added, dissolve 140g of o-acetyltoluene in 150g of dichloroethane, and slowly add it dropwise into the reaction bottle. Control the temperature in the bottle to 65-70°C, and the dropping time is 2-3h. After the dropping is completed, the system is kept at this temperature for 2 hours, and the reaction is completed.

[0038] Step 2: Add 123.7g of water to another reaction bottle in advance, and cool it to 5-10°C. Slowly drop the product in S1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining aminosulfonic acid and thionyl chloride, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2h and stop; after the aminosulfonic acid and thionyl chloride are hydrolyzed and destroyed, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-acetyl-4-methylbenzenesulfonyl chloride 213.7g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0039] Step 3: Place a new reaction bottle and add 427.4g of water, raise the temperature to 60°C, start the stirrer, add 117.9g of sodium sulfite and 99.2g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-acetyl-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep warm at this temperature for 1 hour.

[0040] Step 4: After the insulation, filter while hot, the mother liquor enters the reactor, and then replace the air in the reactor with nitrogen three times, start to add dimethyl carbonate dropwise, and after the addition is completed, keep warm for 1 hour. After the mid-control reaction is completed, transfer the material to a flask, and adjust the pH to 5 with liquid alkali in the flask; after adjusting the pH value, start to cool with cooling water, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 179g of 2-acetyl-4-methylsulfonyltoluene.

[0041] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 1.2:1.1:0.2:1; the weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.02:1.02:1.

[0042] After testing, the product yield can reach 91%, and the HPLC purity can reach 99.81%. Figure 4 The test results.

[0043] Take the production of 2-trichloromethyl-4-methylsulfonyltoluene as an example.

[0044] Embodiment 5, this synthesis method specifically comprises the following steps: Step 1: In a reaction vessel, add 125.4g of fuming sulfuric acid and 128.2g of chlorosulfonic acid, start the stirrer, and add 26.75g of ammonium chloride in batches. After the addition of ammonium chloride, dissolve 209g of o-trichloromethyltoluene in 150g of ethyl acetate, and slowly drop it into the reaction bottle. Control the temperature in the bottle to 65-70°C, and the dropwise addition time is 2-3h. After the dropwise addition is completed, the system is kept at this temperature for 2 hours, and the reaction is completed; Step 2: Add 126.8g of water to another reaction bottle in advance, and cool it to 5-10°C. Slowly drop the product in S1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining fuming sulfuric acid and chlorosulfonic acid, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2h and stop; after the hydrolysis destroys fuming sulfuric acid and chlorosulfonic acid, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-trichloromethyl-4-methylbenzenesulfonyl chloride 278.1g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0045] Step 3: Place a new reaction bottle and add 536.4g of water, raise the temperature to 60°C, start the stirrer, add 170g of sodium sulfite and 98.3g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-trichloromethyl-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep the temperature at this temperature for 1 hour.

[0046] Step 4: After the heat preservation, filter while hot, the mother liquor enters the reactor, and then replace the air in the reactor with nitrogen three times, start to add methyl bromide dropwise, and after the addition is completed, keep warm for 1 hour. After the mid-control reaction is completed, transfer the material to a flask, and adjust the pH to 9 with liquid alkali in the flask; after adjusting the pH value, start to cool with cooling water, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 233.9g of 2-trichloromethyl-4-methylsulfonyltoluene.

[0047] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 1.1:1.1:0.5:1; the weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.5:1.03:1.

[0048] Embodiment 6, this synthesis method specifically comprises the following steps: Step 1: In the reaction container, add 251.3g chlorosulfonic acid, start the stirrer, add 53.5g ammonium chloride in batches, after the ammonium chloride is added, dissolve 209g o-trichloromethyltoluene in 150g dichloroethane, slowly drop it into the reaction bottle, control the temperature in the bottle to 65-70°C, the dropping time is 2-3h, after the dropping is completed, the system is kept at this temperature for 2 hours, and the reaction is completed.

[0049] Step 2: Add 209g of water to another reaction bottle in advance, and cool it to 5-10°C, slowly drop the product in S1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining chlorosulfonic acid, the hydrolysis system releases a lot of heat, and stop stirring after the drop is completed for 2h; after the hydrolysis destroys the chlorosulfonic acid, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the dichloro product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 3-trichloromethyl-4-methylbenzenesulfonyl chloride 230.7g of crystals. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled.

[0050] Step 3: Place a new reaction bottle and add 461.4g of water, raise the temperature to 60°C, start the stirrer, add 117.2g of sodium sulfite and 101.9g of sodium carbonate, raise the temperature to 75°C, and slowly add 3-trichloromethyl-4-methylbenzenesulfonyl chloride in batches. Keep the temperature at 80-82°C during the addition process. After the addition is completed, keep the temperature at this temperature for 1 hour; Step 4: After the heat preservation, filter while hot, the mother liquor enters the reactor, and then replace the air in the reactor with nitrogen three times, start to add DMF-DMA dropwise, and after the addition is completed, keep warm for 1 hour. After the mid-control reaction is completed, transfer the material to a flask, and adjust the pH to 9 with liquid alkali in the flask; after adjusting the pH value, start to cool with cooling water, stir until crystals precipitate, and filter and wash the material at about 50°C. The washed material is dried to obtain 236.2g of 2-trichloromethyl-4-methylsulfonyltoluene.

[0051] In this embodiment, the molar ratio of sulfonating agent: chlorinating agent: ammonium chloride: o-derivative toluene is 1.1:1.1:1:1; the weight ratio of process water: sulfonating agent and chlorinating agent is 0.5:1; the molar ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 1.02:1.03:1.

[0052] After testing, the product yield can reach 90%, and the HPLC purity can reach 99.83%. Figure 6 The test results.

[0053] The embodiments of the present invention are described in detail above, but the contents described are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the present invention.

Claims

1. A method for synthesizing a 4-methylsulfonyltoluene derivative, characterized in that: The synthesis process is: ， Wherein, the substituents are defined as follows: R is one of NO2, CN, COCH3, COC2H5, COOCH3, COOC2H5, CH3CONH, CF3, and CCl3 groups.

2. The method for synthesizing the 4-methylsulfonyltoluene derivative according to claim 1, comprising the following steps: Step 1, add a sulfonating agent and a chlorinating agent into a reaction bottle, start the stirrer, add ammonium chloride in batches, after the ammonium chloride is added, dissolve the ortho-derivative toluene in a solvent or without adding a solvent, slowly dropwise add it into the reaction bottle, control the temperature in the bottle to 65-70°C, and the dropwise addition time is 2-3h. After the dropwise addition is completed, the system is kept at this temperature for 2 hours to react, and the reaction is terminated; Step 2: Add process water to another reaction bottle in advance and cool it to 5-10°C, slowly drop the product in step 1 into the bottle, control the temperature at 15-25°C, hydrolyze and destroy the remaining sulfonating agent and chlorinating agent, and the hydrolysis system releases a lot of heat. After the drop is completed, stir for 2 hours and then stop; after the sulfonating agent and chlorinating agent are hydrolyzed and destroyed, the system is allowed to stand for stratification, the lower layer is the waste acid water layer, and the upper layer is the product solution layer. The product solution layer is reduced pressure to concentrate a part of the solvent, and the remaining system is cooled and crystallized twice to obtain the target product 4-methylbenzenesulfonyl chloride derivative. The mother liquor contains a small amount of by-products. After the solvent is recovered, the kettle residue can be treated as hazardous waste, and the solvent can be recycled; Step 3, add water to a new reaction bottle, raise the temperature to 60°C, start the stirrer, add sodium sulfite and sodium carbonate, raise the temperature to 75°C, slowly add 4-methylbenzenesulfonyl chloride derivative in batches, maintain the temperature at 80-82°C during the addition process, and keep the temperature at this temperature for 1 hour after the addition is completed; Step 4, after the heat preservation, filter while hot, the mother liquor enters the autoclave, and then replaces the air in the autoclave with nitrogen three times, and then replaces the nitrogen in the autoclave with a gaseous methylating agent three times, and starts to pass the gaseous methylating agent, and adjusts the pressure. When the pressure in the autoclave no longer decreases after the air is stopped, keep warm for 1 hour, and confirm that the pressure in the autoclave remains unchanged, then the reaction is over, and the material is transferred to a flask, and the pH value is adjusted in the flask with liquid alkali; after the pH value is adjusted, cooling water is started to cool, and the material is stirred until crystals are precipitated, and the material is filtered and washed at a set temperature, and the washed material is dried to obtain a 4-methylsulfonyltoluene derivative; Alternatively, after the heat preservation, the mixture is filtered while hot, the mother liquor enters the reactor, the air in the reactor is replaced with nitrogen three times, and the liquid methylation reagent is added dropwise. After the addition is completed, the mixture is kept warm for 1 hour. After the intermediate control reaction is completed, the material is transferred to a flask, and the pH value is adjusted in the flask with liquid alkali. After the pH value is adjusted, cooling water is passed to cool the mixture, and the mixture is stirred until crystals are precipitated. The material is filtered and washed at the set temperature, and the washed material is dried to obtain a 4-methylsulfonyltoluene derivative.

3. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: The sulfonating agent is one of concentrated sulfuric acid, oleum, chlorosulfonic acid, sulfonyl chloride, sulfonyl fluoride, sulfur trioxide, aminosulfonic acid, sulfite, a mixture of sulfur dioxide and chlorine, and a mixture of sulfur dioxide and oxygen.

4. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: The chlorinating agent is one of chlorosulfonic acid, thionyl chloride, sulfuryl chloride, phosphorus pentachloride, phosphorus oxychloride, diphosgene, triphosgene and oxalyl chloride.

5. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: The methylating agent is one of methyl chloride, methyl bromide, methyl iodide, dimethyl sulfate, dimethyl carbonate, methyl p-toluenesulfonate, methyl methanesulfonate, methanol, DMF-DMA, trimethyl phosphate, trimethyl orthoformate, methyl trifluoromethanesulfonate, and sodium chloroacetate.

6. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: The solvent used in step 1 is one of dichloroethane, dichloromethane, chloroform, toluene and ethyl acetate.

7. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: In the step 1, the molar ratio of the sulfonating agent: the chlorinating agent: the ammonium chloride: the derivative of o-methylbenzene is 0-4:0-2:0-1:

1.

8. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: The total weight ratio of process water to sulfonating agent and chlorinating agent used in step 2 is 0.5:

1.

9. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: In the step 3, the mixing ratio of sodium sulfite: sodium carbonate: 4-methylbenzenesulfonyl chloride derivative is 0.5-1.5:0.5-1.5:1 in molar ratio.

10. The method for synthesizing 4-methylsulfonyltoluene derivatives according to claim 1, characterized in that: In step 4, the pressure is adjusted in the range of 0 to 2.0 MPa; the pH value of the liquid alkali is adjusted in the range of 5 to 14.

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