Background and overview[1]
Sulfone compounds are a class of organic compounds with wide applications. The sulfonyl groups they contain are widely found in various chemical substances such as pharmaceuticals, agricultural chemicals, and functional materials. Selective oxidation using thioethers is one of the most common methods for the synthesis of sulfones. Methyl p-toluene sulfone is widely used in the synthesis of medical antibiotic methylsulfone toxin, veterinary antibacterial drug flurofen, agricultural herbicide sulfotrione and important intermediates in organic synthesis, and is of great value. According to the starting materials, there are three synthesis methods:
1) Use 4-toluenesulfonyl chloride as raw material, reduce it with sodium sulfite to obtain sodium 4-methylbenzenesulfinate, and then undergo methyl chloride methylation reaction to obtain 4-methylsulfonyltoluene, with a yield of 78 %-82%. Although the reagents used in this method are relatively cheap, there are many steps and the reaction time is long;
2) Use 4-methylsulfonyltoluene as the raw material, hydrogen peroxide as the oxidant, and oxidize it under the action of a catalyst to obtain 4-methylsulfonyltoluene. For example, the literature uses imidazole acidic ionic liquids as the catalyst, and the literature uses acidic graphene oxide. Catalysts, in addition there are reports of metal or zeolite catalysts. This method has short steps and a nearly quantitative yield, but the raw materials and catalysts are expensive and the cost is high.
3) Using toluene as the raw material, the methanesulfonation reaction is carried out directly under the action of a catalyst. The literature uses methanesulfonyl chloride and methanesulfonic anhydride as the sulfonation reagents, and bismuth salt as the catalyst, but the proportion of the 4-position methanesulfonation product is only 65%, poor selectivity. Another team switched to zeolite as the catalyst and methanesulfonic anhydride as the sulfonation reagent to synthesize 4-methylsulfonyltoluene. The proportion of the 4-position methanesulfonation product was higher than 90%, but the reaction conversion rate was low, and the final yield was less than 60 %.
Preparation[1-2]
Method 1: Add TEMPO (3.9 mg, 0.025 mmol), methanol (1 mL), CuSO (4.0 mg, 0.025 mmol), and 3,5-lutidine (28.2 μL, 0.25 mmol) to a 100 mL Schlenk reaction tube. , 4-methylanisole sulfide (67.1 μL, 0.5 mmol) was filled with 1 atm of oxygen, and the sealed reaction tube was heated to 65°C for 24 hours. After the reaction is completed, cool to room temperature, add an appropriate amount of ethyl acetate, and a blue solid precipitates in the reaction solution. Filter, and the filtrate is concentrated under reduced pressure, and separated and purified by column chromatography to obtain the product with a yield of 90%. The reaction formula is:
Product characterization is: HNMR (500MHz, CDCl) δ7.83 (d, J=8.0Hz, 2H), 7.37 (d, J=8.0Hz, 2H), 3.04 (s, 3H), 2.46 (s, 3H). CNMR (125MHz, CDCl) δ 144.7, 137.8, 130.0, 127.4, 44.6, 21.6.
Method 2: A method of synthesizing 4-methylsulfonyltoluene, which is characterized by including the following steps: mixing the material methanesulfonation reagent and phosphorus pentoxide and storing it in the first storage tank, and storing toluene in the third storage tank. In the two storage tanks, the materials in the two storage tanks are sent to the mixer at the same time through an infusion pump for mixing. After mixing evenly, they enter the tubular reactor. The reactor is controlled by adjusting the back pressure regulator at the end of the tubular reactor. Internal pressure, the methanesulfonation reaction is carried out under a certain temperature and pressure. The reaction residence time is 10min~4h. The reaction solution is directly passed into water, filtered and washed with water to obtain the target product 4-methylsulfonyltoluene.
Main reference materials
[1] CN201811104682.5 Preparation method of aryl sulfone compound and extraction method of catalyst and aryl sulfone compound
[2] CN201810262950.X A method for synthesizing 4-methylsulfonyltoluene
