Preparation process of trifluoroethyl diphenyl sulfonium salt

Abstract

The invention relates to the technical field of compound preparation, in particular to a preparation process of 2, 2, 2-trifluoroethyl diphenyl sulfonium trifluoromethanesulfonate. Comprising the following steps: reacting 2, 2, 2-trifluoroethanol, formic acid and acetic anhydride, rectifying the reaction liquid, and collecting a target fraction to obtain 2, 2, 2-trifluoroethyl formate; according to the method, 2, 2, 2-trifluoroethyl formate, diphenyl sulfide and trifluoromethanesulfonic acid are subjected to a reaction, reaction liquid is cooled, solids are separated out, organic solvent washing is carried out, 2, 2, 2-trifluoroethyl diphenyl sulfonium trifluoromethanesulfonate is obtained, the purity can reach 99.7%, and the total reaction yield can reach 78.93%. The preparation process provided by the invention has the advantages of cheap and easily available raw materials, simple operation, high reaction yield, mild reaction conditions, high safety and simple reaction post-treatment, and is suitable for industrial large-scale production.

Description

Technical Field

[0001] This invention relates to the field of compound preparation technology, and to a preparation process of trifluoroethyl diphenyl sulfonium salt, specifically to a preparation process of 2,2,2-trifluoroethyl diphenyl sulfonium trifluoromethanesulfonate. Background Technology

[0002] 2,2,2-Trifluoroethyl diphenylsulfonium trifluoromethanesulfonate (CAS: 135654-49-8) is an important fluorinating agent with a wide range of applications due to its excellent stability, availability, and ease of handling. It has been used in many innovative trifluoroalkylation reactions, including photoredox trifluoroethylation, iron-catalyzed insertion reactions, cyclopropanation reactions, Johnson-Corey-Chaykovsky reactions, and [4+1] cycloaddition reactions. 2,2,2-Trifluoroethyl diphenylsulfonium trifluoromethanesulfonate is used to synthesize trifluoroethyl compounds and various trifluoromethylated cyclopropanes, epoxides, aziridines, pyrrole derivatives, and pyrazolines, exhibiting high diastereoselectivity.

[0003] However, there are currently only two reports on the preparation methods of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate, and the preparation methods are relatively complex and not suitable for large-scale preparation.

[0004] Umemoto first reported the preparation of 2,2,2-trifluoroethylated onium salts of Nitrogen, Sulfur, and Phosphorus with (2,2,2-trifluoroethyl)phenyliodonium triflate in 1991. The specific reaction equation is as follows: .

[0005] The advantage of this preparation method is that it uses dichloromethane as a solvent and reacts at room temperature, resulting in mild reaction conditions. However, the preparation of 2,2,2-trifluoroethyl(phenyl)iodonium trifluoromethanesulfonate is relatively complicated, requires harsh reaction conditions, and cannot be prepared in large quantities.

[0006] The Xiao Jichang research group optimized the preparation method of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate (CN105523873A). The specific reaction equation is as follows: .

[0007] This method uses 2,2,2-trifluoroethyltrifluoromethanesulfonate and diphenyl sulfide as raw materials. The raw materials are mixed and heated to 150°C in a closed reactor for 24 hours. After the reaction solution cools to room temperature, a white solid precipitates, which can be obtained by filtration with a yield of 80%. However, this preparation method has two significant drawbacks: 1) the price of the raw material 2,2,2-trifluoroethyltrifluoromethanesulfonate is relatively high; 2) the boiling point of 2,2,2-trifluoroethyltrifluoromethanesulfonate is 89-91°C, while the reaction temperature is 150°C, so the reaction needs to be carried out in a closed reactor, resulting in high pressure and potential danger. Furthermore, 2,2,2-trifluoroethyltrifluoromethanesulfonate is prone to decomposition at high temperatures, making large-scale preparation using this method difficult. Summary of the Invention

[0008] The purpose of this invention is to overcome the shortcomings of the prior art and provide a preparation process for 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate. This method uses inexpensive and readily available raw materials, is simple to operate, has a high yield, mild reaction conditions, and high safety, making it suitable for industrial-scale production.

[0009] This invention provides a process for preparing 2,2,2-trifluoroethyl diphenylsulfonate trifluoromethanesulfonate, comprising the following steps: Step 1: 2,2,2-Trifluoroethanol, formic acid, and acetic anhydride are reacted. The reaction solution is then distilled, and the target fraction is collected to obtain 2,2,2-trifluoroethyl carbamate. ; Step 2: 2,2,2-Trifluoroethyl carbamate, diphenyl sulfide, and trifluoromethanesulfonic acid are reacted. The reaction solution is cooled, the solid precipitates, and it is washed with an organic solvent to obtain 2,2,2-trifluoroethyl diphenylsulfonate. .

[0010] Further, the molar ratio of 2,2,2-trifluoroethanol, formic acid and acetic anhydride in step one is 1:1~1.5:1~2; the molar ratio of 2,2,2-trifluoroethyl carbamate, diphenyl sulfide and trifluoromethanesulfonic acid in step two is 1:2~4:1~1.5.

[0011] Further, in step one, formic acid and acetic anhydride are added sequentially to the reaction vessel, and 2,2,2-trifluoroethanol is added dropwise to obtain 2,2,2-trifluoroethyl formate. When adding 2,2,2-trifluoroethanol, the system temperature is controlled at 35~40℃. The reaction temperature is 35~45℃ and the reaction time is 1.5~2.5 h.

[0012] Furthermore, the distillation in step one uses a distillation column filled with glass spring packing, the column length is 25~35cm, and the target fraction is the fraction collected at a top temperature of 58~62℃.

[0013] Further, in step two, diphenyl sulfide and trifluoromethanesulfonic acid are added sequentially to the reaction vessel, followed by the dropwise addition of 2,2,2-trifluoroethyl carbamate to obtain 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate. The system temperature is controlled at 50~55℃ during the dropwise addition of 2,2,2-trifluoroethyl carbamate. The reaction temperature is 50~55℃, and the reaction time is 1.5~2.5 h.

[0014] Furthermore, the cooling temperature in step two is -5~5℃, the solid precipitation time is 0.5~2 h, and the organic solvent is one of petroleum ether, n-hexane, or n-heptane.

[0015] Beneficial effects: This invention proposes a preparation process for 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate. The process is based on the reaction of 2,2,2-trifluoroethanol and formic acid. The reaction solution is distilled, and the target fraction is collected to obtain 2,2,2-trifluoroethyl formate. The reaction of 2,2,2-trifluoroethanol and formic acid is reversible. The added acetic anhydride consumes the water produced by the reaction of trifluoroethanol and formic acid, promoting complete conversion of 2,2,2-trifluoroethanol. The reaction yield can reach 85.19%, and the purity can reach 97.5%. The process also includes the reaction of 2,2,2-trifluoroethanol with diphenyl sulfide and trifluoromethanesulfonate. After cooling the reaction solution, the solid precipitates and is washed with an organic solvent to obtain 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate. The reaction yield can reach 92.65%, and the purity can reach 99.7%.

[0016] The preparation method proposed in this invention uses inexpensive and readily available raw materials, is simple to operate, has a high reaction yield (up to 78.93%), mild reaction conditions, high safety, and simple post-reaction processing, making it suitable for industrial-scale production and possessing high economic value. Attached Figure Description

[0017] Figure 1 The gas chromatographic spectrum of 2,2,2-trifluoroethyl carbamate is shown. Figure 2 The liquid chromatography chromatogram is for the detection of 2,2,2-trifluoroethyl diphenylsulfonate trifluoromethanesulfonate. Detailed Implementation

[0018] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. These embodiments are implemented under the premise of the technical solution of the present invention. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0019] Example 1: Preparation of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate Preparation of 2,2,2-trifluoroethyl carbamate

[0020] Formic acid (73.6 g, 1.6 mol, 1.1 eq) was poured into a four-necked flask, and a magnetic stirrer was turned on. Acetic anhydride (163.36 g, 1.6 mol, 1.1 eq) was then added in one go. The reaction solution was heated in an oil bath. When the internal temperature was 30-35℃, 2,2,2-trifluoroethanol (150 g, 1.5 mol, 1 eq) was added dropwise using a constant pressure dropping funnel. The reaction was exothermic during the dropwise addition. The addition was slow, and the internal temperature was maintained at 35-40℃. The addition was completed in about 3 hours. The reaction was then maintained at 40℃ for 2 hours. GC analysis showed that the starting material 2,2,2-trifluoroethanol reacted completely. The reaction solution was transferred to a single-necked flask, and a 30 cm long distillation column was added. The column was packed with a glass spring, and the fraction with a top temperature of 58–62 °C was collected to obtain 163.7 g of a colorless liquid, with a yield of 85.19% and a GC purity of 97.5%. The gas chromatographic spectrum of 2,2,2-trifluoroethyl carbamate is shown below. Figure 1 As shown.

[0021] Preparation of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate

[0022] Diphenyl sulfide (558.9 g, 3 mol, 3 eq) and trifluoromethanesulfonic acid (150 g, 1 mol, 1 eq) were added sequentially to a four-necked flask. Magnetic stirring was turned on, and the reaction solution was heated in an oil bath. When the internal temperature was 50-55℃, 2,2,2-trifluoroethyl carbamate (128.1 g, 1 mol, 1 eq) was added dropwise using a constant pressure dropping funnel. The addition was completed in about 1 hour, and the reaction was then maintained at 50-55℃ for 2 hours. Heating was stopped, and stirring was continued. A white solid gradually precipitated out. The four-necked flask was then placed in an ice-water bath and stirred for 1 hour at an internal temperature of 0°C. The mixture was then filtered, and the filter cake was washed once with 500 mL of petroleum ether to obtain 387.6 g of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate, with a yield of 92.65% and an HPLC purity of 99.7%. The HPLC chromatogram of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate is shown below. Figure 2 As shown.

[0023] Example 2: Preparation of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate Preparation of 2,2,2-trifluoroethyl carbamate

[0024] Formic acid (103.57 g, 2.25 mol, 1.5 eq) was poured into a four-necked flask, and a magnetic stirrer was turned on. Acetic anhydride (306.27 g, 3 mol, 2 eq) was then added in one go. The reaction mixture was heated in an oil bath. When the internal temperature reached 30–35 °C, 2,2,2-trifluoroethanol (150 g, 1.5 mol, 1 eq) was added dropwise using a constant-pressure dropping funnel. The reaction was exothermic during the dropwise addition, so the addition was slow, maintaining the internal temperature at 35–40 °C, and the addition was completed in about 3 hours. The reaction was then maintained at 40 °C for 2 hours. GC analysis showed that the starting material, 2,2,2-trifluoroethanol, had reacted completely. The reaction mixture was transferred to a single-necked flask, and a 30 cm long distillation column was added. The column was filled with a glass spring, and the fraction with a top temperature of 58–62 °C was collected to obtain 158.6 g of a colorless liquid, with a yield of 82.57% and a GC purity of 96.2%.

[0025] Preparation of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate

[0026] Diphenyl sulfide (745.08 g, 4 mol, 4 eq) and trifluoromethanesulfonic acid (225.11 g, 1.5 mol, 1.5 eq) were added sequentially to a four-necked flask. A magnetic stirrer was turned on, and the reaction mixture was heated in an oil bath. At an internal temperature of 50–55 °C, 2,2,2-trifluoroethyl carbamate (128.1 g, 1 mol, 1 eq) was added dropwise using a constant-pressure dropping funnel, completing the addition in approximately 1 hour. The reaction was then maintained at 50–55 °C for 2 hours. Heating was stopped, but stirring was continued, and a white solid gradually precipitated. The four-necked flask was then placed in an ice-water bath and stirred at 0 °C for 1 hour. The mixture was filtered, and the filter cake was washed once with 500 mL of n-hexane to obtain 375.6 g of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate, with a yield of 89.78% and an HPLC purity of 98.6%.

Claims

1. A preparation process for 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate, characterized in that, Includes the following steps: Step 1: 2,2,2-trifluoroethanol, formic acid and acetic anhydride are reacted, the reaction solution is distilled, and the target fraction is collected to obtain 2,2,2-trifluoroethyl formate; ； Step 2: 2,2,2-Trifluoroethyl carbamate, diphenyl sulfide, and trifluoromethanesulfonic acid are reacted. The reaction solution is cooled, the solid precipitates, and it is washed with an organic solvent to obtain 2,2,2-trifluoroethyl diphenylsulfonate trifluoromethanesulfonate. 。 2. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 1, characterized in that, The molar ratio of 2,2,2-trifluoroethanol, formic acid and acetic anhydride in step one is 1:1~1.5:1~2; the molar ratio of 2,2,2-trifluoroethyl carbamate, diphenyl sulfide and trifluoromethanesulfonic acid in step two is 1:2~4:1~1.

5.

3. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 1, characterized in that, In step one, formic acid and acetic anhydride are added sequentially to the reaction vessel, followed by the dropwise addition of 2,2,2-trifluoroethanol, and the reaction yields 2,2,2-trifluoroethyl carbamate.

4. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 3, characterized in that, When adding 2,2,2-trifluoroethanol dropwise, the system temperature is controlled at 35~40℃; the reaction temperature is 35~45℃, and the reaction time is 1.5~2.5 h.

5. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 1, characterized in that, The distillation in step one uses a distillation column filled with glass spring packing, with a column length of 25-35 cm. The target fraction is the fraction collected at a top temperature of 58-62°C.

6. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 1, characterized in that, In step two, diphenyl sulfide and trifluoromethanesulfonic acid are added sequentially to the reaction vessel, followed by the dropwise addition of 2,2,2-trifluoroethyl carbamate, to obtain 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate.

7. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 6, characterized in that, When adding 2,2,2-trifluoroethyl carbamate dropwise, the system temperature is controlled at 50~55℃; the reaction temperature is 50~55℃, and the reaction time is 1.5~2.5 h.

8. The preparation process of 2,2,2-trifluoroethyl diphenylsulfonium trifluoromethanesulfonate according to claim 1, characterized in that, The cooling temperature is -5~5℃, the solid precipitation time is 0.5~2 h, and the organic solvent is one of petroleum ether, n-hexane or n-heptane.

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