Preparation method of fluorine-containing phenyl sulfoxide compound

Abstract

The invention relates to a preparation method of a fluorine-containing phenyl sulfoxide compound, and belongs to the technical field of organic chemical synthesis. The preparation method comprises the following steps: S1, performing condensation reaction on fluorine-containing phenyl halide # imgabs0 # and sulfide in a first solvent under the action of a copper-based catalyst and alkali to obtain fluorine-containing phenyl sulfide # imgabs1 #; S2, performing oxidation reaction on the fluorine-containing phenyl sulfide # imgabs2 # and an oxidizing agent in a second solvent under a protective atmosphere to obtain fluorine-containing phenyl sulfide # imgabs2 #; the fluorine-containing phenyl sulfoxide compound # imgabs3 is obtained through extraction and recrystallization, R1, R2 and R3 are independently selected from H or F, and R1, R2 and R3 are not H at the same time. And the fluorine-containing phenyl sulfoxide compound is synthesized with high purity and high yield through condensation and oxidation two-step reaction. The route has the advantages of cheap and easily available raw materials, mild reaction, simple operation, simple post-treatment, high purity and yield of the obtained product, and good industrial production prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and in particular relates to a method for preparing fluorine-containing phenyl sulfoxide compounds. Background Art

[0002] Photoacid generators are important components of photoresists. Photoacid generators are divided into ionic photoacid generators and non-ionic photoacid generators. In 193nm photoresists, the main photoacid generators are iodonium salts and sulfonium salts. Among the sulfonium photoacid generators, fluorinated phenyl sulfoxide compounds have a large market demand, and fluorinated phenyl sulfoxide compounds have great advantages in properties, but the synthesis routes have great defects.

[0003] Patent CN 115784953 A discloses a method for synthesizing fluorinated phenyl sulfoxides, which comprises taking fluorinated phenyl halides as raw materials, ensuring that the reaction system is in a nitrogen atmosphere, cooling to -80°C, slowly dropping n-butyl lithium to prepare a fluorinated phenyl lithium reagent, and dropping thionyl chloride at -30°C to react to prepare fluorinated phenyl sulfoxides; the method obtains fluorinated phenyl sulfoxides by a two-step one-pot reaction, and the route has a medium yield, but is relatively dangerous and requires ultra-low temperature conditions, which is difficult to meet the needs and is not suitable for industrial production.

[0004] Patent WO 2024 / 100964 A1 discloses a method for synthesizing fluorinated phenyl sulfoxides, which uses fluorinated phenyl halide as a raw material, ensures that the reaction system is in a nitrogen atmosphere, and prepares a fluorinated phenyl Grignard reagent with magnesium chips at room temperature, and then adds thionyl chloride dropwise at -30°C to react to obtain a fluorinated phenyl sulfoxide; the method obtains the fluorinated phenyl sulfoxide by a two-step one-pot reaction. This route has a low yield but moderate risk, is difficult to meet demand, and is not suitable for industrial production.

[0005] In summary, the current methods for synthesizing fluorinated phenyl sulfoxide compounds have the problems of harsh reaction conditions, expensive raw materials, and low yields. Therefore, a new method is urgently needed to prepare fluorinated phenyl sulfoxide compounds. Summary of the invention

[0006] Therefore, the technical problem to be solved by the present invention is to overcome the problems of low yield, harsh reaction conditions, and difficult purification of fluorinated phenyl sulfoxide compounds in the prior art.

[0007] In order to solve the above technical problems, the present invention provides a method for preparing fluorinated phenyl sulfoxide compounds, which uses fluorinated phenyl halide as a starting material, and synthesizes fluorinated phenyl sulfoxide compounds with high purity and high yield through two steps of condensation and oxidation. The raw materials of this route are cheap and easy to obtain, the reaction is mild, the operation is simple, the post-treatment is simple, the purity and yield of the obtained product are both high, and it has good prospects for industrial production.

[0008] The object of the present invention is to provide a method for preparing a fluorinated phenyl sulfoxide compound, comprising the following steps:

[0009] S1, a fluorinated phenyl halide and a sulfide of formula I are subjected to a condensation reaction in a first solvent under the action of a copper-based catalyst and a base to obtain a fluorinated phenyl sulfide of formula II;

[0010] S2, under a protective atmosphere, the fluorinated phenyl sulfide of formula II described in S1 and an oxidant are subjected to an oxidation reaction in a second solvent, and a fluorinated phenyl sulfoxide compound of formula III is obtained by extraction and recrystallization;

[0011] Wherein, the structural formulas of Formula I, Formula II and Formula III are as follows,

[0012]

[0013] R1, R2, and R3 are independently selected from H or F, and R1, R2, and R3 are not H at the same time.

[0014] In one embodiment of the present invention, in S1, the sulfide is selected from one or more of thiourea, sulfur powder and sodium sulfide;

[0015] The copper-based catalyst is selected from one or more of copper oxide, copper acetate and cuprous iodide;

[0016] The base is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, triethylamine and diisopropylethylamine;

[0017] The first solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide and diethylene glycol dimethyl ether.

[0018] In one embodiment of the present invention, in S1, the molar ratio of the fluorinated phenyl halide and the sulfide of the formula I is 2:(1-1.5).

[0019] In one embodiment of the present invention, in S1, the condensation reaction temperature is 105°C-115°C, and the time is 12h-18h.

[0020] In one embodiment of the present invention, in S2, the oxidant is selected from one or more of hydrogen peroxide, meta-chloroperbenzoic acid and tert-butyl peroxide;

[0021] The second solvent is selected from one or more of ethanol, tetrahydrofuran and toluene.

[0022] In one embodiment of the present invention, in S2, the molar ratio of the fluorinated phenyl sulfide of formula II to the oxidant is 1:(1-1.4).

[0023] In one embodiment of the present invention, in S2, the oxidation reaction temperature is 15°C-25°C, and the time is 3h-4h.

[0024] In one embodiment of the present invention, in S2, the extraction specifically comprises the following steps: firstly extracting with a dichloromethane / water mixture, and then drying with anhydrous sodium sulfate.

[0025] In one embodiment of the present invention, in S2, the recrystallization specifically comprises the following steps: dissolving the crude fluorinated phenyl sulfoxide compound obtained by extraction in dichloromethane, filtering and concentrating through silica gel, and then adding a third solvent for recrystallization to obtain a fine fluorinated phenyl sulfoxide compound.

[0026] In one embodiment of the present invention, the third solvent is selected from one or more of n-hexane, cyclohexane, n-pentane, isopentane, cyclopentane, isooctane, trimethylpentane and heptane.

[0027] In one embodiment of the present invention, the general reaction equation of the preparation method is as follows:

[0028]

[0029] The technical solution of the present invention has the following advantages over the prior art:

[0030] (1) The preparation method of the present invention uses fluorinated phenyl halides and sulfides as raw materials, reacts under the action of a copper-based catalyst and a base, and directly synthesizes fluorinated phenyl sulfide; fluorinated phenyl sulfide is directly synthesized into fluorinated phenyl sulfoxide compounds under the action of an oxidant. This method avoids the use of dangerous reagents such as Grignard reagents or lithium reagents, and has been greatly improved in safe production, which is conducive to scaled-up production. Secondly, since fluorinated phenyl halides have poor stability in lithium reagents or Grignard reagents, some fluorine in the product will leave under strong alkaline conditions, resulting in the generation of analog impurities, and the impurities are difficult to remove in a limited manner. The preparation method of the present invention can effectively solve this problem. Therefore, the present invention has obvious advantages in cost, yield and purity, and provides ideas for scaled-up synthesis of fluorinated phenyl sulfoxide compounds.

[0031] (2) The preparation method of the present invention has cheap and readily available raw materials, mild reaction, simple operation, simple post-treatment, and the purity (above 99%) and yield (above 80%) of the obtained product are both high, and has good prospects for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0033] Figure 1 This is the GC spectrum of bis(3,5-difluorophenyl)sulfide of Example 1 of the present invention;

[0034] Figure 2 is the HNMR spectrum of bis(3,5-difluorophenyl)sulfide of Example 1 of the present invention;

[0035] Figure 3 is the FNMR spectrum of bis(3,5-difluorophenyl)sulfide of Example 1 of the present invention;

[0036] Figure 4 This is the HPLC spectrum of bis(3,5-difluorophenyl)sulfoxide of Example 1 of the present invention;

[0037] Figure 5 is the HNMR spectrum of bis(3,5-difluorophenyl)sulfoxide of Example 1 of the present invention;

[0038] Figure 6 is the FNMR spectrum of bis(3,5-difluorophenyl)sulfoxide of Example 1 of the present invention;

[0039] Figure 7 is the GC spectrum of bis(3-fluorophenyl)sulfide of Example 6 of the present invention;

[0040] Figure 8 is the HNMR spectrum of bis(3-fluorophenyl)sulfide of Example 6 of the present invention;

[0041] Fig. 9 is the FNMR spectrum of bis(3-fluorophenyl)sulfide of Example 6 of the present invention;

[0042] Fig.10 This is the HPLC spectrum of bis(3-fluorophenyl)sulfoxide of Example 6 of the present invention;

[0043] Fig.11 is the HNMR spectrum of bis(3-fluorophenyl)sulfoxide of Example 6 of the present invention;

[0044] Fig.12 is the FNMR spectrum of bis(3-fluorophenyl)sulfoxide of Example 6 of the present invention;

[0045] Fig.13 is the GC spectrum of bis(4-fluorophenyl)sulfide of Example 7 of the present invention;

[0046] Fig.14 is the HNMR spectrum of bis(4-fluorophenyl)sulfide of Example 7 of the present invention;

[0047] Fig.15 This is the FNMR spectrum of bis(4-fluorophenyl)sulfide of Example 7 of the present invention. DETAILED DESCRIPTION

[0048] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. It should be understood that the specific embodiments are only used to explain the present invention, but the embodiments are not intended to limit the present invention.

[0049] In the present invention, unless otherwise explained, technical and scientific terms used in the present invention have the same meanings as commonly understood by those skilled in the art to which the present invention belongs.

[0050] In the present invention, unless otherwise stated, the term "and / or" used in the present invention includes any and all combinations of one or more of the associated listed items.

[0051] In the present invention, unless otherwise stated, the experimental methods used in the embodiments of the present invention are conventional methods unless otherwise stated, and the materials, reagents, etc. used are all commercially available unless otherwise stated.

[0052] Example 1

[0053] The preparation method of bis(3,5-difluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0054] S1. Synthesis of bis(3,5-difluorophenyl)sulfide: Under nitrogen atmosphere, 3,5-difluorophenylbromobenzene (100 g, 518.16 mmol) and thiourea (19.72 g, 259.08 mmol) were added to a 1L three-necked flask and dissolved in 300 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.06 g, 25.91 mmol) and cesium carbonate (168.83 g, 518.16 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating reaction for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane and purified by silica gel filtration to obtain bis(3,5-difluorophenyl)sulfide with a yield of 65%; the GC spectrum is shown in Figure 1 , HNMR spectrum see Figure 2 , FNMR spectrum see Figure 3 .

[0055] S2. Synthesis of bis(3,5-difluorophenyl)sulfoxide: Under nitrogen atmosphere, bis(3,5-difluorophenyl)sulfide (100 g, 387.25 mmol) and hydrogen peroxide (15.81 g, 464.70 mmol) were added to a 1L three-necked flask, dissolved in 500 mL of anhydrous ethanol, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3,5-difluorophenyl)sulfoxide with a yield of 92%; HPLC spectrum is shown in Figure 4 , HNMR spectrum see Figure 5 , FNMR spectrum see Figure 6 .

[0056] Example 2

[0057] The preparation method of bis(3,5-difluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0058] S1. Synthesis of bis(3,5-difluorophenyl)sulfide: Under a nitrogen atmosphere, 3,5-difluorophenylbromobenzene (100 g, 518.16 mmol) and thiourea (21.69 g, 284.99 mmol) were added to a 1L three-necked flask and dissolved in 300 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.06 g, 25.91 mmol) and cesium carbonate (168.83 g, 518.16 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating to react for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane and purified by silica gel filtration to obtain bis(3,5-difluorophenyl)sulfide in a yield of 76%.

[0059] S2. Synthesis of bis(3,5-difluorophenyl)sulfoxide: Under a nitrogen atmosphere, bis(3,5-difluorophenyl)sulfide (100 g, 387.25 mmol) and hydrogen peroxide (15.81 g, 464.70 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3,5-difluorophenyl)sulfoxide in a yield of 87%.

[0060] Example 3

[0061] The preparation method of bis(3,5-difluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0062] S1. Synthesis of bis(3,5-difluorophenyl)sulfide: Under a nitrogen atmosphere, 3,5-difluorophenylbromobenzene (100 g, 518.16 mmol) and thiourea (23.66 g, 310.90 mmol) were added to a 1L three-necked flask and dissolved in 300 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.06 g, 25.91 mmol) and cesium carbonate (168.83 g, 518.16 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating to react for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane and purified by silica gel filtration to obtain bis(3,5-difluorophenyl)sulfide in a yield of 85%.

[0063] S2. Synthesis of bis(3,5-difluorophenyl)sulfoxide: Under a nitrogen atmosphere, bis(3,5-difluorophenyl)sulfide (100 g, 387.25 mmol) and hydrogen peroxide (15.81 g, 464.70 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3,5-difluorophenyl)sulfoxide in a yield of 93%.

[0064] Example 4

[0065] The preparation method of bis(3,5-difluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0066] S1. Synthesis of bis(3,5-difluorophenyl)sulfide: Under a nitrogen atmosphere, 3,5-difluorophenylbromobenzene (100 g, 518.16 mmol) and thiourea (25.64 g, 336.80 mmol) were added to a 1L three-necked flask and dissolved in 300 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.06 g, 25.91 mmol) and cesium carbonate (168.83 g, 518.16 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating to react for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane and purified by silica gel filtration to obtain bis(3,5-difluorophenyl)sulfide in a yield of 76%.

[0067] S2. Synthesis of bis(3,5-difluorophenyl)sulfoxide: Under a nitrogen atmosphere, bis(3,5-difluorophenyl)sulfide (100 g, 387.25 mmol) and hydrogen peroxide (15.81 g, 464.70 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3,5-difluorophenyl)sulfoxide in a yield of 84%.

[0068] Example 5

[0069] The preparation method of bis(3,5-difluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0070] S1. Synthesis of bis(3,5-difluorophenyl)sulfide: Under a nitrogen atmosphere, 3,5-difluorophenylbromobenzene (100 g, 518.16 mmol) and thiourea (29.58 g, 388.62 mmol) were added to a 1L three-necked flask and dissolved in 300 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.06 g, 25.91 mmol) and cesium carbonate (168.83 g, 518.16 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating to react for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane and purified by silica gel filtration to obtain bis(3,5-difluorophenyl)sulfide in a yield of 67%.

[0071] S2. Synthesis of bis(3,5-difluorophenyl)sulfoxide: Under a nitrogen atmosphere, bis(3,5-difluorophenyl)sulfide (100 g, 387.25 mmol) and hydrogen peroxide (15.81 g, 464.70 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3,5-difluorophenyl)sulfoxide in a yield of 91%.

[0072] Example 6

[0073] The preparation method of bis(3-fluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0074] S1. Synthesis of bis(3-fluorophenyl)sulfide: Under nitrogen atmosphere, 3-fluorophenyl bromobenzene (100.00 g, 571.43 mmol) and thiourea (26.10 g, 342.86 mmol) were added to a 1L three-necked flask and dissolved in 500 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.27 g, 28.57 mmol) and cesium carbonate (186.18 g, 571.43 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating reaction for 15 h, and the reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled, and then 20 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane, and purified by silica gel filtration to obtain bis(3-fluorophenyl)sulfide with a yield of 87%; GC spectrum is shown in Figure 7 , HNMR spectrum see Figure 8 , FNMR spectrum see Fig. 9 .

[0075] S2. Synthesis of bis(3-fluorophenyl)sulfoxide: In a nitrogen atmosphere, bis(3-fluorophenyl)sulfide (100 g, 449.94 mmol) and hydrogen peroxide (18.37 g, 539.93 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(3-fluorophenyl)sulfoxide with a yield of 90%; HPLC spectrum is shown in Fig.10 , HNMR spectrum see Fig.11 , FNMR spectrum see Fig.12 .

[0076] Example 7

[0077] The preparation method of bis(4-fluorophenyl)sulfoxide of the present embodiment specifically comprises the following steps:

[0078] S1. Synthesis of bis(4-fluorophenyl)sulfide: Under nitrogen atmosphere, 4-fluorophenyl bromobenzene (100.00 g, 571.43 mmol) and thiourea (26.10 g, 342.86 mmol) were added to a 1L three-necked flask and dissolved in 500 mL of dimethyl sulfoxide, and stirred at room temperature until dissolved; nano copper oxide (2.27 g, 28.57 mmol) and cesium carbonate (186.18 g, 571.43 mmol) were added to the system, and the temperature was slowly raised to 110°C for heating reaction for 15 h, and the reaction progress was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled to room temperature, and copper oxide was filtered out, and then 300 mL of ethyl acetate / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in n-hexane, and purified by silica gel filtration to obtain bis(4-fluorophenyl)sulfide with a yield of 88%; GC spectrum is shown in Fig.13 , HNMR spectrum see Fig.14 , FNMR spectrum see Fig.15 .

[0079] S2. Synthesis of bis(4-fluorophenyl)sulfoxide: Under a nitrogen atmosphere, bis(4-fluorophenyl)sulfide (100 g, 449.94 mmol) and hydrogen peroxide (18.37 g, 539.93 mmol) dissolved in 500 mL of anhydrous ethanol were added to a 1 L three-necked flask, stirred at room temperature to form a solution and reacted for 3 h, and the reaction progress was monitored by thin layer chromatography (TLC); after the reaction was completed, the reaction mixture was cooled, and then a dichloromethane / water (1:1) mixture was added, and the organic extract was dried over anhydrous sodium sulfate; the filtrate was concentrated under reduced pressure to obtain a crude product; the crude product was dissolved in dichloromethane, filtered through silica gel, concentrated, and a dichloromethane and n-hexane (1:3) mixture was added for recrystallization to obtain bis(4-fluorophenyl)sulfoxide in a yield of 88%.

[0080] Comparative Example 1

[0081] Under nitrogen atmosphere, add 12.5g magnesium chips and 20mL tetrahydrofuran to a 1L three-necked flask; control the temperature at 30℃, add 100g 3,5-difluorobromobenzene and 100mL tetrahydrofuran mixture, add 400mL tetrahydrofuran to dilute the reaction solution after completion, maintain the temperature T = 25℃ and continue stirring for 5h; reduce the reaction temperature to -10℃, control the temperature at 5℃ and add 15g thionyl chloride and 30mL tetrahydrofuran mixture dropwise to react, maintain T = 10℃, and continue to react overnight for 16h; monitor the reaction process by thin layer chromatography, after the reaction is completed, cool to 0℃, add 200mL water to quench the reaction, separate the liquids, and concentrate to obtain fluorinated phenyl sulfoxide with a yield of 38%.

[0082] Comparative Example 2

[0083] Weigh 100 g of 3,5-difluorobromobenzene and add it to a 2L reaction bottle, replace the nitrogen atmosphere three times, add 300 mL of tetrahydrofuran to the reaction system, cool to -70°C, drop a mixture of n-butyl lithium and tetrahydrofuran to the reaction, maintain the current reaction temperature for 2 hours; weigh a mixture of thionyl chloride and tetrahydrofuran and drop it to the reaction, control the temperature to 0°C and react for 8 hours; monitor the reaction process by thin layer chromatography, after the reaction is completed, lower the reaction temperature to 0°C, drop a saturated aqueous ammonium chloride solution to quench the reaction, add dichloromethane to extract, wash with water, wash with saturated sodium bicarbonate and saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate to obtain fluorinated phenyl sulfoxide with a yield of 32%.

[0084] Obviously, the above embodiments are merely examples for clear explanation and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the protection scope of the invention.

Claims

1. A method for preparing a fluorinated phenyl sulfoxide compound, characterized in that: The following steps are involved: S1, a fluorinated phenyl halide and a sulfide of formula I are subjected to a condensation reaction in a first solvent under the action of a copper-based catalyst and a base to obtain a fluorinated phenyl sulfide of formula II; S2, under a protective atmosphere, the fluorinated phenyl sulfide of formula II described in S1 and an oxidant are subjected to an oxidation reaction in a second solvent, and a fluorinated phenyl sulfoxide compound of formula III is obtained by extraction and recrystallization; Wherein, the structural formulas of Formula I, Formula II and Formula III are as follows, R1, R2, and R3 are independently selected from H or F, and R1, R2, and R3 are not H at the same time.

2. The method for preparing a fluorinated phenyl sulfoxide compound according to claim 1, wherein In S1, the sulfide is selected from one or more of thiourea, sulfur powder and sodium sulfide; The copper-based catalyst is selected from one or more of copper oxide, copper acetate and cuprous iodide; The base is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, triethylamine and diisopropylethylamine; The first solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide and diethylene glycol dimethyl ether.

3. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S1, the molar ratio of the fluorinated phenyl halide and the sulfide of the formula I is 2:(1-1.5).

4. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S1, the condensation reaction temperature is 105°C-115°C, and the time is 12h-18h.

5. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S2, the oxidant is selected from one or more of hydrogen peroxide, m-chloroperbenzoic acid and tert-butyl peroxide; The second solvent is selected from one or more of ethanol, tetrahydrofuran and toluene.

6. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S2, the molar ratio of the fluorinated phenyl sulfide of formula II to the oxidant is 1:(1-1.4).

7. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S2, the oxidation reaction temperature is 15°C-25°C, and the time is 3h-4h.

8. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S2, the extraction specifically includes the following steps: firstly extracting with a dichloromethane / water mixture, and then drying with anhydrous sodium sulfate.

9. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 1, characterized in that: In S2, the recrystallization specifically comprises the following steps: dissolving the crude fluorinated phenyl sulfoxide compound obtained by extraction in dichloromethane, filtering and concentrating through silica gel, and then adding a third solvent for recrystallization to obtain a fine fluorinated phenyl sulfoxide compound.

10. The method for preparing the fluorinated phenyl sulfoxide compound according to claim 9, characterized in that: The third solvent is selected from one or more of n-hexane, cyclohexane, n-pentane, isopentane, cyclopentane, isooctane, trimethylpentane and heptane.

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