Method for synthesizing sulfoxide compound or sulfone compound by taking thioether as raw material

Abstract

The invention relates to a method for synthesizing a sulfoxide compound or a sulfone compound by taking thioether as a raw material, which comprises the following steps: adding a reaction raw material, an oxidant aqueous solution and a pH control agent into a reaction solvent for reaction to generate a sulfoxide compound (II) or a sulfone compound (III); the reaction raw material is thioether (I), the oxidizing agent is sodium chlorite, and the pH control agent is carbon dioxide or organic acid; the pH control agent is carbon dioxide, and the reaction is performed to generate a sulfoxide compound (II); the pH control agent is an organic acid and reacts to generate a sulfone compound (III) and # imgabs0 #, and R1 and R2 are independently selected from a benzene ring, a substituted benzene ring or an alkyl group. The method has the advantages of easily available and cheap raw materials, greenness, high efficiency, simple reaction operation, mild reaction conditions, high yield, convenience in post-treatment and easiness in industrial application.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and particularly relates to a new method for directly oxidizing sulfide compounds with sodium chlorite to synthesize sulfoxide compounds and sulfone compounds. Background Art

[0002] Sulfoxide and sulfone compounds are very important in the chemical industry, involving a wide variety of varieties and a wide range of applications. In the pharmaceutical field: Omeprazole, the core functional group of the world's first proton pump inhibitor launched by AstraZeneca in 1989, is sulfoxide. Under the action of gastric acid, it undergoes a Smile rearrangement to obtain sulfenic acid-like active compounds, which is the best drug for treating common stomach diseases. Pantoprazole, Rabeprazole, Lansoprazole, etc. derived from its structure have also become important varieties. Modafinil, a wakefulness promoter launched by Lafon Company in France in 1994 for enhancing cognition, is also a sulfoxide drug. Sulbactam sodium, a β-lactamase inhibitor, is a sulfone drug. It has weak antibacterial activity itself, but can be used in combination with β-lactam antibiotics. For example, in combination with ampicillin, it can enhance the antibacterial activity of bacteria that were originally resistant to ampicillin (due to the production of β-lactamase), expand the antibacterial spectrum, and effectively deal with some drug resistance problems caused by bacteria producing β-lactamase, and is used to treat various bacterial infectious diseases such as respiratory tract infections and urinary tract infections. In the pesticide field: For example, Fipronil, a sulfoxide phenylpyrazole insecticide launched by Bayer in 1993, has broad-spectrum insecticidal activity. It causes insects to have muscle spasms, act disorderly, stop feeding, and die by inhibiting the nervous system. Ethiprole and Butiprole are sulfoxide insecticides derived from the fipronil skeleton, and have higher activity and lower toxicity than fipronil in controlling rice pests. Sulfosulfuron, a sulfonylurea herbicide, is mainly used to control annual weeds and broad-leaved weeds, and exerts its effect by inhibiting the acetolactate synthase of weeds, interfering with the cell division of weeds, thereby achieving the purpose of weed control. In essence and flavor: The spices alliin and allicin containing sulfoxide are widely used as food additives due to their strong antibacterial and anti-tumor activities and the ability to scavenge free radicals. p-Toluenesulfonylacetone has a unique aroma and can be used to prepare certain special flavor essences. Bulk chemicals: Dimethyl sulfoxide is widely used in organic solvents, extractants in the printing and dyeing industry, antifreeze in the automotive industry, etc., and its added value is more than 4 times higher than that of its raw material dimethyl sulfide. Diphenyl sulfone is an important organic synthesis intermediate, which can be used to prepare high molecular materials such as polysulfone, and is also used in the fields of medicine, pesticides, etc.

[0003] As more and more fine chemicals such as medicines contain sulfoxide or sulfone structures, the synthesis of such compounds has received increasing attention. Selective oxidation of sulfide to sulfoxide or sulfone is the most important method and one of the core processes of sulfur chemical industry. The current synthesis methods can be divided into two categories: 1) Traditional oxidation method, such as using hydrogen peroxide, manganese dioxide and iodophenyl, etc., which has problems such as poor oxidation control, explosive oxidation reagents, and poor atom economy. 2) Oxygen oxidation method, 2,6,6-tetramethylpiperidinium oxide (TEMPO), ferric bromide (FeBr 3 ), iron nitrate (Fe(NO 3 ) 3 ), photocatalysis and electrocatalysis, etc., often have problems such as narrow substrate application range and strong amplification heat effect. Therefore, the development of oxidation methods with simple reaction system, mild conditions, no catalyst or low cost is of great industrial significance. Summary of the invention

[0004] In order to solve the above problems in the prior art, the present invention provides a new synthesis method for directly oxidizing sulfide to sulfoxide or sulfone compounds which is green, efficient, mild in reaction conditions, high in yield, convenient in post-treatment and easy for industrial application.

[0005] In order to achieve the above object, the present invention provides a method for synthesizing a sulfoxide compound or a sulfone compound using thioether as a raw material, characterized in that the method comprises: adding a reaction raw material, an oxidant aqueous solution, and a pH control agent to a reaction solvent to react to generate a sulfoxide compound (II) or a sulfone compound (III);

[0006] The reaction raw material is thioether (I), the oxidant is sodium chlorite, and the pH control agent is carbon dioxide or an organic acid;

[0007] The pH control agent is carbon dioxide, which reacts to form a sulfoxide compound (II); the pH control agent is an organic acid, which reacts to form a sulfone compound (III).

[0008]

[0009] Among them, R 1 , R 2 are each independently selected from substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted phenyl, substituted C 1-8 The substituents of the alkyl or phenyl groups are selected from C 1-8 Alkyl, halogen, C 1-8 Alkoxy, hydroxy, cyano, C 1-8The alkyl group can be methyl, propyl, butyl, isobutyl, pentyl, etc., and the substituted phenyl group can be 4-methylphenyl, 4-chlorophenyl, 4-iodophenyl, 4-fluorophenyl, 2-bromophenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-cyanophenyl.

[0010] Preferably, in the reaction for generating the sulfoxide compound (II), the molar ratio of the thioether to water is 1:5 to 1:20, and preferably 1:6 to 1:13.

[0011] Preferably, in the reaction for generating the sulfoxide compound (II), the molar ratio of the thioether to sodium chlorite is 1:0.6 to 1:3, and preferably 1:0.6 to 1:1.5.

[0012] Preferably, in the reaction for generating the sulfone compound (III), the molar ratio of the thioether to sodium chlorite is 1:3 to 1:10, and preferably 1:3 to 1:6; the molar ratio of the thioether to the organic acid is 1:5 to 1:30, and preferably 1:5 to 1:10.

[0013] Preferably, in the reaction for generating the sulfoxide compound (II), the pressure of carbon dioxide is 0.1 MPa to 1 MPa, and preferably 0.1 - 0.3 MPa.

[0014] Preferably, in the reaction for generating the sulfone compound (III), the organic acid is selected from formic acid, acetic acid, propionic acid or butyric acid, and preferably acetic acid.

[0015] Preferably, in the reaction for generating the sulfoxide compound (II), the reaction solvent is selected from one or more of acetonitrile, propionitrile, butyronitrile, dioxane, N-methylpyrrolidone, acetone or 1,2-dichloroethane, and preferably acetonitrile.

[0016] Preferably, in the reaction for generating the sulfoxide compound (II), the reaction temperature is 20 - 60 °C, preferably 30 - 40 °C, and the reaction time is 3 - 24 hours.

[0017] Preferably, in the reaction for generating the sulfone compound (III), the reaction temperature is 40 - 80 °C, preferably 50 - 70 °C, and the reaction time is 5 - 24 hours.

[0018] The present invention synthesizes the sulfoxide and sulfone compounds of the formula through the sodium chlorite / acid oxidation system, which has significant advantages: using the water purification agent sodium chlorite as a single oxidant, it is relatively stable, easy to obtain, and low in price; sodium chlorite is a common sodium salt and will not cause the metal element impurities to exceed the standard; in addition, the oxidant is easily soluble in water, and after the reaction, it can be removed by the conventional water washing and layering operation, avoiding the generation of a large amount of solid waste. Carbon dioxide is used as the pH control agent in the synthesis of the sulfoxide compound. It is a stable gas, and after dissolving in water, it generates carbonic acid. This reaction itself is also a reversible reaction. In carbon dioxide... 2 As the pH control agent, it is a stable gas, and after dissolving in water, it generates carbonic acid. This reaction itself is also a reversible reaction. In carbon dioxide...2 Under an atmosphere (maintained at a relatively low pressure), the reaction system can maintain a stable carbonic acid microenvironment, thus ensuring that the reaction proceeds smoothly and gently. After the reaction, CO 2 leaves the reaction system immediately, reducing the processing steps and causing no environmental pollution, making it more suitable for industrial application. Organic weak acids such as acetic acid are used as pH control agents in the synthesis of sulfone compounds, which are inexpensive, easily available, recyclable, and cause less corrosion to equipment. The reaction system is simple and does not use any catalysts. The whole reaction process is gentle, controllable, and complete, with high product yields, simple operation, easy availability of products, high efficiency, and environmental friendliness, having strong industrial application value. Detailed implementation manners

[0019] In order to make the technical means, creative features, achieved purposes, and functions of the present invention easy to understand, the present invention will be further described below in conjunction with specific embodiments.

[0020] In the following embodiments, unless otherwise specified, the reagents used are all commercially available reagents, and the detection means and methods used are all conventional detection means and methods in the art.

[0021] Reagents and solvents: All are commercially available products; the solvents used are domestic analytical pure reagents, all purchased from Sinopharm Chemical Reagent Co., Ltd., and have not been treated in any way before use.

[0022] Gas chromatography: Shimadzu GC 2010.

[0023] Liquid chromatography: Agilent HPLC1260.

[0024] Nuclear magnetic resonance spectrometer: Bruker DRX-400FT (Germany), 1 HNMR was measured in CDCl 3 , DMSO-d 6 and D 2 O, and the chemical shift was based on tetramethylsilane (TMS), with the unit ppm.

[0025] The synthesis method of the selective synthesis of sulfoxide compounds of formula (II) and sulfone compounds of formula (III) of the present invention uses thioether (I) as the reaction raw material and sodium chlorite as the oxidant in a reaction solvent. When carbon dioxide is used as the pH control agent, sulfoxide compound (II) is selectively generated; when an organic acid is used as the pH control agent, sulfone compound (III) is selectively generated.

[0026] Example 1

[0027] Synthesis of Compound 2a and Compound 3a

[0028]

[0029] Synthesis of Compound 2a

[0030] (1) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), slowly add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) to the reaction system. Heat the reaction mixture to 40 °C and continue the reaction for about 8 hours. Monitor the reaction by HPLC until completion. Then perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Purify by column chromatography to obtain white solid diphenyl sulfoxide 2a (0.974 g) with a yield of 96.4% and an HPLC purity of 97.5%.

[0031] 1 H NMR (400 MHz, CDCl 3 ) δ 7.70–7.62 (m, 4H), 7.59–7.38 (m, 6H).

[0032] (2) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), heat the reaction mixture to 40 °C and continue the reaction for about 8 hours. Monitor the reaction by HPLC and no reaction occurs.

[0033] (3) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Slowly add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) to the reaction system. Heat the reaction mixture to 40 °C and continue the reaction for about 8 hours. Monitor the reaction by HPLC and no reaction occurs.

[0034] (4) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of 1,2-dichloroethane to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), slowly add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) to the reaction system. Heat the reaction mixture to 40 °C and continue the reaction for about 8 hours. Monitor the reaction by HPLC until completion. Then perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4It was dried and concentrated under reduced pressure to obtain a yellow viscous substance. Column chromatography was performed to obtain white solid diphenyl sulfoxide 2a (0.40 g), with a yield of 39.6% and an HPLC purity of 98.3%.

[0035] (5) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetone to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), a 2 g aqueous solution of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) was added dropwise to the reaction system. The temperature was raised to 40 °C and the reaction was continued for about 8 hours. After monitoring the reaction by HPLC until completion, extraction was carried out (30 ml of EA × 2). The organic phases were combined, 0.6 g of sodium sulfite was added, and the mixture was stirred at room temperature for 10 min. Anhydrous Na 2 SO 4 It was dried and concentrated under reduced pressure to obtain a yellow viscous substance. Column chromatography was performed to obtain white solid diphenyl sulfoxide 2a (0.47 g), with a yield of 46.5% and an HPLC purity of 97.7%.

[0036] (6) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), a 3.5 g aqueous solution of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) was added dropwise to the reaction system. The temperature was raised to 40 °C and the reaction was continued for about 8 hours. After monitoring the reaction by HPLC until completion, extraction was carried out (30 ml of EA × 2). The organic phases were combined, 0.6 g of sodium sulfite was added, and the mixture was stirred at room temperature for 10 min. Anhydrous Na 2 SO 4 It was dried and concentrated under reduced pressure to obtain a yellow viscous substance. Column chromatography was performed to obtain white solid diphenyl sulfoxide 2a (0.92 g), with a yield of 91.1% and an HPLC purity of 98.7%.

[0037] (7) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), a 5 g aqueous solution of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) was added dropwise to the reaction system. The temperature was raised to 40 °C and the reaction was continued for about 8 hours. After monitoring the reaction by HPLC until completion, extraction was carried out (30 ml of EA × 2). The organic phases were combined, 0.6 g of sodium sulfite was added, and the mixture was stirred at room temperature for 10 min. Anhydrous Na 2 SO 4 It was dried and concentrated under reduced pressure to obtain a yellow viscous substance. Column chromatography was performed to obtain white solid diphenyl sulfoxide 2a (0.81 g), with a yield of 80.1% and an HPLC purity of 98%.

[0038] (8) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), add a 1 g oxidant suspension (where sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) is mixed with water (0.15 g)) dropwise into the reaction system. Heat the mixture to 40 °C and continue the reaction for about 8 hours. Monitor the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and then use anhydrous Na 2 SO 4 to dry. Concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain white solid diphenyl sulfoxide 2a (0.971 g) with a yield of 96.1% and an HPLC purity of 97.9%.

[0039] (9) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) dropwise into the reaction system. Heat the mixture to 30 °C and continue the reaction for about 8 hours. Monitor the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and then use anhydrous Na 2 SO 4 to dry. Concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain white solid diphenyl sulfoxide 2a (0.913 g) with a yield of 90.4% and an HPLC purity of 97.5%.

[0040] (10) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) dropwise into the reaction system. Heat the mixture to 50 °C and continue the reaction for about 8 hours. Monitor the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and then use anhydrous Na 2 SO 4 to dry. Concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain white solid diphenyl sulfoxide 2a (0.933 g) with a yield of 92.4% and an HPLC purity of 99.3%.

[0041] (11) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.33 g of sodium chlorite (80 wt%, 0.57 g, 0.005 mol, 1 equiv) to the reaction system. Heat the temperature to 40 °C and continue the reaction for about 8 hours. After monitoring the reaction by HPLC until completion, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid diphenyl sulfoxide 2a (0.762 g) by column chromatography, with a yield of 75.4% and an HPLC purity of 98.3%.

[0042] (12) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 4 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) to the reaction system. Heat the temperature to 40 °C and continue the reaction for about 8 hours. After monitoring the reaction by HPLC until completion, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid diphenyl sulfoxide 2a (0.941 g) by column chromatography, with a yield of 93.2% and an HPLC purity of 97.4%.

[0043] Synthesis of compound 3a

[0044] (1) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 7 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) to the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the reaction by HPLC until completion, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid diphenyl sulfone 3a (1.061 g) by column chromatography, with a yield of 97.3% and an HPLC purity of 97.9%.

[0045] 1 H NMR (400 MHz, CDCl 3)δ 7.95 (dt, J = 7.0, 1.4 Hz, 4H), 7.60 - 7.54 (m, 2H), 7.51 (dd, J = 8.2, 6.6 Hz, 4H).

[0046] (2) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 10 ml of butyric acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 7 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system. Heat up to 70 °C and continue the reaction for about 7 hours. Monitor the completion of the reaction by HPLC, extract (30 ml EA - ×2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance. Column chromatography gives white solid diphenyl sulfone 3a (1.039 g), yield 95.3%, HPLC purity 97.9%.

[0047] (3) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 7 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system. Heat up to 60 °C and continue the reaction for about 7 hours. Monitor the completion of the reaction by HPLC, extract (30 ml EA ×2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance. Column chromatography gives white solid diphenyl sulfone 3a (1.05 g), yield 96.3%, HPLC purity 98.1%.

[0048] (4) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 5 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 7 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system. Heat up to 70 °C and continue the reaction for about 7 hours. Monitor the completion of the reaction by HPLC, extract (30 ml EA ×2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance. Column chromatography gives white solid diphenyl sulfone 3a (1.04 g), yield 95.4%, HPLC purity 97.5%.

[0049] (5) Add diphenyl sulfide 1a (0.95 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of sodium chlorite (80 wt%, 2.55 g, 0.025 mol, 5 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid diphenyl sulfone 3a (1.06 g) by column chromatography, with a yield of 97.2% and an HPLC purity of 97.9%.

[0050] Example 2

[0051] Synthesis of Compounds 2b and 3b

[0052]

[0053] Synthesis of Compound 2b

[0054] Add 1b (0.31 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 0.8 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain colorless liquid 2b (0.35 g) by column chromatography, with a yield of 90% and a GC purity of 98.6%.

[0055] 1 1H NMR (400 MHz, CDCl 3 ) δ 2.62 (s, 6H).

[0056] Synthesis of Compound 3b

[0057] Add 1b (0.31 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO4 It was dried and concentrated under reduced pressure to obtain a white solid 3b (0.464 g), with a yield of 98.7% and a GC purity of 99.3%.

[0058] 1 H NMR (400 MHz, CDCl 3 ) δ 2.99 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 42.65.

[0059] Example 3

[0060] Synthesis of Compounds 2c and 3c

[0061]

[0062] Synthesis of Compound 2c

[0063] 1c (0.59 g, 0.005 mol) and 15 ml of acetonitrile were added to a 100 mL reaction flask. An aqueous solution of 0.8 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) was added dropwise to the reaction system under a CO 2 atmosphere (about 0.1 MPa). The temperature was raised to 40 °C and the reaction was continued for about 3 hours. After monitoring the completion of the reaction by GC, extraction was performed (30 ml EA × 2). The organic phases were combined, 0.6 g of sodium sulfite was added, and the mixture was stirred at room temperature for 10 min. After anhydrous Na 2 SO 4 It was dried and concentrated under reduced pressure to obtain a yellow viscous substance. Column chromatography gave a pale yellow liquid 2c (0.63 g), with a yield of 94% and a GC purity of 98.9%.

[0064] 1 H NMR (400 MHz, CDCl 3 ) δ 2.70 (dddd, J = 13.0, 8.0, 6.4, 1.3 Hz, 2H), 2.64–2.54 (m, 2H), 1.82 (hept, J = 7.1 Hz, 4H), 1.09 (td, J = 7.4, 1.3 Hz, 6H).

[0065] Synthesis of Compound 3c

[0066] Add 1c (0.59 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) to the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain white solid 3c (0.745 g), with a yield of 99.3% and a GC purity of 99.8%.

[0067] 1 H NMR (400 MHz, CDCl 3 ) δ 2.98–2.88 (m, 4H), 1.95–1.82 (m, 4H), 1.09 (td, J = 7.5, 1.5 Hz, 6H).

[0068] Example 4

[0069] Synthesis of Compounds 2d and 3d

[0070]

[0071] Synthesis of Compound 2d

[0072] Add 1d (0.73 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 0.8 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) to the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain white solid 2d (0.76 g), with a yield of 93.8% and a GC purity of 99.4%.

[0073] 1 H NMR (400 MHz, CDCl 3 ) δ 2.75–2.57 (m, 4H), 1.82–1.68 (m, 4H), 1.49 (qq, J = 19.1, 7.0 Hz, 4H), 1.02–0.92 (m, 6H).

[0074] Synthesis of Compound 3d

[0075] Add 1d (0.73 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction by GC until completion, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a white solid 3d (0.88 g), with a yield of 98.9% and a GC purity of 99.6%.

[0076] 1 H NMR (400 MHz, CDCl 3 ) δ 2.99–2.90 (m, 4H), 1.82 (p, J = 7.8 Hz, 4H), 1.48 (h, J = 7.4 Hz, 4H), 0.97 (t, J = 7.4 Hz, 6H).

[0077] Example 5

[0078] Synthesis of Compounds 2e and 3e

[0079]

[0080] Synthesis of Compound 2e

[0081] Add 1e (0.87 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 0.8 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the reaction by GC until completion, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and perform column chromatography to obtain a white solid 2e (0.9 g), with a yield of 94.7% and a GC purity of 98.3%.

[0082] 1 H NMR (400 MHz, CDCl 3 ) δ 2.74–2.56 (m, 4H), 1.77 (tdd, J = 9.3, 6.0, 2.4 Hz, 4H), 1.54–1.31 (m, 8H), 0.92 (t, J = 6.9 Hz, 6H).

[0083] Synthesis of Compound 3e

[0084] Add 1e (0.87 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a white solid 3e (1.02 g), with a yield of 99% and a GC purity of 99.3%.

[0085] 1 1H NMR (400 MHz, CDCl 3 ) δ 2.99–2.88 (m, 4H), 1.84 (ddd, J = 11.9, 9.6, 6.4 Hz, 4H), 1.50–1.27 (m, 8H), 0.93 (t, J = 7.0 Hz, 6H).

[0086] Example 6

[0087] Synthesis of Compounds 2f and 3f

[0088]

[0089] Synthesis of Compound 2f

[0090] Add 1f (0.73 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 0.8 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain a white solid 2f (0.76 g), with a yield of 93.8% and a GC purity of 99.2%.

[0091] 1 1H NMR (400 MHz, CDCl 3 ) δ 2.68 (dd, J = 12.6, 4.7 Hz, 2H), 2.36 (dd, J = 12.6, 9.4 Hz, 2H), 2.31–2.11 (m, 2H), 1.10 (t, J = 6.9 Hz, 12H).

[0092] Synthesis of Compound 3f

[0093] Add 1f (0.73 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.015 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. Monitor the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain white solid 3f (0.884 g) with a yield of 99.3% and a GC purity of 98.9%.

[0094] 1 H NMR (400 MHz, CDCl 3 ) δ 2.85 (d, J = 6.5 Hz, 4H), 2.37 (dh, J = 13.4, 6.7 Hz, 2H), 1.13 (d, J = 6.7 Hz, 12H).

[0095] Example 7

[0096] Synthesis of Compounds 2g and 3g

[0097]

[0098] Synthesis of Compound 2g

[0099] Add 1g (1.02 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. Monitor the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Purify by column chromatography to obtain pale yellow liquid 2g (1.09 g) with a yield of 99.1% and a GC purity of 99.5%.

[0100] 1 H NMR (400 MHz, CDCl 3 ) δ 7.95 (dd, J = 7.8, 1.7 Hz, 1H), 7.61–7.55 (m, 2H), 7.38 (td, J = 7.8, 1.7 Hz, 1H), 2.83 (s, 3H).

[0101] Synthesis of Compound 3g

[0102] Add 1 g (1.02 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. Monitor the reaction completion by HPLC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and perform column chromatography to obtain 3 g (0.916 g) of a white solid with a yield of 77.62% and a GC purity of 98.6%.

[0103] 1 H NMR (400 MHz, CDCl 3 ) δ 8.21 (dd, J = 7.7, 1.9 Hz, 1H), 7.78 (dd, J = 7.7, 1.4 Hz, 1H), 7.51 (dtd, J = 21.2, 7.5, 1.6 Hz, 2H), 3.29 (s, 3H).

[0104] Example 8

[0105] Synthesis of Compounds 2h and 3h

[0106]

[0107] Synthesis of Compound 2h

[0108] Add 1h (1.25 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. Monitor the reaction completion by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and perform column chromatography to obtain 2h (1.00 g) of a white solid with a yield of 75% and a GC purity of 98.9%.

[0109] 1 H NMR (400 MHz, CDCl 3 ) δ 7.97–7.93 (m, 2H), 7.69–7.63 (m, 2H), 3.05 (s, 3H).

[0110] Synthesis of Compound 3h

[0111] Add 1h (1.25 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. Monitor the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a white solid 3h (1.40 g), with a yield of 99.3% and a GC purity of 98.3%.

[0112] 1 H NMR (400 MHz, CDCl 3 ) δ 7.90–7.86 (m, 2H), 7.40–7.36 (m, 2H), 2.72 (s, 3H).

[0113] Example 9

[0114] Synthesis of Compounds 2i and 3i

[0115]

[0116] Synthesis of Compound 2i

[0117] Add 1i (0.71 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. Monitor the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain a white solid 2i (0.76 g), with a yield of 96.2% and a GC purity of 99.26%.

[0118] 1 H NMR (400 MHz, CDCl 3 ) δ 7.73–7.60 (m, 2H), 7.29–7.19 (m, 2H), 2.72 (s, 3H).

[0119] Synthesis of Compound 3i

[0120] Add 1i (0.71 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain white solid 3i (0.87 g), yield 99.9%, GC purity 98.6%.

[0121] 1 H NMR (400 MHz, CDCl 3 ) δ 8.10–7.87 (m, 2H), 7.28–7.23 (m, 2H), 3.06 (s, 3H). Example 10

[0122] Synthesis of Compounds 2j and 3j

[0123]

[0124] Synthesis of Compound 2j

[0125] Add 1j (0.77 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain pale yellow liquid 2j (0.82 g), yield 96.5%, GC purity 98.8%.

[0126] 1 H NMR (400 MHz, CDCl 3 ) δ 7.63–7.57 (m, 2H), 7.06–7.01 (m, 2H), 3.86 (s, 3H), 2.70 (s, 3H).

[0127] Synthesis of Compound 3j

[0128] Add 1j (0.77 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain white solid 3j (0.92 g) with a yield of 98.9% and a GC purity of 99.3%.

[0129] 1 H NMR (400 MHz, CDCl 3 ) δ 7.89–7.83 (m, 2H), 7.05–7.01 (m, 2H), 3.89 (s, 3H), 3.03 (s, 3H).

[0130] Example 11

[0131] Synthesis of Compounds 2k and 3k

[0132]

[0133] Synthesis of Compound 2k

[0134] Add 1k (0.79 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. After monitoring the completion of the reaction by HPLC, perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain pale yellow liquid 2k (0.85 g) with a yield of 97.7% and a GC purity of 99.4%.

[0135] 1 H NMR (400 MHz, CDCl 3 ) δ 7.62–7.57 (m, 2H), 7.54–7.49 (m, 2H), 2.72 (s, 3H).

[0136] Synthesis of Compound 3k

[0137] Add 1k (0.79 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction by GC until completion, perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain white solid 3k (0.95 g), with a yield of 99.9% and a GC purity of 98.6%.

[0138] 1 H NMR (400 MHz, CDCl 3 ) δ 7.92–7.87 (m, 2H), 7.60–7.52 (m, 2H), 3.06 (s, 3H). Example 12

[0139] Synthesis of Compounds 2l and 3l

[0140]

[0141] Synthesis of Compound 2l

[0142] Add 1l (0.75 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 8 hours. After monitoring the reaction by GC until completion, perform extraction (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and perform column chromatography to obtain yellow solid 2l (0.77 g), with a yield of 92.7% and a GC purity of 98.6%.

[0143] 1 H NMR (400 MHz, CDCl 3 ) δ 7.85 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 2.78 (s, 3H).

[0144] Synthesis of Compound 3l

[0145] Add 1l (0.75 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain an orange solid 3a (0.90 g), with a yield of 98.9% and a GC purity of 99.5%.

[0146] 1 H NMR (400 MHz, CDCl 3 ) δ 8.12–8.07 (m, 2H), 7.92–7.87 (m, 2H), 3.10 (d, J = 0.8 Hz, 3H).

[0147] Example 13

[0148] Synthesis of Compounds 2m and 3m

[0149]

[0150] Synthesis of Compound 2m

[0151] Add 1m (0.83 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain a white solid 2m (0.87 g), with a yield of 95.6% and a GC purity of 99.3%.

[0152] 1 H NMR (400 MHz, CDCl 3 ) δ 8.13–8.09 (m, 2H), 7.77–7.73 (m, 2H), 2.77 (s, 3H), 2.66 (s, 3H).

[0153] Synthesis of Compound 3m

[0154] Add 1m (0.83 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain a pale yellow solid 3m (0.91 g) by column chromatography, with a yield of 91.9% and a GC purity of 98.3%.

[0155] 1 H NMR (400 MHz, CDCl 3 ) δ 8.14 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.5 Hz, 2H), 3.09 (s, 3H), 2.68 (s, 3H).

[0156] Example 14

[0157] Synthesis of Compounds 2n and 3n

[0158]

[0159] Synthesis of Compound 2n

[0160] Add 1n (0.85 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain a white solid 2n (0.90 g) by column chromatography, with a yield of 96.8% and a GC purity of 97.6%.

[0161] 1 H NMR (400 MHz, CDCl 3 ) δ 8.40 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H), 2.80 (s, 3H).

[0162] Synthesis of Compound 3n

[0163] Add 1n (0.85 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain white solid 3n (1.0 g) with a yield of 99% and a GC purity of 98.7%.

[0164] 1 H NMR (400 MHz, CDCl 3 ) δ 8.46–8.41 (m, 2H), 8.21–8.14 (m, 2H), 3.13 (s, 3H).

[0165] Example 15

[0166] Synthesis of Compounds 2o and 3o

[0167]

[0168] Synthesis of Compound 2o

[0169] Add 1o (0.62 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the completion of the reaction by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain white solid 2o (0.67 g) with a yield of 95.7% and a GC purity of 98.2%.

[0170] 1 H NMR (400 MHz, CDCl 3 ) δ 7.66 (dt, J = 7.6, 1.4 Hz, 2H), 7.57–7.47 (m, 3H), 2.73 (d, J = 1.5 Hz, 3H).

[0171] Synthesis of Compound 3o

[0172] Add 1o (0.62 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After the reaction is completed monitored by GC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain white solid 3o (0.77 g), yield 98.7%, GC purity 97.6%.

[0173] 1 H NMR (400 MHz, CDCl 3 ) δ 7.99–7.93 (m, 2H), 7.71–7.63 (m, 1H), 7.58 (t, J = 7.6 Hz, 2H), 3.06 (d, J = 0.9 Hz, 3H).

[0174] Example 16

[0175] Synthesis of Compounds 2p and 3p

[0176]

[0177] Synthesis of Compound 2p

[0178] Add 1p (1.00 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.025 mol, 1.5 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 8 hours. After the reaction is completed monitored by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid 2p (0.91 g) by column chromatography, yield 84.3%, HPLC purity 98.3%.

[0179] 1 H NMR (400 MHz, CDCl 3 ) δ 7.66–7.60 (m, 2H), 7.56–7.50 (m, 2H), 7.48–7.39 (m, 3H), 7.28–7.24 (m, 2H), 2.36 (s, 3H).

[0180] Synthesis of Compound 3p

[0181] Add 1p (1.00 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain white solid 3p (1.11 g) by column chromatography, with a yield of 95.7% and an HPLC purity of 99.2%.

[0182] 1 H NMR (400 MHz, CDCl 3 ) δ 7.96–7.91 (m, 2H), 7.85–7.80 (m, 2H), 7.57–7.46 (m, 3H), 7.29 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H).

[0183] Example 17

[0184] Synthesis of Compounds 2q and 3q

[0185]

[0186] Synthesis of Compound 2q

[0187] Add 1q (0.92 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.025 mol, 1.5 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 8 hours. After monitoring the completion of the reaction by HPLC, filter to obtain white solid 2q (0.95 g), with a yield of 95% and an HPLC purity of 98.3%.

[0188] 1 H NMR (400 MHz, CDCl 3 ) δ 7.99 (d, J = 7.7 Hz, 2H), 7.81 (d, J = 7.6 Hz, 2H), 7.60 (td, J = 7.6, 1.1 Hz, 2H), 7.50 (td, J = 7.5, 1.1 Hz, 2H).

[0189] Synthesis of Compound 3q

[0190] Add diphenyl sulfide 1q (0.92 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction by HPLC until completion, filter by suction to obtain white solid 3q (0.98 g), with a yield of 90.7% and an HPLC purity of 99.1%.

[0191] 1 H NMR (400 MHz, CDCl 3 ) δ 8.21 (d, J = 7.8 Hz, 2H), 8.00 (dt, J = 7.7, 0.9 Hz, 2H), 7.82 (td, J = 7.6, 1.1 Hz, 2H), 7.67 (td, J = 7.6, 1.0 Hz, 2H).

[0192] Example 18

[0193] Synthesis of Compounds 2r and 3r

[0194]

[0195] Synthesis of Compound 2r

[0196] Add 1r (1.06 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.025 mol, 1.5 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 8 hours. After monitoring the reaction by HPLC until completion, filter by suction to obtain white solid 2r (1.07 g), with a yield of 93.8% and an HPLC purity of 99.3%.

[0197] 1 H NMR (400 MHz, CDCl 3 ) δ 7.60 (d, J = 7.6 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.26–7.21 (m, 2H), 2.74 (s, 6H).

[0198] Synthesis of Compound 3r

[0199] Add 1r (1.06 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the mixture to 70 °C and continue the reaction for about 7 hours. Monitor the completion of the reaction by HPLC. After filtration, a white solid 3r (0.93 g) is obtained with a yield of 76.2% and an HPLC purity of 98.7%.

[0200] 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 (d, J = 7.7 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.26–7.23 (m, 2H), 2.71 (s, 6H).

[0201] Example 19

[0202] Synthesis of Compounds 2s and 3s

[0203]

[0204] Synthesis of Compound 2s

[0205] Add 1s (0.87 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system. Heat the mixture to 40 °C and continue the reaction for about 3 hours. Monitor the completion of the reaction by HPLC. After extraction (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance. Column chromatography gives a white solid 2s (0.88 g) with a yield of 92.6% and an HPLC purity of 98.6%.

[0206] 1 H NMR (400 MHz, CDCl 3 ) δ 8.25–8.17 (m, 1H), 8.02–7.86 (m, 3H), 7.60 (ddd, J = 7.3, 4.0, 2.1 Hz, 3H), 2.80 (s, 3H).

[0207] Synthesis of Compound 3s

[0208] Add 1s (0.87 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by HPLC, extract (30 ml of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain white solid 3s (1.02 g), with a yield of 99% and an HPLC purity of 98.9%.

[0209] 1 H NMR (400 MHz, CDCl 3 ) δ 8.57–8.49 (m, 1H), 8.08–7.86 (m, 4H), 7.67 (dddd, J = 17.5, 8.1, 6.9, 1.4 Hz, 2H), 3.13 (s, 3H).

[0210] Example 20

[0211] Synthesis of Compounds 2t and 3t

[0212]

[0213] Synthesis of Compound 2t

[0214] Add 1t (1.00 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) into the reaction system. Heat the temperature to 40 °C and continue the reaction for about 8 hours. After monitoring the completion of the reaction by HPLC, filter to obtain white solid 2t (0.97 g), with a yield of 89.8% and an HPLC purity of 97.3%.

[0215] 1 H NMR (400 MHz, d-DMSO) δ 8.06 (dd, J = 7.7, 1.7 Hz, 2H), 7.78 (ddd, J = 8.6, 7.3, 1.7 Hz, 2H), 7.59 (dd, J = 8.4, 1.1 Hz, 2H), 7.49 (td, J = 7.5, 1.2 Hz, 2H).

[0216] Synthesis of Compound 3t

[0217] Add 1t (1.00 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction by HPLC until completion, perform suction filtration to obtain white solid 3t (0.76 g), with a yield of 65.5% and an HPLC purity of 98.6%.

[0218] 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (dd, J = 7.9, 1.7 Hz, 2H), 7.65 (ddd, J = 8.8, 7.5, 1.7 Hz, 2H), 7.46–7.35 (m, 4H).

[0219] Example 21

[0220] Synthesis of Compounds 2u and 3u

[0221]

[0222] Synthesis of Compound 2u

[0223] Add 1u (1.08 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 2 g of sodium chlorite (80 wt%, 0.85 g, 0.0075 mol, 1.5 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 8 hours. After monitoring the reaction by HPLC until completion, perform suction filtration to obtain white solid 2u (0.51 g), with a yield of 44% and an HPLC purity of 98.3%.

[0224] 1 H NMR (400 MHz, CDCl 3 ) δ 7.94 (dd, J = 7.8, 1.4 Hz, 2H), 7.63 (dd, J = 7.6, 1.2 Hz, 2H), 7.56 (td, J = 7.6, 1.2 Hz, 2H), 7.43 (td, J = 7.5, 1.4 Hz, 2H).

[0225] Synthesis of Compound 3u

[0226] Add 1u (1.08 g, 0.005 mol) and 10 ml of acetic acid into a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction by HPLC until completion, perform suction filtration to obtain white solid 3u (0.95 g), with a yield of 76.6% and an HPLC purity of 97.5%.

[0227] 1 H NMR (400 MHz, CDCl 3 ) δ 8.11–8.03 (m, 4H), 7.75–7.69 (m, 4H).

[0228] Example 22

[0229] Synthesis of Compounds 2v and 3v

[0230]

[0231] Synthesis of Compound 2v

[0232] Add 1v (0.69 g, 0.005 mol) and 15 ml of acetonitrile into a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 3 hours. After monitoring the reaction by GC until completion, perform extraction (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and perform column chromatography to obtain light yellow solid 2v (0.73 g), with a yield of 94.8% and a GC purity of 98.7%.

[0233] 1 H NMR (400 MHz, CDCl 3 ) δ 7.64–7.58 (m, 2H), 7.56–7.47 (m, 3H), 2.91 (dq, J = 13.2, 7.4 Hz, 1H), 2.78 (dq, J = 13.3, 7.4 Hz, 1H), 1.20 (t, J = 7.4 Hz, 3H).

[0234] Synthesis of Compound 3v

[0235] Add 1v (0.69 g, 0.005 mol) and 10 ml of acetic acid to a 100 mL reaction flask. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system, heat up to 70 °C, and continue the reaction for about 7 hours. After monitoring the reaction completion by GC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a light yellow solid 3v (0.84 g) with a yield of 98.8% and a GC purity of 98.3%.

[0236] 1 H NMR (400 MHz, CDCl 3 ) δ 7.95–7.88 (m, 2H), 7.71–7.63 (m, 1H), 7.58 (ddt, J = 8.2, 6.6, 1.3 Hz, 2H), 3.12 (q, J = 7.4 Hz, 2H), 1.28 (t, J = 7.4 Hz, 3H).

[0237] Example 23

[0238] Synthesis of Compounds 2w and 3w

[0239]

[0240] Synthesis of Compound 2w

[0241] Add 1w (0.86 g, 0.005 mol) and 15 ml of acetonitrile to a 100 mL reaction flask. Under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.51 g, 0.0045 mol, 0.9 equiv) into the reaction system, heat up to 40 °C, and continue the reaction for about 8 hours. After monitoring the reaction completion by HPLC, extract (30 ml EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow viscous substance. Perform column chromatography to obtain a colorless liquid 2w (0.87 g) with a yield of 92.5% and an HPLC purity of 98.5%.

[0242] 1 H NMR (400 MHz, CDCl 3) δ 7.70–7.61 (m, 2H), 7.60–7.49 (m, 3H), 3.97 (dt, J = 11.6, 7.5 Hz, 1H), 3.66 (ddd, J = 11.7, 6.6, 5.8 Hz, 1H), 3.17 (ddd, J = 7.4, 6.2, 1.2 Hz, 2H).

[0243] Synthesis of Compound 3w

[0244] Add 1w (0.86 g, 0.005 mol) to a 100 mL reaction flask, add 10 mL of acetic acid, and dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) to the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the reaction by HPLC is completed, extract (30 mL of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain a white solid 3w (1.00 g) by column chromatography, with a yield of 98% and a GC purity of 99.3%.

[0245] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.96–7.90 (m, 2H), 7.74–7.68 (m, 1H), 7.65–7.56 (m, 2H), 3.79–3.72 (m, 2H), 3.57–3.50 (m, 2H).

[0246] Example 24

[0247] Synthesis of Compounds 2x and 3x

[0248]

[0249] Synthesis of Compound 2x

[0250] Add 1x (0.44 g, 0.005 mol) to a 100 mL reaction flask, add 15 mL of acetonitrile, and under a CO 2 atmosphere (about 0.1 MPa), dropwise add an aqueous solution of 1.2 g of sodium chlorite (80 wt%, 0.34 g, 0.003 mol, 0.6 equiv) to the reaction system. Heat the temperature to 40 °C and continue the reaction for about 3 hours. After monitoring the reaction by GC is completed, extract (30 mL of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure to obtain a yellow viscous substance, and obtain a yellow liquid 2x (0.5 g) by column chromatography, with a yield of 96.2% and a GC purity of 99.3%.

[0251] 1 1H NMR (400 MHz, CDCl 3 ) δ 2.97–2.78 (m, 4H), 2.52–2.39 (m, 2H), 2.09–1.97 (m, 2H).

[0252] Synthesis of Compound 3x

[0253] Add 1x (0.44 g, 0.005 mol) to a 100 mL reaction flask and 10 mL of acetic acid. Dropwise add an aqueous solution of 10 g of sodium chlorite (80 wt%, 1.7 g, 0.05 mol, 3 equiv) into the reaction system. Heat the temperature to 70 °C and continue the reaction for about 7 hours. After monitoring the completion of the reaction by GC, extract (30 mL of EA × 2), combine the organic phases, add 0.6 g of sodium sulfite, stir at room temperature for 10 min, and dry with anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a yellow liquid 3x (0.60 g) with a yield of 99.9% and a GC purity of 98.9%.

[0254] 1 1H NMR (400 MHz, CDCl 3 ) δ 3.10–2.97 (m, 4H), 2.30–2.16 (m, 4H).

[0255] In this specification, the present invention has been described with reference to specific embodiments thereof. However, it is obvious that various modifications and variations can still be made without departing from the spirit and scope of the present invention. Therefore, the specification should be regarded as illustrative rather than restrictive.

Claims

1. A method for synthesizing a sulfoxide compound or a sulfone compound using a thioether as a raw material, characterized in that: The method comprises: adding a reaction raw material, an oxidant aqueous solution, and a pH control agent to a reaction solvent to react and generate a sulfoxide compound (II) or a sulfone compound (III); The reaction raw material is thioether (I), the oxidant is sodium chlorite, and the pH control agent is carbon dioxide or an organic acid; The pH control agent is carbon dioxide, which reacts to form a sulfoxide compound (II); the pH control agent is an organic acid, which reacts to form a sulfone compound (III). Wherein, R1 and R2 are each independently selected from substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted phenyl, substituted C 1-8 The substituents of the alkyl or phenyl groups are selected from C 1-8 Alkyl, halogen, C 1-8 Alkoxy, hydroxy, cyano.

2. The method according to claim 1, characterized in that In the reaction to produce the sulfoxide compound (II), the molar ratio of sulfide to water is 1:5 to 1:

20.

3. The method according to claim 1, characterized in that In the reaction to produce the sulfoxide compound (II), the molar ratio of sulfide to water is 1:6 to 1:

13.

4. The method according to claim 1, characterized in that: In the reaction of generating the sulfoxide compound (II), the molar ratio of the sulfide to the sodium chlorite is 1:0.6 to 1:3; in the reaction of generating the sulfone compound (III), the molar ratio of the sulfide to the sodium chlorite is 1:3 to 1:10, and the molar ratio of the sulfide to the organic acid is 1:5 to 1:

30.

5. The method according to claim 1, characterized in that The pressure of carbon dioxide is 0.1MPa-1Mpa; the organic acid is selected from formic acid, acetic acid, propionic acid or butyric acid.

6. The method according to claim 1, characterized in that The reaction solvent is selected from one or more of acetonitrile, propionitrile, butyronitrile, dioxane, nitrogen methyl pyrrolidone, acetone or 1,2-dichloroethane.

7. The method according to claim 1, characterized in that The reaction temperature in the reaction for producing the sulfoxide compound (II) is 20 to 60°C; the reaction temperature in the reaction for producing the sulfone compound (III) is 40 to 80°C.

8. The method according to claim 1, characterized in that The reaction temperature in the reaction to form the sulfoxide compound (II) is 30 to 40°C; the reaction temperature in the reaction to form the sulfone compound (III) is 50 to 70°C.

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