A trifluoromethyl sulfoxide reagent, its preparation method and application

Abstract

This invention discloses a method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is an electrophilic trifluoromethyl sulfoxide reagent with an O-S backbone. The preparation method includes the following steps: (1) using hydroxylamine as a raw material, mixing it with a first solvent, adding an alkali, reacting at room temperature to 150°C for 0.5-24 h, filtering, and obtaining the corresponding hydroxylamine metal salt; (2) adding a second solvent to the hydroxylamine metal salt, adding CF3SOCl under stirring at -78-0°C, reacting at -78-80°C for 0.5-24 h, filtering, and desolvating the filtrate under reduced pressure to obtain the product, which is the trifluoromethyl sulfoxide reagent. This invention also discloses the trifluoromethyl sulfoxide reagent obtained by the above preparation method and its applications. The preparation method is simple, and the trifluoromethyl sulfoxide reagent has high activity.

Description

Technical Field

[0001] This invention belongs to the field of organofluorine compound technology, specifically relating to a trifluoromethyl sulfoxide reagent, its preparation method, and its application. Background Technology

[0002] Organofluorine compounds hold immense potential in agrochemicals, pharmaceuticals, bioactive compounds, and novel materials. Introducing fluoroalkyl groups into desired drug candidates has been a hot topic in the pharmaceutical and agrochemical industries. Trifluoromethyl sulfoxide (CF3S(O)), a combination of sulfoxide (S(O)) and a trifluoromethyl substituent (CF3), is a valuable fragment in drug design and can significantly alter the physical, chemical, and biological properties of drug molecules. Compared to SO2CF3 and CF3, CF3S(O) exhibits moderate electron-withdrawing effects and negative lipophilicity, which can aid pharmacologists in fine-tuning fluoroalkyl groups. Furthermore, CF3S(O) possesses an "intermediate valence" between its homologs SCF3 and SO2CF3, allowing it to be converted into other important fluorinated residues, including CF3S, CF3SO2, and CF3SO(NH), thus enabling medicinal chemists to fine-tune the functional fluoroalkyl groups in drug molecules. Due to the unique physicochemical properties of CF3S(O), its introduction into pesticide and pharmaceutical molecules has shown special pharmacological and biological activities, such as the well-known insecticides fipronil and flufiprole, as well as antibacterial, antihypertensive, and anti-arthritis drugs.

[0003] The synthesis of trifluoromethyl sulfoxides is significantly more challenging than that of trifluoromethyl sulfoxides (CF3S) and trifluoromethyl sulfones (CF3SO2), primarily due to the intermediate oxidation state of CF3S(O). Traditionally, the construction of trifluoromethyl sulfoxides involves nucleophilic trifluoromethylation of hard-to-obtain sulfinyl halides or sulfinic esters using TMSCF3 under fluoride anion activation. Alternatively, the strategy of oxidizing trifluoromethyl sulfides can be used to synthesize trifluoromethyl sulfoxide products, but this process requires multiple steps to prepare trifluoromethyl sulfide RSCF3 and may be accompanied by over-oxidation to trifluoromethyl sulfonated products (CF3SO2) and other sulfides. For example: [Reaction details omitted]. F - =KF (reference Inorg. Chem. 1992, 31, 2537-2540), or TASF (reference J. Fluorine Chem. 1995, 70, 255-257), or CsF (reference J. Org. Chem. 1999, 64, 2873-2876); reaction Oxidant(O) = m-CPBA (Reference J. Am. Chem. Soc. 1993, 115, 2156-2164), or TCCA (Reference J. Fluorine Chem. 2007, 128, 636-640), or TBAN (Reference J. Org. Chem. 2011, 76, 5240-5246), or PCC / H5IO6 (Reference Green Technologies for the Environment, ACS Publications, 2014, 117-128), or H2O2 (Reference RSC Adv. 2020, 10, 34534-34540).

[0004] Compared to these indirect methods, the methods developed in recent years that directly introduce the CF3S(O) group into the target molecule are more attractive, especially in the later stages of multi-step synthetic sequences, where directly introducing the desired CF3S(O) group is particularly advantageous. Using this strategy, deoxytrifluoromethyl sulfinylation reactions derived from CF3SO2- sources (CF3SO2Na, CF3SO2Cl, 2-BT-SO2CF3) have been developed, which can prepare trifluoromethyl sulfoxide-derived heteroaromatics in the presence of phosphine additives such as PCl3, POCl3, PCy3, or Ph2P(O)Cl. However, these CF3SO2-derived reagents (CF3SO2Na, CF3SO2Cl, 2-BT-SO2CF3) suffer from the drawback of over-reduction to the trifluoromethylthioylation product (RSCF3), and also have problems such as low operating temperatures (CF3SO2Cl, -78℃) or complex synthesis (2-BT-SO2CF3). For example: (Reference: Tetrahedron, 1999, 55, 7243-7250.) (Reference: J.Org.Chem. 2017, 82, 9175-9181); (Reference: Eur. J. Org. Chem. 2017, 3505-3511); (Reference: J. Fluorine Chem. 2017, 198, 82-88); (Reference: Adv Synth Catal. 2019, 361, 5528-5533).

[0005] Compared to deoxygenation strategies, trifluoromethyl sulfoxide sulfoxide reactions using direct electrophilic trifluoromethyl sulfoxide reagents are more advantageous for organic molecules, especially complex substrates with multifunctional groups that are sensitive to oxidants or reductants. Methods for directly obtaining trifluoromethyl sulfoxide compounds, such as the trifluoromethyl sulfoxide reactions of alkyl alcohols and alkylamines, have been reported in the literature. (Reference: Tetrahedron. 1976, 32, 1627-1635); (Reference: Inorg. Chem. 1985, 24, 2126-2129). However, the specific difficulties and limitations of this method restrict its further application: 1) CF3S(O)Cl is easily decomposed; 2) It has poor thermal stability and requires low-temperature reaction conditions; 3) It has physiological toxicity and high volatility (31℃); 4) It is highly sensitive to air or moisture, and the decomposition rate accelerates rapidly in the presence of polar media or organic bases. Therefore, developing new CF3S(O)Cl substitutes for the preparation of trifluoromethyl sulfoxide compounds has high scientific significance and application demand.

[0006] The Larock research group in the United States discovered that aniline-based trifluoromethyl sulfoxides can serve as bifunctional amino-trifluoromethyl sulfoxide alkylating agents, reacting well with benzyne precursors to obtain o-trifluoromethyl sulfoxide-based aniline compounds in high yields. (Reference: J. Am. Chem. Soc. 2005, 127, 13112-13113). Bertrand's group developed a stable electrophilic reagent—N-trifluoromethyl sulfoxide succinimide—which can undergo trifluoromethyl sulfoxide reaction with a few nucleophilic substrates such as pyrrole, borneol, and N-methylaniline to give the target product in moderate yields. (Reference: Chem. Commun. 2003, 14, 1680-1681). However, there are few reports on the reactivity of these reagents, and the substrate range is relatively narrow, so further improvements in their activity are needed.

[0007] Direct trifluoromethyl sulfoxide sulfoxide sulfoxide reactions of aromatic hydrocarbons have been poorly studied, with only one reported case. This is mainly due to the weak electrophilicity of existing electrophilic trifluoromethyl sulfoxide sulfoxide reagents. In 2001, Saint-Jalmes' group reported the direct sulfoxide sulfoxide sulfoxide reaction of simple aromatic hydrocarbons in the strong acid trifluoromethanesulfonic acid via trifluoromethyl sulfoxide. (Reference: Synlett, 2001, 550-552). However, the strategy M = Na, K The use of trifluoromethanesulfonic acid, a strong acid, as a solvent does not meet the requirements of green chemistry industry, and it has a narrow substrate range and poor functional group compatibility (incompatible with acid-sensitive functional groups).

[0008] Currently, direct trifluoromethyl sulfoxide sulfonating reagents are mainly based on the NS skeleton (EP1331222A1, CN 114957086A, J.Am.Chem.Soc.2005, 127, 13112-13113). However, these skeletons suffer from limited reactivity, harsh reaction conditions (requiring additives), and poor conversion of less reactive aromatic substrates. Further modification of the reagent skeleton is needed to improve its activity in transferring the trifluoromethyl sulfoxide group. Therefore, finding a simple and stable reagent that can serve as a broad-spectrum and highly efficient trifluoromethyl sulfonating reagent under mild reaction conditions is crucial. This reagent could enable the trifluoromethyl sulfonation of various substrates, especially currently difficult-to-achieve aromatic compounds and bioactive compounds, possessing significant scientific value and application demand. Summary of the Invention

[0009] To overcome the shortcomings of existing technologies, such as cumbersome preparation steps, harsh reaction conditions, limited applicable substrates, low yield and conversion rate, and unsuitability for industrial production, this invention provides a trifluoromethyl sulfoxide-based reagent, its preparation method, and its application. The preparation method is simple, and the trifluoromethyl sulfoxide-based reagent has high activity.

[0010] A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is represented as follows: The preparation method of the electrophilic trifluoromethyl sulfoxide reagent with an OS backbone includes the following steps: (1) Using hydroxylamine as a raw material, after mixing with the first solvent, alkali is added to it, and the reaction is carried out at room temperature to 150°C for 0.5-24h. After filtration, the corresponding hydroxylamine metal salt is obtained. (2) Add a second solvent to the hydroxylamine metal salt, add CF3SOCl to it under stirring at -78-0℃, and react at -78-80℃ for 0.5-24h. Filter, and desolvate the filtrate under reduced pressure. The product obtained is the trifluoromethyl sulfoxide reagent. The first solvent is at least one of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, nitrile solvents, ester solvents, ketone solvents, amide solvents, or alcohol solvents. The second solvent is at least one of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, nitrile solvents, ester solvents, ketone solvents, sulfoxide solvents, amide solvents, or alcohol solvents. The base is a base corresponding to lithium, sodium, potassium, or cesium.

[0011] More preferably, step (1) is carried out at 60-80°C for 1-10 hours; step (2) is carried out at 0-25°C for 1-10 hours.

[0012] Preferably, the hydroxylamine is an acyl-protected hydroxylamine, a sulfonyl-protected hydroxylamine, a heterocyclic-protected hydroxylamine, or a ketone-protected hydroxylamine.

[0013] Preferably, the acyl-protected hydroxylamine is any one of compounds 1a-1m, the sulfonyl-protected hydroxylamine is any one of compounds 1n-1p, the heterocyclic-protected hydroxylamine is compound 1q, and the ketone-protected hydroxylamine is compound 1r. Wherein, R is hydrogen, or a halogen, trifluoromethyl, ester or cyano group with mono- or poly-substituted halogen on the benzene ring, and R' is a C1-C12 chain or cyclic alkyl group.

[0014] More preferably, the hydroxylamine is N-hydroxyphthalimide (i.e., compound 1f in this invention).

[0015] Preferably, the molar ratio of hydroxylamine to base in step (1) is 1:1, and the molar ratio of hydroxylamine metal salt to CF3SOCl in step (2) is 1:(1-1.5).

[0016] Preferably, the alkali is any one of LiOH, NaOH, KOH, CsOH, Li2CO3, Na2CO3, K2CO3, Cs2CO3, NaHCO3, KHCO3, Na3PO4, Na2HPO4, NaH2PO4, K3PO4, K2HPO4, and KH2PO4.

[0017] More preferably, the alkali is KOH or NaOH.

[0018] Preferably, the first solvent is an alcohol solvent and the second solvent is a halocarbon solvent.

[0019] More preferably, the alcohol solvent is any one of methanol, ethanol, n-propanol, and isopropanol, and the halohydrocarbon solvent is any one of chloromethane, dichloromethane, chloroform, and carbon tetrachloride.

[0020] A trifluoromethyl sulfoxide reagent prepared by any of the above preparation methods.

[0021] Application of a trifluoromethyl sulfoxide reagent: The trifluoromethyl sulfoxide reagent is used to react with a target molecule to directly introduce a trifluoromethyl sulfoxide group into the target molecule. The target molecule is any one of aromatic ring compounds and their corresponding bioactive molecules, aromatic heterocyclic compounds and their corresponding bioactive molecules, amines and their corresponding bioactive molecules, and alkyl alcohols and their corresponding bioactive molecules. The trifluoromethyl sulfoxide reagent is the trifluoromethyl sulfoxide reagent described in this invention.

[0022] Preferably, the application specifically involves: mixing the target molecule and the trifluoromethyl sulfoxide reagent under an inert gas atmosphere, adding a solvent, reacting at room temperature to 80°C for 3-20 hours, removing the solvent by vacuum evaporation, purifying the residue to obtain the trifluoromethyl sulfoxide product; wherein the solvent is one or more of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, nitrile solvents, ester solvents, ketone solvents, and amide solvents; when the aromatic ring compound is a weakly electron-donating group-substituted aromatic ring compound, a Lewis acid or Brønsted acid needs to be added to it before adding the solvent.

[0023] Preferably, the molar ratio of the target molecule to the trifluoromethyl sulfoxide reagent is 1:(1.0-2.0).

[0024] The reaction mechanism involved in this invention is as follows: Wherein, compound 1 is the hydroxylamine described in this invention, compound 2 is the corresponding metal salt generated, and compound 3 is the trifluoromethyl sulfoxide reagent corresponding to the target product of compound 1.

[0025] Advantages of this invention: (1) The trifluoromethyl sulfoxide reagent prepared by the present invention is a novel OS skeleton electrophilic trifluoromethyl sulfoxide reagent. This reagent has high reactivity and can react with electron-rich aromatic hydrocarbons, electron-rich aromatic heterocycles, amines, alkyl alcohols and some bioactive molecules under mild conditions. It realizes the direct introduction of trifluoromethyl sulfoxide groups into target molecules and provides a reference research strategy for introducing trifluoromethyl sulfoxide groups in the fields of medicine, pesticides and other fields. (2) The preparation method of the present invention is simple and convenient, low in cost, and has a wide range of applicable substrates, mild reaction conditions, high reaction conversion rate, high yield, good purity of the obtained product, and has broad prospects for industrial production. Detailed Implementation

[0026] Example 1 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is N-trifluoromethyl sulfinyl succinimide, referred to as reagent 3a in this invention, and has the structural formula as follows: The preparation method is as follows: (1) Preparation of N-hydroxysuccinimide sodium salt: N-hydroxysuccinimide (100 mmol, 11.5 g, compound 1a in this invention) and 250 mL of methanol were added to a round-bottom flask. NaOH (100 mmol, 4.0 g) was added under stirring. The mixture was refluxed at 80 °C for 12 h. The reaction solution was filtered, and the filter cake was dried to obtain a white solid (13.3 g, 97.1%), which is N-hydroxysuccinimide sodium salt. (2) Preparation of N-trifluoromethyl sulfinyl succinimide: Sodium N-hydroxysuccinimide (10 mmol, 1.37 g) and chloroform (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was completed, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 970 mg of white solid, with a yield of 42%.

[0027] Analysis of the obtained white solid confirmed that it was N-trifluoromethanesulfinatesuccinimide. The analytical results are as follows: N-trifluoromethanesulfinatesuccinimide: 1 H NMR (400MHz, CDCl3) δ2.86 (s, 4H); 19 F NMR (375MHz, CDCl3) δ-75.8 (s, 3F); 13 CNMR (100MHz, CDCl3) δ169.2, 124.36 (q, J=336.0Hz), 25.5ppm.

[0028] Example 2 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yltrifluoromethyl sulfinate, with the structural formula [insert structural formula here]. The preparation method is as follows: (1) 1-hydroxy-1H-pyrrole-2,5-dione (100 mmol, 11.3 g, compound 1b in this invention) and 250 mL of n-propanol were added to a round-bottom flask. KOH (100 mmol, 5.61 g) was added while stirring. The mixture was refluxed at 80 °C for 12 h. The reaction solution was filtered, and the filter cake was dried under vacuum to obtain the corresponding potassium salt (14.6 g, 96.7%), which was a white solid. (2) Add the potassium salt (10 mmol, 1.51 g) and chlorobenzene (50 mL) obtained in step (1) to a round-bottom flask. Add CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) under stirring at -78 °C. After the addition is complete, react at -78 °C for 12 h. Filter the reaction solution and desolvate the filtrate under reduced pressure to obtain 916 mg of white solid, with a yield of 40%.

[0029] Analysis of the obtained white solid confirmed that it was 2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl trifluoromethanesulfinate. The analytical results are as follows: 2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ7.05 (s, 2H); 19 F NMR (375MHz, CDCl3) δ-75.8 (s, 3F); 13 C NMR (100MHz, CDCl3) δ166.2, 131.3, 124.10 (q, J = 335.3Hz) ppm.

[0030] Example 3 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 1,3-dioxooctanoic acid-2H-isoindole-2-yltrifluoromethyl sulfinate, referred to as reagent 3c in this invention, and has the structural formula as follows: The preparation method is as follows: (1) 2-hydroxyhexahydro-1H-isoindole-1,3(2H)-dione (100mmol, 16.9g, compound 1c of the present invention) and 250mL chloroform were added to a round-bottom flask. LiOH (100mmol, 2.4g) was added under stirring. The mixture was refluxed at 80°C for 12h. The reaction solution was filtered, and the filter cake was dried to obtain the corresponding lithium salt solid (17.3g, 98.8%). (2) The lithium salt (10 mmol, 1.75 g) and tetrahydrofuran (50 mL) obtained in step (1) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was complete, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 1.17 g of white solid, with a yield of 41%.

[0031] Analysis of the obtained white solid confirmed that it was 1,3-dioxooctahydro-2H-isoindol-2-yl trifluoromethanesulfinate. The analytical results are as follows: 1,3-dioxooctahydro-2H-isoindol-2-yl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ1.57(m,4H),1.73(m,4H),2.82(m,2H); 19 F NMR (375MHz, CDCl3) δ-76.0 (s, 3F); 13 CNMR (100MHz, CDCl3) δ170.2, 124.73 (q, J = 336.8Hz), 34.3, 26.7, 24.8ppm.

[0032] Example 4 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 2,6-dioxadiazine-1-yltrifluoromethyl sulfinate, with the structural formula [insert structural formula here]. The preparation method is as follows: (1) 1-hydroxypiperidine-2,6-dione (100 mmol, 12.9 g, compound 1d of the present invention) and 250 mL of toluene were added to a round-bottom flask. KOH (100 mmol, 5.61 g) was added under stirring, and the mixture was refluxed at 110 °C for 0.5 h. The reaction solution was filtered, and the filter cake was dried to obtain the corresponding potassium salt solid (16.4 g, 98.0%). (2) Add the potassium salt (10 mmol, 1.67 g) obtained in step (1) and acetonitrile (50 mL) to a round-bottom flask, place it in an ice-water bath at 0 °C, and add CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) with stirring. After the addition is complete, turn the mixture to room temperature and react for 12 h. Filter the reaction solution, and remove the solvent from the filtrate under reduced pressure to obtain 1.05 g of white solid, with a yield of 43%.

[0033] Analysis of the obtained white solid confirmed that it was 2,6-dioxopiperidin-1-yltrifluoromethanesulfinate. The analytical results are as follows: 2,6-dioxopiperidin-1-yltrifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ2.37(m,2H),1.95(m,2H); 19 FNMR(375MHz, CDCl3)δ-75.8(s,3F); 13C NMR (100MHz, CDCl3) δ164.6, 124.73 (q, J=336.8Hz), 28.8, 17.2ppm.

[0034] Example 5 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 2,4,6-trioxo-1,3,5-triazine-1-trifluoromethyl sulfinic acid ester, referred to as reagent 3e in this invention, and has the structural formula as follows: The preparation method is as follows: (1) 1-hydroxy-1,3,5-triazine-2,4,6-trione (100 mmol, 14.5 g, compound 1e of the present invention) and 250 mL of acetonitrile were added to a round-bottom flask. KOH (100 mmol, 5.61 g) was added under stirring. The mixture was refluxed at 80 °C for 12 h. The reaction solution was filtered and the filter cake was dried to obtain solid potassium salt 2,4,6-trioxo-1,3,5-triazine-1-ol potassium (18.1 g, 99.0%). (2) Potassium 2,4,6-trioxo-1,3,5-triazine-1-ol (10 mmol, 1.83 g) and ethyl acetate (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was complete, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 914 mg of white solid, with a yield of 35%.

[0035] Analysis of the obtained white solid confirmed that it was 2,4,6-trioxo-1,3,5-triazinan-1-yl trifluoromethanesulfinate. The analytical results are as follows: 2,4,6-trioxo-1,3,5-triazinan-1-yl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ9.74 (s, 2H); 19 F NMR (375MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ150.5, 150.4, 125.60 (q, J = 336.8Hz) ppm.

[0036] Example 6 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is N-trifluoromethyl sulfinyl phthalimide, with the structural formula [insert structural formula here]. In this invention, it is simply referred to as reagent 3f, and its preparation method is as follows: (1) Preparation of N-hydroxyphthalimide potassium salt: N-hydroxyphthalimide (200 mmol, 32.6 g, compound 1f in this invention) and 500 mL of ethanol were added to a round-bottom flask. KOH (200 mmol, 11.22 g) was added under stirring. The mixture was refluxed at 80 °C for 12 h. The reaction solution was filtered, and the filter cake was dried to obtain a brownish-red solid, which was N-hydroxyphthalimide potassium salt (39.9 g, 99.5%). (2) Preparation of N-trifluoromethyl sulfinyl phthalimide: Potassium N-hydroxyphthalimide (143 mmol, 28.7 g) and chloroform (450 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (171.6 mmol, 1.2 equiv, 26.2 g) was added with stirring. After the addition was completed, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 27.9 g of white solid, with a yield of 70%.

[0037] Analysis of the obtained white solid confirmed that it was N-trifluoromethanesulfinate phthalimide. The analytical results are as follows: N-trifluoromethanesulfinate phthalimide: 1 H NMR (400MHz, CDCl3) δ7.95-7.92(m,2H),7.87-7.84(m,2H); 19 F NMR (375MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 161.7, 135.6, 128.4, 124.6, 122.8 (q, J = 336.3Hz) ppm.

[0038] Example 7 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 4-nitro-N-trifluoromethyl sulfinate phthalimide, with the structural formula [insert structural formula here]. The preparation method is as follows: (1) Add 4-nitro-N-hydroxyphthalimide (100 mmol, 20.8 g, compound 1i in this invention) and 250 mL of tetrahydrofuran to a round-bottom flask, add KOH (100 mmol, 5.61 g) while stirring, react at room temperature for 12 h, filter the reaction solution, dry the filter cake to obtain potassium salt of 4-nitro-N-hydroxyphthalimide (24.3 g, 98.9%). (2) Potassium 4-nitro-N-hydroxyphthalimide (10 mmol, 2.46 g) and chloroform (50 mL) were added to a round-bottom flask. The flask was placed in an ice-water bath at 0 °C, and CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was complete, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to give 1.2 g of white solid, with a yield of 37%.

[0039] Analysis of the obtained white solid confirmed that it was 4-nitro-N-trifluoromethyl sulfinyl phthalimide. The analytical results are as follows: 4-nitro-N-trifluoromethyl sulfinyl phthalimide (5-nitro-1,3-dioxoisoindolin-2-yl trifluoromethanesulfinate): 1 H NMR (400MHz, CDCl3) δ8.64(m,1H),8.55(m,1H),8.14(m,1H); 19 F NMR (375MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 166.2, 165.9, 151.5, 136.6, 133.4, 129.0, 123.8, 122.60 (q, J = 336.1Hz), 117.6ppm.

[0040] Example 8 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 4,5,6,7-tetrachloro-1,3-dioxoisoindole-2-yltrifluoromethyl sulfinate, abbreviated as reagent 3j, with the structural formula [insert structural formula here]. The preparation method is as follows: (1) In a round-bottom flask, N-hydroxytetrachlorophthalimide (100 mmol, 30.0 g, compound 1j of this invention) and 250 mL of ethyl acetate were added. KOH (100 mmol, 5.61 g) was added with stirring, and the mixture was refluxed at 90 °C for 12 h. The reaction solution was filtered, and the filter cake was dried under vacuum to obtain an orange solid N-hydroxytetrachlorophthalimide potassium salt (33.2 g, 98.0%). (2) Add N-hydroxytetrachlorophthalimide potassium salt (10 mmol, 3.38 g) and dimethyl sulfoxide (50 mL) to a round-bottom flask, place it in an ice-water bath at 0 °C, and add CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) with stirring. After the addition is complete, turn to room temperature and react for 12 h. Filter the reaction solution, remove the solvent from the filtrate under reduced pressure, and give 1.7 g of white solid, with a yield of 41%.

[0041] Analysis of the white solid confirmed it to be 4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl trifluoromethanesulfinate. The analytical results are as follows: 4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl trifluoromethanesulfinate. 19 F NMR (375MHz, CDCl3) δ-75.3 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 166.3, 141.2, 130.7, 124.8, 122.8 (q, J = 336.5Hz) ppm.

[0042] Example 9 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 1,3-dioxy-1H-benzisoquinoline-2(3H)-trifluoromethyl sulfinic acid ester, abbreviated as reagent 3l, and has the structural formula as follows: The preparation method is as follows: (1) 2-hydroxy-1H-benzoisoquinoline-1,3(2H)-dione (100mmol, 21.3g, compound 1l of the present invention) and 250mL isopropanol were added to a round-bottom flask, and CsOH (100mmol, 15.0g) was added under stirring. The mixture was refluxed at 80°C for 12h. The reaction solution was filtered, and the filter cake was dried to obtain solid cesium salt (33.6g, 97.5%). (2) The obtained solid cesium salt (10 mmol, 3.45 g) and ethanol (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was completed, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered and the filtrate was desolvated under reduced pressure to obtain 1.68 g of white solid, with a yield of 51%.

[0043] Analysis of the white solid confirmed it to be 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yltrifluoromethanesulfinate, with the following results: 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yltrifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ8.62-8.64(d,2H),8.29-8.26(d,2H),7.82-7.76(t,2H); 19F NMR (375MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (101MHz, CDCl3) δ 159.5, 134.0, 131.9, 127.6, 127.1, 122.7 (q, J = 336.1Hz), 122.3ppm.

[0044] Example 10 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 1,1-dioxo-3-oxobenzisothiazol-2(3H)-trifluoromethyl sulfinic acid ester, abbreviated as reagent 3n, and has the structural formula as follows: The preparation method is as follows: (1) 1,2-benzisothiazol-3(2H)-one, 2-hydroxy-1,1-dioxide (100 mmol, 19.9 g, compound 1n of this invention) and 250 mL of acetone were added to a round-bottom flask. KOH (100 mmol, 5.61 g) was added while stirring, and the mixture was refluxed at 150 °C for 12 h. The reaction solution was filtered, and the filter cake was dried to obtain solid potassium salt 3-oxobenzisothiazol-2(3H)-alkoxide potassium 1,1-dioxide (22.4 g, 95.1%). (2) Add 10 mmol (2.37 g) of 3-oxobenzisothiazol-2(3H)-ol potassium 1,1-dioxide and 50 mL of N,N-dimethylformamide to a round-bottom flask, place it in an ice-water bath at 0 °C, and add CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) with stirring. After the addition is complete, the reaction is carried out at room temperature for 0.5 h. Filter the reaction solution, remove the solvent from the filtrate under reduced pressure, and give 2.2 g of white solid, with a yield of 70%.

[0045] Analysis of the obtained white solid confirmed that it was 1,1-dioxido-3-oxobenzoisothiazol-2(3H)-yltrifluoromethanesulfinate. The analytical results are as follows: 1,1-dioxido-3-oxobenzoisothiazol-2(3H)-yltrifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ8.16(m,1H),7.99–7.92(m,2H),7.92–7.86(m,1H); 19 F NMR (375MHz, CDCl3) δ-75.7 (s, 3F); 3C NMR (101MHz, CDCl3) δ 180.4, 156.2, 136.4, 135.0, 126.5, 125.8, 123.0 (q, J = 336.1Hz) 121.4ppm.

[0046] Example 11 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is N-(phenylsulfonyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzenesulfonamide, referred to as reagent 3o in this invention, and has the structural formula as follows: The preparation method is as follows: (1) In a round-bottom flask, add N-hydroxy-N-(phenylsulfonyl)benzenesulfonamide (100 mmol, 31.3 g, compound 1o of this invention), 250 mL of N,N-dimethylformamide, and KOH (100 mmol, 5.61 g) under stirring. Reflux at 80 °C for 24 h. Filter the reaction solution, dry the filter cake, and obtain solid potassium salt (34.2 g, 97.8%). (2) The obtained solid potassium salt (10 mmol, 3.51 g) and chloroform (50 mL) were added to a round-bottom flask. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added under stirring at 0 °C. After the addition was completed, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 1.93 g of white solid, with a yield of 45%.

[0047] Analysis of the obtained white solid confirmed that it was N-(phenylsulfonyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzenesulfonamide, and the analytical results are as follows: N-(phenylsulfonyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzenesulfonamide: 1 H NMR (400MHz, CDCl3) δ7.98(m,4H),7.65(m,2H),7.56-7.52(m,4H); 19 F NMR (375MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (101MHz, CDCl3) δ 137.89, 135.03, 129.27, 129.10, 124.3 (q, J = 336.1Hz) ppm.

[0048] Example 12 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is N-(tert-butyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzamide, referred to as reagent 3m in this invention, and has the structural formula as follows: The preparation method is as follows: (1) In a round-bottom flask, N-(tert-butyl)-N-hydroxybenzamide (100 mmol, 19.3 g, the compound described in this invention 1 m) and 250 mL of ethanol were added. KOH (100 mmol, 5.61 g) was added while stirring, and the mixture was refluxed at 80 °C for 12 h. The reaction solution was filtered, and the filter cake was dried to obtain a solid potassium salt (22.6 g, 98.1%). (2) The obtained solid potassium salt (10 mmol, 2.31 g) and chloroform (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was complete, the mixture was allowed to react at room temperature for 10 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 1.18 g of white solid, with a yield of 38%.

[0049] Analysis of the white solid confirmed it to be N-(tert-butyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzamide, with the following results: N-(tert-butyl)-N-(((trifluoromethyl)sulfinyl)oxy)benzamide: 1 H NMR (400MHz, CDCl3) δ8.08(m,2H),7.97(m,3H),1.61(s,9H); 19 F NMR (375MHz, CDCl3) δ-75.3 (s, 3F); 13 C NMR (101MHz, CDCl3) δ171.6, 136.3, 129.8, 127.8, 127.6, 124.3 (q, J = 334.3Hz), 63.0, 28.0ppm.

[0050] Example 13 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is N-methyl-N-(((trifluoromethyl)sulfinyl)oxy)4-chlorobenzenesulfonamide, referred to as reagent 3p in this invention, and has the structural formula as follows: The preparation method is as follows: (1) Add N-hydroxy-N-methyl-4-chlorobenzenesulfonamide (100mmol, 22.0g, compound 1p of the present invention) and 250mL of ethanol to a round-bottom flask, add KOH (100mmol, 5.61g) while stirring, reflux at 80°C for 12h, filter the reaction solution, dry the filter cake to obtain solid potassium salt (25.1g, 97%). (2) The obtained solid potassium salt (10 mmol, 2.59 g) and tetrahydrofuran (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was completed, the reaction was carried out at 80 °C for 10 h. The reaction solution was filtered and the filtrate was desoluble under reduced pressure to obtain 1.18 g of white solid, with a yield of 35%.

[0051] Analysis of the white solid confirmed it to be N-methyl-N-(((trifluoromethyl)sulfinyl)oxy)-4-chlorobenzenesulfonamide. The analytical results are as follows: N-methyl-N-(((trifluoromethyl)sulfinyl)oxy)-4-chlorobenzenesulfonamide 1 H NMR (400MHz, CDCl3) δ7.68(m,2H),7.38(m,2H),2.47(s,3H); 19 F NMR (375MHz, CDCl3) δ-75.9 (s, 3F); 13 CNMR (101MHz, CDCl3) δ 137.6, 130.8, 129.3, 128.3, 124.7 (q, J = 334.7Hz), 31.3ppm.

[0052] Example 14 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is 1H-benzo[1,2,3]triazol-1-yltrifluoromethyl sulfinate, referred to as reagent 3q in this invention, and has the structural formula as follows: The preparation method is as follows: (1) 1H-benzo[1,2,3]triazol-1-ol (100mmol, 13.5g, compound 1q of the present invention) and 250mL of ethanol were added to a round-bottom flask. KOH (100mmol, 5.61g) was added while stirring, and the mixture was refluxed at 80°C for 10h. The reaction solution was filtered, and the filter cake was dried to obtain solid potassium salt (17.1g, 98.8%). (2) The obtained solid potassium salt (10 mmol, 1.73 g) and acetone (50 mL) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was completed, the mixture was allowed to react at room temperature for 12 h. The reaction solution was filtered and the filtrate was desolvated under reduced pressure to obtain 930 mg of white solid, with a yield of 37%.

[0053] Analysis of the obtained white solid confirmed that it was 1H-benzo[1,2,3]triazol-1-yl trifluoromethanesulfinate. The analytical results are as follows: 1H-benzo[1,2,3]triazol-1-yl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ7.96 (m, 2H), 7.40 (m, 2H); 19 FNMR(375MHz, CDCl3)δ-75.2(s,3F); 13 C NMR (101MHz, CDCl3) δ143.2, 126.2, 123.3 (q, J = 333.7Hz), 119.6ppm.

[0054] Example 15 A method for preparing a trifluoromethyl sulfoxide reagent, wherein the trifluoromethyl sulfoxide reagent is diphenyl ketone O-((trifluoromethyl)sulfinyl)oxime, referred to as reagent 3r in this invention, and has the structural formula as follows: The preparation method is as follows: (1) Add diphenyl ketone oxime (100 mmol, 19.7 g, compound 1r described in this invention) and 250 mL of ethanol to a round-bottom flask, and add KOH (100 mmol, 5.61 g) while stirring. Reflux at 80 °C for 12 h. Filter the reaction solution and dry the filter cake to obtain solid potassium salt (23.0 g, 97.9%). (2) The obtained solid potassium salt (10 mmol, 2.35 g) and chloroform (50 ml) were added to a round-bottom flask and placed in an ice-water bath at 0 °C. CF3SOCl (12 mmol, 1.2 equiv, 1.83 g) was added with stirring. After the addition was completed, the mixture was allowed to react at room temperature for 24 h. The reaction solution was filtered, and the filtrate was desolvated under reduced pressure to obtain 1.60 g of white solid, with a yield of 51%.

[0055] Analysis of the obtained white solid confirmed that it was diphenylmethanone O-((trifluoromethyl)sulfinyl)oxime. The analytical results are as follows: Diphenylmethanone O-((trifluoromethyl)sulfinyl)oxime: 1 H NMR (400MHz, CDCl3) δ7.48(m,2H),7.43-7.40(m,3H),7.34-7.28(m,5H); 19 F NMR (375MHz, CDCl3) δ-75.7 (s, 3F); 13 C NMR (101MHz, CDCl3) δ 156.7, 136.4, 133.3, 129.3, 129.2, 128.8, 128.3, 128.1, 127.9, 125.3 (q, J = 334.3Hz) ppm.

[0056] Example 16 Compound 3f was reacted with the aromatic compound 1,3-dimethoxybenzene, as follows: Under argon atmosphere, 0.5 mmol of 1,3-dimethoxybenzene and 1.0 mmol of reagent 3f were placed in a 25 ml sealed tube, and then 4 ml of DCE was added. The reaction was carried out for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain the corresponding trifluoromethyl sulfoxide product. The specific reaction conditions and results are shown in Table 1. Table 1. Reaction conditions and results of aromatic compound 1,3-dimethoxybenzene (A) with reagent 3f (B) In Table 1, 73.6 mg of the product was obtained in Experiment 2, with a yield of 58%. Analysis of the obtained product yielded the following results: 2,4-Dimethoxy-1-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.80 (m, J=8.9, 2.1Hz, 1H), 6.70 (dt, J=8.9, 2.4Hz, 1H), 6.49 (t, J=2.3Hz, 1H), 3.86 (t, J=2.9Hz, 6H); 19 F NMR (376MHz, CDCl3) δ-74.8 (s, 3F); 3C NMR (100MHz, CDCl3) δ 165.6, 159.4, 128.5, 125.2 (q, J = 333.3Hz), 114.8, 106.5, 98.8, 56.1, 55.9 ppm. Therefore, the obtained substance is... A trifluoromethyl sulfoxide group was successfully incorporated into 1,3-dimethoxybenzene.

[0057] Example 17 Compound 3f was reacted with the aromatic compound 1-methyl-3-methoxybenzene, as follows: Under argon atmosphere, 0.5 mmol of 1-methyl-3-methoxybenzene and 1.0 mmol of reagent 3f were placed in a 25 ml sealed tube, followed by the addition of 4 ml of DCE. The reaction was carried out at room temperature for 12 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 57.1 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 48%. The product was analyzed, and the results are as follows: 4-Methoxy-2-methyl-1-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.91(d,J=8.8Hz,1H),6.96(dd,J=8.9,2.6Hz,1H),6.78(d,J=3.3Hz,1H),3.84(s,3H),2.43(s,3H); 19 F NMR (376MHz, CDCl3) δ-74.3 (s, 3F); 3 C NMR (100MHz, CDCl3) δ 163.6, 140.3, 128.2, 125.3 (q, J = 333.3Hz), 125.1, 116.7, 113.1, 55.6, 18.6 ppm. Therefore, the obtained substance is... A trifluoromethyl sulfoxide group was successfully incorporated into 1-methyl-3-methoxybenzene.

[0058] Example 18 Compound 3f was reacted with the aromatic compound 4-(cyclopropylmethoxy)-2-methoxybenzene, replacing 1-methyl-3-methoxybenzene, with the other steps being the same as in Example 17. This yielded 76.5 mg of the trifluoromethyl sulfoxide product, with a yield of 52%. The product was analyzed, and the results are as follows: 4-(Cyclopropylmethoxy)-2-methoxy-1-((trifluoromethyl)sulfinyl)benzene: 1H NMR (400MHz, CDCl3) δ7.74 (d, J=8.7Hz, 1H), 6.65 (dd, J=8.8, 2.3Hz, 1H), 6.49 (d, J=2.3Hz, 1H),3.83(d,J=7.4Hz,5H),1.27–1.21(m,1H),0.64(q,J=6.1Hz,2H),0.34(q,J=4.7Hz,2H); 19 F NMR (376MHz, CDCl3) δ-74.8 (s, 3F); 13 C NMR (100MHz, CDCl3) δ165.0, 159.4, 128.4, 125.2 (q, J = 333.3Hz), 114.5, 106.9, 99.3, 73.4, 56.0, 10.1, 3.3ppm. 2-(Cyclopropylmethoxy)-4-methoxy-1-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.79 (d, J=8.8Hz, 1H), 6.68 (dd, J=8.8, 2.3Hz, 1H), 6.43 (d, J=2.3H z,1H),3.85(d,J=4.6Hz,5H),1.23(s,1H),0.63(d,J=8.5Hz,2H),0.32(d,J=5.0Hz,2H); 19 F NMR (376MHz, CDCl3) δ-74.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ165.4, 158.8, 128.4, 125.3 (q, J = 333.3Hz), 115.0, 106.4, 99.5, 73.6, 55.8, 9.8, 3.3, 3.1ppm. Therefore, it can be concluded that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 4-(cyclopropylmethoxy)-2-methoxybenzene, generating two products. (Molar ratio is 7:2).

[0059] Example 19 Reagent 3c was reacted with the aromatic compound 4-(4-trifluoromethylbenzyloxy)-2-methoxybenzene, replacing 1-methyl-3-methoxybenzene, otherwise the same as in Example 17, yielding 107.4 mg of the trifluoromethyl sulfoxide product, with a yield of 54%. Analysis of the product yielded the following results: 2-Methoxy-4-((4-(trifluoromethyl)benzyl)oxy)-1-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.81(d,J=8.7Hz,1H),7.66(d,J=8.0Hz,2H),7.55(d,J=8.0Hz ,2H),6.76(dd,J=8.7,2.1Hz,1H),6.59(d,J=2.1Hz,1H),5.17(s,2H),3.86(s,3H); 19 F NMR(376MHz, CDCl3)δ-62.4(s,3F),-74.6(s,3F); 13 C NMR (100MHz, CDCl3) δ164.3,159.4,139.9,130.8,130.5,128.7,127.6,125.8,125. 8,125.2(q,J=335.2Hz),124.1(q,J=271.5Hz),115.7,107.0,99.7,69.7,56.1ppm. 4-methoxy-2-((4-(trifluoromethyl)benzyl)oxy)-1-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.7Hz,1H),7.67(d,J=8.1Hz,2H),7.50(d,J=7.9Hz ,2H),6.75(dd,J=8.8,2.2Hz,1H),6.53(d,J=2.2Hz,1H),5.19(s,2H),3.85(s,3H); 19 F NMR(376MHz, CDCl3)δ-62.5(s,3F),-74.6(s,3F); 13C NMR (100MHz, CDCl3) δ 165.51, 158.00, 139.48, 130.85, 130.53, 128.86, 127.23, 125.90, 125.87, 125.3 (q, J = 335.1 Hz), 124.0 (q, J = 270.8 Hz), 106.92, 100.07, 69.97, 55.90 ppm. It can be seen that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 4-(4-trifluoromethylbenzyloxy)-2-methoxybenzene, generating two products. (Molar ratio is 7:3).

[0060] Example 20 Compound 3f was reacted with the aromatic compound 1,2-dimethoxybenzene, as follows: Under argon atmosphere, 0.5 mmol of 1,2-dimethoxybenzene, 1.0 mmol of reagent 3f, and 0.75 mmol of trifluoromethanesulfonic acid were placed in a 25 mL sealed tube, followed by the addition of 4 mL of DCE. The reaction was carried out at room temperature for 12 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 66.2 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 52%. Analysis of the product yielded the following results: 1,2-Dimethoxy-4-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.27 (s, 2H), 6.98 (d, J = 4.9Hz, 1H), 3.90 (s, 6H); 19 F NMR (376MHz, CDCl3) δ-74.9 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 153.7, 150.4, 126.4, 124.7 (q, J = 333.3Hz), 120.4, 111.2, 107.6, 56.3 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 1,2-dimethoxybenzene, generating...

[0061] Example 21 The aromatic compound was 1-methyl-2-methoxybenzene, and other parameters were the same as in Example 20. 69.3 mg of the trifluoromethyl sulfoxide product was obtained, with a yield of 58%. The product was analyzed, and the results are as follows: 1-methoxy-2-methyl-4-((trifluoromethyl)sulfinyl)benzene: 1H NMR (400MHz, CDCl3) δ7.58(d,J=8.7Hz,1H),7.54(s,1H),6.97(d,J=8.6Hz,1H),3.88(s,3H),2.25(s,3H); 19 FNMR(376MHz, CDCl3)δ-75.2(s,3F); 13 C NMR (100MHz, CDCl3) δ 162.3, 129.1, 127.9, 126.2, 125.5, 124.8 (q, J = 333.3Hz), 110.5, 55.8, 16.4 ppm. This indicates that a trimethyl sulfoxide group was successfully incorporated into the aromatic ring compound 1-methyl-2-methoxybenzene, generating...

[0062] Example 22 The aromatic compound was methyl 2-(2-methoxyphenyl)acetate, and other parameters were the same as in Example 20. 87.3 mg of the trifluoromethyl sulfoxide product was obtained, with a yield of 59%. The product was analyzed, and the results are as follows: Methyl 2-(2-methoxy-5-((trifluoromethyl)sulfinyl)phenyl)acetate: 1 HNMR (400MHz, CDCl3) δ7.68(dd,J=8.7,2.3Hz,1H),7.59(d,J=1.8Hz,1H),7.04(d,J=8.7Hz,1H),3.87(s,3H),3.66(d,J=1.8Hz,2H),3.66(s,3H); 19 F NMR (376MHz, CDCl3) δ-75.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 171.2, 162.0, 129.7, 128.7, 127.6, 125.9, 125.3, 124.7 (q, J = 333.3Hz), 119.7, 111.3, 56.1, 52.2, 35.5ppm. Therefore, it can be concluded that a trimethyl sulfoxide group was successfully incorporated into the aromatic ring compound methyl 2-(2-methoxyphenyl)acetate, generating...

[0063] Example 23 The aromatic compound was 2,3-dihydrobenzofuran, and other parameters were the same as in Example 20. 61.4 mg of the trifluoromethyl sulfoxide product was obtained, with a yield of 52%. The product was analyzed, and the results are as follows: 5-((Trifluoromethyl)sulfinyl)-2,3-dihydrobenzofuran: 1 H NMR (400MHz, CDCl3) δ7.62(s,1H),7.49(d,J=8.4Hz,1H),6.90(d,J=8.4Hz,1H),4.67(t,J=9.7Hz,2H),3.30–3.24(m,2H); 19 F NMR (376MHz, CDCl3) δ-75.3 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 165.2, 129.6, 127.9, 126.1, 124.8 (q, J = 333.3Hz), 123.0, 110.4, 72.4, 29.1 ppm. This indicates that a trimethyl sulfoxide group was successfully incorporated into the aromatic compound 2,3-dihydrobenzofuran, generating...

[0064] Example 24 The aromatic compound was 2-methoxynaphthalene, and other parameters were the same as in Example 17, yielding 71.2 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 52%. Analysis of the product yielded the following results: 2-Methoxy-1-((trifluoromethyl)sulfinyl)naphthalene: 1 H NMR (400MHz, CDCl3) δ9.02 (d, J = 5.4Hz, 1H), 8.04 (dd, J = 9.3, 4.3Hz, 1H), 7.82 (d, J = 8.3Hz, 1H) ,7.63–7.54(m,1H),7.44(q,J=7.6Hz,1H),7.25(dd,J=9.0,5.1Hz,1H),3.99(d,J=4.7Hz,3H); 19 F NMR (376MHz, CDCl3) δ-69.8 (s, 3F); 13 C NMR (100MHz, CDCl3) δ159.2, 137.0, 132.7, 129.6, 129.0, 128.8, 126.7 (q, J = 333.3Hz), 125.1, 123.3, 113.8, 112.3, 57.1ppm. Therefore, it can be concluded that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 2-methoxynaphthalene, generating [the desired compound].

[0065] Example 25 The aromatic compound was anisole. Reagent 3e was substituted for 3f, and all other steps were the same as in Example 20. 66.0 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 59%. Analysis of the product yielded the following results: 1-Methoxy-4-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.71 (d, J = 8.7Hz, 2H), 7.07 (d, J = 8.1Hz, 2H), 3.86 (s, 3H); 19 F NMR (376MHz, CDCl3) δ-75.2 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 164.1, 134.9, 128.2, 126.3, 124.8 (q, J = 333.3Hz), 121.8, 115.3, 55.7 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic compound anisole, generating...

[0066] Example 26 The aromatic compound was 1-(2-bromoethoxy)benzene, and other parameters were the same as in Example 20. 145.3 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 92%. The product was analyzed, and the results are as follows: 1-(2-Bromoethoxy)-4-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.72(d,J=8.8Hz,2H),7.09(d,J=8.9Hz,2H),4.35(t,J=6.0Hz,2H),3.66(t,J=6.1Hz,2H); 19 FNMR(376MHz, CDCl3)δ-75.0(s,3F); 13 C NMR (100MHz, CDCl3) δ 162.6, 134.9, 128.3, 124.7 (q, J = 333.3Hz), 115.8, 68.2, 28.6 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 1-(2-bromoethoxy)benzene, generating...

[0067] Example 27 The aromatic ring compound was 1-(phenoxymethyl)-4-(trifluoromethyl)benzene. Reagent 3j was substituted for 3f, and all other procedures were the same as in Example 20. 90.1 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 49%. Analysis of the product yielded the following results: 1-(Trifluoromethyl)-4-((4-((trifluoromethyl)sulfinyl)phenoxy)methyl)benzene: 1 HNMR (400MHz, CDCl3) δ7.74(d,J=8.5Hz,2H),7.67(d,J=7.9Hz,2H),7.55(d,J=8.0Hz,2H),7.16(d,J=8.9Hz,2H),5.20(s,2H); 19 F NMR(376MHz, CDCl3)δ-62.5(s,3F),-75.0(s,3F); 13 CNMR (100MHz, CDCl3) δ 162.8, 139.9, 130.6, 130.5, 128.3, 127.6, 127.1, 125.9, 125.8, 124.8 (q, J = 333.2 Hz), 124.1 (q, J = 271.0 Hz), 116.0, 69.6 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 1-(phenoxymethyl)-4-(trifluoromethyl)benzene, generating...

[0068] Example 28 The aromatic compound was methyl 2-phenoxyacetate, and other parameters were the same as in Example 20, yielding 76.0 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 54%. The product was analyzed, and the results are as follows: Methyl 2-(4-((trifluoromethyl)sulfinyl)phenoxy)acetate: 1 H NMR (400MHz, CDCl3) δ7.72 (d, J = 8.6 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.71 (d, J = 4.3 Hz, 2H), 3.80 (s, 3H); 19 F NMR (376MHz, CDCl3) δ-75.0 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 168.5, 134.8, 128.2, 124.7 (q, J = 333.3Hz), 115.9, 65.2, 52.6 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 2-phenoxyacetic acid methyl ester, generating...

[0069] Example 29 The aromatic compound was 1-(3-chloropropyl)benzene, and other details were the same as in Example 20, yielding 77.0 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 57%. Analysis of the product yielded the following results: 1-(3-Chloropropyl)-4-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.72(d,J=7.9Hz,2H),7.44(d,J=8.0Hz,2H),3.53(t,J=6.2Hz,2H),2.88(t,J=7.5Hz,2H),2.12(q,J=6.8Hz,2H); 19 F NMR (376MHz, CDCl3) δ-74.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 147.4, 133.4, 129.9, 126.3, 124.8 (q, J = 333.3Hz), 43.9, 33.6, 32.8 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 1-(3-chloropropyl)benzene, generating the product...

[0070] Example 30 The aromatic compound was 4-fluoroanisole, and other parameters were the same as in Example 20, yielding 55.7 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 46%. Analysis of the product yielded the following results: 4-Fluoro-1-methoxy-2-((trifluoromethyl)sulfinyl)benzene: 1 H NMR (400MHz, CDCl3) δ7.60(dd,J=7.4,3.1Hz,1H),7.25(ddd,J=8.9,7.5,3.0Hz,1H),6.95(dd,J=9.1,3.6Hz,1H),3.87(s,3H); 19 F NMR(376MHz, CDCl3)δ-73.4(s,3F),-119.9(s,1F); 13 C NMR (100MHz, CDCl3) δ 158.8, 156.3, 154.0, 125.2, 125.1 (q, J = 333.3Hz), 121.7, 121.4, 113.9, 113.7, 112.8, 112.7, 56.6 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 4-fluoroanisole, generating...

[0071] Example 31 The aromatic compound was 2,5-dimethylphenol, and other parameters were the same as in Example 17. 88.1 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 74%. The product was analyzed, and the results are as follows: 3,6-Dimethyl-2-((trifluoromethyl)sulfinyl)phenol: 1 H NMR (400MHz, DMSO-d6) δ10.44(s,1H),7.52(s,1H),6.75(s,1H),2.29(s,3H),2.13(s,3H); 19 F NMR(376MHz,DMSO-d6)δ-74.4(s,3F); 13 C NMR (100MHz, DMSO-d6) δ 160.9, 138.3, 128.2, 125.8 (q, J = 333.3Hz), 124.5, 122.2, 117.5, 18.0, 16.0 ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 2,5-dimethylphenol, generating...

[0072] Example 32 The aromatic compound was 5-indenol, and other parameters were the same as in Example 17, yielding 88.7 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 71%. Analysis of the product yielded the following results: 6-((Trifluoromethyl)sulfinyl)-2,3-dihydro-1H-inden-5-ol: 1 H NMR (400MHz, CDCl3) δ9.34 (s, 1H), 7.26 (s, 1H), 7.05 (s, 1H), 3.11 (t, J = 7.5Hz, 2H), 3.04 (t, J = 7.2Hz, 2H), 2.28 (q, J = 7.5Hz, 2H); 19 F NMR (376MHz, CDCl3) δ-73.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ159.8, 153.9, 136.7, 125.3 (q, J = 333.3Hz), 122.4, 115.6, 111.0, 33.4, 31.7, 25.6ppm. Therefore, it can be concluded that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic compound 5-indanol, generating...

[0073] Example 33 The aromatic compound was tetrahydronaphthol, and other parameters were the same as in Example 17, yielding 103.0 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 78%. Analysis of the product yielded the following results: 4-((Trifluoromethyl)sulfinyl)-5,6,7,8-tetrahydronaphthalen-1-ol: 1 H NMR (400MHz, CDCl3) δ7.73(d,J=8.6Hz,1H),7.04(s,1H),6.91(d,J=8.6Hz,1H),3.01(d,J= 16.6Hz, 1H), 2.74 (d, J = 17.1Hz, 1H), 2.63 (d, J = 19.2Hz, 2H), 1.81 (dd, J = 68.7, 5.0Hz, 4H); 19 F NMR (376MHz, CDCl3) δ-73.9 (s, 3F); 13 C NMR (100MHz, CDCl3) δ159.1, 139.8, 125.5, 125.3, 125.2 (q, J = 333.3Hz), 123.3, 113.8, 26.3, 23.0, 22.1, 21.8ppm. Therefore, it can be concluded that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound tetrahydronaphthol, generating [a compound].

[0074] Example 34 The aromatic compound was 2-isopropyl-5-methylphenol. Reagent 3l was substituted for 3f, and all other procedures were the same as in Example 17. 98.4 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 74%. The product was analyzed, and the results are as follows: 2-Isopropyl-5-methyl-4-((trifluoromethyl)sulfinyl)phenol: 1 H NMR (400MHz, CDCl3) δ7.77(s,1H),7.14(s,1H),6.73(s,1H),3.24(p,J=6.9Hz,1H),2.36(s,3H),1.21(dd,J=12.6,6.9Hz,6H); 19 F NMR (376MHz, CDCl3) δ-74.0 (s, 3F); 13C NMR (100MHz, CDCl3) δ 158.9, 137.8, 135.4, 125.2 (q, J = 333.3Hz), 124.8, 122.5, 117.9, 27.0, 22.2, 17.9ppm. This indicates that a trifluoromethyl sulfoxide group was successfully incorporated into the aromatic ring compound 2-isopropyl-5-methylphenol, generating...

[0075] Example 35 The reaction of compound 3f with the aromatic heterocyclic compound indole is as follows: Under argon atmosphere, 0.5 mmol of indole and 0.6 mmol of reagent 3f were placed in a 25 ml sealed tube, and then 4 ml of DCE was added. The reaction was carried out for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain the corresponding trifluoromethyl sulfoxide product. The specific reaction conditions and results are shown in Table 2. Table 2. Reaction conditions and results of the aromatic heterocyclic compound indole (A) with reagent 3f (B). In Table 2, 115 mg of product was obtained in Experiment 1, with a yield of 99%. The product was analyzed, and the results are as follows: 3-((Trifluoromethyl)sulfinyl)-1H-indole: 1 H NMR (400MHz, CDCl3) δ10.32(s,1H),7.99(d,J=7.8Hz,1H),7.73(s,1H),7.48(d,J=8.1Hz,1H),7.31(m,2H); 19 F NMR (376MHz, CDCl3) δ-72.4(s,3F); 13 C NMR (100MHz, CDCl3) δ137.0, 131.5, 125.6 (q, J = 333.3Hz), 124.5, 124.1,122.7,120.1,112.8,107.6ppm. Therefore, we have obtained... A trifluoromethyl sulfoxide group was successfully incorporated into indole.

[0076] Example 36 The reaction of compound 3f with the aromatic heterocyclic compound 2-methylindole is as follows: Under argon atmosphere, 0.5 mmol of 2-methylindole and 0.6 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of DCE. The reaction was carried out at room temperature for 12 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 83.3 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 67%. The product was analyzed, and the results are as follows: 2-Methyl-3-((trifluoromethyl)sulfinyl)-1H-indole: 1 H NMR (400MHz, DMSO-d6) δ12.32(s,1H),7.78(d,J=7.8Hz,1H),7.48(d,J=8.7Hz,1H),7.23(t,J=8.0Hz,1H),7.19(t,J=8.0Hz,1H),2.58(s,3H); 19 F NMR(376MHz,DMSO-d6)δ-72.2(s,3F); 13 C NMR (100MHz, DMSO-d6) δ 145.2, 136.3, 126.7 (q, J = 333.3Hz), 125.5, 123.3, 122.0, 119.7, 112.5, 102.7, 12.2ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the aromatic heterocyclic compound 2-methylindole, forming...

[0077] Example 37 The aromatic heterocyclic compound was 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole. Other details were the same as in Example 36, yielding 114.8 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 99%. Analysis of the product yielded the following results: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-((trifluoromethyl)sulfinyl)-1H-indole: 1 H NMR (400MHz, CDCl3) δ10.57(s,1H),8.08(s,1H),7.86(d,J=7.1Hz,1H),7.67(d,J=8.2Hz,1H),7.33(t,J=7.7Hz,1H),1.42(s,12H); 19 F NMR (376MHz, CDCl3) δ-74.8 (s, 3F); 13C NMR (100MHz, CDCl3) δ 137.1, 131.0, 129.9, 127.7, 125.8 (q, J = 333.3Hz), 123.0, 116.1, 110.9, 84.5, 25.0, 24.6 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the aromatic heterocyclic compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole, generating...

[0078] Example 38 The aromatic heterocyclic compound was 5-thiophen-2-yl-1H-indole. Reagent 3n was substituted for 3f, and all other procedures were the same as in Example 36, yielding 118.1 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 75%. Analysis of the product yielded the following results: 5-(Thiophen-2-yl)-3-((trifluoromethyl)sulfinyl)-1H-indole: 1 H NMR (400MHz, CDCl3) δ10.29(s,1H),8.18(s,1H),7.74(d,J=3.0Hz,1H),7.56(dd,J=8 .5,1.8Hz,1H),7.46(d,J=8.6Hz,1H),7.29–7.23(m,2H),7.07(dd,J=5.1,3.6Hz,1H); 19 F NMR (376MHz, CDCl3) δ-72.2 (s, 3F); 13 CNMR (100MHz, CDCl3) δ 144.5, 136.5, 132.0, 129.6, 128.1, 125.6 (q, J = 333.3Hz), 124.7, 124.7, 123.5, 123.2, 117.2 (d, J = 2.2Hz), 113.2, 107.9 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the aromatic heterocyclic compound 5-thiophene-2-yl-1H-indole, generating...

[0079] Example 39 The aromatic heterocyclic compound was 5,6-dihydro-4H-pyrrolo[3,2,1-IJ]quinoline. Reagent 3o was substituted for 3f, and all other procedures were the same as in Example 36. 133.7 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 98%. Analysis of the product yielded the following results: 1-((Trifluoromethyl)sulfinyl)-5,6-dihydro-4H-pyrrolo[3,2,1-IJ]quinoline: 1HNMR(400MHz, CDCl3)δ7.75(d,J=8.1Hz,1H),7.69(s,1H),7.23(t,J=8.0Hz,1H),7. 09(d,J=7.1Hz,1H),4.24(t,J=5.8Hz,2H),3.03(t,J=6.1Hz,2H),2.32–2.24(m,2H); 19 F NMR (376MHz, CDCl3) δ-73.4 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 135.1, 131.4, 125.7 (q, J = 343.4 Hz), 123.1, 123.1, 123.0, 121.2, 118.0 (d, J = 1.8 Hz), 107.2, 45.2, 24.3, 22.5 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the aromatic heterocyclic compound 5,6-dihydro-4H-pyrrolo[3,2,1-IJ]quinoline, generating...

[0080] Example 40 The aromatic heterocyclic compound was ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate, and other parameters were the same as in Example 36, yielding 113 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 80%. The product was analyzed, and the results are as follows: Ethyl 2,4-dimethyl-5-((trifluoromethyl)sulfinyl)-1H-pyrrole-3-carboxylate: 1 H NMR (400MHz, CDCl3) δ10.91 (s, 1H), 4.30 (d, J = 7.5Hz, 2H), 2.56 (s, 3H), 2.41 (s, 3H), 1.35 (t, J = 7.0Hz, 3H); 19 F NMR (376MHz, CDCl3) δ-73.1 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 164.6, 144.7, 134.1, 124.7 (q, J = 343.4Hz), 114.8, 113.6, 59.8, 14.3, 13.9, 11.3 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the aromatic heterocyclic compound ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate, forming...

[0081] Example 41 The aromatic heterocyclic compound was 3,4-ethylenedioxythiophene. Reagent 3M was substituted for 3F, and all other procedures were the same as in Example 36. 83.8 mg of the corresponding trifluoromethyl sulfoxide product was obtained, with a yield of 65%. Analysis of the product yielded the following results: 5-((Trifluoromethyl)sulfinyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine: 1 H NMR (400MHz, CDCl3) δ6.87(s,1H),4.36–4.32(m,2H),4.28–4.24(m,2H); 19 F NMR (376MHz, CDCl3) δ-73.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ147.4, 141.2, 125.0 (q, J = 333.3Hz), 110.2, 109.2, 65.5, 64.4ppm. It is known that the introduction of a trifluoromethyl sulfoxide group into the aromatic heterocyclic compound 3,4-ethylenedioxythiophene generates...

[0082] Example 42 Compound 3f was reacted with the amine substrate 4-iodobenzylamine, as follows: Under argon atmosphere, 0.5 mmol of 4-iodobenzylamine and reagent 3f were placed in a 25 ml sealed tube, and then 4 ml of DCE was added. The reaction was carried out for 3 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain the corresponding trifluoromethyl sulfoxide product. The specific reaction conditions and results are shown in Table 3. Table 3. Reaction conditions and results of amine substrate 4-iodobenzylamine (A) with reagent 3f (B). In Table 3, 130.8 mg of the product was obtained in Experiment 2, with a yield of 75%. The product was analyzed, and the results are as follows: 1,1,1-Trifluoro-N-(4-iodobenzyl)methanesulfinamide: 1 H NMR (400MHz, CDCl3) δ7.74(d,J=8.3Hz,2H),7.11(d,J=8.2Hz,2H),5.30(d,J=11.6Hz,1H),5.01(d,J=11.6Hz,1H); 19 FNMR(376MHz, CDCl3)δ-77.8(s,3F); 13C NMR (100MHz, CDCl3) δ138.2, 133.4, 130.6, 123.1 (q, J = 333.3Hz), 95.7, 68.9ppm. Therefore, the substance obtained is A trifluoromethyl sulfoxide group was successfully incorporated into 4-iodobenzylamine.

[0083] Example 43 Compound 3f was reacted with the amine substrate 4-tert-butylbenzylamine, as follows: Under argon atmosphere, 0.5 mmol of 4-tert-butylbenzylamine and 0.6 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of THF. The reaction was carried out at room temperature for 3 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 117.7 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 84%. The product was analyzed, and the results are as follows: N-(4-(tert-butyl)benzyl)-1,1,1-trifluoromethanesulfinamide: 1 H NMR (400MHz, CDCl3) δ7.39(d,J=8.1Hz,2H),7.26(d,J=8.3Hz,2H),4.79(s,1H),4.43(dd,J=14.0,6.2Hz,1H),4.26(dd,J=13.9,5.4Hz,1H),1.31(s,9H); 19 F NMR (376MHz, CDCl3) δ-76.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ151.6, 133.7, 128.1, 126.0, 123.8 (q, J = 333.3Hz), 46.2, 34.7, 31.4ppm. It is known that a trifluoromethyl sulfoxide group was introduced into the amine substrate 4-tert-butylbenzylamine, resulting in...

[0084] Example 44 The amine substrate was m-acetylaniline, and reagent 3q was substituted for 3f. All other procedures were the same as in Example 43, yielding 81.4 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 65%. The product was analyzed, and the results are as follows: N-(3-acetylphenyl)-1,1,1-trifluoromethanesulfinamide: 1H NMR (400MHz, CDCl3) δ7.98 (s, 1H), 7.74 (s, 1H), 7.67 (d, J = 7.7Hz, 1H), 7.39 (t, J = 7.9Hz, 1H), 7.32 (d, J = 8.1Hz, 1H), 2.56 (s, 3H); 19 F NMR (376MHz, CDCl3) δ-77.1 (s, 3F); 13 C NMR (100MHz, CDCl3) δ198.2, 139.5, 138.4, 130.2, 125.0, 123.9, 123.8 (q, J = 333.3Hz), 119.1, 26.7ppm. It can be seen that the introduction of a trifluoromethyl sulfoxide group into the amine substrate m-aminoacetophenone generates...

[0085] Example 45 The amine substrate was 4-phenylpiperidine, and other parameters were the same as in Example 43, yielding 116.4 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 84%. The product was analyzed, and the results are as follows: 4-Phenyl-1-((trifluoromethyl)sulfinyl)piperidine: 1 H NMR (400MHz, CDCl3) δ7.33(t,J=7.5Hz,2H),7.28–7.18(m,3H),3.93(d,J=12.7Hz,1H),3.77(d,J=14.3Hz,1 H),3.08(t,J=12.5Hz,1H),3.00(t,J=12.4Hz,1H),2.72(t,J=12.2Hz,1H),1.94(s,2H),1.85–1.68(m,2H); 19 F NMR (376MHz, CDCl3) δ-74.0 (s, 3F); 13 C NMR (100MHz, CDCl3) δ144.9, 128.8, 126.8, 124.5 (q, J = 343.4Hz), 46.7, 44.1, 42.2, 33.5 (d, J = 10.0Hz) ppm. It is known that the introduction of a trifluoromethyl sulfoxide group into the amine substrate 4-phenylpiperidine generates...

[0086] Example 46 Compound 3f was reacted with the alkyl alcohol p-iodobenzyl alcohol, as follows: Under argon atmosphere, 0.3 mmol of p-iodobenzyl alcohol and reagent 3f were placed in a 25 ml sealed tube, and then 3 ml of solvent was added for reaction. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by rapid silica gel column chromatography to obtain the corresponding trifluoromethyl sulfoxide product. The specific reaction conditions and results are shown in Table 4. Table 4. Reaction conditions and results of alkyl alcohols with iodobenzyl alcohol (A) and reagent 3f (B).

[0087] Example 47 Compound 3f was reacted with the alkyl alcohol compound 4-trifluoromethylbenzyl alcohol, as follows: Under argon atmosphere, 0.5 mmol of 4-trifluoromethylbenzyl alcohol and 1.0 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of toluene. The reaction was carried out at room temperature for 3 hours. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 121.1 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 83%. The product was analyzed, and the results are as follows: 4-(Trifluoromethyl)benzyl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ7.66(d,J=7.8Hz,2H),7.50(d,J=7.9Hz,2H),5.43(dd,J=12.0,7.1Hz,1H),5.14(dd,J=12.2,6.9Hz,1H); 19 F NMR(376MHz, CDCl3)δ-62.9(s,3F),-78.2(s,3F); 13 C10 NMR (100MHz, CDCl3) δ 137.8, 131.5 (q, J = 32.6 Hz), 128.8, 125.9 (q, J = 3.7 Hz), 123.8 (q, J = 272.7 Hz), 123.1 (q, J = 333.3 Hz), 68.2 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the alkyl alcohol compound 4-trifluoromethylbenzyl alcohol, generating...

[0088] Example 48 The alkyl alcohol compound was 0.5 mmol of 3,7-dimethyl-6-en-1-ol, with reagent 3r replacing 3f, and all other steps were the same as in Example 47, yielding 91.2 mg of the corresponding trifluoromethyl sulfoxide product, in 67% yield. Analysis of the product yielded the following results: 3,7-Dimethyloct-6-en-1-yl trifluoromethanesulfinate: 1H NMR (400MHz, CDCl3) δ5.17–4.94(m,1H),4.44–4.32(m,1H),4.21–4.08(m,1H),2.04–1.87(m,2H),1.8 4–1.71(m,1H),1.65(s,3H),1.58(s,4H),1.39–1.28(m,1H),1.25–1.14(m,2H),0.90(d,J=6.1Hz,3H); 19 F NMR (376MHz, CDCl3) δ-78.6 (s, 3F); 13 C NMR (100MHz, CDCl3) δ 131.6, 124.3, 123.0 (q, J = 333.3 Hz), 67.5, 36.8 (d, J = 8.9 Hz), 36.6 (d, J = 4.0 Hz), 28.9, 25.7, 25.3, 19.1 (d, J = 6.4 Hz), 17.6 ppm. It can be seen that a trifluoromethyl sulfoxide group was introduced into the alkyl alcohol compound 3,7-dimethyl-6-octen-1-ol, generating...

[0089] Example 49 The alkyl alcohol compound was 1-adamantanol, and other parameters were the same as in Example 47, yielding 104.5 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 78%. The product was analyzed, and the results are as follows: (3s,5s,7s)-Adamantan-1-yl trifluoromethanesulfinate: 1 H NMR (400MHz, CDCl3) δ2.24 (s, 3H), 2.02 (s, 6H), 1.64 (q, J = 11.9Hz, 6H); 19 F NMR (376MHz, CDCl3) δ-80.7 (s, 3F); 13 CNMR (100MHz, CDCl3) δ122.9 (q, J=333.3Hz), 86.5, 43.4, 35.4, 31.3ppm. It is known that the introduction of a trifluoromethyl sulfoxide group into the alkyl alcohol compound 1-adamantanol produces...

[0090] Example 50 Compound 3f was reacted with the indole bioactive molecule 1H-indol-4-yl-2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate, as follows: Under argon atmosphere, 0.5 mmol of 1H-indol-4-yl-2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate and 0.6 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of DCE. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 151 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 55%. The product was analyzed, and the results are as follows: 3-((Trifluoromethyl)sulfinyl)-1H-indol-4-yl 2-(4-(4-chlorobenzoyl)-phenoxy)-2-methylpropanoate: 1 H NMR (400MHz, CDCl3) δ10.82(s,1H),7.80(d,J=8.5Hz,2H),7.77(d,J=3.1Hz,1H),7.69(d,J=8.2Hz,2H),7. 40(d,J=8.2Hz,2H),7.25(t,J=4.2Hz,1H),7.18,7.11(d,J=8.6Hz,2H),7.00(d,J=7.7Hz,1H),1.91(s,6H); 19 F NMR (376MHz, CDCl3) δ-74.8 (s, 3F); 13 C NMR (100MHz, CDCl3) δ195.1, 172.7, 159.7, 142.8, 138.9 (d, J = 12.8Hz), 136.2, 132.3 (d, J = 24. 6Hz), 131.4 (d, J = 9.2Hz), 130.9, 130.8 (d, J = 9.9Hz), 128.7 (d, J = 21.8Hz), 125.1 (q, J = 333.3Hz ),124.2(d,J=30.9Hz),118.4(d,J=35.6Hz),117.9,114.5(d,J=25.5Hz),111.2(d,J=31.6Hz) ,106.6,80.1,26.02(d,J=16.8Hz),25.76,25.55(d,J=6.9Hz),25.35,25.09(d,J=16.7Hz)ppm. It is known that a trifluoromethyl sulfoxide group was introduced into the indole bioactive molecule 1H-indole-4-yl-2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate, resulting in...

[0091] Example 51 Compound 3f was reacted with the aromatic bioactive molecule methyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate as follows: Under argon atmosphere, 0.5 mmol of methyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate and 0.6 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of DCE. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 127.3 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 67%. The product was analyzed, and the results are as follows: Methyl 5-(2,5-dimethyl-4-((trifluoromethyl)sulfinyl)phenoxy)-2,2-dimethylpentanoate: 1 H NMR (400MHz, CDCl3) δ7.68(s,1H),6.62(s,1H),3.95(s,2H),3.63(s,3H),2.39(s,3H),2.21(s,3H),1.70(s,4H),1.19(s,6H); 19 F NMR (376MHz, CDCl3) δ-74.4 (s, 3F); 13 C NMR (100MHz, CDCl3) δ178.2, 161.2, 137.9, 127.7, 126.7, 125.4 (q, J = 333.3Hz), 123.7, 112.9, 68.4, 51.8, 42.1, 37.0, 25.2, 25.0, 18.3, 15.9ppm. It is known that the introduction of a trifluoromethyl sulfoxide group into the aromatic bioactive molecule methyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate produces...

[0092] Example 52 Compound 3f was reacted with the amine bioactive molecule 4-aminophenyl(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate, as follows: Under argon atmosphere, 0.5 mmol of 4-aminophenyl(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate and 0.6 mmol of reagent 3f were placed in a 25 mL sealed tube, followed by the addition of 4 mL of THF. The reaction was carried out at room temperature for 3 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 162.0 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 80%. The product was analyzed, and the results are as follows: 4-(((Trifluoromethyl)sulfinyl)amino)phenyl(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate: 1 H NMR(400MHz, CDCl3)δ7.30(s,1H),7.12(d,J=8.5Hz,2H),7.06(d,J=8.9Hz,2H),2.59–2.47(m,1H) ,2.20–2.12(m,1H),2.08–1.92(m,1H),1.78–1.69(m,1H),1.14(s,3H),1.11(s,3H),1.05(s,3H); 19 F NMR (376MHz, CDCl3) δ-77.2 (s, 3F); 13 C NMR (100MHz, CDCl3) δ178.2, 166.3, 147.1, 136.6, 123.7 (q, J = 333.3Hz), 122.7, 121.7, 91.0, 55.0, 54.9, 30.8, 29.0, 16.9, 9.8ppm. It is known that a trifluoromethyl sulfoxide group was introduced into the amine bioactive molecule compound 4-aminophenyl(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate, resulting in the formation of...

[0093] Example 53 Compound 3f was reacted with the alkyl alcohol bioactive molecule (3S,5R,10R,13R,14S,17R)-4,4,10,13,14 pentamethyl-17-((R)-6-methylhept-5-en-2-yl)hexadecyl-1H-cyclopentane[a]phenanthrene-3-ol under argon atmosphere. 0.5 mmol of (3S,5R,10R,13R,14S,17R)-4,4,10,13,14 pentamethyl-17-((R)-6-methylhept-5-en-2-yl)hexadecyl-1H-cyclopentane[a]phenanthrene-3-ol and 0.6 mmol of reagent 3f were placed in a 25 ml sealed tube, followed by the addition of 4 ml of toluene. The reaction was carried out at room temperature for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 196.0 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 72%. The product was analyzed, and the results are as follows: (3S,5R,10R,13R,14S,17R)-4,4,10,13,14-Pentamethyl-17-((R)-6-methylhept-5-en-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yltrifluoromethanesulfinate: 1 H NMR(400MHz, CDCl3)δ5.08(t,J=7.0Hz,1H),3.21(dd,J=11.5,4.6Hz,1H),2.08–1.94(m,6H), 1.74–1.39(m,19H),0.98(s,4H),0.96(s,3H),0.91–0.83(m,11H),0.79(s,3H),0.67(s,3H); 19 F NMR(376MHz, CDCl3)δ-80.0(d,3F); 13 C NMR (100MHz, CDCl3) δ135.0 (d, J = 10.1Hz), 133.8 (d, J = 10.7Hz), 130.8, 125.3, 122.8 (dq, J = 333.3, 11.1Hz), 92.2 (d, J = 84.9H z),50.8(d,J=12.8Hz),50.5(d,J=14.3Hz),49.8,44.5,39.6,39.0(d,J=19.3Hz),36.8,36.6(d,J=4.6Hz),36.4(d,J=8.6Hz) ,35.4(d,J=9.6Hz),30.9(d,J=12.6Hz),28.2(d,J=20.3Hz),27.7(d,J=22.6Hz),26.6(d,J=40.8Hz),25.9(d,J=27.9Hz),25. 0, 24.3 (d, J = 4.6Hz), 22.7 (d, J = 28.0Hz), 21.1, 19.1, 18.7 (d, J = 8.1Hz), 18.3 (d, J = 6.1Hz), 17.6, 15.9 (d, J = 9.4Hz), 15.8ppm. It is known that a trifluoromethyl sulfoxide group was introduced into the alkyl alcohol bioactive molecular compound (3S,5R,10R,13R,14S,17R)-4,4,10,13,14 pentamethyl-17-((R)-6-methylhept-5-en-2-yl)hexadecylhydro-1H-cyclopentane[a]phenanthrene-3-ol, generating a...

[0094] Reactivity Comparison Experiment 1 Under argon atmosphere, the aromatic substrate 1,3-dimethoxybenzene (0.5 mmol) and reagent 3f (1.0 mmol) were placed in a 25 mL sealed tube, and then 4 mL of DCE was added. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 73.6 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 58% (i.e., Experiment 2 in Table 1 of this invention).

[0095] Under the same conditions, when reagent 3f was replaced with N-trifluoromethylsulfinyl phthalimide provided in CN 114957086 A, the corresponding trifluoromethyl sulfoxide-based product was not observed.

[0096] Comparative Experiment 2 Under argon atmosphere, indole (0.5 mmol) and reagent 3f (0.6 mmol) were placed in a 25 ml sealed tube, and then 4 ml of DCE was added. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 115 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 99% (i.e., Experiment 1 in Table 2 of this invention).

[0097] Under the same conditions, when reagent 3f was replaced with N-trifluoromethyl sulfinyl phthalimide provided in CN 114957086 A, the corresponding trifluoromethyl sulfoxide product was not observed; the trifluoromethyl sulfoxide product could only be generated when an activator (e.g., TMSCl) was added.

[0098] Comparative Experiment 3 Under argon atmosphere, p-iodoaniline (0.5 mmol) and reagent 3f (0.6 mmol) were placed in a 25 ml sealed tube, and then 4 ml of THF was added. The reaction was carried out at room temperature for 3 hours. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to obtain 130.8 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 75% (i.e., Experiment 2 in Table 3 of this invention).

[0099] Under the same conditions, when N-trifluoromethylsulfinyl phthalimide provided in CN 114957086 A was used to replace reagent 3f, the corresponding trifluoromethyl sulfoxide product was not observed; the trifluoromethyl sulfoxide product could only be generated when an activator (e.g., Ph2P(O)Cl) was added.

[0100] Comparative Experiment 4 Under argon atmosphere, p-iodobenzyl alcohol (0.5 mmol) and reagent 3f (0.6 mmol) were placed in a 25 mL sealed tube, followed by the addition of 4 mL of toluene. The reaction was carried out at room temperature for 3 hours. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to give 145.3 mg of the corresponding trifluoromethyl sulfoxide product, with a yield of 83%.

[0101] Under the same conditions, when reagent 3f was replaced with N-trifluoromethyl sulfinyl phthalimide provided in CN 114957086 A, the corresponding trifluoromethyl sulfoxide product was not observed; only the addition of triethylamine could produce the trifluoromethyl sulfoxide product.

[0102] Therefore, the trifluoromethyl sulfoxide reagent provided by the present invention has high activity, does not require the addition of an activator, and has mild reaction conditions, thus realizing the direct introduction of trifluoromethyl sulfoxide groups into the target molecule.

Claims

1. A method for preparing a trifluoromethyl sulfoxide reagent, characterized in that: The trifluoromethyl sulfoxide reagent is represented as follows: , is an electrophilic trifluoromethyl sulfoxide reagent with an OS backbone, and the preparation method includes the following steps: (1) Using hydroxylamine as a raw material, after mixing with the first solvent, add alkali and react at room temperature to 150°C for 0.5-24h, filter to obtain the corresponding hydroxylamine metal salt; (2) Add a second solvent to the hydroxylamine metal salt, add CF3SOCl to it under stirring at -78-0℃, and react at -78-80℃ for 0.5-24h. Filter, desolvent the filtrate under reduced pressure, and the product obtained is the trifluoromethyl sulfoxide reagent. Wherein, the first solvent is at least one of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, nitrile solvents, ester solvents, ketone solvents, amide solvents, or alcohol solvents; The second solvent is at least one of the following: haloalkanes, aromatics, ethers, nitriles, esters, ketones, sulfoxides, amides, or alcohols. The alkali is the alkali corresponding to lithium, sodium, potassium, or cesium; The hydroxylamine is an acyl-protected hydroxylamine, a sulfonyl-protected hydroxylamine, a heterocyclic-protected hydroxylamine, or a diphenyl ketone oxime; The acyl-protected hydroxylamine is any one of the following compounds 1a-1m, the sulfonyl-protected hydroxylamine is any one of the following compounds 1n-1p, and the heterocyclic-protected hydroxylamine is the following compound 1q. ， Wherein, R is hydrogen, or a halogen, trifluoromethyl or cyano group monosubstituted or polysubstituted on the benzene ring, and R' is a C1-C12 chain or cyclic alkyl group.

2. The method for preparing the trifluoromethyl sulfoxide reagent according to claim 1, characterized in that: In step (1), the molar ratio of hydroxylamine to base is 1:1, and in step (2), the molar ratio of hydroxylamine metal salt to CF3SOCl is 1:(1-1.5).

3. The method for preparing the trifluoromethyl sulfoxide reagent according to claim 2, characterized in that: The alkali is any one of LiOH, NaOH, KOH, CsOH, Li2CO3, Na2CO3, K2CO3, Cs2CO3, NaHCO3, KHCO3, Na3PO4, Na2HPO4, NaH2PO4, K3PO4, K2HPO4, and KH2PO4.

4. The method for preparing the trifluoromethyl sulfoxide reagent according to claim 3, characterized in that: The first solvent is an alcohol solvent, and the second solvent is a halohydrocarbon solvent.

5. The application of a trifluoromethyl sulfoxide ionizing agent, characterized in that: The application is as follows: a trifluoromethyl sulfoxide reagent is reacted with a target molecule to directly introduce a trifluoromethyl sulfoxide group into the target molecule. The target molecule is any one of an aromatic ring compound, an aromatic heterocyclic compound, an amine, or an alkyl alcohol. The trifluoromethyl sulfoxide reagent is a trifluoromethyl sulfoxide reagent prepared by the preparation method described in claim 1.

6. The application of the trifluoromethyl sulfoxide reagent according to claim 5, characterized in that: The specific application involves mixing the target molecule and the trifluoromethyl sulfoxide reagent under an inert gas atmosphere, adding a solvent, reacting at room temperature to 80°C for 3-20 hours, removing the solvent by vacuum evaporation, purifying the residue to obtain the trifluoromethyl sulfoxide product; wherein the solvent is one or more of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, nitrile solvents, ester solvents, ketone solvents, and amide solvents; when the target molecule is a weakly electron-donating substituted aromatic ring compound, a Lewis acid or Brønsted acid needs to be added to it before adding the solvent.

7. The application of the trifluoromethyl sulfoxide reagent according to claim 6, characterized in that: The molar ratio of the target molecule to the trifluoromethyl sulfoxide reagent is 1:(1.0-2.0).

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