An arylsulfonyl fluoride and a preparation method using arylsulfonium salt as a substrate

Abstract

The present invention relates to an arylsulfonyl fluoride and a preparation method using an arylsulfonium salt as a substrate, comprising: in an inert gas atmosphere, mixing an arylsulfonium salt, a sulfur dioxide source, a fluorine source, and a photosensitizer in an organic solvent, and stirring and reacting under light irradiation conditions to obtain arylsulfonyl fluoride; wherein, the structural formula of the arylsulfonium salt is as follows: #imgabs0# Correspondingly, the structural formula of the arylsulfonyl fluoride is as follows: #imgabs1# In the formula, R1 is a C1-C10 straight-chain or branched-chain alkyl group, a methoxy group, an aldehyde group, an acetyl group, an acetamido group, a heteroaryl group, etc.; R2 and R3 are each a hydrogen atom, a methyl group, a methoxy group, etc.; the anion X ‑ is a trifluoromethanesulfonate anion, etc. Compared with the prior art, the reaction conditions of the present invention are mild, the use of transition metals is avoided, the tolerance range for different substituent functional groups is wide, and it has the selectivity of in-situ introducing a sulfonyl fluoride group, providing more possibilities for introducing a sulfonyl fluoride group into a molecule.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and relates to an arylsulfonyl fluoride and a preparation method using an arylsulfonium salt as a substrate. Background Art

[0002] Fluorosulfonyl (SO2F) is a unique fluorine- and sulfur-containing functional group. Due to the extremely strong electron-withdrawing ability of fluorine atoms, the S-F bond is difficult to break by homolytic cleavage. Compared with other S(VI)-X bonds, it also has hydrolytic stability, anti-reductibility, and sulfur-centered chemoselective reactivity. In 2014, the hypervalent sulfur-fluorine exchange reaction (SuFEx) proposed by Professor K. Barry Sharpless and his colleagues (Angew. Chem. Int. Ed., 2014, 53, 9430.) has become an effective and reliable tool for creating modular intermolecular linkages as a new generation of click chemistry. Fluorosulfonyl (SO2F), as the core group in "Click chemistry", has unique stability and a good balance of reactivity. With the increasing application of the SuFEx reaction, aryl fluorosulfonyl groups can be found in almost all fields of modern chemistry, such as drug discovery, chemical biology, and materials science.

[0003] The construction of the sulfonyl fluoride compound of the C-SO2F bond in aromatic hydrocarbon sulfonyl fluoride compounds (Ar-SO2F) can be classified into the following categories according to the source of the substrate: (a) Oxidative fluorination or fluorine-chlorine exchange of the corresponding sulfur-containing precursor compounds, and the reaction does not involve the construction of the C-SO2F bond. The sulfur-containing precursor substrates used are often difficult to obtain or prepare ( J. Org. Chem. 2013, 78 , 11262. Tetrahedron 2014, 70 , 2464-2471. Green Chem . 2016, 18 ,1224. Tetrahedron 2017, 58 , 2244. J. Am. Chem. Soc. 2019, 141 , 11832. Eur. J. Org. Chem. 2020, 17, 2497.); (b) Involving radical or metal-catalyzed coupling processes to obtain a non-sulfur-containing aromatic compound precursor and then adding a SO2 source and fluorination ( Chem. Sci. 2017, 8 , 3249. J. Org. Chem. 2017, 82 ,2294. Org. Lett. 2020, 22 , 3072.Org. Lett. 2020, 22 , 2281.). At present, the methods for synthesizing arylsulfonyl fluorides have disadvantages such as difficult access to precursor substrates, the use of transition metal catalysis, and relatively harsh reaction conditions, which limit the further application of sulfonyl fluoride compounds. Therefore, it is of great significance to explore new methods for efficiently constructing sulfonyl fluoride compounds. Summary of the Invention

[0004] The object of the present invention is to provide a method for preparing arylsulfonyl fluorides and using arylsulfonium salts as substrates, which has the advantages of simple synthesis method and selectivity of in-situ introduction of sulfonyl fluoride groups.

[0005] The object of the present invention can be achieved by the following technical solutions:

[0006] Based on the "radical sulfur dioxide insertion fluorination" strategy, the present invention generates aryl radicals through the redox reaction of arylsulfonium salts and photosensitizers under light induction, and rapidly reacts with sulfur dioxide sources and fluorine sources in sequence, realizing the metal-free catalytic and efficient preparation of arylsulfonyl fluorides under light conditions. Compared with the prior art, the present invention avoids the use of transition metals, realizes the efficient construction of various arylsulfonyl fluoride compounds under mild conditions, and has a wide tolerance range for different substituent functional groups, providing more possibilities for introducing sulfonyl fluoride groups into molecules.

[0007] A method for preparing arylsulfonyl fluorides, comprising: in an inert gas atmosphere, mixing an arylsulfonium salt, a sulfur dioxide source, a fluorine source, and a photosensitizer in an organic solvent, and stirring and reacting under light conditions to obtain arylsulfonyl fluoride;

[0008] Among them, the structural formula of the arylsulfonium salt is shown as follows:

[0009]

[0010] Correspondingly, the structural formula of the arylsulfonyl fluoride is shown as follows:

[0011]

[0012] In the formula, R1 is a C1-C10 straight-chain or branched-chain alkyl group, a methoxy group, an aldehyde group, an acetyl group, an acetamido group, a trifluoromethoxy group, a nitro group, a cyano group, a fluorine atom, a chlorine atom, an aryl group or a substituted aryl group, a heteroaryl group or a substituted heteroaryl group; wherein the heteroatoms in the heteroaryl group and the substituted heteroaryl group are any one or a combination of several of nitrogen, oxygen, and sulfur, and the number of heteroatoms is 1-3;

[0013] R2 is a hydrogen atom, any one of a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group;

[0014] R3 is a hydrogen atom, any one of a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group;

[0015] Anionic X - may be one of trifluoromethanesulfonate anion, p-toluenesulfonate anion, tetrafluoroborate anion, perchlorate anion, hexafluorophosphate anion, hexafluoroarsenate anion, hexafluoroantimonate anion, tetraphenylborate anion.

[0016] Further, the sulfur dioxide source is one or a combination of several of 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), sodium dithionite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complexed sulfur dioxide, sodium formaldehyde bisulfite, sodium sulfite, sodium trifluoromethanesulfinate, sulfur dioxide, thiourea disulfide.

[0017] Further, the fluorine source is one or a combination of several of N-fluorobenzenesulfonimide (NFSI), sodium fluoride, potassium bifluoride, potassium fluoride, silver fluoride, cesium fluoride or tetramethylammonium fluoride.

[0018] Further, the photosensitizer is one of camphorquinone (CQ), 10-phenylphenothiazine, 3-formyl-7-thienyl-10-hexylphenothiazine, 2-naphthyl p-toluenesulfonate, acid red 92, eosin Y, tris(2-phenylpyridine)iridium, tris(2,2'-bipyridine)ruthenium bis(tetrafluoroborate), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate).

[0019] Further, the organic solvent is one or a combination of several of N,N-dimethylformamide, N,N-dimethylacetamide, N,N-dimethylpropionamide, N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, acetonitrile, acetone, chloroform, ethyl acetate, water, dichloroethane.

[0020] Further, in the stirring reaction, the reaction temperature is room temperature and the reaction time is 1 - 12 h.

[0021] Further, the molar ratio of the arylsulfonium salt, sulfur dioxide source, fluorine source, photosensitizer is 1 : (0.1~0.2) : (1~4) : (1~4).

[0022] Further, in the light irradiation condition, the light source used is one of ultraviolet lamp, blue light lamp, incandescent lamp, fluorescent lamp.

[0023] Further, when a blue light lamp is selected as the light source, the blue light wavelength is 440 - 445 nm.

[0024] An arylsulfonyl fluoride is prepared by the method described above.

[0025] Compared with the prior art, the present invention has the following characteristics:

[0026] 1) The present invention directly in-situ removes a group from a cheap and readily available ordinary aromatic hydrocarbon compound to generate a sulfonyl fluoride, and in-situ directionally introduces a sulfonyl fluoride group, which fully expands the compound library of arylsulfonyl fluorides and provides a new method for constructing fluorosulfonyl-containing drug molecules;

[0027] 2) The synthesis method of the present invention is simple, has the selectivity of in-situ introducing a sulfonyl fluoride group, and has a good yield;

[0028] 3) The present invention is easy to realize large-scale production. Experimental results show that the fluorine spectrum yield of obtaining arylsulfonyl fluoride compounds can reach 50%-90%;

[0029] 4) The present invention uses a sulfonium salt as a raw material, and the aryl radical generated under light captures SO2 from a "SO2" source and combines with a fluorination reagent to generate arylsulfonyl fluoride. This process avoids the use of transition metals, has mild conditions and is more environmentally friendly. Description of the Drawings

[0030] Figure 1 1H NMR spectrum of 4-isopropylbenzenesulfonyl fluoride compound in Example 2 of the present invention;

[0031] Figure 2 19F NMR spectrum of 4-isopropylbenzenesulfonyl fluoride compound in Example 2 of the present invention;

[0032] Figure 3 13C NMR spectrum of 4-isopropylbenzenesulfonyl fluoride compound in Example 2 of the present invention;

[0033] Figure 4 1H NMR spectrum of 3-aldehyde-4-methoxybenzenesulfonyl fluoride compound in Example 3 of the present invention;

[0034] Figure 5 19F NMR spectrum of 3-aldehyde-4-methoxybenzenesulfonyl fluoride compound in Example 3 of the present invention;

[0035] Figure 6 13C NMR spectrum of 3-aldehyde-4-methoxybenzenesulfonyl fluoride compound in Example 3 of the present invention;

[0036] Figure 7 1H NMR spectrum of quinoline-7-sulfonyl fluoride compound in Example 4 of the present invention;

[0037] Figure 8 19F NMR spectrum of quinoline-7-sulfonyl fluoride compound in Example 4 of the present invention;

[0038] Figure 9 This is the carbon-13 NMR spectrum of the quinoline-7-sulfonyl fluoride compound in Example 4 of the present invention;

[0039] Figure 10 This is the proton NMR spectrum of the 4-methoxybenzenesulfonyl fluoride compound in Example 7 of the present invention. Detailed implementation manners

[0040] The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0041] An arylsulfonyl fluoride, and its preparation method includes:

[0042] In an inert gas atmosphere, an arylsulfonium salt, a sulfur dioxide source, a fluorine source, and a photosensitizer are mixed in an organic solvent at a molar ratio of 1:(0.1 - 0.2):(1 - 4):(1 - 4), and stirred at room temperature for 1 - 12 h (preferably 10 h) under light irradiation conditions to obtain arylsulfonyl fluoride;

[0043]

[0044] In the formula, R1 is a C1 - C10 straight-chain or branched-chain alkyl group, a methoxy group, an aldehyde group, an acetyl group, an acetamido group, a trifluoromethoxy group, a nitro group, a cyano group, a fluorine atom, a chlorine atom, an aryl group or a substituted aryl group, a heteroaryl group or a substituted heteroaryl group; wherein the heteroatoms in the heteroaryl group and the substituted heteroaryl group are any one or a combination of several of nitrogen, oxygen, and sulfur, and the number of heteroatoms is 1 - 3;

[0045] R2 is any one of a hydrogen atom, a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group;

[0046] R3 is any one of a hydrogen atom, a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group;

[0047] Anion X - can be one of a trifluoromethanesulfonate anion, a p-toluenesulfonate anion, a tetrafluoroborate anion, a perchlorate anion, a hexafluorophosphate anion, a hexafluoroarsenate anion, a hexafluoroantimonate anion, and a tetraphenylborate anion.

[0048] Among them, the sulfur dioxide source is one or a combination of several of 1,4-diazabicyclo[2.2.2]octane-1,4-diium-1,4-disulfinate (DABSO), sodium dithionite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complexed sulfur dioxide, sodium formaldehyde bisulfite, sodium sulfite, sodium trifluoromethanesulfinate, sulfur dioxide, and dithiourea; and preferably DABSO.

[0049] The fluorine source is a nucleophilic fluorination reagent, including one or a combination of several of N-fluorobenzenesulfonimide (NFSI), sodium fluoride, potassium bifluoride, potassium fluoride, silver fluoride, cesium fluoride, or tetramethylammonium fluoride; and is preferably potassium bifluoride.

[0050] The photosensitizer is one of camphorquinone (CQ), 10-phenylphenothiazine, 3-formyl-7-thiophene-10-hexylphenothiazine, 2-naphthyl p-toluenesulfonate, acid red 92, eosin Y, tris(2-phenylpyridine)iridium, tris(2,2'-bipyridine)ruthenium bis(tetrafluoroborate), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate); and is preferably 3-formyl-7-thiophene-10-hexylphenothiazine.

[0051] The organic solvent is one or a combination of several of N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N,N-dimethylpropanamide, N-methylpyrrolidone (NMP), tetrahydrofuran, dimethyl sulfoxide (DMSO), acetonitrile (MeCN), acetone, chloroform, ethyl acetate, water, 1,2-dichloroethane (DCE).

[0052] In the light irradiation condition, the light source used is any one of a purple lamp (390 nm), a blue lamp (410 nm), a blue lamp (440 - 445 nm), and an ordinary fluorescent lamp; preferably a blue lamp (440 - 445 nm).

[0053] Compared with the prior art, the reaction conditions of the present invention are mild, the use of transition metals is avoided, the tolerance range for different substituent functional groups is wide, and it has the selectivity of in-situ introducing a sulfonyl fluoride group, providing more possibilities for introducing a sulfonyl fluoride group into a molecule.

[0054] This example is implemented on the premise of the technical solution of the present invention, and detailed implementation manners and specific operation processes are given, but the protection scope of the present invention is not limited to the following examples. Table 1 shows the specifications and manufacturers of commercially available reagents used in the text. The arylthianthrenium salts were prepared according to the literature (Org. Lett. 2020, 22, 19, 7716–7720; Org. Lett. 2021, 23(11), 4400 - 4405), and 3-formyl-7-thiophene-10-hexylphenothiazine was prepared according to the literature (Polym. Chem., 2016, 7, 5147 - 5156; Synthesis and Functional Research of Thiophene-Substituted Heterocyclic Compounds [D]. Beijing University of Chemical Technology, 2018).

[0055] Table 1 Reagent Specifications and Sources

[0056] Reagent Name Specification Manufacturer Anhydrous Acetonitrile AR Tianlian DABSO 94% TCI Potassium Fluoride RG Adamas Dichloromethane AR Sinopharm Chemical Reagent Anhydrous Diethyl Ether AR Shanghai Experiment Reagent Toluene AR Sinopharm Chemical Reagent Isopropylbenzene >99% TCI tert-Butylbenzene >98% TCI Chlorobenzene AR Sinopharm Chemical Reagent Fluorobenzene 99% J&K 1,2-Dichloroethane AR Sinopharm Chemical Reagent N,N-Dimethylformamide AR Shanghai Experiment Reagent Co., Ltd. N-Methylpyrrolidone AR J&K N,N-Dimethylacetamide AR Aladdin Silica Gel for Column Chromatography 300 - 400 Mesh Yantai Jiangyou Ferric Acid NonaHydrate 100g Maclean Sodium Bromide 25g Maclean Nitrobenzene 5ml Aladdin Glacial Acetic Acid AR Kunshan Jincheng Chemical Industry Thianthrene 100g Bidepharm 1,3,5-Trimethylbenzene CP Sinopharm Chemical Reagent Anisole CP Tianlian Ethyl Acetate AR GENERAL-REAGENT Ethylbenzene AR Aladdin 2-Methoxybenzaldehyde 100g Bidepharm Phenyl Acetate 25g Aladdin N-Phenylmorpholine 10g Bidepharm Quinoline 25g Aladdin Biphenyl 100g Bidepharm Petroleum Ether AR GENERAL-REAGENT Phenothiazine 100g Beijing InnoChem Technology 3-Thienylphenylboronic Acid 25g Maclean Bromohexane 25g Energy Chemical N-Bromosuccinimide (NBS) 25g Bidepharm Phosphorus Oxychloride 10g Bidepharm

[0057] Raw material preparation examples:

[0058] The reaction formula is as follows:

[0059]

[0060] Taking the case where R1 is methyl and R2, R3 are hydrogen atoms as an example, under an argon atmosphere, 1.5 mL (10 mmol) of toluene, 2.5 g (10 mmol) of thianthrene-S-oxide (TTO), and 1.0 mL (1 mmol) of trifluoromethanesulfonic anhydride (Tf2O) were added to a round-bottom flask, and 100 mL of dichloromethane was added as a solvent. The reaction flask was placed in a constant-temperature cold bath, stirred at -30 o °C for 1 hour, then the round-bottom flask was taken out of the cold bath and stirred at room temperature for 3 - 5 hours. After the reaction was completed, the mixture was filtered through diatomaceous earth or a silica gel thin layer, and then rinsed with dichloromethane. The filtrate was collected, and the solvent was removed under reduced pressure. It was purified by column chromatography or crystallization to obtain the desired arylsulfonium salt raw material.

[0061] All the arylsulfonium salt raw materials of the present invention were prepared according to this method.

[0062] Example 1: Synthesis of 4-methylbenzenesulfonyl fluoride

[0063] The reaction formula is as follows:

[0064]

[0065] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 94 mg (0.2 mmol) of 4-methylarylsulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-formyl-7-thiophene-10-hexylphenothiazine and add them into it. Purge with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as a solvent and stir the reaction at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction was completed, the solid impurities were filtered off, the filtrate was concentrated and evaporated to dryness, and the target compound 4-methylbenzenesulfonyl fluoride, a pale yellow liquid product, was obtained by column chromatography technology with a separation yield of 72%.

[0066] 11H NMR (400 MHz, CDCl3): δ 7.90 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H); 19 19F NMR (376 MHz, CDCl3): δ 66.3 ppm. GC-MS (EI): m / z = 174.0 (M+).

[0067] Comparative Example 1:

[0068] The synthesis of 4-methylbenzenesulfonyl fluoride uses 4-methylarylsulfonium salt as the template substrate, Na2S2O4 as the sulfur dioxide source, NFSI as the fluorine source, and MeCN as the solvent. The reaction is carried out under inert gas protection and light irradiation conditions to generate sulfonyl fluoride. The reaction formula is shown as follows:

[0069]

[0070] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 94 mg (0.2 mmol) of 4-methylarylsulfonium salt, 52.3 mg (0.3 mmol) of Na2S2O4, 126 mg (0.4 mmol) of NFSI, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine and add them into it. Evacuate and refill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir and react at room temperature and under a blue light (440 - 445 nm) for 10 hours. After the reaction is completed, add 4-methoxytrifluoromethoxybenzene as the internal standard, and the fluorine spectrum yield obtained by nuclear magnetic resonance analysis is 0%.

[0071] Comparative Example 2:

[0072] The synthesis of 4-methylbenzenesulfonyl fluoride uses 4-methylarylsulfonium salt as the template substrate, DABSO as the sulfur dioxide source, NFSI as the fluorine source, and MeCN as the solvent. The reaction is carried out under inert gas protection and light irradiation conditions to generate sulfonyl fluoride. The reaction formula is shown as follows:

[0073]

[0074] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 94 mg (0.2 mmol) of 4-methyl aryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 126 mg (0.4 mmol) of NFSI, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexyl phenothiazine and add them into the tube. Flush with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir the reaction for 12 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, add 4-methoxytrifluoromethoxybenzene as an internal standard, and the fluorine spectrum yield obtained by NMR analysis is 0%.

[0075] Comparative Example 3:

[0076] Synthesis of 4-methylbenzenesulfonyl fluoride: Using 4-methyl aryl sulfonium salt as the template substrate, DABSO as the sulfur dioxide source, KHF₂ as the fluorine source, and MeCN as the solvent, the reaction is carried out under inert gas protection and light irradiation conditions to generate sulfonyl fluoride. The reaction formula is as follows:

[0077]

[0078] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 94 mg (0.2 mmol) of 4-methyl aryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF₂, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexyl phenothiazine and add them into the tube. Flush with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir the reaction for 12 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, add 4-methoxytrifluoromethoxybenzene as an internal standard, and the fluorine spectrum yield obtained by NMR analysis is 28%.

[0079] Comparative Example 4:

[0080] On the basis of Example 1, while keeping the molar amounts of each component unchanged, the types of reagents such as reaction solvent, sulfur dioxide source, fluorination reagent, and photosensitizer were screened, and the results are shown in Table 1.

[0081]

[0082] Table 2

[0083] Number Solvent Sulfur Source Fluorine Source Photosensitizer Yield (%) 1 MeCN DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 72 2 DCE DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 54 3 DMF DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 10 4 DMAC DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 48 5 DMSO DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 25 6 NMP DABSO <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 16 7 MeCN <![CDATA[Na2S2O4]]> <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 46 8 MeCN <![CDATA[K2S2O5]]> <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 26 9 MeCN <![CDATA[Na2S2O5]]> <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 13 10 MeCN <![CDATA[SO2]]> <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 32 11 MeCN Thiourea Disulfide <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 12 12 MeCN 4-Dimethylaminopyridine Complexed Sulfur Dioxide <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 43 13 MeCN Sodium Trifluoromethanesulfinate <![CDATA[KHF2]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 20 14 MeCN DABSO KF 3-Aldehyde-7-thiophene-10-hexylphenothiazine 48 15 MeCN DABSO AgF 3-Aldehyde-7-thiophene-10-hexylphenothiazine 65 16 MeCN DABSO <![CDATA[Me4NF]]> 3-Aldehyde-7-thiophene-10-hexylphenothiazine 34 17 MeCN DABSO NFSI 3-Aldehyde-7-thiophene-10-hexylphenothiazine 5 18 MeCN DABSO CsF 3-Formyl-7-thiophene-10-hexylphenothiazine 46 19 MeCN DABSO <![CDATA[KHF2]]> 10-Phenylphenothiazine 64 20 MeCN DABSO <![CDATA[KHF2]]> Acid Red 92 34 21 MeCN DABSO <![CDATA[KHF2]]> Iridium(III) tris(2-phenylpyridine) 49 22 MeCN DABSO <![CDATA[KHF2]]> <![CDATA[Ru(bpy)2(BF4)2]]> 10 23 MeCN DABSO <![CDATA[KHF2]]> Eosin Y 25 24 MeCN DABSO <![CDATA[KHF2]]> 2-Naphthyl p-toluenesulfonate 24 25 MeCN DABSO <![CDATA[KHF2]]> Iridium(III) bis[2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine][2-2'-bi(4-tert-butylpyridine)] bis(hexafluorophosphate) 50 26 MeCN DABSO <![CDATA[KHF2]]> Ruthenium(II) tris(2,2'-bipyridine) bis(tetrafluoroborate) 43 27 MeCN DABSO <![CDATA[KHF2]]> CQ 15

[0084] In addition, we screened the light sources. Compared with Example 1, the only difference is that the light source (i.e., blue light lamp (440 - 445 nm)) was replaced with a purple light (390 nm), a blue light (410 nm), or an incandescent lamp (CFL) of equal power, and the rest was the same as in Example 1. The results are shown in Table 3.

[0085] Table 3

[0086] Entry hv Yield(%) 1 Violet lamp (390 nm) 43 2 CFL 53 3 Blue lamp (410 nm) 62

[0087] Through the above - mentioned condition screening, the optimal conditions were obtained as follows: sulfonium salt substrate (0.2 mmol, 1.0 equiv.), DABSO (0.24 mmol, 2.0 equiv.), KHF2 (0.6 mmol, 3.0 equiv.), the photosensitizer was 3 - formyl - 7 - thienyl - 10 - hexylphenothiazine (0.04 mmol, 20 mmol % equiv.), acetonitrile as the solvent, in an argon atmosphere at room temperature, irradiated with a blue light lamp with a wavelength of 440 - 445 nm for 12 hours.

[0088] Example 2:

[0089] The synthesis of 4 - fluorobenzenesulfonyl fluoride is shown by the following reaction formula:

[0090]

[0091] Put a magnetic stir bar into a 10 - mL sealed tube. Weigh 92 mg (0.2 mmol) of 4 - fluoroaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3 - formyl - 7 - thienyl - 10 - hexylphenothiazine and add them into it. Purge with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir and react at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction, filter out the solid impurities, concentrate and rotary - evaporate the filtrate, and obtain the target compound 4 - fluorobenzenesulfonyl fluoride, a pale - yellow liquid product, with a separation yield of 56%. The NMR spectrum of this product is as Figures 1-3 shown.

[0092] 1 H NMR (400 MHz, CDCl3): δ 8.10−8.04 (m, 2H), 7.34−7.29 (m, 2H) ; 19 F NMR(376 MHz, CDCl3): δ 66.2 ppm. GC - MS (EI): m / z = 178.0 (M+ ).

[0093] Example 3:

[0094] The synthesis of 4-ethylbenzenesulfonyl fluoride is shown by the following reaction formula:

[0095]

[0096] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 94 mg (0.2 mmol) of 4-ethylaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine and add them into it. Evacuate and refill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction for 10 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 4-ethylbenzenesulfonyl fluoride, a pale yellow liquid product, with a separation yield of 68%. The NMR spectrum of this product is as Figures 4-6 shown.

[0097] 1 H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 8.3Hz, 2H), 2.78 (q, J = 7.6 Hz, 2H), 1.29 (td, J = 7.6, 0.7 Hz, 3H); 13 C NMR (101MHz, CDCl3): 153.1, 129.1, 128.6, 128.4, 29.1, 15.0 ppm. 19 F NMR (376 MHz,CDCl3): δ 65.9 ppm. GC-MS (EI): m / z = 188.0 (M + ).

[0098] Example 4:

[0099] The synthesis of 4-isopropylbenzenesulfonyl fluoride is shown by the following reaction formula:

[0100]

[0101] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 96.8 mg (0.2 mmol) of 4-isopropyl aryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexyl phenothiazine and add them into the tube. Flush with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction for 10 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 4-isopropyl benzenesulfonyl fluoride, a pale yellow liquid product, with a separation yield of 75%. The NMR spectrum of this product is as shown in Figures 7-9 shown below.

[0102] 1 H NMR (400 MHz, CDCl3): δ 1.31 (d, J = 6.9 Hz, 6H), 3.03 - 3.08 (m,1H), 7.51 (d, J = 7.5 Hz, 2H), 7.95 (d, J = 7.2 Hz, 2H); 19 F NMR (376 MHz,CDCl3): δ 65.9 ppm. GC-MS (EI): m / z = 202.0 (M + ).

[0103] Example 5:

[0104] Synthesis of 4-tert-butyl benzenesulfonyl fluoride, and the reaction formula is as shown below:

[0105]

[0106] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 99.6 mg (0.2 mmol) of 4-tert-butyl aryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexyl phenothiazine and add them into the tube. Flush with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction for 10 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 4-tert-butyl benzenesulfonyl fluoride, a white solid product, with a separation yield of 70%.

[0107] 1 H NMR (400 MHz, CDCl3): δ 7.94 (d,J = 8.5 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 1.37 (s, 9H); 19 19F NMR (376 MHz, CDCl3): δ 66.2 ppm. GC-MS (EI): m / z = 216.0 (M + ).

[0108] Example 6:

[0109] Synthesis of 2,4,6-trimethylbenzenesulfonyl fluoride, the reaction formula is as follows:

[0110]

[0111] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 96.8 mg (0.2 mmol) of 2,4,6-trimethylaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-formyl-7-thiophene-10-hexylphenothiazine and add them into it. Evacuate and refill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction for 10 hours at room temperature under a blue light (440 - 445 nm). After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 2,4,6-trimethylbenzenesulfonyl fluoride, a white solid product, with a separation yield of 60%.

[0112] 1 1H NMR (400 MHz, CDCl3): δ 7.03 (s, 2H), 2.64 (d, J = 1.5 Hz, 6H), 2.35 (s, 3H); 19 19F NMR (376 MHz, CDCl3): δ 68.1 ppm. GC-MS (EI): m / z = 202.0 (M + ).

[0113] Example 7:

[0114] Synthesis of 4-methoxybenzenesulfonyl fluoride, the reaction formula is as follows:

[0115]

[0116] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 95 mg (0.2 mmol) of 4-methoxyaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-formyl-7-thiophen-10-hexylphenothiazine and add them into the tube. Evacuate and backfill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir the reaction at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 4-methoxybenzenesulfonyl fluoride, a pale yellow liquid product, with a separation yield of 72%. The NMR spectrum of this product is as shown in Figure 10 shown below.

[0117] 1 H NMR (400 MHz, CDCl3): δ 7.94 (d, J J = 9.0 Hz, 2H), 7.06 (d, J J = 9.0 Hz, 2H), 3.92 (s, 3H); 19 F NMR (376 MHz, CDCl3): δ 67.3 ppm. GC-MS (EI): m / z = 190.0 (M + +).

[0118] Example 8:

[0119] Synthesis of 3-formyl-4-methoxybenzenesulfonyl fluoride, and the reaction formula is as shown below:

[0120]

[0121] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 100 mg (0.2 mmol) of 3-formyl-4-methoxyaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-formyl-7-thiophen-10-hexylphenothiazine and add them into the tube. Evacuate and backfill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir the reaction at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 3-formyl-4-methoxybenzenesulfonyl fluoride, a pale yellow solid product, with a separation yield of 68%.

[0122] 11H NMR (400 MHz, CDCl3): δ 10.46 (s, 1H), 8.47 (s, 1H) 8.16 (d, J J = 8.0Hz, 1H), 7.22 (d, J J = 8.0 Hz, 1H), 4.09 (s, 3H); 13 13C NMR (101 MHz, CDCl3): 187.1,166.1, 135.5, 129.9, 125.4, 125.1, 113.0, 56.7 ppm. 19 19F NMR (376 MHz, CDCl3): δ66.7 ppm. GC-MS (EI): m / z = 218.0 (M + +).

[0123] Example 9:

[0124] Synthesis of 4-acetoxybenzenesulfonyl fluoride, the reaction formula is as follows:

[0125]

[0126] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 100 mg (0.2 mmol) of 4-acetoxyaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine and add them into it. Evacuate and refill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent, and stir the reaction at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 3-aldehyde-4-methoxybenzenesulfonyl fluoride, a pale yellow solid product, with a separation yield of 60%.

[0127] 1 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J J = 8.4 Hz, 2H), 7.50 (d, J J = 8.4 Hz,2H) 2.31 (s, 3H); 13 13C NMR (101 MHz, CDCl3): 169.0, 158.8, 130.7, 128.7, 123.1,20.3, ppm. 1919F NMR (376 MHz, CDCl3): δ 66.2 ppm. GC-MS (EI): m / z = 218.0 (M + ).

[0128] Example 10:

[0129] Synthesis of 4-morpholinobenzenesulfonyl fluoride, the reaction formula is as follows:

[0130]

[0131] Take a 10 mL sealed tube and place a magnetic stir bar in it. Weigh 95 mg (0.2 mmol) of 4-morpholinylaryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine and add them into it. Evacuate and refill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction at room temperature under a blue light (440 - 445 nm) for 10 hours. After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound 3-aldehyde-4-methoxybenzenesulfonyl fluoride, a pale yellow liquid product, with a separation yield of 58%.

[0132] 1 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J J = 8.0 Hz, 2H), 7.06 (d, J J = 8.0 Hz,2H), 3.73 (t, J J = 4.0 Hz, 2H), 3.15 (t, J J = 4.0 Hz, 2H); 13 13C NMR (101 MHz, CDCl3): 131.2, 136.4, 121.7, 115.8, 110.6, 66.3, 60.8, 53.3, 48.6, ppm. 19 19F NMR (376MHz, CDCl3): δ 67.6 ppm. GC-MS (EI): m / z = 245.0 (M + ).

[0133] Example 11:

[0134] Synthesis of quinoline-7-sulfonyl fluoride, the reaction formula is as follows:

[0135]

[0136] Place a magnetic stir bar into a 10 mL sealed tube. Weigh 98.6 mg (0.2 mmol) of quinoline-7-aryl sulfonium salt, 57.7 mg (0.24 mmol) of DABSO, 46.8 mg (0.6 mmol) of KHF2, and 15.7 mg (0.04 mmol) of 3-formyl-7-thiophene-10-hexylphenothiazine and add them thereto. Evacuate and backfill with argon three times. Under argon protection, add 2 mL of acetonitrile (MeCN) as the solvent and stir the reaction at room temperature under a blue lamp (440 - 445 nm) for 10 hours. After the reaction is completed, filter off the solid impurities, concentrate and rotary evaporate the filtrate, and obtain the target compound quinoline-7-sulfonyl fluoride, a white solid product, with a separation yield of 68%.

[0137] 1 H NMR (400 MHz, CDCl3): δ 9.12 (d, J J = 3.1 Hz, 1H), 8.86 (s, 1H), 8.30(d, J J = 8.3 Hz, 1H), 8.12 – 7.99 (m, 2H), 7.65 (dd, J J = 8.4, 4.2 Hz, 1H); 19 F NMR(376 MHz, CDCl3): δ 66.1; 13 C NMR (101 MHz, CDCl3): 152.9, 146.8, 136.0, 132.2,131.7, 130.2, 126.4, 124.6, 123.1 ppm. HRMS (EI) m / z: [M] + Calcd for C9H6FNO2S211.0103; Found 211.0101.

[0138] The above description of the embodiments is provided to enable those of ordinary skill in the art to understand and use the invention. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative efforts. Therefore, the present invention is not limited to the above embodiments, and all improvements and modifications made by those skilled in the art without departing from the scope of the present invention according to the disclosure of the present invention should be within the protection scope of the present invention.

Claims

1. A method for preparing arylsulfonyl fluoride, characterized in that, Comprising: In an inert gas atmosphere, an arylsulfonium salt, a sulfur dioxide source, a fluorine source, and a photosensitizer are mixed in an organic solvent and stirred under light irradiation to obtain arylsulfonyl fluoride; Among them, the structural formula of the arylsulfonium salt is as follows: ， Correspondingly, the structural formula of the arylsulfonyl fluoride is as follows: ， In the formula, R1 is a C1-C10 straight-chain or branched-chain alkyl group, a methoxy group, an aldehyde group, an acetyl group, an acetamido group, a trifluoromethoxy group, a nitro group, a cyano group, a fluorine atom, a chlorine atom, an aryl group or a substituted aryl group, a heteroaryl group or a substituted heteroaryl group; wherein the heteroatom in the heteroaryl group or the substituted heteroaryl group is any one or a combination of several of nitrogen, oxygen, and sulfur, and the number of heteroatoms is 1-3; R2 is a hydrogen atom, any one of a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group; R3 is a hydrogen atom, any one of a methyl group, a methoxy group, an ester group, a halogen atom, a phenyl group, and a tolyl group; Anion X - is one of trifluoromethanesulfonate anion, p-toluenesulfonate anion, tetrafluoroborate anion, perchlorate anion, hexafluorophosphate anion, hexafluoroarsenate anion, hexafluoroantimonate anion, tetraphenylborate anion; The sulfur dioxide source is one or a combination of several of 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct, sodium dithionite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complexed sulfur dioxide, sodium formaldehyde bisulfite, sodium sulfite, sodium trifluoromethanesulfinate, sulfur dioxide, and thiourea disulfide; The fluorine source is one or a combination of several of N-fluorobenzenesulfonimide, sodium fluoride, potassium bifluoride, potassium fluoride, silver fluoride, cesium fluoride, or tetramethylammonium fluoride; The photosensitizer is one of camphorquinone, 10-phenylphenothiazine, 3-formyl-7-thiophene-10-hexylphenothiazine, 2-naphthyl p-toluenesulfonate, Acid Red 92, eosin Y, tris(2-phenylpyridine)iridium, tris(2,2'-bipyridine)ruthenium bis(tetrafluoroborate), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, and bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate); The organic solvent is one or a combination of several of N,N-dimethylformamide, N,N-dimethylacetamide, N,N-dimethylpropionamide, N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, acetonitrile, acetone, chloroform, ethyl acetate, water, and dichloroethane.

2. The method for preparing arylsulfonyl fluoride according to claim 1, wherein During the stirring reaction, the reaction temperature is room temperature, and the reaction time is 1-12 h.

3. The method for preparing arylsulfonyl fluoride according to claim 1, characterized in that, The molar ratio of the arylsulfonium salt, the sulfur dioxide source, the fluorine source, and the photosensitizer is 1 : (0.1~0.2) : (1~4) : (1~4).

4. A method for preparing arylsulfonyl fluoride according to claim 1, characterized in that, Among the light irradiation conditions, the light source used is one of an ultraviolet lamp, a blue light lamp, an incandescent lamp, and a fluorescent lamp.

5. A method for preparing arylsulfonyl fluoride according to claim 4, characterized in that, When a blue light lamp is selected as the light source, the blue light wavelength is 440-445 nm.

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