CN117024312A - Aryl sulfonyl fluoride and preparation method using aryl sulfonium salt as substrate - Google Patents

Aryl sulfonyl fluoride and preparation method using aryl sulfonium salt as substrate Download PDF

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CN117024312A
CN117024312A CN202211494576.9A CN202211494576A CN117024312A CN 117024312 A CN117024312 A CN 117024312A CN 202211494576 A CN202211494576 A CN 202211494576A CN 117024312 A CN117024312 A CN 117024312A
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fluoride
aryl
sulfonyl fluoride
mmol
anion
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刘超
单玲玲
马晓玉
马占虎
欧彩云
罗轶凡
黄雨筝
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Shanghai Institute of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/36—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to an aryl sulfonyl fluoride and a preparation method taking aryl sulfonium salt as a substrate, comprising the following steps: mixing aryl iodonium salt, a sulfur dioxide source, a fluorine source and a photosensitizer in an organic solvent in an inert gas atmosphere, and stirring for reaction under the illumination condition to obtain aryl sulfonyl fluoride; wherein the structural formula of the aryl iodonium salt is shown as follows:correspondingly, the aryl sulfonyl fluoride has the structural formula shown as follows:wherein R is 1 Is a C1-C10 straight or branched alkyl, methoxy, aldehyde, acetyl, acetamido, heteroaryl, or the like; r is R 2 、R 3 Respectively a hydrogen atom, a methyl group, a methoxy group and the like; anions X ‑ Is trifluoro methane sulfonate anion, etc. Compared with the prior art, the method has mild reaction conditions, avoids the use of transition metal, has wide tolerance range on different substituent functional groups, has the selectivity of introducing sulfonyl fluoride groups in situ, and provides more possibility for introducing the sulfonyl fluoride groups in molecules.

Description

Aryl sulfonyl fluoride and preparation method using aryl sulfonium salt as substrate
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to arylsulfonyl fluoride and a preparation method using aryl sulfonium salt as a substrate.
Background
Fluorosulfonyl (SO) 2 F) Is a unique fluorine-containing sulfur-containing functional group, and because fluorine atoms have super electron-withdrawing capability, S-F bonds are difficult to break in a homolytic way. It also has hydrolytic stability, resistance to reduction and chemoselective reactivity with sulfur as compared to other S (VI) -X bonds. In 2014, K.Barry Sharpless professor and its colleagues proposed a high-valent sulfur-fluorine exchange reaction (SuFEx) (Angew.chem.int.ed., 2014,53,9430.) which has become an effective and reliable tool for creating modular intermolecular junctions as a new generation of click chemistry. Fluorosulfonyl (SO) 2 F) As a core group in "Click chemistry", it has unique stability and good reactivity balance. With the increasing use of the SuFEx reaction, aryl fluorosulfonyl groups can be found in almost all fields of modern chemistry, such as drug discovery, chemical biology, and material science.
Aromatic hydrocarbon sulfonyl fluoride compound (Ar-SO) 2 F) Middle C-SO 2 The construction of sulfonyl fluoride compounds for the F bond can be categorized into the following classes depending on the source of the substrate: (a) From corresponding sulfur-containing precursorsOxidative fluorination or exchange of fluorine and chlorine of the material, the reaction not involving C-SO 2 Construction of the F bond, the sulfur-containing precursor substrates used are often not readily available or are relatively difficult to 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) Obtaining a non-sulfur-containing aromatic compound precursor and then adding SO 2 Source refolding involves free radical or metal catalyzed coupling processes (Chem.Sci.2017, 8,3249.J.Org.Chem.2017,82,2294.Org.Lett.2020,22,3072.Org.Lett.2020,22,2281.). The prior method for synthesizing aryl sulfonyl fluoride has the defects of difficult acquisition of precursor substrates, use of transition metal catalysis, harsh reaction conditions and the like, and limits the further application of sulfonyl fluoride compounds. Therefore, it is of great importance to explore a novel method for efficiently constructing sulfonyl fluoride compounds.
Disclosure of Invention
The invention aims to provide aryl sulfonyl fluoride and a preparation method using aryl sulfonium salt as a substrate, and the preparation method has the advantages of simple synthesis method, selectivity of in-situ introduction of sulfonyl fluoride groups and the like.
The aim of the invention can be achieved by the following technical scheme:
the invention is based on the "free radical sulfur dioxide insertion fluorination" strategy. The aryl free radical is generated by the oxidation-reduction reaction of the photoinduction aryl sulfonium salt and the photosensitizer, and the aryl free radical reacts with a sulfur dioxide source and a fluorine source in sequence, so that the efficient preparation of the aryl sulfonyl fluoride under the illumination condition without metal catalysis is realized. Compared with the prior art, the invention avoids the use of transition metal, realizes the efficient construction of various aryl sulfonyl fluoride compounds under mild conditions, has wide tolerance range for different substituent functional groups, and provides more possibility for introducing sulfonyl fluoride groups into molecules.
A method of preparing arylsulfonyl fluorides comprising: mixing aryl iodonium salt, a sulfur dioxide source, a fluorine source and a photosensitizer in an organic solvent in an inert gas atmosphere, and stirring for reaction under the illumination condition to obtain aryl sulfonyl fluoride;
wherein the structural formula of the aryl iodonium salt is shown as follows:
correspondingly, the aryl sulfonyl fluoride has the structural formula shown as follows:
wherein R is 1 Is a C1-C10 straight or branched alkyl, methoxy, aldehyde, acetyl, acetamido, trifluoromethoxy, nitro, cyano, fluoro, chloro, aryl or substituted aryl, heteroaryl or substituted heteroaryl group; wherein the hetero atom in the heteroaryl and the substituted heteroaryl is any one or the combination of more than one of nitrogen, oxygen and sulfur, and the number of the hetero atom is 1-3;
R 2 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
R 3 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
anions X - Can be one of trifluoro methane sulfonate anion, p-toluene sulfonate anion, tetrafluoroborate anion, perchlorate anion, hexafluorophosphate anion, hexafluoroarsenate anion, hexafluoroantimonate anion and tetraphenylborate anion.
Further, the sulfur dioxide source is one or a combination of more of 1, 4-diazabicyclo [2.2.2] octane bis (sulfur Dioxide) Adduct (DABSO), sodium dithionite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complex sulfur dioxide, sodium formaldehyde sulfoxylate, sodium sulfite, sodium trifluoromethylsulfite, sulfur dioxide and urea disulfide.
Further, the fluorine source is one or a combination of a plurality of N-fluoro-bis-benzene sulfonamide (NFSI), sodium fluoride, potassium fluoride hydride, potassium fluoride, silver fluoride, cesium fluoride or tetramethyl ammonium fluoride.
Further, the photosensitizer is one of Camphorquinone (CQ), 10-phenylphenothiazine, 3-aldehyde-7-thiophene-10-hexylphenothiazine, 2-naphthalene p-toluenesulfonate, acid red 92, eosin Y, tris (2-phenylpyridine) iridium, tris (2, 2 '-bipyridine) ruthenium bis (tetrafluoroborate), bis [ (2-pyridinyl) phenyl ] iridium (III) hexafluorophosphate, bis [2- (2, 4-difluorophenyl) -5-trifluoromethylpyridine ] [2-2' -bis (4-tert-butylpyridine) ] iridium bis (hexafluorophosphate).
Further, the organic solvent is one or a combination of a plurality of N, N-dimethylformamide, N-dimethylacetamide, N-dimethylpropionamide, N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, acetonitrile, acetone, chloroform, ethyl acetate, water and dichloroethane.
Further, in the stirring reaction, the reaction temperature is room temperature and the reaction time is 1-12h.
Further, the molar ratio of the aryl iodonium salt to the sulfur dioxide source to the fluorine source to the photosensitizer is 1 (0.1-0.2): 1-4.
Further, in the lighting condition, the light source is one of an ultraviolet lamp, a blue light lamp, an incandescent lamp and a fluorescent lamp.
Further, when a blue light lamp is selected as the light source, the wavelength of blue light is 440-445nm.
An arylsulfonyl fluoride prepared by the method described above.
Compared with the prior art, the invention has the following characteristics:
1) The invention takes the cheap and easily available common aromatic hydrocarbon compounds as raw materials to directly remove the groups in situ to generate sulfonyl fluoride, and introduces sulfonyl fluoride groups in situ and directionally, thereby fully expanding the compound library of aryl sulfonyl fluoride and providing a new method for constructing fluorine-containing sulfonyl drug molecules;
2) The synthesis method is simple, has the selectivity of introducing sulfonyl fluoride groups in situ, and has good yield;
3) The invention is easy to realize large-scale production, and experimental results show that the fluorine spectrum yield of the obtained aryl sulfonyl fluoride compound can reach 50% -90%;
4) The invention takes sulfonium salt as raw material, and aryl free radical generated under illumination is generated from SO 2 "capturing SO in Source 2 The combination of the fluorinating reagent produces arylsulfonyl fluoride. The process avoids the use of transition metals, and is mild in condition and more environment-friendly.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a 4-isopropylbenzenesulfonyl fluoride compound of example 2 of the present invention;
FIG. 2 is a nuclear magnetic resonance fluorine spectrum of 4-isopropylbenzenesulfonyl fluoride in example 2 of the present invention;
FIG. 3 is a nuclear magnetic resonance carbon spectrum of 4-isopropylbenzenesulfonyl fluoride in example 2 of the present invention;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of 3-formyl-4-methoxybenzenesulfonyl fluoride in example 3 of the present invention;
FIG. 5 is a nuclear magnetic resonance fluorine spectrum of 3-formyl-4-methoxybenzenesulfonyl fluoride in example 3 of the present invention;
FIG. 6 is a nuclear magnetic resonance carbon spectrum of 3-aldehyde-4-methoxybenzenesulfonyl fluoride in example 3 of the present invention;
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of a quinoline-7-sulfonyl fluoride compound of example 4 of the present invention;
FIG. 8 is a nuclear magnetic resonance fluorine spectrum of quinoline-7-sulfonyl fluoride compound of example 4 of the present invention;
FIG. 9 is a nuclear magnetic resonance carbon spectrum of quinoline-7-sulfonyl fluoride compound of example 4 of the present invention;
FIG. 10 is a nuclear magnetic resonance hydrogen spectrum of 4-methoxybenzenesulfonyl fluoride in example 7 of the present invention.
Detailed Description
The invention will now be described in detail with reference to the drawings and specific examples.
An arylsulfonyl fluoride, the method of making comprising:
in an inert gas atmosphere, mixing aryl iodonium salt, a sulfur dioxide source, a fluorine source and a photosensitizer in a molar ratio of 1 (0.1-0.2) (1-4) in an organic solvent, and stirring and reacting for 1-12h (preferably 10 h) at room temperature under the condition of illumination to obtain aryl sulfonyl fluoride;
wherein R is 1 Is a C1-C10 straight or branched alkyl, methoxy, aldehyde, acetyl, acetamido, trifluoromethoxy, nitro, cyano, fluoro, chloro, aryl or substituted aryl, heteroaryl or substituted heteroaryl group; wherein the hetero atom in the heteroaryl and the substituted heteroaryl is any one or the combination of more than one of nitrogen, oxygen and sulfur, and the number of the hetero atom is 1-3;
R 2 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
R 3 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
anions X - Can be one of trifluoro methane sulfonate anion, p-toluene sulfonate anion, tetrafluoroborate anion, perchlorate anion, hexafluorophosphate anion, hexafluoroarsenate anion, hexafluoroantimonate anion and tetraphenylborate anion.
Wherein the sulfur dioxide source is one or a combination of a plurality of 1, 4-diazabicyclo [2.2.2] octane-1, 4-diimmonium-1, 4-Disulfonic Acid (DABSO), sodium hydrosulfite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complex sulfur dioxide, sodium formaldehyde sulfoxylate, sodium sulfite, sodium trifluoromethylsulfite, sulfur dioxide and carbamide disulfide; and is preferably DABSO.
The fluorine source is nucleophilic fluoride reagent, including one or a combination of several of N-fluoro-bis-benzene sulfonamide (NFSI), sodium fluoride, potassium fluoride hydride, potassium fluoride, silver fluoride, cesium fluoride or tetramethyl ammonium fluoride; and is preferably potassium fluorohydride.
The photosensitizer is one of Camphorquinone (CQ), 10-phenylphenothiazine, 3-aldehyde-7-thiophene-10-hexylphenothiazine, 2-naphthyl p-toluenesulfonate, acid red 92, eosin Y, tris (2-phenylpyridine) iridium, tris (2, 2 '-bipyridine) ruthenium bis (tetrafluoroboric acid) salt, (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' -bis (4-tert-butylpyridine) ] iridium bis (hexafluorophosphate); and is preferably 3-aldehyde-7-thiophene-10-hexylphenothiazine.
The organic solvent is one or more of N, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), N-dimethylpropionamide, N-methylpyrrolidone (NMP), tetrahydrofuran, dimethyl sulfoxide (DMSO), acetonitrile (MeCN), acetone, chloroform, ethyl acetate, water and Dichloroethane (DCE).
In the illumination condition, the light source is any one of a violet lamp (390 nm), a blue lamp (410 nm), a blue lamp (440-445 nm) and a common fluorescent lamp; blue lamps (440-445 nm) are preferred.
Compared with the prior art, the method has mild reaction conditions, avoids the use of transition metal, has wide tolerance range on different substituent functional groups, has the selectivity of introducing sulfonyl fluoride groups in situ, and provides more possibility for introducing the sulfonyl fluoride groups in molecules.
The present embodiment is implemented on the premise of the technical scheme of the present invention, and a detailed implementation manner and a specific operation process are given, but the protection scope of the present invention is not limited to the following examples. Table 1 shows the specifications and manufacturer of the commercial reagents used herein, arylthianthrene salts prepared according to the literature (org. Lett.2020,22,19,7716-7720; org. Lett.2021,23 (11), 4400-4405), 3-aldehyde-7-thiophene-10-hexylphenothiazine prepared according to the literature (Polym. Chem.,2016,7,5147-5156; synthesis of thiophene-substituted heterocyclic compounds and functional research [ D ]. Beijing university of chemical industry, 2018).
TABLE 1 reagent specification and sources
Raw material preparation examples:
the reaction formula is as follows:
by R 1 Is methyl, R 2 、R 3 As an example of a hydrogen atom, 1.5mL (10 mmol) of toluene, 2.5g (10 mmol) of thianthrene-S-oxide (TTO), 1.0mL (1 mmol) of trifluoromethanesulfonic anhydride (Tf) are charged to a round-bottomed flask under an argon atmosphere 2 O) 100mL of methylene chloride was added as solvent. The reaction flask was placed in a constant temperature cold bath and stirred for 1 hour at-30 ℃, then the round bottom flask was removed from the cold bath and stirred for 3-5 hours at room temperature. After the reaction, the mixture was filtered through a thin layer of celite or silica gel and then rinsed with dichloromethane. The filtrate was collected and the solvent was removed under reduced pressure. Purification by column chromatography or crystallization yields the desired aryl sulfonium salt starting material.
All aryl sulfonium salt starting materials of the invention are prepared according to this method.
Example 1: synthesis of 4-methylbenzenesulfonyl fluoride
The reaction formula is as follows:
10mL of the tube was capped and placed in a magnet, 94mg (0.2 mmol) of 4-methylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-methylbenzenesulfonyl fluoride by a column chromatography technology, wherein the separation yield is 72 percent.
1 H NMR(400MHz,CDCl 3 ):δ7.90(d,J＝8.3Hz,2H),7.42(d,J＝8.0Hz,2H),2.49(s,3H)； 19 F NMR(376MHz,CDCl 3 ):δ66.3ppm.GC-MS(EI):m/z＝174.0(M+).
Comparative example 1:
synthesis of 4-methylbenzenesulfonyl fluoride, 4-methyl aryl sulfonium salt as template substrate, na 2 S 2 O 4 As a sulfur dioxide source, NFSI is a fluorine source, and the solvent is MeCN, and the sulfonyl fluoride is generated by reaction under the protection of inert gas and under the condition of illumination. The reaction formula is as follows:
10mL of the tube was capped, and then a magnet was placed therein, 94mg (0.2 mmol) of 4-methyl aryl sulfonium salt, 52.3mg (0.3 mmol) of Na was weighed 2 S 2 O 4 126mg (0.4 mmol) of NFSI and 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine are added, argon is exchanged for three times, 2mL of acetonitrile (MeCN) is added as a solvent under the protection of the argon, stirring reaction is carried out for 10 hours at room temperature under the condition of a blue lamp (440-445 nm), after the reaction is finished, 4-methoxy trifluoro-methoxybenzene is added as an internal standard, and the fluorine spectrum yield is 0% by nuclear magnetic resonance analysis.
Comparative example 2:
synthesizing 4-methylbenzenesulfonyl fluoride, namely reacting 4-methyl aryl sulfonium salt serving as a template substrate, DABSO serving as a sulfur dioxide source, NFSI serving as a fluorine source and MeCN serving as a solvent under the protection of inert gas and under the condition of illumination to generate sulfonyl fluoride. The reaction formula is as follows:
10mL of the tube was sealed, and then a magneton was placed therein, 94mg (0.2 mmol) of 4-methyl aryl sulfonium salt, 57.7mg (0.24 mmol) of DABSO, 126mg (0.4 mmol) of NFSI, 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine were weighed, argon was purged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the mixture was stirred at room temperature under the condition of a blue lamp (440-445 nm) for reaction for 12 hours. After the reaction is finished, 4-methoxy trifluoro-methoxybenzene is added as an internal standard, and the fluorine spectrum yield is 0% by nuclear magnetic analysis.
Comparative example 3:
synthesis of 4-methylbenzenesulfonyl fluoride, wherein 4-methyl aryl sulfonium salt is used as a template substrate, DABSO is used as a sulfur dioxide source, and KHF 2 The method is characterized in that the solvent is MeCN, and sulfonyl fluoride is generated by reaction under the protection of inert gas and under the illumination condition. The reaction formula is as follows:
10mL of the tube was capped and placed in a magnet, 94mg (0.2 mmol) of 4-methylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 12 hours. After the reaction is finished, 4-methoxy trifluoro-methoxybenzene is added as an internal standard, and the fluorine spectrum yield is 28% by nuclear magnetic analysis.
Comparative example 4:
the types of reagents such as reaction solvent, sulfur dioxide source, fluorinating reagent, photosensitizer, etc. were selected on the basis of example 1, with the molar amounts of the components unchanged, and the results are shown in table 1.
TABLE 2
Furthermore, we screened the light sources, differing from example 1 only in: the light source (i.e., blue lamp (440-445 nm)) was replaced with an equal power violet lamp (390 nm), blue lamp (410 nm) or incandescent lamp (CFL), the remainder being the same as in example 1, and the results are shown in table 3.
TABLE 3 Table 3
Through the condition screening, the optimal conditions are as follows: sulfonium salt substrate (0.2 mmol,1.0 equiv.), DABSO (0.24 mmol,2.0 equiv.), KHF 2 (0.6 mmol,3.0 equiv.) the photosensitizer was 3-aldehyde-7-thiophene-10-hexylphenothiazine (0.04 mmol,20mmol% equiv.) acetonitrile as solvent and irradiated with a blue lamp having a wavelength of 440-445nm at room temperature under argon atmosphere for 12 hours.
Example 2:
the synthesis of 4-fluorobenzenesulfonyl fluoride has the following reaction formula:
10mL of the tube was capped, and then a magnet was placed therein, 92mg (0.2 mmol) of 4-fluoroarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, and 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-fluorobenzenesulfonyl fluoride by a column chromatography technology, wherein the separation yield is 56 percent. The nuclear magnetic pattern of the product is shown in figures 1-3.
1 H NMR(400MHz,CDCl 3 ):δ8.10-8.04(m,2H),7.34-7.29(m,2H)； 19 F NMR(376MHz,CDCl 3 ):δ66.2ppm.GC-MS(EI):m/z＝178.0(M + ).
Example 3
The synthesis of 4-ethyl benzene sulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped and placed in a magnet, 94mg (0.2 mmol) of 4-ethyl aryl sulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-ethyl benzenesulfonyl fluoride by a column chromatography technology, wherein the separation yield is 68 percent. The nuclear magnetic pattern of the product is shown in figures 4-6.
1 H NMR(400MHz,CDCl 3 ):δ7.92(d,J＝8.3Hz,2H),7.44(d,J＝8.3Hz,2H),2.78(q,J＝7.6Hz,2H),1.29(td,J＝7.6,0.7Hz,3H)； 13 C NMR(101MHz,CDCl3):153.1,129.1,128.6,128.4,29.1,15.0ppm. 19 F NMR(376MHz,CDCl 3 ):δ65.9ppm.GC-MS(EI):m/z＝188.0(M + ).
Example 4
The synthesis of 4-isopropylbenzenesulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped and placed in a magnet, and 96.8mg (0.2 mmol) of 4-isopropylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-isopropylbenzenesulfonyl fluoride by a column chromatography technology, wherein the separation yield is 75 percent. The nuclear magnetic pattern of the product is shown in figures 7-9。
1 H NMR(400MHz,CDCl 3 ):δ1.31(d,J＝6.9Hz,6H),3.03-3.08(m,1H),7.51(d,J＝7.5Hz,2H),7.95(d,J＝7.2Hz,2H)； 19 F NMR(376MHz,CDCl 3 ):δ65.9ppm.GC-MS(EI):m/z＝202.0(M + ).
Example 5
The synthesis of 4-tert-butylbenzenesulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped, and then a magnet was placed therein, and 99.6mg (0.2 mmol) of 4-t-butylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, and 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-tert-butylbenzenesulfonyl fluoride through a column chromatography technology, wherein the white solid product has the separation yield of 70%.
1 H NMR(400MHz,CDCl 3 ):δ7.94(d,J＝8.5Hz,2H),7.63(d,J＝8.2Hz,2H),1.37(s,9H)； 19 F NMR(376MHz,CDCl 3 ):δ66.2ppm.GC-MS(EI):m/z＝216.0(M + ).
Example 6
The synthesis of 2,4, 6-trimethylbenzenesulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped, and then a magnet was placed therein, and 96.8mg (0.2 mmol) of 2,4, 6-trimethylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, and 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon,the reaction was stirred at room temperature under blue light (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 2,4, 6-trimethylbenzenesulfonyl fluoride through a column chromatography technology, wherein the separation yield is 60 percent.
1 H NMR(400MHz,CDCl 3 ):δ7.03(s,2H),2.64(d,J＝1.5Hz,6H),2.35(s,3H)； 19 F NMR(376MHz,CDCl 3 ):δ68.1ppm.GC-MS(EI):m/z＝202.0(M + ).
Example 7
The synthesis of 4-methoxybenzene sulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped, and then a magneton was placed therein, and 95mg (0.2 mmol) of 4-methoxyarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, and 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 4-methoxybenzene sulfonyl fluoride by a column chromatography technology, wherein the separation yield is 72 percent. The nuclear magnetic spectrum of the product is shown in FIG. 10.
1 H NMR(400MHz,CDCl 3 ):δ7.94(d,J＝9.0Hz,2H),7.06(d,J＝9.0Hz,2H),3.92(s,3H)； 19 F NMR(376MHz,CDCl 3 ):δ67.3ppm.GC-MS(EI):m/z＝190.0(M + ).
Example 8
The synthesis of 3-aldehyde-4-methoxybenzene sulfonyl fluoride is shown in the following reaction formula:
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taking 10mL of sealed tube, placing the sealed tube into a magnet, and weighing100mg (0.2 mmol) of 3-aldehyde-4-methoxyarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 3-aldehyde-4-methoxybenzenesulfonyl fluoride through a column chromatography technology, wherein the separation yield is 68 percent.
1 H NMR(400MHz,CDCl 3 ):δ10.46(s,1H),8.47(s,1H)8.16(d,J＝8.0Hz,1H),7.22(d,J＝8.0Hz,1H),4.09(s,3H)； 13 C NMR(101MHz,CDCl 3 ):187.1,166.1,135.5,129.9,125.4,125.1,113.0,56.7ppm. 19 F NMR(376MHz,CDCl 3 ):δ66.7ppm.GC-MS(EI):m/z＝218.0(M + ).
Example 9
The synthesis of 4-acetoxyl benzenesulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped, and then a magnet was placed therein, and 100mg (0.2 mmol) of 4-acetoxyarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, and 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 3-aldehyde-4-methoxybenzenesulfonyl fluoride through a column chromatography technology, wherein the separation yield is 60 percent.
1 H NMR(400MHz,CDCl 3 ):δ7.80(d,J＝8.4Hz,2H),7.50(d,J＝8.4Hz,2H)2.31(s,3H)； 13 C NMR(101MHz,CDCl 3 ):169.0,158.8,130.7,128.7,123.1,20.3,ppm. 19 F NMR(376MHz,CDCl 3 ):δ66.2ppm.GC-MS(EI):m/z＝218.0(M + ).
Example 10
The synthesis of 4-morpholinyl benzenesulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped and placed in a magnet, and 95mg (0.2 mmol) of 4-morpholinylarylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, concentrating and spin-drying filtrate, and obtaining the target compound 3-aldehyde-4-methoxybenzene sulfonyl fluoride through a column chromatography technology, wherein the separation yield is 58 percent.
1 H NMR(400MHz,CDCl 3 ):δ7.62(d,J＝8.0Hz,2H),7.06(d,J＝8.0Hz,2H),3.73(t,J＝4.0Hz,2H),3.15(t,J＝4.0Hz,2H)； 13 C NMR(101MHz,CDCl 3 ):131.2,136.4,121.7,115.8,110.6,66.3,60.8,53.3,48.6,ppm. 19 F NMR(376MHz,CDCl 3 ):δ67.6ppm.GC-MS(EI):m/z＝245.0(M + ).
Example 11
The synthesis of quinoline-7-sulfonyl fluoride is shown in the following reaction formula:
10mL of the tube was capped and placed in a magnet, 98.6mg (0.2 mmol) of quinoline-7-arylsulfonium salt, 57.7mg (0.24 mmol) of DABSO, 46.8mg (0.6 mmol) of KHF were weighed 2 15.7mg (0.04 mmol) of 3-aldehyde-7-thiophene-10-hexylphenothiazine was added thereto, argon was exchanged three times, 2mL of acetonitrile (MeCN) was added as a solvent under the protection of argon, and the reaction was stirred at room temperature under the condition of a blue lamp (440-445 nm) for 10 hours. After the reaction is finished, filtering out solid impurities, andthe filtrate is concentrated and dried, and the target compound quinoline-7-sulfonyl fluoride is obtained through a column chromatography technology, and the white solid product is separated and the yield is 68%.
1 H NMR(400MHz,CDCl 3 ):δ9.12(d,J＝3.1Hz,1H),8.86(s,1H),8.30(d,J＝8.3Hz,1H),8.12–7.99(m,2H),7.65(dd,J＝8.4,4.2Hz,1H)； 19 F NMR(376MHz,CDCl 3 ):δ66.1； 13 C NMR(101MHz,CDCl 3 ):152.9,146.8,136.0,132.2,131.7,130.2,126.4,124.6,123.1ppm.HRMS(EI)m/z:[M] + Calcd for C 9 H 6 FNO 2 S 211.0103；Found211.0101.
The previous description of the embodiments is provided to facilitate a person of ordinary skill in the art in order to make and use the present invention. It will be apparent to those skilled in the art that various modifications can be readily made to these embodiments and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above-described embodiments, and those skilled in the art, based on the present disclosure, should make improvements and modifications without departing from the scope of the present invention.

Claims (10)

1. A process for preparing arylsulfonyl fluorides comprising: mixing aryl iodonium salt, a sulfur dioxide source, a fluorine source and a photosensitizer in an organic solvent in an inert gas atmosphere, and stirring for reaction under the illumination condition to obtain aryl sulfonyl fluoride;
wherein the structural formula of the aryl iodonium salt is shown as follows:
correspondingly, the aryl sulfonyl fluoride has the structural formula shown as follows:
wherein R is 1 Is a C1-C10 straight or branched alkyl, methoxy, aldehyde, acetyl, acetamido, trifluoromethoxy, nitro, cyano, fluoro, chloro, aryl or substituted aryl, heteroaryl or substituted heteroaryl group; wherein the hetero atom in the heteroaryl and the substituted heteroaryl is any one or the combination of more than one of nitrogen, oxygen and sulfur, and the number of the hetero atom is 1-3;
R 2 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
R 3 is any one of hydrogen atom, methyl, methoxy, ester group, halogen, phenyl and tolyl;
anions X - Is one of trifluoro methane sulfonate anion, p-toluene sulfonate anion, tetrafluoroborate anion, perchlorate anion, hexafluorophosphate anion, hexafluoroarsenate anion, hexafluoroantimonate anion and tetraphenyl borate anion.
2. The method for preparing arylsulfonyl fluoride of claim 1, wherein the sulfur dioxide source is one or more of 1, 4-diazabicyclo [2.2.2] octane bis (sulfur dioxide) adduct, sodium dithionite, potassium metabisulfite, sodium metabisulfite, 4-dimethylaminopyridine complex sulfur dioxide, sodium formaldehyde sulfoxylate, sodium sulfite, sodium trifluoromethylsulfite, sulfur dioxide, and urea disulfide.
3. The method for preparing arylsulfonyl fluoride of claim 1 wherein the fluorine source is one or a combination of several of N-fluoro bis-benzenesulfonamide, sodium fluoride, potassium bifluoride, potassium fluoride, silver fluoride, cesium fluoride or tetramethyl ammonium fluoride.
4. The method for preparing arylsulfonyl fluoride according to claim 1, wherein the photosensitizer is one of camphorquinone, 10-phenylphenothiazine, 3-aldehyde-7-thiophene-10-hexylphenothiazine, 2-naphthalene 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-pyridinyl) phenyl ] iridium (III) hexafluorophosphate, bis [2- (2, 4-difluorophenyl) -5-trifluoromethylpyridine ] [2-2' -bis (4-tert-butylpyridine) ] iridium bis (hexafluorophosphate).
5. The method for preparing arylsulfonyl fluoride according to claim 1, wherein the organic solvent is one or a combination of several of N, N-dimethylformamide, N-dimethylacetamide, N-dimethylpropionamide, N-methylpyrrolidone, tetrahydrofuran, dimethylsulfoxide, acetonitrile, acetone, chloroform, ethyl acetate, water or dichloroethane.
6. The method for preparing arylsulfonyl fluoride according to claim 1, wherein the reaction temperature is room temperature and the reaction time is 1 to 12 hours in the stirring reaction.
7. The method for preparing arylsulfonyl fluoride according to claim 1, wherein the molar ratio of the aryl iodonium salt, the sulfur dioxide source, the fluorine source and the photosensitizer is 1 (0.1-0.2): 1-4.
8. The method for preparing arylsulfonyl fluoride according to claim 1, wherein the light source used in the illumination condition is one of ultraviolet lamp, blue lamp, incandescent lamp and fluorescent lamp.
9. The method for producing arylsulfonyl fluoride according to claim 8, wherein when a blue light lamp is selected as the light source, the blue light wavelength is 440-445nm.
10. Arylsulfonyl fluorides, characterized in that they are obtainable by a process according to any one of claims 1 to 9.
CN202211494576.9A 2022-11-25 2022-11-25 Aryl sulfonyl fluoride and preparation method using aryl sulfonium salt as substrate Pending CN117024312A (en)

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