Synthesis method of nitrogen-fluorine reagent mediated sulfur-fluorine compound

Abstract

The invention discloses a synthesis method of a nitrogen-fluorine reagent mediated sulfur-fluorine compound, which comprises the following steps: by taking sulfenamide as a raw material and a cheap and easily available nitrogen-fluorine reagent as a fluorine source, adding a proper amount of alkali, and carrying out one-step reaction to synthesize sulfimide acyl fluoride and sulfodiimine fluorine compounds. According to the method, sulfenamide is subjected to one-step oxidation and fluorination to generate sulfimide acyl fluoride and sulfodiimine fluorine, the raw materials are easy to obtain, the reaction condition is mild, the reaction time is short, the substrate range is wide, post-treatment is simple and convenient, no catalyst is needed, and the popularization and application prospects are wide.

Description

Technical Field

[0001] The invention belongs to the technical field of sulfur-fluorine compound synthesis, and particularly relates to a method for synthesizing sulfur-fluorine compounds mediated by nitrogen-fluorine reagents. Background Art

[0002] Sulfur compounds are an important class of compounds due to their wide range of biological and pharmaceutical properties. Introducing a fluorine atom from a sulfur atom transforms the compound into a sulfur-fluorine compound. These compounds can then undergo a hexavalent sulfur-fluorine exchange reaction (SuFEx) by leveraging the unique properties of the sulfur-fluorine bond, thereby yielding a wider range of sulfur-containing compounds.

[0003] Sulfonyl imide fluorides and sulfondiimide fluorides are both sulfur-fluoride compounds. Unlike other common sulfonyl fluorides, these compounds introduce nitrogen atoms directly linked to the sulfur atom, altering the physical and chemical properties of the sulfur-containing compound. More importantly, these compounds offer greater potential for constructing chiral compounds. Therefore, developing more methods for synthesizing sulfonyl imide fluorides and sulfondiimide fluorides holds great promise for future applications.

[0004] Numerous methods have been reported for synthesizing sulfonyl imide fluorides, but these often utilize difficult-to-synthesize raw materials or toxic reagents. Furthermore, the reaction requires oxidation and chlorination, followed by a fluorine-chlorine exchange process to obtain the compound. These procedures are complex and have limited substrate compatibility. Reports on sulfonyl imide fluorides are relatively limited, and the synthesis of these compounds remains a challenge in organic synthesis. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a method for preparing sulfur-fluorine compounds (sulfonyl imide fluorides and sulfondiimide fluoride derivatives) which is simple, safe and highly efficient in synthesis.

[0006] To achieve the above object, the present invention adopts the following technical solutions: A method for synthesizing sulfur-fluorine compounds mediated by a nitrogen-fluorine reagent comprises the following steps: mixing a sulfenamide derivative, a base and a nitrogen-fluorine reagent in an organic solvent and reacting the mixture for 1 to 2 hours to obtain a sulfonimide fluoride derivative or a sulfondiimide fluoride derivative.

[0007] Furthermore, the chemical structural formula of the sulfenamide derivative is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated groups containing alkenyl, alkynyl, ester, acyl, etc.

[0008] Furthermore, the base is sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, copper hydroxide, iron hydroxide, lead hydroxide, cobalt hydroxide, chromium hydroxide, zirconium hydroxide, nickel hydroxide, ammonium hydroxide, cesium hydroxide, rubidium hydroxide, sodium sulfate, potassium sulfate, sodium sulfite, potassium sulfite, sodium bisulfite, potassium bisulfite, potassium phosphate, potassium hydrogen phosphate, sodium phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium chlorate, sodium chlorate, potassium perchlorate, perchlorate At least one of sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, silver fluoride, lithium fluoride, potassium fluoride, sodium fluoride, cesium fluoride, potassium bifluoride, sodium bifluoride, sodium hydride, methyl sodium, ethyl sodium, n-butyl sodium, phenyl sodium, naphthyl sodium, sodium phenolate, allyl sodium, sodium acetylide, sodium phenylacetylide, sodium amide, sodium acetate, sodium methoxide, sodium tert-butoxide, methyl potassium, ethyl potassium, cyclohexyl potassium, phenyl potassium, naphthalene potassium, potassium methoxide, potassium acetate, potassium triphenylmethylate, potassium oxalate, potassium amide, diisopropyl potassium, and potassium tert-butoxide.

[0009] Furthermore, the nitrogen-fluorine reagent is at least one of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt (selective fluorine reagent), 1-fluoro-4-methyl-1,4-diazabicyclo[2.2.2]octane tetrafluoroborate, and N-fluorobisbenzenesulfonamide (NFSI).

[0010] Furthermore, the organic solvent is at least one of carbon tetrachloride, tetrahydrofuran, dimethylformamide, ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, 1,4-dioxane, acetonitrile, ethyl acetate, acetone, methanol, ethanol, isopropanol, and dimethyl sulfoxide.

[0011] Specifically, the sulfonyl imide fluoride derivative is prepared by mixing a sulfenamide derivative, a crown ether, a base, a nitrogen-fluorine reagent, water and an organic solvent under an air atmosphere, stirring the mixture for 1 hour at room temperature, and then separating and purifying the mixture.

[0012] Wherein, the crown ether is at least one of 15-crown-5, 12-crown-4, 18-crown-6, benzo-15-crown-5, aza-18-crown-6, dibenzo-18-crown-6, dibenzo-28-crown-8, diaza-18-crown-6, monoaza-15-crown-5, 1,4-dicarboxybenzo-15-crown-5, aza-12-crown-4, monoaza-12-crown-4, 4'aminodibenzo-18-crown-6, 1,4-diiodobenzo-18-crown-6, 4-acyl-18-crown, and 1,1-dimethylsilyl-11-crown-4.

[0013] The molar ratio of the sulfenamide derivative, base, nitrogen-fluorine reagent and crown ether used is 1:2:3:3.

[0014] The volume ratio of water to organic solvent used was 1:10.

[0015] The chemical structural formula of the obtained sulfonyl imide fluoride derivative is: , its R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated groups containing alkenyl, alkynyl, ester, acyl, etc.

[0016] The sulfonyl diimide fluorine derivative is prepared by mixing a sulfonamide derivative, a halogenated benzamide, a base and an organic solvent under a nitrogen atmosphere, stirring and reacting for 1 hour at room temperature, then adding a nitrogen fluoride reagent, continuing to stir and react for 1 hour, and then separating and purifying to obtain the product.

[0017] The molar ratio of the sulfenamide derivative, base, nitrogen-fluorine reagent and halobenzamide is 1:5:3:2.

[0018] The chemical structural formula of the obtained sulfonimide fluorine derivative is: , its R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated groups containing alkenyl, alkynyl, ester, acyl, etc.

[0019] The beneficial effects of the present invention are: The invention uses simple and readily available raw materials to synthesize sulfonyl imide fluoride and sulfondiimide fluoride compounds in one step, does not require the use of a catalyst, has mild reaction conditions, a short reaction time, a wide substrate range, and simple and environmentally friendly post-processing. DETAILED DESCRIPTION

[0020] A method for synthesizing a sulfur-fluorine compound mediated by a nitrogen-fluorine reagent, wherein the sulfur-fluorine compound is a sulfonyl imide fluoride derivative or a sulfondiimide fluoride derivative.

[0021] Specifically, the sulfonyl imide fluoride derivative is prepared by mixing a sulfenamide derivative, a base, a nitrogen-fluorine reagent, and a crown ether in a molar ratio of 1:2:3:3 under an air atmosphere, adding water and an organic solvent in a volume ratio of 1:10, stirring the reaction at room temperature for 1 hour, and then separating and purifying the obtained product. Its chemical structure is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated groups containing alkenyl, alkynyl, ester, acyl, etc.

[0022] The sulfonyl diimide fluorine derivative is prepared by mixing a sulfenamide derivative, a halogenated benzamide, a base and an organic solvent under a nitrogen atmosphere, stirring and reacting at room temperature for 1 hour, then adding a nitrogen fluoride reagent, continuing to stir and react for 1 hour, and then separating and purifying to obtain the obtained product. Its chemical structure is: , where R 1 、R 2 The molar ratio of the sulfenamide derivative, base, nitrogen-fluorine reagent and halobenzamide used is 1:5:3:2.

[0023] Wherein, the chemical structural formula of the sulfenamide derivative is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated groups containing alkenyl, alkynyl, ester, acyl, etc.

[0024] The alkali is sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, copper hydroxide, iron hydroxide, lead hydroxide, cobalt hydroxide, chromium hydroxide, zirconium hydroxide, nickel hydroxide, ammonium hydroxide, cesium hydroxide, rubidium hydroxide, sodium sulfate, potassium sulfate, sodium sulfite, potassium sulfite, sodium bisulfite, potassium bisulfite, potassium phosphate, potassium hydrogen phosphate, sodium phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium chlorate, sodium chlorate, potassium perchlorate, sodium perchlorate , potassium phosphate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, silver fluoride, lithium fluoride, potassium fluoride, sodium fluoride, cesium fluoride, potassium bifluoride, sodium bifluoride, sodium hydride, methyl sodium, ethyl sodium, n-butyl sodium, phenyl sodium, naphthyl sodium, sodium phenolate, allyl sodium, sodium acetylide, sodium phenylacetylene, sodium amide, sodium acetate, sodium methoxide, sodium tert-butoxide, methyl potassium, ethyl potassium, cyclohexyl potassium, phenyl potassium, naphthalene potassium, potassium methoxide, potassium acetate, potassium triphenylmethylate, potassium oxalate, potassium amide, diisopropyl potassium, potassium tert-butoxide.

[0025] The nitrogen-fluorine reagent is at least one of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt (selective fluorine reagent), 1-fluoro-4-methyl-1,4-diazabicyclo[2.2.2]octane tetrafluoroborate, and N-fluorobisbenzenesulfonamide (NFSI).

[0026] The organic solvent is at least one of carbon tetrachloride, tetrahydrofuran, dimethylformamide, ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, 1,4-dioxane, acetonitrile, ethyl acetate, acetone, methanol, ethanol, isopropanol, and dimethyl sulfoxide.

[0027] The crown ether is at least one of 15-crown-5, 12-crown-4, 18-crown-6, benzo-15-crown-5, aza-18-crown-6, dibenzo-18-crown-6, dibenzo-28-crown-8, diaza-18-crown-6, monoaza-15-crown-5, 1,4-dicarboxybenzo-15-crown-5, aza-12-crown-4, monoaza-12-crown-4, 4'aminodibenzo-18-crown-6, 1,4-diiodobenzo-18-crown-6, 4-acyl-18-crown, and 1,1-dimethylsilyl-11-crown-4.

[0028] In order to make the contents of the present invention easier to understand, the technical solutions of the present invention are further described below in conjunction with specific implementation methods, but the present invention is not limited thereto.

[0029] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0030] Used in the examples N -(p-methoxyphenylthio)benzamide, N -(p-trifluoromethylphenylthio)benzamide, N -(2-methylphenylthio)formamide, N -(3,5-dimethylphenylthio)benzamide, N -(naphthalene-2-ylthio)benzamide, N -(p-toluenethio)thiophene-2-carboxamide, tert-butyl(p-toluenethio)carbamate, N-(cyclohexylthio)benzamide, N -(Methylthio)benzamide, N -(hexadecylthio)benzamide, N -(p-Nitrophenylthio)benzamide, N -(Phenethylthio)benzamide, N -(p-Tolyl)thiobenzamide References Zhao, B.; Zeng, D.-B.; He, X.-L.; Li, J.-H.; Lin, Y.; Ye, K.-Y. JACS Au .2025, DOI: 10.1021 / jacsau.5c00374; Greenwood, NS; Champlin, AT; Ellman, JA J. Am.Chem. Soc. 2022, 144 , 17808-17814 for preparation.

[0031] The chlorobenzamide, tert-butylchlorocarbamate, and chloronaphthamide used in the examples are from the literature Gwon, D.; Hwang, H.; Kim, HK; Marder, SR; Chang, S. Chem. - Eur. J. 2015, 21 ,17200-17204 for preparation.

[0032] Example 1 N Preparation of benzoyl-4-methoxybenzenesulfonyl imide fluoride

[0033] Under air atmosphere conditions, N 0.2 mmol of 4-(p-methoxyphenylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of selective fluorine reagent (selectfluor), and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, separation was performed on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 50 mg of the desired product in an 85% yield. Characterization of this compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.11 - 8.06 (m, 4H), 7.51 (t, J = 7.3 Hz, 1H),7.39 (t, J = 7.7 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 3.93 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ 66.9.

[0034] Example 2 N Preparation of benzoyl-4-trifluoromethylbenzenesulfonyl imide fluoride

[0035] Under air atmosphere conditions, N0.2 mmol of 4-(trifluoromethylphenylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 49 mg of the desired product in a 74% yield. Characterization of the compound is as follows: 1 H NMR (500 MHz, CDCl3) δ 8.29 (d, J = 8.4 Hz, 2H), 8.09 - 8.07 (m, 2H), 7.90 (d, J = 8.5 Hz, 2H), 7.56 - 7.52 (m, 1H), 7.43 - 7.40 (m, 2H). 19 F NMR (471MHz, CDCl3) δ 65.2 (s, 1F), -63.4 (s, 3F).

[0036] Example 3 N Preparation of benzoyl-2-methylbenzenesulfonyl imide fluoride

[0037] Under air atmosphere conditions, N 0.2 mmol of 2-methylphenylthio)formamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 39 mg of the desired product in a yield of 71%. Characterization of the compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 7.8 Hz,2H), 7.65 (t, J = 7.5 Hz, 1H), 7.56 (t, J = 7.3 Hz, 1H), 7.48 - 7.42 (m, 4H), 2.77 (s, 3H). 19F NMR (376 MHz, CDCl3) δ 58.0.

[0038] Example 4 N Preparation of benzoyl-3,5-dimethylbenzenesulfonyl imide fluoride

[0039] Under air atmosphere conditions, N 0.2 mmol of 3-(3,5-dimethylphenylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 47 mg of the desired product in an 80% yield. Characterization of the compound is as follows: 1 H NMR (500 MHz, CDCl3) δ 8.16 - 8.14 (m, 2H), 7.77 (s, 2H), 7.59 -7.55 (m, 1H), 7.47 - 7.44 (m, 2H), 7.40 (s, 1H), 2.46 (s, 6H). 19 F NMR (471 MHz, CDCl3) δ 64.5.

[0040] Example 5 Preparation of N-benzoylnaphthalene-2-sulfonylimide fluoride

[0041] Under air atmosphere conditions, N 0.2 mmol of 2-(naphthalen-2-ylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 51 mg of the desired product in an 82% yield. Characterization of the compound is as follows: 1 H NMR (500 MHz, CDCl3) δ 8.77 (s, 1H), 8.20 - 8.18 (m, 2H), 8.11 -8.10 (m, 2H), 8.07 (d, J = 8.2 Hz, 1H), 7.99 (d,J = 8.0 Hz, 1H), 7.78 - 7.75 (m,1H), 7.72 - 7.69 (m, 1H), 7.60 - 7.57 (m, 1H), 7.48 - 7.45(m, 2H). 19 F NMR (471MHz, CDCl3) δ 65.8.

[0042] Example 64-Methyl- N Preparation of -(thiophene-2-carbonyl)benzenesulfonyl imide fluoride

[0043] Under air atmosphere conditions, N 0.2 mmol of 2-(p-tolylthio)thiophene-2-carboxamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 45 mg of the desired product in an 80% yield. Characterization of the compound is as follows: IR (neat, cm -1 ):2928 (w), 2857 (w), 1643 (m), 1405 (m), 1236 (s), 1135 (s), 708 (s), 517 (s). 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.8 Hz, 2H), 7.85(s, 1H), 7.58 (d, J = 4.3 Hz, 1H), 7.44 (d, J = 7.9 Hz, 2H), 7.11 - 7.10 (m, 1H), 2.50 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.4, 147.5, 139.6, 133.9, 133.5,131.1 (d, J = 20.3 Hz), 130.4, 128.2, 128.1, 22.0. 19 F NMR(376 MHz, CDCl3) δ66.8.HRMS (ESI)calculated for C 12 H11 FNO2S2 + [M+H] + : 284.0210; found: 284.0202.

[0044] Example 7 tert-Butyl (fluoro (oxo) (p-tolyl) -λ 6 Preparation of -sulfonyl) carbamate

[0045] Under air, 0.2 mmol of tert-butyl (p-toluenethio)carbamate, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 29 mg of the desired product in a yield of 56%. Characterization of the compound is as follows: IR (neat, cm -1 ):2976 (w), 1704 (m), 1244 (s), 1143 (s), 1085 (s), 817 (s), 667 (m), 525 (m). 1H NMR(500 MHz , CDCl3) δ 8.05 - 7.91 (m, 2H), 7.46 - 7.34 (m, 2H), 2.47 (s, 3H), 1.51 (s, 9H).13 C NMR (126 MHz, CDCl3) δ152.7, 147.2, 130.7 (d, J = 20.8 Hz), 130.2, 128.2, 82.7, 28.0, 21.9. 19 F NMR(471MHz, CDCl3) δ 68.9.HRMS (ESI)calculated for C 12 H 17 FNO3S + [M+H] + : 274.0908; found:274.0900.

[0046] Example 8 N -Preparation of Benzoylcyclohexanesulfonyl imide fluoride

[0047] Under air atmosphere conditions, N0.2 mmol of 1-(cyclohexylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 46 mg of the desired product in an 85% yield. Characterization of the compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.3 Hz,1H), 7.43 (t, J = 7.4 Hz, 2H), 3.81 (t, J = 12.0 Hz, 1H), 2.38 (d, J = 12.5 Hz,1H), 2.31 (d, J = 12.5 Hz, 1H), 1.98 (t, J = 12.1 Hz, 2H), 1.86 - 1.70 (m, 3H), 1.40 - 1.33 (m, 2H), 1.31 (d, J = 14.3 Hz, 1H). 19 F NMR (471 MHz, CDCl3) δ 40.7.

[0048] Example 9 N -Preparation of benzoylmethanesulfonyl imide fluoride

[0049] Under air atmosphere conditions, N 0.2 mmol of 1-(methylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 27 mg of the desired product in a 68% yield. Characterization of the compound is as follows: 1H NMR (500 MHz, CDCl3) δ 8.14 - 8.11 (m, 2H), 7.59 - 7.56 (m, 1H), 7.46 - 7.43 (m, 2H), 3.64 (d, J = 5.3 Hz, 3H). 19 F NMR (471 MHz, CDCl3) δ 61.2 (q, J = 5.4 Hz).

[0050] Example 10 N Preparation of benzoyloctadecane-1-sulfonylimide fluoride compound

[0051] Under air atmosphere conditions, N 0.2 mmol of 1-(hexadecylthio)benzamide, 0.6 mmol of 18-crown-6, 0.4 mmol of KHCO₃, 0.6 mmol of a selective fluorine reagent, and 0.5 mL of water were added to a reaction tube. 5 mL of acetonitrile was added and stirred at room temperature for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 38 mg of the desired product in a 46% yield. Characterization of the compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.13 - 8.11 (m, 2H), 7.57 (t, J = 7.2 Hz, 1H),7.44 (t, J = 7.4 Hz, 2H), 3.76 (t, J = 7.1 Hz, 2H), 2.04 - 1.97 (m, 2H), 1.53 -1.47 (m, 2H), 1.28 - 1.22 (m, 28H), 0.88 (t, J = 6.0 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ 53.1.

[0052] Example 11 Preparation of {[(Benzoylazepine)(Fluoro)(4-methoxyphenyl)λ6-sulfinyl]amino}benzophenone

[0053] Under nitrogen atmosphere, the N0.2 mmol of -(p-methoxyphenylthio)benzamide, 0.4 mmol of chlorobenzamide, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 61 mg of the desired product in a 77% yield. Characterization of this compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.21 - 8.17 (m, 6H), 7.57 - 7.53 (m, 2H), 7.45 - 7.42 (m, 4H), 7.10 - 7.08 (m, 2H), 3.89 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ 64.5.

[0054] Example 12 Preparation of {[(Benzoylazepine)(Fluoro)(4-nitrophenyl)λ6-sulfinyl]amino}benzophenone

[0055] Under nitrogen atmosphere, the N 0.2 mmol of -(p-nitrophenylthio)benzamide, 0.4 mmol of chlorobenzamide, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 64 mg of the desired product in a yield of 78%. Characterization of this compound is as follows: IR (neat, cm -1 ): 3106 (w), 3059 (w), 1655 (s), 1535 (s), 1452 (m), 1243 (s), 999 (m), 705 (s). 1 H NMR (400 MHz, CDCl3) δ 8.49 - 8.43 (m, 4H), 8.15 (d, J =7.6 Hz, 4H), 7.61 - 7.57 (m, 2H), 7.47 - 7.44 (m, 4H). 13 C NMR(101 MHz, CDCl3)δ 170.3, 151.3, 141.6 (d, J= 23.9 Hz), 133.8, 133.6, 130.3, 129.4, 128.6,124.9. 19 F NMR(376 MHz, CDCl3) δ 59.5.HRMS (ESI)calculated for C 20 H 15 FN3O4S + [M+H] + : 412. 0762; found: 412.0752.

[0056] Example 13 {[(Benzoylaminoxylbenzene)(fluoro)(2-naphthyl)-λ6-sulfonyl]amino}phenyl ketone

[0057] Under nitrogen atmosphere, the N 0.2 mmol of 2-(naphthalen-2-ylthio)benzamide, 0.4 mmol of chlorobenzamide, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 39 mg of the desired product in a 66% yield. Characterization of this compound is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.24 - 8.18 (m, 5H), 8.10 -8.03 (m, 2H), 7.96 (d, J = 8.0 Hz, 1H), 7.74 - 7.65 (m, 2H), 7.59 - 7.56 (m,2H), 7.48 - 7.44 (m, 4H). 19 F NMR (471 MHz, CDCl3) δ 61.7.

[0058] Example 14 {[(Benzoylamine)(Fluoro)(2-phenylethyl)-λ 6 Preparation of [sulfonyl]amino]phenyl ketone

[0059] Under nitrogen atmosphere, the N0.2 mmol of -(phenethylthio)benzamide, 0.4 mmol of chlorobenzamide, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 45 mg of the desired product in a 58% yield. Characterization of this compound is as follows: 1 H NMR (500 MHz, CDCl3) δ 8.20 - 8.19 (m, 4H), 7.65 - 7.62 (m, 2H), 7.52 - 7.49 (m, 4H), 7.36 - 7.31 (m, 4H), 7.27 - 7.24 (m, 1H), 4.62 -4.59 (m,2H), 3.41 - 3.38 (m,2H). 19 F NMR (471 MHz, CDCl3) δ 55.7.

[0060] Example 15 tert-butyl N -({[(tert-Butoxy)carbonyl]imino}(fluoro)(4-methylphenyl)-λ 6 Preparation of -sulfonamide) carbamate

[0061] Under nitrogen atmosphere, the N 0.2 mmol of 1-(p-tolyl)thiobenzamide, 0.4 mmol of tert-butylchlorocarbamate, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 20:1, v / v) to obtain 30 mg of the desired product in a 40% yield. Characterization of the compound is as follows: IR (neat, cm -1 ):2993 (w), 2934 (w), 1703 (m), 1232 (s), 1135 (s), 867 (m), 730 (s), 455 (m). 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.3 Hz, 2H), 7.37(d, J= 8.1 Hz, 2H), 2.45 (s, 3H), 1.48 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ152.9, 146.7, 131.9 (d, J = 23.4 Hz), 130.1, 127.7, 82.4, 27.9, 21.7. 19 F NMR(376 MHz, CDCl3) δ 69.8.HRMS (ESI)calculated for C 17 H 26 FN2O4S + [M+H] + : 373.1592;found: 373.1582.

[0062] Example 16 N -[Fluoro(4-methylphenyl)[(naphthalene-2-carbonyl)imino]-λ 6 Preparation of [-sulfonamide] naphthalene-2-carboxamide

[0063] Under nitrogen atmosphere, the N 0.2 mmol of 1-(p-tolyl)thiobenzamide, 0.4 mmol of chloronaphthamide, and 1.0 mmol of sodium hydride were added to a reaction tube. 5 mL of acetonitrile was added and stirred for 1 hour. Subsequently, 0.6 mmol of a selective fluorine reagent was added and stirring continued for 1 hour. After the reaction, the product was separated by chromatography on a 300-400 mesh silica gel column (eluent: petroleum ether:ethyl acetate = 10:1, v / v) to obtain 66 mg of the desired product in a 69% yield. Characterization of this compound is as follows: IR (neat, cm -1 ):2922 (w), 2856 (w), 1662 (s), 1465 (w), 1279 (s), 1183 (s), 754 (m), 467 (w). 1 H NMR (400 MHz, CDCl3) δ 8.79 (s, 2H), 8.20 (t, J = 6.9Hz, 4H), 7.98 (d, J = 8.0 Hz, 2H), 7.88 (d, J = 8.5 Hz, 4H), 7. 61 - 7.52 (m, 4H), 7.48 (d, J= 8.0 Hz, 2H), 2.51 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 170.8,146.9, 135.9, 132.6 (d, J = 20.3 Hz), 132.7, 132.0, 131.7, 130.5, 129.8, 128.5,128.2, 128.0, 127.9, 126.7, 125.7, 22.0. 19 F NMR(376 MHz, CDCl3) δ 60.4.HRMS(ESI)calculated for C 29 H 22 FN2O2S + [M+H] + : 481.1381; found: 481.1376.

[0064] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A method for synthesizing sulfur-fluorine compounds mediated by nitrogen-fluorine reagents, characterized in that: A sulfenamide derivative, a base and a nitrogen-fluorine reagent are mixed and reacted in an organic solvent for 1 to 2 hours to prepare a sulfonimide fluoride derivative or a sulfondiimide fluoride derivative.

2. The synthesis method according to claim 1, wherein: The chemical structural formula of the sulfenamide derivative is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated group containing alkenyl, alkynyl, ester group, acyl group.

3. The synthesis method according to claim 1, wherein: The alkali is sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, copper hydroxide, iron hydroxide, lead hydroxide, cobalt hydroxide, chromium hydroxide, zirconium hydroxide, nickel hydroxide, ammonium hydroxide, cesium hydroxide, rubidium hydroxide, sodium sulfate, potassium sulfate, sodium sulfite, potassium sulfite, sodium bisulfite, potassium bisulfite, potassium phosphate, potassium hydrogen phosphate, sodium phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium chlorate, sodium chlorate, potassium perchlorate, sodium perchlorate , potassium phosphate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, silver fluoride, lithium fluoride, potassium fluoride, sodium fluoride, cesium fluoride, potassium bifluoride, sodium bifluoride, sodium hydride, methyl sodium, ethyl sodium, n-butyl sodium, phenyl sodium, naphthyl sodium, sodium phenolate, allyl sodium, sodium acetylide, sodium phenylacetylene, sodium amide, sodium acetate, sodium methoxide, sodium tert-butoxide, methyl potassium, ethyl potassium, cyclohexyl potassium, phenyl potassium, naphthalene potassium, potassium methoxide, potassium acetate, potassium triphenylmethylate, potassium oxalate, potassium amide, diisopropyl potassium, potassium tert-butoxide.

4. The synthesis method according to claim 1, wherein: The nitrogen-fluorine reagent is at least one of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate), 1-fluoro-4-methyl-1,4-diazabicyclo[2.2.2]octane tetrafluoroborate, and N-fluorobisbenzenesulfonamide.

5. The synthesis method according to claim 1, wherein: The organic solvent is at least one of carbon tetrachloride, tetrahydrofuran, dimethylformamide, ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, 1,4-dioxane, acetonitrile, ethyl acetate, acetone, methanol, ethanol, isopropanol, and dimethyl sulfoxide.

6. The synthesis method according to claim 1, wherein: Crown ether and water are also added to the reaction system of the sulfonyl imide fluoride derivative; the molar ratio of the sulfenamide derivative, base, nitrogen fluoride reagent and crown ether is 1:2:3:3; and the volume ratio of water and organic solvent is 1:

10.

7. The synthesis method according to claim 6, characterized in that: The crown ether is at least one of 15-crown-5, 12-crown-4, 18-crown-6, benzo-15-crown-5, aza-18-crown-6, dibenzo-18-crown-6, dibenzo-28-crown-8, diaza-18-crown-6, monoaza-15-crown-5, 1,4-dicarboxybenzo-15-crown-5, aza-12-crown-4, monoaza-12-crown-4, 4'aminodibenzo-18-crown-6, 1,4-diiodobenzo-18-crown-6, 4-acyl-18-crown, and 1,1-dimethylsilyl-11-crown-4.

8. The synthesis method according to claim 1 or 6, characterized in that: The chemical structural formula of the obtained sulfonyl imide fluoride derivative is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated group containing alkenyl, alkynyl, ester group, acyl group.

9. The synthesis method according to claim 1, wherein: The reaction for preparing the sulfonimide fluorine derivative is carried out under a nitrogen atmosphere, and a halogenated benzamide is also added to the reaction system; the molar ratio of the sulfonamide derivative, base, nitrogen-fluorine reagent and halogenated benzamide used is 1:5:3:

2.

10. The synthesis method according to claim 1 or 9, characterized in that: The chemical structural formula of the obtained sulfonimide fluorine derivative is: , where R 1 、R 2 Independently selected from aryl, substituted aryl, heterocycle, alkyl, alkoxy, or unsaturated group containing alkenyl, alkynyl, ester group, acyl group.

Images