A method for synthesizing 3-trifluoromethyl chromone compounds
By using the inexpensive and easy-to-get CF3Br and aryl enamine tandem cyclization reaction in the presence of a photocatalyst, the problem of expensive and low utilization of trifluoromethyl reagents was solved, and the efficient synthesis of high-purity 3-trifluoromethyl chromoketone compounds was achieved.
Patent Information
- Application Number
- CN202410172480.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-02-07
- Publication Date
- 2025-09-02
- Estimated Expiration
- 2044-02-07
AI Technical Summary
In the existing synthesis methods of 3-trifluoromethylchromeketone compounds, trifluoromethyl reagents are expensive and have low atomic utilization, resulting in complex and high cost.
The inexpensive and easy-to-get CF3Br is used as the trifluoromethyl source, and free radical cyclization reaction is carried out under light conditions. The chelate of iridium and pyridine is used, and the organic dyes 4CzIPN or 3DPA2FBN, alkalis such as K2CO3, Na2CO3, etc. are dissolved in an organic solvent for synthesis.
The synthesis of 3-trifluoromethylchromoketone compounds is achieved at a low cost and efficient manner, with a product purity of no less than 98%, providing a new synthesis method and overcoming the shortcomings of the original method.
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Figure CN118026978B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 3-trifluoromethyl chromone compounds. Background Art
[0002] Chromones are widely found in natural products and pharmaceutical molecules, attracting considerable attention from chemists due to their unique skeletal structure and excellent physiological activities. Research has shown that these compounds can be used for antibacterial, antiasthmatic, anti-allergic, tumor cell growth inhibition, and lipid- and blood sugar-lowering activities. Medicinal chemists have achieved enhanced and broadened biological activities by modifying the chromone matrix with other functional groups. Chromone compounds substituted at the 3-position, in particular, have demonstrated potent antitumor, antibacterial, and antiviral properties.
[0003] The trifluoromethyl group is a unique functional group. Its introduction into organic compounds can significantly alter the chemical, physical, and biological properties of the compound, such as acidity, bioavailability, metabolic stability, lipid solubility, and protein binding. Given the importance of the trifluoromethyl group and 3-substituted chromones, the introduction of a trifluoromethyl group into chromone molecules, such as 3-trifluoromethylchromone, is of great significance.
[0004] Among them, the main synthesis methods of 3-trifluoromethyl chromone compounds are as follows:
[0005]
[0006] Professor Yang Hua's research group at Central South University used Langlois reagent and 2-hydroxyaryl enaminone to construct 3-trifluoromethyl chromone compounds (Org. Lett. 2017, 19, 146-149). The disadvantage of this method is that the Langlois reagent used contains a large leaving group and has the characteristic of low atom utilization. The DMSO used has a high boiling point and is more complicated to process. Summary of the Invention
[0007] To address the shortcomings of the prior art, the present invention provides a method for synthesizing 3-trifluoromethyl chromone compounds. This method utilizes inexpensive, readily available, and atom-efficient CF3Br as a trifluoromethyl source, which reacts with aryl enaminones under light to produce 3-trifluoromethyl chromone compounds through a free radical tandem cyclization reaction. This overcomes the drawbacks of the expensive trifluoromethyl reagent and low atom utilization rate in the synthesis of 3-trifluoromethyl chromone compounds.
[0008] To achieve the above object, the present invention provides the following technical solutions:
[0009] One of the technical solutions of the present invention is to provide a method for synthesizing 3-trifluoromethyl chromone compounds, comprising the following steps:
[0010] 2-Hydroxyaryl enaminoketone compounds, photocatalysts, and alkali are dissolved in an organic solvent, CF3Br gas is introduced, and the mixture is reacted under 390-460nm blue light irradiation to obtain 3-trifluoromethyl chromone compounds;
[0011] The structural formula of the 2-hydroxyaryl enaminone compound is as follows:
[0012] wherein R is H, methyl, methoxy or halogen.
[0013] The specific synthesis process is as follows:
[0014]
[0015] Preferably, the photocatalyst is a chelate of iridium and pyridine, an organic dye 4CzIPN or an organic dye 3DPA2FBN.
[0016] Preferably, the base is an organic base or an inorganic base.
[0017] Preferably, the inorganic base includes K2CO3, Na2CO3, KHCO3, Li2CO3, K3PO4, K2HPO4 or NaOAc; the organic base includes Et3N or 2,6-lutidine.
[0018] Preferably, the organic solvent is acetonitrile, DMF, DMSO, THF, acetone or 1,4-dioxane.
[0019] Preferably, the added amount of the photocatalyst is 0.5 to 1.5% of the molar amount of the 2-hydroxyaryl enaminone compound.
[0020] Preferably, the added amount of the base is 2 times the molar amount of the 2-hydroxyaryl enaminone compound.
[0021] Preferably, the CF3Br is added in excess.
[0022] Preferably, the intensity of the blue light is 5 to 15 W, and the irradiation time is 12 to 48 hours. The catalytic effect of blue light is better than that of white light.
[0023] Preferably, a purification step is further included after the blue light irradiation.
[0024] More preferably, the purification step is column chromatography, the stationary phase is silica gel, and the eluent is a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 3:1 to 30:1.
[0025] After column chromatography, the purity of the target compound obtained is not less than 98% (based on 1 H NMR, 13CNMR, 19 F NMR and high-resolution mass spectrometry).
[0026] The beneficial technical effects of the present invention are as follows:
[0027] This invention discloses for the first time the synthesis of 3-trifluoromethyl chromones through a free radical tandem cyclization reaction between inexpensive and readily available bromotrifluoromethane and 2-hydroxyaryl enaminones, providing a novel method for the synthesis of 3-trifluoromethyl chromones. In the presence of a photocatalyst, bromotrifluoromethane generates a trifluoromethyl radical. The intramolecular hydroxyl group acts as an intermediate capture group. The trifluoromethyl radical then adds to the carbon-carbon double bond, forming a tandem C / O bond cyclization. The removal of the small amine allows the synthesis of a 3-substituted chromone in a single step, yielding the desired target product—a 3-trifluoromethyl chromone. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 The 3-trifluoromethyl chromone prepared in Example 1 1 H NMR spectrum.
[0029] Figure 2 The 3-trifluoromethyl chromone prepared in Example 1 13 C NMR spectrum.
[0030] Figure 3 The 3-trifluoromethyl chromone prepared in Example 1 19 F NMR spectrum.
[0031] Figure 4 This is a high-resolution mass spectrometry monitoring chart of 3-trifluoromethylchromone prepared in Example 1.
[0032] Figure 5 The 6-methyl-3-trifluoromethyl chromone prepared in Example 2 1 H NMR spectrum.
[0033] Figure 6 The 6-methyl-3-trifluoromethyl chromone prepared in Example 2 13 C NMR spectrum.
[0034] Figure 7 The 6-methyl-3-trifluoromethyl chromone prepared in Example 2 19 F NMR spectrum.
[0035] Figure 8 This is a high-resolution mass spectrum monitoring chart of 6-methyl-3-trifluoromethylchromone prepared in Example 2.
[0036] Figure 9 The 6-methoxy-3-trifluoromethyl chromone prepared in Example 3 1 H NMR spectrum.
[0037] Figure 10 The 6-methoxy-3-trifluoromethyl chromone prepared in Example 3 13 C NMR spectrum.
[0038] Figure 11 The 6-methoxy-3-trifluoromethyl chromone prepared in Example 3 19 F NMR spectrum.
[0039] Figure 12 This is the high-resolution mass spectrum monitoring chart of 6-methoxy-3-trifluoromethylchromone prepared in Example 3.
[0040] Figure 13 The 6-bromo-3-trifluoromethyl chromone prepared in Example 4 1 H NMR spectrum.
[0041] Figure 14 The 6-bromo-3-trifluoromethyl chromone prepared in Example 4 13 C NMR spectrum.
[0042] Figure 15 The 6-bromo-3-trifluoromethyl chromone prepared in Example 4 19 F NMR spectrum.
[0043] Figure 16 This is a high-resolution mass spectrum monitoring chart of 6-bromo-3-trifluoromethylchromone prepared in Example 4.
[0044] Figure 17 The 6-fluoro-3-trifluoromethyl chromone prepared in Example 5 1 H NMR spectrum.
[0045] Figure 18 The 6-fluoro-3-trifluoromethyl chromone prepared in Example 5 13 C NMR spectrum.
[0046] Figure 19 The 6-fluoro-3-trifluoromethyl chromone prepared in Example 5 19 F NMR spectrum.
[0047] Figure 20 This is the high-resolution mass spectrum monitoring chart of 6-fluoro-3-trifluoromethylchromone prepared in Example 5. DETAILED DESCRIPTION
[0048] Various exemplary embodiments of the present invention are now described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention.
[0049] In addition, for numerical ranges in the present invention, it is understood that each intervening value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any stated value or stated range, and any other stated value or intervening value in the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
[0050] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention.
[0051] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.
[0052] Example 1
[0053] Synthesis of 3-Trifluoromethylchromone
[0054] The synthesis process is shown below:
[0055]
[0056] The specific synthesis process is as follows:
[0057] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.5 mol%, based on the amount of enaminone added), K2HPO4 (70.0 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in 82% yield.
[0058] The 3-trifluoromethyl chromone synthesized above is 1 H NMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (detection spectra are as follows Figures 1 to 4 The product is a pure target compound.
[0059] 1 H NMR (400MHz, CDCl3), δ8.32 (s, 1H), 8.27 (d, J = 6.8Hz, 1H), 7.76 (t, J = 7.2Hz, 1H), 7.51 (m, 2H).
[0060] 13 C NMR (150MHz, CDCl3), δ172.7,156.0,155.7(q,J C-F =6.9Hz),134.8,126.4,126.1,124.2,122.1(q,J C-F =270.2Hz),118.3,115.9(q,J C-F =29.9Hz).
[0061] 19 F NMR(376MHz, CDCl3)δ-64.52(s).
[0062] HRMS(ESI):m / z calcd for C 10 H6F3O2[M+H] + 215.0344,found 215.0344.
[0063] Example 2
[0064] Synthesis of 6-Methyl-3-trifluoromethylchromone
[0065] The synthesis process is shown below:
[0066]
[0067] The specific synthesis process is as follows:
[0068] Enaminone (41 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.5 mol%, based on the amount of enaminone added), K2HPO4 (70.0 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as observed by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as eluents (V(PE):V(EA) = 7:1) to obtain a white solid in 84% yield.
[0069] The above-mentioned 6-methyl-3-trifluoromethyl chromone is 1 H NMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (detection spectra are as follows Figures 5 to 8 The product is a pure target compound.
[0070] 1 H NMR (400MHz, CDCl3), δ8.29(s,1H),8.05(s,1H),7.56(d,J=8.7Hz,1H),7.42(d,J=8.6Hz,1H),2.48(s,3H).
[0071] 13 C NMR(150MHz,CDCl3)δ172.8,155.6(q,J C-F =6.9Hz),154.3,136.7,136.0,125.4,123.9,121.9(q,J C-F =271.1Hz),118.0,115.7(q,J C-F =29.9Hz),20.9.
[0072] 19 F NMR (376MHz, CDCl3): δ-64.43 (s).
[0073] HRMS(ESI):m / z calcd for C 11 H8F3O2[M+H] + 229.04709,found 229.04713.
[0074] Example 3
[0075] Synthesis of 6-methoxy-3-trifluoromethylchromone
[0076] The synthesis process is shown below:
[0077]
[0078] The specific synthesis process is as follows:
[0079] Enaminone (44.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.5 mol%, based on the amount of enaminone added), K2HPO4 (70.0 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as observed by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as eluents (V(PE):V(EA) = 5:1) to obtain a white solid in 86% yield.
[0080] The above-synthesized 6-methoxy-3-trifluoromethyl chromone was 1 HNMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (detection spectra are as follows Figures 9-12 The product is a pure target compound.
[0081] 1 H NMR (400MHz, CDCl3), δ8.23(s,1H),7.61(s,1H),7.61(s,1H),7.46(d,J=8.8Hz,1H),7.33(d,J=9.2Hz,1H),3.91(s,3H).
[0082] 13 C NMR (150MHz, CDCl3) δ172.7,157.8,155.4(q,J C-F =6.6Hz),150.8,125.1,124.7,122.4(q,J C-F =270.6Hz),119.7,115.2(q,J C-F =30.5Hz),105.2,56.0.
[0083] 19 F NMR (376MHz, CDCl3): δ-64.38(s).
[0084] HRMS(ESI):m / z calcd for C 11 H8O3F3[M+H] + 245.04201,found 245.04208.
[0085] Example 4
[0086] Synthesis of 6-bromo-3-trifluoromethylchromone
[0087] The synthesis process is shown below:
[0088]
[0089] The specific synthesis process is as follows:
[0090] Enaminone (54 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.5 mol%, based on the amount of enaminone added), K2HPO4 (70.0 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as observed by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as eluents (V(PE):V(EA) = 5:1) to obtain a white solid in a yield of 76%.
[0091] The above-mentioned 6-bromo-3-trifluoromethyl chromone was 1 HNMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (detection spectra are as follows Figures 13-16 The product is a pure target compound.
[0092] 1 H NMR (400MHz, CDCl3), δ8.37(s,1H),8.32(s,1H),7.84(d,J=8.8Hz,1H),7.43(d,J=8.8Hz,1H).
[0093] 13 C NMR(150MHz,CDCl3)δ171.4,155.9(q,J C-F =6.8Hz),154.7,137.8,128.7,125.5,121.9(q,J C-F =270.8Hz),120.2,120.1,116.1(q,J C-F =30.5Hz).
[0094] 19 F NMR (376MHz, CDCl3): δ-64.53 (s).
[0095] HRMS(ESI):m / z calcd for C 10 H5O2BrF3[M+H] + 292.94159,found292.94186.
[0096] Example 5
[0097] Synthesis of 6-Fluoro-3-trifluoromethylchromone
[0098] The synthesis process is shown below:
[0099]
[0100] The specific synthesis process is as follows:
[0101] Enaminone (41.8 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.5 mol%, based on the amount of enaminone added), K2HPO4 (70.0 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as eluents (V(PE):V(EA) = 5:1) to obtain a white solid in a yield of 71%.
[0102] The above-mentioned 6-fluoro-3-trifluoromethyl chromone is 1 HNMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (detection spectra are as follows Figures 17-20 The product is a pure target compound.
[0103] 1 H NMR (400MHz, CDCl3), δ8.33 (s, 1H), 7.89 (dd, J=8.0, 2.8Hz, 1H), 7.55 (dd, J=9.2, 4.0Hz, 1H), 7.48 (m, 1H).
[0104] 13 C NMR(150MHz,CDCl3)δ172.0,160.1(d,J C-F =247.8Hz),155.9(q,J C-F =6.9Hz),152.2(d,J C-F=2.1Hz),125.6(d,J C-F =6.5Hz),122.0(q,J C-F =270.8Hz),123.1(d,J C-F =25.4Hz),120.6(d,J C-F =8.0Hz),115.4(q,J C-F =30.3Hz),111.2(d,J C-F =24Hz).
[0105] 19 F NMR (376MHz, CDCl3): δ-64.51(s),-112.648--112.70(m).
[0106] HRMS(ESI):m / z calcd for C 10 H4F4O2[M+H] + 233.02202,found 233.02206.
[0107] Example 6
[0108] Synthesis of 3-Trifluoromethylchromone
[0109] 2-Hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1 mol%), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of DMSO were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (observed by a barometer). The reaction mixture was exposed to 15 W blue light and stirred at room temperature for 24 h. After the reaction, the reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over sodium sulfate, and the ethyl acetate was removed using a rotary evaporator. The remaining residue was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a yield of 59%.
[0110] Example 7
[0111] Synthesis of 3-Trifluoromethylchromone
[0112] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1 mol%, based on the amount of enaminone added), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetone. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 52% yield.
[0113] Example 8
[0114] Synthesis of 3-Trifluoromethylchromone
[0115] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1 mol%, based on the amount of enaminone added), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 72% yield.
[0116] Example 9
[0117] Synthesis of 3-Trifluoromethylchromone
[0118] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1 mol%, based on the amount of enaminone added), K2CO3 (55.2 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 47% yield.
[0119] Example 10
[0120] Synthesis of 3-Trifluoromethylchromone
[0121] 2-Hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), Ir[dFppy]2(dtbbpy)PF6 (1 mol%, based on the amount of enaminone added), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 60% yield.
[0122] Example 11
[0123] Synthesis of 3-Trifluoromethylchromone
[0124] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (5 mol%, based on the amount of enaminone added), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 58% yield.
[0125] Example 12
[0126] Synthesis of 3-Trifluoromethylchromone
[0127] A 50 mL Schlenk flask was charged with 2-hydroxyaryl enaminone (38.2 mg, 0.2 mmol, 1.0 equiv), 3DPA2FBN (5 mol%, based on the amount of enaminone added), NaOAc (32.8 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetonitrile. The Schlenk flask was evacuated and then introduced with CF3Br gas three times (in excess). The pressure in the Schlenk flask was maintained at 1.0 atm (as measured by the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h. After the reaction, the solvent was evaporated and the product was separated by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (V(PE):V(EA) = 6:1) to obtain a white solid in a 45% yield.
[0128] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.
Claims
1. A method for synthesizing 3-trifluoromethylchromone, characterized in that: Here are the steps: 38.2 mg, 0.2 mmol, 1.0 equiv of 2-hydroxyaryl enaminone, 0.5% molar weight of fac-Ir(ppy)3, 70.0 mg, 0.4 mmol, 2.0 equiv of K2HPO4, and 3 mL of acetonitrile were added to a 50 mL Schlenk flask; the Schlenk flask was evacuated and then introduced with CF3Br gas, repeated three times, and the pressure in the Schlenk flask was maintained at 1.0 atm; the reaction mixture was placed under 15 W blue light and stirred at room temperature for 24 h; after the reaction, the solvent was evaporated and the mixture was separated by column chromatography using silica gel as the stationary phase and a mixture of petroleum ether and ethyl acetate as the eluent to obtain 3-trifluoromethylchromone; The volume ratio of petroleum ether to ethyl acetate in the mixture of petroleum ether and ethyl acetate is 6:1; The chemical structural formula of the 2-hydroxyaryl enaminone is: .