Benzyl benzoyl or fluoroalkane substituted phenol compound as well as synthesis method and application thereof

Abstract

The invention discloses a benzyl benzoyl or fluoroalkane substituted phenol compound as well as a synthesis method and application thereof, and belongs to the technical field of medicine synthesis. The synthesis method comprises the following steps: step 1, adding 0.3 mmol of anthranilamide, 0.3 mmol of ketone, 10 mol% of I2 and 5 mL of absolute ethyl alcohol into a 10 mL round-bottom flask at one time, stirring at 80 DEG C for 24 hours, after the reaction is completed, placing to room temperature, pouring a reaction solution into ice water according to a volume ratio of the reaction solution to the ice water of 1: 10, extracting with ethyl acetate, washing an organic layer with saturated salt water, drying with anhydrous Na2SO4, and spin-drying to obtain an anthranilamide intermediate; a crude product is obtained. The synthesis method is mild in reaction condition, few in side reaction and simple and convenient to operate. And the benzyl benzoyl or fluoroalkane substituted phenol compound obtained by the invention has the effect of resisting colon cancer.

Description

Technical Field

[0001] The present invention relates to a benzyl benzoyl or fluoroalkane-substituted phenol compound, its synthesis method and application, and belongs to the technical field of pharmaceutical synthesis. Background Art

[0002] Benzyl benzoyl or fluoroalkane-substituted phenol compounds play an important role in organic chemistry and have extensive applications in the fields of pharmaceutical synthesis, materials science, and fine chemicals. Due to their specific structures and properties, these compounds exhibit unique activities and selectivities in chemical reactions, making them important objects of chemical research.

[0003] However, the existing synthesis methods of benzyl benzoyl or fluoroalkane-substituted phenol compounds have problems such as many side reactions, complex reaction steps, and the need for multiple steps to prepare. And in the prior art, there is no application of benzyl benzoyl or fluoroalkane-substituted phenol compounds in the treatment of colon cancer. Summary of the Invention

[0004] In view of the above problems, the object of the present invention is to provide a benzyl benzoyl or fluoroalkane-substituted phenol compound.

[0005] Meanwhile, the present invention provides a synthesis method of a benzyl benzoyl or fluoroalkane-substituted phenol compound. This synthesis method has mild conditions, few side reactions, and is simple and convenient to operate.

[0006] Meanwhile, the present invention provides an application of a benzyl benzoyl or fluoroalkane-substituted phenol compound in the preparation of anti-colon cancer drugs.

[0007] To solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0008] A benzyl benzoyl or fluoroalkane-substituted phenol compound, with the molecular formula:

[0009]

[0010] Wherein, R 1 includes a benzyl benzoyl or fluoroalkane group;

[0011] R 2 includes phenyl,

[0012] any one of.

[0013] Preferably, the benzyl benzoyl includes

[0014]

[0015] Any one of Bn groups.

[0016] Preferably, the fluoroalkyl group includes

[0017] Preferably, a benzyl benzoyl or fluoroalkyl-substituted phenol compound includes the following Compounds 1 to 30:

[0018]

[0019] A method for synthesizing a benzyl benzoyl or fluoroalkyl-substituted phenol compound includes the following steps:

[0020] Step 1: Add 0.3 mmol of o-aminobenzamide, 0.3 mmol of ketone, 10 mol% of I2, and 5 mL of absolute ethanol into a 10 mL round-bottom flask at one time, stir at 80 °C for 24 h. After the reaction is complete, let it cool to room temperature, pour the reaction solution into ice water, with the volume ratio of ice water to the reaction solution being 10:1, extract with ethyl acetate, wash the organic layer with saturated brine, dry with anhydrous Na2SO4, and concentrate by rotary evaporation to obtain the crude product;

[0021] Step 2: Without treatment, directly add 0.3 mmol, 1.5 equiv of the crude product, 0.2 mmol, 1.0 equiv of p-QMs, 2 mol% of 4CzIPN, and 2 mL of absolute DMF into a 10 mL sealed tube in one-pot method. Under nitrogen protection, irradiate with a 40 W blue LED, λ = 456 nm, and stir at room temperature for 24 h; Step 3: After the reaction is completed, introduce the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry with anhydrous Na2SO4, concentrate by rotary evaporation, and then perform silica gel column chromatography separation with mobile phases prepared from petroleum ether and ethyl acetate at different volume ratios to obtain the benzyl benzoyl or fluoroalkyl-substituted phenol compound.

[0022] Preferably, in Step 1, the ketone includes any one of benzil, 4,4'-dimethylbenzil, 4,4'-diisopropylbenzil, 4,4'-di-tert-butylbenzil, 4,4'-dimethoxybenzil, 4,4'-dichlorobenzil, 3,3'-dimethoxybenzil, 3,3'-dichlorobenzil, 2,2'-dimethylbenzil, 1,2-bis(3,4-dimethoxyphenyl)ethane-1,2-dione, 2,2-difluoroacetophenone, 2,2,2-trifluoroacetophenone, and acetophenone.

[0023] Preferably, in Step 3, the mobile phase includes petroleum ether:ethyl acetate = 5:1, petroleum ether:ethyl acetate = 10:1, or petroleum ether:ethyl acetate = 50:1 - 10:1.

[0024] Use of a benzyl benzoyl or fluoroalkane-substituted phenol compound in the preparation of an anti-colorectal cancer drug.

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

[0026] The synthesis method of the present invention has mild reaction conditions, few side reactions, and is simple and convenient to operate. Moreover, the benzyl benzoyl or fluoroalkane-substituted phenol compound obtained by the present invention has an anti-colorectal cancer effect.

[0027] The present invention applies 40W blue light (λ = 456 nm) to the synthesis of benzyl benzoyl or fluoroalkane-substituted phenol compounds, making the synthesis route efficient, with mild reaction conditions, few side reactions, and being simple and convenient to operate. Detailed implementation manners

[0028] The present invention will be further described in detail below in conjunction with specific embodiments. The following embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0029] Example 1

[0030] A benzyl benzoyl or fluoroalkane-substituted phenol compound, and the content of Compound 1 is as follows:

[0031] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,2-diphenylethan-1-one(1)

[0032]

[0033] Synthesis process of Compound 1: o-Aminobenzamide (0.3 mmol, 40.8 mg), benzil (0.3 mmol, 63.0 mg), I2 (10 mol%, 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 98.4 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), and stir at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, evaporated to dryness, and column chromatographed with petroleum ether:ethyl acetate = 10:1 to obtain 72.8 mg of a white solid (91%), M.p. = 91 - 93 °C.

[0034] 10 mol% of I2 means 10% of 0.3 mmol; the molecular weight of I2 is 253.8 g / mol, 253.8 g / mol × 0.3 mmol × 10% = 7.614 mg. The actual amount of I2 fed in this invention is 8 mg.

[0035] 1 H NMR (500 MHz, Chloroform-d) δ 8.04–7.98 (m, 2H), 7.51–7.46 (m, 1H), 7.42–7.37 (m, 2H), 7.33–7.28 (m, 4H), 7.25–7.21 (m, 1H), 7.07 (s, 2H), 5.94 (s, 1H), 5.12 (s, 1H), 1.38 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 199.0, 153.0, 139.9, 137.4, 136.0, 132.9, 129.6, 129.2, 129.0, 128.8, 128.7, 127.0, 126.0, 59.4, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] + calcd for C 28 H 32 NaO2 423.2295, found 423.2303.

[0036] Example 2

[0037] The content of Compound 2 is as follows: 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenyl-1-(p-tolyl)ethan-1-one (2)

[0038]

[0039] Synthesis process of Compound 2: o-Aminobenzamide (0.3 mmol, 40.8 mg), 4,4'-dimethylbenzil (0.3 mmol, 71.4 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 106.8 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 72.1 mg of a white solid (87%), M.p. = 167 - 169 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.92 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 4.4 Hz, 4H), 7.24–7.18 (m, 3H), 7.06 (s, 2H), 5.93 (s, 1H), 5.11 (s, 1H), 2.36 (s, 3H), 1.38 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 198.5, 152.9, 143.7, 140.0, 135.9, 134.8, 129.7, 129.4, 129.2, 128.7, 127.0, 126.0, 59.2, 34.5, 30.4, 21.7. HRMS (ESI) m / z: [M+Na] + calcd for C 29 H 34 NaO2 437.2451, found 437.2443.

[0040] Example 3

[0041] The content of Compound 3 is as follows:

[0042] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(4-isopropylphenyl)-2-phenylethan-1-one(3)

[0043]

[0044] Synthesis process of Compound 3: o-Aminobenzamide (0.3 mmol, 40.8 mg), 4,4'-diisopropylbenzil (0.3 mmol, 88.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 123.7 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and evaporated to dryness. Column chromatography was performed with petroleum ether:ethyl acetate = 10:1 to obtain 70.8 mg (80%) of a white solid, M.p. = 148 - 150 °C.

[0045] 1 H NMR(500MHz,Chloroform-d)δ7.96(d,J=8.3Hz,2H),7.31(d,J=4.3Hz,4H),7.28–7.24(m,2H),7.24–7.21(m,1H),7.07(s,2H),5.94(s,1H),5.12(s,1H),2.97–2.87(m,1H),1.38(s,18H),1.24(s,3H),1.23(s,3H). 1313C NMR (126 MHz, Chloroform-d) δ 198.5, 154.4, 152.9, 140.0, 135.9, 135.2, 129.7, 129.3, 129.2, 128.7, 127.0, 126.8, 126.0, 59.3, 34.5, 34.3, 30.4, 23.8. HRMS (ESI) m / z: [M+Na] + calcd for C 31 H 38 NaO2 465.2764, found 465.2771.

[0046] Example 4

[0047] The content of Compound 4 is as follows:

[0048] 1-(4-(tert-butyl)phenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one (4) 3

[0049]

[0050] Synthesis process of Compound 4: o-Aminobenzamide (0.3 mmol, 40.8 mg), 4,4'-di-tert-butylbenzil (0.3 mmol, 96.7 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 132.1 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 75.7 mg (83%) of a white solid, M.p. = 136 - 138 °C. 11H NMR (500 MHz, Chloroform-d) δ 8.08–7.83 (m, 2H), 7.46–7.38 (m, 2H), 7.31 (d, J = 4.5 Hz, 4H), 7.24–7.19 (m, 1H), 7.07 (s, 2H), 5.94 (s, 1H), 5.12 (s, 1H), 1.38 (s, 18H), 1.31 (s, 9H). 13 13C NMR (126 MHz, Chloroform-d) δ 198.5, 156.6, 153.0, 140.0, 135.9, 134.7, 129.7, 129.2, 129.0, 128.7, 127.0, 126.0, 125.7, 59.3, 35.2, 34.5, 31.2, 30.4. HRMS (ESI) m / z: + calcd for C 32 H 40 NaO2 479.2921, found 479.2924.

[0051] Example 5

[0052] The content of Compound 5 is as follows:

[0053] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(4-methoxyphenyl)-2-phenylethan-1-one (5)

[0054]

[0055] Synthesis process of Compound 5: o-Aminobenzamide (0.3 mmol, 40.8 mg), 4,4'-dimethoxybenzil (0.3 mmol, 81.0 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.4 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 73.1 mg (85%) of a white solid, M.p. = 156 - 158 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.03–7.98 (m, 2H), 7.35–7.26 (m, 4H), 7.24–7.20 (m, 1H), 7.09–7.04 (m, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.91 (s, 1H), 5.11 (s, 1H), 3.81 (s, 3H), 1.38 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 197.5, 163.4, 152.9, 140.2, 135.9, 131.4, 130.3, 129.9, 129.2, 128.7, 126.9, 126.0, 113.8, 59.0, 55.5, 34.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 29 H 35 O3 431.2581, found 431.2590.

[0056] Example 6

[0057] The content of Compound 6 is as follows:

[0058] 1-(4-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one(6) 3

[0059]

[0060] Synthesis process of Compound 6: o-Aminobenzamide (0.3 mmol, 40.8 mg), 4,4'-dichlorobenzil (0.3 mmol, 83.4 g), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 118.8 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Column chromatography separation with petroleum ether:ethyl acetate = 10:1 gave 66.0 mg (76%) of a white solid, M.p. = 152 - 154 °C. 1 1H NMR (500 MHz, Chloroform-d) δ 7.93 (d, J = 8.6 Hz, 2H), 7.37 (d, J = 8.6 Hz, 2H), 7.34 - 7.29 (m, 2H), 7.28–7.24 (m, 3H), 7.03 (s, 2H), 5.86 (s, 1H), 5.14 (s, 1H), 1.38 (s, 18H). 13 13C NMR (126 MHz, Chloroform-d) δ 197.8, 153.1, 139.5, 139.3, 136.1, 135.6, 130.5, 129.2, 129.1, 129.0, 128.8, 127.2, 125.9, 59.5, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] + calcd for C 28 H 31 ClNaO2 457.1905, found 457.1913.

[0061] Example 7

[0062] The content of Compound 7 is as follows:

[0063] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-phenylethan-1-one(7) 4

[0064]

[0065] Synthesis process of Compound 7: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time, stirred at 80 °C for 24 h. After the reaction was complete, it was allowed to cool to room temperature, and the reaction solution was poured into ice water (V:V = 1:10). The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.4 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, it was irradiated with a 40 W blue LED (λ = 456 nm) and stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. Column chromatography was performed using petroleum ether:ethyl acetate = 10:1 to obtain 74.0 mg (86%) of a white solid, M.p. = 108 - 110 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.60 (d, J = 7.7 Hz, 1H), 7.56–7.50 (m, 1H), 7.35–7.28 (m, 5H), 7.27–7.22 (m, 1H), 7.07 (s, 2H), 7.04 (dd, J = 8.1, 2.6 Hz, 1H), 5.92 (s, 1H), 5.13 (s, 1H), 3.79 (s, 3H), 1.38 (s, 18H). 1313C NMR (126 MHz, Chloroform-d) δ 198.8, 159.8, 153.0, 139.8, 138.7, 136.0, 129.6, 129.5, 129.1, 128.8, 127.1, 125.9, 121.7, 119.5, 113.3, 59.6, 55.5, 34.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 29 H 35 O3 431.2581, found 431.2573.

[0066] Example 8

[0067] The content of Compound 8 is as follows:

[0068] 1-(3-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one (8)

[0069]

[0070] Synthesis process of Compound 8: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dichlorobenzil (0.3 mmol, 83.4 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time, stirred at 80 °C for 24 h. After the reaction was complete, it was cooled to room temperature, and the reaction solution was poured into ice water (V:V = 1:10). It was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by evaporation. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 118.8 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, it was irradiated with a 40 W blue LED (λ = 456 nm) and stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by evaporation. Column chromatography was carried out with petroleum ether:ethyl acetate = 10:1 to obtain a white solid of 67.7 mg (78%), M.p. = 142 - 144 °C. 11H NMR (500 MHz, Chloroform-d) δ 8.04–7.92 (m, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.51–7.42 (m, 1H), 7.38–7.23 (m, 6H), 7.05 (s, 2H), 5.86 (s, 1H), 5.15 (s, 1H), 1.39 (s, 18H). 13 13C NMR (126 MHz, Chloroform-d) δ 197.7, 153.2, 139.3, 138.9, 136.2, 134.9, 132.8, 130.0, 129.1, 129.0, 128.9, 127.2, 127.1, 125.9, 59.7, 34.5, 30.4. HRMS (ESI) m / z: + calcd for C 28 H 31 ClNaO2 457.1905, found 457.1900.

[0071] Example 9

[0072] The content of Compound 9 is as follows:

[0073] 1-(3-bromophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one (9)

[0074]

[0075] Synthesis process of Compound 9: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-Dibromobenzil (0.3 mmol, 109.8 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 145.2 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 73.6 mg (77%) of a white solid, M.p. = 158 - 160 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.12 (t, J = 1.8 Hz, 1H), 7.94–7.87 (m, 1H), 7.67–7.59 (m, 1H), 7.34–7.25 (m, 6H), 7.05 (s, 2H), 5.86 (s, 1H), 5.15 (s, 1H), 1.39 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 197.6, 153.2, 139.3, 139.1, 136.2, 135.8, 132.1, 130.3, 129.1, 129.0, 128.9, 127.6, 127.2, 126.0, 123.0, 59.6, 34.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 30 H 37 O4 479.1686, found 479.1694

[0076] Example 10

[0077] The content of Compound 10 is as follows:

[0078] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenyl-1-(o-tolyl)ethan-1-one (10)

[0079]

[0080] Synthesis process of Compound 10: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2'-dimethylbenzil (0.3 mmol, 71.4 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and directly add the crude product (0.3 mmol, 1.5 equiv, 106.8 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) into a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 73.6 mg (89%) of a white solid, M.p. = 168 - 170 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.68–7.62 (m, 1H), 7.33 (d, J = 4.4 Hz, 4H), 7.31–7.27 (m, 1H), 7.27–7.24 (m, 1H), 7.21–7.17 (m, 2H), 5.78 (s, 1H), 5.12 (s, 1H), 2.39 (s, 3H), 1.38 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 203.0, 153.0, 139.5, 139.2, 138.3, 136.0, 131.8, 131.0, 129.3, 129.2, 128.7, 128.3, 127.1, 126.0, 125.6, 62.1, 34.5, 30.4, 21.1. HRMS (ESI) m / z: [M+Na] + calcd for C 29 H 34 NaO2 437.2451, found 437.2443.

[0081] Example 11

[0082] The content of Compound 11 is as follows:

[0083] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3,4-dimethoxyphenyl)-2-phenylethan-1-one(11)

[0084]

[0085] Synthesis process of compound 11: o-Aminobenzamide (0.3 mmol, 40.8 mg), 1,2-bis(3,4-dimethoxyphenyl)ethane-1,2-dione (0.3 mmol, 99.0 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 134.4 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 84.7 mg (92%) of a white solid, M.p. = 174 - 176 °C. 1 H NMR(500MHz,Chloroform-d)δ7.73–7.64(m,1H),7.60–7.55(m,1H),7.36–7.28(m,4H),7.24–7.21(m,1H),7.12–7.06(m,2H),6.83(dd,J=8.4,2.2Hz,1H),5.92(s,1H),5.13(s,1H),3.93–3.83(m,6H),1.39(s,18H). 13 C NMR(126MHz,Chloroform-d)δ197.5,153.1,152.9,148.9,140.2,135.9,130.3,129.8,129.1,128.7,126.9,125.9,123.6,111.3,110.1,59.1,56.1,55.9,34.4,30.4.HRMS(ESI)m / z:[M+Na] +Calcd for C 30 H 36 NaO4 483.2506, found 483.2513.

[0086] Example 12

[0087] The content of Compound 12 is as follows:

[0088] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(p-tolyl)ethan-1-one (12)

[0089]

[0090] Synthesis process of Compound 12: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 61.7 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 72.9 mg (82%) of a white solid, M.p. = 181 - 183 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.59 (dt, J = 7.7, 1.3 Hz, 1H), 7.52 (dd, J = 2.7, 1.6 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.22–7.16 (m, 2H), 7.14–7.09 (m, 2H), 7.08 (s, 2H), 7.06–7.00 (m, 1H), 5.87 (s, 1H), 5.11 (s, 1H), 3.79 (s, 3H), 2.30 (s, 3H), 1.38 (s, 18H). 1313C NMR (126 MHz, Chloroform-d) δ 198.9, 159.8, 153.0, 138.8, 136.8, 136.6, 135.9, 129.7, 129.6, 129.5, 129.0, 125.9, 121.6, 119.5, 113.3, 59.3, 55.5, 34.5, 30.4, 21.2. HRMS (ESI) m / z: [M+H] + calcd for C 30 H 37 O3 445.2737, found 445.2730.

[0091] Example 13

[0092] The content of Compound 13 is as follows:

[0093] 2-(4-(tert-butyl)phenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one (13)

[0094]

[0095] Synthesis process of Compound 13: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 70.1 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Column chromatography separation with petroleum ether:ethyl acetate = 5:1 gave a white solid of 78.8 mg (81%), M.p. = 184 - 186 °C. 11H NMR (400 MHz, Chloroform-d) δ 7.61 (d, J = 7.9 Hz, 1H), 7.56–7.49 (m, 1H), 7.40–7.29 (m, 3H), 7.26–7.21 (m, 2H), 7.13–7.08 (m, 2H), 7.04 (dd, J = 8.2, 2.6 Hz, 1H), 5.88 (s, 1H), 5.12 (s, 1H), 3.79 (s, 3H), 1.39 (s, 18H), 1.28 (s, 9H). 13 13C NMR (101 MHz, Chloroform-d) δ 198.9, 159.8, 153.0, 149.8, 138.8, 136.8, 136.0, 129.6, 128.7, 125.9, 125.7, 121.7, 119.5, 113.3, 59.2, 55.5, 34.5, 31.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 33 H 43 O3 487.3207, found 487.3216.

[0096] Example 14

[0097] The content of Compound 14 is as follows:

[0098] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(4-methoxyphenyl)ethan-1-one (14)

[0099]

[0100] Synthesis process of Compound 14: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 64.9 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 5:1 to obtain 70.0 mg (76%) of a white solid, M.p. = 180 - 182 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.62–7.57 (m, 1H), 7.55–7.50 (m, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.25–7.19 (m, 2H), 7.08–7.03 (m, 3H), 6.93–6.81 (m, 2H), 5.86 (s, 1H), 5.12 (s, 1H), 3.80 (s, 3H), 3.77 (s, 3H), 1.38 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 199.0, 159.8, 158.6, 152.9, 138.7, 135.9, 131.9, 130.2, 129.9, 129.6, 125.8, 121.6, 119.5, 114.2, 113.3, 58.8, 55.5, 55.4, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] + calcd for C 30 H 36 NaO4 483.2506, found 483.2511.

[0101] Example 15

[0102] The content of Compound 15 is as follows:

[0103] 2-([1,1'-biphenyl]-4-yl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one(15)

[0104]

[0105] Synthesis process of Compound 15: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 74.1 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 5:1 to obtain 89.1 mg (88%) of a white solid, M.p. = 186 - 188 °C. 1 H NMR(500MHz,Chloroform-d)δ7.66–7.61(m,1H),7.58–7.53(m,5H),7.44–7.37(m,4H),7.34–7.29(m,2H),7.13(s,2H),7.07–7.04(m,1H),5.96(s,1H),5.14(s,1H),3.80(s,3H),1.40(s,18H). 13 C NMR(126MHz,Chloroform-d)δ198.7,159.8,153.1,140.9,139.9,139.0,138.7,136.1,129.7,129.5,129.4,128.9,127.5,127.3,127.2,125.9,121.7,119.6,113.3,59.3,55.5,34.5,30.4.HRMS(ESI)m / z:[M+Na] + calcd forC35 H 38 NaO3 529.2713, found 529.2706.

[0106] Example 16

[0107] The content of Compound 16 is as follows:

[0108] 2-(4-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one (16)

[0109]

[0110] Synthesis process of Compound 16: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 65.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), and stir at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and evaporated to dryness. Column chromatography was carried out with petroleum ether:ethyl acetate = 10:1 to obtain 67.8 mg (73%) of a white solid, M.p. = 182 - 184 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.57 (d, J = 7.8 Hz, 1H), 7.51 (s, 1H), 7.34–7.26 (m, 3H), 7.24–7.20 (m, 2H), 7.08–7.02 (m, 3H), 5.88 (s, 1H), 5.16 (s, 1H), 3.79 (s, 3H), 1.38 (s, 18H). 1313C NMR (126 MHz, Chloroform-d) δ 198.4, 159.9, 153.2, 138.5, 138.5, 136.2, 132.9, 130.5, 129.7, 129.1, 128.8, 125.8, 121.6, 119.7, 113.3, 58.8, 55.5, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] + calcd for C 29 H 33 ClNaO3 487.2010, found 487.2019.

[0111] Example 17

[0112] The content of Compound 17 is as follows:

[0113] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(3-phenoxyphenyl)ethan-1-one (17)

[0114]

[0115] Synthesis process of Compound 17: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 77.3 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 75.2 mg (72%) of a white solid, M.p. = 188 - 190 °C. 11H NMR (500 MHz, Chloroform-d) δ 7.58 (d, J = 7.8 Hz, 1H), 7.54–7.48 (m, 1H), 7.32–7.24 (m, 4H), 7.08–7.02 (m, 5H), 7.00–6.94 (m, 3H), 6.87 (dd, J = 8.2, 2.1 Hz, 1H), 5.88 (s, 1H), 5.13 (s, 1H), 3.79 (s, 3H), 1.38 (s, 18H). 13 13C NMR (126 MHz, Chloroform-d) δ 198.3, 159.8, 157.4, 157.2, 153.1, 141.8, 138.5, 136.0, 129.9, 129.8, 129.6, 129.1, 125.8, 124.1, 123.3, 121.6, 119.8, 119.6, 118.8, 117.5, 113.2, 59.3, 55.4, 34.4, 30.4. HRMS (ESI) m / z: [[M+Na]] + calcd for C 35 H 38 NaO4 545.2662, found 545.2670.

[0116] Example 18

[0117] The content of Compound 18 is as follows:

[0118] 2-(3-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one (18)

[0119]

[0120] Synthesis process of Compound 18: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-Dimethoxybenzil (0.3 mmol, 81.1 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at once. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness. Without further treatment, directly add the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 65.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) into a 10 mL sealed tube. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), stir at room temperature for 24 h. After the reaction ended, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, evaporate to dryness, and separate by column chromatography with petroleum ether:ethyl acetate = 10:1 to obtain 74.3 mg (80%) of a white solid, M.p. = 171 - 173 °C. 1 H NMR (500 MHz, Chloroform-d) δ 7.60–7.55 (m, 1H), 7.53–7.49 (m, 1H), 7.33 (t, J = 7.9 Hz, 1H), 7.30–7.28 (m, 1H), 7.25–7.20 (m, 2H), 7.19–7.16 (m, 1H), 7.10–7.05 (m, 3H), 5.87 (s, 1H), 5.17 (s, 1H), 3.81 (s, 3H), 1.39 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 198.1, 159.9, 153.3, 141.9, 138.4, 136.3, 134.5, 129.9, 129.7, 129.4, 128.8, 127.3, 127.3, 125.8, 121.6, 119.8, 113.3, 59.1, 55.5, 34.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 29 H 34 ClO3 465.2191, found 465.2184.

[0121] Example 19

[0122] The content of Compound 19 is as follows:

[0123] 2-(3-Bromophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one (19)

[0124]

[0125] Synthesis process of Compound 19: o-Aminobenzamide (0.3 mmol, 40.8 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.1 mg), I₂ (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na₂SO₄, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 116.5 mg), p-QMs (0.2 mmol, 1.0 equiv, 74.7 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na₂SO₄, rotary evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 through about 100 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 300 mL) by column chromatography to obtain 76.2 mg (75%) of a white solid, M.p. = 178 - 180 °C. 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 7.7 Hz, 1H), 7.53–7.48 (m, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.31 (t, J = 8.0 Hz, 1H), 7.16 (d, J = 8.3 Hz, 2H), 7.08–6.99 (m, 3H), 5.87 (s, 1H), 5.16 (s, 1H), 3.79 (s, 3H), 1.38 (s, 18H). 13 C NMR (101 MHz, Chloroform-d) δ 198.3, 159.8, 153.2, 139.0, 138.4, 136.2, 131.8, 130.9, 129.7, 129.0, 125.7, 121.6, 121.1, 119.7, 113.3, 58.9, 55.5, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] +Calcd for C 29 H 33 BrNaO3 531.1505, found 531.1513.

[0126] Example 20

[0127] The content of Compound 20 is as follows:

[0128] 2,6 - di - tert - butyl - 4 - (1,2 - diphenylethyl)phenol (20)

[0129]

[0130] Synthesis process of Compound 20: o - aminobenzamide (0.3 mmol, 40.8 mg), acetophenone (0.3 mmol, 58.9 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 - mL round - bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary - evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 94.3 mg), p - QMs (0.2 mmol, 1.0 equiv, 58.9 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 - mL sealed tube in one - pot method. Under nitrogen protection, irradiate with a 40 - W blue - light LED (λ = 456 nm), and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary - evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 150 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 200 mL) by column chromatography to obtain 59.5 mg of colorless oil (77%). 1 H NMR (400 MHz, Chloroform - d) δ 7.28–7.20 (m, 4H), 7.19–7.05 (m, 4H), 7.03–6.90 (m, 4H), 5.01 (s, 1H), 4.11 (t, J = 7.8 Hz, 1H), 3.37–3.21 (m, 2H), 1.36 (s, 18H). 1313C NMR (101 MHz, Chloroform-d) δ 152.1, 144.9, 140.9, 135.5, 135.2, 129.3, 128.3, 128.3, 128.1, 126.1, 125.8, 124.6, 53.4, 43.1, 34.5, 30.4. HRMS (ESI) m / z: [M+Na] + calcd for C 28 H 34 NaO 409.2502, found 409.2511.

[0131] Example 21

[0132] The content of Compound 21 is as follows:

[0133] 2,6-di-tert-butyl-4-(2,2-difluoro-1-phenylethyl)phenol (21)

[0134]

[0135] Synthesis process of Compound 21: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2-difluoroacetophenone (0.3 mmol, 46.8 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time, and stirred at 80 °C for 24 h. After the reaction was complete, it was allowed to cool to room temperature, and the reaction solution was poured into ice water (V:V = 1:10). The organic layer was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by evaporation. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 82.3 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.9 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot under nitrogen protection. Irradiated with a 40 W blue LED (λ = 456 nm) at room temperature and stirred for 24 h. After the reaction was completed, the reaction solution was poured into ice water, and the organic layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by evaporation. First, eluted with petroleum ether:ethyl acetate = 50:1 for about 150 mL, and then changed to elute with petroleum ether:ethyl acetate = 10:1 (about 200 mL) by column chromatography to obtain a yellow oil (53.3 mg, 77%). 11H NMR (500 MHz, Chloroform-d) δ 7.38–7.30 (m, 4H), 7.29–7.25 (m, 1H), 7.09 (s, 2H), 6.25 (td, J = 56.1, 4.4 Hz, 1H), 5.16 (s, 1H), 4.30 (td, J = 16.2, 4.4 Hz, 1H), 1.41 (s, 18H). 13 13C NMR (126 MHz, Chloroform-d) δ 153.2, 137.8, 136.0, 129.2, 128.7, 127.8, 127.4, 125.8, 117.4 (t, J C-F = 244.5 Hz), 55.2 (t, J C-F = 20.4 Hz), 34.5, 30.4. 19 19F NMR (471 MHz, Chloroform-d) δ -117.2 (d, J = 276.9 Hz), -118.2 (d, J = 277.5 Hz). HRMS (ESI) m / z: [M+H] + calcd for C 22 H 29 F2O347.2181, found 347.2188.

[0136] Example 22

[0137] The content of Compound 22 is as follows: 4-(1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2,2-difluoroethyl)benzonitrile (22)

[0138]

[0139] Synthesis process of Compound 22: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2-Difluoroacetophenone (0.3 mmol, 46.8 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at once. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 82.3 mg), p-QMs (0.2 mmol, 1.0 equiv, 63.9 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one-pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm), stir at room temperature for 24 h. After the reaction, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 150 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 200 mL) by column chromatography to obtain 52.0 mg of yellow oil, 70%. 1 H NMR (400 MHz, Chloroform-d) δ 7.64 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 7.04 (s, 2H), 6.26 (td, J = 55.7, 3.9 Hz, 1H), 5.24 (s, 1H), 4.50–4.27 (m, 1H), 1.41 (s, 18H). 13 C NMR (101 MHz, Chloroform-d) δ 153.6, 143.0, 136.5, 132.4, 130.2, 126.4 (q, J C-F =2.7 Hz), 125.6, 118.8, 116.7 (t, J C-F =246.1 Hz), 111.4, 55.0 (t, J C-F =20.7 Hz), 34.5, 30.3. 19 F NMR (376 MHz, Chloroform-d) δ -116.1 (d, J = 279.3 Hz), -119.6 (d, J = 279.0 Hz). HRMS (ESI) m / z: [M+H] + calcd for C 23 H 28 F2NO 372.2133, found 372.2128.

[0140] Example 23

[0141] The content of Compound 23 is as follows: 2,6-di-tert-butyl-4-(1-(4-(tert-butyl)phenyl)-2,2-difluoroethyl)phenol (23)

[0142]

[0143] Synthesis process of Compound 23: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2-difluoroacetophenone (0.3 mmol, 46.8 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 82.3 mg), p-QMs (0.2 mmol, 1.0 equiv, 70.1 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. First, elute with petroleum ether:ethyl acetate = 50:1 for about 150 mL, and then change to elute with petroleum ether:ethyl acetate = 10:1 (about 230 mL) by column chromatography to obtain 67.6 mg of a yellow oil, with a yield of 84%. 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (d, J = 8.3 Hz, 2H), 7.30–7.24 (m, 2H), 7.11 (s, 2H), 6.23 (td, J = 56.2, 4.4 Hz, 1H), 5.15 (s, 1H), 4.26 (td, J = 16.3, 4.4 Hz, 1H), 1.41 (s, 18H), 1.30 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 153.2, 150.2, 136.0, 134.6 (t, J C-F = 3.3 Hz), 128.8, 127.9 (t, J C-F = 3.7 Hz), 125.8, 125.6, 117.6 (t, J C-F = 245.3 Hz), 54.9 (t, J C-F= 20.4 Hz), 34.5, 31.5, 30.4. 19 19F NMR (376 MHz, Chloroform-d) δ -116.9 (d, J = 275.6 Hz), -118.3 (d, J = 275.6 Hz). HRMS (ESI) m / z: [M+H] + calcd for C 26 H 37 F2O 403.2807, found 403.2813.

[0144] Example 24

[0145] The content of compound 24 is as follows: 4-(1-(3-bromophenyl)-2,2-difluoroethyl)-2,6-di-tert-butylphenol (24)

[0146]

[0147] Synthesis process of compound 24: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2-difluoroacetophenone (0.3 mmol, 46.8 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and concentrate by rotary evaporation. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 82.3 mg), p-QMs (0.2 mmol, 1.0 equiv, 74.7 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. First, elute with petroleum ether:ethyl acetate = 50:1 for about 150 mL, and then change to elute with petroleum ether:ethyl acetate = 10:1 (about 270 mL) by column chromatography to obtain 70.4 mg of a yellow oil, with a yield of 83%. 11H NMR (400 MHz, Chloroform-d) δ 7.48 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.07 (s, 2H), 6.23 (td, J = 56.0, 4.1 Hz, 1H), 5.22 (s, 1H), 4.28 (ddd, J = 18.4, 14.5, 4.1 Hz, 1H), 1.43 (s, 18H). 13 13C NMR (101 MHz, Chloroform-d) δ 153.4, 136.7 (t, J C-F = 3.1 Hz), 136.2, 131.8, 131.0, 127.2 (t, J C-F = 3.6 Hz), 125.6, 121.5, 117.0 (t, J C-F = 245.7 Hz), 54.6 (t, J C-F = 20.7 Hz), 34.5, 30.4. 19 19F NMR (376 MHz, Chloroform-d) δ -116.7 (d, J = 277.9 Hz), -119.1 (d, J = 277.9 Hz). HRMS (ESI) m / z: [M+H] + calcd for C 22 H 28 BrF2O 425.1286, found 425.1291.

[0148] Example 25

[0149] The content of Compound 25 is as follows: 2,6-di-tert-butyl-4-(2,2,2-trifluoro-1-phenylethyl)phenol (25)

[0150]

[0151] Synthesis process of Compound 25: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2-trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p-QMs (0.2 mmol, 1.0 equiv, 58.9 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, rotary evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 200 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 230 mL) by column chromatography to obtain 64.8 mg of a yellow oil, with a yield of 89%. 1 H NMR (500 MHz, Chloroform-d) δ 7.45–7.38 (m, 2H), 7.36 (t, J = 7.5 Hz, 2H), 7.33–7.29 (m, 1H), 7.17 (s, 2H), 5.21 (s, 1H), 4.58 (q, J = 10.2 Hz, 1H), 1.42 (s, 18H). 13 C NMR (126 MHz, Chloroform-d) δ 153.6, 136.2, 136.0, 129.2, 128.7, 127.8, 126.1, 125.9, 125.5, 55.6 (q, J C-F = 27.6 Hz), 34.5, 30.4. HRMS (ESI) m / z: [M+H] + calcd for C 22 H 28 F3O 365.2087, found 365.2080.

[0152] Example 26

[0153] The content of Compound 26 is as follows: 2,6-di-tert-butyl-4-(1-(4-(tert-butyl)phenyl)-2,2,2-trifluoroethyl)phenol (26)

[0154]

[0155] Synthesis process of Compound 26: Add o-aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2-trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) into a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction is complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10), extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary evaporate. Without further treatment, directly add the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p-QMs (0.2 mmol, 1.0 equiv, 70.1 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) into a 10 mL sealed tube. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction is completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 200 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 240 mL) by column chromatography to obtain 70.1 mg of a colorless oil, with a yield of 83%. 1 H NMR (400 MHz, Chloroform-d) δ 7.44–7.32 (m, 4H), 7.20 (s, 2H), 5.21 (s, 1H), 4.55 (q, J = 10.3 Hz, 1H), 1.44 (s, 18H), 1.33 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 153.5, 150.7, 136.0, 133.1, 128.8, 126.7 (q, J C-F =281.7 Hz), 126.3, 125.9, 125.7, 55.3 (q, J C-F =27.4 Hz), 34.6, 34.5, 31.4, 30.4. 19 F NMR (376 MHz, Chloroform-d) δ -66.0. HRMS (ESI) m / z: [M+H] + calcd for C 26 H 36 F3O 421.2713, found 421.2706.

[0156] Example 27

[0157] The content of Compound 27 is as follows: 2,6 - di - tert - butyl - 4 - (1 - (4 - chlorophenyl) - 2,2,2 - trifluoroethyl)phenol(27)

[0158]

[0159] Synthesis process of Compound 27: o - aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2 - trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and absolute ethanol (5 mL) were added to a 10 - mL round - bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary - evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p - QMs (0.2 mmol, 1.0 equiv, 65.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 - mL sealed tube in one - pot. Under nitrogen protection, irradiate with a 40 - W blue - light LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary - evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 200 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 200 mL) by column chromatography to obtain 58.1 mg of a colorless oil, with a yield of 73%. 1 H NMR (400 MHz, Chloroform - d) δ 7.33 (s, 4H), 7.12 (s, 2H), 5.24 (s, 1H), 4.56 (q, J = 10.0 Hz, 1H), 1.42 (s, 18H). 13 C NMR (101 MHz, Chloroform - d) δ 153.7, 136.2, 134.7, 133.8, 130.5, 128.9, 126.4 (q, J C-F = 60.3 Hz), 125.8, 55.0 (q, J C-F = 27.5 Hz), 34.5, 30.3. 19 F NMR (376 MHz, Chloroform - d) δ - 66.1. HRMS (ESI) m / z: [M + H] + calcd for C 22 H 27ClF3O 399.1697, found 399.1702.

[0160] Example 28

[0161] The content of Compound 28 is as follows: 2,6 - di - tert - butyl - 4-(1-(3 - chlorophenyl)-2,2,2 - trifluoroethyl)phenol (28)

[0162]

[0163] Synthesis process of Compound 28: o - aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2 - trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 - mL round - bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary - evaporate. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p - QMs (0.2 mmol, 1.0 equiv, 65.8 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 - mL sealed tube in one - pot. Under nitrogen protection, irradiate with a 40 - W blue - light LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, and rotary - evaporate. First, elute with petroleum ether:ethyl acetate = 50:1 for about 200 mL, then change to elute with petroleum ether:ethyl acetate = 10:1 (about 210 mL) by column chromatography to obtain 60.5 mg of a colorless oil, with a yield of 76%. 1 H NMR (400 MHz, Chloroform - d) δ 7.39 (s, 1H), 7.36–7.27 (m, 3H), 7.14 (s, 2H), 5.25 (s, 1H), 4.55 (q, J = 9.9 Hz, 1H), 1.43 (s, 18H). 13 C NMR (101 MHz, Chloroform - d) δ 153.8, 138.1, 136.2, 134.6, 130.0, 129.5, 128.1, 127.2, 126.3 (q, J C-F = 281.8 Hz), 125.9, 125.3, 55.3 (q, J C-F = 27.7 Hz), 34.5, 30.3. 1919F NMR (376 MHz, Chloroform-d) δ -66.0. HRMS (ESI) m / z:

[0164] [M+H] + calcd for C 22 H 27 ClF3O 399.1697, found 399.1692.

[0165] Example 29

[0166] The content of compound 29 is as follows: 4-(1-(3-bromophenyl)-2,2,2-trifluoroethyl)-2,6-di-tert-butylphenol (29)

[0167]

[0168] Synthesis process of compound 29: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2-trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time, stirred at 80 °C for 24 h. After the reaction was complete, it was cooled to room temperature, and the reaction solution was poured into ice water (V:V = 1:10). The organic layer was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p-QMs (0.2 mmol, 1.0 equiv, 74.7 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, it was irradiated with a 40 W blue LED (λ = 456 nm) and stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was poured into ice water, and the organic layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated by rotary evaporation. First, it was eluted with petroleum ether:ethyl acetate = 50:1 for about 200 mL, and then changed to elute with petroleum ether:ethyl acetate = 10:1 (about 220 mL) by column chromatography to obtain 59.9 mg of a colorless oil, with a yield of 68%. 1 1H NMR (400 MHz, Chloroform-d) δ 7.48 (d, J = 8.5 Hz, 2H), 7.27–7.24 (m, 2H), 7.10 (s, 2H), 5.23 (s, 1H), 4.53 (q, J = 10.0 Hz, 1H), 1.41 (s, 18H). 1313C NMR (101 MHz, Chloroform-d) δ 153.7, 136.2, 135.2, 131.9, 130.9, 126.3 (q, J C-F = 281.7 Hz), 125.8, 122.0, 55.1 (q, J C-F = 27.7 Hz), 34.5, 30.3. 19 19F NMR (376 MHz, Chloroform-d) δ -66.1. HRMS (ESI) m / z: [M+H] + calcd for C 22 H 27 BrF3O 443.1192, found 443.1201.

[0169] Example 30

[0170] The content of Compound 30 is as follows: 2,6-di-tert-butyl-4-(2,2,2-trifluoro-1-(o-tolyl)ethyl)phenol (30)

[0171]

[0172] Synthesis process of Compound 30: o-Aminobenzamide (0.3 mmol, 40.8 mg), 2,2,2-trifluoroacetophenone (0.3 mmol, 52.2 mg), I2 (10 mol% [10% of 0.3 mmol], 8 mg), and anhydrous ethanol (5 mL) were added to a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction was complete, let it cool to room temperature. Pour the reaction solution into ice water (V:V = 1:10). Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. Without further treatment, the crude product (0.3 mmol, 1.5 equiv, 87.7 mg), p-QMs (0.2 mmol, 1.0 equiv, 61.7 mg), 4CzIPN (2 mol%, 15.8 mg), and anhydrous DMF (2 mL) were added to a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED (λ = 456 nm) and stir at room temperature for 24 h. After the reaction was completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to dryness. First, elute with petroleum ether:ethyl acetate = 50:1 for about 200 mL, and then change to elute with petroleum ether:ethyl acetate = 10:1 (about 220 mL) by column chromatography to obtain 59.8 mg of a colorless oil, with a yield of 79%. 11H NMR (500 MHz, Chloroform-d) δ 7.57 (d, J = 7.8 Hz, 1H), 7.26 - 7.22 (m, 1H), 7.21 - 7.14 (m, 2H), 7.11 (s, 2H), 5.18 (s, 1H), 4.79 (q, J = 10.2 Hz, 1H), 2.30 (s, 3H), 1.39 (s, 18H). 13 13C NMR (126 MHz, Chloroform-d) δ 153.5, 136.7, 135.9, 134.7, 131.0, 127.7, 126.8 (q, J C-F = 281.2 Hz), 126.3, 126.3, 125.5, 51.0 (q, J C-F = 27.1 Hz), 34.5, 30.4, 20.3. 19 19F NMR (376 MHz, Chloroform-d) δ -65.2. HRMS (ESI) m / z: [M+H] + calcd for C 23 H 30 F3O 379.2243, found 379.2251. The compounds of Examples 1 to 30 were subjected to pharmacological activity experiments:

[0173] CCK8 anti-tumor activity test:

[0174] Logarithmically growing HCT-116 cells, SW-480 cells, and Caco-2 cells were trypsinized and counted. The cell density was 2000 cells / well and they were evenly seeded in a 96-well plate. They were incubated at 37 °C and 5% CO2 for 24 h. The culture medium was removed, and then a drug-containing medium at 0.5 μmol / L was added. An experimental group and a control group (5-fluorouracil) were set up, with 4 replicate wells in each group. After adding the drug, incubation was continued for 24 h. After the incubation ended, 10 μL of CCK8 solution was added to each well and incubated for 3 h. Then, the absorbance value of each well was measured at a wavelength of 450 nm using an enzyme-linked immunosorbent assay reader. The cell viability of Compounds 1 - 30 was calculated based on the absorbance and the IC 50 value was calculated. The calculation results are shown in Table 1 below.

[0175] Table 1 IC 50 values

[0176]

[0177]

[0178]

[0179] Conclusion:

[0180] From the CCK8 data, we know that compounds 1 - 30 have good inhibitory effects on colon cancer cells (HCT - 116 cells, SW - 480 cells, Caco - 2 cells).

[0181] For the inhibitory effect on HCT - 116 cells, the IC of compounds 1 - 20 50 is between 79.64 - 172.34 μM, and the IC of compounds 21 - 24 50 is between 45.08 - 63.57 μM, and the IC of compounds 25 - 30 50 is between 9.73 - 46.35 μM. The anti - tumor activity of compounds 21 - 30 is significantly better than that of compounds 1 - 20.

[0182] For the inhibitory effect on SW480 cells, the IC of compounds 1 - 20 50 is between 51.98 - 149.62 μM, and the IC of compounds 21 - 24 50 is between 15.46 - 31.00 μM, and the IC of compounds 25 - 30 50 is between 10.11 - 35.21 μM. The anti - tumor activity of compounds 21 - 30 is significantly better than that of compounds 1 - 20, and the inhibitory effect of this kind of compounds on SW480 cells is stronger than that on HCT - 116 cells.

[0183] For the inhibitory effect on Caco - 2 cells, the IC of compounds 1 - 20 50 is between 40.64 - 135.42 μM, and the IC of compounds 21 - 24 50 is between 9.62 - 19.51 μM, and the IC of compounds 25 - 30 50 is between 4.90 - 17.72 μM. The anti - tumor activity of compounds 21 - 30 is significantly better than that of compounds 1 - 20. Therefore, the inhibitory effects of compounds 21 - 30 on HCT - 116 cells, SW - 480 cells, and Caco - 2 cells are stronger than those of compounds 1 - 20, which indicates that the substitution of benzyl trifluoromethyl and difluoromethyl is more active than benzoyl substitution.

[0184] The inhibition of compounds 1 - 30 on Caco - 2 cells is generally stronger than that on HCT - 116 cells and SW - 480 cells. Among them, compound 29 (IC 50 = 4.90 μM, 9.73 μM) has a stronger inhibitory effect on Caco - 2 cells and HCT - 116 cells than the positive drug 5 - fluorouracil, and the inhibitory effect of compound 29 (IC 50 = 10.11 μM) on SW480 cells is equivalent to that of the positive drug 5 - fluorouracil.

[0185] Use of a benzyl benzoyl or fluoroalkane-substituted phenol compound in the preparation of an anti-colorectal cancer drug.

[0186] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A benzyl benzoyl or fluoroalkane-substituted phenol compound, characterized in that, Molecular formula: Among them, R 1 includes a benzyl benzoyl group or a fluoroalkyl group; R 2 including phenyl, any one of 2. The benzyl benzoyl or fluoroalkane-substituted phenol compound according to claim 1, characterized in that, The benzyl benzoyl group includes Any one of Bn groups.

3. A benzyl benzoyl or fluoroalkane-substituted phenol compound according to claim 1, characterized in that, The fluoroalkyl group includes 4. A benzyl benzoyl or fluoroalkane-substituted phenol compound according to claim 1, characterized in that, including the following compounds 1 to 30:

5. A method for synthesizing a benzyl benzoyl or fluoroalkane-substituted phenol compound according to any one of claims 1 to 4, characterized in that, including the following steps: Step 1: Add 0.3 mmol of o-aminobenzamide, 0.3 mmol of ketone, 10 mol% of I2, and 5 mL of anhydrous ethanol into a 10 mL round-bottom flask at one time. Stir at 80 °C for 24 h. After the reaction is complete, let it cool to room temperature. Pour the reaction solution into ice water. The volume ratio of the reaction solution to ice water is 1:

10. Extract with ethyl acetate, wash the organic layer with saturated brine, dry over anhydrous Na2SO4, and rotary evaporate to obtain the crude product. Step 2: Without treatment, directly add 0.3 mmol, 1.5 equiv of the crude product, 0.2 mmol, 1.0 equiv of p-QMs, 2 mol% of 4CzIPN, and 2 mL of anhydrous DMF into a 10 mL sealed tube in one pot. Under nitrogen protection, irradiate with a 40 W blue LED, λ = 456 nm, and stir at room temperature for 24 h; after the reaction is completed, pour the reaction solution into ice water, extract with ethyl acetate, combine the organic layers, wash the organic layers with saturated brine, dry over anhydrous Na2SO4, rotary evaporate, and then perform silica gel column chromatography separation with mobile phases prepared from petroleum ether and ethyl acetate with different volume ratios to obtain benzyl benzoyl group or fluorinated alkane-substituted phenol compounds.

6. The synthesis method according to claim 5, wherein In Step 1, the ketone includes any one of benzil, 4,4'-dimethylbenzil, 4,4'-diisopropylbenzil, 4,4'-di-tert-butylbenzil, 4,4'-dimethoxybenzil, 4,4'-dichlorobenzil, 3,3'-dimethoxybenzil, 3,3'-dichlorobenzil, 2,2'-dimethylbenzil, 1,2-bis(3,4-dimethoxyphenyl)ethane-1,2-dione, 2,2-difluoroacetophenone, 2,2,2-trifluoroacetophenone, and acetophenone.

7. The synthesis method according to claim 5, characterized in that, In Step 3, the mobile phase includes petroleum ether:ethyl acetate = 5:1, petroleum ether:ethyl acetate = 10:1, or petroleum ether:ethyl acetate = 50:1 - 10:

1.

8. Use of a benzyl benzoyl group or fluorinated alkane-substituted phenol compound according to any one of claims 1 to 4 in the preparation of an anti-colorectal cancer drug.

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