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 1M of absolute ethyl alcohol into a 100mL 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 the volume ratio of the reaction solution to the ice water being 10: 1, 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 invention relates to a phenol compound substituted with a benzyl benzoyl or a fluoroalkane, a synthesis method and application thereof, and belongs to the technical field of drug synthesis. Background Art

[0002] Phenol compounds substituted with benzyl benzoyl or fluoroalkane play an important role in organic chemistry and are widely used in drug synthesis, material science, and fine chemicals. Due to their specific structures and properties, these compounds exhibit unique activity and selectivity in chemical reactions, making them important objects of chemical research.

[0003] However, the existing synthesis methods of phenolic compounds substituted with benzyl benzoyl or fluoroalkane have many side reactions, complicated reaction steps, and require multiple steps for preparation. In addition, there is no application of phenolic compounds substituted with benzyl benzoyl or fluoroalkane in the treatment of colon cancer in the prior art. Summary of the invention

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

[0005] At the same time, the present invention provides a method for synthesizing a phenol compound substituted with a benzyl benzoyl or a fluoroalkane, and the synthesis method has mild conditions, few side reactions, and is simple and convenient to operate.

[0006] At the same time, the present invention provides an application of a phenol compound substituted with a benzyl benzoyl or a fluoroalkane in the preparation of an anti-colon cancer drug.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is:

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

[0009]

[0010] Among them, R 1 including benzyl benzoyl or fluoroalkyl;

[0011] R 2 Including phenyl,

[0012] Any one of .

[0013] Preferably, the benzyl benzoyl group includes

[0014]

[0015] Any one of the Bn groups.

[0016] Preferably, the fluoroalkane group comprises

[0017] Preferably, a phenol compound substituted with a benzyl benzoyl or a fluoroalkane includes the following compounds 1 to 30:

[0018]

[0019] A method for synthesizing a phenol compound substituted with a benzyl benzoyl or a fluoroalkane, comprising the following steps:

[0020] Step 1: 0.3 mmol of o-aminobenzamide, 0.3 mmol of ketone, 10 mol% of I 2 and 1M anhydrous ethanol were added into a 100 mL round-bottom flask at once, stirred at 80 °C for 24 h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water, the volume ratio of the reaction solution to ice water was 10:1, extracted with ethyl acetate, the organic layer was washed with saturated brine, and anhydrous Na 2 SO 4 Dry and spin dry to obtain a crude product;

[0021] Step 2: 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 were added to a 10 mL sealed tube in one pot without treatment, and irradiated with a 40 W blue LED, λ = 456 nm, under nitrogen protection, and stirred at room temperature for 24 h;

[0022] Step 3: After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, the organic layers are combined, washed with saturated brine, and then added to anhydrous Na 2 SO 4 The product is dried and spin-dried, and then separated by a silica gel column using mobile phases of petroleum ether and ethyl acetate in different volume ratios to obtain phenol compounds substituted with benzyl benzoyl or fluoroalkane.

[0023] 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 diphenylacetophenone.

[0024] Preferably, in step three, the mobile phase comprises petroleum ether:ethyl acetate=5:1, petroleum ether:ethyl acetate=10:1 or petroleum ether:ethyl acetate=50:1.

[0025] The invention discloses an application of a phenol compound substituted with a benzyl benzoyl or a fluoroalkane in the preparation of an anti-colon cancer drug.

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] The synthesis method of the invention has mild reaction conditions, few side reactions, and is simple and convenient to operate. In addition, the phenolic compounds substituted with benzyl benzoyl or fluoroalkane obtained by the invention have the effect of resisting colon cancer.

[0028] The present invention applies 40W blue light (λ=456nm) to the synthesis of phenolic compounds substituted with benzyl benzoyl or fluoroalkane, so that the synthesis route has the characteristics of high efficiency, mild reaction conditions, few side reactions, simple and convenient operation, etc. DETAILED DESCRIPTION

[0029] The present invention will be further described in detail below in conjunction with specific examples. The following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0030] Example 1

[0031] A phenol compound substituted with a benzyl benzoyl or fluoroalkane, wherein the content of compound 1 is as follows:

[0032] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,2-diphenylethan-1-one(1) 3

[0033]

[0034] Compound 1 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), benzil (0.3mmol, 63.01mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 98.49mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate (10:1) to obtain 72.8 mg (91%) of a white solid, Mp = 91-93°C.

[0035] 1 H NMR(500MHz,Chloroform-d)δ8.04–7.98(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).

[0036] 13 C NMR (126MHz, Chloroform-d) δ199.0,153.0,139.9,137.4,136.0,132.9,129.6,129.2,129.0,128.8,128.7,127.0,126.0,59.4,34.5,30.4.

[0037] HRMS(ESI)m / z:[M+Na] + Calculate for C 28 H 32 NaO 2 423.2295, found 423.2303. Example 2

[0038] The content of compound 2 is as follows:

[0039] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenyl-1-(p-tolyl)ethan-1-one(2) 3

[0040]

[0041] Compound 2 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 4,4'-dimethylbenzil (0.3mmol, 71.48mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 106.93mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 72.1 mg of a white solid (87%), Mp = 167-169°C.

[0042] 1 H NMR(500MHz,Chloroform-d)δ7.92(d,J=8.3Hz,2H),7.30(d,J=4.4Hz,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).

[0043] 13 C NMR (126MHz, Chloroform-d) δ198.5,152.9,143.7,140.0,135.9,134.8,129.7,129.4,129.2,128.7,127.0,126.0,59.2,34.5,30.4,21.7.

[0044] HRMS(ESI)m / z:[M+Na] + Calculate for C 29 H 34 NaO 2 437.2451, found 437.2443. Example 3

[0045] The content of compound 3 is as follows:

[0046] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(4-isopropylphenyl)-2-phenylethan-1-one(3) 3

[0047]

[0048] Compound 3 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 4,4'-diisopropylbenzil (0.3mmol, 88.32mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 123.76mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 70.8 mg (80%) of a white solid, Mp = 148-150°C.

[0049] 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).

[0050] 13C NMR(126MHz,Chloroform-d)δ198.5,154.4,152.9,140.0,135.9,135.2,129.7,129.3, 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] + Calculate for C 31 H 38 NaO 2 465.2764, found 465.2771. Example 4

[0051] The content of compound 4 is as follows:

[0052] 1-(4-(tert-butyl)phenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one(4) 3

[0053]

[0054] Compound 4 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 4,4'-di-tert-butylbenzil (0.3mmol, 96.74mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 132.18mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried and spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 75.7 mg (83%) of a white solid, Mp = 136-138°C.

[0055] 1H NMR(500MHz,Chloroform-d)δ8.08–7.83(m,2H),7.46–7.38(m,2H),7.31(d,J=4.5Hz,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).

[0056] 13 C NMR(126MHz,Chloroform-d)δ198.5,156.6,153.0,140.0,135.9,134.7,129.7,129.2, 129.0,128.7,127.0,126.0,125.7,59.3,35.2,34.5,31.2,30.4.HRMS(ESI)m / z:[M+Na] + Calculate for C 32 H 40 NaO 2 479.2921, found 479.2924. Example 5

[0057] The content of compound 5 is as follows:

[0058] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(4-methoxyphenyl)-2-phenylethan-1-on e(5) 3

[0059]

[0060] Compound 5 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 4,4'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 108.12mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried and spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 73.1 mg (85%) of a white solid, Mp = 156-158°C.

[0061] 1 H NMR(500MHz,Chloroform-d)δ8.03–7.98(m,2H),7.35–7.26(m,4H),7.24–7.20(m,1H),7.0 9–7.04(m,2H),6.88(d,J=8.7Hz,2H),5.91(s,1H),5.11(s,1H),3.81(s,3H),1.38(s,18H).

[0062] 13 C NMR (126MHz, Chloroform-d) δ197.5,163.4,152.9,140.2,135.9,131.4,130.3,129.9,129.2,128.7,126.9,126.0,113.8,59.0,55.5,34.5,30.4.

[0063] HRMS(ESI)m / z:[M+H] + Calculate for C 29 H 35 O 3 431.2581, found 431.2590.

[0064] Example 6

[0065] The content of compound 6 is as follows:

[0066] 1-(4-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one(6) 3

[0067]

[0068] Compound 6 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 4,4'-dichlorobenzil (0.3mmol, 88.74mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 119.18mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 66.0 mg (76%) of a white solid, Mp = 152-154°C.

[0069] 1 H NMR(500MHz,Chloroform-d)δ7.93(d,J=8.6Hz,2H),7.37(d,J=8.6Hz,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).

[0070] 13 C NMR (126MHz, Chloroform-d) δ197.8,153.1,139.5,139.3,136.1,135.6,130.5,129.2,129.1,129.0,128.8,127.2,125.9,59.5,34.5,30.4.

[0071] HRMS(ESI)m / z:[M+Na] + Calculate for C 28 H 31 ClNaO 2 457.1905, found 457.1913. Example 7

[0072] The content of compound 7 is as follows:

[0073] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-phenylethan-1-on e(7) 4

[0074]

[0075] Compound 7 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 108.13mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 74.0 mg (86%) of a white solid, Mp = 108-110°C.

[0076] 1 H NMR(500MHz,Chloroform-d)δ7.60(d,J=7.7Hz,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=8.1,2.6Hz,1H),5.92(s,1H),5.13(s,1H),3.79(s,3H),1.38(s,18H).

[0077] 13C NMR(126MHz,Chloroform-d)δ198.8,159.8,153.0,139.8,138.7,136.0,129.6,129.5,129 .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] + Calculate for C 29 H 35 O 3 431.2581, found 431.2573.

[0078] Example 8

[0079] The content of compound 8 is as follows:

[0080] 1-(3-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one(8)

[0081]

[0082] Compound 8 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dichlorobenzil (0.3mmol, 83.74mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 119.18mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 67.7 mg (78%) of a white solid, Mp = 142-144°C.

[0083] 1H NMR(500MHz,Chloroform-d)δ8.04–7.92(m,1H),7.86(d,J=8.1Hz,1H),7.51–7.4 2(m,1H),7.38–7.23(m,6H),7.05(s,2H),5.86(s,1H),5.15(s,1H),1.39(s,18H).

[0084] 13 C NMR (126MHz, Chloroform-d) δ197.7,153.2,139.3,138.9,136.2,134.9,132.8,130.0,129.1,129.0,128.9,127.2,127.1,125.9,59.7,34.5,30.4.

[0085] HRMS(ESI)m / z:[M+Na] + Calculate for C 28 H 31 ClNaO 2 457.1905, found 457.1900. Example 9

[0086] The content of compound 9 is as follows:

[0087] 1-(3-bromophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenylethan-1-one(9)

[0088]

[0089] Compound 9 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dibromobenzil (0.3mmol, 110.41mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 145.85mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 73.6 mg (77%) of a white solid, Mp = 158-160°C.

[0090] 1 H NMR(500MHz,Chloroform-d)δ8.12(t,J=1.8Hz,1H),7.94–7.87(m,1H),7.67–7.5 9(m,1H),7.34–7.25(m,6H),7.05(s,2H),5.86(s,1H),5.15(s,1H),1.39(s,18H).

[0091] 13 C NMR(126MHz,Chloroform-d)δ197.6,153.2,139.3,139.1,136.2,135.8,132.1,130.3,1 29.1,129.0,128.9,127.6,127.2,126.0,123.0,59.6,34.5,30.4.HRMS(ESI)m / z:[M+H] + Calculate for C 30 H 37 O 4 461.2686, found 461.2694

[0092] Example 10

[0093] The content of compound 10 is as follows:

[0094] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenyl-1-(o-tolyl)ethan-1-one(10)

[0095]

[0096] Compound 10 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2'-dimethylbenzil (0.3mmol, 71.52mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 106.93mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 73.6 mg (89%) of a white solid, Mp = 168-170°C.

[0097] 1 H NMR(500MHz,Chloroform-d)δ7.68–7.62(m,1H),7.33(d,J=4.4Hz,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).

[0098] 13 C NMR(126MHz,Chloroform-d)δ203.0,153.0,139.5,139.2,138.3,136.0,131.8,131.0,129. 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] + Calculate for C 29 H 34 NaO 2 437.2451, found 437.2443. Example 11

[0099] The content of compound 11 is as follows:

[0100] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3,4-dimethoxyphenyl)-2-phenylethan-1-one(11)

[0101]

[0102] Synthesis process of compound 11: o-aminobenzamide (0.3 mmol, 40.85 mg), 1,2-bis(3,4-dimethoxyphenyl)ethane-1,2-dione (0.3 mmol, 99.10 mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 146.54mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 84.7 mg (92%) of a white solid, Mp = 174-176°C.

[0103] 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).

[0104] 13C 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.

[0105] HRMS(ESI)m / z:[M+Na] + Calculate for C 30 H 36 NaO 4 483.2506, found 483.2513. Example 12

[0106] The content of compound 12 is as follows:

[0107] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(p-tolyl)ethan-1-one(12)

[0108]

[0109] Compound 12 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 61.70mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 72.9 mg (82%) of a white solid, Mp = 181-183°C.

[0110] 1 H NMR(500MHz,Chloroform-d)δ7.59(dt,J=7.7,1.3Hz,1H),7.52(dd,J=2.7,1.6Hz,1H),7.29(t,J=8.0Hz,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).

[0111] 13 C NMR(126MHz,Chloroform-d)δ198.9,159.8,153.0,138.8,136.8,136.6,135.9,129 .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.

[0112] HRMS(ESI)m / z:[M+H] + Calculate for C 30 H 37 O 3 445.2737, found 445.2730.

[0113] Embodiment 13

[0114] The content of compound 13 is as follows:

[0115] 2-(4-(tert-butyl)phenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphe nyl)ethan-1-one(13)

[0116]

[0117]

[0118] Synthesis process of compound 13: o-aminobenzamide (0.3 mmol, 40.85 mg), 3,3'-dimethoxybenzil (0.3 mmol, 81.10 mg), I 2(10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 70.11mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 5:1 to obtain 78.8 mg (81%) of a white solid, Mp = 184-186°C.

[0119] 1 H NMR(400MHz,Chloroform-d)δ7.61(d,J=7.9Hz,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=8.2,2.6Hz,1H),5.88(s,1H),5.12(s,1H),3.79(s,3H),1.39(s,18H),1.28(s,9H).

[0120] 13 C NMR(101MHz,Chloroform-d)δ198.9,159.8,153.0,149.8,138.8,136.8,136.0,129.6,128 .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] + Calculate for C 33 H 43 O 3 487.3207, found 487.3216.

[0121] Embodiment 14

[0122] The content of compound 14 is as follows:

[0123] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(4-methoxypheny l)ethan-1-one(14)

[0124]

[0125] Compound 14 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 70.11mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 5:1 to obtain 70.0 mg (76%) of a white solid, Mp = 180-182°C.

[0126] 1 H NMR(500MHz,Chloroform-d)δ7.62–7.57(m,1H),7.55–7.50(m,1H),7.30(t,J=8.0Hz,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).

[0127] 13C NMR(126MHz,Chloroform-d)δ199.0,159.8,158.6,152.9,138.7,135.9,131.9,130 .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.

[0128] HRMS(ESI)m / z:[M+Na] + Calculate for C 30 H 36 NaO 4 483.2506, found 483.2511. Example 15

[0129] The content of compound 15 is as follows:

[0130] 2-([1,1'-biphenyl]-4-yl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphe nyl)ethan-1-one(15)

[0131]

[0132] Compound 15 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 74.11mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried and spin-dried, and separated by column chromatography with petroleum ether:ethyl acetate = 5:1 to obtain 89.1 mg (88%) of a white solid, Mp = 186-188°C.

[0133] 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).

[0134] 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.

[0135] HRMS(ESI)m / z:[M+Na] + Calculate for C 35 H 38 NaO 3 529.2713, found 529.2706. Example 16

[0136] The content of compound 16 is as follows:

[0137] 2-(4-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one(16)

[0138]

[0139] Compound 16 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 65.78mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 67.8 mg (73%) of a white solid, Mp = 182-184°C.

[0140] 1 H NMR(500MHz,Chloroform-d)δ7.57(d,J=7.8Hz,1H),7.51(s,1H),7.34–7.26(m,3H),7.2 4–7.20(m,2H),7.08–7.02(m,3H),5.88(s,1H),5.16(s,1H),3.79(s,3H),1.38(s,18H).

[0141] 13 C NMR(126MHz,Chloroform-d)δ198.4,159.9,153.2,138.5,138.5,136.2,132.9,130.5,129. 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] + Calculate for C 29 H 33 ClNaO 3 487.2010, found 487.2019. Example 17

[0142] The content of compound 17 is as follows:

[0143] 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)-2-(3-phenoxypheny l)ethan-1-one(17)

[0144]

[0145] Compound 17 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 77.31mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried and spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 75.2 mg (72%) of a white solid, Mp = 188-190°C.

[0146] 1 H NMR(500MHz,Chloroform-d)δ7.58(d,J=7.8Hz,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=8.2,2.1Hz,1H),5.88(s,1H),5.13(s,1H),3.79(s,3H),1.38(s,18H).

[0147] 13 C NMR(126MHz,Chloroform-d)δ198.3,159.8,157.4,157.2,153.1,141.8,138.5,136.0,129.9,129.8, 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.

[0148] HRMS(ESI)m / z:[M+Na] + Calculate for C 35 H38 NaO 4 545.2662, found 545.2670. Example 18

[0149] The content of compound 18 is as follows:

[0150] 2-(3-chlorophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one(18)

[0151]

[0152] Compound 18 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 65.78mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The product was dried and spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 74.3 mg (80%) of a white solid, Mp = 171-173°C.

[0153] 1 H NMR(500MHz,Chloroform-d)δ7.60–7.55(m,1H),7.53–7.49(m,1H),7.33(t,J=7.9Hz,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). 13C NMR(126MHz,Chloroform-d)δ198.1,159.9,153.3,141.9,138.4,136.3,134.5,129.9, 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.

[0154] HRMS(ESI)m / z:[M+H] + Calculate for C 29 H 34 C1O 3 465.2191, found 465.2184.

[0155] Embodiment 19

[0156] The content of compound 19 is as follows:

[0157] 2-(3-bromophenyl)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-(3-methoxyphenyl)ethan-1-one(19)

[0158]

[0159] Compound 19 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 3,3'-dimethoxybenzil (0.3mmol, 81.10mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 116.53mg), p-QMs (0.2mmol, 1.0equiv, 74.67mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. 2 SO 4The product was dried, spin-dried, and separated by column chromatography using petroleum ether:ethyl acetate = 10:1 to obtain 76.2 mg (75%) of a white solid, Mp = 178-180°C.

[0160] 1 H NMR(400MHz,Chloroform-d)δ7.57(d,J=7.7Hz,1H),7.53–7.48(m,1H),7.43(d,J=8.4Hz,2H),7.31(t,J=8.0Hz,1H),7.16(d,J=8.3Hz,2H),7.08–

[0161] 6.99(m,3H),5.87(s,1H),5.16(s,1H),3.79(s,3H),1.38(s,18H).

[0162] 13 C NMR(101MHz,Chloroform-d)δ198.3,159.8,153.2,139.0,138.4,136.2,131.8,130.9,129. 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] + Calculate for C 29 H 33 BrNaO 3 531.1505, found 531.1513. Example 20

[0163] The content of compound 20 is as follows:

[0164] 2,6-di-tert-butyl-4-(1,2-diphenylethyl)phenol(20) 7

[0165]

[0166] Compound 20 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), diphenylacetone (0.3mmol, 58.87mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 59.5 mg of a colorless oil, 77%.

[0167] 1 H NMR(400MHz,Chloroform-d)δ7.28–7.20(m,4H),7.19–7.05(m,4H),7.03–6.9 0(m,4H),5.01(s,1H),4.11(t,J=7.8Hz,1H),3.37–3.21(m,2H),1.36(s,18H).

[0168] 13 C NMR (101MHz, Chloroform-d) δ152.1,144.9,140.9,135.5,135.2,129.3,128.3,128.3,128.1,126.1,125.8,124.6,53.4,43.1,34.5,30.4.

[0169] HRMS(ESI)m / z:[M+Na] + Calculate for C 28 H 34 NaO 409.2502, found 409.2511.

[0170] Embodiment 21

[0171] The content of compound 21 is as follows:

[0172] 2,6-di-tert-butyl-4-(2,2-difluoro-1-phenylethyl)phenol(21) 5

[0173]

[0174] Synthesis process of compound 21: o-aminobenzamide (0.3 mmol, 40.85 mg), 2,2-difluoroacetophenone (0.3 mmol, 46.84 mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 90.68mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The solution was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain a yellow oil (53.3 mg, 77%).

[0175] 1 H NMR(500MHz,Chloroform-d)δ7.38–7.30(m,4H),7.29–7.25(m,1H),7.09(s,2H),6. 25(td,J=56.1,4.4Hz,1H),5.16(s,1H),4.30(td,J=16.2,4.4Hz,1H),1.41(s,18H).

[0176] 13 C NMR(126MHz,Chloroform-d)δ153.2,137.8,136.0,129.2,128.7,127.8,127.4,125.8,117.4(t,J C-F =244.5Hz),55.2(t,J C-F =20.4Hz),34.5,30.4.

[0177] 19 F NMR (471MHz, Chloroform-d) δ -117.2 (d, J = 276.9Hz), -118.2 (d, J = 277.5Hz).

[0178] HRMS(ESI)m / z:[M+H] +Calculate for C 22 H 29 F 2 O 347.2181, found 347.2188.

[0179] Embodiment 22

[0180] The content of compound 22 is as follows:

[0181] 4-(1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2,2-difluoroethyl)benzonitrile(22) 5

[0182]

[0183] Compound 22 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2-difluoroacetophenone (0.3mmol, 46.84mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 90.68mg), p-QMs (0.2mmol, 1.0equiv, 63.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 52.0 mg of a yellow oil, 70%.

[0184] 1 H NMR(400MHz,Chloroform-d)δ7.64(d,J=8.4Hz,2H),7.44(d,J=8.1Hz,2H),7.04(s ,2H),6.26(td,J=55.7,3.9Hz,1H),5.24(s,1H),4.50–4.27(m,1H),1.41(s,18H).

[0185] 13 C NMR(101MHz,Chloroform-d)δ153.6,143.0,136.5,132.4,130.2,126.4(q,J C-F =2.7Hz),125.6,118.8,116.7(t,J C-F =246.1Hz),111.4,55.0(t,J C-F =20.7Hz),34.5,30.3.

[0186] 19 F NMR(376MHz,Chloroform-d)δ-116.1(d,J=279.3Hz),-119.6(d,J=279.0Hz)

[0187] HRMS(ESI)m / z:[M+H] + Calculate for C 23 H 28 F 2 NO 372.2133, found 372.2128. Example 23

[0188] The content of compound 23 is as follows:

[0189] 2,6-di-tert-butyl-4-(1-(4-(tert-butyl)phenyl)-2,2-difluoroethyl)phenol(23)

[0190]

[0191]

[0192] Compound 23 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2-difluoroacetophenone (0.3mmol, 46.84mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 90.68mg), p-QMs (0.2mmol, 1.0equiv, 70.11mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 67.6 mg of a yellow oil, 84%.

[0193] 1 H NMR(400MHz,Chloroform-d)δ7.35(d,J=8.3Hz,2H),7.30–7.24(m,2H),7.11(s,2H),6.23(t d,J=56.2,4.4Hz,1H),5.15(s,1H),4.26(td,J=16.3,4.4Hz,1H),1.41(s,18H),1.30(s,9H).

[0194] 13 C NMR(101MHz,Chloroform-d)δ153.2,150.2,136.0,134.6(t,J C-F =3.3Hz),128.8,127.9(t,J C-F =3.7Hz),125.8,125.6,117.6(t,J C-F =245.3Hz),54.9(t,J C-F =20.4Hz),34.5,31.5,30.4.

[0195] 19 F NMR(376MHz,Chloroform-d)δ-116.9(d,J=275.6Hz),-118.3(d,J=275.6Hz)

[0196] HRMS(ESI)m / z:[M+H] + Calculate for C 26 H 37 F 2 O 403.2807, found 403.2813.

[0197] Embodiment 24

[0198] The content of compound 24 is as follows:

[0199] 4-(1-(3-bromophenyl)-2,2-difluoroethyl)-2,6-di-tert-butylphenol(24)

[0200]

[0201] Compound 24 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2-difluoroacetophenone (0.3mmol, 46.84mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 90.68mg), p-QMs (0.2mmol, 1.0equiv, 74.67mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 70.4 mg of a yellow oil, 83%.

[0202] 1 H NMR(400MHz,Chloroform-d)δ7.48(d,J=8.2Hz,2H),7.21(d,J=8.4Hz,2H),7.07(s,2H),6. 23(td,J=56.0,4.1Hz,1H),5.22(s,1H),4.28(ddd,J=18.4,14.5,4.1Hz,1H),1.43(s,18H).

[0203] 13 C NMR(101MHz,Chloroform-d)δ153.4,136.7(t,J C-F =3.1Hz),136.2,131.8,131.0,127.2(t,J C-F =3.6Hz),125.6,121.5,117.0(t,JC-F =245.7Hz),54.6(t,J C-F =20.7Hz),34.5,30.4.

[0204] 19 F NMR(376MHz,Chloroform-d)δ-116.7(d,J=277.9Hz),-119.1(d,J=277.9Hz)

[0205] HRMS(ESI)m / z:[M+H] + Calculate for C 22 H 28 F 2 O 425.1286, found 425.1291. Example 25

[0206] The content of compound 25 is as follows:

[0207] 2,6-di-tert-butyl-4-(2,2,2-trifluoro-1-phenylethyl)phenol(25) 5

[0208]

[0209] Compound 25 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 58.89mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 64.8 mg of a yellow oil, 89%.

[0210] 1 H NMR(500MHz,Chloroform-d)δ7.45–7.38(m,2H),7.36(t,J=7.5Hz,2H),7.33– 7.29(m,1H),7.17(s,2H),5.21(s,1H),4.58(q,J=10.2Hz,1H),1.42(s,18H).

[0211] 13 C NMR(126MHz,Chloroform-d)δ153.6,136.2,136.0,129.2,128.7,127.8,126.1,125.9,125.5,55.6(q,J C-F =27.6Hz),34.5,30.4.

[0212] HRMS(ESI)m / z:[M+H] + Calculate for C 22 H 28 F 3 O 365.2087, found 365.2080.

[0213] Embodiment 26

[0214] The content of compound 26 is as follows:

[0215] 2,6-di-tert-butyl-4-(1-(4-(tert-butyl)phenyl)-2,2,2-trifluoroethyl)phenol(26) 6

[0216]

[0217] Compound 26 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 70.11mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 70.1 mg, 88% of a colorless oil.

[0218] 1 H NMR (400MHz, Chloroform-d) δ7.44–7.32(m,4H),7.20(s,2H),5.21(s,1H),4.55(q,J=10.3Hz,1H),1.44(s,18H),1.33(s,9H).

[0219] 13 C NMR(101MHz,Chloroform-d)δ153.5,150.7,136.0,133.1,128.8,126.7(q,J C-F =281.7Hz),126.3,125.9,125.7,55.3(q,J C-F =27.4Hz),34.6,34.5,31.4,30.4.

[0220] 19 F NMR(376MHz,Chloroform-d)δ-66.0.

[0221] HRMS(ESI)m / z:[M+H] + Calculate for C 26 H 36 F 3 O 421.2713, found 421.2706.

[0222] Embodiment 27

[0223] The content of compound 27 is as follows:

[0224] 2,6-di-tert-butyl-4-(1-(4-chlorophenyl)-2,2,2-trifluoroethyl)phenol(27) 6

[0225]

[0226] Compound 27 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 65.78mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 58.1 mg of a colorless oil, 73%.

[0227] 1 H NMR (400MHz, Chloroform-d) δ7.33 (s, 4H), 7.12 (s, 2H), 5.24 (s, 1H), 4.56 (q, J = 10.0Hz, 1H), 1.42 (s, 18H).

[0228] 13 C NMR(101MHz,Chloroform-d)δ153.7,136.2,134.7,133.8,130.5,128.9,126.4(q,J C-F =60.3Hz),125.8,55.0(q,J C-F =27.5Hz),34.5,30.3.

[0229] 19 F NMR(376MHz,Chloroform-d)δ-66.1.

[0230] HRMS(ESI)m / z:[M+H] + Calculate for C 22 H27 CIF 3 O 399.1697, found 399.1702. Example 28

[0231] The content of compound 28 is as follows:

[0232] 2,6-di-tert-butyl-4-(1-(3-chlorophenyl)-2,2,2-trifluoroethyl)phenol(28) 5

[0233]

[0234] Compound 28 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 65.78mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 60.5 mg of a colorless oil, 76%.

[0235] 1 H NMR (400MHz, Chloroform-d) δ7.39 (s, 1H), 7.36–7.27 (m, 3H), 7.14 (s, 2H), 5.25 (s, 1H), 4.55 (q, J = 9.9Hz, 1H), 1.43 (s, 18H).

[0236] 13C NMR(101MHz,Chloroform-d)δ153.8,138.1,136.2,134.6,130.0,129.5,128.1,127.2,126.3(q,J C-F =281.8Hz),125.9,125.3,55.3(q,J C-F =27.7Hz),34.5,30.3.

[0237] 19 F NMR(376MHz,Chloroform-d)δ-66.0.

[0238] HRMS(ESI)m / z:[M+H] + Calculate for C 22 H 27 CIF 3 O 399.1697, found 399.1692. Example 29

[0239] The content of compound 29 is as follows:

[0240] 4-(1-(3-bromophenyl)-2,2,2-trifluoroethyl)-2,6-di-tert-butylphenol(29) 6

[0241]

[0242] Compound 29 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg), anhydrous ethanol (1M) were added into a 100mL round-bottom flask at once, stirred at 80℃ for 24h, and after the reaction was complete, cooled to room temperature, the reaction solution was poured into ice water (V:V=10:1), extracted with ethyl acetate, and the organic layer was washed with saturated brine. 2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 74.67mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, and the organic layers are combined, washed with saturated brine, and stirred in anhydrous Na 2 SO4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 59.9 mg of a colorless oil, 71%.

[0243] 1 H NMR (400MHz, Chloroform-d) δ7.48(d,J=8.5Hz,2H),7.27–7.24(m,2H),7.10(s,2H),5.23(s,1H),4.53(q,J=10.0Hz,1H),1.41(s,18H).

[0244] 13 C NMR(101MHz,Chloroform-d)δ153.7,136.2,135.2,131.9,130.9,126.3(q,J C-F =281.7Hz),125.8,122.0,55.1(q,J C-F =27.7Hz),34.5,30.3.

[0245] 19 F NMR(376MHz,Chloroform-d)δ-66.1.

[0246] HRMS(ESI)m / z:[M+H] + Calculate for C 22 H 27 F 3 O 443.1192, found 443.1201. Example 30

[0247] The content of compound 30 is as follows:

[0248] 2,6-di-tert-butyl-4-(2,2,2-trifluoro-1-(o-tolyl)ethyl)phenol(30)

[0249]

[0250] Compound 30 synthesis process: o-aminobenzamide (0.3mmol, 40.85mg), 2,2,2-trifluoroacetophenone (0.3mmol, 52.24mg), I 2 (10mol%, 8mg),.

[0251] Anhydrous ethanol (1M) was added to a 100 mL round-bottom flask at once and stirred at 80 °C for 24 h. After the reaction was complete, the mixture was cooled to room temperature and poured into ice water (V:V = 10:1). The mixture was extracted with ethyl acetate and the organic layer was washed with saturated brine.2 SO 4 Dry, spin dry, and directly add the crude product (0.3mmol, 1.5equiv, 96.08mg), p-QMs (0.2mmol, 1.0equiv, 61.69mg), 4CzIPN (2mol%, 8mg) and anhydrous DMF (2mL) into a 10mL sealed tube in one pot without treatment. Irradiate with a 40W blue LED (λ=456nm) under nitrogen protection and stir at room temperature for 24h. After the reaction, the reaction solution was introduced into ice water, extracted with ethyl acetate, and the organic layers were combined, washed with saturated brine, and stirred in anhydrous Na 2 SO 4 The mixture was dried, spin-dried, and separated by column with petroleum ether:ethyl acetate = 50:1 to obtain 59.8 mg of a colorless oil, 79%.

[0252] 1 H NMR(500MHz,Chloroform-d)δ7.57(d,J=7.8Hz,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=10.2Hz,1H),2.30(s,3H),1.39(s,18H).

[0253] 13 C NMR(126MHz,Chloroform-d)δ153.5,136.7,135.9,134.7,131.0,127.7,126.8(q,J C-F =281.2Hz),126.3,126.3,125.5,51.0(q,J C-F =27.1Hz),34.5,30.4,20.3.

[0254] 19 F NMR(376MHz,Chloroform-d)δ-65.2.

[0255] HRMS(ESI)m / z:[M+H] + Calculate for C 23 H 30 F 3 O 379.2243, found 379.2251.

[0256] The compounds of Examples 1 to 30 were used for pharmacological activity experiments:

[0257] CCK8 anti-tumor activity test:

[0258] Logarithmically growing HCT-116 cells, SW-480 cells, and Caco-2 cells were digested with trypsin and counted. The cell density was 2000 cells / well and the cells were evenly inoculated in a 96-well plate at 37°C and 5% CO. 2 The cells were cultured at a constant temperature for 24 hours under the same conditions, the culture medium was removed, and then 0.5 μmol / L of drug-containing culture medium was added to set up the experimental group, control group (5-fluorouracil), and blank group, with 4 replicate wells in each group. After adding the drug, the cells were incubated for 24 hours. After the incubation, 10 μL of CCK8 solution was added to each well and incubated for 3 hours. The absorbance of each well was measured at a wavelength of 450 nm using an ELISA reader. The cell survival rate of compound 1-30 was calculated based on the absorbance, and the IC 50 The calculation results are shown in Table 1 below.

[0259] Table 1 IC of compounds 50 value

[0260]

[0261]

[0262] in conclusion:

[0263] From the CCK8 data, we can see that compound 1-30 has a good inhibitory effect on colon cancer cells (HCT-116 cells, SW-480 cells, Caco-2 cells).

[0264] Inhibitory effect on HCT-116 cells, IC of compounds 1-20 50 The IC values ​​of compounds 21-24 were between 79.64 and 172.34 μM. 50 The IC values ​​of compounds 25-30 were between 45.08 and 63.57 μM. 50 The anti-tumor activity of compounds 21-30 was significantly better than that of compounds 1-20 at a concentration between 9.73 and 46.35 μM.

[0265] Inhibitory effect on SW480 cells, IC values ​​of compounds 1-20 50 The IC values ​​of compounds 21-24 were between 51.98 and 149.62 μM. 50 The IC values ​​of compounds 25-30 were between 15.46 and 31.00 μM. 50 In the range of 10.11 to 35.21 μM, the antitumor activity of compounds 21-30 was significantly better than that of compounds 1-20, and the inhibitory effect of this type of compounds on SW480 cells was stronger than that on HCT-116 cells.

[0266] Inhibitory effect on Caco-2 cells, IC values ​​of compounds 1-20 50The IC values ​​of compounds 21-24 were between 40.64 and 135.42 μM. 50 The IC values ​​of compounds 25-30 were between 9.62 and 19.51 μM. 50 In the range of 4.90 to 17.72 μM, the antitumor activity of compounds 21-30 was significantly better than that of compounds 1-20. Therefore, the inhibitory effect of compounds 21-30 on HCT-116 cells, SW-480 cells, and Caco-2 cells was stronger than that of compounds 21-30, which indicated that the activity of benzyl trifluoromethyl and difluoromethyl substitution was better than that of benzoyl substitution.

[0267] Compounds 1-30 generally have stronger inhibitory effects on Caco-2 cells than HCT-116 cells and SW-480 cells, among which compound 29 (IC 50 =4.90μM, 9.73μM) had a stronger inhibitory effect on Caco-2 cells and HCT-116 cells than the positive drug 5-fluorouracil (IC 50 =10.11 μM), and the inhibitory effect on SW480 cells was similar to that of the positive drug 5-fluorouracil (IC 50 =9.53 μM).

[0268] The invention discloses an application of a phenol compound substituted with a benzyl benzoyl or a fluoroalkane in the preparation of an anti-colon cancer drug.

[0269] It should be understood that in order to streamline the present disclosure and aid in understanding one or more of the various inventive aspects, in the above description of exemplary embodiments of the present invention, various features of the present invention are sometimes grouped together into a single embodiment, or description thereof. However, this disclosed method should not be interpreted as reflecting the intention that the claimed invention requires more features than those expressly recited in each claim. Rather, as reflected in the claims, inventive aspects lie in less than all of the features of the previously disclosed embodiments. Therefore, the claims that follow the detailed description are hereby expressly incorporated into the detailed description, with each claim itself serving as a separate embodiment of the present invention.

[0270] Although the present invention has been described according to a limited number of embodiments, it will be apparent to those skilled in the art, with the benefit of the above description, that other embodiments may be envisioned within the scope of the invention thus described. In addition, it should be noted that the language used in this specification is selected primarily for readability and teaching purposes, rather than for explaining or defining the subject matter of the present invention. Therefore, many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the appended claims. The disclosure of the present invention is illustrative, not restrictive, with respect to the scope of the present invention, which is defined by the appended claims.

[0271] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A phenol compound substituted with a benzyl benzoyl or a fluoroalkane, characterized in that: The molecular formula is: Among them, R 1 including benzyl benzoyl or fluoroalkyl; R 2 Including phenyl, Any one of .

2. A phenol compound substituted with a benzyl benzoyl or a fluoroalkane according to claim 1, characterized in that: Benzylic benzoyl groups include 3. A phenol compound substituted with a benzyl benzoyl or a fluoroalkane according to claim 1, characterized in that: Fluorinated alkyl groups include or 4. A phenol compound substituted with a benzyl benzoyl or fluoroalkane according to claim 1, characterized in that: The invention comprises the following compounds 1 to 30:

5. The method for synthesizing a phenol compound substituted with a benzyl benzoyl or a fluoroalkane according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step 1, add 0.3 mmol of o-aminobenzamide, 0.3 mmol of ketone, 10 mol% of I2 and 1 M of anhydrous ethanol into a 100 mL round-bottom flask at once, stir at 80 ° C for 24 h, and after the reaction is complete, cool to room temperature, pour the reaction solution into ice water, the volume ratio of the reaction solution to ice water is 10:1, extract with ethyl acetate, wash the organic layer with saturated brine, dry with anhydrous Na2SO4, and spin dry to obtain a crude product; Step 2: 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 were added to a 10 mL sealed tube in one pot without treatment, and irradiated with a 40 W blue LED, λ = 456 nm, under nitrogen protection, and stirred at room temperature for 24 h; Step 3, after the reaction is completed, the reaction solution is introduced into ice water, extracted with ethyl acetate, the organic layers are combined, washed with saturated brine, dried over anhydrous Na2SO4, spin-dried, and then separated by silica gel column using mobile phases prepared with petroleum ether and ethyl acetate in different volume ratios to obtain phenol compounds substituted with benzyl benzoyl or fluoroalkane.

6. The synthesis method according to claim 5, characterized in that 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 diphenylacetophenone.

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.

8. Use of a phenol compound substituted with a benzyl benzoyl or a fluoroalkane according to any one of claims 1 to 4 in the preparation of an anti-colon cancer drug.

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