A method for preparing fluorinated aryl ketone compounds and their applications

Abstract

This invention discloses a method for preparing fluorinated aryl ketone compounds and their applications, relating to the field of organic synthesis technology. The method includes the following steps: using fluorinated olefins, benzoyl cyanates, and boric acid compounds as raw materials, and reacting them under visible light irradiation in the presence of a photocatalyst, a base, and an organic solvent to prepare fluorinated aryl ketone compounds. This invention uses fluorinated olefins as the key fluorinated substrate and achieves a multi-component synergistic reaction through visible light catalysis, solving problems such as substrate limitations, poor selectivity, and low yield in existing methods. The prepared fluorinated aryl ketone compounds can be used in the preparation of antibacterial, anti-inflammatory, and anticancer drugs, offering significant economic benefits.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing fluorinated aryl ketone compounds and their applications. Background Technology

[0002] Fluorinated organic compounds possess irreplaceable application value in fields such as medicine, pesticides, and functional materials due to their unique physicochemical properties and biological activities. Among them, α-branched fluorinated aryl ketones serve as important fluorinated synthetic building blocks. The trifluoromethyl group (-CF3) in their molecular structure not only significantly improves the lipophilicity, metabolic stability, and bioavailability of the compounds, but also allows for the derivation of various high-value functional molecules through structural modification, showing broad prospects in the research and development of drugs, antitumor agents, and high-performance materials.

[0003] Currently, methods for synthesizing α-branched fluorinated aryl ketones have several limitations: traditional methods rely on cross-coupling reactions catalyzed by transition metals (such as palladium and rhodium), requiring expensive noble metal catalysts, complex ligands, and harsh reaction conditions (high temperature, strong base), resulting in low atom economy; while some photocatalytic methods offer milder conditions, they are limited by specific fluorinated substrates and cannot efficiently accommodate sterically hindered fluorinated alkenes such as α-trifluoromethyl alkenes, and suffer from poor product regioselectivity and low functional group tolerance. Furthermore, existing technologies struggle to precisely control the position of the trifluoromethyl group in the molecule, leading to low yields of the target product and failing to meet the demands of industrial production.

[0004] α-Trifluoromethyl olefins, as an important class of fluorinated synthons, possess unique reactivity due to the synergistic effect of their C=C double bond and trifluoromethyl group. However, the strong electron-withdrawing and steric hindrance effects of the trifluoromethyl group pose challenges to their participation in bifunctionalization reactions, including difficulties in controlling regioselectivity and numerous side reactions. Therefore, developing a mild, efficient, and highly selective method for the synthesis of α-branched fluorinated aryl ketones using α-trifluoromethyl olefins as the core substrate is of great significance for promoting synthetic innovation and industrial applications of fluorinated organic compounds. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the first objective of the present invention is to provide a fluorinated aryl ketone compound.

[0006] The technical solution adopted in this invention is as follows:

[0007] A fluorinated aryl ketone compound has the following structural formula:

[0008] ;

[0009] Where: R 1 Selected from aryl or substituted aryl, alkyl or substituted alkyl; said R2 Selected from aryl or substituted aryl; the R 3 Selected from hydrogen, fluorine, or methyl.

[0010] Furthermore: the R 1 Selected from one of p-tolyl, phenethyl, and n-butyl; the R 2 It is selected from one of phenyl, p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-tert-butylphenyl, p-methoxyphenyl, etc.

[0011] Furthermore, the fluorinated aryl ketone compound is any one of the following structural formulas:

[0012] .

[0013] A second objective of this invention is to provide a method for preparing fluorinated aryl ketone compounds that is readily available, operates under mild conditions, and exhibits high regioselectivity.

[0014] The technical solution adopted in this invention is as follows:

[0015] A method for preparing fluorinated aryl ketone compounds includes the following steps: using fluorinated olefins, benzoyl cyanides, and boric acid compounds as raw materials, and reacting them under visible light in the presence of a photocatalyst, an alkali, and an organic solvent to prepare fluorinated aryl ketone compounds.

[0016] This invention uses fluorinated olefins as key fluorinated substrates and achieves multi-component synergistic reactions through visible light photocatalysis, solving the problems of substrate limitation, poor selectivity, and low yield in existing methods, while also expanding the application scenarios of this type of fluorinated compound.

[0017] Further settings include:

[0018] The fluorinated olefin is an α-trifluoromethyl olefin; particularly preferably, the α-trifluoromethyl olefin is any one of (3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-fluoro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-bromo-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-en-yl)benzene, and 1-(methoxy)-4-(3,3,3-trifluoroprop-1-en-yl)benzene.

[0019] The benzoyl cyanide compound is any one of benzoyl cyanide, o-methylbenzoyl cyanide, and o-fluorobenzoyl cyanide.

[0020] The boric acid compound is an arylboronic acid or an alkylboronic acid, specifically selected from any one of 4-methylphenylboronic acid, phenylethylboronic acid, and n-butylboronic acid.

[0021] The preferred molar ratio of the reactants for the reaction is: fluorinated olefins: benzoyl cyanides: boric acid compounds = 4:1:3.

[0022] The organic solvent is any one of acetonitrile (MeCN), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), ethanol (EtOH), N,N-dimethylformamide (DMF), acetone (Acetone), dichloromethane (DCM), toluene (Toluene), ethyl acetate (EA), N-methylpyrrolidone (NMP), 1,4-dioxane (1,4-Dioxane), cyclohexane (Cyclohexane), methyl tert-butyl ether (MTBE), and chlorobenzene (MCB).

[0023] The photocatalyst is any one of Ir[dF(Me)ppy]2(dtbbpy)PF6, [Ir(dtbbpy)(ppy)2]PF6, Ir[dF(CF3)ppy]2(bpy)PF6, 4CzIPN, and 3DPA2FBN; the amount of photocatalyst used is 1-5 mol% of benzoyl cyanide, preferably 1-2 mol% of benzoyl cyanide, based on the amount of benzoyl cyanide added.

[0024] The alkali is any one of cesium carbonate (Cs2CO3), cesium acetate (CsOAc), potassium carbonate (K2CO3), potassium phosphate (K3PO4), potassium acetate (KOAc), potassium hydroxide (KOH), sodium carbonate (Na2CO3), sodium hydroxide (NaOH), and potassium benzoate (PhCOOK).

[0025] The visible light is preferably blue light with a wavelength of 420-460 nm.

[0026] The preferred reaction temperature is 20-30℃, and the reaction time is 12-36 hours.

[0027] A third aspect of this invention aims to provide the application of fluorinated aryl ketone compounds in the synthesis of antibacterial drugs. The fluorinated aryl ketone compounds prepared by this invention have an α-trifluoromethyl-substituted quaternary carbon center in their molecular structure, exhibiting good chemical stability and structural modifiability, and can be used in the synthesis of antibacterial drugs.

[0028] The beneficial effects of this invention are as follows:

[0029] (1) This invention uses fluorinated olefins (α-trifluoromethyl olefins) as the core fluorinated substrates, which breaks through the limitations of traditional methods on fluorinated substrates. For the first time, it realizes the efficient three-component coupling of this type of highly sterically hindered olefin with benzoyl cyanide and boric acid, providing a new route for the synthesis of α-branched fluorinated aryl ketones.

[0030] (2) The reaction conditions are mild and do not require high temperature, high pressure or strong alkaline environment. It can be carried out under blue light irradiation at room temperature. The amount of photocatalyst used is small and the catalytic efficiency is high. The raw materials are cheap and readily available, which is in line with the development trend of green chemistry.

[0031] (3) Excellent regioselectivity. The trifluoromethyl group in the product is precisely positioned at the α-position, forming a stable quaternary carbon center. The fluorinated aryl ketone compounds prepared by this invention have α-trifluoromethyl substituted quaternary carbon centers in their molecular structure, which have good chemical stability and structural modifiability. They can be used to prepare antibacterial, anti-inflammatory and anticancer drugs, and have high economic benefits.

[0032] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0033] Figure 1 The antibacterial activity of the fluorinated aryl ketone compounds prepared in Example 1 against Escherichia coli; Figure 1 In the sample: 1 is the antibacterial agent DMSO; 2 is a sample solution of antibacterial agent at 20 mg / mL; 3 is a sample solution of antibacterial agent at 40 mg / mL; 4 is a sample solution of antibacterial agent at 80 mg / mL. Detailed Implementation

[0034] The technical solution of the present invention is described in detail below with reference to specific embodiments. The raw materials and reagents used in the embodiments of the present invention are all commercially available analytical grade products. Specifically, α-trifluoromethyl olefin can be commercially available or prepared using the following method: Under a nitrogen atmosphere, arylboronic acid (10.0 mmol), Pd(PPh3)4 (346.7 mg, 0.3 mmol, 3 mol%), potassium carbonate (2.76 g, 20.0 mmol), and tetrahydrofuran (30.0 mL) are added to a three-necked flask. Then, 2-bromo-3,3,3-trifluoropropene (3.50 g, 20.0 mmol) is added dropwise to the mixture. The mixture is heated to 60°C and reacted for 12 hours. The reaction solution is extracted with distilled water and ethyl acetate, the organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is purified by column chromatography (pure petroleum ether) to obtain α-trifluoromethylstyrene, i.e., (3,3,3-trifluoroprop-1-en-2-yl)benzene.

[0035] Example 1

[0036] This embodiment describes the preparation of 3,3,3-trifluoro-2-(4-methylbenzyl)-1,2-diphenylpropanone.

[0037] 4-Methylphenylboronic acid (0.6 mmol, 3.0 equivalent), benzoyl cyanide (0.2 mmol, 1.0 equivalent), Ir[dF(Me)ppy]2(dtbbpy)PF6 (0.0025 mmol), sodium carbonate (0.4 mmol, 2.0 equivalent), (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol, 4.0 equivalent), and acetonitrile (MeCN, 2 mL) were added sequentially to a glass reaction flask. The reaction mixture was irradiated with a 3 W blue LED (420 nm) at room temperature for 24 hours. After the reaction was complete (monitored by TLC), the crude mixture was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 30:1). The eluents were combined, dried over anhydrous sodium sulfate, and concentrated under vacuum to give the target product 3,3,3-trifluoro-2-(4-methylbenzyl)-1,2-diphenylpropanone in 58% yield.

[0038] The reaction equations involved are as follows:

[0039] .

[0040] Product characterization:

[0041] 1 H NMR (400 MHz, CDCl3) δ 7.50 – 7.45 (m, 2H), 7.44 – 7.36 (m, 6H), 7.26 – 7.21 (m, 2H), 6.87 (d, J = 7.9 Hz, 2H), 6.67 (d, J = 8.0 Hz, 2H), 3.84(dd, J = 65.5, 14.5 Hz, 2H), 2.22 (s, 3H).

[0042] 13 C NMR (101 MHz, CDCl3)δ 194.5, 136.6, 136.2, 135.4, 132.6, 131.8,130.7, 130.4, 128.9, 128.8 128.6, 128.5, 128.2, 125.6 (d, J = 285.6 Hz), 65.6(q, J = 21.9 Hz), 39.2 (d, J = 1.1 Hz), 21.0.

[0043] 19 F NMR (377 MHz, CDCl3) δ -64.63.

[0044] HRMS (ESI-TOF) for C 23 H 20 F3O ([M+H) + Theoretical value: 369.1460; Measured value: 369.1452.

[0045] Replacement Examples 1-9

[0046] To investigate the effect of different catalysts on the synthesis yield of fluorinated aryl ketones, the following experiments were conducted.

[0047] The preparation method is the same as in Example 1, except that the type of catalyst is adjusted and its effect on the reaction is tested, as shown in Table 1.

[0048] The catalyst structure is as follows:

[0049] .

[0050] Table 1: Effect of different catalysts on the reaction

[0051]

[0052] In the table above: Trace indicates trace amount, and NR indicates no reaction.

[0053] As can be seen from Table 1: Under the same preparation conditions, Mes-Acr + When PF6, [Ir(dtbbpy)(ppy)2]PF6, Ir[dF(CF3)ppy]2(bpy)PF6, Ir(ppy)3, Ru(bpy)3(PF6)2, 4CzIPN, EosinY, and 3DPA2FBN were used as photocatalysts, the yields were all lower than those obtained when Ir[dF(Me)ppy]2(dtbbpy)PF6 was used as a photocatalyst. Therefore, it is concluded that Ir[dF(Me)ppy]2(dtbbpy)PF6 is the optimal catalyst.

[0054] Replacement Example 10-23

[0055] To investigate the effect of different solvents on the synthesis yield of fluorinated aryl ketones, the following experiments were conducted.

[0056] The preparation method is the same as in Example 1, except that the type of solvent is adjusted and its effect on the reaction is tested, as shown in Table 2.

[0057] Table 2: Effect of solvent on the reaction

[0058]

[0059] In the table above: Trace indicates trace amount, and NR indicates no reaction.

[0060] As can be seen from Table 2, under the same preparation conditions, the yield is lower when N,N-dimethylformamide (DMF), 1,4-dioxane, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), toluene, dichloromethane (DCM), ethyl acetate (EA), ethanol (EtOH), cyclohexane, methyl tert-butyl ether (MTBE), chlorobenzene (MCB), or acetone is used as solvents.

[0061] Replacement Example 24-32

[0062] To investigate the effect of different bases on the synthesis yield of fluorinated aryl ketones, the following experiments were conducted.

[0063] The preparation method is the same as in Example 1, except that the type of alkali is adjusted and its effect on the reaction is tested, as shown in Table 3.

[0064] Table 3: Effect of base on reaction

[0065]

[0066] In the table above: Trace indicates trace amount.

[0067] As can be seen from Table 3, under the same preparation conditions, the yield of the reaction is much lower when cesium carbonate (Cs2CO3), cesium acetate (CsOAc), potassium carbonate (K2CO3), potassium phosphate (K3PO4), potassium acetate (KOAc), potassium hydroxide (KOH), sodium hydroxide (NaOH), or potassium benzoate (PhCOOK) are used as bases.

[0068] Replacement Examples 33-39

[0069] To investigate the effect of different molar ratios of raw materials on the synthesis yield of fluorinated aryl ketones, the following experiments were conducted.

[0070] The preparation method is the same as in Example 1, except that the molar ratio of the raw materials is adjusted to be different, and the effect of each is tested on the reaction, as shown in Table 4.

[0071] Table 4: Effect of different molar ratios of reactants on the reaction

[0072] .

[0073] As can be seen from Table 4, under the same preparation conditions, the yield is highest when the ratio of α-trifluoromethyl olefin 1a: benzoyl cyanide compound 3a: boric acid compound 2a is 4:1:3.

[0074] Example 2

[0075] This embodiment has the same setup as Example 1, except that: when adding raw materials, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and n-butylboronic acid (0.6 mmol) is used instead of 4-methylphenylboronic acid (0.6 mmol). The pure product 2-(4-chlorophenyl)-1-phenyl-2-(trifluoromethyl)hepta-1-one (4b) is obtained with a yield of 45%.

[0076] .

[0077] Product characterization:

[0078] 1 H NMR (400 MHz, CDCl3) δ 7.47 – 7.42 (m, 3H), 7.40 – 7.32 (m, 4H), 7.29 – 7.24 (m, 2H), 2.66 – 2.56 (m, 1H), 2.39 – 2.28 (m, 1H), 1.69 – 1.53(m, 1H), 1.26 – 1.01 (m, 5H), 0.72 (t, J = 7.1 Hz, 3H).

[0079] 13 C NMR (101 MHz, CDCl3) δ 194.8, 135.4, 135.1, 134.3, 132.8, 129.9,129.5, 129.2, 128.3, 125.8 (d, J = 285.0 Hz), 63.1 (q, J = 22.5 Hz), 33.5, 32.3,24.2, 21.8, 13.7.

[0080] 19 F NMR (377 MHz, CDCl3) δ -67.96.

[0081] HRMS (ESI-TOF) for C 20 H 21 ClF3O ([M+H) + Theoretical value: 369.1228; Measured value: 369.1229.

[0082] Example 3

[0083] This embodiment has the same setup as Example 1, except that: when adding raw materials, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and phenylethyl boric acid is used instead of 4-methylphenylboronic acid. The pure product 3,3,3-trifluoro-2-(4-methylbenzyl)-1,2-diphenylpropanone (4c) is obtained with a yield of 65%.

[0084] .

[0085] Product characterization:

[0086] 1 H NMR (400 MHz, CDCl3) δ 7.47 – 7.41 (m, 1H), 7.40 – 7.27 (m, 6H), 7.25 – 7.20 (m, 2H), 7.19 – 7.09 (m, 3H), 6.89 (d, J = 7.3 Hz, 2H), 2.68 – 2.54(m, 2H), 2.44 – 2.29 (m, 2H), 2.04 – 1.91 (m, 1H), 1.48 – 1.34 (m, 1H).

[0087] 13 C NMR (101 MHz, CDCl3)δ 194.6, 140.6, 135.2, 135.2, 134.1, 132.9,129.8, 129.5, 129.2, 128.4, 128.2, 125.7 (d, J = 285.0 Hz), 126.0, 63.1 (q, J =22.5 Hz), 36.0, 32.9, 25.7.

[0088] 19 F NMR (377 MHz, CDCl3) δ -67.81, -67.82.

[0089] HRMS (ESI-TOF) for C 24 H 21 ClF3O ([M+H) + Theoretical value: 417.1228; Measured value: 417.1224.

[0090] Example 4

[0091] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-fluoro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 3,3,3-trifluoro-2-(4-fluorophenyl)-2-(4-methylbenzyl)-1-phenylpropanone (5a) is obtained with a yield of 71%.

[0092] .

[0093] Product characterization:

[0094] 1 H NMR (400 MHz, CDCl3) δ 7.51 – 7.42 (m, 3H), 7.39 – 7.32 (m, 2H), 7.31 – 7.23 (m, 2H), 7.12 – 7.04 (m, 2H), 6.88 (d, J = 7.9 Hz, 2H), 6.66 (d, J =7.9 Hz, 2H), 3.81 (dd, J = 73.4, 14.4 Hz, 2H), 2.23 (s, 3H).

[0095] 13 C NMR (101 MHz, CDCl3)δ 194.1, 162.8 (d, J = 249.7 Hz), 136.7, 135.9,132.8, 131.4, 131.2 (d, J = 3.6 Hz), 130.7, 130.5, 130.4, 128.6, 128.3, 125.5(d, J = 285.5 Hz), 115.9 (d, J = 21.6 Hz), 65.1 (q, J = 21.8 Hz), 39.3, 21.0.

[0096] 19F NMR (377 MHz, CDCl3)δ -64.96, -112.40.

[0097] HRMS (ESI-TOF) for C 23 H 19 F4O ([M+H) + Theoretical value: 387.1367; Measured value: 387.1363.

[0098] Example 5

[0099] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 2-(4-chlorophenyl)-3,3,3-trifluoro-2-(4-methylbenzyl)-1-phenylpropanone (5b) is obtained with a yield of 82%.

[0100] .

[0101] Product characterization:

[0102] 1 H NMR (400 MHz, CDCl3)δ 7.52 – 7.42 (m, 3H), 7.37 – 7.23 (m, 6H), 6.88 (d, J = 7.9 Hz, 2H), 6.66 (d, J = 7.9 Hz, 2H), 3.80 (dd, J = 73.6, 14.4 Hz, 2H), 2.23 (s, 3H).

[0103] 13 C NMR (101 MHz, CDCl3)δ 194.0, 136.8, 135.8, 135.1, 133.9, 132.9,131.3, 130.7, 130.4, 130.0, 129.1, 128.6, 128.3, 125.4 (d, J = 285.6 Hz), 65.2(q, J = 22.0 Hz), 39.2 (d, J = 0.9 Hz), 21.0.

[0104] 19F NMR (377 MHz, CDCl3) δ -64.78.

[0105] HRMS (ESI-TOF) for C 23 H 19 ClF3O ([M+H) + Theoretical value: 403.1071; Measured value: 403.1062.

[0106] Example 6

[0107] This embodiment has the same setup as Example 1, except that when adding the raw materials, 1-bromo-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 2-(4-chlorophenyl)-3,3,3-trifluoro-2-(4-methylbenzyl)-1-phenylpropanone (5c) is obtained with a yield of 75%.

[0108] .

[0109] Product characterization:

[0110] 1 H NMR (400 MHz, CDCl3)δ 7.54 – 7.43 (m, 5H), 7.31 – 7.22 (m, 4H), 6.88 (d, J = 7.9 Hz, 2H), 6.66 (d, J = 7.8 Hz, 2H), 3.80 (dd, J = 73.7, 14.4 Hz, 2H), 2.23 (s, 3H).

[0111] 13 C NMR (101 MHz, CDCl3)δ 193.9, 136.8, 135.8, 134.5, 132.9, 132.0,131.3, 130.7, 130.4, 130.3, 128.6, 128.3, 125.3 (d, J = 285.5 Hz), 123.3, 65.3(q, J = 22.5 Hz), 39.1, 21.0.

[0112] 19 F NMR (377 MHz, CDCl3) δ -64.77.

[0113] HRMS (ESI-TOF) for C 23 H 19 BrF3O ([M+H] + Theoretical value: 447.0566; Measured value: 447.0569.

[0114] Example 7

[0115] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 3,3,3-trifluoro-2-(4-methylbenzyl)-1-phenyl-2-(4-(trifluoromethyl)phenyl)acetone (5d) is obtained with a yield of 76%.

[0116] .

[0117] Product characterization:

[0118] 1 H NMR (400 MHz, CDCl3)δ 7.64 (d, J = 8.4 Hz, 2H), 7.53 – 7.41 (m, 5H), 7.30 – 7.25 (m, 2H), 6.88 (d, J = 7.9 Hz, 2H), 6.66 (d, J = 8.0 Hz, 2H), 3.84(dd, J = 85.9, 14.4 Hz, 2H), 2.23 (s, 3H).

[0119] 13 C NMR (101 MHz, CDCl3)δ 193.6, 139.4, 136.9, 135.5, 133.0, 131.1,131.0 (d, J = 32.9 Hz), 130.8, 130.4, 129.1, 128.6, 128.3, 125.9 (d, J = 164.5Hz), 125.7 (q, J = 3.6 Hz), 123.1 (d, J = 151.2 Hz), 65.7 (q, J = 22.0 Hz), 39.3,21.0.

[0120] 19 F NMR (377 MHz, CDCl3) δ -62.78, -64.46.

[0121] HRMS (ESI-TOF) for C 24 H 18 F6ONa ([M+Na) + Theoretical value: 459.1154; Measured value: 459.1155.

[0122] Example 8

[0123] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-enyl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 2-(4-(tert-butyl)phenyl)-3,3,3-trifluoro-2-(4-methylbenzyl)-1-phenylpropanone (5e) is obtained with a yield of 75%.

[0124] .

[0125] Product characterization:

[0126] 1 H NMR (400 MHz, CDCl3)δ 7.48 (d, J = 8.4 Hz, 2H), 7.45 – 7.37 (m, 3H), 7.33 (d, J = 8.3 Hz, 2H), 7.28 – 7.23 (m, 2H), 6.87 (d, J = 7.8 Hz, 2H), 6.66 (d, J = 7.6 Hz, 2H), 3.83 (dd, J = 58.9, 14.5 Hz, 2H), 2.22 (s, 3H), 1.33 (s, 9H).

[0127] 13 C NMR (101 MHz, CDCl3)δ 194.7, 152.0, 136.5, 136.3, 132.6, 132.2,131.9, 130.6, 130.4, 128.5, 128.2, 128.2, 125.8, 125.7 (d, J = 285.5 Hz), 65.2(q, J= 21.8 Hz), 39.1, 34.6, 31.3, 21.0.

[0128] 19 F NMR (377 MHz, CDCl3) delta -64.83.

[0129] HRMS (ESI-TOF) for C 27 H 28 F3O ([M+H) + Theoretical value: 425.2087; Measured value: 425.2089.

[0130] Example 9

[0131] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-(methoxy)-4-(3,3,3-trifluoroprop-1-enyl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and the pure product 3,3,3-trifluoro-2-(4-methoxyphenyl)-2-(4-methylbenzyl)-1-phenylpropanone (5f) is obtained with a yield of 79%.

[0132] .

[0133] Product characterization:

[0134] 1 H NMR (400 MHz, CDCl3)δ 7.54 – 7.47 (m, 2H), 7.46 – 7.41 (m, 1H),7.33 (d, J = 7.6 Hz, 2H), 7.26 (t, J = 8.0 Hz, 2H), 6.96 – 6.86 (m, 4H), 6.67 (d, J = 6.6 Hz, 2H), 3.92 – 3.72 (m, 5H), 2.23 (s, 3H).

[0135] 13 C NMR (101 MHz, CDCl3)δ 194.6, 159.8, 136.6, 136.2, 132.6, 131.8,130.6, 130.5, 129.8, 128.5, 128.2, 127.1, 124.2, 114.3, 64.9 (q, J = 21.9 Hz),55.3, 39.1, 21.0.

[0136] 19 F NMR (377 MHz, CDCl3)δ -65.23.

[0137] HRMS (ESI-TOF) for C 24 H 22 F3O2([M+H) + Theoretical value: 399.1566; Measured value: 399.1573.

[0138] Example 10

[0139] This embodiment is set up the same as in Example 1, except that when adding raw materials, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and 2-methylbenzoyl cyanide (0.2 mmol) is used instead of benzoyl cyanide (0.2 mmol). Other conditions and procedures are the same as in Example 3. The pure product 2-(4-chlorophenyl)-3,3,3-trifluoro-2-(4-methylbenzyl)-1-(o-methylphenyl)prop-1-one (6a) is obtained with a yield of 53%.

[0140] .

[0141] Product characterization:

[0142] 1 H NMR (400 MHz, CDCl3)δ 7.44 – 7.35 (m, 4H), 7.28 – 7.18 (m, 2H), 6.90 (t, J = 9.1 Hz, 3H), 6.73 (d, J = 7.8 Hz, 2H), 6.67 (d, J = 7.9 Hz, 1H), 3.66(dd, J = 43.3, 14.5 Hz, 2H), 2.26 (s, 3H), 2.21 (s, 3H).

[0143] 13 C NMR (101 MHz, CDCl3)δ 197.9, 139.1, 137.6, 136.6, 134.9, 133.6,131.9, 131.7, 131.0, 130.9, 129.5, 129.2, 128.5, 128.0, 125.8 (d, J= 285.7Hz), 124.6, 66.8 (q, J = 22.1 Hz), 40.2, 21.0, 20.7.

[0144] 19 F NMR (377 MHz, CDCl3) delta -61.80.

[0145] HRMS (ESI-TOF) for C 24 H 20 ClF3ONa ([M+H) + Theoretical value: 439.1047; Measured value: 439.1065.

[0146] Example 11

[0147] This embodiment has the same setup as Example 1, except that when adding raw materials, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol) is used instead of (3,3,3-trifluoroprop-1-en-2-yl)benzene (0.8 mmol), and 2-fluorobenzoyl cyanide (0.2 mmol) is used instead of benzoyl cyanide (0.2 mmol). The pure product 2-(4-chlorophenyl)-3,3,3-trifluoro-1-(2-fluorophenyl)-2-(4-methylbenzyl)propanone (6b) is obtained with a yield of 77%.

[0148] .

[0149] Product characterization:

[0150] 1 H NMR (400 MHz, CDCl3)δ 7.44 – 7.33 (m, 3H), 7.29 (d, J = 8.6 Hz, 2H),7.06 – 6.97 (m, 3H), 6.96 – 6.91 (m, 2H), 6.78 (d, J = 8.0 Hz, 2H), 3.71 (q, J =14.7 Hz, 2H), 2.25 (s, 3H).

[0151] 13 C NMR (101 MHz, CDCl3)δ 193.5, 159.6 (d, J = 255.9 Hz), 136.7, 134.8,133.6 (d, J= 8.9 Hz), 132.8, 131.6, 130.8, 130.0, 129.7, 129.0, 128.6, 126.6(d, J = 12.1 Hz), 125.6 (d, J = 285.6 Hz), 123.6 (d, J = 3.6 Hz), 116.7 (d, J = 22.9Hz), 67.0 (q, J = 22.3 Hz), 39.2, 21.0.

[0152] 19 F NMR (377 MHz, CDCl3)δ -62.73, -62.73, -109.01.

[0153] HRMS (ESI-TOF) for C 23 H 17 ClF4ONa ([M+Na) + Theoretical value: 443.0796; Measured value: 443.0784.

[0154] Application Examples

[0155] This embodiment mainly examines the antibacterial properties of fluorinated aryl ketone compounds.

[0156] The antibacterial properties of the fluorinated aryl ketone compounds prepared in Example 1 were evaluated using the following test methods:

[0157] 1. Sample preparation for testing antibacterial materials

[0158] Accurately weigh the sample and prepare sample solutions (using DMSO) with concentrations of 20 mg / mL, 40 mg / mL, and 80 mg / mL, respectively, to test their inhibitory effect on Escherichia coli.

[0159] 2. Preparation of bacterial suspension

[0160] Take a strain of *E. coli* and place it in a test tube. Add 5 mL of culture medium to the test tube and incubate at 37°C for 8 hours. Then, use an inoculation loop to streak the bacterial culture evenly onto nutrient broth agar medium. Incubate the medium for 16 hours to obtain a single *E. coli* colony. Pick a single *E. coli* colony with a pipette tip and incubate it in 5 mL of LB medium at 37°C for 8 hours to obtain the OD. 600 =1.0 bacterial solution.

[0161] 3. Antibacterial zone experiment

[0162] After turning on the ultra-clean hood for 30 minutes, perform aseptic operations. Soak blank drug sensitivity test strips in the sample solution for 5 minutes. Take 40 μL of the test bacterial solution and spread it evenly on nutrient broth agar medium. Then, attach the drug sensitivity test strips soaked in the drug solution to the medium. Incubate the medium in a 37°C incubator overnight and then observe the size of the inhibition zone.

[0163] The antibacterial properties of sample solutions at different concentrations are shown in Table 5. Figure 1 As shown.

[0164] Table 5: Antibacterial Properties

[0165] .

[0166] Table 5 shows that different concentrations of the product have different antibacterial effects against Escherichia coli; the higher the concentration, the stronger the bactericidal effect. This demonstrates that the fluorinated aryl ketone compound prepared in this invention has good antibacterial effects and can be used to prepare antibacterial drugs.

[0167] The above-described embodiments are merely illustrative of several feasible implementations of the present invention, and their descriptions are relatively specific and detailed. However, they should not be construed as limiting the scope of the present invention, nor are the embodiments intended to limit the scope of protection in the claims of the present invention. For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention. All equivalent implementations or changes that do not depart from the present invention should be included in the technology of the present invention.

Claims

1. A fluorinated aryl ketone compound, characterized in that, The structural formula is as follows: 。 2. A method for preparing a fluorinated aryl ketone compound as described in claim 1, characterized in that: Includes the following steps: Fluorinated aryl ketones were prepared by reacting fluorinated olefins, benzoyl cyanides, and boric acid compounds under visible light irradiation in the presence of a photocatalyst, alkali, and organic solvent. The photocatalyst is Ir[dF(Me)ppy]2(dtbbpy)PF6 or 4CzIPN; The solvent is acetonitrile, DCM, EA, MCB or acetone; The alkali is CsOAc, K2CO3, KOAc, KOH, Na2CO3, NaOH, or PhCOOK.

3. The method for preparing a fluorinated aryl ketone compound according to claim 2, characterized in that: The fluorinated olefin is an α-trifluoromethyl olefin; the benzoyl cyanide compound is any one of benzoyl cyanide, o-methylbenzoyl cyanide, and o-fluorobenzoyl cyanide; the boric acid compound is arylboronic acid or alkylboronic acid.

4. The method for preparing a fluorinated aryl ketone compound according to claim 3, characterized in that: The α-trifluoromethyl olefin is any one of (3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-fluoro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-bromo-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, 1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-en-yl)benzene, and 1-(methoxy)-4-(3,3,3-trifluoroprop-1-en-yl)benzene.

5. The method for preparing a fluorinated aryl ketone compound according to claim 2, characterized in that: The amount of photocatalyst used, based on the amount of benzoyl cyanide added, is 1-5 mol of benzoyl cyanide.

6. The method for preparing a fluorinated aryl ketone compound according to claim 2, characterized in that: The visible light is blue light with a wavelength of 420-460 nm; the temperature of the visible light irradiation reaction is 20-30℃, and the reaction time is 12-36 hours.

7. The use of the fluorinated aryl ketone compound of claim 1 in the synthesis of an anti-Escherichia coli drug.

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