Carbon-fluorine bond hydrogenation defluorination method for multi-(hetero) aromatic hydrocarbon substance

Abstract

The invention provides a multi-(hetero) aromatic hydrocarbon substance carbon-fluorine bond hydrogenation defluorination reaction with HP (O) Ph2 as a defluorination reagent and H2O as an environment-friendly accelerant under a metal-free condition. The method is mild in reaction condition and good in functional group tolerance, has the characteristics of simple post-treatment, green steps, low pollution, high economic benefits and the like, can smoothly realize carbon-fluorine bond hydrogenation defluorination of multi-(hetero) aromatic hydrocarbon substances containing complex molecules, and is expected to promote green and sustainable defluorination chemical development.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances. Background Art

[0002] Organofluorine molecules containing partially fluorinated aromatic rings play an important role in medicine, materials, and agricultural chemistry due to their unique stability, lipophilicity, and bioavailability (Angew. Chem., Int. Ed. 1999, 38, 2741-2745; Science 2007, 317, 1881-1886). This importance is strongly supported by the fact that 30-40% of agricultural chemicals and 25% of drug molecules on the market currently contain fluorine atoms (Chem. Rev. 2014, 114, 2432-2506). Therefore, efficient methods for the construction of fluoroaromatic hydrocarbons have attracted much attention in recent years. Some fluorinated aromatic hydrocarbons remain in the environment for a long time, not only enriching the food chain and harming the ecosystem, but also entering the human body through diet, drinking water, etc., threatening public health (Environ. Sci. Technol. 2020, 54, 11951-11960); while the traditional way of treating fluorinated waste is prone to secondary pollution, defluorination technology can achieve the recycling of fluorine resources, reduce dependence on natural fluorine resources, and promote the development of a circular economy. At the same time, due to the high stability of the C-F bond in polyfluoroaromatic hydrocarbons, its defluorination research can also promote multidisciplinary technological innovations such as catalytic chemistry, provide ideas for the treatment of other difficult-to-degrade organic matter, and promote the green transformation of industries such as chemical industry.

[0003] We recently discovered that the combined action of HP(O)R'R" / H2O can be used to achieve carbon-fluorine hydrogenation defluorination of poly(hetero)aromatic substances. We proposed a carbon-fluorine hydrogenation defluorination reaction of poly(hetero)aromatic substances under transition metal-free conditions using HP(O)Ph2 as a defluorination reagent and H2O as an environmentally friendly promoter. The reaction has the following characteristics: (1) a wide range of substrate applicability; (2) excellent functional group tolerance; and (3) scalable synthesis scale. Compared with existing reports, our method effectively avoids the use of expensive photocatalysts (Synlett 2014, 25, 1946-1952) and H-negative reagents (Org. Lett. 2021, 23, 1588-1593), and is expected to promote the development of green and sustainable defluorination chemistry. Summary of the Invention

[0004] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0005] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0006] One of the objects of the present invention is to provide a method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances.

[0007] In order to solve the above technical problems, the present invention provides the following technical solutions: a product of hydrogenation and defluorination of multiple carbon-fluorine bonds, the structural formula of which is shown in Formula I or Formula II;

[0008]

[0009] Among them, R 1 One selected from the group consisting of methoxy-substituted phenyl, benzyloxy-substituted phenyl, trifluoromethoxy-substituted phenyl, methyl-substituted phenyl, tert-butyl-substituted phenyl, biphenyl, halogen-substituted phenyl, trifluoromethyl-substituted phenyl, cyano-substituted phenyl, naphthyl, 1,2-methylenedioxyphenyl, pyridyl, thienyl, N,N-dimethyl-substituted benzoyl, N,N-diformyl, mercapto, phenoxy, trifluoromethyl, and phenyl;

[0010] R 2 One selected from halogen (F and Cl).

[0011] Another object of the present invention is to provide a method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic hydrocarbons as described above. The method has mild reaction conditions, good functional group tolerance, simple post-processing, environmentally friendly steps, low pollution, and high economic benefits. The specific method includes:

[0012] Poly(hetero)aromatic substances undergo a carbon-fluorine bond hydrogenation and defluorination reaction in a solvent under the promotion of diphenylphosphine oxide and cesium carbonate to obtain the target compound;

[0013]

[0014] Wherein, R in formula III and IV 1 、R 2 With R in formula I and II 1 、R 2 The corresponding consistency.

[0015] As a preferred embodiment of the carbon-fluorine bond hydrogenation defluorination method of poly(hetero)aromatic hydrocarbons of the present invention, the polyfluoroaromatic hydrocarbons include 2,3,4,5,6-pentafluoro-4′-methoxy-1,1′-biphenyl, 2,3,4,5,6-pentafluoro-3′-methoxy-1,1′-biphenyl, 2,3,4,5,6-pentafluoro-2′-methoxy-1,1′-biphenyl, 4′-(benzyloxy)-2,3,4,5,6-pentafluoro-1,1′-biphenyl, 4′-(trifluoromethoxy)-2,3,4,5,6-pentafluoro-1,1′-biphenyl, 4′-(methyl)-2,3 ,4,5,6-pentafluoro-1,1′-biphenyl, 4′-(tert-butyl)-2,3,4,5,6-pentafluoro-1,1′-biphenyl, 2,3,4,5,6-pentafluoro-1,1′:4′,1″-terphenyl, 2,3,4,4′,5,6-hexafluoro-1,1′-biphenyl, 4′-chloro-2,3,4,5,6-pentafluoro-1,1′-biphenyl, 4′-bromo-2,3,4,5,6-pentafluoro-1,1′-biphenyl, 2,3,4,5,6-pentafluoro-4′-trifluoromethyl-1,1′-biphenyl, 2,3,4,5,6-pentafluoro-3′-cyano-1 , 1′-biphenyl, 2-(perfluorophenyl)naphthalene, 1-(perfluorophenyl)naphthalene, 5-(perfluorophenyl)benzo[d][1,3]dioxole, 3-(perfluorophenyl)pyridine, 2-(perfluorophenyl)thiophene, (4-dimethylaminophenyl)(perfluorophenyl)methanone, N,N-diethyl-2,3,4,5,6-pentafluorobenzamide, 1,2,3,4,5-pentafluoro-6-phenylthiobenzene, 1,2,3,4,5-pentafluoro-6-phenoxybenzene, octafluorotoluene, decafluorobiphenyl, 1,4-bis(phenylthio)tetrafluorobenzene, pentafluoropyridine, 3,5-dichloro-2,4,6- One of trifluoropyridine, (8R,9S,13S,14S)-13-methyl-3-(perfluorophenyl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one, 4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl(pentafluorophenyl)methanone, 1-[(4-chlorophenyl)(phenyl)methyl]-4-(pentafluorobenzoyl)piperazine, and (E)-4′-(3,5-dimethoxyphenyl)-2,3,4,5,6-pentafluoro-1,1′-biphenyl.

[0016] As a preferred embodiment of the carbon-fluorine bond hydrogenation defluorination method of poly(hetero)aromatic substances of the present invention, the molar ratio of the polyfluoroaromatic hydrocarbon to diphenylphosphine oxide is 1:0-1.5, preferably 1:1.5.

[0017] As a preferred embodiment of the carbon-fluorine bond hydrogenation defluorination method of poly(hetero)aromatic hydrocarbon substances of the present invention, the solvent comprises one of dimethyl sulfoxide, ethyl acetate, acetonitrile, 1,2-dibromoethane, toluene, tetrahydrofuran, methanol, N,N-dimethylacetamide, n-hexane and water; the preferred solvent is dimethyl sulfoxide.

[0018] As a preferred embodiment of the method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances of the present invention, the defluorination reaction is carried out at a temperature of 75 to 125° C., preferably 125° C.

[0019] As a preferred solution for the hydrogenation defluorination of carbon-fluorine bonds of poly(hetero)aromatic substances of the present invention, the defluorination reaction is carried out for 12 to 24 hours, preferably 12 hours.

[0020] As a preferred embodiment of the carbon-fluorine bond hydrogenation defluorination method of poly(hetero)aromatic substances of the present invention, the molar ratio of the polyfluoroaromatic hydrocarbon to the cesium carbonate is 1:0 to 3.5, preferably 1:3.

[0021] In summary, the optimal reaction equation of the present invention is as follows:

[0022]

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The present invention provides a carbon-fluorine bond hydrogenation and defluorination reaction of polyfluoroaromatic hydrocarbons under metal-free conditions under the promotion of diphenylphosphine oxide, water and cesium carbonate; the reaction conditions are mild, the functional group tolerance is good, and the post-processing is simple, the steps are green, the pollution is low, and the economic benefits are high; and the carbon-fluorine bond hydrogenation and defluorination of complex polyfluoroaromatic compounds can be smoothly achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0026] Figure 1 This is the hydrogen spectrum of the target product a in Example 1 of the present invention;

[0027] Figure 2 is the fluorine spectrum of the target product a in Example 1 of the present invention;

[0028] Figure 3The carbon spectrum of the target product a in Example 1 of the present invention is shown below:

[0029] Figure 4 This is the hydrogen spectrum of the target product b in Example 2 of the present invention;

[0030] Figure 5 This is the fluorine spectrum of the target product b in Example 2 of the present invention;

[0031] Figure 6 The carbon spectrum of the target product b in Example 2 of the present invention;

[0032] Figure 7 This is the hydrogen spectrum of the target product c in Example 3 of the present invention;

[0033] Figure 8 This is the fluorine spectrum of the target product c in Example 3 of the present invention;

[0034] Figure 9 The carbon spectrum of the target product c of Example 3 of the present invention;

[0035] Figure 10 This is the hydrogen spectrum of the target product d in Example 4 of the present invention;

[0036] Figure 11 This is the fluorine spectrum of the target product d of Example 4 of the present invention;

[0037] Figure 12 This is the carbon spectrum of the target product d of Example 4 of the present invention;

[0038] Figure 13 This is the hydrogen spectrum of the target product e in Example 5 of the present invention;

[0039] Figure 14 This is the fluorine spectrum of the target product e of Example 5 of the present invention;

[0040] Figure 15 This is the carbon spectrum of the target product e of Example 5 of the present invention;

[0041] Figure 16 This is the hydrogen spectrum of the target product f in Example 6 of the present invention;

[0042] Figure 17 This is the fluorine spectrum of the target product f in Example 6 of the present invention;

[0043] Figure 18 This is the carbon spectrum of the target product f in Example 6 of the present invention. DETAILED DESCRIPTION

[0044] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0045] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0046] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0047] The polyfluoroaromatic raw materials used in the examples were prepared according to the method reported in the literature (Org. Biomol. Chem. 2025, DOI: 10.1039 / D5OB00528K: Angew. Chem. Int. Ed. 2009, 48, 9350-9354). Other raw materials were purchased commercially unless otherwise specified.

[0048] The first method for synthesizing raw material polyfluoroaromatic hydrocarbons is as follows:

[0049]

[0050] Step a): A round-bottom flask was charged with phenol substrate (5 mmol, 1 equiv), N,N′-sulfonyldiimidazole (2.0 g, 10 mmol, 2 equiv), cesium carbonate (814.6 mg, 2.5 mmol, 0.5 equiv), and tetrahydrofuran (THF, 0.05 g / mL). The reaction was stirred at room temperature for 4-16 hours, then quenched with saturated ammonium chloride solution and extracted with ethyl acetate (EtOAc). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to yield the crude product. The product was purified by silica gel column chromatography (ethyl acetate / petroleum ether as eluent) to obtain the desired product. The spectral data of the product were consistent with those reported in the literature.

[0051]

[0052] Step b): Pentafluorobenzoic acid (2.1207 g, 10 mmol, 1 equivalent) and deionized water (50 mL) were added to a 200 mL round-bottom flask equipped with a magnetic stirrer, and the reaction mixture was stirred at 60°C for 0.5 hours. Zinc hydroxide (497 mg, 5 mmol, 0.5 equivalent) was then added to the flask, and the reaction mixture was vigorously stirred at 60°C for 6 hours. The solvent was then evaporated, and the solid residue was dried under vacuum at 50°C for 6 hours to obtain the polyfluorobenzoic acid zinc salt.

[0053]

[0054] Step c): A dried, sealed tube equipped with a magnetic stirrer was replaced three times under a nitrogen atmosphere. Subsequently, arylimidazole sulfonate (1 mmol, 1 equivalent), zinc 2,3,4,5,6-pentafluorobenzoate (485.6 mg, 1 mmol, 1 equivalent), and tetrakis(triphenylphosphine)palladium (57.8 mg, 0.05 mmol, 5 mol%) were added to the tube. Anhydrous DMF (3 mL) was then added, and the reaction mixture was stirred at 120°C for 12 hours. The mixture was then quenched with saturated ammonium chloride solution (10 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product, which was then purified by silica gel column chromatography (ethyl acetate / petroleum ether as eluent) to obtain the desired product.

[0055] The second method for synthesizing raw material polyfluoroaromatic hydrocarbons is as follows:

[0056]

[0057] Step a): 2,3,4,5,6-polyfluorobenzoic acid (2.12 g, 10 mmol, 1 equivalent) and ethanol (10 mL) were added to a 200 mL round-bottom flask equipped with a magnetic stirrer. The reaction mixture was stirred at room temperature for 30 minutes. A solution of potassium tert-butoxide (1.12 g, 10 mmol, 1 equivalent) in ethanol (10 mL) was then slowly added dropwise over 30 minutes. The reaction mixture was stirred vigorously at room temperature for 1 hour. The solvent was then evaporated, and the solid residue was dried under vacuum at 30°C for 6 hours to yield the potassium salt of the polyfluorobenzoic acid.

[0058]

[0059] Step b): Copper (I) iodide (95-190 mg, 0.5-1 mmol, 10-20 mol%), potassium pentafluorobenzoate (6-7.5 mmol, 1.2-1.5 equivalents), 1,10-phenanthroline (0-180 mg, 0-1 mmol, 0-20 mol%), and an aryl halide (5 mmol, 1 equivalent) were dissolved in diethylene glycol diethyl ether (5 mL) and stirred at 130° C. (oil bath) under a nitrogen atmosphere for 24 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate or petroleum ether (30 mL), and filtered through a short silica gel column to remove the precipitate. The organic phase was washed sequentially with water (30 mL×3) and saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (300-400 mesh) using petroleum ether / ethyl acetate (200 / 1-1 / 1) as eluent to give pure polyfluoro(hetero)arene product 4.

[0060] Example 1

[0061] (1) To a 10 mL Schlenk tube were added 2,3,4,5,6-pentafluoro-4′-methoxy-1,1′-biphenyl (82.3 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL). The reaction mixture was stirred at 125° C. for 12 h in air.

[0062] (2) After the reaction in step (1) was completed, the mixture was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL×3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:200, and finally 69.3 mg of the target product a was obtained.

[0063] The target product a is characterized as follows: Figure 1 、 2 As shown in 3, the results are: white solid;

[0064] 1 H NMR (400MHz, CDCl3): δ7.44-7.39 (m, 2H), 7.06-6.99 (m, 3H), 3.87 (s, 3H)ppm.

[0065] 19 F NMR (376MHz, CDCl3): δ-139.45 (dd, J=22.5, 12.8Hz, 2F), -144.30 (dd, J=22.4, 12.5Hz, 2F) ppm.

[0066] 13 C NMR (100MHz, CDCl3): δ160.4, 147.8-142.5 (m, 2C), 131.6 (t, J=2.4Hz), 121.4 (t, J=16.5Hz), 119.7, 114.3, 104.4 (t, J=22.8Hz), 55.4ppm.

[0067] HRMS (m / z): calculated for C 13 H9F4O[M+H] + 257.0584, found: 257.0582.

[0068] According to the characterization data, the obtained reaction product is 2,3,5,6-tetrafluoro-4′-methoxy-1,1′-biphenyl (purity>98%), and the structural formula of the compound is:

[0069]

[0070] The product yield was calculated to be 90%.

[0071] Example 2

[0072] (1) To a 10 mL Schlenk tube were added 2-(perfluorophenyl)naphthalene (88.3 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL) in sequence, and the reaction mixture was stirred at 125° C. for 12 h in air.

[0073] (2) After the reaction in step (1) was completed, the mixture was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL×3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:200, and finally 69.2 mg of the target product b was obtained.

[0074] The target product b was characterized as follows: Figure 4 、 5 As shown in 6, the results are: white solid;

[0075] 1 H NMR (400MHz, CDCl3): δ8.02-7.95 (m, 2H), 7.95-7.88 (m, 2H), 7.57 (qq, J=4.0, 1.8Hz, 3H), 7.11 (tt, J=9.7, 7.3Hz, 1H)ppm.

[0076] 19 F NMR (376MHz, CDCl3): δ-138.88 (dt, J=22.4, 11.1Hz, 2F), -143.45--143.63 (m, 2F)ppm.

[0077] 13C NMR (100MHz, CDCl3): δ 147.9-142.6 (m, 2C), 133.4, 133.1, 130.2, 128.5, 128.4, 127.9, 127.23, 127.20, 126.7, 124.9, 121.6 (t, J=16.7Hz), 105.1 (t, J=22.7Hz)ppm.

[0078] HRMS (m / z): calculated for C 16 H9F4[M+H] + 277.0635, found: 277.0633.

[0079] According to the characterization data, the obtained reaction product is 2-(2,3,5,6-tetrafluorophenyl)naphthalene (purity>98%), and the structural formula of the compound is:

[0080]

[0081] The product yield was calculated to be 84%.

[0082] Example 3

[0083] (1) To a 10 mL Schlenk tube were added (4-dimethylaminophenyl)(perfluorophenyl)methanone (94.6 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL). The reaction mixture was stirred at 125° C. for 12 h in air.

[0084] (2) After the reaction in step (1) was completed, the reaction was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL×3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:200, and finally 26.3 mg of the target product c was obtained.

[0085] The target product c was characterized as follows: Figure 7 , 8 and 9, the results are: white solid;

[0086] 1H NMR (400MHz, CDCl3): δ7.73 (d, J=8.6Hz, 2H), 7.14 (tt, J=9.6, 7.1Hz, 1H), 6.66 (d, J=9.2Hz, 2H), 3.09 (s, 6H)ppm.

[0087] 19 F NMR (376MHz, CDCl3): δ-137.65 (t, J=13.1Hz, 2F), -141.35 (t, J=18.0Hz, 2F) ppm.

[0088] 13 C NMR (100MHz, CDCl3): δ183.3, 154.6, 147.3-141.7 (m, 2C), 132.4, 123.8, 121.0 (t, J=21.2Hz), 111.0, 106.8 (t, J=22.6Hz), 40.2ppm.

[0089] HRMS (m / z): calculated for C 15 H 12 F4NO[M+H] + 298.0850, found: 298.0849.

[0090] According to the characterization data, the obtained reaction product is 4-dimethylamino-2′, 3′, 5′, 6′-tetrafluorobenzophenone (purity> 98%), and the structural formula of the compound is:

[0091]

[0092] The product yield was calculated to be 29%.

[0093] Example 4

[0094] (1) To a 10 mL Schlenk tube were added 1,2,3,4,5-pentafluoro-6-phenoxybenzene (78.0 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL). The reaction mixture was stirred at 125° C. for 12 h in air.

[0095] (2) After the reaction in step (1) was completed, the mixture was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL×3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:200, and finally 36.7 mg of the target product d was obtained.

[0096] The target product d was characterized as follows: Figure 10 , as shown in 11 and 12, the results are: white solid;

[0097] 1 H NMR (400MHz, CDCl3): δ7.38-7.31 (m, 2H), 7.13 (td, J=7.3, 1.1Hz, 1H), 7.01-6.92 (m, 3H)ppm.

[0098] 19 F NMR (376MHz, CDCl3): δ-138.65--138.79(m, 2F), -153.95--154.08(m, 2F)ppm.

[0099] 13 C NMR (100MHz, CDCl3): δ157.2, 146.7 (dm, J=248.4Hz), 141.8 (dm, J=250.6Hz), 130.0, 123.9, 115.6, 115.3, 102.0 (t, J=22.9Hz) ppm.

[0100] HRMS (m / z): calculated for C 12 H7F4O[M+H] + 243.0428, found: 243.0424.

[0101] According to the characterization data, the obtained reaction product is 1,2,4,5-tetrafluoro-3-phenoxybenzene (purity>98%), and the structural formula of the compound is:

[0102]

[0103] The product yield was calculated to be 51%.

[0104] Example 5

[0105] (1) To a 10 mL Schlenk tube were added decafluorobiphenyl (100.2 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL) in sequence, and the reaction mixture was stirred at 125° C. for 12 h in air.

[0106] (2) After the reaction in step (1) was completed, the mixture was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL×3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:200, and finally 65.1 mg of the target product e was obtained.

[0107] The target product e was characterized as follows: Figure 13 , 14 and 15, the results are: white solid;

[0108] 1 H NMR (400MHz, CDCl3): δ7.33-7.21(m, 2H)ppm.

[0109] 19 F NMR (376MHz, CDCl3): δ-137.75--138.03(m, 4F), -138.30--138.56(m, 4F)ppm.

[0110] 13 C NMR (100MHz, CDCl3): δ146.3 (dm, J=246.7Hz), 144.3 (dm, J=250.6Hz), 108.0 (t, J=22.4Hz, 2C)ppm.

[0111] HRMS (m / z): calculated for C 12 H3F8[M+H]+299.0102, found: 299.0107.

[0112] According to the characterization data, the obtained reaction product is 2,2′,3,3′,5,5′,6,6′-octafluoro-1,1′-biphenyl (purity>98%), and the structural formula of the compound is:

[0113]

[0114] The product yield was calculated to be 73%.

[0115] Example 6

[0116] Example 6 is basically the same as Example 1, except that in step (1), dimethyl sulfoxide is used as the solvent and the base is different, as shown in Table 1 below:

[0117] Table 1

[0118]

[0119]

[0120] As can be seen from Table 1, under the same reaction conditions, when cesium carbonate (Cs2CO3) is used as the base, the reaction yield is the highest, which is 93%.

[0121] Example 7

[0122] Example 7 is basically the same as Example 1, except that in step (1), the phosphine oxide compound used is different, as shown in Table 2 below:

[0123] Table 2

[0124]

[0125] As can be seen from Table 2, under the same reaction conditions, the reaction yield is the highest when diphenylphosphine is used.

[0126] Example 8

[0127] Example 8 is basically the same as Example 1, except that in step (1), the reaction solvent is different, as shown in Table 3 below:

[0128] Table 3

[0129] Reaction solvent Yield (%) DMSO 93 EtOAc 57 MeCN 57 DCE trace Toluene 30 THF 40 MeOH 46 DMA 55 hexane 15 <![CDATA[H2O]]> 8

[0130] As can be seen from Table 3, under the same reaction conditions, the yield is lower when using solvents such as 1,2-dichloroethane (DCE), toluene, tetrahydrofuran (THF), methanol (MeOH), n-hexane, and water (H2O); when using ethyl acetate (EtOAc) and acetonitrile (MeCN), the reaction yield is 57%; when using N,N-dimethylacetamide (DMA) as the solvent, the reaction yield is 55%; when using dimethyl sulfoxide (DMSO) as the solvent, the reaction yield is the highest.

[0131] Example 9

[0132] Example 9 is basically the same as Example 1, except that in step (1), the temperature is different in tetrahydrofuran as solvent, as shown in Table 4 below:

[0133] Table 4

[0134]

[0135]

[0136] It can be seen from Table 4 that under the same reaction conditions, the reaction yield is highest at a reaction temperature of 125°C.

[0137] Example 10

[0138] Example 10 is basically the same as Example 1, except that in step (1), the reaction time is different, as shown in Table 5 below:

[0139] Table 5

[0140] Reaction time Yield (%) 12h 93 18h 89 24h 71

[0141] It can be seen from Table 5 that under the same reaction conditions, prolonging the reaction time is beneficial to increasing the reaction yield; when the reaction time is 12 h, the reaction yield is the highest.

[0142] Example 11

[0143] Example 11 is basically the same as Example 1, except that in step (1), the polyfluoroaromatic hydrocarbon is different. The target products obtained are shown in Table 6 below:

[0144] Table 6

[0145]

[0146]

[0147]

[0148] Example 12

[0149] The carbon-fluorine bond hydrogenation and defluorination of polyfluoroaromatic hydrocarbons containing complex molecules, such as estrone, can be successfully achieved.

[0150] (1) To a 10 mL Schlenk tube were added (8R,9S,13S,14S)-13-methyl-3-(perfluorophenyl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one (126.1 mg, 0.3 mmol, 1 equiv.), diphenylphosphine oxide (91 mg, 0.45 mmol, 1.5 equiv.), water (27 mg, 1.5 mmol, 5 equiv.), cesium carbonate (293.2 mg, 0.9 mmol, 3 equiv.), and dimethyl sulfoxide (2 mL). The reaction mixture was stirred at 125° C. for 12 h in air.

[0151] (2) After the reaction in step (1) was completed, the reaction was quenched with saturated NH4Cl solution and extracted with ethyl acetate (10 mL × 3); the combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a crude product; the crude product was purified by silica gel column chromatography, and the column chromatography separation conditions were as follows: the stationary phase was 300-400 mesh silica gel powder, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:10, and finally 64.7 mg of the target product f was obtained.

[0152] The target product f was characterized as follows: Figure 16 , as shown in 17 and 18, the results are: white solid;

[0153] 1 H NMR (400MHz, CDCl3): δ7.42 (d, J=8.1Hz, 1H), 7.28-7.22 (m, 1H), 7.21 (s, 1H), 7.10-6.99 (m, 1H), 2.98 (dd, J=9.1, 4.2Hz, 2H), 2.58-2.43 (m , 2H), 2.37 (td, J=10.8, 4.2Hz, 1H), 2.22-2.03 (m, 3H), 2.03-1.96 (m, 1H), 1.73-1.61 (m, 2H), 1.61-1.44 (m, 4H), 0.94 (d, J=1.2Hz, 3H)ppm.

[0154] 19 F NMR (376MHz, CDCl3): δ-140.08--140.31(m, 2F), -144.72--144.95(m, 2F)ppm.

[0155] 13 C NMR (100 MHz ，CDCl3): δ220.9, 147.7-142.4 (m, 2C), 141.1, 137.0, 130.6, 127.4, 125.7, 124.9, 121.4 (t, J N =16.6Hz), 104.6 (t, J=22.8Hz), 50.5, 48.0, 44.5, 37.9, 35.9, 31.6, 29.4, 26.4, 25.6, 21.6, 13.9ppm.

[0156] HRMS (m / z): calculated for C 24 H 23 F4O[M+H]+403.1680, found: 403.1672.

[0157] According to the characterization data, the obtained reaction product is (8R,9S,13S,14S)-13-methyl-3-(2,3,5,6-tetrafluorophenyl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one (purity>98%), and the structural formula of the compound is:

[0158]

[0159] The product yield was calculated to be 54%.

[0160] Example 13

[0161] Example 13 is basically the same as Example 12, except that in step (1), the polyfluoroaromatic hydrocarbon is different. The target products obtained are shown in Table 7 below:

[0162] Table 7

[0163]

[0164] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances, wherein the product is characterized by: Its structural formula is shown in Formula I or Formula II; Among them, R 1 One selected from the group consisting of methoxy-substituted phenyl, benzyloxy-substituted phenyl, trifluoromethoxy-substituted phenyl, methyl-substituted phenyl, tert-butyl-substituted phenyl, biphenyl, halogen-substituted phenyl, trifluoromethyl-substituted phenyl, cyano-substituted phenyl, naphthyl, 1,2-methylenedioxyphenyl, pyridyl, thienyl, N,N-dimethyl-substituted benzoyl, N,N-diformyl, mercapto, phenoxy, trifluoromethyl, and phenyl; R 2 One selected from halogen (F and Cl).

2. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic hydrocarbons according to claim 1, wherein: include, The poly(hetero)aromatic hydrocarbons represented by formula III and IV are subjected to a hydrodefluorination reaction in dimethyl sulfoxide under the promotion of diphenylphosphine oxide and cesium carbonate to obtain the target compound; Among them, R in formula III and IV 1 、R 2 With R in formula I and II 1 、R 2 The corresponding consistency.

3. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to claim 2, wherein: The phosphine oxide compound is selected from one of bis(p-methylphenyl)phosphine oxide, bis(p-fluorophenyl)phosphine oxide, diethyl phosphite, ethyl phenylphosphonate, and triphenylphosphine oxide.

4. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to claim 2, wherein: The molar ratio of the polyfluoroaromatic hydrocarbon to diphenylphosphine oxide is 1:0 to 1.

5.

5. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic hydrocarbons according to claim 4, wherein: The molar ratio of the polyfluoroaromatic hydrocarbon to water is 1:0-5.

6. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to any one of claims 2 to 5, wherein: The solvent includes one of dimethyl sulfoxide, ethyl acetate, acetonitrile, 1,2-dibromoethane, toluene, tetrahydrofuran, methanol, N,N-dimethylacetamide, n-hexane and water.

7. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to any one of claims 2 to 5, wherein: The reaction temperature is 75-125°C.

8. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to claim 7, wherein: The carbon-fluorine bond hydrogenation defluorination reaction has a reaction time of 12 to 24 hours.

9. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic substances according to any one of claims 2 to 5, wherein: The molar ratio of the polyfluoroaromatic hydrocarbon to the cesium carbonate is 1:0 to 3.

5.

10. The method for hydrogenating and defluorinating carbon-fluorine bonds of poly(hetero)aromatic hydrocarbons according to any one of claims 2 to 5, wherein: The base includes cesium carbonate, sodium acetate, potassium phosphate, lithium hydroxide, triethylamine, and triethylenediamine.

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