A controllable defluorination hydrogenation method of polyfluoroamide

Abstract

The invention discloses a controllable defluorination hydrogenation method of polyfluoroamide, wherein the invention uses fluorine-substituted N-phenylacetamide derivatives as raw materials, adds boric ester, hydrogen source, magnesium powder and solvent, completes the reaction under certain conditions, and controls the usage ratio of substrate and magnesium powder and substrate and boric ester, thereby realizing the controllable defluorination hydrogenation or defluorination hydrogenation reaction of polyfluoroamide, and obtaining a higher yield. The controllable defluorination reaction provided by the invention has wide adaptability of reactants, few by-products, high product yield, and low reagent toxicity, which is of great significance to the development of organic synthetic chemistry.

Description

Technical Field

[0001] The invention relates to a defluorination method of polyfluoroamide, in particular to a controllable defluorination hydrogenation method of polyfluoroamide. Background Art

[0002] Organic fluorine compounds are widely used in medicine, agrochemicals, materials and other fields. Difluoromethyl compounds are very valuable fluorinated intermediates in synthetic chemistry and pharmaceutical engineering. About 20-25% of drugs on the market contain fluorine atoms. In particular, adding fluoroalkyl moieties such as difluoromethyl (CFH2) or monofluoromethyl (CFH2) groups to the structure of natural products and bioactive molecules can improve hydrogen bonding ability, metabolic stability and lipophilicity. Compared with fluorine-free analogues, the binding effect is enhanced.

[0003] At present, among the numerous methods for synthesizing difluoromethyl compounds, directly selecting catalysis CF activation trifluoromethyl to generate corresponding difluoromethyl free radicals is a powerful method for synthesizing difluoromethyl compounds. And the low cost and universality of trifluoroacetamide, trifluoroacetate and various trifluoromethylated (hetero) aromatic hydrocarbons make CF activation trifluoromethyl to generate this direct conversion of corresponding difluoromethyl free radicals more attractive to people to study. But in the prior art, many methods for selective defluorination have high cost, large danger, many problems such as strong reagent toxicity.

[0004] In 2016, Lalic reported the defluorination of trifluoromethyl aromatics using a palladium-copper-pyridone catalytic system (Chem. Sci., 2016, 7, 505-509). However, the method has cumbersome steps and poor atom economy. Prakash reported the controlled defluorination of bis(trifluoromethyl)benzene in 2017 (Eur. J. Org. Chem. 2017, 2322- 2326). The use of magnesium powder as a catalyst can obtain a product of defluorination, however, the substrate of the reaction is very limited and defluorination cannot be achieved. In 2021, Wang and Houk reported a new strategy for the continuous CF bond functionalization of trifluoroacetamide and acetate (Science. 2021 Mar 19;371(6535):1232-1240.), in which 1,2-di-tert-butoxydiazene was used as a free radical initiator, 4-dimethylaminopyridine deuterated borane DMAP-BH was used as a hydrogen source, thiol and sodium dihydrogen phosphate were added as additives, and the spin center was transferred after boron free radical addition under a nitrogen atmosphere to produce a controllable defluorination product. However, this method system is complex and the reagents used are highly toxic. In 2023, Shen, Zhu et al. used an electrochemical cell with magnesium metal as the anode and graphite as the cathode (Angew. Chem. Int. Ed. 2023, 62, e202217244), and achieved a controllable defluorination hydrogenation reaction by adding boron ester and electrolyte, but the reaction cannot be expanded and is not used for industrial production.

[0005] Most of the methods reported above for the controllable defluorination of trifluoromethyl or defluorination of difluoromethane are complex and toxic. The main reason is that after the first fluorine atom leaves, the bond dissociation energy of the subsequent carbon-fluorine bond decreases, making the subsequent defluorination reaction easier and the amount of defluorination difficult to control. Given the high value of difluoromethyl compounds, how to choose appropriate reaction conditions for a convenient and controllable defluorination hydrogenation reaction is of great research value. Summary of the invention

[0006] In view of the above technical problems, the present invention provides a controllable defluorination hydrogenation method of polyfluoroamide. The method provided by the present invention has easy-to-obtain raw materials, simple operation, and a wide range of reactants; the method has few by-products, high product yield, and can effectively control the production of monofluoro or difluoromethyl compounds, which is suitable for industrial production.

[0007] The technical solution of the present invention is as follows:

[0008] The controllable defluorination and hydrogenation method of polyfluoroamide of the present invention is to realize the controllable demonofluorination and hydrogenation reaction or dedifluorination and hydrogenation reaction of polyfluoroamide in a solvent in air or nitrogen atmosphere, using acetic acid / water as a hydrogen source, using magnesium powder to initiate the reaction, adding boric ester as an additive.

[0009] The reaction route is shown below:

[0010]

[0011] The polyfluoroamide is a 2,2,2-trifluoro-N-phenylacetamide derivative or a 2,2,3,3,3-pentafluoro-N-phenylpropionamide derivative, and its general structural formula is shown in the following formula I:

[0012]

[0013] In Formula I, R 2 When it is hydrogen, R 1 is one or a combination of hydrogen, ethyl, isopropyl, tert-butyl, dioxolanyl, fluorine, trifluoromethyl, ethyl acetate, phenyl ether; when R 2 When it is methyl, R 1 When R is trifluoromethyl, R 1 Methyl, R 2 For hydrogen.

[0014] The controllable defluorination hydrogenation method of polyfluoroamide of the present invention comprises a defluorination hydrogenation reaction and a defluorination hydrogenation reaction.

[0015] Further, when the main generated product is II, the molar ratio of the substrate to the magnesium powder is 1:3-5; the molar ratio of the substrate to the boric grease is 1:0.5-1. Preferably, the molar ratio of the substrate to the magnesium powder is 1:3; the molar ratio of the substrate to the boric grease is 1:1.

[0016] Furthermore, when the main product is controlled to be III, the molar ratio of the substrate to the magnesium powder is 1:7-13; the molar ratio of the substrate to the boric grease is 1:2.5-5. Preferably, the molar ratio of the substrate to the magnesium powder is 1:10; the molar ratio of the substrate to the boric grease is 1:3.

[0017] Furthermore, the volume ratio of acetic acid to water is 1-4:2-1.

[0018] Furthermore, the volume ratio of acetic acid to water is 2:1.

[0019] Furthermore, the added volume of the acetic acid-water is 2-5 times the molar amount of polyfluoroamide.

[0020] Furthermore, the volume of the solvent is 60 times the molar amount of polyfluoroamide.

[0021] The present invention realizes a controllable defluorination hydrogenation reaction of polyfluoroamide, and can realize a monofluorination removal reaction or a difluorination removal reaction by adjusting the usage ratio of substrate to magnesium powder and substrate to boric ester. The reaction operation of the present invention is relatively simple, the reaction adaptability is extremely wide, and the toxicity is low, thereby providing an effective way for the later modification of fluorine-containing molecules. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 HNMR diagram of the product prepared in Example 1;

[0023] Figure 2 HNMR diagram of the product prepared in Example 2;

[0024] Figure 3 HNMR diagram of the product prepared in Example 3;

[0025] Figure 4 HNMR diagram of the product prepared in Example 4;

[0026] Figure 5 HNMR diagram of the product prepared in Example 5;

[0027] Figure 6 HNMR diagram of the product prepared in Example 6;

[0028] Figure 7 HNMR diagram of the product prepared in Example 7;

[0029] Figure 8 HNMR diagram of the product prepared in Example 8;

[0030] Fig. 9 HNMR diagram of the product prepared in Example 9;

[0031] Fig.10 HNMR diagram of the product prepared in Example 10;

[0032] Fig.11 HNMR diagram of the product prepared in Example 11;

[0033] Fig.12 HNMR diagram of the product prepared in Example 12;

[0034] Fig.13 This is the HNMR diagram of the product prepared in Example 13;

[0035] Fig.14 This is the HNMR diagram of the product prepared in Example 14;

[0036] Fig.15 This is the HNMR diagram of the product prepared in Example 15;

[0037] Fig.16This is the HNMR pattern of the product prepared in Example 16;

[0038] Fig.17 This is the HNMR pattern of the product prepared in Example 17;

[0039] Fig.18 This is the HNMR diagram of the product prepared in Example 18;

[0040] Fig.19 This is the HNMR chart of the product prepared in Example 19. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. It should be understood that these descriptions are only exemplary and are not intended to limit the scope of the present invention. In addition, in the following description, the description of well-known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention.

[0042] The following are examples of preparing compounds of the structures shown.

[0043] Example 1

[0044]

[0045] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro-N-phenylacetamide, 1.05mmol (1eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol (3eq) of magnesium powder, 5mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) in the air, and stir the reaction at 60°C until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, and the mixture is extracted three times with ethyl acetate. The organic phase is collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent is removed by rotary evaporation and separated by column chromatography. The eluent is petroleum ether to ethyl acetate in a ratio of 10:1. The yield is 166mg, and the yield is 93%.

[0046] 1 HNMR (800 MHz, CDCl 3 ) 7.95–7.85 (m, 1H), 7.53 – 7.47 (m, 2H), 7.30 (dd, J = 8.6, 7.4 Hz, 2H), 7.14 (t, J = 7.5 Hz, 1H), 5.94 (t, J = 54.4 Hz, 1H).

[0047] Example 2

[0048]

[0049] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro-N-phenylacetamide, 3.15mmol (3eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10.5mmol of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) in the air, and stir the reaction at 60°C until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, and the mixture is extracted three times with ethyl acetate. The organic phase is collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent is removed by rotary evaporation and separated by column chromatography. The eluent is petroleum ether to ethyl acetate in a ratio of 10:1. The yield is 147mg, and the yield is 91%.

[0050] 1 H NMR (800 MHz, CDCl 3 ) 7.87 (s, 1H), 7.50 (dd, J = 8.6, 1.2 Hz, 2H),7.29 (dd, J = 8.6, 7.4 Hz, 2H), 7.11 – 7.08 (m, 1H), 4.85 (d, J = 47.4 Hz, 2H).

[0051] Example 3

[0052]

[0053] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N -(3-fluorophenyl)acetamide, 0.525mmol (0.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol (3eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (1:2) were stirred at 50°C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 110mg and the yield was 60%.

[0054] 1 H NMR (800 MHz, CDCl 3 ) 7.85 (s, 1H), 7.46 (dt, J = 10.3, 2.3 Hz,1H), 7.27 (td, J = 8.2, 6.3 Hz, 1H), 7.16 (ddd, J = 8.1, 2.1, 0.9 Hz, 1H), 6.85(tdd, J = 8.3, 2.5, 0.9 Hz, 1H), 5.99 (t, J = 54.3 Hz, 1H).

[0055] Example 4

[0056]

[0057] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol of ethyl {4-[(trifluoroacetyl)amino]phenyl}acetate, 1.05mmol of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol of magnesium powder, 5mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (3:1) in the air, seal it and stir at 60 °C until the raw materials are almost completely reacted; after the reaction is completed and cooled, add water, extract with ethyl acetate three times, collect the organic phase, wash with brine, dry with anhydrous sodium sulfate, remove the solvent by rotary evaporation, and separate by column chromatography. The eluent is petroleum ether and ethyl acetate in a ratio of 10:1. The yield is 140mg and the yield is 75%.

[0058] 1 H NMR (800 MHz, CDCl 3 ) 8.04 (s, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.19(d, J = 6.8 Hz, 2H), 5.96 (d, J = 54.5 Hz, 1H), 4.08 (q, J = 7.1 Hz, 2H), 3.53 (s,2H), 1.18 (t, J = 7.2 Hz, 3H).

[0059] Example 5

[0060]

[0061] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N -[4-isopropylphenyl]acetamide, 1.05mmol (1eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol (3eq) of magnesium powder, 5mL of methanol, 0.2mL of acetic acid / water (3:1), sealed and stirred at 60 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, extracted three times with ethyl acetate, the organic phase was collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate 10:1. The yield was 107mg, and the yield was 58%.

[0062] 1 H NMR (800 MHz, CDCl3) 7.75 (s,1H), 7.42 – 7.40 (m,2H), 7.17 (d,J = 8.4 Hz,2H), 5.94 (t, J = 54.5 Hz,1H), 2.84 (dt, J = 13.8, 6.9 Hz,1H), 1.17 (d, J = 6.9 Hz, 6H).

[0063] Example 6

[0064]

[0065] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N -[4-isopropylphenyl]acetamide, 3.15mmol (3eq) of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10.5mmol of magnesium powder, 10mL of dimethyl sulfoxide, 0.2mL of acetic acid / water (3:1), sealed and stirred at 60 °C until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, extracted three times with ethyl acetate, the organic phase is collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation and separated by column chromatography. The eluent is petroleum ether to ethyl acetate 10:1. The yield is 116mg and the yield is 69%.

[0066] 1 H NMR (800 MHz, CDCl 3 ) 7.79 (s,1H), 7.40 (d, J = 8.5 Hz,2H), 7.15 (d, J = 8.4 Hz,2H), 4.85 (d, J = 47.4 Hz,2H), 2.83 (dt, J = 13.8, 6.9 Hz,1H), 1.17 (d, J = 6.9 Hz, 6H).

[0067] Example 7

[0068]

[0069] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol of 2,2,2-trifluoro- N -[4-tert-butylphenyl]acetamide, 1.05mmol of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol of magnesium powder, 5mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (4:1) were stirred at 70°C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 118mg and the yield was 64%.

[0070] 1 H NMR (800 MHz, CDCl 3 ) 7.75 (s,1H), 7.43 – 7.41 (m,2H), 7.34 –7.32 (m,2H), 5.95 (t, J = 54.5 Hz,1H), 1.25 (s,9H).

[0071] Example 8

[0072]

[0073] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N-[4-tert-butylphenyl]acetamide, 3.15mmol (3eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10.5mmol of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (4:1) were stirred at 70°C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 130mg and the yield was 76%.

[0074] 1 H NMR (400 MHz, CDCl 3 ) 7.92 (s, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 4.92 (d, J = 47.6 Hz, 2H), 1.32 (s, 9H).

[0075] Example 9

[0076]

[0077] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N -[4-trifluoromethylphenyl]acetamide, 0.525mmol (0.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 5.25mmol (5eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 50 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 124mg and the yield was 67%.

[0078] 1 H NMR (800 MHz, CDCl 3 ) 7.99 (s, 1H), 7.66 (d, J = 8.5 Hz, 2H), 7.58(d, J = 8.6 Hz, 2H), 6.01 (d, J = 54.2 Hz, 1H).

[0079] Example 10

[0080]

[0081] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro- N -[4-trifluoromethylphenyl]acetamide, 2.625mmol (2.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10.5mmol of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 70 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 115mg and the yield was 67%.

[0082] 1 H NMR (800 MHz, CDCl 3 ) 8.05 (s, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.54(d, J = 8.5 Hz, 2H), 4.88 (d, J = 47.3 Hz, 2H).

[0083] Embodiment 11

[0084]

[0085] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of N -(Benzo[2,1- d [1,3]dioxole)-2,2,2-trifluoroacetamide, 2.10mmol (2eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 5.25mmol (5eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 60°C to react until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 5:1. The yield was 127mg and the yield was 69%.

[0086] Example 12

[0087]

[0088] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of N -(Benzo[2,1- d [1,3]dioxole)-2,2,2-trifluoroacetamide, 3.15mmol (3eq) of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10.5mmol of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 60 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 8:1. The yield was 103mg and the yield was 61%.

[0089] 1 H NMR (800 MHz, CDCl 3 ) 7.79 (s, 1H), 7.20 – 7.17 (m, 1H), 6.79 (dd, J = 8.3, 2.2 Hz, 1H), 6.70 (d, J = 8.3 Hz, 1H), 5.90 (s, 2H), 4.84 (d, J= 47.4 Hz, 2H).

[0090] Embodiment 13

[0091]

[0092] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of N -(3-ethylphenyl)-2,2,2-trifluoroacetamide, 1.05mmol (1eq) of bipyraclostrobin, 5.25mmol (5eq) of magnesium powder, 10mL of methanol, and 0.2mL of acetic acid / water (2:1) were stirred at 60 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 8:1. The yield was 148mg and the yield was 78%.

[0093] 1 H NMR (800 MHz, CDCl 3 ) 7.86 – 7.77 (m, 1H), 7.70 (s, 1H), 7.17(d, J = 7.1 Hz, 2H), 7.13 (dd, J = 7.4, 1.4 Hz, 1H), 5.95 (t, J = 54.4 Hz, 1H),2.53 (q, J = 7.6 Hz, 2H), 1.16 (t, J = 7.9 Hz, 3H).

[0094] Embodiment 14

[0095]

[0096] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of N -(3-ethylphenyl)-2,2,2-trifluoroacetamide, 4.20mmol (4eq) of bipyraclostrobin, 11.55mmol (11eq) of magnesium powder, 10mL of methanol, and 0.2mL of acetic acid / water (2:1) were stirred at 60 °C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate 8:1. The yield was 167mg and the yield was 70%.

[0097] 1 H NMR (800 MHz, CDCl 3 ) 7.84 (s, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.16(d, J = 7.3 Hz, 2H), 7.09 (s, 1H), 4.88 (d, J = 47.5 Hz, 2H), 2.55 (d, J = 7.7 Hz,2H), 1.18 (d, J = 7.5 Hz, 3H).

[0098] Embodiment 15

[0099]

[0100] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro-N-diphenyletheracetamide, 5.25mmol (5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 10mmol of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) in the air, and stir the reaction at 70 °C until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, and the mixture is extracted three times with ethyl acetate. The organic phase is collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent is removed by rotary evaporation and separated by column chromatography. The eluent is petroleum ether to ethyl acetate in a ratio of 3:1. The yield is 138mg, and the yield is 74%.

[0101] 1 H NMR (800 MHz, CDCl 3 ) 7.91 (s, 1H), 7.48 – 7.41 (m, 2H), 7.24(dd, J = 8.6, 7.3 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.98 – 6.75 (m, 4H), 4.84(d, J = 47.4 Hz, 2H).

[0102] Example 16

[0103]

[0104] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro-N-methyl-N-phenylacetamide, 0.525mmol (0.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 5.25mmol (5eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) in the air, and stir the reaction at 45 °C until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, and the mixture is extracted three times with ethyl acetate. After the organic phase is collected, it is washed with brine, dried with anhydrous sodium sulfate, and the solvent is removed by rotary evaporation. After separation by column chromatography, the eluent is petroleum ether to ethyl acetate in a ratio of 10:1. The yield is 154mg, and the yield is 85%.

[0105] 1 H NMR (800 MHz, CDCl 3 ) 7.37 (dt, J = 36.2, 7.3 Hz, 3H), 7.21 –7.17 (m, 2H), 5.70 (t, J = 53.4 Hz, 1H), 3.27 (d, J = 1.1 Hz, 3H).

[0106] Embodiment 17

[0107]

[0108] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,2-trifluoro-N-methyl-N-phenylacetamide, 2.625mmol (2.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 7.35mmol (7eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) in the air, and stir at 60°C to react until the raw materials are almost completely reacted; after the reaction is completed and cooled, water is added, and the mixture is extracted three times with ethyl acetate. After the organic phase is collected, it is washed with brine, dried with anhydrous sodium sulfate, and the solvent is removed by rotary evaporation. After separation by column chromatography, the eluent is petroleum ether to ethyl acetate in a ratio of 10:1. The yield is 90mg and the yield is 55%.

[0109] 1 H NMR (800 MHz, CDCl 3 ) 7.45– 7.30 (m, 3H), 7.13 (d, J = 8.0 Hz, 2H), 4.57 (d, J = 47.1 Hz, 2H), 3.23 (s, 3H).

[0110] Embodiment 18

[0111]

[0112] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,3,3,3-pentafluoro- N-(4-methylphenyl)propionamide, 0.525mmol (0.5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 3.15mmol (3eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 60°C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 161mg and the yield was 87%.

[0113] 1 H NMR (800 MHz, CDCl 3 ) 7.81 (s, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), 5.16 – 5.09 (m, 1H), 2.27 (s, 3H).

[0114] Embodiment 19

[0115]

[0116] Take a 50ml flask with a magnetic pole and dry it, add 1.05mmol (1eq) of 2,2,3,3,3-pentafluoro- N -(4-methylphenyl)propionamide, 5.25mmol (5eq) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)benzonitrile, 13.65mmol (13eq) of magnesium powder, 10mL of dimethyl sulfoxide, and 0.2mL of acetic acid / water (2:1) were stirred at 70°C until the raw materials were almost completely reacted; after the reaction was completed and cooled, water was added, and the mixture was extracted three times with ethyl acetate. The organic phase was collected and washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation and separated by column chromatography. The eluent was petroleum ether to ethyl acetate in a ratio of 10:1. The yield was 128mg and the yield was 75%.

[0117] 1 H NMR (800 MHz, CDCl 3 ) 7.81 (s, 1H), 7.31 – 7.29 (m, 2H), 7.07 (d,J = 8.0 Hz, 2H), 3.15 (q, J = 10.5 Hz, 2H), 2.25 (s, 3H).

[0118] In the embodiment of the present invention, magnesium powder and hydrogen source acetic acid / water are low-cost and easily available, and the reaction does not require air and water sensitive reagents, is easy to operate, does not require the use of thiols with a foul odor, and no foul odor is generated during the entire reaction process.

Claims

1. A method for controlled defluorination and hydrogenation of polyfluoroamide, characterized in that: A fluorine-substituted N-phenylacetamide derivative having the general formula as shown in Formula I is used as a raw material, a boric ester, a hydrogen source, magnesium powder and a solvent are added, reacted and separated to obtain a product; The specific reaction route is: ； In formula I, R is fluorine, R2 is hydrogen, R1 is one of hydrogen, ethyl, isopropyl, tert-butyl, dioxolanyl, fluorine, ethyl acetate, trifluoromethyl, and phenyl ether; or R is fluorine, R2 is methyl, and R1 is hydrogen; or R is trifluoromethyl, R1 is methyl, and R2 is hydrogen; The boron ester is one of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborol)benzonitrile, 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborol)benzonitrile and biboronic acid pinacol ester; The molar ratio of the substrate to the magnesium powder is 1:3-5, the molar ratio of the substrate to the boric acid is 1:0.5-1, and the amount of the generated product II is ≥55%; Alternatively, the molar ratio of the substrate to the magnesium powder is 1:7-13, the molar ratio of the substrate to the boric acid is 1:2.5-5, and the amount of the generated product III is ≥55%; The hydrogen source is acetic acid-water, and the volume ratio of acetic acid-water is 4:1-2:

1.

2. The method for controlled defluorination and hydrogenation of polyfluoroamide according to claim 1, characterized in that: The molar ratio of the substrate to the magnesium powder is 1:3; the molar ratio of the substrate to the boric grease is 1:

1.

3. The method for controlled defluorination and hydrogenation of polyfluoroamide according to claim 1, characterized in that: The molar ratio of the substrate to the magnesium powder is 1:10; the molar ratio of the substrate to the boric grease is 1:

3.

4. The method for controlled defluorination and hydrogenation of polyfluoroamide according to claim 1, characterized in that: The volume ratio of acetic acid to water is 2:

1.

5. The method for controlled defluorination and hydrogenation of polyfluoroamide according to claim 1, characterized in that: The added volume of the acetic acid-water is 2-5 times the molar amount of the compound of formula I.

6. A method for controlled defluorination and hydrogenation of polyfluoroamide according to claim 1, characterized in that: The volume of the solvent used is 60 times the molar amount of the compound of formula I.

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