Preparation method of alpha-difluoroseleno methyl ketone derivative

Abstract

The invention provides a preparation method of an alpha-difluoroselenomethyl ketone derivative, which is a method for preparing the alpha-difluoroselenomethyl ketone derivative by using 2, 2-difluoroolefin and dialkyl diselenide in the presence of iodosobenzene diacetate. The preparation method specifically comprises the following steps: dissolving 2, 2-difluoroolefin and a dialkyl diselenide compound in an organic solvent, uniformly mixing, adding iodobenzene diacetate, and stirring and reacting at a certain temperature in an air atmosphere to obtain the product alpha-difluoro (seleno) methyl ketone derivative. The alpha-difluoroselenomethyl ketone derivative can be mildly and efficiently obtained by only adopting iodobenzene diacetate without necessary catalysts, alkali, persulfide and persulfate compounds in the prior art. Wherein R1 and R2 are aliphatic hydrocarbon, substituted and unsubstituted benzene, substituted and unsubstituted naphthalene or other aromatic groups.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically involving the preparation of α-difluoroselenomethyl ketone derivatives by reacting 2,2-difluoroolefins and dialkyl diselenyl ethers. Background Technology

[0002] Due to the small atomic radius, high electronegativity, and low polarizability of fluorine atoms, selectively introducing fluorine atoms or fluorine-containing groups into compounds typically results in significant enhancements to the physicochemical and physiological properties (such as electronegativity, chemical and metabolic stability, binding affinity to target proteins, bioavailability, lipid solubility, membrane permeability, and antioxidant activity) of the compounds compared to their parent molecules. Because naturally occurring fluorine-containing organic compounds are extremely rare, their artificial synthesis in the fields of medicine, pesticides, and materials has been a major focus for chemists. The difluoromethyl (methylene) group, with its excellent metabolic stability and electron-withdrawing effect that influences the electronic, chemical, and biological properties of adjacent functional groups, is highly valued in medicinal chemistry and is often used as a bioisostere for primary alcohols, thiols, hydroxamic acids, and amides in the design of drugs and bioactive molecules.

[0003] α-Difluoroselenomethyl ketone derivatives are selenized derivatives containing a difluoromethyl group, playing an indispensable role in pharmaceuticals, pesticides, and new materials. Therefore, developing efficient synthetic methods for the efficient preparation of these fluorinated derivatives is of significant academic and applied value. Currently, there are few reports on synthetic methods for such compounds. Patent CN 110156646 A reports a method for synthesizing difluoroalkyl or difluoromethyl sulfur (selenium) compounds, but it has the following shortcomings, limiting the large-scale synthesis of these compounds: ① The atom economy of the reaction is not high, and unnecessary byproducts are generated during the reaction. ② The substrate expansion process of this reaction mainly focuses on thiolated products, and the substrate compatibility of selenized products in this reaction system is poor, with low yields. A mature, reliable, and scalable synthetic strategy for α-difluoroselenomethyl ketones has not been developed. Therefore, the above method has insurmountable shortcomings, which undoubtedly hinder the large-scale industrial production and application of these compounds. Therefore, developing a green, non-toxic, simple, and substrate-compatible method to obtain α-difluoroselenomethyl ketone derivatives with high conversion rates using inexpensive and readily available reagents is a highly challenging and urgent problem to be solved. Currently, only one method for conveniently introducing difluoroalkyl or difluoromethyl groups into selenium-containing compounds has been reported, namely, patent CN115215778 A, which describes a method for preparing α-difluoro(selenomethyl) ketone derivatives in the presence of potassium persulfate. Therefore, developing a mild and efficient new method for synthesizing sulfur (selenium)-containing compounds with difluoroalkyl and difluoromethyl groups is of great significance. Against this backdrop, this invention utilizes a method for obtaining α-difluoro(selenomethyl) ketone derivatives in high yield in the presence of iodobenzene acetate. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing α-difluoroselenomethyl ketone derivatives, overcoming the shortcomings of existing technologies. This method offers a green, efficient, and low-cost synthetic approach for α-difluoroselenomethyl ketone derivatives, requiring no catalysts or persulfates to achieve high selectivity and high yield of the target product. Furthermore, the reaction process is simple, eliminating the need for cumbersome anhydrous and oxygen-free procedures, and can be carried out in air, facilitating industrial-scale production. This method can also be easily scaled up to the gram level, enabling large-scale synthesis and application of such compounds.

[0005] The preparation method of α-difluoroselenomethyl ketone derivative provided by the present invention includes the following steps: dissolving the 2,2-difluoroolefin derivative of formula (I) or formula (II) and the dialkyl diselenoether of formula (III) in an organic solvent, mixing them evenly, adding iodobenzene acetate of formula (IV), heating the reaction to complete, rotary evaporating the solvent, and then separating and purifying by silica gel column chromatography to obtain the α-difluoroselenomethyl ketone derivative; ; The dialkyl diselenyl ether shown is as shown in formula (III): ; The iodobenzene acetate shown is as shown in formula (IV): ; The structures of the α-difluoroselenomethyl ketone derivatives are shown in formulas (V) and (VI): ; The reaction route is as follows: ; Among them, R 1 R 2 It can be a substituted or unsubstituted aliphatic hydrocarbon, a substituted or unsubstituted benzene, or a substituted or unsubstituted other aromatic groups.

[0006] Preferably, the molar ratio of the 2,2-difluoroolefin derivative, dialkyl diselenyl ether, and iodobenzene acetate is 1.0:0.5-1:1.0~3.0.

[0007] Preferably, the organic solvent is selected from acetonitrile, tetrahydrofuran, benzene, toluene, dimethyl sulfoxide, or N,N-dimethylformamide.

[0008] Preferably, the reaction temperature is 25~80 ℃ and the reaction time is 2~12 hours.

[0009] Preferably, the reaction is carried out in air.

[0010] Preferably, the solvent used for silica gel column chromatography separation and purification is a mixture of petroleum ether and ethyl acetate.

[0011] The beneficial effects of this invention are as follows: This reaction overcomes the shortcomings of existing technologies and provides a method for the synthesis of α-difluoroselenomethyl ketones. Furthermore, the reaction requires no catalyst or base, nor does it require persulfate; the operation is simple, and the target product can be obtained with high selectivity and high yield in air. This method can also be easily scaled up to the gram scale, making the industrial synthesis and application of such compounds possible. Attached Figure Description

[0012] Figure 1 The 1H NMR spectrum of the product obtained in Example 5; Figure 2 The carbon NMR spectrum of the product obtained in Example 5; Figure 3 The NMR fluorine spectrum of the product obtained in Example 5 is shown. Detailed Implementation

[0013] To make the technical solution and advantages of the present invention clearer, the following description is provided in conjunction with embodiments and appendices. Figure 1-3 The present invention will be further described in detail below. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention. Unless otherwise specified, the experimental methods described in the following embodiments are conventional methods; the reagents and raw materials, unless otherwise specified, can be obtained commercially or prepared according to known methods.

[0014] Example 1

[0015] Add the 2,2-difluoroolefin derivative (38 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 1 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 72%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.48 (d, J = 8.5 Hz, 1H), 8.18 (dd, J = 7.3, 1.1Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.67 (d, J = 7.0 Hz, 2H), 7.64 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H), 7.60 – 7.55 (m, 1H), 7.51 – 7.45 (m,1H), 7.45 – 7.39 (m, 1H), 7.32 (dd, J = 10.7, 4.6 Hz, 2H). 13 C NMR (150 MHz, CDCl3) δ 188.24 (t, J = 25.3 Hz), 137.4, 134.5, 133.8, 131.1, 130.15 (t, J= 5.0Hz), 129.9, 129.3, 128.7, 128.6, 126.8, 125.3, 124.0, 123.6, 121.78 (t, J =309.3 Hz). 19 F NMR (565 MHz, CDCl3) δ -75.8. Example 2

[0016]

[0017] Add the 2,2-difluoroolefin derivative (43 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 2 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 68%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.3 Hz, 2H), 7.68 (dd, J = 8.2, 1.8Hz, 4H), 7.63 (d, J = 7.3 Hz, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.46 – 7.39 (m, 2H), 7.35 (t, J = 7.6 Hz, 2H). 13 C NMR (150 MHz, CDCl3) δ 185.19 (t, J = 25.7 Hz),147.2, 139.4, 137.6, 131.02 (t, J = 2.7 Hz), 130.0, 129.6, 129.4, 129.0, 128.7,127.35, 127.30, 123.3, 120.75 (t, J = 306.7 Hz). 19 F NMR (565 MHz, CDCl3) δ -76.3.

[0018] Example 3

[0019] Add the 2,2-difluoroolefin derivative (40 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 3 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 62%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 7.2 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.39 – 7.30 (m, 2H), 1.35 (s,9H). 13 C NMR (150 MHz, CDCl3) δ 185.26 (t, J = 25.6 Hz), 158.75, 137.57, 130.41(t, J = 2.7 Hz), 129.97, 129.33, 128.26, 125.74, 123.44, 120.81 (t, J = 307.1Hz), 35.35, 30.97. 19 F NMR (565 MHz, CDCl3) δ -76.17.

[0020] Example 4

[0021] Add the 2,2-difluoroolefin derivative (42 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 4 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 95%. The NMR data of the product are as follows: 11H NMR (600 MHz, CDCl3) δ 8.60 (d, J J = 8.7 Hz, 1H), 8.22 (dd, J J = 7.5, 6.1Hz, 1H), 8.19 (d, J J = 8.3 Hz, 1H), 7.74 – 7.68 (m, 1H), 7.64 (dd, J J = 8.2, 7.4Hz, 3H), 7.43 (t, J J = 7.5 Hz, 1H), 7.32 (t, J J = 7.7 Hz, 2H), 7.18 – 7.01 (m, 1H). 13 13C NMR (150 MHz, CDCl3) δ 186.85 (t, J J = 25.1 Hz), 162.27 (d, J J = 263.1 Hz),137.45, 133.57 (d, J J = 5.8 Hz), 131.9 (dt, J J = 10.4 Hz, J J = 5.6 Hz), 130.00,129.80, 129.30, 127.21 (d, J J = 1.8 Hz), 125.55 (d, J J = 2.3 Hz), 124.62 (d, J J = 3.9Hz), 124.23 (d, J J = 15.7 Hz), 123.57, 121.97 (t, J J = 309.0 Hz), 121.07 (d, J J = 6.5Hz), 108.19 (d, J J = 21.2 Hz). 19 19F NMR (565 MHz, CDCl3) δ -75.1, -110.6。

[0022] Example 5

[0023] Add the 2,2-difluoroolefin derivative (44 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 5, dissolved in acetonitrile (MeCN, 3 mL), to a 10 mL reaction flask. Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 65%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.53 (s, 1H), 8.03 (dd, J = 8.7, 1.4 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.72 – 7.63 (m, 2H), 7.48 –7.40 (m, 1H), 7.34 (dd, J = 10.6, 4.7 Hz, 2H), 7.20 (dd, J = 8.9, 2.5 Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 3.95 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 185.29 (t, J =25.5 Hz), 160.70, 138.07, 137.64, 133.02 (t, J = 3.8 Hz), 131.81, 130.02,129.35, 127.53, 127.30, 126.01, 125.79, 123.56, 122.2 (t, J = 307.1 Hz), 120.0,105.8, 55.5. 19 F NMR (565 MHz, CDCl3) δ -75.0.

[0024] Example 6

[0025] Add the 2,2-difluoroolefin derivative (44 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 6 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 45%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.14 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.84 –7.70 (m, 1H), 7.64 (d, J = 7.9 Hz, 2H), 7.55 – 7.39 (m, 1H), 7.40 – 7.30 (m, 3H). 13 C NMR (150 MHz, CDCl3) δ 184.30 (t, J = 26.4 Hz), 137.55, 137.41, 133.12(t, J = 3.0 Hz), 132.74, 130.27, 130.22, 129.48, 128.80 (t, J = 3.2 Hz), 122.99,122.92, 121.1 (t, J = 306.7 Hz). 19 F NMR (565 MHz, CDCl3) δ -77.4.

[0026] Example 7

[0027] Add the 2,2-difluoroolefin derivative (46 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 7, dissolved in acetonitrile (MeCN, 3 mL), to a 10 mL reaction flask. Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 48%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.98 (d,J = 8.8 Hz, 2H), 7.59 (d, J = 7.1 Hz,2H), 7.36 – 7.25 (m, 5H), 7.20 – 7.12 (m, 1H), 7.02 (d, J = 7.8 Hz, 2H), 6.95 –6.71 (m, 2H). 13 C NMR (150 MHz, CDCl3) δ 184.23 (t, J = 25.6 Hz), 163.46, 154.80,137.56, 132.96 (t, J = 2.8 Hz), 130.21, 130.0, 129.35, 125.1, 125.07, 123.38,121.9 (t, J = 306.7 Hz), 120.60, 117.05. 19 F NMR (565 MHz, CDCl3) δ -75.7. Example 8

[0028]

[0029] Add the 2,2-difluoroolefin derivative (36 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 8 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 78%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 7.3 Hz, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.39 – 7.26 (m, 4H), 3.24 – 2.67 (m, 1H), 1.28 (d, J =6.9 Hz, 6H). 13 C NMR (150 MHz, CDCl3) δ 185.27 (t, J= 25.6 Hz), 156.53, 137.56,130.70 (t, J = 2.7 Hz), 129.97, 129.32, 128.66, 126.88, 123.43, 121.85 (t, J =306.9 Hz), 34.43, 23.52. 19 F NMR (565 MHz, CDCl3) δ -76.0. Example 9

[0030]

[0031] Add the 2,2-difluoroolefin derivative (56 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 9 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent to dryness using a rotary evaporator, and then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 95%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.67 (d, J = 7.9 Hz, 2H), 7.47 – 7.40 (m, 1H), 7.34 (t, J = 7.4 Hz, 2H), 7.26 (d, J = 5.3 Hz, 1H), 7.13 (s, 1H), 3.94 (s, 3H), 3.83 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 185.36 (t, J = 26.3 Hz), 152.58, 147.44,137.48, 130.04, 129.30, 124.72, 123.39, 121.03 (t, J = 309.2 Hz), 117.33,114.77, 112.95 (t, J = 4.8 Hz), 56.38, 56.13. 19 F NMR (565 MHz, CDCl3) δ -77.0. Example 10

[0032]

[0033] Add the 2,2-difluoroolefin derivative (34 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 10 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 92%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.01 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 7.7 Hz, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 2.73 (q, J = 7.6 Hz, 2H), 1.49 – 0.78 (m, 3H). 13 C NMR (150 MHz, CDCl3) δ 185.28(t, J = 25.6 Hz), 152.02, 137.56, 130.64 (t, J = 2.7 Hz), 129.98, 129.33, 128.54,128.27, 123.42, 121.8 (t, J = 307.1 Hz), 29.12, 14.98. 19 F NMR (565 MHz, CDCl3) δ-76.0. Example 11

[0034]

[0035] Add the 2,2-difluoroolefin derivative (63 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 11 to a 10 mL reaction flask, dissolved in acetonitrile (MeCN, 3 mL). Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 90%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.75 (d, J = 8.6 Hz, 1H), 8.31 (d, J = 7.9 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 7.0 Hz, 2H), 7.59 (ddd, J = 8.5, 6.9,1.3 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.41 (dd, J = 8.5, 5.4 Hz, 2H), 7.35 (t, J =7.4 Hz, 1H), 7.26 (t, J = 7.6 Hz, 2H), 7.05 (dd, J = 12.0, 5.3 Hz, 2H), 6.78 (d, J = 8.4 Hz, 1H), 5.21 (s, 2H). 13 C NMR (150 MHz, CDCl3) δ 185.32 (t, J = 23.7 Hz), 161.73 (d, J = 247.3 Hz), 158.55, 136.50, 133.03 (t, J = 5.9 Hz), 132.19, 130.58 (d, J = 3.2 Hz), 128.78, 128.56, 128.39 (d, J = 8.3 Hz), 128.18, 125.32, 124.97,124.55, 122.94, 122.05(t, J= 307.1 Hz), 121.51, 119.26, 114.75 (d, J = 21.6Hz), 102.28, 68.96. 19 F NMR (565 MHz, CDCl3) δ -72.2, -113.3. Example 12

[0036]

[0037] Add the 2,2-difluoroolefin derivative (65 mg, 0.2 mmol), diphenyldiselenes (62 mg, 0.2 mmol), and iodobenzene acetate (132 mg, 0.4 mmol) shown in Formula 12, dissolved in acetonitrile (MeCN, 3 mL), to a 10 mL reaction flask. Stir the reaction mixture at 80 °C in air for 4 h. After the reaction, concentrate the reaction solvent using a rotary evaporator until dry, then purify the product by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent. The product yield was 48%. The NMR data of the product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.84 (d, J = 8.6 Hz, 1H), 8.56 – 8.36 (m,1H), 8.32 (d, J = 8.4 Hz, 1H), 7.73 – 7.69 (m, 2H), 7.67 (ddd, J = 8.5, 6.9, 1.3Hz, 1H), 7.60 – 7.50 (m, 1H), 7.43 (t, J = 7.4 Hz, 1H), 7.39 – 7.30 (m, 3H), 7.10 (d, J = 7.6 Hz, 1H), 7.07 (s, 1H), 6.93 (dd, J = 8.2, 2.3 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H), 5.32 (s, 2H), 3.84 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 186.33(t, J = 24.1 Hz), 159.98, 159.76, 137.55, 137.45, 134.21 (t, J= 5.8 Hz), 133.25,129.90, 129.81, 129.57, 129.22, 126.32, 126.07, 125.57, 123.11, 122.6 (t, J =307.1 Hz), 119.61, 113.64, 113.15, 103.43, 70.5, 55.3. 19 F NMR (565 MHz, CDCl3)δ -72.1. Example 13

[0038]

[0039] 1.0 g (4.8 mmol) of the 2,2-difluoroolefin derivative shown in Formula 13, 1.5 g (4.8 mmol) of diphenyldiselenes, and iodobenzene acetate (3.1 g, 9.6 mmol) were added to a 100 mL reaction flask in acetonitrile (MeCN, 30 mL). The reaction was stirred at 80 °C in air for 8 h. After the reaction was completed, the reaction solvent was concentrated to dryness by rotary evaporation and then purified by silica gel column chromatography. The eluent was ethyl acetate / petroleum ether, yielding the corresponding product (yield 82%). The successful implementation of the above gram-scale experiment indicates that this reaction is easily synthesized on a large scale. It is expected to provide technical support for the industrial synthesis of α-difluoroselenomethyl ketone derivatives.

[0040] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. For those skilled in the art, any obvious modifications made to the present invention without departing from its principles and spirit should be considered to be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing an α-difluoroselenomethyl ketone derivative, characterized in that: The method is as follows: using 2,2-difluoroolefin and dialkyl diselenyl ether as raw materials, the reaction is carried out in a solvent under air atmosphere and at a certain temperature in the presence of iodobenzene acetate to obtain an α-difluoroselenomethyl ketone derivative. The structure of the 2,2-difluoroolefin derivative is shown in formula (I) or (II). ； The dialkyl diselenyl ether shown is as shown in formula (III): ； The iodobenzene acetate shown is as shown in formula (IV): ； The structures of the α-difluoroselenomethyl ketone derivatives are shown in formulas (V) and (VI): ； In general formulas (I), (II), (III), (V) and (VI): R 1 It is an aliphatic hydrocarbon, substituted and unsubstituted benzene, substituted and unsubstituted naphthalene, or other aromatic groups; R 2 It is an aliphatic hydrocarbon, substituted and unsubstituted benzene, substituted and unsubstituted naphthalene, or other aromatic groups.

2. The method for preparing the α-difluoroselenomethyl ketone derivative according to claim 1, characterized in that, In molar quantities, the ratio of 2,2-difluoroolefin derivatives: dialkyl diselenyl ether: iodobenzene acetate is 1.0~3.0 : 0.5~2.0 : 1.0~3.

0.

3. The method for preparing the α-difluoroselenomethyl ketone derivative according to claim 1, characterized in that, The reaction time is 2 to 12 hours; the reaction temperature is 25 to 80 °C.

4. The method for preparing the α-difluoroselenomethyl ketone derivative according to claim 1, characterized in that, The reaction takes place in air.

5. The method for preparing the α-difluoroselenomethyl ketone derivative according to claim 1, characterized in that, The organic solvent is selected from acetonitrile, tetrahydrofuran, dichloroethane, dioxane, benzene, toluene, dimethyl sulfoxide, or... N,N -Dimethylformamide.

6. The method for preparing the α-difluoroselenomethyl ketone derivative according to claim 1, characterized in that, The reaction requires no catalyst or base, no persulfide, no potassium persulfate, and no other salts.

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