A method for synthesizing a fluoroalkyl-substituted quinoxalinone derivative

Abstract

The present application relates to the field of organic synthesis, specifically a method for synthesizing C3 fluorine alkyl substituted quinoxaline ketone derivatives from olefin derivatives and quinoxaline ketone derivatives under photocatalysis by using [bis(fluoroalkyl acetoxy)iodo] benzene as different fluorine alkyl sources. [Bis(fluoroalkyl acetoxy)iodo] benzene is used as a fluorine alkylating agent to generate fluorine alkyl radicals under photocatalysis, then the radicals add to olefin derivatives to obtain alkyl radicals, the alkyl radicals then add to quinoxaline ketone, and finally, after oxidation and deprotonation, C3 fluorine alkyl substituted quinoxaline ketone derivatives are obtained. The present application uses simple and stable [bis(fluoroalkyl acetoxy)iodo] benzene as a fluorine alkyl source to prepare C3 different fluorine alkyl substituted quinoxaline ketone derivatives from quinoxaline ketone and olefin derivatives in a three-component reaction without the action of photocatalysts. The synthesis method is simple and easy to operate, and different fluorine alkyl group substituted quinoxaline ketone derivatives can be quickly obtained.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and relates to a method for synthesizing C3-fluoroalkyl-substituted quinoxalone derivatives from [bis(fluoroalkylacetoxy)iodo]benzene, olefin derivatives and quinoxalone derivatives under photocatalysis, using [bis(fluoroalkylacetoxy)iodo]benzene as different fluoroalkyl sources. Background Technology

[0002] Quinoxalones, as important structural units, are frequently found in a large number of natural products and bioactive molecules, possessing a wide range of biological properties, including antihistamine, antibacterial, antimalarial, antiviral, and anticancer activities. C3-functionalized quinoxalones, in particular, have attracted considerable synthetic interest from pharmaceutical and chemical researchers due to their significant and intriguing pharmacological properties. Therefore, many efficient methods exist for constructing 3-substituted quinoxalone derivatives through C3-functionalization of quinoxalones. Through these strategies, a range of functional groups, such as aryl, acyl, alkoxy, amino, oxoalkyl, cyano, phosphorus, and sulfonyl groups, can be readily introduced into this framework.

[0003] On the other hand, the incorporation of fluoroalkyl groups has a significant impact on the physical and pharmacological properties of organic molecules (i.e., electronegativity, lipophilicity, metabolic stability, and bioavailability). Therefore, efficient synthesis of quinoxaline-2(1H)-ones represents a special class of unit structures found in various functional materials, bioactive natural products, and pharmaceutical compounds. Among them, C3-substituted quinoxaline-2(1H)-one derivatives possess a wide range of biological activities, including antitumor, anti-HIV, antibacterial, bronchodilator, and protein kinase inhibitory activities.

[0004] In recent years, visible light-induced photoredox catalysis has attracted great interest from chemists because it can provide a particularly attractive method for constructing a variety of valuable compounds, with advantages such as simple operation, mild conditions, and environmental friendliness. Meanwhile, significant progress has been made in the C3 functionalization of quinoxaline-2(1H)-ones, including a series of functionalizations such as arylation, alkylation, benzylation, acylation, alkoxylation, alkoxycarbonylation, amination, and phosphorylation. In 2020, Professor Wei Wei's research group at Qufu Normal University developed a method for the metal-free trifluoroalkylation of quinoxaline-2(1H)-ones with inactive alkenes and Langlois reagents. In 2021, Professor Wei Wei further developed this method, creating a visible light-induced three-component reaction of quinoxaline-2(1H)-ones, alkenes, and CF3SO2Na. In the same year, Professor Xu Xiuhua's research group at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, developed a photocatalytic 2,2,2-difluoroethylation reaction to introduce quinoxaline-2(1H)-ones into a multi-component reaction.

[0005]

[0006] This patent utilizes a visible light-induced direct CH fluoroalkylation method for a three-component quinoxalin-2(1H)-one derivative involving olefin derivatives, using [bis(fluoroalkylacetoxy)iodo]benzene as the fluoroalkylating agent. Specifically, under photocatalysis, a high-valent iodine reagent generates a fluoroalkyl radical source, which subsequently adds to the olefin derivative. Finally, it undergoes radical addition, oxidation, and deprotonation with the quinoxalin-2(1H)-one to obtain the fluoroalkyl-substituted quinoxalinone derivative. [bis(fluoroalkylacetoxy)iodo]benzene can be easily prepared by reacting iodobenzene acetate with a fluoroalkyl acid. Furthermore, the method used in this patent does not require a photocatalyst and can rapidly construct quinoxalin-2(1H)-one derivatives with different fluoroalkyl substitutions at the C3 position. Summary of the Invention

[0007] The purpose of this invention is to rapidly construct C3-substituted fluoroalkyl quinoxaline-2(1H)-one derivatives by multi-component reaction of [bis(fluoroalkylacetoxy)iodo]benzene reagent and olefin derivatives.

[0008] A method for the direct CH fluoroalkylation reaction of quinoxalin-2(1H)-one with olefin derivatives induced by visible light under photocatalytic and metal-free catalytic conditions is characterized by using a newly developed [bis(fluoroalkylacetoxy)iodo]benzene as the fluoroalkyl source. Specific steps include: adding quinoxalin-2(1H)-one, [bis(fluoroalkylacetoxy)iodo]benzene, 1,4-dioxane, [bis(trifluoroacetoxy)iodo]benzene, and olefin derivatives under anhydrous and oxygen-free conditions, and reacting at room temperature under a 24W blue LED light. After the reaction, the fluoroalkyl-substituted quinoxalin-2(1H)-one derivative is obtained by extraction, washing, drying, and column chromatography.

[0009] The fluoroalkylation method described herein has the following general reaction formula, wherein R 1 Selected from hydrogen, halogen, phenyl; R 2 Selected from methyl, ethyl, and p-methylbenzyl; R 3 Selected from phenyl, p-methylphenyl; R f Selected from difluoroethyl, difluoromethyl, and difluoroethyl acetate.

[0010]

[0011] Reaction mechanism:

[0012]

[0013] Table 1 shows the structures of quinoxalinone derivatives synthesized by the present invention via multi-component synthesis and the [bis(fluoroalkylacetoxy)iodo]benzene as follows:

[0014]

[0015]

[0016] Compared with the prior art, the present invention has the following advantages:

[0017] 1. The reaction used in this invention does not require a photocatalyst, and the operation is simple and the conditions are mild;

[0018] 2. It can rapidly and efficiently synthesize derivatives of quinoxaline-2(1H)-one with different fluoroalkyl substitutions at the C3 position;

[0019] 3. [bis(fluoroalkylacetoxy)iodo]benzene is stable and easy to prepare. Attached Figure Description

[0020] Figure 1 The 1H spectrum is for the compound in Example 1.

[0021] Figure 2 The 1H spectrum is for the compound in Example 1.

[0022] Figure 3 The 1H spectrum is for the compound in Example 1.

[0023] Figure 4 The 1H spectrum is for the compound in Example 1.

[0024] Figure 5 The 1H spectrum is for the compound in Example 1.

[0025] Figure 6 The 1H spectrum is for the compound in Example 1.

[0026] Figure 7 The 1H spectrum is for the compound in Example 1.

[0027] Figure 8 The 1H spectrum is for the compound in Example 1.

[0028] Figure 9 The 1H spectrum is for the compound in Example 1.

[0029] Figure 10 The 1H spectrum is for the compound in Example 1.

[0030] Specific implementation methods:

[0031] The method and reaction formula for synthesizing fluoroalkyl-substituted quinoxalone derivatives from quinoxaline-2(1H)-one provided by this invention are shown below:

[0032]

[0033] The operation steps are as follows:

[0034] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A hot torch was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, quinoxaline-2(1H)-one and its derivatives (0.30 mmol), olefins and their derivatives (0.60 mmol), [bis(trifluoroacetoxy)iodo]benzene (0.6 mmol), and [bis(fluoroalkylacetoxy)iodo]benzene (0.60 mmol) were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, the product was washed with a large amount of water, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain the product (the mobile phase system was petroleum ether: ethyl acetate).

[0035] The following examples illustrate this point:

[0036] Example 1

[0037]

[0038] Iodophenylacetic acid (4 mmol) was added to a stirred solution of toluene (4 mL), and 2,2-difluoropropionic acid (1.00 mL, 16 mmol) was added dropwise at room temperature. After stirring for 30 min, the solvent was evaporated to dryness. Toluene (2 mL) was added to the crude mixture, and the mixture was then concentrated again to completely remove unreacted acid. After evaporation, no further purification was required to give the corresponding [bis(2,2-difluoropropionyloxy)iodo]benzene, a white solid, in 96% yield. 1 H NMR (400MHz, CDCl3) δ8.14 (d, 2H), 7.67 (t, J=3.6, 1H), 7.56 (t, J=7.8, 2H), 1.71 (t, J=9.4, 6H). 13 C NMR (100MHz, CDCl3) δ168.44 (t, J=33.0Hz, 2C), 134.89, 132.89, 131.61, 131.31, 122.49, 114.36 (t, J=248.0Hz, 2C), 21.81 (t, J=25.0Hz, 2C). 19 F NMR (376MHz, CDCl3) δ-96.74 (s, 4F).

[0039] Example 2

[0040]

[0041] Iodophenylacetic acid (4 mmol) was added to a stirred solution of toluene (4 mL), and 2-(ethoxycarbonyl)-2,2-difluoroacetic acid (1.00 mL, 16 mmol) was added dropwise at room temperature. After stirring for 30 min, the solvent was evaporated to dryness. Toluene (2 mL) was added to the crude mixture, and the mixture was then concentrated again to completely remove unreacted acid. After evaporation, no further purification was required to give the corresponding [bis(2-(ethoxycarbonyl)-2,2-difluoroacetoxy)iodo]benzene, a white solid, in 92% yield. 1 H NMR (400MHz, CDCl3) δ8.32 (s, 1H), 8.17-8.15 (d, 2H), 7.69 (t, J=7.6Hz, 1H), 7.55 (t, J=6.0Hz, 2H), 4.27 (q, J=7.2Hz, 4H), 1.24 (t, J=7.2Hz, 6H). 13 C NMR (100MHz, CDCl3) δ164.41 (t, J=30.0Hz, 2C), 162.58, 161.40, 161.20 (t, J=20 .0Hz, 2C), 161.10, 160.89, 160.79, 137.46, 135.07, 134.99, 133.36, 131.82, 131 .79, 130.28, 129.05, 128.25, 127.50, 125.32, 123.09, 122.98, 104.89 (t, J=262. 0Hz, 2C), 63.99 (t, J=12.0Hz, 2C), 29.68, 29.35, 21.41, 13.70 (t, J=40.0Hz, 2C). 19 F NMR (376MHz, CDCl3) δ-109.88 (s, 4F).

[0042] Example 3

[0043]

[0044] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A hot heat gun was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-methylquinoxalo-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2,2-difluoropropionyloxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, a large amount of water was added for washing, followed by extraction with ethyl acetate three times, washing with saturated sodium chloride solution, drying the organic phase with anhydrous sodium sulfate, removing the solvent by rotary evaporation, and purifying the residue by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 98%. 1 H NMR (400MHz, CDCl3) δ7.90 (dd, J=7.9, 1.6Hz, 1H), 7.49-7.47 (m, 3H), 7.35-7.22 (m, 5H), 5.08 (dd, J=8.1, 5.5Hz, 1H), 3.61 (s, 3H), 3.34-3.21 (m, 1H), 2.54 (dtd, J=17.6, 14.8, 5.5Hz, 1H), 1.52 (t, J=18.9Hz, 3H). 13 C NMR (100MHz, CDCl3) δ159.94, 157.08, 154.10 (d, J=15.0Hz, 1C), 140.85, 133.10, 132.53, 13 2.30, 130.49, 130.34, 130.09, 130.05, 129.97, 129.06, 128.93, 128.89, 128.55 (t, J=15.0Hz , 1C), 128.34, 128.32, 128.22, 127.06, 126.09, 125.78 (t, J=186.0Hz, 1C), 123.92, 113.71, 68.67, 46.26, 44.72, 44.61, 42.38 (d, J=27.0Hz, 1C), 35.68, 29.19, 24.02 (t, J=28.0Hz, 1C). 19 F NMR (376MHz, CDCl3) δ-87.42, -88.06, -88.81, -89.52 (m, 2F).

[0045] Example 4

[0046]

[0047] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A high-temperature drying torch was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 1-methyl-6,7-dichloroquinoxalin-2(1H)-one (0.30 mmol), styrene (0.60 mmol), [bis(trifluoroacetoxy)iodo]benzene (0.6 mmol), and [bis(2,2-difluoropropionyloxy)iodo]benzene (0.60 mmol) were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, a large amount of water was added for washing, followed by extraction with ethyl acetate three times, washing with saturated sodium chloride solution, drying the organic phase with anhydrous sodium sulfate, removing the solvent by rotary evaporation, and purifying the residue by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 58%. 1 H NMR (400MHz, CDCl3) δ8.00 (s, 1H), 7.45-7.43 (m, 2H), 7.33-7.27 (m, 1H), 7.25-7.21 (m, 2H), 7.19-7.17 (m, 1H), 5.07 (dd, J=8.5, 5 .1Hz, 1H), 3.57 (s, 3H), 3.24 (dddd, J=19.9, 14.7, 11.5, 8.5Hz, 1H), 2.48 (dtd, J=19.6, 14.6, 5.2Hz, 1H), 1.53 (t, J=18.8Hz, 3H). 13 C NMR (100MHz, CDCl3) δ161.56, 153.67, 140.19, 134.01, 132.51, 131.56, 131.04, 130.84, 128.67, 127.93, 127.33, 126.06, 125.67, 123.68 (t, J=199.0Hz, 1C), 121.31, 115.28, 115.19 (t, J=9.0Hz, 1C), 115.10, 41.73, 41.53, 29.46, 24.05 (t, J=27.0Hz, 1C), 23.77. 19 F NMR (376MHz, CDCl3) δ-87.81, -88.45, -89.6.-90.26 (m, 2F).

[0048] Example 5

[0049]

[0050] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. Residual moisture was removed from the tube walls, openings, and interior using a high-temperature drying torch. Nitrogen and air were then exchanged in the tube through a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-methyl-6,7-diphenylquinoxalo-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2,2-difluoropropionyloxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After confirming the reaction was complete by TLC, the product was washed with a large amount of water, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain the product, a yellow oily substance, with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ8.00 (s, 1H), 7.50-7.48 (m, 2H), 7.27-7.22 (m, 8H), 7.19-7.17 (m, 6H), 5.12 (dd, J=8. 4, 5.2Hz, 1H), 3.66 (s, 3H), 3.32 (dtd, J=18.6, 13.9, 8.3Hz, 1H), 2.60-2.46 (m, 1H), 1.54 (t, J=18.6Hz, 3H). 13 C NMR (100MHz, CDCl3) δ160.31, 154.34, 142.75, 140.87, 140.61, 139.97, 136.60 (d, J=30.0Hz, 1C), 132 .22, 131.82, 131.65, 129.92, 129.83, 129.58, 128.91, 128.73 (t, J=19.0Hz, 1C), 128.69, 128.60, 128 .58, 128.23, 128.19, 128.14, 128.08, 127.94, 127.55, 127.36, 127.02, 126.99, 126.87, 125.70 (t, J= 180.0Hz, 1C), 115.57, 68.68, 53.46, 41.62 (t, J=25.0Hz, 1C), 29.74, 29.30, 24.07 (t, J=27.0Hz, 1C). 19F NMR (376MHz, CDCl3) δ-87.53, -88.17, -88.91, -89.55 (m, 2F).

[0051] Example 6

[0052]

[0053] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. Residual moisture was removed from the tube walls, openings, and interior using a high-temperature drying torch. Nitrogen and air were then exchanged in the tube through a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-ethylquinoxalo-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2,2-difluoropropionyloxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, a large amount of water was added for washing, followed by extraction with ethyl acetate three times, washing with saturated sodium chloride solution, drying the organic phase with anhydrous sodium sulfate, removing the solvent by rotary evaporation, and purifying the residue by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ7.92 (dd, J=8.0, 1.5Hz, 1H), 7.90-7.49 (m, 3H), 7.48-7.21 (m, 3H), 7.20-7.09 (m, 2H), 5.08 (dt, J=7.8, 4.4Hz, 1H), 4.22 (dd q, J=28.3, 14.2, 7.1Hz, 2H), 3.25 (dtd, J=18.1, 14.2, 7.9Hz, 1H), 2.56 (d td, J=17.4, 14.8, 5.7Hz, 1H), 1.47 (t, J=18.8Hz, 3H), 1.31-1.24 (m, 3H). 13C NMR (100MHz, CDCl3) δ160.00, 157.15, 153.59 (d, J=22.0Hz, 1C), 140.91, 140.22, 139.94, 139.37, 136.43, 132. 85, 132.62, 132.14, 132.03, 130.37 (t, J = 24.0Hz, 1C), 129.84, 129.62, 129.04, 128.93, 128.53 (t, J = 40.0Hz, 1C ), 127.97, 126.93 (t, J = 237.0Hz, 1C), 123.95, 123.27 (t, J = 13.0Hz, 1C), 113.33, 113.23, 71.81, 71.46, 68.82, 44.61 (d, J=18.0Hz, 1C), 44.43, (t, J=25.0Hz, 1C), 41.42, 41.09, 36.25, 35.77, 24.01 (t, J=27.0Hz, 1C), 12.30. 19 F NMR (376MHz, CDCl3) δ-87.25, -87.89, -88.80, -89.44 (m, 2F).

[0054] Example 7

[0055]

[0056] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A high-temperature drying torch was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-p-methylbenzylquinoxaloline-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2,2-difluoropropionyloxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, a large amount of water was added for washing, followed by extraction with ethyl acetate three times, washing with saturated sodium chloride solution, drying the organic phase with anhydrous sodium sulfate, removing the solvent by rotary evaporation, and purifying the residue by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 85%. 11H NMR (400 MHz, CDCl3) δ 7.90 - 7.88 (m, 1H), 7.51 - 7.49 (m, 2H), 7.37 - 7.24 (m, 5H), 7.05 - 7.03 (m, 5H), 5.48 (dd, J = 15.5, 6.6 Hz, 1H), 5.28 - 5.24 (m, 1H), 5.17 - 5.12 (m, 1H), 3.35 - 3.22 (m, 1H), 2.58 (dtd, J = 17.6, 14.9, 5.7 Hz, 1H), 2.27 (s, 3H), 1.54 (t, J = 18.8 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 160.17, 154.37, 1​​​​​​​​​​First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A high-temperature drying torch was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, quinoxaline-2(1H)-one and its derivatives (0.30 mmol), p-methylstyrene (0.60 mmol), [bis(trifluoroacetoxy)iodo]benzene (0.6 mmol), and [bis(2,2-difluoropropionyloxy)iodo]benzene (0.60 mmol) were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in a double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After the reaction was confirmed to be complete by TLC, a large amount of water was added for washing, followed by extraction with ethyl acetate three times, washing with saturated sodium chloride solution, drying the organic phase with anhydrous sodium sulfate, removing the solvent by rotary evaporation, and purifying the residue by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 87%. 1 H NMR (400MHz, CDCl3) δ7.90 (dt, J=8.0, 2.3Hz, 2H), 7.88-7.46 (m, 2H), 7.37-7.21 (m, 2H), 7.11-7.03 (m, 2H), 5.06-5.02 (m, 1H) , 3.60 (s, 3H), 3.26 (dtd, J = 18.1, 14.2, 8.0Hz, 1H), 2.53 (dtd, J = 17.6, 14.9, 5.6Hz, 1H), 2.26 (s, 3H), 1.51 (t, J = 18.4Hz, 3H). 13 CNMR (100MHz, CDCl3) δ160.09, 157.23, 154.24, 137.65 (t, J=15.0Hz, 1C), 136.89, 136.27, 133.22, 33. 01, 132.31, 130.31 (t, J = 23.0Hz, 1C), 130.06, 129.89, 1129.41 (t, J = 48.0Hz, 1C), 129.22, 128.82, 128 .63, 128.19, 128.11, 123.99 (t, J=237.0Hz, 1C), 123.51, 123.44, 113.69, 113.55, 113.41, 68.70, 65.3 7, 45.93, 41.79 (t, J=19.0Hz, 1C), 41.29, 41.24, 36.17, 35.71, 29.17, 24.03 (t, J=27.0Hz, 1C), 21.06. 19F NMR (376MHz, CDCl3) δ-87.24, -87.88, -88.79, -89.43 (m, 2F).

[0060] Example 9

[0061]

[0062] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. A hot heat gun was used to remove residual moisture from the tube walls, openings, and interior. Nitrogen and air were then exchanged in a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-methylquinoxaloline-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2,2-difluoroacetoxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After confirming the reaction was complete by TLC, the product was washed with a large amount of water, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain the product, a colorless oily substance with a yield of 60%. 1 H NMR (400MHz, CDCl3) δ7.93-7.91 (m, 1H), 7.55-7.51 (m, 1H), 7.51-7.42 (m, 2H), 7.38-7.34 (m, 2H), 7.26-7.18 (m, 3H), 5.89 (t, J=5.0Hz, 1H ), 5.75-5.73 (m, 1H), 5.60 (t, J=5.0Hz, 1H), 5.34-5.23 (m, 1H), 4.90 (t, J=7.8Hz, 1H), 3.60 (s, 3H), 2.94-2.83 (m, 1H), 2.67-2.54 (m, 1H). 13C NMR (100MHz, CDCl3) δ159.08, 154.13, 139.58, 133.20, 132.61, 132.40 (t, J=21.0Hz, 1 C), 130.49, 130.34, 130.20, 130.04, 129.77, 128.95, 128.89, 128.76, 128.49 (t, J=22 .0Hz, 1C), 128.23, 127.92, 127.88, 126.89, 123.87 (t, J=237.0Hz, 1C), 123.41, 116.6 6, 113.64, 68.67, 46.26, 44.93, 41.95, 41.83, 38.07 (t, J=22.0Hz, 1C), 29.19, 28.99. 19 F NMR (376MHz, CDCl3) δ-115.47, -116.22, -116.72, --117.47 (m, 2F).

[0063] Example 10

[0064]

[0065] First, the 10 mL Schlenk tube was subjected to anhydrous and oxygen-free treatment. Residual moisture was removed from the tube walls, openings, and interior using a high-temperature drying torch. Nitrogen and air were then exchanged in the tube through a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube cooled in a nitrogen atmosphere, 0.30 mmol of 1-methylquinoxaloline-2(1H)-one, 0.60 mmol of styrene, 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene, and 0.60 mmol of [bis(2-(ethoxycarbonyl)-2,2-difluoroacetoxy)iodo]benzene were added sequentially to the reaction tube. Using a long-needle syringe under nitrogen protection in the double-row tube, 1.50 mL of anhydrous 1,4-dioxane was added to the reaction tube. The two reactants were dissolved with stirring, and the reaction was carried out at room temperature under a 24W blue LED light. After confirming the reaction was complete by TLC, the product was washed with a large amount of water, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain the product, which was a colorless oil with a yield of 46%. 1H NMR(400MHz,CDCl3)δ7.96(d,J=8.2Hz,1H),7.59-7.55(m,1H),7.43-7.41(m,3H),7.33-7.31(m,2H),7.26-7.19(m,2H),5.04(t,J=7.1Hz,1H),4.01(p,J=8.8,8.2Hz,2H),3.66(s,3H),3.39(tt,J=15.6,7.7Hz,1H),2.87(qd,J=15.7,6.2Hz,1H),136(t,J=7.0Hz,3H). 13 C NMR(100MHz,CDCl3)δ164.53,164.21(t,J=33.0Hz),1C,163.88,161.25,160.95(t,J=31.0Hz),158.68,154.37,139.06,132.67,130.69,130.45(t,J=27.0Hz),130.14,128.92,128.72,128.60,128.27,127.56,124.42(t,J=179.0Hz,1C,118.16,115.67(t,J=250.0Hz),114.03,64.00,63.01,62.95,41.13,38.52,38.29(t,J=23.0Hz,1C),38.06,31.94,31.40,30.19,29.83,29.67,22.70,14.13,13.86. 19 F NMR(376MHz,CDCl3)δ-102.38,-103.07,-104.65,-105.34(m,2F).

Claims

1. A method for synthesizing C3-fluoroalkyl-substituted quinoxalone derivatives from olefin derivatives and quinoxalone derivatives under photocatalysis using [bis(fluoroalkylacetoxy)iodo]benzene as different fluoroalkyl sources and [bis(trifluoroacetoxy)iodo]benzene as an oxidant, characterized in that... The general reaction formula is as follows: Where R 1 Selected from hydrogen, halogen, phenyl; R 2 Selected from methyl, ethyl, and p-methylbenzyl; R 3 Selected from phenyl, p-methylphenyl: R f Selected from difluoroethyl, difluoromethyl, and difluoroethyl acetate.

2. The method according to claim 1, using [bis(fluoroalkylacetoxy)iodo]benzene as a source of different fluoroalkyl groups and [bis(trifluoroacetoxy)iodo]benzene as an oxidant, to synthesize C3-fluoroalkyl-substituted quinoxalone derivatives from olefin derivatives and quinoxalone derivatives under photocatalysis, is characterized in that: Specific steps: Quinoxalone derivatives, olefin derivatives, [bis(trifluoroacetoxy)iodine]benzene, [bis(fluoroalkylacetoxy)iodine]benzene and 1,4-dioxane were added under anhydrous and oxygen-free conditions, and the reaction was carried out at room temperature under blue 24W LED light. After the reaction was completed, quinoxalone derivatives with different C3-position fluoroalkyl substitutions were obtained by extraction, washing, drying and column chromatography separation.

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