Method for preparing quinoxalinone trifluoromethylation product

Abstract

The invention relates to a method for preparing a quinoxalinone trifluoromethylation product. The method comprises the following steps: in an inert gas atmosphere, adding a quinoxaline ketone compound, 4-(dimethylamino)-1-((trifluoromethyl) sulfonyl) pyridine-1-trifluoromethanesulfonic acid onium, alkali and a photosensitizer into a solvent, reacting for 10-12 hours at the temperature of 10-30 DEG C under blue light irradiation, and separating and purifying through column chromatography to obtain the quinoxaline ketone compound. And finally, obtaining the quinoxaline ketone compound substituted by the trifluoromethyl at the C3 position. The preparation conditions are mild, no heavy metal is left, only column chromatography separation is needed, and post-treatment is simple.

Description

Technical Field

[0001] This invention belongs to the field of organic catalytic synthesis technology and is a method for preparing trifluoromethylated quinoxalinone derivatives. Background Technology

[0002] As intermediates in natural product and drug development, quinoxalinone compounds and their synthetic derivatives not only possess pharmacological activities such as antioxidation, anti-inflammation, and broad-spectrum anti-infective (antibacterial and antiviral) properties, but also show breakthrough potential in areas such as antithrombosis, hypoglycemia, neuroprotection, antitumor activity, and liver protection. For example, quinoxalinone derivatives with a trifluoromethyl substituted position 3 on the parent ring, as shown in Formula 1, constitute a novel class of type 1 HIV reverse transcriptase inhibitors (Bioorg. Med. Chem. Lett. 2000, 10, 1729–1731.), and their trifluoromethylation modification has demonstrated significant value in constructing active drug molecules. Currently, the main trifluoromethylation sources for the quinoxalinone skeleton are CF3SO2Na, Togni reagent, and CF3SO2Cl. In 2025, Chu Xiaoxiao et al. from Ludong University (Org. Biomol. Chem. 2025, 23, 3612–3618.) reported the direct trifluoromethylation reaction of quinoxalinone at the C-3 position using CF3SO2Na (sodium trifluoromethyl sulfinate) as the fluorine source. However, this reaction requires excess CF3SO2Na, and some parts of the reaction depend on strong oxidants such as (NH4)2S2O8. In 2024, Wang Dawei et al. from Jiangnan University reported the N-benzylquinoxalin-2(1 H )-Ketones react with Togni reagent (Org. Biomol. Chem. 2024, 22, (8317–8322.) A visible light-induced, photosensitizer-free synthesis method was developed. This method eliminates the need for an oxidant, but the trifluoromethyl reagent used in the reaction process still suffers from high cost. In 2022, Cui Xiuling et al. from Zhengzhou University reported a visible light-induced CH trifluoromethylation reaction without an external photocatalyst (Tetrahedron Lett. 2022, 93, 153693.), using CF3SO2Cl as the trifluoromethyl radical source to synthesize 3-trifluoromethylquinoxaline-2(1 H The reaction of )-ketones does not require oxidants and exogenous photosensitizers in part of the system, but CF3SO2Cl itself also poses safety hazards such as easy hydrolysis and deterioration and strong corrosivity. Therefore, we need to develop a new method that uses inexpensive, environmentally friendly, and stable trifluoromethyl reagents as the trifluoromethyl source.

[0003]

[0004] Formula 1, quinoxalinone derivatives with trifluoromethyl substitution at position 3 Summary of the Invention

[0005] The purpose of this invention is to address the limitation of high cost of trifluoromethyl sources in current quinoxalinone trifluoromethylation reactions by providing a method for quinoxalinone trifluoromethylation using TFSP as the trifluoromethyl source. This method uses inexpensive and readily available 4-(dimethylamino)-1-((trifluoromethyl)sulfonyl)pyridine-1-trifluoromethanesulfonate ononium (TFSP) as the trifluoromethyl source, and completes the direct C3-position trifluoromethylation reaction of quinoxalinone compounds under visible light-mediated conditions to obtain the corresponding trifluoromethylated products. The preparation conditions of this invention are mild (reaction temperature 10-30°C), with no heavy metal residues, requiring only column chromatography separation, and the post-processing is simple.

[0006] The technical solution of this invention is as follows: A method for preparing trifluoromethylated products of quinoxalinone, the method comprising the following steps: In an inert gas atmosphere, quinoxalone compounds, 4-(dimethylamino)-1-((trifluoromethyl)sulfonyl)pyridine-1-trifluoromethanesulfonate TFSP, a base, and a photosensitizer were added to a solvent and reacted under blue light at 10-30 °C for 10-12 hours. After separation and purification by column chromatography, quinoxalone compounds with C3-trifluoromethyl substitution were finally obtained. The molar ratio is quinoxalinone compound: base: trifluoromethyl source (TFSP): photosensitizer = 1:1.5-2:2-2.5:0.01~0.09; The quinoxalone compounds mentioned are either monosubstituted benzene ring quinoxalone compounds or disubstituted benzene ring quinoxalone compounds; The benzene ring monosubstituted quinoxalone compounds are:

[0007] Among them, R 1 For hydrogen atoms, methyl, benzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-fluorobenzyl, methyl acetate or tert-butyl acetate, R 2 It consists of a methoxy group at position 6 or 7, a fluorine atom at position 6, a bromine atom, or a hydrogen atom; Specifically, it is 1-methylquinoxaline-2( 1H )-ketone, 1-(2-methoxy-2-oxoethyl)quinoxaline-2( 1H )-ketone, methyl 2-(2-oxo-1,2-dihydroquinoxalin-1-yl)acetate, 2-(2-oxoquinoxalin-1-yl) 2H 1-Butylquinoxaline-2-( 1H )-ketone, 1-tert-butylquinoxaline-2 ( 1H )-ketone, 1-allylquinoxaline-2(1H )-ketone, 1-methylquinoxaline-2(1 H )-keto-dimethyl ether (1 / 1), 1-benzylquinoxaline-2 ( 1H )-ketone, 1-(4-methylbenzyl)quinoxaline-2( 1H )-ketone, 1-(4-methoxybenzyl)quinoxaline-2( 1H )-ketone, 1-(4-fluorobenzyl)quinoxaline-2( 1H )-ketone, quinoxaline-2 ( 1H )-ketone; The benzene ring disubstituted quinoxalone compounds are:

[0008] Among them, R 2 and R 3 It consists of a methyl, fluorine, or bromine atom; Specifically, it is 1,6,7-trimethylquinoxaline-2(1 H )-ketone, 6,7-dibromo-1-methylquinoxaline-2(1 H )-ketone, 6,7-difluoro-1-methylquinoxaline-2(1 H )-ketone, 6-bromo-1-methylquinoxaline-2(1 H )-ketone, 6-fluoro-1-methylquinoxaline-2(1 H )-ketone, 1-methylbenzo[g]quinoxaline-2(1 H )-ketone; The blue light is a blue LED light with a luminous intensity of 8~12mW / cm². -2 The irradiation distance is 2-3cm; The solvent is acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, or dimethyl carbonate; The alkalis mentioned are triethylamine (Et3N), 4-dimethylaminopyridine (DMAP), potassium carbonate (K2CO3), sodium carbonate (NaCO3), potassium bicarbonate (KHCO3), tripotassium phosphate (K3PO4), magnesium oxide (MgO), and calcium oxide (CaO).

[0009] The photosensitizer is 4CzIPN, Eosin Y, Eosin B, or rhodamine; The inert gas is nitrogen or argon.

[0010] The essential features of this invention are: This invention provides a method for preparing trifluoromethylated products of quinoxalinones using an inexpensive and stable trifluoromethyl source (TFSP). This method not only reduces costs and industrialization difficulties but also exhibits good substrate tolerance to quinoxalinone compounds. Furthermore, addressing the limitation of the trifluoromethylation of quinoxalinones, which relies on strong oxidants and transition metal catalysts, this method eliminates concerns about oxidant and metal residues.

[0011] The beneficial effects of this invention are: This invention utilizes inexpensive, readily available, stable, and easily prepared TFSP as a trifluoromethyl source. The solvent used is a common organic solvent that requires no special treatment. The reaction does not require an oxidant or a transition metal as a catalyst. The direct C3-position trifluoromethylation of quinoxalinone compounds is completed under visible light-mediated conditions. The method is mild (reaction temperature 10-30℃), leaves no heavy metal residue, requires only column chromatography separation, and has simple post-processing. It is suitable for the preparation and synthesis of fine chemicals or drug precursors. In terms of preparation cost, each gram of TFSP is about 130 yuan cheaper than Togni reagent, and the cost of synthesizing each gram of product is reduced by about 150 yuan. Compared with the characteristics of CF3SO2Cl, which is easily hydrolyzed and deteriorated and unstable, TFSP is stable and does not require peroxides. The cost reduction in the process synthesis far exceeds the actual reagent price difference. Detailed Implementation

[0012] This invention differs fundamentally from previously reported methods for preparing trifluoromethylated products of quinoxalinones. It utilizes readily available and inexpensive 4-(dimethylamino)-1-((trifluoromethyl)sulfonyl)pyridine-1-trifluoromethanesulfonate (TFSP) as the trifluoromethyl source, and performs a direct C3-position trifluoromethylation reaction of quinoxalinone compounds under visible light to obtain the corresponding trifluoromethylated products (as shown in the reaction formula below).

[0013]

[0014] The direct trifluoromethylation reaction at the C3 position of quinoxalinone compounds was completed under visible light-mediated reaction. The technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments. It should be understood that the described embodiments are only some embodiments of the present invention, and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0015] Example 1: The substrate 1-methylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol% of 1-methylquinoxaloline-2(1H)-one), and a magnetic pole were added. The mixture was purged with argon five times, followed by the addition of anhydrous 1,2-dichloroethane (5 mL). The mixture was then reacted under electromagnetic stirring, at room temperature, and under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the product 1-methyl-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 64%.

[0016] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.99 (dd, J = 8.0, 1.6 Hz, 1H), 7.76 – 7.71 (m, 1H), 7.48 – 7.42 (m, 1H), 7.40 (dd, J =8.5, 1.1 Hz, 1H), 3.75 (s, 3H), which is consistent with the structural formula.

[0017] Example 2: The substrate 1-methylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (6.25 mmol), TFSP (15.625 mmol), MgO (12.5 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (78 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the product 1-methyl-3-(trifluoromethyl)quinoxaline-2(1H)-one. The yield was 63%.

[0018] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1H NMR (600 MHz, CDCl3) δ 7.99 (dd, J = 8.0, 1.6 Hz, 1H), 7.76 – 7.71 (m, 1H), 7.48 – 7.42 (m, 1H), 7.40 (dd, J =8.5, 1.1 Hz, 1H), 3.75 (s, 3H), which is consistent with the structural formula.

[0019] Example 3: 2-(2-oxo-1,2-dihydroquinoxalin-1-yl)methyl acetate was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), and analysis by thin-layer chromatography (TLC) revealed that the substrate methyl 2-(2-oxo-1,2-dihydroquinoxalo-1-yl)acetate was... After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio to obtain the product methyl 2-[2-oxo-3-(trifluoromethyl)quinoxalin-1(2H)-yl]acetate. Its yield was 61%.

[0020] The hydrogen nuclear magnetic resonance (NMR) spectra of the obtained product were 1H NMR (600 MHz, CDCl3) δ 8.03 (dd, J = 8.0, 1.5 Hz, 1H), 7.70 (d, J = 1.3 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 5.08 (s, 2H), 3.80 (s, 3H), which are consistent with the structural formula.

[0021] Example 4: The substrate 2-(2-oxo-1,2-dihydroquinoxalin-1-yl)tert-butyl acetate was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), and thin-layer chromatography (TLC) was used to detect the substrate tert-butyl 2-(2-oxo-1,2-dihydroquinoxalo-1-yl)acetate. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:4 ratio to obtain the product 2-[2-oxo-3-(trifluoromethyl)quinoxalin-1(2H)-yl]tert-butyl acetate. Its yield was 63%.

[0022] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 ¹H NMR (600 MHz, CDCl₃) δ 8.01 (dd, J = 8.1, 1.7 Hz, 1H), 7.70 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.47 – 7.41 (m, 1H), 7.17 – 7.13 (m, 1H), 4.97 (d, J = 2.0 Hz, 2H), 1.47 (d, J = 1.9 Hz, 9H), consistent with the structural formula.

[0023] Example 5: The substrate 1-butylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-butylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:5 ratio as the eluent, yielding the product 1-butyl-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 56%.

[0024] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1H NMR (600 MHz, CDCl3) δ 8.00 (dd, J = 8.1, 1.7 Hz, 1H), 7.70 (d, J = 1.6 Hz, 1H), 7.45 – 7.36 (m, 2H), 4.18 (d, J = 7.5 Hz, 2H), 1.03 (dd, J = 6.7, 1.6 Hz, 6H), which is consistent with the structural formula.

[0025] Example 6: The substrate 1-(tert-butyl)quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), and monitoring by thin-layer chromatography (TLC), the substrate 1-(tert-butyl)quinoxaline-2(1H)-one was... After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:5 ratio to obtain the product 1-(tert-butyl)-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 63%.

[0026] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.00 (dd, J = 8.1, 1.7 Hz, 1H), 7.70 (ddd, J = 8.7, 7.2, 1.6 Hz, 1H), 7.45 – 7.36 (m,2H), 4.18 (d, J = 7.5 Hz, 2H), 2.28 (dt, J = 6.9 Hz, 1H), 1.03 (dd, J = 6.7, 1.6 Hz, 6H), which is consistent with the structural formula.

[0027] Example 7: The substrate 1-benzylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-benzylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a ratio of 1:15 to obtain the product 1-benzyl-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 49%.

[0028] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 ¹H NMR (600 MHz, CDCl₃) δ 7.99 (dd, J = 8.0, 1.1 Hz, 1H), 7.63 – 7.58 (m, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.35 – 7.31 (m, 2H), 7.28 (t, J = 7.8 Hz, 3H), 5.53 (s, 2H), consistent with the structural formula.

[0029] Example 8: The substrate 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), and monitoring by thin-layer chromatography (TLC), the substrate 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one was analyzed. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a ratio of 1:15 to obtain the product 1-[(4-methylphenyl)methyl]-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 41%.

[0030] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows:1 H NMR (600 MHz, CDCl3) δ 7.99 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.39 (t, J = 7.2 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 5.49 (s, 2H), 2.31 (s, 3H), which is consistent with the structural formula.

[0031] Example 9: The substrate 1-[(4-methoxyphenyl)methyl]quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 The irradiation distance was 3 cm. Thin-layer chromatography (TLC) was used to detect the substrate 1-[(4-methoxyphenyl)methyl]quinoxalin-2(1H)-one. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:5 ratio to obtain the trifluoromethylated product 1-[(4-methylphenyl)methyl]-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 41%.

[0032] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.99 (dd, J = 8.1, 1.6 Hz, 1H), 7.44 – 7.38 (m, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.88 –6.84 (m, 2H), 5.46 (s, 2H), 3.77 (s, 3H), which is consistent with the structural formula.

[0033] Example 10: The substrate 1-[(4-fluorophenyl)methyl]quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-[(4-fluorophenyl)methyl]quinoxaline-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:5 ratio as the eluent, yielding the product 1-[(4-fluorophenyl)methyl]-3-(trifluoromethyl)quinoxaline-2(1H)-one. Its yield was 56%.

[0034] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.01 (dd, J = 8.0, 1.5 Hz, 1H), 7.63 (t, J = 1.5 Hz, 1H), 7.45 – 7.39 (m, 1H), 7.36 (dd, J = 8.6, 1.1 Hz, 1H), 7.31 – 7.25 (m, 3H), 7.02 (t, J = 8.6 Hz, 2H), 5.49 (s, 2H), which is consistent with the structural formula.

[0035] Example 11: The substrate quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), and monitoring by thin-layer chromatography (TLC), the substrate quinoxaline-2(1H)-one was analyzed. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:5 ratio as the eluent, yielding the trifluoromethylated product. Its yield is 30%.

[0036] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, DMSO) δ 12.98 (s,1H), 7.84 (d, J = 8.1 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 9.1 Hz, 3H), which is consistent with the structural formula.

[0037] Example 12: The substrate 1,6,7-trimethylquinoxalin-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1,6,7-trimethylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the trifluoromethylated product. Its yield was 54%.

[0038] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.73 (s, 1H), 7.15 (s, 1H), 3.72 (s, 3H), 2.27 (s, 3H), 2.37 (s, 3H), consistent with the structural formula.

[0039] Example 13: The substrate 6,7-dibromo-1-methylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 6,7-dibromo-1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the trifluoromethylated product. Its yield was 48%.

[0040] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 ¹H NMR (600 MHz, CDCl₃) δ 8.23 ​​(s, 1H), 7.68 (s, 1H), 3.70 (s, 3H), consistent with the structural formula.

[0041] Example 14: The substrate 6,7-difluoro-1-methylquinoxalin-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 6,7-difluoro-1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the trifluoromethylated product. Its yield was 57%.

[0042] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.82 (s,1H), 7.21 (d, J = 4.1 Hz, 1H), 3.71 (d, J = 2.0 Hz, 3H), which is consistent with the structural formula.

[0043] Example 15: Add the substrate 1-methylquinoxaloline-2(1H)-one-dimethyl ether (1 / 1) sequentially to a dry Schlenk sealing tube. (0.4 mmol) TFSP, (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2(Irradiation distance 3 cm), and monitoring by thin-layer chromatography (TLC), the substrate 1-methylquinoxaline-2(1H)-one-dimethyl ether (1 / 1) was analyzed. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:10 ratio to obtain the trifluoromethylated product. Its yield is 35%.

[0044] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 ¹H NMR (600 MHz, CDCl₃) δ 7.42 (d, J = 9.0 Hz, 1H), 7.11 (dd, J = 9.0, 2.9 Hz, 1H), 7.08 (d, J = 2.8 Hz, 1H), 3.81 (s, 3H), 3.60 (s, 3H), consistent with the structural formula.

[0045] Example 16: The substrate 6-bromo-1-methylquinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 6-bromo-1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:10 ratio to obtain the trifluoromethylated product. Its yield is 45%.

[0046] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.08 (d, J =2.3 Hz, 1H), 7.76 (dd, J = 9.0, 2.2 Hz, 1H), 7.24 (d, J = 9.0 Hz, 1H), 3.69(d, J = 2.9 Hz, 3H), which is consistent with the structural formula.

[0047] Example 17: The substrate 6-fluoro-1-methylquinoxalin-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 6-fluoro-1-methylquinoxalin-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the trifluoromethylated product. Its yield was 58%.

[0048] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.69 (dd, J = 8.2, 2.9 Hz, 1H), 7.51 – 7.47 (m, 1H), 7.38 (dd, J = 9.3, 4.5 Hz, 1H), 3.75 (s, 3H), which is consistent with the structural formula.

[0049] Example 18: The substrate 1-methylbenzo[g]quinoxaline-2(1H)-one was added sequentially to a dry Schlenk sealing tube. (0.4 mmol), TFSP (1 mmol), MgO (0.8 mmol), 4CzIPN (5 mol%), and magnetic particles were added, and the mixture was purged five times with argon gas. Then, anhydrous 1,2-dichloroethane (5 mL) was added, and the reaction was carried out in a sealed environment at room temperature under blue light irradiation for 10 h (light intensity 9.5 mW / cm²). -2 (Irradiation distance 3 cm), the substrate 1-methylbenzo[g]quinoxaline-2(1H)-one was monitored by thin-layer chromatography (TLC). After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was then subjected to column chromatography using silica gel column chromatography with ethyl acetate and petroleum ether in a 1:3 ratio as the eluent, yielding the trifluoromethylated product. Its yield is 30%.

[0050] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.56 (s,1H), 8.03 (d,J = 8.3 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 9.4 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H), 3.82 (s, 3H), which is consistent with the structural formula.

[0051] Matters not covered in this invention are common knowledge.

Claims

1. A method for preparing trifluoromethylated products of quinoxalinone, characterized in that, The method includes the following steps: In an inert gas atmosphere, quinoxalone compounds, 4-(dimethylamino)-1-((trifluoromethyl)sulfonyl)pyridine-1-trifluoromethanesulfonate TFSP, a base, and a photosensitizer were added to a solvent and reacted under blue light at 10-30 °C for 10-12 hours. After separation and purification by column chromatography, quinoxalone compounds with C3-trifluoromethyl substitution were finally obtained. Wherein, the molar ratio is quinoxalone compound: base: trifluoromethyl source (TFSP): photosensitizer = 1:1.5-2:2-2.5:0.01~0.09; the quinoxalone compound is a benzene ring monosubstituted quinoxalone compound or a benzene ring disubstituted quinoxalone compound; The benzene ring monosubstituted quinoxalone compounds are: , Among them, R 1 For hydrogen atoms, methyl, benzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-fluorobenzyl, methyl acetate or tert-butyl acetate, R 2 It consists of a methoxy group at position 6 or 7, a fluorine atom at position 6, a bromine atom, or a hydrogen atom; The benzene ring disubstituted quinoxalone compounds are: , Among them, R 2 and R 3 It can be a methyl, fluorine, or bromine atom.

2. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that, The blue light is a blue LED light with a luminous intensity of 8~12mW / cm². -2 The irradiation distance is 2-3cm.

3. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that... The solvent is acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, or dimethyl carbonate.

4. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that... The monosubstituted benzene ring quinoxalone compound is 1-methylquinoxaline-2 ( 1H )-ketone, 1-(2-methoxy-2-oxoethyl)quinoxaline-2( 1H )-ketone, methyl 2-(2-oxo-1,2-dihydroquinoxalin-1-yl)acetate, 2-(2-oxoquinoxalin-1-yl) 2H 1-Butylquinoxaline-2-( 1H )-ketone, 1-tert-butylquinoxaline-2 ( 1H )-ketone, 1-allylquinoxaline-2( 1H )-ketone, 1-methylquinoxaline-2(1 H )-keto-dimethyl ether (1 / 1), 1-benzylquinoxaline-2 ( 1H )-ketone, 1-(4-methylbenzyl)quinoxaline-2( 1H )-ketone, 1-(4-methoxybenzyl)quinoxaline-2( 1H )-ketone, 1-(4-fluorobenzyl)quinoxaline-2( 1H )-ketone, quinoxaline-2 ( 1H )-ketone.

5. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that... The benzene ring-disubstituted quinoxalone compound is: 1,6,7-trimethylquinoxaline-2(1 H )-ketone, 6,7-dibromo-1-methylquinoxaline-2(1 H )-ketone, 6,7-difluoro-1-methylquinoxaline-2(1 H )-ketone, 6-bromo-1-methylquinoxaline-2(1 H )-ketone, 6-fluoro-1-methylquinoxaline-2(1 H )-ketone, 1-methylbenzo[g]quinoxaline-2(1 H )-ketone.

6. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that... The alkali is triethylamine, 4-dimethylaminopyridine, potassium carbonate, sodium carbonate, potassium bicarbonate, tripotassium phosphate, magnesium oxide, and calcium oxide.

7. The method for preparing the trifluoromethylated product of quinoxalinone according to claim 1, characterized in that... The photosensitizer is 4CzIPN, Eosin Y, Eosin B, or rhodamine.

8. The method for preparing the trifluoromethylated product of quinoxalinone as described in claim 1, characterized in that... The inert gas is nitrogen or argon.

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