Quinoxaline-2 (1H)-ketone arylation method based on photocatalysis

Abstract

The invention relates to an arylation method of quinoxaline-2 (1H)-ketone based on photocatalysis. The invention relates to a photocatalysis-based quinoxaline-2 (1H)-ketone arylation method, which comprises the following steps of: mixing a quinoxaline-2 (1H)-ketone compound, aryl iodide, a photocatalyst and a solvent, and stirring and reacting at room temperature under the illumination of visible light to obtain a quinoxaline-2 (1H)-ketone arylation product. According to the quinoxaline-2 (1H)-ketone arylation method based on photocatalysis, on the basis of quinoxaline-2 (1H)-ketone, a quinoxaline-2 (1H)-ketone arylation reaction is completed through visible light induction, and a novel efficient, simple, convenient and environment-friendly quinoxaline-2 (1H)-ketone arylation strategy is established; and through wide quinoxaline-2 (1H)-ketone substrates, the expansibility is increased, and a new method is provided for arylation of quinoxaline-2 (1H)-ketone.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a photocatalytic arylation method for quinoxaline-2(1H)-one. Background Technology

[0002] Quinoxalones are an important class of nitrogen-containing benzo[a] heterocyclic structures whose skeletons are widely found in natural products, drug molecules, and functional materials, exhibiting a variety of biological activities such as antitumor, antibacterial, anticoagulant, and hypoglycemic effects. Through organic synthesis, the structure of quinoxalones can be systematically modified, thereby expanding their pharmacological activities and applications.

[0003] Early reports used phenylhydrazine hydrochloride, arylhydrazine, or aryl diazo compounds as aryl donors, resulting in mild reaction conditions and high atom economy. However, these precursors exhibit poor storage stability, require stoichiometric strong bases (such as t-BuOK) or inorganic additives (such as Cs₂CO₃) for activation, have limited functional group tolerance, and require multiple extractions and neutralizations in post-processing, leading to high costs. Currently, diaryliodonium trifluoroate can solve the raw material stability problem and offers high reactivity and a broad substrate spectrum. However, the system relies on noble metal photosensitizers such as Ir(ppy)₃ and Ru(bpy)₃(PF₆)₂ or acridine organic dyes, and requires the addition of excess organic bases; the photocatalysts are expensive and difficult to recover, resulting in high process costs and making it unsuitable for large-scale production.

[0004] Aryl bromides / iodides are widely available and inexpensive, theoretically making them the most industrially promising aryl sources. Currently, there are two main strategies for achieving their CH arylation: a) Rare metal photocatalysis: This requires photo / thermal dual-catalytic cycles using Ir, Ru, Ni, etc., and metal residues require additional purification. b) Photoinduced single-electron transfer: While atom-economical, free radical ions are easily converted or proton-coupled electrons are transferred, leading to hydrogenation byproducts; the system requires basic additives to quench protons and is highly sensitive to oxygen, resulting in a sharp increase in post-processing and inert atmosphere costs during scale-up.

[0005] In view of this, the present invention proposes a method for the arylation of quinoxaline, which is a novel method for the direct arylation of quinoxaline-2(1H)-one at the C3 position. The arylation reaction is completed by visible light induction, using a dye-based photocatalyst and without the participation of additives, and a high-energy free radical intermediate is generated in a mild manner. This establishes a new strategy for the functionalization of quinoxaline-2(1H)-one aromatic hydrocarbons that is efficient, simple and environmentally friendly. Summary of the Invention

[0006] The present invention aims to provide a photocatalytic arylation method for quinoxaline-2(1H)-ones, using iodoaryl hydrocarbons as inexpensive and stable aryl sources. Single-electron transfer can be excited using only a dye-type photocatalyst, thioxanthone (TX, E0(TX* / TX-)≈-1.65V), without any basic or ligand additives. The reaction is carried out via a visible light-driven photoredox cycle, through which aryl radicals generated from aryl halides are transferred via energy transfer to achieve regioselective addition to quinoxaline-2(1H)-ones, realizing efficient and atom-economical CH arylation. This provides a green and low-cost solution for the large-scale synthesis of this type of skeleton.

[0007] To achieve the above objectives, the technical solution adopted is as follows:

[0008] A photocatalytic arylation method for quinoxaline-2(1H)-ones involves mixing quinoxaline-2(1H)-one compounds, iodoaromatics, a photocatalyst, and a solvent, and then stirring the mixture under visible light at room temperature to obtain the arylated product of quinoxaline-2(1H)-one.

[0009] Furthermore, the general reaction formula for the arylation method is:

[0010]

[0011] Wherein, the R 1 Substituents at the 7- and / or 8- positions on the benzene ring;

[0012] The R mentioned 2 It is an alkyl group.

[0013] Furthermore, the aforementioned R 1 Selected from one of H, Cl, F, and CF3;

[0014] The R mentioned 2 It is a C1-C5 alkyl group.

[0015] Furthermore, the solvent is acetonitrile;

[0016] The photocatalyst is a thioxanone catalyst;

[0017] The reaction is carried out in an inert gas atmosphere.

[0018] Furthermore, the wavelength of the visible light is 390-456 nm;

[0019] The molar ratio of the quinoxaline-2(1H)-one compound to the iodoaromatic hydrocarbon is 1:3-5;

[0020] The amount of the photocatalyst used is 10-30 wt% of the quinoxaline-2(1H)-one compound.

[0021] Furthermore, the wavelength of the visible light is 390 nm;

[0022] The molar ratio of the quinoxaline-2(1H)-one compound to the iodoaromatic hydrocarbon is 1:4;

[0023] The amount of the photocatalyst used is 30 wt% of the quinoxaline-2(1H)-one compound.

[0024] Furthermore, the iodinated aromatic hydrocarbon is an iodinated biphenyl.

[0025] Another objective of this invention is to provide a quinoxaline-2(1H)-one arylated product, which is a quinoxaline-2(1H)-one C3-arylated product, obtained by the above method.

[0026] To achieve the above objectives, the technical solution adopted is as follows:

[0027] An arylated product of quinoxaline-2(1H)-one was obtained by the above-described arylation method.

[0028] Furthermore, the quinoxaline-2(1H)-one arylized product is any of the following compounds:

[0029] 3-Biphenyl-1-methylquinoxalin-2(1H)-one, 3-Biphenyl-1-(N-isobutyl)quinoxalin-2(1H)-one, 3-Biphenyl-1-(N-butyl)quinoxalin-2(1H)-one, 3-Biphenyl-1-(N-pentyl)quinoxalin-2(1H)-one, 3-Biphenyl-8-(fluoro)-1-methylquinoxalin-2(1H)-one, 3-Biphenyl-8-(trifluoromethyl)-1-methylquinoxalin-2(1H)-one, 3-Biphenyl-7,8-(di) 3-(4-butyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one, 3-(4-pentyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one, 3-(9,9-dimethylfluorene)-1-methylquinoxalin-2(1H)-one, 3-biphenyl-7,8-(dimethyl)-1-methylquinoxalin-2(1H)-one, 3-(benzophenone)-1-methylquinoxalin-2(1H)-one.

[0030] Another objective of this invention is to provide the application of the above-mentioned quinoxaline-2(1H)-one aryl products in drug synthesis, materials science, and catalysts.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] 1. In the technical solution of the present invention, based on quinoxaline-2(1H)-one, an arylation reaction involving a dye-type photocatalyst and no additives is completed through visible light induction, generating a high-energy free radical intermediate in a mild manner, thus establishing a new strategy for the functionalization of quinoxaline-2(1H)-one aromatic hydrocarbons.

[0033] 2. In the technical solution of this invention, the arylation reaction of quinoxaline-2(1H)-one is directly completed through visible light induction. This system is simple to operate, has mild conditions, and high atom economy, significantly improving the step economy and scalability of the arylation reaction of quinoxaline-2(1H)-one, and providing a green, efficient, and easily scalable new method for constructing a library of structurally diverse quinoxaline derivatives. Attached Figure Description

[0034] Figure 1-2 The NMR spectrum of 3-biphenyl-quinoxaline-2(1H)-one in Example 1 is shown. Detailed Implementation

[0035] To further illustrate the photocatalytic arylation method for quinoxaline-2(1H)-ones according to the present invention and achieve the intended purpose of the invention, the following detailed description, in conjunction with preferred embodiments, details the specific implementation, structure, features, and effects of the photocatalytic arylation method for quinoxaline-2(1H)-ones proposed in this invention. In the following description, different "examples" or "examples" do not necessarily refer to the same example. Furthermore, specific features, structures, or characteristics in one or more examples can be combined in any suitable manner.

[0036] The following will provide a more detailed description of the photocatalytic arylation method for quinoxaline-2(1H)-one of the present invention, with reference to specific embodiments:

[0037] This invention discloses a photocatalytic arylation method for quinoxaline-2(1H)-one, which is a photocatalytic energy transfer method for arylation of quinoxaline-2(1H)-one. It uses ultraviolet light as a light source, thioxanthone as a catalyst, and quinoxaline-2(1H)-one and iodoaromatic hydrocarbons as reactants to carry out the arylation reaction.

[0038] The technical solution of this invention is as follows:

[0039] A photocatalytic arylation method for quinoxaline-2(1H)-ones involves mixing quinoxaline-2(1H)-one compounds, iodoaromatics, a photocatalyst, and a solvent, and then stirring the mixture under visible light at room temperature to obtain the arylated product of quinoxaline-2(1H)-one.

[0040] The above technical solution includes a step of purifying the obtained product after the reaction is completed.

[0041] Preferably, the general reaction formula of the arylation method is:

[0042]

[0043] Wherein, the R 1 Substituents at the 7- and / or 8- positions on the benzene ring;

[0044] The R mentioned 2 It is an alkyl group.

[0045] More preferably, the R 1 Selected from one of H, Cl, F, and CF3;

[0046] The R mentioned 2 It is a C1-C5 alkyl group.

[0047] Preferably, the solvent is acetonitrile (MeCN);

[0048] The photocatalyst is a thioxanone catalyst;

[0049] The reaction is carried out in an inert gas atmosphere.

[0050] Preferably, the wavelength of the visible light is 390-456 nm;

[0051] The molar ratio of the quinoxaline-2(1H)-one compound to the iodoaromatic hydrocarbon is 1:3-5;

[0052] The amount of the photocatalyst used is 10-30 wt% of the quinoxaline-2(1H)-one compound.

[0053] More preferably, the wavelength of the visible light is 390 nm;

[0054] The molar ratio of the quinoxaline-2(1H)-one compound to the iodoaromatic hydrocarbon is 1:4;

[0055] The amount of the photocatalyst used is 30 wt% of the quinoxaline-2(1H)-one compound.

[0056] Furthermore, the iodinated aromatic hydrocarbon is an iodinated biphenyl, with the following structure:

[0057] An arylated product of quinoxaline-2(1H)-one was obtained by the above-described arylation method.

[0058] Furthermore, the quinoxaline-2(1H)-one arylized product is any of the following compounds:

[0059] 3-Biphenyl-quinoxaline-2(1H)-one, 3-Biphenyl-1-(N-isobutyl)quinoxaline-2(1H)-one, 3-Biphenyl-1-(N-butyl)quinoxaline-2(1H)-one, 3-Biphenyl-1-(N-pentyl)quinoxaline-2(1H)-one, 3-Biphenyl-8-(fluoro)quinoxaline-2(1H)-one, 3-Biphenyl-8-(trifluoromethyl)quinoxaline-2(1H)-one, 3-Biphenyl- 7,8-(dichloro)-quinoxaline-2(1H)-one, 3-(4-butyl-4'-iodobiphenyl)quinoxaline-2(1H)-one, 3-(4-pentyl-4′-iodobiphenyl)-quinoxaline-2(1H)-one, 3-(9,9-dimethylfluorene)-quinoxaline-2(1H)-one, 3-biphenyl-7,8-(dimethyl)-quinoxaline-2(1H)-one, 3-(benzophenone)-quinoxaline-2(1H)-one.

[0060] Applications of the above-mentioned quinoxaline-2(1H)-one arylized products in drug synthesis, materials science, and catalysts.

[0061] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0062] TXT in the reaction formula is a thioxanthone catalyst.

[0063] Example 1: Synthesis of 3-biphenyl-quinoxaline-2(1H)-ones

[0064] The reaction formula is shown below:

[0065]

[0066] The specific synthesis steps of 3-biphenyl-quinoxaline-2(1H)-one in this embodiment are as follows:

[0067] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube with a branch end. Under argon protection, iodobiphenyl (0.4 mmol, 0.1120 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) as solvent were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-1-methylquinoxalin-2(1H)-one (23.3 mg), with a yield of 74%.

[0068] The proton and carbon spectra of 3-biphenyl-1-methylquinoxalin-2(1H)-one are shown below. Figure 1-2 As shown, it is: 1 H NMR (400MHz, CDCl3) δ8.46-8.41(m, 2H), 7.96(dd, J=8.0, 1.5Hz, 1H), 7.75-7.69(m, 2H), 7.69-7.64(m , 2H), 7.57 (ddt, J=8.4, 7.3, 1.2Hz, 1H), 7.49-7.44 (m, 2H), 7.40-7.32 (m, 3H), 3.78 (d, J=1.2Hz, 3H). 13 C NMR (101MHz, CDCl3) δ153.75, 143.13, 135.12, 133.49, 133.28, 130.57, 130.43, 130.18, 128.95, 127.80, 127.35, 126.93, 123.90, 113.72, 29.46.

[0069] Example 2: Synthesis of 3-biphenyl-1-(N-isobutyl)quinoxaline-2(1H)-one

[0070] The reaction formula is shown below:

[0071]

[0072] The specific synthetic steps of 3-biphenyl-1-(N-isobutyl)quinoxaline-2(1H)-one in this embodiment are as follows:

[0073] 1-(N-isobutyl)quinoxalin-2(1H)-one (0.1 mmol, 0.0200 g) was loaded into a 10 mL quartz reaction tube. Under argon protection, iodobiphenyl (0.4 mmol, 0.1120 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) as solvent were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-1-(N-isobutyl)quinoxalin-2(1H)-one (23.7 mg), with a yield of 67%.

[0074] 3-Biphenyl-1-(N-isobutyl)quinoxaline-2(1H)-one: 1H NMR (400MHz, CDCl3) δ8.47-8.39 (m, 2H), 7.96 (dd, J=7.9, 1.5Hz, 1H), 7.74-7.69 (m, 2H), 7.69-7.63 (m, 2H), 7.54 (ddd, J=8.7 , 7.4, 1.6Hz, 1H), 7.49-7.43 (m, 2H), 7.40-7.30 (m, 3H), 4.23 (d, J=7.4Hz, 2H), 2.39-2.25 (m, 1H), 1.06 (s, 3H), 1.04 (s, 3H). 13 C NMR (101MHz, CDCl3) δ155.04, 143.09, 140.79, 135.23, 133.00, 130.83, 130.20, 130.17, 128.94, 127.77, 127.35, 126.90, 123.66, 114.15, 49.31, 27.46, 20.44.

[0075] Example 3: Synthesis of 3-biphenyl-1-(N-butyl)quinoxaline-2(1H)-one

[0076] The reaction formula is shown below:

[0077]

[0078] The specific synthetic steps of 1-(N-butyl)-quinoxaline-2(1H)-one in this embodiment are as follows:

[0079] 1-(N-Butyl)-quinoxalin-2(1H)-one (0.1 mmol, 0.0200 g) was loaded into a 10 mL quartz reaction tube. Under argon protection, iodobiphenyl (0.4 mmol, 0.1120 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) as solvent were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-1-(N-Butyl)quinoxalin-2(1H)-one (21.6 mg), with a yield of 61%.

[0080] 3-Biphenyl-1-(N-Butyl)quinoxaline-2(1H)-one: 1H NMR (400MHz, CDCl3) δ8.48-8.40 (m, 2H), 7.97 (dd, J=7.9, 1.5Hz, 1H), 7.74-7.69 (m, 2H), 7.68-7.64 (m, 2H), 7.56 (ddd, J=8.6, 7.4, 1 .5Hz, 1H), 7.49-7.43(m, 2H), 7.40-7.32(m, 3H), 4.38-4.29(m, 2H), 1.86-1.75(m, 2H), 1.53(h, J=7.4Hz, 2H), 1.03(t, J=7.4Hz, 3H). 13 C NMR (101MHz, CDCl3) δ154.50, 142.96, 140.67, 135.05, 133.48, 132.57, 130.71, 130.22 , 130.10, 128.83, 127.66, 127.23, 126.79, 123.56, 113.61, 42.44, 29.37, 20.39, 13.85.

[0081] Example 4: Synthesis of 3-biphenyl-1-(N-pentyl)-quinoxaline-2(1H)-one

[0082] The reaction formula is shown below:

[0083]

[0084] The specific synthetic steps of 1-(N-pentyl)-quinoxaline-2(1H)-one in this embodiment are as follows:

[0085] 1-(N-pentyl)-quinoxalin-2(1H)-one (0.1 mmol, 0.0220 g) was loaded into a 10 mL quartz reaction tube. Under argon protection, iodobiphenyl (0.4 mmol, 0.1120 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) as solvent were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-1-(N-pentyl)-quinoxalin-2(1H)-one (26.6 mg), with a yield of 72%.

[0086] 3-Biphenyl-1-(N-pentyl)-quinoxaline-2(1H)-one: 1H NMR (400MHz, CDCl3) δ8.47-8.42 (m, 2H), 7.96 (dd, J=8.0, 1.5Hz, 1H), 7.74-7. 69 (m, 2H), 7.68-7.63 (m, 2H), 7.55 (ddd, J=8.6, 7.3, 1.6Hz, 1H), 7.46 (dd, J=8 .4, 6.8Hz, 2H), 7.40-7.36(m, 1H), 7.36-7.30(m, 2H), 4.37-4.25(m, 2H), 1.82 (t, J=7.8Hz, 2H), 1.53-1.46 (m, 2H), 1.45-1.37 (m, 2H), 0.94 (t, J=7.0Hz, 3H). 13 C NMR (101MHz, CDCl3) δ154.48, 142.95, 140.67, 135.06, 133.48, 132.57, 130.70, 130.23, 13 0.11, 128.84, 127.67, 127.23, 126.78, 123.55, 113.60, 42.67, 29.21, 27.02, 22.47, 14.03.

[0087] Example 5: Synthesis of 3-biphenyl-8-(fluoro)-1-methylquinoxalin-2(1H)-one

[0088] The reaction formula is shown below:

[0089]

[0090] The specific synthetic steps of 3-biphenyl-8-(fluoro)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0091] 0.1 mmol (0.0180 g) of 8-(fluoro)-1-methylquinoxalin-2(1H)-one was added to a 10 mL quartz reaction tube with a branch end. Under argon protection, 0.4 mmol (0.1120 g) of iodobiphenyl, 0.03 mmol (0.0064 g) of thioxanthone catalyst, and 4 mL of acetonitrile were added as solvent. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-8-(fluoro)-1-methylquinoxalin-2(1H)-one (22.2 mg), with a yield of 67%.

[0092] 3-Biphenyl-8-(fluoro)-1-methylquinoxalin-2(1H)-one: 1H NMR (400MHz, CDCl3) δ8.45-8.35(m, 2H), 7.92(dd, J=8.8, 6.0Hz, 1H), 7.73-7.68(m, 2H), 7.68-7.63(m, 2H), 7.50-7.42(m, 2H), 7.42-7.33(m, 2H), 7.12-7.04(m, 1H), 7.04-6.97(m, 1H), 3.72(d, J=1.0Hz, 3H). 13 C NMR (101MHz, CDCl3) δ143.02, 140.55, 134.75, 132.41, 132.30, 129.94, 128.85, 127.71, 127.21, 126.81, 111.81, 111.58, 100.67, 100.39.

[0093] Example 6: Synthesis of 3-biphenyl-8-(trifluoromethyl)-1-methylquinoxalin-2(1H)-one

[0094] The reaction formula is shown below:

[0095]

[0096] The specific synthetic steps of 3-biphenyl-8-(trifluoromethyl)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0097] 0.1 mmol (0.0230 g) of 8-(trifluoromethyl)-1-methylquinoxalin-2(1H)-one was loaded into a 10 mL quartz reaction tube. Under argon protection, 0.4 mmol (0.1120 g) of iodobiphenyl, 0.03 mmol (0.0064 g) of thioxanthone catalyst, and 4 mL of acetonitrile were added as solvent. The mixture was stirred for 24 h at room temperature and a 390 nm light source. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-8-(trifluoromethyl)-quinoxalin-2(1H)-one (27.6 mg), with a yield of 72%.

[0098] 3-Biphenyl-8-(trifluoromethyl)-1-methylquinoxalin-2(1H)-one: 1H NMR (400MHz, CDCl3) δ8.46 (d, J=8.5Hz, 2H), 8.03 (s, 1H), 7.72 (d, J=8.5Hz, 2H), 7.69 -7.64 (m, 2H), 7.56 (d, J=1.8Hz, 2H), 7.46 (d, J=7.9Hz, 2H), 7.38 (s, 2H), 3.80 (s, 3H). 13 C NMR (101MHz, CDCl3) δ154.46, 143.70, 140.36, 134.35, 133.29, 131.05, 130.29, 1 28.89, 127.88, 127.22, 127.06, 126.87, 120.24, 120.21, 111.05, 111.01, 29.51.

[0099] Example 7: Synthesis of 3-biphenyl-7,8-(dichloro)-1-methylquinoxalin-2(1H)-one

[0100] The reaction formula is shown below:

[0101]

[0102] The specific synthetic steps of 3-biphenyl-7,8-(dichloro)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0103] 0.1 mmol (0.0230 g) of 7,8-(dichloro)-1-methylquinoxalin-2(1H)-one was loaded into a 10 mL quartz reaction tube. Under argon protection, 0.4 mmol (0.1120 g) of iodobiphenyl, 0.03 mmol (0.0064 g) of thioxanthone catalyst, and 4 mL of acetonitrile were added as solvent. The mixture was stirred for 24 h at room temperature and a 390 nm light source. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-biphenyl-7,8-(dichloro)-1-methylquinoxalin-2(1H)-one (26.9 mg), with a yield of 70%.

[0104] 3-Biphenyl-7,8-(dichloro)-1-methylquinoxalin-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.42 (d, J=8.5Hz, 2H), 8.00 (s, 1H), 7.70 (d, J=8.5Hz, 2H) , 7.67-7.62 (m, 2H), 7.45 (d, J=7.9Hz, 2H), 7.38 (d, J=4.3Hz, 2H), 3.70 (s, 3H).13 C NMR (101MHz, CDCl3) δ154.45, 143.55, 140.33, 134.27, 134.22, 132.65, 132.20, 131. 01, 130.17, 128.88, 128.81, 127.86, 127.53, 127.20, 127.05, 126.82, 115.06, 29.58.

[0105] Example 8: Synthesis of 3-(4-butyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one

[0106] The reaction formula is shown below:

[0107]

[0108] The specific synthetic steps of 3-(4-butyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0109] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube. Under argon protection, 4-butyl-4'-iodobiphenyl (0.4 mmol, 0.1345 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) as solvent were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, the solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1). The crude product was diluted with dichloromethane and transferred to give the final product 3-(4-butyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one (27.8 mg), with a yield of 71%.

[0110] 3-(4-Butyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.42 (d, J=8.5Hz, 2H), 7.96 (dd, J=8.0, 1.3Hz, 1H), 7.71 (d, J=8.5Hz, 2H), 7.62-7.54 (m, 3H), 7.42-7.31 (m, 2H ), 7.28 (d, J=8.2Hz, 2H), 3.79 (s, 3H), 2.75-2.58 (m, 2H), 1.65 (p, J=7.5Hz, 2H), 1.40 (dq, J=14.6, 7.3Hz, 2H), 0.95 (t, J=7.3Hz, 3H). 13C NMR (101MHz, CDCl3) δ154.81, 153.70, 143.00, 142.61, 137.91, 134.68, 133.35, 133.17, 130.42 , 130.25, 130.02, 128.92, 127.04, 126.60, 123.76, 113.58, 35.36, 33.65, 29.33, 22.43, 14.00.

[0111] Example 9: Synthesis of 3-(4-pentyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one

[0112] The reaction formula is shown below:

[0113]

[0114] The specific synthetic steps of 3-(4-pentyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0115] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube with a branch end. Under argon protection, 4-pentyl-4'-iodobiphenyl (0.4 mmol, 0.1400 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-(4-pentyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one (23.6 mg), with a yield of 75%.

[0116] 3-(4-pentyl-4'-iodobiphenyl)-1-methylquinoxalin-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.42 (d, J=8.5Hz, 2H), 7.95 (dd, J=8.0, 1.3Hz, 1H), 7.71 (d, J=8.5Hz, 2H), 7.63-7.52 (m, 3H), 7.40-7.31 (m, 2H), 7. 28 (d, J=8.1Hz, 2H), 3.78 (s, 3H), 2.71-2.61 (m, 2H), 1.70-1.62 (m, 2H), 1.37 (d, J=3.4Hz, 2H), 1.35 (d, J=3.0Hz, 2H), 0.95-0.87 (m, 3H). 13C NMR (101MHz, CDCl3) δ154.80, 142.98, 142.65, 137.91, 134.71, 133.35, 130.43, 130.24, 13 0.02, 128.92, 127.05, 126.60, 123.75, 113.58, 35.65, 31.58, 31.20, 29.32, 22.59, 14.08.

[0117] Example 10: Synthesis of 3-(9,9-dimethylfluorene)-1-methylquinoxalin-2(1H)-one

[0118] The reaction formula is shown below:

[0119]

[0120] The specific synthesis steps of 3-(9,9-dimethylfluorene)-1-methylquinoxalin-2(1H)-one in this embodiment are as follows:

[0121] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube with a branch end. Under argon protection, 2-iodine-9,9-dimethylfluorene (0.4 mmol, 0.1281 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile as solvent (4 mL) were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-(9,9-dimethylfluorene)-1-methylquinoxalin-2(1H)-one (24.7 mg), with a yield of 64%.

[0122] 3-(9,9-dimethylfluorene)-1-methylquinoxalin-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.47 (s, 1H), 8.41-8.33 (m, 1H), 7.97 (dd, J=8.0, 1.4Hz, 1H), 7.82 (d, J=8.0Hz, 1H), 7.8 0-7.77 (m, 1H), 7.60-7.51 (m, 1H), 7.50-7.43 (m, 1H), 7.39-7.31 (m, 4H), 3.78 (d, J=1.2Hz, 3H), 1.57 (s, 6H). 13C NMR (101MHz, CDCl3) δ154.98, 154.70, 153.29, 141.55, 138.79, 135.13, 133.37, 133.29, 130.46, 130 .22, 129.10, 127.92, 127.15, 124.17, 123.84, 122.80, 120.69, 119.68, 113.67, 47.19, 29.44, 27.26.

[0123] Example 11: Synthesis of 3-(phenanthyl)-1-methylquinoxalin-2(1H)-one

[0124] The reaction formula is shown below:

[0125]

[0126] The specific synthetic steps of 3-(phenanthroline)-1-methylquinoxaline-2(1H)-one in this embodiment are as follows:

[0127] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube with a branch end. Under argon protection, 9-iodophenanthrene (0.4 mmol, 0.1216 g), thioxanthone catalyst (0.03 mmol, 0.0064 g), and acetonitrile (4 mL) were added as solvent. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-(phenanthrene)-1-methylquinoxalin-2(1H)-one (16.8 mg), with a yield of 54%.

[0128] 3-(phenanthroline)-1-methylquinoxalin-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.77-8.70 (m, 2H), 8.03-7.99 (m, 2H), 7.93 (dd, J=8.0, 1.4Hz, 1H), 7.86 (dd, J=8.2, 1.3Hz, 1H), 7.70-7.64(m, 3H), 7.61-7.54(m, 2H), 7.45-7.42(m, 2H), 3.82(s, 3H). 13C NMR (101MHz, CDCl3) δ133.53, 132.86, 132.77, 130.86, 130.66, 130.43, 129.13, 128. 69, 127.29, 126.55, 126.50, 126.48, 125.94, 123.74, 122.84, 122.39, 113.63, 29.36.

[0129] Example 12: Synthesis of 3-(benzophenone)-methylquinoxaline-2(1H)-one

[0130] The reaction formula is shown below:

[0131]

[0132] The specific synthesis steps of 3-(benzophenone)-1-methylquinoxaline-2(1H)-one in this embodiment are as follows:

[0133] 1-Methylquinoxalin-2(1H)-one (0.1 mmol, 0.0160 g) was loaded into a 10 mL quartz reaction tube with a branch end. Under argon protection, 4-iodobenzophenone (0.4 mmol, 0.1232 g) and solvent (4 mL) were added. After mixing, the mixture was stirred for 24 h at room temperature and a light source at 390 nm. After the reaction was complete, dichloromethane was added to dilute and transfer the crude product. The solvent was removed under reduced pressure. Finally, the crude product was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the final product 3-(benzophenone)-1-methylquinoxalin-2(1H)-one (19.4 mg), with a yield of 56%.

[0134] 3-(benzophenone)-1-methylquinoxaline-2(1H)-one: 1 H NMR (400MHz, CDCl3) δ8.48-8.44 (m, 2H), 7.98 (dd, J=8.0, 1.5Hz, 1H), 7.93-7.89 (m, 2H), 7.87-7.8 3 (m, 2H), 7.60 (dt, J=7.5, 1.4Hz, 2H), 7.50 (dd, J=8.2, 6.9Hz, 2H), 7.44-7.33 (m, 2H), 3.80 (s, 3H). 13 C NMR (101MHz, CDCl3) δ196.52, 154.74, 153.13, 139.78, 138.80, 137.63, 133.63, 133. 20, 132.69, 131.09, 130.86, 130.26, 129.81, 129.58, 128.46, 124.08, 113.83, 29.51.

[0135] Example 13.

[0136] The operating steps of Example 13 are the same as those of Example 1, except for the visible light wavelength, the molar ratio of quinoxaline-2(1H)-one to iodoaryl hydrocarbons, and the amount of thioxanthone catalyst used. See Table 1 for details.

[0137] Table 1

[0138]

[0139]

[0140] Example 14.

[0141] The reaction formula is shown below:

[0142]

[0143] The specific operating steps are as follows:

[0144] (1) The operation steps of Example 14 are the same as those of Example 1, except that different catalysts are used for catalysis, such as: catalyst 1 (thioxanthone), catalyst 2 (terpyridine ruthenium chloride hexahydrate), and catalyst 3 ([Ir(dFCF3ppy)2(dtbbpy)](PF6)). See Table 2 for details.

[0145] Table 2

[0146] deal with catalyst Yield % 1 Catalyst 1 72 2 Catalyst 2 Trace 3 Catalyst 3 20

[0147] Reaction conditions: 1-methylquinoxalone (1 mmol), iodobiphenyl (4 mmol), catalyst (30 mol%), acetonitrile (4 mL), 390 nm (40 W), argon gas.

[0148] As shown in Table 2, under the same conditions, catalyst 1 showed the best performance and the highest yield when using different catalysts. Catalysts 2 and 3 did not have sufficient energy to break the (CI bond) of the iodobiphenyl, thus preventing the reaction from proceeding.

[0149] (2) The operation steps of Example 14 are the same as those of Example 1, except that different solvents are used, such as acetonitrile, dimethyl sulfoxide, 1,2-dichloroethane, and N,N-dimethylformamide. See Table 3 for details.

[0150] Table 3

[0151] deal with Solvent (4 mL) Yield % 1 Acetonitrile 72 2 Dimethyl sulfoxide 19 3 1,2-Dichloroethane 16 4 N,N-Dimethylformamide Trace

[0152] Reaction conditions: 1-methylquinoxalone (1 mmol), iodobiphenyl (4 mmol), thioxanthone (30 mol%), 390 nm (40 W), argon gas.

[0153] As shown in Table 3, under the same conditions, acetonitrile is the most effective solvent for the reaction, yielding the highest yield. Dimethyl sulfoxide, 1,2-dichloroethane, and N,N-dimethylformamide have poor solubility effects on this reaction.

[0154] (3) The operation steps of Example 14 are the same as those of Example 1, except that the reaction is carried out under conditions with and without light source, as shown in Table 4.

[0155] Table 4

[0156] deal with light source Yield % 1 have 72 2 none NR

[0157] Reaction conditions: 1-methylquinoxalone (1 mmol), iodobiphenyl (4 mmol), thioxanthone (30 mol%), acetonitrile (4 mL), 390 nm (40 W), argon gas.

[0158] As shown in Table 4, under the same conditions, this reaction can only be carried out under light.

[0159] (4) The operation steps of Example 14 are the same as those of Example 1, except that the reaction system is under argon (Ar) and air conditions, as shown in Table 5.

[0160] Table 5

[0161] deal with gas Yield % 1 Argon 72 2 Air NR

[0162] Reaction conditions: 1-methylquinoxalone (1 mmol), iodobiphenyl (4 mmol), thioxanone (30 mol%), acetonitrile (4 mL), 390 nm (40 W)

[0163] As shown in Table 5, under the same conditions, this reaction requires an argon atmosphere to proceed and does not occur in air.

[0164] For common quinoxalinone arylation reactions, phenylhydrazine, diazonium salts, etc., are typically used as the aryl group source. However, these raw materials are unstable, require precious metal catalysts, or necessitate the addition of excess organic bases, leading to disadvantages such as atom economy and high cost. The technical solution of this invention uses aryl halides as the aryl group source, which is readily available, low in cost, and stable. However, compared to common reactants such as phenylhydrazine and diazonium salts, aryl halides are more inert and less prone to initiation, making the arylation reaction practically difficult to occur, i.e., it suffers from a problem of difficult catalysis.

[0165] This invention utilizes a dye-based catalyst (thioxanthone) as a photocatalyst, eliminating the need for additional base addition; and directly achieves the arylation reaction of quinoxaline-2(1H)-one through an energy transfer strategy. This system is simple to operate, operates under mild conditions, and boasts high atom economy. Through condition screening of the catalyst, solvent, presence or absence of visible light, and gas atmosphere, this invention enables aryl halides to participate in the arylation reaction of quinoxaline-2(1H)-one, achieving optimal conditions for catalyzing aromatic hydrocarbons.

[0166] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A method for arylation of quinoxaline-2(lH)-one based on photocatalysis, characterized by, The arylating method is: mixing quinoxaline-2(1H)-ketone compound, iodoarene, photocatalyst and solvent, stirring and reacting at room temperature under visible light irradiation to obtain quinoxaline-2(1H)-ketone arylated product.

2. The arylating method according to claim 1, wherein, The reaction general formula of the arylating method is: wherein R 1 is a substituent at the 7- and / or 8-position of the phenyl ring; The R mentioned 2 It is an alkyl group.

3. The arylating method according to claim 2, wherein, R1is selected from H, F, Cl, Br, I, CF3, CH3, CN, and NO2; 1 one selected from H, Cl, F, CF3; The R mentioned 2 It is a C1-C5 alkyl group.

4. The arylating method according to claim 1, wherein, The solvent is acetonitrile; The photocatalyst is thioxanthone catalyst; The reaction is carried out under inert gas atmosphere.

5. The arylating method according to claim 1, wherein, The wavelength of the visible light is 390-456 nm; The molar ratio of the quinoxaline-2(1H)-ketone compound to iodoarene is 1:3-5; The amount of the photocatalyst is 10-30 wt% of the quinoxaline-2(1H)-ketone compound.

6. The arylating method according to claim 5, wherein, The wavelength of the visible light is 390 nm; The molar ratio of the quinoxaline-2(1H)-ketone compound to iodoarene is 1:4; The amount of the photocatalyst is 30 wt% of the quinoxaline-2(1H)-ketone compound.

7. The arylating method according to claim 1, wherein, The iodoarene is iodo-biphenyl.

8. A quinoxaline-2(lH)-one arylation product characterized by, The quinoxaline-2(1H)-ketone arylated product is obtained by the arylating method according to any one of claims 1-7.

9. The quinoxaline-2(lH)-one arylation product according to claim 5, characterized in that, The quinoxaline-2(1H)-ketone arylated product is any one of the following compounds: 3-biphenyl-1-methyl quinoxaline-2(1H)-ketone, 3-biphenyl-1-(N-isobutyl) quinoxaline-2(1H)-ketone, 3-biphenyl-1-(N-butyl) quinoxaline-2(1H)-ketone, 3-biphenyl-1-(N-pentyl) quinoxaline-2(1H)-ketone, 3-biphenyl-8-(fluoro)-1-methyl quinoxaline-2(1H)-ketone, 3-biphenyl-8-(trifluoromethyl)-1-methyl quinoxaline-2(1H)-ketone, 3-biphenyl-7,8-(dichloro)-1-methyl quinoxaline-2(1H)-ketone, 3-(4-butyl-4'-iodobiphenyl)-1-methyl quinoxaline-2(1H)-ketone, 3-(4-pentyl-4'-iodobiphenyl)-1-methyl quinoxaline-2(1H)-ketone, 3-(9,9-dimethylfluorene)-1-methyl quinoxaline-2(1H)-ketone, 3-biphenyl-7,8-(dimethyl)-1-methyl quinoxaline-2(1H)-ketone, 3-(benzophenone)-1-methyl quinoxaline-2(1H)-ketone.

10. Use of the quinoxaline-2(1H)-ketone arylated product according to any one of claims 8-9 in synthesis of drugs, material science and catalysts.

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