A method for photocatalytic preparation of difluoroquinoxalineone derivatives from iodonium salts containing iodine

Abstract

This invention discloses a photocatalytic method for preparing difluoroquinoxalinone derivatives from iodine-containing phosphonium salts. A quinoxalinone compound of formula (I), a difluoromethyltriphenyl phosphonium iodide salt compound of formula (II), and a base are added to a reaction solvent. Under nitrogen protection, the reaction is stirred under blue light irradiation. After the reaction, the reaction solution is post-treated to obtain the target compound, formula (III), a difluoromethylated quinoxalinone derivative with antifungal activity. The reaction equation is as follows: [The substituent R...] 1 Selected from H or methyl, substituent R 2 Selected from H, methyl or methoxy, substituent R 3 The derivative is selected from H, methyl, ester, alkynyl, phenyl, naphthyl, or substituted phenyl groups, where the substituent of the substituted phenyl group is methyl or halogen, and n is 0, 1, or 2. This invention features a simple process, inexpensive and readily available raw materials, mild reaction conditions, and is environmentally friendly, while also exhibiting antifungal activity as a difluoromethylated quinoxalone derivative.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to a method for preparing difluoroquinoxalone derivatives by photocatalysis of iodine-containing phosphonium salts. Background Technology

[0002] N-heterocyclic compounds are ubiquitous in bioactive natural products and pharmaceutically related compounds. Among them, quinoxaline-2(1H)-ones are crucial N-heterocyclic moieties, possessing surprisingly broad-spectrum biological properties, such as antifungal (Eur. J. Org. Chem. 2022, e202100896), anticancer, antiviral, anticonvulsant, and anticoagulant properties. In particular, 3-substituted quinoxaline-2(1H)-one derivatives are considered to possess the most privileged pharmacophores. Therefore, considerable interest has been generated in developing novel and effective synthetic schemes for quinoxaline-one derivatives, and significant achievements have been made in the synthesis of 3-substituted quinoxaline-2(1H)-one derivatives. Consequently, the development of direct and effective synthetic methods for compounds with potentially pharmacologically active quinoxaline-2(1H)-one lead structural skeletons has attracted widespread attention.

[0003]

[0004] On the other hand, the preparation of organofluorine compounds is a significant field in pharmaceuticals, agrochemicals, and materials science because the introduction of fluorine substituents into organic molecules has profound positive effects on their physical properties, including metabolic stability, solubility, and lipophilicity. Among various fluoroalkyl groups, difluoromethyl has attracted particular attention in medicinal chemistry because the CF2H moiety is isomeric and isopolar with both hydroxyl and thiol groups, and may also serve as a lipophilic hydrogen donor. Therefore, a large body of research has been dedicated to the efficient introduction of difluoromethyl into organic compounds. Traditionally, difluoromethylated compounds are prepared by deoxyfluorination of aldehydes using SF4 or trifluorodialkylaminosulfonates (such as N,N-dimethylaminosulfonate (DAST) or bis(2-methoxyethyl)aminosulfonate (Deoxo Fluor)). However, these methods often suffer from functional compatibility issues and require expensive and / or toxic fluorinating agents. Alternatively, photo-oxidative radical difluoromethylation has been achieved by using difluoromethanesulfonyl chloride, difluoromethylphosphonium salts, difluoromethyl sulfones, or sulfonylimides as sources of difluoromethyl radicals. The synthetic utility of these methods is still offset by the costly and / or gaseous starting materials required for the preparation of these reagents, as well as the necessity of high temperatures, additional oxidants, and / or transition metal catalysts for the generation of difluoromethyl radicals. Therefore, alternative strategies for generating mild, efficient, and cost-effective difluoromethyl radicals should be highly desirable. Building upon previous work on radical coupling, a photocatalyst-free difluoromethylation reaction of visible light-induced quinoxalinone and difluoromethyltriphenylphosphonium iodide salts is proposed to construct difluoromethylated quinoxalinone compounds with antifungal activity. Summary of the Invention

[0005] To address the aforementioned technical problems in the existing technology, the purpose of this invention is to provide a simple, mild, high-purity, and green method for preparing antifungal difluoroquinoxalone derivatives from iodine-containing phosphonium salts via photocatalysis.

[0006] To achieve the above objectives, the present invention proposes the following technical solution:

[0007] A method for photocatalytic preparation of difluoroquinoxalinone derivatives from iodine-containing phosphonium salts includes the following steps: adding a quinoxalinone compound of formula (I), a difluoromethyltriphenyl iodide phosphonium salt compound of formula (II), and a base to a reaction solvent; under nitrogen protection, stirring the reaction mixture under blue light irradiation; after the reaction is completed, the reaction solution is post-treated to obtain a difluoromethylated quinoxalinone derivative with antifungal activity, as shown in formula (III). The reaction equation is as follows:

[0008]

[0009] The substituent R 1 Selected from H or methyl, substituent R2 Selected from H, methyl or methoxy, substituent R 3 It is selected from H, methyl, ester, alkynyl, phenyl, naphthyl or substituted phenyl, wherein the substituent of the substituted phenyl is methyl or halogen, and n is 0, 1 or 2.

[0010] The mechanism of this invention is as follows:

[0011] Under visible light, the base interacts with difluoromethyltriphenylphosphonium iodide salt via a single-electron transfer reaction, generating a base radical cation, a difluoromethyl radical, and an iodide anion, while releasing the byproduct PPh3. The difluoromethyl radical attacks the C3 position of quinoxalone, and the resulting intermediate reacts with the base radical cation through a single-electron transfer process and undergoes deprotonation, ultimately generating difluoromethylated quinoxalone compounds.

[0012] Furthermore, the reaction solvent is selected from tetrahydrofuran or dichloromethane, preferably dichloromethane.

[0013] Furthermore, the base is selected from N,N,N',N'-tetramethylethylenediamine (TMEDA) or N,N,N,N',N'-pentamethyldiethylenetriamine (PMDETA), preferably N,N,N',N'-tetramethylethylenediamine (TMEDA).

[0014] Furthermore, the molar ratio of the quinoxalone compound shown in formula (I), the difluoromethyltriphenylphosphonium iodide salt compound shown in formula (II), and the base shown in formula (III) is 1:2:0.2 to 1.0, preferably 1:2:0.2.

[0015] Further, the reaction solution underwent post-treatment as follows: saturated brine was added to the reaction solution for washing, followed by extraction with ethyl acetate. The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography to obtain the target compound. The eluent used for column chromatography purification was a mixture of petroleum ether and ethyl acetate at a volume ratio of 3–8:1.

[0016] Further, in a reaction tube equipped with a magnetic stirrer, a quinoxalone compound of formula (I), a difluoromethyltriphenylphosphonium iodide salt of formula (II), an alkali, and a reaction medium were added. After nitrogen purging three times, the reaction system was placed under light source irradiation and stirred at 30-40°C. After the reaction was completed, saturated brine was added to the reaction solution for washing. The mixture obtained after washing was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by chromatographic column chromatography to obtain the difluoromethylated quinoxalone compound of formula (III) with antifungal activity.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] 1) This invention can synthesize difluoromethylated quinoxalone compounds with antifungal activity using only blue light irradiation conditions, without the need to add any photocatalyst, thus avoiding the use of oxidants, transition metal catalysts and specific ligands in conventional technologies, and effectively controlling the cost of the reaction.

[0019] 2) This invention uses a one-step synthesis method to prepare the target compound. Compared with conventional techniques, this method is simple to operate and does not require prefunctionalization of the reaction substrate.

[0020] 3) This invention has the advantages of simple operation, mild reaction conditions, simple post-processing, and antifungal activity, which are in line with the development concept of green chemistry and are suitable for industrial promotion and application. Detailed Implementation

[0021] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0022] Example 1 3-(difluoromethyl)-1-methylquinoxaline-2(1H)-one

[0023]

[0024] Compound (Ⅰ-a)N-methylquinoxalin-2(1H)-one (32.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 71% and an HPLC purity of 98.6%.

[0025] 1 H NMR (600MHz, CDCl3) δ8.00(d,J=7.6Hz,1H),7.68(t,J=7.8Hz,1H),7.45-7.41(m,1H),7.38(d,J=8.4Hz,1H),6.95(t,J=53.7Hz,1H),3.73(s,3H).

[0026] 13C NMR (151MHz, CDCl3) δ = 153.2, 148.7 (t, J C-F =22.6Hz),134.0,132.6,131.9,131.5,124.4,113.9,110.1(t,J C-F =241.6Hz), 28.9.

[0027] 19 F NMR (565MHz, CDCl3) δ = -124.4.

[0028] Example 2 3-(difluoromethyl)quinoxaline-2(1H)-one

[0029]

[0030] Compound (Ⅰ-b) quinoxaline-2(1H)-one (29.2 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 3:1 to obtain the target product with a yield of 70% and an HPLC purity of 98.8%.

[0031] 1 H NMR (600MHz, DMSO-d6) δ12.81(s,1H),7.87(d,J=8.1Hz,1H),7.65(t,J=7.8Hz,1H),7.37(t,J=7.7Hz,2H),7.05(t,1H).

[0032] 13 C NMR(151MHz,DMSO-d6)δ=153.1,149.7(t,J C-F =22.6Hz),132.8,132.2,130.7,129.4,123.9,115.7,110.3(t,J C-F =240.1Hz).

[0033] 19 F NMR (565MHz, DMSO-d6) δ = -124.3.

[0034] Example 3 3-(difluoromethyl)-1,6,7-trimethylquinoxaline-2(1H)-one

[0035]

[0036] Compound (Ⅰ-c)1,6,7-trimethylquinoxalin-2(1H)-one (37.6 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 79% and an HPLC purity of 98.5%.

[0037] 1 H NMR (600MHz, CDCl3) δ7.71 (s, 1H), 7.12 (s, 1H), 6.93 (t, J = 53.9Hz, 1H), 3.69 (s, 3H), 2.44 (s, 3H), 2.35 (s, 3H).

[0038] 13 C NMR (151MHz, CDCl3) δ = 153.3, 147.2 (t, J C-F =22.6Hz),143.1,133.5,132.1,131.2,130.4,114.3,110.2(t,J C-F =241.6Hz), 28.8, 20.8, 19.1.

[0039] 19 F NMR (565MHz, CDCl3) δ = -124.0.

[0040] Example 4 3-(difluoromethyl)-7-methoxy-1-methylquinoxaline-2(1H)-one

[0041]

[0042] Compound (Ⅰ-d)7-methoxy-1-methylquinoxalin-2(1H)-one (38.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 68% and an HPLC purity of 98.8%. 1 H NMR (600MHz, CDCl3) δ7.43 (s, 1H), 7.29 (d, J = 1.2Hz, 2H), 6.97 (t, J = 53.8Hz, 1H), 3.89 (s, 3H), 3.71 (s, 3H).

[0043] 13 C NMR (151MHz, CDCl3) δ = 156.4, 152.9, 149.0 (t, J C-F =22.6Hz),132.7,128.4,122.4,114.8,112.1,109.9(t,J C-F =241.6Hz), 55.8, 29.1.

[0044] 19 F NMR (565MHz, CDCl3) δ = -124.5.

[0045] Example 5 3-(difluoromethyl)-1-(prop-2-yn-1-yl)quinoxaline-2(1H)-one

[0046]

[0047] Compound (Ⅰ-e)1-(prop-2-yn-1-yl)quinoxaline-2(1H)-one (36.8 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 56% and an HPLC purity of 98.9%. 1 H NMR (600MHz, CDCl3) δ8.01(d,J=8.0Hz,1H),7.72(t,J=7.1Hz,1H),7.54(d,J=8.5Hz,1 H),7.45(t,J=8.3Hz,1H),6.94(t,J=53.6Hz,1H),5.07(d,J=2.6Hz,2H),2.32(s,1H).

[0048] 13 C NMR (151MHz, CDCl3) δ = 152.2, 148.6 (t, J C-F =22.6Hz),132.7,132.5,132.1,131.6,124.7,114.5,110.0(t,J C-F =243.1Hz), 76.1, 73.8, 31.4.

[0049] 19 F NMR (565MHz, CDCl3) δ = -124.2.

[0050] Example 6 3-(difluoromethyl)-1-(4-methylbenzyl)quinoxaline-2(1H)-one

[0051]

[0052] Compound (Ⅰ-f)1-(4-methylbenzyl)quinoxaline-2(1H)-one (50.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 75% and an HPLC purity of 98.6%.

[0053] 1 H NMR (600MHz, CDCl3) δ7.99(d,J=8.0Hz,1H),7.56(t,J=7.9Hz,1H),7.37(t,J=8 .2Hz,2H),7.18-7.12(m,4H),7.02(t,J=53.7Hz,1H),5.47(s,2H),2.31(s,3H).

[0054] 13 C NMR (151MHz, CDCl3) δ = 153.3, 148.8 (t, J C-F =22.6Hz),137.8,133.4,132.5,132.2,131.5,131.5,129.7,127.0,124.3,114.7,110.0(t,J C-F =241.6Hz), 45.6, 21.0.

[0055] 19 F NMR (565MHz, CDCl3) δ = -124.1.

[0056] Example 7: 2-(3-(difluoromethyl)-2-oxoquinoxaline-1(2H)-yl)tert-butyl acetate

[0057]

[0058] Compound (Ⅰ-g) 2-(2-oxoquinoxalo-1(2H)-yl)tert-butyl acetate (52.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 64% and an HPLC purity of 98.8%.

[0059] 1 H NMR (600MHz, CDCl3) δ8.01(d,J=8.0Hz,1H),7.65(t,J=7.9Hz,1H),7.42(t,J=7.7 Hz,1H),7.13(d,J=8.4Hz,1H),6.95(t,J=53.6Hz,1H),4.95(s,2H),1.46(s,9H).

[0060] 13 C NMR (151MHz, CDCl3) δ = 165.5, 152.8, 148.6 (t, J C-F =22.6Hz),133.3,132.7,132.0,131.7,124.5,113.5,110.0(t,J C-F =241.6Hz), 83.6, 44.0, 27.9.

[0061] 19 F NMR (565MHz, CDCl3) δ = -124.3.

[0062] Example 8 3-(difluoromethyl)-1-(p-tolyl)quinoxaline-2(1H)-one

[0063]

[0064] Compound (Ⅰ-h)1-(p-tolyl)quinoxaline-2(1H)-one (47.2 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 65% and an HPLC purity of 98.6%.

[0065] 1 H NMR (600MHz, CDCl3) δ8.05(dd,J=8.1,1.5Hz,1H),7.49(ddd,J=8.6,7.2,1.6Hz,1H),7.45(d,J=8.0Hz,2H),7.41(d dd,J=8.3,7.2,1.3Hz,1H),7.20(d,J=8.3Hz,2H),7.02(t,J=53.7Hz,1H),6.82(dd,J=8.4,1.3Hz,1H),2.50(s,3H).

[0066] 13 C NMR(151MHz, CDCl3)δ=153.1,149.4(t,J C-F =22.6Hz),140.0,135.0,132.2,132.0,131.8,131.0,130.9,127.7,124.4,115.8,109.6(t,J C-F =241.6Hz), 21.3.

[0067] 19 F NMR (565MHz, CDCl3) δ = -124.2.

[0068] Example 9 1-(4-chlorophenyl)-3-(difluoromethyl)quinoxaline-2(1H)-one

[0069]

[0070] Compound (Ⅰ-i) 1-(p-chlorophenyl)quinoxalin-2(1H)-one (51.2 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 68% and an HPLC purity of 98.5%.

[0071] 1 H NMR (600MHz, CDCl3) δ8.04(dd,J=8.0,1.5Hz,1H),7.61(d,J=8.5Hz,2H),7.49(t,J=8.6Hz,1H ),7.42(t,J=7.6Hz,1H),7.27(d,J=8.4Hz,2H),6.96(t,J=53.6Hz,1H),6.77(d,J=8.4Hz,1H).

[0072] 13 C NMR (151MHz, CDCl3) δ = 152.8, 149.3 (t, J C-F =22.6Hz),136.0,134.6,133.1,132.4,131.8,131.2,130.7,129.6,124.7,115.5,109.7(t,J C-F =241.6Hz).

[0073] 19 F NMR (565MHz, CDCl3) δ = -124.2.

[0074] Example 10 3-(difluoromethyl)-1-phenylethylquinoxaline-2(1H)-one

[0075]

[0076] Compound (Ⅰ-j) 1-phenylethylquinoxalin-2(1H)-one (50.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and PMDETA (6.9 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to obtain the target product with a yield of 55% and an HPLC purity of 98.5%.

[0077] 1 H NMR (600MHz, CDCl3) δ8.01(d,J=8.0Hz,1H),7.66(t,J=7.8Hz,1H),7.42(t,J=7.7Hz,1H),7.38(d,J=8.5Hz ,1H),7.35-7.27(m,5H),6.95(t,J=53.8Hz,1H),4.48(dd,J=9.5,6.9Hz,2H),3.05(dd,J=9.6,6.9Hz,2H).

[0078] 13 C NMR (151MHz, CDCl3) δ = 152.8, 148.6 (t, J C-F =22.6Hz),137.3,133.2,132.6,132.1,131.8,128.8,128.7,127.1,124.2,113.7,110.1(t,J C-F =241.6Hz), 43.7, 33.3.

[0079] 19 F NMR (565MHz, CDCl3) δ = -124.2.

[0080] Example 11 3-(difluoromethyl)-1-(naphth-2-ylmethyl)quinoxaline-2(1H)-one

[0081]

[0082] Compound (Ⅰ-k)1-(naphth-2-ylmethyl)quinoxalin-2(1H)-one (57.2 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Tetrahydrofuran (3.0 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35 ± 5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine. The resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 42% and an HPLC purity of 98.7%.

[0083] 1 H NMR (600MHz, CDCl3) δ8.02 (d, J = 8.0Hz, 1H), 7.86-7.78 (m, 2H), 7.77-7.73 (m, 1H), 7.66 (s, 1H), 7 .52(t,J=7.9Hz,1H),7.48-7.43(m,2H),7.43-7.34(m,3H),7.07(t,J=53.7Hz,1H),5.67(s,2H).

[0084] 13 C NMR (151MHz, CDCl3) δ = 153.4, 148.8 (t, J C-F =22.6Hz),133.4,133.3,132.9,132.6,132.2,132.0,131.6,129.1,127.7,126.6,126.3,125.8,124.6,124.4,119.8,114.8,110.1(t,J C-F =241.6Hz), 46.1.

[0085] 19 F NMR (565MHz, CDCl3) δ = -124.1.

[0086] Example 12 3-(difluoromethyl)-1-methylquinoxaline-2(1H)-one

[0087]

[0088] Compound (Ⅰ-a)N-methylquinoxalin-2(1H)-one (32.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (4.7 mg, 0.04 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under white / violet / green light and stirred at 35±5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. TLC analysis showed that no target product was produced.

[0089] Example 13 3-(difluoromethyl)-1-methylquinoxaline-2(1H)-one

[0090]

[0091] Compound (Ⅰ-a)N-methylquinoxalin-2(1H)-one (32.0 mg, 0.2 mmol), compound (Ⅱ) difluoromethyltriphenylphosphonium iodide (175.6 mg, 0.4 mmol), and TMEDA (23.5 mg, 0.2 mmol) were added to a reaction flask equipped with a magnetic stirrer. Dichloromethane (3.0 mL) was added to the mixture, and after purging with nitrogen three times, the reaction system was irradiated under blue light and stirred at 35±5 °C for 42 hours. After the reaction was completed, the reaction solution was washed with saturated brine, and the resulting mixture was extracted with ethyl acetate. The organic layers were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 8:1 to obtain the target product with a yield of 11% and an HPLC purity of 98.0%.

[0092] The contents described in this specification are merely an enumeration of the implementation forms of the inventive concept, and the scope of protection of this invention should not be regarded as limited to the specific forms described in the embodiments.

Claims

1. A method for photocatalytic preparation of difluoroquinoxalone derivatives from iodine-containing phosphonium salts, characterized in that, The reaction includes the following steps: adding a quinoxalone compound of formula (I), a difluoromethyltriphenylphosphonium iodide salt compound of formula (II), and a base to a reaction solvent, under nitrogen protection, stirring under blue light irradiation, and after the reaction is completed, the reaction solution is post-treated to obtain the difluoroquinoxalone derivative of the target compound of formula (III), and its reaction equation is as follows: ， Substituent R 1 Selected from H or methyl, substituent R 2 Selected from H, methyl or methoxy, substituent R 3 Selected from H, methyl, ester, alkynyl, phenyl, naphthyl or substituted phenyl, wherein the substituent of the substituted phenyl is methyl or halogen, and n is 0, 1 or 2; Alkali selected N,N,N',N' -Tetramethylethylenediamine or N,N,N,N',N' -Pentamethyldiethylenetriamine; The molar ratio of the quinoxalone compound shown in formula (I), the difluoromethyltriphenylphosphonium iodide salt compound shown in formula (II), and the base is 1:2:0.

2.

2. The method for preparing difluoroquinoxalone derivatives by photocatalysis using iodine-containing phosphonium salts as described in claim 1, characterized in that, The reaction solvent is selected from tetrahydrofuran or dichloromethane.

3. The method for preparing difluoroquinoxalone derivatives by photocatalysis of iodine-containing phosphonium salts as described in claim 1, characterized in that, The post-treatment process of the reaction solution is as follows: saturated brine is added to the reaction solution for washing, followed by extraction with ethyl acetate. The combined organic layers are dried with anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product. The crude product is then separated and purified by chromatographic column chromatography to obtain the target compound.

4. A process for the photocatalytic preparation of difluoroquinoxalineone derivatives from iodonium salts containing iodine according to claim 3, characterized in that, The eluent for column separation and purification is a mixture of petroleum ether and ethyl acetate in a volume ratio of 3 to 8:

1.

5. The method for preparing difluoroquinoxalone derivatives by photocatalysis of iodine-containing phosphonium salts as described in claim 4, characterized in that, The reaction solvent is dichloromethane, and the base is... N,N,N',N' -Tetramethylethylenediamine, the molar ratio of the quinoxalone compound shown in formula (I), the difluoromethyltriphenylphosphonium iodide salt compound shown in formula (II), and the base is 1:2:0.2.

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