Synthesis method and application of C-3 hydroxyl fluoroalkyl substituted quinoxalinone derivative

Abstract

The invention belongs to the technical field of organic synthetic chemistry, and discloses a synthesis method of a C-3 hydroxyl fluoroalkyl substituted quinoxalinone derivative, which comprises the following steps: under photocatalysis, taking an N-trifluoroethoxy phthalimide reagent as a hydroxyl fluoroalkylating reagent, and reacting at the room temperature to obtain the quinoxalinone derivative with C-3 hydroxyl fluoroalkyl substituted quinoxalinone derivative. The reagent reacts with quinoxaline-2 (1H)-ketone to obtain the quinoxaline-2 (1H)-ketone C-3 hydroxyl fluoroalkylation derivative. According to the method, high temperature and an oxidizing agent are not needed, the condition is mild, and the tolerance to a reaction substrate is good. According to the method disclosed by the invention, a photosensitizer and a metal catalyst are not needed in the reaction process, the synthetic route is green and environment-friendly, and the quinoxaline-2 (1H)-ketone C-3 hydroxyl fluoroalkylated derivative can be rapidly and efficiently synthesized.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthetic chemistry, and in particular to a synthesis method and application of a C-3 hydroxyfluoroalkyl substituted quinoxalinone derivative. Background Art

[0002] Quinoxaline-2(1H)-ones are important nitrogen-containing heterocyclic structures that are widely present in biologically active natural products and drugs as well as in materials science. They have a wide range of biological activities, including antibacterial, anticancer, antithrombotic, protein kinase inhibitors, and benzodiazepine receptor agonists. In the past decade, significant progress has been made in the direct functionalization of quinoxaline-2(1H)-ones at the C-3 position, including arylation, alkylation, acylation, amination, sulfonation, and phosphorylation.

[0003] Compared with the parent core structure, the introduction of fluorine-containing groups has always been an important means of modifying biologically active structures. This is because fluorine atoms have the characteristics of high electronegativity, small atomic radius and good lipophilicity. After the introduction of fluorine atoms, organic small molecules often show unique physical, chemical and biological properties, such as lipophilicity, membrane permeability, metabolic stability and biological activity. Therefore, fluorine-containing functional molecules have been widely used in the fields of medicine, pesticides, life sciences and materials science, especially playing an important role in drug development. Among them, secondary trifluoromethylmethanol is a unique and interesting trifluoromethyl group with significant applications in medicine and biochemistry, and is a recurring feature in biologically active compounds. The introduction of hydroxyfluoroalkyl groups into the structure of quinoxaline-2(1H)-one can obtain a series of new quinoxaline derivatives, providing more possibilities for subsequent drug development. Hydroxyfluoroalkyl groups can be easily introduced into the molecular structure by free radical initiation. In 2016, Liu Zhongquan and his colleagues developed a free radical-initiated dehydrogenative cross-coupling reaction of fluorinated alcohols with indoles and pyrroles (Scheme a). In 2020, Shen Xiao's research group developed a method to directly transfer trifluoroethanol groups by activating free radicals with organosilicon reagents (Scheme b). In 2023, Sharma and his team used N-trifluoroethoxyphthalimide reagent to achieve the hydroxyfluoroalkylation reaction of isoquinoline (Scheme c). The specific reaction formula is as follows:

[0004]

[0005] Based on the above research background, the related methods in the prior art still have the following defects:

[0006] The introduction of hydroxyfluoroalkyl groups requires the use of transition metals, strong oxidants, or high temperatures, which limits the applicability of these development methods. Therefore, it is necessary to explore new methods for the synthesis of hydroxyfluoroalkyl-substituted quinoxalinones using inexpensive and stable trifluoroethoxy reagents. Summary of the invention

[0007] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a synthesis method and application of a quinoxalinone derivative substituted with a hydroxyfluoroalkyl group at the C-3 position.

[0008] The technical solution adopted by the present invention to solve its technical problem is:

[0009] A method for synthesizing a C-3 hydroxyfluoroalkyl substituted quinoxalinone derivative comprises the following steps: using N-trifluoroethoxyphthalimide as a hydroxyfluoroalkylating agent under photocatalysis, and reacting the agent with quinoxaline-2(1H)-one to obtain a C-3 hydroxyfluoroalkylated quinoxaline-2(1H)-one derivative.

[0010] Furthermore, the reaction formula of the method is as follows:

[0011]

[0012] Wherein, R1=F, Br, Cl, CH3, C4H4; R2=H, CH3, C2H5, C3H7, C3H5, CH2Ph, C3H3, C4H5, CH2COOC2H5, CH2COOC(CH3)3, C8H9, CH2COPh, C7H 13 .

[0013] Further, the reaction mechanism of the method is as follows:

[0014]

[0015] Furthermore, the N-trifluoroethoxyphthalimide reagent is 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione.

[0016] Further, the quinoxaline-2(1H)-one includes 1-methylquinoxaline-2(1H)-one, quinoxaline-2(1H)-one, 1-ethylquinoxaline-2(1H)-one, 1-propylquinoxaline-2(1H)-one, 1-(cyclohexylmethyl)quinoxaline-2(1H)-one, 1-allylquinoxaline-2(1H)-one, 1-(prop-2-ynyl)quinoxaline-2(1H)-one, 1-(but-2-ynyl)quinoxaline-2(1H)-one, ethyl (2-oxyylidenequinoxaline-1-yl)acetate, ethyl (2-oxyylidenequinoxaline-1-yl)acetate, and ethyl (2-oxyylidenequinoxaline-1-yl)acetate. 2-yl ester, 1-benzylquinoxaline-2(1H)-one, 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one, 1-(2-oxyylidene-2-phenylethyl)quinoxaline-2(1H)-one, 6-fluoro-1-methylquinoxaline-2(1H)-one, 6-bromo-1-methylquinoxaline-2(1H)-one, 6-chloro-1-methylquinoxaline-2(1H)-one, 1,5-dimethylquinoxaline-2(1H)-one, 1,6,7-trimethylquinoxaline-2(1H)-one, 1-methylbenzo[2,1-g]quinoxaline-2(1H)-one.

[0017] Furthermore, the structural formula of the quinoxaline-2(1H)-one derivative is as follows:

[0018]

[0019]

[0020] Furthermore, the method comprises the following steps:

[0021] Quinoxaline-2(1H)-one, N-alkoxyphthalimide reagent and trifluoroacetic acid are added under anhydrous and oxygen-free conditions, irradiated under a blue light with a power of 33W and a wavelength of 440-450nm, and the temperature is controlled at 40-50 degrees Celsius to react for 12-24 hours. After the reaction is completed, the mixture is extracted, washed, dried, separated and purified by column chromatography to finally obtain a quinoxaline derivative substituted with a hydroxyfluoroalkyl group at the C-3 position.

[0022] Furthermore, the specific steps are as follows:

[0023] First, the Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. The inert gas and the air in the reaction tube were replaced by a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an inert gas atmosphere, quinoxaline-2(1H)-one and its derivatives, N-alkoxyphthalimide reagent and trifluoroacetic acid were added to the reaction tube in sequence. The molar ratio of quinoxaline-2(1H)-one derivative: N-alkoxyphthalimide reagent: trifluoroacetic acid was 0.30:0.60:0.60. Anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of the inert gas in the double-row tube. The ratio of anhydrous N,N-dimethylacetamide: trifluoroacetic acid was 1.5:0.6 in mL:mmol. It was added to the reaction tube and the reactants were dissolved under stirring. The reaction was carried out under LED light for 12 to 24 hours; after TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product;

[0024] The mobile phase system is petroleum ether:ethyl acetate, and the volume ratio of the two is 10:1 to 3:1.

[0025] Further, the solvent is N,N-dimethylformamide or N,N-dimethylacetamide;

[0026] The inert gas is nitrogen or argon.

[0027] The synthetic method as described above is applied in the synthesis of fluoroalkylated derivatives of the C-3 hydroxyl group of quinoxaline-2(1H)-one.

[0028] The advantages and positive effects achieved by the present invention are:

[0029] 1. The present invention utilizes N-trifluoroethoxyphthalimide reagent as the source of hydroxyl and fluoroalkyl groups, avoiding the use of strong oxidants and high temperatures, and increasing substrate compatibility.

[0030] 2. The present invention avoids the use of transition metal catalysts and photosensitizers, reduces reaction costs, and the synthesis route is green and environmentally friendly.

[0031] 3. The raw materials used in the present invention are cheap and easily available, the solvent used is a common organic solvent and does not require special treatment, and the post-treatment is simple. The product can be separated by simple column chromatography, and the C-3 hydroxyl fluoroalkylated quinoxaline-2(1H)-one derivative can be synthesized quickly and efficiently, which is suitable for the preparation and synthesis of fine chemicals or drug molecule precursors.

[0032] 4. The quinoxalinone derivatives prepared by the present invention are all new compounds, which provide a new scheme for preparing drug molecular structures with biological activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is the H spectrum of the compound of Example 1 of the present invention;

[0034] Figure 2 is the H spectrum of the compound of Example 2 of the present invention;

[0035] Figure 3 is the H spectrum of the compound of Example 3 of the present invention;

[0036] Figure 4 is the H spectrum of the compound of Example 4 of the present invention;

[0037] Figure 5 is the H spectrum of the compound of Example 5 of the present invention;

[0038] Figure 6 is the H spectrum of the compound of Example 6 of the present invention;

[0039] Figure 7 is the H spectrum of the compound of Example 7 of the present invention;

[0040] Figure 8 is the H spectrum of the compound of Example 8 of the present invention;

[0041] Fig. 9 is the H spectrum of the compound of Example 9 of the present invention;

[0042] Fig.10 is the H spectrum of the compound of Example 10 of the present invention;

[0043] Fig.11 is the H spectrum of the compound of Example 11 of the present invention;

[0044] Fig.12 is the H spectrum of the compound of Example 12 of the present invention;

[0045] Fig.13 is the H spectrum of the compound of Example 13 of the present invention;

[0046] Fig.14 is the H spectrum of the compound of Example 14 of the present invention;

[0047] Fig.15 is the H spectrum of the compound of Example 15 of the present invention;

[0048] Fig.16 is the H spectrum of the compound of Example 16 of the present invention;

[0049] Fig.17 is the H spectrum of the compound of Example 17 of the present invention;

[0050] Fig.18 is the H spectrum of the compound of Example 18 of the present invention;

[0051] Fig.19 This is the H spectrum of the compound of Example 19 of the present invention. DETAILED DESCRIPTION

[0052] The present invention will be further described below in conjunction with the embodiments. The following embodiments are descriptive rather than restrictive, and the protection scope of the present invention cannot be limited by the following embodiments.

[0053] The various experimental operations involved in the specific embodiments are all routine techniques in the art. For parts not specially annotated in this document, ordinary technicians in the art can implement them by referring to various commonly used reference books, scientific and technological literature or related instructions, manuals, etc. before the filing date of this invention.

[0054] A method for synthesizing a C-3 hydroxyfluoroalkyl substituted quinoxalinone derivative comprises the following steps: using N-trifluoroethoxyphthalimide as a hydroxyfluoroalkylating agent under photocatalysis, and reacting the agent with quinoxaline-2(1H)-one to obtain a C-3 hydroxyfluoroalkylated quinoxaline-2(1H)-one derivative.

[0055] Preferably, the reaction formula of the method is as follows:

[0056]

[0057] Wherein, R1=F, Br, Cl, CH3, C4H4; R2=H, CH3, C2H5, C3H7, C3H5, CH2Ph, C3H3, C4H5, CH2COOC2H5, CH2COOC(CH3)3, C8H9, CH2COPh, C7H 13 .

[0058] Preferably, the reaction mechanism of the method is as follows:

[0059]

[0060] Preferably, the N-trifluoroethoxyphthalimide reagent is 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione.

[0061] Preferably, the quinoxaline-2(1H)-one includes 1-methylquinoxaline-2(1H)-one, quinoxaline-2(1H)-one, 1-ethylquinoxaline-2(1H)-one, 1-propylquinoxaline-2(1H)-one, 1-(cyclohexylmethyl)quinoxaline-2(1H)-one, 1-allylquinoxaline-2(1H)-one, 1-(prop-2-ynyl)quinoxaline-2(1H)-one, 1-(but-2-ynyl)quinoxaline-2(1H)-one, ethyl (2-oxyylidenequinoxaline-1-yl)acetate, ethyl (2-oxyylidenequinoxaline-1-yl)acetate, -yl esters, 1-benzylquinoxaline-2(1H)-one, 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one, 1-(2-oxyylidene-2-phenylethyl)quinoxaline-2(1H)-one, 6-fluoro-1-methylquinoxaline-2(1H)-one, 6-bromo-1-methylquinoxaline-2(1H)-one, 6-chloro-1-methylquinoxaline-2(1H)-one, 1,5-dimethylquinoxaline-2(1H)-one, 1,6,7-trimethylquinoxaline-2(1H)-one, 1-methylbenzo[2,1-g]quinoxaline-2(1H)-one.

[0062] Preferably, the structural formula of the quinoxaline-2(1H)-one derivative is as follows:

[0063]

[0064]

[0065] Preferably, the method comprises the following steps:

[0066] Quinoxaline-2(1H)-one, N-alkoxyphthalimide reagent and trifluoroacetic acid are added under anhydrous and oxygen-free conditions, irradiated under a blue light with a power of 33W and a wavelength of 440-450nm, and the temperature is controlled at 40-50 degrees Celsius to react for 12-24 hours. After the reaction is completed, the mixture is extracted, washed, dried, separated and purified by column chromatography to finally obtain a quinoxaline derivative substituted with a hydroxyfluoroalkyl group at the C-3 position.

[0067] Preferably, the specific steps are as follows:

[0068] First, the Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. The inert gas and the air in the reaction tube were replaced by a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an inert gas atmosphere, quinoxaline-2(1H)-one and its derivatives, N-alkoxyphthalimide reagent and trifluoroacetic acid were added to the reaction tube in sequence. The molar ratio of quinoxaline-2(1H)-one derivative: N-alkoxyphthalimide reagent: trifluoroacetic acid was 0.30:0.60:0.60. Anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of the inert gas in the double-row tube. The ratio of anhydrous N,N-dimethylacetamide: trifluoroacetic acid was 1.5:0.6 in mL:mmol. It was added to the reaction tube and the reactants were dissolved under stirring. The reaction was carried out under LED light for 12 to 24 hours; after TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product;

[0069] The mobile phase system is petroleum ether:ethyl acetate, and the volume ratio of the two is 10:1 to 3:1.

[0070] Preferably, the solvent is N,N-dimethylformamide or N,N-dimethylacetamide;

[0071] The inert gas is nitrogen or argon.

[0072] The synthetic method as described above is applied in the synthesis of fluoroalkylated derivatives of the C-3 hydroxyl group of quinoxaline-2(1H)-one.

[0073] Specifically, the relevant preparation and detection are as follows:

[0074] Example 1

[0075]

[0076] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-methylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 4:1 by volume. White solid, yield 75%. 1 H NMR (400MHz, CDCl3) δ7.94(d,J=1.5Hz,1H),7.68(d,J=1.5Hz,1H),7.48-7.37(m,2H),5.57-5.44(m,1H),4.92(d,J=10.1Hz,1H),3.76(s,3H); 13 CNMR(100MHz, CDCl3)δ154.03,150.83,133.57,132.16,131.76,130.55,128.63-120.53(m),124.47,114.08,69.86(q,J=32.4Hz),29.31; 19 F NMR (376MHz, CDCl3) δ-76.27. Figure 1 shown.

[0077] Example 2

[0078]

[0079] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 1:1 by volume. White solid, yield 78%. 1 H NMR (400MHz, DMSO) δ12.71 (s, 1H), 7.84 (d, J = 8.3Hz, 1H), 7.60 (t, J = 7.7Hz, 1H), 7.44-7.26 (m, 2H), 6.87 (d, J = 7.5Hz, 1H), 5.64 (t, J = 7.0Hz, 1H); 13 CNMR(100MHz,DMSO)δ154.39(d,J=8.9Hz),132.63,131.97,131.58,129.51,125.00(d,J=283.9Hz),124.23,116.14,66.88-65.13(m); 19 FNMR (376MHz, DMSO) δ-74.18. Figure 2 shown.

[0080] Example 3

[0081]

[0082] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-ethylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 5:1 by volume. White solid, yield 89%. 1 H NMR (400MHz, CDCl3) δ7.95 (dd, J=8.3, 1.5Hz, 1H), 7.72-7.64 (m, 1H), 7.46-7.40 (m, 2H),5.55-5.44(m,1H),4.98(d,J=10.0Hz,1H),4.37(t,2H),1.41(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ153.69, 150.88, 132.65, 130.93, 124.38, 123.93 (q, J = 285.83Hz), 70.04 (q, J = 32.3Hz), 37.80, 12.54; 19 F NMR (376MHz, CDCl3) δ-76.34. Figure 3 shown.

[0083] Example 4

[0084]

[0085] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-propylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 6:1 by volume) to obtain the product. White solid, yield 47%. 1 H NMR (400MHz, CDCl3) δ7.94 (dd, J=7.9, 1.5Hz, 1H), 7.74-7.60 (m, 1H), 7.50-7.34 (m, 2H), 5.57-5 .44(m,1H),4.99(d,J=10.0Hz,1H),4.31-4.17(m,2H),1.95-1.74(m,2H),1.06(t,J=7.4Hz,3H); 13 C NMR(100MHz,CDCl3)δ153.85,150.73,132.77,132.02(d,J=3.1Hz),130.76, 124.23, 123.82 (q, J = 286.84Hz), 114.09, 69.95 (q, J = 32.2Hz), 20.69, 11.29; 19 FNMR (376MHz, CDCl3) δ-76.35. Figure 4 shown.

[0086] Example 5

[0087]

[0088] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-cyclohexylmethylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 10: 1 by volume) to obtain the product as a white solid with a yield of 57%. 1 H NMR (400MHz, CDCl3) δ7.93 (dd, J=8.0, 1.5Hz, 1H), 7.69-7.61 (m, 1H), 7.47-7.31 (m, 2H), 5.56-5.43 (m, 1H),4.99(d,J=10.1Hz,1H),4.18(dd,J=7.5,3.6Hz,2H),1.89(s,1H),1.78-1.60(m,3H),1.18(s,2H); 13 C NMR (100MHz, CDCl3) δ154.30,150.72,133.13,132.02,131.87,130.73,124.19,123.84( q,J=284.8Hz),114.53,69.97(q,J=32.3Hz),48.21,36.60,30.81,30.74,26.06,25.71; 19 F NMR (376MHz, CDCl3) δ-76.21. Figure 5 shown.

[0089] Example 6

[0090]

[0091] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-allylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: dichloromethane: ethyl acetate, the ratio was 3:1:0.1 by volume) to obtain a white solid with a yield of 57%. 1 H NMR (400MHz, CDCl3) δ7.94 (dd, J=8.1, 1.6Hz, 1H), 7.73-7.59 (m, 1H), 7.53-7.31 (m, 1H), 6.03-5. 83(m,1H),5.58-5.45(m,1H),5.31(d,J=10.5Hz,1H),5.18(d,J=17.2Hz,1H),5.01-4.85(m,1H); 13 C NMR(100MHz, CDCl3)δ153.61,150.87(d,J=1.6Hz),132.81,132.05,131.93,130.28 (d,J=66.7Hz),124.43,123.78(d,J=284.8Hz),114.62,69.79(q,J=32.2Hz),44.69; 19 F NMR (376MHz, CDCl3) δ-76.34. Figure 6 shown.

[0092] Example 7

[0093]

[0094] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-(prop-2-ynyl)quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: dichloromethane: ethyl acetate, the ratio was 3:1:0.1 by volume) to obtain a white solid with a yield of 34%. 1 H NMR (400MHz, CDCl3) δ7.96(d,J=7.9Hz,1H),7.72(t,J=7.9Hz,1H),7.56(d,J=7.8Hz,1H),7.47(t,J=7.7 Hz,1H),5.59-5.44(m,1H),5.09(qd,J=17.5,2.6Hz,2H),4.75(d,J=10.1Hz,1H),2.33(t,J=2.6Hz,1H); 13 C NMR (100MHz, CDCl3) δ152.96,150.94,132.26,132.09,131.92,130.67,124.8 1,128.68(q,J=284.82Hz),114.62,76.02,73.94,69.54(q,J=32.3Hz),31.72; 19 F NMR (376MHz, CDCl3) δ-76.30. Figure 7 shown.

[0095] Example 8

[0096]

[0097] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-(but-2-ynyl)quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: dichloromethane: ethyl acetate, the ratio was 2:1:0.1 by volume) to obtain a white solid with a yield of 75%. 1 H NMR (400MHz, CDCl3) δ7.94 (dd, J=8.1, 1.5Hz, 1H), 7.74-7.67 (m, 1H), 7.58 (d, J=8.5Hz, 1H), 7.45 (t ,J=7.7Hz,1H),5.58-5.43(m,1H),5.09-4.96(m,2H),4.83(d,J=10.1Hz,1H),1.78(t,J=2.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ153.08,150.88,132.30,132.14,131.95,130.51,124.59, 123.73(d,J=284.9Hz),114.90,81.91,71.42,69.70(q,J=32.5Hz),32.32,3.58; 19 F NMR (376MHz, CDCl3) δ-76.29. Figure 8 shown.

[0098] Example 9

[0099]

[0100] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, (2-oxyylidenequinoxaline-1-yl)ethyl acetate (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: dichloromethane: ethyl acetate, the ratio was 3:1:0.1 by volume) to obtain a white solid with a yield of 84%. 1 H NMR(400MHz, CDCl3) δ7.97(dd,J=8.0,1.6Hz,1H),7.68-7.61(m,1H),7.48-7.41(m,1H),7.17(d,J=8.5Hz,1 H),5.58-5.48(m,1H),5.14-4.98(m,2H),4.75(d,J=10.0Hz,1H),4.30-4.21(m,2H),1.29(d,J=7.1Hz,3H); 13 CNMR(100MHz,CDCl3)δ166.46,153.55,150.90,132.79,132.31,131.78,130.85,12 4.71,123.68(d,J=284.6Hz),113.53,72.56-66.17(m),62.39,43.60,29.71,14.07; 19 FNMR (376MHz, CDCl3) δ-76.33. Fig. 9 shown.

[0101] Example 10

[0102]

[0103] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, (2-oxyylidenequinoxaline-1-yl)acetic acid propan-2-yl ester (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 2: 1 by volume) to obtain the product. White solid, yield 49%. 1 H NMR (400MHz, CDCl3) δ7.96 (dd, J=8.1, 1.5Hz, 1H), 7.68-7.62 (m, 1H), 7.46-7.41 (m, 1H), 7.17 (d,J=8.0Hz,1H),5.57-5.48(m,1H),5.03-4.90(m,2H),4.77(d,J=10.0Hz,1H),1.45(s,9H); 13 C NMR (100MHz, CDCl3) δ165.45,153.55,150.88,132.86,132.21,131.74,130.79,12 4.61,123.22(q,J=285.83Hz),113.55,83.68,69.47(q,J=32.4Hz),44.32,27.92; 19 FNMR (376MHz, CDCl3) δ-76.35. Fig.10 shown.

[0104] Embodiment 11

[0105]

[0106] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-benzylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: dichloromethane: ethyl acetate, the ratio was 4:1:0.1 by volume), and the product was obtained as a white solid with a yield of 91%. 1 H NMR (400MHz, CDCl3) δ7.94 (dd, J=8.1, 1.5Hz, 1H), 7.58-7.52 (m, 1H), 7.43-7.28 (m, 5H),7.24(d,J=7.3Hz,2H),5.62-5.55(m,1H),5.54(s,2H),4.91(d,J=10.1Hz,1H); 13 C NMR (100MHz, CDCl3) δ154.29,151.13,134.63,133.03,132.23,132.15,130.72,129.25 ,128.17,127.01,124.61,123.94(d,J=284.6Hz),114.98,69.95(q,J=32.3Hz),46.21; 19 FNMR (376MHz, CDCl3) δ-76.28. Fig.11 shown.

[0107] Example 12

[0108]

[0109] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 24 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 10:1 by volume) to obtain the product as a white solid with a yield of 75%. 1 H NMR (400MHz, CDCl3) δ7.93 (dd, J=8.4, 1.6Hz, 1H), 7.58-7.52 (m, 1H), 7.41-7.35 (m, 2 H),7.13(s,4H),5.61-5.53(m,1H),5.49(s,2H),4.93(d,J=10.1Hz,1H),2.31(s,3H); 13 C NMR (100MHz, CDCl3) δ154.18,150.97,137.87,132.93,132.06,132.04,131.51,130.62, 129.77,126.93,124.42,128.56-119.17(m),114.88,69.98(q,J=32.5Hz),45.88,21.10; 19 FNMR (376MHz, CDCl3) δ-76.29. Fig.12 shown.

[0110] Embodiment 13

[0111]

[0112] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-(2-oxyylidene-2-phenylethyl)quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 10: 1 by volume) to obtain the product. White solid, yield 49%. 1 H NMR (400MHz, CDCl3) δ8.07(d,J=7.7Hz,2H),7.97(d,J=8.0Hz,1H),7.69(t,J=7.5Hz,1H),7.56(t,J=7.7Hz,3H ),7.41(t,J=7.6Hz,1H),7.04(d,J=8.4Hz,1H),5.86-5.69(m,2H),5.57-5.48(m,1H),4.80(d,J=10.0Hz,1H); 13 CNMR(100MHz,CDCl3)δ190.39,153.77,150.67,134.63,134.25,133.09,132.20,131.89,13 0.77,129.18,128.21,124.57,123.75(d,J=284.7Hz),113.98,69.50(d,J=32.4Hz),48.53; 19 F NMR (376MHz, CDCl3) δ-76.29. Fig.13 shown.

[0113] Embodiment 14

[0114]

[0115] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 6-fluoro-1-methylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 5:1 by volume) to obtain the product. White solid, yield 61%. 1 H NMR (400MHz, CDCl3) δ7.64 (dd, J=8.4, 2.8Hz, 1H), 7.48-7.41 (m, 1H), 7.38 (d d,J=9.2,4.8Hz,1H),5.54-5.44(m,1H),4.86(d,J=10.2Hz,1H),3.75(s,3H); 13 C NMR (100MHz, CDCl3) δ158.96(d,J=245.9Hz),153.68,152.51,132.27(d,J=11.3Hz),130.28,123.68(d,J= 284.8Hz), 120.16 (d, J = 24.2Hz), 115.89 (d, J = 22.8Hz), 115.38 (d, J = 8.7Hz), 70.00 (q, J = 32.4Hz), 29.60; 19 F NMR (376MHz, CDCl3)δ-76.22,-117.17. Fig.14 shown.

[0116] Embodiment 15

[0117]

[0118] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 6-bromo-1-methylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 3:1 by volume) to obtain the product. White solid, yield 46%. 1 H NMR (400MHz, CDCl3) δ8.09(d,J=2.3Hz,1H),7.76(dd,J=9.0,2.3Hz,1H),7.28(d,J=8.9Hz,1H),5.53-5.45(m,1H),4.78(d,J=10.2Hz,1H),3.73(s,3H); 13 C NMR (100MHz, CDCl3) δ153.77, 152.47, 135.04, 132.98, 132.80, 132.57, 123.76 (d, J = 284.8Hz), 117.25, 115.66, 69.93 (q, J = 32.4Hz), 29.62; 19 F NMR (376MHz, CDCl3) δ-76.20. Fig.15 shown.

[0119] Example 16

[0120]

[0121] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 6-chloro-1-methylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 3:1 by volume), and the product was obtained as a white solid with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 2.4Hz, 1H), 7.63 (dd, J = 9.0, 2.4Hz, 1H), 7.34 (d, J = 9.0Hz, 1H), 5.55-5.45 (m, 1H), 4.79 (d, J = 10.2Hz, 1H), 3.74 (s, 3H); 13 C NMR (100MHz, CDCl3) δ153.79, 152.54, 132.37, 132.33, 132.29, 130.09, 129.92, 123.76 (d, J = 284.4Hz), 115.40, 69.98 (d, J = 32.4Hz), 29.64; 19 F NMR (376MHz, CDCl3) δ-76.22. Fig.16 shown.

[0122] Embodiment 17

[0123]

[0124] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1,5-dimethylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 5:1 by volume), and the product was obtained as a white solid with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ7.58-7.52(m,1H),7.28(d,J=7.5Hz,1H),7.23(d,J=8. 5Hz,1H),5.55-5.45(m,1H),4.95(d,J=9.9Hz,1H),3.74(s,3H),2.70(s,3H); 13 C NMR (100MHz, CDCl3) δ154.06,148.97,139.55,133.89,132.09,130.51,125.84,123.93(q,J=284.8Hz),112.08,69.99(q,J=32.2Hz),29.55,17.58; 19 F NMR (376MHz, CDCl3) δ-76.41. Fig.17 shown.

[0125] Embodiment 18

[0126]

[0127] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1,6,7-trimethylquinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 5:1 by volume) to obtain the product as a white solid with a yield of 55%. 1 H NMR (400MHz, CDCl3) δ7.58-7.52(m,1H),7.28(d,J=7.5Hz,1H),7.23(d,J=8. 5Hz,1H),5.55-5.45(m,1H),4.95(d,J=9.9Hz,1H),3.74(s,3H),2.70(s,3H); 13 C NMR (100MHz, CDCl3) δ154.26, 149.25 (d, J = 1.7Hz), 142.66, 133.81, 131.72, 130.5 1,130.41,128.60-121.58(m),114.62,70.08(q,J=32.2Hz),29.30,20.93,19.31; 19 F NMR (376MHz, CDCl3) δ-76.47. Fig.18 shown.

[0128] Embodiment 19

[0129]

[0130] First, a 10 mL Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. Argon gas and air in the reaction tube were replaced by double-row tubes to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an argon atmosphere, 1-methyl-benzo[2,1-g]quinoxaline-2(1H)-one (0.30 mmol), 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione (0.60 mmol), and trifluoroacetic acid (0.60 mmol) were added to the reaction tube in sequence. 1.50 mL of anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of double-row argon gas and added to the reaction tube. The reactants were dissolved under stirring and reacted under blue 33 W LED light for 12 hours. After TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted with ethyl acetate three times, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (the mobile phase system was petroleum ether: ethyl acetate, the ratio was 3:1 by volume), yellow solid, yield 41%. 1 H NMR (400MHz, CDCl3) δ7.58-7.52(m,1H),7.28(d,J=7.5Hz,1H),7.23(d,J=8. 5Hz,1H),5.55-5.45(m,1H),4.95(d,J=9.9Hz,1H),3.74(s,3H),2.70(s,3H); 13 C NMR (100MHz, CDCl3) δ153.93, 151.67, 134.65, 131.17 (d, J = 53.4Hz), 130.45, 129.98,129.08,128.90,127.49,126.13,110.80,69.87(d,J=32.0Hz),29.39; 19 F NMR (376MHz, CDCl3) δ-76.16. Fig.19 shown.

[0131] Although the embodiments of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments.

Claims

1. A method for synthesizing a C-3 hydroxyfluoroalkyl substituted quinoxalinone derivative, characterized in that: The method comprises the following steps: using N-trifluoroethoxyphthalimide reagent as a hydroxyl fluoroalkylation reagent under photocatalysis, and reacting the reagent with quinoxaline-2(1H)-one to obtain a quinoxaline-2(1H)-one C-3 hydroxyl fluoroalkylation derivative.

2. The synthesis method according to claim 1, characterized in that: The reaction formula of the method is as follows: Wherein, R1=F, Br, Cl, CH3, C4H4; R2=H, CH3, C2H5, C3H7, C3H5, CH2Ph, C3H3, C4H5, CH2COOC2H5, CH2COOC(CH3)3, C8H9, CH2COPh, C7H 13 .

3. The synthesis method according to claim 1, characterized in that: The reaction mechanism of the method is as follows:

4. The synthesis method according to claim 1, characterized in that: The N-trifluoroethoxyphthalimide reagent is 2-(2,2,2-trifluoroethoxy)isoindoline-1,3-dione.

5. The synthesis method according to claim 1, characterized in that: The quinoxaline-2(1H)-one includes 1-methylquinoxaline-2(1H)-one, quinoxaline-2(1H)-one, 1-ethylquinoxaline-2(1H)-one, 1-propylquinoxaline-2(1H)-one, 1-(cyclohexylmethyl)quinoxaline-2(1H)-one, 1-allylquinoxaline-2(1H)-one, 1-(prop-2-ynyl)quinoxaline-2(1H)-one, 1-(but-2-ynyl)quinoxaline-2(1H)-one, ethyl (2-oxyylidenequinoxaline-1-yl)acetate, and prop-2-yl (2-oxyylidenequinoxaline-1-yl)acetate. Esters, 1-benzylquinoxaline-2(1H)-one, 1-[(4-methylphenyl)methyl]quinoxaline-2(1H)-one, 1-(2-oxyylidene-2-phenylethyl)quinoxaline-2(1H)-one, 6-fluoro-1-methylquinoxaline-2(1H)-one, 6-bromo-1-methylquinoxaline-2(1H)-one, 6-chloro-1-methylquinoxaline-2(1H)-one, 1,5-dimethylquinoxaline-2(1H)-one, 1,6,7-trimethylquinoxaline-2(1H)-one, 1-methylbenzo[2,1-g]quinoxaline-2(1H)-one.

6. The synthesis method according to claim 1, characterized in that: The structural formula of the quinoxaline-2(1H)-one derivative is as follows:

7. The synthesis method according to any one of claims 1 to 6, characterized in that: The method comprises the following steps: Quinoxaline-2(1H)-one, N-alkoxyphthalimide reagent and trifluoroacetic acid are added under anhydrous and oxygen-free conditions, irradiated under a blue light with a power of 33W and a wavelength of 440-450nm, and the temperature is controlled at 40-50 degrees Celsius to react for 12-24 hours. After the reaction is completed, the mixture is extracted, washed, dried, separated and purified by column chromatography to finally obtain a quinoxaline derivative substituted with a hydroxyfluoroalkyl group at the C-3 position.

8. The synthesis method according to claim 7, characterized in that: The specific steps are as follows: First, the Schlenk tube was treated to be anhydrous and oxygen-free. The residual water on the reaction tube wall, the tube mouth and the inside of the tube was removed by high temperature with a drying gun. The inert gas and the air in the reaction tube were replaced by a double-row tube to create an anhydrous and oxygen-free environment. After the Schlenk tube was cooled in an inert gas atmosphere, quinoxaline-2(1H)-one and its derivatives, N-alkoxyphthalimide reagent and trifluoroacetic acid were added to the reaction tube in sequence. The molar ratio of quinoxaline-2(1H)-one derivative: N-alkoxyphthalimide reagent: trifluoroacetic acid was 0.30:0.60:0.

60. Anhydrous N,N-dimethylacetamide was taken with a long needle syringe under the protection of the inert gas in the double-row tube. The ratio of anhydrous N,N-dimethylacetamide: trifluoroacetic acid was 1.5:0.6 in mL:mmol. It was added to the reaction tube and the reactants were dissolved under stirring. The reaction was carried out under LED light for 12 to 24 hours; after TLC confirmed that the reaction was complete, a large amount of water was added for washing, extracted three times with ethyl acetate, washed with saturated sodium chloride solution, the organic phase was dried with anhydrous sodium sulfate, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the product; The mobile phase system is petroleum ether:ethyl acetate, and the volume ratio of the two is 10:1 to 3:

1.

9. The synthesis method according to claim 8, characterized in that: The solvent is N,N-dimethylformamide or N,N-dimethylacetamide; The inert gas is nitrogen or argon.

10. Use of the synthesis method according to any one of claims 1 to 8 in the synthesis of fluoroalkylated derivatives of the C-3 hydroxyl group of quinoxaline-2(1H)-one.

Images