C3-site difluoroalkyl quinoxalinone derivative as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic matter synthesis, and particularly relates to a C3-site difluoroalkyl quinoxalinone derivative as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving a quinoxalinone compound, a difluoroalkyl bromide compound, an olefin compound and a hydrotropy additive in an organic solvent in an inert atmosphere, and reacting under the irradiation of a purple light source to obtain the quinoxalinone compound. In the preparation process of the C3-position difluoroalkyl quinoxalinone derivative, transition metal and a photosensitizer do not need to be added.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a C3-position difluoroalkyl quinoxalone derivative and its preparation method and application. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Difluoroalkyl compounds have important applications in agrochemicals, pharmaceuticals, and materials preparation due to their unique chemical and biological properties. Quinoxaline-2(1H)-ones are an important class of heterocyclic units with significant pharmacological activities, including aldose reductase inhibition, antitumor activity, antibacterial activity, and antihistamine activity. Currently, compounds that simultaneously possess the activities of difluoroalkyl compounds and quinoxaline-2(1H)-ones, namely difluoroalkylquinoxaline ones or their derivatives, generally exhibit good biological activity and pharmaceutical properties. For example, 3-substituted quinoxaline-2(1H)-ones have shown significant biological activities, including antifungal, antitumor, and anti-inflammatory effects.

[0004] Currently, methods for synthesizing such compounds include: (1) direct dual catalysis of C3-H by transition metal catalysis or photocatalysis; and (2) photocatalysis of three components of olefins with bifunctional groups. Both of these methods require the use of photosensitizers, and the first method requires the use of transition metals, which is costly and not conducive to large-scale industrial production, and also pollutes the environment. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, the present invention provides a C3-position difluoroalkyl quinoxalone derivative, its preparation method and application, which does not require the addition of transition metals or photosensitizers during the preparation process.

[0006] In a first aspect, the present invention provides a C3-position difluoroalkyl quinoxalone derivative, the structure of which is shown in formula (I): (I) Among them, R 1 It is an aryl, halogen, cyano, alkoxy, or ester group; R 2 It can be a hydrogen atom, a carbon atom, an alkyl group, an alkylbenzene group, an ester group, an alkynyl group, or a nitrile group; R 3 It can be methyl, methoxy, or fluorine; EWG can be ester or amide groups.

[0007] In a second aspect, the present invention provides a method for preparing the C3-position difluoroalkyl quinoxalone derivative described in the first aspect, comprising the following steps: In an inert atmosphere, the quinoxalone compound shown in formula (II), the difluoroalkyl bromide compound shown in formula (III), the olefin compound shown in formula (IV), and the solubilizing additive are dissolved in an organic solvent and reacted under a purple light source to obtain the product. Among them, R 1 R 2 R 3 The meaning is the same as the first aspect.

[0008] It can be seen that the preparation method provided by the present invention does not require the use of transition metal catalysts, photosensitizers, etc. The preparation method is simple, the raw materials are readily available and the cost is low, making it suitable for large-scale industrial production. Furthermore, since no transition metal catalysts or photosensitizers are added, it is beneficial to environmental protection.

[0009] Furthermore, quinoxalone compounds include 1-methylquinoxalin-2(1H)-one, 1,6-dimethylquinoxalin-2(1H)-one, 1,7-dimethylquinoxalin-2(1H)-one, 6-methoxy-1-methylquinoxalin-2(1H)-one, 6-fluoro-1-methylquinoxalin-2(1H)-one, 6-chloro-1-methylquinoxalin-2(1H)-one, 6-bromo-1-methylquinoxalin-2(1H)-one, 6-cyano-1-methylquinoxalin-2(1H)-one, and 1,6,7-trimethylquinoxalin-2(1H)-one. One or more of the following: quinoxalin-2(1H)-one, 6,7-dichloro-1-methylquinoxalin-2(1H)-one, quinoxalin-2(1H)-one, 1-ethylquinoxalin-2(1H)-one, 1-tert-butylquinoxalin-2(1H)-one, 1-(2-propyn-1-yl)quinoxalin-2(1H)-one, 1-benzylquinoxalin-2(1H)-one, 1-phenylethyldibenzoquinoxalin-2(1H)-one, 2-(2-oxoquinoxalin-1(2H)-yl)acetonitrile, and 1-phenylquinoxalin-2(1H)-one.

[0010] Alternatively, the difluoroalkyl bromide compounds include one or more of ethyl difluorobromoacetate, 2-bromo-N-(cyclopropylmethyl)-2,2-difluoroacetamide, 4-bromodifluoromethylmorpholine, and 2-bromo-2,2-difluoro-1-morpholinylethane-1-one. In one embodiment verified by this invention, ethyl difluorobromoacetate (CAS Registry No. 565-53-7) is used.

[0011] Alternatively, the olefinic compounds include one or more of allylbenzene, 2-methylallylbenzene, 4-methoxyallylbenzene, 3,4-dimethoxyallylbenzene, 4-allyl-2-methoxyphenol, and 1-allyl-2,3,4,5,6-pentafluorobenzene.

[0012] Furthermore, the solubilizing additive is an organic solubilizing additive; preferably, the solubilizing additive includes one or more of hansyl ester, N,N,N',N'-tetramethylethylenediamine, N,N-diisopropylethylamine, and N,N,N',N',N''-pentamethyldiethylenetriamine.

[0013] Organic solvents include one or more of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, 1,2-dichloroethane, dichloromethane, or tetrahydrofuran.

[0014] It should be noted that the above-mentioned limitations on quinoxalone compounds, difluoroalkyl bromides, olefin compounds, solubilizers, and organic solvents are merely illustrative examples and not exhaustive. In fact, any of the above-mentioned components that can produce the final product, a C3-position difluoroalkyl quinoxalone derivative, are acceptable to this invention.

[0015] Furthermore, the molar ratio of quinoxaline, difluoroalkyl bromide, and solubilizing additive is 0.1-1.0: 0.15-3.0: 0.15-3.0.

[0016] It should be noted that if the molar ratios of the above substances are not within the above range, it may have an adverse effect on the reaction. For example, if the content of any one of quinoxalone, difluoroalkyl bromide, or solubilizer is below or exceeds the range, it may lead to side reactions, thereby reducing the product yield.

[0017] Alternatively, the molar volume ratio of quinoxaline to organic solvent is 0.1-1.0:1-10, with units of mmol and mL, respectively.

[0018] Furthermore, the purple LEDs are sourced from LEDs with a wavelength of 390-400 nm. Alternatively, the reaction time is 18-48 h, preferably 24 h; Alternatively, the method may further include: stopping irradiation when the reaction is detected as complete; preferably, the detection method is TLC detection.

[0019] It should be noted that the reaction time can be preset or the reaction termination method can be determined by periodically detecting whether the reaction is completed.

[0020] Furthermore, the inert gas is one or more of argon and nitrogen.

[0021] Furthermore, the method also includes: after the reaction is completed, the reaction mixture is concentrated under vacuum and separated by column chromatography; Preferably, before column chromatography separation, a cleaning process is included, wherein the cleaning agent is one or a mixture of petroleum ether and ethyl acetate; more preferably, the cleaning agent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 1-8:1.

[0022] In a third aspect, the present invention provides the use of the C3-position difluoroalkyl quinoxalone derivative described in the first aspect, or the product prepared by the method described in the second aspect.

[0023] The applications include, but are not limited to, the following aspects: 1) Applications in the preparation of agricultural chemicals; 2) Applications in pharmaceutical preparation; 3) Application as a fluorescent indicator for cobalt ions and / or copper ions.

[0024] Compared with the prior art, the beneficial effects of the present invention are: 1) The preparation method of the present invention uses cheap and readily available quinoxalone as raw material and clean light energy as reaction promoter to prepare the product under mild conditions. That is, the preparation method of the present invention does not require heating, does not require the use of any metal catalysts and dangerous peroxide oxidants, and does not require the use of photosensitizers, which greatly reduces energy consumption, avoids metal pollution, improves reaction safety, and is conducive to large-scale industrial production.

[0025] 2) The preparation method provided by the present invention also has the advantages of high atom economy, simple operation, high synthesis efficiency and regioselectivity, and good substrate applicability.

[0026] 3) The difluoroalkylquinoxaline compounds prepared by this invention can be used to prepare anticancer drugs, antibacterial drugs, hypoglycemic drugs and protein kinase inhibitors, etc.; the difluoroalkylquinoxaline derivatives can be used for ion detection and have important application value. Attached Figure Description

[0027] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0028] Figure 1 This is a diagram illustrating the equipment used in the preparation method of the C3-position difluoroalkyl quinoxalone derivative in the embodiments of this application. Figure 2 The proton spectrum of product 4a in Example 1; Figure 3 The carbon spectrum of product 4a in Example 1; Figure 4 The fluorine spectrum of product 4a in Example 1; Figure 5The fluorescence and ultraviolet spectra of products 4a, 4e, 4f, 4m, 5d, and 5c in Example 26 are shown. Figure 5 (a) is the ultraviolet spectrum. Figure 5 (b) is the fluorescence spectrum; Figure 6 The fluorescence spectrum of compound 4a in response to metal ions as described in Example 26 is shown. Figure 6 (a) shows the fluorescence spectrum of compound 4a in detecting cobalt ions. Figure 6 (b) shows the fluorescence spectrum of compound 4a in detecting copper ions; Figure 7 The fluorescence spectrum of compound 4e in response to metal ions described in Example 26 is shown. Figure 7 (a) shows the fluorescence spectrum of compound 4e for detecting cobalt ions. Figure 7 (b) shows the fluorescence spectrum of compound 4e for detecting copper ions; Figure 8 The fluorescence spectrum of compound 4f in response to metal ions described in Example 26 is shown. Figure 8 (a) shows the fluorescence spectrum of compound 4f for detecting cobalt ions. Figure 8 (b) shows the fluorescence spectrum of compound 4f for detecting copper ions; Figure 9 The fluorescence spectrum of compound 4m in response to metal ions described in Example 26 is shown. Figure 9 (a) shows the fluorescence spectrum of compound 4m for detecting cobalt ions. Figure 9 (b) shows the fluorescence spectrum of compound 4m for detecting cobalt ions; Figure 10 The fluorescence spectrum of compound 5c in response to metal ions described in Example 26 is shown. Figure 10 (a) shows the fluorescence spectrum of compound 5c for detecting cobalt ions. Figure 6 (b) shows the fluorescence spectrum of compound 5c for detecting cobalt ions. Detailed Implementation

[0029] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0030] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0031] In the context of this specification, the word "comprising" is considered to mean "especially including". It should not be interpreted as "consisting of only".

[0032] Terminology Explanation TLC: Thin-layer chromatography, also known as thin-layer chromatography, is a chromatographic separation technique that uses a support coated on a support plate as the stationary phase and a suitable solvent as the mobile phase to separate, identify, and quantify mixed samples.

[0033] As described in the background section, both existing methods for preparing difluoroalkylquinoxalinone require the use of photosensitizers. The first method, in particular, requires the use of transition metals, resulting in high costs, hindering large-scale industrial production, and causing environmental pollution. Therefore, this invention provides a C3-position difluoroalkylquinoxalinone derivative, its preparation method, and its applications, which eliminate the need for the addition of transition metals and photosensitizers during preparation.

[0034] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0035] Example 1 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4a, with a separation yield of 86%.

[0036] Product NMR data: 1 H NMR (400 MHz, CDCl3): d7.84-7.82 (m, 1H), 7.56-7.52 (m,1H), 7.36-7.24 (m, 6H), 7.21-7.17 (m, 1H), 4.17-4.06 (m, 3H), 3.70 (s, 3H),3.23-3.18 (m, 1H), 3.11-2.97 (m, 1H), 2.81-2.75 (m, 1H), 2.41-2.27 (m, 1H),1.20 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J = 32.3 Hz),160.7, 154.3, 138.9, 133.1, 132.4, 130.1, 129.9, 129.3, 128.4, 126.5, 123.6,115.9 (t, J = 252.5 Hz), 113.6, 62.7, 39.7, 37.5, 35.5 (t, J = 23.2 Hz), 29.2, 13.8. 19 F NMR (376 MHz, CDCl3): d -113.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 12 H 23 F2N2O3 401.1677, found 401.1681. Its proton, carbon, and fluorine spectra are as follows: Figure 2-4 As shown.

[0037] Example 2 Add 0.2 mmol of 1,6-dimethylquinoxaline-2 (1...) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4b, with a yield of 55%.

[0038] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.64-7.57 (m, 1H), 7.29-7.27 (m,1H), 7.21-7.09 (m, 6H), 4.09-3.95 (m, 3H), 3.60 (s, 3H), 3.25-3.10 (m, 1H),3.02-2.88 (m, 1H), 2.73-2.67 (m, 1H), 2.41 (d, J = 24.0 Hz, 3H), 2.33-2.19 (m,1H), 1.13 (t, J = 8.0 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 163.9 (d, J = 32.3Hz), 160.6, 154.3, 138.9, 133.4, 131.2, 130.9, 129.7, 129.3, 128.4, 126.4,124.9, 115.9 (d, J = 218.2 Hz), 113.4, 62.7, 39.8, 37.5, 35.5 (t, J = 23.2 Hz), 29.2, 20.6, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25 F2N2O3415.1833, found 415.1844. Example 3 Add 0.2 mmol of 1,7-dimethylquinoxaline-2 (1...) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the reaction was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4c, with a yield of 55%.

[0039] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.64-7.57 (m, 1H), 7.29-7.15 (m,5H), 7.13-7.01 (m, 2H), 4.07-3.95 (m, 3H), 3.60 (s, 3H), 3.15-3.09 (m, 1H), 3.03-2.88 (m, 1H), 2.73-2.67 (m, 1H), 2.41 (d, J = 24.0 Hz, 3H), 2.33-2.19 (m,1H), 1.13 (t, J = 8.0 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.3 (d, J = 33.3Hz), 160.6, 159.3, 154.3, 140.8, 138.9, 133.4, 132.9, 132.3, 131.2, 130.9,130.6, 129.2, 129.6, 129.3, 128.4, 126.4, 124.9, 115.9 (t, J = 251.5 Hz),113.4, 62.7, 39.8, 37.5, 35.5 (t, J = 22.2 Hz), 29.2, 20.6, 13.8. 19 F NMR (376MHz, CDCl3): d -103.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25 F2N2O3415.1833,found 415.1850. Example 4 Add 0.2 mmol of 6-methoxy-1-methylquinoxaline-2 (1) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4d, with a separation yield of 76%.

[0040] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.31-7.14 (m, 8H), 4.16-4.03 (m,3H), 3.90 (s, 3H), 3.68 (s, 3H), 3.23-3.18 (m, 1H), 3.11-2.97 (m, 1H), 2.81-2.75 (m, 1H), 2.41-2.27 (m, 1H), 1.20 (d, J = 8.0 Hz, 3H). 13 C{ 1 H NMR (101 MHz, CDCl3): d 164.1 (t, J = 33.3 Hz), 161.2, 160.0, 154.0, 138.9, 133.2, 129.3,128.5, 127.3, 126.5, 119.2, 115.9 (d, J = 251.5 Hz), 114.5, 111.3, 62.7, 55.8,39.7, 37.7, 35.4 (d, J = 23.2 Hz), 29.3, 13.8. 19F NMR (376 MHz, CDCl3): d -103.6,103.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25 F2N2O4431.1782, found 431.1778. Example 5 Add 0.2 mmol of 6-fluoro-1-methylquinoxaline-2 (1 mmol) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide under a nitrogen atmosphere and stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1 and subjected to rapid silica gel column chromatography to obtain the target product 4e in a yield of 77%.

[0041] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.53 (dd, J = 8.7, 2.7 Hz, 1H),7.33-7.17 (m, 7H), 4.17-4.08 (m, 3H), 3.68 (s, 3H), 3.19 (dd, J = 13.6, 5.9 Hz,1H), 3.08-2.94 (m, 1H), 2.78 (dd, J = 13.6, 8.8 Hz, 1H), 2.41-2.28 (m, 1H),1.22 (t, J = 7.2 Hz, 3H) . 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.0 (t, J = 33.3 Hz),162.4, 159.9, 157.5, 154.0, 138.7, 132.9 (d, J= 11.1 Hz), 129.7 (d, J = 2.0 Hz),129.3, 128.5, 126.5, 117.8 (d, J = 24.2 Hz), 115.8 (t, J = 252.5 Hz), 115.3 (d, J =22.2 Hz), 114.7 (d, J = 9.1 Hz), 62.8, 39.7, 37.6, 35.5 (t, J = 23.2 Hz), 29.4, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.6, -103.7, -119.1. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 22 H 22 F3N2O3419.1583,found 419.1574. Example 6 Add 0.2 mmol of 6-chloro-1-methylquinoxaline-2 (1) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4f, with a separation yield of 75%.

[0042] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.83 (d, J = 2.4 Hz, 1H), 7.48 (dd, J = 8.9, 2.4 Hz, 1H), 7.28-7.17 (m, 6H), 4.18-4.07 (m, 3H), 3.66 (s, 3H), 3.18 (dd,J = 13.5, 6.0 Hz, 1H), 3.07-2.93 (m, 1H), 2.78 (dd, J = 13.5, 8.7 Hz,1H), 2.41-2.28 (m, 1H), 1.23 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.0 (t, J = 33.3 Hz), 162.3, 154.0, 138.6, 132.9, 131.8, 130.0, 129.3, 129.2,128.9, 128.5, 126.6, 115.8 (t, J = 251.5 Hz), 114.8, 62.8, 39.7, 37.5, 35.5 (t, J = 23.2 Hz), 29.4, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.7. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd forC 22 H 22 ClF2N2O3435.1287, found 435.1281. Example 7 Add 0.2 mmol of 6-bromo-1-methylquinoxaline-2 (1 mmol) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide in a nitrogen atmosphere. The mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1 and subjected to rapid silica gel column chromatography to obtain 4 g of the target product, with a separation yield of 55%.

[0043] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.92 (d, J = 2.2 Hz, 1H), 7.55 (dd, J = 8.9, 2.3 Hz, 1H), 7.21-7.08 (m, 6H), 4.11-4.00 (m, 3H), 3.58 (s, 3H), 3.13-3.08 (m, 1H), 2.99-2.85 (m, 1H), 2.73-2.68 (m, 1H), 2.33-2.20 (m, 1H),1.16 (t, J = 7.1 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.0 (t, J = 33.3 Hz),162.2, 154.0, 138.6, 133.2, 132.8, 132.2, 132.2, 129.3, 128.5, 126.6, 116.1,115.8 (t, J = 252.5 Hz), 115.1, 62.8, 39.8, 37.5, 35.6 (t, J = 22.2 Hz), 29.3, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd forC 22 H 22 BrF2N2O3479.0782, found 479.0775. Example 8 Add 0.2 mmol of 6-cyano-1-methylquinoxaline-2 (1-) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide in a nitrogen atmosphere. The mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 2:1 and subjected to rapid silica gel column chromatography to obtain the target product in 4 h, with a separation yield of 38%.

[0044] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 8.06 (d, J = 1.9 Hz, 1H), 7.69 (dd, J = 8.6, 2.0 Hz, 1H), 7.29 (d, J = 8.7 Hz, 1H), 7.20-7.10 (m, 5H), 4.10-4.05(m, 3H), 3.61 (s, 3H), 3.11-3.06 (m, 1H), 2.96-2.86 (m, 1H), 2.76-2.70 (m,1H), 2.36-2.22 (m, 1H), 1.17 (t, J = 7.1 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 163.9 (t, J = 32.3 Hz), 163.3, 153.9, 138.3, 136.3, 134.1, 132.6, 131.9, 129.2,128.5, 126.7, 118.0, 115.7 (t, J = 252.5 Hz), 114.8, 107.1, 62.9, 39.8, 37.4,35.6 (t, J = 22.2 Hz), 29.5, 13.8. 19 F NMR (376 MHz, CDCl3): d -102.7, -103.4, -104.1, -104.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H22 F2N3O3426.1624, found 426.1627. Example 9 In a dry 20 mL Schleck reaction tube equipped with a magnetic stir bar, 0.2 mmol of methyl 1-methyl-2-oxo-1,2-dihydroquinoxaloline-6-carboxylate, 0.4 mmol of ethyl dibromofluoroacetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added. Under a nitrogen atmosphere, 2.0 mL of dimethyl sulfoxide was slowly injected into the reaction tube. The reaction was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The crude product was concentrated under vacuum until solvent-free to obtain crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 and subjected to rapid silica gel column chromatography to obtain the target product 4i, with a separation yield of 58%.

[0045] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 8.44 (d, J = 2.1 Hz, 1H), 8.11(dd, J = 8.8, 2.0 Hz, 1H), 7.25 (d, J = 8.8 Hz, 1H), 7.20-7.11 (m, 5H), 4.09-4.00(m, 3H), 3.89 (s, 3H), 3.62 (s, 3H), 3.14-3.09 (m, 1H), 3.01-2.87 (m, 1H),2.75-2.69 (m, 1H), 2.35-2.12 (m, 1H), 1.15 (t, J = 7.1 Hz, 3H). 13 C{ 1 H NMR (101MHz, CDCl3): d 166.1, 164.0 (t, J = 33.3 Hz), 161.8, 154.2, 138.6, 136.3, 131.7,131.6, 130.8, 129.3, 128.5, 126.6, 125.5, 115.8 (t, J = 251.5 Hz), 113.7, 62.8,52.4, 39.8, 37.4, 35.6 (t, J= 22.2 Hz), 29.5, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.6, -103.7. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 24 H 25 F2N2O5459.1727, found 459.1733. Example 10 Add 0.2 mmol of 6,7-trimethylquinoxaline-2 (1 mmol) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4j, with a yield of 64%.

[0046] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.51 (s, 1H), 7.20-7.14 (m, 4H), 7.11-7.08 (m, 1H), 6.97 (s, 1H), 4.04-3.92 (m, 3H), 3.58 (s, 3H), 3.11 (dd, J =13.5, 5.8 Hz, 1H), 3.02-2.87 (m, 1H), 2.69 (dd, J = 13.6, 8.9 Hz, 1H), 2.32 (s, 3H), 2.26 (s, 3H), 1.11 (t, J = 7.1 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1(t, J= 32.3 Hz), 159.3, 154.4, 139.9, 139.0, 132.5, 131.1, 130.8, 129.9,129.4, 128.4, 126.4, 116.0 (t, J = 252.5 Hz), 114.2, 62.7, 39.8, 37.5, 35.5 (t, J = 23.2 Hz), 29.1, 20.6, 19.2, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.5. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 24 H 27 F2N2O3429.1990, found 429.1987. Example 11 Add 0.2 mmol of 6,7-dichloro-1-methylquinoxaline-2 (1...) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide under a nitrogen atmosphere and stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1 and subjected to rapid silica gel column chromatography to obtain the target product 4k with a separation yield of 57%.

[0047] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.76 (d, J = 2.4 Hz, 1H), 7.42(dd, J= 8.9, 2.4 Hz, 1H), 7.21-7.12 (m, 5H), 4.10-4.01 (m, 3H), 3.59 (s, 3H), 3.13-3.08 (m 1H), 2.99-2.85 (m, 1H), 2.74-2.68 (m, 1H), 2.34-2.20 (m, 1H),1.16 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J = 33.3 Hz),162.3, 154.0, 138.6, 132.9, 131.8, 130.0, 129.3, 129.2, 128.9, 128.5, 126.5,115.8 (t, J = 252.5 Hz), 114.8, 62.8, 39.7, 37.5, 35.5 (t, J = 23.2 Hz), 29.4, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd forC 22 H 21 Cl2F2N2O3469.0897, found 469.0904. Example 12 Add 0.2 mmol of quinoxaline-2 (1) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) and subjected to rapid silica gel column chromatography to obtain 4 μL of the target product, with a yield of 47%.

[0048] Product NMR data: 1H NMR (400 MHz, CDCl3): d 12.2 (s, 1H), 7.77-7.75 (m, 1H),7.47-7.43 (m, 1H), 7.30-7.25 (m, 2H), 7.18-7.15 (m, 4H), 7.11-7.08 (m, 1H),4.17-4.10 (m, 1H), 4.02-3.97 (m, 2H), 3.19-3.14 (m, 1H), 3.07-2.92 (m, 1H), 2.83-2.77 (m, 1H), 2.40 -2.27 (m, 1H), 1.12 (t, J = 7.1 Hz, 3H). 13 C{ 1 H NMR (101MHz, CDCl3): d 164.1 (t, J = 33.3 Hz), 161.3, 156.0, 138.7, 132.6, 130.8, 130.2,129.3, 128.9, 128.5, 126.5, 124.2, 115.8 (t, J = 252.5 Hz), 115.74, 62.8, 40.0,36.6, 35.9 (t, J = 23.2 Hz), 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 21 H 21 F2N2O3387.1520,found 387.1532. Example 13 Add 0.2 mmol of 1-ethylquinoxaline-2 (1) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide in a nitrogen atmosphere. The mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1 and subjected to rapid silica gel column chromatography to obtain 4 μm of the target product, with a separation yield of 53%.

[0049] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.85-7.83 (m, 1H), 7.55-7.51 (m,1H), 7.35-7.30 (m, 2H), 7.27-7.21 (m, 4H), 7.20-7.16 (m, 1H), 4.35-4.24 (m,2H), 4.19-4.02 (m, 3H), 3.19 (dd, J = 13.5, 6.1 Hz, 1H), 3.11-2.97 (m, 1H), 2.81 (dd, J = 13.5, 8.8 Hz, 1H), 2.42-2.29 (m, 1H), 1.34 (t, J = 7.2 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1, 160.7, 153.8,138.9, 132.7, 132.0, 130.1, 130.0, 129.3, 128.4, 126.4, 123.3, 115.9, 113.4,62.7, 39.9, 37.4, 35.6 (t, J = 23.2 Hz), 13.8, 12.4. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.5. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 24F2N2O3415.1833,found 415.1831. Example 14 Add 0.2 mmol of 1-tert-butyl-2-(2-oxoquinoxaline-1(2-)-to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4n, with a separation yield of 55%.

[0050] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.84 (dd, J = 8.0, 1.5 Hz, 1H),7.52-7.48 (m, 1H), 7.35-7.31 (m, 1H), 7.28-7.16 (m, 5H), 7.06 (d, J = 2.0 Hz,1H), 4.99-4.85 (m, 2H), 4.31-4.03 (m, 3H), 3.21 (dd, J = 13.6, 5.8 Hz, 1H), 3.12-2.97 (m, 1H), 2.80 (dd, J = 13.6, 8.8 Hz, 1H), 2.41-2.28 (m, 1H), 1.43 (s,9H), 1.20 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 166.1, 164.1 (t, J =32.3 Hz), 160.5, 153.9, 138.7, 132.4, 132.3, 130.1, 129.3, 128.5, 126.5,123.8, 115.9 (t, J= 252.5 Hz), 113.1, 83.1, 62.7, 44.4, 39.7, 37.6, 35.4 (t, J =23.2 Hz), 27.9, 13.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 27 H 31 F2N2O5501.2201, found 501.2224. Example 15 Add 0.2 mmol of 1-(2-propyn-1-yl)quinoxaline-2(1-) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL of dimethyl sulfoxide under a nitrogen atmosphere and stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free, and washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1. The crude product was then subjected to rapid silica gel column chromatography to obtain the target product 4O, with a separation yield of 53%.

[0051] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.78-7.76 (m, 1H), 7.52-7.48 (m,1H), 7.39-7.36 (m, 1H), 7.32-7.28 (m, 1H), 7.21-7.09 (m, 5H), 5.03-4.90 (m,2H), 4.08-3.95 (m, 3H), 3.13 (dd, J = 13.6, 5.9 Hz, 1H), 3.00-2.92 (m, 1H),2.72 (dd, J = 13.6, 8.9 Hz, 1H), 2.34-2.20 (m, 2H), 1.12 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J= 32.3 Hz), 160.6, 153.3, 138.7, 132.6,131.5, 130.2, 130.0, 129.3, 128.5, 126.5, 124.0, 115.8 (t, J = 252.5 Hz),114.1, 73.3, 62.8, 39.8, 37.6, 35.5 (t, J = 23.2 Hz), 31.6, 29.7, 13.8. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 24 H 23 F2N2O3425.1677, found 425.1685. Example 16 Add 0.2 mmol of 1-benzylquinoxaline-2(1) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H )-ketone, 0.4 mmol dibromofluoroethyl acetate, 0.4 mmol allylbenzene, 0.4 mmol N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL dimethyl sulfoxide in a nitrogen atmosphere. The mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1 and subjected to rapid silica gel column chromatography to obtain the target product 4p with a separation yield of 84%.

[0052] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.74 (dd, J = 7.9, 1.6 Hz, 1H),7.21-7.07 (m, 11H), 7.02-7.00 (m, 2H), 5.43-5.29 (m, 2H), 4.22-4.15 (m, 1H),3.99 (q, J = 7.1 Hz, 2H), 3.14 (dd, J = 13.4, 7.0 Hz, 1H), 3.05-2.91 (m, 1H), 2.83 (dd, J = 13.4, 8.2 Hz, 1H), 2.42-2.29 (m, 1H), 1.11 (t, J= 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J = 33.3 Hz), 161.0, 154.5, 138.7, 135.2,132.7, 132.3, 130.1, 129.9, 129.4, 129.0, 128.5, 127.6, 126.7, 126.5, 123.6,116.0 (t, J = 252.5 Hz), 114.5, 62.8, 45.9, 40.3, 37.3, 36.3 (t, J = 23.2 Hz), 13.8. 19 F NMR (376 MHz, CDCl3): d -103.3, -103.3. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 28 H 27 F2N2O3477.1990, found 477.1989. Example 17 Add 0.2 mmol of 1-phenylethyldibenzoquinoline-2(1-) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 4q, with a yield of 60%.

[0053] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.78-7.76 (m, 1H), 7.46-7.42 (m,1H), 7.26-7.09 (m, 12H), 4.42-4.28 (m, 2H), 4.12-3.97 (m, 3H), 3.09 (dd,J =13.5, 6.2 Hz, 1H), 3.02-2.88 (m, 3H), 2.74 (dd, J = 13.5, 8.7 Hz, 1H), 2.35-2.22 (m, 1H), 1.14 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J =33.3 Hz), 160.7, 153.9, 138.8, 137.8, 132.6, 132.1, 130.2, 130.0, 129.4,128.8, 128.8, 128.4, 126.9, 126.5, 123.4, 117.2 (d, J = 252.5 Hz), 113.4, 62.7,43.8, 39.9, 37.3, 35.6 (t, J = 22.2 Hz), 33.3, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 29 H 29 F2N2O3491.2146,found 461.2159. Example 18 Add 0.2 mmol of 2-(2-oxoquinoxaline-1(2-)-to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H Acetonitrile, 0.4 mmol dibromofluoroethyl acetate, 0.4 mmol allylbenzene, and 0.4 mmol N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL dimethyl sulfoxide in a nitrogen atmosphere. The mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 7:1 and subjected to rapid silica gel column chromatography to obtain the target product 4r, with a separation yield of 71%.

[0054] Product NMR data: 1H NMR (400 MHz, CDCl3): d 7.82 (dd, J = 8.0, 1.5 Hz, 1H),7.57-7.53 (m, 1H), 7.38-7.34 (m, 1H), 7.23-7.17 (m, 3H), 7.13-7.10 (m, 3H),5.18-4.96 (m, 2H), 4.06-4.02 (m, 3H), 3.09 (dd, J = 13.5, 6.4 Hz, 1H), 3.01-2.86 (m, 1H), 2.76 (dd, J = 13.5, 8.6 Hz, 1H), 2.37-2.24 (m, 1H), 1.15 (t, J =7.1 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.0 (t, J = 33.3 Hz), 160.6, 153.0,138.4, 132.5, 130.9, 130.7, 130.6, 129.2, 128.6, 126.7, 124.9, 115.8 (t, J =251.5 Hz), 113.6, 113.0, 62.9, 40.0, 37.4, 35.8 (t, J = 23.2 Hz), 29.5, 13.8. 19 FNMR (376 MHz, CDCl3): d -103.6, -103.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 22 F2N3O3426.1629, found 426.1626. Example 19 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of 2-methylallylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the reaction was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until complete. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (7:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 5b, with a yield of 50%.

[0055] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.76 (dd, J = 8.0, 1.5 Hz, 1H),7.47-7.43 (m, 1H), 7.28-7.17 (m, 2H), 7.08-6.98 (m, 4H), 4.15-3.94 (m, 3H),3.58 (s, 3H), 3.12-2.92 (m, 2H), 2.73 (dd, J = 13.7, 9.1 Hz, 1H), 2.36 (s, 3H), 2.30-2.21 (m, 1H), 1.12 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1(t, J = 33.3 Hz), 161.0, 154.4, 136.9, 136.9, 133.1, 132.4, 130.5, 130.2,130.1, 129.8, 126.6, 125.8, 123.6, 116.0 (t, J = 251.5 Hz), 113.6, 62.7, 37.6,35.8 (t, J = 12.1 Hz), 35.5, 29.2, 19.5, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25F2N2O3415.1833, found 415.1825. Example 20 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of 4-methoxyallylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until complete. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 5c, with a yield of 63%.

[0056] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.83 (dd, J = 8.0, 1.5 Hz, 1H),7.56-7.51 (m, 1H), 7.36-7.26 (m, 2H), 7.15 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 8.6Hz, 2H), 4.11-4.04 (m, 3H), 3.77 (s, 3H), 3.69 (s, 3H), 3.14 (dd, J = 13.6, 5.9Hz, 1H), 3.05-2.95 (m, 1H), 2.73 (dd, J = 13.7, 8.9 Hz, 1H), 2.40-2.27 (m, 1H),1.21 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1 (t, J = 33.3 Hz),160.8, 158.2, 154.3, 133.0, 132.4, 130.9, 130.3, 130.0, 129.8, 123.6, 115.9(t, J= 252.5 Hz), 113.8, 113.6, 62.7, 55.2, 38.9, 37.7, 35.6 (t, J = 22.2 Hz), 29.2, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -103.6. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25 F2N2O4431.1782, found 431.1781. Example 21 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of 3,4-dimethoxyallylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 5d, with a separation yield of 56%.

[0057] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.83 (dd, J = 7.9, 1.5 Hz, 1H),7.56-7.51 (m, 1H), 7.36-7.27 (m, 2H), 6.76 (s, 3H), 4.16-4.05 (m, 3H), 3.84(s, 3H), 3.80 (s, 3H), 3.69 (s, 3H), 3.18-2.95 (m, 2H), 2.75 (dd, J = 13.7, 8.8Hz, 1H), 2.42-2.29 (m, 1H), 1.21 (t, J = 7.1 Hz, 3H). 13 C{ 1H NMR (101 MHz, CDCl3): d 164.1 (t, J = 32.3 Hz), 160.8, 154.3, 148.8, 147.5, 133.0, 132.4,131.3, 130.1, 129.8, 123.6, 121.4, 115.9 (t, J = 251.5 Hz), 113.6, 112.2,111.0, 62.7, 55.8, 55.8, 39.4, 37.4, 35.6 (t, J = 23.2 Hz), 29.2, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.6, -103.7. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 24 H 27 F2N2O5461.1888, found 461.1909. Example 22 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of dibromofluoroethyl acetate, 0.4 mmol of 4-allyl-2-methoxyphenol, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the mixture was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (3:1 v / v) and subjected to rapid silica gel column chromatography to obtain the target product 5e, with a yield of 38%.

[0058] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.75 (dd, J = 8.0, 1.5 Hz, 1H),7.49-7.44 (m, 1H), 7.29-7.19 (m, 2H), 6.72-6.70 (m, 2H), 6.61 (dd, J= 8.0, 1.9Hz, 1H), 5.47 (s, 1H), 4.08-3.96 (m, 3H), 3.75 (s, 3H), 3.62 (s, 3H), 3.06(dd, J = 13.7, 6.0 Hz, 1H), 3.00-2.88 (m, 1H), 2.64 (dd, J = 13.7, 8.9 Hz, 1H),2.33-2.20 (m, 1H), 1.13 (t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 164.1(t, J = 33.3 Hz), 160.8, 154.4, 146.5, 144.2, 133.0, 132.4, 130.6, 130.1,129.8, 123.6, 122.2, 115.9 (t, J = 251.5 Hz), 114.1, 113.6, 111.6, 62.7, 55.9,39.5, 37.5, 35.4 (t, J = 23.2 Hz), 29.2, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.6, -103.7 High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 25 F2N2O5447.1732, found 447.1725. Example 23 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H)-ketone, 0.4 mmol dibromofluoroethyl acetate, 0.4 mmol 1-allyl-2,3,4,5,6-pentafluorobenzene, 0.4 mmol N,N,N',N'-tetramethylethylenediamine were reacted with 2.0 mL dimethyl sulfoxide under a nitrogen atmosphere and stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until the reaction was complete. The crude product was concentrated under vacuum until solvent-free to obtain crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 3:1 and subjected to rapid silica gel column chromatography to obtain the target product 5f, with a separation yield of 52%.

[0059] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.70 (dd, J = 8.0, 1.5 Hz, 1H),7.51-7.47 (m, 1H), 7.29-7.19 (m, 2H), 4.13-4.07 (m, 3H), 3.62 (s, 3H), 3.26-3.20 (m, 1H), 3.11-3.05 (m, 1H), 3.03-2.91 (m, 1H), 2.39-2.25 (m, 1H), 1.20(t, J = 7.2 Hz, 3H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 163.9 (t, J = 32.3 Hz), 158.7,154.2, 146.5, 144.1, 138.8, 138.6, 136.1, 133.1, 132.2, 130.5, 130.0, 123.8,115.6 (t, J = 252.5 Hz), 113.7, 112.2, 112.0, 111.8, 63.0, 36.2 (t, J = 23.2 Hz),35.8, 29.2, 26.3, 13.8. 19 F NMR (376 MHz, CDCl3): d -103.5, -104.0, -141.9 - -142,0 (m, 2F), -156.1 - -156.2 (m, 1F), -162.4 - -162.5 (m, 1F). High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 22 H 18 F7N2O3491.1206,found 491.1220. Example 24 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of 2-bromo-N-(cyclopropylmethyl)-2,2-difluoroacetamide, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to a reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the reaction was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (3:1 v / v) and subjected to rapid silica gel column chromatography to obtain 5 g of the target product, with a yield of 61%.

[0060] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.75 (dd, J = 8.0, 1.5 Hz, 1H),7.48-7.44 (m, 1H), 7.29-7.16 (m, 6H), 7.12-7.09 (m, 1H), 4.23-4.16 (m, 1H),3.62 (s, 3H), 3.57-3.36 (m, 8H), 3.16-3.03 (m, 2H), 2.72 (dd, J = 13.6, 9.1 Hz,1H), 2.37-2.23 (m, 1H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 162.0 (t, J = 29.3 Hz),161.5, 154.5, 139.0, 133.1, 132.5, 129.9, 129.8, 129.4, 128.4, 126.4, 123.6,118.9 (t, J = 245.5 Hz), 113.7, 66.7, 46.4 (t, J= 6.1 Hz), 43.2, 40.1, 36.9,35.7 (t, J = 22.2 Hz), 29.2. 19 F NMR (376 MHz, CDCl3): d -102.8, -103.5, -104.5, -105.2. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 23 H 24 F2N2O3426.1993, found 426.2007. Example 25 Add 0.2 mmol of 1-methylquinoxaline-2 (1-methylquinoxaline-2) to a dry 20 mL Schleck reaction tube containing a magnetic magnet. H 0.4 mmol of 2-bromo-2,2-difluoro-1-morpholinylethane-1-one, 0.4 mmol of allylbenzene, and 0.4 mmol of N,N,N',N'-tetramethylethylenediamine were added to the reaction tube under a nitrogen atmosphere. 2.0 mL of dimethyl sulfoxide was slowly injected into the tube, and the reaction was stirred for 24 h at room temperature under a purple LED lamp. The reaction was monitored by TLC until completion. The mixture was then concentrated under vacuum until solvent-free to obtain the crude product. The crude product was then washed with a 1:1 mixture of petroleum ether and ethyl acetate as eluent, followed by rapid silica gel column chromatography to obtain the target product after 5 h, with a separation yield of 62%.

[0061] Product NMR data: 1 H NMR (400 MHz, CDCl3): d 7.75 (dd, J = 8.0, 1.5 Hz, 1H),7.48-7.44 (m, 1H), 7.29-7.16 (m, 6H), 7.12-7.09 (m, 1H), 4.23-4.16 (m, 1H),3.62 (s, 3H), 3.57-3.36 (m, 8H), 3.16-3.03 (m, 2H), 2.72 (dd, J = 13.6, 9.1 Hz,1H), 2.37-2.23 (m, 1H). 13 C{ 1 ¹H NMR (101 MHz, CDCl₃): d 162.0 (t, J= 29.3 Hz),161.5, 154.5, 139.0, 133.1, 132.5, 129.9, 129.8, 129.4, 128.4, 126.4, 123.6,118.9 (t, J = 254.5 Hz), 113.7, 66.7, 46.43 (t, J = 6.1 Hz), 43.2, 40.1, 36.9,35.7 (t, J = 22.2 Hz), 29.2. 19 F NMR (376 MHz, CDCl3): d -98.3. High-resolution mass spectrometry data of the product: LCMS (ESI) m / z: [M+H] + calcd for C 24 H 26 F2N3O3442.1942, found 442.1955. As can be seen from Examples 1 to 25, none of the above 25 examples used any metal catalysts or dangerous peroxide oxidants, and no photosensitizers were used, which greatly reduced energy consumption, avoided metal pollution, improved reaction safety, and facilitated large-scale industrial production.

[0062] As can be seen from Examples 1-25, the product yields of the embodiments of the present invention are mostly around 60%. This shows that the preparation method provided by the present invention, when selecting different types of raw materials with the same function in the embodiments, such as different quinoxalinone compounds, still produces products with high yields. This indicates that the method of the present application is universally applicable to a variety of raw materials, namely, different quinoxalinone compounds of formula (II), difluoroalkyl bromides of formula (III), olefins of formula (IV), solubilizers, and organic solvents, which further facilitates industrial production. Among them, the yield of Example 1 reached 86%, and the yield of Example 16 reached 84%. Examples 1 and 16 are the optimal examples among the above 25 examples, which shows that the combination and ratio of the raw materials in Examples 1 and 16 also have a synergistic effect, further improving the product yield.

[0063] Example 26 Products 4a, 4e, 4f, 4m, 5d, and 5c from Example 1 were dissolved in tetrahydrofuran (5.0 × 10⁻⁶ ppm). -4 M) Ultraviolet and fluorescence spectroscopy tests were performed, and the results are as follows: Figure 5 As shown.

[0064] Compound 4a: Figure 6 Image (a) shows the fluorescence spectrum of compound 4a for detecting cobalt ions. Figure 6 (b) shows the fluorescence spectrum of compound 4a for detecting copper ions. The fluorescence test results indicate that the fluorescence intensity of compound 4a increases with increasing cobalt ion concentration, but the fluorescence intensity for copper ions remains unchanged, suggesting that compound 4a can be used for the detection of cobalt ions in solutions or contaminants.

[0065] Compound 4e: Figure 7 (a) shows the fluorescence spectrum of compound 4e for detecting cobalt ions. Figure 7 (b) shows the fluorescence spectrum of compound 4e for detecting copper ions. The fluorescence test results indicate that the fluorescence intensity of compound 4e increases with increasing cobalt ion concentration, and also increases with increasing copper ion concentration, suggesting that compound 4e can be used for the detection of cobalt and copper ions in solutions or contaminants.

[0066] Compound 4f: Figure 8 (a) is the fluorescence spectrum of compound 4f detecting cobalt ions. Figure 8 (b) shows the fluorescence spectrum of compound 4f for detecting copper ions. The fluorescence test results indicate that the fluorescence intensity of compound 4f increases with increasing cobalt ion concentration, and also increases with increasing copper ion concentration, suggesting that compound 4f can be used for the detection of cobalt and copper ions in solutions or contaminants.

[0067] Compound 4m: Figure 9 (a) is the fluorescence spectrum of compound 4m for detecting cobalt ions. Figure 9 (b) shows the fluorescence spectrum of compound 4m for detecting copper ions. The fluorescence test results indicate that the fluorescence intensity of compound 4m increases with increasing cobalt ion concentration, and also increases with increasing copper ion concentration, suggesting that compound 4m can be used for the detection of cobalt and copper ions in solutions or contaminants.

[0068] Compound 5c: Figure 10 (a) is the fluorescence spectrum of compound 5c for detecting cobalt ions. Figure 10 (b) shows the fluorescence spectrum of compound 5c for detecting copper ions. The fluorescence test results indicate that the fluorescence intensity of compound 5c increases with increasing cobalt ion concentration, and also increases with increasing copper ion concentration, suggesting that compound 5c can be used for the detection of cobalt and copper ions in solutions or contaminants.

[0069] The difluoroalkylquinoxaline compounds provided in other embodiments also have similar effects, indicating that the difluoroalkylquinoxaline compounds constructed in this invention can be used for ion detection.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A C3-position difluoroalkyl quinoxalone derivative, characterized in that, The structure of the C3-position difluoroalkyl quinoxalone derivative is shown in formula (I): （I） Wherein, the R 1 It is an aryl, halogen, cyano, alkoxy, or ester group; the R 2 The R group is a hydrogen atom, carbon atom, alkyl group, alkylbenzene group, ester group, alkynyl group, or nitrile group; 3 It is methyl, methoxy, or fluorine; the EWG is an ester group or an amide group.

2. A method for preparing a C3-position difluoroalkyl quinoxalone derivative, characterized in that, Includes the following steps: In an inert atmosphere, the quinoxalone compound shown in formula (II), the difluoroalkyl bromide compound shown in formula (III), the olefin compound shown in formula (IV), and the solubilizing additive are dissolved in an organic solvent and reacted under a purple light source to obtain the product. Among them, R 1 R 2 R 3 The meaning is the same as that of claim 1.

3. The method for preparing the C3-position difluoroalkyl quinoxalone derivative according to claim 2, characterized in that, The quinoxalone compounds include 1-methylquinoxalin-2(1H)-one, 1,6-dimethylquinoxalin-2(1H)-one, 1,7-dimethylquinoxalin-2(1H)-one, 6-methoxy-1-methylquinoxalin-2(1H)-one, 6-fluoro-1-methylquinoxalin-2(1H)-one, 6-chloro-1-methylquinoxalin-2(1H)-one, 6-bromo-1-methylquinoxalin-2(1H)-one, 6-cyano-1-methylquinoxalin-2(1H)-one, and 1,6,7-trimethylquinoxalin-2(1H)-one. One or more of the following: lin-2(1H)-one, 6,7-dichloro-1-methylquinoxalin-2(1H)-one, quinoxalin-2(1H)-one, 1-ethylquinoxalin-2(1H)-one, 1-tert-butylquinoxalin-2(1H)-one, 1-(2-propyn-1-yl)quinoxalin-2(1H)-one, 1-benzylquinoxalin-2(1H)-one, 1-phenylethyldibenzoquinoxalin-2(1H)-one, 2-(2-oxoquinoxalin-1(2H)-yl)acetonitrile, and 1-phenylquinoxalin-2(1H)-one; Alternatively, the difluoroalkyl bromide compounds include one or more of ethyl difluorobromoacetate, 2-bromo-N-(cyclopropylmethyl)-2,2-difluoroacetamide, 4-bromodifluoromethylmorpholine, and 2-bromo-2,2-difluoro-1-morpholinylethane-1-one; Alternatively, the olefinic compound may include one or more of allylbenzene, 2-methylallylbenzene, 4-methoxyallylbenzene, 3,4-dimethoxyallylbenzene, 4-allyl-2-methoxyphenol, and 1-allyl-2,3,4,5,6-pentafluorobenzene.

4. The method for preparing the C3-position difluoroalkyl quinoxalone derivative according to claim 2, characterized in that, The solubilizing additive is an organic solubilizing additive; preferably, the solubilizing additive includes one or more of the following: hansyl ester, N, N, N', N'-tetramethylethylenediamine, N, N-diisopropylethylamine, and N, N, N', N', N''-pentamethyldiethylenetriamine. The organic solvent includes one or more of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, 1,2-dichloroethane, dichloromethane, and tetrahydrofuran.

5. The method for preparing the C3-position difluoroalkyl quinoxalone derivative according to claim 2, characterized in that, The molar ratio of quinoxalone, difluoroalkyl bromide, and solubilizing additive is 0.1-1.0: 0.15-3.0: 0.15-3.0; Alternatively, the molar volume ratio of the quinoxaline to the organic solvent is 0.1-1.0:1-10, with units of mmol and mL, respectively.

6. The method for preparing the C3-position difluoroalkyl quinoxalinone derivative according to claim 2, characterized in that, The purple LEDs are LEDs with a wavelength of 390-400 nm. Alternatively, the reaction time is 18-48 h, preferably 24 h; Alternatively, the method may further include: stopping irradiation when the reaction is detected as complete; preferably, the detection method is TLC detection.

7. The method for preparing the C3-position difluoroalkyl quinoxalone derivative according to claim 2, characterized in that, The inert gas is one or more of argon and nitrogen.

8. The method for preparing the C3-position difluoroalkyl quinoxalone derivative according to claim 2, characterized in that, The method further includes: After the reaction was completed, the reaction mixture was concentrated under vacuum and separated by column chromatography. Preferably, before column chromatography separation, a cleaning process is included, wherein the cleaning agent is one or a mixture of petroleum ether and ethyl acetate; more preferably, the cleaning agent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 1-8:

1.

9. The use of the C3-position difluoroalkyl quinoxalone derivative of claim 1, or the product prepared by the method of any one of claims 2-8.

10. The application as described in claim 9, characterized in that, The applications include, but are not limited to, the following aspects: 1) Applications in the preparation of agricultural chemicals; 2) Applications in pharmaceutical preparation; 3) Application as a fluorescent indicator for cobalt ions and / or copper ions.

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