Process for the photocatalytic preparation of quinoxaline-2,3-diones

Abstract

The application belongs to the field of compound synthesis and particularly relates to a photocatalytic preparation method of quinoxaline-2,3-dione compounds, which comprises the following steps: preparing a raw material solution containing quinoxaline-2-ketone, mercaptan, a photocatalyst and acetonitrile, and performing a photocatalytic reaction under light to obtain a quinoxaline-2,3-dione compound product; the mercaptan is C1-C4 alkyl mercaptan, and the -SH is connected to a primary carbon or a secondary carbon. The application adopts a photocatalytic method to perform hydroxylation on the C3 position of quinoxaline-2-ketone, and further controls the combination of the mercaptan and acetonitrile solvent to improve the photocatalytic reaction effect of C3 hydroxylation.

Description

Technical Field

[0001] This invention relates to the field of green organic synthesis, specifically to a method for preparing quinoxaline-2,3-dione compounds. Background Technology

[0002] Developing C(sp2)-H functionalization reactions is an effective and direct strategy for constructing carbon-carbon and carbon-heteroatom bonds. Direct hydroxylation of the CH bond in aromatic compounds has attracted increasing attention in the synthetic community due to its wide applications in pesticides, pharmaceuticals, and functional materials. Hydroxylated N-heterocyclic compounds, in particular, possess broad biological activities and are an important class of organic synthetic intermediates. Currently, research on the direct C(sp2)-H functionalization of nitrogen heterocyclic compounds to introduce hydroxyl groups is still limited. However, due to the broad development and application prospects of these substances, they are increasingly favored by researchers.

[0003] Quinoxalo-2-ones, as an important class of nitrogen heterocyclic derivatives, have been widely used in natural products, pharmaceuticals, and materials science, exhibiting rich biological and pharmacological activities. To date, researchers have conducted extensive studies on the functionalization of the C3 position of quinoxalo-2-ones, including alkylation, alkoxylation, amination, sulfonation, acylation, arylation, phosphonylation, and trifluoromethylation. Among these studies, the direct hydroxylation of quinoxalo-2-ones at the C3 position has shown great appeal, but has been relatively limited in research. In 2009, we developed a method for the 3-hydroxylation of quinoxalo-2-ones (Adv. Synth. Catal. 2019, 361, 5721), which uses (NH4)2S2O8 as both an oxidant and an oxygen source. However, this method suffers from drawbacks, including the use of excessive amounts of environmentally unfriendly strong inorganic oxidants and harsh reaction conditions, resulting in chemical waste and increased manufacturing costs. Recently, P. Mal's group reported a nitration-in-situ substitution reaction at the C3 position of quinoxalin-2-one promoted by tert-butyl nitrite, synthesizing 3-hydroxyquinoxalin-2-one in a one-pot process (Eur. J. Org. Chem. 2022, doi:10.1002 / ejoc.202200425). However, the high reaction temperature (100℃) and the highly toxic nitrating reagent limit the application of this type of reaction in industrial production. Therefore, from an environmentally friendly perspective, there is an urgent need for a more sustainable and greener solution for the direct hydroxylation of quinoxalin-2-one. Summary of the Invention

[0004] To address the lack of 3-position hydroxylation technology for quinoxaline-2-ones, the present invention aims to provide a photocatalytic preparation method for quinoxaline-2,3-dione compounds, with the goal of successfully preparing quinoxaline-2,3-dione compounds and improving product yield.

[0005] A photocatalytic preparation method for quinoxaline-2,3-dione compounds involves carrying out a photocatalytic reaction of a raw material solution containing quinoxaline-2-one of formula 1, a thiol, a photocatalyst, and acetonitrile under light irradiation to obtain quinoxaline-2,3-dione compound products of formula 2.

[0006]

[0007] R1 is H, a C1-C6 alkyl group, or a substituted alkyl group;

[0008] R2 to R5 are individually H, C1 to C6 alkyl, C1 to C6 alkoxy, halogen, cyano, amino, acyl, hydroxy, trifluoromethyl, ester, or substituted alkyl; or, adjacent substituents are cyclized to form a five- or six-membered ring.

[0009] The substituent in the substituted alkyl group is at least one selected from halogen, alkoxy, nitro, ester, alkenyl, alkynyl, and phenyl.

[0010] The thiol is a C1 to C4 alkyl thiol, wherein the -SH group is attached to a primary or secondary carbon.

[0011] This invention attempts to use photocatalytic methods to photocatalytically hydroxylate the C3 position of quinoxaline-2-one. However, early research revealed that the photocatalytic hydroxylation of the C3 position of quinoxaline-2-one exhibited low reactivity, making it difficult to effectively obtain the target product. To address this issue, this invention, through in-depth research, innovatively employs the required primary or secondary C1-C4 alkyl thiols as auxiliaries, combined with acetonitrile as a solvent. This unexpectedly achieves synergistic effects, effectively solving the problem of low reactivity in the photocatalytic hydroxylation of the C3 position of quinoxaline-2-one and significantly improving the conversion rate of quinoxaline-2,3-dione compounds.

[0012] In this invention, the alkyl group is a straight-chain or branched alkyl group. In this invention, the substituted alkyl group is a group with a substituent on a saturated carbon atom of a C1-C6 alkyl group (preferably a C1-C2 alkyl group), and the substituent is, for example, at least one selected from halogen, C1-C6 alkoxy, nitro, C2-C6 ester, alkenyl, alkynyl, and phenyl.

[0013] In this invention, under the aforementioned photocatalytic approach, the combined control of thiol and acetonitrile solvents enables synergistic effects, which helps to synergistically improve the C3-position hydroxylation activity of quinoxaline-2-one. The study also found that further control of the thiol component, photocatalyst component, and raw material structure helps to further improve the synergistic effect and further improve the product preparation effect.

[0014] Preferably, R1 is methyl or ethyl. R2 to R5 are individually H, halogen, trifluoromethyl, or ester groups; more preferably H. Studies have found that combining the preferred raw materials with the process described in this invention can lead to a better synergistic effect, further improving the preparation effect of the product.

[0015] Preferably, the thiol is a C2-C3 alkylthiol, preferably 2-propylthiol or 1-propylthiol. This invention has found that photocatalytic treatment with the preferred thiol can be further combined and synergistically integrated with other processes to help improve the C3 hydroxylation activity of quinoxalin-2-one, thereby further improving the product preparation effect.

[0016] Preferably, the molar ratio of the quinoxaline-2-one raw material of Formula 1 to the thiol is 1:1 to 5; more preferably, it is 1:1.5 to 3.

[0017] In this invention, the photocatalyst is a heterogeneous photocatalyst and / or a homogeneous photocatalyst. In this invention, the homogeneous photocatalyst refers to a catalyst that is soluble in acetonitrile, and the heterogeneous photocatalyst refers to a catalyst that is insoluble in acetonitrile. Preferably, it is g-C3N4 (graphite carbon nitride), Ru(bpy)3Cl2, rose red, Rhodamine 6G, or eosin B(C) 20 H6Br2N2Na2O9), water-soluble eosin (Eosin Y, C) 20 At least one of H6Br4Na3O5, eosin alcohol, rhodamine B, and food coloring red; more preferably g-C3N4. In this invention, the preferred catalyst, combined with other processes, can further improve the synergistic preparation effect.

[0018] In this invention, there are no special requirements for the amount of photocatalyst used. Considering the preparation effect and cost, the molar ratio of the quinoxaline-2-one raw material of Formula 1 to the homogeneous photocatalyst is 1:0.02 to 0.1. The ratio of the quinoxaline-2-one raw material of Formula 1 to the heterogeneous photocatalyst is 1 mmol / 10 mg to 1 mmol / 40 mg.

[0019] In this invention, using acetonitrile as a solvent helps to achieve synergistic effects with other conditions, significantly improving the C3 hydroxylation activity of quinoxaline-2-one and increasing the product yield. In this invention, the amount of acetonitrile is not particularly required and can be adjusted as needed. Considering the preparation cost, the molar volume ratio of the quinoxaline-2-one raw material of Formula 1 to acetonitrile in the acetonitrile raw material is 0.1–0.5 mol / L.

[0020] In this invention, the photocatalytic reaction is carried out in an oxygen-containing atmosphere. The oxygen-containing atmosphere is at least one of oxygen, an oxygen-protective gas mixture, or air. The photocatalytic reaction of this invention can be carried out by exposing the raw material solution to an oxygen-containing atmosphere (e.g., placing it in an open container and exposing it to an oxygen-containing atmosphere), or by utilizing an oxygen-containing atmosphere dispersed within the raw material solution. Similarly, the reaction can be further enhanced by bubbling an oxygen-containing atmosphere into the raw material solution.

[0021] In this invention, the light source is a white light or a blue light source; preferably, the white light source is provided by an LED incandescent lamp with a power of 3W-120W; the blue light source is provided by a blue LED lamp with a power of 3W-120W.

[0022] In this invention, the temperature of the photocatalytic reaction is 15–40°C, preferably 20–28°C.

[0023] In this invention, the reaction time can be controlled according to existing central control methods. Considering the processing efficiency, the reaction time is preferably 5-24 hours, and more preferably 10-16 hours.

[0024] In this invention, after the photocatalytic reaction, a crude product is collected, and then washed with a washing solvent to remove impurities, thereby obtaining the target product. In this invention, the washing solvent is a mixture of ethyl acetate and petroleum ether. The volume ratio of ethyl acetate to petroleum ether is not particularly required, for example, 2:1 to 5:1, preferably 3:1. During the washing process, the amount of washing solvent can be adjusted as needed. Considering processing costs, the ratio of the washing solvent to the quinoxaloline-2-one raw material can be 4 to 10 mL / mmol.

[0025] In this invention, different crude product collection steps can be preferably adopted according to the physical characteristics of the catalyst. For example, for homogeneous catalysts, water can be added to the reaction system, and extraction can be performed using a hydrophobic solvent. The extracted supported organic phase can then be concentrated to obtain the crude product. When the photocatalyst is a heterogeneous catalyst, a hydrophobic solvent can be directly added for dilution, followed by solid-liquid separation to separate the heterogeneous catalyst. The resulting solution can then be concentrated to obtain the crude product. In this invention, the hydrophobic solvent is, for example, at least one of DCM, EA, and diethyl ether.

[0026] The preparation method of this invention has high conversion rate, low side reaction, and the product does not require chromatographic purification. Effective separation and purification can be achieved based on simple extraction, concentration, and solvent washing purification operations.

[0027] In this invention, the quinoxaline-2,3-dione compound product exhibits the following tautomerism.

[0028] However, Equation 2 has better thermodynamic stability.

[0029]

[0030] In this invention, N-methylquinoxaloline-2-one is used as the raw material, and g-C3N4 is used as the photocatalyst. The principle of photocatalytic preparation is as follows:

[0031]

[0032] Beneficial effects

[0033] (1) This invention uses photocatalysis to prepare quinoxaline-2,3-dione. Furthermore, it was discovered that using the thiol as a promoter and acetonitrile as a solvent can unexpectedly achieve synergistic effects, significantly improving the low photocatalytic hydroxylation activity at the C3 position of quinoxaline-2-one. In addition, further joint control of the substrate, thiol structure, and photocatalyst conditions can further achieve synergistic effects, further improving the photocatalytic hydroxylation activity at the C3 position of quinoxaline-2-one and thus further improving the product yield. This invention found that the product yield can reach 96% using the process described in this invention, which is significantly better than existing methods.

[0034] (2) The raw materials used, such as quinoxaline-2-one derivatives, are inexpensive and readily available. This method can obtain the product in one step, and the post-processing is simple and economically applicable.

[0035] (3) The reaction is carried out through a photocatalytic system, which uses visible light catalysis, avoiding the need for an equivalent amount of peroxidant in traditional methods, and the catalyst can be recycled under heterogeneous photocatalyst conditions.

[0036] (4) The reaction conditions are mild and can be carried out at room temperature under light. The operation is environmentally friendly and conducive to industrial production.

[0037] (5) No additional oxidant is needed for the reaction. Air can be used directly as the oxidant and oxygen source, avoiding the need to add too much oxidant and reducing the economic and environmental burden.

[0038] (6) The functional groups of this scheme have good applicability and are conducive to industrial production. Its application prospects in the fields of chemical engineering, materials and medicine are very promising. The method of this invention provides a new green synthetic route for the synthesis of 3-hydroxyquinoxaline-2-one derivatives. Detailed Implementation

[0039] In the following examples, the room temperature (rt) is, for example, 20–28°C;

[0040] Example 1

[0041]

[0042] 1-Methylquinoxaline-2(1H)-one (1a: 0.3 mmol), photocatalyst (homogeneous or heterogeneous catalysts from Table 1), thiol (RSH; formulas 2a to 2e), and reaction solvent (1.5 mL) were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm).

[0043] After the reaction is complete, if the catalyst is a homogeneous catalyst (such as EosinY, Rose Bengal, Rhodamine 6G, Ru(bpy)3Cl2), water (10 mL) is added to the reaction mixture beforehand, and the mixture is extracted with dichloromethane (10 mL). The organic phase is dried with anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. If the catalyst is a heterogeneous catalyst (g-C3N4), DCM (10 mL) is added to the reaction system for dilution, followed by solid-liquid separation. The filtrate is then concentrated to obtain the crude product.

[0044] The crude product was washed to remove impurities with a mixed solvent of ethyl acetate and petroleum ether (volume ratio of ethyl acetate to petroleum ether 3:1), filtered, and dried to obtain a solid product of 1-methylquinoxaline-2,3(1H,4H)-dione. The yield of the product is shown in Table 1.

[0045] Table 1

[0046]

[0047] Note: In Table 1, 'a' refers to the isolated yield.

[0048] The term 'b' refers to the reaction occurring in darkness without any light exposure.

[0049] Example 2

[0050] The present invention will be further illustrated by the following embodiments, but it is not intended to imply that the content of the present invention is limited to the embodiments.

[0051]

[0052] 0.048 g (0.3 mmol) of 1-methylquinoxalo-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of solvent acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for about 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum to obtain the crude product. The crude product was then treated with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE The crude product was washed with a mixture of 1-methylquinoxaline-2,3(1H,4H)-dione (3:1 ratio), filtered, and dried to obtain a yellow solid product; 50.7 mg (96% separation yield); melting point 284-285 °C. 1 H NMR(400MHz, DMSO-d6)δ12.01(s,1H),7.41–7.30(m,1H),7.23–7.13(m,3H),3.51(s,3H); 13 C NMR (100MHz, DMSO-d6) δ155.7,154.0,127.7,126.0,124.0,123.7,115.8,115.5, 30.1.

[0053] Example 3

[0054]

[0055] 0.0522 g (0.3 mmol) of 1-ethylquinoxalo-2(1H)-one, 10.7 mg (0.015 mmol) of Eosin Y (photocatalyst), 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of acetonitrile (solvent) were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for about 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of water was added to the reaction mixture and extracted with 10 mL of dichloromethane. The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to obtain a crude product. The crude product was then extracted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V). EA :V PE The crude product was washed with a mixture of 3:1, filtered, and dried to give a solid product of 1-ethylquinoxaline-2,3(1H,4H)-dione. Yellow solid; 49.0 mg (86% separation yield); melting point 281-282 °C. 1H NMR (400MHz, DMSO-d6) δ7.39(d,J=7.5Hz,1H),7.27–7.07(m,3H),4.13(q,J=7.1Hz,2H),1.21(t,J=7.1Hz,3H); 13 C NMR (100 MHz, DMSO-d6) δ 155.2, 154.1, 126.3, 126.3, 123.9, 123.8, 116.3, 115.2, 37.8, 12.5.

[0056] Example 4

[0057]

[0058] 0.070 g (0.3 mmol) of 1-pentylquinoxalin-2(1H)-one, 4.32 mg (0.009 mmol) of Rhodamine 6G (photocatalyst), 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of water was added to the reaction mixture, and the mixture was extracted with 10 mL of dichloromethane. The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to obtain the crude product. The crude product was then diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Washed (ratio 3:1), filtered, and dried to give a solid product of 1-pentylquinoxaline-2,3(1H,4H)-dione. Yellow solid; 58.5 mg (84% separation yield); melting point 274–275 °C. 1 H NMR(400MHz,DMSO-d6)δ12.03(s,1H),7.36 (d,J=7.8Hz,1H),7.17(q,J=8.2,6.7Hz,3H),4.13–4.02(m,2H),1.59(q,J=6.9Hz,2H),1.33(q,J=5.3,3.5Hz,4H),0.86(t,J=6.8Hz,3H); 13 C NMR (100MHz, DMSO-d6) δ155.5,154.0,126.6,126.2,123.9,123.8,116.2,115.3,42.6,28.9,26.7, 22.4,14.3.

[0059] Example 5

[0060]

[0061] 0.071 g (0.3 mmol) of 1-benzylquinoxaline-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (3 mL, V... EA :V PE =3:1) Wash, filter, and dry to give 1-benzylquinoxaline-2,3(1H,4H)-dione solid product. Yellow solid; 66.5 mg (88% separation yield); melting point 292-293℃. 1 H NMR(400MHz,DMSO-d6)δ12.11(s, 1H),7.31(d,J=5.5Hz,4H),7.28–7.23(m,1H),7.19(t,J=8.7Hz,2H),7.13(t,J=7.3Hz,1H),7.06(t,J=7.3Hz,1H),5.38(s,2H); 13 C NMR (100MHz, DMSO-d6) δ156.2,154.1,136.2,129.1,127.7,127.1,126.7,126.4,124.1,123.5,116.2,115.9,46.1.

[0062] Example 6

[0063]

[0064] 0.059 g (0.3 mmol) of 1-allylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (3 mL, V... EA :V PE Wash, filter, and dry with a 3:1 ratio to obtain 1-allylquinoxaline-2,3(1H,4H)-dione. Yellow solid; 53.9 mg (89% separation yield); melting point 269-270 °C. 1H NMR(400MHz,DMSO-d6) δ12.04(s,1H),7.26(dd,J=6.0,3.4Hz,1H),7.22–7.11(m,3H),5.91(ddd,J=21.9,10.1,4.8Hz,1H),5.25–5.07(m,2H),4.83–4.67(m,2H); 13 C NMR (100 MHz, DMSO-d6) δ 155.5, 154.0, 132.0, 126.6, 126.2, 124.0, 123.5, 117.4, 116.1, 115.8, 44.9.

[0065] Example 7

[0066]

[0067] In a quartz tube, 0.055 g (0.3 mmol) of 1-propargylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of solvent acetonitrile were added sequentially. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Wash, filter, and dry with a 4:1 ratio to give 1-propynylquinoxaline-2,3(1H,4H)-dione. Yellow solid; 49.2 mg (82% separation yield); melting point 277–278 °C. 1 H NMR (400MHz, DMSO-d6) δ12.10(s,1H),7.42(d,J=6.4Hz,1H),7.26–7.19(m,3H),4.95(d,J=2.1Hz,2H),3.33–3.30(m,1H); 13 C NMR (100MHz, DMSO-d6) δ155.1,153.8, 126.2,126.0,124.4,123.7,116.2,115.8,78.5,75.6,32.4.

[0068] Example 8

[0069]

[0070] 0.070 g (0.3 mmol) of 1-esteroquinoxaline-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of isopropanethiol, and 1.5 mL of solvent acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Wash with a 3:1 ratio, filter, and dry to give quinoxaline-2,3(1H,4H)-dione. White solid; 64.7 mg (87% separation yield); melting point 274–275 °C. 1 H NMR (400MHz, DMSO-d6) δ12.20 (s, 1H), 7.34–7.25 (m, 1H), 7.26–7.11 (m, 3H), 4.98 (s, 2H), 4.17 (q, J = 7.1Hz, 2H), 1.21 (t, J = 7.1Hz, 3H); 13 C NMR (100MHz, DMSO-d6) δ168.0,155.7,153.7,126.8, 125.9,124.4,123.9,116.3,115.3,61.8,44.7,14.5.

[0071] Example 9

[0072]

[0073] 0.078 g (0.3 mmol) of 1-esteroquinoxaline-2(1H)-one, 10 mg (10 mg) of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of isopropanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6 W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Wash with a 3:1 ratio, filter, and dry to give quinoxaline-2,3(1H,4H)-dione. White solid; 67.1 mg (81% separation yield); melting point 265–266 °C. 1H NMR (400MHz, DMSO-d6) δ12.18(s,1H),7.35–7.12(m, 4H),4.87(s,2H),1.42(s,9H); 13 C NMR (100MHz, DMSO-d6) δ167.0,155.6,153.7,126.9,125.9,124.4,123.8,116.3,115.2,82.5,45.2,28.1.

[0074] Example 10

[0075]

[0076] 0.054 g (0.3 mmol) of 6-fluoro-1-methylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of isopropanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent (2 mL, V) of petroleum ether (PE) and ethyl acetate (EA). EA :V PE Wash, filter, and dry with a 3:1 ratio to give 6-fluoro-1-methylquinoxalin-2(1H)one. Yellow solid; 47.1 mg (81% separation yield); melting point >300℃. 1 H NMR (400MHz, DMSO-d6) δ12.07 (s, 1H), 7.36 (dd, J=9.1, 5.0Hz, 1H), 7.04 (td, J=8.7, 2.8Hz, 1H), 6.95 (dd, J=9.3, 2.8Hz, 1H), 3.50 (s, 3H); 13 C NMR(101MHz,DMSO-d6)δ158.5(d,J C-F =240.3 Hz),155.2,154.1,127.2(d,J C-F =11.1Hz), 124.6(d,J C-F =2.0Hz), 117.1(d,J C-F = 9.1Hz), 110.1(d,J C-F =23.2Hz), 102.4(d,J C-F =27.3Hz), 30.4; 19 F NMR(376MHz, DMSO-d6)δ-119.4.

[0077] Example 11

[0078]

[0079] 0.078 g (0.3 mmol) of 6-trifluoromethylfluoro-1-methylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of isopropanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Washed (ratio 3:1), filtered, and dried to obtain 6-trifluoromethyl-1-methylquinoxalin-2(1H)one solid product. Yellow solid; 63.0 mg (separation yield 86%); melting point >300℃. 1 H NMR (400MHz, DMSO-d6) δ12.18(s,1H),7.55–7.47(m,2H),7.43(s,1H),3.53(s,3H); 13 C NMR(101MHz,DMSO-d6)δ155.8,153.9,130.9,124.5(q,J C-F =272.7Hz), 124.1 (q,J C-F =32.3Hz), 120.1(q,J C-F =4.0Hz),126.6,116.3,112.3(q,J C-F =4.0Hz), 30.4; 19 F NMR(376MHz,DMSO-d6)δ-60.50; HRMS(ESI):m / z[M+H] + calcd for C 10 H8F3N2O2:245.0532; found:245.0538.

[0080] Example 12

[0081]

[0082] 0.065 g (0.3 mmol) of 6-ester-1-methylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of solvent acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (3 mL, V... EA :V PE Wash, filter, and dry with a 3:1 ratio to obtain 6-ester-1-methylquinoxalin-2(1H)-one. Yellow solid; 61.1 mg (87% separation yield); melting point >300℃. 1 H NMR (400MHz, DMSO-d6) δ12.27(s,1H),7.76(d,J=8.1Hz,2H),7.23(d,J=8.1Hz,1H),3.86(s,3H),3.54(s,3H); 13 C NMR (100MHz, DMSO-d6) δ166.1,155.4,154.1,130.2,127.8,125.1,124.5, 116.0,115.9,52.7,30.1.

[0083] Example 13

[0084]

[0085] 0.065 g (0.3 mmol) of 7-fluoro-1-methylquinoxalin-2(1H)one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of solvent acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE =3:1) Wash, filter, and dry to give 7-fluoro-1-methylquinoxalin-2(1H)one solid product. Yellow solid; 51.8 mg (separation yield 89%); melting point >300℃. 1H NMR (400MHz, DMSO-d6) δ12.00(s,1H), 7.27(dd,J=10.8,2.4Hz,1H),7.20–7.10(m,1H),7.02(td,J=8.6,2.5Hz,1H), 3.48(s,3H); 13 C NMR(100MHz,DMSO-d6)δ158.6(d,J C-F =238.4Hz),155.7, 153.5,128.9(d,J C-F =11.1Hz), 122.7, 116.9 (d, J) C-F =10.1Hz), 110.5(d,J C-F =24.2 Hz), 103.0 (d, J) C-F =28.3Hz), 30.4; 19 F NMR (376MHz, DMSO-d6) δ-118.6.

[0086] Example 14

[0087]

[0088] 0.065 g (0.3 mmol) of 8-chloro-1-methylquinoxalin-2(1H)one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of solvent acetonitrile were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE =2:1) ​​Wash, filter, and dry to give 8-chloro-1-methylquinoxalin-2(1H)one solid product. Yellow solid; 52.9 mg (separation yield 84%); melting point >300℃. 1 H NMR (400MHz, DMSO-d6) δ12.05 (s, 1H), 7.23 (dd, J=6.6, 2.8Hz, 1H), 7.18–7.10 (m, 2H), 3.69 (s, 3H); 13 C NMR(100MHz, DMSO-d6)δ157.7,153.6,129.3,126.7,126.0,125.1,120.6,115.4,37.4; HRMS(ESI):m / z[M+H] +calcd for C9H8ClN2O2:211.0269; found:211.0272.

[0089] Example 15

[0090]

[0091] 0.058 g (0.3 mmol) of 6,7-difluoro-1-methylquinoxalin-2(1H)-one, 10 mg of photocatalyst g-C3N4, 0.0456 g (0.6 mmol) of n-propanethiol, and 1.5 mL of acetonitrile solvent were added sequentially to a quartz tube. The reaction mixture was placed in air and stirred for approximately 12 h at room temperature under irradiation with a 6W blue LED lamp (445-450 nm). After the reaction was complete, 10 mL of dichloromethane was added to the reaction mixture, and g-C3N4 was filtered out from the mixture. The filtrate was concentrated under vacuum. The crude product was diluted with a mixed solvent of petroleum ether and ethyl acetate (2 mL, V... EA :V PE Wash, filter, and dry with a 3:1 ratio to obtain 6,7-difluoro-1-methylquinoxalin-2(1H)-one. Yellow solid; 54.1 mg (85% separation yield); melting point >300℃. 1 H NMR (400MHz, DMSO-d6) δ12.04 (s, 1H), 7.56 (dd, J=12.1, 7.9Hz, 1H), 7.11 (dd, J=10.6, 8.0Hz, 1H), 3.46 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.4, 153.7, 145.6 (dd, J1=243.4Hz, J2= 4.0Hz), 145.5 (dd, J1=242.4Hz, J2=16.1Hz), 124.7 (dd, J1=9.1Hz, J2=3.0Hz), 122.7 (dd, J1=9.1Hz, J2=3.0Hz), 105.3 (dd, J1=21.2Hz, J2=3.0Hz), 104.2 (d, J=21.2Hz), 30.8; 19 F NMR(376MHz,DMSO-d6)δ-144.1(d,J F-F =22.6Hz), -144.2 (d,J F-F =26.3Hz).

Claims

1. A method for photocatalytic preparation of quinoxaline-2,3-dione compounds, characterized by, A raw material solution containing quinoxaline-2-one of formula 1, thiol, photocatalyst, acetonitrile is subjected to photocatalytic reaction under light irradiation to produce quinoxaline 2,3-dione compound of formula 2; Formula 1 Formula 2 R1 is methyl or ethyl; R2-R5 are independently H, halogen or trifluoromethyl; The thiol is C2-C3 alkyl thiol, and the -SH is connected to a primary carbon or a secondary carbon; The molar ratio of quinoxaline-2-one of formula 1 to thiol is 1:1-5; The photocatalyst is a heterogeneous photocatalyst and / or a homogeneous photocatalyst; it is at least one of g-C3N4, Ru(bpy)3Cl2, Rose Bengal, Rhodamine 6G; The molar ratio of quinoxaline-2-one of formula 1 to the homogeneous photocatalyst is 1:0.02-0.1; The ratio of quinoxaline-2-one of formula 1 to the heterogeneous photocatalyst is 1 mmol / 10 mg-1 mmol / 40 mg; The light source for light irradiation is a blue light source; the blue light source is provided by a blue LED lamp with a power of 3W-120W.

2. The method for photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein The thiol is 2-propyl mercaptan or 1-propyl mercaptan.

3. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein The molar ratio of quinoxaline-2-one of formula 1 to thiol is 1:1.5-3.

4. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein In the raw material acetonitrile, the molar volume ratio of quinoxaline-2-one of formula 1 to acetonitrile is 0.1-0.5 moL / L.

5. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein The photocatalytic reaction is carried out in an oxygen-containing atmosphere; the oxygen-containing atmosphere is at least one of oxygen, a mixture of oxygen-protective gas, and air.

6. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein The temperature of the photocatalytic reaction is 15-40°C.

7. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein The reaction time is 5-24 hours.

8. The method of photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 1, wherein After the photocatalytic reaction, the crude product is collected, and then impurities are removed by washing with a washing solvent to produce the target product.

9. The method for photocatalytic preparation of quinoxaline-2,3-dione compounds according to claim 8, wherein The washing solvent is a mixed solvent of ethyl acetate and petroleum ether.

10. The method for photocatalytic preparation of quinoxaline-2, 3-dione compounds according to claim 9, wherein The amount of washing solvent relative to quinoxaline-2-one raw material is 4-10 mL / mmoL.

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