A method for photocatalytic preparation of 3-aminoquinoxalin-2(1H)-one compounds

Abstract

The application discloses a method for photocatalytically preparing 3-aminoquinoxalin-2(1 H )-ketone compounds, and belongs to the field of organic synthesis. The application comprises the following steps: quinoxalin-2(1 H )-ketone compounds, fatty amine compounds, a photocatalyst mpg-C3N4 (mesoporous graphite phase carbon nitride) and an alkali DABCO (1,4-diazabicyclo (2.2.2) octane) are added into an organic solvent and uniformly mixed; the reaction is carried out under the irradiation of light in an oxygen atmosphere; and after the reaction is completed, the 3-aminoquinoxalin-2(1 H )-ketone product is obtained through treatment and separation. The application uses DABCO as an alkali and an electron transfer agent, and adopts mpg-C3N4 to photocatalytically prepare 3-aminoquinoxalin-2(1 H )-ketone compounds under the auxiliary condition of DABCO, and it is concluded from DABCO quenching experiments and cyclic voltammetry experiments that there is a single electron transfer relationship between them; and the application has the advantages of mild reaction conditions, simple operation and the ability to synthesize 3-aminoquinoxalin-2(1 H )-ketone compounds in one step.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a method for photocatalytic preparation of 3-aminoquinoxalin-2(1H)-one compounds. BACKGROUND

[0002] The development of C-N bond formation reactions has always been a dynamic field in organic synthesis, including synthetic chemistry, agriculture, medicinal chemistry, biology, materials science, etc. (Org. Biomol. Chem., 2022, 20, 5125). The preparation of aryl C-N bonds is crucial because many biologically active target compounds or fine chemicals contain amine functional groups. Aliphatic amines are an important functional group in organic chemistry, with only H or alkyl substituents on the nitrogen atom. Due to its environmental friendliness and low cost, aliphatic amines are widely used as amino sources for C-N bond formation (J. Org. Chem. 2024, 89, 5371-5381).

[0003] Quinoxalin-2(1H)-one is an important bioactive skeleton, which has been studied in medicinal chemistry and material chemistry. In particular, 3-aminoquinoxalin-2(1H)-one compounds have attracted increasing attention from chemists due to their significant biological activity. Their skeleton derivatives are widely present in various biologically active drug molecules and have various biological and pharmacological activities, such as anticancer, antibacterial, antiviral, anti-inflammatory, antidiabetic, antihypertensive, etc. (Org. Lett. 2018, 20, 7125-7130). Currently, the following compounds have been developed for clinical treatment, compound A is used as a calcium ion channel blocker, compound B is used as an aldose reductase inhibitor, compound C is a PAS kinase modulator, compound D is a histamine-4 receptor antagonist, compound E is a COX-2 inhibitor, which can be used for advanced receptor-positive breast cancer, and compound F is an EBV virus inhibitor, etc. Therefore, it is of great significance to construct this type of nitrogen-containing molecules (Eur. J. Med. Chem. 2014, 80, 383-392; Bioorg. Med. Chem. Lett. 2005, 15, 4790-4793; WO 2009045382A1; WO 2012119046A2; US20050070527A1).

[0004]

[0005] In view of the important biological activity and medicinal value of 3-aminoquinoxalin-2(lH)-one, its synthetic methods have attracted widespread interest. The traditional methods for synthesizing 3-aminoquinoxalin-2(lH)-one mainly include: (1) a step-by-step method for quinoxalin-2(lH)-one ring (Eur. J. Med. Chem. 2014, 80, 383-392); (2) nucleophilic substitution reaction of amine compound with halogen or other leaving groups substituted quinoxalin-2(lH)-one (Chin. Chem. Soc. 2000, 47, 351-357); but these reactions have obvious shortcomings, including the need for pre-preparation of functionalized starting materials, tedious multi-step reactions, relatively harsh reaction conditions and narrow substrate range, etc.

[0006] 3-aminoquinoxalin-2(lH)-one is usually prepared by direct C-H / N-H cross-dehydrogenative coupling (CDC) amination method with aliphatic amine, which is of great significance to the atom economy and step economy. A number of methods including oxidant oxidation method, transition metal catalysis, electrocatalysis, photocatalysis and other methods have achieved some results, but there are still some shortcomings in this type of reaction, as shown in the following reaction formula, route (a) needs potassium permanganate metal reagent or AgPy2MnO4 as oxidant, which is serious pollution to the environment (Tetrahedron 2008, 64, 696-707); route (b) uses transition metal copper salt as catalyst, and the reaction needs high reaction temperature, and the metal ion residue is difficult to handle (Org. Biomol. Chem. 2016, 14, 8428-8432); route (c) needs iodine molecule as catalyst and tert-butyl hydroperoxide as oxidant, the use of peroxide has potential danger in reaction scale-up (J. Org. Chem. 2017, 82, 4784-4792); electrocatalysis of route (d) has the problems of high cost and resource scarcity (Adv. Synth. Catal. 10.1002 / adsc.201800989); the photo-catalysis of route (e) uses eosin Y photosensitizer as photo-catalyst, which has poor stability, is difficult to separate, increases the difficulty of purification, is difficult to recycle, and has high reaction cost (Org. Lett. 2018, 20, 7125-7130).

[0007]

[0008] In summary, the above methods for synthesizing 3-aminoquinoxalin-2(lH)-one need stoichiometric amounts of harmful chemical oxidants, excessive transition metals and harsh reaction conditions. Therefore, it is still imperative to avoid the addition of heavy metals in the step of drug synthesis and to develop more environmentally friendly and milder synthetic methods to produce these compounds.

[0009] Visible light catalysis has been attracting more and more attention in organic synthesis due to its low energy consumption, mild reaction conditions, high selectivity and other advantages. Organic semiconductors are used as photocatalysts, and carbon nitride photocatalysts are of great concern due to their unique properties such as suitable energy band gap, visible light excitation, easy synthesis and modification. Of course, carbon nitride has been reported in the literature for catalyzing amine functional groups, such as the following reaction formula: route (f) carbon nitride photocatalytic aromatic amine, under ultraviolet light, the light source range is narrow and needs to participate in the oxidation agent (ChemSusChem 2021, 14, 5265-5270); route (g) is the carbon nitride photocatalytic aromatic amine reaction published by our research group (Asian J. Org. Chem. 2022, 11, e202200195 (1 of 8)).

[0010]

[0011] Currently, there is no literature reported on the direct C-H / N-H amination of quinoxalin-2(1H)-one and aliphatic amine catalyzed by carbon nitride. SUMMARY

[0012] The present application provides a method for photocatalytic preparation of 3-amino quinoxalin-2(1H)-one compounds, using mpg-C3N4 (mesoporous graphite phase carbon nitride) as a catalyst and base DABCO (1,4-diazabicyclo〔2.2.2〕octane) to synthesize 3-amino quinoxalin-2(1H)-one compounds at room temperature. No metal reagent, equivalent of strong oxidant, high temperature and complicated operation steps are used, the reaction has low energy consumption, and the reaction safety and efficiency are high.

[0013] To achieve the above purpose, the technical scheme adopted by the present application is:

[0014] A method for photocatalytic preparation of 3-amino quinoxalin-2(1H)-one compounds, comprising the following steps:

[0015] The quinoxaline-2(1H)-one compound shown in structural formula 1, the aliphatic amine shown in structural formula 2, and the photocatalyst mpg-C3N4 and DABCO are added to a Schlenk tube, an organic solvent is added, and they are mixed uniformly; the reaction is carried out under an oxygen atmosphere, LED light irradiation, and 20-50 DEG C for 12-48 hours; after the reaction is completed, the reaction liquid is subjected to centrifugal treatment, the carbon nitride is separated, saturated brine solution is added to wash the reaction liquid, then ethyl acetate is added for extraction, the extract is dried over anhydrous sodium sulfate, and then the extract is subjected to concentration treatment until no solvent is left, to obtain a crude product, which is then subjected to column chromatography treatment, eluted with a mixed eluent of ethyl acetate and petroleum ether in a volume ratio of 1:3, and about 1% triethylamine is added, so that the product is better precipitated in silica gel, and after rapid column chromatography, the 3-aminoquinoxaline-2(1H)-one product is obtained, including several important pharmaceutical intermediates synthesized, and the reaction general formula is as follows:

[0016]

[0017] In the compound 1, R 1 is hydrogen, fluorine, bromine, methyl formate group, alkoxy, methyl, aryl; in the compound 2, morpholine, 2,6-dimethylmorpholine, 2-methylmorpholine, piperidine, 4-methylpiperidine, 4-cyanopiperidine, 4-phenylpiperidine, 1-tert-butoxycarbonylpiperazine, thiomorpholine, tetrahydropyrrole, dimethylamine, methylamine, ethylamine, butylamine, heptylamine, isobutylamine, phenethylamine;

[0018] The mass of the photocatalyst mesoporous graphite phase carbon nitride is 10 mg-30 mg, and the alkali DABCO is 2 equivalents;

[0019] The molar ratio of the quinoxaline-2(1H)-one compound and the aliphatic amine is 0.2:0.4-0.2:0.6;

[0020] The organic solvent is tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, toluene, chlorobenzene, nitrobenzene or 1,4-dioxane;

[0021] The light source of the visible light lamp is selected from a blue LED lamp of 450-455 nm and an ultraviolet LED lamp of 390-400 nm;

[0022] The pharmaceutical intermediate is a PAS kinase modulator.

[0023] Beneficial effects: the application provides a method for photocatalytically preparing a 3-aminoquinoxaline-2(1H)-one compound, which has the following advantages compared with the prior art:

[0024] 1. The present application does not need to pre-functionalize quinoxalin-2(1H)-one, and 3-aminoquinoxalin-2(1H)-one compounds are synthesized by one-step operation under visible light catalysis, the reaction condition is mild, the energy is clean, strong oxidants are not needed, the safety of the reaction is high, and the functional group compatibility is good;

[0025] 2. The present application effectively avoids the use of metal reagents, reduces metal pollution, and saves reaction cost and is environmentally friendly because a non-metal photocatalyst is used.

[0026] 3. The present application uses DABCO as a base and an electron transfer agent, mpg-C3N4 is used to photocatalytically prepare 3-aminoquinoxalin-2(1H)-one compounds under the assistance of DABCO, and the single electron transfer relationship between them is obtained from DABCO quenching experiments and cyclic voltammetry experiments, and has a synergistic catalytic effect. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 The reaction flow chart of photocatalysis in the embodiments of the present application is shown in the figure;

[0028] Figure 2 The cyclic experiment results of carbon nitride in the embodiments of the present application are shown in the figure;

[0029] Figure 3 The emission quenching experiment results of DABCO in the embodiments of the present application are shown in the figure;

[0030] Figure 4 The cyclic voltammetry experiment results of DABCO in the embodiments of the present application are shown in the figure. DETAILED DESCRIPTION

[0031] The present application will be described in detail below in combination with the drawings and specific embodiments:

[0032] The experimental methods used in the following embodiments are conventional methods unless otherwise specified, the reaction temperature is room temperature around the temperature of light and is any temperature between 20-50℃, the materials and reagents used are commercially available or synthesized from commercially available raw materials unless otherwise specified.

[0033] Example 1

[0034]

[0035] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2a, 0.60 mmol), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction was stirred under O2 balloon atmosphere, under blue LED light (450-455 nm) irradiation at room temperature for 24 h; TLC test, centrifugation, extraction, column chromatography treatment, 3-morpholinyl quinoxalin-2(lH)-one product 3a was obtained as a white solid 12.1 mg, separation yield 26%.

[0036] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, Chloroform-d) δ 11.65 (s, 1H), 7.57 (p, J = 4.2 Hz, 1H), 7.30-7.25 (m, 2H), 7.20 (q, J = 5.1, 4.5 Hz, 1H), 4.06 (t, J = 4.7 Hz, 4H), 3.91 (t, J = 4.7 Hz, 4H).

[0037] Example 2

[0038] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg) and tetrahydrofuran (3.0 mL) were added and mixed well. The reaction was stirred under O2 balloon atmosphere, under blue LED light (450-455 nm) irradiation at room temperature for 24 h. TLC test, centrifugation, extraction, column chromatography treatment, 3-morpholinyl quinoxalin-2(lH)-one product 3a of this example was obtained as a white solid 4.7 mg, separation yield 10%.

[0039] Example 3

[0040] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction was stirred under O2 balloon atmosphere, under blue LED light (450-455 nm) irradiation at room temperature for 24 h; TLC test, centrifugation, extraction, column chromatography treatment, 3-morpholinyl quinoxalin-2(lH)-one product 3a was obtained as a white solid 41.6 mg, separation yield 90%.

[0041] From the above comparative experiments, it can be seen that the effect is poor and the yield is low when carbon nitride or DABCO is used alone as a catalyst, and the yield is greatly improved to 90% when DABCO is used as an auxiliary catalyst, which shows that there is some interaction between mpg-C3N4 and DABCO in the catalyst system, which jointly promotes the reaction. The yield of 3a under the optimal conditions of Example 3 is 90%, which shows that the use of mpg-C3N4 and the auxiliary catalyst DABCO in the present application has certain advantages in terms of green environmental protection.

[0042] Example 4

[0043] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2a, 0.40 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed uniformly; the reaction was stirred under the atmosphere of O2 balloon and irradiation of blue LED lamp (450-455 nm) at room temperature for 24 h; TLC detection, after centrifugation, extraction and column chromatography, 3-morpholinyl quinoxalin-2(lH)-one product 3a was obtained as a white solid 27.7 mg, with a separation yield of 59%.

[0044] Example 5

[0045]

[0046] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), 2,6-dimethylmorpholine (2b, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and N,N-dimethylformamide (3.0 mL) were added and mixed uniformly; the reaction vessel was stirred under the atmosphere of O2 balloon and irradiation of blue LED lamp (450-455 nm) at room temperature for 26 h; TLC detection, after centrifugation, extraction and column chromatography, 3-(2,6-dimethylmorpholinyl) quinoxalin-2(lH)-one product 3b of the present example was obtained as a white solid 44.5 mg, with a yield of 86%.

[0047] The obtained product had the following nuclear magnetic spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.17 (s, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.16 (dt, J = 12.5, 4.3 Hz, 3H), 4.77 (d, J = 12.9 Hz, 2H), 3.67 (ddt, J = 12.7, 6.4, 3.2 Hz, 2H), 2.58 (s, 2H), 1.14 (d, J = 6.3 Hz, 6H).

[0048] Example 6

[0049] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), 2,6-dimethylmorpholine (2b, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well. The reaction vessel was stirred under O2 balloon atmosphere at room temperature under UV light LED lamp (390-400 nm) irradiation for 12 h. After TLC monitoring, the product 3-(2,6-dimethylmorpholine)quinoxalin-2(lH)-one 3b was obtained as a white solid 33.1 mg, 64% yield, after centrifugation, extraction, column chromatography.

[0050] Example 7

[0051]

[0052] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), 2-methylmorpholine (2c, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and dimethyl sulfoxide (3.0 mL) were added and mixed well. The reaction vessel was stirred under O2 balloon atmosphere at room temperature under blue light LED lamp (450-455 nm) irradiation for 27 h. After TLC monitoring, the product 3-(2-methylmorpholine)quinoxalin-2(lH)-one 3c was obtained as a white solid 43.7 mg, 89% yield, after centrifugation, extraction, column chromatography.

[0053] The product obtained had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.17 (s, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.23 - 7.11 (m, 3H), 4.72 (d, J = 13.1 Hz, 2H), 3.88 (dd, J = 11.5, 3.4 Hz, 1H), 3.62 (tdd, J = 14.0, 9.5, 3.8 Hz, 2H), 3.02 - 2.92 (m, 1H), 2.67 (dd, J = 13.1, 10.3 Hz, 1H), 1.14 (d, J = 6.1 Hz, 3H).

[0054] Example 8

[0055]

[0056] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), piperidine (2d, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and acetonitrile (3.0 mL) were added and mixed well. The reaction vessel was stirred under O2balloon atmosphere at room temperature under blue LED lamp (450-455 nm) irradiation for 22 h. TLC detection, centrifugation, extraction, column chromatography treatment, 3-piperidine quinoxalin-2(lH)-one product 3d was obtained as a white solid 31.3 mg, yield 68%.

[0057] The obtained product NMR spectrum data are: 1 H NMR (400 MHz, Chloroform-d) δ 11.63 (s, 1H), 7.58-7.53 (m, 1H), 7.21 (tdd, J = 9.8, 6.4, 3.7 Hz, 3H), 3.98 (t, J = 4.7 Hz, 4H), 1.76 (s, 4H).

[0058] Example 9

[0059]

[0060] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), 4-methylpiperidine (2e, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and toluene (3.0 mL) were added and mixed well. The reaction vessel was stirred under O2balloon atmosphere at room temperature under blue LED lamp (450-455 nm) irradiation for 18 h. TLC detection, centrifugation, extraction, column chromatography treatment, 3-(4-methyl)piperidine quinoxalin-2(lH)-one product 3e of this example was obtained as a white solid 31.9 mg, yield 65%.

[0061] The obtained product NMR spectrum data are: 1 H NMR (400 MHz, Chloroform-d) δ 11.63 (s, 1H), 7.58-7.53 (m, 1H), 7.21 (tdd, J = 9.8, 6.4, 3.7 Hz, 3H), 3.98 (t, J = 4.7 Hz, 4H), 1.76 (s, 4H).

[0062] Example 10

[0063]

[0064] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), 4- cyanopiperidine (2f, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and chlorobenzene (3.0 mL), mixed well. The reaction vessel was stirred under O2 balloon atmosphere, room temperature blue LED light (450-455 nm) irradiation for 26 h. TLC indicated, after centrifugation, extraction, column chromatography, the 3-(4-cyanopiperidin-l-yl) quinoxalin-2(lH)-one product 3f of this example was obtained as a white solid 40.2 mg, 79% yield.

[0065] The resulting product NMR spectrum data were: 1 H NMR (400 MHz, DMSO-d6) δ 12.15 (s, 1H), 7.40 (d, J = 7.5 Hz, 1H), 7.24 - 7.10 (m, 3H), 4.21 (dd, J = 6.5, 3.5 Hz, 2H), 3.63 (ddd, J = 12.9, 8.9, 3.1 Hz, 2H), 3.15 (tt, J = 8.4, 4.1 Hz, 1H), 1.99 (ddt, J = 13.7, 7.0, 3.6 Hz, 2H), 1.82 (dtd, J = 12.6, 8.7, 3.5 Hz, 2H).

[0066] Example 11

[0067]

[0068] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), 4- cyanopiperidine (2f, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and chlorobenzene (3.0 mL), mixed well. The reaction vessel was stirred under O2 balloon atmosphere, room temperature blue LED light (450-455 nm) irradiation for 26 h. TLC indicated, after centrifugation, extraction, column chromatography, the 3-(4-cyanopiperidin-l-yl) quinoxalin-2(lH)-one product 3f of this example was obtained as a white solid 40.2 mg, 79% yield.

[0069] The resulting product NMR spectrum data were: 1H NMR (400 MHz, DMSO-d6) δ 12.12 (s, 1H), 7.45 - 7.38 (m, 1H), 7.35 - 7.24 (m, 4H), 7.24 - 7.11 (m, 4H), 5.06 (d, J = 12.9 Hz, 2H), 2.98 (td, J = 12.8, 2.5 Hz, 2H), 2.83 (ddt, J = 12.3, 7.7, 3.7 Hz, 1H), 1.87 (dd, J = 13.4, 3.6 Hz, 2H), 1.74 (qd, J = 12.6, 3.9 Hz, 2H).

[0070] Example 12

[0071]

[0072] In a Schlenk tube was added quinoxalin-2(lH)-one (la, 0.20 mmol), 1-tert- butyloxycarbonylpiperazine (2h, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL), mixed well. The reaction vessel was stirred under O2 balloon atmosphere, room temperature blue light LED lamp (450-455 nm) irradiation for 48 h. TLC detection, after centrifugation, extraction, column chromatography, 3-(N-tert- butyloxycarbonylpiperazine)quinoxalin-2(lH)-one product 3h was obtained as a white solid 63.4 mg, yield 96%.

[0073] The obtained product NMR spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.41 (s, 1H), 7.57 (dd, J = 7.4, 2.9 Hz, 1H), 7.27 (p, J = 4.2 Hz, 2H), 7.19 (dd, J = 7.1, 3.0 Hz, 1H), 4.01 (t, J = 5.1 Hz, 4H), 3.63 (t, J = 5.1 Hz, 4H), 1.52 (s, 9H).

[0074] Example 13

[0075]

[0076] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2h, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and 1,4-dioxane (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere at room temperature under blue LED light (450-455 nm) irradiation for 46 h. TLC detection, centrifugation, extraction, column chromatography treatment, 3-morpholinyl quinoxalin-2(lH)-one product 3h was obtained as a white solid 27.2 mg, yield 55%.

[0077] The obtained product NMR spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.62 (s, 1H), 7.59-7.53 (m, 1H), 7.29-7.25 (m, 2H), 7.20-7.15 (m, 1H), 4.39-4.31 (m, 4H), 2.89-2.80 (m, 4H).

[0078] Example 14

[0079]

[0080] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), morpholine (2h, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and 1,4-dioxane (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere at room temperature under blue LED light (450-455 nm) irradiation for 46 h. TLC detection, centrifugation, extraction, column chromatography treatment, 3-morpholinyl quinoxalin-2(lH)-one product 3h was obtained as a white solid 27.2 mg, yield 55%.

[0081] The obtained product NMR spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.62 (s, 1H), 7.59-7.53 (m, 1H), 7.29-7.25 (m, 2H), 7.20-7.15 (m, 1H), 4.39-4.31 (m, 4H), 2.89-2.80 (m, 4H).

[0082] Example 15

[0083]

[0084] In a Schlenk tube, add quinoxalin-2(lH)-one (la, 0.20 mmol), dimethylamine (2k, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (30.0 mg) and tetrahydrofuran (3.0 mL), mix well; the reaction vessel is under O2 balloon atmosphere, stirring at room temperature under blue LED light (450-455 nm) irradiation for 24 h; TLC detection, after centrifugation, extraction, column chromatography, the product of this example 3- tetrahydropyrroloquinoxalin-2(lH)-one 3k is obtained as a white solid 19.3 mg, yield 51%.

[0085] The obtained product nuclear magnetic spectrum data are: 1 H NMR (400 MHz, DMSO-d6) δ 11.98 (s, 1H), 7.38-7.32 (m, 1H), 7.12 (ddt, J = 7.1, 4.9, 2.9 Hz, 3H), 3.28 (s, 6H).

[0086] Example 16

[0087]

[0088] In a Schlenk tube, add 6-fluoroquinoxalin-2(lH)-one (ll, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL), mix well; the reaction vessel is under O2 balloon atmosphere, stirring at room temperature under blue LED light (450-455 nm) irradiation for 26 h; TLC detection, after centrifugation, extraction, column chromatography, the product of this example 6-fluoro-3-morpholinoquinoxalin-2(lH)-one 3l is obtained as a white solid 29 mg, yield 58%.

[0089] The obtained product nuclear magnetic spectrum data are: 1 H NMR (400 MHz, DMSO-d6) δ 12.20 (s, 1H), 7.20-7.12 (m, 2H), 7.05 (td, J = 8.7, 2.9 Hz, 1H), 3.94 (t, J = 4.6 Hz, 4H), 3.76-3.67 (m, 4H).

[0090] Example 17

[0091]

[0092] In a Schlenk tube, 6-bromoquinoxalin-2(lH)-one (1m, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere, at room temperature under blue LED lamp (450-455 nm) irradiation for 24 h; TLC monitoring, centrifugation, extraction, column chromatography gave the product 6-bromo-3-morpholinoquinoxalin-2(lH)-one 3m of this example as a white solid 33.9 mg, 55% yield.

[0093] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.50 (d, J = 2.1 Hz, 1H), 7.31 (dd, J = 8.5, 2.2 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 3.98 - 3.90 (m, 4H), 3.71 (t, J = 4.7 Hz, 4H).

[0094] Example 18

[0095]

[0096] In a Schlenk tube, 6-bromoquinoxalin-2(lH)-one (1m, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere, at room temperature under blue LED lamp (450-455 nm) irradiation for 24 h; TLC monitoring, centrifugation, extraction, column chromatography gave the product 6-bromo-3-morpholinoquinoxalin-2(lH)-one 3m of this example as a white solid 33.9 mg, 55% yield.

[0097] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.50 (d, J = 2.1 Hz, 1H), 7.31 (dd, J = 8.5, 2.2 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 3.98 - 3.90 (m, 4H), 3.71 (t, J = 4.7 Hz, 4H).

[0098] Example 19

[0099]

[0100] In a Schlenk tube, 6,7-dibromoquinoxalin-2(lH)-one (lp, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere, at room temperature under blue LED light (450-455 nm) irradiation for 24 h; after TLC detection, the product of this example, 6,7-dibromo-3-morpholinquinoxalin-2(lH)-one 3p, was obtained as a white solid 64 mg, 82% yield, after centrifugation, extraction, column chromatography.

[0101] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 7.29 (tt, J = 8.5, 5.0 Hz, 3H), 3.90 (t, J = 4.7 Hz, 4H), 3.71 (t, J = 4.7 Hz, 4H).

[0102] Example 20

[0103]

[0104] In a Schlenk tube, 6,7-dibromoquinoxalin-2(lH)-one (lp, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere, at room temperature under blue LED light (450-455 nm) irradiation for 24 h; after TLC detection, the product of this example, 6,7-dibromo-3-morpholinquinoxalin-2(lH)-one 3p, was obtained as a white solid 64 mg, 82% yield, after centrifugation, extraction, column chromatography.

[0105] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 7.29 (tt, J = 8.5, 5.0 Hz, 3H), 3.90 (t, J = 4.7 Hz, 4H), 3.71 (t, J = 4.7 Hz, 4H).

[0106] Example 21

[0107]

[0108] In a Schlenk tube, 6,7-dimethylquinoxalin-2(lH)-one (1q, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere at room temperature under blue LED light (450-455 nm) irradiation for 41 h; TLC detection, centrifugation, extraction, column chromatography treatment, to obtain the product 6,7-dimethyl-3-morpholinquinoxalin-2(lH)-one 3q of this example, white solid 26 mg, yield 50%.

[0109] The nuclear magnetic spectrum data of the product obtained are: 1 H NMR (400 MHz, Chloroform-d) δ 10.79 (s, 1H), 7.33 (s, 1H), 6.89 (s, 1H), 3.95 (dd, J = 5.7, 3.5 Hz, 4H), 3.87 (dd, J = 5.6, 3.6 Hz, 4H), 2.30 (d, J = 5.2 Hz, 6H).

[0110] Example 22

[0111]

[0112] In a Schlenk tube, benzochinolin-2(lH)-one (1r, 0.20 mmol), morpholine (2a, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL) were added and mixed well; the reaction vessel was stirred under O2 balloon atmosphere at room temperature under blue LED light (450-455 nm) irradiation for 36 h; TLC detection, centrifugation, extraction, column chromatography treatment, to obtain the product benzochinolin-2(lH)-one 3r of this example, white solid 47.8 mg, yield 85%.

[0113] The nuclear magnetic spectrum data of the product obtained are: 1 H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 7.94 - 7.83 (m, 3H), 7.55 (s, 1H), 7.39 (dq, J = 13.1, 6.6 Hz, 2H), 3.97 (t, J = 4.7 Hz, 4H), 3.74 (t, J = 4.7 Hz, 4H).

[0114] Example 23

[0115]

[0116] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), methanamine (2s, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2 balloon atmosphere, room temperature blue light LED lamp (450-455 nm) irradiation for 46 h; TLC detection, after centrifugation, extraction, column chromatography, the product of this example 3-methanamine quinoxalin-2(lH)-one 3s was obtained as a white solid 23.3 mg, yield 67%.

[0117] The obtained product nuclear magnetic spectrum data were: 1 H NMR (400 MHz, DMSO-d6) δ 12.11 (s, 1H), 7.60 (q, J = 4.9 Hz, 1H), 7.37 (dd, J = 6.7, 2.3 Hz, 1H), 7.17 - 7.07 (m, 3H), 2.90 (d, J = 4.9 Hz, 3H).

[0118] Example 24

[0119]

[0120] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), methanamine (2s, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4 (20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2 balloon atmosphere, room temperature blue light LED lamp (450-455 nm) irradiation for 46 h; TLC detection, after centrifugation, extraction, column chromatography, the product of this example 3-methanamine quinoxalin-2(lH)-one 3s was obtained as a white solid 23.3 mg, yield 67%.

[0121] The obtained product nuclear magnetic spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.96 (s, 1H), 7.69 - 7.63 (m, 1H), 7.38 - 7.27 (m, 3H), 6.41 (t, J = 5.7 Hz, 1H), 3.72 (qd, J = 7.2, 5.5 Hz, 2H), 1.45 (d, J = 7.2 Hz, 3H).

[0122] Example 25

[0123]

[0124] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), 3- chlorobutylamine (2p, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2 balloon atmosphere, irradiated by blue LED lamp (450-455 nm) at room temperature for 23 h; TLC detection, after centrifugation, extraction, column chromatography, the product 3-chlorobutylamine quinoxalin-2(lH)-one 3p of this example was obtained as a white solid 18.3 mg, yield 42%.

[0125] The obtained product nuclear magnetic spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.90 (s, 1H), 7.58 (dd, J = 7.8, 1.4 Hz, 1H), 7.30 - 7.17 (m, 3H), 6.35 (t, J = 5.7 Hz, 1H), 3.60 (td, J = 7.2, 5.7 Hz, 2H), 1.78 - 1.68 (m, 2H), 1.54 - 1.45 (m, 2H), 1.02 (t, J = 7.3 Hz, 3H).

[0126] Example 26

[0127]

[0128] A Schlenk tube was charged with quinoxalin-2(lH)-one (la, 0.20 mmol), 3- chlorobutylamine (2p, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2 balloon atmosphere, irradiated by blue LED lamp (450-455 nm) at room temperature for 23 h; TLC detection, after centrifugation, extraction, column chromatography, the product 3-chlorobutylamine quinoxalin-2(lH)-one 3p of this example was obtained as a white solid 18.3 mg, yield 42%.

[0129] The obtained product nuclear magnetic spectrum data were: 1 H NMR (400 MHz, Chloroform-d) δ 11.90 (s, 1H), 7.58 (dd, J = 7.8, 1.4 Hz, 1H), 7.30 - 7.17 (m, 3H), 6.35 (t, J = 5.7 Hz, 1H), 3.60 (td, J = 7.2, 5.7 Hz, 2H), 1.78 - 1.68 (m, 2H), 1.54 - 1.45 (m, 2H), 1.02 (t, J = 7.3 Hz, 3H).

[0130] Example 27

[0131]

[0132] In a Schlenk tube was added quinoxalin-2(lH)-one (la, 0.20 mmol), isobutylamine (2w, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2balloon atmosphere, room temperature blue LED light (450-455 nm) irradiation for 48 h; TLC detection, after centrifugation, extraction, column chromatography, to obtain the product 3-isobutylamine quinoxalin-2(lH)-one 3w of this example, white solid 27.4 mg, yield 63%.

[0133] The obtained product nuclear magnetic spectrum data are: 1 H NMR (400 MHz, Chloroform-d) δ 11.57 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.30-7.24 (m, 1H), 7.21 (d, J = 2.4 Hz, 2H), 6.42 (t, J = 6.1 Hz, 1H), 3.44 (t, J = 6.4 Hz, 2H), 2.06 (dp, J = 13.5, 6.8 Hz, 1H), 1.07 (d, J = 6.6 Hz, 6H).

[0134] Example 28

[0135]

[0136] In a Schlenk tube was added quinoxalin-2(lH)-one (la, 0.20 mmol), isobutylamine (2w, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL), mixed well; the reaction vessel was stirred under O2balloon atmosphere, room temperature blue LED light (450-455 nm) irradiation for 48 h; TLC detection, after centrifugation, extraction, column chromatography, to obtain the product 3-isobutylamine quinoxalin-2(lH)-one 3w of this example, white solid 27.4 mg, yield 63%.

[0137] The obtained product nuclear magnetic spectrum data are: 1H NMR (400 MHz, Chloroform-d) δ 11.71 (s, 1H), 7.63-7.58 (m, 1H), 7.40-7.29 (m, 5H), 7.28-7.19 (m, 3H), 6.44 (t, J = 5.7 Hz, 1H), 3.88 (q, J = 6.8 Hz, 2H), 3.06 (t, J = 7.2 Hz, 2H).

[0138] Example 29

[0139]

[0140] In a Schlenk tube, quinoxalin-2(lH)-one (la, 0.20 mmol), 2- methylimidazole (2y, 0.60 mmol), DABCO (2 equiv, 44.8 mg), mpg-C3N4(20.0 mg) and tetrahydrofuran (3.0 mL) were mixed homogeneously; the reaction vessel was stirred under O2 balloon atmosphere, irradiated by blue light LED lamp (450-455 nm) at room temperature for 45 h; TLC detection, after centrifugation, extraction, column chromatography, the 2-methylimidazole quinoxalin-2(lH)-one product 3y of this example was obtained as a white solid 26.2 mg, yield 48%; the product can be used as a PAS kinase modulator.

[0141] The obtained product had the following NMR spectrum data: 1 H NMR (400 MHz, DMSO-d6) δ 12.03 (s, 1H), 7.69 (d, J = 1.9 Hz, 1H), 7.62 (dd, J = 8.4, 1.9 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 4.12 (s, 2H), 3.83 (s, 3H), 3.60 (d, J = 6.6 Hz, 2H), 1.87 (s, 4H).

[0142] As shown in Figure 2 The recycling experiment of mpg-C3N4 proved that the catalytic activity of mpg-C3N4 remained basically unchanged after 4 times of recycling and reuse.

[0143] As shown in Figure 3 The effect of increasing DABCO concentration on the fluorescence quenching of mpg-C3N4 was shown in Figure 6, which followed the Stern-Volmer plot: Io / I = 1 + Ksv[C], where Io and I determined the fluorescence intensity in the absence and presence of the quencher, and [C] was the quencher concentration. All mpg-C3N4 solutions were measured at 350 nm, and the emission intensity was collected at 360-700 nm. Three measurements were made at different concentrations using the corresponding quencher. With the increase of DABCO concentration, the emission intensity of the excited photocatalyst was significantly reduced, and fluorescence quenching phenomenon occurred.

[0144] like Figure 4 As shown, cyclic voltammetry studies of DABCO in acetonitrile were performed on a Chi660e workstation using a glassy carbon working electrode, an Ag / AgCl in 3M NaCl reference electrode, and a platinum counter electrode. The sample (0.2 mmol) was dissolved in 0.1M tetrabutylammonium hexafluorophosphate (TBAPF6) solution (25 mL) to prepare a solution. At 100 mV / s, the potential range was typically scanned between 0 V and 1.8 V. The half-wave potential of DABCO was 0.72 V (E ox =+0.80V vs.SCE,E red =+0.64V vs.SCE,E 1 / 2 ox = +0.72 V vs. SCE.) Literature indicates that the conduction band reduction potential of mesoporous graphitic carbon nitride is -1.5 V vs. SCE, the valence band oxidation potential is +1.2 V vs. SCE, and its band gap is 2.7 V. DABCO not only acts as a base to assist in the deprotonation of the final cationic adduct, but also, as shown by fluorescence quenching experiments and cyclic voltammetry, DABCO can function as an electron transfer agent, suggesting the possibility of single electron transfer from DABCO to carbon nitride.

[0145] There are other technical features that are the same or similar to those of using the compounds represented by general formulas 1 and 2 as starting materials, using carbon nitride to carry out a 3-amination reaction of quinoxaline-2(1H)-one under oxygen and light reaction conditions to obtain the compound represented by general formula 3, which are all one embodiment of the present invention, and the various technical features of the above-mentioned embodiments can be combined arbitrarily. The above embodiment is only one implementation form of the method for preparing 3-aminoquinoxaline-2(1H)-one compounds based on carbon nitride photocatalysis provided by the present invention. According to other variations of the scheme provided by the present invention, adding or reducing components or steps therein, or applying the present invention to other technical fields close to the present invention, all fall within the scope of protection of the present invention.

Claims

1. A method for photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds, characterized by, The method comprises the following steps: A quinoxaline-2(l H )-ketone compound, a fatty amine compound, a photocatalyst mesoporous graphite phase carbon nitride mpg-C3N4 and a base DABCO are added into an organic solvent and uniformly mixed; the reaction is carried out under light irradiation in an oxygen atmosphere; after the reaction is completed, a 3-aminoquinoxaline-2(l H )-ketone product is obtained by treatment and separation; the general reaction formula is as follows: ， wherein R in structural formula 1 is hydrogen, fluorine, bromine, formate, alkoxy, methyl, or aryl; and wherein structural formula 2 is morpholine, 2,6-dimethylmorpholine, 2-methylmorpholine, piperidine, 4-methylpiperidine, 4-cyanopiperidine, 4-phenylpiperidine, 1-tert-butoxycarbonylpiperazine, thiomorpholine, tetrahydropyrrole, dimethylamine, methylamine, ethylamine, butylamine, heptylamine, isobutylamine, or phenethylamine. 1 wherein R in structural formula 1 is hydrogen, fluorine, bromine, formate, alkoxy, methyl, or aryl; and wherein structural formula 2 is morpholine, 2,6-dimethylmorpholine, 2-methylmorpholine, piperidine, 4-methylpiperidine, 4-cyanopiperidine, 4-phenylpiperidine, 1-tert-butoxycarbonylpiperazine, thiomorpholine, tetrahydropyrrole, dimethylamine, methylamine, ethylamine, butylamine, heptylamine, isobutylamine, or phenethylamine.

2. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, The mass of the photocatalyst mesoporous graphite phase carbon nitride is 10 mg-30 mg.

3. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, The base DABCO is 2 equivalents.

4. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, The molar ratio of the quinoxaline-2(l H )-ketone compound and the aliphatic amine compound is 0.2:0.4-0.2:0.

6.

5. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, The organic solvent is tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, toluene, chlorobenzene, nitrobenzene or 1,4-dioxane.

6. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, The light source of the light irradiation is a blue LED lamp of 450-455 nm or an ultraviolet LED lamp of 390-400 nm.

7. The method of photocatalytic preparation of 3-aminoquinoxaline-2(l H )-ketone compounds according to claim 1, characterized by, After the reaction is completed, the reaction solution is subjected to centrifugal treatment to separate the catalyst, saturated brine solution is added to wash the reaction solution, then ethyl acetate is added for extraction, the extract is dried with anhydrous sodium sulfate, then the extract is subjected to concentration treatment until no solvent is left, to obtain a crude product, then column chromatography treatment is performed, the product is eluted with a mixed eluent of ethyl acetate and petroleum ether in a volume ratio of 1:3, and 1% triethylamine is added, so that the product is better separated out in silica gel, and the 3-aminoquinoxaline-2(1 H )-one product is obtained after rapid column chromatography.

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