Method for preparing 2-aminoquinoline derivative

Abstract

The invention discloses a method for preparing a 2-aminoquinoline derivative, which comprises the following steps: taking a compound 1 and a compound 2 as reaction substrates, carrying out electrocatalytic reaction in an electrolyte solution, and purifying to obtain the 2-aminoquinoline derivative. According to the preparation method, alkali metal does not need to participate in reaction, high-temperature heating is not needed, and meanwhile the reaction time needed by a traditional synthesis route can be shortened.

Description

Technical Field

[0001] The present invention belongs to the technical field of compound preparation, and particularly relates to a method for preparing 2-aminoquinoline derivatives. Background Art

[0002] 2-Aminoquinoline derivatives are a class of heterocyclic compounds with diverse structures and rich functions. With their unique quinoline skeletons and modifiable amino functional groups, they exhibit extensive application values in fields such as medicine, materials science, and agrochemistry. In the pharmaceutical field, 2-aminoquinoline derivatives have antibacterial and antimalarial effects and play an important role in anti-infective drugs. Among them, chloroquine and its structural analogs are the most representative, and it can inhibit the growth of Plasmodium falciparum by chelating heme. 2-Aminoquinoline derivatives also have antitumor effects. The 2-aminoquinoline skeleton can intervene in tumor growth through kinase inhibition. For example, CX-4945 (Silmitasertib) selectively inhibits casein kinase 2 (CK2) to block the proliferation and survival signaling pathways of tumor cells. In the field of materials science, 2-aminoquinoline derivatives can be used as fluorescent probes (such as quinoline fluorescent probes) for detecting metal ions, cell imaging, or biothiols. In addition, they also have extensive applications in pesticides and can be used as fungicides and insecticides.

[0003] In the future, 2-aminoquinoline derivatives will achieve breakthrough applications in fields such as precision medicine, intelligent sensing, and sustainable agriculture through the integration of artificial intelligence-assisted design, multi-target drug development, and green synthesis technologies. In recent years, the design synthesis, structural modification, and application research of 2-aminoquinoline derivatives have become research hotspots in the fields of organic chemistry and medicinal chemistry, attracting extensive attention from many research teams.

[0004] In 2018, the Quan research group reported a method for synthesizing N,4-diphenylquinolin-2-amine using potassium phosphate as the base and 1,4-dioxane as the solvent under conventional heating conditions.

[0005]

[0006] However, in the process of synthesizing N,4-diphenylquinolin-2-amine compounds, the above synthesis method requires expensive and highly toxic reaction substrates and base reagents, and this preparation route has a high reaction temperature, a long synthesis time, and the reaction conditions also need to be carried out at 100 °C, and the reaction conditions are relatively harsh. Therefore, exploring a new method for synthesizing 2-aminoquinoline derivatives with high yield and mild reaction conditions has become the current main demand. Summary of the Invention

[0007] In view of this, the present invention provides a method for preparing 2-aminoquinoline derivatives, which does not require the participation of alkali metals in the reaction, does not require high-temperature heating, and can also reduce the reaction time required by the traditional synthesis route.

[0008] To solve the above problems, the present invention provides a method for preparing 2-aminoquinoline derivatives, comprising the following steps:

[0009] Using compound 1 and compound 2 as reaction substrates, an electrocatalytic reaction is carried out in an electrolyte solution, and after purification, 2-aminoquinoline derivatives are obtained;

[0010] The compound 1 has the structure shown in formula a, the compound 2 has the structure shown in formula b, and the 2-aminoquinoline derivative has the structure shown in formula c:

[0011]

[0012] Wherein R1 and R2 are independently selected from hydrogen, aryl, methyl, methoxy, halogen substituents or phenyl;

[0013] The electrocatalytic reaction is carried out under the condition of passing a direct current constant current between the electrode anode and the electrode cathode, and the direct current constant current is 5-20 mA; the temperature of the electrocatalytic reaction is 20-50 °C, and the reaction time is 3-5 h.

[0014] Preferably, the molar ratio of the compound 1 to the compound 2 is 1:0.5-2.

[0015] Preferably, the molar / volume ratio of the electrolyte to acetonitrile in the solution is 0.1-0.4 mmol:4-5 ml.

[0016] Preferably, the volume ratio of acetonitrile to water in the solution is 10:1-2:1.

[0017] Preferably, the electrolyte includes one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium acetate, and sodium iodide.

[0018] Preferably, the electrolyte includes tetrabutylammonium iodide and / or sodium iodide.

[0019] Preferably, the solution further includes a magnetic stir bar.

[0020] Preferably, the electrocatalytic reaction is carried out in an electrolytic cell, and the electrode materials in the electrolytic cell are one or more of carbon rods, carbon plates, platinum sheets, nickel sheets, and iron sheets.

[0021] Preferably, the purification process is carried out by column chromatography separation in a silica gel column.

[0022] Preferably, the eluent for purification has a composition of petroleum ether: ethyl acetate = 10:1.

[0023] Beneficial effects:

[0024] The present invention provides a method for preparing 2 - aminoquinoline derivatives. Using compound 1 and compound 2 as reaction substrates, an electrocatalytic reaction is carried out in an electrolyte solution to obtain 2 - aminoquinoline derivatives through purification. The present invention proposes a novel route for synthesizing 2 - aminoquinoline derivatives by electrocatalysis. Without the need for alkali metal catalysts and high - temperature heating conditions, it can efficiently react to prepare 2 - aminoquinoline derivatives only under the conditions of a direct - current constant current of 5 - 20 mA and a reaction temperature of 25 °C (room temperature).

[0025] The results of the examples show that the method for preparing 2 - aminoquinoline derivatives provided by the present invention can not only react at 25 °C (room temperature) to obtain 2 - aminoquinoline derivatives without the need for expensive alkaline catalysts and harsh reaction conditions. At the same time, this preparation route can also achieve a product yield of 88% within a relatively short time of 3 - 5 h. Compared with the reaction cycle of 12 h in synthetic route 1 using an alkali catalyst in Comparative Example 1, the highest product yield is 84%. While the yield is improved, the reaction time is significantly shortened.

[0026] The preparation route of 2 - aminoquinoline derivatives provided by the present invention has high reaction tolerance. Among them, various types of substituents of compound 2 can all react and achieve a relatively high yield, with high generality. Description of the Drawings

[0027] Figure 1 1H NMR spectrum of the target product 3a prepared in Example 1 1 1H NMR spectrum;

[0028] Figure 2 1H NMR spectrum of the target product 3a prepared in Example 1 13 13C NMR spectrum;

[0029] Figure 3 1H NMR spectrum of the target product 3b prepared in Example 2 1 1H NMR spectrum;

[0030] Figure 4 1H NMR spectrum of the target product 3b prepared in Example 2 13 13C NMR spectrum;

[0031] Figure 5 1H NMR spectrum of the target product 3c prepared in Example 3 1 1H NMR spectrum;

[0032] Figure 6 1H NMR spectrum of the target product 3c prepared in Example 3 1313C NMR spectrum;

[0033] Figure 7 of the target product 3d prepared in Example 4 1 1H NMR spectrum;

[0034] Figure 8 of the target product 3d prepared in Example 4 13 13C NMR spectrum;

[0035] Figure 9 of the target product 3e prepared in Example 5 1 1H NMR spectrum;

[0036] Figure 10 of the target product 3e prepared in Example 5 13 13C NMR spectrum;

[0037] Figure 11 of the target product 3f prepared in Example 6 1 1H NMR spectrum;

[0038] Figure 12 of the target product 3f prepared in Example 6 13 13C NMR spectrum;

[0039] Figure 13 of the target product 3g prepared in Example 7 1 1H NMR spectrum;

[0040] Figure 14 of the target product 3g prepared in Example 7 13 13C NMR spectrum;

[0041] Figure 15 of the target product 3h prepared in Example 8 1 1H NMR spectrum;

[0042] Figure 16 of the target product 3h prepared in Example 8 13 13C NMR spectrum;

[0043] Figure 17 of the target product 3i prepared in Example 9 1 1H NMR spectrum;

[0044] Figure 18 of the target product 3i prepared in Example 9 13 13C NMR spectrum. Detailed implementation mode

[0045] The present invention provides a method for preparing 2-aminoquinoline derivatives, comprising the following steps:

[0046] Using compound 1 and compound 2 as reaction substrates, an electrocatalytic reaction is carried out in an electrolyte solution, and after purification, 2-aminoquinoline derivatives are obtained.

[0047] In the present invention, the compound 1 has the structure shown in formula a,

[0048]

[0049] The R1 is independently preferably any one of hydrogen, aryl, methyl, methoxy, halogen substituent or phenyl; in the present invention, the halogen substituent is preferably any one of Cl, Br, F.

[0050] In the present invention, the compound 2 has the structure shown in formula b,

[0051]

[0052] The R2 is independently preferably any one of hydrogen, aryl, methyl, methoxy, halogen substituent or phenyl; in the present invention, the halogen substituent is preferably any one of Cl, Br, F.

[0053] In the present invention, the 2-aminoquinoline derivative has the structure shown in formula c:

[0054]

[0055] In the present invention, the electrocatalytic reaction is carried out under the condition of passing a direct current constant current between the electrode anode and the electrode cathode; the electrocatalytic reaction is carried out in an electrolytic cell, the electrolytic cell is provided with an electrode anode and an electrode cathode, and the electrolytic cell is configured with an electrolyte solution.

[0056] In the present invention, the direct current constant current is 5-20 mA, preferably 10-15 mA; in the present invention, the temperature of the electrocatalytic reaction is 20-50 °C, preferably 25-35 °C; the time of the electrocatalytic reaction is 3-5 h, preferably 4 h;

[0057] In the present invention, the molar ratio of the compound 1 to the compound 2 is 1:0.5-2, further preferably 1:2, 1:1 or 2:1.

[0058] In the present invention, the molar ratio of the compound 1 to the electrolyte is 1:0.25-2, further preferably 4:1, 2:1, 1:1 or 1:2.

[0059] In the present invention, the electrolyte solution comprises an electrolyte, acetonitrile and water. The electrolyte solution is prepared in an electrolytic cell. The present invention uses inexpensive acetonitrile and water as solvents, which are green and environmentally friendly.

[0060] In the present invention, the molar volume ratio of the electrolyte to acetonitrile in the solution is 0.1 - 0.4 mmol: 4 - 5 ml, preferably 0.2 - 0.3 mmol: 4 - 5 ml. In the present invention, the volume ratio of acetonitrile to water in the solution is 10:1 - 2:1, preferably 4:1 - 5:1.

[0061] In the present invention, the electrolyte preferably comprises one or more of ammonium tetrabutylborate, ammonium tetrabutylhexafluorophosphate, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium acetate, sodium iodide.

[0062] In the present invention, the electrolyte is preferably tetrabutylammonium iodide and / or sodium iodide; in the present invention, the I in sodium iodide in the electrolyte solution - has a relatively high reducibility, can promote the reduction reaction at the cathode, accelerate the formation of reaction products, and improve the product yield.

[0063] In the present invention, the solution preferably further comprises a magnetic stirrer, and the magnetic stirrer is preferably a magnetic stirring bar. The main function of the magnetic stirrer in the present invention is to stir the solution, promote electron transfer or prevent the accumulation of deposits on the electrode surface, ensure that the reactants are evenly mixed and distributed in the electrolytic cell, and prevent precipitation or stratification phenomena. This uniform distribution can ensure that there are sufficient reactants on the electrode surface for electrochemical reactions, which helps to increase the reaction rate and improve the yield of the target product.

[0064] In the present invention, the electrocatalytic reaction is carried out in an electrolytic cell, and an electrode anode and an electrode cathode are provided in the electrolytic cell, and a direct current constant current can be passed through both ends of the electrodes. In the present invention, the preferred electrode materials for the electrocatalytic reaction are one or more of carbon rods, carbon plates, platinum sheets, nickel sheets, iron sheets, and further preferably platinum sheets.

[0065] After the electrocatalytic reaction in the present invention, the product is purified to obtain a 2 - aminoquinoline derivative.

[0066] In the present invention, the purification process preferably performs column chromatography separation on a silica gel column. The silica gel column chromatography separation includes the following steps:

[0067] 1. Prepare the chromatography column

[0068] Select a suitable chromatography column: Select a glass chromatography column with a matching size and length according to the needs.

[0069] Fill the silica gel: Slowly pour the silica gel into the chromatography column to ensure uniform filling, and place glass wool or other filtering materials at the bottom to prevent the loss of silica gel particles.

[0070] Wet silica gel: Moisten the silica gel with an eluent to make it fully expand so as to better adsorb compounds.

[0071] 2. Load the product

[0072] Dissolve the product: Dissolve the product to be separated in ethyl acetate, a low-polarity solvent.

[0073] Load into the chromatography column: Slowly pour the dissolved product into the chromatography column, ensuring that the compounds are fully adsorbed on the silica gel and avoiding the solution from flowing too fast to improve the separation effect.

[0074] 3. Elute and separate

[0075] Select an eluent for elution, slowly add the eluent, observe the color change of the effluent or use a detector to monitor the elution situation. When the target compound flows out, collect the corresponding fractions;

[0076] The composition of the eluent is petroleum ether:ethyl acetate = 10:1.

[0077] 4. Collect and analyze the fractions

[0078] Collect the fractions: Collect the effluent in segments, and the volume collected for each segment can be adjusted as needed.

[0079] Analyze the purity: Use thin-layer chromatography (TLC) or other analytical methods to detect the purity of the collected fractions and confirm whether the target compound is completely separated.

[0080] 5. Purification treatment

[0081] Concentrate the fractions: Concentrate the fractions containing target compound 3, and remove the eluent by rotary evaporation. Repeat the above operations on the concentrated product for chromatography separation 0 - 2 times.

[0082] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0083] Example 1

[0084] Configure an electrolyte solution in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL), water (1 mL). Add compound 1 (0.2 mmol) and a magnetic stir bar to the electrolytic cell in sequence, and add compound 2a (0.4 mmol) drop by drop.

[0085] Using a platinum sheet as the cathode and anode respectively, a direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin-layer chromatography until the reaction was complete. Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3a with a yield of 88%.

[0086] The reaction equation is as follows:

[0087]

[0088] The 1H NMR spectrum of the target product 3a obtained in Example 1 is as Figure 1 shown, and the 13C NMR spectrum is as Figure 2 shown:

[0089] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.85 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.62 - 7.56 (m, 3H), 7.50 - 7.47 (m, 5H), 7.85 (t, J = 7.6 Hz, 2H), 7.27 - 7.23 (m, 2H), 7.11 - 7.07 (m, 1H), 6.94 (s, 1H);

[0090] 13 C NMR (100 MHz, CDCl3, ppm): δ 154.0, 150.4, 148.1, 140.1, 138.2, 129.9, 129.4, 129.4, 128.6, 128.4, 127.0, 125.8, 123.2, 123.1, 123.0, 120.6, 111.6.

[0091] Example 2

[0092] An electrolyte solution was prepared in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL) and water (1 mL). Compound 1b (0.2 mmol) and a magnetic stir bar were successively added to the electrolytic cell, and finally compound 2 (0.4 mmol) was added dropwise.

[0093] Using a platinum sheet as the cathode and anode respectively, a direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin-layer chromatography until the reaction was complete. Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3b with a yield of 84%.

[0094] The reaction equation is as follows:

[0095]

[0096] The 1H NMR spectrum of the target product 3b obtained in Example 2 is as follows Figure 3 shown, and the 13C NMR spectrum is as follows Figure 4 shown:

[0097] 1 H NMR(400MHz,CDCl3,ppm):δ7.76(d,J=8.4Hz,1H),7.55(d,J=8.0Hz,2H),7.48-7.40(m,7H),7.50-7.47(m,5H),7.33(t,J=7.6Hz,2H),7.03(t,J=7.2Hz,1H),6.92(s,1H),6.88(s,1H);

[0098] 13 C NMR(100MHz,CDCl3,ppm):δ153.5,149.7,146.6,140.5,138.5,132.8,131.8,129.4,129.3,128.5,128.3,127.0,124.8,123.1,122.9,120.3,111.7,21.51.

[0099] Example 3

[0100] An electrolyte solution was prepared in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL) and water (1 mL). Compound 1 (0.2 mmol) and a magnetic stir bar were successively added to the electrolytic cell, and finally compound 2c (0.4 mmol) was added dropwise.

[0101] A platinum plate was used as the cathode and anode respectively. A direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin layer chromatography until the reaction was complete.

[0102] Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3c with a yield of 85%.

[0103] The reaction equation is as follows:

[0104]

[0105] The 1H NMR spectrum of the target product 3c obtained in Example 3 is as follows Figure 5 shown, and the 13C NMR spectrum is as follows Figure 6 shown:

[0106] 11H NMR (400 MHz, CDCl3, ppm): δ 7.82 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.2 Hz, 1H), 7.48 - 7.40 (m, 7H), 7.24 - 7.20 (m, 7H), 7.16 (d, J = 8.0 Hz, 2H), 6.90 (s, 1H);

[0107] 13 13C NMR (100 MHz, CDCl3, ppm): δ 154.5, 150.2, 148.4, 138.4, 137.5, 133.1, 129.9, 129.7, 129.4, 128.5, 128.3, 127.0, 125.8, 123.1, 122.9, 121.4, 111.2, 20.90.

[0108] Example 4

[0109] An electrolyte solution was prepared in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL) and water (1 mL). Compound 1 (0.2 mmol) and a magnetic stir bar were successively added to the electrolytic cell, and finally compound 2d (0.4 mmol) was added dropwise.

[0110] Platinum plates were used as the cathode and anode respectively. A direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin-layer chromatography until the reaction was complete.

[0111] Finally, purification was carried out by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3d with a yield of 79%. The reaction equation is as follows:

[0112]

[0113] The 1H nuclear magnetic resonance spectrum of the target product 3d obtained in Example 4 is as Figure 7 shown, and the 13C nuclear magnetic resonance spectrum is as Figure 8 shown:

[0114] 1 1H NMR (400 MHz, CDCl3, ppm): δ 7.89 (d, J = 8.4 Hz, 1H), 7.82 - 7.81 (m, 1H), 7.71 - 7.69 (m, 1H), 7.61 - 7.57 (m, 1H), 7.51 - 7.43 (m, 6H), 7.27 - 7.20 (m, 2H), 7.01 - 6.99 (m, 1H), 6.95 (s, 1H), 6.80 (s, 1H);

[0115] 1313C NMR (100 MHz, CDCl3, ppm): δ 153.2, 150.4, 148.0, 141.7, 138.0, 134.8, 130.1, 129.9, 129.4, 128.6, 128.5, 127.4, 125.8, 123.6, 123.3, 122.6, 119.7, 117.7, 112.2.

[0116] Example 5

[0117] An electrolyte solution was prepared in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL), and water (1 mL). Compound 1 (0.2 mmol) and a magnetic stir bar were successively added to the electrolytic cell, and finally, compound 2e (0.4 mmol) was added dropwise.

[0118] A platinum sheet was used as both the cathode and the anode. A direct current of 10 mA was passed between the anode and the cathode, and the reaction was carried out at 25 °C for 4 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete.

[0119] Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3e in 80% yield. The reaction equation is as follows:

[0120]

[0121] The 1H NMR spectrum of the target product 3e obtained in Example 5 is as shown in Figure 9 and the 13C NMR spectrum is as shown in Figure 10 as follows:

[0122] 1 1H NMR (400 MHz, CDCl3, ppm): δ 7.85 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.61 - 7.56 (m, 3H), 7.49 - 7.43 (m, 5H), 7.30 - 7.22 (m, 3H), 6.94 (s, 1H), 6.81 (s, 1H);

[0123] 13 13C NMR (100 MHz, CDCl3, ppm): δ 153.5, 150.4, 148.0, 138.9, 138.1, 129.9, 129.3, 129.2, 128.6, 128.5, 127.6, 127.2, 125.8, 123.5, 123.2, 121.3, 111.9.

[0124] Example 6

[0125] Prepare an electrolyte solution in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL), and water (1 mL). Add compound 1 (0.2 mmol) and a magnetic stir bar to the electrolytic cell in sequence, and finally add compound 2f (0.4 mmol) dropwise.

[0126] Use platinum plates as the cathode and anode respectively. Pass a direct constant current of 10 mA between the electrode anode and the electrode cathode, and react at 25 °C for 4 h. Monitor the reaction process by thin-layer chromatography until the reaction is complete.

[0127] Finally, separate and purify by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3f with a yield of 76%.

[0128] The reaction equation is as follows:

[0129]

[0130] The 1H NMR spectrum of the target product 3f obtained in Example 6 is as Figure 11 shown, and the 13C NMR spectrum is as Figure 12 shown:

[0131] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.88 (d, J = 8.4 Hz, 1H), 7.74 - 7.67 (m, 2H), 7.59 - 7.55 (m, 1H), 7.48 - 7.40 (m, 5H), 7.25 - 7.17 (m, 3H), 7.06 (s, 1H), 6.79 (s, 1H), 6.73 - 6.68 (m, 1H);

[0132] 13 C NMR (100 MHz, CDCl3, ppm): δ 163.4 (d, J = 242.2 Hz, 1C), 153.3, 150.4, 148.1, 142.1 (d, J = 11.0 Hz, 1C), 138.1, 130.1 (d, J = 9.7 Hz, 1C), 129.9, 129.4, 128.6, 128.5, 127.4, 125.8, 123.6, 123.3, 115.0 (d, J = 2.6 Hz, 1C), 112.3, 109.1 (d, J = 21.4 Hz, 1C), 106.8 (d, J = 25.8 Hz, 1C).

[0133] Example 7

[0134] Prepare an electrolyte solution in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL), and water (1 mL). Add compound 1 (0.2 mmol) and a magnetic stir bar to the electrolytic cell in sequence, and finally add compound 2g (0.4 mmol) dropwise.

[0135] Use platinum plates as the cathode and anode respectively. Pass a direct constant current of 10 mA between the electrode anode and the electrode cathode, and react at 25 °C for 4 h. Monitor the reaction progress by thin-layer chromatography until the reaction is complete.

[0136] Finally, separate and purify by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3g with a yield of 79%. The reaction equation is as follows:

[0137]

[0138] The 1H NMR spectrum of the target product 3g obtained in Example 7 is as Figure 13 shown, and the 13C NMR spectrum is as Figure 14 shown:

[0139] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.83 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.50 - 7.43 (m, 5H), 7.39 - 7.37 (m, 1H), 7.33 (s, 1H), 7.25 - 7.20 (m, 2H), 6.93 - 6.88 (m, 3H), 2.35 (s, 3H);

[0140] 13 C NMR (100 MHz, CDCl3, ppm): δ 154.2, 150.2, 148.4, 140.1, 139.2, 138.3, 129.7, 129.4, 129.1, 128.5, 128.3, 127.1, 125.8, 124.1, 123.1, 123.1, 121.4, 117.8, 111.6, 21.6.

[0141] Example 8

[0142] Prepare an electrolyte solution in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL), and water (1 mL). Add compound 1 (0.2 mmol) and a magnetic stir bar to the electrolytic cell in sequence, and finally add compound 2h (0.4 mmol) dropwise.

[0143] Using a platinum sheet as the cathode and anode respectively, a direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin-layer chromatography until the reaction was complete.

[0144] Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3h with a yield of 76%. The reaction equation is as follows:

[0145]

[0146] The 1H NMR spectrum of the target product 3h obtained in Example 8 is as Figure 15 shown, and the 13C NMR spectrum is as Figure 16 shown:

[0147] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.79 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.60 - 7.56 (m, 1H), 7.47 - 7.43 (m, 5H), 7.26 - 7.20 (m, 3H), 7.08 (t, J = 7.6 Hz, 1H), 6.81 (s, 1H), 6.74 (s, 1H), 2.33 (s, 3H);

[0148] 13 C NMR (100 MHz, CDCl3, ppm): δ 155.1, 150.4, 148.5, 138.4, 138.1, 131.6, 131.1, 129.8, 129.4, 128.5, 128.3, 127.0, 126.7, 125.9, 124.8, 123.5, 123.1, 122.9, 110.6, 18.2.

[0149] Example 9

[0150] An electrolyte solution was prepared in an electrolytic cell: sodium iodide (0.4 mmol), acetonitrile (4 mL) and water (1 mL). Compound 1 (0.2 mmol) and a magnetic stir bar were added to the electrolytic cell in sequence, and finally compound 2i (0.4 mmol) was added dropwise.

[0151] Using a platinum sheet as the cathode and anode respectively, a direct current of 10 mA was passed between the electrode anode and the electrode cathode, and the reaction was carried out at 25 °C for 4 h. The reaction process was monitored by thin-layer chromatography until the reaction was complete.

[0152] Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3i with a yield of 80%. The reaction equation is as follows:

[0153]

[0154] The 1H NMR spectrum of the target product 3i obtained in Example 9 is as follows Figure 17 shown, and the 13C NMR spectrum is as follows Figure 18 shown:

[0155] 1 H NMR(400MHz,CDCl3,ppm):δ7.82(d,J=8.4Hz,1H),7.69-7.66(m,1H),7.60-7.55(m,1H),7.48-7.42(m,7H),7.24-7.17(m,3H),6.91(s,1H),2.66-2.60(m,2H),1.24(t,J=7.6Hz,3H);

[0156] 13 C NMR(100MHz,CDCl3,ppm):δ154.5,150.2,148.4,139.5,138.4,137.6,129.7,129.4,128.7,128.5,128.3,127.0,125.8,123.1,123.0,121.3,111.2,28.4,15.8.

[0157] Comparative Example 1

[0158] Reactants and reagents were added to the reactor: potassium phosphate (0.2 mol), compound 1 - vinyl aniline (0.2 mmol), solvent 1,4 - dioxane (3 mL), water (1 mL), and compound 2 - isothiocyanate (0.4 mmol) was added dropwise;

[0159] The reaction was carried out at 100 °C for 12 h, and the reaction process was monitored by thin - layer chromatography until the reaction was complete. Finally, it was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain compound 3a with a yield of 84%.

[0160] The reaction equation is as follows:

[0161]

[0162] By comparing the different synthetic routes of Example 1 and Comparative Example 1, it can be seen that on the premise of preparing the same target product, the yield of the target product 3a obtained by the preparation method provided in Example 1 is higher than that of Comparative Example 1, and the reaction time required is greatly reduced.

[0163] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on this embodiment without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing 2-aminoquinoline derivatives, characterized in that, It includes the following steps: Using Compound 1 and Compound 2 as reaction substrates, an electrocatalytic reaction is carried out in an electrolyte solution, and after purification, a 2-aminoquinoline derivative is obtained; Compound 1 has the structure shown in Formula a, Compound 2 has the structure shown in Formula b, and the 2-aminoquinoline derivative has the structure shown in Formula c: wherein R1 and R2 are independently selected from hydrogen, aryl, methyl, methoxy, halogen substituents or phenyl; The electrocatalytic reaction is carried out under the condition of passing a direct current constant current between the electrode anode and the electrode cathode, and the direct current constant current is 5-20 mA; the temperature of the electrocatalytic reaction is 20-50 °C, and the reaction time is 3-5 h.

2. The preparation method according to claim 1, characterized in that, The molar ratio of Compound 1 to Compound 2 is 1:0.5-2.

3. The preparation method according to claim 1, wherein The molar / volume ratio of the electrolyte to acetonitrile in the solution is 0.1-0.4 mmol:4-5 ml.

4. The preparation method according to claim 1, characterized in that, The volume ratio of acetonitrile to water in the solution is 10:1 - 2:

1.

5. The preparation method according to claim 1, wherein The electrolyte includes one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium acetate, sodium iodide.

6. The preparation method according to claim 5, characterized in that The electrolyte includes tetrabutylammonium iodide and / or sodium iodide.

7. According to the preparation method described in claim 1, characterized in that, The solution also includes a magnetic stir bar.

8. According to the preparation method described in claim 1, wherein, The electrocatalytic reaction is carried out in an electrolytic cell, and the electrode material in the electrolytic cell is one or more of carbon rods, carbon plates, platinum sheets, nickel sheets, iron sheets.

9. The preparation method according to claim 1, wherein The purification process is carried out by column chromatography separation in a silica gel column.

10. The preparation method according to claim 1, characterized in that, The eluent for purification has a composition of petroleum ether:ethyl acetate = 10:1.

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