N-(dioxolane ketone group) indole compound and preparation method thereof

Abstract

The invention discloses an N-(dioxolame ketone) indole compound and a preparation method thereof, and belongs to the technical field of pharmaceutical chemical industry and related chemistry. According to the method, vinylene carbonate and an indole compound are used as raw materials to prepare the novel N-(dioxolame ketone) indole compound under the synergistic catalysis of copper-alkali, and green and efficient synthesis of the N-(dioxolame ketone) indole compound is realized. The method has the advantages of high selectivity, mild reaction conditions, good functional group compatibility, wide substrate range, environmental friendliness and the like. The indole compound is an important organic synthesis intermediate and has very wide application in the fields of fine chemical engineering and pharmacy, so that the indole compound has relatively high application value and social and economic benefits.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical and chemical intermediates and related chemistry, and relates to an N-(dioxolanonyl)indole compound and a method for preparing an N-(dioxolanonyl)indole compound using an indole compound and a vinylene carbonate compound as raw materials. Background Art

[0002] N-functionalized indole compounds are important intermediates for synthesizing natural products, drugs, or functional molecules, and have very wide applications in the field of organic synthesis. Since the discovery of indole, organic chemists have carried out various studies on its synthesis and functionalization reactions; N-functionalized indole compounds, especially in the synthesis of pharmaceuticals and pesticides, etc., show great uses, so the synthesis of N-functionalized indole compounds is one of the current research hotspots. With the increasing attention of people to sustainable development and human health, green chemistry, which features high efficiency, low pollution, and high atom economy, has been increasingly concerned; N-(dioxolanonyl)indole compounds are a new type of N-functionalized indole. However, in the currently reported indole N-functionalization reactions, there are no relevant reports on using vinylene carbonate as an indole N-functionalization reagent. Summary of the Invention

[0003] To solve the problems existing in the prior art, the present invention uses indole and vinylene carbonate to react, and provides a method for synthesizing N-(dioxolanonyl)indole compounds with high selectivity, high yield, mild reaction conditions, high atom economy, and good catalytic effect, which is of great significance. This method uses indole and vinylene carbonate as raw materials to achieve the addition reaction of copper-base synergistic catalyzed indole and vinylene carbonate to synthesize N-(dioxolanonyl)indole compounds. This method has the advantages of simple catalytic system, good selectivity, mild conditions, good atom economy, environmental friendliness, and easy industrialization. The present invention has great application value and social and economic benefits.

[0004] The technical solution adopted by the present invention is: an N-(dioxolanonyl)indole compound, characterized in that the general structural formula of the compound is as follows:

[0005] Wherein: the substituent R on the indole ring = hydrogen, C 1-6 a straight-chain or branched-chain alkyl group, an aryl group, an amino group, a hydroxyl group, an alkoxy group, an alkoxycarbonyl group, a cyano group, a nitro group, a halogen, and the substituent R is at the 2, 3, 4, 5, 6, or 7 position of the indole ring. Using vinylene carbonate and indole compounds as raw materials, a series of N-(dioxolanonyl)indole compounds are synthesized through a copper-base synergistic catalytic addition reaction. This method includes the following steps:

[0006] The synthetic route is as follows:

[0007]

[0008] Wherein: R = hydrogen, C 1-6 a straight-chain or branched-chain alkyl group, aryl group, amino group, hydroxyl group, alkoxy group, alkoxycarbonyl group, cyano group, nitro group, halogen.

[0009] (1) Add the indole compound, copper-base synergistic catalyst, vinylene carbonate and organic solvent into the reactor in sequence, and react at 25 - 150 °C for 4 - 36 h; the molar ratio of the indole compound to vinylene carbonate is 1:1 - 1:5, the molar ratio of the indole compound to the copper catalyst is 1:0.01 - 1:0.2, and the molar ratio of the indole compound to the base catalyst is 1:0.01 - 1:0.7;

[0010] (2) After the reaction is completed, remove the solvent by distillation under reduced pressure, and perform silica gel column separation with an eluent to obtain the N-(dioxolanonyl) indole compound.

[0011] The indole compounds include indoles containing hydrogen, containing C 1-6 a straight-chain or branched-chain alkyl group, containing an aryl group, containing an amino group, containing a hydroxyl group, containing an alkoxy group, containing an alkoxycarbonyl group, containing a cyano group, containing a nitro group, containing a halogen; R on the indole compound can be substituted at the 2nd, 3rd, 4th, 5th, 6th or 7th position, and the substituent R is hydrogen, C 1-6 a straight-chain or branched-chain alkyl group, aryl group, amino group, hydroxyl group, alkoxy group, alkoxycarbonyl group, cyano group, nitro group, halogen; the molar ratio of the indole compound to vinylene carbonate is 1:1 - 1:5.

[0012] The reaction temperature range is 25 - 150 °C, preferably 70 - 100 °C.

[0013] The reaction time range is 4 - 36 h, preferably 10 - 18 h.

[0014] The copper catalyst is selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous oxide, cuprous cyanide, bis(triphenylphosphine)cuprous borohydride, copper fluoride, copper chloride, copper bromide, copper acetate monohydrate, copper nitrate, copper sulfate, copper trifluoromethanesulfonate, copper trifluoroacetate, copper tartrate, basic copper carbonate, copper nitrate trihydrate, bis(acetylacetone)copper, copper oxide.

[0015] The base used is an inorganic base or an organic base, and the base catalyst is selected from potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium hydroxide, sodium hydroxide, lithium carbonate, potassium carbonate, sodium carbonate, cesium carbonate, ammonium carbonate, potassium bicarbonate, sodium bicarbonate, ammonium bicarbonate, sodium formate dihydrate, potassium formate, sodium acetate, potassium acetate, sodium propionate, potassium propionate, sodium pivalate, potassium pivalate, sodium trifluoroacetate, potassium trifluoroacetate, ammonium formate, ammonium acetate, pyridine, piperidine, piperazine, pyrrolidine, triethylamine, diisopropylethylamine, lithium hexamethyldisilazide, potassium hexamethyldisilazide;

[0016] The amount of the organic solvent is 1 to 500 mL, and the organic solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, trifluoroethanol, dichloromethane, chloroform, benzene, toluene, cyclohexane, n-pentane, n-hexane, n-heptane, diethyl ether, isopropyl ether, n-butyl ether, methyl tert-butyl ether, ethyl acetate, petroleum ether, fluorobenzene, trifluorotoluene, nitromethane, 1,4-dioxane, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, acetonitrile, dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate, water.

[0017] The molar ratio of the indole compound to the copper catalyst is 1:0.01 to 1:0.2.

[0018] The molar ratio of the indole compound to the base catalyst is 1:0.01 to 1:0.7.

[0019] The molar ratio of the indole compound to vinylene carbonate is 1:1 to 1:5.

[0020]

[0021]

[0022]

[0023] Advantages of the present invention: The N-(dioxolanone group) indole compounds and the preparation method thereof of the present invention have the advantages of high selectivity, mild reaction conditions, wide substrate applicability, environmental friendliness, etc. Specifically:

[0024] (1) The N-(dioxolanone group) indole compounds prepared by this method are a new type of N-functionalized indole compounds.

[0025] (2) This method is for the addition reaction of indole and vinylene carbonate. In the prior art, due to the addition reaction of indole to the carbon-carbon double bond, generally precious metal catalysis is required to proceed smoothly, and the catalyst cost is relatively high. In this application, due to the use of vinylene carbonate as an N-functionalization reagent, the addition reaction of indole can be achieved under mild and simple conditions.

[0026] (3) In this method, a synergistic catalytic system composed of copper and base is used, which reduces the cost of the catalytic system; the post-treatment of the reaction is simple.

[0027] (4) The catalytic effect is good, the selectivity and yield are high, and the yield is above 70%. This method is a synthesis method of N-(dioxolanyl)indole compounds with good selectivity, mild reaction conditions, high atom economy, good catalytic effect and high yield. Since N-functionalized indole compounds are an important organic synthesis intermediate and have very wide applications in the fields of medicine, pesticides and materials, therefore, the present invention has great application value and social and economic benefits.

[0028] (5) The N-(dioxolanyl)indole compounds prepared by this method have excellent inhibitory effects on Staphylococcus aureus and Escherichia coli, and the antibacterial rate reaches more than 99%. At the same time, such compounds can be used for the further functionalization transformation of indole compounds to synthesize N-vinyl indole and N-acetyl indole compounds, as shown in the following figure.

[0029]

[0030] In summary, this method is a synthesis method of N-(dioxolanyl)indole compounds with good selectivity, mild reaction conditions, high atom economy, good catalytic effect and high yield. Since N-functionalized indole compounds are an important organic synthesis intermediate and antibacterial active substance and have very wide applications in the fields of medicine, pesticides and materials, therefore, the present invention has great application value and social and economic benefits. Description of the Drawings

[0031] Figure 1 is the 1 1H-NMR of the compound in Example 26.

[0032] Figure 2 is the 13 13C-NMR of the compound in Example 26.

[0033] Figure 3 is the 1 1H-NMR of the compound in Example 28.

[0034] Figure 4 is the 13 13C-NMR of the compound in Example 28.

[0035] Figure 5 is the 1 1H-NMR of the compound in Example 29.

[0036] Figure 6 is the 13C-NMR.

[0037] Figure 7 It is the antibacterial test chart of Example 25.

[0038] Figure 8 It is the antibacterial test chart of Example 27. Detailed implementation manners

[0039] The preparation method of N-(dioxolan-2-one-yl) indole compounds described in the present invention has the advantages of inexpensive and easily available raw materials, good reaction selectivity, mild reaction conditions, environmental friendliness, high atom economy, etc., showing good application prospects.

[0040] The following combines specific examples to further illustrate the present invention. These examples are only used to illustrate the present invention and not to limit the scope of the present invention. Simple substitutions or improvements made by those skilled in the art to the present invention fall within the scope of the technical solutions protected by the present invention.

[0041] Using vinylene carbonate and indole compounds as raw materials, a series of N-(dioxolan-2-one-yl) indole compounds are synthesized through a copper-base synergistic catalytic addition reaction. The method includes the following steps:

[0042] The synthesis route is as follows:

[0043]

[0044] Wherein: R = hydrogen, C 1-6 Straight-chain or branched-chain alkyl, aryl, amino, hydroxyl, alkoxy, alkoxycarbonyl, cyano, nitro, halogen.

[0045] (1) Add indole compounds, copper-base synergistic catalyst, vinylene carbonate and organic solvent into the reactor in sequence, and react at 25 - 150 °C for 4 - 36 h; the molar ratio of indole compounds to vinylene carbonate is 1:1 - 1:5, the molar ratio of indole compounds to copper catalyst is 1:0.01 - 1:0.2, and the molar ratio of indole compounds to base catalyst is 1:0.01 - 1:0.7;

[0046] (2) After the reaction is completed, remove the solvent by vacuum distillation, and perform silica gel column separation with an eluent to obtain N-(dioxolan-2-one-yl) indole compounds.

[0047] Example 1: Synthesis of 4-(1H-indol-1-yl)-1,3-dioxolan-2-one (3a)

[0048]

[0049] Accurately weigh indole (0.12 g, 1.0 mmol), vinylene carbonate (0.26 g, 3.0 mmol), copper(I) chloride (5.0 mg, 0.05 mmol), and sodium carbonate (10.6 mg, 0.1 mmol), and successively add them to a 50 mL Schlenk flask. Add tetrahydrofuran (5.0 mL), and react in an oil bath at 90 °C for 18 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 4:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(1H-indol-1-yl)-1,3-dioxolan-2-one is 82%. 1 H NMR (400 MHz, d6-DMSO) δ 7.74 - 7.56 (m, 3H), 7.32 - 7.14 (m, 3H), 6.69 (d, J = 3.3 Hz, 1H), 5.04 (d, J = 6.3 Hz, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 154.1, 136.0, 129.5, 126.2, 123.2, 121.6, 121.6, 110.4, 105.6, 82.3, 68.4。

[0050] Example 2: Synthesis of methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-3-carboxylate (3b)

[0051]

[0052] Accurately weigh methyl indole-3-carboxylate (0.35 g, 2.0 mmol), vinylene carbonate (0.34 g, 4.0 mmol), copper(II) acetate monohydrate (20.0 mg, 0.10 mmol), and triethylamine (50.6 mg, 0.5 mmol), and successively add them to a 50 mL Schlenk flask. Add dichloromethane (6.0 mL), and react in an oil bath at 40 °C for 10 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:1) as the eluent, and separate by silica gel column chromatography. The yield of the product methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-3-carboxylate is 92%. 1 H NMR (400 MHz, d6-DMSO) δ 8.53 (s, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H), 7.42 - 7.33 (m, 2H), 7.28 - 7.21 (m, 1H), 5.17 - 4.99 (m, 2H), 3.86 (s, 3H).13 13C NMR (101 MHz, d6-DMSO) δ 164.5, 153.8, 136.0, 133.5, 126.9, 124.4, 123.5, 121.7, 111.2, 109.5, 82.4, 68.3, 51.6.

[0053] Example 3: Synthesis of 4-(4-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one (3c)

[0054]

[0055] Accurately weigh 4-methylindole (0.39 g, 3.0 mmol), vinylene carbonate (0.60 g, 7.0 mmol), copper(I) iodide (19.1 mg, 0.10 mmol), and sodium bicarbonate (40.0 mg, 0.5 mmol), and successively add them to a 50 mL Schlenk flask. Add N,N-dimethylformamide (9.0 mL), and react in an oil bath at 65 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure, and use petroleum ether / ethyl acetate (v / v 3:1) as the eluent for silica gel column chromatography separation. The yield of the product 4-(4-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one is 75%. 1 1H NMR (400 MHz, d6-DMSO) δ 7.68 (d, J = 3.4 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.23 - 7.14 (m, 2H), 6.98 (d, J = 7.2 Hz, 1H), 6.72 (d, J = 3.3 Hz, 1H), 5.03 (d, J = 6.4 Hz, 2H), 2.49 (s, 3H). 13 13C NMR (101 MHz, d6-DMSO) δ 154.1, 135.7, 130.6, 129.4, 125.6, 123.3, 121.7, 107.9, 104.1, 82.5, 68.4, 18.7.

[0056] Example 4: Synthesis of 4-(4-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one (3d)

[0057]

[0058] Accurately weigh 4-methoxyindole (1.47 g, 10.0 mmol), vinylene carbonate (1.72 g, 20.0 mmol), copper(II) bromide (223.4 mg, 1.0 mmol), and potassium hydrogen carbonate (100.1 mg, 1.0 mmol), and successively add them to a 100 mL Schlenk flask. Add dimethyl sulfoxide (40.0 mL), and place it in an oil bath at 75 °C for reaction for 20 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 4:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(4-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one is 70%. 1 H NMR (400 MHz, d6-DMSO) δ 7.59 (d, J = 3.4 Hz, 1H), 7.23 - 7.15 (m, 3H), 6.70 - 6.65 (m, 2H), 5.01 (d, J = 6.4 Hz, 2H), 3.89 (s, 3H). 13 C NMR (101 MHz, d6-DMSO) δ 154.0, 153.4, 137.3, 124.7, 124.4, 119.7, 103.5, 102.6, 101.9, 82.5, 68.4, 55.6。

[0059] Example 5: Synthesis of 4-(4-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one (3e)

[0060]

[0061] Accurately weigh 4-benzyloxyindole (0.11 g, 0.5 mmol), vinylene carbonate (0.26 g, 3.0 mmol), cuprous bromide (14.4 mg, 0.10 mmol), and pyridine (15.8 mg, 0.2 mmol), and successively add them to a 50 mL Schlenk flask. Add benzene (3.0 mL), and place it in an oil bath at 80 °C for reaction for 18 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 4:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(4-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one is 78%. 11H NMR (400 MHz, d6-DMSO) δ 7.61 (d, J = 3.4 Hz, 1H), 7.51 (d, J = 7.6 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.1 Hz, 1H), 7.21 - 7.14 (m, 3H), 6.78 (d, J = 6.5 Hz, 1H), 6.71 (d, J = 3.3 Hz, 1H), 5.26 (s, 2H), 5.02 (d, J = 6.4 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 154.0, 152.4, 137.8, 137.4, 128.9, 128.2, 127.9, 124.9, 124.3, 120.1, 103.7, 103.4, 102.6, 82.5, 69.6, 68.4。

[0062] Example 6: Synthesis of 4-(4-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one (3f)

[0063]

[0064] Accurately weigh 4-chloroindole (0.30 g, 2.0 mmol), vinylene carbonate (0.69 g, 8.0 mmol), copper(II) fluoride (5.1 mg, 0.05 mmol), and potassium hydroxide (11.2 mg, 0.2 mmol), and successively add them to a 50 mL Schlenk flask. Add methanol (6.0 mL) and place it in an oil bath at 45 °C for reaction for 36 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(4-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one is 91%. 1 1H NMR (400 MHz, d6-DMSO) δ 7.86 (d, J = 3.5 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.33 - 7.22 (m, 3H), 6.73 (d, J = 3.3 Hz, 1H), 5.05 (d, J = 6.3 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 153.9, 136.8, 127.8, 127.5, 125.5, 124.2, 121.2, 109.7, 103.4, 82.3, 68.5。

[0065] Example 7: Synthesis of 4-(4-bromo-1H-indol-1-yl)-1,3-dioxolan-2-one (3g)

[0066]

[0067] Accurately weigh 4-bromoindole (0.98 g, 5.0 mmol), vinylene carbonate (0.86 g, 10.0 mmol), copper(I) oxide (71.5 mg, 0.50 mmol), and sodium hydroxide (40.0 mg, 1.0 mmol), and sequentially add them to a 50 mL Schlenk flask. Add ethanol (15.0 mL), and react in an 85 °C oil bath for 20 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 4:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(4-bromo-1H-indol-1-yl)-1,3-dioxolan-2-one is 89%. 1 H NMR (400 MHz, d6-DMSO) δ 7.87 (d, J = 3.4 Hz, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.23 (t, J = 7.3 Hz, 2H), 6.65 (d, J = 3.4 Hz, 1H), 5.05 (d, J = 6.3 Hz, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 153.9, 136.4, 133.2, 129.7, 127.5, 124.5, 124.3, 114.5, 110.2, 105.1, 82.3, 68.5.

[0068] Example 8: Synthesis of methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-4-carboxylate (3h)

[0069]

[0070] Accurately weigh methyl indole-4-carboxylate (0.18 g, 1.0 mmol), vinylene carbonate (0.26 g, 3.0 mmol), copper(II) nitrate trihydrate (24.2 mg, 0.10 mmol), and sodium formate dihydrate (10.4 mg, 0.1 mmol), and successively add them to a 50 mL Schlenk flask. Add toluene (4.0 mL), and react in an oil bath at 75 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 2:1) as the eluent, and separate by silica gel column chromatography. The yield of the product methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-4-carboxylate is 86%. 1 H NMR (400 MHz, d6-DMSO) δ 7.93 - 7.87 (m, 3H), 7.41 (t, J = 7.9 Hz, 1H), 7.30 (t, J = 6.2 Hz, 1H), 7.19 (d, J = 3.3 Hz, 1H), 5.09 - 5.06 (m, 2H), 3.92 (s, 3H). 13 C NMR (101 MHz, d6-DMSO) δ 167.1, 153.9, 136.9, 128.8, 128.3, 124.5, 122.7, 121.8, 115.6, 106.2, 82.0, 68.5, 52.4。

[0071] Example 9: Synthesis of 4-(4-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one (3i)

[0072]

[0073] Accurately weigh 4-nitroindole (0.47 g, 3.0 mmol), vinylene carbonate (0.86 g, 10.0 mmol), copper(I) bis(triphenylphosphine) borohydride (30.1 mg, 0.05 mmol), and potassium carbonate (13.8 mg, 0.1 mmol), and successively add them to a 50 mL Schlenk flask. Add toluene (10.0 mL), and react in an oil bath at 50 °C for 24 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:2) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(4-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one is 94%. 11H NMR (400 MHz, d6-DMSO) δ 8.21 - 8.14 (m, 3H), 7.53 (t, J = 8.1 Hz, 1H), 7.36 (t, J = 6.2 Hz, 1H), 7.26 (d, J = 3.3 Hz, 1H), 5.13 - 5.04 (m, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 153.8, 140.2, 138.2, 131.0, 123.1, 122.8, 119.0, 118.1, 104.8, 81.9, 68.67。

[0074] Example 10: Synthesis of 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-4-carbonitrile (3j)

[0075]

[0076] Accurately weigh 4-cyanoindole (0.28 g, 2.0 mmol), vinylene carbonate (0.43 g, 5.0 mmol), copper(I) trifluoromethanesulfonate (18.1 mg, 0.05 mmol), and sodium carbonate (21.2 mg, 0.2 mmol), and successively add them to a 50 mL Schlenk flask. Add tetrahydrofuran (5.0 mL), and react in an oil bath at 40 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:1) as the eluent and separate by silica gel column chromatography. The yield of the product 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-4-carbonitrile is 88%. 1 1H NMR (400 MHz, d6-DMSO) δ 8.05 (d, J = 3.4 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 7.4 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.30 (t, J = 6.3 Hz, 1H), 6.85 (d, J = 3.3 Hz, 1H), 5.06 (d, J = 6.3 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 153.8, 135.9, 130.4, 129.6, 126.9, 123.4, 118.4, 116.0, 103.5, 102.8, 82.0, 68.6。

[0077] Example 11: Synthesis of 4-(5-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one (3k)

[0078]

[0079] Accurately weigh 5-methylindole (0.13 g, 1.0 mmol), vinylene carbonate (0.10 g, 1.2 mmol), copper oxide (8.0 mg, 0.10 mmol), and cesium carbonate (16.3 mg, 0.05 mmol), and successively add them to a 50 mL Schlenk flask. Add chloroform (3.0 mL), and react in an oil bath at 55 °C for 16 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(5-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one is 79%. 1 H NMR (400 MHz, d6-DMSO) δ 7.64 (d, J = 3.4 Hz, 1H), 7.47 - 7.40 (m, 2H), 7.18 (t, J = 6.3 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 3.3 Hz, 1H), 5.02 (d, J = 6.3 Hz, 2H), 2.39 (s, 3H). 13 C NMR (101 MHz, d6-DMSO) δ 154.1, 134.3, 133.2, 130.3, 129.9, 126.3, 124.6, 121.2, 110.1, 105.1, 82.5, 68.3, 21.4.

[0080] Example 12: Synthesis of 4-(5-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one (3l)

[0081]

[0082] Accurately weigh 5-methoxyindole (0.59 g, 4.0 mmol), vinylene carbonate (0.60 g, 7.0 mmol), copper(I) iodide (9.5 mg, 0.05 mmol), and sodium acetate (24.6 mg, 0.3 mmol), and successively add them to a 50 mL Schlenk flask. Add toluene (9.0 mL), and react in an oil bath at 90 °C for 12 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(5-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one is 72%. 11H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.6 Hz, 1H), 7.21 (d, J = 3.4 Hz, 1H), 7.15 (d, J = 1.9 Hz, 1H), 7.00 (dd, J = 8.9, 2.0 Hz, 1H), 6.73 (dd, J = 7.2, 5.1 Hz, 1H), 6.64 (d, J = 3.3 Hz, 1H), 4.98 - 4.85 (m, 2H), 3.91 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 155.5, 153.3, 130.5, 130.2, 124.9, 113.4, 110.1, 106.2, 103.7, 82.2, 67.9, 55.8。

[0083] Example 13: Synthesis of 4-(5-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one (3m)

[0084]

[0085] Accurately weigh 5-benzyloxyindole (0.45 g, 2.0 mmol), vinylene carbonate (0.43 g, 5.0 mmol), copper(I) chloride (9.9 mg, 0.10 mmol), and potassium acetate (29.4 mg, 0.3 mmol), and successively add them to a 50 mL Schlenk flask. Add ethyl acetate (3.0 mL), and react in an oil bath at 70 °C for 15 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(5-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one is 80%. 1 1H NMR (400 MHz, d6-DMSO) δ 7.66 (d, J = 3.2 Hz, 1H), 7.47 (d, J = 8.1 Hz, 3H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (d, J = 6.9 Hz, 1H), 7.23 (s, 1H), 7.16 (t, J = 6.2 Hz, 1H), 7.00 (d, J = 8.9 Hz, 1H), 6.59 (d, J = 3.2 Hz, 1H), 5.13 (s, 2H), 5.01 (d, J = 6.3 Hz, 2H). 1313C NMR (101 MHz, d6-DMSO) δ 154.10, 154.08, 137.9, 131.0, 130.2, 128.9, 128.2, 128.1, 126.9, 113.5, 111.1, 105.4, 105.0, 82.6, 70.1, 68.3.

[0086] Example 14: Synthesis of 4-(5-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one (3n)

[0087]

[0088] Accurately weigh 5-chloroindole (0.15 g, 1.0 mmol), vinylene carbonate (0.26 g, 3.0 mmol), copper(II) chloride (6.7 mg, 0.05 mmol), and potassium formate (16.8 mg, 0.2 mmol), and add them successively to a 50 mL Schlenk flask. Add methyl tert-butyl ether (6.0 mL), and react in an oil bath at 65 °C for 28 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(5-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one is 86%. 1 1H NMR (400 MHz, d6-DMSO) δ 7.81 - 7.79 (m, 1H), 7.70 (s, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 8.7 Hz, 1H), 7.22 (t, J = 6.3 Hz, 1H), 6.68 (d, J = 3.4 Hz, 1H), 5.04 (d, J = 6.3 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 154.0, 134.6, 130.7, 127.8, 126.1, 123.1, 120.8, 112.0, 105.2, 82.2, 68.5.

[0089] Example 15: Synthesis of 4-(5-bromo-1H-indol-1-yl)-1,3-dioxolan-2-one (3o)

[0090]

[0091] Accurately weigh 5-bromoindole (0.39 g, 2.0 mmol), vinylene carbonate (0.22 g, 2.5 mmol), copper(II) acetate monohydrate (10.0 mg, 0.05 mmol), and triethylamine (50.6 mg, 0.5 mmol), and successively add them to a 50 mL Schlenk flask. Add 1,4-dioxane (4.0 mL), and react in an oil bath at 105 °C for 12 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 2:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(5-bromo-1H-indol-1-yl)-1,3-dioxolan-2-one is 84%. 1 H NMR (400 MHz, d6-DMSO) δ 7.85 (s, 1H), 7.79 (d, J = 3.3 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.22 (t, J = 6.3 Hz, 1H), 6.68 (d, J = 3.2 Hz, 1H), 5.03 (d, J = 6.3 Hz, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 153.9, 134.9, 131.4, 127.7, 125.7, 123.8, 114.1, 112.5, 105.1, 82.2, 68.4。

[0092] Example 16: Synthesis of 4-(5-iodo-1H-indol-1-yl)-1,3-dioxolan-2-one (3p)

[0093]

[0094] Accurately weigh 5-iodoindole (0.24 g, 1.0 mmol), vinylene carbonate (0.17 g, 2.0 mmol), cuprous bromide (7.2 mg, 0.05 mmol), and sodium carbonate (10.6 mg, 0.1 mmol), and successively add them to a 50 mL Schlenk flask. Add n-heptane (2.0 mL), and react in an oil bath at 75 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 4:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 4-(5-iodo-1H-indol-1-yl)-1,3-dioxolan-2-one is 78%. 11H NMR (400 MHz, d6-DMSO) δ 8.02 (s, 1H), 7.73 (d, J = 3.3 Hz, 1H), 7.55 (d, J = 8.6 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.20 (t, J = 6.3 Hz, 1H), 6.65 (d, J = 3.2 Hz, 1H), 5.02 (d, J = 6.3 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 153.9, 135.3, 132.1, 131.1, 130.0, 127.2, 112.9, 104.8, 85.6, 82.1, 68.4。

[0095] Example 17: Synthesis of methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-5-carboxylate (3q)

[0096]

[0097] Accurately weigh methyl indole-5-carboxylate (0.88 g, 5.0 mmol), vinylene carbonate (0.69 g, 8.0 mmol), copper(II) fluoride (5.1 mg, 0.05 mmol), and potassium tert-butoxide (56.1 mg, 0.5 mmol), and add them successively to a 50 mL Schlenk flask. Add dimethyl sulfoxide (15.0 mL), and react in an oil bath at 60 °C for 16 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:1) as the eluent and separate by silica gel column chromatography. The yield of the product methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-5-carboxylate is 90%. 1 1H NMR (400 MHz, d6-DMSO) δ 8.33 (s, 1H), 7.91 - 7.85 (m, 2H), 7.71 (d, J = 8.7 Hz, 1H), 7.28 (t, J = 6.3 Hz, 1H), 6.85 (d, J = 3.3 Hz, 1H), 5.05 (d, J = 6.2 Hz, 2H), 3.87 (s, 3H). 13 13C NMR (101 MHz, d6-DMSO) δ 167.2, 153.9, 138.7, 129.2, 127.7, 124.0, 123.8, 123.1, 110.6, 106.7, 82.1, 68.6, 52.4。

[0098] Example 18: Synthesis of 4-(5-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one (3r)

[0099]

[0100] Accurately weigh 5-nitroindole (0.32 g, 2.0 mmol), vinylene carbonate (0.52 g, 6.0 mmol), copper(I) chloride (9.9 mg, 0.10 mmol), and sodium carbonate (42.4 mg, 0.4 mmol), and successively add them to a 50 mL Schlenk flask. Add tetrahydrofuran (6.0 mL), and react in an oil bath at 60 °C for 20 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(5-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one is 87%. 1 H NMR (400 MHz, d6-DMSO) δ 8.64 (s, 1H), 8.18 (d, J = 9.1 Hz, 1H), 8.00 (d, J = 3.4 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.32 (t, J = 6.3 Hz, 1H), 6.97 (d, J = 3.4 Hz, 1H), 5.12 - 4.99 (m, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 153.8, 142.6, 139.2, 129.5, 128.9, 118.4, 118.3, 111.2, 107.6, 81.9, 68.7.

[0101] Example 19: Synthesis of 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-5-carbonitrile (3s)

[0102]

[0103] Accurately weigh 5-cyanoindole (0.85 g, 6.0 mmol), vinylene carbonate (1.03 g, 12.0 mmol), copper(I) iodide (38.2 mg, 0.20 mmol), potassium carbonate (110.6 mg, 0.8 mmol), and add them successively into a 100 mL Schlenk flask. Add ethanol (20.0 mL), and react in an oil bath at 45 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 1:2) as the eluent and separate by silica gel column chromatography. The yield of the product 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-5-carbonitrile is 84%. 1 H NMR (400 MHz, d6-DMSO) δ 8.19 (s, 1H), 7.95 (d, J = 3.4 Hz, 1H), 7.81 (d, J = 8.6 Hz, 1H), 7.67 (d, J = 8.6 Hz, 1H), 7.30 (t, J = 6.2 Hz, 1H), 6.83 (d, J = 3.3 Hz, 1H), 5.05 (d, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 153.8, 137.9, 129.3, 128.6, 127.0, 126.1, 120.5, 111.9, 106.2, 103.9, 81.9, 68.6。

[0104] Example 20: Synthesis of 4-(6-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one (3t)

[0105]

[0106] Accurately weigh 6-methylindole (0.13 g, 1.0 mmol), vinylene carbonate (0.13 g, 1.5 mmol), copper(II) chloride (13.4 mg, 0.10 mmol), sodium carbonate (26.5 mg, 0.25 mmol), and add them successively into a 50 mL Schlenk flask. Add benzene (4.0 mL), and react in an oil bath at 65 °C for 36 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(6-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one is 72%. 11H NMR (400 MHz, d6-DMSO) δ 7.61 (d, J = 3.4 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.18 (t, J = 6.3 Hz, 1H), 7.01 (d, J = 8.1 Hz, 1H), 6.61 (d, J = 3.2 Hz, 1H), 5.02 (d, J = 6.3 Hz, 2H), 2.44 (s, 3H). 13 13C NMR (101 MHz, d6-DMSO) δ 154.1, 133.2, 132.5, 127.3, 125.4, 123.2, 121.2, 110.3, 105.5, 82.3, 68.3, 22.0。

[0107] Example 21: Synthesis of 4-(6-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one (3u)

[0108]

[0109] Accurately weigh 6-methoxyindole (0.93 g, 4.0 mmol), vinylene carbonate (0.52 g, 6.0 mmol), copper(I) chloride (5.0 mg, 0.05 mmol), and sodium acetate (16.4 mg, 0.2 mmol), and add them successively to a 50 mL Schlenk flask. Add petroleum ether (10.0 mL), and react in an oil bath at 50 °C for 30 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(6-methoxy-1H-indol-1-yl)-1,3-dioxolan-2-one is 80%. 1 1H NMR (400 MHz, d6-DMSO) δ 7.55 - 7.48 (m, 2H), 7.24 - 7.19 (m, 2H), 6.82 (d, J = 8.6 Hz, 1H), 6.60 (d, J = 3.3 Hz, 1H), 5.02 (d, J = 6.3 Hz, 2H), 3.81 (s, 3H). 13 13C NMR (101 MHz, d6-DMSO) δ 157.0, 154.1, 137.2, 124.4, 123.2, 122.0, 111.2, 105.7, 94.4, 82.1, 68.4, 55.9。

[0110] Example 22: Synthesis of 4-(6-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one (3v)

[0111]

[0112] Accurately weigh 6-benzyloxyindole (2.23 g, 10.0 mmol), vinylene carbonate (1.30 g, 15.0 mmol), copper(II) acetate monohydrate (100.0 mg, 0.5 mmol), and sodium hydroxide (80.0 mg, 2.0 mmol), and sequentially add them to a 250 mL Schlenk flask. Add methyl tert-butyl ether (50.0 mL), and react in an oil bath at 55 °C for 32 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(6-(benzyloxy)-1H-indol-1-yl)-1,3-dioxolan-2-one is 76%. 1 H NMR (400 MHz, d6-DMSO) δ 7.55 (d, J = 3.4 Hz, 1H), 7.52 - 7.48 (m, 3H), 7.41 (t, J = 7.4 Hz, 2H), 7.37 - 7.31 (m, 2H), 7.21 (t, J = 6.3 Hz, 1H), 6.90 (d, J = 8.7 Hz, 1H), 6.60 (d, J = 3.3 Hz, 1H), 5.19 - 5.12 (m, 2H), 5.02 (d, J = 6.3 Hz, 2H). 13 C NMR (101 MHz, d6-DMSO) δ 156.0, 154.1, 137.6, 137.2, 133.2, 128.9, 128.3, 128.2, 124.6, 123.5, 122.1, 111.7, 105.7, 95.8, 82.1, 70.2, 68.3。

[0113] Example 23: Synthesis of methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-6-carboxylate (3w)

[0114]

[0115] Accurately weigh methyl indole-6-carboxylate (0.35 g, 2.0 mmol), vinylene carbonate (0.43 g, 5.0 mmol), copper(II) chloride (13.5 mg, 0.1 mmol), potassium carbonate (13.8 mg, 0.10 mmol), and successively add them to a 50 mL Schlenk flask. Add dimethyl carbonate (5.0 mL), and react in an oil bath at 70 °C for 18 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 2:1) as the eluent and separate by silica gel column chromatography. The yield of the product methyl 1-(2-oxo-1,3-dioxolan-4-yl)-1H-indole-6-carboxylate is 85%. 1 H NMR (400 MHz, d6-DMSO) δ 8.28 (s, 1H), 7.98 (d, J = 3.3 Hz, 1H), 7.80 - 7.73 (m, 2H), 7.38 (t, J = 6.3 Hz, 1H), 6.80 (d, J = 3.3 Hz, 1H), 5.16 - 4.92 (m, 2H), 3.89 (s, 3H). 13 C NMR (101 MHz, d6-DMSO) δ 167.3, 153.9, 135.6, 133.2, 129.7, 124.3, 122.2, 121.5, 112.2, 105.87, 82.0, 68.5, 52.5。

[0116] Example 24: Synthesis of 4-(6-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one (3x)

[0117]

[0118] Accurately weigh 6-chloroindole (1.21 g, 8.0 mmol), vinylene carbonate (0.86 g, 10.0 mmol), copper(I) iodide (95.3 mg, 0.5 mmol), triethylamine (101.2 mg, 1.0 mmol), and successively add them to a 250 mL Schlenk flask. Add trifluoroethanol (25.0 mL), and react in an oil bath at 65 °C for 24 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 3:1) as the eluent and separate by silica gel column chromatography. The yield of the product 4-(6-chloro-1H-indol-1-yl)-1,3-dioxolan-2-one is 90%. 11H NMR (400 MHz, d6-DMSO) δ 7.76 (s, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.30 - 7.17 (m, 2H), 6.72 (d, J = 3.3 Hz, 1H), 5.03 (d, J = 6.0 Hz, 2H). 13 13C NMR (101 MHz, d6-DMSO) δ 153.9, 136.7, 133.2, 128.1, 128.0, 126.9, 122.9, 121.9, 110.6, 105.9, 82.0, 68.5。

[0119] It can be concluded from the examples that when the R group is a substituent with electron-withdrawing properties, the reaction yield is higher than that when the R group is a substituent with electron-donating properties. This method is a synthetic method for N-(dioxolan-2-one) indole compounds with good selectivity, mild reaction conditions, high atom economy, good catalytic effect and high yield. Since N-functionalized indole compounds are an important organic synthesis intermediate and have very wide applications in the fields of medicine, pesticides and materials, therefore, the present invention has great application value and social and economic benefits.

[0120] Example 25: Antibacterial rate test of the compound 4-(5-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one in Example 18 against Escherichia coli

[0121] (1) Material pretreatment: After ultraviolet disinfection in a clean bench for 2 h, it is ready for use.

[0122] (2) Streak the test strain Escherichia coli (ATCC25922) on an LB solid plate and culture it overnight at 37 °C until obvious bacterial colonies are visible.

[0123] (3) Pick an appropriate amount of mature colonies, inoculate them into 10 ml of LB liquid medium and culture at 37 °C for 6 - 8 h until the OD600 is about 0.6. After adjusting to 0.6 with normal saline, inoculate them into the LB solution at a ratio of 0.1%, and take 5 mL of the bacterial solution to co-culture with the material. Culture at 37 °C for 24 h.

[0124] (4) Collect the bacterial solution on the surface of the material and perform gradient dilution: Take several centrifuge tubes, label them as No. 1 - n, add 900 μL of normal saline to each tube, take 100 μL of the stock solution and add it to tube No. 1 to obtain a 10-fold dilution solution. After mixing, take 100 μL from tube No. 1 and add it to the second tube, and dilute sequentially to tube No. n. Then take 100 μL of the liquid from the appropriate dilution gradient tube and spread it on an LB plate, and take a photo and count after culturing at 37 °C for 18 h.

[0125] (5) Select one appropriate dilution gradient for each group to calculate the antibacterial rate. After calculation, the antibacterial rate of 4-(5-nitro-1H-indol-1-yl)-1,3-dioxolan-2-one against Escherichia coli reached 100%. (The results are shown in Figure 7 (shown)

[0126] Example 26: Preparation of 4-chloro-5-(1H-indol-1-yl)-1,3-dioxolan-2-one

[0127]

[0128] Indole (0.23 g, 2.0 mmol), 4-chlorovinylene carbonate (0.30 g, 2.5 mmol), and sodium hydroxide (8.0 mg, 0.2 mmol) were accurately weighed and added to a 50 mL Schlenk bottle in sequence, and methyl tert-butyl ether (4.0 mL) was added, and the mixture was placed in an 80°C oil bath for reaction for 12 h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and petroleum ether / ethyl acetate (v / v 3:1) was used as the eluent, and silica gel column chromatography was used for separation, and the yield of the product 4-chloro-5-(1H-indol-1-yl)-1,3-dioxolan-2-one was 99%. 1 H NMR(400MHz,d6-DMSO)δ7.81-7.79(m,1H),7.70(s,1H),7.62(d,J=8.8Hz,1H),7.30( d,J=8.7Hz,1H),7.22(t,J=6.3Hz,1H),6.68(d,J=3.4Hz,1H),5.04(d,J=6.3Hz,2H). 13 C NMR (101MHz, d6-DMSO) δ154.0,134.6,130.7,127.8,126.1,123.1,120.8,112.0,105.2,82.2,68.5.

[0129] Example 27: Test of the antibacterial rate of the compound in Example 26 against Staphylococcus aureus

[0130] (1) Material pretreatment: sterilize with ultraviolet light in a clean bench for 2 hours before use.

[0131] (2) Streak the test strain Staphylococcus aureus (ATCC29213) on a TSA solid plate and culture it overnight at 37 °C until obvious bacterial plaques are visible. (3) Pick an appropriate amount of mature colonies and transfer them to 10 mL of TSB liquid medium. Culture at 37 °C for 6 - 8 h until the OD600 is approximately 0.6. After adjusting to 0.6 with normal saline, inoculate into the TSB solution at a ratio of 0.1%. Take 5 mL of the bacterial solution and co-culture it with the material at 37 °C for 24 h.

[0132] (4) Collect the bacterial solution on the surface of the material and perform gradient dilution: Take several centrifuge tubes, label them as tubes 1 to n. Add 900 μL of normal saline to each tube. Take 100 μL of the original solution and add it to tube 1 to obtain a 10-fold dilution. After mixing, take 100 μL from tube 1 and add it to the second tube, and dilute sequentially to the nth tube. Then take 100 μL of the liquid from the appropriate dilution gradient tube and spread it on a TSA plate. After culturing at 37 °C for 18 h, take a photo and count.

[0133] (5) Select one appropriate dilution gradient for each group to calculate the antibacterial rate. After calculation, the antibacterial rate of 4-chloro-5-(1H-indol-1-yl)-1,3-dioxolan-2-one (3f) against Staphylococcus aureus is 99.35%. (The results are as Figure 8 shown)

[0134] It can be seen from Example 25 and Example 27 that N-(dioxolanone-based) indole compounds have good inhibitory effects on Escherichia coli and Staphylococcus aureus and can be applied to the preparation of medicines or pesticides.

[0135] Example 28: Application of 4-(1H-indol-1-yl)-1,3-dioxolan-2-one in the synthesis of N-vinylindole (4)

[0136]

[0137] Accurately weigh 4-(1H-indol-1-yl)-1,3-dioxolan-2-one (3a) (101.6 mg, 0.5 mmol), palladium acetylacetonate (Pd(acac)2, 7.6 mg, 0.025 mmol), and manganese dioxide (MnO2, 86.9 mg, 1.0 mmol), and add them sequentially to a 25 mL Schlenk flask. Add acetonitrile and water (3.0 mL / 0.1 mL), and react in an oil bath at 40 °C for 24 h. After the reaction is completed, remove the solvent by reduced pressure distillation. Use petroleum ether / ethyl acetate (v / v 10:1) as the eluent and separate by silica gel column chromatography. The yield of the product N-vinylindole (4) is 96%. 11H NMR (600 MHz, CDCl3) δ 7.67 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 7.30 - 7.27 (m, 1H), 7.25 - 7.15 (m, 2H), 6.57 (d, J = 3.2 Hz, 1H), 5.60 (d, J = 6.1 Hz, 2H), 2.62 (t, J = 6.1 Hz, 1H); 13 13C NMR (151 MHz, CDCl3) δ 135.6, 129.3, 127.4, 122.3, 121.2, 120.4, 109.5, 103.0, 69.8.

[0138] Example 29: Application of 4-(5-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one in the synthesis of 5-methyl-N-acetylindole (5)

[0139]

[0140] Accurately weigh 4-(5-methyl-1H-indol-1-yl)-1,3-dioxolan-2-one (217.2 g, 1.0 mmol) and potassium tert-butoxide (224.4 mg, 2.0 mmol), and successively add them to a 50 mL Schlenk flask. Add 1,4-dioxane (4.0 mL), and react in an oil bath at 90 °C for 24 h. After the reaction is completed, remove the solvent by distillation under reduced pressure. Use petroleum ether / ethyl acetate (v / v 5:1) as the eluent, and separate by silica gel column chromatography. The yield of the product 5-methyl-N-acetylindole (5) is 92%. 1 1H NMR (500 MHz, CDCl3): δ = 8.29 (br s, 1H), 7.33 (s, 2H), 7.15 (d, J = 8.1 Hz, 1H), 6.54 (d, J = 3.2 Hz, 1H), 2.59 (s, 3H), 2.43 (s, 3H). 13 13C NMR (126 MHz, CDCl3): δ = 168.4, 133.1, 130.6, 126.3, 125.2, 120.7, 116.1, 108.9, 23.8, 21.3.

[0141] The N-(dioxolan-2-one-yl)indole compounds prepared by this method can be used for the further functionalization transformation of indole compounds to synthesize N-vinylindole and N-acetylindole compounds; the compounds 4 and 5 prepared in Example 28 and Example 29 are important intermediates for the preparation of medicines or pesticides, and thus it can be proved that N-(dioxolan-2-one-yl)indole compounds can also be applied to the preparation of medicines or pesticides.

Claims

1. An N-(dioxolanone group) indole compound, characterized in that, The general structural formula of the compound is as follows: Wherein: the indole ring is substituted with a substituent R = hydrogen, C 1-6 a straight-chain or branched alkyl group, an aryl group, an amino group, a hydroxyl group, an alkoxy group, an alkoxycarbonyl group, a cyano group, a nitro group, a halogen, and the substituent R is at the 2, 3, 4, 5, 6 or 7 position of the indole ring.

2. The preparation method of an N-(dioxolanyl)indole compound according to claim 1, characterized in that: Using vinylene carbonate and indole compounds as raw materials, a series of N-(dioxolanonyl)indole compounds are synthesized through a copper-base synergistic catalytic addition reaction. The method includes the following steps: The synthetic route is as follows: Wherein: R = hydrogen, C 1-6 a straight-chain or branched-chain alkyl group, an aryl group, an amino group, a hydroxyl group, an alkoxy group, an alkoxycarbonyl group, a cyano group, a nitro group, a halogen; (1) Add the indole compound, copper catalyst, base catalyst, vinylene carbonate and organic solvent into the reactor in sequence, and react at 25-150 °C for 4-36 h; the molar ratio of the indole compound to vinylene carbonate is 1:1-1:5, the molar ratio of the indole compound to the copper catalyst is 1:0.01-1:0.2, and the molar ratio of the indole compound to the base catalyst is 1:0.01-1:0.7; (2) After the reaction is completed, remove the solvent by vacuum distillation, and perform silica gel column separation with an eluent to obtain the N-(dioxolanonyl)indole compound.

3. A method for preparing an N-(dioxolanone group) indole compound according to claim 2, characterized in that: The copper catalyst is selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous oxide, cuprous cyanide, bis(triphenylphosphine)cuprous borohydride, copper fluoride, copper chloride, copper bromide, copper acetate monohydrate, copper nitrate, copper sulfate, copper trifluoromethanesulfonate, copper trifluoroacetate, copper tartrate, basic copper carbonate, copper nitrate trihydrate, bis(acetylacetone)copper, copper oxide.

4. A method for preparing an N-(dioxolanyl)indole compound according to claim 2, characterized in that: The base catalyst is selected from potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium hydroxide, sodium hydroxide, lithium carbonate, potassium carbonate, sodium carbonate, cesium carbonate, ammonium carbonate, potassium bicarbonate, sodium bicarbonate, ammonium bicarbonate, sodium formate dihydrate, potassium formate, sodium acetate, potassium acetate, sodium propionate, potassium propionate, sodium pivalate, potassium pivalate, sodium trifluoroacetate, potassium trifluoroacetate, ammonium formate, ammonium acetate, pyridine, piperidine, piperazine, pyrrolidine, triethylamine, diisopropylethylamine, lithium hexamethyldisilazide, potassium hexamethyldisilazide.

5. The preparation method of an N-(dioxolanyl)indole compound according to claim 2, wherein: The organic solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, trifluoroethanol, dichloromethane, chloroform, benzene, toluene, cyclohexane, n-pentane, n-hexane, n-heptane, diethyl ether, isopropyl ether, n-butyl ether, methyl tert-butyl ether, ethyl acetate, petroleum ether, fluorobenzene, trifluorotoluene, nitromethane, 1,4-dioxane, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, acetonitrile, dimethyl carbonate, diethyl carbonate, methyl ethyl carbonate, water.

6. The preparation method of an N-(dioxolanone group) indole compound according to claim 2, characterized in that, The amount of the organic solvent is 1-500 mL.

7. A method for preparing an N-(dioxolanone group) indole compound according to claim 2, characterized in that, The structures of the raw material indole compound, vinylene carbonate and the corresponding product N-(dioxolanonyl)indole compound are as follows:

8. A N-(dioxolanyl)indole compound according to claim 1, characterized in that: The N-(dioxolanonyl)indole compound is applied to the preparation of medicines and pesticides.

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