A method for preparing an oxidized indole compound

Abstract

The application relates to a preparation method of an oxidized indole compound and belongs to the technical field of catalytic synthesis. The application aims at solving the problems of high energy consumption, high cost and harsh reaction conditions in the existing synthesis method. The method comprises the following steps: adding heteroaryl formic acid compounds, N-aryl acrylamide compounds, DABCO, K2S2O8 and Fe(acac)3 into a solvent in sequence to obtain a mixed solution, irradiating the mixed solution with a light source under room temperature and in an inert gas atmosphere, and obtaining the oxidized indole compound. The method has the advantages of simple operation, preparation of the oxidized indole compound at room temperature, mild reaction conditions, use of cheap iron salt as a metal catalyst, cheap and easily-obtained raw materials, simple, convenient and efficient reaction, efficient realization of the reaction of the kilogram scale synthesis through the one-pot method with a catalytic amount of iron salt, and great potential large-scale application value. The application can be applied to the field of organic synthesis.

Description

Technical Field

[0001] This invention belongs to the field of catalytic synthesis technology, specifically relating to a method for preparing indole oxide compounds. Background Technology

[0002] Oxyindoles are widely found in various organic frameworks, including natural products, bioactive molecules, and drug molecules. Examples include anticancer drugs, tumor suppressor p53, and N-channel antagonists. Their structures are shown below. Given the wide range of biological activities and rich synthetic applications of oxidindole compounds, the construction of this framework has become an important goal in synthetic organic chemistry.

[0003] Cyclolation reactions are a widely used strategy for constructing oxidized indole skeletons. However, traditional methods often require the use of ortho-functionalized aryl groups and 2-substituted activated anilines. These transformations not only complicate substrate preparation but also severely limit the synthetic range. In recent years, the synthesis of 3-substituted oxyglycosides from N-arylacrylamides via radical addition reactions has attracted attention. Currently, the application of these methods requires expensive transition metal catalysts (Pd, Rh, and Ir, etc.) or the pre-preparation of complex metal catalysts, high temperatures, and highly toxic radical initiators. These drawbacks limit the widespread application of these schemes. Therefore, the preparation of oxidized indole derivatives using green, efficient, low-cost, mild, inexpensive, and commercially available metal methods is a crucial problem that urgently needs to be solved. Summary of the Invention

[0004] This invention aims to address the problems of high energy consumption, high cost, and harsh reaction conditions in existing synthesis methods, and provides a method for preparing oxidized indole compounds.

[0005] This invention utilizes photocatalysis to decarbonate heteroarylcarboxylic acids through a ligand-to-metal charge transfer (LMCT) process using a catalytic amount of photocatalyst Fe(acac)3, generating heteroaryl radicals. These heteroaryl radicals then undergo radical addition reactions with N-arylacrylamide compounds, leading to cyclization and ultimately achieving the efficient preparation of oxidized indole compounds.

[0006] A method for preparing an indole oxide compound, specifically comprising the following steps:

[0007] 1. Under a nitrogen atmosphere and at room temperature, heteroarylformic acid compounds, N-arylacrylamide compounds, DABCO, K2S2O8 and Fe(acac)3 were sequentially added to an ultra-dry solvent to obtain a mixed solution;

[0008] 2. The mixed solution is irradiated with an LED light source, then extracted, and the solvent is removed by rotary evaporation. The solution is then separated and purified by thin-layer chromatography. The resulting product is an indole oxide compound, thus completing the preparation.

[0009] The general reaction formula of this invention is as follows:

[0010]

[0011] The preparation reaction formula for N-methyl-N-phenylmethylacrylamide is as follows:

[0012]

[0013] The preparation method of N-methyl-N-phenylmethylacrylamide is as follows:

[0014] Add the corresponding aniline S1 (2.0 mmol), DCM (15 mL), and triethylamine (4.0 mmol, 2.0 equiv) to a 50 mL round-bottom flask; stir the mixture at 0 °C, and slowly add methacryloyl chloride S2 (3.0 mmol, 1.5 equiv) under an argon atmosphere; stir the resulting solution at room temperature for 12 hours, quench the reaction with water (50 mL), and extract with DCM (15 mL × 3); wash the organic layer with saturated brine (15 mL × 3), dry the organic layer with sodium sulfate, and then concentrate under reduced pressure; separate and purify by thin-layer chromatography using petroleum ether and ethyl acetate (15:1 to 10:1, v / v) as eluent to obtain the corresponding substrate 2a.

[0015] Taking oxidized indole compound 1c as an example, the reaction mechanism of this invention is as follows:

[0016]

[0017] Initially, 2-pyridinecarboxylic acid 1a reacted with Fe... 3+ A complexation process occurs, followed by further decarbonylation via the LMCT process under light to obtain pyridyl radical intermediate II. Pyridyl radical intermediate II undergoes a radical addition reaction with N-methyl-N-phenylmethylacrylamide 2a to obtain radical intermediate III. This radical intermediate further undergoes cyclization to obtain intermediate IV, which is then converted into intermediate V under the action of an oxidant. Intermediate V is deprotonated under the action of the base DABCO to generate the final product 1c.

[0018] Beneficial effects of this invention:

[0019] Compared with existing technologies, this invention provides a simple, green, and efficient method for constructing indole oxide compounds, and has the following main advantages:

[0020] (1) The reaction system can achieve the synthesis of challenging indole oxides under room temperature and inert gas atmosphere by irradiation with 390±10nm LEDs light source, and the reaction conditions are mild.

[0021] (2) The heteroarylformic acid compounds, N-arylacrylamide compounds, DABCO, K2S2O8, Fe(acac)3 and dimethyl sulfoxide used as solvents in this catalytic system are all simple, inexpensive and readily available commercial compounds. The iron salt photocatalyst used is also relatively inexpensive. The reaction substrate has good universality, and the whole reaction system shows the green nature of organic synthesis chemistry.

[0022] (3) Gram-scale reactions can be achieved at room temperature by light irradiation, and the yield is good, which shows high efficiency; and the use of a catalytic amount of photocatalyst shows that the reaction is economical and environmentally friendly, and has potential commercial application value.

[0023] This invention is used for the preparation of oxidized indole compounds. Attached Figure Description

[0024] Figure 1 It is the indole oxide compound-1c obtained in Example 1. 1 H NMR spectrum;

[0025] Figure 2 It is the indole oxide compound-1c obtained in Example 1. 13 C10 NMR spectrum. Detailed Implementation

[0026] Specific Implementation Method 1: This implementation method provides a method for preparing an indole oxide compound, specifically following these steps:

[0027] 1. Under a nitrogen atmosphere and at room temperature, heteroarylformic acid compounds, N-arylacrylamide compounds, DABCO, K2S2O8 and Fe(acac)3 were sequentially added to an ultra-dry solvent to obtain a mixed solution;

[0028] 2. The mixed solution is irradiated with an LED light source, then extracted, and the solvent is removed by rotary evaporation. The solution is then separated and purified by thin-layer chromatography to obtain an indole oxide compound, thus completing the preparation. Other steps are the same as in Specific Implementation Method 1.

[0029] Specific Implementation Method Two: This implementation method differs from Specific Implementation Method One in that the heteroaryl carboxylic acid compound mentioned in step one is 5-cyano-2-pyridinecarboxylic acid, quinoline-2-carboxylic acid, 2-methylpyridine-4-carboxylic acid, 6-(methoxycarbonyl)-2-pyridinecarboxylic acid, 3-chloropyridine-2-carboxylic acid, 4-chloropyridine-2-carboxylic acid, 3-bromopyridine-2-carboxylic acid, 2-pyrimidinecarboxylic acid, or 2-pyrazinic acid. Everything else is the same as in Specific Implementation Method One.

[0030] Specific Implementation Method Three: This implementation method differs from Specific Implementation Method One or Two in that the N-arylacrylamide compound mentioned in step one is N-methyl-N-phenylmethylacrylamide, with the following structural formula:

[0031] The preparation method of N-methyl-N-phenylmethylacrylamide is as follows: aniline, DCM, and triethylamine are stirred and mixed at 0°C, and methacryloyl chloride is added under an argon atmosphere; the resulting solution is then stirred at room temperature for 12 hours, the reaction is quenched with water, and extracted with DCM; the organic layer is washed with saturated brine, dried with sodium sulfate, and then concentrated under reduced pressure; N-methyl-N-phenylmethylacrylamide is obtained by thin-layer chromatography using petroleum ether and ethyl acetate as eluents. Other steps are the same as in specific embodiments one or two.

[0032] Specific Implementation Method Four: This implementation method differs from one of Specific Implementation Methods One to Three in that the DABCO mentioned in step one is 1,4-diazabicyclo[2.2.2]octane. Everything else is the same as in one of Specific Implementation Methods One to Three.

[0033] Specific Implementation Method Five: This implementation method differs from one of Specific Implementation Methods One to Four in that the solvent used in step one is dimethyl sulfoxide. Everything else is the same as in one of Specific Implementation Methods One to Four.

[0034] Specific Implementation Method Six: This implementation method differs from Specific Implementation Methods One to Five in that: the ratio of the heteroarylformic acid compound to the solvent in step one is 0.16–0.2 mmol:1 mL; the ratio of the N-arylacrylamide compound to the solvent is 0.08–0.1 mmol:1 mL; the ratio of DABCO to the solvent is 0.16–0.2 mmol:1 mL; the ratio of K₂S₂O₈ to the solvent is 0.16–0.2 mmol:1 mL; and the ratio of Fe(acac)₃ to the solvent is 4–6 mg:1 mL. Everything else is the same as in Specific Implementation Methods One to Five.

[0035] Specific Implementation Method Seven: This implementation method differs from Specific Implementation Methods One to Six in that the wavelength of the LED light source described in step two is 380–400 nm, the illumination time is 6–16 hours, and the power is 10–50 W. Everything else is the same as in Specific Implementation Methods One to Six.

[0036] Specific Implementation Method Eight: This implementation method differs from Specific Implementation Methods One to Seven in that step two uses ethyl acetate for extraction. Everything else is the same as in Specific Implementation Methods One to Seven.

[0037] Specific Implementation Method Nine: This implementation method differs from Specific Implementation Methods One to Eight in that the solvent used for separation and purification in step two is a mixture of petroleum ether and ethyl acetate. Everything else is the same as in Specific Implementation Methods One to Eight.

[0038] Specific Embodiment Ten: This embodiment differs from Specific Embodiments One to Nine in that the volume ratio of petroleum ether to ethyl acetate is 3:1. Everything else is the same as in Specific Embodiments One to Nine.

[0039] The scope of this invention is not limited to the above-described embodiments; a combination of one or more specific embodiments can also achieve the purpose of the invention.

[0040] Example 1:

[0041] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0042] 1. Take 0.4 mmol of 2-pyridinecarboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 and add them to the photoreaction tube in sequence. Then add 2 mL of dimethyl sulfoxide and dissolve them completely to obtain a mixed solution.

[0043] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0044] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 1c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0045]

[0046] Purity 99%, yield 72%; its NMR data analysis is as follows: 1 H NMR (400MHz, Chloroform-d) δppm = 8.31 (d, J = 4.7Hz, 1H), 7.42 (t, J = 7.7Hz, 1H), 7.17-7.11 (m, 2H), 7.00-6. 91(m,3H),6.65(d,J=7.7Hz,1H),3.39(d,J=13.3Hz,1H),3.23(d,J=13.2Hz,1H),3.11(s,3H),1.50(s,3H). 13 C NMR (101MHz, Chloroform-d) δppm=180.17(s), 156.94(s), 148.50(s), 142.98(s), 135.86(s), 132.87(s), 127 .74(s),123.96(s),123.56(s),122.21(s),121.53(s),107.70(s),49.02(s),45.91(s),26.17(s),23.52(s).

[0047] Example 2:

[0048] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0049] 1. Take 0.4 mmol quinoline-2-carboxylic acid, 0.2 mmol N-methyl-N-phenylmethylacrylamide, 0.2 mmol DABCO, 0.2 mmol K2S2O8 and 10 mg Fe(acac)3 and add them to the photoreaction tube in sequence, then add 2 mL of dimethyl sulfoxide and dissolve them completely to obtain a mixed solution;

[0050] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0051] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 2c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0052]

[0053] Purity 99%, yield 61%; its NMR data analysis is as follows: 1H NMR (400MHz, Chloroform-d) δppm=7.88(d,J=8.4Hz,1H),7.79(d,J=8.4Hz,1H),7.66(d,J=8.1Hz,1H),7.58(t,J=7.7Hz,1H),7.41(t,J=7.9Hz, 1H),7.17-7.02(m,3H),6.93(t,J=7.5Hz,1H),6.66(d,J=7.6Hz,1H),3. 60(d,J=14.0Hz,1H),3.44(d,J=14.0Hz,1H),3.17(s,3H),1.54(s,3H). 13 CNMR(101MHz,Chloroform-d)δppm=180.52(s),157.52(s),147.49(s),143.31(s),135.56(s),133.30(s),129.14(s),129.05(s) ),127.68(s),127.37(s),126.66(s),125.89(s),123.25(s),122.09(s),121.93(s),107.73(s),46.26(s),26.29(s),24.06(s).

[0054] Example 3:

[0055] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0056] 1. Take 0.4 mmol of 2-methylpyridine-4-carboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 and add them to the photoreaction tube in sequence. Then add 2 mL of dimethyl sulfoxide and dissolve them completely to obtain a mixed solution.

[0057] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0058] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 3c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0059]

[0060] Purity 99%, yield 52%; its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δppm=8.14(d,J=5.1Hz,1H),7.24-7.15(m,2H),7.06(t,J=7.5Hz,1H),6.64(d,J=7.3Hz ,2H),6.55(d,J=5.0Hz,1H),3.11(d,J=12.7Hz,1H),3.00(s,3H),2.94(d,J=12.7Hz,1H),2.35(s,3H),1.49(s,3H). 13 C NMR (101MHz, Chloroform-d) δppm=179.33(s), 157.70(s), 148.32(s), 145.50(s), 143.09(s), 132.29(s), 128.22(s) ),124.54(s),123.09(s),122.37(s),122.02(s),108.14(s),49.59(s),43.73(s),25.97(s),24.20(s),23.23(s).

[0061] Example 4:

[0062] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0063] 1. 0.4 mmol 6-(methoxycarbonyl)-2-pyridinecarboxylic acid, 0.2 mmol N-methyl-N-phenylmethylacrylamide, 0.2 mmol DABCO, 0.2 mmol K2S2O8 and 10 mg Fe(acac)3 were added sequentially to the photoreaction tube, followed by 2 mL of dimethyl sulfoxide, and the mixture was thoroughly dissolved to obtain a mixed solution.

[0064] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0065] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 4c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0066]

[0067] Purity 99%, yield 58%; its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δppm=7.80(d,J=8.5Hz,1H),7.56(t,J=7.8Hz,1H),7.17-7.11(m,3H),6.96(t,J=7.5Hz ,1H),6.67(d,J=7.5Hz,1H),3.91(s,3H),3.53(d,J=13.9Hz,1H),3.35(d,J=13.9Hz,1H),3.15(s,3H),1.49(s,3H). 13 C NMR (101MHz, Chloroform-d) δppm=180.14(s), 166.82(s), 157.61(s), 147.10(s), 143.15(s), 136.60(s), 132.86(s), 127 .71(s),126.92(s),123.38(s),122.98(s),122.14(s),107.75(s),52.67(s),48.62(s),45.38(s),26.20(s),23.94(s).

[0068] Example 5:

[0069] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0070] 1. Add 0.4 mmol of 2-pyrimidinecarboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 sequentially to the photoreaction tube, then add 2 mL of dimethyl sulfoxide and dissolve thoroughly to obtain a mixed solution;

[0071] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0072] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 5c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0073]

[0074] Purity 99%, yield 68%; its NMR data analysis is as follows: 1 H NMR(400MHz,Chloroform-d)δppm=8.42(d,J=4.9Hz,2H),7.19-7.05(m,2H),6.97-6.87(m,2H), 6.72(d,J=7.8Hz,1H), 3.71(d,J=14.8Hz,1H), 3.45(d,J=14.8Hz,1H), 3.24(s,3H), 1.52(s,3H). 13 C NMR (101MHz, Chloroform-d) δppm=180.74(s), 167.19(s), 156.54(s), 143.64(s), 133.08(s), 127 .67(s),122.79(s),122.02(s),118.64(s),107.68(s),47.70(s),46.43(s),26.41(s),24.64(s).

[0075] Example 6:

[0076] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0077] 1. Add 0.4 mmol of 2-pyrazine carboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 sequentially into the photoreaction tube, then add 2 mL of dimethyl sulfoxide and dissolve thoroughly to obtain a mixed solution;

[0078] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0079] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 6c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0080]

[0081] Purity 99%, yield 64%; its NMR data analysis is as follows: 1H NMR(400MHz,Chloroform-d)δppm=8.26(dd,J=7.9,1.9Hz,3H),8.18(s,1H),7.20-7.09(m,2H),7.00 (t,J=7.5Hz,1H),6.67(d,J=7.8Hz,1H),3.44(d,J=13.6Hz,1H),3.23(d,J=13.6Hz,1H),3.13(s,3H). 13 CNMR(101MHz,Chloroform-d)δppm=178.66(s),152.94(s),145.14(s),143.56(s),142.97(s),142.58(s) ),132.23(s),128.12(s),123.22(s),122.45(s),107.97(s),48.73(s),43.25(s),26.25(s),23.67(s).

[0082] Example 7:

[0083] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0084] 1. Add 0.4 mmol of 3-bromo-2-pyridinecarboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 sequentially to the photoreaction tube, then add 2 mL of dimethyl sulfoxide and dissolve thoroughly to obtain a mixed solution;

[0085] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0086] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 7c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0087]

[0088] Purity 99%, yield 58%; its NMR data analysis is as follows: 1H NMR(400MHz,Chloroform-d)δppm=8.14(d,J=4.5Hz,1H),7.63(d,J=8.0Hz,1H),7.18-7.05(m,2 H),6.92-6.72(m,3H),3.64(d,J=17.1Hz,1H),3.51(d,J=15.6Hz,1H),3.25(s,3H),1.50(s,3H). 13 C NMR(101MHz,Chloroform-d)δppm=181.06(s),155.90(s),147.13(s),143.87(s),139.67(s),133.51(s),127 .56(s),122.56(s),122.35(s),121.82(s),121.54(s),107.60(s),47.72(s),43.33(s),26.42(s),24.73(s).

[0089] Example 8:

[0090] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0091] 1. Add 0.4 mmol of 3-chloro-2-pyridinecarboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 sequentially to the photoreaction tube, then add 2 mL of dimethyl sulfoxide and dissolve completely to obtain a mixed solution;

[0092] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0093] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 8c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0094]

[0095] Purity 99%, yield 62%; its NMR data analysis is as follows: 1H NMR (400MHz, Chloroform-d) δppm=8.12(d,J=4.7Hz,1H),7.44(d,J=8.0Hz,1H),7.15(t,J=8.3Hz,1H),7.06(d,J=7.9Hz, 1H),6.92-6.87(m,2H),6.73(d,J=7.7Hz,1H),3.63(d,J=15.4Hz,1H),3.46(d,J=15.4Hz,1H),3.24(s,3H),1.50(s,3H). 13 C NMR(101MHz,Chloroform-d)δppm=181.00(s),154.74(s),146.60(s),143.77(s),136.35(s),133.43(s) ),131.17(s),127.61(s),122.44(s),121.84(s),107.62(s),47.68(s),41.26(s),26.42(s),24.59(s).

[0096] Example 9:

[0097] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0098] 1. Add 0.4 mmol of 4-chloro-2-pyridinecarboxylic acid, 0.2 mmol of N-methyl-N-phenylmethylacrylamide, 0.2 mmol of DABCO, 0.2 mmol of K2S2O8 and 10 mg of Fe(acac)3 sequentially into the photoreaction tube, then add 2 mL of dimethyl sulfoxide and dissolve thoroughly to obtain a mixed solution;

[0099] 2. After purging with nitrogen for 5 minutes, the mixture obtained in step 1 was irradiated with an LED light source with a power of 10W and a wavelength of 390nm for 16 hours under the stirring condition of a magnetic stirrer at a speed of 660r / min. The reaction progress was monitored by TLC. The mixture was then extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The product was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, thus completing the preparation.

[0100] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 9c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0101]

[0102] Purity 99%, yield 65%; its NMR data analysis is as follows: 1H NMR (400MHz, Chloroform-d) δppm=8.18(d,J=5.3Hz,1H),7.17(t,J=7.2Hz,1H),7.11(d,J=7.0Hz,1H),7.02- 6.93(m,3H),6.68(d,J=7.7Hz,1H),3.39(d,J=13.4Hz,1H),3.18(d,J=13.4Hz,1H),3.14(s,3H),1.49(s,3H). 13 C NMR(101MHz,Chloroform-d)δppm=179.97(s),158.77(s),149.56(s),143.60(s),143.02(s),132.55(s) ,127.93(s),124.01(s),123.36(s),122.30(s),121.89(s),107.85(s),48.83(s),26.22(s),23.63(s).

[0103] Example 10:

[0104] This embodiment describes a method for preparing an indole oxide compound, which is carried out according to the following steps:

[0105] 1. Take 12 mmol of 2-pyridinecarboxylic acid, 6 mmol of N-methyl-N-phenylmethylacrylamide, 6 mmol of DABCO, 6 mmol of K2S2O8 and 300 mg of Fe(acac)3 and add them to a round-bottom flask in sequence. Then add 60 mL of dimethyl sulfoxide and dissolve them completely to obtain a mixed solution.

[0106] 2. Nitrogen gas was purged for 15 minutes to remove oxygen. Then, under the stirring conditions of a magnetic stirrer, the stirrer speed was controlled at 660 r / min. The mixed solution obtained in step 1 was irradiated with an LED light source with a power of 50W and a wavelength of 390nm for 16 hours. The reaction progress was monitored by TLC. Then, the solution was extracted with ethyl acetate, and the solvent was removed by rotary evaporation. The solution was then separated and purified by thin-layer chromatography. The obtained product was an indole oxide compound, and the preparation was completed.

[0107] The indole oxide compound prepared in this embodiment was identified as indole oxide compound 1c by 1H NMR, 1C NMR, and mass spectrometry, and its structural formula is as follows:

[0108]

[0109] Purity 99%, yield 76%; its NMR data analysis is as follows: 1H NMR (400MHz, Chloroform-d) δppm = 8.31 (d, J = 4.7Hz, 1H), 7.42 (t, J = 7.7Hz, 1H), 7.17-7.11 (m, 2H), 7.00-6. 91(m,3H),6.65(d,J=7.7Hz,1H),3.39(d,J=13.3Hz,1H),3.23(d,J=13.2Hz,1H),3.11(s,3H),1.50(s,3H). 13 C NMR (101MHz, Chloroform-d) δppm=180.17(s), 156.94(s), 148.50(s), 142.98(s), 135.86(s), 132.87(s), 127 .74(s),123.96(s),123.56(s),122.21(s),121.53(s),107.70(s),49.02(s),45.91(s),26.17(s),23.52(s).

[0110] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Other variations and modifications are possible without departing from the technical solutions described in the claims.

Claims

1. A method for preparing an indole oxide compound, characterized in that... This method is specifically carried out in the following steps:

1. Under a nitrogen atmosphere and at room temperature, heteroarylformic acid compounds, N-arylacrylamide compounds, DABCO, K2S2O8 and Fe(acac)3 were sequentially added to an ultra-dry solvent to obtain a mixed solution; 2. The mixed solution is irradiated with an LED light source, then extracted, and the solvent is removed by rotary evaporation. The product is then separated and purified by thin-layer chromatography. The obtained product is an oxidized indole compound, thus completing the preparation. The heteroaryl carboxylic acid compound mentioned in step one is 2-pyridinecarboxylic acid, quinoline-2-carboxylic acid, 2-methylpyridine-4-carboxylic acid, 6-(methoxycarbonyl)-2-pyridinecarboxylic acid, 3-chloropyridine-2-carboxylic acid, 4-chloropyridine-2-carboxylic acid, 3-bromopyridine-2-carboxylic acid, 2-pyrimidinecarboxylic acid, or 2-pyrazinic acid; The N-arylacrylamide compound mentioned in step one is N-methyl-N-phenylmethylacrylamide, with the following structural formula: ; The wavelength of the LED light source mentioned in step two is 390nm; The structural formula of the indole oxide compound is as follows: , , , , , , , or .

2. The method for preparing an indole oxide compound according to claim 1, characterized in that... The preparation method of N-methyl-N-phenylmethylacrylamide is as follows: aniline, DCM and triethylamine are stirred and mixed at 0°C, and methacryloyl chloride is added under an argon atmosphere; the resulting solution is stirred at room temperature for 12 hours, the reaction is quenched with water, and extracted with DCM; the organic layer is washed with saturated brine, dried with sodium sulfate, and then concentrated under reduced pressure; N-methyl-N-phenylmethylacrylamide is obtained by thin-layer chromatography using petroleum ether and ethyl acetate as eluents.

3. The method for preparing an indole oxide compound according to claim 1, characterized in that... The DABCO mentioned in step one is 1,4-diazabicyclo[2.2.2]octane.

4. The method for preparing an indole oxide compound according to claim 1, characterized in that... The solvent used in step one is dimethyl sulfoxide.

5. The method for preparing an indole oxide compound according to claim 1, characterized in that... The ratio of the heteroarylformic acid compound to the solvent in step one is 0.16~0.2 mmol:1mL; the ratio of the N-arylacrylamide compound to the solvent is 0.08~0.1 mmol:1mL; the ratio of DABCO to the solvent is 0.16~0.2 mmol:1mL; the ratio of K2S2O8 to the solvent is 0.16~0.2 mmol:1mL; and the ratio of Fe(acac)3 to the solvent is 4~6 mg:1mL.

6. The method for preparing an indole oxide compound according to claim 1, characterized in that... Step 2: Illumination time is 6-16 hours, and power is 10-50W.

7. The method for preparing an indole oxide compound according to claim 1, characterized in that... Step two involves extraction with ethyl acetate.

8. The method for preparing an indole oxide compound according to claim 1, characterized in that... The solvent used for separation and purification in step two is a mixture of petroleum ether and ethyl acetate.

9. The method for preparing an indole oxide compound according to claim 8, characterized in that... The volume ratio of petroleum ether to ethyl acetate is 3:1.

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