A method for light-induced synthesis of carbazole compounds

Abstract

The invention discloses a method for photoinduced synthesis of carbazole compounds. The method uses easily available nitroaromatic hydrocarbons and aromatic Grignard reagents as substrates, realizes continuous C-N bond and C-C bond coupling reactions between molecules by illumination under an argon atmosphere, and obtains a series of carbazole compounds. The reaction system of the invention is simple, easy to operate, mild reaction conditions, and good yield; starting from easily available nitroaromatic hydrocarbons, the preparation of complex substrates is avoided; and the use of traditional noble metal catalysts is avoided. The invention provides a new transition metal-free, green, and efficient way to synthesize carbazole compounds for the pharmaceutical industry and organic materials.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of carbazole compounds, and particularly relates to a method for synthesizing carbazole compounds by light induction using nitroaromatic hydrocarbons and aromatic Grignard reagents as raw materials. Background Art

[0002] Carbazole is a common structural skeleton in natural products, medicines and new organic materials. Therefore, in the past few decades, a variety of strategies for the synthesis of carbazole have been developed. The synthesis strategies can be divided into three categories: the first category is through the coupling reaction of the CN bond within the molecule; the second category is through the coupling reaction of the CC bond within the molecule; the third category is through the coupling reaction of the continuous CC bond and CN bond between molecules. Representative CN bond coupling cyclization strategies include: (1) transition metal catalyzed amination reaction of 2-amino-2'-halogenated biphenyl or 2-aminobiphenyl (Bioorg. Med. Chem. Lett., 2007, 17, 1043–1046; J. Am. Chem. Soc., 2008, 130, 16184–16186; J. Am. Chem. Soc., 2011, 133, 5996–6005). (2) Transition metal-catalyzed or photocatalyzed insertion reaction of 2-azidobiphenyl into a nitro intermediate (Tetrahedron, 2007, 63, 10320–103291; J. Org. Chem., 2009, 74, 3225–3228). (3) Reductive coupling of 2-nitrobiphenyl (J. Chem. Soc. C, 1969, 2808–2813; Angew. Chem., Int. Ed., 2014, 53, 2701–2705). In addition, transition metal-catalyzed coupling of CC bonds within diarylamine molecules can also construct carbazole skeletons (J. Am. Chem. Soc., 2006, 128, 581–590; J. Org. Chem. 2008, 73, 5022–5028). Although these methods have high yields and are tolerant to most organic functional groups, they require the preparation of complex starting materials (such as 2-amino or azide or nitrobiphenyl and diarylamine) to synthesize carbazole compounds. The Bedford group and the Ackermann group reported palladium-catalyzed CH bond activation and Buchwald-Hartwig amination tandem reactions (J. Org. Chem., 2006, 71, 940–39410; Angew. Chem., Int. Ed., 2007, 46, 1627–1629). The Jean group reported palladium-catalyzed Suzuki cross-coupling and SNAr reaction tandem reactions (Org. Lett., 2007, 9, 4893–4896). Therefore, it is an efficient and economical strategy to develop a continuous CC and CN bond coupling reaction using commercially available or easily prepared starting materials.

[0003] The above reactions usually use functionalized aromatic amines, biphenyls, and diphenylamines as raw materials, while aromatic amines are generally prepared by nitro reduction, and complex functionalized biphenyls and diphenylamines often require transition metal-catalyzed coupling or Buchwald-Hartwig amination reactions. In addition, these reactions or the preparation of their raw materials require the participation of transition metal catalysis, and the residual transition metals have a great toxic effect on drug activity and material properties. Therefore, organic synthesis reactions without transition metal catalysis are favored by researchers in pharmaceutical and organic material process development. Nitroaromatics are common intermediates in medicines, pesticides, and functional materials. Directly using nitroaromatics as a nitrogen source can not only achieve step economy, but also improve the compatibility of functional groups. Therefore, the development of transition metal-free catalysis, using simple and readily available nitroaromatics as nitrogen sources, and directly synthesizing high-value-added carbazole compounds has important research significance in organic synthesis. Summary of the invention

[0004] The purpose of the present invention is to provide a method for synthesizing high value-added carbazole compounds by directly inducing continuous CN bonds and CC bonds coupling reaction between nitroaromatic hydrocarbons and aromatic Grignard reagents without transition metal catalysis and external reducing agents. The method not only solves the problem of difficult preparation of substrates, but also avoids the use of transition metal catalysts and external reducing agents, and is an economical and efficient method for synthesizing carbazole compounds.

[0005] In view of the above purpose, the technical solution adopted by the present invention is: adding a nitroaromatic hydrocarbon represented by formula I or I′ or I″ and an aromatic Grignard reagent represented by formula II or II′ to an organic solvent, performing continuous CN bond and CC bond coupling reactions between molecules by light under argon protection conditions, quenching after the reaction is complete, separating and purifying the product, and obtaining a carbazole compound represented by formula III or III′ or III″.

[0006]

[0007] In the formula, R 1 , R 2 Each independently represents any one or two of H, C1-C4 alkyl, C1-C4 alkoxy, phenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, pyrazolyl, C1-C4 alkyl-substituted pyrazolyl, C1-C4 alkoxy-substituted pyrazolyl, and R 1 , R 2 They are not H at the same time; X represents any one of CH2, O, S, and N-CH3; Y represents O or CH.

[0008] In the above synthesis method, the amount of the aromatic Grignard reagent used is preferably 4.0 to 5.0 times the molar amount of the nitroarene.

[0009] In the above synthesis method, the organic solvent is preferably tetrahydrofuran, or a mixed solvent of tetrahydrofuran and any one of 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, diethyl ether, toluene, and 1,4-dioxane.

[0010] In the above synthesis method, it is preferred that the reaction be carried out in an argon atmosphere at 60 to 80° C. for 5 to 12 hours under irradiation with near-violet light having a wavelength of 365 to 420 nm.

[0011] The beneficial effects of the present invention are as follows:

[0012] The reaction system of the invention is simple. Without the need for transition metal catalysts and external reducing agents, high value-added carbazole compounds are synthesized by direct continuous CN bond and CC bond coupling reaction between light-induced nitroaromatic hydrocarbons and aromatic Grignard reagents. The method is used to synthesize carbazole alkaloids Glycozoline and Glycborine with anti-HIV activity from simple raw materials in one step. In addition, Glycozoline is further derivatized to prepare Glycozolinol and carbazole alkaloids with anti-tuberculosis; and carbazole compounds containing naphthalene rings with large conjugated structures are also prepared. Since the method avoids the use of transition metals and the step of reducing nitroaromatic hydrocarbons to aromatic amines, the reaction provides a new, simple and efficient way for synthesizing carbazole compounds in the pharmaceutical and material industries. In addition, the method is consistent with the concepts of environmental protection, economy and green chemistry and has important application potential. DETAILED DESCRIPTION

[0013] The present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0014] Example 1

[0015] Under argon atmosphere, the Schlenk tube equipped with magnetic drying was evacuated and filled with argon for 3 times. 51 μL (0.5 mmol) of nitrobenzene and 0.8 mL of tetrahydrofuran were added in sequence, and then 1.25 mL of 2.0 mol / L (2.5 mmol) of phenylmagnesium chloride in tetrahydrofuran solution was slowly added under ice-water bath conditions. The Schlenk tube was irradiated with two 9W LED lamps with a wavelength of 390-395 nm, and refluxed at 70 ° C for 5 h. After the reaction was completed and cooled to room temperature, the reaction was quenched with a saturated NH4Cl aqueous solution, extracted with ethyl acetate (3 times × 15.0 mL), and the obtained organic phase was washed with a saturated NaCl aqueous solution, and the organic phase was dried with anhydrous Na2SO4, and concentrated under reduced pressure to obtain a crude product; the crude product was separated and purified by column chromatography using a 20:2:1 eluent of petroleum ether: dichloromethane: ethyl acetate to obtain a white solid carbazole with the following structural formula, and the yield was 60%.

[0016]

[0017] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, DMSO-d6) δ11.25(br s,1H),8.11(d,J=8.0Hz,2H),7.49(d,J=8.0Hz,2H),7.38(t,J=7.6Hz,2H),7.15(t,J=7.6Hz,2H); 13 CNMR (100 MHz, DMSO-d6) δ 139.9, 125.7, 122.5, 120.3, 118.7, 111.1. The data are consistent with the known literature reports (Green Chem., 2018, 20, 1362–1366).

[0018] Example 2

[0019] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 4-nitrotoluene, and the other steps were the same as those in Example 1 to obtain white solid 3-methylcarbazole with the following structural formula, with a yield of 68%.

[0020]

[0021] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz,DMSO-d6)δ11.09(br s,1H),8.05(d,J=7.8Hz,1H),7.89(s,1H),7.44(d,J=8.0Hz,1H),7.39–7.31(m,2H),7.23–7.17(m,1H),7.15–7.08(m,1H),2.46(s,3H); 13 C NMR (100 MHz, DMSO-d6) δ 140.1, 138.1, 127.3, 127.0, 125.5, 122.7, 122.4, 120.2, 120.0, 118.4, 111.0, 110.8, 21.2. The data are consistent with the known literature reports (Green Chem., 2018, 20, 1362–1366).

[0022] Example 3

[0023] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 4-nitrobenzene methyl ether, and the other steps were the same as those in Example 1 to obtain white solid 3-methoxycarbazole with the following structural formula, with a yield of 55%.

[0024]

[0025] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ8.04 (d, J = 7.8Hz, 1H), 7.90 (br s,1H),7.57(d,J=2.4Hz,1H),7.46–7.37(m,2H),7.33(d,J=8.8Hz,1H),7.25–7.15(m,1H),7.08(dd,J=8.8,2.4Hz,1H),3.94(s,3H); 13 C NMR (100 MHz, CDCl3) δ 154.1, 140.4, 134.5, 125.9, 123.9, 123.5, 120.4, 119.2, 115.2, 111.4, 110.9, 103.4, 56.2. The data are consistent with the known literature reports (Green Chem., 2018, 20, 1362–1366).

[0026] Example 4

[0027] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 4-nitrobiphenyl, and the other steps were the same as in Example 1 to obtain white solid 3-phenylcarbazole with the following structural formula, and the yield was 45%.

[0028]

[0029] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz,DMSO-d6)δ11.33(br s,1H),8.45(d,J=1.6Hz,1H),8.22(d,J=7.8Hz,1H),7.81–7.73(m,2H),7.71(dd,J=8.4,1.8Hz,1H),7. 57(d,J=8.4Hz,1H),7.54–7.45(m,3H),7.43–7.38(m,1H),7.33(t,J=7.4Hz,1H),7.18(t,J=7.8Hz,1H); 13 C NMR (100 MHz, DMSO-d6) δ 141.3, 140.2, 139.3, 131.0, 128.8, 126.7, 126.3, 125.7, 124.6, 123.1, 122.6, 120.4, 118.6, 118.3, 111.3, 111.1. The data are consistent with the known literature reports (Green Chem., 2018, 20, 1362–1366).

[0030] Example 5

[0031] In this example, 1-(4-nitrophenyl)-1H-pyrazole was used to replace the nitrobenzene in Example 1 in an equal mole ratio, and the other steps were the same as those in Example 1 to obtain a white solid product with the following structural formula, and the yield was 57%.

[0032]

[0033] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz,DMSO-d6)δ11.39(br s,1H),8.70–8.34(m,2H),8.19(d,J=7.8Hz,1H),7.96–7.83(m,1H),7.80–7.66(m,1H),7.58(d,J= 8.8Hz,1H),7.52(d,J=8.0Hz,1H),7.42(t,J=7.4Hz,1H),7.19(t,J=7.4Hz,1H),6.68–6.39(m,1H). 13 C NMR(100MHz,DMSO-d6)δ140.6,140.1,138.1,132.5,127.7,126.1,122.6,122.4,120.5,118.7,117.6,111.4,111.2,110.6,107.2; HRMS(ESI)(m / z)C 15 H 12 N3[M+H] + :Theoretical value 234.1026, actual value 234.1022.

[0034] Example 6

[0035] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 5-nitro-2-methylanisole, and the other steps were the same as in Example 1 to obtain a white solid product with the following structural formula, and the yield of 4-methoxy-3-methylcarbazole was 39%, and the yield of 2-methoxy-3-methylcarbazole was 28%.

[0036]

[0037] The NMR spectrum data of 4-methoxy-3-methylcarbazole are: 1 H NMR(400MHz,DMSO-d6)δ11.21(br s,1H),8.10(d,J=7.8Hz,1H),7.46(d,J=8.0Hz,1H),7.36(t,J=7.6Hz,1H),7.25–7.10(m,3H),3.90(s,3H),2.37(s,3H); 13C NMR(100MHz,DMSO-d6)δ153.0,140.1,139.6,128.6,125.1,121.9,120.6,119.0,118.7,115.4,110.7,106.8,59.4,14.9; HRMS(ESI)(m / z)C 14 H 14 NO[M+H] + :Theoretical value 212.1070, actual value 212.1075.

[0038] The NMR data of 2-methoxy-3-methylcarbazole are: 1 H NMR(400MHz,DMSO-d6)δ11.00(br s,1H),7.93(d,J=7.6Hz,1H),7.81(s,1H),7.40(d,J=8.0Hz,1H),7.25(t,J =7.4Hz,1H),7.08(t,J=7.2Hz,1H),6.96(s,1H),3.87(s,3H),2.28(s,3H); 13 C NMR (100 MHz, DMSO-d6) δ 156.7, 139.5, 139.4, 123.7, 122.6, 121.1, 119.0, 118.3, 117.3, 115.2, 110.5, 92.7, 55.3, 16.6. The data are consistent with the known literature reports (Org. Biomol. Chem., 2016, 14, 122-130).

[0039] Example 7

[0040] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 6-nitro-1,4-benzodioxane, and the other steps were the same as in Example 1 to obtain a white solid product with the following structural formula, and the yield was 61%.

[0041]

[0042] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ8.22 (d, J = 7.8Hz, 1H), 7.73 (br s,1H),7.34(t,J=7.6Hz,1H),7.29–7.12(m,2H),6.96(d,J=8.6Hz,1H),6.77(d,J=8.6Hz,1H),4.50–4.37(m,2H),4.35–4.24(m,2H); 13C NMR(100MHz, CDCl3)δ139.7,139.1,136.4,135.5,125.3,123.0,122.4,119.3,116.1,112.9,110.2,103.0,65.1,64.4; HRMS(ESI)(m / z)C 14 H 12 NO2[M+H] + :Theoretical value 226.0863, actual value 226.0871.

[0043] Example 8

[0044] In this example, 2-nitronaphthalene was used in place of nitrobenzene in Example 1 in equal moles, and the reflux reaction time was extended to 12 hours. The other steps were the same as in Example 1 to obtain a white solid product having the following structural formula, with a yield of 63%.

[0045]

[0046] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ8.80(d,J=8.4Hz,1H),8.59(d,J=8.0Hz,1H),8.36(br s,1H),8.02(d,J=8.0Hz,1H),7.87(d,J=8.8Hz,1H),7.71(t,J=7.2Hz,1H),7.66–7.35(m,5H); 13 C NMR (100 MHz, CDCl3) δ 138.6, 137.2, 130.1, 129.3, 127.6, 127.0, 124.5, 124.1, 123.4, 123.2, 122.2, 120.4, 115.6, 112.7, 111.3. The data are consistent with the known literature reports (Org. Biomol. Chem., 2016, 14, 122-130).

[0047] Example 9

[0048] In this example, 5-nitrobenzene in Example 1 was replaced by an equal mole of 5-nitrobenzene, and the reflux reaction time was extended to 12 hours. The other steps were the same as in Example 1 to obtain a white solid product with the following structural formula, and the yield was 55%.

[0049]

[0050] The NMR spectrum data of the obtained product are: 1H NMR(400MHz,DMSO-d6)δ11.55(br s,1H),8.41(d,J=7.8Hz,1H),8.20(d,J=5.2Hz,1H),8.10–7.84(m,1H),7.69–7.51(m,2H),7.42(t,J=7.6Hz,1H),7.25(t,J=7.4Hz,1H); 13 C NMR(100MHz,DMSO-d6)δ138.8,137.2,133.1,131.0,128.2,124.7,121.8,121.8,121.1,119.8,118.9,115.6,111.2,109.7; HRMS(APCI)(m / z)C 14 H 10 NS[M+H] + :Theoretical value 224.0528, actual value 224.0527.

[0051] Example 10

[0052] In this example, nitrobenzene in Example 1 was replaced by an equal mole of N-methyl-5-nitroindole, and the reflux reaction time was extended to 12 hours. The other steps were the same as in Example 1 to obtain a white solid product with the following structural formula, and the yield was 53%.

[0053]

[0054] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ8.25 (d, J = 7.8Hz, 1H), 7.92 (br s,1H),7.42–7.33(m,3H),7.31–7.25(m,1H),7.22(d,J=8.6Hz,1H),7.17(d,J=2.6Hz,1H),7.00(d,J=2.6Hz,1H),3.83(s,3H); 13 C NMR (100MHz, CDCl3) δ139.1,134.4,132.0,128.7,124.3,123.9,121.9,121.4,119.2,114.6,110.6,108.5,106.0,99.2,33.4; HRMS(ESI)(m / z)C 15 H 13 N2[M+H] + :Theoretical value 221.1073, actual value 221.1078.

[0055] Embodiment 11

[0056] In this example, nitrobenzene in Example 1 was replaced by an equal mole of 2-n-butyl 5-nitrobenzofuran, and the reflux reaction time was extended to 12 hours. The other steps were the same as in Example 1 to obtain a white solid product with the following structural formula, and the yield was 60%.

[0057]

[0058] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ8.16 (d, J = 7.8Hz, 1H), 8.09 (br s,1H),7.51(d,J=8.6Hz,1H),7.48–7.36(m,2H),7.33–7.20(m,2H),6.93(s,1H),2 .89(t,J=7.4Hz,2H),1.97–1.72(m,2H),1.58–1.40(m,2H),0.99(t,J=7.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ160.5,150.0,139.6,135.8,125.1,123.5,122.2,121.3,11 9.4,114.8,110.8,109.3,106.0,101.0,30.2,28.6,22.5,14.0; HRMS(ESI)(m / z)C 18 H 18 NO[M+H] + :Theoretical value 264.1383, actual value 264.1389.

[0059] Example 12

[0060] In this example, 4-tolylmagnesium chloride was used to replace the phenylmagnesium chloride in Example 2 in an equal mole ratio, and the other steps were the same as those in Example 2 to obtain a white solid product with the following structural formula, and the yield was 68%.

[0061]

[0062] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.84 (s, 3H), 7.30 (d, J = 8.2Hz, 2H), 7.21 (d, J = 8.2Hz, 2H), 2.52 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 138.2, 128.6, 127.1, 123.6, 120.3, 110.4, 21.6. The data are consistent with those reported in the literature (Angew. Chem. Int. Ed. 2014, 53, 3505-3509).

[0063] Example 13

[0064] In this example, 4-nitrotoluene in Example 12 was replaced by 4-nitroanisole in equal moles, and the other steps were the same as those in Example 12 to obtain white solid carbazole alkaloid Glycozoline with a yield of 70%.

[0065]

[0066] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz,DMSO-d6)δ10.85(br s,1H),7.87(s,1H),7.61(d,J=2.2Hz,1H),7.33(t,J=8.0Hz,2H),7.17(d,J=8.2Hz,1H),6.98(dd,J=8.8,2.2Hz,1H),3.83(s,3H),2.45(s,3H); 13 C NMR (100 MHz, DMSO-d6) δ 152.8, 138.7, 134.8, 126.7, 126.5, 122.6, 122.5, 119.9, 114.5, 111.5, 110.7, 102.9, 55.6, 21.1. The data are consistent with known literature reports (J. Org. Chem., 2018, 83, 7347-7359).

[0067] Embodiment 14

[0068] In this example, 4-nitrotoluene in Example 12 was replaced by 3-nitroanisole in equal moles, and the other steps were the same as those in Example 12 to obtain white solid carbazole alkaloid Glycborine with a yield of 56%.

[0069]

[0070] The NMR spectrum data of the obtained product are: 1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.94(br s,1H),7.37–7.25(m,2H),7.21(d,J=8.2Hz,1H),7.02(d,J=8.0Hz,1H),6.67(d,J=8.0Hz,1H),4.09(s,3H),2.54(s,3H); 13 C NMR (100 MHz, CDCl3) δ 156.4, 141.4, 137.0, 129.0, 126.6, 126.3, 123.1, 123.0, 112.6 109.7, 103.7, 100.3, 55.6, 21.6. The data are consistent with known literature reports (Org. Lett., 2020, 22, 7244-7249).

[0071] Embodiment 15

[0072] In this example, 4-nitrotoluene in Example 2 was replaced by an equal mole of 4-nitroanisole, and phenylmagnesium chloride in Example 2 was replaced by an equal mole of 4-methoxyphenylmagnesium chloride. The other steps were the same as in Example 2 to obtain a white solid product with the following structural formula, and the yield was 60%.

[0073]

[0074] The NMR spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl3) δ7.75 (br s, 1H), 7.49 (d, J = 2.0Hz, 2H), 7.25 (d, J = 8.8Hz, 2H), 7.03 (dd, J = 8.6, 2.4Hz, 2H), 3.91 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ 153.8, 135.4, 123.8, 115.4, 111.7, 103.1, 56.2. The data are consistent with known literature reports (J. Org. Chem., 2018, 83, 7347-7359).

[0075] Example 16

[0076] In this example, 2-naphthylmagnesium bromide was used to replace the phenylmagnesium chloride in Example 2 with an equal molar amount, and the reflux reaction time was extended to 12 hours. The other steps were the same as in Example 2 to obtain a white solid product with the following structural formula, and the yield was 56%.

[0077]

[0078] The NMR spectrum data of the obtained product are: 1H NMR (400MHz, CDCl3) δ8.79(d,J=8.4Hz,1H),8.37(s,1H),8.29(s,1H),8.00(d,J=8.0Hz,1H),7.84(d,J= 8.8Hz,1H),7.72(t,J=7.6Hz,1H),7.64–7.56(m,1H),7.54–7.39(m,2H),7.34–7.23(m,1H),2.65(s,3H); 13 C NMR (100 MHz, CDCl3) δ 137.5, 136.9, 130.2, 129.7, 129.3, 129.3, 127.3, 126.9, 125.9, 124.4, 123.4, 130.0, 122.1, 115.4, 112.8, 110.9, 22.0. The data are consistent with the known literature reports (Org. Biomol. Chem., 2016, 14, 122-130).

[0079] Embodiment 17

[0080] In this example, 4-nitrotoluene in Example 16 was replaced by an equal molar amount of 2-nitronaphthalene, and the other steps were the same as in Example 16 to obtain a white solid product with the following structural formula, and the yield was 55%.

[0081]

[0082] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz, CDCl3) δ9.28(d,J=8.4Hz,2H),8.38(s,1H),8.08(d,J=8.0Hz,2H),7.84 (d,J=8.7Hz,2H),7.75(t,J=7.6Hz,2H),7.59(t,J=7.4Hz,2H),7.46(d,J=8.7Hz,2H); 13 C NMR (100 MHz, CDCl3) δ 136.2, 130.1, 129.3, 129.3, 126.9, 125.6, 125.3, 123.4, 117.7, 112.7. The data are consistent with known literature reports (Chem. Commun., 2019, 55, 13749-13752).

[0083] The carbazole alkaloid Glycozoline synthesized in the above Example 13 can be further derivatized to prepare Glycozolinol and carbazole alkaloids with anti-tuberculosis properties, and the specific method is as follows:

[0084] 105.6 mg (0.5 mmol) of Glycozoline was dissolved in 5.0 mL of DCM, cooled to -78°C, and then 1.0 mL of 1 mol / L (1 mmol) of dichloromethane solution of boron tribromide was added, heated to room temperature, and the reaction mixture was stirred at room temperature for 4 hours. Then, it was cooled with methanol, and the mixture was transferred to a separation funnel with ethyl acetate, washed several times with a saturated aqueous NaCl solution, extracted with ethyl acetate, and the organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using an eluent of petroleum ether: acetone in a volume ratio of 3:1 to obtain a white solid product Glycozolinol with the following structural formula, and the yield was 85%.

[0085]

[0086] The NMR spectrum data of the obtained product are: 1 H NMR(400MHz,DMSO-d6)δ10.72(br s,1H),8.89(brs,1H),7.76(s,1H),7.37(s,1H),7.32–7.21(m,2H),7.13(d,J=8.2Hz,1H),6.92–6.82(m,1H),2.43(s,3H); 13 C NMR (100 MHz, DMSO-d6) δ 150.2, 138.7, 134.1, 126.5, 126.2, 122.9, 122.4, 119.8, 114.8, 111.2, 110.5, 104.7, 21.0. The data are consistent with known literature reports (Chem. Commun., 2021, 57, 5274–5277).

[0087] 249.7 mg (1.1 mmol) of DDQ was added to 5.0 mL of a methanol solution containing 105.6 mg (0.5 mmol) of Glycozoline, and 1.5 mL of tetrahydrofuran and 0.5 mL of water were added. The reaction mixture was stirred at room temperature for 1.5 h, diluted with a 10% aqueous NaOH solution, extracted with ether for several times, the collected organic phase was washed with a saturated aqueous NaCl solution, and then the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using an eluent of petroleum ether: ethyl acetate in a volume ratio of 4:1 to obtain a white solid carbazole alkaloid with anti-tuberculosis properties with the following structural formula, and the yield was 70%.

[0088]

[0089] The NMR spectrum data of the obtained product are: 1H NMR(400MHz, CDCl3)δ10.09(s,1H),8.59–8.53(m,1H),8.46(br s,1H),7.95(dd,J=8.6,1.6Hz,1H),7.59(d,J=2.4Hz,1H),7.47(d,J=8.6Hz,1H),7.38(d,J=8.8Hz,1H),7.12(dd,J=8.8,2.4Hz,1H),3.94(s,3H); 13 C NMR (100MHz, CDCl3) δ192.0,154.9,144.1,134.8,128.9,127.3,124.3,123.9,123.7,116.4,112.1,111.2,103.4,56.1; HRMS(ESI)(m / z)C 14 H 12 NO2[M+H] + :Theoretical value 226.0863, actual value 226.0867.

Claims

1. A method for light-induced synthesis of carbazole compounds, characterized in that: The nitroaromatic hydrocarbon represented by formula I or I′ or I″ and the aromatic Grignard reagent represented by formula II or II′ are added to an organic solvent, and irradiated with a light source with a wavelength of 365 to 420 nm under argon protection to carry out continuous CN bond and CC bond coupling reactions between molecules, and after the reaction is complete, the product is quenched, separated and purified to obtain a carbazole compound represented by formula III or III′ or III″; In the formula, R 1 , R 2 Each independently represents any one or two of H, C1-C4 alkyl, C1-C4 alkoxy, phenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, pyrazolyl, C1-C4 alkyl-substituted pyrazolyl, C1-C4 alkoxy-substituted pyrazolyl, and R 1 , R 2 They are not H at the same time; X represents any one of CH2, O, S, and N-CH3; Y represents O or CH; The amount of the aromatic Grignard reagent used is 4.0 to 5.0 times the molar amount of the nitroaromatic hydrocarbon.

2. The method for light-induced synthesis of carbazole compounds according to claim 1, characterized in that: The organic solvent is tetrahydrofuran, or a mixed solvent of any one of 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, ethyl ether, toluene, 1,4-dioxane and tetrahydrofuran.

3. The method for light-induced synthesis of carbazole compounds according to claim 1, characterized in that: Under argon protection, the reaction is carried out at 60-80°C for 5-12 hours under irradiation with a light source with a wavelength of 365-420 nm.

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