A method for synthesizing oxidized indole compounds

Abstract

This invention provides a method for synthesizing indole oxide compounds, belonging to the field of organic synthesis technology. The method involves dissolving an aryl halogen compound in a solvent to obtain a substrate solution; then synthesizing the indole oxide compound under potassium tert-butoxide and blue light. This invention is the first to utilize aryl halogen compounds to synthesize indole oxide compounds under potassium tert-butoxide and blue light conditions. This method provides a simple, efficient, economical, and green synthetic route for indole oxide compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a method for synthesizing oxidized indole compounds. Background Technology

[0002] Indole oxide, also known as diindole ketone, is an important nitrogen-containing heterocyclic compound with high biological and pharmacological activity. It is widely used in pesticides, pharmaceuticals, dyes, feed, food, and additives, and new applications are constantly being developed. Indole and its derivatives are widely distributed in nature; many natural compounds contain an indole ring in their structure, and many indole derivatives are closely related to life activities. Therefore, indole is also a very important heterocyclic skeleton. Indole and its homologues can be synthesized by various methods. As early as the 1990s, 3,3-disubstituted indole oxide derivatives were synthesized via intramolecular Heck coupling reaction using (z)-2-butenylbenzamide as a substrate under Pd-(r)-binap catalysis (j.org.chem.,1993,58,6949-6951). Subsequently, Xu Pengfei's research group synthesized indole oxide derivatives by intramolecular 1,5-hydrogen migration under the action of iridium through photocatalysis (Chem.Commun.,2016,52,6455). Gevorgyan's research group reported visible light-induced Pd-catalyzed CH bond arylation of intramolecular amides. This method generates valuable hydroxyindole and its derivatives by breaking carbon-oxygen bonds to produce a hybrid aryl Pd-radical intermediate, followed by 1,5-hydrogen atom translocation, intramolecular cyclization, and remodeling steps (Angew. Chem. Int. Ed. 2020, 59, 10316-10320). However, these synthetic methods often face problems such as the use of expensive metal catalysts and harsh reaction conditions. Summary of the Invention

[0003] In view of this, the purpose of this invention is to provide a method for synthesizing indole oxide compounds. This invention is the first to utilize aryl halogen compounds to synthesize indole oxide compounds under potassium tert-butoxide and blue light conditions. This method provides a simple, efficient, economical, and green synthetic route for indole oxide compounds.

[0004] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0005] This invention provides a method for synthesizing oxidized indole compounds, comprising the following steps:

[0006] 1) Dissolve the aryl halogen compound in a solvent to obtain a substrate solution;

[0007] 2) The substrate solution obtained in step 1) was used to synthesize indole oxide compounds under potassium tert-butoxide and blue light;

[0008] The aryl halogen compounds include compounds represented by formula V, formula VI, formula VII or formula VIII;

[0009]

[0010] The indole oxide compounds include compounds represented by Formula I, Formula II, Formula III or Formula IV;

[0011]

[0012] In Formula I, R1 is at least one of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted aryl.

[0013] In Formula II, R1 is at least one of halogen group, cyano group, methyl group, and methoxy group;

[0014] In Formula III, R1 is methyl or isopropyl;

[0015] In formulas V, VI, VII, or VIII, R1 is a chlorine atom or an iodine atom, R2 is at least one of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, or a substituted or unsubstituted aryl group, and R3 is at least one of a halogen group, a cyano group, a methyl group, or a methoxy group.

[0016] Preferably, the solvent in step 1) includes toluene, and the molar concentration of the aryl halogen compound in the substrate solution is 0.1 mol / L.

[0017] Preferably, the molar ratio of the aryl halogen compound in step 1) to potassium tert-butoxide in step 2) is 1:3.

[0018] Preferably, the wavelength of the blue light in step 2) is 460nm.

[0019] Preferably, the blue light is provided by a blue LED light with a power of 100W.

[0020] Preferably, the synthesis conditions in step 2) include: a time of 10 to 16 hours and a temperature of 50 to 55°C.

[0021] Preferably, the synthesis time is 12 hours.

[0022] Preferably, the compound represented by Formula I is any one of the compounds represented by Formula I-1 to Formula I-7:

[0023]

[0024] Preferably, the compound represented by Formula II is any one of the compounds represented by Formula II-1 to II-7 below:

[0025]

[0026] Preferably, the compound represented by Formula III is a compound represented by Formula III-1 or a compound represented by Formula III-2:

[0027]

[0028] The synthesis mechanism of this invention is as follows:

[0029] Potassium tert-butoxide removes a hydrogen atom from the toluene methyl group in the solvent, generating a toluene anion. The toluene anion forms an EDA complex with the reactants. Under blue light, electrons are transferred from the toluene anion to the substrate, which forms an aryl radical. Following this, intramolecular cyclization occurs due to 1,5-hydrogen migration. Finally, single-electron oxidation and deprotonation produce the final product. The principle and process are as follows:

[0030]

[0031] The beneficial effects of this invention are as follows:

[0032] This invention is the first to synthesize indole oxide compounds from aryl halogen compounds under potassium tert-butoxide and light conditions. Compared with existing technologies, the synthesis method of indole oxide compounds described in this invention has the advantages of readily available raw materials, simple operation, mild reaction conditions, economy, and environmental friendliness. Attached Figure Description

[0033] Figure 1 This is a synthetic route diagram of indole oxide compounds in a specific embodiment of the present invention. Detailed Implementation

[0034] This invention provides a method for synthesizing oxidized indole compounds, comprising the following steps:

[0035] 1) Dissolve the aryl halogen compound in a solvent to obtain a substrate solution;

[0036] 2) The substrate solution obtained in step 1) was used to synthesize indole oxide compounds under potassium tert-butoxide and blue light;

[0037] The aryl halogen compounds include compounds represented by formula V, formula VI, formula VII or formula VIII;

[0038]

[0039] The indole oxide compounds include compounds represented by Formula I, Formula II, Formula III or Formula IV;

[0040]

[0041] In Formula I, R1 is at least one of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted aryl.

[0042] In Formula II, R1 is at least one of halogen group, cyano group, methyl group, and methoxy group;

[0043] In Formula III, R1 is methyl or isopropyl;

[0044] In formulas V, VI, VII, or VIII, R1 is a chlorine atom or an iodine atom, R2 is at least one of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, or a substituted or unsubstituted aryl group, and R3 is at least one of a halogen group, a cyano group, a methyl group, or a methoxy group.

[0045] This invention involves dissolving an aryl halogen compound in a solvent to obtain a substrate solution. In this invention, the solvent preferably includes toluene, and the molar concentration of the aryl halogen compound in the substrate solution is preferably 0.1 mol / L.

[0046] This invention synthesizes indole oxide compounds from a substrate solution under potassium tert-butoxide and blue light. In this invention, the molar ratio of the aryl halogen compound to potassium tert-butoxide is preferably 1:3. In this invention, the wavelength of the blue light is preferably 460 nm. In this invention, the blue light is preferably provided by a blue LED lamp, and the power of the LED lamp is preferably 100 W. In this invention, the role of potassium tert-butoxide is to remove hydrogen atoms from the toluenemethyl group, and the role of the blue light is to provide energy. In this invention, the synthesis conditions preferably include: a time of 10–16 h and a temperature of 50–55 °C. In this invention, the synthesis time is more preferably 12 h.

[0047] In this invention, the compound represented by Formula I is preferably any one of the compounds represented by Formula I-1 to Formula I-7 below:

[0048]

[0049]

[0050] In this invention, the compound represented by Formula II is preferably any one of the compounds represented by Formula II-1 to II-7 below:

[0051]

[0052] In this invention, the compound represented by Formula III is preferably the compound represented by Formula III-1 or the compound represented by Formula III-2:

[0053]

[0054] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0055] Example 1

[0056] The compound shown in formula I-1 is synthesized

[0057] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-1. The specific steps are as follows:

[0058] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound V-1 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 600 rpm under a 100 W blue LED (460 nm) lamp at 50 °C. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-1.

[0059]

[0060] The structural verification experimental data are as follows:

[0061] White solid (36 mg, 0.177 mmol, yield 88%). 1 H NMR (400MHz, CDCl3) δ8.98(s,1H),7.19(d,J=7.5Hz,2H),7.03–7.06(m,1H),6.96(d,J=8.3Hz,1H),1.41(s,6H). 13 C NMR (101MHz, CDCl3) δ 184.4, 140.0, 136.4, 127.7, 122.7, 122.5, 110.0, 44.8, 24.4. (Equation I-1 can be obtained from relevant literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0062] The obtained compound was verified to be the compound shown in Formula I-1.

[0063] Example 2

[0064] The compound shown in formula I-2 is synthesized

[0065] according to Figure 1The synthetic route diagram shown below illustrates the synthesis of the compound represented by formula I-2. The specific steps are as follows:

[0066] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V-2 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-2).

[0067]

[0068] The structural verification experimental data are as follows:

[0069] White solid (29 mg, 0.166 mmol, yield 83%). 1 H NMR (400MHz, CDCl3) δ8.76(s,1H),7.21–7.21(m,1H),7.04–6.94(m,2H),6.88–6.72(m,1H),1.78–1.75(m,2H),1.56–1.53(m,2H). 13 C NMR (101MHz, CDCl3) δ 179.6, 140.7, 131.4, 126.9, 122.1, 118.7, 109.9, 27.6, 19.6. (Equation I-2 can be obtained from the literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0070] The obtained compound was verified to be the compound shown in Formula I-2.

[0071] Example 3

[0072] The compound shown in formula I-3 is synthesized

[0073] according to Figure 1 The synthetic route diagram shown below synthesizes the compound represented by formula I-3. The specific steps are as follows:

[0074] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V-3 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-3.

[0075]

[0076] The structural verification experimental data are as follows:

[0077] White solid (31 mg, 0.166 mmol, yield 83%). 1 H NMR(400MHz, CDCl3)δ8.67(s,1H),7.48(d,J=7.4Hz,1H),7.21–7.16(m,1H),7.08–7.04 (m,1H),6.89(d,J=7.7Hz,1H),2.72–2.63(m,2H),2.39–2.32(m,3H),2.28–2.21(m,1H). 13 C NMR (101MHz, CDCl3) δ 183.0, 140.3, 135.0, 127.9, 122.8, 122.7, 109.6, 48.7, 31.4, 16.9. (Equation I-4) Relevant supporting data can be obtained from the literature. J.-X. Qiao, T.-C. Wang, R. Ruel, C. Thibeault, A. L'Heureux, W.-A. Schumacher, S.-A. Spronk, S. Hiebert, G. Bouthillier, J. Ll oyd,Z.Pi,D.-M.Schnur,L.-M.Abell,J.Hua,L.-A.Price,E.Liu,Q.Wu,TESteinbacher,J.-S.Bostwick,M.Chang,J.Zh eng,Q.Gao,B.Ma,P.-A.McDonnell,C.-S.Huang,R.Rehfuss,R.-R.Wexler,P.-Y.-S.Lam,J.Med.Chem.,2013,56,9275.)

[0078] The obtained compound was verified to be the compound shown in Formula I-4.

[0079] Example 4

[0080] The compound shown in formula I-4

[0081] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-4. The specific steps are as follows:

[0082] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V-4 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-4.

[0083]

[0084] The structural verification experimental data are as follows:

[0085] White solid (33 mg, 0.142 mmol, yield 71%). 1 H NMR(400MHz, CDCl3)δ8.69(s,1H),7.45(d,J=7.4Hz,1H),7.22–7.18(m,1H),7.03–6.99(m,1H),6 .93(d,J=7.7Hz,1H),1.94–1.89(m,2H),1.87–1.83(m,2H),1.78–1.71(m,3H),1.64–1.58(m,3H). 13 C NMR (101MHz, CDCl3) δ 183.4, 140.1, 135.9, 127.5, 124.4, 122.0, 109.8, 48.1, 33.0, 25.3, 21.2. (Equation I-4 can be obtained from relevant literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0086] The obtained compound was verified to be the compound shown in Formula I-4.

[0087] Example 5

[0088] Synthetic compound shown in formula I-5

[0089] according to Figure 1 The synthetic route diagram shown below synthesizes the compound represented by formula I-5. The specific steps are as follows:

[0090] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V-5 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was obtained by vacuum distillation after collection) to give compound I-5.

[0091]

[0092] The structural verification experimental data are as follows:

[0093] White solid (42 mg, 0.144 mmol, yield 72%). 1 H NMR(400MHz, CDCl3)δ8.55(s,1H),7.25–7.15(m,1H),7.12(d,J=7.4Hz,1H),7.09–6.99(m,1H),6.91(d,J=7.7Hz,1H),2.00–1.85 (m,2H),1.83–1.73(m,2H),1.32–1.13(m,2H),1.11–0.99(m,1H),0.89–0.80(m,1H),0.76(t,J=7.3Hz,3H),0.63(t,J=7.4Hz,3H). 13 C NMR (101MHz, CDCl3) δ182.9,141.4,133.0,127.6,123.2,122.5,109.6,54.4,37.7,31. 2,26.5,23.0,14.0,8.7.IR(ATR)v3205,2959,2929,1700,1619,1470,1192,748,652cm –1 .HRMS(ESI):m / z[M+H] + calcd forC 14 H 20 ON + :218.1539; found:218.1532.Melting Point(Experimental):95℃–96℃.

[0094] The obtained compound was verified to be the compound shown in Formula I-5.

[0095] Example 6

[0096] Synthetic compound shown in formula I-6

[0097] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-6. The specific steps are as follows:

[0098] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V-6 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-6).

[0099]

[0100] The structural verification experimental data are as follows:

[0101] White solid (27 mg, 0.126 mmol, yield 63%). 1 H NMR(400MHz, CDCl3)δ8.70(s,1H),7.33–7.31(m,3H),7.31–7.27(m,1H),7.24–7.22( m,1H),7.13(d,J=7.4Hz,1H),7.10–7.02(m,1H),6.97(d,J=7.8Hz,1H),1.82(s,3H). 13 C NMR (126MHz, CDCl3) δ167.6,150.7,131.8,130.7,128.0,123.9,123.5,64.5,33.0,24.9,24.4,22.5.IR(ATR)v 3213,2928,1706,1619,1472,1215,715,696cm –1 .HRMS(ESI):m / z[M+H] + calcd for C 15 H 14 ON + :224.1069; found:224.1062.Melting Point(Experimental):132℃–133℃.

[0102] The obtained compound was verified to be the compound shown in Formula I-6.

[0103] Example 7

[0104] Synthetic compound shown in formula I-7

[0105] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-7. The specific steps are as follows:

[0106] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound V-7 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound I-7.

[0107]

[0108] The structural verification experimental data are as follows:

[0109] White solid (32 mg, 0.119 mmol, yield 59%). 1 H NMR (400MHz, CDCl3) δ7.86 (s, 1H), 7.30 (s, 1H), 7.21–7.17 (m, 1H), 6.99–6.95 (m, 1H), 6.83 (d, J = 8.1Hz, 1H), 3.13 (s, 1H), 1.12 (s, 9H). 13 C NMR (126MHz, CDCl3) δ 179.0, 142.1, 128.4, 128.0, 126.6, 121.7, 109.3, 56.0, 35.1, 27.5. (Equation I-7 can be obtained from the literature A. Mukherjee, R.-B. Dateer, R. Chaudhuri, S. Bhunia, S.-N. Karad and R.-S. Liu, J. Am. Chem. Soc., 2011, 133, 15372–15375.).

[0110] The obtained compound was verified to be the compound shown in Formula I-7.

[0111] Example 8

[0112] The compound shown in Formula II-1

[0113] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-1. The specific steps are as follows:

[0114] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound V (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-1).

[0115]

[0116] The structural verification experimental data are as follows:

[0117] Colorless oil (36 mg, 0.166 mmol, yield 83%). 1 H NMR (500MHz, CDCl3) δ9.02 (s, 1H), 7.19–7.11 (m, 2H), 6.87 (d, J = 8.0Hz, 1H), 1.38 (s, 6H). 13 C NMR (126MHz, CDCl3) δ 183.7, 138.4, 138.1, 128.0, 127.8, 123.4, 111.0, 45.2, 24.3. (Equation II-1 can be obtained from the literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0118] The obtained compound was verified to be the compound shown in Formula II-1.

[0119] Example 9

[0120] The compound shown in formula II-2 is synthesized

[0121] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-2. The specific steps are as follows:

[0122] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound VI-2 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-2).

[0123]

[0124] The structural verification experimental data are as follows:

[0125] White solid (29 mg, 0.124 mmol, yield 62%). 1 H NMR (500MHz, CDCl3) δ9.52(s,1H),6.94–6.82(m,3H),1.39(s,6H). 13 C NMR (101MHz, CDCl3) δ 184.6, 159.4 (d, J = 239.9Hz), 138.0 (d, J = 7.7Hz), 114.0 (d, J = 23.6Hz), 110.8 (d, J = 3.9Hz), 110.6 (d, J = 12.5Hz), 45.5, 24.3. 19 F NMR (471MHz, CDCl3) δ-120.6 (q, J=7.3Hz). (Equation II-2 can be verified by relevant data from the literature A.-T.Vu, S.-T.Cohn, P.Zhang, C.-Y.Kim, P.-E.Mahaney, J.-A.Bray, G.-H.Johnston, E.-J.Koury, S.-A.Cosmi, D.-C.Deecher, V.-A.Smith, J.Med.Chem., 2010, 53, 2051.).

[0126] The obtained compound was verified to be the compound shown in Formula II-2.

[0127] Example 10

[0128] The compound shown in formula II-3

[0129] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-3. The specific steps are as follows:

[0130] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VI-3 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was obtained by vacuum distillation after collection) to give compound II-3.

[0131]

[0132] The structural verification experimental data are as follows:

[0133] Yellow solid (22 mg, 0.114 mmol, yield 57%). 1 H NMR (400MHz, CDCl3) δ9.30 (s, 1H), 7.55 (d, J = 9.7Hz, 1H), 7.47 (s, 1H), 7.05 (d, J = 8.0Hz, 1H), 1.43 (s, 6H). 13 C NMR (101MHz, CDCl3) δ 183.8, 144.1, 137.3, 133.1, 126.4, 119.3, 110.6, 105.9, 44.8, 24.2. (Equation II-2 can be obtained from relevant literature. H.Tye, U.Guertler, M.-H.Hofmann, M.Mayer, G.Rast, M.-P.Sanderson, O.Schaaf, M.Treu and S.-K.Zahn, MedChemComm., 2015, 6, 1244-1251.)

[0134] The obtained compound was verified to be the compound shown in Formula II-3.

[0135] Example 11

[0136] The compound shown in formula II-4

[0137] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-4. The specific steps are as follows:

[0138] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VI-4 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-4).

[0139]

[0140] The structural verification experimental data are as follows:

[0141] White solid (35 mg, 0.150 mmol, yield 75%). 1H NMR (500MHz, CDCl3) δ8.71 (s, 1H), 7.01–6.99 (m, 2H), 6.82 (d, J = 7.4Hz, 1H), 2.32 (s, 3H), 1.38 (s, 6H). 13 C NMR (101MHz, CDCl3) δ 184.3, 137.5, 136.5, 132.0, 128.0, 123.5, 109.7, 44.8, 24.5, 21.3. (Equation II-4 can be obtained from the literature report J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0142] The obtained compound was verified to be the compound shown in Formula II-4.

[0143] Example 12

[0144] Synthetic compound shown in formula II-5

[0145] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-5. The specific steps are as follows:

[0146] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VI-5 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-5).

[0147]

[0148] The structural verification experimental data are as follows:

[0149] Yellow solid (30 mg, 0.124 mmol, yield 62%). 1 H NMR (400MHz, CDCl3) δ7.44(s,1H),7.05–6.97(m,1H),6.83(d,J=7.5Hz,1H),6.79(d,J=8.2Hz,1H),3.88(s,3H),1.39(s,6H). 13C NMR (126MHz, CDCl3) δ182.6,143.8,137.1,128.3,123.1,115.1,110.1,55.7,45.4,24.4.IR(ATR)v 3219,2965,2927,1703,1461,1260,1053,731cm –1 .HRMS(ESI):m / z[M+H] + calcd for C 11 H 14 O2N + :192.1019; found:192.1012.Melting Point(Experimental):120℃-121℃.

[0150] The obtained compound was verified to be the compound shown in Formula II-5.

[0151] Example 13

[0152] The compound shown in Formula II-6

[0153] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-6. The specific steps are as follows:

[0154] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VI-6 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-6).

[0155]

[0156] The structural verification experimental data are as follows:

[0157] White solid (33 mg, 0.142 mmol, yield 71%). 1 H NMR (400MHz, CDCl3) δ8.61(s,1H),6.83(d,J=8.3Hz,1H),6.80(d,J=8.4Hz,1H),6.74–6.71(m,1H),3.80(s,3H),1.40(s,6H). 13C NMR (101MHz, CDCl3) δ 184.1, 156.0, 137.9, 133.3, 112.0, 110.3, 110.2, 55.9, 45.3, 24.5. (Equation II-6. Relevant supporting data can be obtained from the literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0158] Upon verification, the obtained compound is the compound shown in Formula II-6.

[0159] Example 14

[0160] The compound shown in Formula II-7

[0161] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-7. The specific steps are as follows:

[0162] The pre-dried reaction tube was cooled to room temperature under vacuum, and compound VI-7 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound II-7.

[0163]

[0164] The structural verification experimental data are as follows:

[0165] White solid (25 mg, 0.116 mmol, yield 58%). 1 H NMR (500MHz, CDCl3) δ8.77 (s, 1H), 7.04–7.02 (m, 2H), 6.97 (d, J = 7.1Hz, 1H), 2.31 (s, 3H), 1.40 (s, 6H). 13 C NMR (126MHz, CDCl3) δ 184.3, 138.7, 136.0, 129.1, 122.5, 120.1, 119.3, 45.1, 24.5, 16.6. (Equation II-7 can be obtained from the literature HKAbd El-Aal, AAKhalaf. Arkivoc, 2013, 4, 398–405.).

[0166] Upon verification, the obtained compound is the compound shown in Formula II-7.

[0167] Example 15

[0168] The compound shown in Formula III-1

[0169] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula III-1. The specific steps are as follows:

[0170] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VII-1 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound III-1.

[0171]

[0172] The structural verification experimental data are as follows:

[0173] Colorless oil (29 mg, 0.155 mmol, yield 78%). 1 H NMR (500MHz, CDCl3) δ7.84–7.82(m,1H),7.56–7.52(m,1H),7.45–7.41(m,2H),3.01(s,3H),1.44(s,6H). 13 C NMR (126MHz, CDCl3) δ 167.4, 151.6, 131.6, 131.0, 128.1, 123.7, 120.8, 62.2, 25.0, 24.0. (Equation III-1 can be obtained from the literature. K.-Q. Chen, B.-B. Zhang, Z.-X. Wang and X.-Y. Chen, Org. Lett., 2022, 24, 4598–4602.)

[0174] The obtained compound was verified to be the compound shown in Formula III-1.

[0175] Example 16

[0176] The compound shown in Formula III-2 is synthesized

[0177] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula III-2. The specific steps are as follows:

[0178] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound VII-2 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound III-2).

[0179]

[0180] The structural verification experimental data are as follows:

[0181] White solid (18 mg, 0.090 mmol, yield 45%). 1 H NMR(400MHz, CDCl3)δ7.77(d,J=7.4Hz,1H),7.54–7.46(m,1H),7.44–7.36(m,1H) ),7.34(d,J=7.5Hz,1H),3.72–3.58(m,1H),1.56(d,J=6.9Hz,6H),1.48(s,6H). 13 CNMR (101MHz, CDCl3) δ 167.3, 151.4, 132.1, 131.3, 127.9, 123.2, 120.7, 63.3, 44.6, 25.5, 20.6. (Equation III-2 can be obtained from the literature. K.-Q.Chen, B.-B.Zhang, Z.-X.Wang and X.-Y.Chen, Org. Lett., 2022, 24, 4598–4602.).

[0182] The obtained compound was verified to be the compound shown in Formula III-2.

[0183] Example 17

[0184] Synthesize the compound shown in IV-1

[0185] according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula IV-1. The specific steps are as follows:

[0186] The pre-dried reaction tube was cooled to room temperature under vacuum, and then compound IV-1 (0.2 mmol), potassium tert-butoxide (0.6 mmol), and toluene (2.0 mL) were added under nitrogen protection. The mixture was stirred overnight (12 h) at 50 °C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2, mobile phase: petroleum ether; the product was collected and then distilled under vacuum to obtain the compound IV-1.

[0187]

[0188] The structural verification experimental data are as follows:

[0189] Colorless oil (45 mg, 0.167 mmol, yield 84%). 1 H NMR (500MHz, CDCl3) δ9.84(s,1H),8.15(dd,J=5.3,1.6Hz,1H),7.43(dd,J=7.3,1.6Hz,1H),6.95(dd,J=7.3,5.3Hz,1H),1.40(s,6H). 13 C NMR (126MHz, CDCl3) δ 182.2, 155.6, 146.3, 130.6, 130.6, 118.3, 44.8, 24.0. (Equation IV-1. Relevant supporting data can be obtained from the literature J.-C.Hsieh, A.-Y.Cheng, J.-H.Fu and T.-W.Kang, Org. Biomol. Chem., 2012, 10, 6404–6409.).

[0190] The obtained compound was verified to be the compound shown in Formula IV-1.

[0191] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing an indole oxide compound, characterized in that, The following steps are required: The pre-dried reaction tube was cooled to room temperature under vacuum, and 0.2 mmol of the compound shown in Formula V-1, 0.6 mmol of potassium tert-butoxide, and 2.0 mL of toluene were added under nitrogen protection. The mixture was stirred at 600 rpm for 12 h at 50 °C under a 100 W blue LED 460 nm lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography. The stationary phase for column chromatography was SiO2, and the mobile phase was petroleum ether. The collected product was then distilled under vacuum to obtain the compound shown in Formula I-1, which is an oxidized indole compound.

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