A 2-(indole-3-yl)phenol compound and its synthesis method

Abstract

This invention relates to a method for synthesizing 2-(indole-3-yl)phenol and its derivatives. This invention utilizes iodine-based catalysts, oxidants, and acid additives to achieve a highly selective one-pot reaction of indole and cyclohexanone compounds to obtain 2-(indole-3-yl)phenol and its derivatives, yielding structurally stable products with excellent chemical properties and byproducts. The method of this invention features a simple reaction system, mild reaction conditions, fewer reaction devices, convenient experimental operation, wide availability of raw materials, good atom economy, and no need for transition metal catalysts, providing a new synthetic route for the synthesis of 2-(indole-3-yl)phenol compounds. The 2-(indole-3-yl)phenol derivatives and their synthesis method of this invention can be used in the pharmaceutical production field.

Description

Technical Field

[0001] This invention relates to a 2-(indole-3-yl)phenol compound and its synthesis method, belonging to the field of organic synthesis. Background Technology

[0002] Indole-3-ylphenols are a very important class of nitrogen-containing heterocyclic compounds, widely distributed in many natural products and functional materials. Furthermore, indole-3-ylphenols possess a variety of biological and pharmacological activities, such as antioxidant, antibacterial, anti-biofilm, and anti-glioma activities. Indole-3-ylphenols can also act as B-Raf inhibitors, DYRK1A inhibitors, estrogen receptor ligands, and angiogenic disruptors. Indole-3-ylphenols have broad application value and promising prospects in the pharmaceutical field. However, most existing methods for synthesizing these compounds require expensive transition metal catalysts and pre-functionalized raw materials, resulting in high reaction costs, metal residues, and pollution. Summary of the Invention

[0003] Therefore, the purpose of this invention is to provide 2-(indol-3-yl)phenol and its derivatives. These substances have stable molecular structures and excellent chemical properties; they are both important molecular fragments and compound fragments containing physiological and pharmacological activities, exhibiting certain biological and pharmaceutical activities.

[0004] Another objective of this invention is to provide a method for synthesizing 2-(indole-3-yl)phenol and its derivatives, which has the advantages of inexpensive and readily available raw materials, simple reaction conditions, convenient operation, few reaction steps, and simple equipment. This reaction does not require the use of metal catalysts or metal oxidants, and can maintain atom economy to a large extent, with low input and high output, making it easy for industrial production and widespread application.

[0005] To achieve the above objectives, this invention discloses a compound: 2-(indole-3-yl)phenol and its derivatives, with the general formula I:

[0006]

[0007] in:

[0008] R 1 Selected from hydrogen atom, alkyl group, benzyl group;

[0009] R 2 Selected from hydrogen atom, alkyl, halogen, alkoxy, ester group, phenyl;

[0010] R 3 Selected from hydrogen atom, alkyl, ester group, aryl group.

[0011] This invention also discloses a method for synthesizing 2-(indole-3-yl)phenol and its derivatives as described in claim 1, comprising the following steps:

[0012] The product is obtained by mixing indole compounds, cyclohexanone compounds, catalysts, oxidants, additives, and organic solvents, followed by heating and stirring.

[0013] The method of the present invention uses an indole compound with the general formula of Formula II:

[0014]

[0015] in:

[0016] R 1 Selected from hydrogen atom, alkyl group, benzyl group;

[0017] R 2 Selected from hydrogen atom, alkyl, halogen, alkoxy, ester group, phenyl;

[0018] In the method of the present invention, the indole compound is selected from: 1-methylindole, 1-n-octylindole, 1-benzylindole, indole, 1,2-dimethylindole, 1-methyl-2-phenylindole, 1,5-dimethylindole, 5-methoxy-1-methylindole, 5-fluoro-1-methylindole, 5-chloro-1-methylindole, 5-bromo-1-methylindole, 5-ester-1-methylindole, 1,6-dimethylindole, 6-methoxy-1-methylindole, 6-fluoro-1-methylindole, 6-chloro-1-methylindole, 6-bromo-1-methylindole, 1,7-dimethylindole, 7-fluoro-1-methylindole, and 7-bromo-1-methylindole.

[0019] The method of the present invention, wherein the general formula of the cyclohexanone compound in the method of the present invention is Formula III:

[0020]

[0021] in:

[0022] R 3 Selected from hydrogen atom, alkyl, ester group, aryl group;

[0023] In the method of the present invention, the cyclohexanone compound is selected from: 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-n-pentylcyclohexanone, 4-tert-pentylcyclohexanone, 4-tert-butylcyclohexanone, 4-esterylcyclohexanone, 4-phenyl-cyclohexanone, 4-(4-hydroxyphenyl)cyclohexanone, 4-(4-methoxyphenyl)cyclohexanone, 3-methylcyclohexanone, and 2-methylcyclohexanone.

[0024] The catalyst in the method of the present invention is one of the following: sodium iodide, potassium iodide, ammonium iodide, iodine bromide, iodine chloride, hydroiodic acid, elemental iodine, N-iodosuccinimide, potassium iodate, sodium periodate, diacetyl iodobenzene, trimethyliodosilane, trimethyl sulfoxide, iodobenzene, iodine pentoxide, and cuprous iodide.

[0025] In the method of the present invention, the oxidant is one of the following: dimethyl sulfoxide, benzyl phenyl sulfoxide, methyl phenyl sulfoxide, dimethyl sulfone, diphenyl sulfoxide, diphenyl sulfone, sulfolane, potassium persulfate, di-tert-butyl peroxide, tert-butyl hydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone.

[0026] The additive in the method of the present invention is one of the following: trifluoroacetic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid, ferric chloride, aluminum chloride, boron trifluoride ether, pentylene acid, camphor sulfonic acid, benzoic acid, p-methylbenzoic acid, p-nitrobenzoic acid, and p-methoxybenzoic acid.

[0027] In the method of the present invention, the organic solvent is selected from one of chlorobenzene, toluene, trifluorotoluene, o-xylene, m-xylene, nitrobenzene, 1,4-dioxane, 1,2-dichloroethane, N,N-dimethylacetamide, dimethyl sulfoxide, and o-dichlorobenzene.

[0028] In the method of the present invention, the molar ratio of indole compound, cyclohexanone compound, catalyst, oxidant and additive is 1.0:1.0-10.0:0.01-1.0:1.0-10.0:0.01-5.0, the reaction temperature is 80℃-140℃, and the reaction time is 8-36 hours.

[0029] The technical solution of this invention has the following advantages:

[0030] (I) This invention provides a technical solution for the highly selective preparation of 2-(indole-3-yl)phenol and its derivatives from indole and cyclohexanone compounds in an air atmosphere under the action of iodine catalysts, oxidants, and additives. This overcomes the huge waste of manpower, resources, and materials caused by the use of metal catalysts, and saves a lot of research time and shortens the production cycle. (II) The technical solution for the selective preparation of 2-(indole-3-yl)phenol and its derivatives from indole and cyclohexanone compounds by heating and stirring under reaction conditions of catalysts, oxidants, additives, and organic solvents has the advantages of simple reaction system, mild reaction conditions, wide availability of raw materials, good atom economy, simple experimental operation, significant increase in product added value and high availability, and foreseeable market commercialization prospects. (III) The 2-(indole-3-yl)phenol derivatives and their synthesis method of this invention have broad application value and good application prospects in the pharmaceutical field. They are also suitable for the scientific research and development of highly efficient and selective synthesis of bis-2-(indole-3-yl)phenol compounds. Attached Figure Description

[0031] To demonstrate the product of this invention, the present invention provides 1H NMR and 1C NMR spectra of some embodiments. See the accompanying drawings for details.

[0032] Figure 1-1 The hydrogen NMR spectrum of the product in Example 1.

[0033] Figure 1-2 The carbon NMR spectrum of the product in Example 1.

[0034] Figure 2-1 The hydrogen NMR spectrum of the product in Example 2.

[0035] Figure 2-2 The carbon NMR spectrum of the product in Example 2.

[0036] Figure 3-1 This is the 1H NMR spectrum of compound A.

[0037] Figure 3-2 This is the carbon NMR spectrum of compound A.

[0038] Figure 4 It is the synthetic reaction formula for 2-(indol-3-yl)phenol and its derivatives.

[0039] Figure 5 This is a schematic diagram of the reaction principle for the further preparation of compound A with anti-HIV activity using 2-(indol-3-yl)phenol and its derivatives. Detailed Implementation

[0040] The invention will now be described in further detail with reference to the following diagram. The diagram below is a simplified schematic diagram, illustrating only the basic structure of the invention; therefore, it only shows the components relevant to the invention. The reaction formula is shown below. Figure 4 .

[0041] Includes the following steps:

[0042] (1) Add indole compounds, cyclohexanone compounds, catalysts, oxidants, additives and organic solvents to the reaction vessel;

[0043] (2) After thoroughly mixing the reactants, heat them;

[0044] (3) The product is obtained by purification after the reaction.

[0045] Example 1

[0046] Synthesis of 2-(1H-indol-3-yl)phenol

[0047]

[0048] Take a reaction tube and add 0.2 mmol (23.4 mg) indole, 0.6 mmol (62.0 μL) cyclohexanone, 0.04 mmol (10.1 mg) elemental iodine, 1.0 mmol (71.0 μL) dimethyl sulfoxide, 0.08 mmol (9.8 mg) benzoic acid, and 0.5 mL toluene. Seal the tube and stir in an oil bath at 120 °C for 24 hours. After conventional treatment, 18.8 mg of pure product was obtained, with a yield of 45%.

[0049] Example 2-31

[0050] The reactants, reaction conditions, products, and yields are shown in the table below. Other reaction conditions are the same as in Example 1.

[0051]

[0052]

[0053]

[0054]

[0055]

[0056] The product synthesized using the present invention (Example 1) can be further reacted as follows to prepare compound A with anti-HIV activity: the process is as follows. Figure 4 .

[0057] The following are characterization data, including NMR and high-resolution mass spectrometry, of the compounds in some embodiments of the present invention:

[0058] The NMR data of the product from Example 1 are as follows:

[0059] 1 H NMR (400MHz, CDCl3) δ8.42(s,1H),7.64(d,J=8.0Hz,1H),7.46(d,J=8.0Hz,1H),7.41(d,J=7.2Hz,1H),7.34(d,J =2.4Hz,1H),7.32–7.27(m,2H),7.20(t,J=7.4Hz,1H),7.07(d,J=8.0Hz,1H),7.02(t,J=7.4Hz,1H),5.46(s,1H). 13 C NMR (100MHz, CDCl3) δ153.5,136.6,130.9,128.7,126.4,123.3,123.1,121.0,120.8,120.7,119.9,115.5,112.1,111.6.

[0060] The NMR data of the product from Example 2 are as follows:

[0061] 1 H NMR (400MHz, CDCl3) δ7.66(d,J=7.6Hz,1H),7.42(t,J=6.2Hz,2H),7.35(t,J=7.6Hz,1H),7.30(t,J=7. 8Hz,1H),7.22(t,J=7.6Hz,2H),7.09(d,J=8.0Hz,1H),7.03(t,J=7.4Hz,1H),5.51(s,1H),3.88(s,3H). 13 C NMR (100MHz, CDCl3) δ153.4,137.4,130.8,128.5,127.9,126.8,122.6,121.1,120.6,120.3,120.0,115.4,110.3,109.8,33.1.

[0062] The NMR data of the product in Example 3 are as follows:

[0063] 1H NMR (400MHz, CDCl3) δ7.61(d,J=8.0Hz,1H),7.40(dd,J=16.8,8.4Hz,2H),7.32–7.24(m,3H),7.17(t,J=7.4Hz,1H),7.05(d,J=8. 0Hz,1H),6.99(t,J=7.0Hz,1H),5.47(s,1H),4.17(t,J=7.2Hz,2H),1.93–1.82(m,2H),1.36–1.22(m,10H),0.87(t,J=6.8Hz,3H). 13 C NMR (100MHz, CDCl3) δ153.4,136.7,130.9,128.5,126.9,126.9,122.5,121.2,120.6,120.2,12 0.1,115.4,110.3,110.0,46.8,31.9,30.3,29.3,29.3,27.2,22.8,14.2.HRMS(ESI)m / z:[M+Na] + calcd for C 22 H 27 NNaO 344.1985; found 344.1985.

[0064] The NMR data of the product in Example 4 are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ7.69 (d, J=7.6Hz, 1H), 7.47–7.41 (m, 2H), 7.38–7.28 (m, 6H), 7.2 5–7.20(m,3H),7.09(d,J=8.0Hz,1H),7.04(t,J=7.4Hz,1H),5.51(s,1H),5.39(s,2H). 13 C NMR (100MHz, CDCl3) δ153.4,137.0,137.0,130.9,129.0,128.6,128.0,127.2,127.1,127 .0,122.8,121.0,120.6,120.5,120.2,115.5,111.2,110.3,50.4.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 17 NNaO 322.1202; found 322.1201.

[0066] The NMR data of the product in Example 5 are as follows:

[0067] 1 H NMR (400MHz, CDCl3) δ7.38 (dd, J=12.8, 7.6Hz, 2H), 7.34–7.22 (m, 3H), 7.13 (t, J=7.6Hz, 1H),7.07(d,J=8.0Hz,1H),7.01(t,J=7.4Hz,1H),5.25(s,1H),3.78(s,3H),2.38(s,3H). 13 C NMR (100MHz, CDCl3) δ154.1,137.1,135.5,131.8,128.8,127.0,121.7,121.1 ,120.4,120.1,119.0,115.2,109.1,107.0,30.0,11.1.HRMS(ESI)m / z:[M+Na] + calcdfor C 16 H 15 NNaO 260.1046; found 260.1045.

[0068] The NMR data of the product in Example 6 are as follows:

[0069] 1 H NMR(400MHz, CDCl3)δ7.48(dd,J=11.2,8.0Hz,2H),7.40–7.29(m,6H),7.20(t,J=7.6Hz,2H), 7.11(d,J=7.6Hz,1H),6.94(d,J=8.8Hz,1H),6.85(t,J=7.4Hz,1H),5.22(s,1H),3.77(s,3H). 13 C NMR (100MHz, CDCl3) δ154.0,139.4,137.7,132.2,131.0,130.5,128.7,128.7,128.5,127 .3,122.8,120.7,120.7,120.4,119.8,115.2,110.0,108.7,31.5.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 17 NNaO 322.1202; found 322.1201.

[0070] The NMR data of the product in Example 7 are as follows:

[0071] 1H NMR (400MHz, CDCl3) δ7.36(d,J=8.0Hz,2H),7.29(d,J=8.8Hz,1H),7.26–7.23(m,1H),7.14(d,J= 9.2Hz,2H),7.04(d,J=8.0Hz,1H),6.99(t,J=7.4Hz,1H),5.47(s,1H),3.84(s,3H),2.44(s,3H). 13 C NMR (100MHz, CDCl3) δ153.5,135.9,130.9,129.8,128.5,127.9,127.1,124.3 ,121.3,120.6,119.5,115.3,109.8,109.5,33.2,21.6.HRMS(ESI)m / z:[M+Na] + calcd for C 16 H 15 NNaO 260.1046; found 260.1045.

[0072] The NMR data of the product in Example 8 are as follows:

[0073] 1 H NMR (400MHz, CDCl3) δ7.37 (d, J = 9.2Hz, 1H), 7.33–7.26 (m, 2H), 7.17 (s, 1H), 7. 06(d,J=7.4Hz,1H),7.00–6.93(m,3H),5.47(s,1H),3.85(s,3H),3.82(s,3H). 13 C NMR (100MHz, CDCl3) δ154.8,153.5,132.7,130.8,128.5,128.4,127.1,121.2 ,120.6,115.4,113.4,110.7,109.9,101.1,56.0,33.3.HRMS(ESI)m / z:[M+Na] + calcd for C 16 H 15 NNaO2276.0995; found 276.0995.

[0074] The NMR data of the product from Example 9 are as follows:

[0075] 1 H NMR (400MHz, CDCl3) δ7.39–7.23(m,5H),7.12–6.93(m,3H),5.38(s,1H),3.86(s,3H). 13C NMR (100MHz, CDCl3) δ159.6,157.2,153.3,134.0,130.7,129.4,128.6,127.3,124.9 ,120.8,115.6,111.2(d,J=26.5Hz),110.5(d,J=9.9Hz),105.0(d,J=24.0Hz),33.4. 19 F NMR(376MHz,CDCl3)δ-123.8.HRMS(ESI)m / z:[M+H] + calcd for C 15 H 13 FNO242.0976; found 242.0981.

[0076] The NMR data of the product from Example 10 are as follows:

[0077] 1 H NMR (400MHz, CDCl3) δ7.59(s,1H),7.35(d,J=7.2Hz,1H),7.30(s,1H),7.30–7.17(m,3H),7.09–6.97(m,2H),5.32(s,1H),3.86(s,3H). 13 C NMR (100MHz, CDCl3) δ153.3,135.8,130.8,129.1,128.8,128.0,126.2,123.0,120.8,120.5,119.5,115.6,110.8,110.2,33.3.HRMS(ESI)m / z:[M+H] + calcd for C 15 H 13 ClNO 258.0680; found 258.0683.

[0078] The NMR data of the product of Example 11 are as follows:

[0079] 1 H NMR (400MHz, CDCl3) δ7.73(s,1H),7.38–7.30(m,2H),7.28–7.24(m,2H),7.20(s,1H),7.05–6.97(m,2H),5.28(s,1H),3.84(s,3H). 13C NMR (100MHz, CDCl3) δ153.3,136.1,130.9,129.0,128.8,128.6,125.6,122.6,120.8,120.4,115.6,113.8,111.3,110.1,33.3.HRMS(ESI)m / z:[M+H] + calcd for C 15 H 13 BrNO 302.0175; found 302.0174.

[0080] The NMR data of the product of Example 12 are as follows:

[0081] 1 H NMR(400MHz, CDCl3)δ8.36(s,1H),8.01(d,J=8.8Hz,1H),7.43–7.37(m,2H),7.28(s, 1H),7.25(d,J=2.0Hz,1H),7.06–6.99(m,2H),5.34(s,1H),3.90(s,3H),3.89(s,3H). 13 C NMR (100MHz, CDCl3) δ168.1,153.4,139.8,131.0,129.3,128.8,126.7,124.1,12 3.1,122.4,120.9,120.4,115.7,112.3,109.5,52.1,33.4.HRMS(ESI)m / z:[M+Na] + calcdfor C 17 H 15 NNaO3 304.0944; found 304.0944.

[0082] The NMR data of the product in Example 13 are as follows:

[0083] 1 H NMR (400MHz, CDCl3) δ7.50(d,J=8.4Hz,1H),7.38(d,J=7.6Hz,1H),7.26(t,J=7.6Hz,1H ),7.21(s,1H),7.14(s,1H),7.07–6.97(m,3H),5.51(s,1H),3.84(s,3H),2.54(s,3H). 13C NMR (100MHz, CDCl3) δ153.4,137.8,132.7,130.8,128.4,127.2,124.7,122.1 ,121.2,120.6,119.7,115.3,110.2,109.7,33.0,22.0.HRMS(ESI)m / z:[M+Na] + calcd forC 16 H 15 NNaO 260.1046; found 260.1045.

[0084] The NMR data of the product in Example 14 are as follows:

[0085] 1 H NMR (400MHz, CDCl3) δ7.51(dd,J=8.8,5.2Hz,1H),7.35(d,J=7.2Hz,1H),7.28–7.23(m,1H),7.18(s,1H),7.08–6.90(m,4H),5.40(s,1H),3.81(s,3H). 13 C NMR (100MHz, CDCl3) δ161.7, 159.3, 153.4, 137.5 (d, J = 12.0Hz), 130.8, 128.7, 128.1 (d, J = 3.6Hz) ,123.4,121.1(d,J=10.0Hz),120.7,115.5,110.8,109.1(d,J=24.4Hz),96.2(d,J=26.2Hz),33.2. 19 F NMR(376MHz, CDCl3)δ-119.6.HRMS(ESI)m / z:[M+Na] + calcd forC 15 H 12 FNNaO 264.0795; found 264.0795.

[0086] The NMR data of the product in Example 15 are as follows:

[0087] 1 H NMR(400MHz, CDCl3) δ7.53(d,J=8.4Hz,1H),7.42–7.34(m,2H),7.29(d,J=8.0Hz,1H ),7.20(s,1H),7.15(d,J=8.4Hz,1H),7.08–6.97(m,2H),5.41(s,1H),3.82(s,3H). 13C NMR (100MHz, CDCl3) δ153.3,137.8,130.8,128.7,128.7,128.5,125.4,121.0,120.9,120.7,120.6,115.6,110.8,109.8,33.2.HRMS(ESI)m / z:[M+H] + calcd forC 15 H 13 ClNO 258.0680; found 258.0683.

[0088] The NMR data of the product in Example 16 are as follows:

[0089] 1 H NMR (400MHz, CDCl3) δ7.56 (s, 1H), 7.47 (d, J = 8.8Hz, 1H), 7.35 (d, J = 9.2Hz, 1H) ,7.29–7.25(m,2H),7.19(s,1H),7.05–6.98(m,2H),5.37(s,1H),3.83(s,3H). 13 C NMR (100MHz, CDCl3) δ153.3,138.2,130.8,128.7,128.4,125.8,123.5,121.4,120.8,120.5,116.3,115.6,112.9,110.8,33.2.HRMS(ESI)m / z:[M+Na] + calcd for C 15 H 12 BrNNaO323.9994; found 323.9994.

[0090] The NMR data of the product in Example 17 are as follows:

[0091] 1 H NMR(400MHz, CDCl3)δ7.40(d,J=8.0Hz,1H),7.34(d,J=9.2Hz,1H),7.28–7.23( m,1H),7.08(s,1H),7.07–6.94(m,4H),5.43(s,1H),4.13(s,3H),2.82(s,3H). 13C NMR (100MHz, CDCl3) δ153.6,136.2,131.0,129.5,128.6,128.0,125.3,121.9 ,121.0,120.6,120.5,118.1,115.3,110.2,37.1,19.9.HRMS(ESI)m / z:[M+Na] + calcd for C 16 H 15 NNaO260.1046; found 260.1045.

[0092] The NMR data of the product of Example 18 are as follows:

[0093] 1 H NMR (400MHz, CDCl3) δ7.33(t,J=8.6Hz,2H),7.28–7.24(m,1H),7.13(s,1H),7.05–6.90(m,4H),5.35(s,1H),4.06(s,3H). 13 C NMR (100MHz, CDCl3) δ153.4, 151.9, 149.4, 131.0, 130.9, 129.5, 128.8, 125.5 (d, J = 10.1Hz), 120. 7,120.6(d,J=6.4Hz),115.8(d,J=3.6Hz),115.5,111.2,108.1(d,J=17.4Hz),36.1(d,J=5.4Hz). 19 F NMR(376MHz,CDCl3)δ-136.3.HRMS(ESI)m / z:[M+Na] + calcd for C 15 H 12 FNNaO 264.0795; found264.0795.

[0094] The NMR data of the product of Example 19 are as follows:

[0095] 1 H NMR (400MHz, CDCl3) δ7.48(d,J=7.6Hz,1H),7.41(d,J=7.6Hz,1H),7.32–7.24(m,2H),7.13(s,1H),7.06–6.90(m,3H),5.27(s,1H),4.22(s,3H). 13C NMR(100MHz, CDCl3)δ153.5,133.8,131.0,130.9,130.1,128.9,127.7,121.4,120.7,120.3,119.5,115.5,110.4,104.4,37.2.HRMS(ESI)m / z:[M+Na] + calcd for C 15 H 12 BrNNaO 323.9994; found323.9993.

[0096] The NMR data of the product from Example 20 are as follows:

[0097] 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.0Hz,1H),7.42(d,J=8.0Hz,1H),7.32(t,J=7.6Hz,1H),7.28(d,J=7.6H z,1H),7.20(d,J=7.2Hz,2H),6.89(s,1H),6.83(d,J=7.6Hz,1H),5.42(s,1H),3.87(s,3H),2.39(s,3H). 13 C NMR (100MHz, CDCl3) δ153.3,138.7,137.4,130.6,127.8,127.0,122.6,121.4 ,120.2,120.1,118.1,116.0,110.4,109.7,33.1,21.4.HRMS(ESI)m / z:[M+H] + calcd for C 16 H 16 NO 238.1226; found 238.1221.

[0098] The NMR data of the product of Example 21 are as follows:

[0099] 1 H NMR (400MHz, CDCl3) δ7.63(d,J=8.0Hz,1H),7.41(d,J=8.0Hz,1H),7.34–7.28(m,2H),7.19(d,J=8.0Hz,2H) ,6.92(s,1H),6.86(d,J=8.0Hz,1H),5.43(s,1H),3.86(s,3H),2.69(q,J=7.6Hz,2H),1.30(t,J=7.6Hz,3H). 13C NMR (100MHz, CDCl3) δ153.3,145.1,137.4,130.7,127.8,126.9,122.6,120.2,1 20.2,120.1,118.3,114.8,110.4,109.7,33.1,28.8,15.6.HRMS(ESI)m / z:[M+H] + calcd for C 17 H 18 NO 252.1383; found 252.1393.

[0100] The NMR data of the product of Example 22 are as follows:

[0101] 1 H NMR (400MHz, CDCl3) δ7.63(d,J=8.0Hz,1H),7.41(d,J=8.4Hz,1H),7.31(dd,J=16.0,7.6Hz,2H),7.22–7.17(m,2H),6.90(s,1H),6.84 (d,J=7.6Hz,1H),5.41(s,1H),3.87(s,3H),2.64(dd,J=9.6,7.6Hz,2H),1.73–1.65(m,2H),1.44–1.34(m,4H),0.94(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ153.2,143.8,137.4,130.6,127.8,126.9,122.6,120.8,120.2,120 .1,118.2,115.3,110.5,109.7,35.9,33.1,31.7,31.2,22.7,14.2.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 23 NNaO 316.1672; found 316.1684.

[0102] The NMR data of the product of Example 23 are as follows:

[0103] 1H NMR (400MHz, CDCl3) δ7.64(d,J=8.0Hz,1H),7.41(d,J=8.4Hz,1H),7.32(t,J=7.6Hz,2H),7.19(d,J=7.6Hz,2H),7.0 3(s,1H),6.97(d,J=8.0Hz,1H),5.40(s,1H),3.87(s,3H),1.68(q,J=7.4Hz,2H),1.32(s,6H),0.76(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ153.0,150.5,137.4,130.2,127.8,126.9,122.6,120.2,120.1, 118.4,117.9,113.2,110.5,109.7,38.0,37.0,33.1,28.6,9.4.HRMS(ESI)m / z:[M+H] + calcd for C 20 H 24 NO294.1852; found 294.1864.

[0104] The NMR data of the product of Example 24 are as follows:

[0105] 1 H NMR(400MHz, CDCl3) δ7.64(d,J=8.0Hz,1H),7.41(d,J=8.4Hz,1H),7.35–7.29(m,2H),7.2 2–7.16(m,2H),7.11(s,1H),7.04(d,J=8.0Hz,1H),5.41(s,1H),3.88(s,3H),1.38(s,9H). 13 C NMR (100MHz, CDCl3) δ153.0,152.1,137.4,130.3,127.8,126.9,122.6,120.2,1 20.1,118.1,117.7,112.6,110.4,109.7,34.8,33.1,31.5.HRMS(ESI)m / z:[M+H] + calcd for C 19 H 22 NO 280.1696; found 280.1701.

[0106] The NMR data of the product from Example 25 are as follows:

[0107] 1H NMR (400MHz, CDCl3) δ7.71(d,J=1.6Hz,1H),7.67(dd,J=13.6,7.6Hz,2H),7.50(d,J=7.6Hz,1H),7.42 (d,J=8.4Hz,1H),7.33(d,J=6.4Hz,2H),7.21(t,J=7.4Hz,1H),5.68(s,1H),3.94(s,3H),3.88(s,3H). 13 CNMR (100MHz, CDCl3) δ167.2,153.1,137.4,130.4,129.7,128.5,126.5,126.4,12 2.8,121.9,120.6,120.0,116.7,110.0,109.9,52.3,33.2.HRMS(ESI)m / z:[M+Na] + calcd for C 17 H 15 NNaO3 304.0944; found 304.0944.

[0108] The NMR data of the product in Example 26 are as follows:

[0109] 1 H NMR (400MHz, CDCl3) δ7.73(s,1H),7.68(dd,J=14.4,8.0Hz,2H),7.51(d,J=8.0Hz,1H),7.42(d,J=8.0Hz,1H),7 .36–7.31(m,2H),7.21(t,J=7.4Hz,1H),5.79(s,1H),4.40(q,J=7.2Hz,2H),3.88(s,3H),1.42(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ166.7,153.1,137.4,130.3,130.0,128.5,126.4,126.4,122. 8,121.9,120.6,120.0,116.6,109.9,109.8,61.1,33.2,14.5.HRMS(ESI)m / z:[M+H] + calcd for C 18 H 18 NO3296.1281; found 296.1295.

[0110] The NMR data of the product in Example 27 are as follows:

[0111] 1H NMR (400MHz, CDCl3) δ7.57–7.67(m,3H),7.43–7.36(m,4H),7.35–7.28(m,2H),7.27( d,J=1.2Hz,1H),7.24–7.17(m,2H),7.15(d,J=6.8Hz,1H),5.49(s,1H),3.85(s,3H). 13 C NMR (100MHz, CDCl3) δ153.7,141.5,140.9,137.5,131.1,128.9,127.9,127.5,127.1,126 .8,122.7,120.4,120.2,120.1,119.5,114.1,110.2,109.8,33.2.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 17 NNaO 322.1202; found 322.1201.

[0112] The NMR data of the product of Example 28 are as follows:

[0113] 1 H NMR (400MHz, DMSO-d6) δ9.55(d,J=2.4Hz,2H),7.76(d,J=8.0Hz,1H),7.65(s,1H),7.55(d, J=7.6Hz,1H),7.46(t,J=8.2Hz,3H),7.29–7.00(m,4H),6.86(d,J=8.8Hz,2H),3.84(s,3H). 13 C NMR (100MHz, CDCl3) δ155.3,153.6,141.1,137.4,133.5,131.1,128.4,127.9,126.8,122 .7,120.3,120.1,119.6,119.0,115.8,113.6,110.2,109.8,33.1.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 17 NNaO2 338.1151; found 338.1152.

[0114] The NMR data of the product of Example 29 are as follows:

[0115] 1H NMR (400MHz, CDCl3) δ7.66(d,J=8.0Hz,1H),7.59(d,J=8.4Hz,2H),7.42(dd,J=8.0,3.6Hz,2H),7.3 3(t,J=8.2Hz,1H),7.26–7.16(m,4H),6.99(d,J=8.4Hz,2H),5.51(s,1H),3.88(s,3H),3.86(s,3H). 13 C NMR (100MHz, CDCl3) δ159.3,153.7,141.2,137.5,133.4,131.1,128.2,127.9,126.9,122.7 ,120.3,120.1,119.6,119.0,114.3,113.6,110.3,109.8,55.5,33.2.HRMS(ESI)m / z:[M+Na] + calcd for C 22 H 19 NNaO2 352.1308; found352.1308.

[0116] The NMR data of the product of Example 30 are as follows:

[0117] 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.0Hz,1H),7.41(d,J=8.4Hz,1H),7.32(t,J=7.6Hz,1H),7.22–7 .16(m,3H),7.07(d,J=8.4Hz,1H),6.95(d,J=8.0Hz,1H),5.30(s,1H),3.88(s,3H),2.34(s,3H). 13 C NMR (100MHz, CDCl3) δ151.2,137.4,131.3,129.7,129.0,127.8,126.8,122.6 ,120.8,120.2,120.1,115.2,110.6,109.8,33.1,20.7.HRMS(ESI)m / z:[M+H] + calcd for C 16 H 16 NO 238.1226; found 238.1236.

[0118] The NMR data of the product of Example 31 are as follows:

[0119] 1H NMR(400MHz, CDCl3)δ7.58(d,J=8.0Hz,1H),7.39(d,J=8.0Hz,1H),7.32–7.27(m,1H),7.23(s,1H), 7.20–7.16(m,2H),7.14–7.10(m,1H),6.88(t,J=7.6Hz,1H),5.50(s,1H),3.86(s,3H),2.32(s,3H). 13 CNMR (100MHz, CDCl3) δ151.7,137.4,129.9,128.5,127.8,127.0,124.4,122. 7,120.5,120.3,120.2,120.0,110.8,109.8,33.1,16.4.HRMS(ESI)m / z:[M+H] + calcd for C 16 H 16 NO 238.1226; found 238.1236.

[0120] The NMR data for compound A are as follows:

[0121] 1 H NMR(400MHz, CDCl3)δ8.58(s,1H),8.15(d,J=8.0Hz,1H),7.92(s,2H),7.84–7.75(m,3 H),7.63–7.50(m,4H),7.36–7.32(m,2H),7.24(s,1H),7.12–6.94(m,2H),3.83(s,3H). 13 C NMR (100MHz, CDCl3) δ156.9,135.2,135.1,135.1,131.9,130.7,130.4,129.8,129.5,129.4,128.9 ,128.7,127.9,127.8,125.4,124.7,123.4,121.7,121.6,121.3,120.7,119.7,113.7,111.3,55.6.

[0122] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A method for synthesizing 2-(indole-3-yl)phenol and its derivatives, characterized in that, The indole compound, cyclohexanone compound, catalyst, oxidant, additive and organic solvent are mixed and heated and stirred to react, and finally purified to obtain the product; The indole compounds are selected from: 1-methylindole, 1-n-octylindole, 1-benzylindole, indole, 1,2-dimethylindole, 1-methyl-2-phenylindole, 1,5-dimethylindole, 5-methoxy-1-methylindole, 5-fluoro-1-methylindole, 5-chloro-1-methylindole, 5-bromo-1-methylindole, 5-ester-1-methylindole, 1,6-dimethylindole, 6-methoxy-1-methylindole, 6-fluoro-1-methylindole, 6-chloro-1-methylindole, 6-bromo-1-methylindole, 1,7-dimethylindole, 7-fluoro-1-methylindole, and 7-bromo-1-methylindole. The cyclohexanone compounds are selected from: 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-n-pentylcyclohexanone, 4-tert-pentylcyclohexanone, 4-tert-butylcyclohexanone, 4-esterylcyclohexanone, 4-phenyl-cyclohexanone, 4-(4-hydroxyphenyl)cyclohexanone, 4-(4-methoxyphenyl)cyclohexanone, 3-methylcyclohexanone, and 2-methylcyclohexanone; The catalyst is one of the following: sodium iodide, potassium iodide, ammonium iodide, iodine bromide, iodine chloride, hydroiodic acid, elemental iodine, N-iodosuccinimide, potassium iodate, sodium periodate, diacetyl iodobenzene, trimethyliodosilane, trimethyl sulfoxide, iodobenzene, iodine pentoxide, and cuprous iodide. The oxidant is one of the following: dimethyl sulfoxide, benzyl phenyl sulfoxide, methyl phenyl sulfoxide, dimethyl sulfone, diphenyl sulfoxide, diphenyl sulfone, sulfolane, potassium persulfate, di-tert-butyl peroxide, tert-butyl hydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone. The additive is one of the following: trifluoroacetic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid, ferric chloride, aluminum chloride, boron trifluoride ether, pentylamino acid, camphor sulfonic acid, benzoic acid, p-methylbenzoic acid, p-nitrobenzoic acid, and p-methoxybenzoic acid. The organic solvent is selected from one of chlorobenzene, toluene, trifluorotoluene, o-xylene, m-xylene, nitrobenzene, 1,4-dioxane, 1,2-dichloroethane, N,N-dimethylacetamide, dimethyl sulfoxide, and o-dichlorobenzene; The 2-(indol-3-yl)phenol and its derivatives are one of the following:

2. The method according to claim 1, characterized in that, The molar ratio of indole compounds, cyclohexanone compounds, catalysts, oxidants, and additives is 1.0:1.0-10.0:0.01-1.0:1.0-10.0:0.01-5.0, the reaction temperature is 80℃-140℃, and the reaction time is 8-36 hours.

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