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

Abstract

The invention mainly relates to a synthetic method of 2-(indole-3-yl) phenol and a derivative thereof. According to the invention, under the action of the iodine catalyst, the oxidant and the acid additive, one-pot reaction of the indole compound and the cyclohexanone compound is realized to obtain the 2-(indole-3-yl) phenol and the derivative thereof with high selectivity, and the product with stable structure and excellent chemical property and the additional product thereof are prepared. The method disclosed by the invention has the characteristics of simple reaction system, mild reaction conditions, less reaction equipment, simplicity and convenience in experimental operation, wide material source, good atom economy, no need of adding a transition metal catalyst and the like, and a new synthesis path is provided for synthesis of the 2-(indole-3-yl) phenol compound. The 2-(indole-3-yl) phenol derivative and the synthetic method thereof can be used in the field of medicine production.

Description

Technical Field

[0001] The invention relates to a 2-(indol-3-yl)phenol compound and a synthesis method thereof, and belongs to the field of organic synthesis. Background Art

[0002] Indol-3-ylphenol compounds are a very important class of nitrogen-containing heterocyclic compounds, which are widely distributed in many natural products and functional materials. In addition, indol-3-ylphenol compounds have a variety of biological activities and pharmacological effects, such as antioxidant, antibacterial, anti-biofilm and anti-glioblastoma activities. Indol-3-ylphenol can also be used as a B-Raf inhibitor, DYRK1A inhibitor, estrogen receptor ligand and vascular disruptor. Indol-3-ylphenol compounds have wide application value and good application prospects in the medical field. Most of the existing methods for synthesizing such compounds require the use of expensive transition metal catalysts and pre-functionalized raw materials, which have disadvantages such as high reaction cost, metal residues and pollution. Summary of the invention

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

[0004] Another object of the present invention is to provide a method for synthesizing 2-(indol-3-yl)phenol and its derivatives, which has the advantages of cheap and readily available raw materials, simple reaction conditions, convenient operation, few reaction steps, simple required equipment, etc. The reaction does not require the use of metal catalysts and metal oxidants, the reaction can maintain atom economy to a large extent, has low input and high output, and is easy to industrialize and popularize.

[0005] In order to achieve the above object, the present invention discloses a compound: 2-(indol-3-yl)phenol and its derivatives, which have the general formula of Formula I:

[0006]

[0007] in:

[0008] R 1 is selected from a hydrogen atom, an alkyl group, a benzyl group;

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

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

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

[0012] The indole compound, the cyclohexanone compound, the catalyst, the oxidant, the additive and the organic solvent are mixed, heated and stirred for reaction, and finally purified to obtain the product.

[0013] In the method of the present invention, the general formula of the indole compound is Formula II:

[0014]

[0015] in:

[0016] R 1 is selected from a hydrogen atom, an alkyl group, a benzyl group;

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

[0018] According to the method of the present invention, the indole compound is selected from the group consisting of: 1-methylindole, 1-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, the general formula of the cyclohexanone compound described in the method of the present invention is Formula III:

[0020]

[0021] in:

[0022] R 3 is selected from a hydrogen atom, an alkyl group, an ester group, and an aryl group;

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

[0024] In the method of the present invention, the catalyst is one of sodium iodide, potassium iodide, ammonium iodide, iodine bromide, iodine chloride, hydroiodic acid, elemental iodine, N-iodosuccinimide, potassium iodate, sodium periodate, iodobenzene diacetate, trimethyl iodosilane, trimethyl sulfoxide iodide, iodobenzene, diiodine pentoxide and cuprous iodide.

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

[0026] In the method of the present invention, the additive is one of trifluoroacetic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid, ferric chloride, aluminum chloride, boron trifluoride etherate, pivalic acid, camphorsulfonic acid, benzoic acid, p-toluic 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] According to the method of the present invention, the molar ratio of the indole compound, the cyclohexanone compound, the catalyst, the oxidant and the 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°C-140°C, and the reaction time is 8-36 hours.

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

[0030] (I) The present invention realizes a technical solution for preparing 2-(indol-3-yl)phenol and its derivatives with high selectivity from indole compounds and cyclohexanone compounds in an air atmosphere under the action of iodine catalysts, oxidants and additives, thereby overcoming the huge waste of manpower, money and materials caused by the method using metal catalysts, saving a lot of research time and shortening the production cycle; (II) The technical solution for selectively obtaining 2-(indol-3-yl)phenol and its derivatives from indole compounds and cyclohexanone compounds under the reaction conditions of catalysts, oxidants, additives and organic solvents by heating and stirring has the advantages of simple reaction system, mild reaction conditions, wide sources of materials, good atom economy, simple experimental operation, significant increase in product added value and high availability, and foreseeable market commercialization prospects; (III) The 2-(indol-3-yl)phenol derivatives and the synthesis method thereof of the present invention have wide application value and good application prospects in the field of medicine; and are also suitable for scientific research and development and utilization of efficient and selective synthesis of bis-2-(indol-3-yl)phenol compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to prove the product of the present invention, the present invention provides the nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of some embodiments. See the attached drawings of the specification for details.

[0032] Figure 1-1 H NMR spectrum of the product of Example 1.

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

[0034] Figure 2-1 H NMR spectrum of the product of Example 2.

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

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

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

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

[0039] Figure 5 It is a reaction schematic diagram for further preparing compound A having anti-HIV activity using 2-(indol-3-yl)phenol and its derivatives. DETAILED DESCRIPTION

[0040] The present invention will now be described in further detail with reference to the following figure. The following figure is a simplified schematic diagram, which only illustrates the basic structure of the present invention in a schematic manner, and therefore only shows the composition related to the present invention. The reaction formula is shown in Figure 4 .

[0041] The following steps are involved:

[0042] (1) Adding indole compounds, cyclohexanone compounds, catalysts, oxidants, additives and organic solvents into a reaction vessel;

[0043] (2) After the reactants are fully mixed, they are heated;

[0044] ⑶ After the reaction, purification is carried out to obtain the product.

[0045] Example 1

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

[0047]

[0048] Take a reaction tube, add 0.2mmol (23.4mg) indole, 0.6mmol (62.0μL) cyclohexanone, 0.04mmol (10.1mg) elemental iodine, 1.0mmol (71.0μL) dimethyl sulfoxide, 0.08mmol (9.8mg) benzoic acid, 0.5mL toluene, seal it in a 120℃ oil bath, stir and react for 24 hours, and obtain 18.8mg of pure product by conventional treatment, with a yield of 45%.

[0049] Example 2-31

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

[0051]

[0052]

[0053]

[0054]

[0055]

[0056] The product synthesized by the present invention (Example 1) can be further subjected to the following reaction to prepare compound A having anti-HIV activity: Figure 4 .

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

[0058] The NMR data of the product of 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 of 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 of 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] + Calculate for C 22 H 27 NNaO 344.1985; found 344.1985.

[0064] The NMR data of the product of 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] + Calculate for C 21 H 17 NNaO 322.1202; found 322.1201.

[0066] The NMR data of the product of 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 of 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] + Calculate for C 21 H 17 NNaO 322.1202; found 322.1201.

[0070] The NMR data of the product of 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] + Calculate for C 16 H 15 NNaO 260.1046; found 260.1045.

[0072] The NMR data of the product of 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] + Calculate for C 16 H 15 NNaO2276.0995; found 276.0995.

[0074] The NMR data of the product of 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] + Calculate for C 15 H 13 FNO242.0976; found 242.0981.

[0076] The NMR data of the product of 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] + Calculate 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] + Calculate 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 of 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] + Calculate for C 16 H 15 NNaO 260.1046; found 260.1045.

[0084] The NMR data of the product of 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] + Calculate for C 15 H 12 FNNaO 264.0795; found 264.0795.

[0086] The NMR data of the product of 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] + Calculate for C 15 H 13 ClNO 258.0680; found 258.0683.

[0088] The NMR data of the product of 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] + Calculate for C 15 H 12 BrNNaO323.9994; found 323.9994.

[0090] The NMR data of the product of 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] + Calculate 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] + Calculate 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] + Calculate for C 15 H 12 BrNNaO 323.9994; found323.9993.

[0096] The NMR data of the product of 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] + Calculate 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] + Calculate 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] + Calculate 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] + Calculate 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] + Calculate for C 19 H 22 NO 280.1696; found 280.1701.

[0106] The NMR data of the product of 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] + Calculate for C 17 H 15 NNaO3 304.0944; found 304.0944.

[0108] The NMR data of the product of 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] + Calculate for C 18 H 18 NO3296.1281; found 296.1295.

[0110] The NMR data of the product of 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] + Calculate 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] + Calculate 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] + Calculate 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] + Calculate 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] + Calculate for C 16 H 16 NO 238.1226; found 238.1236.

[0120] The NMR data of 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 ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A 2-(indol-3-yl)phenol and its derivatives, which have the general formula I: in: R 1 is selected from a hydrogen atom, an alkyl group, a benzyl group; R 2 is selected from hydrogen atom, alkyl group, halogen group, alkoxy group, ester group, phenyl group; R 3 Selected from hydrogen atom, alkyl group, ester group, aryl group.

2. A method for synthesizing 2-(indol-3-yl)phenol and its derivatives according to claim 1, characterized in that: The indole compound, the cyclohexanone compound, the catalyst, the oxidant, the additive and the organic solvent are mixed, heated and stirred for reaction, and finally purified to obtain the product.

3. The method according to claim 2, characterized in that The general formula of the indole compound is Formula II: in: R 1 is selected from a hydrogen atom, an alkyl group, a benzyl group; R 2 is selected from hydrogen atom, alkyl group, halogen group, alkoxy group, ester group, phenyl group; The indole compound is selected from the group consisting of: 1-methylindole, 1-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.

4. The method according to claim 2, characterized in that: The general formula of the cyclohexanone compound described in the method of the present invention is Formula III: in: R 3 is selected from a hydrogen atom, an alkyl group, an ester group, and an aryl group; The cyclohexanone compound is selected from: 4-methylcyclohexanone, 4-ethylcyclohexanone, 4-n-pentylcyclohexanone, 4-tert-pentylcyclohexanone, 4-tert-butylcyclohexanone, 4-estercyclohexanone, 4-phenyl-cyclohexanone, 4-(4-hydroxyphenyl)cyclohexanone, 4-(4-methoxyphenyl)cyclohexanone, 3-methylcyclohexanone, and 2-methylcyclohexanone.

5. The method according to any one of claims 2 to 4, characterized in that: The catalyst is one of sodium iodide, potassium iodide, ammonium iodide, iodine bromide, iodine chloride, hydroiodic acid, elemental iodine, N-iodosuccinimide, potassium iodate, sodium periodate, iodobenzene diacetate, trimethyl iodosilane, trimethyl sulfoxide iodide, iodobenzene, diiodine pentoxide, and cuprous iodide.

6. The method according to any one of claims 2 to 5, characterized in that The oxidant described in the method of the present invention is one of dimethyl sulfoxide, benzyl phenyl sulfoxide, methyl phenyl sulfoxide, dimethyl sulfone, diphenyl sulfoxide, diphenyl sulfone, cyclopentane, potassium persulfate, di-tert-butyl peroxide, tert-butyl hydroperoxide and 2,3-dichloro-5,6-dicyano-p-benzoquinone.

7. The method according to any one of claims 2 to 6, characterized in that: The additive is one of trifluoroacetic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid, ferric chloride, aluminum chloride, boron trifluoride etherate, pivalic acid, camphorsulfonic acid, benzoic acid, p-toluic acid, p-nitrobenzoic acid, and p-methoxybenzoic acid.

8. The method according to any one of claims 2 to 7, characterized in that: 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.

9. The method according to any one of claims 2 to 8, characterized in that: The molar ratio of the indole compound, the cyclohexanone compound, the catalyst, the oxidant and the 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° C.-140° C., and the reaction time is 8-36 hours.

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