CN113278007B - Synthetic method of 2-hydroxy-indole-3-ketone compound - Google Patents

Synthetic method of 2-hydroxy-indole-3-ketone compound Download PDF

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CN113278007B
CN113278007B CN202110624425.XA CN202110624425A CN113278007B CN 113278007 B CN113278007 B CN 113278007B CN 202110624425 A CN202110624425 A CN 202110624425A CN 113278007 B CN113278007 B CN 113278007B
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hydroxy
indole
chloroform
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acetylphenyl
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CN113278007A (en
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马豪杰
郭翠
张玉琦
王记江
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Yanan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The invention discloses a synthesis method of 2-hydroxy-indole-3-ketone compounds, which comprises the steps of taking N- (2-acetylphenyl) pyridinoline amide and derivatives thereof as raw materials, taking copper salts such as cuprous iodide and the like as catalysts, taking acetic acid and the like as additives, and reacting at 80-110 ℃ in an oxygen atmosphere to obtain the 2-hydroxy-indole-3-ketone compounds. The method has the characteristics of good substrate applicability, atom economy, easy operation, avoidance of substrate preparation, low reagent cost, cost saving, mild reaction conditions, synthesis in one step, high yield and the like, and provides a new strategy for synthesizing the 2-hydroxy-indole-3-ketone compound.

Description

Synthetic method of 2-hydroxy-indole-3-ketone compound
Technical Field
The invention relates to synthesis of 2-hydroxy-indole-3-ketone compounds, in particular to synthesis of 2-hydroxy-indole-3-ketone compounds by using N- (2-acetylphenyl) pyridinamide and derivatives 1 thereof as raw materials and under the catalytic action of cuprous iodide to prepare 2-hydroxy-indole-3-ketone compounds, wherein in the reaction, N- (2-acetylphenyl) pyridinamide and derivatives 2 thereof are subjected to pyridine guide and copper chelation to close rings under the oxidation action of cuprous iodide and oxygen to synthesize the 2-hydroxy-indole-3-ketone compounds.
Background
Indoles are the most common heterocycles found in nature and are found in a variety of biologically active compounds and indole-derived drug molecules. Of the many indole skeletons, indol-3-ones are ubiquitous structures in drugs and natural products, and at the same time, they are widely used in fluorescent dyes and solar cells. In particular, the construction of 2-hydroxy-indol-3-ones with a quaternary carbon center at C2 has attracted a great deal of interest to organic chemists. They are present in many natural products and biologically active compounds, such as notoamide O, iboluteine, cephalolinone B, melochicin, materone, cephalolinone, brevianamide A and B, rupicoline. More importantly, 2-hydroxy-indol-3-ones are versatile synthetic intermediates for various organic transformations and are used as probes to identify specific targets of the endoplasmic reticulum. The alkaloid melochicorin is isolated from the grass Melochia corchorifolia, which has potent hepatoprotective and antioxidant activity. Matemone was first isolated from the Indian sponge Violet (Iotrochota purpurea) in 2000, showed mild cytotoxicity against three cancer cell lines, and inhibited the growth of NSCLC-N6L 16 strain (IC50 ═ 30 nm).
Few papers have reported the synthesis of 2-hydroxy-indol-3-ones in recent years, and the Foote group proposed a synthesis of 2-hydroxy-indol-3-one using 2-methyl-1H-indole and dimethyl dioxirane (DMD) as the oxidant, but this process gave less than 10% yield (J.Am.chem.Soc.1993,115, 8867.). In 2019, the Dash subject group synthesizes a 2-hydroxy-indol-3-one compound (org.lett.2019,21,8044.) by taking 3-hydroxy-indol-2-one and a grignard reagent as raw materials, and the method needs a special raw material of 3-hydroxy-indol-2-one, pre-functionalization of the raw material, and the use of the grignard reagent, so that the reaction conditions are severe and high in requirements.
Disclosure of Invention
The invention aims to provide a method for synthesizing 2-hydroxy-indole-3-ketone compounds, which has the advantages of easily obtained raw materials, simple operation, mild reaction conditions, atom economy, good substrate applicability and high yield.
Aiming at the purposes, the technical scheme adopted by the invention is as follows: adding the compound 1, copper salt and an additive into an organic solvent, and reacting at 80-110 ℃ in an oxygen atmosphere to obtain a target product 2, namely a 2-hydroxy-indole-3-ketone compound, wherein the reaction formula is as follows:
Figure BDA0003101570340000021
in the formula, R1、R2Each independent representative H, C1～C4Any one or two of alkyl, benzene ring and halogen, and X represents CH or N.
The copper salt is any one of cuprous iodide, cupric chloride and cuprous bromide dimethyl sulfide, and the addition amount of the copper salt is 25-40% of the molar amount of the compound 1.
The additive is any one of benzoic acid, acetic acid and trimethylacetic acid, and the addition amount of the additive is 2-3 times of the 1 molar amount of the compound.
In the above synthesis method, the reaction is preferably carried out at 100 ℃ for 4 to 6 hours in an oxygen atmosphere.
The organic solvent is any one of dimethyl sulfoxide, N-dimethylformamide and N, N-dimethylacetamide.
The invention has the following beneficial effects:
the invention takes N- (2-acetylphenyl) pyridinoline amide and derivatives thereof as raw materials, copper salts such as cuprous iodide and the like as catalysts, acetic acid and the like as additives, and efficiently synthesizes the 2-hydroxy-indole-3-ketone compound, and the invention has the characteristics of good substrate applicability, atom economy, easy operation, avoidance of substrate preparation, cheap reagent, cost saving, mild reaction conditions, synthesis in one step, high yield and the like, provides a new strategy for synthesizing the 2-hydroxy-indole-3-ketone compound, can synthesize various types of 2-hydroxy indole and derivatives thereof with chirality, and provides a new strategy for synthesizing the medicaments.
Detailed Description
The present invention will be described in further detail with reference to the following examples, but the scope of the present invention is not limited to these examples.
Example 1
Figure BDA0003101570340000031
To a 10mL reaction tube were added 48.0mg (0.2mmol) of N- (2-acetylphenyl) pyridinamide, 11.4mg (0.06mmol) of cuprous iodide, 24.0mg (0.4mmol) of acetic acid, and 1.5mL of dimethyl sulfoxide, and the reaction tube was evacuated, magnetically stirred, and reacted at 100 ℃ for 5 hours under an oxygen atmosphere. TLC monitors the reaction to be complete, when the reaction solution is cooled to room temperature, the reaction solution is extracted by ethyl acetate for 3 times, an organic phase is washed by saturated saline solution, dried by anhydrous sodium sulfate, concentrated by reduced pressure distillation and separated by column chromatography (eluent is mixed solution of petroleum ether and ethyl acetate with the volume ratio of 5: 1), and a target product 2a is obtained, wherein the chemical name is 2-hydroxy-indol-3-ketone, the yield is 77%, and the structural characterization data is as follows:
1H NMR(400MHz,Chloroform-d)δ8.70–8.61(m,2H),8.40(s,1H),8.30(dt,J＝8.0,1.1Hz,1H),8.04(td,J＝7.8,1.8Hz,1H),7.88–7.82(m,1H),7.79–7.72(m,1H),7.65–7.58(m,1H),7.32(td,J＝7.5,0.9Hz,1H),5.59(s,1H)；13C NMR(100MHz,Chloroform-d)δ194.64,164.46,152.84,151.81,147.29,138.85,137.65,127.06,126.74,125.40,124.65,123.24,119.50,81.67；HRMS C14H11N2O3[M+H]+theoretical 255.0764, found 255.0768.
Example 2
Figure BDA0003101570340000032
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-6-methylphenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2b in a yield of 60%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.70(d,J＝4.1Hz,1H),8.33(d,J＝7.9Hz,1H),8.02(td,J＝7.8,1.8Hz,1H),7.68(d,J＝7.0Hz,1H),7.65–7.60(m,1H),7.58(d,J＝7.5Hz,1H),7.34–7.24(m,2H),5.43(s,1H),2.35(s,3H)；13C NMR(100MHz,Chloroform-d)δ195.20,164.88,152.27,151.15,148.02,139.84,138.49,130.77,127.42,126.36,126.19,125.70,122.25,83.12,20.76；HRMS C15H13N2O3[M+H]+theoretical 269.0921, found 269.0922.
Example 3
Figure BDA0003101570340000041
In this example, the procedure was the same as in example 1 except that N- (2-acetylphenyl) picolinamide used in example 1 was replaced with an equimolar amount of N- (2-acetyl-5-methylphenyl) picolinamide, to give the objective product 2c in a yield of 76%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.65(d,J＝4.5Hz,1H),8.47(s,1H),8.38–8.25(m,2H),8.03(td,J＝7.8,1.8Hz,1H),7.72(d,J＝7.8Hz,1H),7.64–7.58(m,1H),7.13(d,J＝7.8Hz,1H),5.57(s,1H),2.52(s,3H)；13C NMR(100MHz,Chloroform-d)δ193.92,164.45,153.13,151.90,149.65,147.26,138.80,126.97,126.67,124.41,121.04,119.76,82.04,22.84；HRMS C15H13N2O3[M+H]+theoretical 269.0921, found 269.0919.
Example 4
Figure BDA0003101570340000042
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-4-methylphenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2d in a yield of 78%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.68–8.62(m,1H),8.51(d,J＝8.4Hz,1H),8.35(s,1H),8.29(dt,J＝7.9,1.1Hz,1H),8.03(td,J＝7.8,1.7Hz,1H),7.62(s,1H),7.61–7.58(m,1H),7.56(dd,J＝8.5,2.0Hz,1H),5.58(s,1H),2.42(s,3H)；13C NMR(100MHz,Chloroform-d)δ194.65,164.19,151.92,150.93,147.26,138.79,138.64,135.49,126.93,126.68,124.36,123.35,119.24,81.92,20.83；HRMS C15H13N2O3[M+H]+theoretical 269.0921, found 269.0920.
Example 5
Figure BDA0003101570340000051
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-4-ethylphenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2e in a yield of 76%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.65(d,J＝4.9Hz,1H),8.53(d,J＝8.5Hz,1H),8.36(s,1H),8.31–8.27(m,1H),8.03(td,J＝7.8,1.8Hz,1H),7.65(d,J＝2.0Hz,1H),7.63–7.56(m,2H),5.58(s,1H),2.72(q,J＝7.6Hz,2H),1.27(t,J＝7.6Hz,3H)；13C NMR(100MHz,Chloroform-d)δ194.70,164.17,151.88,151.07,147.24,141.85,138.76,137.70,126.92,126.64,123.36,123.09,119.31,81.93,28.16,15.31；HRMS C16H15N2O3[M+H]+theoretical 283.1077, found 283.1079.
Example 6
Figure BDA0003101570340000052
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (6-acetyl-2, 3-dimethylphenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the desired product 2f in 51% yield and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.70(d,J＝4.0Hz,1H),8.31(dt,J＝8.0,1.1Hz,1H),8.01(td,J＝7.8,1.7Hz,1H),7.67–7.56(m,2H),7.20(d,J＝7.7Hz,1H),7.10(s,1H),5.43(s,1H),2.45(s,3H),2.17(s,3H)；13C NMR(100MHz,Chloroform-d)δ194.69,165.26,152.60,151.28,148.47,148.05,138.42,129.24,128.36,127.36,126.30,124.01,121.81,83.73,21.12,17.29；HRMS C16H15N2O3[M+H]+theoretical 283.1077, found 283.1076.
Example 7
Figure BDA0003101570340000061
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-5-chlorophenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give 2g of the objective product in a yield of 68%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.78–8.59(m,2H),8.44(s,1H),8.30(d,J＝7.9Hz,1H),8.06(td,J＝7.8,1.8Hz,1H),7.76(d,J＝8.2Hz,1H),7.67–7.62(m,1H),7.32–7.27(m,1H),5.62(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.28,164.44,153.27,151.30,147.36,144.10,138.97,127.29,126.88,126.00,125.40,121.57,119.80,82.02；HRMS C14H10ClN2O3[M+H]+theoretical 289.0375, found 289.0378.
Example 8
Figure BDA0003101570340000062
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-4-chlorophenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2h in a yield of 70%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.66(d,J＝4.0Hz,1H),8.60(d,J＝8.8Hz,1H),8.36(s,1H),8.29(d,J＝8.0Hz,1H),8.04(td,J＝7.8,1.7Hz,1H),7.77(d,J＝2.3Hz,1H),7.68(dd,J＝8.9,2.3Hz,1H),7.65–7.60(m,1H),5.62(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.40,164.30,151.48,151.19,147.37,138.91,137.24,131.05,127.20,126.83,124.57,124.10,120.76,81.98；HRMS C14H10ClN2O3[M+H]+theoretical 289.0375, found 289.0376.
Example 9
Figure BDA0003101570340000071
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetyl-4-bromophenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2i in a yield of 68%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.67(d,J＝4.9Hz,1H),8.56(d,J＝8.9Hz,1H),8.46(s,1H),8.30(d,J＝7.9Hz,1H),8.06(td,J＝7.8,1.8Hz,1H),7.94(d,J＝2.2Hz,1H),7.83(dd,J＝8.9,2.2Hz,1H),7.67–7.61(m,1H),5.61(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.33,164.33,151.58,151.36,147.36,140.11,138.97,127.27,127.23,126.85,124.85,121.06,118.45,81.79；HRMS C14H10BrN2O3[M+H]+theoretical 332.9870, found 332.9873.
Example 10
Figure BDA0003101570340000072
In this example, the procedure was otherwise the same as in example 1 except that equimolar amounts of N- (2-acetyl-4-iodophenyl) picolinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the desired product 2j in a yield of 66%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ9.13(d,J＝1.3Hz,1H),8.66(d,J＝4.0Hz,1H),8.30(dt,J＝7.9,1.1Hz,1H),8.05(td,J＝7.8,1.8Hz,1H),7.69(dd,J＝8.0,1.4Hz,1H),7.66–7.60(m,1H),7.52(d,J＝8.0Hz,1H),5.58(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.81,164.42,152.83,151.48,147.39,138.96,134.87,128.67,127.23,126.87,125.26,122.59,106.32,81.79；HRMS C14H10IN2O3[M+H]+theoretical 380.9731, found 380.9730.
Example 11
Figure BDA0003101570340000081
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetylphenyl) -6-methylpyridinecarboxylic acid amide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2k in a yield of 70%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.62(d,J＝8.4Hz,1H),8.07(d,J＝7.8Hz,1H),7.90(t,J＝7.8Hz,1H),7.83(d,J＝7.7Hz,1H),7.77–7.70(m,1H),7.45(d,J＝7.7Hz,1H),7.33–7.27(m,1H),5.56(s,1H),2.69(s,3H)；13C NMR(100MHz,Chloroform-d)δ194.81,164.71,156.81,152.88,151.17,138.84,137.57,126.90,125.23,124.57,123.81,123.18,119.43,81.57,23.87；HRMS C15H13N2O3[M+H]+theoretical 269.0921, found 269.0920.
Example 12
Figure BDA0003101570340000082
In this example, the procedure was the same as in example 1 except that an equimolar amount of N- (2-acetylphenyl) -3-methylpyridinamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to obtain 2l as an objective product in a yield of 73%, and the structural characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ8.63(d,J＝8.3Hz,1H),8.46(d,J＝3.8Hz,1H),8.07(s,1H),7.85–7.78(m,2H),7.75(t,J＝7.8Hz,1H),7.47(dd,J＝7.9,4.8Hz,1H),7.31(t,J＝7.5Hz,1H),5.20(s,1H),2.57(s,3H)；13C NMR(100MHz,Chloroform-d)δ194.29,165.14,152.48,150.57,144.71,141.28,137.61,135.81,125.93,125.30,124.78,123.16,119.07,81.11,19.43；HRMS C15H13N2O3[M+H]+theoretical 269.0921, found 269.0918.
Example 13
Figure BDA0003101570340000091
In this example, the procedure was the same as in example 1 except that N- (2-acetylphenyl) picolinamide used in example 1 was replaced with an equimolar amount of N- (2-acetylphenyl) -6-chloropicolinamide, to give the objective product 2m in a yield of 71%, and the structural characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ8.59(d,J＝8.4Hz,1H),8.22(d,J＝7.7Hz,1H),7.99(t,J＝7.9Hz,1H),7.84(d,J＝7.7Hz,1H),7.75(t,J＝7.9Hz,1H),7.62(d,J＝8.0Hz,1H),7.33(t,J＝7.4Hz,1H),7.08(d,J＝4.6Hz,1H),5.68(d,J＝4.3Hz,1H)；13C NMR(100MHz,Chloroform-d)δ194.26,162.99,152.71,151.95,149.73,141.02,137.64,127.71,125.64,125.04,124.72,123.21,119.64,81.65；HRMS C14H10ClN2O3[M+H]+theoretical 289.0375, found 289.0377.
Example 14
Figure BDA0003101570340000092
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetylphenyl) -3-fluoropicolinic acid amide was used instead of the N- (2-acetylphenyl) picolinamide used in example 1, to give the objective product 2N in a yield of 69%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.62(d,J＝8.3Hz,1H),8.48(d,J＝4.6Hz,1H),7.82(d,J＝7.7Hz,1H),7.80–7.71(m,2H),7.65(dt,J＝8.6,4.3Hz,1H),7.43(s,1H),7.33(t,J＝7.3Hz,1H),5.35(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.76,160.18(d,J＝253Hz),158.99(d,J＝269Hz),152.13,143.35(d,J＝6Hz),140.66(d,J＝10Hz),137.79,128.28(d,J＝5Hz),127.04(d,J＝19Hz),125.65,124.78,123.06,119.19,81.10；HRMS C14H10FN2O3[M+H]+theoretical 273.0670, found 273.0669.
Example 15
Figure BDA0003101570340000101
In this example, the procedure was the same as in example 1 except that an equimolar amount of N- (2-acetylphenyl) -6-fluoropyridinecarboxamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, to obtain the objective product 2o in a yield of 62%, and the structural characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ8.58(d,J＝8.4Hz,1H),8.23–8.18(m,1H),8.12(q,J＝7.7Hz,1H),7.88–7.81(m,1H),7.78–7.71(m,1H),7.32(td,J＝7.5,0.9Hz,1H),7.29–7.24(m,1H),6.90(d,J＝4.7Hz,1H),5.71(d,J＝4.6Hz,1H)；13C NMR(100MHz,Chloroform-d)δ194.23,162.87,161.46(d,J＝246Hz),152.73,149.68(d,J＝10Hz),143.52(d,J＝8Hz),137.64,125.60,124.68,124.01(d,J＝4Hz),123.15,119.64,113.44(d,J＝34Hz),81.54；HRMS C14H10FN2O3[M+H]+theoretical 273.0670, found 273.0667.
Example 16
Figure BDA0003101570340000102
In this example, the equimolar amount of N- (2-acetylphenyl) pyrazine-2-carboxamide was used instead of N- (2-acetylphenyl) picolinamide used in example 1, and the other steps were the same as in example 1 to obtain the target product 2p in a yield of 63%, and the structural characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ9.52(s,1H),8.92(d,J＝2.6Hz,1H),8.63(dt,J＝5.0,2.4Hz,2H),7.85(d,J＝8.3Hz,1H),7.77(t,J＝7.9Hz,1H),7.35(t,J＝7.5Hz,1H),7.06(s,1H),5.64(s,1H)；13C NMR(100MHz,Chloroform-d)δ193.83,162.75,152.45,148.36,147.80,146.53,141.23,137.82,125.84,124.78,123.10,119.49,81.45；HRMS C13H10N3O3[M+H]+theoretical 256.0717, found 256.0716.
Example 17
Figure BDA0003101570340000111
In this example, the procedure was otherwise the same as in example 1 except that an equimolar amount of N- (2-acetylphenyl) quinoline-2-amide was used instead of the N- (2-acetylphenyl) pyridinoline amide used in example 1, to give the objective product 2q in a yield of 80%, and the structural characterization data are as follows:
1H NMR(400MHz,Chloroform-d)δ8.86(s,1H),8.69(d,J＝8.4Hz,1H),8.46(d,J＝8.5Hz,1H),8.32(d,J＝8.6Hz,1H),8.18(d,J＝8.5Hz,1H),7.96(d,J＝8.2Hz,1H),7.92–7.84(m,2H),7.80–7.70(m,2H),7.33(t,J＝7.5Hz,1H),5.75(s,1H)；13C NMR(100MHz,Chloroform-d)δ194.74,164.72,152.86,151.62,145.09,138.78,137.69,131.35,129.22,129.20,129.08,127.88,125.44,124.70,123.31,122.19,119.48,81.81；HRMS C18H13N2O3[M+H]+theoretical 305.0921, found 305.0920.

Claims (5)

1. A synthetic method of 2-hydroxy-indole-3-ketone compounds is characterized in that: adding the compound 1, copper salt and an additive into an organic solvent, and reacting at 80-110 ℃ in an oxygen atmosphere to obtain a target product 2, namely a 2-hydroxy-indole-3-ketone compound, wherein the reaction formula is as follows:
Figure DEST_PATH_IMAGE002
in the formula, R1、R2Each independent representative H, C1～C4Any one or two of alkyl, benzene ring and halogen, and X represents CH or N;
the additive is acetic acid; the copper salt is cuprous iodide.
2. The method of synthesizing 2-hydroxy-indol-3-ones according to claim 1, characterized in that: the adding amount of the copper salt is 25 to 40 percent of the molar amount of the compound 1.
3. The method of synthesizing 2-hydroxy-indol-3-ones according to claim 1, characterized in that: the addition amount of the additive is 2-3 times of the 1 molar amount of the compound.
4. The method of synthesizing 2-hydroxy-indol-3-ones according to claim 1, characterized in that: reacting for 4-6 hours at 100 ℃ in an oxygen atmosphere.
5. The method of synthesizing 2-hydroxy-indol-3-ones according to claim 1, characterized in that: the organic solvent is any one of dimethyl sulfoxide, N-dimethylformamide and N, N-dimethylacetamide.
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