CN114232013A - Method for synthesizing indoloquinoline compound under electrochemical condition - Google Patents

Method for synthesizing indoloquinoline compound under electrochemical condition Download PDF

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CN114232013A
CN114232013A CN202111390084.0A CN202111390084A CN114232013A CN 114232013 A CN114232013 A CN 114232013A CN 202111390084 A CN202111390084 A CN 202111390084A CN 114232013 A CN114232013 A CN 114232013A
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黄精美
万金林
崔建丰
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South China University of Technology SCUT
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Abstract

The invention belongs to the field of organic electrochemical synthesis, and discloses a method for synthesizing an indoloquinoline compound under an electrochemical condition. The method utilizes the action of current, and takes n-tetrabutylammonium bromide as a catalyst to circulate in a reaction system and catalyze decarboxylation of a reaction substrate to initiate nitrogen-oxygen bond fracture to generate imine nitrogen free radicals, and finally generates intramolecular carbon-nitrogen bond coupling reaction to generate the indoloquinoline compound; the invention does not need expensive metal catalyst and equivalent oxidant; the reaction conditions are very mild; the whole process is simple and easy to implement, has little pollution and conforms to the concept of green chemistry.

Description

Method for synthesizing indoloquinoline compound under electrochemical condition
Background
The invention relates to the technical field of synthetic drugs with biological activity, in particular to a method for synthesizing an indoloquinoline compound under an electrochemical condition.
Background
The indoloquinoline compounds are skeleton compounds with good biological activity, widely exist in natural products and synthetic drugs with broad-spectrum biological activity, and attract the attention of chemists in recent years. The compounds can be used as candidate drugs for resisting cancers and malaria and high-efficiency inhibitors of protein kinase DYRKIA, can also be used as DNA intercalators for inhibiting DNA replication and transcription, and have important application values in the fields of biology, medicine and the like. The synthesis methods of indoloquinoline compounds reported in the literature at present mainly include aza Wittig reaction of isocyanate (Tetrahedron,1990,46, 1063-1078), gold-catalyzed cyclization reaction of acyclic alkyne (org.biomol.chem.,2012,10, 7801-7808), copper-catalyzed one-pot tandem reaction of 2- (2-bromoaryl) -1H-indole with aldehyde and ammonia (J.org.chem.,2015,80, 10955-50064), palladium-catalyzed Suzuk coupling reaction of o-dihalosubstituted quinoline (Eur.J.org.chem.,2017, 5554-5565), rhodium-catalyzed dimerization reaction of 2-alkynylaniline (org.Lett.,2019,21, 4996-5001), and palladium-catalyzed insertion reaction of isonitrile (org.Lett.2013,15, 3754-3757) and manganese-catalyzed cyclization reaction of isonitrile (Cav-1414-prepared by Adv. 1414-catalyzed cyclization reaction of aldehyde and ammonia. Although the methods for synthesizing the indoloquinoline compounds are various, the methods in the documents have different degrees of defects, such as the use of expensive metal catalysts, harsh reaction conditions, single applicability of substrates, poor reaction repeatability and the like, and are not suitable for production practice. In recent years, electrochemical organic synthesis takes clean electrons as redox reagents to participate in chemical reactions, realizes low pollution and even zero pollution of the chemical reactions, and has gradually remarkable advantages in the field of green chemistry.
Disclosure of Invention
Based on the above background art, the present invention aims to provide a method for synthesizing an indoloquinoline compound under electrochemical conditions. The method for preparing the indoloquinoline compound by using an electrochemical organic synthesis means has the advantages of simple operation, mild reaction conditions, low cost and little pollution, and is undoubtedly a preferred method for synthesizing the indoloquinoline compound.
In order to achieve the technical aim, the invention adopts the following technical scheme.
A method for synthesizing an indoloquinoline compound under electrochemical conditions comprises the following steps:
(1) dissolving different substituted phenylhydrazines and different acetophenones in ethanol, heating to react for 2-6h, heating and stirring the reaction solution for 5-10h, pouring the reaction solution into ice water after the reaction is finished, neutralizing the reaction solution with a potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and spin-drying to obtain 2-phenylindole containing different substituents;
(2) under the ice bath condition, dropwise adding phosphorus oxychloride into a three-neck flask filled with N, N-dimethylacetamide, continuing to react for 1-2 hours under the ice bath condition after dropwise adding is finished, dissolving 2-phenylindole containing different substituents into N, N-dimethylacetamide, dropwise adding the solution into the reaction solution, heating to react for 2-5 hours after dropwise adding is finished, pouring the solution into ice water after the reaction is finished, neutralizing the solution with potassium hydroxide until the pH value is 8, extracting ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and purifying the organic phase through a column after the solvent is dried in a spinning mode to obtain 2-phenyl 3-acetylindole containing different substituents;
(3) dissolving 2-phenyl 3-acetyl indole containing different substituents in dichloromethane, adding sodium hydroxide and n-tetrabutylammonium bromide under an ice bath condition, then adding p-toluenesulfonyl chloride, and then heating to room temperature to react for 10-20 h; or 2-phenyl 3-acetyl indole containing different substituents is dissolved in tetrahydrofuran, adding sodium hydride under the ice bath condition, reacting for 30 min-1.5 h under the ice bath condition, adding methyl iodide or benzyl bromide or di-tert-butyl dicarbonate, heating to room temperature to react for 10-20h, adding ice water to quench the reaction after the reaction is finished, performing suction filtration, extracting dichloromethane or ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, spin-drying the solvent, and performing column chromatography purification to obtain N-p-toluenesulfonyl-2-phenyl 3-acetylindole, N-methyl-2-phenyl 3-acetylindole, N-benzyl-2-phenyl 3-acetylindole or N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents;
(4) dissolving N-p-toluenesulfonyl-2-phenyl 3-acetylindole or N-methyl-2-phenyl 3-acetylindole or N-benzyl-2-phenyl 3-acetylindole or N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents in ethanol, adding 2- (aminooxy) -2-methylpropanoic acid hydrochloride and sodium acetate, heating the reaction solution to 60-80 ℃ for 4-8 h, reacting, cooling to room temperature, extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, spin-drying the solvent, and purifying with column to obtain 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) propionic acid with different substituted reaction substrates;
(5) adding reaction substrates of differently substituted 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) propionic acid, a catalyst and an electrolyte into a reaction bottle with a magnetic stirrer;
(6) adding a solvent, stirring uniformly, inserting an electrode, stirring at room temperature, and electrifying for reaction for 5-9 hours, wherein the current intensity is 2-5 mA;
(7) and after the reaction is finished, extracting, separating and purifying to obtain the indoloquinoline compound.
Further, the step (1) is specifically as follows: dissolving different substituted phenylhydrazines and different acetophenones in ethanol, heating to 80 ℃ for reaction for 2-6h, heating the reaction solution to 120 ℃, stirring for 5-10h, pouring into ice water after the reaction is finished, neutralizing with 2mol/L potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and spin-drying to obtain 2-phenylindole containing different substituents;
further, the step (2) is specifically as follows: under the ice bath condition, dropwise adding phosphorus oxychloride into a three-neck flask containing N, N-dimethylacetamide, continuing to react for 1-2h under the ice bath condition after dropwise adding, dissolving 2-phenylindole containing different substituents into N, N-dimethylacetamide, dropwise adding into the reaction solution, heating to 80 ℃ after dropwise adding, reacting for 2-5h, pouring into ice water after reaction, neutralizing with 2mol/L potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and purifying through a column after spin drying the solvent to obtain the 2-phenyl 3-acetylindole containing different substituents.
Further, the preparation method of the indoloquinoline compound comprises the following steps (6): adding solvent, adding alkali, stirring, inserting electrode, stirring at room temperature, and electrifying for reaction for 5-9 hr with current intensity of 2-5 mA. The rest steps are unchanged, and the indoloquinoline compound can also be prepared.
Further, the alkali is one of cesium carbonate, sodium carbonate, potassium carbonate and sodium acetate, and the molar ratio of the alkali to a reaction substrate is 0.5-1: 1; the base is preferably cesium carbonate, the molar ratio of cesium carbonate to reaction substrate being 0.5: 1;
further, the catalyst is one of n-tetrabutylammonium bromide, sodium bromide, potassium bromide, sodium iodide or potassium iodide, and the molar ratio of the catalyst to a reaction substrate is 0.5-1: 1; the catalyst is preferably n-tetrabutylammonium bromide, and the molar ratio of the n-tetrabutylammonium bromide to the reaction substrate is 0.7: 1;
further, the electrolyte is n-tetrabutylammonium tetrafluoroborate or n-tetrabutylammonium bromide, and the volume ratio of the electrolyte to the solvent is 1:10-1: 5; the electrolyte is preferably n-tetrabutylammonium tetrafluoroborate, and the volume ratio of the substance of the n-tetrabutylammonium tetrafluoroborate to the solvent is 1: 5;
further, the solvent is one of hexafluoroisopropanol/trifluoroethanol mixed solvent, hexafluoroisopropanol/methanol mixed solvent, hexafluoroisopropanol/acetonitrile mixed solvent, hexafluoroisopropanol and trifluoroethanol;
further, the volume ratio of the hexafluoroisopropanol/trifluoroethanol mixed solvent in the solvent is 1:1-4:1, the volume ratio of the hexafluoroisopropanol/methanol mixed solvent in the solvent is 1:1-4:1, and the volume ratio of the hexafluoroisopropanol/acetonitrile mixed solvent in the solvent is 4: 1.
Further, the electrode is: the anode is one of RVC (100PPI,1.0cm x 1.0cm x 0.5cm), platinum sheet (1cm x 1.5cm) or carbon rod (d is 5mm), preferably the anode is RVC (100PPI,1.0cm x 1.0cm x 0.5cm) electrode, the cathode is platinum sheet with the thickness of 10mm x 15mm x 0.1mm, and the distance between the cathode and the anode is 1 cm;
further, the current intensity of the electrifying reaction is 2-5mA, and the time of the electrifying reaction is 5-9 h.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention promotes the reaction by cleaning reagent-electrons through an electrochemical means, avoids the use of metal catalysts and stoichiometric traditional oxidants, thereby reducing the cost, avoiding the discharge of various wastes and reducing the environmental pollution;
(2) according to the method for synthesizing the indoloquinoline compound, the byproducts are carbon dioxide and acetone, so that the method is small in environmental pollution and meets the requirement of green chemistry;
(3) the method for synthesizing the indoloquinoline compound has mild required conditions, does not need high temperature, is simple and easy to implement, and has low cost, and the whole operation process only needs to be carried out by electrifying direct current on the traditional stirring reaction device.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto. It is specifically noted that the different substituted phenylhydrazines and different acetophenones described in general example I are in the following specific examples according to the specific actual conditions of the compounds to be synthesized in each example.
General example I
(1) Synthesis of 2-phenylindoles containing different substituents: dissolving different substituted phenylhydrazine (50mmol) and different aromatic ethanones (50mmol) in ethanol (100mL), adding 1mL of acetic acid, heating to 80 ℃, reacting for 2-6h, cooling to room temperature after the reaction is finished, adding polyphosphoric acid (120mL) for dissolving after the solvent is dried in a spinning mode, heating the reaction solution to 120 ℃, stirring for 5-10h, pouring into ice water after the reaction is finished, neutralizing with 2mol/L potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and drying in a spinning mode to obtain the 2-phenylindole containing different substituents.
(2) Synthesizing 2-phenyl 3-acetyl indole containing different substituents: under the ice bath condition, dropwise adding phosphorus oxychloride (155mmol) into a three-neck flask filled with N, N-dimethylacetamide (311mmol), and continuing to react for 1-2h under the ice bath condition after dropwise adding; dissolving 2-phenyl indole (31mmol) containing different substituents in N, N-dimethylacetamide (30mL), dropwise adding into the reaction solution, heating to 80 ℃ after dropwise adding, reacting for 2-5h, pouring into ice water after the reaction is finished, neutralizing with 2mol/L potassium hydroxide solution until the pH is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and performing column purification after the solvent is dried to obtain the 2-phenyl 3-acetyl indole containing different substituents.
(3) Synthesizing N-p-toluenesulfonyl-2-phenyl 3-acetylindole or N-methyl-2-phenyl 3-acetylindole or N-benzyl-2-phenyl 3-acetylindole or N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents: dissolving 2-phenyl 3-acetyl indole (11mmol) containing different substituents in dichloromethane (30mL), adding sodium hydroxide (44mmol) and n-tetrabutylammonium bromide (1.1mmol) under the ice bath condition, and then adding p-toluenesulfonyl chloride (33 mmol); and then heating to room temperature for reaction for 10-20h, adding ice water to quench the reaction after the reaction is finished, performing suction filtration, extracting by ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, spin-drying the solvent, and performing column chromatography purification to obtain the N-p-toluenesulfonyl-2-phenyl 3-acetylindole, the N-methyl-2-phenyl 3-acetylindole, the N-benzyl-2-phenyl 3-acetylindole or the N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents.
(4) Synthesizing a reaction substrate: dissolving N-p-toluenesulfonyl-2-phenyl 3-acetyl indole or N-methyl-2-phenyl 3-acetyl indole or N-benzyl-2-phenyl 3-acetyl indole or N-tert-butoxycarbonyl-2-phenyl 3-acetyl indole (2.5mmol) containing different substituents in ethanol (10mL), adding 2- (aminooxy) -2-methylpropanoic acid hydrochloride (3mmol) and sodium acetate (6mmol), heating to 80 ℃ for 4H, cooling to room temperature after the reaction is finished, extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, spin-drying the solvent, and purifying by a column to obtain 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) which is different in reaction substrate ) Propionic acid.
Synthesizing a product indoloquinoline compound: 0.25mmol of 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) propionic acid differently substituted as a reaction substrate, 0.175mmol of n-tetrabutylammonium bromide and 0.2mmol/mL of n-tetrabutylammonium tetrafluoroborate (1mmol) were weighed out separately and added to a reaction flask equipped with a magnetic stirrer, 4mL of hexafluoroisopropanol and 1mL of trifluoroethanol were added followed by 0.125mmol of cesium carbonate and inserted into an anode RVC (100PPI,1.0 cm. times.1.0 cm. times.0.5 cm) and a platinum sheet cathode 10 mm. times.15 mm. times.0.1 mm, the distance between the cathode and the anode was 1.0cm, and the reaction mixture was stirred and energized (current intensity 3mA) at room temperature for 6.5H. After the reaction, 10mL of water was added to the reaction solution, the reaction solvent was removed by a rotary evaporator, ethyl acetate was added for extraction (3 × 10mL), the organic layer was dried over anhydrous sodium sulfate, filtered under suction, dried by spinning, and subjected to column chromatography separation using an eluent of petroleum ether and ethyl acetate of 10:1 to 3:1 in polarity to obtain the target compound I. The corresponding yields were calculated and compound I was characterized by Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectrometry (HRMS).
Example 1
Synthesis of the compound 6-methyl-11 tosyl-11H-indolo [3,2-c ] quinoline.
The procedure and conditions were as in general example I to give the product indoloquinolines (I)1) The yield was calculated and characterized as in general example I.
Figure BDA0003368281280000051
Yellow solid, yield 82%; the melting point is 141-142 ℃; 1H NMR(400MHz,CDCl3)δ8.98(d,J＝8.5Hz,1H),8.40(d,J＝8.2Hz,1H),8.13(d,J＝8.4Hz,1H),7.91(d,J＝7.8Hz,1H),7.75–7.71(m,1H),7.64–7.61(m,1H),7.52–7.48(m,1H),7.44–7.40(m Hz,1H),6.96(d,J＝8.2Hz,2H),6.80(d,J＝8.1Hz,2H),3.01(s,3H),2.15(s,3H)； 13C NMR(101MHz,CDCl3)δ153.7,147.5,145.0,142.8,141.2,132.5,129.2,129.1,128.8,127.7,127.0,126.8,126.8,125.9,125.7,121.8,121.5,119.6,119.2,25.0,21.5；HRMS(m/z)calcd.for C23H19N2O2S[M+H]+:387.1162；found:387.1170.
example 2
In the same way as in example 1, except that no product synthesis was carried outBase, product I obtained1The yield of (a) was 45%.
Example 3
As in example 1, with the difference that sodium acetate was used instead of cesium carbonate during the synthesis of the product, in an amount of 0.125mmol, the product I obtained1The yield of (a) was 58%.
Example 4
In the same way as in example 1, except that the amount of cesium carbonate used in the synthesis of the product was 0.25mmol, the product I obtained1The yield of (a) was 72%.
Example 5
In the same way as in example 1, except that sodium carbonate was used in place of cesium carbonate in the course of synthesizing the product in an amount of 0.125mmol, product I was obtained1The yield of (a) was 69%.
Example 6
As in example 1, except that potassium carbonate was used in place of cesium carbonate in the synthesis of the product in an amount of 0.125mmol, product I was obtained1The yield of (a) was 64%.
Example 7
The same as example 1, except that sodium bromide was used in place of n-tetrabutylammonium bromide in the synthesis of the product, the product I was obtained1The yield of (a) was 54%.
Example 8
In the same way as in example 1, except that potassium bromide was used in place of n-tetrabutylammonium bromide in the synthesis of the product, the product I was obtained1The yield of (a) was 59%.
Example 9
The same as example 1, except that sodium iodide was used in the synthesis of the product instead of n-tetrabutylammonium bromide, the product I was obtained1The yield of (a) was 41%.
Example 10
In the same way as in example 1, except that potassium iodide was used in place of n-tetrabutylammonium bromide in the synthesis of the product, product I was obtained1The yield of (a) was 47%.
Example 11
As in example 1, except that 0.125mmol of n-tetrabutylammonium bromide was used instead of 0.175mmol of n-tetrabutylammonium bromide in the synthesis of the product, product I was obtained1The yield of (a) was 61%.
Example 12
As in example 1, except that 0.25mmol of n-tetrabutylammonium bromide was used instead of 0.175mmol of n-tetrabutylammonium bromide in the synthesis of the product, product I was obtained1The yield of (a) was 74%.
Example 13
As in example 1, except that 0.2mmol/mL of n-tetrabutylammonium bromide (1mmol) was used in place of 0.175mmol of n-tetrabutylammonium bromide and 0.2mmol/mL of n-tetrabutylammonium tetrafluoroborate (1mmol) in the synthesis of the product, the product I was obtained1The yield of (b) was 63%.
Example 14
Similar to example 1, except that a platinum sheet (1 cm. times.1.5 cm) was used as an anode instead of RVC in the synthesis of the product, the product I was obtained1The yield of (a) was 18%.
Example 15
The product I obtained in the same way as in example 1, except that the RVC was replaced by a carbon rod (d ═ 5mm) as the anode during the synthesis of the product1The yield of (a) was 25%.
Example 16
The same as example 1, except that 3mA was replaced by 2mA current during the synthesis of the product, the reaction time was 9h, and the product I was obtained1The yield of (a) was 69%.
Example 17
The same as example 1, except that 3mA was replaced by 5mA current during the synthesis of the product, the reaction time was 5h, and the product I was obtained1The yield of (a) was 51%.
Example 18
Similar to example 1, except that the product synthesis procedure used 4mL hexafluoroisopropanol, 1mL methanol instead of 4mL hexafluoroisopropanol, 1mL trifluoroethanol, the product I was obtained1The yield of (a) was 64%.
Example 19
Similar to example 1, except that the product synthesis procedure used 4mL hexafluoroisopropanol, 1mL acetonitrile instead of 4mL hexafluoroisopropanol, 1mL trifluoroethanol, product I was obtained1The yield of (a) was 39%.
Example 20
The same as example 1, except that hexafluoroisopropanol (5mL) was used instead of 4mL hexafluoroisopropanol, 1mL trifluoroethanol,the product I obtained1The yield of (a) was 58%.
Example 21
Similar to example 1, except that the product synthesis procedure used trifluoroethanol (5mL) instead of 4mL hexafluoroisopropanol, 1mL trifluoroethanol, the product I was obtained1The yield of (a) was 36%.
Example 22
In the same way as in example 1, except that no catalyst was added during the synthesis of the product, the product I obtained1The yield of (a) was 41%.
Example 23
The procedure and conditions were as in general example I to give the product indoloquinolines (I)2)：
Figure BDA0003368281280000081
Yellow solid, yield 90%; melting point 195-196 deg.C; 1H NMR(400MHz,CDCl3)δ8.84(d,J＝8.7Hz,1H),8.36(d,J＝8.2Hz,1H),7.90(s,1H),7.85(d,J＝7.8Hz,1H),7.47–7.43(m,2H),7.39–7.36(m,1H),6.95(d,J＝8.2Hz,2H),6.78(d,J＝8.1Hz,2H),2.96(s,3H),2.58(s,3H),2.12(s,3H)； 13C NMR(101MHz,CDCl3)δ153.5,147.7,144.8,142.7,140.9,139.4,132.5,128.9,127.9,127.7,126.6,126.6,126.4,125.7,121.6,120.7,118.9,117.3,24.9,21.7,21.4；HRMS(m/z)calcd.for C24H21N2O2S[M+H]+:401.1318；found:401.1325.
example 24
The procedure and conditions were as in general example I to give the product indoloquinolines (I)3)：
Figure BDA0003368281280000082
Yellow solid, yield 64%; melting point is 209-210 ℃; 1H NMR(500MHz,CDCl3)δ8.89(d,J＝9.4Hz,1H),8.39(d,J＝8.3Hz,1H),7.89(d,J＝7.7Hz,1H),7.49–7.47(m,2H),7.43–7.40(m,1H),7.29(dd,J＝9.4,2.7Hz,1H),6.97(d,J＝8.4Hz,2H),6.82(d,J＝8.2Hz,2H),3.99(s,3H),2.99(s,3H),2.17(s,3H)； 13C NMR(126MHz,CDCl3)δ160.5,154.1,149.6,144.9,143.3,141.0,132.6,129.1,128.1,128.0,126.9,126.6,125.9,121.6,119.9,119.2,118.3,114.3,107.5,55.7,25.0,21.6；HRMS(m/z)calcd.for C24H21N2O3S[M+H]+:417.1267；found:417.1282.
example 25
The procedure and conditions were as in general example I to give the product indoloquinolines (I)4)：
Figure BDA0003368281280000091
Colorless oil, yield 65%; 1H NMR(500MHz,CDCl3)δ8.89(d,J＝9.0Hz,1H),8.39(d,J＝8.3Hz,1H),8.11(s,1H),7.90(d,J＝7.8Hz,1H),7.72(d,J＝7.1Hz,1H),7.50–7.47(m,1H),7.42–7.39(m,1H),7.01(d,J＝8.4Hz,2H),6.83(d,J＝8.2Hz,2H),3.01(s,3H),2.16(s,3H),1.47(s,9H)； 13C NMR(126MHz,CDCl3)δ153.5,152.5,147.8,144.9,142.8,141.0,132.7,129.1,127.8,126.8,126.8,126.4,125.8,124.6,124.3,121.7,120.9,119.0,117.4,35.2,31.3,25.0,21.6；HRMS(m/z)calcd.for C27H27N2O2S[M+H]+:443.1788；found:443.1797.
example 26
The procedure and conditions were as in general example I to give the product indoloquinolines (I)5)：
Figure BDA0003368281280000092
White solid, yield 76%; melting point 169-171 deg.C; 1H NMR(500MHz,CDCl3)δ9.04(d,J＝9.4Hz,1H),8.42(d,J＝8.4Hz,1H),7.98(s,1H),7.94(d,J＝7.8Hz,1H),7.56–7.52(m,1H),7.50–7.44(m,2H),6.98(d,J＝8.3Hz,2H),6.85(d,J＝8.2Hz,2H),3.03(s,3H),2.18(s,3H)；19F NMR(471MHz,CDCl3)δ-57.5； 13C NMR(101MHz,CDCl3)δ155.2,149.3(q,J＝2.0Hz),148.0,145.1,142.5,141.1,132.4,129.1,128.8,127.3,127.2,126.7,126.0,120.6(q,J＝259.2Hz),121.8,121.6,119.2,119.0,118.6,117.8,25.0,21.5；HRMS(m/z)calcd.for C24H18F3N2O3S[M+H]+:471.0985；found:471.0995.
example 27
The procedure and conditions were as in general example I to give the product indoloquinolines (I)6)：
Figure BDA0003368281280000101
Colorless oil, 43% yield; 1H NMR(400MHz,CDCl3)δ9.11(d,J＝9.0Hz,1H),8.44(d,J＝7.6Hz,2H),7.97(d,J＝7.8Hz,1H),7.80(d,J＝8.9Hz,1H),7.59–7.55(m,1H),7.49–7.46(m,1H),6.99(d,J＝8.1Hz,2H),6.85(d,J＝8.0Hz,2H),3.05(s,3H),2.18(s,3H)；19F NMR(471MHz,CDCl3)δ-62.6； 13C NMR(101MHz,CDCl3)δ155.4,146.5,145.4,142.2,141.4,132.5,130.8,130.5,129.3,128.1,127.8,127.2,126.8,126.7(q,JC-F＝4.0Hz),126.2,124.2(q,JC-F＝272.7Hz),122.9,122.2,121.3(q,JC-F＝6.1Hz),119.1,25.1,21.6；HRMS(m/z)calcd.for C24H18F3N2O2S[M+H]+:455.1036；found:455.1054.
example 28
The procedure and conditions were as in general example I to give the product indoloquinolines (I)7)：
Figure BDA0003368281280000102
Yellow solid, yield 62%; melting Point:224-225℃； 1H NMR(500MHz,CDCl3)δ9.09(d,J＝8.8Hz,1H),8.48(s,1H),8.44(d,J＝8.4Hz,1H),7.99(d,J＝7.9Hz,1H),7.77(d,J＝7.4Hz,1H),7.61–7.58(m,1H),7.51–7.48(m,1H),6.98(d,J＝8.4Hz,2H),6.86(d,J＝8.3Hz,2H),3.06(s,3H),2.19(s,3H)； 13C NMR(126MHz,CDCl3)δ156.0,146.2,145.5,141.9,141.6,134.6,132.4,129.3,128.4,128.1,126.9,126.8,126.4,126.3,123.4,122.3,121.9,119.1,118.8,112.2,25.2,21.6；HRMS(m/z)calcd.for C24H18N3O2S[M+H]+:412.1114；found:412.1117.
Example 29
The procedure and conditions were as in general example I to give indoloquinolines (I)8)：
Figure BDA0003368281280000111
Colorless oil, yield 70%; 1H NMR(400MHz,CDCl3)δ9.00–8.96(m,1H),8.38(d,J＝8.2Hz,1H),7.89(d,J＝7.8Hz,1H),7.74(dd,J＝10.1,2.5Hz,1H),7.52–7.48(m,1H),7.44–7.37(m,2H),6.94(d,J＝8.2Hz,2H),6.81(d,J＝8.1Hz,2H),2.98(s,3H),2.16(s,3H)；19F NMR(471MHz,CDCl3)δ-110.4； 13C NMR(101MHz,CDCl3)δ162.8(d,JC-F＝251.5Hz),155.1,148.8(d,JC-F＝12.1Hz),145.2,142.9,141.0,132.4,129.2,129.1,127.6,127.1,126.8,126.0,121.8,121.0(d,JC-F＝2.0Hz),119.1,116.5,115.8(d,JC-F＝24.2Hz),112.7(d,JC-F＝20.2Hz),25.0,21.6；HRMS(m/z)calcd.for C23H18FN2O2S[M+H]+:405.1068；found:405.1083.
example 30
The procedure and conditions were as in general example I to give the product indoloquinolines (I)9)：
Figure BDA0003368281280000112
Colorless oil, yield 63%; 1H NMR(400MHz,CDCl3)δ8.93(d,J＝9.2Hz,1H),8.40(d,J＝8.2Hz,1H),8.12(s,1H),7.92(d,J＝7.8Hz,1H),7.58–7.51(m,2H),7.46–7.42(m,1H),6.96(d,J＝8.2Hz,2H),6.83(d,J＝8.1Hz,2H),3.00(s,3H),2.17(s,3H)； 13C NMR(101MHz,CDCl3)δ155.0,148.0,145.2,142.6,141.2,135.1,132.5,129.2,128.2,127.9,127.4,127.3,126.8,126.6,126.1,121.9,121.6,119.1,118.0,25.1,21.6；HRMS(m/z)calcd.for C23H18ClN2O2S[M+H]+:421.0772；found:421.0782.
example 31
The procedure and conditions were as in general example I to give the product indoloquinolines (I)10)：
Figure BDA0003368281280000121
Colorless oil, yield 54%; 1H NMR(400MHz,CDCl3)δ8.85(d,J＝9.1Hz,1H),8.40(d,J＝8.3Hz,1H),8.30(s,1H),7.92(d,J＝7.8Hz,1H),7.70(d,J＝9.1Hz,1H),7.55–7.51(m,1H),7.46–7.42(m,1H),6.96(d,J＝8.0Hz,2H),6.83(d,J＝8.0Hz,2H),3.00(s,3H),2.17(s,3H)； 13C NMR(101MHz,CDCl3)δ155.0,148.1,145.2,142.6,141.2,132.4,131.2,129.2,129.1,128.2,127.4,127.3,126.8,126.1,123.4,121.9,121.7,119.1,118.2,25.1,21.6；HRMS(m/z)calcd.for C23H18BrN2O2S[M+H]+:465.0267；found:465.0276.
example 32
The procedure and conditions were as in general example I to give the product indoloquinolines (I)11)：
Figure BDA0003368281280000122
Yellow solid, yield 53%; the melting point is 188-190 ℃; 1H NMR(500MHz,CDCl3)δ8.27(d,J＝8.2Hz,1H),8.00(d,J＝8.3Hz,1H),7.74(d,J＝7.8Hz,1H),7.69–7.66(m,1H),7.48–7.45(m,2H),7.38–7.35(m,1H),6.69(d,J＝8.2Hz,2H),6.50(d,J＝8.3Hz,2H),3.16(s,3H),2.91(s,3H),2.14(s,3H)； 13C NMR(126MHz,CDCl3)δ152.7,148.5,144.7,144.0,141.8,136.7,130.2,129.2,129.2,128.6,128.3,127.2,126.9,126.5,126.0,123.6,121.9,121.0,120.0,24.4,22.5,21.5；HRMS(m/z)calcd.for C24H21N2O2S[M+H]+:401.1318；found:401.1327.
example 33
The procedure and conditions were as in general example I to give indoloquinolines (I)12)：
Figure BDA0003368281280000131
Yellow solid, yield 37%; melting point 225-; 1H NMR(500MHz,CDCl3)δ8.28(d,J＝8.2Hz,1H),8.13(d,J＝8.4Hz,1H),7.91(d,J＝7.4Hz,1H),7.79(d,J＝7.8Hz,1H),7.61–7.58(m,1H),7.50–7.47(m,1H),7.38–7.45(m,1H),6.73(d,J＝8.2Hz,2H),6.59(d,J＝8.2Hz,2H),2.99(s,3H),2.15(s,3H)； 13C NMR(126MHz,CDCl3)δ154.0,148.5,144.8,142.7,141.9,132.1,131.2,129.4,128.5,128.1,128.1,127.4,127.0,126.3,124.3,122.1,121.1,119.8,119.5,24.5,21.6；HRMS(m/z)calcd.for C23H18BrN2O2S
example 34
The procedure and conditions were as in general example I to give the product indoloquinolines (I)13) And indoloquinolines (I)13’)，(I13:I13’1:1.1, 69% yield);
Figure BDA0003368281280000132
white solid, melting point 208-; 1H NMR(500MHz,CDCl3)δ8.56(d,J＝8.7Hz,1H),8.42(d,J＝8.3Hz,1H),7.93(d,J＝7.8Hz,1H),7.58–7.55(m,1H),7.54–7.51(m,1H),7.46–7.43(m,1H),7.14(d,J＝7.6Hz,1H),6.89(d,J＝8.4Hz,2H),6.77(d,J＝8.2Hz,2H),4.14(s,3H),3.06(s,3H),2.15(s,3H)； 13C NMR(126MHz,CDCl3)δ154.6,152.6,144.8,143.1,141.5,138.9,132.1,128.8,127.9,127.0,126.7,125.9,125.6,122.3,121.9,120.6,119.5,118.8,107.6,56.2,25.3,21.4；HRMS(m/z)calcd.for C24H21N2O3S[M+H]+:417.1267；found:417.1271.
Figure BDA0003368281280000141
a colorless oil; 1H NMR(500MHz,CDCl3)δ8.43(d,J＝8.3Hz,1H),8.39(d,J＝2.8Hz,1H),8.03(d,J＝9.1Hz,1H),7.92(d,J＝7.8Hz,1H),7.54–7.51(m,1H),7.46–7.43(m,1H),7.39(dd,J＝9.2,2.8Hz,1H),6.96(d,J＝8.4Hz,2H),6.81(d,J＝8.3Hz,2H),4.05(s,3H),2.98(s,3H),2.17(s,3H)； 13C NMR(126MHz,CDCl3)δ157.2,150.8,144.9,143.4,142.2,141.3,132.3,130.1,128.9,128.0,126.9,126.7,125.9,121.9,121.8,121.5,120.4,119.3,105.2,55.8,24.6,21.5；HRMS(m/z)calcd.for C24H21N2O3S[M+H]+:417.1267；found:417.1281.
example 35
The procedure and conditions were as in general example I to give the product indoloquinolines (I)14)：
Figure BDA0003368281280000142
White solid, yield 72%; melting point 199-; 1H NMR(500MHz,CDCl3)δ8.98(d,J＝8.5Hz,1H),8.27(d,J＝8.5Hz,1H),8.12(d,J＝8.4Hz,1H),7.74–7.71(m,1H),7.69(s,1H),7.64–7.60(m,1H),7.31(d,J＝8.5Hz,1H),6.95(d,J＝8.4Hz,2H),6.80(d,J＝8.3Hz,2H),3.00(s,3H),2.49(s,3H),2.15(s,3H)； 13C NMR(126MHz,CDCl3)δ153.8,147.4,144.8,143.0,139.2,135.7,132.5,129.1,129.0,128.8,128.2,127.9,126.8,125.7,122.1,121.5,119.7,118.8,25.1,21.8,21.6；HRMS(m/z)calcd.for C24H21N2O2S[M+H]+:401.1318；found:401.1330.
example 36
The procedure and conditions were as in general example I to give the product, indoloquinoline (I)15)：
Figure BDA0003368281280000143
Yellow solid, yield 65%; the melting point is 190 ℃ and 192 ℃; 1H NMR(400MHz,CDCl3)δ9.41(d,J＝8.2Hz,1H),8.86(d,J＝9.2Hz,1H),8.41(d,J＝8.2Hz,1H),7.96–7.89(m,3H),7.76–7.69(m,2H),7.54–7.51(m,1H),7.46–7.42(m,1H),6.91(d,J＝8.2Hz,2H),6.77(d,J＝8.1Hz,2H),3.09(s,3H),2.14(s,3H)； 13C NMR(101MHz,CDCl3)δ152.0,145.3,144.9,143.6,141.6,133.4,132.2,131.3,129.1,129.1,129.0,128.2,127.8,127.1,126.9,126.2,126.1,125.2,124.0,122.5,122.0,119.5,117.3,25.0,21.6；HRMS(m/z)calcd.for C27H21N2O2S[M+H]+:437.1318；found:437.1322.
example 37
The procedure and conditions were as in general example I to give the product indoloquinolines (I)16)：
Figure BDA0003368281280000151
Yellow oil, yield 65%; 1H NMR(500MHz,CDCl3)δ8.51(d,J＝8.4Hz,1H),8.11(d,J＝7.9Hz,1H),7.80(d,J＝5.7Hz,1H),7.68–7.65(m,3H),7.57–7.54(m,1H),7.50–7.47(m,1H),7.07(d,J＝8.2Hz,2H),3.08(s,3H),2.25(s,3H)； 13C NMR(126MHz,CDCl3)δ155.7,151.5,145.5,139.8,138.2,134.7,131.2,130.0,127.1,127.1,125.9,125.5,125.0,122.2,117.9,117.0,116.0,24.9,21.7；HRMS(m/z)calcd.for C21H17N2O2S2[M+H]+:393.0726；found:393.0735.
example 38
The procedure and conditions were as in general example I to give the product indoloquinolines (I)17)：
Figure BDA0003368281280000152
Pale yellow solid, yield 34%; melting point 241-243 deg.C; 1H NMR(500MHz,CDCl3)δ8.58(d,J＝8.5Hz,1H),8.28(d,J＝7.7Hz,1H),8.15(d,J＝7.9Hz,1H),7.95(d,J＝8.4Hz,2H),7.79(d,J＝8.3Hz,1H),7.62-7.58(m,2H),7.51-7.44(m,2H),7.14(d,J＝8.2Hz,2H),3.13(s,3H),2.26(s,3H)； 13C NMR(126MHz,CDCl3)δ157.0,149.7,145.5,141.8,138.8,135.6,135.5,130.0,128.7,128.1,127.6,127.4,125.5,124.7,123.8,123.8,122.4,121.0,119.8,115.3,112.4,24.7,21.7；HRMS(m/z)calcd.for C25H19N2O3S[M+H]+:427.1111；found:427.1121.
example 39
The procedure and conditions were as in general example I to give the product indoloquinolines (I)18)：
Figure BDA0003368281280000161
White solid, yield 56%; melting point is 220 ℃ and 221 ℃; 1H NMR(500MHz,CDCl3)δ8.74(d,J＝2.8Hz,1H),8.72(d,J＝8.6Hz,1H),8.35(d,J＝8.5Hz,1H),8.26(d,J＝7.9Hz,1H),8.16(d,J＝8.3Hz,2H),7.68–7.65(m,1H),7.58–7.53(m,2H),7.30(d,J＝8.2Hz,2H),3.21(s,3H),2.40(s,3H)； 13C NMR(126MHz,CDCl3)δ155.5,147.4,144.5,141.9,141.0,139.8,138.6,136.4,133.7,129.2,128.0,127.7,124.5,124.4,123.5,122.1,120.6,116.8,25.5,21.8；HRMS(m/z)calcd.for C22H18N3O2S[M+H]+:388.1114；found:388.1129.
example 40
The procedure and conditions were as in general example I to give the product indoloquinolines (I)19)：
Figure BDA0003368281280000162
White solid, yield 48%; melting point 192 ℃ minus 193 ℃; 1H NMR(500MHz,CDCl3)δ9.52(s,1H),8.86(d,J＝6.0Hz,1H),8.68(d,J＝6.0Hz,1H),8.49(d,J＝8.4Hz,1H),8.06(d,J＝7.9Hz,1H),7.63–7.60(m,1H),7.52–7.49(m,1H),7.10(d,J＝8.3Hz,2H),6.89(d,J＝8.2Hz,2H),3.10(s,3H),2.19(s,3H)； 13C NMR(126MHz,CDCl3)δ155.9,153.5,145.5,143.5,142.0,141.4,140.2,133.1,129.5,128.2,126.7,126.4,126.0,123.9,122.8,122.5,118.6,118.5,25.4,21.6；HRMS(m/z)calcd.for C22H18N3O2S[M+H]+:388.1114；found:388.1123.
EXAMPLE 41
The procedure is as in general example I, except that (3) the synthesis of N-tert-butoxycarbonyl-2-phenyl-3-acetylindole is carried out by replacing: dissolving 2-phenyl 3-acetyl indole (10mmol) in tetrahydrofuran (100mL), adding sodium hydride (12mmol) under the ice bath condition, reacting for 1h under ice bath, adding di-tert-butyl dicarbonate (20mmol), then heating to room temperature to react for 12h, after the reaction is finished, adding ice water to quench the reaction, filtering, extracting ethyl acetate, drying an organic phase with anhydrous sodium sulfate, spin-drying the solvent, and purifying by a column to obtain N-tert-butoxycarbonyl-2-phenyl 3-acetyl indole. Finally obtaining the product indoloquinoline compound (I)20)：
Figure BDA0003368281280000171
Yellow oil, yield 59%; 1H NMR(500MHz,CDCl3)δ8.30(d,J＝8.4Hz,1H),8.22(d,J＝8.4Hz,1H),8.17(d,J＝8.4Hz,2H),7.70–7.67(m,1H),7.55–7.52(m,2H),7.48–7.45(m,1H),3.18(s,3H),1.74(s,9H)； 13C NMR(126MHz,CDCl3)δ154.2,151.2,147.0,140.3,139.8,129.5,128.5,126.8,124.8,124.7,124.7,123.9,122.0,118.1,117.7,114.9,85.7,28.2,25.3；HRMS(m/z)calcd.for C21H21N2O2[M+H]+:333.1598；found:333.1603.
example 42
The implementation method is the same as example 31, except that benzyl bromide (20mmol) is used to replace di-tert-butyl dicarbonate in the process of (3) synthesizing N-benzyl-2-phenyl 3-acetyl indole, and the product (I) of the indoloquinoline compound is finally obtained21)：
Figure BDA0003368281280000172
Yellow oil, 43% yield; 1H NMR(500MHz,CDCl3)δ8.32(d,J＝7.9Hz,1H),8.23(d,J＝8.4Hz,1H),8.18(d,J＝8.4Hz,1H),7.66–7.63(m,1H),7.53(d,J＝3.9Hz,2H),7.48–7.45(m,1H),7.42–7.38(m,1H),7.34–7.28(m,3H),7.19(d,J＝7.2Hz,2H),6.00(s,2H),3.25(s,3H)； 13C NMR(126MHz,CDCl3)δ155.0,146.4,140.9,140.1,136.5,129.7,129.3,128.0,127.9,126.0,125.6,125.2,122.7,122.2,121.8,121.7,116.9,114.5,109.8,49.5,25.2；HRMS(m/z)calcd.for C23H19N2[M+H]+:323.1543；found:323.1554.
example 43
The implementation method is the same as that of the general example 31, except that methyl iodide (20mmol) is used to replace di-tert-butyl dicarbonate in the process of (3) synthesizing N-methyl-2-phenyl 3-acetyl indole, and finally the product indoloquinoline is obtainedCompounds of the class (I)22)：
Figure BDA0003368281280000181
Colorless oil, yield 41%; 1H NMR(400MHz,CDCl3)δ8.63(d,J＝8.3Hz,1H),8.28(d,J＝8.1Hz,1H),8.25(d,J＝8.4Hz,1H),7.74–7.70(m,1H),7.64–7.56(m,3H),7.46–7.42(m,1H),4.42(s,3H),3.22(s,3H)； 13C NMR(101MHz,CDCl3)δ154.7,146.3,140.2,139.7,129.6,127.6,124.9,124.6,122.1,121.8,121.7,120.9,117.2,113.7,109.1,33.2,24.9；HRMS(m/z)calcd.for C17H15N2[M+H]+:247.1230；found:247.1238.
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A method for synthesizing an indoloquinoline compound under electrochemical conditions is characterized by comprising the following steps:
(1) dissolving different substituted phenylhydrazines and different acetophenones in ethanol, heating to react for 2-6h, heating and stirring the reaction solution for 5-10h, pouring the reaction solution into ice water after the reaction is finished, neutralizing the reaction solution with a potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and spin-drying to obtain 2-phenylindole containing different substituents;
(2) under the ice bath condition, dropwise adding phosphorus oxychloride into a three-neck flask filled with N, N-dimethylacetamide, continuing to react for 1-2 hours under the ice bath condition after dropwise adding is finished, dissolving 2-phenylindole containing different substituents into N, N-dimethylacetamide, dropwise adding the solution into the reaction solution, heating to react for 2-5 hours after dropwise adding is finished, pouring the solution into ice water after the reaction is finished, neutralizing the solution with potassium hydroxide until the pH value is 8, extracting ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and purifying the organic phase through a column after the solvent is dried in a spinning mode to obtain 2-phenyl 3-acetylindole containing different substituents;
(3) dissolving 2-phenyl 3-acetyl indole containing different substituents in dichloromethane, adding sodium hydroxide and n-tetrabutylammonium bromide under an ice bath condition, then adding p-toluenesulfonyl chloride, and then heating to room temperature to react for 10-20 h; or 2-phenyl 3-acetyl indole containing different substituents is dissolved in tetrahydrofuran, adding sodium hydride under the ice bath condition, reacting for 30 min-1.5 h under the ice bath condition, adding methyl iodide or benzyl bromide or di-tert-butyl dicarbonate, heating to room temperature to react for 10-20h, adding ice water to quench the reaction after the reaction is finished, performing suction filtration, extracting dichloromethane or ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, spin-drying the solvent, and performing column chromatography purification to obtain N-p-toluenesulfonyl-2-phenyl 3-acetylindole, N-methyl-2-phenyl 3-acetylindole, N-benzyl-2-phenyl 3-acetylindole or N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents;
(4) dissolving N-p-toluenesulfonyl-2-phenyl 3-acetylindole or N-methyl-2-phenyl 3-acetylindole or N-benzyl-2-phenyl 3-acetylindole or N-tert-butoxycarbonyl-2-phenyl 3-acetylindole containing different substituents in ethanol, adding 2- (aminooxy) -2-methylpropanoic acid hydrochloride and sodium acetate, heating the reaction solution to 60-80 ℃ for 4-8 h, reacting, cooling to room temperature, extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, spin-drying the solvent, and purifying with column to obtain 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) propionic acid with different substituted reaction substrates;
(5) adding reaction substrates of differently substituted 2-methyl-2- (((1- (2-phenyl-1H-indol-3-yl) ethylidene) amino) oxy) propionic acid, a catalyst and an electrolyte into a reaction bottle with a magnetic stirrer;
(6) adding a solvent, stirring uniformly, inserting an electrode, stirring at room temperature, and electrifying for reaction for 5-9 hours, wherein the current intensity is 2-5 mA;
(7) and after the reaction is finished, extracting, separating and purifying to obtain the indoloquinoline compound.
2. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 1, wherein the step (1) is specifically: dissolving different substituted phenylhydrazines and different acetophenones in ethanol, heating to 80 ℃ for reaction for 2-6h, heating the reaction solution to 120 ℃, stirring for 5-10h, pouring into ice water after the reaction is finished, neutralizing with 2mol/L potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and spin-drying to obtain the 2-phenylindole containing different substituents.
3. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 1, wherein the step (2) is specifically as follows: under the ice bath condition, dropwise adding phosphorus oxychloride into a three-neck flask containing N, N-dimethylacetamide, continuing to react for 1-2h under the ice bath condition after dropwise adding, dissolving 2-phenylindole containing different substituents into N, N-dimethylacetamide, dropwise adding into the reaction solution, heating to 80 ℃ after dropwise adding, reacting for 2-5h, pouring into ice water after reaction, neutralizing with 2mol/L potassium hydroxide solution until the pH value is 8, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, and purifying through a column after spin drying the solvent to obtain the 2-phenyl 3-acetylindole containing different substituents.
4. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 1, wherein the electrode is: the anode is one of RVC electrode, platinum sheet or carbon rod, the cathode is a platinum sheet, and the distance between the cathode and the anode is 1.0 cm.
5. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 1, wherein the step (6) is: adding a solvent, adding alkali, uniformly stirring, inserting an electrode, stirring at room temperature, electrifying for reaction for 5-9h, wherein the current intensity is 2-5mA, and the rest steps are unchanged, so that the indoloquinoline compound can be obtained.
6. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 5, wherein the base is one of cesium carbonate, sodium carbonate, potassium carbonate and sodium acetate, and the molar ratio of the base to the reaction substrate is 0.5-1: 1.
7. The method for synthesizing indoloquinoline compounds under electrochemical conditions as claimed in claim 1, wherein the catalyst in step (5) is one of n-tetrabutylammonium bromide, potassium bromide, sodium iodide or potassium iodide; the molar ratio of the catalyst to the reaction substrate is 0.5-1: 1.
8. The method for synthesizing the indoloquinoline compound under the electrochemical condition according to claim 1, wherein the electrolyte in the step (5) is n-tetrabutylammonium tetrafluoroborate or n-tetrabutylammonium bromide, and the volume ratio of the electrolyte to the solvent is 1:10-1: 5.
9. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 1, wherein the solvent in step (6) is one of hexafluoroisopropanol/trifluoroethanol mixed solvent, hexafluoroisopropanol/methanol mixed solvent, hexafluoroisopropanol/acetonitrile mixed solvent, hexafluoroisopropanol, and trifluoroethanol.
10. The method for synthesizing the indoloquinoline compound under the electrochemical condition as claimed in claim 9, wherein the volume ratio of the hexafluoroisopropanol/trifluoroethanol mixed solvent is 1:1-4:1, the volume ratio of the hexafluoroisopropanol/methanol mixed solvent is 1:1-4:1, and the volume ratio of the hexafluoroisopropanol/acetonitrile mixed solvent is 4: 1.
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