CN110283179B - Method for directly constructing indole-fused ring compound - Google Patents
Method for directly constructing indole-fused ring compound Download PDFInfo
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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Abstract
The invention discloses a method for directly constructing an indole ring compound, which is characterized by taking a 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative as a substrate, reacting a catalyst copper salt and alkali with the 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative according to a molar ratio of 0.02-0.2: 2-4: 1 in a solvent at 90 ℃ for 8-20h, mixing petroleum ether/dichloromethane/ethyl acetate according to a volume ratio of 20-5: 2:1 to obtain an eluent, and separating by using a silica gel column to obtain a target product. The method has the advantages of simple operation, mild conditions and high yield, and is a green and novel synthesis method.
Description
Technical Field
The invention belongs to the technical field of methods for directly constructing an indole-fused ring compound, and particularly relates to a method for directly synthesizing an indole-fused ring compound by activating an aryl side chain C-H bond.
Background
Indole tetra-fused ring structural units are widely present in organic intermediates, pharmaceutical compounds and organisms, so that the reaction for directly constructing the indole fused ring compounds is widely applied to the fields of material chemistry and pharmaceutical chemistry. However, the methods for synthesizing the indolo ring compounds that exist at present basically require the use of a transition metal as a catalyst. The high cost of transition metal complex oxidants and metal residues limits their large-scale application in the industrial and pharmaceutical industries. In addition, most methods for synthesizing indole-fused ring compounds are to synthesize indole-fused ring compounds using indole and derivatives thereof as raw materials, for example (Chunyan Du, Jianming Chen, Yunlong Guo, Kun Lu, Shanghui Ye, Jiann Zheng, Yunqi Liu, Zhuigan Shuai, Gui Yu.J.org.Chem.2009,74,7322 and 7327), etc., it is necessary to construct a part of rings of the indole-fused ring compound and then synthesize the rest of rings.
British Green chemistry (Green chem.,2017,19, 4798-4803) describes a method for producing indole tetracyclic rings by activating C-H bonds using photocatalysis by dissolving 1.0 equivalent of diaryl azide in tetrahydrofuran and pumping the reaction mixture into a 16mL FEP-coiled reactor irradiated with a 254nm light source for 10 minutes to convert to the corresponding indole tetracyclic product. Although the method adopts photocatalysis and does not use transition metal catalysis, the requirement on reaction equipment is higher.
U.S. journal of organic chemistry (J.org.chem.2009,74, 7322-7327) discloses a method for the synthesis of indolyltetrafused rings by activation of the C-H bond using 1.0 equivalent of 4- (benzo [ b ] thiophen-2-yl) -3-nitrobenzaldehyde and 3.0 equivalents of triphenylphosphine in a solution of o-dichlorobenzene under heating and refluxing to give 8-formyl-6H-indolo [3,2-b ] benzo [ b ] thiophene. This approach requires the construction of a portion of the rings of the indolo ring compound prior to the synthesis of the remaining rings.
It can be seen that the prior art mostly uses metal catalysts, so that it is difficult to avoid metal residues in the synthesized drug. The adoption of photocatalysis has the problems of high requirements on equipment and difficult control of reaction selectivity.
Disclosure of Invention
The invention aims to provide a method for directly constructing an indole-fused ring compound, which adopts anhydrous copper sulfate as a catalyst and nitrile as a nitrogen source to catalyze the activation of a C-H bond of an aryl side chain to directly synthesize the indole-fused ring compound.
The invention relates to a method for directly constructing an indole-fused ring compound, which is characterized by comprising the following steps: taking a 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative as a substrate, reacting a catalyst copper salt and an alkali with the 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative according to a molar ratio of 0.02-0.2: 2-4: 1 in a solvent at 90 ℃ for 8-20h, mixing petroleum ether/dichloromethane/ethyl acetate according to a volume ratio of 20-5: 2:1 to obtain an eluent, and separating by using a silica gel column to obtain a target product.
The 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative may be 2- [ (2-iodobenzyl) oxo ] benzonitrile, 2- [ (2-bromophenyl) oxo ] benzonitrile, 2- [ (5-bromo-2-iodobenzyl) oxo ] benzonitrile, 2- [ (2, 5-dibromobenzyl) oxo ] benzonitrile, 2- [ (5-chloro-2-iodobenzyl) oxo ] benzonitrile, 2- [ (5-chloro-2-bromobenzyl) oxo ] benzonitrile, 2- [ (5-chloro-2-bromophenyl) oxo ] benzonitrile, 2- [ (2-iodo-5-methylbenzyl) oxo ] benzonitrile, 2- [ (2-bromo-5-methylbenzyl) oxo ] benzonitrile, 4-bromo-2- [ (2-iodobenzyl) oxo ] benzonitrile, or mixtures thereof, 4-bromo-2- [ (2-bromobenzyl) oxo ] benzonitrile, 2- [ (1-iodonaphthalen-2-yl) methoxy ] benzonitrile, 2- [ (1-bromonaphthalen-2-yl) methoxy ] benzonitrile, 2- [ (2-iodobenzyl) sulfanyl ] benzonitrile, 2- [ (2-bromophenylmethyl) sulfanyl ] benzonitrile, 2- [ (5-chloro-2-iodobenzyl) sulfanyl ] benzonitrile, 2- [ (5-chloro-2-bromophenylmethyl) sulfanyl ] benzonitrile, 2- [ (5-chloro-2-bromobenzyl) sulfanyl ] benzonitrile, 2- [ (5-bromo-2-iodobenzyl) sulfanyl ] benzonitrile, 2- [ (2, 5-dibromobenzyl) sulfanyl ] benzonitrile, 2- [ (2-iodobenzyl) (methyl) amino ] benzonitrile or 2- [ (2- Bromobenzyl) (methyl) amino ] benzonitrile.
The solvent is chlorobenzene, DMF or DMSO.
The copper salt of the catalyst is anhydrous copper sulfate, cuprous iodide, copper iodide, cuprous chloride, cupric chloride, cuprous oxide or cupric oxide.
The alkali is potassium tert-butoxide, potassium hydroxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydride, calcium hydride, cesium carbonate, cesium fluoride or lithium bistrimethylsilyl amide.
The invention discloses a method for synthesizing an indole-fused ring compound in a molecule by using nitrile as a nitrogen source for the first time, which overcomes the defect of complicated steps in the existing method for synthesizing the indole-fused ring compound. The method has the advantages of simple operation, mild conditions and high yield, and is a green and novel synthesis method.
Detailed Description
Example 1:
synthesis of 10H-benzofuro [3,2-b ] indole
0.5mmol of 2- [ (2-iodobenzyl) oxo ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, vacuum dried for 15 minutes, 10mL of chlorobenzene was added under argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the mixture was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering, concentrating and removing the solvent, and carrying out column chromatography separation, wherein an eluent is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 98%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.83(d,J＝7.6Hz,1H),7.66-7.61(m,2H),7.45(d,J＝8.0Hz,1H),7.34-7.21(m,4H).13C NMR(100MHz,CDCl3)δ159.2,143.7,139.7,125.2,123.9,122.9,122.7,120.4,118.7,117.9,117.2,114.3,112.8,112.6.
Example 2:
synthesis of 10H-benzofuro [3,2-b ] indole
0.5mmol of 2- [ (2-bromophenylmethyl) oxo ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, vacuum-dried for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the mixture was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering, concentrating and removing the solvent, and carrying out column chromatography separation, wherein an eluent is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 77%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.83(d,J＝7.6Hz,1H),7.66-7.61(m,2H),7.45(d,J＝8.0Hz,1H),7.34-7.21(m,4H).13C NMR(100MHz,CDCl3)δ159.2,143.7,139.7,125.2,123.9,122.9,122.7,120.4,118.7,117.9,117.2,114.3,112.8,112.6.
Example 3:
synthesis of 3-bromo-10H-benzofuro [3,2-b ] indole
0.5mmol of 2- [ (5-bromo-2-iodobenzyl) oxo ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the resulting mixture was put into an oil bath and reacted at 90 ℃ for 15 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 3-bromo-10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 83%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 3-bromo-10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,CDCl3)δ8.09(s,1H),7.95(t,J＝0.4Hz,1H),7.67(d,J＝4.8Hz,1H),7.62(d,J＝5.6Hz,1H),7.35-7.31(m,4H).13C NMR(100MHz,CDCl3)δ159.4,142.4,138.1,126.3,125.6,124.5,122.9,119.7,118.3,118.1,115.6,113.8,113.4,112.9.
Example 4:
synthesis of 3-chloro-10H-benzofuro [3,2-b ] indole
0.5mmol of 2- [ (5-chloro-2-iodobenzyl) oxo ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the reaction tube was put into an oil bath and reacted at 90 ℃ for 14 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 3-chloro-10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 86%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 3-chloro-10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ11.76(s,1H),7.84-7.81(m,2H),7.72-7.70(m,1H),7.59(d,J＝8.8Hz,1H),7.38-7.36(m,2H),7.22(dd,J＝8.8,2.0Hz,1H).13C NMR(100MHz,DMSO-d6)δ159.3,141.5,138.1,127.5,125.0,124.5,123.5,122.6,119.2,118.7,116.1,114.9,113.9,113.1.
Example 5:
synthesis of 3-methyl-10H-benzofuro [3,2-b ] indole
0.5mmol of 2- [ (2-iodo-5-methylbenzyl) oxo ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the reaction tube was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 3-methyl-10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 72%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 3-methyl-10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ7.91(s,1H),7.62-7.61(m,3H),7.35(d,J＝8.4Hz,1H),7.31-7.28(m,2H),7.09(dd,J＝8.4,1.6Hz,1H).13C NMR(100MHz,DMSO-d6)δ159.2,143.5,138.2,129.8,125.3,124.5,123.7,122.6,118.8,117.8,116.9,114.5,112.7,112.2.
Example 6:
synthesis of 7-bromo-10H-benzofuro [3,2-b ] indole
0.5mmol of 4-bromo-2- [ (2-iodobenzyl) oxo ] benzonitrile, 0.20 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the resulting mixture was put into an oil bath and reacted at 90 ℃ for 14 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 7-bromo-10H-benzofuro [3,2-b ] indole; the yield thereof was found to be 68%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 7-bromo-10H-benzofuro [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ11.56(s,1H),7.99(d,J＝1.6Hz,1H),7.77(d,J＝8.0Hz,1H),7.74(d,J＝8.4Hz,1H),7.58(d,J＝8.0Hz,1H),7.52(dd,J＝8.4,1.6Hz,1H),7.26(t,J＝7.2Hz,1H),7.16(t,J＝7.6Hz,1H).13C NMR(100MHz,DMSO-d6)δ159.2,143.2,140.0,126.5,125.1,123.2,120.2,120.0,118.3,117.0,116.4,116.2,113.7,113.0.
Example 7:
synthesis of 12H-benzo [ g ] benzofuro [3,2-b ] indole
0.5mmol of 2- [ (1-iodonaphthalen-2-yl) methoxy ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, vacuum dried for 15 minutes, 10mL of chlorobenzene was added under argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the reaction tube was put into an oil bath and reacted at 90 ℃ for 13 hours. After completion of the reaction, the solvent was removed by filtration and concentration, and column chromatography was performed with petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1) as eluent to give 12H-benzo [ g ] benzofuro [3,2-b ] indole as a white solid; the yield thereof was found to be 68%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 12H-benzo [ g ] benzofuro [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ12.52(s,1H),8.48(d,J＝8.0Hz,1H),8.00(d,J＝8.0Hz,1H),7.89(d,J＝8.8Hz,1H),7.85(d,J＝7.6Hz,1H),7.74(d,J＝7.6Hz,1H),7.67-7.61(m,2H),7.50(t,J＝7.2Hz,1H),7.42-7.35(m,2H).13C NMR(100MHz,DMSO-d6)δ159.1,143.9,134.1,130.5,129.2,126.5,124.9,124.2,124.1,123.5,123.1,121.1,120.9,119.2,118.4,117.1,113.1,108.4.
Example 8:
synthesis of 10H-benzo [4,5] thieno [3,2-b ] indole
0.5mmol of 2- [ (2-iodobenzyl) sulfanyl ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate and 2.2 equivalents of potassium tert-butoxide are added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene is added under argon (or nitrogen) atmosphere, a polytetrafluoroethylene plug is added to the reaction tube, and the mixture is put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering and concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 10H-benzo [4,5] thieno [3,2-b ] indole; the yield thereof was found to be 98%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 10H-benzo [4,5] thieno [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ12.13(s,1H),8.07(d,J＝7.2Hz,1H),8.02(d,J＝8.4Hz,1H),7.78(d,J＝7.6Hz,1H),7.59(d,J＝8.0Hz,1H),7.49(t,J＝7.2Hz,1H),7.39(t,J＝6.8Hz,1H),7.28(t,J＝7.2Hz,1H),7.15(t,J＝7.2Hz,1H).13C NMR(100MHz,DMSO-d6)δ142.4,141.1,138.0,127.1,125.0,124.9,124.8,123.3,122.0,120.6,119.8,119.3,114.3,113.1.
Example 9:
synthesis of 3-chloro-10H-benzo [4,5] thieno [3,2-b ] indole
0.5mmol of 2- [ (5-chloro-2-iodobenzyl) sulfanyl ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, vacuum-dried for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a Teflon plug was added to the reaction tube, and the resulting mixture was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering and concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 3-chloro-10H-benzo [4,5] thieno [3,2-b ] indole; the yield thereof was found to be 98%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 3-chloro-10H-benzo [4,5] thieno [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ12.35(s,1H),8.08(d,J＝7.6Hz,1H),8.04(d,J＝8.0Hz,1H),7.92(s,1H),7.61(d,J＝8.8Hz,1H),7.51(t,J＝7.2Hz,1H),7.42(t,J＝7.6Hz,1H),7.28(dd,J＝8.8,2.0Hz,1H).13C NMR(100MHz,DMSO-d6)δ142.9,139.5,139.4,126.8,125.3,125.1,125.0,124.3,123.1,123.0,120.9,118.7,114.5,113.8.
Example 10:
synthesis of 3-bromo-10H-benzo [4,5] thieno [3,2-b ] indole
0.5mmol of 2- [ (5-bromo-2-iodobenzyl) sulfanyl ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate, and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, vacuum-dried for 15 minutes, 10mL of chlorobenzene was added under argon (or nitrogen) atmosphere, a Teflon plug was added to the reaction tube, and the resulting mixture was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 3-bromo-10H-benzo [4,5] thieno [3,2-b ] indole; the yield thereof was found to be 98%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 3-bromo-10H-benzo [4,5] thieno [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ12.37(s,1H),8.10-8.03(m,3H),7.58(d,J＝8.8Hz,1H),7.51(t,J＝7.2Hz,1H),7.43-7.38(m,2H).13C NMR(100MHz,DMSO-d6)δ142.9,139.7,139.2,126.8,125.7,125.3,125.1,124.9,123.7,121.7,120.9,115.0,113.7,112.1.
Example 11:
synthesis of 5-methyl-5, 10-indolino [3,2-b ] indole
0.5mmol of 2- [ (2-iodobenzyl) (methyl) amino ] benzonitrile, 0.05 equivalent of anhydrous copper sulfate and 2.2 equivalents of potassium tert-butoxide were added to a 100mL Schlenk reaction tube, dried under vacuum for 15 minutes, 10mL of chlorobenzene was added under an argon (or nitrogen) atmosphere, a polytetrafluoroethylene stopper was added to the reaction tube, and the mixture was put into an oil bath and reacted at 90 ℃ for 12 hours. After the reaction is finished, filtering, concentrating to remove the solvent, and carrying out column chromatography separation, wherein an eluant is petroleum ether/dichloromethane/ethyl acetate (v: v: v ═ 20:2:1), and the obtained white solid is 5-methyl-5, 10-indolino [3,2-b ] indole; the yield thereof was found to be 98%.
The white solid was analyzed by chemical shift and fragmentation by hydrogen nuclear magnetic resonance (1H NMR) and carbon nuclear magnetic resonance (13C NMR) as 5-methyl-5, 10-indolino [3,2-b ] indole.
1H NMR(400MHz,DMSO-d6)δ11.20(s,1H),7.96(d,J＝7.6Hz,1H),7.76(d,J＝7.6Hz,1H),7.55(d,J＝8.0Hz,1H),7.50(d,J＝8.0Hz,1H),7.26-7.18(m,2H),7.12(d,J＝7.6Hz,1H),7.08(d,J＝7.2Hz,1H),4.10(s,3H).13C NMR(100MHz,DMSO-d6)δ141.3,140.7,127.3,124.6,122.0,121.9,118.5,118.4,118.1,117.8,115.0,114.7,112.7,110.4,31.9.
The above examples summarize that: the method for directly constructing the indole-fused ring compound comprises the steps of taking a 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative as a substrate, enabling the molar ratio of a catalyst copper salt to the 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative to be 0.02-0.2: 1, enabling the molar ratio of alkali to the 2- [ (2-iodobenzyl) oxo ] benzonitrile derivative to be 2-4: 1, reacting in a solvent at 90 ℃ for 8-20h, mixing petroleum ether/dichloromethane/ethyl acetate according to the volume ratio of 20-5: 10:1 to serve as an eluent, and separating through a silica gel column to obtain a target product. The invention relates to a method for synthesizing an indole-fused ring compound by directly constructing the indole-fused ring compound by catalyzing the activation of a C-H bond of an aryl side chain, and using nitrile as a nitrogen source for the first time.
Claims (1)
1. A method for directly constructing an indolo-cyclic compound, which is characterized by comprising the following steps: by 2- [ (2-iodobenzyl) oxo]Using benzonitrile derivative as substrate, copper salt and alkali as catalyst, and 2- [ (2-iodobenzyl) oxo]The cyanobenzene derivative is dissolved in a solvent at a molar ratio of 0.02-0.2: 2-4: 1 to 90%oC, reacting for 8-20h, mixing petroleum ether/dichloromethane/ethyl acetate according to the volume ratio of 20-5: 2:1 to serve as an eluent, and separating through a silica gel column to obtain a target product, namely the 2- [ (2-iodobenzyl) oxo group]The benzonitrile derivative is 2- [ (2-iodobenzyl) oxo]Benzonitrile, 2- [ (2-bromophenyl) methyl) oxo]Benzonitrile, 2- [ (5-bromo-2-iodobenzyl) oxo]Benzonitrile, 2- [ (2, 5-dibromobenzyl) oxo]Benzonitrile, 2- [ (5-chloro-2-iodobenzyl) oxo]Benzonitrile, 2- [ (5-chloro-2-bromophenyl) methyl) oxo]Benzonitrile, 2- [ (2-iodo-5-methylbenzyl) oxo]Benzonitrile, 2- [ (2-bromo-5-methyl)Benzyl) oxo]Benzonitrile, 4-bromo-2- [ (2-iodobenzyl) oxo]Benzonitrile, 4-bromo-2- [ (2-bromophenyl) methyl) oxo]Benzonitrile, 2- [ (1-iodonaphthalen-2-yl) methoxy]Benzonitrile, 2- [ (1-bromonaphthalen-2-yl) methoxy]Benzonitrile, 2- [ (2-iodobenzyl) sulfanyl]Benzonitrile, 2- [ (2-bromophenyl methyl) sulfanyl]Benzonitrile, 2- [ (5-chloro-2-iodobenzyl) sulfanyl]Benzonitrile, 2- [ (5-chloro-2-bromophenylmethyl) sulfanyl]Benzonitrile, 2- [ (5-bromo-2-iodobenzyl) sulfanyl]Benzonitrile, 2- [ (2, 5-dibromobenzyl) sulfanyl]Benzonitrile, 2- [ (2-iodobenzyl) (methyl) amino]Benzonitrile or 2- [ (2-bromophenyl) (methyl) amino]Benzonitrile, chlorobenzene as the solvent, anhydrous copper sulfate as the catalyst copper salt, and potassium tert-butoxide as the base.
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Non-Patent Citations (5)
| Title |
|---|
| 2-Aryl and 2-Heteroaryl Indoles from 1-Alkynes and o-Iodotrifluoroacetanilide through a Domino Copper-Catalyzed Coupling-Cyclization Process;Sandro Cacchi et al.;《Org. Lett.》;20030926;第3843-3846页 * |
| CuSO4-Catalyzed dual annulation to synthesize O,S or N-containing tetracyclic heteroacenes;Xiang-Huan Shan et al.;《Chem. Commun.》;20200304;第4063-4066页 * |
| Dicyanovinyl Heterotetracenes: Synthesis, Solid-State Structures, and Photophysical Properties;Chunyan Du et al.;《J. Org. Chem.》;20090827;第7322-7327页 * |
| Photochemical intramolecular amination for the synthesis of heterocycles;Shawn Parisien-Collette et al.;《Green Chemistry》;20170926;第4798-4803页 * |
| Synthesis of a 7-Azaindole by Chichibabin Cyclization: Reversible Base-Mediated Dimerization of 3-Picolines;Yun ma et al.;《J. Org. Chem.》;20081231;第9610-9618页 * |
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