CN103214408B - A kind of method of synthesizing bisindole methane derivative - Google Patents

A kind of method of synthesizing bisindole methane derivative Download PDF

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CN103214408B
CN103214408B CN201310164506.1A CN201310164506A CN103214408B CN 103214408 B CN103214408 B CN 103214408B CN 201310164506 A CN201310164506 A CN 201310164506A CN 103214408 B CN103214408 B CN 103214408B
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indole derivatives
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methane derivative
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CN103214408A (en
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李峰
孙春楼
邹小媛
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Nanjing University of Science and Technology
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Abstract

The invention discloses a kind of method of synthesizing bisindole methane derivative; under nitrogen protection; in reaction vessel, add indole derivatives, methyl alcohol, transition-metal catalyst iridium, ruthenium or rhodium complex and alkali, reaction mixture under solvent-free or p-Xylol are solvent condition at 120-150 ounder C after reaction, cool to room temperature, wherein, transition-metal catalyst is metal iridium, rhodium or ruthenium complex; Alkali is selected from one or more in sodium hydroxide, potassium hydroxide, salt of wormwood, cesium carbonate, potassiumphosphate or potassium tert.-butoxide; Transition-metal catalyst consumption is 0.1-0.2 mol% relative to indole derivatives mol ratio; Alkali is 0.1-1.0 equiv. relative to indole derivatives mol ratio; Methanol phase is 3 ~ 12.4:1 for indole derivatives mol ratio; Reaction times is 4 ~ 12 hours.Compared with the existing technology, the present invention from indole derivatives, by the alcohol generation linked reaction more friendly with environment, the bisindole methane derivative obtained.Therefore, this reaction meets the requirement of Green Chemistry, has vast potential for future development.

Description

A kind of method of synthesizing bisindole methane derivative
Technical field
The invention belongs to technical field of organic synthetic chemistry, be specifically related to a kind of method of synthesizing bisindole methane derivative.
Background technology
Indole ring is a large amount of natural products, the important feature unit of medicine and other bioactive compoundss.Many diindolylmethane derivatives derive from Lu Sheng or marine organisms.They present biological activity widely.Such as, anti-various tumour, antibacterial, microbiotic, disease (the K. V. Sashidhara such as antiviral; M. Kumar, R. Sonkar, B. S. Singh, A. K. Khanna; Gitika Bhatia, J. Med. Chem. 2012,55,2769-2779; W. Chao, D. Yean, K. Amin, C. Green, L. Jong, J. Med. Chem. 2007,50,3412-3415; D. Maciejewska, M. Rasztawicka, I. Wolska, E. Anuszewska, B.Gruber, Eur. J. Med. Chem. 2009,44,4136-4147; S.B. Bharate, J. B. Bharate, S. I. Khan, B. L. Tekwani, M. R. Jacob, R. Mudududdla, R. Yadav, B.Singh, P. R. Sharma, S. Maity, B. Singh, I. A. Khan, R. A. Vishwakarma, Eur. J. Med. Chem. 2013,63,435-443.)
The prior synthesizing method of bisindole methane derivative is in the presence of acid or alkali, indole derivatives and aldehyde react, obtain target compound (M. Shiri, M. A. Zolfigo, H. G. Kruger, Z. Tanbakouchian, Chem. Rev. 2010,110,2250-2293).Although use widely, but the toxicity of raw material aldehyde that this method uses is larger, and it is apt to deteriorate, not easily preserve for a long time, compared to aldehyde, alcohol has low price, stable, be convenient to store, advantages of environment protection. therefore, developing a kind of alcohol that uses has very important meaning to the preparation realizing bisindole methane derivative to organic synthesis to replace aldehyde synthesis aldehyde or ketone as reagent.
Summary of the invention
The invention provides a kind of novel method of synthesis bisindole methane derivative (formula I)
It comprises makes indole derivatives (formula II)
React with methyl alcohol (formula III)
Reaction occurs under catalyzer and alkali exist,
Its reaction expression is
Wherein, R 1be selected from alkyl, alkoxyl group, halogen or nitro;
X=C or N.
Described alkyl preferable methyl or ethyl; The preferred methoxyl group of alkoxyl group.
Concrete preparation process is as follows:
Under nitrogen protection, in reaction vessel, add indole derivatives, methyl alcohol, transition-metal catalyst iridium, ruthenium or rhodium complex and alkali, reaction mixture under solvent-free or p-Xylol are solvent condition at 120-150 ounder C after reaction, cool to room temperature.
Wherein, transition-metal catalyst is metal iridium, rhodium or ruthenium complex, preferably [Cp*IrCl 2] 2(Cp*=pentamethylcyclopentadienyl), [IrCl (cod)] 2(cod=1,5-cyclooctadienyl), [Cp*RhCl 2] 2or [Ru (p-cymene) Cl 2] 2in one or more; Alkali is selected from one or more in sodium hydroxide, potassium hydroxide, salt of wormwood, cesium carbonate, potassiumphosphate or potassium tert.-butoxide; Transition-metal catalyst consumption is 0.1-0.2 mol% relative to indole derivatives mol ratio; Alkali is 0.1-1.0equiv. relative to indole derivatives mol ratio; Methanol phase is 3 ~ 12.4: 1 for indole derivatives mol ratio; Reaction times is 4 ~ 12 hours.
Compared with the existing technology, the present invention from indole derivatives, by the alcohol generation linked reaction more friendly with environment, the bisindole methane derivative obtained.Therefore, this reaction meets the requirement of Green Chemistry, has vast potential for future development.
Accompanying drawing explanation
Accompanying drawing 1 is embodiment 1-product nucleus magnetic hydrogen spectrum figure.
Accompanying drawing 2 is embodiment 1-product nuclear-magnetism carbon spectrogram.
Accompanying drawing 3 is embodiment 2-product nucleus magnetic hydrogen spectrum figure.
Accompanying drawing 4 is embodiment 2-product nuclear-magnetism carbon spectrogram.
Embodiment
Show that example is to illustrate some embodiment of the present invention, and should not be construed as and limit the scope of the invention.Simultaneously from material, method and reaction conditions can carry out many improvement to content disclosed by the invention, change and change.All these improve, and change and change fall within the spirit and scope of the present invention all definitely.
Embodiment 1: two (1H-indoles) methane
Di(1H-indol-3-yl)methane
Under nitrogen protection, by indoles (234 mg, 2 mmol), [Cp*IrCl 2] 2(3.2mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml, 790 mg, 24.7 mmol, 12.4 equiv.) be added to successively in 25 ml Schlenk reaction flasks.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 86%
1H NMR (500 MHz, DMSO-d 6) δ 10.73 (br s, 2H, 2xNH), 7.52 (d, J = 7.7 Hz, 2H, ArH), 7.31 (d, J =8.0 Hz, 2H, ArH), 7.13 (s, 2H, ArH), 7.02 (t, J =7.4 Hz, 2H, ArH), 6.91 (t, J = 7.4 Hz, 2H, ArH), 4.12 (s, 2H, CH 2); 13C NMR (125 MHz, DMSO-d 6) δ136.4, 127.2, 122.7, 120.7, 118.7, 118.0, 114.2, 111.3, 20.9.
Embodiment 2: two (4-Methyl-1H-indole) methane
bis(4-methyl-1H-indol-3-yl)methane
Under nitrogen protection, by 4-skatole (262 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 81%
1H NMR (500 MHz, CDCl 3) δ 7.82 (br s, 2H, 2xNH),7.18 (d, J = 8.2 Hz, 2H, ArH), 7.07 (t, J = 7.7Hz, 2H, ArH), 6.84 (d, J = 7.2 Hz, 2H, ArH), 6.68(s, 2H, ArH), 4.55 (s, 2H, CH 2), 2.65 (s, 6H, 2xCH 3); 13C NMR (125 MHz, CDCl 3) δ 137.0, 131.3, 125.9, 122.9, 122.0, 120.7, 117.5, 108.9, 25.7, 20.1.
Embodiment 3: two (5-Methyl-1H-indole) methane
bis(5-methyl-1H-indol-3-yl)methane
Under nitrogen protection, by 5-skatole (262 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 85%
1H NMR (500 MHz, CDCl 3) δ 7.78 (br s, 2H, 2xNH),7.41 (s, 2H，ArH), 7.24 (d, J = 8.3 Hz, 2H, ArH),7.02 (d, J = 7.9 Hz, 2H, ArH), 6.87 (d, J = 5.1Hz, 2H, ArH), 4.18 (s, 2H, CH 2), 2.43 (s, 6H, 2xCH 3); 13C NMR (125 MHz, CDCl 3) δ 134.8, 128.3, 127.8,123.4, 122.4, 118.8, 115.2, 110.7, 21.5, 21.1; HRMS-EI (70 eV) m/z calcd for C 19H 18N 2Na [M+Na] +297.1368,found 297.1373.
Embodiment 4: two (7-Methyl-1H-indole) methane
bis(7-methyl-1H-indol-3-yl)methane
Under nitrogen protection, by 7-skatole (262 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 83%
1H NMR (500 MHz, CDCl 3) δ 7.81 (br s, 2H, 2xNH),7.48 (d, J = 7.5 Hz, 2H, ArH), 7.03-6.98 (m, 4H,ArH), 6.92 (s, 2H, ArH), 4.23 (s, 2H, CH 2), 2.48 (s, 6H, 2xCH 3); 13C NMR (125 MHz, CDCl 3) δ 136.0, 127.1, 122.3, 121.9, 120.2, 119.4, 117.0, 116.2, 21.4,16.6; HRMS-EI (70 eV) m/z calcd for C 19H 18N 2Na [M+Na] +297.1368, found 297.1375.
Embodiment 5: two (7-ethyl-1H-indoles) methane
bis(7-ethyl-1H-indol-3-yl)methane
Under nitrogen protection, by 7-ethylindole (290 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 80%
1H NMR (500 MHz, CDCl 3) δ 7.81 (br s, 2H, 2xNH),7.49 (d, J = 7.4 Hz, 2H, ArH), 7.07-7.02 (m, 4H,ArH), 6.90 (s, 2H, ArH), 4.22 (s, 2H, CH 2), 2.84 (q, J = 7.6 Hz, 4H, 2xCH 2), 1.35 (t, J = 7.6 Hz,6H, 2xCH 3); 13C NMR (125 MHz, CDCl 3) δ 135.3, 127.3, 126.4, 121.8, 120.4, 119.4, 117.0, 116.2, 24.0, 21.4, 13.8.
Embodiment 6: two (5-methoxyl group-1H-indoles) methane
bis(5-methoxy-1H-indol-3-yl)methane
Under nitrogen protection, by 5-methoxy-Indole (294 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 mlSchlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 86%
1H NMR (500 MHz, CDCl 3) δ 7.81 (br s, 2H, 2xNH),7.25 (d, J = 7.5 Hz, 2H, ArH), 7.06 (d, J = 1.7Hz, 2H, ArH), 6.91 (s, 2H, ArH), 6.86 (dd, J = 8.8 Hz and 2.1 Hz, 2H, ArH), 4.17 (s, 2H, CH 2), 3.81 (s, 6H, 2xOCH 3); 13C NMR (125 MHz, CDCl 3) δ 153.8, 131.6, 127.9, 123.1, 115.2, 112.0, 111.8, 101.0,55.9, 21.2.
Embodiment 7: two (6-methoxyl group-1H-indoles) methane
bis(6-methoxy-1H-indol-3-yl)methane
Under nitrogen protection, by 6-methoxy-Indole (294 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 mlSchlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 78%
1H NMR (500 MHz, DMSO-d 6) δ 10.50 (br s, 2H, 2xNH), 7.34 (d, J = 6.0 Hz, 2H, ArH), 6.96 (s, 2H, ArH), 6.81 (s, 2H, ArH), 6.56 (s, 2H, ArH), 4.02 (s, 2H, CH 2), 3.72 (s, 6H, 2xOCH 3); 13C NMR (125 MHz,DMSO-d 6) δ 155.3, 137.0, 121.7, 121.3, 119.2, 114.2,108.2, 94.4, 55.1, 21.1.
Embodiment 8: two (the fluoro-1H-indoles of 5-) methane
bis(5-fluoro-1H-indol-3-yl)methane
Under nitrogen protection, by 5-fluoro indole (270 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 88%
1H NMR (500 MHz, CDCl 3) δ 7.93 (br s, 2H, 2xNH),7.25-7.20 (m, 4H, ArH), 7.00 (s, 2H, ArH), 6.92 (t,J = 8.8 Hz, 2H, ArH), 4.14 (s, 2H, CH 2); 13C NMR(125 MHz, CDCl 3) δ 157.6 (d, J C-F = 233.0 Hz), 133.0, 127.8 (d, J C-F = 9.5 Hz), 123.9, 115.4 (d, J C-F = 4.5Hz), 111.7 (d, J C-F = 9.5 Hz), 110.3 (d, J C-F = 26.2 Hz), 104.0 (d, J C-F = 23.4 Hz), 21.2.
Embodiment 9: two (the fluoro-1H-indoles of 6-) methane
bis(6-fluoro-1H-indol-3-yl)methane (3h)
Under nitrogen protection, by 6-fluoro indole (270 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 91%
1H NMR (500 MHz, CDCl 3) δ 7.88 (br s, 2H, 2xNH),7.47 (dd, J = 8.7 Hz and 3.4 Hz, 2H, ArH), 7.03(dd, J = 9.7 Hz and 2.2 Hz, 2H, ArH), 6.90 (s, 2H, ArH), 6.84 (td, J = 9.2 Hz and 2.2 Hz, 2H, ArH), 4.18 (s, 2H, CH 2); 13C NMR (125 MHz, CDCl 3) δ160.0 (d, J C-F = 236.1 Hz), 136.3 (d, J C-F = 12.2 Hz), 124.1, 122.3 (d, J C-F = 3.1 Hz), 119.8 (d, J C-F = 10.0Hz), 115.5, 108.0 (d, J C-F = 24.4 Hz), 97.3 (d, J C-F = 25.7 Hz), 21.2; HRMS-EI (70 eV) m/z calcd for C 17H 12N 2F 2Na [M+Na] +305.0866, found 305.0863.
Embodiment 10: two (the chloro-1H-indoles of 5-) methane
bis(5-chloro-1H-indol-3-yl)methane
Under nitrogen protection, by 5-chloro-indole (302 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 87%
1H NMR (500 MHz, CDCl 3) δ 7.98 (br s, 2H, 2xNH),7.54 (s, 2H, ArH), 7.27-7.26 (m, 2H, ArH), 7.13 (d,J = 8.4 Hz, 2H, ArH), 6.97 (s, 2H, ArH), 4.14 (s, 2H, CH 2); 13C NMR (125 MHz, CDCl 3) δ 134.8, 128.5, 125.0, 123.6, 122.3, 118.6, 115.0, 112.1, 21.1.
Embodiment 11: two (the chloro-1H-indoles of 6-) methane
bis(6-chloro-1H-indol-3-yl)methane
Under nitrogen protection, by 6-chloro-indole (302 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 85%
1H NMR (500 MHz, CDCl 3) δ 7.92 (br s, 2H, 2xNH),7.47 (d, J = 8.3 Hz ,2H, ArH), 7.35 (s, 2H, ArH),7.05 (d, J = 8.5 Hz, 2H, ArH), 6.92 (s, 2H, ArH), 4.18 (s, 2H, CH 2); 13CNMR (125 MHz, CDCl 3) δ 136.8, 127.9, 126.1, 122.7,120.0, 115.6, 111.0, 21.1; HRMS-EI (70 eV) m/z calcdfor C 17H 12N 2Cl 2Na [M+Na] +337.0275, found 337.0269.
Embodiment 12: two (the bromo-1H-indoles of 5-) methane
bis(5-bromo-1H-indol-3-yl)methane (3k)
Under nitrogen protection, by 5-bromo indole (392 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 88%
1H NMR (500 MHz, CDCl 3) δ 7.97 (br s, 2H, 2xNH),7.70 (s, 2H, ArH), 7.28-7.22 (m, 4H, ArH), 6.94 (s,2H, ArH), 4.13 (s, 2H, CH 2); 13C NMR (125 MHz, CDCl 3) δ 135.1, 129.1, 124.8, 123.4, 121.7, 114.8, 112.6, 112.5, 121.0.
Embodiment 13: two (the bromo-1H-indoles of 6-) methane
bis(6-bromo-1H-indol-3-yl)methane
Under nitrogen protection, by 6-bromo indole (392 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 86%
1H NMR (500 MHz, CDCl 3) δ 7.91 (br s, 2H, 2xNH),7.51 (s, 2H, ArH), 7.42 (d, J = 8.4 Hz, 2H, ArH),7.17 (d, J = 8.3 Hz, 2H, ArH), 6.91 (s, 2H, ArH), 4.17(s, 2H, CH 2); 13CNMR (125 MHz, CDCl 3) δ 137.2, 126.4, 122.7, 122.6,120.4, 115.6, 114.0, 21.1.
Embodiment 14: two (5-nitro-1H-indoles) methane
bis(5-nitro-1H-indol-3-yl)methane
Under nitrogen protection, by 5-nitroindoline (324 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (112 mg, 1 mmol, 0.5 equiv.) and methyl alcohol (1 ml) are added in 25 mlSchlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 77%
1H NMR (500 MHz, DMSO-d 6) δ 11.6 (br s, 2H, 2xNH), 8.51 (s, 2H, ArH), 7.96 (d, J = 8.9 Hz, 2H, ArH), 7.52-7.51 (m, 4H, ArH), 4.33 (s, 2H, CH 2); 13C NMR (125 MHz, DMSO-d 6) δ 140.1, 139.6, 126.9, 126.3,116.6, 116.4, 115.8, 111.9, 20.2.
Embodiment 15: two (4-Methyl-1H-indole) methane
di(1H-pyrrolo[2,3-b]pyridin-3-yl)methane (3l)
Under nitrogen protection, by 7-azaindole (236 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 80%
1H NMR (500 MHz, DMSO-d 6) δ 11.3 (br s, 2H, 2xNH), 8.14 (s, 2H, ArH), 7.88 (s, 2H, ArH), 7.31 (s,2H, ArH), 6.96 (s, 2H, ArH), 4.13 (s, 2H, CH 2); 13CNMR (125 MHz, DMSO-d 6) δ 148.7, 142.2, 126.6, 123.2, 119.2, 114.7, 112.7, 21.0.
Embodiment 16: two (2-Methyl-1H-indole) methane
bis(2-methyl-1H-indol-3-yl)methane
Under nitrogen protection, by 2 methyl indole (262 mg, 2 mmol), [Cp*IrCl 2] 2(3.2 mg, 0.004 mmol, 0.2 mol%), potassium tert.-butoxide (224 mg, 2 mmol, 1 equiv.) and methyl alcohol (1 ml) are added in 25 ml Schlenk reaction flasks successively.Reaction mixture is 150 oreact under C after 12 hours, cool to room temperature.Rotary evaporation, except desolventizing, then obtains pure target compound, productive rate by column chromatography (developping agent: ethyl acetate/petroleum ether): 75%
1H NMR (500 MHz, DMSO-d 6) δ 10.6 (br s, 2H, 2xNH), 7.22 (d, J = 7.8 Hz, 2H, ArH), 7.17 (d, J = 8.1 Hz, 2H, ArH), 6.89 (t, J = 7.4 Hz, 2H, ArH),6.78 (t, J = 7.3 Hz, 2H, ArH), 3.97 (s, 2H, CH 2),2.36 (s, 6H, 2xCH 3); 13C NMR (125 MHz, DMSO-d 6) δ135.1, 131.1, 128.5, 119.6, 117.8, 117.7, 110.2, 109.7, 18.8, 11.6; HRMS-EI (70 eV) m/z calcd for C 19H 18N 2Na [M+Na] +297.1368, found 297.1367.
Embodiment 17:
Except using [IrCl (cod)] 2(2.5 mg, 0.004 mmol, 0.2 mol%) replaces [Cp*IrCl 2] 2, other reaction raw materials, condition and product with embodiment 1, productive rate: 51%
Embodiment 18:
Except using [Cp*RhCl 2] 2(2.5 mg, 0.004 mmol, 0.2 mol%) replaces [Cp*IrCl 2] 2, other reaction raw materials, condition and product with embodiment 1, productive rate: 6%
Embodiment 19:
Except using [Ru (p-cymene) Cl 2] 2(2.4mg, 0.004 mmol, 0.2 mol%) replaces [Cp*IrCl 2] 2, other reaction raw materials, condition and product with embodiment 1, productive rate: 45%
Embodiment 20:
Except with salt of wormwood (276 mg, 2 mmol, 1 equiv.) replace potassium tert.-butoxide, other reaction raw materials, condition and product with embodiment 1, productive rate: 8%
Embodiment 21:
Except with cesium carbonate (652 mg, 2 mmol, 1 equiv.) replace potassium tert.-butoxide, other reaction raw materials, condition and product with embodiment 1, productive rate: 31%
Embodiment 22:
Except with potassiumphosphate (425mg, 2 mmol, 1 equiv.) replace potassium tert.-butoxide, other reaction raw materials, condition and product with embodiment 1, productive rate: 19%
Embodiment 23:
Except with potassium hydroxide (112 mg, 2 mmol, 1 equiv.) replace potassium tert.-butoxide, other reaction raw materials, condition and product with embodiment 1, productive rate: 42%
Embodiment 24:
Except [Cp*IrCl 2] 2consumption be 2.4 mg, 0.003 mmol, 0.15 mol%, other reaction raw materials, condition and product with embodiment 1, productive rate: 83%
Embodiment 25:
Except [Cp*IrCl 2] 2consumption be 1.6 mg, 0.002 mmol, 0.1 mol%, other reaction raw materials, condition and product with embodiment 1, productive rate: 75%
Embodiment 26:
Consumption except potassium tert.-butoxide is 112 mg, 1.0 mmol, 0.5 equiv., other reaction raw materials, condition and product with embodiment 1, productive rate: 30%
Embodiment 27:
Consumption except potassium tert.-butoxide is 44.8 mg, 0.4 mmol, 0.2 equiv., other reaction raw materials, condition and product with embodiment 1, productive rate: 5%
Embodiment 28:
Except temperature of reaction is 130 oc, other reaction raw materials, condition and product with embodiment 1, productive rate: 42%.
Embodiment 29:
Except temperature of reaction is 120 oc, other reaction raw materials, condition and product with embodiment 1, productive rate: 11%.
Embodiment 30:
Except the reaction times is 8 hours, other reaction raw materials, condition and product with embodiment 1, productive rate: 71%.
Embodiment 31:
Except the reaction times is 4 hours, other reaction raw materials, condition and product with embodiment 1, productive rate: 35%.
Embodiment 32:
Consumption except methyl alcohol is 320 mg (10 mmol, 5 quiv.), p-Xylol (1ml) as solvent, other reaction raw materials, condition and product with embodiment 1, productive rate: 46%.
Embodiment 33:
Consumption except methyl alcohol is 192 mg (6 mmol, 3 quiv.), p-Xylol (1 ml) as solvent, other reaction raw materials, condition and product with embodiment 1, productive rate: 22%.

Claims (8)

1. synthesize a method for bisindole methane derivative, it is characterized in that reaction product I
By indole derivatives II
React with methyl alcohol III
CH 3OH
III
In formula, R 1be selected from alkyl, alkoxyl group, halogen or nitro; X=C or N;
Its concrete preparation process is as follows: in reaction vessel, add indole derivatives, methyl alcohol, transition metal iridium, ruthenium or using rhodium complex catalysts and alkali, reaction mixture reacts at 120-150 DEG C, obtains target product after cool to room temperature, wherein, catalyzer is [Cp*IrCl 2] 2, [Ir (cod) Cl] 2, [Cp*RhCl 2] 2or [Ru (p-cymene) Cl 2] 2in one or more.
2. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that described alkyl is methyl or ethyl; Described alkoxyl group is methoxyl group.
3. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that one or more that described alkali is selected from sodium hydroxide, potassium hydroxide, salt of wormwood, cesium carbonate, potassiumphosphate or potassium tert.-butoxide.
4. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that the relative indole derivatives of described catalyst levels is 0.1-0.2mol%.
5. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that the molar weight of described alkali is 0.1-1.0equiv. relative to the molar weight of indole derivatives.
6. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that described methanol phase is 3 ~ 12.4:1 for the mol ratio of indole derivatives.
7. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that adopting p-Xylol to be solvent in described reaction.
8. the method for synthesis bisindole methane derivative according to claim 1, is characterized in that the described reaction times is 4-12 hour.
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