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Method for cyclization reaction to synthesize indole through co-catalysis of palladium-organic nitrite

A technology of organic nitrite and chemical synthesis, applied in the direction of organic chemistry, which can solve the problems of narrow application range and inability to better realize the synthesis of functionalized indole, and achieve the effect of simple operation and mild reaction conditions

Active Publication Date: 2017-09-01
UNIV OF SCI & TECH OF CHINA
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AI Technical Summary

Problems solved by technology

[0011] It can be seen that most of the substrates in the prior art have a narrow scope of application, and there is regioselectivity in functionalization, which cannot better realize the synthesis of functionalized indole

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] N-(4-Tosyl)indole Synthesis

[0021] Add Pd(PhCN) to a 25 mL Schlenk reaction tube 2 Cl 2 (0.025mmol), after vacuum drying for 15 minutes, replace oxygen three times, in an oxygen atmosphere, add 2mL tert-butanol, tert-butyl nitrite (0.05mmol), N-(4-toluenesulfonyl)-2- Vinylaniline (0.25mmol) was reacted at 70°C for 7h. After the reaction was completed, the obtained product was separated by flash column chromatography, and the eluent was petroleum ether / diethyl ether (v:v=200:1), and N-(4-tosyl)indole was obtained by column chromatography. Product yield 74%, yellow liquid; 1 HNMR (400MHz, CDCl 3 )δppm: 8.00-7.97(m, 1H), 7.77-7.74(m, 2H), 7.56(d, J=3.6Hz, 1H), 7.52(d, J=8.0Hz, 1H), 7.32-7.28(m ,1H),7.24-7.20(m,3H),6.65(dd,J=3.6,0.8Hz,1H),2.33(s,3H). 13 C NMR (100MHz, CDCl 3 )δ145.3, 135.6, 135.1, 131.1, 130.2, 127.1, 126.7, 124.9, 123.6, 121.7, 113.9, 109.4, 21.9. HRMS (ESI) calcd for C 15 h 14 NO 2 S[M+H] + 272.0745, found 272.0743.

Embodiment 2

[0023] Indole N-methylformate Synthesis

[0024] Add Pd(PhCN) to a 25 mL Schlenk reaction tube 2 Cl 2 (0.025mmol), after vacuum drying for 15 minutes, replace oxygen three times, in an oxygen atmosphere, add 2mL tert-butanol, tert-butyl nitrite (0.05mmol), N-methyl formate-2-vinylaniline (0.25 mmol), react at 70°C for 24h. After the reaction was completed, the obtained product was separated by flash column chromatography, the eluent was petroleum ether / diethyl ether (v:v=200:1), and N-methyl formate indole was obtained by column chromatography. Yield 56%, yellow liquid; 1 HNMR (400MHz, CDCl 3 )δppm: 8.19(d, J=8.0Hz, 1H), 7.61(s, 1H), 7.57(d, J=7.6Hz, 1H), 7.34(t, J=7.6Hz, 1H), 7.27-7.23( m,1H),6.60(d,J=2.8Hz,1H),4.05(s,3H). 13 C NMR (100MHz, CDCl 3 )δ152.0, 135.5, 130.8, 125.8, 124.8, 123.3, 121.3, 115.4, 108.5, 54.1.

Embodiment 3

[0026] N-tert-butyl carbonate indole Synthesis

[0027] Add Pd(PhCN) to a 25 mL Schlenk reaction tube 2 Cl 2 (0.025mmol), after vacuum drying for 15 minutes, replace oxygen three times, in oxygen atmosphere, add 2mL tert-butyl alcohol, tert-butyl nitrite (0.05mmol), N-tert-butyl carbonate-2-vinylaniline ( 0.25mmol), reacted at 70°C for 14h. After the reaction was completed, the obtained product was separated by fast flash column chromatography, and the eluent was petroleum ether / diethyl ether (v:v=200:1), and N-tert-butyl carbonate indole was obtained by column chromatography. Yield 50%. yellow liquid; 1 HNMR (400MHz, CDCl 3 )δppm: 8.14(d, J=7.6Hz, 1H), 7.59(s, 1H), 7.56(d, J=8.0Hz, 1H), 7.31(t, J=7.6Hz, 1H), 7.22(t, J=7.6Hz, 1H), 6.56(d, J=2.4Hz, 1H), 1.67(s, 9H), 13 C NMR (100MHz, CDCl 3 )δ150.1, 135.5, 130.9, 126.2, 124.5, 122.9, 121.2, 115.5, 107.6, 83.9, 28.5.

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Abstract

The invention discloses a method for cyclization reaction to synthesize indole through co-catalysis of palladium-organic nitrite. The method is characterized by comprising the steps of mixing at the molar ratio of a palladium compound to a 2-vinyl aniline compound containing a substituent group in oxygen atmosphere being 7.5:100 and the molar ratio of the organic nitrite to the 2-vinyl aniline compound containing the substituent group being 20:100; reacting in a solvent at 70 DEG C for 7-24h and mixing at the volume ratio of petroleum ether / diethyl ether being (200-50):1 as an eluent for column chromatography separation to obtain a target product. The organic nitrite is adopted as a cocatalyst, so that use of Cu<2+> or benzoquinone as a synergistic catalyst is avoided, a catalyst system is oxidized by using oxygen, and the method is green, economical and environmentally friendly. Corresponding Cl<->-substituted indole is efficiently synthesized through introducing a Cl<-> substituent group to an aromatic ring of 2-vinyl aniline in advance and then functionalization of different positions of the indole can be achieved through coupling reaction, so that introduction of a directing group to the indole N and control on the region selectivity are avoided, the operation is simple and a novel method is provided for functionalization of the indole.

Description

technical field [0001] The invention belongs to the technical field of catalyzing 2-aminostyrene to synthesize indole compounds, and in particular relates to a method for oxidizing 2-aminostyrene into indole through reverse Markov Wacker oxidation. Background technique [0002] The reaction of synthesizing indole is widely used in the fields of chemical industry and organic drug synthesis. The traditional method of indole synthesis is Emil Fischer (Emil Fischer) indole synthesis method, but the reaction needs to be heated to 180-250 Occurs under the condition of ℃. In recent years, the use of transition metals as catalysts has been developed to directly oxidize the C-H bond of 2-aminostyrene to indole, but the reaction needs to add an additional equivalent of benzoquinone or divalent copper as a co-oxidant, N,N-dimethylformamide Or dimethyl sulfoxide as solvent. Although metal-free catalysts have also been developed in this field, the equivalent of 2,3-dichloro-5,6-dicyano...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/08C07D209/10C07D209/12C07D491/056
CPCC07D209/08C07D209/10C07D209/12C07D491/056
Inventor 康彦彪宁小山
Owner UNIV OF SCI & TECH OF CHINA
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