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Preparation method of substituted indole C3 alkylation derivative

A substituent and alkylation technology, applied in the field of organic synthesis, can solve the problems of high price and complex catalyst preparation

Active Publication Date: 2018-11-02
ZHEJIANG UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the above light-induced indole alkylation reaction, although the reaction conditions are mild, transition metal catalysts (photosensitizers) are still required, which has the disadvantages of complex catalyst preparation and high price.

Method used

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  • Preparation method of substituted indole C3 alkylation derivative
  • Preparation method of substituted indole C3 alkylation derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Derivative Ia (R 1 =R 2 = H, R 3 = methyl) synthesis

[0023] Weigh indole (0.5 mmol), N , N -Dimethylaniline (5 eq.) and 1.5 mol% Eosin B were placed in a 25 mL Schlenk reaction tube, then 4 mL of acetonitrile and 1 mL of water were added, and the reaction was carried out under a 15 W LED white light under the condition of air ventilation, at room temperature The reaction was stirred at lower temperature and monitored by TLC. After 24 h, the reaction was completed, the solvent was removed, and the concentrated solution was separated by column chromatography (petroleum ether / ethyl acetate=10: 1, V / V) to obtain a white solid, i.e. derivative Ia . Melting point 139-141 ° C, yield 71%.

[0024] of the compound 1 H NMR, 1 C NMR analysis data are described below,

[0025] 1 H NMR (CDCl 3 , 500 MHz) δ 7.94 (brs, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.35-7.37 (d, J = 8.0 Hz, 1H), 7.17-7.20 (m, 3H), 7.09 (t, J = 7.5 Hz, 1H), 6.91(s, 1H), 6.71 (d, J = 8.5 ...

Embodiment 2

[0026] Example 2 Derivatives Ib (R 1 = N -Methyl, R 2 = H, R 3 = methyl) synthesis

[0027] weigh N -Methylindole (0.5 mmol), N , N -Dimethylaniline (5.5 eq.) and 2.0 mol% Eosin Y-2Na were placed in a 25 mL Schlenk reaction tube, and then 5 mL of acetonitrile was added, and the reaction was placed under a 20 W LED white light under the condition of air ventilation, and the reaction was carried out at room temperature The reaction was stirred and followed and monitored by TLC. After 24 h, the reaction was completed, the solvent was removed, and the concentrated solution was separated by column chromatography (petroleum ether / ethyl acetate=20:1, V / V) to obtain a white solid, namely derivative Ib. Melting point 151-154 ° C, yield 70%.

[0028] of the compound 1 H NMR, 1 C NMR analysis data are described below,

[0029] 1 H NMR (CDCl 3 , 500 MHz) δ 7.62 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.5 Hz,1H), 7.28 (m, 1H), 7.26-7.21 (m, 2H), 7.14 (t, J = 8.0 Hz, 1H), 6.80-6...

Embodiment 3

[0030] Example 3 Derivatives Ic (R 1 = N , 2-Dimethyl, R 2 = H, R 3 = methyl) synthesis

[0031] weigh N ,2-Dimethylindole (0.5 mmol), N , N -Dimethylaniline (6.0 eq.) and 2.2 mol% Eosin Y were placed in a 25 mL Schlenk reaction tube, then 5 mL of acetonitrile and 1 mL of water were added, and the reaction was carried out under a 15 W LED white light under the condition of air ventilation, Stir the reaction at room temperature, track and monitor with TLC, after 30 h, the reaction is complete, the solvent is removed, and the concentrated solution is separated by column chromatography (petroleum ether / ethyl acetate=10:1, V / V) to obtain a white solid, the derivative Ic. Melting point 126-128 ° C, yield 67%.

[0032] of the compound 1 H NMR, 1 C NMR analysis data are described below,

[0033] 1 H NMR (CDCl 3 , 500 MHz) δ 7.45 (dd, J = 8.0, 7.5 Hz, 2H), 7.27-7.20 (m,2H), 7.11 (t, J = 8.0 Hz, 2H), 6.98 (t, J = 7.5 Hz, 1H), 6.67 (d, J = 8.5 Hz,1H), 4.17 (s, 2H), ...

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Abstract

The invention relates to a preparation method of a substituted indole C3 alkylation derivative, and belongs to the technical field of organic synthesis. The preparation method of the substituted indole C3 alkylation derivative comprises the following steps: performing normal-temperature stirring reaction on substituted indole and a substituted N-methylaniline compound serving as raw materials in asolvent under the action of an organic dye photosensitizer and under the irradiation of an LED white light lamp, performing TLC monitoring until the reactions ends, and separating and purifying the reaction liquid to prepare the substituted indole C3 alkylation derivative. By adoption of the above technology, the invention provides a new method for synthesizing an indole C3 alkylation derivativeby taking cheap and easily available organic dye as a catalyst and under the induction of the visible light. According to the method, the reaction condition is mild, the catalyst is cheap and easily available, the yield is high, and the acid catalysis or transition metal catalysis synthesis method commonly used for indole alkylation is replaced.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of substituted indole C3 alkylated derivatives. Background technique [0002] Indole structures widely exist in natural products and bioactive molecules, and are important intermediates in organic synthesis. Because the indole structure has good physiological activity, it has become one of the important precursors for the creation of new drugs. Some indole compounds have been successfully developed into clinical drugs, such as reserpine (Reserpine), active natural indole alkaloid lysergic acid (Lysergic acid), triptan drug (Zolmitriptan) effective in treating migraine, and anticancer drug Vinorelbine and the antibacterial molecule Spiroindimicin A et al. Therefore, more and more attention has been paid to the research on synthetic methods based on indole and its derivatives. [0003] The alkylation reaction of indole refers to the rea...

Claims

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Application Information

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IPC IPC(8): C07D209/14
CPCC07D209/14
Inventor 翁建全汪洲洋周智勇周亮戴小强刘幸海
Owner ZHEJIANG UNIV OF TECH
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