Method for synthesizing substituted indole compounds through one-pot method

A technology for indoles and compounds, which is applied in the field of one-pot synthesis of substituted indole compounds, can solve the problems of expensive catalysts, high reaction temperature, and difficulty in industrialization, and achieve the effects of simple operation, mild reaction conditions, and cost saving

Active Publication Date: 2013-02-13
YANTAI INST OF COASTAL ZONE RES CHINESE ACAD OF SCI
View PDF6 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction temperature of this method is relatively high, and there are many by-products, and the productive rate is not high; ) with aniline as raw material, in AlCl 3 Catalyzed with BCl 3 and ClCH 2 CN reaction, the middle undergoes a B-containing + The cyclic transition state of , acidified to 2-amino-α-chloroacetylbenzene, and then used NaBH in dioxane 4 Reduction of indole compounds, although the steps are simple, but the yield is low; the palladium-catalyzed cross-linking reaction of organotin reagents and various e

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing substituted indole compounds through one-pot method
  • Method for synthesizing substituted indole compounds through one-pot method
  • Method for synthesizing substituted indole compounds through one-pot method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Compound A: In a 100ml three-necked flask, add 50ml m-trimethylbenzene, raw material 1 (4-chloro-2-nitrotoluene, the same below) (0.69g, 4mmol), N,N-dimethylformamide dimethyl acetal (0.95g, 8mmol), pyrrolidine (1.14g, 16mmol), under nitrogen protection, stir well to completely dissolve the substrate. The temperature was raised to 145° C., condensed to reflux, and the reaction process was tracked by TLC until thin-layer chromatography showed that the starting point disappeared, and then cooled to room temperature. Then add a catalytic amount (20mg) of palladium carbon, and pass through hydrogen (10ml / min), control the reaction temperature at 45-50°C, react for 2 hours, cool to room temperature, filter with suction, and rinse the filter residue with dichloromethane several times. Extraction and recrystallization (cyclohexane:dichloromethane:methanol=2:1:8 (v / v)) gave an off-white solid with a yield of 92.3%.

[0029] The preparation method of compound B-H is the same as...

Embodiment 2

[0031] Compound A: In a 100ml three-necked flask, add 50ml N,N-dimethylformamide (DMF), raw material 1 (0.69g, 4mmol), N,N-dimethylformamide dimethyl acetal (0.95g, 8mmol ), pyrrolidine (1.14g, 16mmol), under nitrogen protection, and fully stirred to completely dissolve the substrate. The temperature was raised to 130° C., condensed to reflux, and the reaction process was tracked by TLC until thin-layer chromatography showed that the raw material point disappeared, and then cooled to room temperature. Then add a catalytic amount (100mg) of Raney nickel, slowly drop in 85% hydrazine hydrate (0.35g, 6mmol) with a dropping funnel, raise the temperature to 30°C, add the same amount of hydrazine hydrate every 30 minutes, and control the reaction temperature At 45-50°C, follow TLC until thin layer chromatography shows that the component point of the intermediate product disappears, cool to room temperature, and remove the catalyst by filtration with celite (do not drain to prevent t...

Embodiment 3

[0034] Compound A: Add 50ml tetrahydrofuran (THF), raw material 1 (0.69g, 4mmol), N,N-dimethylformamide dimethyl acetal (0.95g, 8mmol), pyrrolidine (1.14g, 16mmol), under nitrogen protection, fully stirred to dissolve the substrate completely. Raise the temperature to 80°C, condense to reflux, track the reaction process with TLC, until thin layer chromatography shows that the raw material point disappears, and cool to room temperature. Then add ferrous acetate (1.4g, 8mmol), control the reaction temperature at 45-50°C, track with TLC, until thin layer chromatography shows that the component point of the intermediate product disappears, cool to room temperature, filter with suction, and filter the residue with dichloromethane Wash several times, extract and recrystallize (cyclohexane:dichloromethane:methanol=2:1:8) to obtain an off-white solid with a yield of 78.5%.

[0035] Using raw materials 2-14 instead of raw material 1, the feed ratio is the same as that of compound 1, and...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a synthesis method of substituted indole compounds, and particularly relates to a method for synthesizing substituted indole compounds through a one-pot method. The method comprises the following steps: under alkaline and anaerobic conditions, reacting ortho-nitrotoluene derivatives and N,N-dimethylformamide dimethyl acetal or triethyl orthoformate used as raw materials in an organic solvent; and then, adding a reducer, and performing reduction and cyclization reaction to obtain indole derivatives, wherein R is a monosubstitution or polysubstitution located on site 4, 5, 6 or 7; and the R substituent is hydrogen, alkyl, substituted alkyl, alkoxy, amino or halogen atom. According to the invention, a one-pot method is adopted; the conventional and readily accessible ortho-nitrotoluene compounds are directly used as raw materials for reaction; separation and purification of intermediate compounds are not required; and the indole derivatives can be synthesized through the one-pot method by effectively controlling the reaction conditions, the charging sequence and the charging ratio. According to the invention, the technological operation procedure is simplified, the reaction time is shortened, the cost is saved, the total yield is improved, and better production and practical values can be achieved.

Description

technical field [0001] The invention relates to a method for synthesizing substituted indole compounds, in particular to a method for synthesizing substituted indole compounds in one pot. Background technique [0002] Indole compounds widely exist in nature, and many indole containing substituents on the benzene ring have biological activity. Indole and its derivatives are also an important chemical raw material, widely used in medicine, pesticides, dyes, food and Spices and many other fields. Pineal gland, also known as melatonin, is mainly produced from 5-methoxyindole. It directly acts on the hypothalamus, and has various physiological effects such as promoting sleep, regulating endocrine, and enhancing immunity. Indomethacin can play an anti-inflammatory effect by inhibiting the mRNA and protein expression of IL-6 and other cytokines in FLS without affecting the growth of fibroblast synoviocytes (FLS) in patients with rheumatoid arthritis . The indole alkaloid 5,6-dib...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D209/08
Inventor 夏传海张志凯刘苏静
Owner YANTAI INST OF COASTAL ZONE RES CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap