Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for synthesizing quinoline derivative

A synthesis method and a technology of derivatives, applied in the field of quinoline derivatives, can solve the problems of limited catalyst activity, high reaction temperature, and difficult to handle by-products, and achieve the omission of protection and deprotection synthesis steps, simple reaction substrates, and easy reaction The effect of cheap substrates

Active Publication Date: 2017-02-01
NANYANG NORMAL UNIV
View PDF2 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this patent still has some shortcomings: it is impossible to prepare quinoline derivatives with electron-withdrawing ester groups at the 2 and 4 positions
[0005] There are many disadvantages in the current synthetic method: the main reason is that the reaction conditions are harsh, the reaction temperature is high, some require high temperature and high pressure, separation is difficult, and the substrate restriction of the reaction is strong , so a method for the synthesis of quinoline derivatives with substituents is limited
In addition, in the process of using metal catalysis, the activity of the catalyst is limited. These shortcomings make the operation of the preparation process more difficult, endanger the health of operators, and cause serious environmental pollution.
Yet the method for existing synthetic quinoline derivatives is ubiquitous: need active reaction substrate, reaction rate is low, reaction time is longer, by-product is much difficult to handle and the form of reaction is too single (resulting in the product that is synthesized has very little large limitations) and other disadvantages

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 quinoline derivative
  • Method for synthesizing quinoline derivative
  • Method for synthesizing quinoline derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] A kind of synthetic method of 4-phenylquinoline-2-formic acid methyl ester, comprises the following steps:

[0027] 1.0mmol (93mg) of aniline, 1.0mmol (142.1mg) of dimethyl butynedate, 1.2mmol (122.4mg) of phenylacetylene, 0.005mmol (1.3mg) of catalyst AgOTf, and 0.01mmol (1.5 mg), solvent hexanitrile 2mL, reacted in an oil bath at 100°C for 8h, cooled to room temperature, added 5mL of water, extracted three times with ethyl acetate, combined the organic layers, concentrated under reduced pressure, and the product was purified by column chromatography, 300-400 mesh Silica gel column, the eluent was a mixture of ethyl acetate and petroleum ether, the volume ratio of the two was 1:10, and 235.1 mg of a white solid product was obtained with a yield of 89% and a purity of 99.9%. 1H NMR (400MHz, CDCl 3 )δppm: 8.38(d, J=8.8Hz, 1H), 8.16(s, 1H), 7.98(d, J=8.8Hz, 1H), 7.77-7.81(t, 1H), 7.53-7.62(m, 6H ),4.10(s,3H); 13 C NMR (100MHz, CDCl 3 )δppm: 166.0, 149.9, 148.2, 147.5,...

Embodiment 2

[0031] A synthetic method of 6-fluoro-4-phenylquinoline-2-carboxylic acid methyl ester, comprising the following steps:

[0032] Add 1.0mmol (111mg) of p-fluoroaniline, 1.0mmol (142.1mg) of dimethyl butyndioate, 1.2mmol (122.4mg) of phenylacetylene, 0.005mmol (1.3mg) of catalyst AgOTf, and 0.01mmol of HOTf in the reaction vessel (1.5mg), solvent nitrile 2mL, reacted in 120°C oil bath for 12h, cooled to room temperature, added 5mL of water, extracted three times with ethyl acetate, combined organic layers, concentrated under reduced pressure, the product was purified by column chromatography, 300- 400-mesh silica gel column, the eluent was a mixture of ethyl acetate and petroleum ether, the volume ratio of the two was 1:10, and 220.0 mg of a white solid product was obtained with a yield of 78% and a purity of 99.9%. 1 H NMR (400MHz, CDCl 3 )δppm: 7.38 (d, J=8.8Hz, 1H), 8.17 (s, 1H), 7.52-7.54 (m, 7H), 4.09 (s, 3H); 13 C NMR (100MHz, CDCl 3 )δppm: 165.8, 163.2, 160.7, 149.4 (...

Embodiment 3

[0036] A kind of synthetic method of 6-chloro-4-phenylquinoline-2-formic acid methyl ester, comprises the following steps:

[0037] Add 1.0mmol (127mg) of p-chloroaniline, 1.0mmol (142.1mg) of dimethyl butyndioate, 1.2mmol (122.4mg) of phenylacetylene, 0.005mmol (1.3mg) of catalyst AgOTf, and 0.01mmol of HOTf in the reaction vessel (1.5mg), solvent nitrile 2mL, reacted in an oil bath at 100°C for 12h, cooled to room temperature, added 5mL of water, extracted three times with ethyl acetate, combined organic layers, concentrated under reduced pressure, the product was purified by column chromatography, 300- 400-mesh silica gel column, the eluent was a mixture of ethyl acetate and petroleum ether, the volume ratio of the two was 1:5, and 241.4 mg of a white solid product was obtained with a yield of 81% and a purity of 99.9%. 1 HNMR (400MHz, CDCl 3 )δppm: 8.31(d, J=9.2Hz, 1H), 8.17(s, 1H), 7.95(s, 1H), 7.74(d, J=8.8Hz, 1H), 7.51-7.60(m, 5H), 4.10(s,3H); 13 C NMR (100MHz, CDCl ...

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 provides a method for synthesizing a quinoline derivative. Aromatic amine, electrophilic alkyne and alkyne are sequentially added into a reaction vessel according to the molar ratio of 1:1:(1.2-4), solvent is added according to the proportion that 2-4 mL of solvent is added into 1 mmol of aromatic amine, then catalyst silver trifluoromethanesulfonate (AgOTf) with the molar weight being 0.8-5% that of aromatic amine and additive trifluoromethanesulfonic acid (HOTf) with the molar weight being 1.8-10% that of aromatic amine are added, reaction is conducted for 8-24 h at 100-120 DEG C in oil bath, the product is cooled to room temperature, water is added, the product is extracted three times with ethyl acetate, organic layers are combined, decompressive condensing is conducted, the product is subjected to column chromatography purification, and the product, namely the quinoline derivative, is obtained. The quinoline derivative has the advantages that reaction substrates are low in price, the yield is high, selectivity is good, separation and purification are easy, pollution is little, and steps are simple.

Description

technical field [0001] The invention relates to quinoline derivatives, in particular to a synthesis method of quinoline derivatives. Background technique [0002] Quinoline and its derivatives are an important class of organic heterocyclic compounds, which widely exist in nature and are widely used in drug screening, chemical analysis, dye industry and other fields. Synthetic quinoline derivative method has a lot, mainly contains: Skraup-Doebner-Miller synthetic method, Friedlander-Pfitzinge-Combes synthetic method, Bischler-Napieralski synthetic method (Tetrahedron.Lett, 2000,41,531-533; Org.lett, 2004, 6, 3965-3968; Eur.J.Org.Chem, 2008, 2693-2696 and J.Org.Chem, 2003, 68, 3966-3975), the most widely used method is the Skraup-Doebner-Miller method. The synthetic method of quinoline compound has been the focus of people's research (referring to: G.R.Humphrey, J.T.Kuethe, Chem, Rev, 2006,106,2875) always, the most representative method of synthetic quinoline in industry has...

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): C07D215/48C07D215/20C07D215/12
CPCC07D215/12C07D215/20C07D215/48
Inventor 张旭徐学锋
Owner NANYANG NORMAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com