Method for preparing 2,3-dichloroquinoxaline derivatives in one pot

A technology of dichloroquinoxaline and derivatives, which is applied in the field of drug synthesis, can solve the problems of corrosion of reaction vessel, inconvenient post-processing, complicated operation and the like, and achieves the effects of mild reaction conditions, simple operation and easy industrialization

Active Publication Date: 2021-03-02
CHONGQING MEDICAL UNIVERSITY
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there are two main methods for preparing 2,3-dichloroquinoxaline derivatives. One is to use substituted o-phenylenediamine and oxalic acid as raw materials, and first react in aqueous hydrochloric acid to obtain 2,3-dihydroxyquinoxaline Derivatives, after separation and purification, react with chlorinated reagents such as phosphorus pentachloride or phosphorus oxychloride. This method needs to be carried out in two steps. The 2,3-dihydroxyquinoxaline derivatives obtained by the reaction must be separated before they can be The chlorination reaction is cumbersome to operate, and the cost of manpower and reagents is high. A large amount of hydrochloric acid reagents used at the same time have problems such as reaction vessel corrosion and environmental pollution; another method is to replace o-phenylenediamine and diethyl oxalate as raw materials , using diethyl oxalate or ethanol as a solvent to react to obtain 2,3-dihydroxyquinoxaline derivatives, and then react with chlorinated reagents such as phosphorus pentachloride or phosphorus oxychloride after separation and purification. This method also requires separation Two steps, wherein, if diethyl oxalate is used as solvent, the amount of diethyl oxalate must be greatly excessive to make the reaction proceed, which not only causes a lot of waste of reagents, increases production costs, but also makes post-processing inconvenient and seriously pollutes the environment , if ethanol is used as a solvent, the obtained 2,3-dihydroxyquinoxaline derivatives must also be separated to carry out subsequent chlorination reactions, all of which have defects such as cumbersome operations and high labor costs

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 preparing 2,3-dichloroquinoxaline derivatives in one pot
  • Method for preparing 2,3-dichloroquinoxaline derivatives in one pot
  • Method for preparing 2,3-dichloroquinoxaline derivatives in one pot

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The preparation of embodiment 1 2,3-dichloroquinoxaline

[0021] Weigh 1g of o-phenylenediamine, 1.28g of oxalic acid and 3g of 200-300 mesh silica gel in a reaction bottle, add 15ml of toluene, and react at 110°C for 5 hours. After the reaction is complete, add 8.4ml of phosphorus oxychloride and 5ml of DMF, Continue to react for 1 hour, when the reaction is complete, add 50ml of ice water to quench, add 50ml of ethyl acetate, filter, separate the liquids, continue to extract the water layer with ethyl acetate, combine the ethyl acetate layers, wash with saturated sodium chloride, anhydrous sulfuric acid Dry over sodium, filter, and dry under reduced pressure to obtain a white solid with a yield of 92% and a melting point of 148-150°C.

[0022] IR(KBr,ν,cm -1 ):3104,3042,1557,1530,1484,1457,1271,1179,1125,1018, 991,768,599,436; 1 H NMR (600MHz, CDCl 3 )(δ,ppm):7.76-7.84(m,2H), 7.99-8.06(m,2H).;ESI–MS:[M+H] + m / z 198.9.

Embodiment 2

[0023] Embodiment 2 The preparation of 2,3-dichloroquinoxaline

[0024] Weigh 1g of o-phenylenediamine, 1.17g of oxalic acid and 4g of 200-300 mesh silica gel in a reaction flask, add 15ml of toluene, and react at 100°C for 5 hours. After the reaction is complete, add 6.7ml of phosphorus oxychloride and 5ml of DMF, Continue to react for 1 hour, when the reaction is complete, add 50ml of ice water to quench, add 50ml of ethyl acetate, filter, separate the liquids, continue to extract the water layer with ethyl acetate, combine the ethyl acetate layers, wash with saturated sodium chloride, anhydrous sulfuric acid Dry over sodium, filter, and dry under reduced pressure to obtain a white solid with a yield of 90% and a melting point of 148-150°C.

Embodiment 3

[0025] The preparation of embodiment 3 2,3-dichloroquinoxaline

[0026] Weigh 1g of o-phenylenediamine, 1.40g of oxalic acid and 5g of 100-200 mesh silica gel in a reaction bottle, add 15ml of toluene, and react at 110°C for 5 hours. After the reaction is complete, add 4.5ml of phosphorus oxychloride and 5ml of DMF, Continue to react for 1 hour, when the reaction is complete, add 50ml of ice water to quench, add 50ml of ethyl acetate, filter, separate the liquids, continue to extract the water layer with ethyl acetate, combine the ethyl acetate layers, wash with saturated sodium chloride, anhydrous sulfuric acid Dry over sodium, filter, and dry under reduced pressure to obtain a white solid with a yield of 88% and a melting point of 148-150°C.

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 belongs to the field of drug synthesis, and specifically relates to a new method for preparing 2,3-dichloroquinoxaline derivatives in one pot. Friendly silica gel or methanesulfonic acid is used as the catalyst, and the intermediate separation and purification steps are omitted, the operation is simple, the cost is low, the reaction conditions are mild, and it is environmentally friendly, and it is easy to industrialize large-scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a novel method for preparing 2,3-dichloroquinoxaline derivatives in one pot. Background technique [0002] 2,3-Dichloroquinoxaline derivatives, whose structure is shown in formula I, are an important class of pharmaceutical and fine chemical intermediates, which can undergo nucleophilic aromatic substitution reactions under mild conditions without the need for metal catalysts. A series of drugs or compounds with anti-tumor, anti-inflammatory, anti-psychotic and other pharmacological effects can be synthesized by introducing substituents at the 2-position and / or 3-position of quinoxaline. Therefore, they have received extensive attention in the field of biomedicine. [0003] [0004] At present, there are two main methods for preparing 2,3-dichloroquinoxaline derivatives. One is to use substituted o-phenylenediamine and oxalic acid as raw materials, and first react in ...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D241/44
CPCC07D241/44
Inventor 甘宗捷余瑜张培明李耀伟
Owner CHONGQING MEDICAL UNIVERSITY
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