A kind of preparation method of 2-chloro-5-nitropyridine

A technology of nitropyridine and alkyl, which is applied in the field of preparation of 2-chloro-5-nitropyridine, which can solve the problem of poor safety and operability of diazotization hydrolysis reaction, which is not conducive to production scale-up and safe operation, and does not meet the requirements of green production and other problems, to achieve low cost, avoid diazotization hydrolysis reaction, and less by-products

Active Publication Date: 2021-07-20
XINFA PHARMA
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In the above-mentioned synthetic route 1, 2-aminopyridine will produce a large amount of waste water in the mixed acid nitration treatment process, pollutes greatly, does not meet the green production requirement; Simultaneously nitration reaction produces more by-products, as 2-amino-3-nitropyridine (the ratio is as high as 15%), the separation and purification are cumbersome; the diazotization hydrolysis reaction has poor safety and operability, which is not conducive to production amplification and safe operation

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
  • A kind of preparation method of 2-chloro-5-nitropyridine
  • A kind of preparation method of 2-chloro-5-nitropyridine
  • A kind of preparation method of 2-chloro-5-nitropyridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Embodiment 1: Preparation of 2-hydroxyl-5-nitropyridine (Ⅴ) (approach 1 of step (1))

[0074] To a 500 ml four-necked flask connected with stirring, a thermometer, and a reflux condenser, add 200 g of dichloromethane, 27.0 g (0.2 moles) of 2-nitroacetaldehyde dimethyl acetal (II1), 0.5 g of piperidine, 25.3 gram (0.21 moles) of methyl 2-chloroacrylate (Ⅲ1), stirred and reacted at 40-45°C for 3 hours, lowered the reaction solution to 25°C, added 5.0 grams of ammonium chloride, 100 grams of 17% ammonia water, 35-40°C The reaction was stirred for 5 hours. Add 100 grams of water, recover dichloromethane under reduced pressure, cool to 20-25°C, filter, wash once with 20 grams of water, and dry to obtain 25.8 grams of 2-hydroxy-5-nitropyridine with a liquid phase purity of 99.6% , yield 92.1%.

Embodiment 2

[0075] Embodiment 2: the preparation of 2-hydroxyl-5-nitropyridine (Ⅴ) (way 1 of step (1))

[0076] In a 500 ml four-necked flask connected with stirring, a thermometer and a reflux condenser, add 200 grams of tetrahydrofuran, 26.6 grams (0.2 moles) of 2-nitroacetaldehyde ethylene acetal (II2), 0.5 grams of DBU, 34.7 grams ( 0.21 moles) methyl 2-bromoacrylate (Ⅲ2), stirred and reacted at 40-45°C for 3 hours, lowered the reaction solution to 25°C, added 3.5 grams of ammonium chloride, 100 grams of 17% ammonia in methanol solution, 50-55 The reaction was stirred at °C for 3 hours. Add 150 grams of water, recover tetrahydrofuran and methanol under reduced pressure, cool to 20-25°C, filter, wash once with 20 grams of water, and dry to obtain 26.2 grams of 2-hydroxy-5-nitropyridine, with a liquid phase purity of 99.5% , yield 93.6%.

Embodiment 3

[0077] Embodiment 3: Preparation of 2-hydroxyl-5-nitropyridine (Ⅴ) (way 1 of step (1))

[0078] To a 500 ml four-necked flask connected with stirring, a thermometer, and a reflux condenser, add 200 g of 1,2-dichloroethane, 27.0 g (0.2 moles) of 2-nitroacetaldehyde dimethyl acetal (II1), 0.5 Kepiperidine, 28.2 grams (0.21 moles) of ethyl 2-chloroacrylate (Ⅲ3), stirred and reacted at 55-60°C for 2 hours, lowered the reaction solution to 25°C, added 3.5 grams of ammonium chloride, 100 grams of 17% ammonia water , Stir the reaction at 50-55°C for 3 hours. Add 100 grams of water, recover 1,2-dichloroethane under reduced pressure, cool to 20-25°C, filter, wash once with 20 grams of water, and dry to obtain 25.3 grams of 2-hydroxy-5-nitropyridine, liquid The phase purity was 99.2%, and the yield was 90.4%.

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 preparation method of 2-chloro-5-nitropyridine. 2-Hydroxy-5-nitropyridine is prepared by two methods with 2-nitroacetaldehyde acetal as the initial raw material; then 2-hydroxy-5-nitropyridine and chlorination reagent are prepared by chlorination reaction to prepare 2-chloro ‑5‑nitropyridine. The method of the invention has cheap and easy-to-obtain raw materials and low cost; does not involve diazotization hydrolysis reaction, and is safe and convenient to operate; does not use mixed acid, produces less waste water, and is environmentally friendly; at the same time does not involve nitrification reaction, has high reaction selectivity and few side reactions , the post-treatment is simple, the product yield and purity are high, and it is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of 2-chloro-5-nitropyridine, which belongs to the technical field of medicinal chemistry. Background technique [0002] 2-Chloro-5-nitropyridine is an important pharmaceutical intermediate, which can be used to prepare drugs such as pyronaridine, sononejib and other fine chemicals. Research and optimize the preparation method of 2-chloro-5-nitropyridine It is of great significance to the development of its downstream products. [0003] 2-Chloro-5-nitropyridine (I), the molecular formula is C 5 h 3 ClN 2 o 2 (The English name is 2-Chloro-5-Nitropyridine), the CAS number is 4548-45-2, and the structural formula is as follows: [0004] [0005] At present, the synthesis of 2-chloro-5-nitropyridine is mainly prepared from 2-aminopyridine through nitration reaction, diazotization hydrolysis reaction and chlorination reaction. [0006] For example, patent documents CN102040554A and CN105523995A use 2-ami...

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): C07D213/61
CPCC07D213/61
Inventor 徐欣戚聿新王保林王全龙
Owner XINFA PHARMA
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