Synthesis method of 2-fluoro-4-nitrobenzonitrile

A technology of nitrobenzonitrile and synthetic method, which is applied in the field of synthesis of 2-fluoro-4-nitrobenzonitrile, and can solve the problem of lack of 2-fluoro-4-nitrobenzonitrile reaction conditions and yield, etc. problems, to achieve the effect of reducing production costs

Active Publication Date: 2012-07-25
CHANGZHOU XIAOGUO INFORMATION SERVICES
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] The paper "Synthesis and Some Properties of 3-Fluoro-4-Cyanophenyl 4'-n- alkylbenzoates", Hu Yufeng, Luo Jun, Lv Chunxu et al. in "Fine Chemical Industry", 2008, 25(4): 401-404. Chemical Reagents", 2002, 24(3): 163-164. All mentioned in the paper "Research on Tetramethylammonium Fluoride Fluoride-Denitrification Reaction" that the meta-position on the benzene ring A nitro compound with an electron-withdrawing group reacts with KF, and the nitro group is replaced by a fluorine atom to generate the corresponding fluoride, but there is a lack of data on the reaction conditions and yield of 2-fluoro-4-nitrobenzonitrile; Nubia Boechat and James H.Clark introduced the use of TMAF (tetramethylammonium fluoride) as a phase transfer catalyst in the article "Fluorodenitrationsusing Tetramethylammonium Fluoride" published on Journal of the Chemical Society, Chemical Communications, 1993, 921-922. -Dinitrobenzonitrile reacts with KF as a raw material, and KF replaces the nitro group at the 2nd position of the benzene ring into a fluorine atom to generate 2-fluoro-4-nitrobenzonitrile, but the result is that 40% of the raw material has not been converted , and a small amount of 2,4-difluorobenzonitrile is produced by-product

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
  • Synthesis method of 2-fluoro-4-nitrobenzonitrile
  • Synthesis method of 2-fluoro-4-nitrobenzonitrile
  • Synthesis method of 2-fluoro-4-nitrobenzonitrile

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0032] The preparation of example 1,2-fluoro-4-nitroaniline

[0033] Put 1200mL of industrial alcohol, 750mL of 28% ammonia water, 27g of cuprous oxide and 480g of 3,4-difluoronitrobenzene into the high-pressure reactor, mix the above materials, raise the temperature to 120°C and control the pressure of the reactor at 1.7MPa , heat preservation reaction for 18 hours, GC tracking reaction is basically over; after cooling down, the material is pressed into water, and 451.5g of crude product 2-fluoro-4-nitroaniline is precipitated, the filter cake is washed with water and dried, and its content is 98.61%. (GC), the molar yield was 96.4% (based on 3,4-difluoronitrobenzene).

example 2

[0035] (1), pour the concentration of 2000g into a 5000mL four-necked flask and be 20% by weight sulfuric acid and 156g of 2-fluoro-4-nitroaniline prepared in Example 1, heat up to 90°C and keep it warm for 1 hour and then cool down to 0~5℃; Slowly add 235g of NaNO with a concentration of 30% by weight in this solution 2 Aqueous solution, keep warm at 0-5°C for 0.5 hours after adding, filter and remove a small amount of solid impurities to obtain about 2110mL of clear and transparent diazonium liquid, and store at 0-5°C;

[0036] (2), in another 5000mL four-neck flask, add 530g of hydrobromic acid solution with a concentration of 6.5% by weight of copper powder, stir and heat up, cool down to 65°C after being kept at 100°C for 1 hour, and add the above-mentioned prepared solution dropwise. Cold diazonium solution; keep warm for 0.5 hours after dripping, drop to room temperature, filter out orange solid crude product 2-fluoro-4-nitrobromobenzene, wash with water, the content of...

example 3

[0039] (1), in the four-neck flask of 5000mL, pour the concentration of 2000g into the 2-fluoro-4-nitroaniline that makes in the sulfuric acid of 24% by weight and 156g example 1, be heated up to 85 ℃ of insulation 1 hour and cool down to 0~5℃; Slowly add 210g of NaNO with a concentration of 33% by weight in this solution 2 Aqueous solution, keep warm at 0-5°C for 0.5 hours after adding, filter and remove a small amount of solid impurities to obtain about 2100mL clear and transparent diazonium solution, keep it at 0-5°C;

[0040] (2), in another 5000mL four-neck flask, add 530g of hydrobromic acid solution with a concentration of 6.0% by weight of copper powder, stir and heat up, cool down to 65°C after being kept at 100°C for 1 hour, and add the above-mentioned prepared solution dropwise. Cold diazonium solution; keep warm for 0.5 hours after dripping, lower to room temperature, filter out the orange solid crude 2-fluoro-4-nitrobromobenzene, wash with water, the crude 2-fluor...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention relates to a synthesis method of 2-fluoro-4-nitrobenzonitrile and the method comprises the following steps: adopting 2-fluoro-4-nitrophenylamine as raw material, using diazotization bromination to convert -NH2 in 2-fluoro-4-nitrophenylamine to -Br and then using NMP as solvent to perform cyaniding and obtain 2-fluoro-4-nitrobenzonitrile. The invention has the advantage of cheap and accessible raw material, lower toxicity of raw material and capability of industrialized production.

Description

1. Technical field [0001] The invention relates to a synthesis method of 2-fluoro-4-nitrobenzonitrile, in particular to a drug intermediate which can be used as an irreversible inhibitor of tyrosine kinase. 2. Background technology [0002] The English name of 2-fluoro-4-nitrobenzonitrile is 2-Fluoro-4-nitrobenzonitrile, and the molecular formula is C 7 h 3 FN 2 o 2 , is a pharmaceutical intermediate, a pharmaceutical intermediate that can be used as an irreversible inhibitor of tyrosine kinase, which can be used to treat diseases such as cancer, atherosclerosis, restenosis, endometriosis or psoriasis . [0003] At present, there are four main methods for synthesizing 2-fluoro-4-nitrobenzonitrile: [0004] 1. First oxidize 2-fluoro-4-nitrotoluene to 2-fluoro-4-nitrobenzoic acid, then to 2-fluoro-4-nitrobenzamide, and finally to 2-fluoro-4-nitrotoluene benzonitrile; [0005] [0006] Among them, the paper "Exploiting Subsite S1 of Trypsin-Like Serine Proteases for S...

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): C07C255/50C07C253/14
Inventor 赵昊昱蒋涛吴朝华
Owner CHANGZHOU XIAOGUO INFORMATION SERVICES
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