CN113121358A - Preparation method of 2-bromo-5-fluoro-4-nitroaniline - Google Patents
Preparation method of 2-bromo-5-fluoro-4-nitroaniline Download PDFInfo
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- CN113121358A CN113121358A CN201911409371.4A CN201911409371A CN113121358A CN 113121358 A CN113121358 A CN 113121358A CN 201911409371 A CN201911409371 A CN 201911409371A CN 113121358 A CN113121358 A CN 113121358A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
- C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
- C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst
- C07C209/365—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst by reduction with preservation of halogen-atoms in compounds containing nitro groups and halogen atoms bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
Abstract
The invention relates to the field of chemistry, in particular to a preparation method of 2-bromo-5-fluoro-4-nitroaniline. Step A: adding 1.3 parts of iron powder and 0.1 part of ammonium chloride into a reaction system, refluxing and adding 1 part of raw material, adjusting alkali after the reaction is finished, adjusting the pH to 9, and distilling water vapor to obtain a product for later use; and B: adding 0.6 part of acetic anhydride with the concentration of 99% into 1 part of the product obtained in the step A, heating to 80 ℃, keeping for 1 hour, and reacting to obtain a product for later use; and C: adding 6.5 parts of sulfuric acid with the concentration of 98% into 1 part of the product obtained in the step B, dropwise adding 0.4 part of nitric acid, reacting for 1 hour at 20-30 ℃, performing ice decomposition, and centrifuging to obtain a product for later use; step D: and C1 parts of the product obtained in the step C is added into 4 parts of dilute hydrochloric acid with the concentration of 15%, the temperature is increased to 100 ℃, hydrolysis is carried out for 3 hours, the temperature is reduced to T <40 ℃, and the product is obtained after centrifugation. The invention has the advantages of simple and easily obtained raw materials, low cost, no toxicity of intermediate products and high production efficiency.
Description
Technical Field
The invention relates to the field of chemistry, in particular to a preparation method of 2-bromo-5-fluoro-4-nitroaniline.
Background
2-bromo-5-fluoro-4-nitroaniline is an antitumor drug, and most of the existing preparation methods of 2-bromo-5-fluoro-4-nitroaniline adopt 3-fluoro-4-nitrobenzoic acid to react with sodium azide to generate 3-fluoro-4-nitroaniline which is then brominated to obtain a final product; in the process, the market demand of the raw material 3-fluoro-4-nitrobenzoic acid is small, and sodium azide is generated in the generation process and is extremely toxic, so that the risk of the sodium azide in the use process is avoided, and the production process is high in cost and poor in safety.
Disclosure of Invention
Aiming at the problems, the invention provides a preparation method of 2-bromo-5-fluoro-4-nitroaniline to solve the defects in the prior art.
The technical scheme of the invention is as follows:
a process for preparing 2-bromo-5-fluoro-4-nitroaniline with the following reaction formula
The preparation method comprises the following steps: the dosage is calculated according to the weight portion ratio,
step A: adding 1.3 parts of iron powder and 0.1 part of ammonium chloride into a reaction system, refluxing and adding 1 part of raw material, adjusting alkali after the reaction is finished, adjusting the pH to 9, and distilling water vapor to obtain a product for later use;
and B: adding 0.6 part of acetic anhydride with the concentration of 99% into 1 part of the product obtained in the step A, heating to 80 ℃, keeping for 1 hour, and reacting to obtain a product for later use;
and C: adding 6.5 parts of sulfuric acid with the concentration of 98% into 1 part of the product obtained in the step B, dropwise adding 0.4 part of nitric acid, reacting for 1 hour at 20-30 ℃, performing ice decomposition, and centrifuging to obtain a product for later use;
step D: and C1 parts of the product obtained in the step C is added into 4 parts of dilute hydrochloric acid with the concentration of 15%, the temperature is increased to 100 ℃, hydrolysis is carried out for 3 hours, the temperature is reduced to T <40 ℃, and centrifugation is carried out to obtain the product, wherein P is more than 98%.
The base was 30% NaOH.
The nitric acid is fuming nitric acid.
The main advantages of the invention are: the invention has the advantages of simple and easily obtained raw materials, low cost, no toxicity of intermediate products and high production efficiency.
Detailed Description
The present invention is described in detail below by way of examples.
Example 1
A preparation method of 2-bromo-5-fluoro-4-nitroaniline is characterized by comprising the following steps: the reaction chemical formula is as follows
The preparation method comprises the following steps:
1. a preparation method of 2-bromo-5-fluoro-4-nitroaniline is characterized by comprising the following steps: the reaction chemical formula is as follows
The preparation method comprises the following steps: the dosage is calculated according to the weight portion ratio,
step A: adding 1.3kg of iron powder and 0.1kg of ammonium chloride into a reaction system, refluxing and adding 1kg of raw materials, adjusting alkali after the reaction is finished, wherein the alkali is 30% NaOH, adjusting the pH value to 9, and distilling water vapor to obtain a product for later use;
and B: adding 0.6kg of 99% acetic anhydride into 1kg of the product obtained in the step A, heating to 80 ℃, keeping for 1h, and reacting to obtain a product for later use;
and C: adding 6.5kg of 98% sulfuric acid into 1kg of the product obtained in the step B, dropwise adding 0.4kg of nitric acid which is fuming nitric acid, reacting at 20-30 ℃ for 1h, carrying out ice decomposition, wherein ice exists in an ice decomposition solution all the time, and centrifuging to obtain a product for later use;
step D: and (3) adding 1kg of the product obtained in the step (C) into 4kg of dilute hydrochloric acid with the concentration of 15%, heating to 100 ℃, hydrolyzing for 3h, cooling to T <40 ℃, and centrifuging to obtain a product, wherein P is greater than 98%.
Effect
After the product is produced, the product is transferred to a QC department, and the product is detected by HPLC/GC to obtain the product meeting the customer index, wherein the final yield is about 64 percent, and the purity is 99.4 percent through detection.
Claims (3)
1. A preparation method of 2-bromo-5-fluoro-4-nitroaniline is characterized by comprising the following steps: the reaction chemical formula is as follows
The preparation method comprises the following steps: the dosage is calculated according to the weight portion ratio,
step A: adding 1.3 parts of iron powder and 0.1 part of ammonium chloride into a reaction system, refluxing and adding 1 part of raw material, adjusting alkali after the reaction is finished, adjusting the pH to 9, and distilling water vapor to obtain a product for later use;
and B: adding 0.6 part of acetic anhydride with the concentration of 99% into 1 part of the product obtained in the step A, heating to 80 ℃, keeping for 1 hour, and reacting to obtain a product for later use;
and C: adding 6.5 parts of sulfuric acid with the concentration of 98% into 1 part of the product obtained in the step B, dropwise adding 0.4 part of nitric acid, reacting for 1 hour at 20-30 ℃, performing ice decomposition, and centrifuging to obtain a product for later use;
step D: and C1 parts of the product obtained in the step C is added into 4 parts of dilute hydrochloric acid with the concentration of 15%, the temperature is increased to 100 ℃, hydrolysis is carried out for 3 hours, the temperature is reduced to T <40 ℃, and centrifugation is carried out to obtain the product, wherein P is more than 98%.
2. The process for producing 2-bromo-5-fluoro-4-nitroaniline according to claim 1, wherein: the base was 30% NaOH.
3. The process for producing 2-bromo-5-fluoro-4-nitroaniline according to claim 1, wherein: the nitric acid is fuming nitric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911409371.4A CN113121358A (en) | 2019-12-31 | 2019-12-31 | Preparation method of 2-bromo-5-fluoro-4-nitroaniline |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911409371.4A CN113121358A (en) | 2019-12-31 | 2019-12-31 | Preparation method of 2-bromo-5-fluoro-4-nitroaniline |
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| CN113121358A true CN113121358A (en) | 2021-07-16 |
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| CN201911409371.4A Pending CN113121358A (en) | 2019-12-31 | 2019-12-31 | Preparation method of 2-bromo-5-fluoro-4-nitroaniline |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1974540A (en) * | 2006-12-18 | 2007-06-06 | 上海染料研究所有限公司 | Prepn process of 2,5-dichloro-p-phenylenediamine |
| US20130237725A1 (en) * | 2012-03-09 | 2013-09-12 | Zhang-Lin Zhou | 2,5-disubstituted-1,4-diaminobenzenes |
| CN105130948A (en) * | 2010-04-22 | 2015-12-09 | 弗特克斯药品有限公司 | Pharmaceutical compositions and administrations thereof |
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2019
- 2019-12-31 CN CN201911409371.4A patent/CN113121358A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1974540A (en) * | 2006-12-18 | 2007-06-06 | 上海染料研究所有限公司 | Prepn process of 2,5-dichloro-p-phenylenediamine |
| CN105130948A (en) * | 2010-04-22 | 2015-12-09 | 弗特克斯药品有限公司 | Pharmaceutical compositions and administrations thereof |
| US20130237725A1 (en) * | 2012-03-09 | 2013-09-12 | Zhang-Lin Zhou | 2,5-disubstituted-1,4-diaminobenzenes |
Non-Patent Citations (1)
| Title |
|---|
| ZAIRA DOMINGUEZ ET AL.: "Molecular Compasses and Gyroscopes with Polar Rotors:Synthesis and Characterization of Crystalline Forms", 《J. AM. CHEM. SOC.》 * |
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Application publication date: 20210716 |