5-Fluoro-2-nitroaniline is an important nitrogen-containing aromatic compound, which is widely used in pharmaceuticals, dyes, materials and other fields. Various synthetic methods of 5-fluoro-2-nitroaniline will be introduced below.
1. Firstly, the synthesis of 5-fluoro-2-nitroaniline by aromatic nitration reaction is introduced. The raw materials for the reaction are p-fluoronitrobenzene and concentrated nitric acid, the reaction conditions are generally at room temperature, the mass ratio of the reactants is 1:1.3~1.5, and the reaction time is more than 10 hours. During the reaction, it is necessary to control the temperature and add a diluent to promote the reaction. The synthesized product is a reddish-brown mud, which can be crystallized and washed to obtain 5-fluoro-2-nitroaniline. The principle is that under the action of strong electrophilic nitrogen ion (Nitronium ion, NO2+), the hydrogen atom on the aromatic ring of the aromatic compound is replaced by a nitro group (Nitro group, -NO2), thereby forming a nitro compound. Specific steps are as follows:
Step 1: Preparation of nitrated mixed acid
Before preparing 5-fluoro-2-nitroaniline, it is necessary to prepare nitrated mixed acid. Nitrating mixed acid, that is, a mixture of nitric acid and concentrated sulfuric acid, is a commonly used nitrating agent in the preparation of nitro compounds. Concrete preparation steps are as follows:
(1.) Under certain cooling conditions, slowly drop concentrated sulfuric acid into the cooled concentrated nitric acid;
(2.) The prepared mixed nitrating acid should be fully cooled and stored in a closed organic solvent distillation device.
Step 2: Synthesis of 5-fluoro-2-nitroaniline
After preparing the nitrated mixed acid, the synthesis of 5-fluoro-2-nitroaniline can be carried out. Specific steps are as follows:
(1.) Dissolve 5-fluoro-2-aminophenylacetic acid in sodium hydroxide solution, extract with ether and dry. The product was obtained: 5-fluoro-2-nitrophenylacetic acid.
(2.) Dissolve 5-fluoro-2-nitrophenylacetic acid in nitrating mixed acid, and add excess concentrated sulfuric acid. The theoretical molar ratio of the reactants is 1:2:3.
(3.) While adding the reactants, keep the temperature of the reaction mixture not exceeding 5°C. After reacting for 1-2 hours, filter and wash the precipitate with ice water, and finally extract it with ether to obtain 5-fluoro-2-nitroaniline .
Summarize:
Through the above steps, 5-fluoro-2-nitroaniline can be successfully synthesized. It should be noted that the aromatic nitration reaction is very dangerous, and the operator needs to have very high chemical experiment skills and operating experience. When carrying out this reaction, the safety operating procedures of the laboratory should be strictly followed, and safety should be the primary consideration.
2. The second method is through the nitrification reaction catalyzed by phosphorus pentoxide. The specific operation is to dissolve 2-amino-5-fluorophenol in acetone, and then add a small amount of phosphorus pentoxide. Add nitric acid into the reaction system in a titration form, and maintain the temperature of the reaction system below 0°C during the reaction. After the reaction is completed, the reaction product is washed with water, dissolved with dilute acid and purified by crystallization to obtain 5-fluoro-2-nitroaniline. Specific steps are as follows:
1. Prepare the reactants: mix the organic compound containing amino groups with nitric acid, and add phosphorus pentoxide catalyst.
2. The catalyst works: the phosphorus pentoxide catalyst plays a catalytic role and accelerates the reaction rate.
3. Dehydration reaction: Under the catalysis of phosphorus pentoxide, the hydrogen ion (H+) in the nitric acid molecule undergoes a dehydration reaction to generate nitroso ion (NO2-) and water molecule (H2O).
4. Oxidation reaction: Nitroso ions react with phosphorus pentoxide catalyst to produce oxygen and nitrate ions (NO2+).
5. Addition reaction: Nitro ions attack the amino groups in organic molecules to form nitroso compounds.
6. Further oxidation: The nitroso compound is further oxidized by the phosphorus pentoxide catalyst and converted into a nitro compound.
7. Crystallization or extraction: According to needs, the obtained nitro compounds are separated by crystallization or extraction.
In conclusion, through the nitration reaction catalyzed by phosphorus pentoxide, we can convert the amino groups in organic molecules into nitro groups. This reaction has a wide range of applications in medicine, chemical industry, dyes and other fields.
3. The third synthetic method is to obtain the target product from the amino compound through the amination reaction of C-N bond formation. The reaction first obtains ethyl 2-amino-5-fluorobenzoate, and then carries out ammonolysis reaction through the action of a catalyst. Commonly used catalysts are ferrous salts, copper salts, etc. Add alkaline substances such as sodium hydroxide into the reaction system, heat the reaction, and under the abnormal action of sodium salt, the reaction will generate 5-fluoro-2-nitroaniline.
The experimental steps are as follows:
(1.) First dry the isopropylamine in a desiccator to ensure that the isopropylamine used in the reaction does not contain moisture.
(2.) Mix 5-fluoro-2-nitrobenzoic acid and isopropylamine at a ratio of 1:2 and add to a 500ml round bottom flask.
(3.) Add acid catalyst. Generally, concentrated sulfuric acid or phosphoric acid is used as the acid catalyst. In this experiment, we will use concentrated sulfuric acid as the acid catalyst. Slowly add 25 mL of concentrated sulfuric acid into the flask.
(4.) Put the flask into a reaction kettle, and add isopropylamine that has just been boiled dry for the introduction of amino groups. Several spiral stirrers should be added to the reactor to ensure that the reactants at the bottom do not settle.
(5.) Turn on the agitator and react at a temperature of 140-150°C for 2-3 hours. Nitrogen can be used to cool and control the reaction temperature during the reaction.
(6.) After the reaction is over, cool the reaction mixture with cold water, add sodium hydroxide solution to the mixture, and neutralize the sulfuric acid therein.
(7.) Filter the mixture, and wash the filtered solid with hot ethanol.
(8.) The prepared product can be identified by chemical analysis methods such as NMR and IR.
4. The last method presented is the synthesis of 5-fluoro-2-nitroaniline by reduction reaction. Dissolve 5-fluoro-2-nitrophenol in an alcohol solvent, add sodium borohydride as a reducing agent, and heat the reaction until the end of the reaction. After the reaction is finished, acid is added for acidification treatment, and the reaction product is washed with ethanol and water to obtain pure 5-fluoro-2-nitroaniline. The following are the specific steps for the synthesis of 5-fluoro-2-nitroaniline:
(1.) Synthesis of 2-fluoro-5-nitroaniline: react 2-amino-5-fluoronitrobenzene and acetic acid in the presence of sulfuric acid to obtain 2-fluoro-5-nitroaniline.
(2.) Reduction reaction: Dissolve 2-fluoro-5-nitroaniline in acetone, add excess sodium sulfite, and carry out reduction reaction under reflux heating conditions. Stop heating after the reaction is complete, and wash with water to obtain 5-fluoro-2-nitroaniline.
The specific mechanism of the reduction reaction:
Sodium sulfite forms sodium bisulfite in water. This substance has good reducibility and can exchange with the nitro group in nitroaniline to form a more stable nitrosoaniline. Then, under the continuous action of the reducing agent, the addition reaction of hydrogen atoms occurs in the nitrosoaniline to obtain 5-fluoro-2-nitroaniline.
In the experimental operation, it is necessary to control the temperature and reaction time to avoid excessive reduction and by-products. In addition, the excessive use of sodium sulfite can increase the yield of the reduction reaction.
The above are a variety of synthetic methods for 5-fluoro-2-nitroaniline, each method has its own advantages and disadvantages, and a suitable synthetic method can be selected according to actual needs. Among them, the cost of synthesis through nitration reaction is low but the safety risk is high, while the synthesis cost of reduction reaction is high but less dangerous, so it needs to be carefully selected.