4-Aminobenzonitrile is a commonly used intermediate in organic synthesis, and can also be used in the synthesis of liquid crystal materials and fragrances. Its common synthetic methods include:
1. Synthesis by ammonolysis method: 4-chlorobenzonitrile is hydrolyzed at room temperature to generate 4-aminobenzonitrile by using ammonia water in ethanol to catalyze.
The operation steps are as follows:
(1) Weigh 4-chlorobenzonitrile (10 g) in a melting point tube, and add ammonia water (30 mL) and ethanol (100 mL).
(2) Stir the mixture, add sodium hydroxide (NaOH) (5 g), and react at room temperature for 24 hours.
(3) After the reaction, adjust the pH value to neutral with hydrochloric acid (HCl) to form a precipitate.
(4) Filter the precipitate and wash with water to collect the solid product.
(5) Wash the solid product with chloroform (CHCl3), filter and collect the organic phase.
(6) Dry the organic phase with anhydrous sodium sulfuric acid (Na2SO4) and filter.
(7) Remove the organic phase solvent with a rotary evaporator, and collect 4-aminobenzonitrile.
The finally obtained 4-aminobenzonitrile can be further used in the synthesis of other organic compounds or in drug research.
2. Synthesis by cyanide method: react 4-chlorobenzonitrile with potassium cyanide to generate 4-cyanobenzonitrile, and then hydrolyze it with ammonia water to obtain 4-aminobenzonitrile. Proceed as follows:
(1) Dissolve 4-aminobenzene in anhydrous hydrochloric acid and cool at 0°C.
(2) Slowly add concentrated nitric acid, the reaction temperature does not exceed 5 ℃, until complete nitrification.
(3) Add the reactant to ice water, filter and wash with water to obtain the nitrated product, namely nitrobenzene.
(4) React nitrobenzene and hydrocyanic acid in ethanol, add sulfuric acid, and heat to 60-70°C for 4-5 hours.
(5) After the reaction, cool to room temperature, add a large amount of water, filter and wash the product with water.
(6) Dissolve the product in an alkaline saturated sodium chloride solution, distill and dry after extraction to obtain the target product 4-aminobenzonitrile.
Precautions:
Pay attention to safety during the operation process, and chemical reagents are dangerous.
Reaction temperature and time need to be well controlled to avoid side reactions and reduce yield.
The product needs to be fully washed and extracted to ensure a pure product.
3. Synthesis by amination method: 4-aminobenzonitrile is produced by reacting 4-chlorobenzonitrile with ethylenediamine at high temperature. Proceed as follows:
(1) Add 4-nitrobenzonitrile to ammonia water, heat to boiling, and react for 2 hours.
(2) The resulting precipitate was filtered and washed with water to obtain 4-aminobenzonitrile.
(3) Dissolve 4-aminobenzonitrile in concentrated sulfuric acid, heat to 80°C, and react for 2 hours.
(4) Cool the reaction solution, add saturated sodium hydroxide solution, and neutralize the reaction solution with sodium carbonate to make it weakly acidic.
(5) Extract the reaction product with chloroform, repeat 3 times, and combine the organic phases.
(6) The organic phase was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate.
(7) Using petroleum ether as a solvent, recrystallize the product to obtain the pure product of 4-aminobenzonitrile.
4. Ortho-position substitution reaction synthesis: through an ortho-position substitution reaction, an amino group is introduced at the ortho-position of 4-nitrobenzonitrile, and 4-aminobenzonitrile is generated after reduction treatment. Proceed as follows:
(1) Put 4-aminobenzonitrile together with aldehyde compounds and acid catalysts into a reaction kettle, heat it to the reaction temperature (usually 100-150°C), and stir during the reaction.
(2) After a period of reaction, stop heating, and let the reaction solution cool down to room temperature.
(3) Add activated carbon into the reaction solution, stir for a period of time, and filter to remove the activated carbon.
(4) Purify the reaction product by washing and crystallization to obtain the desired ortho-substituted product.
Precautions:
Pay attention to safety during the reaction process, and chemical reagents are dangerous.
Reaction temperature and time need to be well controlled to avoid side reactions and reduce yield.
The product needs to be fully washed and extracted to ensure a pure product.
Adding activated carbon in step 3 can remove color impurities in the reaction and improve product purity.
5. Aromatic amination reaction synthesis: 4-phenylacetophenone is produced by reacting acetophenone and aniline under copper catalysis, and then undergoes hydrogen reduction, amidation and hydrolysis to obtain 4-aminobenzonitrile. Proceed as follows:
(1) Add 4-nitrobenzonitrile and reducing agent to ammonia water and react at room temperature for 2-3 hours.
(2) Add hydrochloric acid to the reaction solution, and adjust the pH value to about 3.
(3) Extract the reaction product with chloroform, repeat 3 times, and combine the organic phases.
(4) The organic phase was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate.
(5) Using petroleum ether as a solvent, recrystallize the product to obtain the pure product of 4-aminobenzonitrile.
Precautions:
Pay attention to safety during the reaction process, and chemical reagents are dangerous.
Reaction temperature and time need to be well controlled to avoid side reactions and reduce yield.
The product needs to be fully washed and extracted to ensure a pure product.
Adjusting the pH in step 2 can improve the reaction yield.
Recrystallization in step 5 can improve product purity.
6. Synthesis by nitration reduction reaction: 4-aminobenzonitrile is obtained through nitrosation reduction reaction of p-nitrobenzonitrile. Proceed as follows:
(1) Add benzaldehyde, nitric acid and sulfuric acid into the reaction kettle, and control the reaction temperature at 0-5°C for nitration reaction.
(2) Add hydrogen gas source and platinum black catalyst to carry out reduction reaction. The reaction temperature was controlled at room temperature, and the reaction time was 1 hour.
(3) Add ammonia water to the reaction solution, and adjust the pH value to about 8.
(4) Extract the reaction product with chloroform, repeat 3 times, and combine the organic phases.
(5) The organic phase was washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate.
(6) Using petroleum ether as a solvent, recrystallize the product to obtain the pure product of 4-aminobenzonitrile.
Precautions:
Pay attention to safety during the reaction process, and chemical reagents are dangerous.
Reaction temperature and time need to be well controlled to avoid side reactions and reduce yield.
The product needs to be fully washed and extracted to ensure a pure product.
Adjusting the pH in step 3 can improve the reaction yield.
Recrystallization in step 6 can improve product purity.
The synthesis methods mentioned above have their own advantages and disadvantages, and an appropriate method can be selected for synthesis according to actual needs.