What is Acetanilide?
Acetanilide is an important organic compound that is vastly used in the pharmaceutical industry. It is an odourless, white, solid, or flaky compound. Its preparation method is used to introduce students to the synthesis of organic compounds in chemistry labs. It is prepared by acetylation of aniline.
Aim
To prepare acetanilide from aniline, glacial acetic acid (acetic anhydride) and zinc dust.
Theory
On heating, aniline reacts with acetic anhydride in presence of zinc dust and glacial acetic acid and yields acetanilide. Thus, formed acetanilide is recrystallized to get pure crystals. The purpose of using zinc dust is to prevent the oxidation of aniline during the reaction. The chemical reaction involved in the preparation of acetanilide is given below
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Acetanilide is also known as N-phenylacetamide, N-phenylethylamine, and methanol.
Requirements
Round bottom flask of 100 ml, wire gauze, tripod stand, burner, clamp, reflux condenser, stirrer, filter paper, beaker, pipette, electronic balance, iron stand, measuring cylinder, aniline (20 ml), acetic anhydride, and glacial acetic acid mixture (40 ml), zinc dust.
Procedure
Wash all the apparatus with distilled water carefully before starting the experiment.
Add a 20 ml aniline and 40 ml mixture of acetic anhydride and glacial acetic acid in a round bottom flask of 100 ml.
Keep stirring the reaction mixture.
Now add zinc dust to the flask.
Fix a water reflux condenser to the round bottom flask containing the reaction mixture using clamps and an iron stand.
Now fix the round bottom flask on the burner for heating the reaction mixture using a tripod stand, wire gauze, and sand bath. Keep heating the mixture for 30-40 min.
Keep stirring the mixture.
Now pour the reaction mixture from the round bottom flask into a beaker containing ice-cold water.
Keep stirring the mixture.
Once all acetanilide is precipitated, filter the reaction mixture.
Thus, obtained acetanilide crystals are crude or not pure so a recrystallization process should be carried out.
For Recrystallization
Dissolve crude acetanilide in 50 ml distilled water using a beaker and stirrer.
Add a bit of ethanol as well.
Now heat this solution until it gets clear and keep stirring it as well. After this you will get a solution almost like this
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Now cool down the solution and filter it.
Let the crystals dry. You will get the crystals almost looking like this
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If you want to get more pure crystals of acetanilide then you can perform the recrystallization process twice.
Determine the melting point of the crystals obtained.
Observation Table
Result
Weight of the acetanilide crystals obtained = _____g. Its melting point is 115℃.
Precautions
Aniline is a carcinogenic compound so it must be handled very carefully.
Don’t inhale the fumes of acetic anhydride.
Always dry the crystals before taking their weight and melting point to avoid any error due to moisture.
Keep stirring the reaction mixture during the experiment. Vigorous heating is a must when the mixture is added to ice-cold water.
Various Acetanilide Tests
Beilstein Test
Acetylation reaction will usually convert aniline into acetanilide during the Beilstein test. Through the acetylation process, the amine will be converted into its acetamide analogue. The goal was to test two reactions and identify an unknown amine/acetamide product.
Aniline HCl (concentrated HCl is 37% w/w) is used during this process.
Experiment Process
In 14 ml of water, dissolve the aniline 500 mg. It should be noted that aniline is not water-resistant and two layers must be considered. 0.45 mL of concentrated acid is added.
Prepare a 530 mg solution of sodium acetate in 3 mL of water and 0.6 mL of anhydride. Swipe the aniline hydrochloride anhydride solution in water, and immediately add the sodium acetate solution
As acetanilide passes, the response becomes white. Cool the solution in the ice bath before vacuum filtering to collect solid acetanilide. Rehydrate water from 95 percent ethanol - a small amount of tiny water is needed.
To start the Beilstein test, clean the copper cord by holding it in place for a while. Return the cord to the oven after touching it in a composite sample. The presence of halogen is indicated by the presence of blue within the flames. Before trying the procedure on your own, it is a good idea to test it on a compound known to contain halogen.
Green Method
Green Process: Acetanilide is soluble in ethanol in a very round flask. Water is then added to dissolve the barrier and ceric nitrate. This solution has been added to the add-on. call drop, this solution was added to the acetanilide solution during the conical flask.
After completion of the addition, white crystals are formed after stirring the reaction mixture for 10 minutes in the heat. Then pour a glass of cold drinking water. The solid was separated from the white crystals using a dry Buchner panel. The melting point is 114.3 °C.
Because aniline cannot be replaced by p - due to re-activation (aniline nitration produces trinitroaniline), acetylation is performed before chlorosulfonation. As a result, monosubstituted sulfonamide cannot be detected.
When aniline is used, electrophilic switching occurs in o- and p-positions, but in acetanilide, electrons are exposed to the ring and rarely contain C carbonyl, resulting in electron deficiency due to polarization.
During chemical reactions, zinc is used to stop aniline from oxidizing. Acetanilide is an important component of the drug and is used as a febrifuge.
Acetylating aniline containing anhydride within strong acids may also produce acetanilide. Aniline is dissolved in acid, then anhydride is added and mixed well. Pour the mixture into a glass of water containing sodium acetate. Ethyl alcohol is usually absorbed by the isolate and also acts on acetanilide.
Uses of Acetanilide in Daily Life
Acetanilide is a colourless, glossy chemical that can be used to make plates.
It is used in photography.
Acetanilide is also used as a mild anaesthetic to treat high fever.
FAQs on Preparation of Acetanilide
1. What is acetanilide and what is its chemical nature?
Acetanilide, also known as N-phenylacetamide, is an odourless, white, flaky solid organic compound. It is an amide derived from aniline. The preparation of acetanilide is a classic example of an acetylation reaction, a type of nucleophilic acyl substitution, commonly performed in school and college chemistry labs to demonstrate organic synthesis.
2. What is the basic principle behind the preparation of acetanilide from aniline?
The preparation of acetanilide is based on the acetylation of aniline. In this reaction, the lone pair of electrons on the nitrogen atom of aniline's amino group (-NH₂) acts as a nucleophile, attacking the electrophilic carbonyl carbon of acetic anhydride. An acetyl group (CH₃CO-) replaces one of the hydrogen atoms of the amino group, forming an amide linkage and converting aniline into acetanilide.
3. What are the main reagents used to prepare acetanilide and what is the specific role of each?
The key reagents and their functions in the synthesis of acetanilide are:
- Aniline (C₆H₅NH₂): This is the primary substrate or starting material which gets acetylated.
- Acetic Anhydride ((CH₃CO)₂O) and Glacial Acetic Acid: This mixture acts as the acetylating agent, providing the acetyl group that attaches to the aniline molecule.
- Zinc Dust (Zn): This is added to prevent the oxidation of aniline. Aniline can be easily oxidised, especially upon heating, which would result in unwanted coloured by-products. Zinc acts as a reducing agent, preserving the aniline for the main reaction.
4. Why is recrystallization a crucial final step in the preparation of acetanilide?
Recrystallization is essential for purification. The initially formed acetanilide is a crude product, often contaminated with unreacted aniline, excess acetic acid, and other side-products. This process exploits the fact that acetanilide is sparingly soluble in cold water but highly soluble in hot water. By dissolving the crude solid in a minimum amount of hot water and then allowing it to cool, pure acetanilide crystallizes out, while the impurities remain dissolved in the cold water (mother liquor).
5. What is the reaction mechanism for preparing acetanilide from aniline and acetic anhydride?
The mechanism is a nucleophilic acyl substitution. It begins with the nucleophilic attack of the nitrogen atom of aniline on one of the carbonyl carbons of acetic anhydride. This forms a tetrahedral intermediate. Subsequently, the intermediate collapses, eliminating an acetate ion (a good leaving group), and a proton is transferred from the nitrogen atom to form the stable amide product, acetanilide, along with acetic acid as a by-product.
6. Why is acetic anhydride preferred over acetyl chloride for acetylating aniline in a typical laboratory setting?
Acetic anhydride is preferred over acetyl chloride for several practical reasons:
- Reactivity: The reaction with acetic anhydride is less vigorous and more easily controlled than the highly exothermic and rapid reaction with acetyl chloride.
- By-products: Acetylation with acetic anhydride produces acetic acid, which is a weak acid and relatively easy to handle. In contrast, using acetyl chloride produces corrosive and hazardous hydrochloric acid (HCl) gas.
- Safety and Handling: Due to its more moderate reactivity and less hazardous by-product, acetic anhydride is considered safer for student laboratory experiments.
7. What are the main industrial or commercial applications of acetanilide?
Acetanilide is an important chemical intermediate with several applications. It is primarily used in the synthesis of pharmaceuticals, particularly sulpha drugs. Historically, it was used as an analgesic (painkiller) and antipyretic (fever-reducer) under the name Antifebrin, though this use is now limited due to its toxicity. It also serves as a precursor in the production of certain dyes and as a stabiliser for hydrogen peroxide solutions.
8. What are the most important safety precautions to follow while preparing acetanilide in the lab?
When preparing acetanilide, it is crucial to observe the following safety measures:
- Handle aniline with care, preferably in a fume hood, as it is toxic and potentially carcinogenic.
- Avoid inhaling the fumes of acetic anhydride, as it is corrosive and irritating to the respiratory system.
- Always wear appropriate personal protective equipment (PPE), including safety goggles and gloves.
- Ensure the setup, especially the reflux condenser, is properly clamped to prevent the escape of volatile reagents.
