Preparation of Acetaminophen (Paracetamol)

Synthesizing an analgesic by amide bond formation

Organic Synthesis Advanced (University) 80 min ~$18.00

Objective

Synthesize acetaminophen (paracetamol) by the acetylation of p-aminophenol with acetic anhydride, demonstrating amide bond formation.

Background

Acetaminophen is one of the world's most widely used over-the-counter analgesics. Its synthesis involves the reaction of p-aminophenol with acetic anhydride to form an amide bond. The reaction is selective for the amine group over the phenol group under mild conditions.

Safety Warnings

  • Acetic anhydride is corrosive and has a strong odor
  • p-Aminophenol can cause skin irritation
  • Do not consume the product
  • Work in a fume hood

Required PPE

goggles gloves lab_coat

Materials

  • p-Aminophenol (1.5 g)
  • Acetic anhydride (2 mL)
    Corrosive
  • Distilled water (100 mL)
    Ice-cold for crystallization
  • Acetone (10 mL)
    For recrystallization

Equipment

250 mL Erlenmeyer flask Hot water bath Buchner funnel Filter flask Melting point apparatus Ice bath

Procedure

1

Dissolve 1.5 g p-aminophenol in 15 mL distilled water in the Erlenmeyer flask. Warm gently if needed.

5 min Handle p-aminophenol with gloves
2

Add 2 mL acetic anhydride to the solution. Stir vigorously for 10 minutes.

10 min Fume hood — pungent vapors
3

Heat the mixture in a water bath at 70°C for 10 minutes to complete the reaction.

12 min
4

Cool the mixture in an ice bath until crystals form.

15 min
5

Collect crude product by vacuum filtration. Wash with cold water.

8 min
6

Recrystallize from hot water or acetone/water mixture. Cool slowly for larger crystals.

15 min
7

Collect purified crystals. Dry and determine melting point (pure: 168-170°C).

10 min
8

Calculate percent yield.

5 min

Expected Results

White crystalline solid with melting point 167-170°C. Typical yield is 70-85%. The product should be pure white; discoloration indicates impurities from p-aminophenol oxidation.

Cleanup

Do not consume the product. Dispose of organic waste properly. Rinse all glassware.

Details

Category
Organic Synthesis
Difficulty
Advanced (University)
Duration
80 min
Est. Cost
$18.00
Steps
8
Materials
4

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Frequently Asked Questions

What is the objective of Preparation of Acetaminophen (Paracetamol)?
Synthesize acetaminophen (paracetamol) by the acetylation of p-aminophenol with acetic anhydride, demonstrating amide bond formation.
How difficult is Preparation of Acetaminophen (Paracetamol)?
This experiment is rated as Advanced (University). It takes approximately 80 minutes to complete.
What safety precautions are needed for Preparation of Acetaminophen (Paracetamol)?
Key safety precautions include: Acetic anhydride is corrosive and has a strong odor; p-Aminophenol can cause skin irritation; Do not consume the product.
What materials are needed for Preparation of Acetaminophen (Paracetamol)?
The main materials required are: p-Aminophenol, Acetic anhydride, Distilled water, Acetone.
What results should I expect from Preparation of Acetaminophen (Paracetamol)?
White crystalline solid with melting point 167-170°C. Typical yield is 70-85%. The product should be pure white; discoloration indicates impurities from p-aminophenol oxidation.