University of Puthisastra

Department of Pharmacy

PW of Organic chemistry

Unit 7: Synthesis of Acetylcysteine by acetylation

 Synthesis of Acetylcysteine by acetylation

Objective :
1. Understand of Principle of acetylation
2. Able use acetylation to synthesis interest compounds as
acetycysteine
 Synthesis of Acetylcysteine by acetylation
I. Introduction
- Acetylcysteine (mucolytic agent ) is used to help thin and loosen
mucus in the airways
- Acetylcysteine was indication in
● Pulmonary Disease

● Acetaminophen Overdose
 Synthesis of Acetylcysteine by acetylation
II. Principle of reaction
➔ Chemical reaction that one atom of compound ( normally H) replaced by the

acetyl radical.

➔ L-Cysteine is directly acetylated with acetic anhydride ( Catalyst : H 2SO4 )

to produce acetylcysteine and a mole of acetic acid.
 Synthesis of Acetylcysteine by acetylation
III. Synthesis of acetylcysteine
➔ Chemicals Required :
- L-Cysteine : 5.4 g ;
- Acetic anhydride : 9.0 ml ;
- Sulphuric acid : 3–4 drops

➔ Procedure of synthesis
- Weigh 5.4 g of L-cysteine and transfer to a conical flask
- Add to the flask 9 ml of acetic anhydride and 3 to 4 drops
of concentrated H2SO4 carefully
- Mix the contents over water-bath at 60°C (20 min )
- Allow the contents of the flask to attain room temperature
 Synthesis of Acetylcysteine by acetylation
III. Synthesis of acetylcysteine
➔ Purify :
- Allow the contents of the flask to attain room temperature
- Pour this solution to 100 ml of cold water in beaker with
frequent stirring with a glass rod
- Filter the crude product on a Büchner funnel using suction, wash
it generously with cold water
- dry the product in an oven maintained at 80°C
- recrystallized from a mixture of rectified spirit and water
(1 : 1)
 Synthesis of Acetylcysteine by acetylation
III. Synthesis of acetylcysteine
➔ Identify :
- Physical Parameters :
● white, crystalline powder having a very slight acetic odour
● Melting point = 104–110°C
● pH of a 1 in 100 solution ranges between 2 to 2.75
● Boiling point = 202°C
● Solubility :
- Water : 1 g in 5 ml - EtOH:1 g in 4 ml
- Ether or chloroform : insoluble
- Coloration identify : 0.5 mL of solution (1g/20ml) + 0.05 mL of a 50 g/L
solution of sodium nitroprusside R and 0.05 mL of concentrated NH 3 → dark
violet colour
References
- A microscale Approach to organic laboratory techniques , Donald
th
L.Pavia,Gary M. Lampman ,5 edition
- Experimental Organic Chemistry : A Miniscale and Microscale
th
Approach, John C. Gilbert ,Stephen F.Martin ,5 edition
th
- Quantitative Chemical Analysis 7 edition , Daniel C.Harris.
- Introduction to Laboratory techniques , Pavia Kriz ,Lampman Engel ,
1998
rd
- Techniques in Organic Chemistry , 3 edition , Jerry R.Mohrig ,
Christina Noring Hammond Paul F.Schatz
th
- Pharmacopeia European ,7 edition ,2010