Preparation of
Acetanilide
O
H3C
N
H
Acetanilide
N-Phenyl-acetamide
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Contents:- An introduction to Amides.
- Classification of amides.
- Physical properties of acetanilide.
- Solubility of acetanilide.
- Uses of acetanilide.
- Preparation method.
- Mechanism of reaction.
- Procedure.
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An introduction to amides
Amides are derivatives of organic acid
(Carboxylic acid) with the general formula (RCO-NR2)
in which a carbon atom is attached to oxygen in double
bond and also attached to an amino group.
R1
O
R
C
N
R2
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Classification of amides
Amides are divided into three types, according to
the substituents on nitrogen.
1- Primary amides:When R1 and R2 equal to hydrogen group.
R1
O
R
C
H
N
C
H3C
N
H
O
H
O
C
N
H
H
R2
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Formamide
Acetamide
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Classification of amides
2- Secondary amides:When R1 or R2 substituted by an alkyl or phenyl group.
CH3
O
H
C
N
H
H
N-Methyl-formamide
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C
CH3
O
O
H3C
N
H
N-Phenyl-formamide
C
N
H
N-Methyl-acetamide
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Classification of amides
3- Tertiary amides:When both R1 and R2 substituted by an alkyl or phenyl group.
CH3
O
H
C
N
H
CH3
N,N-Dimethyl-formamide
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C
CH3
O
O
H3C
N
CH3
C
N
CH3
N-Methyl-N-phenyl-formamide N,N-Dimethyl-acetamide
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Amides in daily life:
The simplest naturally occurring amide is urea, a water-soluble white solid produced in
the human body from carbon dioxide and ammonia through a complex series of
metabolic reactions
Urea is a one-carbon diamide. Its molecular structure is
Urea formation is the human body’s primary method for eliminating “waste” nitrogen.
The kidneys remove urea from the blood and provide for its excretion in urine. With
malfunctioning kidneys, urea concentrations in the body can build to toxic levels.
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The complex amide melatonin is a hormone that is synthesized by the pineal gland
and that regulates the sleep–wake cycle in humans. Melatonin levels within the body
increase in evening hours and then decrease as morning approaches. High melatonin
levels are associated with longer and more sound sleeping
Lidocaine (xylocaine), a substance commonly administered by injection as a dental
anesthetic, is a synthetic molecule that contains both amide and amine functional
groups
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Acetanilide
O
H3C
N
H
Acetanilide
N-Phenyl-acetamide
1- Acetanilide is a solid organic compound, type secondary amide
with white to grey color, an odorless.
2- The molecular weight of acetanilide (135) and molecular
formula is (C8H9NO), with melting point (115C0) and boiling point
(304C0).
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Solubility of acetanilide
Acetanilide soluble in hot water ,alcohol (small alcohol) ethanol
and methanol, ether, chloroform, acetone, glycerol, and benzene.
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Preparation method
1- Reaction of aniline with acetyl chloride.
NH2
O
O
C
+
Aniline
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H3C
NH C
CH3
+ HCl
Cl
Acetyl chloride
Acetanilide
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Preparation method
2- Reaction of aniline with an ester.
NH2
O
O
C
+
Aniline
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H3C
An ester
R
NH
C
CH3
+
R
OH
O
Acetanilide
Al cohol
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Preparation method
3- Reaction of aniline with acetic acid.
NH2
O
O
C
+
Aniline
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H3C
NH
C
CH3
+ H2O
OH
Acetic acid
Acetanilide
Water
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Preparation method
4- Reaction of aniline with acetic anhydride.
Today’s Reaction
The Synthesis of Acetanilide, an Amide, through a
Nucleophilic Acyl Substitution (addition / elimination)
reaction between Aniline, an Amine, acting as the
Nucleophile, and an Acyl group from Acetic Anhydride
acting as the Electrophile.
The Reaction
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Uses of acetanilide
1- Chemically it used to prepare several substituted
aromatic compounds, such as sulfanilamide
O
H2N
S
NH2
O
sulfanilamide
2- Industrially it used as a dye in dying process.
3-Pharmaceutically it used as intermediate to prepare
several drugs such as acetaminophen
OH
O
N
H
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acetaminophen
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Procedure
1-In a conical flask containing (60ml) of distilled water add (2ml) of concentrated
hydrochloric acid (HCl).
2- Add (3ml) of aniline to the solution with shaking.
3- Add (3ml) of acetic anhydride to the solution in a small portion, using a
burette for such addition. then boil the solution to about (5min).
4- Add (10ml) of (10%) sodium bicarbonate to the hot solution.
5- Cool the solution at room temperature, then in an ice bath.
6- Separate the produced precipitate from the solution by filtration process.
7- Dry, weight out then calculate percentage yield of the prepared acetanilide.
8- All the addition should be stepwise inside the hood.
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 Safety
 Acetic Anhydride causes irritation of tissue,
especially the nasal passages.
 Aniline is toxic, can be absorbed through the
skin
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