ACYLATION
ACYL CHLORIDES & ACID ANHYDRIDES
Acyl chlorides, for example ethanoyl chloride CH3COCl, contain the functional group
C=O
Cl
Acid anhydrides, for example ethanoic anhydride (CH3CO)2O, contain the functional
group
C=O
O
C=O
Both acyl chlorides and acid anhydrides are used to carry out acylation reactions.
ACYLATION is the introduction of an RC=O group
Acylation
When acyl chlorides and acid anhydrides react with nucleophiles such as water,
alcohols, ammonia or primary amines, they react via a nucleophilic addition –
elimination reaction.
Acyl chlorides and acid anhydrides both contain a carbonyl group. The carbonoxygen bond in the carbonyl group is polar, because oxygen is more electronegative
than carbon. However, the presence of an additional electron-withdrawing group
polarises the carbonyl group to a greater extent than in aldehydes and ketones. The
carbon atom forms the positive end of the dipole.
+ -
C=O
Cl
The increased electron-deficiency of the carbon atom makes acyl chlorides and acid
anhydrides much more susceptible to attack by nucleophiles than aldehydes and
ketones.
Since the carbon atom of the carbonyl group is sp 2 hybridised, the first step in the
mechanism is addition.
Cl- ions, formed from acyl chlorides, and R.CO.O- ions, formed from acid anhydrides,
are both good leaving groups; this means that elimination follows as a second step in
the mechanism.
The reactions taking place with water and alcohols are:
ethanoyl chloride + water:
CH3COCl + H2O
CH3COOH + HCl carboxylic acid
ethanoic acid
ethanoyl chloride + ethanol:
CH3COCl + C2H5OH
CH3COOC2H5 + HCl
ester
ethyl ethanoate
TOPIC 13.6: ACYLATION 1
ethanoic anhydride + water:
(CH3CO)2O + H2O
2CH3COOH
ethanoic acid
ethanoic anhydride + ethanol:
(CH3CO)2O + C2H5OH
CH3COOC2H5 + CH3COOH
ethyl ethanoate
The mechanisms with water and alcohols are identical.
H3C
C
Cl
O
nucleophilic
addition
CH3
Cl
C
H3C
..
elimination
O
C
+O H
:O H
+O
H
H
O
H
H
:Cl
-
H3C
C
O
HCl
HO
ethanoic acid
H3C
C
Cl
O
nucleophilic
addition
:O R
H
You need to know the
mechanisms of the reactions
with acyl chlorides. The
mechanisms of the reactions
with acid anhydrides are not
required.
CH3
Cl
C
H3C
..
O - elimination
C
+O R
+O
H
O
R
H
:Cl
-
H3C
C
RO
O
HCl
alkyl ethanoate
The mechanisms with ammonia and primary amines are identical. Here, an
intermediate cation is formed, from which a proton is removed by a second molecule
of ammonia or primary amine, acting as a base.
TOPIC 13.6: ACYLATION 2
The reactions taking place with ammonia and amines are:
ethanoyl chloride + ammonia:
CH3COCl + 2NH3
CH3CONH2 + NH4Cl primary amide
ethanamide
ethanoyl chloride + methylamine:
CH3COCl + 2CH3NH2
CH3CONHCH3 + CH3NH3Cl secondary
N-methyl ethanamide
amide
ethanoic anhydride + ammonia:
(CH3CO)2O + 2NH3
CH3CONH2 + CH3COONH4
ethanamide
ethanoic anhydride + methylamine:
(CH3CO)2O + 2CH3NH2
CH3CONHCH3 + CH3COONH3CH3
N-methyl ethanamide
The mechanisms with ammonia and primary amines are identical.
H3C
C
Cl
O
nucleophilic
addition
CH3
Cl
H3C
..
O - elimination
C
C
+
H N H
..
H N H
H
H
O
N+ H
H
H
:NH3
:Cl
H3C
C
O
NH4Cl
H2N
ethanamide
H3C
C
Cl
O
nucleophilic
addition
..
H N R
CH3
Cl
C
+
H N R
H3C
..
elimination
OC
H
H
N+ R
H
H
:NH2R
:Cl
H3C
C
O
RHN
N-alkyl ethanamide
TOPIC 13.6: ACYLATION 3
O
RNH3Cl
Acylation Reactions
Large scale acylation reactions are usually carried out with acid anhydrides. Ethanoic
anhydride is manufactured on a large scale as an acylating agent and is preferred to
ethanoyl chloride because:
 it is cheaper than the acyl chloride
 it is less corrosive, since HCl is not produced
 it is less easily hydrolysed by atmospheric moisture
 it is less dangerous to use: it is less reactive than the acyl chloride and its
reactions are therefore less violent
Ethanoic anhydride is used in the manufacture of the man-made fibre, Tricel from
cellulose and in the manufacture of aspirin (2-ethanoyloxybenzenecarboxylic acid), a
widely used analgesic drug.
Aspirin is made by the acylation of 2-hydroxybenzenecarboxylic acid.
COOH
COOH
OH
+ (CH3CO)2O
TOPIC 13.6: ACYLATION 4
OCOCH3
+ CH3COOH