Study of Friedal-Crafts Acylation reaction
Rabiya Javed Awan
Contribution from Department of Chemistry, SBA School of Science and Engineering, Opposite U
Block, 54792, DHA
Received March 5, 2021; Email: 20130026@lums.edu.pk
ABSTRACT: Friedel craft acylation involves the preparation of functionalized aromatic ketones
by the electrophilic substitution reaction of benzene derivative with acetyl chloride in the
presence of a Lewis acid catalyst. In this experiment, p-methyl acetophenone was synthesized
by the electrophilic substitution reaction of toluene and acetyl chloride in presence catalyst
AlCl3. Product (methyl acetophenone) was obtained in a form of viscous liquid in a moderate
yield. TLC was taken to signify that the reaction is complete. IR spectrum, GC-MS data showed
close correspondence with literature values, ascertaining the formation and purity of the
product.
INTRODUCTION
Friedel–Crafts (FC) reaction is a fundamental
method for obtaining functionalized aromatic
ketones. It follows electrophilic aromatic
substitution mechanism. Traditionally, the FC
acylation of benzenes with acid chlorides has
been carried out in the presence of protic acids
or strong Lewis acid catalyst. When an alkyl
halide is treated with a Lewis acid in the presence
of an aromatic ring, the alkyl group can be added
to the ring (forming C-C) with the loss of a C-H
bond. This electrophilic aromatic substitution
reaction is known as the Friedel-Crafts
alkylation reaction. A process related to the
Friedel-Crafts alkylation, called Friedel-Crafts
acylation, also was discovered by Friedel and
Crafts. A Friedel-Crafts acylation is an
electrophilic aromatic substitution reaction that
introduces an acyl group onto an aromatic ring.
The electrophile is an acyl cation that is often
coupled to a Lewis acid catalyst, such as
aluminum chloride. For the reaction to take
place, the aromatic ring system must be very
electron rich and thus cannot contain any
electron withdrawing groups. The reaction was
discovered around the same time (1877) when
Friedel Crafts worked on alkylation 1.
Friedal craft acylation has few limitations such as
the halide must be an alkyl halide. Vinyl or aryl
halides do not react (their intermediate
carbocations are too unstable). Alkylation
reactions
are
prone
to
carbocation
rearrangements. Polyalkylation can be a problem
since the product is more reactive than the
starting material. This can usually be controlled
with an excess of the benzene. The Lewis acid
catalyst AlCl3 often complexes to aryl amines
making them very unreactive 2.
Traditionally, the FC acylation of benzenes with
acid chlorides has been carried out in the
presence of protic acids or strong Lewis acid
catalysts. Lewis acids such as AlCl3, BF3, TiCl4,
Rabiya Javed Awan, LUMS School of Science and Engineering
ZnCl2, SbCl5, Fe2(SO4)3 and strong protic acids
such as HF and H2SO4 have been employed in
these reactions. In particular, the use of metal
halides causes problems 1) associated with the
strong complex formed between the ketone
product and the metal halide itself which
provokes the use of more than stoichiometric
amounts of catalyst. The workup commonly
requires hydrolysis of the complex, leading to the
loss of the catalyst and giving large amounts of
corrosive waste streams. 2) Moreover, these
Lewis acids are moisture sensitive and cannot be
recovered and reused after the reactions are
complete. Due to these draw backs, during the
past decade, the setting up of more ecocompatible Friedel-Crafts acylations has become
a fundamental goal of the general “green
revolution” that has spread in all fields of
synthetic chemistry3. Moreover, following are the
few limitations of Friedel craft acylation:




Acylation can only be used to give
ketones. This is because HCOCl
decomposes to CO and HCl under the
reaction conditions.
Deactivated benzenes are not reactive to
Friedel-Crafts conditions
The Lewis acid catalyst AlCl3 often
complexes to aryl amines making them
very unreactive.
Amines and alcohols can give competing
N or O acylations rather than the require
ring acylation.
Besides its limitation, Friedel craft acylation is has a
significant importance in the field of chemistry,
Vitamin D, DNA, and many other important
compounds in our bodies all includes an aromatic
portion 4 5. But it is very difficult for an aromatic ring
to react with other compounds because it is so stable.
So, to add an aromatic ring to the rest of the molecule
to form these important molecules in our body,
Friedel-Crafts Acylation method is used by
scientist. The reaction is used commonly in food
additives6 and fragrances among other uses.
Development of new catalytic transformations
with easy separation and recyclability of the
catalyst is an essential task in chemical synthesis
due to a very high importance of the aromatic
ketones which are key intermediates in several
fields
including
fine
chemicals
and
7
pharmaceuticals . Friedel–Crafts acylation of
substituted benzenes proceeded smoothly in the
presence of a catalytic amount (5–20%) of
lanthanide triflates. Aluminium, titanium and
ytterbium bis(triflate)imides were found to be
highly effective in acylation reactions of anisole
and diphenyl ether. Aromatic ketones can also be
prepared by the reaction of carboxylic acids with
aromatic compounds catalyzed by Brønsted
acids
such
as
methane-sulfonic
acid,
polyphosphoric
acid,
NafionH,
trifluoromethanesulfonic acid and combinations
of Lewis acids–Bronsted acids 3.
Another important factor is regioselectivity.
Regioselectivity is a process that favors
bond formation at a particular atom over other
possible atoms. The selectivity of the reaction is
determined by the the ability of existing
functional groups on the benzene ring to stabilize
the high energy arenium intermediate in the
reaction. The arenium ion formed by ortho paraattack is more stabilized due to complete octet.
Moreover, the arenium ion formed by Meta
attack is in return slightly stabilized than benzene
because charge is slightly reduced by electronRabiya Javed Awan, LUMS School of Science and Engineering
donating character of the group. Electron
donating stabilizes the arenium ion by dispersing
the positive charge 8.
Electron donating groups (EDG) with lone pairs
(e.g. -OMe, -NH2) on the atoms adjacent to the π
system activate the aromatic ring by increasing
the electron density on the ring through a
resonance donating effect 9. The resonance only
allows electron density to be positioned at the
ortho- and para- positions. Hence these sites are
more nucleophilic, and the system tends to react
with electrophiles at these ortho- and paraposition.
Figure 1: Resonating structure
substituted with activating group.
for
benzene
Electron withdrawing groups (EWG) with π bonds
to electronegative atoms (e.g. -C=O, -NO2)
adjacent to the π system deactivate the aromatic
ring by decreasing the electron density on the
ring through a resonance withdrawing effect. The
resonance only decreases the electron density at
the ortho- and para- positions 10. Hence these
sites are less nucleophilic, and so the system
tends to react with electrophiles at the Meta
sites.
Figure 2: Resonating structure
substituted with deactivating group.
for
benzene
Halogen’s substitutions are little unusual as they
are very electronegative. This means that
inductively they are electron withdrawing.
However, due to their ability to donate a lone
pair of electrons in resonance forms, they are
activators and ortho/para directing. The
inductive effect lowers the reactivity, but the
resonance effect controls the regio-chemistry
due the stability of the intermediates. Because
they are electron withdrawing, halogens are very
weak activators. Friedel Craft acylation of
benzene produces both orth para directing
acetophenone.
Figure 3 (a): p- methylacetophenone and (b): omethylacetophenone
This investigation aims at acylation of aromatic
compound according to the following reaction:
First step is the formation of acylium ion to form
strong electrophile by reaction with lewis acid 5.
Rabiya Javed Awan, LUMS School of Science and Engineering
EXPERIMENTAL SECTION
Chemicals and materials:
Chlorobenzene,
Dichloromethane,
Acetyl
chloride, aluminum chloride, heptane, and
ethanol.
Figure 4: Synthesis of Acylium ion.
Acylium ion formed is resonance stabilized.
Figure 5: Resonance structure of acylium ion.
This acylium ion is then attacked by the benzene
ring.
Figure 6: Mechanism for acylation of Toluene
Glassware and equipment:
Round bottom flask (100 mL), stir bar, reflux
condenser, hot plate, stem funnel, beaker (100
mL +250 mL), extension clamps and fasteners,
grease, aluminum foil, watch glass, ice bath,
melting point capillaries, oil bath and Buchner
funnel.
Procedure:
Anhydrous aluminum chloride (27.17 mmol) was
suspended in methylene chloride (7 ml) in a twoneck round-bottomed flask suspended in an ice
bath. A solution of acetyl chloride (27.17 mmol)
in methylene chloride (5 ml) was added dropwise
to the flask using a syringe at 0οC and the
resulting mixture was stirred for 10 minutes
followed by the addition of a solution of the
aromatic compound (5.43 mmol) in methylene
chloride (5 ml) using a syringe. Once the addition
was completed, heat the reaction to a gentle
reflux for 1 hour. A small quantity of the product
was used to be spotted on a TLC plate, along with
the reactants and standard. TLC was run in a
solvent system of ethyl acetate and hexane in 7:
13 ratios to analyze the completion of reaction.
Isolation of Product: After that the reaction
mixture was poured slowly to three-fold water.
Extraction process in this experiment was carried
out by separating funnel. By carefully planning
out and washing sequences (using DCM and
water), the desired products was separated from
most of the unwanted impurities. The solution
Rabiya Javed Awan, LUMS School of Science and Engineering
was then dried on MgSO4, filtered and solvent
was evaporated on rotary evaporator to get the
final product. The yield of final product was
calculated. Finally, product was analyzed using IR
spectrum and GC-MS.
Mass of product obtained
(Actual Yield)
Percentage yield of product
𝐴𝑐𝑡𝑢𝑎𝑙 𝑦𝑖𝑒𝑙𝑑
𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑦𝑖𝑒𝑙𝑑
RESULTS AND DISCUSSION
0.54 g
0.54
× 100
0.72
= 75 %
× 100 %
The percentage yield obtained is around 75 %.
The loss of product in yield could be due to
improper handling.
GC-MS:
Figure 7: Balanced equations for the reactions
C:\Xcalibur\...\AM-LAB-4_200305112641
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RT: 0.00 - 31.10
7.67
100
Physical properties of reactants:
NL:
3.60E8
TIC MS
AM-LAB4_2003051
12641
90
Relative Abundance
80
Table 1: Physical properties of reactants
70
60
50
40
30
20
10
Toluene
Molar
mass
Density
g/cm3
Melting/boiling
point °C
92.14
0.865
g/mL
110.6
3.60 3.92
4.47 5.81
0
1.104
g/mL
52
Aluminum
chloride
133.34
-
190
2
3
4
5
6
7
9.66
8
9
10
10.76
11.82
11
12
13.14 13.63
13
14
15.08 15.60 16.44
15
16
Time (min)
17
18.11 18.86
18
19
20.77 21.29 22.44 23.26
20
21
22
23
24
24.89
26.09
25
26
27.36
27
28.72 29.24
28
70
Moles of acetyl chloride
0.02717
Limiting Reagent
Toluene
Moles of product expected
0.00543
Mass of product expected
(Theoretical Yield)
= 0.00543
× 134.17
= 0.72 𝑔
31
91.17
60
50
40
134.17
30
65.15
90.33
77.14
92.16
136.20
0
50
100
176.25
150
207.22
200
245.99 267.17 280.88
250
300
327.10 340.78
383.90 398.81
350
400
425.87
466.33
450
504.08
500
528.41
595.12 611.41
550
600
m/z
Figure 3: GC-MS of methyl acetophenone
Table 2: Percentage yield of (methyl)acetophenone
0.00543
30.74
30
80
Percentage yield of the product:
Moles of toluene used
29
90
10
78.5
1
AM-LAB-4_200305112641 #250 RT: 7.67 AV: 1 NL: 1.18E8
T: {0,0} + c EI Full ms [50.00-700.00]
119.16
100
20
Acetyl
chloride
7.57
0
Relative Abundance
Reagent
Figure 4: MS fragmentation pathway for p-methyl
acetophenone
The spectrum attached shows that retention time
for sample is 31.10 minutes.
Molecular ions peak at m/z = 134.17
Rabiya Javed Awan, LUMS School of Science and Engineering
665.69
650
813
Para
substitution
Out-of-Plane
C-H Bending
735
Ortho
substitution
Out-of-Plane
C-H Bending
IR Spectrum:
The C=O stretching peak in acetophenone is
lower than the C=O peak of ketone due to
conjugation. The large intense peak at 813 cm-1
shows that the para methyl acetophenone is
obtained as major product while ortho is minor
product. This is due to the steric hindrance effect.
As methyl group, which is already substituted on
benzene, slightly creates steric hindrance on the
close carbons making the attack difficult for the
acylium ion on the adjacent positions (ortho
position) of substituent. The IR spectrum was in
consonance with those reported in literature 6.
4000
3500
3000
2500
Wavenumber cm-1
2000
1500
813.57
735.70
672.17
636.54
590.69
566.73
1429.92
1405.65
1356.98
1265.63
1181.44
1112.56
1075.09
1044.86
953.28
1736.67
1678.98
1605.39
1573.63
1933.58
3030.67
3003.15
2924.33
2872.19
30
40
50
Transmittance [%]
60
70
80
90
100
The base peak at m/z =119.21
The fragment ion peak at m/z = 91.17: elucidate
the structure of toluene (loss of acetyl group)
while the peak at 77.13 elucidates the pattern of
benzene.
1000
500
Figure 5: IR spectrum of 4-methylacetophenone.
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Post Lab Questions
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The major peaks obtained in the IR spectrum of
Product methyl acetophenone are interpreted as
follow:
Table 3: The peaks and associated groups with methyl
acetophenone
Frequency (cm-1)
Functional
Group
Vibration
1679
C=O (sp2)
Stretching
1429 - 1605
C=C (sp2)
Aromatic
Stretching
3000 - 3030
C-H (sp2)
Stretching
2872.19 -3003
C-H (sp3)
Stretching
1356 - 1405
C-H (sp3)
Bending
1. Discussion of the lab report related to
this experiment should encompass the
directing ability of substrate, electronic
and steric effects of preexisting
substitutes on the benzene ring.
The pre-existing functional substituents are any
functional group which is already attached to
benzene ring before it undergoes Friedel craft
reaction. The groups determine the reaction
direct by resonance and induction effect.
Resonance effect is the conjugation between the
ring and the substituent, which means the
delocalizing of the ππ electrons between the ring
and the substituent. Inductive effect is the
withdraw of the sigma (the single bond) electrons
away from the ring toward the substituent, due
to the higher electronegativity of the substituent
compared to the carbon of the ring.
Rabiya Javed Awan, LUMS School of Science and Engineering
The reaction of a substituted ring with an
activating pre-existing group is faster than
benzene. On the other hand, a substituted ring
with a deactivated group is slower than benzene.
The activating group directs the reaction to the
ortho or para position, which means the
electrophile substitute the hydrogen that is on
carbon 2 (ortho) or carbon 4 (para). The
deactivating group directs the reaction to the
meta position, which means the electrophile
substitute the hydrogen that is on carbon 3
(meta) except for the halogens that is a
deactivating group but directs the ortho or para
substitution.
intermediate step, thus; the activation energy is
increased which slows down the reaction.
Figure 7: Substate with activating group or electron
donating group.
Ortho and Para products produces a resonance
structure which stabilizes the arenium ion. This
causes the ortho and para products for form
faster than meta. Generally, the para product is
preferred because of steric effects. As Existing
groups can provide steric hindrance on the
positions in close carbons making the attack of
adjacent positions by the substituents difficult.
Figure 6: Products of activating and deactivating
group.
The substrate has a huge role to determine the
reactivity of benzene ring and moreover the
possible product to come out. Activating groups
speed up the reaction because of the resonance
effect. The presence of the unpaired electrons
that can be donated to the ring, stabilize the
carbocation in the transition state. Thus,
stabilizing the intermediate step, speeds up the
reaction; and this is due to the decrease of the
activating energy. On the other hand, the
deactivating groups, withdraw the electrons
away from the carbocation formed in the
Figure 8: Substrate with deactivating group or
electron withdrawing group.
Whereas. Electron withdrawing groups are resonance
deactivators. Ortho and para-attack on such
substrates produces a resonance structure which
places the arenium cation next to and additional
cation. This destabilizes the arenium cation and slows
down ortho and para reaction. Hence, the meta
product forms faster because it lacks this destabilizing
resonance structure.
CONCLUSIONS
Rabiya Javed Awan, LUMS School of Science and Engineering
Methyl acetophenone was synthesized in
moderate yield (75%) by the reaction of toluene
with acetyl chloride in the presence of Lewis acid
as a catalyst, through Friedel craft acylation
reaction. The reactants along with catalyst were
moderately heated with gentle reflux for 1 hr.
The product was extracted through separating
funnel with dichloromethane and dried through
rotavap. Around 75% of the product yield was
obtained. The product was successfully
characterized through IR, GCMS and NMR. The
peak at 1678 cm-1 in IR spectrum depicts the
presence of C=O of acetophenone in product.
The peak at 813 cm-1 shows that para methyl
acetophenone is obtained as major product. The
results of GCMS and IR are in accordance with
the literature value.
6.
7.
8.
9.
10.
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Rabiya Javed Awan, LUMS School of Science and Engineering