SCH 2304 Aromatic

Reactions
LECTURE 7

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Objectives
• Electrophilic Aromatic Substitution
• Friedel-Crafts alkylation,
• Friedel Crafts acylation, electrophilic metallation.

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EAS Reactions– Friedel-Crafts Acylation and Friedel-Crafts Alkylation discovered
by Charles Friedel and James Crafts:

• Aromatic rings will form C-C bonds when treated with alkyl or acyl halides in the
presence of a strong Lewis acid (e.g. AlCl3). These are known as Friedel Crafts
reactions and are examples of electrophilic aromatic substitution reactions.
• The Lewis acid coordinates to a lone pair on the halogen, making the halogen a
better leaving group.
• In Friedel-Crafts alkylation, an alkyl halide treated with a Lewis acid results in a
carbocation electrophile (or a species very similar to a carbocation) that is then
attacked by the aromatic ring.
• Carbocation rearrangements can occur if they result in a more stable carbocation!
• Friedel-Crafts acylation is performed with acyl halides and Lewis acids. No
rearrangements are observed.

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These reactions follow the familiar three-step pattern seen in previous
electrophilic substitution reactions, namely:
•activation of electrophile with a Lewis acid
•attack of the “activated” electrophile by the aromatic ring
•deprotonation to restore aromaticity
• Friedel-Crafts Alkylation Of Aromatic Rings
•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.
•Generally, no reaction occurs in the absence of Lewis acid. A common choice for
the Lewis acid is aluminum chloride, AlCl3 , but many others may be used, such
as FeCl3 among others.
•Alkyl halides (typically chlorides, bromides, and iodides) must be used, the
reaction fails completely for alkenyl and alkynyl halides
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Alkyl Halide
The role of the Lewis acid here.
Lewis acids “activate” the electrophile by coordinating to the leaving group, making it a
weaker base, and a better leaving group (AlCl4– is a weaker base than Cl– ). The end result is
that coordination of the Lewis acid to the electrophile makes the species
a better electrophile.
For example, with isopropyl chloride (below), the first step is coordination of coordination
of AlCl3 to the chlorine atom. This weakens the C-Cl bond, with the result that the Cl can
depart (as AlCl4– ) to give a secondary carbocation (a
better electrophile than isopropyl chloride itself).
•With secondary and tertiary halides, full dissociation to a carbocation can occur.
•In the case of primary (and methyl) alkyl halides, the electrophile is likely not a “free”
carbocation, but a “carbocation-like” species where the C–Cl bond is considerably
weakened/lengthened.
•As we mentioned briefly, no reaction occurs with alkenyl or alkynyl halides, largely because
the carbocations of these species are so unstable andOnditi
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 The Key C-C Bond Forming Step Is Attack Of The
Aromatic Ring Upon The Carbocation (or carbocation-
like) Electrophile
Once the electrophile has been activated, the next step of
the Friedel-Crafts is attack of the
activated electrophile by the aromatic ring. This is also
the rate-determining step, as it disrupts the aromaticity
of the ring (and its ~36 kcal/mol of resonance energy).

In this step a C–C (pi) bond from the aromatic ring

breaks, and a new C–C sigma bond is formed, leading
to a carbocation intermediate:

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 Intramolecular Friedel-Crafts Alkylation reaction
Mechanism

Intramolecular Friedel-Crafts
Alkylation
The nucleophile is the aromatic
ring, and the electrophile is
the alkyl chloride.
Add a little catalyst (AlCl3) and
boom! electrophilic aromatic
substitution.

note that the overall pattern of bonds that form and bonds
that break is exactly the same in the intramolecular case as it
is in the intermolecular case, namely: form C-C and H-
Cl, break C-H and C-Cl.
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Predict the product from the reaction below.
Answer.

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Limitations of the Freidel-Crafts Alkylation Friedel-Crafts Acylation
1. carbocation rearrangements can occur. [There are A process related to the Friedel-Crafts alkylation,
ways of circumventing this issue indirectly, which we’ll called Friedel-Crafts acylation, was discovered by
hint at below. Friedel and Crafts around the same time (1877). If a
•2. the Friedel-Crafts alkylation tends not to work Lewis acid is added to an acyl halide in the presence
well with electron-poor aromatic rings, particularly of an aromatic ring, an electrophilic
strongly deactivating substituents such as CF3, NO2, aromatic substitution reaction can occur whereby
SO3H,. Halogens are OK. the acyl group adds to the aromatic ring (with loss
• 3. The product of the FC alkylation is often a of HX).
better nucleophile than the starting material. (Recall As with the F.C. alkylation, the specific Lewis acid
that alkyl groups are activating.) it can’t stop at just in the Friedel-Crafts acylation can vary. Aluminum
one, resulting in multiple alkylations. chloride (AlCl3) is often used, but FeCl3 and other
Lewis acids will also do the job.

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A specific example is the reaction between
acetyl chloride and benzene catalyzed by
aluminum chloride.

The acylium ion is the active electrophile in the

Friedel-Crafts acylation reaction. Once formed, the
acylium ion is attacked by the aromatic ring

The Mechanism Of The Friedel-Crafts

Acylation Reaction
Like in FC alkylation, the first step is activation
of the electrophile. Lewis acid coordinates to
the halogen, and departure of the halogen (as
AlCl4–) results in a fairly stable, resonance-
stabilized carbocation know as the “acylium
ion”. Dr Mariah Onditi 12
 The first step here is to perform a Friedel-Crafts
acylation reaction between benzene and
propionylchloride, catalyzed by AlCl3. This gives us
ethyl phenyl ketone.
The next step gives us 1-propylbenzene.
No Rearrangements Occur In The Friedel-Crafts
Acylation
Unlike the Friedel-Crafts alkylation, no
rearrangement occurs with the Friedel-Crafts
acylation.
Friedel-Crafts acylation is used to obtain products
that are otherwise difficult to obtain through the
Friedel-Crafts alkylation due to carbocation
rearrangements. For example, propylbenzene, could
not be made from the Friedel-Crafts alkylation
reaction of benzene with AlCl3 and 1-propylchloride.Dr Mariah Onditi 13
Summary: Friedel-Crafts Alkylation and
Limitations of The Friedel-Crafts Acylation
Acylation
•Similarly to alkylation, Friedel-Crafts
Since they form carbon-carbon bonds, the
acylation tends to fail on aromatic rings with
Friedel-Crafts alkylation and acylation
strongly deactivating groups such as nitro,
reactions are particularly important
CF3, sulfonyl and so on. Halogenated
electrophilic aromatic substitution
aromatics still work, however
reactions. Together with bromination,
chlorination, nitration, and sulfonylation
they round out the six core electrophilic
aromatic substitution reactions.

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The Intramolecular Friedel-Crafts Reaction

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