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Friedel-Crafts Alkylation and Acylation: Mechanisms, Problems, and Solutions, Study notes of Chemistry

An overview of the Friedel-Crafts alkylation and acylation reactions, their mechanisms, and the problems associated with each process. It also discusses methods to address these issues, such as the use of reducing agents and nucleophilic substitution reactions. useful for students and researchers in the field of organic chemistry.

Typology: Study notes

2021/2022

Uploaded on 09/12/2022

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Friedel-Crafts Alkylation
General scheme:
AlCl3or
FeBr3
(R = alkyl) or
Friedel-Crafts Alkylation
Depends on formation of alkyl cation (or “incipient” cation) intermediate:
+
+
or 3° halide:
or CH3halide:
These intermediates react identically in the Friedel-Crafts
alkylation reaction.
pf3
pf4
pf5

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Friedel-Crafts Alkylation

General scheme:

AlCl 3 or FeBr (^3)

(R = alkyl) or

Friedel-Crafts Alkylation

Depends on formation of alkyl cation (or “incipient” cation) intermediate:

2° or 3° halide:

1° or CH 3 halide:

These intermediates react identically in the Friedel-Crafts

alkylation reaction.

Problems with Friedel-Crafts Alkylation

1. Only succeeds for benzene, activated aromatics.

2. Alkylation makes aromatic ring more reactive to

further alkylation.

CH 3 Br FeBr (^3)

CH 3 Br FeBr (^3)

further alkylation

2 nd^ reaction is faster than the 1st^ (because

aromatic ring is activated);

Can’t stop reaction at monoalkylated product.

(Can address by using excess starting material.)

Problems with Friedel-Crafts Alkylation

3. Intermediate cation can rearrange (leading to

unexpected products).

FeBr (^3)

NOT

due to rearrangement of

Characteristics of Combined Friedel-Crafts

Acylation/Clemmensen Reduction

1. Still only succeeds for benzene, activated

aromatics.

2. Acylation makes aromatic ring less reactive to

further acylation.

3. Acylium ion is resonance-stabilized, doesn’t

rearrange.

Electron-withdrawing C=O

deactivates product.

Reducing Carbonyls to Alkyl Carbons

Zn(Hg), HCl/H 2 O

Both useful for converting Friedel-Crafts acylation products to alkylated

aromatic molecules that can’t be made by Friedel-Crafts alkylation.

Clemmensen Reduction Wolff-Kishner Reduction

(acidic conditions)

1. N 2 H 4

2. KOH, 

(basic conditions)

Nucleophilic Aromatic Substitution

Electron-withdrawing groups/atoms facilitate substitution

with nucleophiles. But mechanism not quite like S N 1/S N 2.

Examples:

NaOCH 3 NaOH

Successful only if electron-withdrawing group is ortho- or para- to site of substitution.

Nucleophilic Aromatic Substitution

via the Benzyne Mechanism

NaNH (^2)

NH 3

Pretty unusual.

Works only for -^ OH/H 2 O, -^ NH 2 /NH 3.

benzyne