CHEM2401, CHEM2911, CHEM2915

Lecture 16

Friedel & Crafts

A/Prof Peter Rutledge

peter.rutledge@sydney.edu.au
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From Lecture 15:

General reaction mechanism

E+ (E+ = electrophile)

slow = rate determining step

E E E

H H H

WHELAND INTERMEDIATE
fast

Intermediate is resonance stabilised but not aromatic

E
Positive charge is shared at ortho and para positions to
point of attachment of the incoming electrophile
Friedel-Crafts alkylation – 1
Discovered accidentally by Charles Friedel and James Crafts, when
trying to make Cl from I in a reaction with AlCl
3

in benzene - they obtained alkyl benzenes instead

Charles Friedel James Mason Crafts

(1832–1899) (1839–1917)

Figures from www.todayinsci.com

 Friedel-Crafts alkylation – 2

R
R X
AlX3

Requires presence of Lewis acid (AlCl3 or AlBr3)

Reaction of the Lewis acid with the alkyl halide genrates a carbocation equivalent (very good electrophile!)

e.g.

H
AlCl3
Cl + HCl

85%

Worksheet – Q1
 The reaction mechanism – 1
2

3 3 3

3 3 3

4
Worksheet – Q2: Mechanism
The reaction mechanism – 2

From secondary alkyl halide

The reaction mechanism – 3

From tertiary alkyl halide

SN
Other routes to carbocations for Freidel-Crafts
F H
H

HF

62% yield
0 °C

HF

0 °C

OH H2SO4

0 °C
Limitations of the Freidel-Crafts alkylation – 1

Worksheet – Q3
Limitations of the Freidel-Crafts alkylation – 2
Limitations of the Freidel-Crafts alkylation – 3
It is difficult to stop after a single substitution. Polyalkylation often occurs.

e.g.

AlCl3
Cl + +

exactly 1:1 ratio

of starting materials

major product

forms first, but is more reactive than

benzene itself

Worksheet – Q4
Limitations of the Freidel-Crafts alkylation – 4
Carbocation electrophiles can undergo rearrangements, leading to a mixture of products
e.g.
AlCl3
+ Cl
5 oC +

45% 55%

AlCl3
+ Cl +
0 oC
35%
65%
Why? Carbocations can rearrange - generally to give more stable carbocation

CH2 CH3
AlCl4 AlCl4
H H H

For more on carbocation rearrangements, see Week 4 Video and Pre-lecture Quiz
Limitations of the Freidel-Crafts alkylation – 5
Remember that carbocations can rearrange by either a hydride shift or an alkyl shift:
H
Hydride shift H
CH2
AlCl4 H AlCl4
H H H
Alkyl shift

AlCl3
+
Cl
only product!
H3C alkyl shift CH3
CH2 AlCl4 CH2 AlCl4

reacting electrophile

For more on carbocation rearrangements, see Week 4 Video and Pre-lecture Quiz
 Friedel-Crafts acylation
O

AlCl3 R
O O
O acyl group
AlCl3 R H3 O + R
+ R Cl
80 oC
+ HCl

Electrophile:

O O O
O AlCl3
AlCl3 + AlCl4
R Cl
R Cl
R R

acylium cation
Worksheet – Q5: Mechanism
Mechanism of the Friedel-Crafts acylation
Scope of the Friedel-Crafts acylation
 tert-Butylation is reversible (like sulfonation)
This is useful for synthesis of compounds with unusual substitution patterns.

SO3H H
99% H2SO4 dil. aq.
SO3
or SO3/conc. H2SO4 H2SO4, 160 °C

CH3
CH3
C H
(CH3)3Cl/AlCl3 CH3 dil. aq.
H3C CH3
H2SO4, 160 °C

Driving force is increase in entropy. Both these reactions are

electrophilic aromatic substution with H+ as the electrophile
Worksheet – Q6
Lecture 16 – Summary
1. Friedel-Crafts reactions follow an electrophilic aromatic substitution (SEAr) mechanism to make new C–
C bonds to aromatic rings.
2. Friedel-Crafts alkylations use alkyl halides, Friedel-Crafts acylations use acyl halides; both require
Lewis acid catalysis
3. No reaction with vinyl or aryl halides, nor when there is an electron withdrawing group attached to the
aromatic ring.
4. Multi-alkylation and carbocation rearrangements are also potential problems with Friedel-Crafts
alkylation reactions.
5. Friedel-Crafts acylation reactions offer greater control: no rearrangement issues, no multiple acylation.
Home reading …

Electrophilic aromatic substitution overview – 1

Home reading …

Electrophilic aromatic substitution overview – 2

E+ (E+ = electrophile)

slow = rate detemining step

E E E

H H H

WHELAND INTERMEDIATE
fast

Intermediate is resonance stabilised but not aromatic

E
Positive charge is shared at ortho and para positions to
point of attachment of the incoming electrophile
Home reading …

Electrophilic aromatic substitution overview – 3

Clayden, Greeves & Warren: Organic Chemistry, 2e. p478

Home reading …

Electrophilic aromatic substitution overview – 4

Clayden, Greeves & Warren: Organic Chemistry, 2e. p478