23.

8
The Elimination-Addition Mechanism
of Nucleophilic Aromatic Substitution:
Benzyne
Aryl Halides Undergo Substitution When
Treated With Very Strong Bases

KNH2, NH3
Cl NH2
–33°C

(52%)
 Regiochemistry

new substituent becomes attached to either

the carbon that bore the leaving group or
the carbon adjacent to it

CH3 CH3 CH3

Br NaNH2, NH2
NH3
+
–33°C
NH2
 Regiochemistry

new substituent becomes attached to either

the carbon that bore the leaving group or
the carbon adjacent to it
CH3 CH3 CH3

NaNH2, NH3
+
–33°C
NH2

Br NH2
Regiochemistry CH3

NH2
NaNH2, NH3 –33°C

CH3 CH3 CH3

NH2
+ +
NH2

NH2
Same result using 14C label

* Cl

KNH2, NH3 –33°C

NH2

* + * NH2

(52%) (48%)
 Mechanism

Step 1

H
••
H Cl ••
••
–
• NH2
H H •••

H
 Mechanism

Step 1

H H
•• •• –
•• Cl •
H Cl •• H ••
•
••
–
• NH2
H H ••• H
H NH2
••
H H
compound formed in this step is called benzyne
 Benzyne

H
Benzyne has a strained triple bond.
It cannot be isolated in this reaction, but is
formed as a reactive intermediate.
 Mechanism

Step 2

H
–
•• NH2
••
H

H
 Mechanism

Step 2

H H

H H –
– ••
•• NH2
••
H H NH2
••
H H
Angle strain is relieved. The two sp-hybridized
ring carbons in benzyne become sp2 hybridized
in the resulting anion.
 Mechanism

Step 3

H H NH2
••
H –
••

H NH2
••
H
 Mechanism

Step 3
–
H •• NH2 H H NH2
•• ••
H H H –
••

H NH2 H NH2
•• ••
H H
 Hydrolysis of Chlorobenzene

14C labeling * Cl
indicates that
the high-
temperature NaOH, H2O 395°C
reaction of
chlorobenzene
OH
with NaOH
goes via
benzyne. * + * OH

(43%) (54%)
 23.9
Diels-Alder Reactions of Benzyne
 Other Routes to Benzyne

Benzyne can be prepared as a reactive

intermediate by methods other than treatment of
chlorobenzene with strong bases.
Another method involves loss of fluoride ion
from the Grignard reagent of 1-bromo-2-
fluorobenzene.
 Other Routes to Benzyne

Br MgBr
Mg, THF
•• heat ••
F •• F ••
•• ••

+ FMgBr
 Benzyne as a Dienophile

Benzyne is a fairly reactive dienophile, and

gives Diels-Alder adducts when generated in
the presence of conjugated dienes.
 Benzyne as a Dienophile

Br
Mg, THF
+
heat
F
(46%)