Chemistry Reference
In-Depth Information
Pyridine, on the other hand, is more reactive
than benzene towards
nucleophilic aromatic sub-
stitution
. This is effectively reaction towards the
C
=
N 'imine' function, as described above. Attack is
principally at positions 2 and 4, as predictable from
resonance structures of reaction intermediates. Attack
at the 3 position does not allow the nitrogen to help
stabilize the negative charge.
H
−
−
attack at
position 2
2
H
Nu
H
Nu
H
Nu
Nu
N
N
N
N
Nu
N
Nu
Nu
H
Nu
H
Nu
H
Nu
H
−
attack at
position 4
−
4
N
N
N
N
N
H
H
H
attack at
position 3
Nu
Nu
Nu
Nu
3
N
N
N
N
However, for an unsubstituted pyridine, the leaving
group to finish off this reaction is hydride, which
is a strong base and thus a poor leaving group
(see Section 6.1.4). It may be necessary to use an
oxidizing agent to function as hydride acceptor to
facilitate this type of hydride transfer. Nevertheless,
there is a classic example of this process, known
as the
Chichibabin reaction
, in which pyridine is
converted into 2-aminopyridine through heating with
sodium amide.
Chichibabin reaction
NaNH
2
H
H
H
NH
2
NH
2
N
N
N
N
H
H
2
O
H
2
N
NH
2
N
NH
The hydride released appears to abstract a proton
from the product since the other product of the
reaction is gaseous hydrogen. The aminopyridine
anion is finally quenched with water. The product is
mainly 2-aminopyridine, probably the result of the
enhanced inductive effect on carbons immediately
adjacent to the electronegative nitrogen.
It is much more effective to have a better leav-
ing
4-
chloropyridines
react with a number of nucle-
ophiles to generate substituted products. Note that
one can predict from the resonance structures
that 3-chloropyridine, despite having a satisfactory
leaving group, would not be susceptible to nucle-
ophilic substitution at position 3. It is not possi-
ble in the addition anion to share the charge with
nitrogen.
group
in
the
pyridine
system.
Thus
2-
or
