444
HETEROCYCLES
N
H
N
H
H
N
H
H
+
H
H
N
H
H
H
N
H
H
H
N
H
H
H
favourable resonance
unfavourable resonance;
destroys benzene aromaticity
loss of pyrrole aromaticity;
retains benzene aromaticity
2
3
Similar behaviour is encountered with other
electrophiles, with substitution occurring at C-3.
N
H
N
H
E +
E
H
N
E
H
H
N
H
H
E
N
H
E
H
favourable resonance
unfavourable resonance;
destroys benzene aromaticity
− H +
N
H
E
Indole is very reactive towards electrophiles,
and it is usually necessary to employ reagents
of low reactivity. Nitration with HNO 3 –H 2 SO 4 is
unsuccessful (compare pyrrole), but can be achieved
using benzoyl nitrate.
N
H
O
Ph
O
NO 2
N
H
NO 2
N
H
Br 2
pyridine
N
H
Br
N
H
N
H
Me
MeI
DMF
benzoyl nitrate