than thiazole itself. Some examples of electrophilic substitutions of oxazole,
imidazole and thiazoles and their derivatives are presented below.
S
N
OMe
N
S
O 2 N
OMe
S
N
OMe
O 2 N
N
N
H
N
N
H
O 2 N
H 2 SO 4
− H +
+
+ HNO 3
H 2 SO 4
+ HNO 3
∆
F 3 C
O
CF 3
O
O
O
N
N
Me
Me
Ph
O
N
N
Me
Me
O
F 3 C
Ph
O
N
N
Me
Me
O
F 3 C
Ph
+
− CF 3 CO 2
−
− H +
+
Nucleophilic aromatic substitutions 1,3-azoles are more reactive than
pyrrole, furan or thiaphene towards nucleophilic attack. Some examples of
nucleophilic aromatic substitutions of oxazole, imidazole and thiazoles and
their derivatives are given below. In the reaction with imidazole, the
presence of a nitro-group in the reactant can activate the reaction because
the nitro-group can act as an electron acceptor.
N
N
H
S
Br
O 2 N
N
N
S
O 2 N
+
+ HBr
No activation is required for 2-halo-1,3-azoles, which can undergo nucleophilic aromatic substitutions quite easily.
O
N
Cl
NH 2
O
N
N
H
Ph
+
∆
+ HCl
S
N
Br
S
N
OMe
+ NaOMe
∆
+ NaBr
4.7.7 Isoxazole, pyrazole and isothiazole
Isoxazole, pyrazole and isothiazole constitute the 1,2-azole family of
heterocycles that contain two hetero-atoms, one of which is a nitrogen
atom. The second hetero-atom is oxygen, nitrogen or sulphur, respectively,
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CH4 ORGANIC FUNCTIONAL GROUPS