for isoxazole, pyrazole and isothiazole. The aromaticity of these compounds
is due to the delocalization of a lone pair of electrons from the second
hetero-atom to complete the aromatic sextet.
O
N
N
N
H
S
N
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5
Isoxazole
Pyrazole
Isothiazole
The 1,2-azole family of heterocycles is important in medicine. For example,
the following drug used in the treatment of bronchial asthma possesses a
substituted isoxazole system.
N
O
Br
N
OH H
Me
Me
Me
Physical properties of isoxazole, pyrazole and isothiazole
The 1,2-azoles are basic compounds because of the lone pair of electrons on
the nitrogen atom, which is available for protonation. However, these
compounds are much less basic than their isomers, 1,3-azoles, owing to
the electron-withdrawing effect of the adjacent hetero-atom. Some of the
physical properties of these compounds are as follows.
1,2-azoles
pK a
b.p. (
C)
m.p. (
C)
Physical state
Isoxazole
À2.97
95
–
Liquid
Pyrazole
2.52
186–188
60–70
Solid
Isothiazole
–
114
–
Liquid
Preparation of isoxazole, pyrazole and isothiazole
Isoxazole and pyrazole synthesis While 1,3-diketones undergo condensation with hydroxylamine to produce isoxazoles, with hydrazine they yield
corresponding pyrazoles.
R
O
O
R'
N
O
R
R'
N
N R''
R
R'
NH 2 OH
H 2 NNHR''
4.7.4 PYRROLE, FURAN AND THIOPHENE:
159