Chemistry Reference
In-Depth Information
HNO
3
/Ac
2
O
AcOH
10
o
C
NO
2
S
S
70-85%
Scheme 84
Use of HNO
3
with Ac
2
O in AcOH for nitration of thiophene [
127
]
NO
2
S
Cu(NO
3
)
2
+
S
S
S
Ac
2
O
62
17%
23%
Scheme 85
Use of Cu(NO
3
)
2
in Ac
2
O for nitration of 2,5-dimethylthiophene [
132
,
133
]
NO
2
(NH
4
)
2
Ce(NO
3
)
5
NO
2
+
Ac
2
O, rt
S
S
S
58%
12%
Scheme 86
Use of CAN in Ac
2
O for nitration of thiophene [
135
]
Early attempts to nitrate thiophene and to reduce a nitro-product, in analogy with
benzene chemistry, were unsuccessful until the conditions for nitration of thiophene
were found. Eventually, rather special conditions were developed: thiophene
vapour mixed with air was passed for several hours through fuming nitric acid.
After work-up, mononitrothiophene and a dinitrothiophene were isolated [
125
].
Later it became clear that the failure in thiophene nitration with nitric acid is
due to the presence of nitrous acid that led to the formation of nitrosothiophene,
which is prone to decomposition [
126
]. Amixture of nitric acid with acetic anhydride
in glacial acetic acid can mononitrate thiophene very effectively (Scheme
84
)[
127
].
Other useful thiophene-nitrating reagents include copper(II) nitrate in acetic
anhydride and aluminium nitrate in acetic anhydride [
128
,
129
]. Nitration of
substituted thiophenes is subject to the usual mesomeric and inductive effects of
the substituents [
130
]. Nitration can also take place at already substituted positions,
replacing bromine or iodine (see, e.g. [
131
]). The nitration of
2,5-dimethylthiophene using copper(II) nitrate in acetic anhydride led to
2,5-dimethyl-3-nitrothiophene along with a product containing two thiophene
rings - 3-(5-methylthien-2-ylmethyl)-2,5-dimethylthiophene
62
(Scheme
85
)
[
132
,
133
]. Apparently, the cation ThCH
2
+
was formed under the reaction condi-
tions which reacted as electrophile towards a second molecule of starting thiophene.
Cerium(III) ammonium nitrate (CAN) in acetic anhydride is also an efficient
nitrating reagent for aromatic compounds [
135
]. The nitration of thiophene by CAN
gave a mixture of 2-nitro- (58%) and 3-nitrothiophene (12%) (Scheme
86
)[
134
].
