Chemistry Reference
In-Depth Information
H
H
Cl
H
Cl
Cl
2
+
+
H
Cl
Cl
Cl
Cl
Cl
S
S
S
S
substitution products
addition product
Scheme 55
Substitution and addition products from reaction of thiophene with chlorine [
84
]
+
NCS/H
4
NNO
3
Cl
Cl
Cl
S
S
S
CH
3
CN
59%
10%
Scheme 56
Use of NCS in the presence of ammonium nitrate for chlorination of thiophene [
89
]
When thiophene is treated with chlorine at an equimolar ratio, a mixture of
2-chlorothiophene and 2,5-dichlorothiophene, along with several addition products, is
obtained [
84
]. For the successful isolation of both substitution products, it is necessary
to eliminate addition products. This can be done by heating with solid sodium hydro-
xide or potassium hydroxide, prolonged pyrolysis or steam distillation of the reaction
mixture from aqueous alkali or from a suspension of zinc or iron powder in water. As a
result, the formation of mixtures containing mono-, di-, tri- and tetrachlorinated
thiophenes is observed. The ratio of products is dependent on the reagents ratio,
reaction temperature and dehydro-halogenation method (Scheme
55
)[
84
].
Investigations led to the conclusion that
N
-chlorosuccinimide (NCS) in acetic
acid is the reagent of choice for the selective monochlorination of various thio-
phenes [
85
]. Other chlorinating agents such as sulfuryl chloride, hypochlorous acid
[
86
], benzyltrimethylammonium tetrachloroiodate [
87
] or tin(IV) chloride in the
presence of lead(IV) acetate [
88
] were shown to be useful reagents for thiophene
chlorination.
Ammonium nitrate can be usefully added to NCS for selective aromatic chlori-
nation reactions; thus, 2-chlorothiophene (59% yield) and 2,5-dichlorothiophene
(10%) were obtained after treatment of thiophene with NCS/NH
4
NO
3
in aceto-
nitrile (Scheme
56
)[
89
].
For the bromination of thiophene, bromine and
N
-bromosuccinimide (NBS) are
the most useful reagents [
90
]. As in any electrophilic substitution of thiophene,
halogenations take place preferentially at
-positions. 2-Substituted thiophenes are
usually halogenated at C-5, and 3-substituted thiophenes are halogenated either at
C-2 or at C-5 depending on the substituent.
N
-Bromosuccinimide in a mixture of chloroform and acetic acid (1:1) was
shown to brominate various 3-substituted thiophenes exclusively at C-2 [
91
,
92
]
in yields of 60-97% in 5-30 min (Scheme
57
)[
93
].
In contrast, the bromination of 3-phenylthiophene under ultrasound irradiation
gave exclusively 2-bromo-4-phenylthiophene even with a twofold excess of NBS
(Scheme
58
)[
82
]:
ʱ
