Chemistry Reference
In-Depth Information
Me
Me
O
Me
O
Me
K
2
CO
3
,DMF
then
R
2
NH
DMF, 70 °C
CS
2
then
M
e
I
O
MeS
O
85%
SMe
57
Me
Me
O
O
Me
Me
HSCH
2
CO
2
Et
DMF, 70 °C
O
N
O
N
CO
2
Et
S
SMe
O
Scheme 79 The synthesis of a 3-acyl-2-aminothiophene starting from carbon disulfide [
127
]
N
N
N
N
N
N
R
2
NH
DMF, 70 °C
·
Na
2
S
9H
2
O, 70 °C
-
Na
+
MeS
SMe
N
SMe
N
S
58
N
N
Bn
Bn
N
NH
2
BrCH
2
CO
2
Et, 50 °C
K
2
CO
3
,50°C
50%
N
CO
2
Et
S
N
Bn
Scheme 80 The synthesis of a 3-aminothiophene-4-nitrile [
127
]
Cl
Cl
Cl
NC
NC
NC
HSCH
2
CO
2
Et
Et
3
N, EtOH
NaH, DMF
then
CS
2
,
then i
-PrI, 60 °C
i
-PrS
O
O
i
-PrS
CO
2
Et
92%
59
82%
S
i
-Pr
S
Scheme 81 The reaction of a 2-cyanoketone enolate with carbon disulfide giving a 3-cyano
thiophene [
128
]
A comparable ketene dithioacetal 58 derived from malononitrile in the same
way can also be converted into thiophenes, in these cases with an additional primary
amino group at C-3, derived from one of the nitrile substituents (Scheme
80
)[
127
].
Similar use of the enolate from a 2-cyanoketone, e.g. 59, results in the formation
of a 3-cyanothiophene (Scheme
81
)[
128
].
If two equivalents of the 2-halo-carbonyl compound (or 2-halo-nitrile) are
utilised to react with an enolate/carbon disulfide adduct, double S-alkylation and
then double ring closure produce thieno[2,3-
b
]thiophenes [
129
]; Scheme
82
shows
how this works. Taking this idea further, if a malonate is used as the 1,3-dicarbonyl
component, 3,4-dihydroxythieno[2,3-
b
]thiophenes are the final result (Scheme
83
)
[
130
], the ring closure steps then having the character of Claisen condensations. If
malononitrile is used instead of a 1,3-dicarbonyl compound, the product is a
3,4-diaminothieno[2,3-
b
]thiophene - product 60 in Scheme
84
is the result of
using chloroacetonitrile in the alkylation step [
131
].
