Chemistry Reference
In-Depth Information
O
MeO
OMe
O
O
O
O
R
R
EtO
OEt
O
O
=
,
,
,
S
S
S
S
S
70
69
R
R
R
R
HCHO (aq), HNR
1
R
2
NR
1
R
2
AcOH
S
S
HNR
1
R
2
= HNMe
2
, piperidine, morpholine
HCHO, HNR
3
R
4
2 equiv HCHO, 2 equiv HNR
1
R
2
AcOH
AcOH
R
R
R
R
R
1
R
2
N
NR
1
R
2
R
1
R
2
N
NR
1
R
2
S
S
71
Scheme 98
Mannich reactions of 3,4-dialkoxythiophenes [
153
]
For the synthesis of compounds
66
and
67
(Fig.
3
), 3-methoxythiophene was
treated with chlorosulfonic acid initially at
78
C. Reaction with dimethylamine
gave the sulfonamide
68
(Scheme
97
), which was further converted through several
steps into final products [
151
].
2.7 Aminoalkylation of Thiophene: The Mannich Reaction
Thiophene was successfully aminoalkylated for the first time [
152
] by heating
thiophene with formaldehyde and ammonium chloride in 45% yield, together
with several side products [
21
].
The Mannich reaction of 3,4-dialkoxy-thiophenes was investigated [
153
]: sev-
eral Mannich bases and bis-Mannich bases were obtained under standard condi-
tions: secondary amine and aqueous formaldehyde (37%) in glacial acetic acid
(Scheme
98
)[
153
].
It was shown that thiophene
70
is the most reactive and thiophene
69
is the least
reactive in Mannich reactions [
153
]. Moreover, mixed aminomethyl thiophenes
71
could also obtained by this simple method [
153
].
Thiophenes reacted with methylamines through oxidative C-H/C-H cross-
coupling in the presence of iron(II) chloride tetrahydrate, KI, and 2,2
0
-bypyridine
[
154
], giving products
72
in moderate to good yields (Scheme
99
).
