Chemistry Reference
In-Depth Information
SH
3.0 eq Li
NH
3
(liq)
+
+
+
COOR
COOR
COOH
COOH
COOH
S
SH
S
7%
5%
78%
9.5%
Scheme 116
Birch reduction of thiophene-2-carboxylic acid [
135
]
R
2
R
2
R
2
R
1
=H,R
2
=H
R
1
=CH
3
,R
2
=H
R
1
=H,R
2
=CH
3
heating
5.0 eq Li
NH
3
(liq)
R
1
R
1
COOH
COOH
SH
S
R
1
S
O
Scheme 117
Ring opening of thiophene-2-carboxylic acids under Birch conditions [
135
]
R
2
R
2
R
1
R
2
Yield (%)
1. Li/NH
3
2. NH
4
Cl
Me
H
75
50
R
1
R
1
COOLi
COOH
S
S
Me
H
Scheme 118
Birch reduction of lithium thiophene carboxylate salts [
136
]
this compound was difficult, due to its susceptibility to further reduction or reduc-
tive cleavage under the reaction conditions. Therefore, a final mixture of partially
reduced product and ring-opened compounds was obtained, as illustrated in
Scheme
116
[
135
].
When five equivalents of lithium metal were employed in the Birch reduction of
thiophene-2-carboxylic acid, ring-opened
-unsaturated
carboxylic acid were obtained. Upon heating at 150-160
C, dehydration to the
corresponding
ʴ
-mercapto product and
ʲ
,
ʳ
-thiolactone occurred. It is noteworthy that the
double bond was in a
cis
conformation. Substituted thiophene-2-carboxylic acids
exhibited similar behavior (Scheme
117
).
Subsequently, it was found that the preparation of substituted
2,5-dihydrothiophenes can be conveniently realized by the lithium/ammonia reduc-
tion of the corresponding lithium thiophene carboxylate salts, instead of the acid
[
136
]. As depicted in Scheme
118
, the substituted thiophene-2-carboxylic acid was
initially converted into the corresponding lithium salt by treatment with equivalent
amount of lithium hydroxide, and then the reduction was accomplished with
lithium/ammonia and ammonia chloride as the proton source. Through this proce-
dure, the ultimate target products were obtained in yields of 75% and 50%,
respectively, but as a mixture of approximately equal amounts of 2,5-
cis
- and -
trans
-isomers.
Birch reduction of more heavily substituted thiophene carboxylic acid salts
proceeded readily to afford the corresponding substituted 2,5-dihydrothiophenes;
however, the ring-opened by-product (
Z
)-5-mercapto-3-pentenoic acid was still
detectable. Reduction of dilithium 3,4-dimethylthiophene-2,5-dicarboxylate also
ʲ
,
ʳ
-unsaturated
ʴ
