Vol. 25, No. 15 (2013)
Non-Acidic Mediated Friedel-Craft Reaction of Thiophene Using EtAlCl 8773
2
1
4
1
(
2-Thienyl)(p-tolyl)methanone (4) : (R
f
= 0.36) H
We speculated that during the acylation of thiophene, ethyl
anion abstract the hydrogen form thiophene during the aroma-
tization or after the aromatization (Scheme-I). It is clear that
the reaction media is non-acidic because ethyl anion have
neutralized the proton produced during the acylation.
NMR δ 7.72 (t, J = 13.5 Hz, 2H), 7.64-7.58 (m, 1H), 7.55 (dd,
J = 3.8, 1.1 Hz, 1H), 7.26-7.18 (m, 2H), 7.07 (dd, J = 4.9, 3.8
Hz, 1H), 2.38 (s, 3H). C NMR δ 135.62, 134.20, 133.37,
29.80, 129.21, 127.74, 21.66. IR : 1704, 1632, 1513, 1413,
289, 1048, 848, 740.
-Benzoylthiophene (5) : (R = 0.28) H NMR δ 7.90-
.71 (m, 1H), 7.65-7.57 (m, 1H), 7.52 (dd, J = 3.8, 1.1 Hz,
H), 7.50-7.43 (m, 1H), 7.41-7.35 (m, 1H), 7.04 (dd, J = 4.9,
.8 Hz, 1H)). C NMR δ 187.57, 143.75, 138.20, 135.33,
34.79, 134.21, 132.13, 129.15, 128.34, 127.80. IR : 1627,
513, 1410, 1288, 1051, 836, 721.
13
1
1
14
1
O
2
f
R C O
+
EtAlCl
3
7
1
3
1
1
EtAlCl2
S
+
R
Cl
-
+
O
13
S
+
R
+
R C O
+
O
O
S
1
5
1
S
(
Z)-1-(2-Thienyl)but-2-en-1-one (6) : (R
NMR δ 7.79-7.59 (m, 1H), 7.58-7.36 (m, 1H), 7.16-6.92 (m,
H), 6.81-6.66 (m, 1H), 1.87 (dd, J = 6.9, 1.6 Hz, 3H). C
f
= 0.37) H
R
+
EtAlCl
-
3
R
+
EtH (ethane gas)
+
H
13
2
2 A
Scheme-I: EtAlCl as Brønsted base in E S reaction
NMR δ 181.43, 145.13, 143.67, 133.39, 131.54, 128.00,
1
1
26.88, 18.32 . IR : 1659, 1614, 1514, 1440, 1415, 1294, 1234,
063, 907, 784.
Among eight derivatives of thiophene synthesized
(Scheme-II), 1,4-bis(2-thienyl) butane-1,4-dione (3) is the
16
1
1
,8-Bis(2-thienyl)octane-1,8-dione (7) : (R
NMR δ 7.70-7.58 (m, 2H), 7.52 (dd, J = 4.9, 1.1 Hz, 2H),
.03 (dd, J = 4.9, 3.8 Hz, 2H), 2.87-2.77 (m, 4H), 1.77-1.61
f
= 0.15) H
most commonly used one because it is the precursor for SNS
2
,21
type conductive polymers . Therefore, we searched the
optimization condition for 3. The best yield observed was 0.15
M of succinyl chloride and 0.315 M of thiophene were used.
On the other hand, the catalyst loading showed that the highest
7
13
(
m, 4H), 1.35 (dt, J = 14.1, 5.2 Hz, 4H). C NMR δ 192.06,
1
1
44.08, 132.59, 130.92, 127.41, 38.66, 28.57, 23.99 . IR :
647, 1411, 1242, 1185, 927, 851, 727.
yield obtained when 1.5 equivalent of EtAlCl was used in
2
1
7
1
(
Furan-2-yl)(2-thienyl)methanone (8) : (R
f
= 0.28) H
accord with thiophene.
NMR δ 8.07 (d, J = 2.4 Hz, 1H), 7.62-7.53 (m, 2H), 7.33-7.25
13
O
O
(
m, 1H), 7.07 (dt, J = 3.8, 3.2 Hz, 1H), 6.49 (s, 1H). C NMR
S
S
δ 171.60, 151.26, 144.81, 141.14, 132.34, 126.73, 117.20,
O
S
1
1
11.08. IR; 1622, 1566, 1464, 1413, 1305, 808, 740. IR: 1622,
566, 1464, 1413, 1305, 1179, 1013, 884, 808.
O
S
3
S
3
H C
18
1
1
-(1H-Pyrrol-2-yl)ethanone (9) : (R
f
= 0.22) H NMR
99%
2
4
9
2%
δ 6.98 (td, J = 2.8, 1.4 Hz, 1H), 6.81 (ddd, J = 3.8, 2.4, 1.4 Hz,
8
9%
13
O
O
1H), 6.14 (dt, J = 3.8, 2.4 Hz, 1H), 2.36 (s, 3H). C NMR δ
187.95, 132.13, 125.43, 117.31, 119.42, 25.53. IR: 1645, 1547,
1428, 1364, 1129, 1045, 841, 773.
S
S
S
7
3%
3
H C
88%
1
5
6
9
9%
O
8
3%
O
RESULTS AND DISCUSSION
8
9%
O
S
S
H C
Snider and co-workers accomplished many Lewis acid
3
catalyzed reactions using alkyl Lewis acids. They reported that
proton-initiated rearrangements do not occur since alkyl Lewis
acids give a non-acidic reaction media due to basicity of alkyl
parts, which are proton scavengers and rapidly turn into ethane
or methane gases . When alkyl-acid chlorides are employed
in the acylating agent, the formation of acidic proton is thus
not to be expected.
On the other hand, Watt and co-workers reported that
acylation of ferrocene with acryloyl chloride would not yield
the corresponding unsaturated ferrocenyl ketone, instead
afforded propanoyl ferrocene and ferrocenophane derivative
O
O
8
S
S
(
CH2)6
7
19
Scheme-II: Thiophene derivative syntheses in the presence of EtAlCl
2
Different routes are available leading to 1,4-bis(2-thienyl)-
butane-1,4-dione (3) . Among these methods, the Friedel-
2
2-24
Craft reaction, which is the first reported by Merz and Ellenger
2
5
albeit with long reaction period (24 h), is mostly used .
Recently, the reaction time has been reduced under forcing
2
1
conditions (reflux) .
using AlCl as a catalyst. They synthesized acryloylferrocene
3
1
9,20
High yields were observed for (furan-2-yl)(2-thienyl)-
methanone (8) and succinylthiophene (3) (99 % for each) while
the lowest yield (73 %) was obtained for acetyl thiophene (1)
in two steps starting from ferrocene . In first step, 3-chloro-
propanoylferrocene was obtained through the Friedel-Crafts
acylation and in second step, dehydrochlorination of 3-chloro-
propanoyl ferrocene via silica gel (column chromatography)
afforded acryloylferrocene. However, Dogan and co-workers
have synthesized acryloylferrocene in one step using EtAlCl
Me Al Lewis acids. The aforementioned attributes have
prompted us to use EtAlCl
acylation of thiophene.
(
Scheme-II). Even in the case of more long substrates, such
11
as suberoylthiophene (7) and crotonoylthiophene (6) good
yields (up to 89) were obtained. Our protocol can be extended
to the acylation of other aromatics. For this purpose, 1-(1H-
pyrrole-2-yl)ethanone (9) was synthesized with the yield of
2
/
3
2
as lewis acid in Friedel-Crafts
9
0 %. Unfortunately, acylation of pyridine and pyrrole with