Palladium-catalyzed direct arylation of thiophenes bearing SO2R substituents

Article abstract of DOI:10.1021/jo200918n

The palladium-catalyzed direct arylation of SO₂R-substituted thiophene derivatives was found to proceed regioselectively at C5 and in high yields using a variety of aryl bromides and as low as 0.5-0.1 mol % of phosphine-free Pd(OAc)₂

Full text of DOI:10.1021/jo200918n

NOTE
pubs.acs.org/joc
Palladium-Catalyzed Direct Arylation of Thiophenes Bearing
SO2R Substituents
Charles Beromeo Bheeter,† Jitendra K. Bera,‡ and Henri Doucet†,*
†Institut Sciences Chimiques de Rennes, UMR 6226 CNRS, Universitꢀe de Rennes “Catalyse et Organometalliques”,
Campus de Beaulieu, 35042 Rennes, France
‡Department of Chemistry, Indian Institute of Technology Kanpur, 208016 Kanpur, India
S Supporting Information
b
ABSTRACT: The palladium-catalyzed direct arylation of SO2R-
substituted thiophene derivatives was found to proceed regiose-
lectively at C5 and in high yields using a variety of aryl bromides
and as low as 0.5ꢀ0.1 mol % of phosphine-free Pd(OAc)2 as the
catalyst. For these reactions, sulfonyls, sulfonamides, or even a
sulfonic ester as the thiophene substituents were successfully employed.
he palladium-catalyzed direct arylation of several heteroaro-
conversions of 4-bromobenzonitrile, and the target compound
1 was obtained in low yields (Table 1, entries 1 and 2). The use of
acetates such as NaOAc, KOAc, or CsOAc as base gave better
results, as complete conversions of 4-bromobenzonitrile were
obseved in the presence of 0.5 mol % of catalyst (Table 1,
entries 3ꢀ5). The good performance of acetates as the base is
consistent with a concerted metalation deprotonation (CMD)
pathway.9 Then, we performed reactions using 0.1 mol % catalyst.
CsOAc or NaOAc led to partial conversions of 4-bromobenzoni-
trile, whereas a complete conversion was observed in the
presence of KOAc (Table 1, entries 6ꢀ8). The nature of the
solvent often modifies the catalyst activity in cross-coupling
reactions; thus we observed that NMP and DMF in the presence
of 0.1 mol % of PdCl(C3H5)(dppb) as the catalyst also gave 1 in
moderate yields (Table 1, entries 9 and 10). We then evaluated
the influence of the palladium source. Interestingly, 0.5 mol % of
Pd(OAc)2 gave 1 very selectively (Table 1, entry 11). Moreover,
the use of only 0.1 mol % of Pd(OAc)2 gave 1 in 100%
conversion and in 82% yield (Table 1, entry 12). This phos-
phine-free catalyst had already been found to be very efficient for
the direct arylation of other thiophene derivatives.5h
T
matics via a CꢀH bond activation using aryl halides has led
to successes in recent years.1ꢀ4 However, there are still limita-
tions for these reactions in terms of heteroaromatic functional
group tolerance. The presence of acetyl, formyl, nitrile, hydro-
xyalkyl, amino, or silyl as the functional groups on the thiophenes
for palladium-catalyzed arylation has been described.5 A direct
arylation of a furan substituted by a methyl sulfide in the presence
of an iridium catalyst has also been reported.6 On the other hand,
to our knowledge, direct arylations in the presence of hetero-
aromatics bearing sulfonyls, sulfonamides, or sulfonic esters as
the substituents has not been described, although they are very
common groups in bioactive molecules (Figure 1).
Arylated SO2R-substituted thiophenes can be prepared by
Suzuki coupling using halothiophenes with arylboronic acids7 or
by reaction of arylthiophenes with sulfuric acid.8 However,
Suzuki coupling requires the preparation of an arylboronic acid
and provides an organometallic salt (MX) as byproduct, and the
use of sulfuric acid requires very stable reactants. Therefore, the
direct arylation of thiophenes bearing SO2R functions via a CꢀH
bond activation would be very convenient since it would provide
a more environmentally and economically attractive access to
such arylated thiophenes.
Here, we wish to report on the reaction of thiophene
derivatives bearing sulfonyls, sulfonamides, or sulfonic esters as
substituents with a set of electronically and sterically diverse aryl
bromides in the presence of a low loading of a phosphine-free
palladium catalyst.
We decided to employ commercially available 2-methanesul-
fonylthiophene and 4-bromobenzonitrile as the test substrates
for our study (Table 1). We initially examined the influence of
the nature of the base on the product distribution for this reaction
using DMAc as the solvent and PdCl(C3H5)(dppb) as the
catalyst. This palladium complex was recently demonstrated to
be one of the best catalyst for the direct arylation of some furans,
thiophenes, or thiazoles.5g,5o K2CO3 or Na2CO3 gave poor
Then, 2-methanesulfonylthiophene was coupled with three
other aryl bromides in the presence of 0.1 mol % of Pd(OAc)2
and KOAc as the base (Table 2). Selective 5-arylations
were observed using 4-bromoacetophenone, 4-bromobenzalde-
hyde, or 2-bromobenzonitrile, resulting in 71ꢀ74% yields of the
products 2ꢀ4.
Very similar results were obtained in the presence of an
isopropyl instead of a methyl substituent on the sulfonyl group
(Table 3). A wide range of aryl bromides was employed, and in all
cases, the expected 5-arylated thiophenes were selectively ob-
tained using 0.5ꢀ0.1 mol % of Pd(OAc)2 as the catalyst and
KOAc as the base. The reaction of methyl 4-bromobenzoate or
Received: May 9, 2011
Published: June 22, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
NOTE
Table 3. Direct Arylation of 2-(Propane-2-sulfonyl)-
thiophenea
entry
R or aryl bromide
4-CO2Me
product
yield (%)
Figure 1. Examples of bioactive thiophenes bearing SO2R substituents.
1
2
5
6
67b
61
73
75
70b
72
78
77
91
72
68
4-NO2
Table 1. Influence of the Reaction Conditions on the Aryla-
tion of 2-Methanesulfonylthiophene with
4-Bromobenzonitrilea
3
4-Cl
7
4
4-F
8
5
4-t-Bu
9
6
3-COMe
10
11
12
13
14
15
7
2-CN
8
1-bromonaphthalene
5-bromopyrimidine
4-bromoisoquinoline
4-bromopyridine hydrochloride
9
entry
solvent
base
catalyst (mol %)
convn (%)
10
11
1
2
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
NMP
K2CO3
Na2CO3
CsOAc
NaOAc
KOAc
PdCl(C3H5)(dppb) (0.5)
PdCl(C3H5)(dppb) (0.5)
PdCl(C3H5)(dppb) (0.5)
PdCl(C3H5)(dppb) (0.5)
PdCl(C3H5)(dppb) (0.5)
PdCl(C3H5)(dppb) (0.1)
PdCl(C3H5)(dppb) (0.1)
PdCl(C3H5)(dppb) (0.1)
PdCl(C3H5)(dppb) (0.1)
PdCl(C3H5)(dppb) (0.1)
Pd(OAc)2 (0.5)
25
a Conditions: Pd(OAc)2 (0.001 equiv.), aryl bromide (1 equiv), 2-
(propane-2-sulfonyl)thiophene (1.5 equiv), KOAc (2 equiv), 16 h,
130 °C. b Pd(OAc)2 (0.005 equiv).
42
3
100
100
100
51
4
5
Table 4. Direct Arylation of 2-Benzenesulfonylthiophenea
6
CsOAc
NaOAc
KOAc
7
32
8
100 (80)
62
9
KOAc
10
11
12
DMF
KOAc
70
DMAc
DMAc
KOAc
100
entry
R
product
yield (%)
KOAc
Pd(OAc)2 (0.1)
100 (82)
a Conditions: [Pd], 4-bromobenzonitrile (1 equiv), 2-methanesulfo-
nylthiophene (1.5 equiv), base (2 equiv), 16 h, 130 °C, conversion of
4-bromobenzonitrile, isolated yields of 1 in parentheses.
1
2
3
4
4-CHO
4-CN
16
17
18
19
72
71
73
76
4-CO2Me
2-CN
a Conditions: Pd(OAc)2 (0.001 equiv), aryl bromide (1 equiv), 2-ben-
Table 2. Direct Arylation of 2-Methanesulfonylthiophenea
zenesulfonylthiophene (1.5 equiv), KOAc (2 equiv), 16 h, 130 °C.
bromide was observed and a yield of 70% in 9 was obtained. The
meta-substituted aryl bromide, 3-bromoacetophenone, gave 10
in 72% yield. More congested substrates, such as 2-bromoben-
zonitrile or 1-bromonaphthalene, were also found to be suitable
coupling partners and gave 11 and 12 in 78% and 77% yields,
respectively. On the other hand, chlorobenzene and the electron-
rich aryl bromide 4-bromoanisole were found to be unreactive.
We observed that the coupling of 4-bromopyridine, 4-bromoiso-
quinoline, or 5-bromopyrimidine with 2-(propane-2-sulfonyl)-
thiophene also proceed nicely to give 13ꢀ15 in 68ꢀ91% yields.
Again, similar results were obtained for the coupling with of
2-benzenesulfonylthiophene (Table 4). In the presence of 2- or
4-bromobenzonitriles, 4-bromobenzaldehyde or methyl 4-bro-
mobenzoate and 0.1 mol % Pd(OAc)2, the products 16ꢀ19 were
obtained in 71ꢀ76% yields. It should be noted that a regiose-
lective arylation at carbon 5 of thiophene was observed and that
no trace of arylation on the benzene ring was detected.
entry
R
product
yield (%)
1
2
3
4-COMe
4-CHO
2-CN
2
3
4
73
74
71
a Conditions: Pd(OAc)2 (0.001 equiv), aryl bromide (1 equiv),
2-methanesulfonylthiophene (1.5 equiv), KOAc (2 equiv), 16 h, 130 °C.
4-bromonitrobenzene gave products 5 and 6 in 67% and 61%
yields, respectively. It should be noted that even 4-chlorobro-
mobenzene could be employed to give 7 in 73% yield. In the
course of this reaction, no cleavage of the CꢀCl bond was
observed, allowing further transformations. 4-Fluorobromoben-
zene was also successfully coupled with 2-(propane-2-sulfonyl)-
thiophene to give 8 in 75% yield. The reaction of electron-rich
aryl bromide, 4-tert-butylbromobenzene, led to 9 in a slightly
lower yield of 56% when 0.1 mol % catalyst was employed due to
a partial conversion of this aryl bromide. In the presence of
0.5 mol % of Pd(OAc)2, a complete conversion of this aryl
Then, we performed several reactions using thiophene-2-
sulfonic acid diethylamide as the coupling partner (Table 5).
The target products 20ꢀ27 were obtained in 75ꢀ87% yields
using only 0.1 mol % of Pd(OAc)2 as the catalyst at 130 °C as
the reaction temperature. In all cases, the reactions were found
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NOTE
Table 5. Direct Arylation of Thiophene-2-sulfonic Acid
Diethylamidea
Table 7. Direct Arylation of Thiophene-2-sulfonic Acid
Benzylamide or Thiophene-2-sulfonic Acid Phenylamidea
R0
product yield (%)
entry
R or aryl bromide
poduct
yield (%)
entry
R or aryl bromide
1
2
3
4
5
6
7
8
4-CN
20
21
22
23
24
25
26
27
79
87
80
75
81
79
91
86
1
2
3
4
5
6
4-CN
CH2Ph
CH2Ph
CH2Ph
31
32
33
34
35
36
71
66
74
73
61
60
4-CHO
4-COMe
2-CN
4-CO2Me
4-COMe
4-bromopyridine hydrochloride CH2Ph
4-COPh
4-CN
Ph
2-CN
4-NO2
Ph
a Conditions: Pd(OAc)2 (0.005 equiv), aryl bromide (1 equiv), thio-
phene-2-sulfonic acid benzylamide or thiophene-2-sulfonic acid pheny-
lamide (1.5 equiv), KOAc (2 equiv), 16 h, 150 °C.
4-bromopyridine hydrochloride
4-bromoisoquinoline
a Conditions: Pd(OAc)2 (0.001 equiv), aryl bromide (1 equiv), thio-
phene-2-sulfonic acid diethylamide (1.5 equiv), KOAc (2 equiv), 16 h,
130 °C.
Table 8. Direct Arylation of Thiophene-2-sulfonic Acid
Phenyl Estera
Table 6. Direct Arylation of Thiophene-2-sulfonic Acid
n-Butylphenylamidea
entry
R or aryl bromide
4-CN
product
yield (%)
1
2
3
4
37
38
39
40
72
76
75
83
entry
R or aryl bromide
4-CN
product
yield (%)
2-CN
3-COMe
1
2
3
28
29
30
75
82
76
4-bromoisoquinoline
1-bromonaphthalene
a Conditions: Pd(OAc)2 (0.005 equiv), aryl bromide (1 equiv), thio-
phene-2-sulfonic acid phenyl ester (1.5 equiv), KOAc (2 equiv), 16 h,
130 °C.
3-bromopyridine
a Conditions: Pd(OAc)2 (0.005 equiv.), aryl bromide (1 equiv), thio-
phene-2-sulfonic acid n-butylphenylamide (1.5 equiv), KOAc (2 equiv),
16 h, 150 °C.
catalyst. In the presence of 4-bromobenzonitrile or 4-bromoni-
trobenzene, the desired coupling products 35 and 36 were
obtained in 61% and 60% yields, respectively (Table 7).
Finaly, the palladium-catalyzed reaction of four aryl bromides
with thiophene-2-sulfonic acid phenyl ester has been examined
(Table 8). The arylations using this substrate might give side
products, as the palladium-catalyzed direct arylation of hetero-
aromatics using toylates or mesylates is possible in the presence
of K2CO3/t-BuCO2H.10 However, the reaction of thiophene-2-
sulfonic acid phenyl ester with 2- or 4-bromobenzonitriles,
3-bromoacetophenone, or 4-bromoisoquinoline gave cleanly
37ꢀ40 in 72ꢀ83% yield. In the course of these reactions no
cleavage of the PhꢀO bond was observed.
to be very clean, as only the arylation at C5 of thiophene was
detected.
The reaction is not limited to the use of sulfonic acid
dialkylamides. The reaction of 4-bromobenzonitrile, 1-bromo-
naphthalene, or 3-bromopyridine with thiophene-2-sulfonic acid
n-butylphenylamide was also found to give very cleanly the direct
arylation products 28ꢀ30 in 75ꢀ82% yields (Table 6). How-
ever, with this thiophene derivative, we had to employ a more
elevated reaction temperature of 150 °C and a higher catalyst
loading of 0.5 mol % in order to reach complete conversions of
the aryl bromides.
Thiophene-2-sulfonic acid benzylamide was also found to be
less reactive than 2-sulfonic acid diethylamide. At 130 °C, using
0.1 mol % of Pd(OAc)2 as the catalyst, a moderate conversion of
4-bromobenzonitrile was observed. The presence of a free NH
on this reactant might partially poison the catalyst. Again, we had
to employ a reaction temperature of 150 °C and 0.5 mol % of
catalyst loading of in order to obtain full conversions of the aryl
bromides (Table 7). Using these conditions, the reaction of 2- or
4-bromobenzonitriles, 4-bromoacetophenone, or 4-bromopyri-
dine gave 31ꢀ34 in 66ꢀ74% yields.
In summary, we report here conditions for the palladium-
catalyzed regioselective direct arylation at C5 of a range of SO2R-
substituted thiophene derivatives. As low as 0.5ꢀ0.1 mol % of
phosphine-free Pd(OAc)2 as the catalyst associated to KOAc
promotes the arylation of thiophenes bearing sulfonyls, sulfona-
mides, and even a sulfonic acid phenyl ester.
’ EXPERIMENTAL SECTION
Thiophene-2-sulfonic acid phenylamide has also a lower
reactivity than thiophene-2-sulfonic acid diethylamide, and the
reactions had to be performed at 150 °C with 0.5 mol % of
General Procedure. As a typical experiment, the reaction of the
aryl bromide (1 mmol), thiophene derivative (1.5 mmol), and KOAc
(0.196 g, 2 mmol) at 130 or 150 °C (see Tables 1ꢀ8) during 16 h in
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NOTE
DMAc (4 mL) in the presence of Pd(OAc)2 (0.224 mg, 0.001 mmol or
1.12 mg, 0.005 mmol, see tables) under argon affords the coupling
product after addition of water (20 mL), extraction with dichloromethane
(20 mL), drying on MgSO4, evaporation, and purification on silica gel.
3-(5-Methanesulfonylthiophene-2-yl)benzonitrile (1). 4-Bro-
mobenzonitrile (0.182 g, 1 mmol) and 2-methanesulfonylthiophene
(0.243 g, 1.5 mmol) afford 1 in 82% (0.216 g) yield. 1H NMR (300 MHz,
DMSO-d6): δ 7.92 (d, J = 8.5 Hz, 2H), 7.83 (d, J = 8.5 Hz, 2H), 7.79 (d,
J = 4.0 Hz, 1H), 7.67 (d, J = 4.0 Hz, 1H), 3.30 (s, 3H). 13C NMR
(75 MHz, DMSO-d6): δ 148.8, 142.7, 136.7, 135.0, 133.7, 127.3, 127.2,
118.9, 111.9, 45.7. Anal. Calcd for C12H9NO2S2 (263.34): C, 54.73; H,
3.44. Found: C, 54.89; H, 3.30.
1-[4-(5-Methanesulfonylthiophene-2-yl)-phenyl]ethanone
(2). 4-Bromoacetophenone (0.199 g, 1 mmol) and 2-methanesulfo-
nylthiophene (0.243 g, 1.5 mmol) afford 2 in 73% (0.204 g) yield. 1H
NMR (300 MHz, DMSO-d6):δ8.03(d,J= 8.4 Hz, 2H), 7.91 (d, J=8.4Hz,
2H), 7.86 (d, J = 4.0 Hz, 1H), 7.81 (d, J = 4.0 Hz, 1H), 3.41 (s, 3H), 2.61
(s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 197.6, 149.7, 142.1, 137.3,
136.5, 135.0, 129.7, 126.7, 45.7, 27.2. Anal. Calcd for C13H12O3S2
(280.36): C, 55.69; H, 4.31. Found: C, 55.47; H, 4.50.
2-(4-Fluorophenyl)-5-(propane-2-sulfonyl)thiophene (8).
4-Bromofluorobenzene (0.175 g, 1 mmol) and 2-(propane-2-sulfo-
nyl)thiophene (0.285 g, 1.5 mmol) afford 8 in 75% (0.213 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 7.83 (dd, J = 8.6, 5.3 Hz, 2H), 7.75
(d, J = 4.0 Hz, 1H), 7.66 (d, J = 4.0 Hz, 1H), 7.32 (d, J = 8.6 Hz, 2H), 3.49
(sept,J= 7.5 Hz, 1H), 1.26 (d, J= 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-
d6): δ 163.1 (d, J = 247.6 Hz), 151.3, 136.8, 135.8, 129.1 (d, J = 3.3 Hz),
128.9 (d, J= 8.5 Hz), 125.4, 116.8 (d, J= 22.0 Hz), 56.3, 16.0. Anal. Calcd for
C13H13FO2S2 (284.37): C, 54.91; H, 4.61. Found: C, 54.87; H, 4.47.
2-(4-tert-Butylphenyl)-5-(propane-2-sulfonyl)thiophene
(9). 4-tert-Butylbromobenzene (0.213 g, 1 mmol) and 2-(propane-2-
sulfonyl)thiophene (0.285 g, 1.5 mmol) afford 9 in 70% (0.225 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 7.65 (d, J = 4.0 Hz, 1H), 7.63 (d, J =
8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 4.0 Hz, 1H), 3.41 (sept,
J = 7.5 Hz, 1H), 1.35 (d, J = 7.5 Hz, 6H), 1.34 (s, 9H). 13C NMR (75
MHz, DMSO-d6): δ 153.6, 152.7, 135.9, 134.8, 129.6, 125.9, 125.7,
123.2, 56.7, 34.2, 30.2, 14.9. Anal. Calcd for C17H22O2S2 (322.49): C,
63.31; H, 6.88. Found: C, 63.42; H, 6.82.
1-[3-[5-(Propane-2-sulfonyl)-thiophene-2-yl]phenyl]etha-
none (10). 3-Bromoacetophenone (0.199 g, 1 mmol) and 2-(propane-
2-sulfonyl)thiophene (0.285 g, 1.5 mmol) afford 10 in 72% (0.222 g)
4-(5-Methanesulfonylthiophene-2-yl)benzaldehyde (3).
4-Bromobenzaldehyde (0.185 g, 1 mmol) and 2-methanesulfonylthio-
1
yield. H NMR (300 MHz, DMSO-d6): δ 8.23 (s, 1H), 8.01 (d, J =
8.5 Hz, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.82 (d, J = 4.0 Hz, 1H), 7.79 (d, J =
4.0 Hz, 1H), 7.63 (t, J = 8.0 Hz, 1H), 3.54 (sept, J = 7.5 Hz, 1H), 2.66 (s,
3H), 1.27 (d, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): δ 198.0,
151.3, 138.2, 136.7, 136.5, 132.8, 131.0, 130.3, 129.3, 126.1, 126.0, 56.3,
27.4, 16.0. Anal. Calcd for C15H16O3S2 (308.42): C, 58.41; H, 5.23.
Found: C, 58.43; H, 5.30.
1
phene (0.243 g, 1.5 mmol) afford 3 in 74% (0.197 g) yield. H NMR
(300 MHz, DMSO-d6): δ 10.04 (s, 1H), 8.00 (s, 4H), 7.87 (d, J = 4.0 Hz,
1H), 7.85(d, J= 4.0 Hz, 1H), 3.41 (s, 3H). 13C NMR (75 MHz, DMSO-d6):
δ 192.9, 149.5, 142.5, 137.8, 136.7, 135.0, 130.9, 127.1, 127.0, 45.7. Anal.
Calcd for C12H10O3S2 (266.34): C, 54.11; H, 3.78. Found: C, 54.21;
H, 3.59.
2-[5-(Propane-2-sulfonyl)thiophene-2-yl]-benzonitrile
(11). 2-Bromobenzonitrile (0.182 g, 1 mmol) and 2-(propane-2-sulfo-
nyl)thiophene (0.285 g, 1.5 mmol) afford 11 in 78% (0.227 g) yield. 1H
NMR (300 MHz, DMSO-d6): δ 8.01 (d, J = 8.5 Hz, 1H), 7.86 (d, J =
4.0 Hz, 1H), 7.85ꢀ7.80 (m, 2H), 7.74 (d, J = 4.0 Hz, 1H), 7.70ꢀ7.65
(m, 1H), 3.56 (sept, J = 7.5 Hz, 1H), 1.27 (d, J = 7.5 Hz, 6H). 13C NMR
(75 MHz, DMSO-d6): δ 147.5, 138.7, 136.1, 135.2, 135.1, 134.5, 130.7,
130.4, 129.4, 118.5, 110.1, 56.4, 16.0. Anal. Calcd for C14H13NO2S2
(291.39): C, 57.71; H, 4.50. Found: C, 57.88; H, 4.31.
2-(5-Methanesulfonylthiophene-2-yl)benzonitrile (4). 2-Bro-
mobenzonitrile (0.182 g, 1 mmol) and 2-methanesulfonylthiophene
(0.243 g, 1.5 mmol) afford 4 in 71% (0.187 g) yield. 1H NMR (300 MHz,
DMSO-d6): δ 8.02 (d, J = 7.7 Hz, 1H), 7.92 (d, J = 4.0 Hz, 1H),
7.85ꢀ7.80 (m, 2H), 7.71 (d, J = 4.0 Hz, 1H), 7.70ꢀ7.65 (m, 1H), 3.45
(s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 146.3, 143.5, 135.2, 135.1,
134.5, 134.3, 130.7, 130.3, 129.4, 118.5, 110.2, 45.7. Anal. Calcd for
C12H9NO2S2 (263.34): C, 54.73; H, 3.44. Found: C, 54.84; H, 3.57.
Methyl 4-[5-(Propane-2-sulfonyl)thiophene-2-yl]benzoate
(5). Methyl 4-bromobenzoate (0.215 g, 1 mmol) and 2-(propane-2-
sulfonyl)thiophene (0.285 g, 1.5 mmol) afford 5 in 67% (0.217 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 8.03 (d, J = 8.2 Hz, 2H), 7.94 (d, J =
8.2 Hz, 2H), 7.85 (d, J = 4.0 Hz, 1H), 7.81 (d, J = 4.0 Hz, 1H), 3.88 (s,
3H), 3.53 (sept, J = 7.5 Hz, 1H), 1.26 (d, J = 7.5 Hz, 6H). 13C NMR
(75 MHz, DMSO-d6): δ 166.1, 150.7, 137.3, 136.8, 136.7, 130.6, 130.4,
126.8, 126.7, 56.3, 52.8, 16.0. Anal. Calcd for C15H16O4S2 (324.42): C,
55.53; H, 4.97. Found: C, 55.31; H, 4.80.
2-Naphthalen-1-yl-5-(propane-2-sulfonyl)thiophene (12).
1-Bromonaphthalene (0.207 g, 1 mmol) and 2-(propane-2-sulfonyl)-
1
thiophene (0.285 g, 1.5 mmol) afford 12 in 77% (0.243 g) yield. H
NMR (300 MHz, DMSO-d6): δ 8.15ꢀ8.00 (m, 3H), 7.86 (d, J =
4.0 Hz, 1H), 7.70ꢀ7.55 (m, 4H), 7.51 (d, J = 4.0 Hz, 1H), 3.59 (sept, J =
7.5 Hz, 1H), 1.32 (d, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): δ
150.1, 137.2, 135.9, 133.9, 130.9, 130.3, 130.0, 129.4, 129.1, 129.0, 127.9,
127.0, 126.0, 124.9, 56.4, 16.1. Anal. Calcd for C17H16O2S2 (316.44): C,
64.52; H, 5.10. Found: C, 64.41; H, 5.18.
2-(4-Nitrophenyl)-5-(propane-2-sulfonyl)thiophene (6).
4-Bromonitrobenzene (0.202 g, 1 mmol) and 2-(propane-2-sulfonyl)-
thiophene (0.285 g, 1.5 mmol) afford 6 in 61% (0.190 g) yield. 1H NMR
(300 MHz, CDCl3): δ 8.31 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H),
7.69 (d, J = 4.0 Hz, 1H), 7.50 (d, J = 4.0 Hz, 1H), 3.35 (sept, J = 7.5 Hz,
1H), 1.43 (d, J = 7.5 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 149.9,
147.9, 138.7, 138.5, 135.8, 126.9, 125.7, 124.6, 57.0, 16.0. Anal. Calcd
for C13H13NO4S2 (311.38): C, 50.14; H, 4.21. Found: C, 50.01;
H, 4.40.
2-(4-Chlorophenyl)-5-(propane-2-sulfonyl)thiophene (7).
4-Bromochlorobenzene (0.191 g, 1 mmol) and 2-(propane-2-sulfonyl)-
thiophene (0.285 g, 1.5 mmol) afford 7 in 73% (0.219 g) yield. 1H NMR
(300 MHz, DMSO-d6): δ 7.81 (d, J = 8.5 Hz, 2H), 7.77 (d, J = 4.0 Hz,
1H), 7.75 (d, J = 4.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 3.53 (sept, J =
7.5 Hz, 1H), 1.26 (d, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): δ
151.0, 136.8, 136.3, 134.5, 131.3, 129.8, 128.3, 125.8, 56.3, 16.0. Anal.
Calcd for C13H13ClO2S2 (300.83): C, 51.90; H, 4.36. Found: C, 52.00;
H, 4.44.
5-[5-(Propane-2-sulfonyl)thiophene-2-yl]pyrimidine (13).
5-Bromopyrimidine (0.159 g, 1 mmol) and 2-(propane-2-sulfonyl)thio-
phene (0.285 g, 1.5 mmol) afford 13 in 91% (0.244 g) yield. 1H NMR
(300 MHz, MeOD-d4): δ 9.22 (s, 2H), 9.20 (s, 1H), 7.90 (d, J = 4.0 Hz,
1H), 7.83 (d, J = 4.0 Hz, 1H), 3.55 (sept, J = 7.5 Hz, 1H), 1.28 (d, J =
7.5 Hz, 6H). 13C NMR (75 MHz, MeOD-d4): δ 157.8, 153.9, 144.7,
138.7, 135.9, 127.5, 126.5, 56.7, 14.8. Anal. Calcd for C11H12N2O2S2
(268.36): C, 49.23; H, 4.51. Found: C, 49.42; H, 4.21.
4-[5-(Propane-2-sulfonyl)thiophene-2-yl]isoquinoline (14).
4-Bromoisoquinoline (0.208 g, 1 mmol) and 2-(propane-2-sulfonyl)-
1
thiophene (0.285 g, 1.5 mmol) afford 14 in 72% (0.228 g) yield. H
NMR (300 MHz, DMSO-d6): δ 9.24 (s, 1H), 8.48 (s, 1H), 8.13 (d,
J = 8.1 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.85ꢀ7.65 (m, 2H), 7.72 (t, J =
7.7 Hz, 1H), 7.44 (d, J = 4.0 Hz, 1H), 3.59 (sept, J = 7.5 Hz, 1H), 1.32 (d,
J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): δ 153.3, 146.3, 142.3,
138.2, 135.4, 133.5, 132.1, 129.2, 128.4, 128.3, 128.1, 124.7, 123.3, 56.7,
14.9. Anal. Calcd for C16H15NO2S2 (317.43): C, 60.54; H, 4.76. Found:
C, 60.41; H, 4.89.
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NOTE
4-[5-(Propane-2-sulfonyl)thiophene-2-yl]pyridine (15).
4-Bromopyridine hydrochloride (0.194 g, 1 mmol) and 2-(propane-2-
sulfonyl)thiophene (0.285 g, 1.5 mmol) afford 15 in 68% (0.182 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 8.66 (d, J = 6.0 Hz, 2H), 7.96 (d, J =
4.0 Hz, 1H), 7.84 (d, J = 4.0 Hz, 1H), 7.77 (d, J = 6.0 Hz, 2H), 3.54 (sept,
J = 7.5 Hz, 1H), 1.26 (d, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-
d6): δ 151.1, 149.0, 139.3, 138.3, 136.7, 127.8, 120.5, 56.3, 15.9. Anal.
Calcd for C12H13NO2S2 (267.37): C, 53.91; H, 4.90. Found: C, 53.81;
H, 4.88.
(d, J = 8.5 Hz, 2H), 7.77 (d, J = 4.0 Hz, 1H), 7.70 (d, J = 4.0 Hz, 1H), 3.87
(s, 3H), 3.22 (q, J = 7.5 Hz, 4H), 1.11 (t, J = 7.5 Hz, 6H). 13C NMR
(75 MHz, DMSO-d6): δ 166.1, 147.9, 140.1, 136.8, 133.3, 130.6, 130.1,
126.6, 126.4, 52.8, 42.9, 14.6. Anal. Calcd for C16H19NO4S2 (353.46): C,
54.37; H, 5.42. Found: C, 54.21; H, 5.30.
5-(4-Acetylphenyl)thiophene-2-sulfonic Acid Diethyla-
mide (23). 4-Bromoacetophenone (0.199 g, 1 mmol) and thio-
phene-2-sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 23 in
1
75% (0.253 g) yield. H NMR (300 MHz, DMSO-d6): δ 8.02 (d, J =
4-(5-Benzenesulfonylthiophene-2-yl)benzaldehyde (16).
4-Bromobenzaldehyde (0.185 g, 1 mmol) and 2-benzenesulfonylthio-
phene (0.336 g, 1.5 mmol) afford 16 in 72% (0.236 g) yield. 1H NMR
(300 MHz, DMSO-d6): δ 10.04 (s, 1H), 8.03 (d, J = 8.5 Hz, 2H), 8.00
(s, 4H), 7.93 (d, J = 4.0 Hz, 1H), 7.80 (d, J = 4.0 Hz, 1H), 7.74 (t, J = 7.7
Hz, 1H), 7.67 (t, J = 7.7 Hz, 2H). 13C NMR (75 MHz, DMSO-d6): δ
192.9, 150.8, 142.4, 141.7, 137.5, 136.7, 135.8, 134.5, 130.8, 130.4, 127.5,
127.3, 127.1. Anal. Calcd for C17H12O3S2 (328.41): C, 62.17; H, 3.68.
Found: C, 62.24; H, 3.50.
4-(5-Benzenesulfonylthiophene-2-yl)benzonitrile (17).
4-Bromobenzonitrile (0.182 g, 1 mmol) and 2-benzenesulfonylthio-
phene (0.336 g, 1.5 mmol) afford 17 in 71% (0.231 g) yield. 1H NMR
(300 MHz, DMSO-d6): δ 8.03 (d, J = 8.5 Hz, 2H), 7.95ꢀ7.88 (m, 5H),
7.81 (d, J = 4.0 Hz, 1H), 7.74 (t, J = 8.2 Hz, 1H), 7.67 (t, J = 8.2 Hz, 2H).
13C NMR (75 MHz, DMSO-d6): δ 150.1, 142.6, 141.7, 136.5, 135.8,
134.6, 133.7, 130.4, 127.7, 127.5, 127.3, 118.8, 112.1. Anal. Calcd for
C17H11NO2S2 (325.41): C, 62.75; H, 3.41. Found: C, 62.84; H, 3.54.
Methyl 4-(5-Benzenesulfonylthiophene-2-yl)benzoate
(18). Methyl 4-bromobenzoate (0.215 g, 1 mmol) and 2-benzenesulfo-
nylthiophene (0.336 g, 1.5 mmol) afford 18 in 73% (0.261 g) yield. 1H
NMR (300 MHz, DMSO-d6): δ 8.03 (d, J = 8.5 Hz, 2H), 8.00 (d, J =
8.5 Hz, 2H), 7.93 (d, J = 4.0 Hz, 1H), 7.87 (d, J = 8.5 Hz, 2H), 7.78ꢀ7.60
(m, 4H), 3.86 (s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 166.0, 150.9,
142.0, 141.7, 136.5, 135.8, 134.5, 130.5, 130.4, 130.3, 127.4, 127.0, 126.8,
52.8. Anal. Calcd for C18H14O4S2 (358.43): C, 60.32; H, 3.94. Found: C,
60.40; H, 3.79.
8.5 Hz, 2H), 7.89 (d, J = 8.5 Hz, 2H), 7.76 (d, J = 4.0 Hz, 1H), 7.69 (d, J =
4.0 Hz, 1H), 3.21 (q, J = 7.5 Hz, 4H), 2.60 (s, 3H), 1.11 (t, J = 7.5 Hz,
6H). 13C NMR (75 MHz, DMSO-d6): δ 197.6, 148.0, 140.1, 137.1,
136.7, 133.3, 129.7, 126.4, 126.3, 43.0, 27.2, 14.6. Anal. Calcd for
C16H19NO3S2 (337.46): C, 56.95; H, 5.68. Found: C, 56.81; H, 5.55.
5-(4-Benzoylphenyl)thiophene-2-sulfonic Acid Diethyla-
mide (24). 4-Bromobenzophenone (0.261 g, 1 mmol) and thiophene-
2-sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 24 in 81%
(0.323 g) yield. 1H NMR (300 MHz, DMSO-d6): δ 7.91 (d, J = 8.2 Hz,
2H), 7.80 (d, J = 8.2 Hz, 2H), 7.78ꢀ7.65 (m, 5H), 7.56 (t, J = 7.5 Hz,
2H), 3.21 (q, J = 7.5 Hz, 4H), 1.11 (t, J = 7.5 Hz, 6H). 13C NMR (75
MHz, DMSO-d6): δ 195.3, 148.0, 140.2, 137.4, 137.3, 136.3, 133.3,
133.2, 131.1, 130.0, 129.1, 126.3, 126.2, 42.9, 14.6. Anal. Calcd for
C21H21NO3S2 (399.53): C, 63.13; H, 5.30. Found: C, 63.23; H, 5.28.
5-(2-Cyanophenyl)thiophene-2-sulfonic Acid Diethyla-
mide (25). 2-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-
sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 25 in 79% (0.253
g) yield. 1H NMR (300 MHz, DMSO-d6): δ 7.99 (d, J = 8.5 Hz, 1H),
7.85ꢀ7.77 (m, 2H), 7.75 (d, J = 4.0 Hz, 1H), 7.66 (d, J = 4.0 Hz, 1H),
7.65ꢀ7.61 (m, 1H), 3.24 (q, J = 7.5 Hz, 4H), 1.12 (t, J = 7.5 Hz, 6H). 13C
NMR (75 MHz, DMSO-d6): δ 144.6, 141.3, 135.3, 135.1, 134.4, 132.6,
130.5, 130.1, 128.9, 118.5, 110.0, 42.9, 14.6. Anal. Calcd for
C15H16N2O2S2 (320.43): C, 56.22; H, 5.03. Found: C, 56.29; H, 5.22.
5-Pyridin-4-ylthiophene-2-sulfonic Acid Diethylamide (26).
4-Bromopyridine hydrochloride (0.194 g, 1 mmol) and thiophene-2-
sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 26 in 91% (0.270
g) yield. 1H NMR (300 MHz, DMSO-d6): δ 8.63 (d, J = 6.1 Hz, 2H),
7.88 (d, J = 4.0 Hz, 1H), 7.75ꢀ7.70 (m, 3H), 3.22 (q, J = 7.5 Hz, 4H),
1.10 (t, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): δ 151.1, 146.2,
141.0, 139.5, 133.2, 127.4, 120.4, 43.0, 14.6. Anal. Calcd for
C13H16N2O2S2 (296.41): C, 52.68; H, 5.44. Found: C, 52.81; H, 5.34.
5-Isoquinolin-4-ylthiophene-2-sulfonic Acid Diethylamide
(27). 4-Bromoisoquinoline (0.208 g, 1 mmol) and thiophene-2-sulfonic
acid diethylamide (0.329 g, 1.5 mmol) afford 27 in 86% (0.298 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 9.39 (s, 1H), 8.61 (s, 1H), 8.24 (d,
J = 8.0 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H), 7.79 (d,
J = 4.0 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.53 (d, J = 4.0 Hz, 1H), 3.26 (q,
J = 7.5 Hz, 4H), 1.14 (t, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-
d6): δ 154.1, 143.8, 143.4, 140.8, 133.2, 132.7, 132.5, 129.7, 128.9, 128.6,
128.3, 124.2, 123.8, 43.0, 14.7. Anal. Calcd for C17H18N2O2S2 (346.47):
C, 58.93; H, 5.24. Found: C, 59.04; H, 5.39.
2-(5-Benzenesulfonylthiophene-2-yl)benzonitrile (19).
2-Bromobenzonitrile (0.182 g, 1 mmol) and 2-benzenesulfonylthio-
phene (0.336 g, 1.5 mmol) afford 19 in 76% (0.247 g) yield. 1H NMR
(300 MHz, DMSO-d6): δ 8.10ꢀ7.95 (m, 4H), 7.80ꢀ7.60 (m, 7H). 13
C
NMR (75 MHz, DMSO-d6): δ 147.6, 143.5, 141.6, 135.2, 135.1, 135.0,
134.6, 134.4, 130.7, 130.5, 130.4, 129.7, 127.5, 118.4, 110.2. Anal. Calcd
for C17H11NO2S2 (325.41): C, 62.75; H, 3.41. Found: C, 62.87; H, 3.37.
5-(4-Cyanophenyl)thiophene-2-sulfonic Acid Diethyla-
mide (20). 4-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-
2-sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 20 in 79%
(0.253 g) yield. 1H NMR (300 MHz, DMSO-d6): δ 7.96 (d, J = 8.5 Hz,
2H), 7.93 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 4.0 Hz, 1H), 7.70 (d, J = 4.0 Hz,
1H), 3.22 (q, J = 7.5 Hz, 4H), 1.11 (t, J = 7.5 Hz, 6H). 13C NMR (75 MHz,
DMSO-d6): δ 147.1, 140.7, 136.8, 133.7, 133.3, 127.0, 118.9, 111.6, 42.9,
14.6. Anal. Calcd for C15H16N2O2S2 (320.43): C, 56.22; H, 5.03.
Found: C, 56.31; H, 5.10.
5-(4-Cyanophenyl)thiophene-2-sulfonic Acid Butylphenyla-
mide (28). 4-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-
sulfonic acid n-butylphenylamide (0.443 g, 1.5 mmol) afford 28 in 75%
(0.297 g) yield. 1H NMR (300 MHz, DMSO-d6): δ 7.93 (d, J = 8.5 Hz,
2H), 7.89 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 4.0 Hz, 1H), 7.51 (d, J = 4.0 Hz,
1H), 7.40ꢀ7.30 (m, 3H), 7.16 (d, J = 7.8 Hz, 2H), 3.65ꢀ3.60 (m, 2H),
1.37ꢀ1.22 (m, 4H), 0.80 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
DMSO-d6): δ 148.0, 138.7, 138.6, 136.7, 134.3, 133.7, 129.6, 128.9,
128.7, 127.0, 126.9, 118.9, 111.7, 50.2, 30.1, 19.4, 13.8. Anal. Calcd for
C21H20N2O2S2 (396.53): C, 63.61; H, 5.08. Found: C, 63.47; H, 5.01.
5-Naphthalen-1-ylthiophene-2-sulfonic Acid Butylpheny-
lamide (29). 1-Bromonaphthalene (0.207 g, 1 mmol) and thiophene-
2-sulfonic acid n-butylphenylamide (0.443 g, 1.5 mmol) afford 29 in 82%
(0.345 g) yield. 1H NMR (300 MHz, DMSO-d6): δ 8.03 (d, J = 8.5 Hz,
5-(4-Formylphenyl)thiophene-2-sulfonic Acid Diethyla-
mide (21). 4-Bromobenzaldehyde (0.185 g, 1 mmol) and thiophene-
2-sulfonic acid diethylamide (0.329 g, 1.5 mmol) afford 21 in 87%
1
(0.281 g) yield. H NMR (300 MHz, DMSO-d6): δ 10.03 (s, 1H),
8.00ꢀ7.95 (m, 4H), 7.79 (d, J = 4.0 Hz, 1H), 7.70 (d, J = 4.0 Hz, 1H),
3.21 (q, J = 7.5 Hz, 4H), 1.11 (t, J = 7.5 Hz, 6H). 13C NMR (75 MHz,
DMSO-d6): δ 192.8, 147.8, 140.5, 137.9, 136.4, 133.3, 130.9, 126.9,
126.7, 43.0, 14.6. Anal. Calcd for C15H17NO3S2 (323.43): C, 55.70;
H, 5.30. Found: C, 55.83; H, 5.21.
Methyl 4-(5-Diethylsulfamoylthiophene-2-yl)benzoate (22).
Methyl 4-bromobenzoate (0.215 g, 1 mmol) and thiophene-2-sulfonic
acid diethylamide (0.329 g, 1.5 mmol) afford 22 in 80% (0.283 g)
yield. 1H NMR (300 MHz, DMSO-d6): δ 8.01 (d, J = 8.5 Hz, 2H), 7.90
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NOTE
1H), 8.00 (d, J = 8.3 Hz, 2H), 7.62ꢀ7.50 (m, 5H), 7.43ꢀ7.30 (m,
4H), 7.21 (d, J = 7.8 Hz, 2H), 3.65 (t, J = 7.5 Hz, 2H), 1.37ꢀ1.22 (m,
4H), 0.78 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, DMSO-d6): δ 148.2,
138.9, 137.8, 133.9, 133.4, 131.0, 130.1, 129.5, 129.1, 129.0, 128.9, 128.7,
128.6, 127.8, 127.0, 125.9, 125.0, 50.1, 30.2, 19.4, 13.8. Anal. Calcd for
C24H23NO2S2 (421.58): C, 68.38; H, 5.50. Found: C, 68.24; H, 5.31.
5-Pyridin-3-ylthiophene-2-sulfonic Acid Butylphenylamide
(30). 3-Bromopyridine (0.158 g, 1 mmol) and thiophene-2-sulfonic acid
n-butylphenylamide (0.443 g, 1.5 mmol) afford 30 in 76% (0.283 g)
5-(4-Nitrophenyl)thiophene-2-sulfonic Acid Phenylamide
(36). 4-Bromonitrobenzene (0.202 g, 1 mmol) and thiophene-2-
sulfonic acid phenylamide (0.359 g, 1.5 mmol) afford 36 in 60%
(0.216 g) yield. 1H NMR (300 MHz, DMSO-d6): δ 10.65ꢀ10.60
(m, 1H), 8.24 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 8.5 Hz, 2H), 7.74 (d,
J = 4.0 Hz, 1H), 7.60 (d, J = 4.0 Hz, 1H), 7.29 (t, J = 7.8 Hz, 2H), 7.18 (d,
J = 8.2 Hz, 2H), 7.09 (t, J = 7.8 Hz, 1H). 13C NMR (75 MHz, DMSO-
d6): δ 147.7, 147.0, 141.5, 138.5, 137.6, 134.0, 129.8, 127.4, 127.2, 125.2,
124.9, 121.0. Anal. Calcd for C16H12N2O4S2 (360.41): C, 53.32; H, 3.36.
Found: C, 53.47; H, 3.47.
1
yield. H NMR (300 MHz, DMSO-d6): δ 8.97 (s, 1H), 8.58 (d, J =
5-(4-Cyanophenyl)thiophene-2-sulfonic Acid Phenyl Es-
ter (37). 4-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-
sulfonic acid phenyl ester (0.360 g, 1.5 mmol) afford 37 in 72% (0.245 g)
yield. 1H NMR (300 MHz, DMSO-d6): δ 7.97 (d, J = 8.5 Hz, 2H), 7.91
(d, J = 8.5 Hz, 2H), 7.85 (d, J = 4.0 Hz, 1H), 7.82 (d, J = 4.0 Hz, 1H),
7.50ꢀ7.25 (m, 3H), 7.14 (d, J = 8.2 Hz, 2H). 13C NMR (75 MHz,
DMSO-d6): δ 151.2, 149.5, 138.0, 136.1, 133.7, 133.5, 130.7, 128.3,
127.4, 127.2, 122.4, 118.8, 112.4. Anal. Calcd for C17H11NO3S2
(341.41): C, 59.81; H, 3.25. Found: C, 59.70; H, 3.31.
5-(2-Cyanophenyl)thiophene-2-sulfonic Acid Phenyl Es-
ter (38). 2-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-
sulfonic acid phenyl ester (0.360 g, 1.5 mmol) afford 38 in 76% (0.259 g)
yield. 1H NMR (300 MHz, DMSO-d6): δ 8.01 (d, J = 8.5 Hz, 1H), 7.88
(d, J = 4.0 Hz, 1H), 7.82 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 4.0 Hz, 1H),
7.66ꢀ7.60 (m, 1H), 7.50ꢀ7.30 (m, 3H), 7.15 (d, J = 8.2 Hz, 2H). 13C
NMR (75 MHz, DMSO-d6): δ 149.5, 148.7, 137.3, 135.0, 134.7, 134.4,
134.3, 130.8, 130.7, 130.6, 129.3, 128.4, 122.4, 118.3, 110.5. Anal. Calcd
for C17H11NO3S2 (341.41): C, 59.81; H, 3.25. Found: C, 59.97; H, 3.10.
5-(3-Acetylphenyl)thiophene-2-sulfonic Acid Phenyl Es-
ter (39). 3-Bromoacetophenone (0.199 g, 1 mmol) and thiophene-2-
sulfonic acid phenyl ester (0.360 g, 1.5 mmol) afford 39 in 75% (0.268 g)
yield. 1H NMR (300 MHz, DMSO-d6): δ 8.23 (s, 1H), 8.03ꢀ7.97 (m,
2H), 7.80 (s, 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.48ꢀ7.30 (m, 3H), 7.15 (d,
J = 8.0 Hz, 2H), 2.65 (s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 198.0,
152.6, 149.5, 138.2, 138.1, 132.3, 132.0, 131.1, 130.7, 130.4, 129.7, 128.3,
126.2, 125.9, 122.5, 27.4. Anal. Calcd for C18H14O4S2 (358.43): C,
60.32; H, 3.94. Found: C, 60.41; H, 3.87.
4.7 Hz, 1H), 8.10 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 4.0 Hz, 1H), 7.50 (d, J =
4.0 Hz, 1H), 7.47 (dd, J = 7.9, 4.7 Hz, 1H), 7.40ꢀ7.30 (m, 3H), 7.16 (d,
J = 7.8 Hz, 2H), 3.65ꢀ3.60 (m, 2H), 1.37ꢀ1.22 (m, 4H), 0.80 (t, J = 7.1
Hz, 3H). 13C NMR (75 MHz, DMSO-d6): δ 150.3, 147.1, 146.7, 138.8,
137.7, 134.2, 133.8, 129.6, 128.9, 128.6, 128.5, 125.9, 124.6, 50.2, 30.1,
19.4, 13.8. Anal. Calcd for C19H20N2O2S2 (372.51): C, 61.26; H, 5.41.
Found: C, 61.27; H, 5.69.
5-(4-Cyanophenyl)thiophene-2-sulfonic Acid Benzylamide
(31). 4-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-sulfonic
acid benzylamide (0.380 g, 1.5 mmol) afford 31 in 71% (0.251 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 8.60ꢀ8.55 (m, 1H), 7.94ꢀ7.91 (m,
4H), 7.74 (d, J = 4.0 Hz, 1H), 7.62 (d, J = 4.0 Hz, 1H), 7.35ꢀ7.20
(m, 5H), 4.15ꢀ4.12 (m, 2H). 13C NMR (75 MHz, DMSO-d6): δ 146.9,
142.7, 137.8, 137.0, 133.7, 133.1, 128.7, 128.1, 127.7, 127.0, 126.7, 119.0,
111.6, 46.8. Anal. Calcd for C18H14N2O2S2 (354.45): C, 60.99; H, 3.98.
Found: C, 60.87; H, 4.20.
5-(4-Acetylphenyl)thiophene-2-sulfonic Acid Benzylamide
(32). 4-Bromoacetophenone (0.199 g, 1 mmol) and thiophene-2-sul-
fonic acid benzylamide (0.380 g, 1.5 mmol) afford 32 in 66% (0.245 g)
yield. 1H NMR (300 MHz, DMSO-d6): δ 8.55ꢀ8.52 (m, 1H), 8.03 (d,
J = 8.0 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 4.0 Hz, 1H), 7.62 (d,
J = 4.0 Hz, 1H), 7.35ꢀ7.20 (m, 5H), 4.15ꢀ4.12 (m, 2H), 2.61 (s, 3H).
13C NMR (75 MHz, DMSO-d6): δ 197.6, 147.8, 142.1, 137.8, 137.1,
136.8, 133.1, 129.7, 128.7, 128.1, 127.7, 126.4, 126.0, 46.8, 27.2. Anal.
Calcd for C19H17NO3S2 (371.48): C, 61.43; H, 4.61. Found: C, 61.57;
H, 4.74.
5-(2-Cyanophenyl)thiophene-2-sulfonic Acid Benzylamide
(33). 2-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-sulfonic
acid benzylamide (0.380 g, 1.5 mmol) afford 33 in 74% (0.262 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 8.65ꢀ8.60 (m, 1H), 8.00 (d, J =
8.5 Hz, 1H), 7.85ꢀ7.73 (m, 2H), 7.66 (d, J= 4.0 Hz, 1H), 7.63 (t, J=7.8Hz,
1H), 7.58 (d, J = 4.0 Hz, 1H), 7.35ꢀ7.20 (m, 5H), 4.18 (s, 2H). 13C NMR
(75 MHz, DMSO-d6): δ 144.4, 143.6, 137.7, 135.5, 135.1, 134.5, 132.4,
130.5, 130.1, 128.7, 128.6, 128.1, 127.7, 118.6, 110.0, 46.8. Anal. Calcd for
C18H14N2O2S2 (354.45): C, 60.99; H, 3.98. Found: C, 60.97; H, 4.12.
5-Pyridin-4-ylthiophene-2-sulfonic Acid Benzylamide (34).
4-Bromopyridine hydrochloride (0.194 g, 1 mmol) and thiophene-2-
sulfonic acid benzylamide (0.380 g, 1.5 mmol) afford 34 in 73% (0.241
g) yield. 1H NMR (300 MHz, DMSO-d6): δ 8.64 (d, J = 5.0 Hz, 2H),
7.81 (d, J = 4.0 Hz, 1H), 7.70 (d, J = 5.0 Hz, 2H), 7.64 (d, J = 4.0 Hz, 1H),
7.35ꢀ7.20 (m, 5H), 4.15ꢀ4.13 (m, 2H). 13C NMR (75 MHz, DMSO-
d6): δ 151.1, 146.0, 143.0, 139.7, 137.7, 133.0, 128.7, 128.1, 127.7, 127.1,
120.4, 46.8. Anal. Calcd for C16H14N2O2S2 (330.43): C, 58.16; H, 4.27.
Found: C, 58.41; H, 4.10.
5-Isoquinolin-4-yl-thiophene-2-sulfonic Acid Phenyl Ester
(40). 4-Bromoisoquinoline (0.208 g, 1 mmol) and thiophene-2-sulfonic
acid phenyl ester (0.360 g, 1.5 mmol) afford 40 in 83% (0.305 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 9.39 (s, 1H), 8.60 (s, 1H), 8.22 (d,
J = 8.0 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 3.9 Hz, 1H), 7.88 (t,
J = 7.2 Hz, 1H), 7.76 (t, J = 7.2 Hz, 1H), 7.57 (d, J = 3.9 Hz, 1H),
7.50ꢀ7.35 (m, 3H), 7.20 (d, J = 8.0 Hz, 2H). 13C NMR (75 MHz,
DMSO-d6): δ 154.6, 149.6, 147.7, 143.9, 137.3, 133.6, 133.1, 132.6,
130.6, 130.1, 128.9, 128.6, 128.3, 128.2, 123.7, 123.6, 122.6. Anal. Calcd
for C19H13NO3S2 (367.44): C, 62.11; H, 3.57. Found: C, 62.20; H, 3.41.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of
S
b
compounds 1ꢀ40. This material is available free of charge via the
Internet at http://pubs.acs.org.
5-(4-Cyanophenyl)thiophene-2-sulfonic Acid Phenylamide
(35). 4-Bromobenzonitrile (0.182 g, 1 mmol) and thiophene-2-sulfonic
acid phenylamide (0.359 g, 1.5 mmol) afford 35 in 61% (0.207 g) yield.
1H NMR (300 MHz, DMSO-d6): δ 10.65ꢀ10.55 (m, 1H), 7.88 (d, J =
8.5 Hz, 2H), 7.85 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 4.0 Hz, 1H), 7.57 (d, J =
4.0 Hz, 1H), 7.29 (t, J = 7.8 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.09 (t, J =
7.8 Hz, 1H). 13C NMR (75 MHz, DMSO-d6): δ 147.6, 140.9, 137.6,
136.7, 133.9, 133.7, 129.7, 127.0, 126.7, 125.1, 121.0, 118.9, 111.7. Anal.
Calcd for C17H12N2O2S2 (340.42): C, 59.98; H, 3.55. Found: C, 60.08;
H, 3.68.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: henri.doucet@univ-rennes1.fr.
’ ACKNOWLEDGMENT
This research was supported by a CEFIPRA fellowship. We
thank the CNRS and “Rennes Metropole” for providing financial
support.
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The Journal of Organic Chemistry
NOTE
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