Arylation and heteroarylation of thienylsulfonamides with organotrifluoroborates

Article abstract of DOI:10.1021/jo501323z

A mild, practical protocol has been developed for the Suzuki cross-coupling of unprotected thienylsulfonamides from air- and bench-stable organotrifluoroborates in the absence of a protecting group on the sulfonamide nitrogen. The developed synthetic method can be applied to the preparation of various arylated and heteroarylated thienylsulfonamides under conditions that are tolerant of a broad range of functional groups.

Full text of DOI:10.1021/jo501323z

Note
pubs.acs.org/joc
Open Access on 07/14/2015
Arylation and Heteroarylation of Thienylsulfonamides with
Organotrifluoroborates
Mnaza Noreen,†,‡ Nasir Rasool,‡ Mirna El Khatib,† and Gary A. Molander*,†
†Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
Pennsylvania 19104-6323, United States
‡Department of Chemistry, Government College University, Faisalabad 38000, Pakistan
S
* Supporting Information
ABSTRACT: A mild, practical protocol has been developed
for the Suzuki cross-coupling of unprotected thienylsulfona-
mides from air- and bench-stable organotrifluoroborates in the
absence of a protecting group on the sulfonamide nitrogen.
The developed synthetic method can be applied to the preparation of various arylated and heteroarylated thienylsulfonamides
under conditions that are tolerant of a broad range of functional groups.
ubstituted thiophenes are important motifs in biologically
active molecules and are routinely utilized as heterocyclic
thienylsulfonamides using arylboronic acids.17−19 However, the
need for protection of the sulfonamide nitrogen and the
homocoupling of the boronic acid as a significant side reaction
are perceived shortcomings of this protocol.18 An alternative
method toward protected arylated thienylsulfonamides involves
sulfonylation of arylated thiophenes with sulfuric acid in the
presence of Ac2O, thus requiring very stable substrates.20
Therefore, a general coupling method requiring no nitrogen
protection and tolerating a broader scope of functional groups
would be greatly desired.
S
building blocks.1−6 Their structural rigidity and electronic
features also make them abundant in organic light-emitting
diodes, organic field-effect transistors, and organic solar
cells.7−11
Thienylsulfonamides have been of particular interest in
medicinal chemistry and are abundant in many biologically
active compounds.12 Thienylsulfonamide I (Figure 1), the first
Arylated thienylsulfonamides prepared by methods using
aryltrifluoroborates have never been examined. Trifluorobo-
rates21−28 are increasingly important reagents because of their
favorable physical and chemical properties; additionally, they
offer an alternative to toxic organometallic species such as
organostannanes. The tetracoordinate nature of the trifluor-
oborates makes them resistant to a variety of reaction
conditions. This characteristic allows one to build complexity
into a molecule while leaving the carbon−boron bond intact.
Unlike boronic acids, which are susceptible to undesired side
reactions, organotrifluoroborates have proven to be air-,
moisture-, and bench-stable reagents. The conventional
preparation of aryltrifluoroborates includes (i) transmetalation,
(ii) Miyaura borylation, and (iii) C−H activation.21−28 Herein,
we report an effective and practical protocol for the preparation
of unprotected thienylsulfonamides from various aryl- and
heteroaryltrifluoroborates in the presence of a simple palladium
catalyst and in the absence of a protecting group on the
sulfonamide nitrogen, under conditions that are tolerant of a
broad range of functional groups.
Figure 1. Biologically active thienylsulfonamides.
drug-like compound selective to AT2 receptor agonist M024/
C21, was reported in 2004.13 Additionally, Lawrence and co-
workers reported the design and synthesis of a novel class of
proteasome inhibitors, and their screening efforts led to the
identification of PI 8182 (compound II, Figure 1) containing a
thienylsulfonamide.14 Further, Waters and co-workers identi-
fied substituted thienylsulfonamides as drug targets against
malarial and mammalian cyclin dependent protein kinases.15
Finally, compound III (Tasisulam, LY573636·Na, Figure 1) is
a novel anticancer agent that was classified as a cytotoxic
compound and shown to initiate apoptosis.16
In initial screening, 5-bromothienyl-2-sulfonamide (1) was
treated with phenyltrifluoroborate (1.1 equiv) in the presence
of inexpensive Pd(PPh3)4 (5 mol %) under an argon
atmosphere for 12 h, examining a variety of bases and solvents
To date, the most common access to arylated thienylsulfo-
namides is by Suzuki−Miyaura cross-coupling of protected
Received: June 13, 2014
Published: July 14, 2014
© 2014 American Chemical Society
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Note
(Table 1). The use of K2CO3, Cs2CO3, and KOAc gave low to
zero yields of the desired product, and the reaction proved to
from stable, commercially available, aryl- and heteroaryltri-
fluoroborates using inexpensive Pd(PPh3)4 as a catalyst.
Table 1. Optimization of Reaction Conditions
EXPERIMENTAL SECTION
■
General. Melting points (°C) are uncorrected. All known
compounds were characterized by 1H and 13C NMR and melting
point determination (for solids) and compared with literature values.
All new compounds were characterized by H, 13C, 19F NMR spectra,
1
high-resolution mass spectrometry (HRMS), and melting point
determination (for solids). 1H, 13C, and 19F NMR spectra were
recorded at 500.4, 125.8, and 470.8 MHz, respectively. HRMS (CI)
data were obtained in positive mode, using ethane as the ionizing gas.
HRMS (ESI) data were obtained in positive or negative mode.
Reactions were performed using sealed biotage microwave vials purged
with argon several times before use. Reactions were monitored by thin-
layer chromatography carried out on silica plates using UV light for
visualization. Chromatography was performed on a Combiflash Rf 200
using hexanes and ethyl acetate as eluent.
entry
base
solvent
temp (oC) yield (%)
1
dioxane/H2O (4:1)
dioxane/H2O (4:1)
dioxane/H2O (1:1)
dioxane/H2O (4:1)
dioxane/H2O (1:1)
dioxane/H2O (4:1)
toluene/H2O (4:1)
toluene/H2O (1:1)
dioxane/H2O (4:1)
dioxane/H2O (4:1)
dioxane/H2O (4:1)
dioxane/H2O (4:1)
100
100
100
100
100
100
100
100
90
n.r.
74
2
K3PO4 (2 equiv)
K3PO4 (2 equiv)
K3PO4 (3 equiv)
K3PO4 (3 equiv)
K2CO3(3 equiv)
K3PO4 (2 equiv)
K3PO4 (3 equiv)
K3PO4 (3 equiv)
K3PO4 (3 equiv)
KOAc (3 equiv)
Cs2CO3 (3 equiv)
3
84
4
87
5
83
6
n.r.
n.r.
n.r.
77
7
General Experimental Procedure for Suzuki−Miyaura Cross-
Coupling Reaction of 5-Bromothienyl-2-sulfonamide with
Aryl- and Heteroaryltrifluoroborates. To 5-bromothienyl-2-
sulfonamide (242.1 mg, 1.00 mmol) was added aryl/heteroaryltri-
fluoroborate (1.1 mmol), K3PO4 (636 mg, 3.0 mmol), and Pd(PPh3)4
(58 mg, 0.05 mmol) in a vial, which was sealed and purged with argon
three times. Then, 1,4-dioxane (5 mL) was added, followed by the
addition of H2O (1.25 mL). The solution was stirred at 100 °C, and
the reaction was monitored by GCMS/TLC. After the reaction was
complete, it was cooled to rt. Extraction was performed with EtOAc
(30 mL × 3) to obtain the organic layer, which was filtered and dried
(Na2SO4). The solvent was removed under reduced pressure. The
residue obtained was purified by Combiflash column chromatography
using EtOAc and hexanes to obtain the desired product. The product
was characterized by spectroscopic techniques.
8
9
10
11
12
75
38
100
100
n.r.
<10
be ineffective in the absence of base. Under the conditions
tested, K3PO4 proved to be the best base for this reaction,
affording the highest yield. Lowering the temperature below
100 °C gave lower yields. The nature of the solvent proved to
be critical, with toluene (entries 6 and 7) being ineffective,
while dioxane afforded the best results.
5-Phenylthienyl-2-sulfonamide (3a).14 Obtained as a yellow
solid (208 mg, 87%). mp 200−201 °C; 1H NMR (500 MHz, acetone-
d6) δ 7.74−7.69 (m, 2H), 7.64−7.53 (m, 1H), 7.51−7.38 (m, 4H),
6.94 (br s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 150.7, 145.9,
134.6, 133.0, 131.0, 130.6, 127.7, 127.6, 124.9, 124.9; HRMS (TOF
MS ES−) m/z calcd. for C10H8NO2S2 [M − H]−, 237.9994; found,
237.9996.
Under the conditions developed, the scope of the Suzuki
coupling was evaluated. Various aryl- and heteroaryltrifluor-
oborates were employed, for which the results are described
herein. The coupling reaction between 5-bromothienyl-2-
sulfonamide (1) and aryltrifluoroborates took place efficiently,
giving good to excellent yields (Table 2, 3a−3ee) of arylated
thienylsulfonamides, thus demonstrating the feasibility of this
general method. Both electron-donating and electron-with-
drawing groups were well-tolerated in this reaction and thus
aldehydes, esters, methoxy, hydroxyl, and nitrile groups
afforded good to excellent yields. In addition, there was no
ortho steric effect on the yield of the reaction, with methyl,
aldehyde, methoxy, and hydroxyl groups at that position
leading to no discernible diminution of yield (Table 2,
3f,g,i,p,s,t,z,bb). In those instances where modest yields were
obtained, typically, unreacted starting material was recovered
together with negligible amounts of protodeboronation.
Under the same optimized conditions, heteroaryltrifluor-
oborates were also investigated (Table 3), demonstrating the
effectiveness of this protocol. Diverse nitrogen-, oxygen-, and
sulfur-containing heteroaryltrifluoroborates of various ring sizes
were successfully cross-coupled with 5-bromothienyl-2-sulfona-
mide (1). Isoquinolinyl (5a), pyridinyl (5b,c,h, j), furyl (5o−
q), thienyl (5d,f,g,k,m), isoxazolyl (5e), indolyl (5i,n), and
dibenzothienyl (5l) trifluoroborates were all examined under
the reaction conditions and afforded the desired products in
good to excellent yields. Of note, chloride, nitro, and aldehyde
substituents on the heteroaryltrifluoroborate were well-
tolerated.
5-(3,5-Diisopropylphenyl)thienyl-2-sulfonamide (3b). Ob-
1
tained as a white solid (220 mg, 68%). mp 185−186 °C; H NMR
(500 MHz, acetone-d6) δ 7.58 (dd, J = 4.0, 1.0 Hz, 1H), 7.44 (dd, J =
4.0, 1.0 Hz, 1H), 7.40 (br s, 2H), 7.20 (br s, 1H), 6.87 (br s, 2H),
3.02−2.88 (m, 2H), 1.29 (d, J = 7.0 Hz, 12H); 13C NMR (125.8 MHz,
acetone-d6) δ 150.9, 150.7, 144.6, 133.8, 132.1, 126.3, 123.8, 122.6,
34.8, 24.2; HRMS (TOF MS ES+) m/z calcd. for C16H22NO2S2 [M +
H]+, 324.1092; found, 324.1088.
5-(3-Cyanophenyl)thienyl-2-sulfonamide (3c). Obtained as a
1
yellow solid (232 mg, 88%). mp 168−170 °C; H NMR (500 MHz,
DMSO-d6) δ 8.27 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.0
Hz, 1H), 7.82 (br s, 2H), 7.00 (d, J = 3.5 Hz, 1H), 7.67 (t, J = 8.0 Hz,
1H), 7.59 (d, J = 4.0 Hz, 1H); 13C NMR (125.8 MHz, DMSO-d6) δ
145.6, 145.1, 133.6, 132.2, 131.0, 130.6, 130.5, 129.2, 125.4, 118.3,
112.5; HRMS (TOF MS ES+) m/z calcd. for C11H7N2O2S2 [M −
H]−, 262.9949; found, 262.9948.
5-(2,5-Dimethoxyphenyl)thienyl-2-sulfonamide (3d). Ob-
1
tained as a yellow solid (287 mg, 96%). mp 170−172 °C; H NMR
(500 MHz, acetone-d6) δ 7.64−7.58 (m, 2H), 7.40−7.37 (m, 1H),
7.26 (dd, J = 9.0, 2.0 Hz, 1H), 7.00−6.96 (m, 1H), 6.85 (br s, 2H),
3.97 (s, 3H), 3.86 (s, 3H); 13C NMR (125.8 MHz, acetone-d6) δ
154.7, 150.7, 145.4, 144.5, 130.3, 125.1, 122.9, 115.8, 114.2, 113.5,
56.5, 55.9; HRMS (TOF MS ES+) m/z calcd. for C12H14NO4S2 [M +
H]+, 300.0364; found, 300.0364.
5-(3-Hydroxyphenyl)thienyl-2-sulfonamide (3e). Obtained as
a yellow solid (240 mg, 94%). mp 176−178 °C; 1H NMR (500 MHz,
acetone-d6) δ 7.56 (dd, J = 3.5, 1.5 Hz, 1H), 7.38 (dd, J = 4.0, 1.5 Hz,
1H), 7.31−7.24 (m, 2H), 7.20−7.14 (m, 3H), 6.89 (d, J = 8.0 Hz,
1H); 13C NMR (125.8 MHz, acetone-d6) δ 158.6, 149.7, 144.6, 134.8,
In conclusion, the results described herein reveal that the
approach developed serves as a general, versatile method for the
synthesis of diversely substituted NH2-free thienylsulfonamides
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Note
Table 2. Substrate Scope of Arylated Thienylsulfonamides
132.0, 131.0, 123.7, 118.0, 116.7, 113.3; HRMS (TOF MS ES+) m/z
calcd. for C10H8NO3S2 [M − H]−, 253.9946; found, 253.9943.
5-(2-Methoxyphenyl)thienyl-2-sulfonamide (3f). Obtained as
a yellow solid (248 mg, 92%). mp 180−181 °C; 1H NMR (500 MHz,
acetone-d6) δ 7.85−7.75 (m, 1H), 7.65−7.50 (m, 2H), 7.40−7.30 (m,
1H), 7.20−7.10 (m, 1H), 7.10−7.00 (m, 1H), 6.85 (br s, 2H), 3.98 (s,
3H); 13C NMR (125.8 MHz, acetone-d6) δ 156.0, 144.8, 144.5, 130.4,
130.1, 128.2, 124.6, 121.8, 121.5, 112.5, 55.7; HRMS (TOF MS ES+)
m/z calcd. for C11H12NO3S2 [M + H]+, 270.0259; found, 270.0254.
5-(2-Formylphenyl)thienyl-2-sulfonamide (3g). Obtained as a
yellow solid (246 mg, 92%). mp 177−178 °C; H NMR (500 MHz,
1
acetone-d6) δ 10.18 (s, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.79−7.74 (m,
1H), 7.68−7.62 (m, 3H), 7.26 (dd, J = 7.8, 3.8 Hz, 1H), 7.01 (br s,
2H); 13C NMR (125.8 MHz, acetone-d6) δ 191.3, 147.7, 144.5, 136.7,
135.2, 134.7, 132.3, 131.4, 130.3, 130.2, 128.9; HRMS (TOF MS ES+)
m/z calcd. for C11H9NO3S2Na [M + Na]+, 289.9922; found, 289.9924.
5-(3-Formyl-4-methoxyphenyl)thienyl-2-sulfonamide (3h).
Obtained as a yellow solid (262 mg, 88%). mp 192−193 °C; 1H
NMR (500 MHz, acetone-d6) δ 10.50−10.45 (m, 1H), 8.01−7.95 (m,
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Table 3. Substrate Scope of Heteroarylated Thienylsulfonamides
2H), 7.60−7.56 (m, 1H), 7.50−7.42 (m, 1H), 7.37−7.30 (m, 1H),
6.92 (br s, 2H), 4.10−4.04 (m, 3H); 13C NMR (125.8 MHz, acetone-
d6) δ 189.1, 163.2, 148.6, 144.9, 134.3, 132.4, 126.7, 126.0, 125.8,
124.0, 114.4, 56.8; HRMS (TOF MS ES+) m/z calcd. for
C12H12NO4S2 [M + H]+, 298.0208; found, 298.0213.
Hz, 1H), 6.92 (br s, 2H), 3.89 (s, 3H); 13C NMR (125.8 MHz,
acetone-d6) δ 161.2, 149.7, 145.1, 135.0, 132.1, 131.2, 124.2, 119.2,
115.4, 112.2, 55.7; HRMS (TOF MS ES+) m/z calcd. for
C11H12NO3S2 [M + H]+, 270.0259; found, 270.0272.
5-(Naphthalen-1-yl)thienyl-2-sulfonamide (3l). Obtained as a
1
5-(6-Formylbenzo[d][1,3]dioxol-5-yl)thienyl-2-sulfonamide
white solid (284 mg, 98%). mp 243−244 °C; H NMR (500 MHz,
1
(3i). Obtained as a yellow solid (274 mg, 88%). mp 210−212 °C; H
acetone-d6) δ 8.17−8.15 (m, 1H), 8.04 (d, J = 7.0 Hz, 2H), 7.01 (d, J
= 4.0 Hz, 1H), 7.65 (d, J = 7.0 Hz, 1H), 7.62−7.58 (m, 3H), 7.32−
7.30 (m, 1H), 7.04 (br s, 1H); 13C NMR (125.8 MHz, acetone-d6) δ
147.5, 146.3, 134.9, 132.2, 131.5, 131.5, 130.4, 129.5, 129.3, 128.4,
128.0, 127.3, 126.3, 125.7; HRMS (TOF MS ES+) m/z calcd. for
C14H10NO2S2 [M − H]−, 288.0153; found, 288.0156.
NMR (500 MHz, acetone-d6) δ 9.94 (s, 1H), 7.63 (dd, J = 4.0, 1.5 Hz,
1H), 7.36 (s, 1H), 7.63 (dd, J = 4.0, 1.5 Hz, 1H), 7.07 (s, 1H), 6.99 (br
s, 2H), 6.24 (s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 189.4,
153.4, 150.2, 147.8, 144.3, 133.9, 131.4, 130.8, 130.4, 111.6, 106.9,
104.1; HRMS (TOF MS ES+) m/z calcd. for C12H9NO5S2Na [M +
Na]+, 333.9819; found, 333.9817.
5-(4-(Benzyloxy)-2-formylphenyl)thienyl-2-sulfonamide
(3m). Obtained as a yellow solid (291 mg, 78%). mp 254−255 °C; 1H
NMR (500 MHz, acetone-d6) δ 10.13 (s, 1H), 7.64 (d, J = 4.0 Hz,
1H), 7.60−7.50 (m, 4H), 7.45−7.32 (m, 4H), 7.17 (d, J = 3.5 Hz,
1H), 6.98 (br s, 2H), 5.28 (s, 2H); 13C NMR (125.8 MHz, acetone-d6)
δ 191.0, 160.5, 147.3, 144.7, 137.7, 136.4, 133.9, 131.5, 129.9, 129.6,
129.5, 129.0, 128.6, 122.1, 113.4, 71.0; HRMS (TOF MS ES+) m/z
calcd. for C18H15NO4S2Na [M + Na]+, 396.0340; found, 396.0337.
Methyl 3-(5-Sulfamoylthiophen-2-yl)benzoate (3n). Obtained
5-(3-(Hydroxymethyl)phenyl)thienyl-2-sulfonamide (3j). Ob-
1
tained as a yellow solid (261 mg, 97%). mp 180−181 °C; H NMR
(500 MHz, acetone-d6) δ 7.69 (s, 1H), 7.58−7.56 (m, 2H), 7.44−7.37
(m, 3H), 6.88 (br s, 2H), 4.69 (br s, 2H); 13C NMR (125.8 MHz,
acetone-d6) δ 150.2, 145.1, 144.8, 133.8, 132.3, 130.1, 128.1, 125.4,
125.0, 124.1, 64.3; HRMS (TOF MS ES+) m/z calcd. for
C11H10NO3S2 [M − H]−, 268.0103; found, 268.0104.
5-(3-Methoxyphenyl)thienyl-2-sulfonamide (3k). Obtained as
a yellow solid (199 mg, 74%). mp 170−171 °C; 1H NMR (500 MHz,
acetone-d6) δ 7.60 (dd, J = 8.5, 4.5 Hz, 1H), 7.47 (dd, J = 8.0, 4.0 Hz,
1H), 7.42−7.36 (m, 1H), 7.30−7.22 (m, 2H), 7.01 (dd, J = 8.0, 2.5
1
as a yellow solid (214 mg, 72%). mp 235−236 °C; H NMR (500
MHz, acetone-d6) δ 8.25 (s, 1H), 8.01 (dd, J = 8.0, 1.0 Hz, 1H), 7.95
(d, J = 7.5 Hz, 1H), 7.62−7.57 (m, 2H), 7.53 (dd, J = 4.0, 1.5 Hz, 1H),
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Note
6.95 (br s, 2H), 3.92 (s, 3H); 13C NMR (125.8 MHz, acetone-d6) δ
166.6, 148.4, 145.8, 134.2, 132.3, 132.2, 131.1, 130.5, 130.2, 127.3,
124.9, 52.6; HRMS (TOF MS ES+) m/z calcd. for C12H10NO4S2 [M
− H]−, 296.0051; found, 296.0056.
133.3, 132.5, 132.2, 130.8, 127.3, 126.4, 126.3, 53.1; HRMS (TOF MS
ES+) m/z calc. for C12H10N2O2S2 [M]+, 278.35100; found, 278.35100.
5-(4-Ethoxyphenyl)thienyl-2-sulfonamide (3x). Obtained as a
1
yellow solid (227 mg, 80%). mp 155−156 °C; H NMR (500 MHz,
5-(4-(Methoxymethyl)phenyl)thienyl-2-sulfonamide (3o).
Obtained as a yellow solid (260 mg, 92%). mp 191−192 °C; 1H
NMR (500 MHz, acetone-d6) δ 7.70−7.65 (m, 2H), 7.58 (d, J = 3.5
Hz, 1H), 7.46−7.39 (m, 3H), 6.89 (br s, 2H), 4.47 (s, 2H), 3.36 (s,
3H); 13C NMR (125.8 MHz, acetone-d6) δ 149.8, 145.0, 140.8, 133.1,
132.3, 129.2, 126.8, 124.0, 74.4, 58.3; HRMS (TOF MS ES+) m/z
calc. for C12H12NO3S2 [M − H]−, 282.0259; found, 282.0259.
5-(4-Chloro-2-methylphenyl)thienyl-2-sulfonamide (3p). Ob-
acetone-d6) δ 7.63 (dd, J = 7.0, 2.0 Hz, 2H), 7.54 (d, J = 4.0 Hz, 1H),
7.31 (d, J = 4.0 Hz, 1H), 7.01 (dd, J = 7.0, 2.0 Hz, 2H), 6.85 (br s,
2H), 4.15−4.06 (m, 2H), 1.42−1.35 (m, 3H); 13C NMR (125.8 MHz,
acetone-d6) δ 160.7, 150.2, 143.7, 132.3, 128.2, 126.2, 122.7, 115.9,
64.3, 15.0; HRMS (TOF MS ES+) m/z calcd. for C12H12NO3S2 [M −
H]−, 282.0259; found, 282.0254.
5-(2-(Benzyloxy)phenyl)thienyl-2-sulfonamide (3y). Obtained
1
as a yellow solid (235 mg, 68%). mp 262−264 °C; H NMR (500
1
MHz, acetone-d6) δ 7.89 (dd, J = 7.5, 1.5 Hz, 1H), 7.68−7.60 (m, 4H),
7.51−7.46 (m, 2H), 7.45−7.39 (m, 2H), 7.32 (d, J = 6.5 Hz, 1H),
7.17−7.11 (m, 1H), 6.90 (br s, 2H), 5.45 (s, 2H); 13C NMR (125.8
MHz, acetone-d6) δ 155.4, 145.3, 144.9, 137.6, 130.6, 129.3, 129.1,
128.8, 128.4, 125.4, 122.7, 122.1, 114.3, 71.1; HRMS (TOF MS ES+)
m/z calcd. for C17H15NO3S2Na [M + Na]+, 368.0391; found,
368.0393.
tained as a yellow solid (235 mg, 82%). mp 171−172 °C; H NMR
(500 MHz, acetone-d6) δ 7.70 (d, J = 7.0 Hz, 1H), 7.55−7.45 (m, 2H),
7.39 (dd, J = 8.0, 2.0 Hz, 1H), 7.26−7.22 (m, 1H), 7.01 (br s, 2H),
2.51 (s, 3H); 13C NMR (125.8 MHz, acetone-d6) δ 147.1, 145.8,
139.0, 134.7, 132.3, 132.0, 131.3, 131.2, 127.7, 126.9, 20.7; HRMS
(TOF MS ES+) m/z calcd. for C11H11ClNO2S2 [M + H]+, 287.9913;
found, 287.9912.
5-(o-Tolyl)thienyl-2-sulfonamide (3z). Obtained as a yellow
solid (147 mg, 58%). mp 144−145 °C; 1H NMR (500 MHz, acetone-
d6) δ 7.61 (d, J = 3.5 Hz, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.34 (d, J = 4.5
Hz, 2H), 7.30−7.26 (m, 1H), 7.14 (d, J = 4.0 Hz, 1H), 6.91 (br s, 2H),
2.41 (s, 3H); 13C NMR (125.8 MHz, acetone-d6) δ 148.8, 145.7,
136.9, 133.4, 131.9, 131.3, 131.0, 129.8, 127.5, 127.2, 21.1; HRMS
(TOF MS ES+) m/z calcd. for C11H12NO2S2 [M + H]+, 254.0309;
found, 254.0318.
5-(3-Chloro-4-formylphenyl)thienyl-2-sulfonamide (3q). Ob-
tained as a yellow solid (265 mg, 88%). mp 211−212 °C; H NMR
1
(500 MHz, acetone-d6) δ 10.4 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.88
(s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 4.0 Hz, 1H), 7.64 (d, J =
3.5 Hz, 1H), 7.03 (br s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ
189.1, 147.6, 146.0, 140.1, 138.6, 132.7, 132.2, 130.9, 128.1, 126.9,
125.7; HRMS (TOF MS ES+) m/z calcd. for C11H7ClNO3S2 [M −
H]−, 299.9556; found, 299.9566.
5-(Thianthren-1-yl)thienyl-2-sulfonamide (3aa). Obtained as a
yellow solid (317 mg, 84%). mp 256−258 °C; H NMR (500 MHz,
N-(3-(5-Sulfamoylthiophen-2-yl)phenyl)acetamide (3r). Ob-
tained as a yellow solid (172 mg, 58%). mp 209−210 °C; H NMR
1
1
acetone-d6) δ 7.69−7.65 (m, 2H), 7.60 (dd, J = 7.5, 1.5 Hz, 1H), 7.53
(dd, J = 7.5, 1.5 Hz, 2H), 7.44 (t, J = 7.5 Hz, 1H), 7.39 (td, J = 7.5, 1.5
Hz, 1H), 7.35 (dd, J = 7.5, 1.5 Hz, 1H), 7.33 (d, J = 3.5 Hz, 1H); 13C
NMR (125.8 MHz, acetone-d6) δ 147.0, 146.0, 137.1, 136.6, 136.1,
135.7, 134.1, 131.1, 130.9, 130.4, 129.7, 129.4, 129.3, 129.0, 128.7;
HRMS (TOF MS ES+) m/z calcd. for C16H10NO2S4 [M − H]−,
375.9594; found, 375.9606.
(500 MHz, acetone-d6) δ 9.29 (s, 1H), 8.15 (s, 1H), 7.63−7.58 (m,
2H), 7.44−7.38 (m, 3H), 6.92 (br s, 2H), 2.13 (s, 3H); 13C NMR
(125.8 MHz, acetone-d6) δ 169.3, 149.9, 145.1, 141.4, 134.3, 132.2,
130.5, 124.0, 121.5, 120.2, 117.3, 24.4; HRMS (TOF MS ES+) m/z
calcd. for C12H13N2O3S2 [M + H]+, 297.0374; found, 297.0376.
5-(2-Hydroxy-3-methylphenyl)thienyl-2-sulfonamide (3s).
Obtained as a brown solid (156 mg, 58%). mp 214−215 °C; 1H
NMR (500 MHz, acetone-d6) δ 8.27 (br s, 1H), 7.60−7.50 (m, 3H),
7.18 (d, J = 7.0 Hz, 1H), 6.95−6.90 (m, 1H), 6.79 (br s, 2H), 2.36 (s,
3H); 13C NMR (125.8 MHz, acetone-d6) δ 152.0, 145.7, 144.7, 131.6,
130.3, 126.4, 126.1, 124.7, 121.3, 121.1, 16.5; HRMS (TOF MS ES+)
m/z calcd. for C11H10NO3S2 [M − H]−, 268.0102; found, 268.0112.
5-(2-Methoxynaphthalen-1-yl)thienyl-2-sulfonamide (3t).
Obtained as a yellow solid (275 mg, 86%). mp 256−258 °C; 1H
NMR (500 MHz, acetone-d6) δ 8.05 (d, J = 9.5 Hz, 1H), 7.91 (d, J =
8.0 Hz, 1H), 7.74 (d, J = 3.5 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.53
(d, J = 9.5 Hz, 1H), 7.49−7.44 (m, 1H), 7.43−7.38 (m, 1H), 7.09 (d, J
= 4 Hz, 1H), 6.97 (br s, 2H), 3.93 (br s, 3H); 13C NMR (125.8 MHz,
acetone-d6) δ 155.5, 145.7, 142.5, 134.0, 131.6, 130.5, 129.1, 129.1,
128.5, 127.5, 124.3, 124.1, 115.1, 113.6, 56.4; HRMS (TOF MS ES+)
m/z calcd. for C15H12NO3S2 [M − H]−, 318.0259; found, 318.0258.
5-(4-Vinylphenyl)thienyl-2-sulfonamide (3u). Obtained as a
5-(2-Formyl-5-methoxyphenyl)thienyl-2-sulfonamide (3bb).
Obtained as a yellow solid (268 mg, 90%). mp 208−209 °C; 1H NMR
(500 MHz, acetone-d6) δ 10.06 (s, 1H), 8.01 (d, J = 9.0 Hz, 1H), 7.68
(d, J = 3.5 Hz, 1H), 7.29 (d, J = 4.0 Hz, 1H), 7.23 (dd, J = 9.0, 2.5 Hz,
1H), 7.13 (d, J = 2.0 Hz, 1H), 7.03 (br s, 2H), 4.02 (s, 3H); 13C NMR
(125.8 MHz, acetone-d6) δ 189.7, 164.7, 147.8, 144.5, 139.2, 131.4,
130.2, 130.2, 128.7, 116.9, 116.4, 59.5; HRMS (TOF MS ES+) m/z
calcd. for C12H11NO4S2Na [M + Na]+, 320.0027; found, 320.0020.
5-(Cyclohex-1-en-1-yl)thienyl-2-sulfonamide (3cc). Obtained
1
as a yellow solid (190 mg, 78%). mp 144−146 °C; H NMR (500
MHz, acetone-d6) δ 7.47 (d, J = 3.5 Hz, 1H), 7.02 (d, J = 3.5 Hz, 1H),
6.80 (br s, 2H), 6.33 (m, 1H), 2.43−2.41 (m, 2H), 2.24−2.08 (m,
2H), 1.82−1.75 (m, 2H), 1.70−1.62 (m, 2H); 13C NMR (125.8 MHz,
acetone-d6) δ 152.4, 142.6, 131.4, 131.4, 127.3, 121.8, 27.7, 26.1, 23.1,
22.4; HRMS (TOF MS ES+) m/z calcd. for C10H13NO2S2 Na [M +
Na]+, 266.0285; found, 266.0287.
1
yellow solid (122 mg, 46%). mp 148−150 °C; H NMR (500 MHz,
5-Cyclopropylthienyl-2-sulfonamide (3dd). Obtained as a
acetone-d6) δ 7.73−7.67 (m, 2H), 7.60−7.53 (m, 3H), 7.50−7.44 (m,
1H), 6.92 (br s, 2H), 6.85−6.75 (m, 1H), 5.91 (dd, J = 17.5, 4.5 Hz,
1H), 5.32 (dd, J = 11.0, 4.5 Hz, 1H); 13C NMR (125.8 MHz, acetone-
d6) δ 149.6, 145.2, 139.2, 137.1, 133.3, 132.3, 128.0, 127.1, 124.1,
115.3; HRMS (TOF MS ES+) m/z calcd. for C12H10NO2S2 [M −
H]−, 264.0153; found, 264.0163.
1
yellow solid (93 mg, 46%). mp 155−156 °C; H NMR (500 MHz,
acetone-d6) δ 7.42−7.37 (m, 1H), 6.85−6.81 (m, 1H), 6.73 (br s, 2H),
2.86 (d, J = 7.5 Hz, 1H), 1.16−1.108 (m, 2H), 0.84−0.74 (m, 2H);
13C NMR (125.8 MHz, acetone-d6) δ 155.8, 142.2, 131.4, 123.4, 12.1,
11.1; HRMS (TOF MS ES+) m/z calcd. for C7H8NO2S2 [M + H]+,
204.0153; found, 204.0160.
5-(4-(tert-Butyl)phenyl)thienyl-2-sulfonamide (3v). Obtained
1
as a yellow solid (280 mg, 95%). mp 188−190 °C; H NMR (500
5-(2,3-Difluoro-4-formylphenyl)thienyl-2-sulfonamide (3ee).
Obtained as a yellow solid (227 mg, 75%). mp 212−214 °C; 1H NMR
(500 MHz, acetone-d6) δ 10.36 (s, 1H), 7.90−7.71 (m, 4H), 7.11 (br
s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 186.4, 154.6, 152.5,
149.3, 149.2, 147.3, 147.2, 139.6, 131.7, 129.5, 129.5, 124.8, 124.4;
HRMS (TOF MS ES+) m/z calcd. for C11H6F2NO3S2 [M − H]−,
301.9757; found, 301.9757.
MHz, acetone-d6) δ 7.68−7.50 (m, 5H), 7.42 (d, J = 4 Hz, 1H), 6.90
(br s, 2H), 1.36 (s, 9H); 13C NMR (125.8 MHz, acetone-d6) δ 152.8,
149.9, 144.4, 132.1, 130.9, 126.9, 126.5, 123.4, 35.1, 31.7, 31.3; HRMS
(TOF MS ES+) m/z calcd. for C14H16NO2S2 [M − H]−, 294.0622;
found, 294.0624.
5-(3-Cyano-5-methylphenyl)thienyl-2-sulfonamide (3w). Ob-
1
tained as a yellow solid (111 mg, 40%). mp 196−198 °C; H NMR
5-(Isoquinolin-5-yl)thienyl-2-sulfonamide (5a). Obtained as a
1
(500 MHz, acetone-d6) δ 8.47 (s, 1H), 8.27 (s, 1H), 8.23 (s, 1H), 7.74
(d, J = 4.0 Hz, 1H), 7.66 (d, J = 4.0 Hz, 1H), 7.02 (br s, 2H), 3.99 (s,
3H); 13C NMR (125.8 MHz, acetone-d6) δ 165.4, 147.1, 146.2, 135.6,
yellow solid (273 mg, 94%). mp 236−237 °C; H NMR (500 MHz,
acetone-d6) δ 9.40 (s, 1H), 8.61−8.59 (m, 1H), 8.24 (d, J = 8.0 Hz,
1H), 8.00 (d, J = 5.5 Hz, 1H), 7.92 (dd, J = 7.5, 1.5 Hz, 1H), 7.80−
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The Journal of Organic Chemistry
Note
7.73 (m, 2H), 7.41−7.39 (m, 1H), 7.06 (br s, 2H); 13C NMR (125.8
MHz, acetone-d6) δ 154.0, 147.0, 145.7, 145.3, 134.5, 133.2, 131.7,
130.6, 130.1, 129.9, 128.8, 127.9, 118.2; HRMS (TOF MS ES+) m/z
calcd. for C13H11N2O2S2 [M + H]+, 291.0262; found, 291.0260.
5-(2-Chloropyridin-3-yl)thienyl-2-sulfonamide (5b). Obtained
(TOF MS ES+) m/z calcd. for C9H8ClN2O2S2 [M + H]+, 274.9722;
found, 274.9721.
5′-Formyl-3′-methyl-[2,2′-bithienyl]-5-sulfonamide (5k). Ob-
1
tained as a yellow solid (224 mg, 78%). mp 188−189 °C; H NMR
(500 MHz, acetone-d6) δ 9.92 (s, 1H), 7.85 (s, 1H), 7.64 (d, J = 7.0
Hz, 1H), 7.43 (d, J = 4.0 Hz, 1H), 7.02 (br s, 2H), 2.80 (s, 3H); 13C
NMR (125.8 MHz, acetone-d6) δ 183.9, 147.5, 142.5, 141.7, 140.6,
139.1, 137.9, 131.9, 128.1, 15.8; HRMS (TOF MS ES+) m/z calcd. for
C10H10NO3S3 [M + H]+, 285.9666; found, 285.9673.
1
as a yellow solid (209 mg, 76%). mp 194−195 °C; H NMR (500
MHz, acetone-d6) δ 8.47−8.45 (m, 1H), 8.14−8.11 (m, 1H), 7.65−
7.63 (m, 1H), 7.56−7.52 (m, 1H), 7.52−7.49 (m, 1H), 7.04 (br s,
1H); 13C NMR (125.8 MHz, acetone-d6) δ 150.2, 149.0, 147.7, 143.2,
140.7, 130.9, 129.4, 129.3, 124.1; HRMS (TOF MS ES+) m/z calcd.
for C9H8ClN2O2S2 [M + H]+, 274.9714; found, 274.9709.
5-(Dibenzo[b,d]thiophen-4-yl)thienyl-2-sulfonamide (5l).
Obtained as a yellow solid (311 mg, 90%). mp 248−250 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.48 (dd, J = 8.0, 1.0 Hz, 1H), 8.47−
8.44 (m, 1H), 8.13−8.10 (m, 1H), 7.86 (s, 2H), 7.85 (d, J = 7.5 Hz,
1H), 7.72−7.69 (m, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.62−7.57 (m, 2H);
13C NMR (125.8 MHz, DSMO-d6) δ 145.4, 145.2, 138.1, 136.5, 136.4,
134.9, 130.7, 127.7, 127.6, 126.9, 126.1, 125.8, 125.3, 123.0, 122.6,
122.4; HRMS (TOF MS ES+) m/z calcd. for C16H12NO2S3 [M + H]+,
346.0030; found, 346.0036.
5-(2-Nitropyridin-4-yl)thienyl-2-sulfonamide (5c). Obtained
1
as a yellow solid (223 mg, 78%). mp 202−203 °C; H NMR (500
MHz, acetone-d6) δ 9.02 (d, J = 1.5 Hz, 1H), 8.60−8.53 (m, 1H),
8.45−8.36 (m, 1H), 7.84 (d, J = 6.5 Hz, 1H), 7.71 (d, J = 6.5 Hz, 1H),
7.12 (br s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 157.1, 148.7,
146.5, 143.1, 137.8, 135.3, 132.4, 128.1, 119.5; HRMS (TOF MS ES+)
m/z calcd. for C9H8N3O4S2 [M + H]+, 285.9956; found, 285.9955.
4′-Formyl-[2,3′-bithienyl]-5-sulfonamide (5d). Obtained as a
5′-Formyl-[2,2′-bithienyl]-5-sulfonamide (5m). Obtained as a
1
1
yellow solid (213 mg, 78%). mp 166−167 °C; H NMR (500 MHz,
yellow solid (213 mg, 78%). mp 156−158 °C; H NMR (500 MHz,
acetone-d6) δ 10.06 (s, 1H), 8.59 (d, J = 5.0 Hz, 1H), 7.85 (d, J = 5.0
Hz, 1H), 7.61 (dd, J = 8.5, 3.8 Hz, 1H), 7.41 (dd, J = 8.5, 4.0 Hz, 1H),
6.96 (br s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 185.6, 146.0,
141.5, 140.3, 139.9, 133.7, 131.3, 128.9, 128.2; HRMS (TOF MS ES+)
m/z calcd. for C9H7NO3S3Na [M + Na]+, 295.9486; found, 295.9491.
5-(3,5-Dimethylisoxazol-4-yl)thienyl-2-sulfonamide (5e). Ob-
DMSO-d6) δ 9.93 (s, 1H), 8.04 (d, J = 4.0 Hz, 1H), 7.86 (br s, 2H),
7.68 (d, J = 4.0 Hz, 1H), 7.59 (d, J = 3.5 Hz, 1H), 7.56 (d, J = 4.0 Hz,
1H); 13C NMR (125.8 MHz, DMSO-d6) δ 184.2, 146.1, 143.3, 142.7,
139.1, 139.0, 131.1, 127.0, 126.6; HRMS (TOF MS ES−) m/z calcd.
for C9H5NO3S3 [M − H]−, 271.9510; found, 271.9512.
5-(1H-Indol-6-yl)thienyl-2-sulfonamide (5n). Obtained as a
1
1
tained as a yellow solid (240 mg, 93%). mp 214−215 °C; H NMR
brown solid (150 mg, 54%). mp 209−210 °C; H NMR (500 MHz,
(500 MHz, acetone-d6) δ 7.64 (d, J = 3.5 Hz, 1H), 7.20 (d, J = 4.0 Hz,
1H), 6.96 (br s, 2H), 2.55 (s, 3H), 2.35 (s, 3H); 13C NMR (125.8
MHz, acetone-d6) δ 167.3, 158.4, 145.3, 137.1, 131.3, 126.9, 109.9,
11.8, 10.8; HRMS (TOF MS ES+) m/z calcd. for C9H10N2O3S2Na [M
+ Na]+, 281.0031; found, 281.0027.
DMSO-d6) δ 7.90 (br s, 1H), 7.68 (br s, 2H), 7.53−7.49 (m, 1H),
7.48−7.46 (m, 1H), 7.44−7.38 (m, 3H), 6.51 (s, 1H); 13C NMR
(125.8 MHz, DMSO-d6) δ 150.5, 142.1, 136.2, 131.1, 128.1, 126.9,
123.6, 121.6, 119.5, 117.7, 112.3, 101.8; HRMS (TOF MS ES+) m/z
calcd. for C12H9N2 [M − O2S2]−, 277.0112; found, 277.0117.
5-(Furan-2-yl)thienyl-2-sulfonamide (5o). Obtained as a black-
[2,2′-Bithienyl]-5-sulfonamide (5f). Obtained as a yellow solid
1
1
(182 mg, 74%). mp 188−189 °C; H NMR (500 MHz, DMSO-d6) δ
ish brown solid (188 mg, 82%). mp 165−167 °C; H NMR (500
7.74 (br s, 2H), 7.64 (d, J = 5.5 Hz, 1H), 7.48 (d, J = 2.1 Hz, 1H), 7.46
(dd, J = 3.5, 1.0 Hz, 1H), 7.31 (d, J = 4.0 Hz, 1H), 7.15 (t, J = 4.0 Hz,
1H); 13C NMR (125.8 MHz, DMSO-d6) δ 143.4, 140.9, 134.7, 131.0,
128.7, 127.3, 125.9, 123.7; HRMS (TOF MS ES+) m/z calcd. for
C8H8NO2S3 [M + H]+, 245.9717; found, 245.9712.
MHz, acetone-d6) δ 7.68−7.66 (m, 1H), 7.54 (d, J = 3.5 Hz, 1H), 7.32
(d, J = 4.0 Hz, 1H), 6.94 (br s, 2H), 6.88 (d, J = 3.5 Hz, 1H), 6.61−
6.59 (m, 1H); 13C NMR (125.8 MHz, acetone-d6) δ 148.5, 144.1,
138.7, 131.9, 127.8, 122.8, 113.1, 108.3; HRMS (TOF MS ES+) m/z
calcd. for C8H8NO3S2 [M + H]+, 229.9946; found, 229.9957.
5-(Furan-3-yl)thienyl-2-sulfonamide (5p). Obtained as a brown
solid (179 mg, 78%). mp 186−187 °C; 1H NMR (500 MHz, acetone-
d6) δ 8.04−8.01 (m, 1H), 7.67−7.63 (m, 1H), 7.53−7.49 (m, 1H),
7.23−7.19 (m, 1H), 6.87 (br s, 2H), 6.80 (s, 1H); 13C NMR (125.8
MHz, acetone-d6) δ 145.2, 143.5, 140.4, 131.7, 129.3, 124.0, 120.2,
109.6; HRMS (TOF MS ES+) m/z calcd. for C8H6NO3S2 [M − H]−,
227.9789; found, 227.9781.
[2,3′-Bithienyl]-5-sulfonamide (5g). Obtained as a brown solid
(240 mg, 98%). mp 181−182 °C; 1H NMR (500 MHz, acetone-d6) δ
7.81−7.79 (m, 1H), 7.62 (dd, J = 5.0, 3.0 Hz, 1H), 5.54 (d, J = 4.0 Hz,
1H), 7.46 (dd, J = 5.0, 1.0 Hz, 1H); 13C NMR (125.8 MHz, acetone-
d6) δ 144.8, 144.0, 135.1, 132.1, 128.4, 126.7, 124.0, 122.7; HRMS
(TOF MS ES+) m/z calcd. for C8H6NO2S3 [M − H]−, 243.9561;
found, 243.9572.
5-(Pyridin-3-yl)thienyl-2-sulfonamide (5h). Obtained as a white
solid (190 mg, 79%). mp 200−201 °C; 1H NMR (500 MHz, acetone-
d6) δ 8.94 (d, J = 2.0 Hz, 1H), 8.60 (d, J = 3.0 Hz, 1H), 8.10−8.05 (m,
1H), 7.63 (d, J = 3.5 Hz, 1H), 7.57 (d, J = 4.0 Hz, 1H), 7.50−7.46 (m,
1H), 6.99 (br s, 2H); 13C NMR (125.8 MHz, acetone-d6) δ 150.8,
147.8, 146.5, 146.1, 134.1, 132.3, 130.0, 125.5, 125.0; HRMS (TOF
MS ES+) m/z calcd. for C9H9N2O2S2 [M + H]+, 241.0105; found,
241.0107.
5-(5-Methylfuran-2-yl)thienyl-2-sulfonamide (5q). Obtained
as a brown solid (234 mg, 96%). mp 192−193 °C; H NMR (500
MHz, acetone-d6) δ 7.52 (d, J = 4.0 Hz, 1H), 7.21 (d, J = 4.0 Hz, 1H),
6.88 (br s, 2H), 6.71 (d, J = 3.5 Hz, 1H), 6.19−6.17 (m, 1H), 2.33 (s,
3H); 13C NMR (125.8 MHz, acetone-d6) δ 153.6, 146.6, 142.8, 139.0,
131.7, 121.5, 109.1, 109.0, 13.1; HRMS (TOF MS ES−) m/z calcd. for
C9H9NO3S2 [M − H]−, 241.9946; found, 241.9978.
1
5-(1-(Phenylsulfonyl)-3a,7a-dihydro-1H-indol-3-yl)thienyl-2-
ASSOCIATED CONTENT
sulfonamide (5i). Obtained as a yellow solid (326 mg, 78%). mp
■
1
246−248 °C; H NMR (500 MHz, acetone-d6) δ 8.20 (s, 1H), 8.13
S
* Supporting Information
(d, J = 7.0 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 7.70 (t, J = 6.5 Hz, 1H),
7.65 (d, J = 4.0 Hz, 1H), 7.63−7.59 (m, 2H), 7.53 (d, J = 4.0 Hz, 1H),
7.48 (t, J = 8.0 Hz, 1H), 7.43−7.39 (m, 1H); 13C NMR (125.8 MHz,
acetone-d6) δ 144.7, 140.3, 138.4, 136.1, 135.4, 131.8, 130.5, 128.7,
127.9, 126.5, 125.6, 125.1, 121.1, 116.8, 114.6; HRMS (TOF MS ES+)
m/z calcd. for C18H13N2O4S3 [M − H]−, 417.0037; found, 417.0036.
5-(6-Chloropyridin-3-yl)thienyl-2-sulfonamide (5j). Obtained
Spectral data (1H, 13C, and 19F NMR) for all compounds
prepared. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
1
as a yellow solid (159 mg, 58%). mp 196−197 °C; H NMR (500
Corresponding Author
MHz, DMSO-d6) δ 8.81 (d, J = 2.5 Hz, 1H), 8.20 (dd, J = 8.5, 2.5 Hz,
1H), 7.82 (br s, 2H), 7.69 (d, J = 3.5 Hz, 1H), 7.63 (dd, J = 8.0, 4.5
Hz, 1H), 7.59 (d, J = 4.0 Hz, 1H); 13C NMR (125.8 MHz, DMSO-d6)
δ 150.0, 146.7, 145.8, 142.4, 136.8, 131.0, 128.1, 125.7, 124.7; HRMS
*E-mail: gmolandr@sas.upenn.edu.
Notes
The authors declare no competing financial interest.
7248
dx.doi.org/10.1021/jo501323z | J. Org. Chem. 2014, 79, 7243−7249

The Journal of Organic Chemistry
Note
ACKNOWLEDGMENTS
■
We are grateful to the NIGMS (R01 GM-081376) for financial
support of this research, and the Higher Education
Commission (HEC), Pakistan, for a scholarship (PIN No.
106-2102-Ps6-070) to M.N. We thank Yasmeen Gull (Govern-
ment College University, Pakistan) for assistance with some of
the experiments and Dr. Rakesh Kohli (University of
Pennsylvania) for acquisition of HRMS spectra.
REFERENCES
■
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NOTE ADDED AFTER ASAP PUBLICATION
Table 1 entry 8 was corrected on July 15, 2014.
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