One-Pot Three-Component Route for the Synthesis of Rhodanine Derivatives in Water

Article abstract of DOI:10.1055/s-0034-1380454

A one-pot three-component route for the synthesis of rhodanine derivatives by the reaction of primary amines, carbon disulfide, and maleic anhydride in water is described. The reactions proceed via a sequential Michael addition-intramolecular amide bond formation. Bis(rhodanine) derivatives were also synthesized by using a diamine in this protocol.

Full text of DOI:10.1055/s-0034-1380454

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 3147–3152
paper
3147
A. Ziyaei Halimehjani, S. Hosseinkhany
Paper
Synthesis
One-Pot Three-Component Route for the Synthesis of Rhodanine
Derivatives in Water
Azim Ziyaei Halimehjani*
Samaneh Hosseinkhany
S
O
R
N
H2O
S
CS2
+
+
O
RNH2
Faculty of Chemistry, Kharazmi University,
49 Mofateh St., 15719-14911 Tehran, Iran
ziyaei@khu.ac.ir
O
COOH
O
11 examples
up to 91% isolated yield
S
S
O
S
O
S
S
S
HOOC
COOH
COOH
N
N
N
N
HOOC
O
O
S
S
Received: 12.03.2015
Accepted after revision: 05.05.2015
Published online: 14.07.2015
cules due to their diverse biological activities including an-
timicrobial,3 antiviral,4 anticonvulsant,5 antidiabetic,6 anti-
malarial,7 antifungal,8 antitumor,9 anti-inflammatory,10 and
herbicidal properties.11 These compounds have also found
wide applications as inhibitors of numerous targets for
pharmaceutical interventions in a number of diseases.12
Usually, these compounds have been prepared via the addi-
tion of isothiocyanate to mercaptoacetic acid followed by
acid cyclization,13 or the reaction of in situ prepared dithio-
carbamic acids from primary amines or ammonia with a di-
versity of electrophiles such as chloroacetic acid,13 chloro-
acetyl chloride,14 ethyl chloroacetate,15 diethyl 2-chloro-
malonate,16 dialkyl acetylenedicarboxylates,17 α-chloro-β,γ-
alkenoate esters,18 and 1,2-diaza-1,3-dienes.19
DOI: 10.1055/s-0034-1380454; Art ID: ss-2015-n0163-op
Abstract A one-pot three-component route for the synthesis of
rhodanine derivatives by the reaction of primary amines, carbon disul-
fide, and maleic anhydride in water is described. The reactions proceed
via a sequential Michael addition–intramolecular amide bond forma-
tion. Bis(rhodanine) derivatives were also synthesized by using a di-
amine in this protocol.
Key words rhodanine derivatives, dithiocarbamates, water, primary
amines, carbon disulfide
Multicomponent reactions (MCRs), which can produce a
diversity of complex compounds in a limited number of re-
action steps, provide one of the most efficient and effective
methods for the sustainable and diversity-oriented synthe-
sis of biologically active compounds.1 Therefore, besides the
famous multicomponent reactions reported to date, the de-
sign of novel MCRs has attracted great attention from re-
search groups working in various areas such as drug discov-
ery, organic synthesis, and materials science. In addition,
performing the MCRs under green reaction conditions im-
proves their efficiency in the modern organic synthesis.
Among the different branches of green chemistry, conduct-
ing an organic reaction in water, under solvent- or catalyst-
free conditions, is ideal for the environmentally friendly
synthesis of organic compounds.2 Although the use of cata-
lysts for organic transformations has several advantages,
usually such processes require extra steps for producing the
catalyst or for removing the catalyst from the reaction me-
dium.
Dithiocarbamates are the analogues of carbamates in
which both oxygens are replaced by sulfur. These com-
pounds can be simply accessed via the reaction of an amine,
carbon disulfide, and an electrophile such as an alkyl ha-
lide, epoxide, carbonyl compound, or Michael acceptor.20
Dithiocarbamic acids derived from primary amines are po-
tential bis-nucleophiles due to the sulfur and nitrogen
groups (Scheme 1). At first, they usually attack an electro-
phile through a sulfur atom, and then through the nitrogen
atom or thiocarbonyl group. The second attack via the ni-
trogen or thiocarbonyl group is dependent on the structure
of the electrophile.13–19,21
electrophile
S
SH
electrophile
R
R
N
SH
N
SH
H
electrophile electrophile
Scheme 1 Sulfur and nitrogen nucleophilicity of dithiocarbamates
Among the five-membered heterocyclic compounds
containing N/S heteroatoms, rhodanine (2-thioxo-1,3-thi-
azolidin-4-one) and its derivatives are well-known mole-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3147–3152

3148
A. Ziyaei Halimehjani, S. Hosseinkhany
Paper
Synthesis
In continuation of our research toward the development
of green procedures for the synthesis of dithiocarbamates
and their applications in organic transformations, herein
we report a green one-pot three-component route for the
synthesis of rhodanine derivatives 3 in water at room tem-
perature without using any catalyst, as outlined in Scheme
2. Recently, these compounds have been synthesized by
Alizadeh and Zohreh via a one-pot three-component reac-
tion of primary amines, carbon disulfide, and fumaryl chlo-
ride (2) in water.22 We have found that by replacing the sen-
sitive, expensive, and toxic fumaryl chloride (2) with maleic
anhydride (1), the same products can be obtained in higher
yield and in shorter reaction time. Another report in this
context, by Shahvelayati and co-workers, revealed that the
reaction of primary amines, carbon disulfide, and maleic
anhydride (1) in toluene gave only the Michael adducts 4.
Furthermore, they also claimed that the Michael adducts
are stable in refluxing toluene for 12 hours.23
Reaction of dithiocarbamic acids with maleic anhydride
was optimized with the reaction of benzylamine, carbon di-
sulfide, and maleic anhydride in water by varying the
equivalents of the starting materials and the reaction tem-
perature. Contrary to the report by Shahvelayati and co-
workers,23 we found that simple mixing of benzylamine (3
mmol) and carbon disulfide (5 mmol) in water (10 mL) for
20 minutes, followed by addition of maleic anhydride (3
mmol) and further stirring at room temperature for 5
hours, gave only (3-benzyl-4-oxo-2-thioxothiazolidin-5-
yl)acetic acid (3a) in 73% yield (Table 1, entry 1); no Michael
adduct was observed. Continuing on, the generality of the
reaction was confirmed by using various primary amines
such as butylamine, propylamine, ethylamine, methyl-
amine, isopropylamine, allylamine, hexylamine, cyclohex-
ylamine, 1-phenylethylamine, and 3-phenylpropylamine;
in each case, a high to excellent yield was obtained (Table 1,
entries 2–11). Hindered primary amines such as tert-butyl-
amine and 1-aminoadamantane were also examined, with-
out success.
Then, the generality of the reaction was expanded to di-
amines, namely 1,3-diaminopropane and 3-(aminometh-
yl)benzylamine. We found that by using 3 equivalents of
carbon disulfide and 2 equivalents of maleic anhydride
with 1 equivalent of a diamine under similar conditions as
described above, the corresponding bis(rhodanine) deriva-
tives 5a,b were obtained in high to excellent yield (Scheme
3). The structures of all products were elucidated from their
elemental analyses, and IR, 1H NMR, and 13C NMR spectra. It
is notable that in large-scale syntheses, the product can be
simply collected via decanting in the case of an oily product
or by filtration of the precipitate from the reaction mixture.
O
O
O
S
O
toluene
ref. 23
R
S
N
H
O
4
O
1
S
R
this work
H2O
N
S
CS2
RNH2
+
O
3
COOH
ref. 22
O
Cl
, H2O
Cl
2
O
Scheme 2 One-pot three-component reaction of primary amines, car-
bon disulfide, and maleic anhydride or fumaryl chloride
Table 1 Rhodanine Derivatives from the Reaction of Primary Amines, Carbon Disulfide, and Maleic Anhydride in Watera
Entry
Amine
Product
Yieldb (%)
S
S
NH2
O
O
N
S
S
1
73
OH
OH
O
3a
3b
N
2
3
91
66
NH2
O
S
O
N
S
NH2
OH
O
3c
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3147–3152

3149
A. Ziyaei Halimehjani, S. Hosseinkhany
Paper
Synthesis
Table 1 (continued)
Entry
Amine
Product
Yieldb (%)
S
O
N
S
4
5
76
NH2
OH
S
O
3d
S
O
N
73
NH2
OH
O
3e
S
O
N
S
6
7
71
78
69
80
63
56
NH2
OH
O
3f
S
O
Ph
N
S
S
Ph
NH2
OH
O
3g
Me
O
N
S
Me
8
NH2
OH
O
O
3h
S
N
S
9
NH2
OH
O
3i
S
O
N
S
10
11
NH2
OH
O
3j
S
NH2
O
N
S
OH
O
3k
a Reaction conditions: amine (3 mmol), CS2 (5 mmol), maleic anhydride (1; 3 mmol), H2O (10 mL), r.t., 5 h.
b Isolated yield.
A proposed mechanism for this transformation is given
in Scheme 4. It is conceivable that the initial event is the
formation of a dithiocarbamic acid 6 from a primary amine
and carbon disulfide. Further, Michael addition of the in
situ prepared 6 to maleic anhydride (1) affords the inter-
mediate 7, which then undergoes intramolecular amide
bond formation via a 5-exo-trig nucleophilic attack by ni-
trogen at the anhydride group to give the corresponding
product 3.
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A. Ziyaei Halimehjani, S. Hosseinkhany
Paper
Synthesis
O
S
O
S
O
R
H2O
N
N
S
H2N
R
NH2
CS2
+
+
O
HOOC
COOH
r.t., 3 h
S S
O
5
(3 mmol)
O
(9 mmol) 1 (6 mmol)
O
S
S
S
HOOC
COOH
N
N
N
N
HOOC
COOH
S
S
S
S
O
O
5a (86%)
Scheme 3 Synthesis of bis(rhodanine) derivatives using diamines
5b (66%)
In conclusion, we have demonstrated a facile, highly ef-
ficient, and environmentally benign procedure for the one-
pot synthesis of (3-alkyl-4-oxo-2-thioxothiazolidin-5-
yl)acetic acids (rhodanine derivatives) in water in high to
excellent yields using simple and inexpensive starting ma-
terials. This procedure was also applied for the synthesis of
bis(rhodanine) derivatives from diamines. The presence of a
carboxylic acid group in the structure of the products al-
lows further constructions in synthetic organic chemistry
for the preparation of novel, biologically active compounds.
Rhodanine Derivatives 3; General Procedure
To a magnetically stirred mixture of an amine (3 mmol) and H2O (10
mL), was added CS2 (5 mmol). The mixture was stirred for 20 min,
which was followed by the addition of maleic anhydride (1; 3 mmol)
and further stirring at r.t. for 5 h. On reaction completion, the product
was extracted with EtOAc (2 × 20 mL), and the combined organic lay-
ers were washed with water and dried over anhydrous Na2SO4. The
solvent was evaporated under reduced pressure to give the product in
pure form, without need for additional purification. The products
were characterized by their IR, 1H NMR, and 13C NMR spectra, and
CHN analyses. For the synthesis of bis(rhodanine) derivatives 5, 2
equivalents of maleic anhydride and 3 equivalents of CS2 were ap-
plied. In large-scale syntheses, the product can be simply collected
via decanting in the case of an oily product or by filtration of the pre-
cipitate from the reaction mixture.
S
R
RNH2
CS2
+
N
SH
H
O
6
(3-Benzyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3a)
O
Yield: 0.615 g (73%); yellow solid; mp 92–95 °C.
1
IR (KBr): 3550–2400 (OH), 1704, 1350, 1242, 1194 cm–1
1H NMR (300 MHz, CDCl3): δ = 3.06 (dd, J = 18.0, 8.9 Hz, 1 H), 3.27 (dd,
.
O
O
J = 18.1, 3.8 Hz, 1 H), 4.43 (dd, J = 8.9, 3.8 Hz, 1 H), 5.21 (ABquartet
,
S
R
COOH
S
J = 14.1 Hz, 2 H), 7.26–7.42 (m, 5 H), 8.9 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 36.3, 45.4, 47.8, 128.1, 128.5, 129.1,
134.5, 174.5, 175.4, 200.1.
S
O
N
R
S
N
O
H
O
Anal. Calcd for C12H11NO3S2: C, 51.23; H, 3.94; N, 4.98. Found: C,
51.47; H, 3.72; N, 5.21.
7
3
Scheme 4 Proposed mechanism for the formation of rhodanines 3
(3-Butyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3b)
Yield: 0.674 g (91%); colorless solid; mp 79–81 °C.
IR (KBr): 3350–2400 (OH), 1733, 1707, 1360, 1336, 1282, 1194, 1131
All chemicals and solvents were obtained from commercial sources
and used without further purification. All 1H and 13C NMR spectra
were obtained on a Bruker AMX 300 MHz spectrometer and refer-
enced to internal tetramethylsilane at 0.0 ppm. Reactions were moni-
tored by thin-layer chromatography using Merck TLC silica gel 60
F254 plates. IR spectra were recorded on a Perkin-Elmer Spectrum
RXI FT-IR spectrometer. Elemental analyses were conducted with a
Perkin-Elmer 2004 Series II CHN analyzer.
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.95 (t, J = 7.2 Hz, 3 H), 1.35 (m, 2 H),
1.62 (m, 2 H), 3.00 (dd, J = 17.8, 9.8 Hz, 1 H), 3.25 (dd, J = 17.9, 3.3 Hz,
1 H), 3.99 (t, J = 7.4 Hz, 2 H), 4.41 (dd, J = 8.2, 3.4 Hz, 1 H), 8.36 (br s, 1
H).
13C NMR (75 MHz, CDCl3): δ = 13.6, 19.9, 28.6, 36.7, 44.6, 45.6, 174.2,
175.6, 200.6.
Anal. Calcd for C9H13NO3S2: C, 43.70; H, 5.30; N, 5.66. Found: C, 44.01;
H, 5.48; N, 6.05.
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A. Ziyaei Halimehjani, S. Hosseinkhany
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Synthesis
(3-Ethyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3c)
Yield: 0.433 g (66%); brownish solid; mp 87–90 °C.
(3-Methyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3h)
Yield: 0.424 g (69%); greenish solid; mp 96–100 °C.
IR (KBr): 3450–2400 (OH), 1722, 1709, 1436, 1344, 1252, 1125 cm–1
.
IR (KBr): 3400–2400 (OH), 1700, 1309, 1132 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.22 (t, J = 7.0 Hz, 3 H), 3.08 (dd,
J = 18.1, 8.6 Hz, 1 H), 3.28 (dd, J = 18.0, 3.6 Hz, 1 H), 4.06 (t, J = 6.9 Hz,
2 H), 4.41 (dd, J = 8.5, 3.7 Hz, 1 H), 8.61 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 11.8, 36.3, 40.0, 45.3, 174.9, 175.2,
200.0.
1H NMR (300 MHz, CDCl3): δ = 3.03 (dd, J = 18.1, 9.3 Hz, 1 H), 3.32–
3.40 (m, 4 H), 4.46 (dd, J = 9.3, 3.7 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 31.5, 36.4, 45.7, 174.2, 175.3, 201.3.
Anal. Calcd for C6H7NO3S2: C, 35.11; H, 3.44; N, 6.82. Found: C, 35.24;
H, 3.11; N, 6.62.
Anal. Calcd for C7H9NO3S2: C, 38.34; H, 4.14; N, 6.39. Found: C, 37.99;
H, 4.09; N, 6.07.
(4-Oxo-3-propyl-2-thioxothiazolidin-5-yl)acetic Acid (3i)
Yield: 0.559 g (80%); yellow solid; mp 89–92 °C.
(3-Allyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3d)
IR (KBr): 3300–2400 (OH), 1729, 1707, 1357, 1285, 1242, 1213, 1132
Yield: 0.527 g (76%); yellowish solid; mp 89–92 °C.
cm–1
.
IR (KBr): 3280–2350 (OH), 1728, 1703, 1646, 1333, 1240, 1139 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.93 (t, J = 7.4 Hz, 3 H), 1.60–1.73 (m, 2
H), 3.05 (dd, J = 18.1, 8.7 Hz, 1 H), 3.26 (dd, J = 18.1, 3.8 Hz, 1 H), 3.92–
3.97 (m, 2 H), 4.04 (m, 1 H), 9.88 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 11.1, 20.0, 36.4, 45.2, 46.3, 175.2, 175.5,
200.3.
1H NMR (300 MHz, CDCl3): δ = 3.06 (dd, J = 18.1, 8.8 Hz, 1 H), 3.29 (dd,
J = 18.0, 3.8 Hz, 1 H), 4.44 (dd, J = 8.8, 3.6 Hz, 1 H), 4.60 (d, J = 5.9 Hz, 2
H), 5.23–5.32 (m, 2 H), 5.76 (m, 1 H), 9.41 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 36.4, 45.4, 46.6, 119.6, 129.2, 174.9,
175.0, 199.7.
Anal. Calcd for C8H11NO3S2: C, 41.18; H, 4.75; N, 6.00. Found: C, 41.47;
H, 4.76; N, 5.99.
Anal. Calcd for C8H9NO3S2: C, 41.54; H, 3.92; N, 6.06. Found: C, 41.66;
H, 3.72; N, 6.17.
(3-Isopropyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3j)
(3-Hexyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3e)
Yield: 0.44 g (63%); yellow solid; mp 152–155 °C.
Yield: 0.602 g (73%); yellow syrup.
IR (KBr): 3500–2400 (OH), 1730, 1352, 1183, 1137 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 6.1 Hz, 3 H), 1.28–1.30 (m, 6
H), 1.58 (m, 2 H), 2.95 (dd, J = 17.8, 9.1 Hz, 1 H), 3.22 (dd, J = 17.8, 3.7
Hz, 1 H), 3.94 (m, 2 H), 4.39 (dd, J = 9.1, 3.7 Hz, 1 H), 9.8 (br s, 1 H).
IR (KBr): 3250–2400 (OH), 1723, 1701, 1320, 1263, 1115 cm–1
1H NMR (300 MHz, CDCl3): δ = 1.40–1.49 (m, 6 H), 3.03–3.24 (m, 2 H),
4.24 (m, 1 H), 5.22 (m, 1 H), 10.60 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 17.9, 18.2, 36.2, 43.4, 50.4, 175.3, 175.7,
.
.
201.0.
13C NMR (75 MHz, CDCl3): δ = 13.9, 22.4, 26.3, 26.5, 31.2, 36.7, 44.8,
45.6, 174.1, 175.6, 200.8.
Anal. Calcd for C8H11NO3S2: C, 41.18; H, 4.75; N, 6.00. Found: C, 41.33;
H, 4.31; N, 6.07.
Anal. Calcd for C11H17NO3S2: C, 47.98; H, 6.22; N, 5.09. Found: C,
48.20; H, 6.47; N, 5.36.
[4-Oxo-3-(3-phenylpropyl)-2-thioxothiazolidin-5-yl]acetic Acid
(3k)
(3-Cyclohexyl-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (3f)
Yield: 0.519 g (56%); colorless solid; mp 102–107 °C.
Yield: 0.581 g (71%); cream solid; mp 135–139 °C.
IR (KBr): 3300–2400 (OH), 1743, 1703, 1200, 1137 cm–1
1H NMR (300 MHz, CDCl3): δ = 1.20–1.43 (m, 5 H), 1.84–1.88 (m, 3 H),
2.26–2.34 (m, 2 H), 2.95 (dd, J = 17.9, 8.6 Hz, 1 H), 3.16 (dd, J = 17.8,
3.3 Hz, 1 H), 4.24 (m, 1 H), 4.87 (t, J = 12.2 Hz, 1 H), 9.8 (br s, 1 H).
IR (KBr): 3200–2400 (OH), 1738, 1707, 1262, 1157 cm–1
.
.
1H NMR (300 MHz, CDCl3): δ = 1.96–2.07 (m, 2 H), 2.69 (t, J = 7.8 Hz, 2
H), 2.97 (dd, J = 18.1, 8.8 Hz, 1 H), 3.22 (dd, J = 18.1, 3.8 Hz, 1 H), 4.05
(t, J = 7.5 Hz, 2 H), 4.29 (dd, J = 8.7, 3.8 Hz, 1 H), 7.17–7.32 (m, 5 H),
8.70 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 25.2, 25.9, 27.4, 27.6, 31.0, 36.7, 43.7,
13C NMR (75 MHz, CDCl3): δ = 27.5, 32.9, 36.8, 44.7, 45.1, 126.1, 128.2,
58.3, 174.6, 176.0, 201.7.
128.4, 140.5, 174.6, 175.4, 200.2.
Anal. Calcd for C11H15NO3S2: C, 48.33; H, 5.53; N, 5.12. Found: C,
48.06; H, 5.14; N, 5.59.
Anal. Calcd for C14H15NO3S2: C, 54.35; H, 4.89; N, 4.53. Found: C,
54.63; H, 4.61; N, 4.70.
[4-Oxo-3-(1-phenylethyl)-2-thioxothiazolidin-5-yl]acetic Acid (3g)
{3-[3-(5-Carboxymethyl-4-oxo-2-thioxothiazolidin-3-yl)propyl]-
4-oxo-2-thioxothiazolidin-5-yl}acetic Acid (5a)
Yield: 0.690 g (78%); yellow syrup.
Yield: 1.089 g (86%); cream solid; mp 170–172 °C.
IR (KBr): 3400–2400 (OH), 1743, 1709, 1358, 1229, 1102 cm–1
1H NMR (300 MHz, DMSO-d6): δ = 1.86 (t, J = 7.4 Hz, 2 H), 3.00–3.15
(m, 4 H), 3.88 (m, 4 H), 4.69 (t, J = 6.3 Hz, 2 H), 12.80 (br s, 2 H).
13C NMR (75 MHz, DMSO-d6): δ = 23.8, 35.5, 41.6, 46.0, 171.5, 176.0,
IR (KBr): 3400–2400 (OH), 1730, 1243, 1095 cm–1
1H NMR (300 MHz, CDCl3): δ = 1.82–1.88 (m, 3 H), 3.04–3.12 (m, 2 H),
4.12–4.16 (m, 1 H), 6.40 (m, 1 H), 7.28–7.45 (m, 5 H), 8.06 (br s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 14.5, 36.1, 43.9, 55.0, 127.1, 127.7,
.
.
128.2, 137.9, 174.1, 175.1, 201.3.
202.7.
Anal. Calcd for C13H13NO3S2: C, 52.86; H, 4.44; N, 4.74. Found: C,
52.68; H, 4.28; N, 4.89.
Anal. Calcd for C13H14N2O6S4: C, 36.95; H, 3.34; N, 6.63. Found: C,
37.06; H, 3.56; N, 6.48.
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Synthesis
(3-{3-[(5-Carboxymethyl-4-oxo-2-thioxothiazolidin-3-yl)meth-
yl]benzyl}-4-oxo-2-thioxothiazolidin-5-yl)acetic Acid (5b)
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Chem. Pharm. Bull. 1991, 39, 1440.
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P. M. Eur. J. Med. Chem. 2013, 62, 693.
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Siddigi, M. I.; Chauhan, P. M. S. MedChemComm 2012, 3, 1104.
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Ogawa, K.; Shishido, T.; Chen, L. B. J. Med. Chem. 1998, 41, 130.
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2005, 15, 3374.
Yield: 0.96 g (66%); yellow solid; mp 93–97 °C.
IR (KBr): 3450–2400 (OH), 1731, 1341, 1187 cm–1
1H NMR (300 MHz, DMSO-d6): δ = 3.09 (d, J = 4.5 Hz, 4 H), 4.80 (d,
J = 4.5 Hz, 2 H), 5.01 (ABquartet, J = 15.3 Hz, 4 H), 7.15–7.42 (m, 4 H).
13C NMR (75 MHz, DMSO-d6): δ = 35.6, 46.4, 46.9, 126.4, 126.6, 128.5,
.
135.1, 171.6, 176.2, 202.8.
Anal. Calcd for C18H16N2O6S4: C, 44.61; H, 3.33; N, 5.78. Found: C,
44.47; H, 3.53; N, 5.68.
(11) Tomasic, T.; Masic, L. P. Curr. Med. Chem. 2009, 16, 1596.
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Med. Chem. Lett. 2001, 11, 91. (b) Bruno, G.; Costantino, L.;
Curinga, C.; Maccari, R.; Monforte, F.; Nicolò, F.; Ottanà, R.;
Vigorita, M. G. Bioorg. Med. Chem. 2002, 10, 1077. (c) Grant, E.
B.; Guiadeen, D.; Baum, E. Z.; Foleno, B. D.; Jin, H.; Montenegro,
D. A.; Nelson, E. A.; Bush, K.; Hlasta, D. J. Bioorg. Med. Chem. Lett.
2000, 10, 2179. (d) Free, C. A.; Majchrowicz, E.; Hess, S. M. Bio-
chem. Pharmacol. 1971, 20, 1421.
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Iran. C 2014, 21, 748.
Acknowledgment
We are grateful to the Faculty of Chemistry, Kharazmi University (Tar-
biat Moallem University) for supporting this work.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380454.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(15) (a) Azizi, N.; Hasani, M.; Khajeh, M.; Edrisi, M. Tetrahedron Lett.
2015, 56, 1189. (b) Singh, S. J.; Chauhan, S. M. S. Tetrahedron
Lett. 2013, 54, 2484.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3147–3152