Ionic liquid promoted spiroannulation via hetero-Michael addition and intramolecular heterocyclisation

Article abstract of DOI:10.1039/c3nj41070f

A sequential efficient method for the synthesis of novel spiro-5-thiazolidin-2-one-indolo[1,5]benzothiazepine from readily available isatin, 4-thioxothiazolidin-2-one and 2-aminothiophenol is reported. The synthesis involves formation of N-methyl-3-(2-oxo-4-thioxothiazolidinon-5- ylidene)-1,3-dihydro indol-2-one by [bmIm]OH promoted Knoevenagel condensation of 4-thioxo-2-thiazolidinone with isatin. The Knoevenagel product on ionic liquid promoted thia-Michael addition with 2-aminothiophenol and intramolecular cyclocondensation yielded the title compounds with high atom economy. The ionic liquid, [bmIm]OH was recovered completely and recycled thrice for the synthesis with no appreciable decrease in the efficiency of the process. The whole sequence of reactions proceeded with quantitative transformation of reactants into spiro [1,5]benzothiazepine at ambient temperature. The sequential reaction pathway is supported by the isolation of the thia-Michael adduct of the knoevenagel product with 2-aminothiophenol and quantitative conversion of the adduct into the final products under the same reaction conditions.

Full text of DOI:10.1039/c3nj41070f

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Ionic liquid promoted spiroannulation via hetero-Michael
addition and intramolecular heterocyclisation
Cite this: NewJ.Chem., 2013,
37, 1258
I. R. Siddiqui,* Shireen, Shayna Shamim, Afaf A. H. Abumhdi, Malik A. Waseem,
Arjita Srivastava, Rahila and Anjali Srivastava
A sequential efficient method for the synthesis of novel spiro-5-thiazolidin-2-one-indolo[1,5]benzothiazepine
from readily available isatin, 4-thioxothiazolidin-2-one and 2-aminothiophenol is reported. The synthesis
involves formation of N-methyl-3-(2-oxo-4-thioxothiazolidinon-5-ylidene)-1,3-dihydro indol-2-one by
[bmIm]OH promoted Knoevenagel condensation of 4-thioxo-2-thiazolidinone with isatin. The Knoevenagel
product on ionic liquid promoted thia-Michael addition with 2-aminothiophenol and intramolecular
cyclocondensation yielded the title compounds with high atom economy. The ionic liquid, [bmIm]OH was
recovered completely and recycled thrice for the synthesis with no appreciable decrease in the efficiency of
the process. The whole sequence of reactions proceeded with quantitative transformation of reactants into
spiro [1,5]benzothiazepine at ambient temperature. The sequential reaction pathway is supported by the
isolation of the thia-Michael adduct of the knoevenagel product with 2-aminothiophenol and quantitative
conversion of the adduct into the final products under the same reaction conditions.
Received (in Montpellier, France)
23rd November 2012,
Accepted 5th February 2013
DOI: 10.1039/c3nj41070f
www.rsc.org/njc
common methods for constructing a spirocentre (Fig. 1). Spiro
annulation via 1,4-conjugate addition has been shown for the
Introduction
synthesis of the core structure of alkaloid manzamine A.25
Design and development of reaction sequences leading to
a highly selective approach to complex molecular moieties,
particularly spirocyclics, while combining structural diversity,
versatility and eco-compatiblility, are great challenges for synthetic
chemists in the context of sustainable green chemistry.26–28
Recently, ionic liquids (IL) have received growing attention
due to their tunable features, complete recovery, reusability,
negligible vapour pressure, wide solvating capability, multiple
bond forming efficiency and many other green credentials as
alternative reaction media to molecular solvents, catalysts and
reagents.29–31 Basic ionic liquid [bmim]OH has been previously
used for catalyzing a number of reactions such as Knoevenagel
condensation, Michael addition,32a–d etc.
Spiro-cyclics have attracted attention due to their unique struc-
tural properties and reactivity pattern. Five and six-membered
rings containing spiro-3-indole derivatives exhibit enhanced
biological activities1–3 and are extensively studied,4–7 but those
incorporating a seven membered thiazepine moiety have so far
received little attention.8 The well known drugs Thiazesim9 and
Diltiazem10 as calcium channel blockers have a [1,5]benzothiazepine
skeleton. The literature records show that annulated [1,5]benzo-
thiazepines have been found to display a wide range of pharma-
cological properties.11–15 Therefore, [1,5]benzothiazepines with
spiro-heterocyclics appear to be an attractive scaffold to be utilized
for exploiting chemical diversity and generating a drug-like
library to screen for lead candidates. Along with indoles and
[1,5]benzothiazepines, a wide spectrum of pharmacological
activities are also associated with thiazolidinones.16
Spirocyclic structures are found in a wide range of natural
alkaloids.17–23 The complexity of these ring structures is represented
by the quaternary carbon centre and two fused rings. Syntheses of
spirocyclics by alkylation, rearrangement, cycloaddition, or cleavage
of bridged system, suffer from drawbacks such as functional group
incompatibility at one or more stages.24 1,4 Conjugate addition on
quaternary carbon followed by cyclocondensation is one of the most
Knoevenagel condensation followed by hetero-Michael addition
viz. aza-Michael, thia-Michael, oxa-Michael etc., has considerably
attracted attention as a versatile, expeditious and cost-effective
Fig. 1 Strategy for construction of spirocycles via 1,4-conjugate addition and
Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad,
Allahabad, 211002, India. E-mail: dr.irsiddiqui@gmail.com
subsequent heterocyclisation.
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strategy for the synthesis of heterocycles for drug discovery
processes. Furthermore, utilization of a variety of heteroatoms in
hetero-Michael addition broadens its applicability as an efficient
and atom-economic route for the construction of carbon–
heteroatom bonds in the synthesis of heterocyclic rings.
Owing to the chemical and biological interests of spiro
[1,5]benzothiazepines, the need for developing new and efficient
approaches for their synthesis with additional functional groups
for further modification still remains an attractive goal.
Prompted by the green credentials of task specific ionic
liquids (TSILs) and to avoid the drawbacks in construction of
spirocyclics as well as in continuation of our work on the
development of simple, efficient, versatile synthetic methodologies
for biodynamic heterocyclic scaffolds,32–38 we herein report 1,4-
conjugate addition and subsequent intramolecular cyclo-
condensation as an expeditious strategy for the construction of
novel spiro-5-thiazolidinone indolo[1,5]benzothiazepine based
on Knoevenagel condensation and hetero-Michael addition in
ionic liquid (Scheme 1).
Scheme 2 Plausible mechanism for the formation of spiro-5-thiazolidinone
In order to achieve our objective efficiently and expeditiously,
we utilized [bmIm]OH as an alternative reaction medium as well as
promoter. The strategy involves the initial reaction of isatin 1 with
4-thioxo-2-thiazolidin-2-one 2 in [bmIm]OH without using any base
indolo[1,5]benzothiazepine.
which resulted in the formation of N-methyl-3-(2-oxo-4-thioxo- (R1 = H, R2 = H) were chosen as model reagents for the synthesis
thiazolidinon-5-ylidene)-1,3-dihydroindol-2-one 3, having an of representative compound 6a and the reaction was performed
a,b-unsaturated (enone) moiety. [bmIm]OH promoted Knoevenagel at room temperature or under reflux (Table 1).
condensation gave N-methyl-3-(2-oxo-4-thioxothiazolidinon-
5-ylidene)-1,3-dihydroindol-2-one in good yield (76–80%).
The enone 3 on hetero-Michael addition and subsequent
intramolecular cyclocondensation afforded 6(a–k) with excellent
Table 1 Optimization of reaction conditions for the synthesis of spiro-5-thiazo-
lidinone-indolo[1,5]benzothiazepine
yield (78–86%; Scheme 2).
N-Methyl-3-(2-oxo-4-thioxothiazolidinon-5-ylidene)-1,3-dihydro
indol-2-one was initially obtained in 60 to 65% yield by base-
promoted Knoevenagel condensation of isatin with 4-thioxothiazo-
lidin-2-one in ethanol under reflux for 8 to 10 h. However, when
Knoevenagel condensation was done by using [bmIm]OH without
base, the product was obtained in 77–80% yield at room tempera-
ture by stirring for 2 to 3 h.
In order to make the synthesis of 6 more expeditious and
facile, we turned our attempt to investigate the optimization of
reaction conditions with regard to solvent, base, time and yield
of product. Herein, isatin 1, 4-thioxothiazolidin-2-one 2 and 4
Entry Solvent
Mol% Temp
Base Time (h) Yielda (%)
1
2
3
MeOH
DCM
THF
—
—
—
Reflux
Reflux
Reflux
NaOH 10
NaOH 10
NaOH 10
40
32
28
4
5
20
20
Room temp —
Room temp —
6
80
76
10
6
7
8
9
20
20
15
25
Room temp —
Room temp —
Room temp —
Room temp —
Room temp —
10
10
6
71
78
75
80
6
10
11
a
20
20
8
6
80
80
60 1C
—
Scheme 1 Ionic liquid catalysed synthesis of spiro-5-thiazolidinone-
indolo[1,5]benzothiazepine.
Yield of isolated and purified products.
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Methanol, DCM, THF and several imidazolium-based ionic
Paper
Table 2 (continued )
liquids, with varying alkyl substituents and counter anions,
were used as solvents and [bmIm]OH was found to be the most
efficient solvent and catalyst (Table 1, entry 4) in the reported
synthetic protocol.
Entry 4
6
Time (h) Yielda,b (%)
The optimum catalyst loading for [bmIm]OH was found to
be 20 mol%. By decreasing the amount of catalyst to 15 from
20% relative to substrate, the yield of product 6a is reduced
(Table 1, entry 8), however, by increasing the amount of catalyst
from 20 to 25 mol%, no appreciable change in the yield of product
was observed (Table 1, entry 9). However, low performance at high
temperature in the presence of base was observed by methyl
alcohol (Table 1, entry 1) whereas DCM and THF could not do well
(Table 1, entries 2 and 3). With MeOH, DCM and THF, the
product was obtained under reflux in the presence of a base,
NaOH. It was also observed that a higher reaction temperature
when [bmIm]OH was used as solvent and catalyst led to no
appreciable effect on the yield (Table 1, entry 11).
6
7
5
8
84
78
8
8
7
8
78
78
78
Next, in order to investigate the substrate scope of the
reaction, a variety of 2-aminothiophenols were used as dinucleo-
philes employing the present optimized reaction conditions. The
yield and reaction were found to be fairly equal and good (Table 2).
The highest yield was 86% of 6b (Table 2, entry 2). The present
9
Table 2 Ionic liquid [bmIm]OH promoted synthesis of spiro-5-thiazolidino-
indolo[1,5]benzothiazepine (6a–k)
10
11
5
85
Entry 4
6
Time (h) Yielda,b (%)
a
b
Stirring time at room temperature. Yield of isolated and purified
products.
1
6
4
7
8
8
80
86
78
79
78
optimized synthesis was accomplished by stirring the Knoevenagel
product of isatin 1 with 4-thioxothiazolidin-2-one 2, 2-amino thio-
phenol 4 and [bmIm]OH at room temperature for 4–8 h. Isolation
and recrystallisation afforded the hitherto unknown spiro-5-
thiazolidinonindolo[1,5]benzothiazepine in 78–86% yield (Table 2).
The formation of 6 may be rationalized by the attack of the
more nucleophilic sulphur atom of 2-aminothiophenol at the
b-carbon of the a,b-unsaturated carbonyl moiety of 3 leading to
the formation of adduct 5 which undergoes intramolecular
nucleophilic attack of the relatively more nucleophilic nitrogen
atom of the amino group of 2-aminothiophenol on the carbonyl
group at C2 of the N-methyl-3-(2-oxo-4-thioxothiazolidinon-5-
ylidene)-1,3-dihydroindol-2-one and subsequent dehydration
yielded compound 6 in 78–86% yield. These conclusions are
based on the observation that the intermediate compound 5
could be isolated and converted into the corresponding spiro
[1,5]benzothiazepine in quantitative yield. The ionic liquid
[bmIm]OH was easily recycled after the reaction and reused
2
3
4
5
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extracted with dichloromethane (2 Â 10 mL), dried over MgSO4
and evaporated under reduced pressure to afford [bmIm]OH,
which was reused thrice in subsequent runs without further
purification.
Compound 3
Brownish solid: 441 mg (80%), mp 290–292 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0 (s, 1H, -NH-), 6.95–7.59 (m, 4H,
Ar-H), 2.79(s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/TMS) d:
192, 169, 162.3, 150, 135.9, 134, 128, 126.8, 126.4, 124, 120.3,
35.0, EIMS: (m/z): 276 (M+). Anal. calcd. For C12H8N2O2S2: C,
52.16; N, 10.14; H, 2.92. Found: C, 52.19; N, 10.15; H, 2.90.
Fig. 2 Recyclability of [bmIm]OH.
three times without any loss in activity. Even after three cycles,
the product 6a was obtained in almost the same yield (Fig. 2).
In summary, we have developed an efficient method for the
synthesis of potentially pharmaceutically important spiro-[1,5]-
benzothiazepines from readily available substrates. Easy recovery
of ionic liquid and its reuse without any appreciable decrease in
yield of product and its activity, operational simplicity of the
procedure and enhancement of product yield are some advantages
over conventional processes and are some additional attributes of
the protocol in the context of green chemistry.
Spiro-5-thiazolidinonindolo [1,5]benzothiazepine: general
procedure
A mixture of N-methyl-3-(2-oxo-4-thioxo-thiazolidin-5-ylidene)-
1,3-dihydro-indol-2-one (2 mmol) 3, 2-aminothiophenol (2 mmol)
4(a–k) and [bmIm]OH (0.4 mmol) was stirred at room tempera-
ture for 4–10 h at rt. After completion of the reaction as indicated
by TLC, 20 mL of water was added and the product was extracted
with EtOAc (3 Â 20 mL). The combined organic layers were dried
over anhydrous Na2SO4 and evaporated under reduced pressure
to afford the crude product and recrystallized from ethanol to
afford an analytically pure compound 6a–k. The ionic liquid
[bmIm]OH was recovered by following the same procedure
as above.
Experimental
General
All chemicals were used as received without further purification.
NMR spectra were recorded on a Bruker Avance DPX-400400 FT
spectrometer (400 MHz for 1H NMR, 100 MHz for 13C) using
CDCl3 as solvent and TMS as an internal reference. Mass spectra
were recorded on a JEOL SX-102 (FAB) mass spectrometer at
70 eV. Elemental analyses were carried out in a Coleman auto-
matic carbon, hydrogen and nitrogen analyzer. Silica gel-G was
used for TLC. Melting points were determined by open glass
capillary method and are uncorrected.
Charaterization of 5a
Brownish solid: 641 mg (80%) mp 285–287 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.36–7.19(m, 8H,
Ar-H), 4.2(s, 1H), 4.1(s, 2H, NH2), 2.79(s, 3H, -CH3). 13C NMR
(100 MHz, CDCl3/TMS) d: 205, 171.3, 169, 144.7, 142.1, 130.9,
127.8, 127.7, 127.5, 125.8, 124.5, 122.2, 120.8 118.8, 115.4, 87.3,
54.6, 35.2. EIMS: (m/z): 401 (M+). Anal. calcd. For C18H15N3O2S3:
C, 53.84; N, 10.47; H, 3.77. Found: C, 53.85; N, 10.48; H, 3.75.
Preparation of [bmIm]OH
The task specific basic ionic liquid was synthesized according
to a reported procedure.32a Solid KOH (2.3 g, 40 mmol) was
added to a solution of [bmIm]Br (8.8 g, 40 mmol) in dry CH2Cl2
(20 mL), and the mixture was stirred vigorously at room
temperature for 10 h. The precipitated KBr was filtered off,
and the filtrate was evaporated to leave the crude [bmIm]OH as
a viscous liquid that was washed with ether (2 Â 20 mL) and
dried at 90 1C for 10 h to prepare the pure ionic liquid for use.
Compound 6a
Brownish solid: 613 mg (80%), mp 245–247 1C. 1H NMR (400 MHz,
CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.2 (m, 8H, Ar-H), 3.2(s, 1H),
2.79 (s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/TMS) d: 205, 169,
164, 147.1, 142.9, 129.1, 128.7, 128, 127.2, 126.5, 126.2, 124.0,
122.2, 117, 112.2, 82.8, 47.6, 35.6. EIMS: (m/z): 383 (M+). Anal.
calcd. For C18H13N3OS3: C, 56.37; N, 10.96; H, 3.42. Found: C,
56.39; N, 10.95; H, 3.40.
N-Methyl-3-(2-oxo-4-thioxo-thiazolidin-5-ylidene)-1,3-dihydro-
indol-2-one (3): Procedure
A mixture of isatin 1 (2.0 mmol), 4-thioxothiazolidin-2-one 2
(2.0 mmol) and [bmIm]OH (0.4 mmol) was stirred at room
temperature for (2–4) h. After completion of the reaction as
Compound 6b
indicated by TLC, 20 mL of water was added to the reaction Brownish solid: 710 mg (86%), mp 261–263 1C. 1H NMR
mixture and stirred well. The product was extracted with EtOAc (400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.1 (m, 7H,
(3 Â 20 mL). The combined organic layers were dried over Ar-H), 3.73 (s, 3H, OCH3), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C
anhydrous Na2SO4 to afford the crude product and recrystallized NMR (100 MHz, CDCl3/TMS) d: 205, 169, 164, 160.7, 142.9,
from ethanol to obtain analytically pure compound 3 (80%). 139.4, 130.1, 128.7, 126.5, 124.0, 123.2, 117, 113.5, 112.2, 111.8,
After isolation of the product, the remaining aqueous layer 82.8, 56.0, 47.6, 35.6. EIMS: (m/z): 413(M+). Anal. calcd. For
containing the ionic liquid was washed with ether (2 Â 10 mL)
C19H15N3O2S3: C, 55.18; N, 10.16; H, 3.66. Found: C, 55.15, N,
to remove any organic impurities and filtered. The filtrate was 10.19, H, 3.64.
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Compound 6c
Compound 6i
Brownish solid: 650 mg (78%), mp 212–214 1C. 1H NMR Brownish solid: 650 mg (78%), mp 208–210 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.2 (m, 7H, Ar- (400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.2 (m, 7H,
H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/ Ar-H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz,
TMS) d: 205, 169, 164, 145.2, 142.9, 132.5, 130.5, 128.7, 128.3, CDCl3/TMS) d: 205, 169, 164, 148.5, 142.9, 131.5, 129.3, 128.7,
126.6, 126.5, 124.0, 123.6, 117, 112.2, 82.8, 47.6, 35.6. EIMS: 127.6, 127.2, 126.5, 124.0, 122.6, 117, 112.2, 82.8, 47.6, 35.6.
(m/z): 417, 419 (M+, M+2). Anal. calcd. For C18H12ClN3OS3: C, EIMS: (m/z): 417, 419 (M, M+2). Anal. calcd. For C18H12ClN3OS3:
51.73; N, 10.05; H, 2.89. Found: C, 51.74; N, 10.07; H, 2.84.
C, 51.73; N, 10.05; H, 2.89. Found: C, 51.74; N, 10.07; H, 2.84.
Compound 6j
Compound 6d
Brownish solid: 703 mg (78%), mp 214–216 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H,-NH-), 6.4–7.3 (m, 7H,
Ar-H), 3.2 (s, 1H), 2.79 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3/TMS) d: 205, 169, 164, 147.4, 142.9, 132.4, 128.7, 128.7,
126.5, 124.0, 124.0, 119.3, 119.0, 117, 112.2, 82.8, 47.2, 35.6.
EIMS: (m/z): 451 (M+). Anal. calcd. For C19H12F3N3OS3: C, 50.54;
N, 9.31; H, 2.68. Found: C, 50.57; N, 9.30; H, 2.65.
Brownish solid: 728 mg (79%), mp 201–203 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.3 (m, 7H, Ar-
H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/
TMS) d: 205, 169, 164, 146.1, 142.9, 131.3, 131.2, 129.5, 128.7,
126.5, 124.4, 124.0, 121.8, 117, 112.2, 82.8, 47.6, 35.6. EIMS:
(m/z): 461, 463 (M, M+2). Anal. calcd. For C18H12BrN3OS3: C,
46.75; N, 9.09; H, 2.62. Found: C, 46.77; N, 9.06; H, 2.64.
Compound 6k
Compound 6e
Brownish solid: 726 mg (85%), mp 156–158 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0 (s, 1H, -NH-), 6.4–7.1 (m, 7H,
Ar-H), 3.98 (q, 2H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3), 1.13 (t, 3H).
13C NMR (100 MHz, CDCl3/TMS) d: 205, 169, 164, 157.5, 142.9,
138.7, 129.7, 126.5, 124.0, 123, 117, 113.6, 112.2, 112, 82.8, 65.7,
46.6, 35.6. EIMS: (m/z): 427 (M+). Anal. calcd. For C20H17N3O2S3:
C, 56.18; N, 9.83; H, 4.01. Found: C, 56.16; N, 9.86; H, 4.03.
Brownish solid: 625 mg (78%), mp 192–194 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0 (s, 1H, -NH-), 6.4–7.1 (m, 7H,
Ar-H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/
TMS) d: 205, 169, 164, 160.8, 142.9, 142.7, 130.7, 128.7, 126.5,
124.0, 123.8, 117, 114.9, 113.2, 112.2, 82.8, 47.6, 35.6. EIMS:
(m/z): 401 (M+). Anal. calcd. For C18H12FN3OS3: C, 53.85; N,
10.47; H, 3.01. Found: C, 53.87; N, 10.45; H, 3.02.
Acknowledgements
Compound 6f
Brownish solid: 667 mg (84%), mp 250–252 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.0 (m, 7H,
Ar-H), 3.2 (s, 1H), 2.79(s, 3H, -CH3) 2.35(s, 3H). 13C NMR
(100 MHz, CDCl3/TMS) d: 205, 169, 164, 144.1, 142.9, 136.4,
129.0, 128.7, 128.6, 126.9, 126.5, 124.0, 122.1, 117, 112.2, 82.8,
The authors gratefully acknowledge UGC, New Delhi and the
Department of Chemistry, University of Allahabad, Allahabad.
The authors would also like to thank SAIF, Chandigarh for
spectral analysis.
47.6, 35.6 , 20.5. EIMS: (m/z): 397 (M+). Anal. calcd. For References
19H15N3OS3: C, 57.40; N, 10.57; H, 3.80. Found: C, 57.43; N,
C
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10.55; H, 3.81.
Compound 6g
Brownish solid: 703 mg (78%), 218–220 1C. 1H NMR (400 MHz,
CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–7.4 (m, 7H, Ar-H), 3.2
(s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz, CDCl3/TMS) d:
205, 169, 164, 150.4, 142.9, 129.7, 129.4, 128.7, 126.5, 124.0,
123.0, 122.5, 118.9, 117, 112.2, 82.8, 47.6, 35.6. EIMS: (m/z): 451
(M+). Anal. calcd. For C19H12F3N3OS3: C, 50.54; N, 9.31; H, 2.68.
Found: C, 50.57; N, 9.30; H, 2.65.
´
6 A. Dandia, R. Singh, C. Merienne, G. Morgant and A. Loupy,
Compound 6h
Sulfur Lett., 2003, 26, 201.
Brownish solid: 668 mg (78%), mp 219–221 1C. 1H NMR
(400 MHz, CDCl3/TMS) d: 8.0(s, 1H, -NH-), 6.4–8.1 (m, 7H,
Ar-H), 3.2 (s, 1H), 2.79 (s, 3H, -CH3). 13C NMR (100 MHz,
CDCl3/TMS) d: 205, 169, 164, 148.0, 146.1, 142.9, 135.2, 128.8,
128.7, 126.5, 124.0, 122.3, 117.3,117, 112.2, 82.8, 47.3, 35.6.
EIMS: (m/z): 428 (M+). Anal. calcd. For C18H12N4O3S3: C, 50.45;
N, 13.07; H, 2.82. Found: C, 50.43; N, 13.05; H, 2.81.
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