Synthesis and antioxidant activity of new C-3 sulfenyl indoles

Article abstract of DOI:10.1016/j.tetlet.2013.07.004

A convenient and efficient methodology for the synthesis of new C-3 sulfur-substituted indoles under CeCl₃·7H₂O promotion is reported. Model bis(indol-3-yl)sulfide 4a and bis(indol-3-yl) sulfone 5a proved to display potent antioxidant activity at the low micromolar level, in DPPH, ABTS, and FRAP assays, as well as in the inhibition of the peroxidation of linoleic acid.

Full text of DOI:10.1016/j.tetlet.2013.07.004

Tetrahedron Letters 54 (2013) 4926–4929
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and antioxidant activity of new C-3 sulfenyl indoles
b
a
c
c
Claudio C. Silveira a, , Samuel R. Mendes , Josemar R. Soares , Francine N. Victoria , Débora M. Martinez ,
⇑
Lucielli Savegnago c
a Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
b GAPAM—Departamento de Química, Universidade do Estado de Santa Catarina, 89219-710 Joinville, SC, Brazil
c Centro de Desenvolvimento Tecnológico, Unidade Biotecnologia, Universidade Federal de Pelotas, 96010-610 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient and efficient methodology for the synthesis of new C-3 sulfur-substituted indoles under
CeCl3ꢀ7H2O promotion is reported. Model bis(indol-3-yl)sulfide 4a and bis(indol-3-yl)sulfone 5a proved
to display potent antioxidant activity at the low micromolar level, in DPPH, ABTS, and FRAP assays, as
well as in the inhibition of the peroxidation of linoleic acid.
Received 2 May 2013
Revised 24 June 2013
Accepted 1 July 2013
Available online 6 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Antioxidant activity
Indole sulfide derivatives
Cerium(III) chloride heptahydrate
Microwave-assisted synthesis
Introduction
for good potency.6 Therefore, a facile access to these derivatives
seems important. One of the most widely used protocols toward
Involvement of oxidative stress in the pathogenesis of various
disorders and diseases is well documented.1 Oxidative stress takes
place when the production of reactive oxygen species (ROS), such
as superoxide radical (O2Åꢁ), H2O2, singlet oxygen (1O2) and peroxyl
radical (ROOÅ), exceeds the capacity of the cellular antioxidant de-
fenses to remove these toxic agents.1c ROS can attack membrane
lipids, proteins, and nucleic acids, disrupting normal cell
physiology.1c
Antioxidant pharmacotherapy has emerged as a tool to mini-
mize the biomolecular damage caused by the attack of ROS to these
vital constituents of living organisms,1a and therefore synthetic
antioxidants have received much attention from the pharmaceuti-
cal viewpoint.1 Interestingly, a significant number of research
groups have focused on the role of sulfur- and selenium-containing
compounds as antioxidants.2
The indole scaffold is widely found among natural products and
synthetic compounds, which exhibit a range of important biologi-
cal activities.3 Many indole derivatives have been synthesized in
search of new antioxidants.4 Different functional groups and het-
erocyclic moieties attached to the indole nucleus have been shown
to modulate the antioxidant ability of the resulting compounds,5
and the nature of the C-3 functionalization is regarded as relevant
C-3 substituted indoles involves the Lewis or protic acid-promoted
electrophilic substitution reaction.7
In view of our interest in the development of new and cleaner
alternative methods for classical reactions, promoted by ceriu-
m(III) species,8 and with the aim of preparing new and bioactive
indoles, we decided to study the direct electrophilic substitution
reaction of indoles at the C-3 position with aromatic sulfonothio-
ates9 and investigate the antioxidant activity of the resulting sul-
fur-containing compounds (Scheme 1).
Results and discussion
In preliminary experiments, the best reaction conditions were
established by the use of indole (1a, R1 = R2 = H, 1.0 mmol) and
p-toluene sulfonothioate (2a, R3 = Me, 1.0 mmol) as starting mate-
rials. We examined the effect of the solvent [DMF, N,N0-dimethyl-
acetamide (DMA), 2-propanol, MeCN, and MeNO2], temperature
(70–100 °C), and amount of CeCl3ꢀ7H2O [0.5–1.0 equiv] as the
promoter.
The results revealed that all three variables affected the reac-
tion, being the use 1.0 equiv of CeCl3ꢀ7H2O in DMF at 80 °C the
conditions furnishing the best performance (98%; Table 1, entry
1). A decrease in the yield was observed when the transformation
was carried out at 70 °C (81%), while at 110 °C the presence of bi-
s(indol-3-yl)sulfide (4a) was detected by GC–MS in the crude
reaction mixture and the yield of 3a was significantly lower
(49%).
⇑
Corresponding author. Tel.: +55 55 3220 8754.
E-mail address: silveira@quimica.ufsm.br (C.C. Silveira).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.004

C. C. Silveira et al. / Tetrahedron Letters 54 (2013) 4926–4929
4927
R3
Table 2
R3
O
S
Ce(III)-mediated synthesis of bis(indol-3-yl)sulfides 4a
R1
S
R3
R1
O
CeCl3.7H2O
R1
R1
R1
N
OO
S
2
N
R2
S
S
O
R2
O
S
CeCl3.7H2O
DMA, MW
160 °C, 20 min
1
3
N
O
O
R1
R1
R1
R1
R2
S
S
N
N
S
1a-d
O
O
R2
R2
O
O
[O]
R1= H, Br, 4-Me-C6H4
R2= H, Me
S
S
2a
4a-d
N
N
N
N
R2
R2
R2
R2
5
Entry
R1
R2
Product
Yieldb (%)
4
1
2
3
4
H
H
Br
H
Me
H
4a
4b
4c
4d
89
86
78
70
Scheme 1. Synthesis of 3-substituted indole derivatives (3–5).
4-Me–C6H4
H
In order to explore the scope and limitations of the method, the
protocol was extended to other examples, under the optimized
conditions.10 The corresponding products were obtained in good
to excellent yields from different indoles (Table 1). The reaction
was also studied with the benzenesulfonothioate 2b (R3 = H), with
comparable success, albeit in slightly lower yields.
a
The reactions were carried out with the indoles (1, 2.0 mmol), p-toluene sul-
fonothioate (2a, 1.0 mmol) and CeCl3ꢀ7H2O (2.0 mmol) in DMA (4.0 mL), under
microwave irradiation (160 °C, 100 W) for 20 min.
Isolated yield. All products were characterized by GC–MS, 1H and 13C NMR, and
b
elemental analysis.
Taking into account our observation that higher temperatures
led to the formation of bis(indol-3-yl)sulfides (4) and in view of
the importance of these compounds in general organic synthesis
as well as in materials science and in the pharmaceutical indus-
try,12 we decided to study further the above reaction.
When the reaction was carried out in DMA under microwave
irradiation (160 °C), using Ce(III) as the promoter (1.0 mmol), in-
dole (2.0 mmol) and 2a (1.0 mmol), 53% of bis(indol-3-yl)sulfide
(4a)12e was obtained after 20 min, along with minor amounts of
the monosubstituted product 3a. However, when 2.0 equiv of
CeCl3ꢀ7H2O were employed, 4a was accessed in 89% yield (Table 2,
entry 1). Bis(indol-3-yl)sulfides 4b–d were isolated in good yields
under the same conditions (Table 2), demonstrating that the trans-
formation is general.13
Table 3
Synthesis of bis(indol-3-yl)sulfones 5a
R1
R1
R1
R1
Oxone, H2O/acetone
rt, 4 h
O
O
S
S
N
N
N
N
R1= H, Br, 4-Me-C6H4
R2= H, Me
R2
R2
R2
R2
4a-d
5a-d
Entry
R1
R2
Product
Yieldb (%)
1
2
3
4
H
H
Br
H
Me
H
5a
5b
5c
5d
90
88
85
86
4-Me–C6H4
H
a
In view of the precedent of antioxidant activity among sulfone-
The reactions were carried out with bis(indol-3-yl)sulfides (4, 1.0 mmol) and
linked bis heterocycles,14 the bis(indol-3-yl)sulfides
4 were
oxone (1.0 mmol), in 1:1 (v/v) H2O/acetone (5 mL), at room temperature for 4 h.
b
Isolated yield. All products were characterized by GC–MS, 1H and 13C NMR, and
transformed into the corresponding sulfone derivatives 5.12e The
oxidation reaction was easily performed by treatment of 4a–d with
oxone in a 1:1 (v/v) H2O/acetone medium, which smoothly
provided good yields of 5a–d (Table 3).15
elemental analysis.
DPPH has an unpaired electron which yields a strong absorption
maximum at 517 nm. It is now widely accepted that its reaction
with compounds like phenols proceeds through two different
mechanisms, including the direct hydrogen atom transfer (HAT)
and the sequential proton loss electron transfer.16 Thus, the un-
paired electron becomes paired in the presence of a free radical
scavenging antioxidant or hydrogen donor, decreasing the
absorption.16b
On the other hand, it was proposed that the reaction of indoles
with ABTS involves a single electron transfer process.16c
In the DPPH test,17 compounds 3a and 4a presented radical
scavenging at concentrations as low as 50 and 10
(Table 4). The IC50 values (sample concentration required to inhibit
50% of the radicals) of 185.0 39.7 (3a) and 22.5 10.2 M (4a)
In order to investigate the free radical scavenging ability of 3a
and 4a, the DPPH [di(phenyl)-(2,4,6-trinitrophenyl)imino azani-
um] and ABTS (2,20-azino-bis(3-ethyl benzothiazoline-6-sulfonic
acid) assays were used. Both are synthetic free radicals; however,
they sense different antioxidant mechanisms.
Table 1
Synthesis of C-3 monosubstituted indoles 3
R3
R3
O
S
R1
R3
R1
S
lM, respectively
O
CeCl3.7H2O
DMF, 80°C
20 min
N
O
O
N
R2
R2
S
S
l
S
3a-h
1a-d
O
O
and the maximum inhibition (Imax) results (76.5 2.8% for 3a and
89.9 2.5% for 4a) revealed that 4a is a more effective and more
potent DPPH radical scavenger.
2a-b
R3= H, CH3
R1= H, Br, 4-Me-C6H4
R2= H, Me
In the ABTS assay performed, as disclosed by Re et al.18 the test
Entry
R1
R2
R3
Product
Yielda (%)
compounds were active at 5
l
M levels (Table 4). When the IC50
M) and Imax results (3a:
1
2
3
4
5
6
7
8
H
H
Br
H
Me
H
H
H
Me
H
H
Me
Me
Me
Me
H
H
H
H
3a
3b
3c
3d
3e
3f
98
95
87
90
92
90
86
86
(3a: 27.0 24.2 M; 4a: 3.6 0.5
l
l
99.7 0.5%; 4a: 99.9 0.005%) were compared, it was also con-
cluded that 4a is a more effective and more potent ABTS radical
scavenger.
On the other hand, lipid peroxidation involves a free radical
chain reaction. Radical scavengers may directly react with peroxide
radicals, quench their activity and terminate the peroxidation
chain reactions. In the linoleic acid peroxidation inhibition induced
4-Me–C6H4
H
H
Br
3g
3h
4-Me–C6H4
Isolated yield. All products were characterized by GC–MS, 1H and 13C NMR, and
a
elemental analysis.11

4928
C. C. Silveira et al. / Tetrahedron Letters 54 (2013) 4926–4929
Table 4
Antioxidant activity of compounds 3a and 4a in the ABTS, DPPH, FRAP, and linoleic acid peroxidation assays
Conc.(
lM)
Compound 3a
Linoleic acid
Compound 4a
Linoleic acid
Free radical
scavenging
ABTS (%)
Free radical
scavenging
DPPH (%)
FRAP
(Abs593
Free radical
scavenging
ABTS (%)
Free radical
scavenging
DPPH (%)
FRAP
(Abs593)
peroxidation
inhibition (%)
)
peroxidation
inhibition (%)
Control
1
5
10
50
—
—
NT
NT
—
NT
NT
0.20 0.06
0.25 0.09
0.47 0.22
0.75 0.40
—
—
NT
15.5 23.3
38.6 10.0
79.8 8.8⁄⁄⁄
86.2 6.7⁄⁄⁄
—
—
NT
0.20 0.06
0.23 0.09
10.9 2.9
25.8 8.6⁄
38.1 13.5⁄⁄
77.4 21.9⁄⁄⁄
94.8 5.8⁄⁄⁄
—
25.5 13.5
⁄⁄⁄
68.4 25.3
6.8 2.6⁄⁄⁄
42.0 9.1
66.7 3.7⁄⁄⁄
95.6 8.8⁄⁄⁄
—
0.49 0.24
⁄⁄⁄
15.3 16.3⁄
30.6 15.7
42.1 13.3⁄⁄
78.3 4.1⁄⁄⁄
10.8 5.6⁄⁄
19.5 8.4⁄⁄⁄
58.2 8.7
99.7 0.6⁄⁄⁄
92.6 5.2⁄⁄⁄
0.76 0.33⁄⁄⁄
1.59 0.56⁄⁄⁄ 97.0 3.4⁄⁄⁄
—
—
—
100
500
—
—
96.8 3.5⁄⁄⁄
—
The asterisks denote p < 0.05 (⁄), p < 0.01 (⁄⁄) and p < 0.001 (⁄⁄⁄) as compared to the respective control sample (one-way ANOVA/Newman–Keuls).
IC50: concentration ( M) providing 50% inhibition in the assays; Imax: maximal inhibition (%); NT = no tested. Number of repetition = 5.
l
with Fe-ascorbic acid, carried out as reported by the group of
proton transfer from the cation radical to the anion, generating
species ii.
When the indolic nitrogen is unsubstituted, a direct transfer of
hydrogen between the antioxidant and the active radical may take
place, furnishing the corresponding nitrogen-centered indolyl rad-
ical (ii), which is the resonant form of iii.
The contribution of the C-3 substituent to the electronic density
of the indole nucleus may explain the differences in potency ob-
served between 3a and 4a. Increased activity due to a better stabil-
ization of the indole ring and delocalization of the electrons as a
consequence of the C-3 substitution has been also noticed recently
within the indole family.6
Choi,17 the symmetric sulfide 4a (IC50: 12.5 0.3
more effective than its parent 3a (IC50: 85.5 10
lM) was also
l
M), although
both exhibited similar Imax values (3a: 99.7 0.6%; 4a: 95.6 8.8%).
The FRAP (ferric reducing antioxidant power) assay relates the
electron donation capability, which reflects the reducing power
of the test compound, with its antioxidant activity. When the test
was performed according to Stratil et al.19 indoles 3a and 4a
showed potential reducing power at concentrations of 50 and
10
lM, respectively, and above.
The structural requirements and mode of action of the in vivo
and in vitro antioxidant activity of polysubstituted indoles have
been the subject of several investigations.20 Although the exact
mechanism of action of these indole derivatives is still unknown,
a mechanistic picture can be drawn taking into account that many
naturally-occurring and synthetic indoles display antioxidant
activity, and the reactions of the antioxidant agent melatonin21
and related indoles with free radicals have been recently examined
through computational models,22 and that it has been shown that
melatonin exerts its biological activity as radical scavenger via a
nitrogen centered radical, the indolyl (or melatonyl) cation
radical.23
Accordingly, it can be proposed (Scheme 2) that compounds 3
and 4 interact with a free radical source (FRÅ), through one of
two pathways, involving either single electron transfer (SET) or
hydrogen abstraction.24 In the first case, electron transfer from
the antioxidant to the active radical would yield an anion (FRꢁ)
and a cation radical species like i. A structure resembling i has also
been proposed as an intermediate for the hypervalent iodine-med-
iated SET oxidation of indole derivatives.25 In the case if N-unsub-
stituted compounds, the electron transfer may be followed by
Conclusion
In summary, we have shown that CeCl3ꢀ7H2O is
convenient promoter for the reaction of indoles with aromatic
sulfonothioates, furnishing monosubstituted indoles and
a very
3
bis(indol-3-yl)sulfides 4 under conventional heating or microwave
irradiation, respectively, both in excellent yields. The bis(indol-3-
yl)sulfides were also converted into the very useful sulfones
derivatives 5 under very mild conditions. On the other hand, 3a
and 4a displayed antioxidant activity, bis(indol-3-yl)sulfide 4a
being a more potent antioxidant.
Acknowledgments
The authors thank MCT/CNPq, CAPES, UDESC, and FAPERGS for
financial support.
References and notes
1. (a) Halliwell, B.; Gutteridge, J. M. C., 4th ed. In Free Radicals in Biology and
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Firuzi, O.; Miri, R.; Tavakkoli, M.; Saso, L. Curr. Med. Chem. 2011, 18, 3871; (e)
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2009, 55, 1; (c) Nogueira, C. W.; Rocha, J. B. T. Arch. Toxicol. 2011, 85, 1313.
3. (a) Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York, 1996; (b)
Juwarker, H.; Suk, J.-M.; Jeong, K.-S. Top. Heterocycl. Chem. 2010, 24, 177; (c)
Barluenga, J.; Valdés, C. Five Membered Heterocycles: Indole and Related
Systems In Modern Heterocyclic Chemistry; Wiley: New York, 2011; Vol. 1, pp
377–513; (d) Vicente, R. Org. Biomol. Chem. 2011, 9, 6469; (e) Sharma, V.;
Kumar, P.; Pathak, P. J. Heterocycl. Chem. 2010, 47, 491.
FR.
S
S
N
N
N
N
R
R
4a R= H
4b R= Me
R
R
-
FR
R = H
i
FRH
R= H
FR.
S
S
4. (a) Mor, M.; Spadoni, G.; Diamantini, G.; Bedini, A.; Tarzia, G.; Silva, C.;
Vacondio, F.; Rivara, M.; Plazzi, P. V.; Franceschini, D.; Zusso, M.; Giusti, P. Adv.
Exp. Med. Biol. 2003, 527, 567; (b) Mor, M.; Silva, C.; Vacondio, F.; Plazzi, P. V.;
Bertoni, S.; Spadoni, G.; Diamantini, G.; Bedini, A.; Tarzia, G.; Zusso, M.;
Franceschini, D.; Giusti, P. J. Pineal Res. 2004, 36, 95; (c) Olgen, S.; Coban, T. Arch.
N
N
N
N
iii
ii
_
Pharm. 2002, 335, 331 (Weinheim); (d) Ölgen, S.; Kılıç-Kurt, Z.; Sßener, F.; Ißsgör,
Scheme 2. Proposed mechanism for the antioxidant activity of the bis(indol-3-
yl)sulfides (4).
Y. G.; Çoban, T. Chemotherapy 2011, 57, 1.

C. C. Silveira et al. / Tetrahedron Letters 54 (2013) 4926–4929
4929
5. (a) Lakshmi, N. V.; Thirumurugan, P.; Noorulla, K. M.; Perumal, P. T. Bioorg. Med.
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Lafuente, L.; Villarroya, M.; García, A. G.; Oset-Gasque, M. J.; Marco-Contelles, J.
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D.; Yu, L.; Wang, P. G. Tetrahedron Lett. 1996, 37, 4467; (d) Yadav, J. S.; Reddy, B.
V. S.; Murthy, C. V. S. R.; Kumar, G. M.; Madan, C. Synthesis 2001, 783; (e) Deb,
M. L.; Bhuyan, P. J. Synlett 2008, 325.
13. Typical procedure for the synthesis of bis(indol-3-yl)sulfides 4. CeCl3ꢀ7H2O
(1.0 mmol) was added to mixture of the indole (1.0 mmol) and the
a
appropriate sulfonothioate (0.5 mmol) in DMA (5 mL). The reaction mixture
was submitted to microwave irradiation at 160 °C for 20 min, in a closed vessel
(maximum power 100 W). Water (15 mL) was added and the product was
extracted with EtOAc (3 ꢂ 10 mL). The organic phase was dried over anhydrous
MgSO4 and the solvent was removed under reduced pressure. The product was
purified by column chromatography on silica gel (hexanes–EtOAc, 80:20).
Spectral data of selected compound: 4c: mp 148–150 °C; 1H NMR d 11.41 (s,
2H), 7.80 (s, 2H), 7.72 (s, 2H), 7.34 (d, J = 8.3, 2H), 7.20 (d, J = 8.3, 2H); 13C NMR
d 134.7 (2C), 130.9 (2C), 129.9 (2C), 123.9 (2C), 120.3 (2C), 113.7 (2C), 112.0
(2C), 104.4 (2C); EI-MS (m/z, rel. int., %): 421 [(M+2)+, 98]; 420 [(M+1)+, 18];
419 (M+, 100); 341 (15); 226 (9); 149 (45); Anal. Calcd for C16H10Br2N2S C,
45.52; H, 2.39; N, 6.64; Found C, 45.54; H, 2.62; N, 6.42.
8. (a) Silveira, C. C.; Mendes, S. R.; Rosa, D.; Zeni, G. Synthesis 2009, 4015; (b)
Silveira, C. C.; Mendes, S. R.; Líbero, F. Synlett 2010, 790; (c) Silveira, C. C.;
Mendes, S. R.; Ziembowicz, F. I.; Lenardão, E. J.; Perin, G. J. Braz. Chem. Soc. 2010,
21, 371; (d) Silveira, C. C.; Mendes, S. R.; Martins, G. M. Tetrahedron Lett. 2012,
53, 1567.
14. Padmavathi, V.; Reddy, S. N.; Mahesh, K. Chem. Pharm. Bull. 2009, 57, 1376.
15. Typical procedure for the synthesis of bis(indol-3-yl)sulfones 5. Oxone (1.0 mmol)
was added to a solution of bis(indol-3-yl)sulfides 4 (1.0 mmol) in a 1:1 (v/v)
mixture of water/acetone (5 mL). The reaction mixture was stirred for 4 h at rt.
Then, water (15 mL) was added and the product was extracted with EtOAc
(3 ꢂ 10 mL), the organic phase was dried over anhydrous MgSO4, filtered and
the solvent was removed under reduced pressure. The product was purified by
column chromatography on silica gel eluted with hexane/EtOAc (50:50).
Spectral data of selected compound: 5c: mp 270–271 °C; 1H NMR d 12.24 (s,
2H), 8.53 (s, 2H), 7.92 (s, 2H), 7.45 (d, J = 8.5, 2H), 7.25 (d, J = 8.5, 2H); 13C NMR
d 135.5 (2C), 132.1 (2C), 126.1 (2C), 124.9 (2C), 121.1 (2C), 117.0 (2C), 115.3
(2C), 114.5 (2C); EI-MS (m/z, rel. int., %): 453 [(M+2)+, 98]; 452 [(M+1)+, 5]; 451
(M+, 100); 435 (7); 419 (19); 341 (30); 264 (12); 149 (45); Anal. Calcd for
C16H10Br2N2O2S C, 42.32; H, 2.22; N, 6.17; found C, 42.74; H, 2.44; N, 5.92.
16. (a) Tuba, A. K.; Ilhami, G. Chem. Biol. Interact. 2008, 174, 27; (b) Molyneux, P. J.
Sci. Technol. 2004, 26, 211; (c) Herraiz, T.; Galisteo, J. J. Agric. Food. Chem. 2003,
51, 7156.
9. Allared, F.; Hellberg, J.; Remonen, T. Tetrahedron Lett. 2002, 43, 1553.
10. Typical procedure for the synthesis of monosubstituted indoles 3. To a mixture of
the indole (1.0 mmol) and CeCl3ꢀ7H2O (1.0 mmol) in DMF (5 mL) was added
the appropriate sulfonothioate (1.0 mmol). The reaction mixture was stirred at
80 °C for 20 min. The reaction progress was monitored by TLC. After complete
consumption of the starting materials, the reaction mixture was cooled to rt,
water (15 mL) was added and the resulting mixture was extracted with EtOAc
(3 ꢂ 10 mL). The combined organic phases were successively washed with
water and brine, and dried over anhydrous MgSO4. After filtration, the solvent
was removed under reduced pressure. The product was purified by column
chromatography on silica gel (hexanes–EtOAc, 70:30). Spectral data of selected
compounds:11 3a: mp 140–142 °C; 1H NMR d 11.84 (s, 1H), 7.52 (d, J = 2.9, 1H),
7.46–7.41 (m, 3H), 7.27 (d, J = 8.3, 2H), 7.18–7.14 (m, 2H), 7.01 (t, J = 7.8, 1H),
2.36 (s, 3H); 13C NMR d 144.2, 139.8, 136.0, 134.9, 129.3 (2C), 128.0, 126.8 (2C),
122.2, 120.4, 117.8, 112.1, 96.5, 20.7; EI-MS (m/z, rel. int., %): 303 (M+, 100);
289 (7); 211 (19); 197 (30); 149 (45); Anal. Calcd for C15H13NO2S2 C, 59.38; H,
4.32; N, 4.62; found C, 59.76; H, 4.28; N, 4.72; 3b: mp 119–120 °C; 1H NMR d
7.63 (s, 1H), 7.51 (d, J = 8.0, 1H), 7.43 (d, J = 8.2, 2H), 7.29 (d, J = 8.2, 2H), 7.24–
7.20 (m, 1H), 7.11 (d, J = 7.0, 1H), 7.04 (t, J = 7.0, 1H), 3.88 (s, 3H), 2.37 (s, 3H);
13C NMR d 144.2, 139.8, 136.0, 134.9, 129.3 (2C), 129.0, 126.8 (2C), 122.2,
121.2, 118.8, 112.1, 96.5, 33.5, 20.7; EI-MS (m/z, rel. int., %): 317 (M+, 100); 303
(9); 227 (16); 211 (25); 163 (35); Anal. Calcd for C16H15NO2S2 C, 60.54; H, 4.76;
N, 4.41; found C, 60.64; H, 4.77; N, 4.42; 3f: mp 110–113 °C; 1H NMR d 7.69–
7.65 (m, 2H), 7.57 (d, J = 7.2, 2H), 7.53–7.47 (m, 3H), 7.24 (t, J = 7.2, 1H), 7.09 (d,
J = 7.2, 1H), 7.03 (t, J = 7.2, 1H), 3.82 (s, 3H); 13C NMR d 142.7, 138.4, 136.7,
133.6, 129.0 (2C), 128.4, 126.7 (2C), 122.2, 120.7, 117.8, 110.5, 95.1, 32.8; EI-
MS (m/z, rel. int., %): 303 (M+, 100); 289 (17); 212 (99); 197 (30); 149 (45);
Anal. Calcd for C15H13NO2S2 C, 59.38; H, 4.32; N, 4.62; found C, 59.68; H, 4.33;
N, 4.62.
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