Copper(I) iodide catalyzed 3-sulfenylation of indoles with unsymmetric benzothiazolyl-containing disulfides at room temperature

Article abstract of DOI:10.1055/s-0031-1289705

A highly efficient protocol for the synthesis of 3-sulfenylindoles in moderate to excellent yields via the reaction of indoles with unsymmetric benzothiazolyl-containing disulfides is described. Copper(I) iodide is used as the catalyst and the reactions t

Full text of DOI:10.1055/s-0031-1289705

934
PAPER
Copper(I) Iodide Catalyzed 3-Sulfenylation of Indoles with Unsymmetric
Benzothiazolyl-Containing Disulfides at Room Temperature
3
-Sulfenylation of Indol
e
es
w
ith
U
ns
n
ymmetric
D
l
isulfide
e
s
i Ge, Yunyang Wei*
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. of China
Fax +86(25)84317078; E-mail: ywei@mail.njust.edu.cn
Received 5 December 2011; revised 17 January 2012
in the presence of vanadium and molecular oxygen;13b the
reaction was carried out at 60 °C for 12–48 hours in chlo-
robenzene and gave moderate to good yields. Subsequent-
ly, Fang et al. reported an iron(III) fluoride catalyzed
Abstract: A highly efficient protocol for the synthesis of 3-sulfe-
nylindoles in moderate to excellent yields via the reaction of indoles
with unsymmetric benzothiazolyl-containing disulfides is de-
scribed. Copper(I) iodide is used as the catalyst and the reactions
take place at room temperature. The by-product, 2-mercaptoben- sulfenylation of N-unprotected indoles with disulfides in
the presence of a catalytic amount of iodine.13d Finally, Li
zothiazole, can be easily recovered and reused.
and co-workers described a copper(I) iodide catalyzed
sulfenylation of N-protected indoles with disulfides as the
reaction partners.13e
Key words: indoles, 3-sulfenylindoles, sulfur, copper(I) iodide,
unsymmetric disulfides
Although many synthetic protocols have been developed
for the sulfenylation of indoles, it is still desirable to de-
velop new methods that tolerate both N-protected and N-
unprotected indoles using mild conditions.
Indole and its derivatives are found in a number of impor-
tant drugs. In addition, many bioactive compounds isolat-
ed from natural sources contain the indole functionality.1
In particular, sulfenylindoles are valued due to their utility
in the treatment of HIV, obesity, cancer, heart disease and
allergies.2 They are also used as cyclooxygenase-2 (COX-
2) inhibitors and as potent inhibitors of tubulin polymer-
ization.2b,3 Since the discovery of the important applica-
tions of 3-sulfenylindoles, many strategies have been
developed for their preparation. Several synthetic proto-
cols involve sulfenylation of indoles with electrophilic
sulfur reagents such as succinimide–sulfonium salt,4 acyl-
oxy–sulfonium salt,5 sulfenyl chlorides,6 quinone mono-
O,S-acetals7 and N-thiophthalimides.8 The above methods
can be improved by using stoichiometric amounts of pro-
moters such as iodine or potassium iodide,9 sodium hy-
In this article, we report a novel and efficient copper(I) io-
dide catalyzed selective sulfenylation of indoles at the 3-
position with unsymmetric benzothiazolyl-containing di-
sulfides 2 (BTS-SR) at room temperature (Scheme 1).
The by-product, 2-mercaptobenzothiazole (BTSH), could
be easily recovered and reused to prepare the starting un-
symmetric disulfides.14 To the best of our knowledge,
there are no reports on the sulfenylation of indoles using
readily prepared unsymmetric benzothiazolyl-containing
disulfides.
Initially, we attempted the copper(I) iodide (20 mol%)
catalyzed sulfenylation of 1H-indole (1a) with the sym-
metric disulfide, 2,2¢-dithiobis(benzothiazole) at different
temperatures in dimethyl sulfoxide. We were delighted to
find that the reaction proceeded well at room temperature
in about four hours. According to Li,13e the copper(I) io-
dide catalyzed sulfenylation of N-protected indoles with
disulfides in dimethyl sulfoxide occurred at 110 °C in 10–
18 hours. The high reactivity of 2,2¢-dithiobis(benzothia-
zole) indicated that benzothiazole-2-thiolate (BTS) was a
good leaving group during the sulfenylation of indoles.
Subsequently, we attempted the copper(I) iodide cata-
dride,10
N-chlorosuccinimide,8
phenyliodine(III)
bis(trifluoroacetate)11 and Selectfluor®,12 to activate sul-
fides, disulfides or thiols.
The literature contains several reports on the transition
metal catalyzed sulfenylations of indoles with thiols and
disulfides,8c,13 including a copper(I) iodide (CuI) cata-
lyzed alkylthiation of indole with dimethyl disulfide at
132–160 °C.13a In 2004, Maeda and co-workers described
an efficient method using thiols as sulfenylation reagents
R4
N
S
S
S
R4
R2
S
R3
R3
N
S
2
R2
SH
+
CuI (10 mol%), DMSO, r.t.
N
N
R1
R1
easily recovered
1
3
R1 = H, Me; R2 = H, Me; R3 = H, Br, MeO; R4 = alkyl, aryl
Scheme 1 Copper(I) iodide catalyzed synthesis of 3-sulfenylindoles at room temperature
SYNTHESIS 2012, 44, 934–940
x
x
.x
x
.2
0
1
2
Advanced online publication: 14.02.2012
DOI: 10.1055/s-0031-1289705; Art ID: H113111SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
3-Sulfenylation of Indoles with Unsymmetric Disulfides
935
lyzed sulfenylation of 1H-indole (1a) with unsymmetric amongst those tested, and no product was formed in the
2-benzothiazolyl phenyl disulfide (2a) in dimethyl sulfox- absence of any copper salt (Table 1, entry 9). An investi-
ide at room temperature. The reaction went to completion gation of the effect of the solvent revealed that dimethyl
within four hours and the product, 3-(phenylthio)-1H-in- sulfoxide was the most efficient affording the highest
dole (3a), was obtained in 87% yield (Table 1, entry 1). yield of product (Table 1, entries 1 and 10–15). The effect
Encouraged by this result, we optimized the reaction and of catalyst loading was also studied and it was found that
the results are listed in Table 1.
10 mol% of copper(I) iodide was the optimum amount
(Table 1, entry 16).
A
range of copper salts [CuI, CuCl, CuBr,
Cu(OAc)2·H2O, CuCl2·2H2O, Cu(OTf)2, CuO and Cu2O] When the amount of copper(I) iodide was reduced to 5
was used as catalysts in this reaction (Table 1, entries 1– mol%, the yield of the product decreased from 87% to
8). It was found that copper(I) iodide was the best catalyst 74% (Table 1, entry 17). The reaction also proceeded at
Table 1 Optimization of the Reaction Conditions for the Sulfenylation of Indolesa
S
N
S
S
Cu catalyst
+
S
solvent, temp
N
N
H
3a
H
1a
2a
Entry
Catalyst
CuI
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Temp (°C)
r.t.
Yield (%)g
1
2
87
0
CuCl
CuBr
Cu(OAc)2·H2O
CuCl2·2H2O
Cu(OTf)2
CuO
r.t.
3
r.t.
77
13
48
0
4
r.t.
5
r.t.
6
r.t.
7
r.t.
0
8
Cu2O
–
r.t.
0
9
r.t.
0
10
11
12
13
14
15
16b
17c
18b
19b,d
20b,e
21b,f
CuI
r.t.
62
trace
8
CuI
CH2Cl2
EtOAc
MeCN
toluene
THF
r.t.
CuI
r.t.
CuI
r.t.
16
22
10
87
74
86
80
78
71
CuI
r.t.
CuI
r.t.
CuI
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
r.t.
CuI
r.t.
CuI
50
CuI
r.t.
CuI
50
CuI
r.t.
a Reaction conditions: 1a (1 mmol), 2a (1.1 mmol), catalyst (20 mol%), solvent (2 mL), 4 h.
b CuI (10 mol%) was used.
c CuI (5 mol%) was used.
d 2,2¢-Bipyridine (20 mol%) was added.
e 1,10-Phenanthroline (20 mol%) was added.
f Tetramethylethylenediamine (20 mol%) was added.
g Yield of isolated product after column chromatography.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 934–940

936
W. Ge, Y. Wei
PAPER
50 °C to afford a comparable yield of the expected product the corresponding 3-sulfenylindoles 3 (Table 2, entries 1–
(Table 1, entry 18). To study the effect of ligands, 2,2¢-bi- 8). From analysis of the results, it can be seen that unsym-
pyridine, 1,10-phenanthroline and tetramethylethylenedi- metric disulfides 2 bearing electron-donating groups on
amine were added to the reaction which resulted in a the aromatic substituent (R) (Table 2, entries 2, 7 and 8)
decrease in the yield in each case (Table 1, entries 19–21). typically gave better yields than those possessing elec-
tron-withdrawing functionalities (Table 2, entries 4–6),
In order to evaluate the versatility of this novel system, a
series of unsymmetric disulfides 2a–j was synthesized
and subjected to the sulfenylation reaction with various
which suggests that during the reaction, an electrophilic
species (RS+) might be formed. The presence of an elec-
tron-withdrawing group would be expected to hinder for-
indoles in dimethyl sulfoxide at room temperature. The
mation of this species.
results show that the majority of the studied unsymmetric
disulfides 2 underwent smooth transformations to afford
Table 2 Copper(I) Iodide Catalyzed Sulfenylation of Indoles 1 with Unsymmetric Disulfides 2a
S
R4
R3
R3
R4
N
S
S
CuI (10 mol%)
DMSO, r.t.
R2
R2
+
S
N
N
R1
R1
Entry
1
Indole
Disulfideb
Product
Time (h)
3
Yield (%)c
S
S
N
S
87
S
S
N
H
S
N
H
1a
1a
2a
3a
3b
N
S
2
3
3
4
89
74
S
N
H
2b
Cl
Cl
S
S
S
S
N
1a
S
S
S
S
S
S
S
S
S
N
H
2c
3c
3d
3e
3f
Cl
N
Cl
4
5
6
1a
1a
1a
3
3
5
81
86
51
S
N
H
2d
Br
N
Br
S
N
H
2e
NO2
N
NO2
S
N
H
2f
Synthesis 2012, 44, 934–940
© Thieme Stuttgart · New York

PAPER
3-Sulfenylation of Indoles with Unsymmetric Disulfides
937
Table 2 Copper(I) Iodide Catalyzed Sulfenylation of Indoles 1 with Unsymmetric Disulfides 2a (continued)
S
R4
R2
R3
R3
R4
N
S
S
CuI (10 mol%)
DMSO, r.t.
R2
+
S
N
N
R1
R1
Entry
7
Indole
Disulfideb
Product
Time (h)
Yield (%)c
H2N
H2N
S
N
S
1a
5
80
94
S
S
N
H
2g
3g
S
S
S
OMe
N
S
S
OMe
8
1a
4
S
S
S
N
H
2h
3h
3i
N
9
1a
1a
10
24
50
59
S
N
H
2i
N
S
S
10
S
N
H
2j
3j
S
11
2a
2
88
N
N
Me
Me
1b
3k
S
12
13
14
2a
2a
2a
0.25
93
70
85
N
H
N
H
1c
3l
Br
S
Br
6
N
H
N
H
1d
3m
MeO
S
MeO
0.5
N
H
N
H
1e
3n
a Reaction conditions: 1 (1 mmol), 2 (1.1 mmol), CuI (10 mol%), DMSO (2 mL), r.t.
b Yield of isolated product based on substrate 1.
c Unsymmetric disulfides 2a–e,g–j14a and 2f14b were synthesized according to the literature.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 934–940

938
W. Ge, Y. Wei
PAPER
500 (500 MHz) spectrometer in CDCl3 or DMSO-d6 with TMS as
the internal standard. MS spectra was recorded using a Thermo Sci-
entific TSQ Quantum analyzer. Elemental analyses were recorded
using a Perkin-Elmer C, H, N analyzer. All the products are known
compounds except for 3c and they were identified by comparison of
their physical and spectral data with those reported in the literature.
To our delight, the sulfenylation reaction also proceeded
well with unsymmetric disulfides possessing a benzyl and
an alkyl group (Table 2, entries 9 and 10). Next, substitut-
ed indoles 1b–e were investigated in this sulfenylation re-
action (Table 2, entries 11–14). The expected products
were formed in good to excellent yields showing that the
method tolerated methyl, bromo and methoxy substituents
on the indole.
Unsymmetric Disulfides 2; General Procedure
To a well-stirred suspension of 2,2¢-dithiobis(benzothiazole) (3.32
g, 10 mmol) in CHCl3 (100 mL) was added dropwise, over 30 min,
a soln of the appropriate thiol (10 mmol) in CHCl3 (25 mL). During
this period the mixture gradually became homogeneous. Stirring
was continued at r.t. for ca. 2 h, until TLC indicated complete con-
sumption of the starting material. The mixture was washed succes-
sively with 5% aq NaOH soln (2 × 25 mL) and H2O (2 × 25 mL) to
remove 2-mercaptobenzothiazole and then dried over anhyd
MgSO4. Filtration followed by evaporation of the solvent in vacuo
gave the pure unsymmetric disulfide.
Based on these results, a plausible mechanistic pathway
for this reaction is proposed (Scheme 2).8c,13,15 Initially,
the unsymmetric disulfide (BTS-SR) forms an electro-
philic species, RS+ (A) with copper iodide as previously
described.15 This species then undergoes addition to the
indole to produce intermediate C, deprotonation of which
gives the desired product 3 along with regeneration of the
copper catalyst.
Sulfenylation of Indoles; General Procedure
[BTSCuI]–
A mixture of indole 1 (1 mmol), unsymmetric disulfide 2 (1.1
mmol) and CuI (0.10 mmol, 10 mol%) in DMSO (2 mL) was stirred
at r.t. until TLC indicated complete consumption of the starting in-
dole. The soln was diluted with CH2Cl2 (10 mL) and washed with
H2O (3 × 10 mL). The organic layer was separated and washed with
5% aq NaOH soln (3 × 3 mL). The aq layer was separated and neu-
tralized with concd HCl (to pH 7) to precipitate the by-product, 2-
mercaptobenzothiazole. The organic layer was concentrated under
vacuum and the crude product purified by column chromatography
(PE–EtOAc, 15:1) to provide analytically pure product 3.
B
RS+
A
N
H
1
BTS-SR
SR
2
CuI
N
H
C
3-(Phenylthio)-1H-indole (3a)
[BTSCuI]–
Yield: 195.8 mg (87%); white solid; mp 150–151 °C (Lit.16 149–
151 °C).
B
SR
IR (KBr): 3412, 3126, 3051, 1651, 1579, 1477, 1438, 1406, 1234,
736 cm–1.
N
SH
1H NMR (500 MHz, DMSO-d6): d = 11.68 (br s, 1 H), 7.76 (s, 1 H),
7.49 (d, J = 8.0 Hz, 1 H), 7.39 (d, J = 7.5 Hz, 1 H), 7.21–7.17 (m, 3
H), 7.08–7.05 (m, 2 H), 7.02 (d, J = 8.0 Hz, 2 H).
S
BTSH
N
H
3
13C NMR (125 MHz, CDCl3): d = 139.2, 136.5, 130.7, 129.1, 128.7,
125.9, 124.8, 123.1, 120.9, 119.7, 111.6, 102.8.
Scheme 2 Proposed mechanism for the copper(I) iodide catalyzed
sulfenylation of indoles
3-(p-Tolylthio)-1H-indole (3b)
In conclusion, a simple and efficient method for the cop-
per(I) iodide catalyzed sulfenylation of indoles with un-
symmetric disulfides to give the corresponding 3-
sulfenylindoles in dimethyl sulfoxide at room temperature
has been developed. In comparison with reported sulfur
reagents for the sulfenylation of indoles, the unsymmetric
disulfides employed herein have the advantages of simple
preparation and undergo regioselective reactions with in-
doles. The by-product, 2-mercaptobenzothiazole (BTSH)
can be easily recovered and recycled to prepare the un-
symmetric disulfide substrates.
Yield: 212.8 mg (89%); white solid; mp 123–125 °C (Lit.13b 125–
126 °C).
1H NMR (500 MHz, CDCl3): d = 8.37 (br s, 1 H), 7.64 (d, J = 8.0
Hz, 1 H), 7.50 (d, J = 2.5 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.30–
7.27 (m, 1 H), 7.20–7.17 (m, 1 H), 7.06 (d, J = 8.0 Hz, 2 H), 7.00
(d, J = 8.0 Hz, 2 H), 2.28 (s, 3 H).
3-[(3-Chlorophenyl)thio]-1H-indole (3c)
Yield: 191.7 mg (74%); white solid; mp 89–91 °C (recrystallized
from PE–EtOAc, 5:1).
IR (KBr): 3374, 2931, 1672, 1561, 1488, 1432, 1230, 1092, 784 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 11.78 (br s, 1 H), 7.82 (d,
J = 2.5 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.40 (d, J = 8.0 Hz, 1 H),
7.25–7.19 (m, 2 H), 7.14–7.08 (m, 2 H), 7.00–6.99 (m, 1 H), 6.96
(s, 1 H).
13C NMR (125 MHz, CDCl3): d = 141.6, 136.5, 134.7, 131.0, 129.7,
128.9, 125.5, 125.0, 123.9, 123.3, 121.2, 119.5, 111.7, 101.9.
All chemicals (AR grade) were obtained from commercial sources
and were used without further purification. Petroleum ether (PE) re-
fers to the fraction boiling in the 60–90 °C range. The progress of
the reactions was monitored by TLC (silica gel, Polygram SILG/
UV 254 plates). Column chromatography was performed on Silicy-
cle silica gel (200–300 mesh). Melting points were obtained using a
Yamato MP-21 melting point apparatus and are uncorrected. IR
spectra were recorded on a Shimadzu spectrophotometer using KBr
discs. 1H and 13C NMR spectra were obtained using a Bruker DRX
MS (ESI): m/z = 260 (M+).
Anal. Calcd for C14H10ClNS: C, 66.81; H, 4.95; N, 4.83. Found: C,
66.82; H, 4.97; N, 4.82.
Synthesis 2012, 44, 934–940
© Thieme Stuttgart · New York

PAPER
3-Sulfenylation of Indoles with Unsymmetric Disulfides
939
3-[(4-Chlorophenyl)thio]-1H-indole (3d)
Yield: 209.8 mg (81%); white solid; mp 126–128 °C (Lit.13b 127.5–
128.3 °C).
1H NMR (500 MHz, DMSO-d6): d = 11.74 (br s, 1 H), 7.79 (d,
J = 2.5 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 1 H),
7.26 (dd, J = 2.0, 7.0 Hz, 2 H), 7.21–7.18 (m, 1 H), 7.09–7.06 (m, 1
H), 7.01 (dd, J = 2.0, 7.0 Hz, 2 H).
IR (KBr): 3107, 3045, 2943, 2904, 2874, 1631, 1581, 1479, 1336,
1244, 1126, 740 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.64 (d, J = 8.0 Hz, 1 H), 7.42 (d,
J = 8.5 Hz, 1 H), 7.36 (s, 1 H), 7.34–7.31 (m, 1 H), 7.21–7.16 (m, 3
H), 7.14–7.12 (m, 2 H), 7.08–7.06 (m, 1 H), 3.88 (s, 3 H).
2-Methyl-3-(phenylthio)-1H-indole (3l)
Yield: 222.3 mg (93%); white solid; mp 109–111 °C (Lit.13d 110.9–
111.2 °C).
3-[(4-Bromophenyl)thio]-1H-indole (3e)
Yield: 260.6 mg (86%); white solid; mp 144–146 °C.
IR (KBr): 3402, 3053, 2912, 2835, 1768, 1614, 1583, 1477, 1220,
1078, 1022, 744 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.22 (br s, 1 H), 7.59 (d, J = 8.0
Hz, 1 H), 7.37 (d, J = 8.0 Hz, 1 H), 7.25–7.21 (m, 1 H), 7.20–7.15
(m, 3 H), 7.09–7.06 (m, 3 H), 2.54 (s, 3 H).
IR (KBr): 3385, 2922, 1653, 1556, 1498, 1471, 1410, 1234, 1080,
1003, 808, 748 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 11.74 (br s, 1 H), 7.79 (d,
J = 2.5 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 1 H), 7.40–7.37 (m, 3 H),
7.21–7.18 (m, 1 H), 7.10–7.05 (m, 1 H), 6.95 (d, J = 8.5 Hz, 2 H).
5-Bromo-3-(phenylthio)-1H-indole (3m)
Yield: 212.1 mg (70%); white solid; mp 121–122 °C (Lit.13d 120.9–
123.1 °C).
13C NMR (125 MHz, CDCl3): d = 138.5, 136.5, 131.6, 130.7, 128.8,
127.4, 123.2, 121.1, 119.5, 118.3, 111.7, 102.3.
3-[(4-Nitrophenyl)thio]-1H-indole (3f)
Yield: 137.7 mg (51%); yellow solid; mp 176–178 °C (Lit.13d
176.1–178.0 °C).
1H NMR (500 MHz, CDCl3): d = 8.45 (br s, 1 H), 7.78 (s, 1 H), 7.52
(d, J = 2.5 Hz, 1 H), 7.39–7.33 (m, 2 H), 7.22–7.19 (m, 2 H), 7.11–
7.08 (m, 3 H).
1H NMR (500 MHz, CDCl3): d = 8.71 (br s, 1 H), 8.03–8.00 (m, 2
H), 7.57–7.52 (m, 3 H), 7.35–7.32 (m, 1 H), 7.24–7.20 (m, 1 H),
7.17–7.14 (m, 2 H).
5-Methoxy-3-(phenylthio)-1H-indole (3n)
Yield: 216.8 mg (85%); colorless crystals; mp 78–79 °C (Lit.7a 78–
79 °C).
3-[(2-Aminophenyl)thio]-1H-indole (3g)
IR (KBr): 3412, 3066, 2958, 2937, 2835, 1680, 1627, 1577, 1475,
1282, 1201, 1095, 862, 738 cm–1.
Yield: 192.1 mg (80%); white solid; mp 93–94 °C (Lit.17 93–95 °C).
1H NMR (500 MHz, DMSO-d6): d = 11.47 (br s, 1 H), 7.74–7.73
(m, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 1 H), 7.15–
7.12 (m, 1 H), 7.06–7.00 (m, 2 H), 6.91–6.87 (m, 1 H), 6.65 (d,
J = 8.0 Hz, 1 H), 6.42–6.39 (m, 1 H), 5.27 (s, 2 H).
1H NMR (500 MHz, CDCl3): d = 8.34 (br s, 1 H), 7.47 (dd, J = 2.5,
10.0 Hz, 1 H), 7.35 (d, J = 8.5 Hz, 1 H), 7.21–7.18 (m, 2 H), 7.14–
7.12 (m, 2 H), 7.10–7.06 (m, 2 H), 6.94 (dd, J = 2.5, 10.0 Hz, 1 H),
3.81 (s, 3 H).
3-[(4-Methoxyphenyl)thio]-1H-indole (3h)
Yield: 239.8 mg (94%); pale-yellow solid; mp 111–113 °C (Lit.13d
112.2–114.1 °C).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
1H NMR (500 MHz, DMSO-d6): d = 11.58 (br s, 1 H), 7.72 (d,
J = 2.5 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 1 H),
7.18–7.14 (m, 1 H), 7.08–7.04 (m, 3 H), 6.82–6.79 (m, 2 H), 3.67
(s, 3 H).
13C NMR (125 MHz, CDCl3): d = 157.8, 136.5, 130.0, 129.5, 129.0,
128.6, 123.0, 120.8, 119.7, 114.5, 111.5, 104.7, 55.3.
Acknowledgment
We are grateful to Nanjing University of Science and Technology
for financial support.
References
3-(Benzylthio)-1H-indole (3i)
Yield: 119.5 mg (50%); yellow solid; mp 84–85 °C (Lit.13d 85.2–
87.0 °C).
(1) (a) Sundberg, R. J. In The Chemistry of Indoles; Academic
Press: New York, 1996. (b) Casapullo, A.; Bifulco, G.;
Bruno, I.; Riccio, R. J. Nat. Prod. 2000, 63, 447. (c) Garbe,
T. R.; Kobayashi, M.; Shimizu, N.; Takesue, N.; Ozawa, M.;
Yukawa, H. J. Nat. Prod. 2000, 63, 596. (d) Bao, B.; Sun,
Q.; Yao, X.; Hong, J.; Lee, C. O.; Sim, C. J.; Im, K. S.; Jung,
J. H. J. Nat. Prod. 2005, 68, 711.
(2) (a) Ragno, R.; Coluccia, A.; La Regina, G.; De Martino, G.;
Piscitelli, F.; Lavecchia, A.; Novellino, E.; Bergamini, A.;
Ciaprini, C.; Sinistro, A.; Maga, G.; Crespan, E.; Artico, M.;
Silvestri, R. J. Med. Chem. 2006, 49, 3172. (b) De Martino,
G.; La Regina, G.; Coluccia, A.; Edler, M. C.; Barbera, M.
C.; Brancale, A.; Wilcox, E.; Hamel, E.; Artico, M.;
Silvestri, R. J. Med. Chem. 2004, 47, 6120. (c)Berger, J. P.;
Doebber, T. W.; Leibowitz, M.; Moller, D. E.; Mosley, R.
T.; Tolman, R. L.; Ventre, J.; Zhang, B. B.; Zhou, G. PCT
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320871. (d) Ramakrishna, V. S. N.; Shirsath, V. S.;
1H NMR (500 MHz, DMSO-d6): d = 11.29 (br s, 1 H), 7.53 (d,
J = 8.0 Hz, 1 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.27 (d, J = 2.5 Hz, 1 H),
7.24–7.17 (m, 3 H), 7.15–7.12 (m, 3 H), 7.07–7.04 (m, 1 H), 3.88
(s, 2 H).
13C NMR (125 MHz, CDCl3): d = 139.0, 136.2, 129.8, 129.2, 129.0,
128.2, 126.7, 122.7, 120.5, 119.3, 111.4, 105.3, 41.0.
3-(Ethylthio)-1H-indole (3j)
Yield: 104.5 mg (59%); white solid; mp 142–144 °C (Lit.18 142–
143 °C).
1H NMR (500 MHz, DMSO-d6): d = 11.35 (br s, 1 H), 7.60 (d,
J = 8.0 Hz, 1 H), 7.50 (d, J = 2.5 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 1 H),
7.16–7.13 (m, 1 H), 7.10–7.07 (m, 1 H), 2.64 (q, J = 7.0 Hz, 2 H),
1.11 (t, J = 7.5 Hz, 3 H).
Kambhampati, R. S.; Vishwakarma, S.; Kandikere, N. V.;
1-Methyl-3-(phenylthio)-1H-indole (3k)
Yield: 210.4 mg (88%); white solid; mp 86–87 °C (Lit.13d 84.9–87.2
°C).
© Thieme Stuttgart · New York
Synthesis 2012, 44, 934–940

940
W. Ge, Y. Wei
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Synthesis 2012, 44, 934–940
© Thieme Stuttgart · New York