Metal Free Mono- and 2,3-Bis-sulfenylation of Indoles in Water with Sodium Sulfinates as a Sulfur Source

Article abstract of DOI:10.1002/cjoc.201800164

An iodine-PPh₃ mediated sulfenylation of indoles in water with stable and odorless sodium sulfinates as the sulfur source is described. The reaction could afford monosulfenylated indoles in moderate to excellent yields under metal free conditions. Moreover, double C—H sulfenylation of indoles at 2- and 3-positions has also been achieved by using excess sodium sulfinates under the optimized reaction conditions.

Full text of DOI:10.1002/cjoc.201800164

Metal free mono- and 2,3-bis-sulfenylation of indoles in water
with sodium sulfinates as a sulfur source
Changqing Liu,a,b Jian Fan,a Manyi Wu,a Jiahui Chen,a
*
Yiming Zhao,a Meihua Xiea,
ABSTRACT An iodine-PPh3 mediated sulfenylation of indoles in water with stable and odorless
sodium sulfinates as the sulfur source is described. The reaction could afford monosulfenylated
indoles in moderate to excellent yields under metal free conditions. Moreover, double C-H
sulfenylation of indoles at 2- and 3-positions has also been achieved by using excess sodium
sulfinates under the optimized reaction conditions.
KEYWORDS indole, sodium sulfinate, sulfenylation
Introduction
Sulfur-containing moieties exist in a variety of biologically and medicinally active molecules
and introduction of a sulfur moiety into organic molecules is one of the major research areas in
organic synthesis.[1] Among them, sulfenylated indoles show potent activities such as inhibition of
tubulin polymerization and cell growth, and have a great therapeutic value in the treatment of
cancer, HIV, heart disease, allergies and bacterial diseases (Fig 1).[2] Numerous synthetic methods
[3]
to access sulfenylated indoles have been successfully established by exploiting disulfides,
sulfenyl halides,[4] thiols,[5] and arylsulfonyl chlorides,[6] many of which have disadvantages such
as unpleasant odors, air and moisture sensitive, high cost, or difficult to prepare. In this regard,
development of new and practical methods to synthesize sulfenylated indoles is in great demand.
During recent years, sodium sulfinates have been widely used in organic synthesis as the sulfur
source for its nature of stability, odorlessness and safety.[7] However, the usage of sodium
sulfinates for the synthesis of sulfenylated indoles is rare until now.[8] Especially, double C-H
aKey Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based
Materials, College of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241000, China.
bDepartment of Chemistry, Bengbu Medical College, Bengbu, 233030, China
*E-mail: xiemh@mail.ahnu.edu.cn
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1002/cjoc.201800164
This article is protected by copyright. All rights reserved.

sulfenylation in indoles with sodium sulfinates to give 2,3-bis-sulfenyl indoles remains elusive.
Fig 1 Examples of biologically active 3-(arylsulfanyl)indoles
On the other hand, reactions for organic synthesis that are performed in aqueous conditions
have attracted tremendous attention and are becoming some of the most exciting research areas. [9]
With regard to the green chemistry and environmental protection, it is still challenging and highly
desirable to develop efficient methods for the synthesis of sulfenylated indoles from simple and
readily available starting materials under environmentally benign reaction conditions. To the best
of our knowledge, there are no reports in literature describing the metal-free sulfenylation of
indoles using sodium sulfinates in aqueous medium. Herein, we wish to present an efficient
metal-free synthesis of mono- and 2,3-bis-sulfenylindoles with sodium sulfinates as sulfur sources
in water. Various indoles and sodium sulfinates participated in the reaction to afford the
corresponding products in moderate to excellent yields.
Results and discussion
At the outset of our study, we focused our investigation on indole (1a) as a model reactant
and the experimental results are compiled in Table 1. To our delight, the desired product 3a was
isolated in 55% yield by treatment of indole (1a) and sodium p-toluenesulfinate (2a, 1 equiv.) in
the presence of 2.0 equiv. of PPh3 and 1.0 equiv. of I2 in refluxing CH2Cl2 for 24 h (Table 1, entry
1). A number of organic solvents were examined (Table 1, entries 2-10) and the results show that
1,2-dichloroethane gave the best efficiency in terms of product yield (83% yield). Surprisingly,
product 3a was isolated in 82% yield when the green and cheap medium of water was used as the
reaction solvent (Table 1, entry 11). Considering the environmental benign and sustainable process
in organic synthesis, we chose water as the solvent for the further optimization. Screening of the
This article is protected by copyright. All rights reserved.

amount of PPh3 or I2 showed that less PPh3 or I2 resulted in a poor yield (Table 1, entries 12 and
14) and increasing the amount of PPh3 or I2 did not improve the yield of 3a (Table 1, entries 13
and 15). In these cases, 3a was obtained as the sole sulfenylated product when indole reacts with
1.0 equiv. sodium sulfinate. While 3a was obtained only in 52% yield along with the formation of
22% yield of 2,3-bis-sulfenylindoles 4a when 1.5 equiv. sodium p-toluenesulfinate was used
(Table 1, entry 16). Lower yield of 3a was obtained when the reaction was conducted in air (Table
1, entry 17). Thus, the suitable reaction conditions selected for 3-sulfenylation of indoles are the
following: indole (1 equiv.), sodium sulfinate (1 equiv.), I2 (1 equiv.), and PPh3 (2 equiv.) in water
at refluxing temperature under argon atmosphere.
Optimization of reaction conditions for 3-sulfenylation of indolesa
Table 1
I2
PPh3
2a
Entry
solvent
CH2Cl2
Yield (%)b
55
(equiv.
） (equiv.)
(equiv.)
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
THF
23
3
2
toluene
26
4
2
1,4-dioxane
CH3CN
59
5
2
42
6
2
ClCH2CH2Cl
acetone
83
7
2
Trace
25
8
2
ethyl acetate
DMF (100 oC)
DMSO (100 oC)
H2O
9
2
80
10
11
12
2
72
2
82
1.5
H2O
46
This article is protected by copyright. All rights reserved.

13
1
1
2.5
2
H2O
H2O
H2O
H2O
H2O
80
18
76
52
70
14
1
0.5
1.5
1.5
1
15
1
2
16c
1.5
3
17d
1
2
aReaction conditions: 1a (0.25 mmol), sodium p-toluenesulfinate, I2 and PPh3 in 2 mL
b
c
of solvent. Isolated yield based on 1a. 2,3-bis-sulfenylindoles 4a was isolated in 22%
yield. dUnder air.
With the optimal reaction conditions established, the reactions of variously substituted
indoles and sodium sulfinates were investigated to demonstrate the scope and generality of this
method. The results are summarized in Table 2. Sodium sulfinates 2a-2c reacted smoothly with
indole 1a to produce the corresponding 3-sulfenylated indoles (Table 2, 3aa-3ac). Indoles with
electron-donating substituents such as phenyl (Table 2, 3ba-3bd) and methyl (Table 2, 3ca-3cc
and 3da-3dc) gave higher yields in comparison to indole. Various functional groups, such as
methoxyl (Table 2, 3ea-3ec), fluoro (Table 2, 3fa-3fc), ester (Table 2, 3ha), and ketone (Table 2,
3ia), on the aromatic ring of indoles were well tolerated under the standard conditions. More
importantly, 3-sulfenylated indoles with ester (Table 2, 3ga-3gc) or amide (Table 2, 3ja) groups
on the heterocycle might be of anti-HIV activity. [10] It should be noted that 7-azaindol and pyrrole
could also conduct this reaction smoothly to give the corresponding products 3la and 3ma in 83%
and 35% yields, respectively. 2-Sulfenylated indole 3ka could be isolated in 53% yield when
3-methyl indole was used. Unfortunately, N-tosylindole could not be tolerated in this reaction,
indicating that this reaction involved a nucleophilic process of indoles.
Table 2 Synthesis of monosulfenylindole 3 with sodium sulfinate in watera
This article is protected by copyright. All rights reserved.

3aa, 82%
3ab, 85%
3bb, 96%
3ca, 98%
3ac, 94%
3bc, 95%
3cb, 98%
3db, 95%
3eb, 48%
3fb, 98%
96%
94%
3ba,
3bd,
3cc, 97%
3dc, 90%
3da, 98%
3ea, 52%
61%
3fa, 94%
3ec,
This article is protected by copyright. All rights reserved.

3fc, 82%
3gb, 80%
85%
3ga,
3ha, 75%
3gc, 60%
3ia, 60%
3ma, 35%
3ja, 92%
53%
3ka,
3la, 83%
aReaction condition: 1 (0.25 mmol), 2 (0.25 mmol), I2 (0.25 mmol), PPh3 (0.5 mmol), H2O (2 mL), Ar, reflux;
Isolated yield based on 1.
Compared to the extensive investigation on the synthesis of 3-sulfenylindoles, synthesis of
2,3-bis-sulfenylindoles is sparse. As far as we know, there are no reports in the literature
describing the direct 2,3-bis-sulfenylation of indoles using sodium sulfinates as sulfenylating
agents in aqueous medium. In the course of the optimization of reaction conditions, we noted that
a mixture of mono- and disulfenylindoles were yielded when indole reacted with 1.5 equiv.
sodium sulfinate in the optimal reaction conditions (Table 1, entry 16). Encouraged by this result,
we further investigated the reaction of indole with excess sodium sulfinate, hoping to provide a
simple and convenient method for the synthesis of 2,3-bis-sulfenylindoles. Gratifyingly,
2,3-bis-sulfenylindoles 4 were obtained in moderate to excellent yields when indoles 1 were
subjected to 2.5 equiv. sodium sulfinates 2 under the otherwise similar reaction conditions. The
results are summarized in Table 3. The reaction tolerated a variety of indoles 1 and sodium
This article is protected by copyright. All rights reserved.

sulfinates 2. Indole derivatives could be indole (Table 3, 4a-4c), N-methylindoles (Table 3, 4d-4f),
5-fluoroindole (Table 3, 4g-4i), 5-methoxylindole (Table 3, 4j-4l), methyl indole-5-carboxylate
(Table 3, 4m), and albeit N-tosylindole failed to participate in this reaction to give the desired
product 4. Several commercially available sodium sulfinates 2 such as sodium p-tolylsulfinate,
sodium phenylsulfinate and sodium p-chlorophenylsulfinate could conduct this reaction
successfully to give the desired products. The reaction of 3-sulfenylindole with sodium sulfinate
was also investigated, hoping to install two different sulfur groups on indole. However, a mixture
of two isomers was detected and it was difficult to isolate them from each other when the two
sulfur groups on indole were different.
Table 3 Synthesis of 2,3-bis-sulfenylindoles 4 with sodium sulfinate in watera
, 89%
, 86%
4b
4a
, 60%
, 57%
4d
4c
, 61%
, 47%
4f
, 94%
4g
4e
This article is protected by copyright. All rights reserved.

, 78%
4h
, 56%
4i
, 74%
4j
, 52%
4m
, 82%
4k
, 85%
4l
aReaction conditions: 1 (0.25 mmol), 2 (0.625 mmol), I2 (0.625 mmol), PPh3 (1.25 mmol), H2O (2 mL), Ar, reflux;
Isolated yield based on substrate 1.
To demonstrate the potential applications of the sulfenylation of indole, we scaled up the
reaction to 5 mmol (Scheme 1). The desired product 3-sulfenylindol 3j and 2,3-bis-sulfenylindole
4a could be afforded in 97% yield (1.23 g) and 64% yield (1.16 g ), respectively.
Scheme 1 Gram-scale experiment
Based on the experimental results and the previous work [8], a plausible reaction mechanism
This article is protected by copyright. All rights reserved.

is shown in Scheme 2. Firstly, in the presence of I2 and PPh3, sodium sulfinate 2 was reduced to
disulfide A, which was checked by GC-MS. Then A reacts with I2 to give electrophilic sulfenyl
iodide B, which would attack to indole 1 to form intermediate C. Subsequent deprotonation of
intermediate C gives the desired monosulfenylated indole 3. The second sulfenylation of indole
might proceed by the similar mechanism of the reported literature.[4b,4c and 8a] Product 4 might occur
by initial attack on the 3-position of the indole ring to give rise to 3,3-bis-substituted indolenium
intermediate D, followed by migration of one of the sulfide group from 3-position to 2-position to
generate an episulfonium species E. Finally, release proton of intermediate D affords
2,3-bis-sulfenylindole 4.
Scheme 2 A plausible reaction mechanism for mono- and bis-sulfenylation of indole
Conclusions
In summary, we have developed a simple and convenient protocol to access
monosulfenylated and 2,3-bis-sulfenylated indoles in good to excellent yields. The method not
only could proceed without metal catalyst and organic solvent, but also has successfully employed
the stable, readily accessible and ordorless sodium sulfinate as sulfenylating agents. Compared to
the reported routes, this protocol displays broad substrate scope and several functional groups such
as methoxyl, fluoro, ester, ketone, and amide on indole rings are well tolerated. Moreover, the
reaction can be extended to 7-azaindole and pyrrole. Synthetically, the protocol could be scaled up
to 5 mmol with good efficiency, which makes this reaction practical and attractive.
This article is protected by copyright. All rights reserved.

Experimental
General procedure for the synthesis of 3-sulfenylated indoles 3
Under argon atmosphere, a Schlenk flask equipped with a condenser was charged with 0.25
mmol of indole, 0.25 mmol of sodium sulfinate, 0.25 mmol (63.5 mg) of I2, 0.5 mmol (131 mg) of
PPh3 and 2 mL of water. The reaction mixture was stirred at refluxing temperature until complete
consumption of starting material 1 (monitored by TLC) and then cooled to room temperature. The
reaction was quenched with saturated Na2S2O3 (5 mL) and extracted with ethyl acetate (3 × 10
mL). The organic extracts were dried over anhydrous Na2SO4. After filtration and removal of the
solvent in vacuo, the crude product was purified by flash column chromatography on silica gel
(ethyl acetate/petroleum ether = 1/10) to give product 3.
o
1
3-(p-Tolylthio)-1H-indole (3aa).[3e] White solid; m.p. 122-123 C; H NMR (300 MHz,
CDCl3):  8.38 (s, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.47-7.41 (m, 2H), 7.25 (t, J = 8.2 Hz, 1H), 7.15
(t, J = 7.4 Hz, 1H), 7.00 (q, J = 8.1 Hz, 4H), 2.24 (s, 3H); 13C NMR (125 MHz, CDCl3):  136.9,
135.9, 135.2, 131.0, 130.0, 129.5, 126.7, 123.4, 121.3, 120.1, 112.1, 103.7, 21.3; IR (KBr): ν (cm-1)
3423, 1492, 1453, 1405, 1335, 1239, 1098, 1007, 800, 746; HRMS (APCI) [M+H]+: m/z calcd for
C15H14NS: 240.0841, found: 240.0849.
o
1
3-(Phenylthio)-1H-indole (3ab).[3e] White solid; m.p. 145-146 C; H NMR (300 MHz,
CDCl3):  8.43 (s, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.50-7.43 (m, 2H), 7.29-7.25 (m, 1H), 7.19-7.05
(m, 6H); 13C NMR (125 MHz, d6-DMSO):  140.1, 137.6, 133.3, 129.7, 129.5, 126.2, 125.6,
123.0, 121.0, 119.2, 113.2, 100.1; IR (KBr): ν (cm-1) 3407, 1576, 1475, 1456, 1408, 1232, 1024,
746; HRMS (APCI) [M+H]+: m/z calcd for C14H12NS: 226.0685, found: 226.0682.
3-((4-Chlorophenyl)thio)-1H-indole (3ac).[3e] White solid; m.p. 126-128 oC; 1H NMR (300
MHz, CDCl3):  8.46 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.49-7.40 (m, 2H), 7.30-7.28 (m, 1H),
7.20-7.00 (m, 5H); 13C NMR (125 MHz, d6-DMSO):  139.3, 137.7, 133.5, 130.2, 129.6, 129.3,
127.7, 123.1, 121.1, 119.1, 113.3, 99.6; IR (KBr): ν (cm-1) 3396, 1647, 1505, 1473, 1453, 1405,
1383, 1095, 1011, 811, 745; HRMS (APCI) [M+H]+: m/z calcd for C14H11ClNS: 260.0295, found:
260.0298.
2-Phenyl-3-(p-tolylthio)-1H-indole (3ba).[8e] Dark purple oil; 1H NMR (300 MHz, CDCl3):
 8.34 (s, 1H), 7.60 (d, J = 6.6 Hz, 2H), 7.52 (d, J = 7.5 Hz, 1H), 7.30-7.23 (m, 4H), 7.13 (t, J =
This article is protected by copyright. All rights reserved.

7.1 Hz, 1H), 7.08-7.01 (m, 1H), 6.90-6.82 (m, 4H), 2.11 (s, 3H); 13C NMR (125 MHz,CDCl3): 
142.5, 136.4, 136.2, 135.0, 131.9, 131.8, 130.3, 129.3, 129.2, 128.8, 126.3, 123.9, 121.7, 120.5,
111.9, 100.2, 21.5; IR (KBr): ν (cm-1) 3404, 1488, 1442, 1395, 1324, 1084, 805, 741, 694; HRMS
(APCI) [M+H]+: m/z calcd for C21H18NS: 316.1154, found: 316.1153.
2-Phenyl-3-(phenylthio)-1H-indole (3bb).[3b] Faint yellow oil; 1H NMR (300 MHz, CDCl3):
 8.39 (s, 1H), 7.60 (d, J = 6.7 Hz, 2H), 7.53 (d, J = 7.8 Hz, 1H), 7.30-7.27 (m, 3H), 7.23 (s, 1H),
7.15 (t, J = 7.1 Hz, 1H), 7.08-7.00 (m, 5H), 6.95-6.90 (m, 1H); 13C NMR (125 MHz,CDCl3): 
142.6, 139.8, 136.4, 131.8, 131.6, 129.4, 129.3, 129.2, 128.7, 126.0, 125.2, 123.9, 121.7, 120.4,
111.8, 99.7; IR (KBr): ν (cm-1) 3407, 3057, 1581, 1477, 1452, 1442, 1397, 1320, 1297, 1224, 739,
693; HRMS (APCI) [M+H]+: m/z calcd for C20H16NS: 302.0998, found: 302.0996.
1
3-((4-Chlorophenyl)thio)-2-phenyl-1H-indole (3bc). Brown oil; H NMR (300 MHz,
CDCl3):  8.49 (s, 1H), 7.66 (d, J = 6.7 Hz, 2H), 7.58 (d, J = 7.7 Hz, 1H), 7.41-7.34 (m, 4H), 7.23
(d, J = 8.0 Hz, 1H), 7.15 (t, J = 7.4 Hz, 1H), 7.08-7.05 (m, 2H), 6.98-6.96 (m, 2H); 13C NMR (125
MHz,CDCl3):  142.7, 138.4, 136.4, 131.7, 131.4, 130.9, 129.5, 129.4, 129.3, 128.6, 127.3, 124.0,
121.8, 120.3, 111.9, 99.3; IR (KBr): ν (cm-1) 3407, 1476, 1452, 1444, 1087, 1008, 816, 740, 692;
HRMS (APCI) [M + H] +: m/z calcd for C20H15ClNS: 336.0608, found: 336.0616.
3-(Methylthio)-2-phenyl-1H-indole (3bd). Purple solid; m.p. 97-98 oC; 1H NMR (300 MHz,
CDCl3):  8.35 (s, 1H), 7.85 (t, J = 7.6 Hz, 3H), 7.51 (t, J = 7.3 Hz, 2H), 7.43-7.40 (m, 2H),
7.25-7.21 (m, 2H), 2.31 (s, 3H); 13C NMR (125 MHz,CDCl3):  140.2, 136.1, 132.4, 131.4, 129.1,
128.8, 128.6, 123.5, 121.1, 120.1, 111.6, 105.3 20.2; IR (KBr): ν (cm-1) 3431, 1655, 1450, 1440,
1392, 1224, 772, 736, 696; HRMS (APCI) [M+H]+: m/z calcd for C15H14NS: 240.0841, found:
240.0845.
o
1
2-Methyl-3-(p-tolylthio)-1H-indole (3ca).[3e] Yellow solid. m.p. 96-98 C; H NMR (300
MHz, CDCl3):  8.23 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 7.9 Hz, 1H), 7.18-7.11 (m, 2H),
6.96 (s, 4H), 2.51 (s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz,CDCl3):  141.6, 136.2, 135.9, 134.9,
130.8, 130.0, 126.3, 122.6, 121.1, 119.4, 111.3, 100.1, 21.3, 12.5; IR (KBr): ν (cm-1) 3396, 1542,
1488, 1453, 1399, 1287, 1224, 1087, 800, 748; HRMS (APCI) [M+H]+: m/z calcd for C16H16NS:
254.0998, found: 254.0999.
o
1
2-Methyl-3-(phenylthio)-1H-indole (3cb).[3e] White solid; m.p. 113-114 C. H NMR (300
MHz, CDCl3):  8.25 (s, 1H), 7.54 (d, J = 7.1 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.25-7.12 (m, 4H),
This article is protected by copyright. All rights reserved.

7.05-7.02 (m, 3H), 2.51 (s, 3H); 13C NMR (125 MHz,CDCl3):  141.8, 139.8, 135.9, 130.8, 129.3,
126.0, 125.1, 122.7, 121.2, 119.4, 111.3, 99.6, 12.5; IR (KBr): ν (cm-1) 3404, 1657, 1636, 1561,
1476, 1457, 1437 1081, 743; HRMS (APCI) [M+H]+: m/z calcd for C15H14NS: 240.0841, found:
240.0846.
o
1
3-((4-Chlorophenyl)thio)-2-methyl-1H-indole (3cc).[5f] Yellow solid; m.p. 88-89 C; H
NMR (300 MHz, CDCl3):  8.16 (s, 1H), 7.42 (d, J = 7.7 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H),
7.14-7.00 (m, 4H), 6.86 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H); 13C NMR (125 MHz,CDCl3):  141.7,
138.4, 135.9, 130.7, 130.5, 129.2, 127.2, 122.8, 121.3, 119.2, 111.3, 99.3, 12.5; IR (KBr): ν (cm-1)
3400, 1468, 1406, 1381, 1290, 1093, 1015, 803, 743; HRMS (APCI) [M+H]+: m/z calcd for
C15H13ClNS: 274.0452, found: 274.0445.
o
1
1-Methyl-3-(p-tolylthio)-1H-indole (3da). Yellow solid; m.p. 112-113 C; H NMR (500
MHz, CDCl3):  7.52 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 12.0 Hz, 1H), 7.19-7.16 (m, 2H), 7.09-7.04
(m, 1H), 6.92 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 3.66 (s, 3H), 2.13 (s, 3H); 13C NMR
(125 MHz, CDCl3):  136.4, 134.9, 133.8, 133.4, 128.7, 128.4, 125.0, 121.4, 119.3, 118.7, 108.6,
100.0, 32.0, 19.8; IR (KBr): ν (cm-1) 1487, 1330, 1257, 1229, 1081, 805, 741; HRMS (APCI)
[M+H]+: m/z calcd for C16H16NS: 254.0998, found: 254.0996.
1-Methyl-3-(phenylthio)-1H-indole (3db). Yellow solid; m.p. 74-75 oC; 1H NMR (300 MHz,
CDCl3):  7.52 (d, J = 7.5 Hz, 1H), 7.28-7.20 (m, 3H), 7.06-7.01 (m, 5H), 6.94 (d, J = 6.0 Hz, 1H),
3.69 (s, 3H); 13C NMR (75 MHz, CDCl3):  138.6, 136.5, 134.0, 128.7, 127.6, 124.6, 123.6, 121.5,
119.5, 118.6, 108.7, 99.3, 32.0; IR (KBr): ν (cm-1) 1581, 1505, 1481, 1436, 1336, 1260, 1242, 738;
HRMS (APCI) [M + H] +: m/z calcd for C15H14NS: 240.0841, found: 240.0833.
o
1
3-((4-Chlorophenyl)thio)-1-methyl-1H-indole (3dc). Yellow solid; m.p. 115-116 C; H
NMR (300 MHz, CDCl3):  7.57 (d, J = 7.6 Hz, 1H), 7.41-7.25 (m, 3H), 7.19-7.09 (m, 3H), 7.00
(d, J = 8.2 Hz, 2H), 3.85 (s, 3H); 13C NMR (125 MHz, CDCl3):  137.2, 136.5, 134.0, 129.3,
128.4, 127.6, 125.9, 121.6, 119.6, 118.5, 108.8, 98.9, 32.1; IR (KBr): ν (cm-1) 1508, 1475, 1369,
1242, 1008, 811, 747; HRMS (APCI) [M+H]+: m/z calcd for C15H13ClNS: 274.0452, found:
274.0460.
1
5-Methoxy-3-(p-tolylthio)-1H-indole (3ea).[5f] Yellow oil; H NMR (300 MHz, CDCl3): 
8.31 (s, 1H), 7.39 (d, J = 2.6 Hz, 1H), 7.27 (d, J = 8.8 Hz, 1H), 7.05-6.95 (m, 5H), 6.89 (m, 1H),
3.77 (s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz, CDCl3):  155.5, 136.0, 135.0, 131.8, 131.6,
This article is protected by copyright. All rights reserved.

130.4, 129.9, 126.4, 113.9, 112.8, 103.1, 101.2, 56.2, 21.3; IR (KBr): ν (cm-1) 3415, 1484, 1288,
1204, 1169, 1030, 920, 806; HRMS (APCI) [M+H]+: m/z calcd for C16H16NOS: 270.0947, found:
270.0938.
o
1
5-Methoxy-3-(phenylthio)-1H-indole (3eb).[3e] Yellow solid; m.p. 76-78 C; H NMR (300
MHz, CDCl3):  8.35 (s, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.18-7.04 (m, 6H),
6.91 (m, 1H), 3.77 (s, 3H); 13C NMR (125 MHz, CDCl3):  155.5, 139.8, 131.8, 130.4, 129.1,
126.0, 125.1, 114.0, 112.9, 102.5, 101.2, 56.2; IR (KBr): ν (cm-1) 3411, 1623, 1575, 1473, 1436,
1281, 1201, 1168, 1032, 737; HRMS (APCI) [M+H]+: m/z calcd for C15H14NOS: 256.0791, found:
256.0785.
o
1
3-((4-Chlorophenyl)thio)-5-methoxy-1H-indole (3ec).[5f] White solid; m.p. 81-82 C; H
NMR (300 MHz, CDCl3):  8.41 (s, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 1H),
7.13-7.10 (m, 2H), 7.01-6.98 (m, 3H), 6.92 (m, 1H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3): 
155.6, 138.3, 131.8, 130.9, 130.1, 129.2, 127.3, 114.1, 113.0, 102.1, 101.1, 56.2; IR (KBr): ν (cm-1)
3357, 1472, 1278, 1207, 1158, 1087, 803; HRMS (APCI) [M+H]+: m/z calcd for C15H13ClNOS:
290.0401, found: 290.0394.
o
1
5-Fluoro-3-(p-tolylthio)-1H-indole (3fa).[8d] White solid; m.p. 129-130 C; H NMR (500
MHz, CDCl3):  8.39 (s, 1H), 7.51 (t, J = 2.6 Hz, 1H), 7.34 (m, 1H), 7.25-7.24 (m, 1H), 7.03-6.98
(m, 5H), 2.26 (s, 3H); 13C NMR (125 MHz, d6-DMSO):  158.5 (JF-C = 232.4 Hz), 135.9, 135.2,
135.0, 134.2, 130.4, 130.2 (JF-C = 9.9 Hz), 126.6, 114.5 (JF-C = 9.6 Hz), 111.2 (JF-C = 26.0 Hz),
103.8 (JF-C = 23.6 Hz), 101.2 (JF-C = 4.5 Hz), 21.2; IR (KBr): ν (cm-1) 3419, 1484, 1261, 1157,
1088, 1026, 802; HRMS (APCI) [M+H]+: m/z calcd for C15H13FNS: 258.0747, found: 258.0745.
o
1
5-Fluoro-3-(phenylthio)-1H-indole (3fb).[3b] White solid; m.p. 112-113 C; H NMR (300
MHz, CDCl3):  8.40 (s, 1H), 7.52 (d, J = 2.5 Hz, 1H), 7.35 (m, 1H), 7.27-7.23 (m, 1H), 7.20-7.15
(m, 2H), 7.10-6.97 (m, 4H); 13C NMR (125 MHz, d6-DMSO): . 158.6 (JF-C = 232.6 Hz), 139.7,
135.3, 134.2, 130.3 (JF-C = 9.9 Hz), 129.8, 126.7, 125.8, 114.5 (JF-C = 9.7 Hz), 111.3 (JF-C = 25.9
Hz), 103.8 (JF-C = 23.7 Hz), 100.4 (JF-C = 4.5 Hz); IR (KBr): ν (cm-1) 3415, 1573, 1484, 1449,
1262, 1155, 1023, 813, 734; HRMS (APCI) [M+H]+: m/z calcd for C14H11FNS: 244.0591, found:
244.0593.
3-((4-Chlorophenyl)thio)-5-fluoro-1H-indole (3fc). White solid; m.p. 124-126 oC; 1H NMR
(300 MHz, CDCl3):  8.44 (s, 1H), 7.53 (d, J = 2.6 Hz, 1H), 7.37 (m, 1H), 7.21 (m, 1H), 7.15-7.12
This article is protected by copyright. All rights reserved.

(m, 2H), 7.05-6.98 (m, 3H); 13C NMR (125 MHz,d6-DMSO):  158.6 (JF-C = 232.8 Hz), 138.9,
135.5, 134.2, 130.4, 130.0 (JF-C = 9.9 Hz), 129.7, 127.8, 114.6 (JF-C = 9.6 Hz), 114.4 (JF-C = 25.9
Hz), 103.7 (JF-C = 23.7 Hz), 99.9 (JF-C = 16.9 Hz); IR (KBr): ν (cm-1) 3422, 1485, 1475, 1264,
1161, 1090, 1026, 865, 806; HRMS (APCI) [M+H]+: m/z calcd for C14H10ClFNS: 278.0201,
found: 278.0195.
Ethyl 3-(p-tolylthio)-1H-indole-2-carboxylate (3ga). White solid; mp 116-117 oC; 1H NMR
(500 MHz, CDCl3):  9.50 (s, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.33 (t, J =
7.5 Hz, 1H), 7.13-7.10 (m, 3H), 6.98 (d, J = 8.0 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 2.25 (s, 3H),
1.33 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3):  162.0, 136.3, 135.7, 134.5, 130.4, 129.9,
128.9, 128.3, 126.4, 122.2, 121.7, 112.5, 111.8, 61.9, 21.4, 14.7; IR (KBr): ν (cm-1) 3314, 1677,
1505, 1490, 1329, 1253, 812, 744; HRMS (APCI) [M+H]+: m/z calcd for C18H18NO2S: 312.1053,
found: 312.1058.
o
1
Ethyl 3-(phenylthio)-1H-indole-2-carboxylate (3gb). White solid; mp 113-114 C; H
NMR (500 MHz, CDCl3):  9.54 (s, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.34 (t,
J = 7.2 Hz, 1H), 7.17-7.15 (m, 4H), 7.14-7.12 (m, 1H), 7.09-7.06 (m, 1H), 4.40 (q, J = 7.1 Hz, 2H),
1.30 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3):  161.9, 138.4, 136.3, 130.5, 129.2, 129.1,
127.6, 126.5, 125.7, 122.1, 121.9, 112.6, 110.9, 61.9, 14.6; IR (KBr): ν (cm-1) 3316, 1674, 1508,
1493, 1331, 1261, 807, 742; HRMS (APCI) [M+H]+: m/z calcd for C17H16NO2S: 298.0896, found:
298.0893.
Ethyl 3-((4-chlorophenyl)thio)-1H-indole-2-carboxylate (3gc). White solid; mp 134-135
oC; 1H NMR (500 MHz, CDCl3):  9.47 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H),
7.38-7.35 (m, 1H), 7.18-7.12 (m, 3H), 7.09-7.06 (m, 2H), 4.40 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.1
Hz, 3H); 13C NMR (125 MHz, CDCl3):  161.6, 137.0, 136.2, 131.5, 130.3, 129.3, 129.2, 128.8,
126.7, 122.1, 121.9, 112.6, 110.2, 61.9, 14.6; IR (KBr): ν (cm-1) 3298, 1682, 1511, 1476, 1333,
1257, 809, 749; HRMS (APCI) [M+H]+: m/z calcd for C17H15ClNO2S: 332.0507, found:
332.0510.
o
1
Methyl 3-(p-tolylthio)-1H-indole-5-carboxylate (3ha). White solid; mp 166-167 C; H
NMR (500 MHz, CDCl3):  8.73 (s, 1H), 8.40 (s, 1H), 7.98-7.96 (m, 1H), 7.53 (d, J = 2.5 Hz, 1H),
7.44 (d, J = 8.6 Hz, 1H), 7.04-6.98 (m, 4H), 3.90 (s, 3H), 2.25 (s, 3H); 13C NMR (125 MHz,
CDCl3):  168.4, 139.5, 135.5, 135.4, 132.3, 130.0, 129.3, 126.8, 124.8, 123.4, 122.9, 111.8, 105.8,
This article is protected by copyright. All rights reserved.

52.4, 21.3; IR (KBr): ν (cm-1) 3285, 1692, 1612, 1292, 1209, 804, 744; HRMS (APCI) [M+H]+:
m/z calcd for C17H16NO2S: 298.0896, found: 298.0891.
o
1
1-(3-(p-Tolylthio)-1H-indol-5-yl)ethanone (3ia). White solid; mp 144-145 C; H NMR
(500 MHz, CDCl3):  9.06 (s, 1H), 8.25 (s, 1H), 7.94-7.92 (m, 1H), 7.54 (d, J = 2.5 Hz, 1H), 7.46
(d, J = 8.6 Hz, 1H), 7.05-6.98 (m, 4H), 2.62 (s, 3H), 2.25 (s, 3H); 13C NMR (125 MHz, CDCl3): 
199.2, 139.7, 135.5, 135.3, 132.5, 131.1, 130.0, 129.2, 127.0, 123.4, 122.3, 112.2, 106.1, 27.1,
21.3; IR (KBr): ν (cm-1) 3258, 1660, 1612, 1358, 1277, 907, 801; HRMS (APCI) [M+H]+: m/z
calcd for C17H16NOS: 282.0947, found: 282.0948.
o
1
3-(p-Tolylthio)-1H-indole-2-carboxamide (3ja). White solid; mp 102-103 C; H NMR
(500 MHz, CDCl3):  10.45 (s, 1H), 8.29 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.3 Hz,
1H), 7.35-7.32 (m, 1H), 7.18-7.15 (m, 1H), 7.03-6.99 (m, 4H), 6.26 (s, 1H), 2.25 (s, 3H); 13C
NMR (125 MHz, CDCl3):  163.3, 136.4, 135.9, 132.9, 132.7, 130.6, 130.3, 127.1, 126.0, 122.1,
121.3, 113.0, 104.3, 21.3; IR (KBr): ν (cm-1) 3182, 1647, 1564, 1486, 1348, 799, 744; HRMS
(APCI) [M+H]+: m/z calcd for C16H15 N2OS: 283.0900, found: 283.0904.
o
1
3-methyl-2-(p-tolylthio)-1H-indole (3ka). white solid; m.p. 79-81 C; H NMR (300 MHz,
CDCl3):  7.93 (s, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.29-7.20 (m, 2H), 7.17-7.11 (m, 1H), 7.04-6.97
(m, 4H), 2.40 (s, 3H), 2.27 (s, 3H); 13C NMR (125 MHz, CDCl3):  136.8, 135.8, 133.2, 129.8,
128.5, 127.1, 123.3, 122.2, 119.5, 119.3, 110.8, 20.9, 9.4; IR (KBr): ν (cm-1) 3380, 1716, 1699,
1683, 1656, 1049, 676; HRMS (ESI) [M+H]+: m/z calcd for C16H16NS: 254.0998, found:
254.1004.
o
1
3-(p-Tolylthio)-1H-pyrrolo[2,3-b]pyridine (3la). White solid; mp 151-152 C; H NMR
(500 MHz, CDCl3):  12.48 (s, 1H), 8.40 (d, J = 4.3 Hz, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.70 (s,
1H), 7.15-7.12 (m, 1H), 7.04-6.70 (m, 4H), 2.25 (s, 3H); 13C NMR (125 MHz, CDCl3):  149.7,
143.4, 135.5, 135.4, 132.3, 130.0, 129.0, 126.9, 122.7, 117.1, 102.3, 21.3; IR (KBr): ν (cm-1) 3127,
1493, 1407, 1271, 797, 764, 512; HRMS (APCI) [M+H]+: m/z calcd for C14H13N2S: 241.0794,
found: 241.0795
2-(p-Tolylthio)-1H-pyrrole (3ma). colorless oil; 1H NMR (500 MHz, CDCl3):  8.38 (s, 1H),
7.06-7.05 (m, 2H), 7.02-7.00 (m, 2H), 6.98-6.97 (m, 1H), 6.84-6.82 (m, 1H), 6.31-6.30 (m, 1H),
2.26 (s, 3H); 13C NMR (125 MHz, CDCl3):  137.1, 134.9, 129.8, 126.6, 124.1, 119.7, 114.8,
110.0, 21.2; IR (KBr): ν (cm-1) 3419, 1486, 1041, 927, 806; HRMS (APCI) [M+H]+: m/z calcd for
This article is protected by copyright. All rights reserved.

C11H12NS: 190.0685, found: 190.0686.
General procedure for the synthesis of 2,3-bis-sulfenylated indoles 4
A Schlenk flask equipped with a condenser was charged with 0.25 mmol of indole, 0.625
mmol of sodium sulfinate, 0.625 mmol (159 mg) of I2, 1.25 mmol (327 mg) of PPh3 and 2 mL of
water under argon atmosphere. The reaction mixture was stirred at refluxing temperature until
complete consumption of starting material 1 (monitored by TLC) and then cooled to room
temperature. The reaction was then quenched with saturated Na2S2O3 (5 mL) and extracted with
ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4. After filtration
and removal of the solvent in vacuo, the crude product was purified by flash column
chromatography on silica gel (ethyl acetate/petroleum ether = 1/10) to give product 4.
1
2,3-Bis-(p-tolylthio)-1H-indole (4a).[5e] Yellow oil; H NMR (300 MHz, CDCl3):  8.23 (s,
1H), 7.57 (d, J = 7.7 Hz, 1H), 7.29-7.18 (m, 4H), 7.15-7.02 (m, 5H), 6.96 (d, J = 7.9 Hz, 2H), 2.31
(s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz, CDCl3):  138.2, 137.1, 135.3, 135.0, 134.9, 131.2,
130.6, 130.5, 130.4, 129.9, 127.3, 123.9, 121.5, 120.1, 111.3, 108.7, 21.5, 21.3; IR (KBr): ν (cm-1)
3392, 1490, 1442, 1393, 1337, 1332, 1229, 1084, 1013, 804, 742; HRMS (APCI) [M+H]+: m/z
calcd for C22H20NS2: 362.1032, found: 362.1040.
o
1
2,3-Bis-(phenylthio)-1H-indole (4b).[5e] White solid; m.p. 85-86 C; H NMR (300 MHz,
CDCl3):  8.37 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.35-7.21 (m, 7H), 7.18-7.06 (m, 6H); 13C NMR
(125 MHz, CDCl3):  138.5, 137.3, 134.9, 134.0, 130.4, 130.1, 129.8, 129.2, 127.7, 127.0, 125.6,
124.3, 121.7, 120.4, 111.7, 109.6; IR (KBr): ν (cm-1) 3384, 1580, 1480, 1442, 1227, 1083, 1019,
751; HRMS (APCI) [M+H]+: m/z calcd for C20H16NS2: 334.0719, found: 334.0718.
o
1
2,3-Bis-((4-chlorophenyl)thio)-1H-indole (4c). Yellow solid; m.p. 68-69 C; H NMR (300
MHz, CDCl3):  8.45 (s, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.36-7.24 (m, 2H), 7.19-7.07 (m, 7H), 6.98
(d, J = 8.5 Hz,2H); 13C NMR (125 MHz, CDCl3):  137.3, 136.9, 133.8, 133.3, 133.2, 131.5,
131.1, 130.1, 129.9, 129.2, 128.3, 124.7, 122.0, 120.3, 111.8, 109.9; IR (KBr): ν (cm-1) 3407, 1473,
1437, 1390, 1339, 1226, 1089, 1006, 811, 741; HRMS (APCI) [M+H]+: m/z calcd for
C20H14Cl2NS2: 401.9939, found: 401.9942.
5-Fluoro-2,3-bis-(p-tolylthio)-1H-indole (4d). White solid; m.p. 128-130 oC; 1H NMR (300
MHz, CDCl3):  8.14 (s, 1H), 7.28-7.25 (m, 2H), 7.22-7.19 (m, 2H), 7.11 (d, J = 7.9 Hz, 2H),
This article is protected by copyright. All rights reserved.

7.04-6.90 (m,5H), 2.33 (s, 3H), 2.26 (s, 3H); 13C NMR (125 MHz, d6-DMSO):  158.6 (JF-C
=
233.7 Hz), 137.5, 136.3, 135.6, 134.8, 134.7, 131.8, 130.9, 130.6 (JF-C = 9.9 Hz), 130.5, 129.3,
127.3, 114.3 (JF-C = 9.5 Hz), 112.5 (JF-C = 26 Hz), 108.2 (JF-C = 4.6 Hz), 104.2 (JF-C = 23.6 Hz),
21.4, 21.3; IR (KBr): ν (cm-1) 3442, 1489, 1433, 1259, 1100, 1024, 800; HRMS (APCI) [M+H]+:
m/z calcd for C22H19FNS2: 380.0937, found: 380.0931.
o
1
5-Fluoro-2,3-bis-(phenylthio)-1H-indole (4e). White solid; m.p. 99-100 C; H NMR (300
MHz, CDCl3):  8.34 (s, 1H), 7.29-7.28 (m, 4H), 7.25-7.19 (m, 3H), 7.17-7.05 (m, 5H), 7.02-6.95
(m, 1H); 13C NMR (125 MHz, CDCl3):  159.1 (JF-C = 236.4 Hz), 138.0, 136.4, 134.0, 133.6,
131.3 (JF-C = 10.0 Hz), 130.7, 129.9, 129.2, 128.1, 127.0, 125.7, 112.7 (JF-C = 26.4 Hz), 112.4 (JF-C
= 9.3 Hz), 108.9 (JF-C = 4.7 Hz), 105.2 (JF-C = 23.8 Hz); IR (KBr): ν (cm-1) 3381, 1581, 1490,
1474, 1435, 1278, 1156, 846, 803, 739; HRMS (APCI) [M+H]+: m/z calcd for C20H15FNS2:
352.0624, found: 352.0626.
o
1
2,3-Bis-((4-chlorophenyl) thio)-5-fluoro-1H-indole (4f). White solid; m.p. 157-158 C; H
NMR (500 MHz, CDCl3):  8.42 (s, 1H), 7.28 (m, 1H), 7.23-7.17 (m, 5H), 7.12-7.11 (m, 2H),
7.04-7.00 (m, 1H), 6.98-6.96 (m, 2H); 13C NMR (125 MHz,d6-DMSO):  158.5 (JF-C = 234.6 Hz),
137.5, 135.3, 134.9, 134.6, 132.5, 130.8, 130.7, 130.5 (JF-C = 10.0 Hz), 130.2, 129.7, 128.3, 114.7
(JF-C = 9.4 Hz), 113.1 (JF-C = 26.2 Hz), 107.7 (JF-C = 4.6 Hz) 158.5 (JF-C = 23.9 Hz); IR (KBr): ν
(cm-1) 3431, 1556, 1475, 1259, 1087, 1026, 803; HRMS (APCI) [M+H]+: m/z calcd for
C20H13Cl2FNS2: 419.9845, found: 419.9852.
o
1
5-Methoxy-2, 3-bis-(p-tolylthio)-1H-indole (4g). White solid; m.p. 142-143 C; H NMR
(300 MHz, CDCl3):  8.16 (s, 1H), 7.25-7.16 (m, 3H), 7.08-6.95 (m, 7H), 6.86 (m, 1H), 3.78 (s,
3H), 2.30 (s, 3H), 2.25 (s, 3H); 13C NMR (125 MHz, d6-DMSO):  155.3, 137.1, 135.4, 135.2,
133.9, 133.2, 132.7, 130.8, 130.5, 130.4, 129.3, 129.0, 114.6, 113.9, 107.9, 100.8, 56.1, 21.3, 21.2;
IR (KBr): ν (cm-1) 3396, 1624, 1488, 1421, 1284, 1208, 1172, 1014, 806; HRMS (APCI) [M+H]+:
m/z calcd for C23H22NOS2: 392.1137, found: 392.1133.
5-Methoxy-2, 3-bis-(phenylthio)-1H-indole (4h). White solid; m.p. 91-92 oC; 1H NMR (300
MHz, CDCl3):  8.40 (s, 1H), 7.18-7.15 (m, 5H), 7.13-7.07 (m, 5H), 7.04-7.00 (m, 2H), 6.87 (m,
1H), 3.73 (s, 3H); 13C NMR (125 MHz, CDCl3):  155.6, 138.6, 135.1, 134.2, 132.4, 131.2, 129.8,
129.7, 129.2, 127.5, 126.8, 125.5, 115.0, 112.7, 109.0, 101.4, 56.2; IR (KBr): ν (cm-1) 3373, 1623,
1580, 1487, 1425, 1281, 1205, 798; HRMS (APCI) [M+H]+: m/z calcd for C21H18NOS2: 364.0824,
This article is protected by copyright. All rights reserved.

found: 364.0818.
o
2,3-Bis-((4-chlorophenyl) thio)-5-methoxy-1H-indole (4i). White solid; m.p. 134-135 C;
1H NMR (300 MHz, CDCl3):  8.38 (s, 1H), 7.27-7.22 (m, 1H), 7.19-7.06 (m, 6H), 6.98-6.92 (m,
4H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3):  155.9, 136.9, 133.7, 133.5, 133.4, 132.2, 131.3,
131.1, 130.9, 129.8, 129.2, 128.0, 115.5, 112.7, 109.2, 101.1, 56.2; IR (KBr): ν (cm-1) 3307, 1633,
1579, 1474, 1425, 1289, 1165, 1087, 802; HRMS (APCI) [M+H]+: m/z calcd for C21H16Cl2NOS2:
432.0045, found: 432.0041.
1-Methyl-2,3-bis(p-tolylthio)-1H-indole (4j). Yellow oil; 1H NMR (300 MHz, CDCl3): 
7.65 (d, J = 7.4 Hz, 1H), 7.30-7.30 (m, 2H), 7.15 (t, J = 6.8 Hz, 1H), 7.02-6.91 (m, 8H), 3.75 (s,
3H), 2.23 (s, 3H), 2.22 (s, 3H); 13C NMR (75 MHz, CDCl3):  138.5, 136.3, 135.0, 134.9, 134.8,
132.3, 130.0, 129.5, 129.3, 128.0, 127.1, 123.9, 121.0, 120.4, 111.4, 110.2, 31.2, 21.1, 21.0; IR
(KBr): ν (cm-1) 1490, 1445, 1326, 1220, 1087, 1011, 805, 744; HRMS (APCI) [M+H]+: m/z calcd
for C23H22NS2: 376.1188, found: 376.1185.
o
1
1-Methyl-2,3-bis(phenylthio)-1H-indole (4k). White solid; m.p. 80-81 C; H NMR (300
MHz, CDCl3):  7.58 (d, J = 7.6 Hz, 1H), 7.31-7.22 (m, 2H), 7.09-7.01 (m, 8H), 6.96-6.94 (m,
3H), 3.69(s, 3H); 13C NMR (75 MHz, CDCl3):  137.4, 134.8, 133.2, 128.1, 127.6, 126.3, 125.5,
125.1, 123.9, 122.9, 120.0, 119.3, 110.0, 109.2, 30.1; IR (KBr): ν (cm-1) 1584, 1472, 1451, 1326,
1226, 1154, 744, 684; HRMS (APCI) [M+H]+: m/z calcd for C21H18NS2: 348.0875, found:
348.0871.
o
1
2,3-Bis((4-chlorophenyl)thio)-1-methyl-1H-indole (4l). White solid; m.p. 80-81 C; H
NMR (300 MHz, CDCl3):  7.56 (d, J = 7.5 Hz, 1H), 7.31-7.28 (m, 2H), 7.15-7.11 (m, 1H),
7.06-6.98 (m, 4H), 6.91-6.85 (m, 4H), 3.72 (s, 3H); 13C NMR (75 MHz, CDCl3):  138.5, 136.9,
134.2, 133.9, 132.4, 131.0, 129.4, 129.0, 128.8, 128.7, 127.9, 124.4, 121.4, 120.2, 110.8, 110.4,
31.2; IR (KBr): ν (cm-1) 1475, 1333, 1232, 1081, 999, 808, 732; HRMS (APCI) [M+H]+: m/z
calcd for C21H16Cl2NS2: 416.0096, found: 416.0094.
Methyl 2,3-bis(p-tolylthio)-1H-indole-5-carboxylate (4m). White solid; mp 172-173 oC; 1H
NMR (500 MHz, CDCl3):  8.38 (s, 1H), 8.33 (t, J = 0.75 Hz, 1H), 7.91-7.89 (m, 1H), 7.28-7.26
(m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 7.05-7.03 (m, 2H), 6.98 (d, J = 8.1 Hz, 2H), 3.88 (s, 3H), 2.33 (s,
3H), 2.25 (s, 3H); 13C NMR (125 MHz, CDCl3):  168.0, 139.5, 138.8, 137.8, 135.5, 134.5, 132.0,
130.7, 130.3, 129.9, 129.1, 127.4, 125.0, 123.6, 122.4, 111.0, 108.9, 52.3, 21.4, 21.2; IR (KBr): ν
This article is protected by copyright. All rights reserved.

(cm-1) 3273, 1689, 1490, 1440, 1291, 1246, 976, 807; HRMS (APCI) [M+H]+: m/z calcd for
C24H22NO2S2: 420.1086, found: 420.1081.
Acknowledgements
The authors are grateful to the National Natural Science Foundation of China (No.
20772001) and The Natural Science Foundation of the Higher Education Institutions
of Anhui Province (KJ2018A0222) for financial support of this work.
Supporting Information
The supporting information for this article is available on the WWW under
https://
References
[1] For selected reviews, see: (a) Feng, M. H,; Tang, B. Q.; Liang, S.; Jiang, X. F. Curr. Top. Med.
Chem. 2016, 16, 1200-1216. (b) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111,
1596-1636. (c) Boyd, D. A. Angew. Chem., Int. Ed. 2016, 55, 15486-15502. (d) Hartwig, J. F.
Acc. Chem. Res. 2008, 41, 1534-1544.
[2] (a) Golzar, N.; Nowrouzi, N.; Abbasi, M.; Mehranpour, A. M. New J. Chem. 2017, 41,
11921-11925. (b) He, L.; Li, X. W. Tetrahedron 2017, 73, 6138-6145. (c) Nuth, M.; Guan, H.;
Zhukovskaya, N.; Saw, Y. L.; Ricciardi, R. P. J. Med. Chem. 2013, 56, 3235-3246. (d) Cianchi,
F.; Cortesini, C.; Magnelli, L.; Fanti, E.; Papucci, L.; Schiavone, N.; Messerini, L.; Vannacci,
A.; Capaccioli, S.; Perna, F.; Lulli, M.; Fabbroni, V.; Perigli, G.; Bechi, P.; Masini, E. Mol.
Cancer Ther. 2006, 5, 2716-2726; (e) 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, 3172-3184; (f) Brancale, A.;
Silvestri, R. Med. Res. Rev. 2007, 27, 209-238.
[3] (a) La Regina, G.; Gatti, V.; Famiglini, V.; Piscitelli, F.; Silvestri, R. ACS, Comb. Sci. 2012, 14,
258-262. (b) Sang, P.; Chen, Z. K.; Zou, J. W.; Zhang, Y. H. Green Chem. 2013, 15, 2096-2100.
(c) Azeredo, J. B.; Godoi, M.; Martins, G. M.; Silveira, C. C.; Braga, A. L. J. Org. Chem. 2014,
This article is protected by copyright. All rights reserved.

79, 4125-4130. (d) Prasad, C. D.; Kumar, S.; Sattar, M.; Adhikary, A.; Kumar, S. Org. Biomol.
Chem. 2013, 11, 8036-8040; (e) Ge, W. L.; Wei, Y. Y. Green Chem. 2012, 14, 2066-2070.
[4] (a) Chen, Y.; Cho, C. H.; Larock, R. C. Org. Lett. 2009, 11, 173-176. (b) Hamel, P. J. Org.
Chem., 2002, 67, 2854-2858. (c) Hamel, P.; Préville, P. J. Org. Chem. 1996, 61, 1573-1577.
[5] (a) Guo, W.; Tan, W.; Zhao, M. M.; Tao, K. L.; Zheng, L. Y.; Wu, Y. Q.; Chen, D. L.; Fan, X. L.
RSC Adv. 2017, 7, 37739-37742. (b) Saima; Equbal, D.; Lavekar, A. G.; Sinha, A. K. Org.
Biomol. Chem. 2016, 14, 6111-6118. (c) Liu, X. X.; Cui, H. H.; Yang, D. S.; Dai, S. C.; Zhang,
G. Q.; Wei, W.; Wang, H. Catal Lett. 2016, 146, 1743-1748; (d) Yi, S. L.; Li, M. C.; Mo, W.
M.; Hu, X. Q.; Hu, B. X.; Sun, N.; Jin, L. Q.; Shen, Z. L. Tetrahedron Lett. 2016, 57,
1912-1916; (e) Zhang, H. L.; Bao, X. Z.; Song, Y. M.; Qu, J. P.; Wang, B. M. Tetrahedron
2015, 71, 8885-8891. (f) Liu, Y. Y.; Zhang, Y.; Hu, C. F.; Wan, J. P.; Wen, C. P. RSC Adv.
2014, 4, 35528-35530.
[6] (a) Wu, Q.; Zhao, D. B.; Qin, X. R.; Lan, J. B.; You, J. S. Chem. Commun. 2011, 47,
9188-9190; (b) Kumaraswamy, G.; Raju, R.; Narayanarao, V. RSC Adv. 2015, 5, 22718-22723;
(c) Chen, M.; Huang, Z. T.; Zheng, Q. Y. Chem. Commun. 2012, 48, 11686-11688.
[7] (a) Lin, Y. M.; Yi, W. B. Chin. J. Org. Chem. 2018, 38, 1207-1213. (b) Tang, Q. J.; Xie, P.;
Wang, J.; Lin, J. J.; Feng, C. L.; Pittman Jr., C. U.; Zhou, A. H. Tetrahedron 2017, 73,
5436-5443. (c) Li, W. Y.; Yin, G. X.; Huang, L.; Xiao, Y.; Fu, Z. M.; Xin, X.; Liu, F.; Li, Z. Z.;
He, W. M. Green Chem. 2016, 18, 4879-4883. (d) Yang, Y.; Li, W. M.; Xia, C. C.; Ying, B. B.;
Shen, C.; Zhang, P. F. ChemCatChem. 2016, 8, 304-307. (e) Katrun, P.; Mueangkaew, C.;
Pohmakotr, M.; Reutrakul, V.; Jaipetch, T.; Soorukram, D.; Kuhakarn, C. J. Org. Chem. 2014,
79, 1778-1785. (f) Ding, Y. C.; Wu, W.; Zhao, W. N.; Li, Y. W.; Xie, P.; Huang, Y. Q.; Liu,
Y.; Zhou, A. H. Org. Biomol. Chem. 2016, 14, 1428-1431. (g) Huang, X. H.; Wang, S. C.; Li,
B. W.; Wang, X.; Ge, Z. M.; Li, R. T. RSC Adv. 2015, 5, 22654-22657. (h) Xiao, F. H.; Chen,
H.; Xie, H.; Chen, S. Q.; Yang, L.; Deng, G. J. Org. Lett. 2014, 16, 50-53.
[8] (a) Rahaman, R.; Barman, P. Eur J. Org. Chem. 2017, 6327-6334. (b) Ge, X.; Sun, F. L.; Liu,
X. M.; Chen, X. Z.; Qian, C.; Zhou, S. D. New J. Chem. 2017, 41, 13175-13180. (c) Xiao, F.
H.; Xie, H.; Liu, S. W.; Deng, G. J. Adv. Synth. Catal. 2014, 356, 364-368. (d) Katrun, P.;
Hongthong, S.; Hlekhlai, S.; Pohmakotr, M.; Reutrakul, V.; Soorukram, D.; Jaipetch, T.;
Kuhakarn, C. RSC Adv. 2014, 4, 18933-18938. (e) Rao, H. H.; Wang, P.; Wang, J. C.; Li, Z. F.;
This article is protected by copyright. All rights reserved.

Sun, X. Z.; Cao, S. L. RSC Adv. 2014, 4, 49165-49169.
[9] For recent representative examples, see: (a) Kitanosono, T.; Masuda, K.; Xu, P. Y.; Kabayashi,
S. Chem. Rev. 2018, 118, 679-746. (b) Zhou, Z.; Duan, J. F.; Mu, X. J.; Xiao, S. Y. Chin. J.
Org. Chem. 2018, 38, 585-593 (in chinese). (c) Wu, C.; Yang, P. P.; Fu, Z. M.; Peng, Y.;
Wang, X.; Zhang, Z. Z.; Liu, F.; Li, W. Y.; Li, Z. Z.; He, W. M. J. Org. Chem. 2016, 81,
10664-10671. (d) Vamisetti, G. B.; Chowdhury, R.; Kumar, M.; Ghosh, S. K. Org. Lett., 2016,
18, 1964-1967. (e) Li, W. Y.; Yin, G. X.; Huang, L.; Xiao, Y.; Fu, Z. M.; Xin, X.; Liu, F.; Li,
Z. Z.; He, X. W. Green Chem. 2016, 18, 4879-4883. (f) Pan, X. J.; Gao, J.; Liu, J.; Lai, J. Y.;
Jiang, H. F.; Yuan, G. Q. Green Chem. 2015, 17, 1400-1403.
[10] 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, 3172-3184.
This article is protected by copyright. All rights reserved.

Metal free mono- and 2,3-bis-sulfenylation of indoles in water
with sodium sulfinates as a sulfur source
Changqing Liu, Jian Fan, Manyi Wu, Jiahui Chen, Yiming Zhao, Meihua Xie*
An iodine-PPh3 mediated sulfenylation of indoles in water with stable and odorless sodium
sulfinates as the sulfur source is described. The reaction could afford monosulfenylated indoles in
moderate to excellent yields under metal free conditions. Moreover, double C-H sulfenylation of
indoles at 2- and 3-positions has also been achieved by using excess sodium sulfinates under the
optimized reaction conditions.
This article is protected by copyright. All rights reserved.