Iodine-Catalyzed Mono- and Disulfenylation of Indoles in PEG400 through a Facile Microwave-Assisted Process

Article abstract of DOI:10.1002/ejoc.201701293

An iodine-catalyzed versatile and green method for the synthesis of mono- and 2,3-disulfenylindoles was developed. Various indoles reacted with sodium alkyl- and arylsulfinates by using hydrogen peroxide as the oxidizing agent in PEG₄₀₀ under microwave conditions. This simple method enabled the rapid synthesis of mono- and 2,3-disulfenylindoles in good to excellent yields under metal-free conditions. Furthermore, this protocol is environmentally friendly, odorless, and operationally easy and can be performed within short reaction times under mild reaction conditions with excellent functional-group tolerance.

Full text of DOI:10.1002/ejoc.201701293

A Journal of
Accepted Article
Title: Iodine-Catalyzed Mono- and Bis-Sulfenylation of Indoles in
PEG400 via a facile Microwave-Assisted Process
Authors: Rajjakfur Rahaman and Pranjit Barman
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701293
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701293
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
Iodine-Catalyzed Mono- and Bis-Sulfenylation of Indoles in
PEG400 via a facile Microwave-Assisted Process
[
a]
[a]
Rajjakfur Rahaman and Pranjit Barman *
OCH3
OCH3
Abstract: An iodine-catalyzed versatile green method for the
synthesis of mono- and 2,3-bis-sulfenyl indoles has been presented.
Various indoles can react with alkyl or aryl sodium sulfinates using
hydrogen peroxide as an oxidizing agent in PEG400 under microwave
conditions. This simple method enabled the rapid synthesis of mono-
and 2,3-bis-sulfenylindoles with good to excellent yields under metal
free conditions. The notable features of this protocol include
environmental friendliness, odorless and short reaction time, easy
operation, mild reaction conditions and excellent functional group
tolerance.
S
S
H3CO
OCH3
CO2CH3
Cl
CONH2
N
N
H
H
1
2
Cl
O
Cl
Cl
Cl
Me
NH
S
H
S
Cl
N
S
O
S
O
O
Me
O
N
OH
N
H
Introduction
O
3
4
The sulfur bearing indoles represent a class of very important
organosulfur heterocyclic compounds as they are present in
many biologically and pharmaceutically important molecules.1
According to known results, 3-sulfenylindoles have attracted
researchers considerably because of their greater therapeutic
value in the treatment of several diseases (Figure 1), such as
Figure 1. Some biologically active 3-arylthioindoles.
Although numerous methods have been successfully
demonstrated to construct structurally diverse mono-sulfenyl
indoles, double sulfenylation of indole has not been well
documented to date. Moreover, methods that can accomplish
bis-sulfenylation of indoles at 2- and 3-positions have remained
elusive. Earlier, only 3-sulfenylation of indoles was done with the
help of microwave-irradiation.[21] We also reported two protocol
for the synthesis of 3-sulfenylindoles with sulfonyl hydrazides
and sulfinic acids under microwave-irradiation.[22] However, with
the same protocol bis-sulfenylated product was not observed.
cancer (1),[ HIV (2), vascular (3), heart disease, respiratory
2]
[3]
[4]
[5]
disorders (4),[6] bacterial infections and allergies. They have
also inhibitory effect of both tubulin polymerization and of cancer
cells.[9] In the last few decades, a number of significant methods
have been developed for the synthesis of 3-sulfenylindoles.
During the synthetic efforts a variety of thiolating reagents have
[7]
[8]
been used as the reaction partners. For example, sulfenyl
halides,[10] arylsulfonyl chlorides,
[11]
sulfonium salts,[12] quinine
Previously, Hamel et al. first reported the bis-sulfenylation of
indoles using sulfenyl chlorides as sulfur source.
[
13]
N-thioimides,[14] and sulfinic acids,
[15]
[23,10b]
mono-O,S-acetals,
In addition,
thiols,[16] disulfides, sulfonyl hydrazides,[18] sulfinic acid salts,
and bunte salts.[20] Nevertheless, many of these sulfenylating
reagents are either difficult to prepare, toxic, expensive or air
and moisture sensitive. Moreover, the existing methodologies
have some practical limitations such as long reaction time, harsh
reaction conditions, high temperature, excess additives and
transition metal catalysts, suffers from a narrow substrate scope
or yield hazardous by-products.
[17]
[19]
Sangit Kumar and co-workers described persulfate mediated
mono- and bis-sulfenylation of indoles with equivalent amount of
iodine using disulfides as thiolating agent.[17h] Recently, Wang’s
group disclosed the double sulfenylation of indoles using thiols
as sulfenylating agent with excess amount of iodine.[16i] While
these methodologies rely on the harsh reaction conditions with
excess catalyst loading and long reaction time to achieve bis-
sulfenylation, developing new and straightforward methods
enabling selective bis-sulfenylation of indole under milder
conditions is highly desirable. Thiols and disulfides showed
excellent activities in sulfenylation of indoles, but they have
some practical limitations. Thiols are toxic, volatile and foul
smelling, whereas disulfides are expensive and moisture
sensitive. In addition, the main problem of using disulfide as the
thiolating reagent is that disulfide needs to be prepared via
oxidative coupling of thiols; an extra operational step which
causes low atom economy.[24] Therefore, we wanted to explore a
way to attain the desirable requirement of atom economy and
relative safety. So, our aim is to develop a new methodology for
the synthesis of 2,3-bis-sulfenylindoles which avoid limitations of
existing methods (Scheme 1).
[
a]
Department of Chemistry, National Institute of Technology Silchar
Silchar 788010, India
E-mail: barmanpranjit@yahoo.co.in
http://www.nits.ac.in/departments/chem/chem.php
Supporting information for this article is given via a link at the end of
the document.
Recently, sodium arylsulfinates have been widely applied as
the sulfur sources under reduction conditions for the
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European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
construction of C–S bonds.[25] These are stable to air and
moisture, odorless and easy-to-handle sulfur compounds;
notably, the reaction generates environmentally benign by-
products, as expected.
Microwave-assisted organic synthesis (MAOS) has attained
the status of a new and fascinating discipline in the current
green chemistry scenario.[26] Microwave-assisted synthesis has
reduced reaction times dramatically. By reducing unwanted side
reactions compared to conventional heating methods, it has
increase product purities and yields.[27]
Molecular iodine and its salts recently have emerged as a
promising alternative to catalyse oxidative sulfenylation due to
their ease of handling, commercial availability, low toxicity, mild
reaction conditions, high efficiency, and transition metal free
features.[28] Several methodologies have demonstrated
Afterward, we tested the effect of temperature and influence
of the microwave irradiation power in various levels. However, at
60 C and 100 W provided the desired product 3a in 95 % yield.
Increasing the power from 100 to 120 W did not affect the
reaction since the product 3a was obtained in the same yield
(Table 1, entry 7). However, on decreasing the power to 80 W
o
the yield decreased considerably (Table 1, entry 8).
A
o
temperature higher or lower than 60 C was deleterious to the
reaction (Table 1, entries 5 and 6). Moreover, we examined the
reaction under conventional heating in oil bath and at room
temperature giving the desired product 3a only 50 % and 35 %
but required a very long reaction time (Table 1, entries 9 and 10).
Table 1. Optimization of microwave parameters.[a]
S
impressive advancements of
heterocyclic compounds and C−C unsaturated bonds.
I
2
-catalyzed sulfenylation of
SO Na I2 (10 mol %), H O (1.2 equiv)
2
2
2
[
29]
+
diethyl phosphite
N
H
MW, temperature, time
N
Recently, some polymer media such as polyethylene glycol
PEG) are being used as new solvents in organic synthesis.[
H
PEG400
3a
1a
2a
30]
(
o
Yield (%)b)
Entry
MW (W)
T ( C)
Time
min)
PEG400 is a viscous sustainable liquid soluble in water and many
organic solvents. This medium has the advantage of being non-
toxic, nonvolatile, non-irritating, odorless, and neutral and is
used in a variety of pharmaceuticals and medications. In our
effort to benign protocols, we have continuously tried to promote
the use of non-toxic media and transition metal free
(
1
2
3
4
5
6
7
8
9
100
100
100
100
100
100
120
80
60
60
60
60
70
50
60
60
60
r.t.
3
5
8
10
10
10
10
10
24 h
48 h
50
65
80
95
80
70
95
60
[
31]
conditions. Herein, we wish to report a green protocol for the
synthesis of mono- and bis-sulfenylation of indoles with sodium
sulfinates under microwave irradiation (Scheme 1).
c)
-
-
50
d)
10
35
[
a]
Reaction conditions: indole 1a (0.5 mmol), sodium p-toluenesulfinate 2a (0.6
mmol), catalyst (0.05 mmol; 10 mol %), oxidant (0.6 mmol), reagent (1.5
o
[b]
[c]
R2
RSCl
or
RSSR
equiv.), solvent (2 mL), 60 C, 10 min. Isolated yield. Conventional heating
(open vessel). [ Reaction performed without microwave irradiation at room
temperature (closed vessel).
Previous work
+
d]
N
R1
NaH DMF
After that, catalyst loading was screened to improve the yield
of the product. An increase in the mol % of I
about a reasonable rise in the yield to 85 % (Table 2, entry 2).
However, further increase of I concentration did not enhance
the yield of product (Table 2, entry 3). Higher yield was observed
when 2a was employed in slight excess amount (Table 2, entry
4). Different types of iodine containing catalysts including NIS, KI,
and nBu NI were investigated in the model reaction, and found
4
that these catalysts hardly facilitate the reaction (Table 2, entries
12-14). Screening a range of oxidants such as DMSO, tBuOOH,
K S O , and O revealed that H O is more effective than these
2 2 8 2 2 2
2
to 10 brought
R2
S
R
S
I2 (0.5 equiv)
TBHP
R2
I2 (1 equiv)
NH4)2S2O8
N
(
N
2
R1
R2
R1
+
+
MeCN, 60 o
C
MeOH, reflux
N
R1
R
RSH
RSSR
R
S
Present work
S
R3
R2
R
S
I2 (20 mol %)
H2O2 (2.2 equiv)
diethyl phosphite
I2 (10 mol %)
N
R3
R2 H2O2 (1.2 equiv)
diethyl phosphite
R1
R2
R3
N
or
R1
N
R
MW (100 W), 60 o
+
RSO2Na
MW (100 W), 60 o
10 min, PEG400
C
C
R1
10 min, PEG400
R2 = H
R3
S
oxidants (Table 2, entries 8-11). Moreover, there was no product
formation observed in the absence of iodine and diethyl ether
N
R
R1
Scheme 1. Different routes for the synthesis of 2,3-bis-sulfenylation of indoles.
(
Table 2, entries 15 and 17). The best molar ratio of
indole/sodium p-toluenesulfinate was found to be 0.5/0.6 (Table
). Therefore, the standard reaction conditions for the synthesis
of 3-sulfenylindoles were obtained: indole 1a (0.5 equiv.),
2
Results and Discussion
sodium p-toluenesulfinate 2a (0.6 equiv.), I
mol %), diethyl phosphite (1.5 equiv.) in PEG400 (2 mL) at 60 C
and 100 W for 10 min.
2
(0.05 equiv.; 10
At the outset of this study, we employed indole 1a sodium p-
toluenesulfinate 2a as the model substrate in the presence of
hydrogen peroxide, diethyl phosphite as reagent and iodine as
the catalyst in PEG400 (Table 1). When the reaction was carried
out for 3 min, 3a was obtained in only 50 % yield (entry 1). The
reaction was carried out for reaction times of 3, 5, 8, and 10 min.
The reaction delivered the desired product in almost quantitative
yield in 10 min (Table 1, entry 4).
o
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European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
Table 2. Optimization of reaction conditions.[a]
corresponding desired products with high yields without any
difficulties (Scheme 2, 3s). When C3 position occupied by alkyl
groups such as –Me, C2 position of the indole ring becomes the
active reaction site (Scheme 2, 4a).
S
SO2Na
Catalyst, oxidant, reagent
+
N
MW (100 W), 60 oC, 10 min
PEG400
I2 (10 mol %)
H O (1.2 equiv)
2 2
diethyl phophite
N
H
SR
SR
H
1a
2a
3a
R3
R2 + RSO2Na
R3
R2 or R3
R2
N
MW (100 W),
N
R1
N
R1
o
R1
2
60 C, 10 min
Entry
1
1a
/
2a
Catalyst
Reagent
(Equiv)
R1
Oxidant
(Equiv)
Yield
(%)[
65
4a
1
PEG400
3a-r
b]
(
Equiv)
0.5/0.5
I
2
(0.025)
H
2
O
2
(0.6)
S
S
S
Cl
2
3
4
5
6
7
8
0.5/0.5
0.5/0.5
0.5/0.6
0.5/0.6
0.5/0.6
0.5/0.6
0.5/0.6
I
2
(0.05)
(0.1)
R1
R1
R1
R2
R3
R4
R1
H
H
H
H
H
H
2
2
O
O
2
O
O
O
O
2
2
2
2
2
2
(0.6)
(0.6)
(0.6)
(0.6)
(0.6)
(0.6)
85
85
95
0
55
15
75
I
2
N
N
H
N
H
H
I
2
I
2
I
2
I
2
I
2
(0.05)
(0.05)
(0.05)
(0.05)
(0.05)
3
a, 95 %
3b, 94 %
3c, 91 %
2
2
2
O2N
S
Br
S
NO2
S
DMSO
0.6)
tBuOOH
0.6)
(
9
0.5/0.6
0.5/0.6
I
I
I
2
2
2
(0.05)
(0.05)
(0.05)
R1
R1
45
35
N
H
N
H
N
(
H
1
0
2 2 8
K S O
3
d, 92 %
3e, 85 %
3f, 80 %
(
0.6)
1
1
1
1
1
2
3
4
0.5/0.6
0.5/0.6
0.5/0.6
0.5/0.6
R1
R1
R1
R1
O
2
25
55
50
45
NIS (0.05)
KI (0.05)
nBu NI
4
H
H
H
2
2
2
O
O
O
2
2
2
(0.6)
(0.6)
(0.6)
S
S
OMe
S
I
N
H
N
H
(
0.05)
−
(0.05)
N
H
1
1
5
6
0.5/0.6
0.5/0.6
R1
R1
H
2
O
2
(0.6)
−
0
3
g, 96 %
3h, 96 %
3i, 93 %
I
2
trace
S
S
S
[
a]
Reaction conditions: indole 1a, sodium p-toluenesulfinate 2a, catalyst (0.05
O2N
MeO
mmol; 10 mol %), oxidant (0.6 mmol), diethyl phosphite (1.5 equiv.), solvent (2
o
N
H
N
N
H
mL), 100 W, 60 C, 10 min; R1 = (C
2
H
5 2 3
O) POH, R2 = (PhO) P, R3 =
H
[
b]
PhPO(OH)H, R4 = PhPO(OH) .
2
Isolated yield based on 1a.
3
j, 78 %
3k, 75 %
3l, 97 %
S
S
S
After establishing suitable reaction conditions (Table 2,
entry 4), limitations and generality of the proposed method were
investigated as shown in Scheme 2. First, the substrate scope of
sodium sulfinates towards indole (Scheme 2, 3a–3i) was
examined. The electronic nature of the substrates was shown to
have little influence on the reaction efficiency, and sodium
sulfinates with electron-donating and electron-withdrawing
groups were smoothly reacted with the indole to form their
corresponding sulfenylated product in moderate to excellent
yields (Scheme 2). The sodium sulfinates with electron-donating
groups like –Me, –OMe on the phenyl ring gave the desired
products with higher yields than those with electron-withdrawing
Br
N
H
N
H
N
H
3
m, 90 %
3n, 97 %
3o, 95 %
S
S
S
Br
N
N
H
N
H
CH3
3
p, 92 %
3q, 92 %
3r, 95 %
S
N
H
4
a, 96 %
groups (–Cl, –Br, and –NO
electron-withdrawing substituents such as –NO
the desired 3-sulfenylindoles with lower yield (Scheme 2, 3e and
f). To our delight, besides aromatic sodium sulfinates, aliphatic
2
). Sodium sulfinates with strong
2
group produced
[a]
Reaction conditions: indole 1 (0.5 mmol), sodium sulfinate 2 (0.6 mmol), I
(0.05 mmol; 10 mol %), H (0.6 mmol), diethyl phosphite (1.5 equiv.),
PEG400 (2 mL), MW (100 W), 60 C, 10 min.
2
3
2 2
O
o
sodium sulfinates were also suitable for this transformation,
which produces the corresponding products with moderate yield
Scheme 2. Substrates scope for the reaction of indoles 1 with thiols 2.[a]
(
Scheme 2, 3j). Furthermore, we turned our attention to the
scope of the different indoles derivatives with a variety of sodium
sulfinates coupling partners (Scheme 2, 3k–3r). Indoles bearing
electron donating groups such as –Me and –OMe were
produced the desired products in better yields than those with
electron withdrawing groups like –Cl, –Br. Nevertheless, indoles
Assuming that 2,3-bis-sulfenyl indoles could be generated by
/H mediated reaction in PEG400. To testify our hypothesis,
indole 1a (0.5 equiv) and sodium p-toluenesulfinate 2a (1.2
equiv) were selected as the model substrate in the presence of
different kinds and loadings of oxidants and iodine-containing
a I
2
2 2
O
2
with –NO group gave poor results probably due to its strong
catalysts. Ultimately, 0.1 equiv (20 mol %) of I
2
and 2.2 equiv of
electron withdrawing effect, which could deactivate the C3
position (Scheme 2, 3k). As for substitution patterns, it was
found that C2 substituted electron donating indoles delivered
relatively higher yield compared with their 4- or 6-analogue
2 2
H O
were found to be optimum for the maximum yield (85 %) of
desired 2,3-bis-sulfenylindole 5a (Scheme 3). It is noteworthy
that both electron-donating and withdrawing groups were
introduced into the 2,3-sulfenylation products by employing
(
Scheme 2, 3n–3p). N-Substituted indoles also gave the
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European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
various sodium sulfinate and indoles bearing such groups on the
aromatic ring to give the respective 2,3-bis-sulfenyl indoles in
moderate to excellent yields (Scheme 3, 5a-i). Sodium sulfinate
containing electron-rich aromatic ring gave better result
compared to electron-deficient aromatic ring (Scheme 3, 5a-f).
Substituents effects on indoles ring were also investigated. It
was found that indoles with electron-donating groups delivered
higher yield compared to the electron-withdrawing indoles
between indole 1a and sodium p-toluenesulfinate 2a under the
optimized conditions, in presence of TEMPO proceeds to form
3a in 86 % yield, which indicates that the reaction does not
proceed through a radical mechanism (Scheme 5a). Next, a
reaction of disulfide 6a with indole 1a was performed under the
standard conditions furnishing the sulfenylated product 3a in
85 % yield (Scheme 5b). This experiment support that the
reaction is proceed through
a disulfide intermediate. The
(
Scheme 3, 5g-i).
reaction of sodium p-toluenesulfinate 2a under the standard
conditions resulted in almost complete decomposition of the
starting materials (Scheme 5c). The NMR study of this reaction
has shown the formation of a disulfide intermediate (see the
Supporting Information). However, the reaction of sodium p-
SR
I2 (20 mol %), H2O2 (2.2 equiv)
diethyl phosphite (3.0 equiv)
R2
+
R2
RSO Na
2
SR
MW (100 W), 60 oC, 10 min
PEG400
N
N
R1
R1
1
2
5a-i
toluenesulfinate 2a without the use of iodine and H
2 2
O , S-phenyl
Cl
Br
phosphorothioate 8a was obtained as the major product
Cl
Br
(
Scheme 5d).
S
S
S
S
S
S
N
N
H
N
S
H
H
2
SO Na
standard condition
TEMPO (1.1 equiv)
5
a, 85 %
5b, 80 %
5c, 83 %
+
N
H
3a
N
H
MeO
F
1
a (0.5 mmol) 2a (0.6 mmol)
3
a (86 %)
OMe
F
S
S
S
S
standard condition
+
S
S
S
S
S
N
H
3b
N
H
N
H
N
N
H
H
1
a (0.5 mmol)
6a (0.6 mmol)
3a (85 %)
5
d, 81 %
5e, 88 %
5f, 75 %
SH
S
O
O
standard condition
Iodine (1 equiv)
S
+
S
4c
S
S
S
2
a
6
a
7a
trace
MeO
Br
92 %
S
S
S
N
N
N
H
O
P
F
H
H
2
SO Na
S
standard condition
without I2 and H2O2
S
OEt
5
g, 84 %
5h, 82 %
5i, 70 %
+
3d
OEt
2
2a
8a
6a
45 %
trace
[
a]
Reaction conditions: indole 1 (0.5 mmol), sodium sulfinate 2 (1.2 mmol), I
0.1 mmol; 20 mol %), H (1.1 mmol), diethyl phosphite (3.0 equiv.), PEG400
3 mL), MW (100 W), 60 C, 10 min.
2
Scheme 5. Control experiments.
(
(
2 2
O
o
On the basis of the literature precedence, control
experiments and our observations, a plausible mechanism has
been proposed (Scheme 6). Initially, disulfide A is generated
Scheme 3. 2,3-Bis-sulfenylation of indoles.[a]
from sodium sulfinate 2 in the presence of I
2
or H
2
O
2
with diethyl
phosphite.[ Then, interaction between disulfide with I
may be
2
Gram scale reaction was performed under the optimized
reaction conditions as shown in scheme 4, which demonstrate
practical usefulness of the new protocol. Thereby, the reaction
between 1H-indole 1a (5 mmol) and sodium p-toluenesulfinate
32]
formed the electrophilic RSI.[17f,18a,23a] The nucleophilic attack of
indole 1 on sulfur atom of RSI can occur leading to the formation
of an indolinium intermediate C. C undergoes aromatization to
give the desired mono-sulfenylated indole
concomitant formation of HI. Thereafter, the second
sulfenylation of indole occurs predominantly by initial addition at
2 2 2
2a (6 mmol) in the presence of I (10 mol %) and H O (6 mmol)
3
with the
afforded the desired product 3a in 87 % yield, after 40 minute of
reaction time.
the 3-position of the indole ring, which leads to a 3,3-bis-
substituted indolenium intermediate D.[
17a,h,19a,b]
Migration of one
S
I2 (10 mol %), H2O2 (1.2 equiv)
SO2Na
diethyl phosphite (1.5 equiv)
of the sulfide groups from
3
to
2
position forming an
+
N
H
MW (100 W), 60 oC, 40 min
PEG400
episulfonium species, and subsequent release of proton can give
2,3-bis-sulfenyl indole 5. In the end, reaction between HI and
N
H
1
a (5 mmol)
2a (6 mmol)
3
a (87 %)
2 2 2 2
H O regenerates the catalyst I with the formation of H O.
Scheme 4. Scale-up reaction between 1a and 2a.
To get insight into the reaction mechanism, some control
experiments were performed (Scheme 5). First, a reaction
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European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
SR
Authors are also thankful to CSIR-NEIST Jorhat and SAIC,
Tezpur University for spectral analysis.
SR
2
2
SR
N
2
HI
H2O2
N
H
3
H
Keywords: indole • mono-sulfenylation • 2,3-bis-sulfenylation •
green solvent • microwave-assisted
5
I2
RSO2Na diethyl
SR
SR
N
SR
H
phosphite
2
[1]
a) R. L. Sundberg, Indoles, Academic, London, 1996; (b) A. R. Katritzky,
A. F. Pozharskii, Handbook of Heterocyclic Chemistry, Pergamon,
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N
H
I
I
S
R
D
C
H
R
S
A
H
SR
I2
2
2
RSI
2
N
N
B
1
H
3
H
Scheme 6. Proposed reaction mechanism.
4
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In summary, we have developed
a very efficient and
[
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a
2
2 2
O
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2 2 2
taken in a sealed glass tube and placed in the cavity of microwave
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power 100 W, increasing time 5 min, target temperature 60 oC, standing
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maintain a constant temperature. After 10 min (monitored through TLC),
the reaction mixture was cooled to room temperature. Then diluted with
distilled water and the organic layer was extracted with EtOAc (3 x 10
mL). The combined organic phase was washed with brine (3 x 10 mL),
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This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201701293
COMMUNICATION
Entry for the Table of Contents
Layout 2:
COMMUNICATION
Mono-sulfenylation and 2,3-Bis-
sulfenylation
R
I2 (20 mol %)
H2O2 (2.2 equiv)
diethyl phosphite
MW (100 W), 60 oC
10 min, PEG400
R2 = H
I2 (10 mol %)
H2O2 (1.2 equiv)
diethyl phosphite
S
R
R2
S
R3
S
R3
R2
R3
R2 or
R3
S
+
RSO2Na
Rajjakfur Rahaman, Pranjit Barman*
N
R1
R
N
MW (100 W), 60 oC
10 min, PEG400
N
R1
N
R1
R
R1
Grame-scale synthesis
Mild and simple protoco Green solvent
Broad substrate scope
Metal free
R = aryl, alkyl, naphthyl
R1 = H, Me; R2 = H, Me
R3 = H, Br, Cl, Me, NO2
9
examples
19 examples
up to 97 % yield
up to 88 % yield
Page No. – Page No.
Iodine-Catalyzed Mono- and Bis-
Sulfenylation of Indoles in PEG400 via
a facile Microwave-Assisted Process
An I
2
-catalyzed versatile green method for the synthesis of mono- and 2,3-bis-
in PEG400 under microwave
sulfenyl indoles with sodium sulfinates using H
2
O
2
conditions has been presented. This simple method enabled the rapid synthesis of
mono- and 2,3-bis-sulfenylindoles with good to excellent yields. The notable
features of this protocol include environmental friendliness, odorless and short
reaction time, easy operation and mild reaction conditions.
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