Organocatalytic visible light induced S-S bond formation for oxidative coupling of thiols to disulfides

Article abstract of DOI:10.1016/j.tet.2015.12.036

In this work, we developed a visible light induced oxidative coupling of thiols into the corresponding disulfides in a process catalyzed by an inexpensive and non hazardous Rose Bengal dye. Our optimization study revealed that the use of Rose Bengal catal

Full text of DOI:10.1016/j.tet.2015.12.036

Tetrahedron 72 (2016) 788e793
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Organocatalytic visible light induced SeS bond formation for
oxidative coupling of thiols to disulfides
a
a
b
Theeranon Tankam , Kamolrut Poochampa , Tirayut Vilaivan ,
a
a,
*
Mongkol Sukwattanasinitt , Sumrit Wacharasindhu
Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330,
Thailand
a
b
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, we developed a visible light induced oxidative coupling of thiols into the corresponding
disulfides in a process catalyzed by an inexpensive and non hazardous Rose Bengal dye. Our optimization
study revealed that the use of Rose Bengal catalyst under irradiation with visible light in either 2-
propanol or water at room temperature can convert a variety of thiols into their corresponding disul-
fides in good to excellent yields. Natural sunlight can be applied as a light source to prepare disulfide in
high yield at gram-scale quantity. Our photochemical reaction can be performed in a continuous flow
reactor, demonstrating a short residence time. The key benefits of this reaction include the use of metal-
free, low cost Rose Bengal catalyst and practical operation (room temperature, open flask, undried sol-
vents and simple work up procedure by extraction).
Received 28 September 2015
Received in revised form 30 November 2015
Accepted 15 December 2015
Available online 18 December 2015
Keywords:
Rose Bengal
Disulfide
Photocatalyst
Visible light
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
field of visible light reactions because they are inexpensive,
widely available through the entire visible spectrum range and
1
1e14
Solar light is an attractive way to initiate chemical trans-
formations as it is renewable, environmentally friendly, safe and
scalable. Classically, photochemical reactions are performed un-
der UV irradiation although this often leads to decomposition
and side reactions due to its high energy. The lack of visible light
absorption by most organic molecules has limited the general
utility of photochemical reactions under visible light. Fortunately,
a break-through discovery of photoredox catalysis by Macmillan
have low toxicity.
The formation of SeS bonds plays an important role in the
15
stabilization and folding of proteins in biological systems.
Disulfides also serve as a protecting group for drug delivery sys-
tems. In rubber and textile industry, it is the basis of the well-
known vulcanizing process. In particular, organic disulfides are
common intermediates for organic transformations and have
16
17
18
19,20
found broad applications in pharmaceutical,
science. Common methods for preparing disulfides include the
and material
1,2
21
and Yoon has made visible light sensitization possible.
The
reports has drawn significant attention from the synthetic
stoichiometric or catalytic oxidation of thiols using a metal cata-
2
2,23
chemist communities and since then many elegant chemical
lyst such as Fe, Pb, Ce, Mn, Co, Cr, Cu, or Al (Scheme 1).
commonly used stoichiometric oxidizing agents include halogen
(I , Br ), hydrogen peroxide, azo compounds, DDQ or sodium ni-
trite.
hypervalent iodine (III) reagent or enzyme catalyst such as lac-
Other
3
e5
transformations under visible light irradiation were reported.
Most reactions utilized metal-based photosensitizers such as
ruthenium, rhenium, iron and iridium as a photoredox catalyst
2
2
2
4,25
Recently, the use of purely organic stoichiometric
6
e10
26
due to their high activity and stability.
However, high cost
2
7
and high toxicity have limited their applications. On the other
hands, organic dyes could serve as a promising catalyst in the
case to perform oxidative coupling of thiols were reported.
However, except for the use of enzymes, the high toxicity and cost
of the reagents combined with harsh reaction conditions, long
reaction time and risk of over-oxidation represent significant
disadvantages.
*
Corresponding author. E-mail address: sumrit.w@chula.ac.th (S. Wacharasindhu).
http://dx.doi.org/10.1016/j.tet.2015.12.036
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
0

T. Tankam et al. / Tetrahedron 72 (2016) 788e793
789
to the wide availability of white LED, we thus decided to use it for
further studies.
Table 1
a
Effect of light source in photocatalytic oxidation of thiols
Entry
Light source
Yield(%)b
Scheme 1. Oxidation of thiols into disulfides.
1
2
3
4
5
White LED
Blue LED
Green LED
Red LED
d
90
93
93
c
18
d
Recently, there were several emerging reports on the oxidation
of thiols into disulfide mediated by visible light. In 2010, Ando first
reported the use of diaryl tellurides under photosensitized condi-
0
a
i
Reaction were carried at 0.5 mmol of 1a with 5 mol% of Rose Bengal in PrOH
10 mL.
2
8
b
c
Isolated by extraction.
tions for thiol oxidation. Later, an iron phthalocyanine immobi-
lized on graphene was used as a photosensitizer for the conversion
Isolated by column chromatography.
Vessel was covered with aluminum foil.
d
2
9
of thiols into disulfides. More recently, Wu also demonstrated the
oxidative coupling of thiols using recyclable CdSe quantum dots in
3
0
2
the presence of NiCl to generate disulfide and hydrogen gas.
With the results of light source screening in hand, we next
However, these reports required the use of toxic metal-based cat-
alysts or strong oxidants. Therefore, metal-free photocatalytic
systems for thiol oxidation into disulfide under visible light are
highly desirable. During the preparation of this manuscript, an el-
egant work using Eosin Y dye for oxidation of thiols to disulfides
studied the effects of solvent and catalytic amounts of Rose Bengal
for oxidation of 4-chlorothiophenol (1a). Acetonitrile, DMF, toluene
and 2-propanol were screened as a solvent for the photocatalytic
oxidation of thiols in the presence of 5 mol% of Rose Bengal (Table 2,
1
entries 1e4). All reactions were monitored by H NMR showing
31
under visible-light has been reported. The application of such
organic dyes is less toxic comparing with the heavy metal con-
taining catalysts. We have investigated the reaction based on
a similar approach using an inexpensive organic dye, Rose Bengal as
a photocatalyst and found that it is very efficient for conversion of
thiols into disulfides under visible or sunlight at ambient temper-
ature (Scheme 1). In addition, Rose Bengal is also highly water
soluble, allowing the reaction to be performed in water and the
catalyst can be removed by simple aqueous extraction from the
organodisulfide products.
complete conversion into the corresponding disulfide 2a after 15 h.
Lowering the amount of Rose Bengal to 1 mol% resulted in in-
complete reaction (Table 2, entry 5), while in the absence of cata-
lyst, the reaction did not proceed (Table 2, entry 6). To our surprise,
performing the reaction in water gave complete conversion even
though the thiols 1a was poorly soluble in water (Table 2, entry 7).
These results suggested the broad solvent compatibility and high
efficiency of Rose Bengal as photocatalyst for oxidation of thiols.
Table 2
Effects of solvent and amounts of Rose Bengal in photocatalytic oxidation of thiolsa
2
2
. Results and discussion
.1. Reaction optimization
Various Light Emitting Diodes (LEDs, 1.5 W) were used as a light
Entry
mol%
Solvent
Conversion (%)b
source for oxidative coupling of 4-chlorothiophenol (1a) in the
presence of 5 mol % Rose Bengal (Table 1, Fig. S1). Bearing the
concept of green chemistry in mind, all tested reactions were
conducted in undried 2-propanol, which is one of the preferable
organic solvent choices in the pharmaceutical industries3 at room
temperature in open air for 15 h. Even though Rose Bengal has
absorption maxima at around 550 nm, most of LED sources in-
cluding white, blue and green are compatible with this photo-
catalytic reaction giving the desired disulfide product (2a) in
1
2
3
4
5
6
7
5
5
5
5
1
0
5
Acetonitrile
DMF
100
100
100
100
25
Toluene
i
PrOH
PrOH
PrOH
2
i
i
0
100
Water
a
Reaction were carried on a 0.5 mmol of 1a with 5 mol% of Rose Bengal in 10 mL
solvent.
b
Determined by 1H NMR.
9
0e93% yields (Table 1, entries 1e3). We would like to point out
that the starting material 1a was completely consumed without
over oxidized by-product such as sulfoxide, sulfone or sulfonic acid
detected. Importantly, because no additional base or oxidant was
used in the reaction, the product 2a can simply be purified by
aqueous extraction using 1M NaOH solution to remove the Rose
Bengal (Fig. S2a). However, under Red LED irradiation, only 18% of
Based on the above results, the ability to perform the reaction in
water under open-flask conditions prompted us to investigate the
i
reaction rate of reactions from the entries 4 and 7 (Table 2). In PrOH
under open-flask conditions required only 6 h to complete.
i
Switching the solvent from PrOH to water, it required a longer time
2
a was obtained (Table 1, entry 4). This is perhaps due to the low
required to complete the conversion (ca. 9 h, Figure 1). This is due to
the formation of heterogeneous reaction mixture. Even though the
longer reaction time in water system is necessary, the fact that it is
the most preferable solvent system for green synthesis encouraged
energy of the light source. Also, in the absence of light, the oxidative
coupling of thiol was unable to proceed (Table 1, entry 5), sug-
gesting that the reaction is indeed a photocatalyzed reaction. Due

790
T. Tankam et al. / Tetrahedron 72 (2016) 788e793
us to further investigate the reactions of various substrates in both
PrOH and water).
thiols (1ge1i) generally required shorter reaction times. Based on
these results, the reaction mechanism might involve the formation
of thiol radical. Therefore, the faster conversion observed in aro-
matic substrate is perhaps governed by the stability of the thiol
radical intermediate whereby arylthio radicals are more stable than
i
3
3
alkylthio radicals. To demonstrate the ability to perform the re-
action in water, 1a, 1c, 1e and 1g were selected as representative
substrates for the present photocatalytic oxidative coupling re-
action in water. In all cases, longer irradiation time were required
i
comparing to PrOH, but good to high yields of disulfides 2a, 2c, 2e
and 2g (81e92%) were obtained (Table 4, entries 2, 4, 5 and 7). TLC
monitoring suggested that, in all cases, the starting thiols were
completely consumed without other side-products formation.
Therefore, the product can be purified simply by extraction with
NaOH to remove the Rose Bengal catalyst. This reaction is thus not
only highly functional group tolerant but also shows high atom
economy and generates low waste, making it applicable for modern
green organic reactions.
Table 4
a
Photocatalytic oxidation of various thiols
Fig. 1. Photocatalytic oxidation of thiols 1a irradiated by white LED in a) iPrOH; b)
water under open air. % Conversion was determined from 1H NMR.
2
.2. Scalability
Yields (%)b
Entry
Thiols
T (h)
To investigate scalability of the photolytic oxidation reaction,
one gram-scale reactions were carried out under optimized con-
1
2
1b
1c
15
94
i
dition using white LED in both PrOH and water (Table 3). The
15 (24)
89 (84)
1
monitoring by H NMR revealed the complete consumption of thiol
i
1
a within 6 h in PrOH and disulfide 2a was isolated in excellent
77c
3
1d
15
yield after aqueous extraction (Table 3, entry 1). The reaction time
required in this reaction is similar to a small scale batch (50 mg),
suggesting a high potential for industry scale-up. On the other
hands, when the reaction in water was performed under one gram-
scale, a longer reaction time was required (15 h) in order to convert
all starting 1a into 2a (Table 3, entry 2). Carrying out the reaction in
water, the disulfide 2a was also obtained in good yield after ex-
traction with NaOH.
4
1a
6 (9)
90 (81)
5
6
1e
1f
6 (9)
15
86 (92)
75c
Table 3
a
Gram-scale photocatalytic oxidation of thiol
7
1g
3 (6)
92 (88)
8
9
1h
1i
3
3
86
81
Entry
Solvent
iPrOH
Water
t(h)
Conversion(%)b
Yields(%)c
1
2
6
15
100
100
91
89
a
Reaction conditions: thiol (6.91 mmol, 1.0 g), Rose Bengal (5 mol %) in solvent
5
0 mL under 1.5 W white LED.
b
Determined by 1H NMR.
c
a
i
Isolated yield by extraction.
Reaction conditions: thiol (0.5 mmol), Rose Bengal (5 mol %) in PrOH 10 mL
under 1.5 W white LED; numbers in parentheses are the yields and reaction time
when carried the reaction in water.
b
Isolated yield by extraction.
Isolated by silica gel chromatography.
2
.3. Functional group compatibility
c
With the optimized conditions in hand, we explored the gen-
2
.4. Reaction under sunlight
erality and scope of this reaction by using a variety of aliphatic,
aromatic, and heteroaromatic thiols. Eight thiols were subjected to
the optimized oxidation conditions using either 2-propanol or
water as the solvent (Table 3). In 2-propanol, the oxidative coupling
of all thiols proceeded smoothly and the desired disulfides 2bei
were isolated in good to excellent yields (Table 4). The reactions of
aromatic thiols especially for nitrogen-containing heteroaromatic
Nowadays, a foremost scientific challenge is to harness the en-
ergy from the sun. Therefore, we attempted our reaction in open
round-bottomed flask under sunlight (Scheme 2, Fig. S2a). When
carrying out the reaction in 50 mg scale, the thiols 1a were totally
consumed within 6 h and 90% of the disulfide 2a was isolated.

T. Tankam et al. / Tetrahedron 72 (2016) 788e793
791
Moreover, when 1 g of the thiol 1a was subjected to the above
2.6. Proposed mechanism
reaction condition (6 h), small starting material remained (ca. 5%)
and 86% of disulfide 2a was isolated after extraction. These results
suggested the possibility for a large scale synthesis of disulfide
using Rose Bengal as a photocatalyst under natural sunlight.
A plausible mechanism is outlined in Scheme 3. Based on pre-
vious work on the use of Rose Bengal as a photocatalyst, we hy-
pothesize that the reaction involves the formation of singlet oxygen
3
3,39
and thiol radical.
is converted into a triplet state (3RB*) via intersystem crossing
ISC). This phenomenon transfers the energy to triplet oxygen from
The singlet excited state of rose Bengal (1RB*)
(
air to generate singlet oxygen, which later became an active oxi-
dizing agent. Then singlet oxygen oxidizes thiol into the corre-
sponding thiol radical which undergoes homocoupling to provide
the disulfide. The faster conversion of aromatic than aliphatic thiol
substrates (Table 4) is consistent with the proposed reaction
mechanism.
Scheme 2. Photocatalytic oxidation of thiol under sunlight.
2
.5. Continuous flow reaction
It is well-known that in large scale-batch reactions, the effi-
ciency of the photocatalyst will decrease because the penetration
ability of light decreases exponentially with the path length
according to the BeereLambert law. In order to overcome this
problem, many research groups demonstrated the use of continu-
ous flow reactors mediated by visible-light-active photoredox cat-
Scheme 3. A plausible mechanism for photocatalytic oxidation of thiols using Rose
Bengal.
3
4e36
alysts to achieve high surface area and minimal path length.
Notably, flow chemistry also provides several advantages in the
3. Conclusion
aspect of green chemistry such as safety, low waste generation,
In summary, we have developed a photocatalytic method using
reducing solvent usage and the possibility of a continuous 24/7
production.3
7,38
We used a commercial continuous microflow re-
L chip assembled with 35 white LEDs to test our
Rose Bengal dye as a photocatalyst under visible light for oxidative
coupling of thiols into disulfides. The method offers high selectivity,
high functional group compatibility and produces disulfides in high
yields under mild reaction conditions. The reactions are opera-
tionally simple and can be performed at room temperature in an
open air system. The reaction can be performed in environmentally
benign solvents such as water or isopropanol. Importantly, the use
of Rose Bengal as a photocatalyst eliminates the need for additional
oxidant other than air, and thus simplifies the work up.
actor with a 250
m
reaction (see Supplementary Fig. S3). To further understand of this
transformation, we conducted a systematic study of two reaction
variables: flow rate and reaction concentration (Table 5). Per-
forming the oxidation of 1a under dilute condition (0.01 M) affor-
ded a complete conversion within 5 min of residence time (Table 5,
entries 1 and 2). However, when the reaction concentration was the
same as batch reaction (0.05 M, Table 5, entries 3 and 4), only 39%
conversion were obtained at 5 min residence time. Gratifyingly,
a complete conversion was observed at 30 min residence time.
Even though the concentration of the thiol crucially affected the
reaction efficiency, the present catalytic visible-light reaction of
thiol into disulfide in a flow reactor can lower the reaction time
when compared to the batch reaction.
4. Experimental section
4.1. General information
All chemicals were obtained from commercial suppliers (Sigma
Aldrich), Fluka (Switzerland) or Merck (Germany) and were used
without further purification. All solvents were used directly with-
out drying. Analytical thin-layer chromatography (TLC) was per-
formed on Kieselgel F254 pre-coated plastic TLC plates from EM
Science. Visualization was performed with a 254 nm ultraviolet
lamp. Column chromatography was performed by using Merck and
Table 5
1
13
a
silica gel (60,230e400 mesh) from ICN Silitech. The H and C NMR
Photocatalytic oxidation of thiols using a micro flow reactor
spectra were recorded on a Varian Mercury 400 or Bruker Avance
1
13
4
00 for H (400 MHz) and Bruker Avance 400 for C (100 MHz) in
CDCl or CD OD solution. White, Blue, Green and Red LED reactors
were made from a 250 mL beaker lined with a commercial belt LED
3
3
(
(
1.5 Wꢀ228). Flow reaction was performed in a Microflow reactor
Syriss, FRXTM Model) with Asia microreactor chip (volume
250 mL). Low-resolution mass spectra was obtained from triple
quadrupole GC/MS Agilent technology. Fourier transform infrared
spectra were acquired on Nicolet 6700 FTIR spectrometer equipped
with a mercury-cadmium telluride (MCT) detector (Nicolet, USA).
Entry Conc (M) Flow rate (m
L/min) Residence time (min) Conversion (%)b
1
2
3
4
0.01
0.01
0.05
0.05
8.3
50
8.3
50
30
5
30
5
100
100
100
39
i
4.2. General procedure A for synthesis of disulfides in PrOH
a
Reaction were performed using microflow reactor from Syriss FRXTM with
L chip equipped with a panel of 24 small white LEDs (1.5 W, Fig. S3).
Determined by H NMR.
i
2
50
m
To a mixture of thiol (0.35 mmol) in PrOH in a 10 mL vial, Rose
b
1
Bengal (0.05 equiv) were added and the reaction mixture was

792
T. Tankam et al. / Tetrahedron 72 (2016) 788e793
stirred at room temperature under white LED irradiation. The re-
action mixture was quenched by addition of saturated aqueous
3
NMR (CDCl , 100 MHz):d 39.3, 31.8, 29.2, 28.6, 22.6, 14.1; GCeMS:
m/z: 289.9; IR (ATR, cm ): 2955, 2922, 2852, 1452.
ꢁ
1
NaOH (10 mL), extracted with Et
and evaporated under reduced pressure to give the desired
product.
2
O (3ꢀ10 mL), dried over Na
2 4
SO
4.5.3. 6,6-Disulfanediyldihexan-1-ol (2c).42 [CAS: 80901-86-6]:
Synthesized according to procedure A using 6-mercapto-1-hexanol
i
(
50 mg, 0.372 mmol), Rose Bengal (20 mg, 0.020 mmol) in PrOH
(
oil.
10 mL) for 15 h to afford 2c (44.1 mg, 0.165 mmol, 89%) as a yellow
4
.3. General procedure B for synthesis of disulfides in water
Synthesized according to procedure B using 6-mercapto-1-
hexanol (50 mg, 0.372 mmol), Rose Bengal (20 mg, 0.020 mmol)
To a mixture of thiol (0.35 mmol) in water in 10 mL vial, Rose
Bengal (0.05 equiv) were added and the reaction mixture was
stirred at room temperature under white LED irradiation. The re-
action mixture was quenched by saturated NaOH (10 mL), extracted
in water (10 mL) for 24 h to afford 2c (42.6 mg, 0.159 mmol, 84%) as
1
a yellow oil. H NMR (CDCl
3
, 400 MHz):
d
¼3.64 (t, J¼6.6 Hz, 4H),
13
2
(
2
.69 (m, 4H), 1.70 (m, 4H), 1.56 (m, 4H), 1.41 (m, 8H); C NMR
with Et
2
O (3ꢀ10 mL), dried over Na
2 4
SO and evaporated under
CDCl , 100 MHz): 62.8, 39.0, 32.6, 29.1, 28.2, 25.4; GCeMS: m/z:
3
d
reduced pressure to give the desired product.
ꢁ
1
66.0; IR (ATR, cm ): 3326, 2926, 2854, 1046.
4
.4. General procedure C for synthesis of disulfides in gram
.5.4. 1,2-Dibenzyldisulfane (2d).28 [CAS: 150-60-7]: Synthesized
4
scale (Table 3)
according to procedure A using benzyl mercaptan (50 mg,
i
0
1
CDCl
.402 mmol), Rose Bengal (20 mg, 0.020 mmol) in PrOH (10 mL) for
To a 100 mL of round bottom flask, 4-chlorothiophenol (1.00 g,
1
5 h to afford 2d (38.5 mg, 0.155 mmol, 77%) as white solid. H NMR
i
6
.91 mmol) was dissolved in PrOH (50 mL) and Rose Bengal
13
(
3
, 400 MHz):
3
d 7.28 (m, 10H), 3.63 (s, 4H); C NMR (CDCl ,
(
0.05 equiv 0.40 g, 0.40 mmol) were added and the reaction mix-
1
00 MHz):
d
137.2, 129.3, 128.5, 127.4, 43.3; GCeMS: m/z: 246.0; IR
ture was stirred at room temperature under white LED irradiation
for 6 h until 4-chlorothiophenol disappeared as detected by TLC.
Then the reaction was quenched by saturated NaOH (100 mL). The
ꢁ1
(
ATR, cm ): 3064, 3091, 2927, 2847, 1491, 1459.
.5.5. 1,2-Di-p-tolyldisulfane (2e).28 [CAS: 103-19-5]: Synthesized
according to procedure A using 4-methyl thiophenol (50 mg,
4
product was extracted with Et
evaporated under reduced pressure to give the desired product 2a
0.912 g, 3.19 mmol, 91%).
2
2 4
O (5ꢀ30 mL), dried over Na SO and
i
0
6
.402 mmol), Rose Bengal (20 mg, 0.020 mmol) in PrOH (10 mL) for
h to afford 2e (42.7, 0.173 mmol, 86%) as a yellow solid.
(
Synthesized according to procedure B using 4-methyl thio-
4
.5. General procedure D for synthesis of disulfides in micro
phenol (50 mg, 0.402 mmol), Rose Bengal (20 mg, 0.020 mmol) in
flow reaction (Table 5)
water (10 mL) for 9 h to afford 2e (45.7 mg, 0.185 mmol, 92%) as
a yellow solid.
1
To a solution of 4-chlorothiophenol 144 mg (1.00 mmol) in
00 mL PrOH (0.01 M) was added Rose Bengal (0.05 equiv
H NMR (CDCl
3
, 400 MHz):
d
¼7.36 (d, J¼8.4 Hz, 4H), 7.07 (d,
i
13
1
0
J¼8.4 Hz, 4H), 2.33 (s, 6H); C NMR (CDCl
3
, 100 MHz):
d
137.4,
ꢁ
1
.05 mmol, 51 mg) and the mixture was stirred for 30 s in 250 mL
Erlenmeyer flask). At the same time the Syriss flow reactor was
equipped with Asia microreactor chip (250 L volume, 1 min resi-
dence time at 250 L/min flow rate) and a panel of small White
LEDs (1.5 W ꢀ 35) were attached in front of the chip (Fig. S3). The
133.9, 129.7, 128.5, 21.1; GCeMS: m/z: 245.8; IR (ATR, cm ): 3013,
2917, 2866, 1489.
m
m
4.5.6. 2,2-Disulfanediyldianiline (2f).43 [CAS: 1141-88-4]: Synthe-
sized according to procedure A using 2-aminothiophenol (50 mg,
0.399 mmol), Rose Bengal (20 mg, 0.020 mmol) in PrOH (10 mL) for
16 h to afford 2f (37.5 mg, 0.150 mmol, 75%) as a yellow solid. H
i
i
system was first primed with PrOH. Then a flow rate of 8.3
mL/min
1
(
30 min residence time) were selected and the process were star-
ted. At that point, inlet tube was switched from the solvent reser-
voir to the 250 mL flask containing the reaction mixture. The first
NMR (CDCl
(m, 2H). C NMR (CDCl
118.3, 115.3; GCeMS: m/z: 247.9; IR (ATR, cm ): 3358, 2915, 2845,
1603, 1471.
3
, 400 MHz):
d
¼7.18 (t, J¼11.0 Hz, 4H), 6.75 (m, 2H), 6.61
13
3
, 100 MHz): 148.6, 136.8, 131.6, 118.8,
d
ꢁ
1
5
mL of reaction mixture was collected from the outlet. The mixture
was added saturated NaOH (5 mL) and extracted with Et
3ꢀ5 mL) and solvent was evaporated under reduced pressure. The
2
O
(
1
4.5.7. 1,2-Di(pyridine-2-yl)disulfane (2g).28 [CAS: 2127-03-9]: Syn-
reaction conversion was determined using H NMR.
thesized according to procedure A using 2-mercaptopyridine
(50 mg, 0.450 mmol), Rose Bengal (20 mg, 0.020 mmol) in PrOH
(10 mL) for 3 h to afford 2g (46.2 mg, 0.202 mmol, 92%) as a yellow
oil.
.5.1. 1,2-Bis(4-chlorophenyl)disulfane (2a).40 [CAS: 1142-19-4]:
Synthesized according to procedure A using 4-chlorothiophenol
i
4
i
(
50 mg, 0.345 mmol), Rose Bengal (18 mg, 0.018 mmol) in PrOH
(
10 mL) for 6 h to afford 2a (45.0 mg, 0.159 mmol, 90%) as a yellow
Synthesized according to procedure B using 2-mercaptopyridine
(50 mg, 0.450 mmol), Rose Bengal (20 mg, 0.020 mmol) in water
solid.
Synthesized according to procedure B using 4-chlorothiophenol
50 mg, 0.345 mmol), Rose Bengal (18 mg, 0.018 mmol) in water
10 mL) 9 h to afford 2a (40.6 mg, 0.141 mmol, 81%) as a yellow
(10 mL) 6 h to afford 2g (43.8 mg, 0.199 mmol, 88%) as a yellow oil.
1
(
(
H NMR (CDCl
3
, 400 MHz):
d
¼8.47 (d, J¼8.1 Hz, 2H), 7.63 (m,
1
3
4H), 7.12 (m, 2H); C NMR (CDCl
121.2, 119.9; GCeMS: m/z: 219.8; IR (ATR, cm ): 3046, 2987, 1571,
3
, 100 MHz): 158.9, 149.6, 137.4,
d
ꢁ1
solid.
1
H NMR (CDCl
3
, 400 MHz):
d
7.40 (d, J¼8.7 Hz, 4H), 7.27 (d,
1412.
13
J¼8.7 Hz, 4H); C NMR (CDCl
3
, 100 MHz): 135.1, 133.6, 129.3,
d
ꢁ1
4.5.8. 1,2-Bis(5-bromopyridin-2-yl)disulfane (2h).44 [CAS: 872273-
1
29.3; GCeMS: m/z: 285.8; IR (ATR, cm ): 3081, 2920, 1473, 1387.
3
6-4]: Synthesized according to procedure
A
using 5-
4
.5.2. 1,2-Dioctyldisulfane (2b).41 [CAS: 822-27-5]: Synthesized
bromopyridine-2-thiol (50 mg, 0.263 mmol), Rose Bengal (13 mg,
0.013 mmol) in PrOH (10 mL) for 3 h to afford 2h (43.0 mg,
0.110 mmol, 86%) as a white solid.
i
according to procedure A using 1-octanethiol (50 mg, 0.342 mmol),
Rose Bengal (18 mg, 0.018 mmol) in PrOH (10 mL) for 15 h to afford
2
4
i
1
1
b (47.1 mg, 0.161 mmol, 94%) as a colorless oil. H NMR (CDCl
3
,
C
H NMR (CDCl
3
, 400 MHz):
d
8.55 (d, J¼2.4 Hz, 2H), 7.77 (dd,
13
13
00 MHz): 2.67 (m, 4H), 1.69 (m, 4H), 1.29 (m, 20H), 0.9 (m, 6H);
J¼8.5, 2.4 Hz, 2H), 7.50 (d, J¼8.5 Hz, 2H); C NMR (CDCl
3
,

T. Tankam et al. / Tetrahedron 72 (2016) 788e793
793
1
00 MHz):
d
¼157.7, 150.0, 139.8, 121.0, 118.4; GCeMS: m/z: 377.7; IR
8. Tyson, E. L.; Ament, M. S.; Yoon, T. P. J. Org. Chem. 2013, 78, 2046e2050.
9. Yasu, Y.; Koike, T.; Akita, M. Org. Lett. 2013, 15, 2136e2139.
0. Zou, Y. Q.; Chen, J. R.; Liu, X. P.; Lu, L. Q.; Davis, R. L.; Jørgensen, K. A.; Xiao, W. J.
ꢁ
1
(
ATR, cm ): 3041, 2959, 2922, 2852, 1433.
1
Angew. Chem., Int. Ed. 2012, 51, 784e788.
4
.5.9. 1,2-Di(pyrimidin-2-yl)disulfane (2i).45 [CAS: 15718-46-4]:
11. Fidaly, K.; Ceballos, C.; Falgui eꢀ res, A.; Veitia, M. S. I.; Guy, A.; Ferroud, C. Green
Chem. 2012, 14, 1293e1297.
Synthesized according to procedure A using 2-mercaptopyrimidine
1
1
2. Gu, X.; Li, X.; Chai, Y.; Yang, Q.; Li, P.; Yao, Y. Green Chem. 2013, 15, 357e361.
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i
(
(
50 mg, 0.445 mmol), Rose Bengal (20 mg, 0.02 mmol) in PrOH
10.0 mL) for 3 h to afford 2i (40.5 mg, 0.181 mmol, 81%) as a yellow
1
1
1
solid.
1H NMR (CDCl
, 400 MHz):
d
8.59 (d, J¼4.8 Hz, 4H), 7.13 (t,
, 100 MHz): 169.8, 158.0, 118.1;
3
13
J¼4.8 Hz, 2H) ppm. C NMR (CDCl
3
d
18. Ge, W.; Wei, Y. Green Chem. 2012, 14, 2066e2070.
19. Ayodele, E. T.; Olajire, A. A.; Amuda, O. S.; Oladoye, S. O. Bull. Chem. Soc. Ethiop.
ꢁ
1
GCeMS: m/z: 221.8; IR (ATR, cm ): 3115, 3029, 2961, 2919, 1547.
2003, 17, 53e60.
2
0. Zottola, M. A.; Beigel, K.; Soni, S. D.; Lawrence, R. Chem. Res. Toxicol. 2009, 22,
1948e1953.
Acknowledgments
21. Maddanimath, T.; Khollam, Y. B.; Aslam, M.; Mulla, I. S.; Vijayamohanan, K. J.
Power Sources 2003, 124, 133e142.
2. Mandal, B.; Basu, B. RSC Adv. 2014, 4, 13854e13881.
23. Witt, D. Synthesis 2008, 2491e2509.
This study is financially supported by the Thailand Research
Fund (TRF-RSA5780055) and National Nanotechnology Center
2
(
NANOTEC), NSTDA, Ministry of Science and Technology, Thailand,
24. Harusawa, S.; Yoshida, K.; Kojima, C.; Araki, L.; Kurihara, T. Tetrahedron 2004,
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through its program of the Center of Excellence Network. This work
is part of the Project for Establishment of Comprehensive Center for
Innovative Food, Health Products and Agriculture supported by the
Thai Government Stimulus Package 2 (TKK2555, SP2), the Higher
Education Research Promotion and National Research University
Project of Thailand, Office of the Higher Education Commission
2
8
26. Rattanangkool, E.; Krailat, W.; Vilaivan, T.; Phuwapraisirisan, P.; Sukwattana-
sinitt, M.; Wacharasindhu, S. Eur. J. Org. Chem. 2014, 2014, 4795e4804.
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7. Abdel-Mohsen, H. T.; Sudheendran, K.; Conrad, J.; Beifuss, U. Green Chem. 2013,
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(
AM1006A-56) and the Ratchadaphiseksomphot Endowment Fund
of Chulalongkorn University (RES560530126-AM). The student
scholarship was received from Science Achievement Scholarship of
Thailand (SAST).
31. Talla, A.; Driessen, B.; Straathof, N. J. W.; Milroy, L.-G.; Brunsveld, L.; Hessel, V.;
No e€ l, T. Adv. Synth. Catal. 2015, 357, 2180e2186.
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3. D eꢁ n eꢀ s, F.; Pichowicz, M.; Povie, G.; Renaud, P. Chem. Rev. 2014, 114, 2587e2693.
Supplementary data
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1
1
Supplementary data (Experimental setup and images of H, 13
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Ortin, M. M.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2015, 137, 1679e1684.
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C
NMR and Mass spectrum of all disulfides are available in the Sup-
plementary data.) associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2015.12.036.
3
7. Geyer, K.; Cod eꢁ e, J. D. C.; Seeberger, P. H. Chem.dEur. J. 2006, 12, 8434e8442.
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