HBr/H2O2-mediated formation of C–S bond with thiosulfates

Article abstract of DOI:10.1016/j.tetlet.2018.01.055

A novel, efficient, and green protocol to construct C–S bond has been developed via HBr/H₂O₂-mediated sulfenylation of styrenes and 4-hydroxycoumarins leading to unsymmetrical sulfides. Various unsymmetrical sulfides were prepared in one step with moderate to good yields using environmentally-friendly H₂O₂ as oxidant and HBr as catalyst. Based on the preliminary experimental results, a plausible reaction mechanism was proposed for HBr/H₂O₂-mediated formation of C–S bond with thiosulfates.

Full text of DOI:10.1016/j.tetlet.2018.01.055

Tetrahedron Letters xxx (2018) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
HBr/H2O2-mediated formation of C–S bond with thiosulfates
a,
Rongxing Zhang a, Shengzhou Jin a, Yuanxing Wan b, Sen Lin a, , Zhaohua Yan
⇑
⇑
a College of Chemistry, Nanchang University, Nanchang 330031, PR China
b State Key Laboratory of Food Science and Techology, Nanchang University, Nanchang 330031, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel, efficient, and green protocol to construct C–S bond has been developed via HBr/H2O2-mediated
sulfenylation of styrenes and 4-hydroxycoumarins leading to unsymmetrical sulfides. Various unsym-
metrical sulfides were prepared in one step with moderate to good yields using environmentally-friendly
H2O2 as oxidant and HBr as catalyst. Based on the preliminary experimental results, a plausible reaction
mechanism was proposed for HBr/H2O2-mediated formation of C–S bond with thiosulfates.
Ó 2018 Elsevier Ltd. All rights reserved.
Received 20 December 2017
Revised 18 January 2018
Accepted 19 January 2018
Available online xxxx
Keywords:
Sulfenylation
Unsymmetrical sulfides
Styrenes
Hydroxycoumarins
Thiosulfates
Introduction
beta-hydroxysulfides and sulfenylated 4-hydroxycoumarins have
been developed.7–9 In 2016, Huo reported an auto-oxidative
The formation of C–S bond has captured growing attention for
fundamental field of research in organic synthesis because sul-
fur-containing compounds widely emerged in various research
fields.1 In particular, unsymmetrical sulfides, have been exten-
sively applied in bioactivator, natural products and medicinal
chemistry.2 (Scheme 1). Therefore, facile and effective methods
leading to unsymmetrical sulfides have gained intensive interest
from synthetic chemists and pharmacologists.3
The traditional strategies for the synthesis of unsymmetrical
sulfides are transition metal-catalyzed sulfenylation of arene with
thiols or disulfides.4 In recent years, nonmetal-catalyzed sulfenyla-
tion for the formation of C–S bond, especially, iodine-catalyzed
sulfenylation of arene with diverse sulfur reagents, has been
greatly developed because of these methods with excellent yields,
mild conditions, and good selectivity.5 However, the use of fetid,
sensitive, and toxic sulfenylating agents and transition-metal cata-
lysts involved in these methods might hinder their widespread
application. As a consequence, the development of efficient, facile,
and environmentally-friendly protocol to obtain unsymmetrical
sulfides still remains extremely significant and attractive.
hydroxysulfenylation of alkene to construct C–S bond for beta-
hydroxysulfides.8 Iodine-catalyzed protocol for arylsulfenylation
of 4-hydroxycoumarins with thiols was reported by Peddinti
group. Lee disclosed a CuBr/Me2S-catalyzed synthesis of aryl-
sulfenylated 4-hydroxycoumarins with arylsulfonylhydrazides.9
Although several strategies for the synthesis of beta-hydroxy-
sulfides and arylsulfenylated coumarins have been described, these
methods involved in the use of fetid thiols, environmentally malign
triphenylphosphine, and metallic reagents. Recently, thiosulfates
have gained extensive attention because they are stable, readily
available, and environmentally benign, as a result, thiosulfates
have been widely applied in the formation of C–S bond.10 Here,
we described a novel, efficient, and green method for the formation
of C–S using H2O2 as oxidant with environmentally-friendly and
HBr as catalyst leading to beta-hydroxysulfides and sulfenylated
4-hydroxycoumarins (Scheme 2).
Results and discussion
We initially optimized the reaction of sodium 4-chlorophenyl
thiosulfate 1a and styrene 2a in the presence of various catalysts,
oxidants and acetonitrile as solvent (Table 1). Bromides catalysts
were explored for hydrosulfenylation of syrene 2a to construct
b-hydroxyl sulfide in acetonitrile at 30 °C for 30 min, which
afforded desired product 3a in low yields (Table 1, entries 1–6).
Among the catalysts, HBr produced the best result (Table 1, entry
6). Subsequently, we explored the effect of temperature for
Beta-hydroxysulfides and sulfenylated coumarin derivatives are
vital unsymmetrical sulfides as intermediates widely found in
bioactives and pharmaceutical molecules.6 Because of their avail-
ability and importance, several strategies for the synthesis of
⇑
Corresponding authors.
E-mail address: 990831948@qq.com (Z. Yan).
https://doi.org/10.1016/j.tetlet.2018.01.055
0040-4039/Ó 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Zhang R., et al. Tetrahedron Lett. (2018), https://doi.org/10.1016/j.tetlet.2018.01.055

2
R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
R
Various thiosulfates and styrene derivatives were employed to
H
COOH
S
S
construct bata-hydroxysulfides under the optimized reaction con-
ditions (Table 2). When sodium s-(4-methylphenyl) thiosulfate and
sodium s-(4-chlorophenyl) thiosulfate were respectively subjected
to hydroxysulfenylation with syrene 2a (Table 2, 3a–3b), the
results showed that the desired products were obtained in good
yields. A bad result was gained when sodium butylthiosulfate
(Table 2, 3c), and s-benzylthiosulfate were used as the substrates
under optimized condition, However, an interesting phenomenon
was discovered when the temperature was increased to 100 °C
for s-benzylthiosulfate, the corresponding product was detected
in 65% yield (Table 2, 3da) for 30 min and beta-acetamidosulfide
was gained in moderate yield for 10 h (Table 2, 3db). A class of
styrene derivatives with groups (F, Cl, Br) were conducted to
hydroxysulfenylation with s-(4-chlorophenyl) thiosulfate and
desired products were obtained in moderate to good yields
(Table 2, 3e–3i). Unfortunately, hydroxysulfenylation of cyclohex-
ene did not work under the optimized reaction conditions (Table 2,
3j).
S
R
O
H2N
Z
S
N
O
COOH
Methionine
CTAs
Penicillin
Br
O
OH
N
S
N
O
N
NH
S
N
H
Et
CO2
Arbidol
Albendazole
Scheme 1. Unsymmetrical sulfides applied in medicinal chemistry.
To further extend the substrate scope of this method, alkenes 4,
were next investigated and results showed that the corresponding
thioethers containing five-membered ether and lactone were pro-
duced in good to excellent yields (Table 3, 5a–5c).
Scheme 2. Method for the synthesis of beta-hydroxysulfides and sulfenylated
coumarins via HBr/H2O2.
hydrosulfenylation of styrene 2a with sodium 4-chlorophenyl thio-
sulfate 1a (Table 1, entries 7–10), the results showed that 60 °C
was the best choice and the corresponding product 3a was
obtained in 72% yield (Table 1, entry 9). The yield was improved
when HBr was increased to 0.5 equivalent (Table, entries 10–12).
3a was not formed when HCl or HI were employed as catalyst
Likewise, the method is suitable for the synthesis of
sulfenylated aromatic derivatives under this system. First we
conducted sulfenylation of 4-hydroxycoumarin which is important
pharmaceutical intermediate6c,d and the positive results
were described when reaction temperature was increased to 100
°C for 10 h (Table 4). The reactions of 4-hydroxycoumarin and a
series of thiosulfates afforded sulfenylated 4-hydroxycoumarins
and desired products were obtained in good yields
(Table 4, 7a–7f). Next, we turned our attention to sulfenylation
of 4-hydroxyquinolin-2(1H)-one and cyclohexane-1,3-dione
structurally similar to 4-hydroxycoumarin with thiosulfates and
positive results have been obtained (Table 4, 7g–7h). However,
(Table 1, entries 13–14).
A negative effects emerged when
K2S2O8, DBHP, and TBHP were employed as oxidants (Table 1,
entries 15–17). Thus, the optimized conditions were established
as follows: 4-chlorophenyl thiosulfate 1a (1.2 equiv), styrene 2a
(1.0 equiv), HBr (50 mol%) as catalyst, H2O2 (2.0 equiv) as oxidant,
and nitrile as the solvent for 30 min at 60 °C in a sealed tube.
Table 1
Optimization of reaction conditions for beta-hydroxy sulfides.
Entry
Catalysts (mol%)
Oxidants (equiv.)
Temp (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
À(20)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
H2O2 (2.0)
K2S2O8 (2.0)
DBHP (2.0)
TBHP (2.0)
30
30
30
30
30
30
40
50
60
80
60
60
60
60
60
60
60
N.R.
12
20
15
23
32
54
63
72
68
78
85
N.R.
N.R.
N.R.
Trace
32
NBS (20)
NaBr (20)
TBAB (20)
Br2 (10)
HBr (20)
HBr (20)
HBr (20)
HBr (20)
HBr (20)
HBr (30)
HBr (50)
HCl (50)
HI (50)
9
10
11
12
13
14
15
16
17
HBr (50)
HBr (50)
HBr (50)
aReaction conditions: 1a (0.24 mmol), 2a (0.20 mmol), oxidants (0.40 mmol), MeCN (1.0 mL), 47% wt HBr (0.10 mmol), 30 min, in a sealed tube.
b
Yield of isolated product.
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R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
3
Table 2
Substrate scope of beta-hydroxy sulfides.
aReaction conditions: 1 (0.24 mmol), 2 (0.20 mmol), CH3CN (1.0 mL), 30%wt H2O2 (0.40 mmol),
47% wt HBr (0.10 mmol), in a sealed tube at 60 °C for 30 min. bYield of isolated product. cAt 100 °C.
dAt 100 °C for 10 h.
Table 3
The formation of thioethers with five-membered ether and lactone.
aReaction conditions: 4 (0.20 mmol), 1d (0.24 mmol), CH3CN (1.0 mL), 30%wt H2O2
(0.40 mmol), 47% wt HBr (0.10 mmol), 100 °C, 3–4 h in a sealed tube. bYield of
isolated product.
Table 4
Substrate scope of sulfenylated 4-hydroxycoumarins.
Scheme 3. Control experiments in various conditions.
unsatisfactory result emerged for sulfenylation of coumarin with
thiosulfate (Table 4, 7i).
To gain further insight into these reaction mechanism, several
control experiments were descried under various reaction
aReaction conditions: 1 (0.24 mmol), 6 (0.20 mmol), CH3CN (1.0 mL), 30%wt H2O2
(0.40 mmol), 47% wt HBr (0.10 mmol), in a sealed tube at 100 °C for 10 h. bYield of
isolated product.
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4
R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
m = multiplet, br = broad signal. Chemical shifts (d) and coupling
constants (J) were expressed in ppm and Hz, respectively. Thiosul-
fates were prepared according to the literature13 procedure. The
rest of chemicals were purchased from the Sinopharm Chemical
Reagent Co., Adamas, Aladdin and TCI used as received. HRMS
(ESI) data were obtained in the electron impact (EI) model.
General procedure for compounds 3
47 wt% HBr (0.10 mmol) and styrene derivatives 2 (0.20 mmol)
were added to a solution of thiosulfates 1 (0.24 mmol) in nitrile,
followed by the addition of 30 wt% H2O2 (0.40 mmol). The reaction
mixture was stirred in a sealed tube at 60 °C for 30 min. After com-
pletion of the reaction, the reaction mixture was cooled and puri-
fied by flash column chromatography on silica gel to afford
product. The following compounds have previously been reported
in the literature: 3a8, 3b8, 3db,14a 3e,14b 3h,14b 3k.7c
Scheme 4. Plausible reaction mechanisms for H2O2-mediated formation of C–S
bond with thiosulfates.
conditions Scheme 3. The yield of 3d did not change obviously
when butylated hydroxytoluene was added in the reaction of 1d
with 2a, which suggests that an ionic pathway was involved in
the reaction (Scheme 3, (a)). s-Benzylthiosulfate was transformed
into dibenzylsulfide under optimized conditions (Scheme 3, (b))
and both products 3d and 3k were obtained in good yields by
reactions of styrene 2a with disulfides (Scheme 3, (c) and (d)).
However, only trace of product 3k was observed when system
of hydrobromic acid and hydrogen peroxide was replaced by
enough bromine (Scheme 3, (e)). Similarly, the same phenomenon
were observed for the sulfenylation of 4-hydroxycoumarin 4a
(Scheme 3,(f)–(h)). It clearly indicated that the disulfide may act
as an intermediate and hydrogen peroxide play indispensable roles
for the reaction.
2-((4-Chlorophenyl)thio)-1-phenylethan-1-ol (3a)
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.37–7.25 (m, 9H), 4.72 (dd, J = 6.2,
2.7 Hz, 1H), 3.27 (dd, J = 13.7, 3.7 Hz, 1H), 3.10 (dd, J = 13.8, 9.2 Hz,
1H), 2.80 (d, J = 2.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 141.98,
133.63, 132.78, 131.46, 129.22, 128.60, 128.10, 125.83, 71.84,
44.05.
1-Phenyl-2-(p-tolylthio)ethan-1-ol (3b)
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.38–7.27 (m, 7H), 7.14 (d, J = 7.9
Hz, 2H), 4.71–4.65 (m, 1H), 3.28 (dd, J = 13.8, 3.4 Hz, 1H), 3.04
Based on the above experimental and previous reports,8–12
a
plausible mechanism was proposed in Scheme 4. Initially, the
disulfides C quickly emerged in this reaction system by hydrolysis
of thiosulfate A and oxidant of intermediate B.10d,e Next, the alkyl-
sulfenylbromine D would emerge through the reaction of disulfide
C with bromine.11 Subsequently the electrophilic species E was
quickly released because the RSBr D species was oxidized to the
bromine by catalytic cycle (Scheme 4(d), (e)). Meanwhile, interme-
diates F or G emerged by the attack of electrophilic species E to the
double bond of styrene or 4-hydroxycoumarins.9,12 Finally, the
intermediate F was attacked by water leading to desired product
H and intermediate G was converted to sulfenylated 4-hydroxy-
coumarin I through releasing hydrogen ion.9,12
(dd, J = 13.8, 9.6 Hz, 1H), 2.95 (d, J = 2.2 Hz, 1H), 2.35 (s, 3H).13
C
NMR (100 MHz, CDCl3) d 142.17, 137.11, 131.05, 130.94, 129.94,
128.51, 127.90, 125.85, 71.49, 44.81, 21.06.
2-(Benzylthio)-1-phenylethan-1-ol (3da)
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, CDCl3) d 7.45 (d, J = 8.4 Hz, 2H), 7.39–7.22
(m, 6H), 7.16 (d, J = 8.3 Hz, 2H), 4.60–4.58 (m, 1H), 3.72 (s, 2H),
2.93 (s, 1H), 2.73 (dd, J = 14.0, 3.7 Hz, 1H), 2.60 (dd, J = 13.9, 9.2
Hz, 1H). 13C NMR (100 MHz, CDCl3) d 141.49, 137.72, 131.56,
128.92, 128.68, 127.47, 127.35, 121.58, 71.08, 40.79, 36.21. HRMS
(ESI) (m/z) Calcd for:
C
15H16OS [M+Na]+: 267.0814, found:
Conclusions
267.0802.
In summary, we have successfully developed a novel, efficient,
and green method for the formation C–S bond via HBr/H2O2-medi-
ated sulfenylation of styrene derivatives and 4-hydroxycoumarin
leading to unsymmetrical sulfides, in which stable and odourless
thiosulfates were employed as thiolating reagents, HBr as catalyst,
and environmentally-friendly H2O2 as oxidant. A series of beta-
hydroxysulfides and sulfenylated 4-hydroxycoumarins were pre-
pared in one step with moderate to good yields under simple
and green conditions. The new synthetic method for unsymmetri-
cal sulfides may be used extensively in the future.
N-(2-(Benzylthio)-1-phenylethyl)acetamide (3db)
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, CDCl3) d 7.34–7.20 (m, 10H), 6.15 (d, J = 7.0
Hz, 1H), 5.15 (dd, J = 13.9, 6.8 Hz, 1H), 3.61–3.52 (m, 2H), 2.86–2.77
(m, 2H), 1.96 (s, 3H). 13C NMR (100 MHz, CDCl3) d 169.58, 140.75,
137.9, 128.95, 128.68, 128.56, 127.67, 127.16, 126.45, 52.10, 37.17,
36.40, 23.30.
2-((4-Chlorophenyl)thio)-1-(4-fluorophenyl)ethan-1-ol (3e)
Experimental section
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.29 (dt, J = 13.5, 8.6 Hz, 6H), 7.02
(t, J = 8.7 Hz, 2H), 4.68 (dd, J = 5.9, 3.0 Hz, 1H), 3.23 (dd, J = 13.8,
3.8 Hz, 1H), 3.06 (dd, J = 13.8, 9.1 Hz, 1H), 2.85 (d, J = 2.5 Hz, 1H).
13C NMR (100 MHz, CDCl3) d 163.65, 161.20, 137.71 (d, J = 3.1
Hz), 133.36, 132.96, 131.60, 129.27, 127.54 (d, J = 8.1 Hz), 115.55,
115.34, 71.17, 44.17.
General methods
1H and 13C NMR spectra were recorded on Bruker AscendTM 400
(400 MHz) using tetramethylsilane as an internal reference. NMR
multiplicities are abbreviated as follows: s = singlet, d = doublet,
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R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
5
1-(2-Chlorophenyl)-2-((4-chlorophenyl)thio)ethan-1-ol (3f)
4.88 (m, 1H), 3.82 (s, 2H), 3.30 (dd, J = 15.6, 9.1 Hz, 1H), 3.01 (dd,
J = 15.7, 6.8 Hz, 1H), 2.81 (dd, J = 11.9, 5.9 Hz, 1H), 2.70 (dd, J =
13.7, 6.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 159.13, 138.15,
128.98, 128.56, 128.05, 127.12, 126.27, 124.98, 120.53, 109.40,
82.18, 36.79, 36.07, 34.95. HRMS (ESI) (m/z) Calcd for C16H16OS
[M+Na]+: 279.0814, found: 279.0794.
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.63 (d, J = 7.8 Hz, 1H), 7.38 (d, J =
8.5 Hz, 2H), 7.25 (ddd, J = 15.1, 13.5, 6.8 Hz, 5H), 5.10 (d, J = 9.4 Hz,
1H), 3.46 (dd, J = 14.0, 2.8 Hz, 1H), 2.94–2.87 (m, 2H). 13C NMR
(100 MHz, CDCl3)
d 139.28, 133.02, 133.00, 132.88, 131.55,
129.41, 129.14, 128.96, 127.26, 127.09, 68.24, 42.18. HRMS (ESI)
2-((benzylthio)methyl)tetrahydrofuran (5b)
(m/z) Calcd for: C14H12Cl2OS [M+H]+: 299.0059, found: 299.0069.
Purified by using a flash column chromatography. Yellow oil.
1H NMR (400 MHz, CDCl3) d 7.36–7.18 (m, 5H), 4.03–3.96
(m,1H), 3.92–3.84 (m, 1H), 3.80–3.70 (m, 3H), 2.59 (dd, J = 13.2,
6.1 Hz, 1H), 2.51 (dd, J = 13.3, 5.9 Hz, 1H), 2.04–1.95 (m, 1H),
1.93–1.80 (m, 2H), 1.64–1.53 (m, 1H). 13C NMR (100 MHz, CDCl3)
d 138.46, 128.93, 128.43, 126.92, 78.54, 68.22, 36.83, 36.22,
31.01, 25.77.
1-(3-Chlorophenyl)-2-((4-chlorophenyl)thio)ethan-1-ol (3g)
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.35–7.16 (m, 8H), 4.70–4.64 (m,
1H), 3.25 (dd, J = 13.9, 3.7 Hz, 1H), 3.05 (dd, J = 13.9, 9.2 Hz, 1H),
2.85 (d, J = 2.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 143.95,
134.51, 133.11, 131.10, 131.76, 129.85, 129.31, 128.16, 126.05,
123.97, 71.13, 44.17. HRMS (ESI) (m/z) Calcd for: C14H12Cl2OS [M
+Na]+: 320.9878, found: 320.9866.
5-((Benzylthio)methyl)dihydrofuran-2(3H)-one (5c)
Purified by using a flash column chromatography. Yellow oil.
1H NMR (400 MHz, CDCl3) d 7.45–7.04 (m, 5H), 4.60–4.54 (m,
1H), 3.77 (d, J = 1.9 Hz, 2H), 2.66 (qd, J = 14.2, 5.8 Hz, 2H), 2.57–
2.42 (m, 2H), 2.34–2.25 (m, 1H), 2.00–1.90 (m, 1H). 13C NMR
(100 MHz, CDCl3) d 176.74, 137.73, 129.01, 128.59, 127.25, 79.79,
36.96, 35.33, 28.50, 26.84. HRMS (ESI) (m/z) Calcd for C12H14O2S
[M+Na]+: 245.0607, found: 245.0595.
1-(4-Chlorophenyl)-2-((4-chlorophenyl)thio)ethan-1-ol (3h)
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.45 (d, J = 8.3 Hz, 2H), 7.29 (dd, J =
18.8, 8.6 Hz, 4H), 7.19 (d, J = 8.2 Hz, 2H), 4.65 (dd, J = 6.0, 2.9 Hz,
1H), 3.22 (dd, J = 13.8, 3.7 Hz, 1H), 3.04 (dd, J = 13.8, 9.1 Hz, 1H),
2.86 (d, J = 2.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 140.39,
133.77, 133.19, 133.07, 131.71, 129.30, 128.72, 127.21, 71.10,
44.19.
General procedure for compounds 7
47 wt% HBr (0.10 mmol) and compounds 6 (0.20 mmol) were
added to a solution of thiosulfate 1 (0.24 mmol) in nitrile, followed
by the addition of 30 wt% H2O2 (0.40 mmol). The reaction mixture
was stirred in a sealed tube at 100 °C for 10 h. After completion of
the reaction, the reaction mixture was cooled and purified by flash
column chromatography on silica gel to afford product 7. The fol-
lowing compounds have previously been reported in the literature:
7j,9 7j,9 8d.15b
1-(4-Bromophenyl)-2-((4-chlorophenyl)thio)ethan-1-ol (3i)
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, CDCl3) d 7.45 (d, J = 8.3 Hz, 2H), 7.29 (dd, J =
18.8, 8.6 Hz, 4H), 7.19 (d, J = 8.2 Hz, 2H), 4.65 (dd, J = 6.0, 2.9 Hz,
1H), 3.22 (dd, J = 13.8, 3.7 Hz, 1H), 3.04 (dd, J = 13.8, 9.1 Hz, 1H),
2.86 (d, J = 2.3 Hz, 1H).13C NMR (100 MHz, CDCl3) d 140.92,
133.19, 133.07, 131.70, 131.67, 129.31, 127.55, 121.89, 71.15,
44.10. HRMS (ESI) (m/z) Calcd for:
C
14H12BrClOS [M+Na]+:
3-((4-Chlorophenyl)thio)-4-hydroxy-2H-chromen-2-one (7a)
376.9175, found: 376.9182.
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 7.94 (dd, J = 8.0, 1.7 Hz, 1H),
7.69 (ddd, J = 8.6, 7.2, 1.7 Hz, 1H), 7.43–7.34 (m, 2H), 7.33–7.27
(m, 2H), 7.23–7.16 (m, 2H). 13C NMR (100 MHz, DMSO d6) d
169.12, 161.28, 153.50, 135.64, 134.17, 130.50, 129.37, 128.37,
124.84, 124.70, 116.95, 116.24, 94.29. HRMS (ESI) (m/z) Calcd
for: C15H9ClO3S [M+H]+: 305.0034, found: 305.0040.
1-Phenyl-2-(phenylthio)ethan-1-ol (3k)
Purified by using a flash column chromatography. White oil.
1H NMR (400 MHz, CDCl3) d 7.42 (dd, J = 8.2, 0.8 Hz, 2H), 7.39–
7.20 (m, 8H), 4.75–4.70 (m, 1H), 3.33 (dd, J = 13.8, 3.5 Hz, 1H), 3.10
(dd, J = 13.8, 9.4 Hz, 1H), 2.87 (d, J = 2.4 Hz, 1H). 13C NMR (100
MHz, CDCl3) d 142.12, 134.87, 130.21, 129.13, 128.55, 127.98,
126.78, 125.84, 71.66, 44.03.
4-Hydroxy-3-(p-tolylthio)-2H-chromen-2-one (7b)
General procedure for compounds 5
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 7.92 (dd, J = 7.9, 1.6 Hz, 1H),
7.70–7.65 (m, 1H), 7.41–7.35 (m, 2H), 7.08 (d, J = 2.4 Hz, 4H),
2.21 (s, 3H). 13C NMR (100 MHz, DMSO d6) d 168.41, 161.25,
153.38, 135.61, 134.03, 132.60, 130.13, 127.34, 124.75, 124.70,
116.90, 116.06, 95.64, 20.91. HRMS (ESI) (m/z) Calcd for:
47 wt% HBr (0.10 mmol) and compounds 4 (0.20 mmol) were
added to a solution of s-benzylthiosulfate 1d (0.24 mmol) in nitrile,
followed by the addition of 30 wt% H2O2 (0.40 mmol). The reaction
mixture was stirred in a sealed tube at 100 °C for 5 h. After comple-
tion of the reaction, the reaction mixture was cooled and purified
by flash column chromatography on silica gel to afford product 5.
The following compounds have previously been reported in the lit-
erature: 5b.15
C
16H12O3S [M+Na]+: 307.0399, found: 307.0413.
4-Hydroxy-3-((3-methoxyphenyl)thio)-2H-chromen-2-one (7c)
2-((Benzylthio)methyl)-2,3-dihydrobenzofuran (5a)
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 7.95–7.91 (m, 1H), 7.72–7.66
(m, 1H), 7.42–7.35 (m, 2H), 7.19–7.14 (m, 1H), 6.71 (q, J = 4.0,
3.2 Hz, 3H), 3.68 (s, 3H). 13C NMR (100 MHz, DMSO d6) d 168.90,
161.32, 160.09, 153.48, 137.70, 134.14, 130.47, 124.81, 124.70,
Purified by using a flash column chromatography. Yellow oil.
1H NMR (400 MHz, CDCl3) d 7.38–7.22 (m, 5H), 7.13 (dd, J =
17.6, 7.7 Hz, 2H), 6.85 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H),
Please cite this article in press as: Zhang R., et al. Tetrahedron Lett. (2018), https://doi.org/10.1016/j.tetlet.2018.01.055

6
R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
118.73, 116.95, 116.11, 112.37, 111.46, 94.63, 55.58. HRMS (ESI)
1,2-Dibenzyldisulfane (8d)
(m/z) Calcd for: C16H12O4S [M+Na]+: 329.1182, found: 329.1188.
1H NMR (400 MHz, CDCl3) d 7.38–7.20 (m, 5H), 3.62 (s, 2H). 13
NMR (100 MHz, CDCl3) d 137.37, 129.42, 128.49, 127.43, 43.30.
C
3-(Benzylthio)-4-hydroxy-2H-chromen-2-one (7d)
Acknowledgment
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 7.77 (dd, J = 8.0, 1.6 Hz, 1H),
7.60 (td, J = 7.8, 7.2, 1.6 Hz, 1H), 7.35–7.27 (m, 2H), 7.26–7.16 (m,
4H), 7.14 (dd, J = 6.7, 2.1 Hz, 1H), 3.99 (s, 2H). 13C NMR (100
MHz, DMSO d6) d 166.51, 161.18, 152.86, 137.93, 133.42, 129.37,
128.63, 127.41, 124.58, 124.28, 116.71, 115.74, 97.15, 37.18. HRMS
We thank the National Natural Science Foundation of China
(No. 21362022) for financial support.
A. Supplementary data
(ESI) (m/z) Calcd for:
C
16H12O3S [M+H]+: 285.0580, found:
285.0584.
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.tetlet.2018.01.055.
3-(Butylthio)-4-hydroxy-2H-chromen-2-one (7e)
References
Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 7.85 (dd, J = 7.9, 1.6 Hz, 1H),
7.64–7.59 (m, 1H), 7.37–7.31 (m, 2H), 2.71 (t, J = 7.3 Hz, 2H), 1.43
(dd, J = 10.5, 4.8 Hz, 2H), 1.32 (q, J = 7.3 Hz, 2H), 0.79 (t, J = 7.3 Hz,
3H). 13C NMR (101 MHz, DMSO d6) d 166.53, 161.26, 152.90,
133.36, 124.58, 124.28, 116.72, 115.83, 97.44, 32.96, 31.48, 21.64,
13.94. HRMS (ESI) (m/z) Calcd for: C13H14O3S [M+Na]+: 275.0712,
found: 275.0718.
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Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, CDCl3) d 8.06 (bs, 1H), 7.86 (d, J = 7.8 Hz,
1H), 7.59 (t, J = 7.8 Hz, 1H), 7.35–7.28 (m, 2H), 2.80 (t, J = 7.5 Hz,
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Hz, 8H), 0.84 (t, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) d
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97.85, 33.97, 31.70, 29.81, 29.09, 29.06, 28.69, 22.58, 14.05. HRMS
(ESI) (m/z) Calcd for:
C
17H22O3S [M+Na]+: 323.0349, found:
323.0348.
3-((4-Chlorophenyl)thio)-4-hydroxyquinolin-2(1H)-one (7g)
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Purified by using a flash column chromatography. White solid.
1H NMR (400 MHz, DMSO d6) d 11.57 (s, 1H), 7.94–7.81 (m, 1H),
7.61–7.51 (m, 1H), 7.28 (dd, J = 8.5, 3.6 Hz, 3H), 7.18 (t, J = 7.6 Hz,
1H), 7.13–7.06 (m, 2H). 13C NMR (100 MHz, DMSO d6) d 166.15,
161.96, 139.57, 136.57, 132.58, 130.02, 129.18, 128.11, 124.30,
121.96, 115.72, 114.86, 100.38. HRMS (ESI) (m/z) Calcd for: C15H10
-
NO2S [M+Na]+: 326.0013, found: 304.0023.
2-(Benzylthio)-3-hydroxycyclohex-2-en-1-one (7h)
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Purified by using a flash column chromatography. Yellow oil.
1H NMR (400 MHz, CDCl3) d 7.54 (s, 1H), 7.24 (d, J = 7.9 Hz, 2H),
7.12–7.09 (m, 2H), 3.75 (s, 2H), 2.44 (t, J = 6.6 Hz, 2H), 2.38 (d, J =
6.3 Hz, 2H), 1.92–1.87 (m, 2H). 13C NMR (100 MHz, CDCl3) d
194.71, 179.46, 137.86, 128.79, 128.40, 127.31, 37.69, 37.22,
27.98, 19.90. HRMS (ESI) (m/z) Calcd for: C13H14O2S [M+Na]+:
257.0607, found: 257.0607.
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4-Hydroxy-3-(phenylthio)-2H-chromen-2-one (7j)
1H NMR (400 MHz, DMSO d6) d 7.94 (dd, J = 7.9, 1.1 Hz, 1H),
7.72–7.65 (m, 1H), 7.39 (dd, J = 12.7, 7.7 Hz, 2H), 7.26 (t, J = 7.6
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DMSO d6)
d 168.87, 161.31, 153.47, 136.34, 134.11, 129.51,
126.64, 125.97, 124.79, 124.69, 116.93, 116.13, 94.75.
Please cite this article in press as: Zhang R., et al. Tetrahedron Lett. (2018), https://doi.org/10.1016/j.tetlet.2018.01.055

R. Zhang et al. / Tetrahedron Letters xxx (2018) xxx–xxx
7
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