Pd(II)-catalyzed selective sulfenylation of arene C-H bonds using N-arylthiobenzamides as thiolation reagent and oxidant

Article abstract of DOI:10.1016/j.tet.2015.06.077

The palladium-catalyzed direct sulfenylation of arenes with N-arylthiobenzamides was developed for the synthesis of aryl sulfides. Additional oxidant was not required for the catalytic cycle because N-arylthiobenzamide was used as both thiolation reagent and oxidant. The selective mono- or di-sulfenylation could be controlled by addition of the amount of N-arylthiobenzamide. Excellent functional group tolerance was observed and thioethers or dithioethers were obtained in good yields.

Full text of DOI:10.1016/j.tet.2015.06.077

Accepted Manuscript
Pd(II)-Catalyzed Selective Sulfenylation of Arene C−H Bonds Using N-
Arylthiobenzamides as Thiolation Reagent and Oxidant
Xing-Song Zhang, Guoxing Li, Xing-Guo Zhang, Xiao-Hong Zhang
PII:
S0040-4020(15)00974-6
10.1016/j.tet.2015.06.077
TET 26913
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 May 2015
Revised Date: 15 June 2015
Accepted Date: 20 June 2015
Please cite this article as: Zhang X-S, Li G, Zhang X-G, Zhang X-H, Pd(II)-Catalyzed Selective
Sulfenylation of Arene C−H Bonds Using N-Arylthiobenzamides as Thiolation Reagent and Oxidant,
Tetrahedron (2015), doi: 10.1016/j.tet.2015.06.077.
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Pd(II)-Catalyzed Selective Sulfenylation of Arene C−H
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Bonds Using N-Arylthiobenzamides as Thiolation Reagent
and Oxidant
Xing-Song Zhang, Guoxing Li, and Xing-Guo Zhang*, Xiao-Hong Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
Tel./Fax: (+86)-577-8668-9615; e-mail: zxg@wzu.edu.cn and kamenzxh@wzu.edu.cn

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Tetrahedron
journal homepage: www.elsevier.com
Pd(II)-Catalyzed Selective Sulfenylation of Arene C−H Bonds Using N-Arylthiobenzamides as
Thiolation Reagent and Oxidant
Xing-Song Zhang, Guoxing Li, and Xing-Guo Zhang*, Xiao-Hong Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
Tel./Fax: (+86)-577-8668-9615; e-mail: zxg@wzu.edu.cn and kamenzxh@wzu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The palladium-catalyzed direct sulfenylation of arenes with N-arylthiobenzamides was
developed for the synthesis of aryl sulfides. Additional oxidant was not required for the catalytic
cycle because N-arylthiobenzamide was used as both thiolation reagent and oxidant. The
selective mono- or di- sulfenylation could be controlled by addition of the amount of N-
arylthiobenzamide. Excellent functional group tolerance was observed and thioethers or
dithioethers were obtained in good yields.
Available online
Keywords:
2
009 Elsevier Ltd. All rights reserved.
palladium; N-arylthiobenzamides; aryl sulfides;
selective; mono- or di- sulfenylation
1
. Introduction
The reaction between 2-phenylpyridine 1a and N-
[12]
(
phenylthio)benzamide 2a
was selected as a model reaction to
Aryl sulfides are a class of versatile compounds which are
optimize the reaction conditions, and the results were
summarized in Table 1. Initially, the reaction of 2-
phenylpyridine 1a and N-(phenylthio)benzamide 2a, 10 mol% of
frequently found in biologically active natural products,
pharmaceuticals, and materials, as well as building blocks in
organic synthesis.
cross-coupling reaction of thiols with aryl halides is the most
practical approach for the synthesis of these aryl thioethers.
However, these procedures suffer from the prefunctionalization
of arenes, which limit the substrate scope of thiolation. Lewis
acids catalyzed electrophilic thiolation of electron-rich arenes
and deprotonative thiolation of acidic arenes provide two
routes to some special diaryl sulfides.
Recently, palladium-catalyzed C-H bond functionalization of
arenes bearing directing groups has emerged as a powerful
method for selective synthesis of multi-substituted arenes, and
much attention has been paid to C-C, C-O, and C-N bond
forming reactions.
formation through nonactivated arene C-H bond activation are
[
1]
[
2]
Traditionally, transition-metal-catalyzed
o
Pd(OAc) was carried out in acetic acid at 120 C under N
2
2
atmosphere to afford the desired product 3a in 51% yield (entry
). We next investigated various catalysts, such as PdCl2,
Pd(PPh) Cl , Pd(MeCN) Cl and Cu(OAc) (entries 2-5). It was
[
3]
1
2
2
2
2
2
found that Pd(MeCN) Cl2 provided the best results and the
[
4]
2
product 3a could be isolated in 62% yield (entry 4). Only trace
[
5]
amount of product was observed using Cu(OAc) as catalyst
2
(
entry 5), and the reaction did not occur in the absence of
catalyst (entry 6). Encouraged by these results, we further
screened the reaction conditions by examining different solvents,
including CH CN, DCE, THF, DMSO, DMF and CF COOH
3
3
(
entries 7-12). The results disclosed that DMF was the most
[
6]
However, palladium catalyzed C-S
effective, and the reaction gave product 3a in 73% yield (entry
11). The reaction yield was improved to 86% by increasing the
amount of substrate 2a to 1.5 equiv (entry 13). The similar yield
[
7]
significantly rare,
presumably due to palladium catalyst
[8]
poisoning by the mercapto group. Therefore, stoichiometric or
substoichiometric amounts of copper or silver mediated
sulfenylation of arene C−H bonds were developed as an
alternative route for the synthesis of aryl sulfides.
rhodium or palladium catalyzed thiolation of aryl C-H bonds,
copper salts are also required to be used as assistant oxidant.
Inspired by Sanford’s mechanistic studies on oxidation of
cyclopalladium (II) dimer,
solely catalyzed C−H sulfenylation by regulating the electronic
properties of sulfur reagents to avoid catalyst poisoning. Herein,
we report a Pd (II)-catalyzed selective C−H sulfenylation of
arenes using N-acyl sulfonamides as both reactant and oxidant.
o
was obtained when reaction was carried out at 130 C, while the
o
reaction yield was decreased to 62% at 110 C (entries 14 and
[
9]
15). It was found that the yield was sharply reduced to 45%
when the loading of the Pd catalyst was decreased to 5 mol%
(entry 16). It is worth noting that 29 % yield was observed when
N-phenylthiophthalimide was used as thiolation reagent (entry
17). N-phenylthio-succimimide (1.5 equiv) was also tested,
giving the aimed product 3a in 63% yield, accompanied with the
di-thiolation product in 15 % yield (entry 18). The results
suggested that the electronic property of N-S bond have
significant affection on the C-H sulfenylation reaction and N-
In some
[
10]
[
11]
we envisioned to realize palladium
(
phenylthio)benzamide
2a
was
superior
to
N-
2
. Results and discussion
phenylthiophthalimide and N-phenylthiosuccimimide in view of
yields and selectivity.

2
ACCEPTED MANUSCRIPT
a
Table 1. Screening Conditions
deficient arenes were compatible for the C-H sulfenylation.
Methyl substituted product 3k and 3l were obtained in 78% and
8
8% yields, respectively.
Table 2. Pd-Catalyzed ortho Mono-thiolation of
a
Arene C-H Bonds
o
Entry
Catalyst
Solvent T ( C) Yield (%)
1
2
3
4
5
6
7
8
9
Pd(OAc)2
PdCl2
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
120
120
120
120
120
120
120
120
120
120
120
51
50
Py
Py
Py
Py
Py
Py
F
S
S
S
Ph
Pd(PPh) Cl2
21
2
Me
Pd(MeCN) Cl2
62
3a, 86%
3b, 69%
3c, 75%
2
Py
S
Cu(OAc)2
-
trace
NR
40
Cl
S
S
F
Pd(MeCN) Cl2
MeCN
DCE
Cl
3f, 90%
2
3
d, 70%
3e, 98%
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Pd(MeCN)
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
47
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Py
Py
Py
S
Cl
S
S
THF
26
1
1
1
0
1
2
DMSO
DMF
41
Cl
NO2
Cl
3
i, 74%
73
3g, 81%
3h, 69%b
Py
CF COOH 120
NR
86
Py
Py
3
S
S
S
Ph Me
S
S
b
Ph
Me
Ph
1
3
4
5
DMF
DMF
DMF
DMF
DMF
DMF
120
Me
b
b
Me
1
1
130
110
120
120
120
84
3l, 88%b
3m, 42%b
3
j, 61%
3k, 78%
62
Py
Py
Py
Py
b,c
S
S
S
1
6
45
Ph
Ph
Ph
Ph
S
Ph
d
1
7
29
F
F
C H
OMe
F
2
5
e
1
8
63
3
n, 83%
3o, 62%
3q, 53%b
3
p, 68%
a
Reaction conditions: 1a (0.30 mmol), 2a (0.36 mmol),
catalyst (10 mol %), and 2 mL solvent at the indicated
temperature under N atmosphere for 24 h. 0.45 mmol of 2a
was used.
Py
S
Py
Py
Py
S
S
S
b
Ph
Ph
Ph
2
c
d
catalyst (5 mol %).
0.45 mmol of N-
0.45 mmol of N-
e
phenylthiophthalimide instead of 2a.
Cl
Br
CF3
CN
phenylthiosuccimimide.
3s, 61%c
3r, 75%
3t, 62%
3u, 83%
With the optimized conditions in hand, we next investigated
the substrate scope of C-H sulfenylation by testing the mono-
thiolation reaction between arenes and N-arylthiobenzamides
Py
S
N
N
S
N
N
Ph H C
3
S
S
Ph
(
Table 2). Initially, a wide variety of N-arylthiobenzamides were
Ph
Ph
tested, the results showed that both electron-donating and
electron-withdrawing groups on arylthio moiety were tolerated
well. Methyl substituted benzamide provided product 3b in 69%
yield. Fluoride product 3c and 3d were obtained in 75% and 70%
yields, respectively. o, m, p-(Chlorophenylthio)benzamide
afforded corresponding product in 81-98% yields, while 3,5-
dichloride product 3h was isolated in 69% yield and 2 equiv of
COOEt
3w, 88%b
3x, 87%b
3
v, 79%
3y, 42%
a
Reaction conditions:
Pd(MeCN) Cl (10 mol %) in dry DMF (2.0 mL) at 120 °C for
4 h under N atmosphere. 0.6 mmol 2 were used. 0.3 mmol 2
2
was used.
1 (0.3 mmol), 2 (0.45 mmol),
2
2
b
c
2
2
h was required. Substrate 2i bearing a strong electron-
withdrawing nitro group also afforded product 3i in 74% yield.
Gratifyingly, heteroarylthiobenzamide 2j underwent the
sulfenylation reaction with 1a smoothly to give thiophen-2-yl
thioether 3j in 61% yield. During the examination of substitution
effect on arenes, we found that both electron-rich and electron-
The bulky dimethyl pyridin-2-yl- xylene 1d was also
converted successfully to product 3m in 42% yield although 2
equiv of 2a was used. Ethyl substituted arene afforded product
3n in 83%, and methoxy produced 3o in 62% yields. Fluoride
and chloride products were obtained in 53-75% yields under

3
ACCEPTED MANUSCRIPT
standard conditions, while the loading of 2a must be reduced to
.0 equiv to avoid dithiolation (61%, 3s). The sulfenylation of
product 4j-4l were isolated in 96%-98% yields. Fluoride,
chloride and bromide arenes afforded 4m-4o in 72%-97% yields.
The disulfenylation of electron-deficient arenes bearing CN, CF3
or COOEt group also successfully provided products 4p, 4q and
4r in 97%, 87% and 92% yields, respectively. Gratifyingly, the
present dithiolation reaction was also suitable for 1-
phenylpyrazole, to give the corresponding product 4s in 97%
yield.
1
electron-deficient arenes bearing CF , CN and COOEt group also
3
proceeded smoothly to afforded product 3t, 3u and 3v in 62%
8
3% and 79% yields, respectively. Arenes containing a bulky
directing group, such as 3-methylpyridin-2yl and isoquinolin-1-
yl, were treated with N-(phenylthio)benzamide 2a to produce
corresponding thiolation products in good yields. Notably, other
N-based substrate, such as 1-phenylpyrazole, could also serve as
effective directing group to provide the corresponding mono-
thiolation product 3y in 42 % yield.
Scheme 1. Controlled Experiment.
a
O
Standard
Conditions
N
N
N
Table 3. Pd-Catalyzed ortho Dithiolation of Arene C-H Bonds
S
+
+ Ph
SPh
N
(1)
S
H
Me
Me
1
a
3a
2b
(0.45 mmol)
(
0.3 mmol) (0.3 mmol)
3b, 64% yield
N
O
o
OAc
DMF, N , 120 C
2
(2)
(3)
Pd
N
Ph NHSPh
+
2
SPh
2
a (1.5 equiv)
5
3a, 42%
O
1
0 mol % 5
N
N
Ph NHSPh
o
+
DMF, N , 120 C
2
SPh
1a
2a (1.5 equiv)
3a, 22%
To further study this C-H sulfenylation, thiolation of the
mixture of the 1a and 3a with 2b was conducted in the optimal
condition (scheme 1, eq 1). The results shown that only mono-
thiolation of 1a could proceed to give product 3b in 64% yield,
whereas the dithiolation of 3a or 3b was not observed. These
results suggested that monothiolation is prior to dithiolation.
Furthermore, we also carried out a stoichiometric reaction of the
known
palladacycle
5
with
1.5
equiv
of
N-
o
(phenylthio)benzamide 2a in DMF at 120 C under N2
atmosphere. As expected, the target product 3a could be isolated
in 42% yield (scheme 1, eq 2). Unfortunately, the attempts to
isolate oxidative addition product Pd(IV) complex failed. The
sulfenylation
of
2-phenylpyridine
1a
and
N-
(phenylthio)benzamide 2a catalyzed by 10 mol% palladacycle 5
also proceeded smoothly, albeit affording product 3a in a 22%
yield (scheme 1, eq 3). Compared to monomer palladium
catalyst, less reactive dimer Pd(II) complex resulted in low
yields. These results indicated that the C-H sulfenylation might
be involved a Pd(II)/Pd(IV) pathway.
Scheme 2. Possible Mechanism
a
Reaction conditions:
1 (0.3 mmol), 2 (1.2 mmol),
Pd(MeCN) Cl (10 mol %) in dry DMF (2.0 mL) at 120 °C for
2
2
2
4 h at N atmosphere.
2
Subsequently, we investigated the scope of the double C-H
activation/sulfenylation reaction (Table 3). Under standard
condition, 2-phenylpyridine 1a was treated with 4 equiv of N-
(phenylthio)benzamide 2a to afford dithioether 4a as a solely
product in 98% yield. Methyl substituted dithioether 4b was
obtained in 91% yield. Fluoride or chloride N-
(phenylthio)benzamides provided dithioethers 4c-4g in 88%-98%
yields. As expected, nitro substituted substrate 2i afforded
product 4h in 91% yield and heteroarylthiobenzamide 2j gave
thiophen-2-yl dithioether 4i in 90% yield. The dithiolation of
arenes bearing different substituents were examined, and almost
all arenes afforded the corresponding dithioethers in excellent
yields. For example, methyl, ethyl and methoxy substituted
Based on the above experimental results and previous reports,
7c, 10b]
[
a possible mechanism for selective sulfenylation was
proposed as outlined in Scheme 2. Firstly, the cyclopalladation
of 2-phenylpyridine 1a with Pd(MeCN) Cl2 produces
2
palladacycle complex A, the followed oxidative addition by N-

4
ACCEPTED MANUSCRIPT
[
10a]
(
phenylthio)benzamide 2a affords Pd(IV) intermediate B. The
4.2.2 2-(2-(p-tolylthio)phenyl)pyridine (3b):
white solid
o
1
reductive elimination of B gives product 3a which can udergo
second cyclopalladation to form intermediate C, followed by
oxidative addition of excess N-(phenylthio)-benzamide 2a to
yield intermediate D. Final reductive elimination affords product
(57.4 mg, 69% yield), mp 65-66 C. H NMR (500 MHz, CDCl )
δ 8.70-8.69 (m, 1H), 7.74-7.71 (m, 1H), 7.58 (d, J=7.5 Hz, 1H),
7.50-7.48 (m, 1H), 7.25-7.19 (m, 5H), 7.13-7.09 (m, 3H), 2.32
3
13
(s, 3H); C NMR (125 MHz, CDCl
) δ 158.5, 149.2, 140.6,
3
4
a and regenerate Pd(II) species.
. Conclusions
In summary, we have developed a palladium solely catalyzed
137.9, 136.8, 136.1, 133.3, 131.5, 130.4, 130.3, 130.2, 129.0,
+
1
3
26.2, 124.4, 122.2, 21.3; LRMS (EI, 70 eV) m/z (%): 277 (M ,
7), 186 (100), 276 (30), 206 (20), 187 (13).
3
4
.2.3 2-(2-((2-fluorophenyl)thio)phenyl)pyridine (3c): colorless
sulfenylation of arene C−H bonds by using N-arylthiobenzamide
as both thiolation reagent and oxidant. In the presence of
Pd(MeCN) Cl , a variety of arenes bearing direction group
underwent the selective sulfenylation with various N-
arylthiobenzamides successfully to afford aryl thioethers or
dithioethers in good to excellent yields. This C−H sulfenylation
represents excellent functional group tolerance and avoids the
addition of multi equivalent oxidants, which provides a new
strategy for the green and atom-economical synthesis of aryl
sulfides.
1
oil (63.3 mg, 75% yield). H NMR (500 MHz, CDCl ) δ 8.70-
3
8
.68 (m, 1H), 7.75-7.72 (m, 1H), 7.63-7.61 (m, 1H), 7.55-7.53
2
2
(
m, 1H), 7.33-7.22 (m, 5H), 7.21-7.19 (m, 1H), 7.06-7.01 (m,
H); C NMR (125 MHz, CDCl ) δ 161.7 (d, J = 246.3 Hz),
3 CF
58.3, 149.1, 141.4, 136.1, 134.8, 134.1, 131.1, 130.5, 129.8,
13
2
1
1
29.1, 127.1, 124.8, 124.2, 122.8 (d, J = 17.5 Hz), 122.3, 116.0
CF
19
(d, JCF = 22.5 Hz); F NMR (470MHz, CDCl ) δ -107.93 (s, 1F);
3
+
+
HRMS (ESI) calcd for C H FNS ([M + H] ): 282.0747,
17
13
Found: 282.0746.
4
.2.4 2-(2-((4-fluorophenyl)thio)phenyl)pyridine (3d): white
4
4
. Experimental Section
o
1
solid (59.1 mg, 70% yield), mp 93-95 C. H NMR (500 MHz,
CDCl ) δ 8.70-8.69 (m, 1H), 7.76-7.72 (m, 1H), 7.57 (d, J = 8.0
.1 General
3
Hz, 1H), 7.51-7.50 (m, 1H), 7.33-7.23 (m, 5H), 7.13 (d, J = 8.0
13
Chemicals were either purchased or purified by standard
Hz, 1H), 7.00-6.96 (m, 2H); C NMR (125 MHz, CDCl ) δ
3
1
13
techniques. H NMR and C NMR spectra were measured on a
5
CDCl3, (CD ) CO and d6-DMSO as the solvent with
tetramethylsilane (TMS) as an internal standard at room
temperature. Chemical shifts are given in δ relative to TMS, and
the coupling constants J are given in hertz. 1 F NMR spectra
were recorded on a 500 MHz spectrometer ( F at 470 MHz).
High-resolution mass spectra were recorded on an ESI-Q-TOF
mass spectrometer. All reactions under nitrogen atmosphere
were conducted using standard Schlenk techniques. Melting
points were measured on X4 melting point apparatus (Beijing
Tech. Instrument) and uncorrected. Column chromatography was
performed using EM silica gel 60 (300-400 mesh).
1
1
62.6 (d, JCF = 246.3 Hz), 158.4, 149.2, 140.9, 136.3, 136.2,
35.0, 130.6, 130.5, 130.4, 129.1, 126.6, 124.3, 122.3, 116.5 (d,
1
13
00 MHz spectrometer ( H at 500 MHz, C at 125 MHz), using
19
3 2
JCF = 21.3 Hz); F NMR (470MHz, CDCl ) δ -113.71 (s, 1F);
3
+ +
HRMS (ESI) calcd for C H FNS ([M + H] ): 282.0747,
17
13
Found: 282.0746.
19
9
4.2.5 2-(2-((2-chlorophenyl)thio)phenyl)pyridine (3e): colorless
1
oil (87.6 mg, 98% yield). H NMR (500 MHz, CDCl ) δ 8.66-
3
8
.65 (m, 1H), 7.71-7.68 (m, 1H), 7.62-7.59 (m, 2H), 7.42-7.39
(
m, 1H), 7.33-7.31 (m, 3H), 7.23-7.21 (m, 1H), 7.11-7.09 (m,
13
3
1
1
H); C NMR (125 MHz, CDCl ) δ 158.1, 149.2, 142.9, 136.0,
3
35.9, 134.6, 133.4, 132.7, 132.3, 130.9, 129.9, 129.4, 128.1,
+
27.9, 127.4, 124.3, 122.3; HRMS (ESI) calcd for C H ClNS
1
7
13
+
([M + H] ): 298.0452, Found: 298.0459.
4
.2.6 2-(2-((3-chlorophenyl)thio)phenyl)pyridine (3f): colorless
1
4
.1.1 General Procedure for the Palladium-Catalyzed C-H
oil (80.4 mg, 90% yield). H NMR (500 MHz, CDCl ) δ 8.68-
8
Sulfenylation:
3
.67 (m, 1H), 7.72-7.69 (m, 1H), 7.57-7.52 (m, 2H), 7.38-7.30
13
(m, 3H), 7.25-7.22 (m, 2H), 7.15-7.10 (m, 3H); C NMR (125
Under N2 atmosphere, an oven-dried reaction vessel was
MHz, CDCl ) δ 158.2, 149.1, 142.3, 138.6, 136.0, 134.9, 133.9,
charged
with
2-arylpyridine
1
(0.3
mmol),
N-
3
1
1
2
32.7, 130.8, 130.7, 130.2, 129.3, 129.2, 127.7, 127.1, 124.3,
(arylthio)benzamide 2 (0.45 mmol for monothiolation and 1.2
+ +
22.3; HRMS (ESI) calcd for C H ClNS ([M + H] ):
mmol for dithiolation), Pd(MeCN) Cl2 (0.03 mmol) and dry
17 13
2
98.0452, Found: 298.0453.
DMF (2 mL). The vessel was sealed and heated at 120 °C (oil
bath temperature) for 24 h and then cooled to room temperature.
Brine and ethyl acetate were added to the reaction mixture. The
mixture was extracted with ethyl acetate three times, and the
combined organic layer was dried over MgSO . After removal of
the solvent under reduced pressure, the residue was purified by
silica-gel column chromatography to give the products.
[10a]
4
.2.7 2-(2-((4-chlorophenyl)thio)phenyl)pyridine (3g):
white
o
1
solid (72.4 mg, 81% yield), mp 64-66 C. H NMR (500 MHz,
(CD ) CO) δ 8.66-8.64 (m, 1H), 7.84-7.81 (m, 1H), 7.64-7.62
3 2
4
(m, 1H), 7.60-7.59 (m, 1H), 7.41-7.30 (m, 6H), 7.29-7.24 (m,
13
2
1
1
1
H); C NMR (125 MHz, (CD ) CO) δ 159.0, 149.7, 143.1,
3 2
36.9, 136.4, 135.4, 133.8, 133.5, 132.9, 131.3, 130.1, 129.9,
+
28.1, 124.7, 123.1; LRMS (EI, 70 eV) m/z (%): 297 (M , 18),
4
.2. Characterization data
86 (100), 187, 296 (13), 115 (10).
[
10a]
4
.2.1 2-(2-(phenylthio)phenyl)pyridine (3a):
yellow oil (68.0
1
4
.2.8 2-(2-((3,5-dichlorophenyl)thio)phenyl)pyridine (3h):yellow
mg, 86% yield). H NMR (500 MHz, CDCl ) δ 8.70-8.69 (m,
1
Hz, 1H), 7.31-7.28 (m, 4H), 7.25-7.21 (m, 5H); C NMR (125
MHz, CDCl ) δ 158.4, 149.2, 141.5, 136.0, 135.8, 135.5, 132.2,
3
1
oil (68.8 mg, 69% yield). H NMR (500 MHz, (CD ) CO) δ
8
7
H), 7.74-7.70 (m, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 7.0
3 2
13
.64-8.62 (m, 1H), 7.85-7.81 (m, 1H), 7.66-7.62 (m, 2H), 7.53-
.50 (m, 2H), 7.48-7.45 (m, 1H), 7.35-7.32 (m, 1H), 7.27-7.26
3
13
(m, 1H), 7.11-7.10 (m, 2H); C NMR (125 MHz, (CD ) CO) δ
1
31.7, 130.5, 129.3, 129.1, 127.4, 126.9, 124.4, 122.3; LRMS
3 2
+
1
1
58.8, 149.7, 144.6, 142.9, 137.0, 135.9, 135.0, 132.7, 131.7,
30.4, 129.6, 128.4, 127.0, 124.8, 123.2; HRMS (ESI) calcd for
(
(
EI, 70 eV) m/z (%): 263 (M , 25), 186 (100), 262 (19), 115
14), 187 (13).
+
+
C H Cl NS ([M + H] ): 332.0062, Found: 332.0069.
17
12
2

5
ACCEPTED MANUSCRIPT
4
.2.9 2-(2-((4-nitrophenyl)thio)phenyl)pyridine (3i): yellow solid
4.2.16 2-(4-fluoro-2-(phenylthio)phenyl)pyridine (3p): colorless
o
1
1
(68.5 mg, 74% yield), mp 87-89 C. H NMR (500 MHz, CDCl )
oil (57.4 mg, 68% yield). H NMR (500 MHz, CDCl ) δ 8.72-
3
3
δ 8.62-8.61 (m, 1H), 7.99 (d, J = 9.0 Hz, 2H), 7.68-7.65 (m, 2H),
8.71 (m, 1H), 7.76-7.73 (m, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.49-
7
7
.58 (d, J = 7.5Hz, 1H), 7.54-7.49 (m, 2H), 7.45-7.42 (m, 1H),
.23-7.20 (m, 1H), 7.14 (d, J = 9.0 Hz, 2H); C NMR (125
7.46 (m, 1H), 7.42-7.41 (m, 2H), 7.33-7.25 (m, 4H), 6.95-6.92
13
13
(m, 1H), 6.77-6.75 (m, 1H); C NMR (125 MHz, CDCl ) δ
3
MHz, CDCl ) δ 157.9, 149.3, 148.1, 145.7, 144.7, 136.0, 135.7,
163.0 (d, JCF = 248.8 Hz), 157.6, 149.2, 139.4, 136.3, 136.2,
3
1
31.4, 130.0, 129.8, 129.7, 127.8, 124.3, 124.0, 122.5; HRMS
133.9, 133.8, 131.9, 129.7, 128.5, 124.3, 122.4, 116.5 (d, J
=
CF
+
+
19
(ESI) calcd for C H N O S ([M + H] ): 309.0692, Found:
23.8 Hz), 113.3 (d, JCF = 22.5 Hz); F NMR (470 MHz, CDCl )
3
+ +
17
13
2
2
3
09.0689.
δ -112.59 (s, 1F); HRMS (ESI) calcd for C H FNS ([M + H] ):
17 13
2
82.0747, Found: 282.0744.
4
.2.10 2-(2-(thiophen-2-ylthio)phenyl)pyridine (3j): white solid
o
1
(49.3 mg, 61% yield), mp 63-65 C. H NMR (500 MHz, CDCl )
4.2.17
2-(3,5-difluoro-2-(phenylthio)phenyl)pyridine
(3q):
3
1
δ 8.75-8.74 (m, 1H), 7.81-7.78 (m, 1H), 7.63-7.61 (m, 1H), 7.47-
7
yellow oil (47.6 mg, 53% yield). H NMR (500 MHz, (CD ) CO)
δ 8.65-8.64 (m, 1H), 7.84-7.81 (m, 1H), 7.61 (d, J = 8.0 Hz, 1H),
3 2
13
.46 (m, 2H), 7.31-7.22 (m, 4H), 7.07-7.05 (m, 2H); C NMR
(
1
125 MHz, CDCl ) δ 158.2, 149.1, 138.8, 138.4, 136.8, 136.5,
7.39-7.37 (m, 1H), 7.33-7.30 (m, 1H), 7.28-7.25 (m, 1H), 7.24-
7.21 (m, 2H), 7.15-7.12 (m, 1H), 7.09-7.07 (m, 2H); C NMR
3
1
3
32.0, 131.6, 129.9, 129.1, 128.1, 127.8, 125.8, 124.0, 122.4;
+
+
HRMS (ESI) calcd for C H NS ([M + H] ): 270.0406, Found:
(125 MHz, CDCl ) δ 163.8 (dd, J = 248.5, 12.6 Hz), 163.3 (dd,
15
12
2
3
CF
2
70.0406.
JCF = 250.8, 12.8 Hz), 156.5, 149.5, 148.6 (d, JCF = 9.4 Hz),
[
10a]
136.8, 135.8, 129.1, 127.8, 126.1, 124.9, 123.0, 115.3 (dd, JCF
=
=
4
.2.11 2-(4-methyl-2-(phenylthio)phenyl)pyridine (3k):
white
o
1
19.0, 4.0 Hz), 114.1 (dd, JCF = 22.3, 3.5 Hz), 104.8 (dd, JCF
solide (64.9 mg, 78% yield), mp 63-65 C. H NMR (500 MHz,
CDCl ) δ 8.67-8.66 (m, 1H), 7.69-7.66 (m, 1H), 7.56-7.54 (m,
H), 7.45 (d, J = 7.5 Hz, 1H ), 7.28-7.25 (m, 2H), 7.24-7.17 (m,
H), 7.15-7.11 (m, 2H), 2.29 (s, 3H ); C NMR (125 MHz,
CDCl ) δ 158.5, 149.1, 139.3, 139.1, 136.3, 135.9, 134.5, 132.7,
31.5, 130.5, 129.2, 128.2, 127.0, 124.5, 122.0, 21.2; LRMS (EI,
0 eV) m/z (%): 277 (M , 30), 200 (100), 276 (22), 201 (15),
19
2
7.8, 25.5 Hz); F NMR (470 MHz, CDCl ) δ -98.12 (d,
3
3
J=10.34 Hz, 1F), -107.28 (d, J = 10.34 Hz, 1F); HRMS (ESI)
1
4
+
+
13
calcd for C17
H F NS ([M + H] ): 300.0653, Found: 300.0649.
12 2
[
10a]
4.2.18 2-(4-chloro-2-(phenylthio)phenyl)pyridine (3r):
white
3
o
1
1
7
1
solide (67.0 mg, 75% yield), mp 74-76 C. H NMR (500 MHz,
+
CDCl ) δ 8.71-8.70 (m, 1H), 7.76-7.72 (m, 1H), 7.57 (d, J = 7.5
3
85 (13).
Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.38-7.37 (m, 2H), 7.34-7.26
13
[
10a]
(m, 4H), 7.25-7.23 (m, 1H), 7.10-7.09 (m, 1H); C NMR (125
MHz, CDCl ) δ 157.4, 149.3, 138.9, 138.5, 136.2, 135.0, 134.1,
33.2, 131.5, 129.9, 129.6, 128.3, 126.6, 124.3, 122.5; LRMS
4
.2.12 2-(2-methyl-6-(phenylthio)phenyl)pyridine (3l):
red
1
3
oil (73.3 mg, 88% yield). H NMR (500 MHz, CDCl ) δ 8.67-
3
1
8
(
.66 (m, 1H), 7.71-7.67 (m, 1H), 7.25-7.24 (m, 1H), 7.23-7.19
m, 5H), 7.18-7.14 (m, 3H), 7.12-7.10 (m, 1H), 2.08 (s, 3H);
NMR (125 MHz, (CD ) CO) δ 159.3, 150.2, 143.5, 138.1, 137.1,
36.8, 135.7, 132.0, 130.2, 130.0, 129.9, 129.4, 127.8, 125.6,
+
13
(EI, 70 eV) m/z (%): 297 (M , 31), 220 (100), 222 (37), 206
23), 299 (12).
C
(
3
2
[
10a]
1
1
4.2.19 2-(4-bromo-2-(phenylthio)phenyl)pyridine (3s):
white
+
o
1
23.0, 20.5; LRMS (EI, 70 eV) m/z (%): 277 (M , 52), 200
solid (62.7 mg, 61% yield), mp 92-94 C. H NMR (500 MHz,
(100), 276 (52), 167 (19), 198 (17).
CDCl ) δ 8.63-8.62 (m, 1H), 7.68-7.65 (m, 1H), 7.49 (d, J = 8.0
3
Hz, 1H), 7.33-7.31 (m, 2H), 7.30-7.28 (m, 2H), 7.25-7.22 (m,
4
.2.13 2-(3,5-dimethyl-2-(phenylthio)phenyl)pyridine (3m):
13
o
1
3H), 7.20-7.17 (m, 2H ); C NMR (125 MHz, CDCl
3
) δ 157.4,
white solide (36.7 mg, 42% yield), mp 87-89 C. H NMR (500
MHz, (CD ) CO) δ 8.57-8.56 (m, 1H), 7.71-7.67 (m, 1H), 7.43
1
1
49.3, 139.5, 138.7, 136.3, 134.2, 133.1, 132.8, 131.7, 129.6,
29.5, 128.3, 124.2, 123.1, 122.5; LRMS (EI, 70 eV) m/z (%):
3
2
(d, J = 7.5 Hz, 1H), 7.28-7.25 (m, 3H), 7.20-7.16 (m, 2H), 7.08-
+
13
343/341 (M , 30), 266 (100), 264 (97), 185 (65).
7
.05 (m, 1H), 6.94-6.93 (m, 2H), 2.40 (s, 3H), 2.34 (s, 3H); C
NMR (125 MHz, (CD ) CO) δ 160.5, 149.7, 148.4, 144.3, 140.2,
4.2.20 2-(2-(phenylthio)-4-(trifluoromethyl)phenyl)pyridine (3t):
white solid (61.7 mg, 62% yield), mp 88-90 C. H NMR (500
3
2
o
1
1
1
2
39.5, 136.1, 132.6, 130.3, 129.8, 127.1, 127.0, 125.8, 125.2,
+
+
22.8, 21.6, 21.1; HRMS (ESI) calcd for C H NS ([M + H] ):
MHz, CDCl ) δ 8.74-8.72 (m, 1H), 7.79-7.75 (m, 1H), 7.63-7.60
19
18
3
92.1155, Found: 292.1155.
(m, 2H), 7.52-7.50 (m, 1H), 7.39 (s, 1H), 7.37-7.35 (m, 2H),
13
7
.33-7.29 (m, 4H); C NMR (125 MHz, CDCl ) δ 157.2, 149.4,
3
4
.2.14 2-(4-ethyl-2-(phenylthio)phenyl)pyridine (3n): colorless
1
143.7, 138.1, 136.3, 133.9, 133.2, 131.2 (q, JCF = 32.5 Hz),
oil (72.6 mg, 83% yield). H NMR (500 MHz, CDCl ) δ 8.67-
3
1
1
29.7, 129.6, 128.4, 127.1 , 124.3, 123.8 (q, J = 271.3 Hz),
CF
8
.66 (m, 1H), 7.69-7.66 (m, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.48
19
23.0, 122.9; F NMR (470 MHz, CDCl ) δ -62.87 (s, 3F).
3
(
(
d, J = 8.0 Hz, 1H), 7.28-7.24 (m, 3H) 7.22-7.14 (m, 5H), 2.58
q, J = 8.0 Hz, 2H), 1.17 (t, J = 8.0 Hz, 3H); C NMR (125
+
+
13
HRMS (ESI) calcd for C18
Found: 332.0720.
H F NS ([M + H] ): 332.0716,
13 3
MHz, CDCl ) δ 158.4, 149.1, 145.4, 139.5, 136.4, 135.8, 134.4,
3
[
10a]
1
1
31.8, 131.4, 130.6, 129.1, 127.0, 126.9, 124.4, 122.0, 28.6,
4.2.21 3-(phenylthio)-4-(pyridin-2-yl)benzonitrile (3u):
o 1
+
+
5.4; HRMS (ESI) calcd for C H NS ([M + H] ): 292.1155,
white solid (71.8 mg, 83% yield), mp 77-79 C. H NMR (500
19
18
Found: 292.1159.
MHz, CDCl ) δ 8.75-8.74 (m, 1H), 7.82-7.79 (m, 1H), 7.62 (d, J
3
[
10a]
= 8.0 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.50-7.48 (m, 1H), 7.43-
4
.2.15 2-(4-methoxy-2-(phenylthio)phenyl)pyridine (3o):
13
1
7.36 (m, 6H), 7.35-7.32 (m, 1H); C NMR (125 MHz, CDCl
3
) δ
colorless oil (54.6 mg, 62% yield). H NMR (500 MHz, CDCl )
δ 8.68-8.67 (m, 1H), 7.70-7.67 (m, 1H), 7.57-7.55 (m, 1H), 7.48
d, J = 8.5 Hz, 1H), 7.36-7.34 (m, 2H), 7.29-7.26 (m, 2H), 7.25-
.24 (m, 1H), 7.21-7.18 (m, 1H), 6.8-6.82 (m, 1H), 6.73-6.72 (m,
H), 3.69 (s, 3H); C NMR (125 MHz, CDCl ) δ 160.0, 158.1,
49.1, 137.1, 136.0, 135.3, 133.9, 132.6, 131.6, 129.3, 127.6,
24.3, 121.8, 116.4, 112.5, 55.4; LRMS (EI, 70 eV) m/z (%):
3
1
1
56.6, 149.5, 143.5, 139.8, 136.5, 134.2, 132.6, 132.4, 130.8,
30.0, 129.2, 129.0, 124.1, 123.2, 118.4, 112.9; LRMS (EI, 70
(
+
eV) m/z (%): 288 (M , 29), 211 (100), 287 (21), 212 (15), 140
(11).
7
1
1
1
2
13
3
[
10b]
4.2.22 ethyl 3-(phenylthio)-4-(pyridin-2-yl)benzoate (3v):
1
colorless liquid (79.4 mg, 79% yield). H NMR (500 MHz,
+
93 (M , 32), 216 (100), 292 (22), 173 (20), 217 (18).
CDCl ) δ 8.71-8.70 (m, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.91 (s,
3

6
ACCEPTED MANUSCRIPT
1
6
H), 7.76-7.73 (m, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.31-7.24 (m,
H), 4.31 (q, J = 7.5 Hz, 2H), 1.32 (t, J = 7.5 Hz, 3H); C NMR
(500 MHz, CDCl ) δ 8.72-8.70 (m, 1H), 7.76-7.73 (m, 1H), 7.37
3
13
(d, J = 8.0 Hz, 1H), 7.32-7.28 (m, 5H), 7.11-7.07 (m, 1H), 7.00-
13
(125 MHz, CDCl ) δ 165.9, 157.4, 149.2, 144.9, 136.4, 136.3,
6.97 (m, 4H), 6.91(d, J = 8.0 Hz, 2H); C NMR (125 MHz,
3
1
1
34.8, 132.5, 132.4, 131.2, 130.6, 129.5, 127.8, 127.7, 124.4,
22.7, 61.2, 14.3; LRMS (EI, 70 eV) m/z (%): 335 (M , 42), 258
CDCl ) δ 162.8 (d, J = 247.5 Hz), 156.9, 149.6, 140.0, 138.3,
3
CF
+
136.2, 135.4, 129.4, 129.2, 127.7, 125.6, 122.8, 116.6 (d, J
21.3 Hz); F NMR (470 MHz, CDCl ) δ -113.05 (s, 2F); HRMS
3
+ +
=
CF
19
(100), 230 (45), 259 (18), 334 (16); HRMS (ESI) calcd for
+
+
C H NO S ([M + H] ): 336.1053, Found: 336.1068.
(ESI) calcd for C H F NS ([M + H] ): 408.0687, Found:
23 16 2 2
20
18
2
[
10a]
408.0690.
4
.2.23 3-methyl-2-(2-(phenylthio)phenyl)pyridine (3w):
white
o
1
solid (71.6 mg, 88% yield), mp 71-73 C. H NMR (500 MHz,
CDCl ) δ 8.48-8.47 (m, 1H), 8.56-8.54 (m, 1H), 7.32-7.27 (m,
H), 7.26-7.17 (m, 5H), 2.18 (s, 3H); C NMR (125 MHz,
CDCl ) δ 158.3, 146.7, 141.7, 137.8, 135.7, 135.2, 132.3, 132.1,
4.2.30 2-(2,6-bis((2-chlorophenyl)thio)phenyl)pyridine (4e):
white solid (116.3 mg, 88% yield), mp 98-100 C. H NMR (500
MHz, CDCl ) δ 8.62-8.61 (m, 1H), 7.67-7.63 (m, 1H), 7.35-7.31
(m, 3H), 7.24-7.20 (m, 4H), 7.17-7.13 (m, 6H); C NMR (125
o
1
3
13
5
3
1
3
3
1
7
31.1, 129.6, 129.2, 128.8, 127.4, 126.9, 122.7, 19.2; LRMS (EI,
0 eV) m/z (%): 277 (M , 25), 262 (100), 200 (87), 263, 167
MHz, CDCl ) δ 156.8, 149.2, 143.8, 136.0, 135.6, 135.4, 134.9,
3
+
133.3, 131.1, 130.0, 129.6, 128.5, 127.4, 124.9, 122.8; HRMS
+
+
(20).
(ESI) calcd for C H Cl NS ([M + H] ): 440.0096, Found:
23 16 2 2
[
10a]
440.0113.
4
(
(
.2.24 2-(2-(phenylthio)phenyl)quinoline (3x):
colorless oil
1
81.8 mg, 87% yield). H NMR (500 MHz, CDCl ) δ 8.19-8.16
m, 2H), 7.83 (d, J = 8.0Hz, 1H), 7.74-7.70 (m, 2H), 7.67-7.65
4.2.31 2-(2,6-bis((3-chlorophenyl)thio)phenyl)pyridine (4f):
colorless oil (124.2 mg, 94% yield). H NMR (500 MHz, CDCl )
3
1
3
(
2
m, 1H), 7.56-7.53 (m, 1H), 7.37-7.33 (m, 2H), 7.32-7.30 (m,
H), 7.29-7.28 (m, 1H), 7.26-7.18 (m, 3H); C NMR (125 MHz,
δ 8.65-8.64 (m, 1H), 7.68-7.65 (m, 1H), 7.25-7.23 (m, 4H), 7.20-
7.17 (m, 5H), 7.17-7.14 (m, 2H), 7.13-7.11 (m, 2H); C NMR
13
13
CDCl ) δ 158.6, 147.9, 141.8, 135.9, 135.8, 132.2, 131.9, 130.6,
(125 MHz, CDCl ) δ 156.8, 149.4, 142.9, 137.3, 136.5, 136.0,
3
3
1
1
29.7, 129.6, 129.3, 129.2, 127.6, 127.4, 127.1, 127.0, 126.7,
22.4; LRMS (EI, 70 eV) m/z (%): 313 (M , 14), 236 (100), 237
134.9, 131.4, 130.6, 130.3, 130.0, 129.6, 127.6, 125.3, 122.8;
+
+
+
HRMS (ESI) calcd for C H Cl NS ([M + H] ): 440.0096,
23 16 2 2
(
18), 235 (12), 204 (7).
Found: 440.0103.
4.2.32 2-(2,6-bis((4-chlorophenyl)thio)phenyl)pyridine (4g):
[
10a]
[10a]
4
.2.25 1-(2-(phenylthio)phenyl)-1H-pyrazole (3y):
colorless
1
o
1
oil (31.8 mg, 42% yield). H NMR (500 MHz, CDCl ) δ 7.80-
white solid (129.5 mg, 98% yield), mp 141-143 C. H NMR
3
7
.75 (m, 2H), 7.48-7.47 (m, 1H), 7.38-7.35 (m, 2H), 7.31-7.26
(500 MHz, CDCl ) δ 8.69-8.68 (m, 1H), 7.74-7.71 (m, 1H), 7.34
3
13
(m, 5H ), 7.19-7.18 (m, 1H), 6.45 (m, 1H); C NMR (125 MHz,
(d, J = 7.5 Hz, 1H), 7.30-7.27 (m, 1H), 7.26-7.24 (m, 4H), 7.23-
13
CDCl ) δ 140.7, 139.8, 133.9, 133.2, 132.8, 131.6, 131.2, 129.6,
7.22 (m, 4H), 7.18-7.15 (m, 1H), 7.08 (d, J = 8.0 Hz, 2H);
C
3
1
2
28.8, 128.1, 127.4, 126.9, 106.7; LRMS (EI, 70 eV) m/z (%):
52 (M , 89), 149 (100), 104 (43), 251 (42), 77 (36).
NMR (125 MHz, CDCl ) δ 151.8, 144.5, 136.6, 132.3, 131.1,
3
+
128.9, 128.7, 128.4, 124.5, 124.4, 124.3, 120.4, 117.8; HRMS
+
+
[
10a]
(ESI) calcd for C23
440.0101.
H
16Cl
2
NS
2
([M + H] ): 440.0096, Found:
2-(2,6-bis((4-nitrophenyl)thio)phenyl)pyridine (4h):
o 1
4
.2.26 2-(2,6-bis(phenylthio)phenyl)pyridine (4a):
white
o
1
solid (109.3 mg, 98% yield), mp 127-129 C. H NMR (500
MHz, CDCl ) δ 8.71-8.70 (m, 1H), 7.72-7.69 (m, 1H), 7.35 (d, J
=
4.2.33
3
7.5 Hz, 1H), 7.33-7.31 (m, 4H), 7.29-7.28 (m, 4H), 7.26-7.24
yellow solid (126.0 mg, 91% yield), mp 169-171 C. H NMR
13
(m, 3H), 7.12-7.09 (m, 1H), 7.01 (d, J = 7.5 Hz, 2H); C NMR
(500 MHz, CDCl ) δ 8.50-8.49 (m, 1H), 8.04 (d, J = 8.5 Hz, 4H),
3
1
3
(125 MHz, CDCl ) δ 157.1, 149.5, 141.0, 137.7, 136.1, 134.8,
7.62-7.59 (m, 3H), 7.47-7.44 (m, 1H), 7.21-7.18 (m, 6H);
C
3
1
32.7, 129.3, 129.2, 128.6, 127.7, 125.5, 122.7; LRMS (EI, 70
NMR (125 MHz, CDCl ) δ 156.6, 149.3, 147.7, 146.4, 146.1,
3
+
eV) m/z (%): 371 (M , 37), 294 (100), 185 (29), 295 (20), 216
17).
136.0, 135.5, 133.9, 130.6, 128.8, 124.8, 124.2, 123.0; HRMS
+
+
(
(ESI): calcd for C H N O S ([M + H] ) 462.0577, Found:
23 16 3 4 2
[
10a]
462.0593.
4.2.34 2-(2,6-bis(thiophen-2-ylthio)phenyl)pyridine (4i): white
4
.2.27 2-(2,6-bis(p-tolylthio)phenyl)pyridine (4b):
white
o
1
solid (117.5 mg, 91% yield), mp 137-139 C. H NMR (500
MHz, CDCl ) δ 8.75-8.73 (m, 1H), 7.76-7.73 (m, 1H), 7.41 (d, J
o
1
solid (103.6 mg, 90% yield), mp 141-143 C. H NMR (500
3
=
8.0 Hz, 1H), 7.30-7.24 (m, 5H), 7.10 (d, J = 8.0 Hz, 4H), 7.05-
MHz, CDCl ) δ 8.82-8.81 (m, 1H), 7.86-7.83 (m, 1H), 7.54 (d, J
3
13
7
.02 (m, 1H), 6.87 (d, J = 8.0 Hz, 2H), 2.32 (s, 6H); C NMR
= 8.0 Hz, 1H), 7.46-7.45 (m, 2H), 7.37-7.35 (m, 1H), 7.18-7.17
(m, 2H), 7.09-7.06 (m, 1H), 7.04-7.02 (m, 2H), 6.79 (d, J = 8.0
(125 MHz, CDCl ) δ 157.2, 149.6, 139.4, 138.6, 138.2, 136.2,
3
13
1
7
1
33.6, 130.6, 130.2, 129.0, 127.0, 125.6, 122.8, 21.3; LRMS (EI,
0 eV) m/z (%): 399 (M , 56), 308 (100), 216 (24), 309 (23),
85 (20).
Hz, 2H); C NMR (125 MHz, CDCl ) δ 156.2, 150.0, 139.5,
3
+
136.8, 136.5, 136.4, 131.8, 130.7, 129.2, 128.1, 125.9, 124.6,
+
+
123.2; HRMS (ESI) calcd for C H NS ([M + H] ): 384.0004,
19 14 4
Found: 384.0009.
4.2.35 2-(4-methyl-2,6-bis(phenylthio)phenyl)pyridine (4j):
4
.2.28 2-(2,6-bis((2-fluorophenyl)thio)phenyl)pyridine (4c):
o
1
[10a]
white solid (119.8 mg, 98% yield), mp 75-77 C. H NMR (500
MHz, CDCl ) δ 8.68-8.67 (m, 1H), 7.74-7.71 (m, 1H), 7.44 (d, J
1
colorless oil (112.2 mg, 97% yield). H NMR (500 MHz, CDCl )
3
3
=
7.5 Hz, 1H), 7.30-7.27 (m, 3H), 7.25-7.23 (m, 1H), 7.13-7.10
δ 8.67-8.66 (m, 1H), 7.67-7.63 (m, 1H), 7.31-7.29 (m, 2H), 7.28-
13
13
(m, 1H), 7.07-7.03 (m, 3H), 7.02-7.01 (m, 4H); C NMR (125
MHz, CDCl ) δ 161.8 (d, J = 246.3 Hz), 156.8, 149.5, 141.3,
7.26 (m, 5H), 7.25-7.21 (m, 5H), 6.92 (s, 2H), 2.16 (s, 3H );
C
NMR (125 MHz, CDCl ) δ 157.3, 149.4, 139.4, 139.3, 136.9,
3
CF
3
1
1
36.2, 135.1, 130.1, 129.3, 128.7, 127.8, 125.4, 124.9, 122.8,
21.8 (d, JCF = 18.8 Hz), 116.1 (d, JCF = 21.3 Hz); F NMR (470
135.9, 135.3, 132.2, 130.2, 129.2, 127.4, 125.6, 122.5, 21.3;
19
+
+
HRMS (ESI): calcd for C H NS ([M + H] ): 386.1032,
24 20 2
MHz, CDCl ) δ -107.46 (s, 2F); HRMS (ESI) calcd for
Found: 386.1034.
.2.36 2-(4-ethyl-2,6-bis(phenylthio)phenyl)pyridine
3
+
+
C H F NS ([M + H] ): 408.0687, Found: 408.0695.
23
16
2
2
4
(4k):
o
1
4
.2.29 2-(2,6-bis((4-fluorophenyl)thio)phenyl)pyridine (4d):
yellow solid (115.1 mg, 96% yield), mp 66-68 C. H NMR (500
o
1
white solid (119.8 mg, 98% yield), mp 104-106 C. H NMR
MHz, CDCl ) δ 8.65-8.64 (m, 1H), 7.64-7.61 (m, 1H), 7.28-7.26
3

7
ACCEPTED MANUSCRIPT
(
2
m, 4H), 7.25-7.23 (m, 4H), 7.22-7.18 (m, 4H), 6.94 (s, 2H),
.44 (q, J=7.5 Hz, 2H), 1.04 (t, J = 7.5 Hz, 3H); C NMR (125
165.4, 156.4, 149.6, 144.5, 138.6, 136.2, 134.0, 132.8, 131.4,
129.5, 129.4, 128.1, 125.2, 123.0, 61.3, 14.1; LRMS (EI, 70 eV)
13
+
MHz, CDCl ) δ 157.3, 149.3, 145.5, 139.7, 136.8, 135.8, 135.4,
1
m/z (%): 443 (M , 57), 366 (100), 338 (38), 260 (25), 367 (25);
3
+
+
32.0, 129.2, 129.1, 127.3, 125.5, 122.5, 28.5, 15.3; HRMS
HRMS (ESI) calcd for C H NO S ([M + H] ): 444.1086,
26 22 2 2
+
+
(ESI) calcd for C H NS ([M + H] ): 400.1188, Found:
Found: 444.1089.
.2.44 1-(2,6-bis(phenylthio)phenyl)-1H-pyrazole (4s):
25
22
2
4
00.1193.
[10a]
4
white
[
10a]
o
1
4
.2.37 2-(4-methoxy-2,6-bis(phenylthio)phenyl)pyridine (4l):
solid (104.9 mg, 97% yield). mp 144-146 C. H NMR (500
o
1
white solid (118.1 mg, 98% yield), mp 133-135 C. H NMR
500 MHz, CDCl ) δ 8.69-8.68 (m, 1H), 7.69-7.65 (m, 1H), 7.35-
MHz, CDCl ) δ 7.84 (m, 1H), 7.63 (m, 1H), 7.43 (m, 4H), 7.34
3
(
(m, 6H ), 7.07 (t, J=7.5 Hz, 1H), 6.81 (d, J=8.0 Hz, 2H), 6.51 (m,
3
13
7
2
1
1
.32 (m, 5H), 7.29-7.27 (m, 3H), 7.26-7.22 (m, 4H), 6.53 (s,
1H); C NMR (125 MHz, CDCl ) δ 140.9, 139.2, 134.1, 133.9,
3
13
H), 3.54 (s, 3H); C NMR (125 MHz, CDCl ) δ 159.6, 156.9,
132.5, 131.9, 129.8, 129.6, 128.7, 126.8, 106.6; LRMS (EI, 70
3
+
49.4, 138.9, 136.0, 134.4, 133.8, 132.9, 129.4, 127.9, 126.0,
eV) m/z (%): 360 (M , 100), 257 (72), 148 (30), 361 (28), 359
+
22.5, 114.0, 55.3; LRMS (EI, 70 eV) m/z (%): 401 (M , 22), 73
(26).
(100), 355 (86), 207, 149 (63).
1
13
Supporting Information: Copies of H and C NMR spectra
4
.2.38 2-(4-fluoro-2,6-bis(phenylthio)phenyl)pyridine (4m):
for the products.
o
1
white solid (113.4 mg, 97% yield), mp 103-105 C. H NMR
Acknowledgements
(500 MHz, CDCl ) δ 8.77-8.76 (m, 1H), 7.79-7.75 (m, 1H), 7.44
3
(
7
d, J = 7.5 Hz, 1H), 7.41-7.39 (m, 4H), 7.35-7.33 (m, 3H), 7.32-
.31 (m, 3H), 7.31-7.29 (m, 1H), 6.53 (d, J = 9.0 Hz, 2H); C
We thank the National Natural Science Foundation of China
(No. 21272177 and 21302144) for financial support.
13
NMR (125 MHz, CDCl ) δ 162.5 (d, J = 248.8 Hz), 156.1,
3
CF
References and notes
1
1
1
3
49.8, 140.9, 136.3, 134.7, 133.9, 132.9, 129.6, 128.7, 125.9,
19
22.9, 113.2 (d, JCF = 23.8 Hz); F NMR (470 MHz, CDCl ) δ -
3
[1] For examples, see: (a) Liu, G.; Huth, J. R.; Olejniczak, E.
T.; Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E. B.;
Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med.
Chem. 2001, 44, 1202. (b) Gangjee, A.; Zeng, Y.; Talreja,
T.; McGuire, J. J.; Kisliuk, R. L.; Queener, S. F. J. Med.
Chem. 2007, 50, 3046. (c) Nielsen, S. F.; Nielsen, E. O.;
Olsen, G. M.; Liljefors, T.; Peters, D. J. Med. Chem. 2000,
+
+
11.50 (s, 1F); HRMS (ESI) calcd for C H FNS ([M + H] ):
23
17
2
90.0781, Found: 390.0788.
[
10a]
4
.2.39 2-(4-chloro-2,6-bis(phenylthio)phenyl)pyridine (4n):
1
colorless oil (112.1 mg, 92% yield). H NMR (500 MHz, CDCl )
δ 8.73-8.72 (m, 1H), 7.74-7.71 (m, 1H), 7.38-7.34 (m, 5H), 7.32-
7
3
13
.30 (m, 3H), 7.29-7.27 (m, 4H), 6.84 (s, 2H); C NMR (125
4
3, 2217. (d) Herradura, P. S.; Pendola, K. A.; Guy, R. K.
MHz, CDCl ) δ 156.1, 149.8, 140.2, 137.7, 136.3, 134.9, 133.6,
3
Org. Lett. 2000, 2, 2019. (e) Yan, S-Y.; Liu, Y-J.; Liu, B.;
Liu, Y-H.; Shi, B-F. Chem. Commun., 2015, 51, 4069.
2] (a) Kuninobu, Y.; Takai, K. Chem. Rev. 2011, 111, 1938.
(b) Prim, D.; Campagne, J.-M.; Joseph, D.; Andrioletti, B.
Tetrahedron. 2002, 58, 2041. (c) Ley, S. V.; Thomas, A.
W. Angew. Chem. Int. Ed. 2003, 42, 5400. (d) Bichler, P.;
Love, J. A. Topics in Organometallic Chemistry. 2010, 31,
39. (e) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337. (f) Beletskaya, I. P.; Ananikov, V. P.
Chem. Rev. 2011, 111, 1596.
1
33.1, 129.6, 128.5, 126.6, 125.7, 123.0; HRMS (ESI) calcd for
+ +
C H ClNS ([M + H] ): 406.0486, Found: 406.0475.
23
17
2
[
[
10a]
4
.2.40 2-(4-bromo-2,6-bis(phenylthio)phenyl)pyridine (4o):
1
yellow oil (97.3 mg, 72% yield). H NMR (500 MHz, CDCl ) δ
3
8
7
2
1
.74-8.72 (m, 1H), 7.76-7.72 (m, 1H), 7.39-7.37 (m, 2H), 7.36-
.34 (m, 3H), 7.33-7.30 (m, 6H), 7.29-7.28 (m, 1H), 7.02 (s,
13
H); C NMR (125 MHz, CDCl ) δ 156.1, 149.8, 140.3, 138.4,
3
36.3, 133.4, 133.3, 133.2, 129.6, 129.5, 128.5, 125.6, 123.0;
+
+
HRMS (ESI) calcd for C H BrNS ([M + H] ): 449.9981,
Found: 449.9977.
23
17
2
[3] (a) Kondo, T.; Mitsudo, T.. Chem. Rev. 2000, 100, 3205.
b) Kunz, K.; Scholz, U.; Ganzer, D. Synlett. 2003, 2428.
(
4
.2.41 3,5-bis(phenylthio)-4-(pyridin-2-yl)benzonitrile (4p):
o
1
(c) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534.
4] For selected examples, see: (a) Zhang, S.; Qian, P.; Zhang,
M.; Hu, M.; Cheng, J. J. Org. Chem. 2010, 75, 6732. (b)
Fang, X-L.; Tang, R-Y.; Zhang, X-G.; Li, J-H. Synthesis.
white solid (115.4 mg, 97% yield), mp 101-103 C. H NMR
500 MHz, CDCl ) δ 8.79-8.78 (m, 1H), 7.85-7.82 (m, 1H), 7.47-
[
(
7
3
.45 (m, 1H), 7.40-7.38 (m, 6H), 7.38-7.33 (m, 5H), 6.98-6.96
13
(m, 2H); C NMR (125 MHz, CDCl ) δ 155.3, 150.2, 141.3,
3
2
011, 1099. (c) Prasad, C. D.; Balkrishna, S. J.; Kumar, A.;
1
1
3
36.7, 134.4, 133.0, 131.7, 130.0, 129.4, 128.4, 125.3, 123.6,
+ +
Bhakuni, B. S.; Shrimali, K.; Biswas, S.; Kumar, S. J. Org.
Chem. 2013, 78, 1434. (d) Saravanan, P.; Anbarasan, P.
Org. Lett. 2014, 16, 848.
18.1, 113.3; HRMS (ESI) calcd for C H N S ([M + H] ):
24
17
2 2
97.0828, Found: 397.0815.
4
.2.42 2-(2,6-bis(phenylthio)-4-(trifluoromethyl)phenyl)pyridine
[5] For selected examples, see: (a) Ranjit, S.; Lee, R.; Heryadi,
D.; Shen, C.; Wu, J.; Zhang, P.; Huang, K-W.; Liu, X. J.
Org. Chem. 2011, 76, 8999. (b) Ranjit, S.; Duan, Z.; Zhang,
P.; Liu, X. Org. Lett. 2010, 12, 4134. (c) Zhang, Y.;
Ngeow, K. C.; Ying, J. Y. Org. Lett. 2007, 9, 3495.
[6] For selected recent reviews, see: (a) Wencel-Delord, J.;
Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40,
4740. (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011,
111, 1215; (c) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S.
Chem. Soc. Rev. 2011, 40, 5068. (d) Ackermann, L. Chem.
Rev. 2011, 111, 1315; (e) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. Chem. Rev. 2010, 110, 624. (f) Neufeldt, S.
R. Sanford, M. S. Acc. Chem. Res. 2012, 45, 936.
1
(4q): colorless oil (114.7 mg, 87% yield). H NMR (500 MHz,
CDCl ) δ 8.75-8.74 (m, 1H), 7.79-7.76 (m, 1H), 7.40 (d, J = 8.0
Hz, 1H), 7.37-7.35 (m, 4H), 7.34-7.32 (m, 6H), 7.32-7.31 (m,
1
1
1
3
13
H), 7.12 (s, 2H); C NMR (125 MHz, CDCl ) δ 156.0, 150.0,
3
42.4, 140.1, 136.5, 133.6, 133.0, 131.4 (q, JCF = 32.5 Hz),
19
29.7, 128.7, 125.6 (q, JCF = 272.5 Hz), 125.4, 123.6, 123.3;
F
NMR (470 MHz, CDCl ) δ -63.20 (s, 3F). HRMS (ESI) calcd for
C H F NS ([M + H] ): 440.0749, Found: 440.0754.
3
+
+
24
17
3
2
4
.2.43 ethyl 3,5-bis(phenylthio)-4-(pyridin-2-yl)benzoate (4r)
o 1
white solide (122.5 mg, 92% yield). mp 78-80 C. H NMR (500
MHz, CDCl ) δ 8.71-8.70 (m, 1H), 7.73-7.70 (m, 1H), 7.67 (s,
2
2
3
H), 7.34-7.30 (m, 6H), 7.29-7.26 (m, 6H), 4.21 (q, J = 7.5 Hz,
13
H), 1.23 (t, J = 7.5 Hz, 3H); C NMR (125 MHz, CDCl ) δ
3

8
ACCEPTED MANUSCRIPT
[
[
7] (a) Zhao, X.; Dimitrijevic, E.; Dong, V. M. J. Am. Chem.
Soc. 2009, 131, 3466. (b) Wu, Z.; Song, H.; Cui, X.; Pi, C.;
Du, W.; Wu, Y. Org. Lett. 2013, 15, 1270. (c) Xu, C.;
Shen, Q. Org. Lett. 2014, 16, 2046.
8] (a) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. 2008,
1
20, 2922; Angew. Chem. Int. Ed. 2008, 47, 2880. (b)
Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem. Int.
Ed. 2006, 45, 4473. (c) Yu, M.; Xie, Y.; Xie, C.; Zhang, Y.
Org. Lett. 2012, 14, 2164.
[
9] (a) Chen, X.; Hao, X. -S.; Goodhue, C. E. ; Yu, J. -Q. J.
Am. Chem. Soc. 2006, 128, 6790. (b) Chu, L.; Yue, X.;
Qing, F. -L. Org. Lett. 2010, 12, 1644. (c) Zhang, S.; Qian,
P.; Zhang, M.; Hu, M.; Cheng, J. J. Org. Chem. 2010, 75,
6
732. (d) Tran, L. D.; Popov, I.; Daugulis, O. J. Am. Chem.
Soc. 2012, 134, 18237. (e) Yan, X-B.; Gao, P.; Yang, H-B.;
Li, Y-X.; Liu, X-Y.; Liang, Y-M. Tetrahedron. 2014, 70,
8
730. (f) Yang, L.; Wen, Q.; Xiao, F.; Deng, G-J. Org.
Biomol. Chem. 2014, 12, 9519.
[
10] (a)Yang, Y.; Hou, W.; Qin, L.; Du, J.; Feng, H.; Zhou, B.;
Li, Y. Chem. Eur. J. 2014, 20, 416. (b) Iwasaki, M.;
Iyanaga, M.; Tsuchiya, Y.; Nishimura, Y.; Li, W.; Li, Z.;
Nishihara, Y. Chem. Eur. J. 2014, 20, 2459. (c) Iwasaki,
M.; Kaneshika, W.; Tsuchiya, Y.; Nakajima, K.;
Nishihara, Y. J. Org. Chem. 2014, 79, 11330. (d) Qiu, R.;
Reddy, V. P.; Iwasaki, T.; Kambe, N. J. Org. Chem. 2015,
8
0, 367.
[
[
11] (a) Ye, Y.; Ball, N. D. Kampf, J. W.; Sanford, M. S. J.
Am. Chem. Soc. 2010, 132, 14682. (b) Jia, X.; Yang, D.;
Zhang, S.; Cheng, J. Org. Lett. 2009, 11, 4716. (c) Luo, F.;
Pan, C.; Li, L.; Chen, F.; Cheng, J. Chem. Commun. 2011,
4
7, 5304.
12] (a) Zhang, X -S.; Zhang, X -H.; Phosphorus, Sulfur Silicon
Relat. Elem. 2015, DOI: 10.1080/10426507.2015.1012670.
(b) Chen, Q.; Shen, M.; Tang, Y.; Li, C. Org. Lett. 2005, 7,
1
625.

ACCEPTED MANUSCRIPT
Pd(II)-Catalyzed Selective Sulfenylation of Arene
C−H Bonds Using N-Arylthiobenzamides as
Thiolation Reagent and Oxidant
Xing-Song Zhang, Guoxing Li, and Xing-Guo Zhang*, Xiao-Hong Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou
3
25035, China
zxg@wzu.edu.cn; kamenzxh@wzu.edu.cn
Supporting Information
List of Contents
1
.
Typical experimental procedure for the synthesis of
N-arylthiobenzamides
1
13
19
2
3
. H NMR, C NMR and F NMR of Compounds 3a-3y---- S3-S57
1
13
19
. H NMR, C NMR and F NMR of Compounds 4a-4s--------S58-S99
S1

ACCEPTED MANUSCRIPT
1
. Typical experimental procedure for NaH promoted sulfenylation of
[1]
benzamides with disulfide
The benzamide (0.2 mmol), NaH (3 equiv.) and dry THF (3 mL) were added to a
two necked flask in turn and stirred at room temperature for 1h. Then disulfide (1.5
equiv.) was added into the mixture and stirred for another 36 h at room temperature.
During the whole reaction process, the system was kept turbid owing to the difficult
solubility of NaH in THF. Then the resulting mixture was filtered and washed with
EtOAc to give the solvent, which was concentrated in vacuo and the residue was
purified by flash column chromatography on a silica gel to give the desired product.
[
1] (a) Zhang, X. -S.; Zhang, X. -H.; Phosphorus, Sulfur Silicon Relat. Elem. 2015,
DOI: 10.1080/10426507.2015.1012670. (b) Chen, Q.; Shen, M.; Tang, Y.; Li, C. Org.
Lett. 2005, 7, 1625.
S2

ACCEPTED MANUSCRIPT
1
2
. H NMR of 2-(2-(phenylthio)phenyl)pyridine (3a)
S3

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-(phenylthio)phenyl)pyridine (3a)
S4

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-(p-tolylthio)phenyl)pyridine (3b)
S5

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-(p-tolylthio)phenyl)pyridine (3b)
S6

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((2-fluorophenyl)thio)phenyl)pyridine (3c)
S7

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((2-fluorophenyl)thio)phenyl)pyridine (3c)
S8

ACCEPTED MANUSCRIPT
1
9
F NMR of 2-(2-((2-fluorophenyl)thio)phenyl)pyridine (3c)
S9

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((4-fluorophenyl)thio)phenyl)pyridine (3d)
S10

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((4-fluorophenyl)thio)phenyl)pyridine (3d)
S11

ACCEPTED MANUSCRIPT
1
9
F NMR of 2-(2-((4-fluorophenyl)thio)phenyl)pyridine (3d)
S12

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((2-chlorophenyl)thio)phenyl)pyridine (3e)
S13

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((2-chlorophenyl)thio)phenyl)pyridine (3e)
S14

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((3-chlorophenyl)thio)phenyl)pyridine (3f)
S15

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((3-chlorophenyl)thio)phenyl)pyridine (3f)
S16

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((4-chlorophenyl)thio)phenyl)pyridine (3g)
S17

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((4-chlorophenyl)thio)phenyl)pyridine (3g)
S18

ACCEPTED MANUSCRIPT
1
H NMR of 2-(2-((3,5-dichlorophenyl)thio)phenyl)pyridine (3h)
S19

ACCEPTED MANUSCRIPT
1
3
C NMR of 2-(2-((3,5-dichlorophenyl)thio)phenyl)pyridine (3h)
S20