Copper-Catalyzed C-S Bond Formation via the Cleavage of C-O Bonds in the Presence of S8 as the Sulfur Source

Article abstract of DOI:10.1055/s-0036-1588508

Useful and applicable methods for one-pot and odorless synthesis of unsymmetrical and symmetrical diaryl sulfides via C-O bond activation are presented. First, a new efficient procedure for the synthesis of unsymmetrical sulfides using the cross-coupling reaction of phenolic esters such as acetates, tosylates, and triflates and with arylboronic acid or triphenyltin chloride as the coupling partners is reported. Depending on the reaction, S ₈ /KF or S ₈ /NaO t -Bu system is found to be an effective source of sulfur in the presence of copper salts and in poly(ethylene glycol) as a green solvent. Then, the synthesis of symmetrical diaryl sulfides from phenolic compounds by using S ₈ as the sulfur source and NaO t -Bu in anhydrous DMF at 120 °C under N ₂ is described. By these protocols, the synthesis of a variety of unsymmetrical and symmetrical sulfides become easier than the available protocols in which thiols and aryl halides are directly used for the preparation of the sulfides.

Full text of DOI:10.1055/s-0036-1588508

SYNTHESIS
0
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©
Georg Thieme Verlag Stuttgart · New York
2017, 49, A–N
paper
A
en
Synthesis
A. Rostami et al.
Paper
Copper-Catalyzed C–S Bond Formation via the Cleavage of C–O
Bonds in the Presence of S as the Sulfur Source
8
Abed Rostamia
Amin Rostami*a
Arash Ghaderi*b
Mohammad Gholinejadc
Sajedeh Gheisarzadeha
S
Cu(OAc)2, S8, Ph3 SnCl
Ph
10 examples
79–94%
Ar
OZ
Ar
PEG200, KF, K2CO3, 80 °C
tBu
S
CuI, S8, NaO
10 examples
75–93%
Ar
Ar
DMF (anhyd), N2,120 °C
Z = Ac, Tf, Ts
S
a
Ar
23 examples
Department of Chemistry, Faculty of Science, University of
Kurdistan, 66177-15175 Sanandaj, Iran
a_rostami372@yahoo.com
Ar
7
0–95%
t
PEG200, NaO Bu, 60–80 °C
b
Department of Chemistry, College of Sciences, Hormozgan
University, 71961 Bandar Abbas, Iran
aghaderi@hormozgan.ac.ir
Department of Chemistry, Institute for Advanced Studies in
c
Basic Sciences, Gava Zang, 5137-66731 Zanjan, Iran
Received: 21.06.2017
Accepted after revision: 23.06.2017
Published online: 03.08.2017
susceptible to oxidation producing disulfides as by-prod-
ucts. In addition, thiols can bind to metals acting as a metal
poison.5
DOI: 10.1055/s-0036-1588508; Art ID: ss-2016-n0842-op
Two strategies are usually employed for the C–O bond
activation followed by C–S bond formation. Activated oxy-
gen can be replaced by an organosulfur nucleophile via
two-component or three-component reactions (Scheme
Abstract Useful and applicable methods for one-pot and odorless syn-
thesis of unsymmetrical and symmetrical diaryl sulfides via C–O bond
activation are presented. First, a new efficient procedure for the synthe-
sis of unsymmetrical sulfides using the cross-coupling reaction of phe-
nolic esters such as acetates, tosylates, and triflates and with arylboron-
ic acid or triphenyltin chloride as the coupling partners is reported.
Depending on the reaction, S /KF or S /NaOt-Bu system is found to be
an effective source of sulfur in the presence of copper salts and in po-
ly(ethylene glycol) as a green solvent. Then, the synthesis of symmetri-
cal diaryl sulfides from phenolic compounds by using S8 as the sulfur
6
1).
(b)
(a)
8
8
SR
SR
three-component
OX two-component
R'
R'
thiourea
R (alkyl) source
catalyst: [Cu]
R'
RS source
catalyst: [Pd], [Ni]
X = Tf, Ms
source and NaOt-Bu in anhydrous DMF at 120 °C under N is described.
2
X = Tf, Ts, Ac, P(O)OEt2
By these protocols, the synthesis of a variety of unsymmetrical and
symmetrical sulfides become easier than the available protocols in
which thiols and aryl halides are directly used for the preparation of the
sulfides.
Scheme 1 Two approaches for the construction of C–S bond via C–O
bond activation
Key words phenolic esters, arylboronic acid, triphenyltin chloride,
copper salt, catalyst, sulfides
To date, the most intriguing procedure for thioetherifi-
cation of aromatic compounds is the in situ generation of
thiols or thiolates by the aid of various sulfur sources in-
cluding thiourea, sodium thiosulfate, sulfur powder, and so
Carbon–oxygen bond activation reactions leading to the
functionalized aromatic compounds is one of the most im-
7–14
on.
Recently, sulfur powder has been used for S-aryla-
1
portant reactions in organic chemistry. Activation of phe-
tion due to its low cost and its characteristics of being both
odorless and environmentally benign. Chen et al. studied
the effect of different bases in the synthesis of asymmetri-
cal diaryl disulfides by reacting aryl halides with sulfur
power in the presence of a Cu salt.1 The reaction of penta-
nolic C–O bonds have significant synthetic values due to the
wide commercial availability of phenol derivatives. Since
the hydroxyl group attached to the aromatic ring is almost
inert toward displacement reactions, its activation is neces-
sary by conversion into esters, phosphonates, triflates, to-
3f
fluorobenzene derivatives with S resulted the formation of
8
2
sylates, heteroaryl ethers, etc. These phenol derivatives are
symmetric diaryl sulfides in the presence of RhH(PPh ) as
3
4
the catalyst.1 A copper-mediated C–S/N–S bond-forming
4i
suitable alternatives to aryl halides as the coupling partner
in the cross coupling reactions for the construction of car-
reaction via C–H activation that uses elemental sulfur has
3
14j
bon–heteroatom bonds. Among these, carbon–sulfur bond
been reported. Very recently, oxidative sulfenylation of
formation reaction is of high importance in organic and
medicinal chemistry. Nevertheless, the studies on these
electron-rich heteroarenes and annulation/arylthiolation
reaction to afford functionalized 3-sulfenylbenzofuran with
4
kinds of reactions are limited because thiols, which are
usually used as starting materials in these reactions are
arylboronic and S in the presence of palladium as catalyst
8
has been developed by Wu and co-workers.1 The synthe-
4k,l
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B
Synthesis
A. Rostami et al.
Paper
sis of thioarylated imidazoheterocycles from aryl halides
and elemental sulfur catalyzed by CuI has also been devel-
oped.
Lately, we have reported an odorless method for the
synthesis of unsymmetrical sulfides using the reaction of
Table 1 Optimization of the Reaction Conditions for the Reaction of
Phenyl Acetate with Phenylboronic Acida
14m
OH
OAc
B
S
CuI (cat.), S source, base
solvent, T (°C), 15 h
OH
+
arylboronic acid/S system as a thiolating agent with
8
5a
1
aryl/alkyl halides, and also we have released three proto-
cols for the denitrative thioetherification of different ni-
troarenes via C–N bond activation.15b Very recently, the
synthesis of symmetrical and unsymmetrical aryl sulfides
by the reaction of triphenyltin chloride and aryl halides
Entry S source
Base
Solvent
Temp
GC Yield
(%)
(
°C)
1
2
3
4
5
6
7b
8
9
S
S
8
8
NaOH
CO
Cs CO
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
DMF
60
60
60
60
60
60
80
80
80
80
80
80
80
80
80
80
80
80
–
–
K
2
3
15c
with S8 in poly(ethylene glycol) is described.
The C–S
S8
14
2
3
bond formation reactions using arylboronic acids as the
coupling partners for the copper-catalyzed synthesis of un-
symmetrical sulfides via cleavage of their C–B bonds is
S
S
S
S
S
8
8
8
8
8
Et
3
N
–
DABCO
–
15,16
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
74
100
91
64
34
–
available in the literature.
In order to expand these
methods, we became interested in studying the possibility
for the C–S bond formation of phenolic esters via thiol-free
process by activating the C–O bond. To the best of our
knowledge, the utilization of non-thiolic procedures for the
synthesis unsymmetrical diaryl sulfides by the reaction of
phenolic esters with arylboronic acid or triphenyltin chlo-
ride and also the synthesis of symmetrical sulfides by using
phenolic esters have not been reported.
S8
MeCN
1
0
1
2
3
S
8
1,4-dioxane
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
1
1
1
thiourea
Na
Na
2
2
S
2
O
3
·5H
2
O
–
S
64
58
79
82
74
–
In order to optimize the reaction conditions, the reac-
tion of phenyl acetate with phenylboronic acid was selected
14
PhSH
5c
1
1
1
S
S
S
S
8
8
8
8
as the benchmark in the presence of S and CuI in poly(eth-
8
6d
7e
8
ylene glycol) (PEG 200) (Table 1). Initially, the reaction was
performed in the presence of NaOH at 60 °C (Table 1, entry
1
1
). Under these conditions, the reaction failed to produce
the desired products and phenyl acetate just got converted
into phenol. Changing the base to K CO was not effective
a
Reaction conditions: phenyl acetate (1 mmol), phenylboronic acid (1.1
mmol), sulfur (1.5 mmol), CuI (15 mol%), base (4 mmol), and solvent (2
mL).
2
3
b
for the reaction (entry 2). Only 14% GC yield was observed
with Cs CO as the base in this reaction (entry 3). No prod-
Most effective reaction conditions.
S (1 mmol).
8
NaOt-Bu (3 mmol).
CuI (10 mmol).
c
2
3
d
e
uct was obtained by using Et N and DABCO as the organic
3
bases (entries 4, 5). The GC yield of the desired product was
remarkably improved by switching the base to NaOt-Bu
(
entry 6). By increasing the reaction temperature to 80 °C,
nolic esters (ArOAc, ArOTf, ArOTs) with arylboronic acids
was studied (Table 2). As shown in Table 2, the expected
products were obtained in moderate to high yields irrespec-
tive to the position of substituents on phenolic esters (Table
2, entries 2–15). It has been shown that phenolic esters
with electron-withdrawing groups reacted faster than the
phenolic esters having electron-releasing groups (entries
2–15). Likewise, arylboronic acids containing electron-do-
nating groups showed less reactivity. Among phenolic ester
derivatives, the most reactive were found to be aryl tri-
flates. Interestingly, aryl acetates which are relatively unre-
active substrates got converted into the corresponding un-
symmetrical sulfides in high to excelent yields under the
same reaction conditions (Table 2). Another important as-
pect of this method is the successful reaction of sterically
hindered substrates to give the desired products in high
yields (Table 2, entries 9, 16, 17). Ortho-substituted pheno-
lic esters require longer reaction times giving relatively
the complete conversion of phenyl acetate into the desired
product was observed (entry 7). In order to study the effect
of the solvents, the reaction was conducted in other sol-
vents; DMF, MeCN, and 1,4-dioxane (entries 8–10). The re-
sults showed that the most effective solvent was PEG200
(entry 7). Apart from S , other sulfur sources such as
8
Na S O ·5H O, thiourea, and Na S were also tested.
2
2
3
2
2
Among the sulfur sources studied, Na S O ·5H O and
2
2
3
2
thiourea failed to react (Table 1, entries 11, 12), whereas
Na S gave the desired product in 64% GC yield (entry 13).
Utilizing thiophenol instead of phenylboronic acid/S sys-
tem resulted in only 58% conversion of phenyl acetate (en-
2
8
try 14). The amount of S , NaOt-Bu and the catalyst were
8
also optimized (entries 15–17). The reaction failed in the
absence of the catalyst (entry 18). Under the optimized
conditions (entry 7), the coupling reaction of various phe-
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C
Synthesis
A. Rostami et al.
Paper
lower yields than para-substituted phenolic esters (entries
–9). The reaction of 2-pyridyl esters (acetates, tosylates,
and triflates) as a heteroaromatic compound with arylbo-
ronic acids gave the products in excellent yields (entries 21,
with NaOt-Bu to produce sodium disulfide.13f Then, stable
copper disulfide is formed from the reaction of sodium di-
sulfide with CuI. In the next step, copper disulfide reacts
with arylboronic acid via oxidative addition reaction to give
intermediate I, which gets converted into intermediate II,
subsequently.1 Intermediate II reacts with phenolic esters
via C–O bond cleavage to provide the key intermediate III.
The desired product may result from reductive elimination
of the key intermediate III.
7
22).
3g
Based on these observations and also previously report-
15
ed results, the plausible mechanism for the reaction of ar-
ylboronic acids with phenolic esters in the presence of S is
8
presented in Scheme 2. It is hypothesized that S8 reacts
Table 2 C–S Bond Formation of Phenolic Esters with Arylboronic Acids Using S Catalyzed by CuIa
8
Z
B(OH)2
S
t
CuI (cat.), S8, NaO Bu
+
R2
PEG200, 60–80 °C
R2
R1
R1
Z = OAc, OTs, OTf
Entry
ArZ
ArB(OH)
2
Product
Z = OAc
Z = OTs
Z = OTf
Time (h) Yield (%)b Time (h) Yield (%)b Time (h) Yield (%)b
B(OH)2
S
1
2
Z
Z
15
17
92
93
9
81
79
7
9
84
80
B(OH)2
S
11
Me
Me
Me
Me
B(OH)2
S
3
4
5
6
MeO
Z
Z
24
30
22
25
90
87
92
89
18
21
16
19
80
78
80
77
16
19
13
16
86
82
88
80
MeO
B(OH)2
S
MeO
Me
MeO
Me
Me
B(OH)2
S
S
Z
Z
B(OH)2
Me
Me
Me
Me
B(OH)2
S
Z
Z
7
8
20
23
95
91
15
17
81
76
11
14
89
85
Me
Me
B(OH)2
Me
S
Me
Me
Me
B(OH)2
Z
S
9
26
24
89
80
20
20
74
82
17
15
80
79
Me
B(OH)2
10
Z
S
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Synthesis
A. Rostami et al.
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Table 2 (continued)
Entry
ArZ
ArB(OH)
2
Product
Z = OAc
Z = OTs
Z = OTf
Time (h) Yield (%)b Time (h) Yield (%)b Time (h) Yield (%)b
B(OH)2
Me
11
24
80
22
81
17
78
Z
Me
S
S
B(OH)2
12
13
14
15
O2N
Z
Z
9
11
10
13
95
92
90
89
4
5
6
7
84
81
80
79
2
3
4
5
89
84
88
83
O2N
B(OH)2
S
O2N
NC
Me
O2N
NC
Me
B(OH)2
S
Z
B(OH)2
S
NC
Z
Me
NC
Me
Z
Z
S
Ph
B(OH)2
16
17
18
21
85
93
12
14
74
81
9
80
86
B(OH)2
S
Me
11
Me
Z
B(OH)2
S
Ph
18
19
20
17
19
12
95
91
91
10
13
7
85
80
82
7
10
5
90
86
86
Z
Z
B(OH)2
S
S
Me
Me
B(OH)2
O2N
NO2
N
N
Z
Z
B(OH)2
N
N
S
2
1
2
12
13
88
90
7
8
70
78
5
5
78
80
B(OH)2
S
2
Me
Me
Z
B(OH)2
S
23
10
89
6
88
3
84
Ac
O2N
Ac
NO2
a
Reaction conditions: phenolic ester (1 mmol), arylboronic acid (1.1 mmol), CuI (15 mol %), sulfur (1.5 mmol), NaOt-Bu (4 mmol), PEG200 (2 mL), 60–80 °C.
Isolated yield after column chromatography.
b
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Synthesis
A. Rostami et al.
Paper
presence of S and a catalytic amount of a copper salt. For
this aim, the reaction between p-methoxyphenyl acetate
8
O
O
S
S
S
S
S
S
S
S
S
S
and triphenyltin chloride in the presence S was selected as
8
S
S
S
S
t
15c
2 NaO Bu
a model reaction. Inspired by the preceding results, we
first conducted the reaction in the presence of Cu(OAc)2,
S /KF, and K CO in PEG200 at 60 °C. Under these condi-
+
8
2
3
Na
Na
tions, the desired product was obtained in 81% yield (Table
, entry 1). By increasing the reaction temperature to 80 °C,
S
S
Ar'
3
S
Ar
CuI
the complete conversion of p-methoxyphenyl acetate into
the product was observed (entry 2). As shown in Table 3,
the nature of the base was important affecting the yield of
the desired product (entries 1–5). Among the organic and
inorganic bases, K CO was found to be the most effective
2
Ar'
Cu
Cu
Ar
S
Cu
Z
S
S
2
3
OH
B
III
t
base for this reaction (entry 2). It was also observed when
+
NaO Bu
Ar
OH
Et N was used as a base in the reaction, diphenyl disulfide
3
was found as the only product (entry 5). In order to study
the effect of the solvents, we have conducted the reaction in
PEG200, DMF, 1,4-dioxane, and MeCN (entries 2 and 6–8).
Among these solvents, the most effective was found to be
PEG200 (entry 2). Apart from Cu(OAc) , CuI and CuCl were
B(OH)3
Ar'-Z
CuII
S
CuII
Ar
Ar
S
Cu
I
Ar
S
II
I
2
2
also active catalysts for the synthesis of desired product in
high yields (entries 9 and 10). In the absence of KF, no prod-
uct was observed (entry 14). Only 55% of diphenyl sulfide
was obtained when triphenyltin chloride was replaced with
diphenyl disulfide (entry 15). Diphenyl disulfide was pro-
duced in the absence of p-methoxyphenyl acetate (entry
16). When CuS was used instead of KF/S /Cu(OAc) , longer
Scheme 2 Proposed mechanism for C–S bond formation using the re-
action of arylboronic acid with phenolic esters in the presence of S cat-
8
alyzed by CuI
In continuation of our studies for the C–S bond forma-
tion of phenolic esters by activating the C–O bond, we have
investigated the possibility of the synthesis of phenyl aryl
sulfides using triphenyltin chloride as phenyl source in the
8
2
time is required to complete the reaction (entry 17).
Table 3 Optimization of the Reaction Conditions with Respect to the Effect of Catalysts, Solvent, and Base on the Reaction of p-Methoxyphenyl Ace-
a
tate with Triphenyltin Chloride
OAc
S
Cu salt, S8, KF
+
Ph3SnCl
Ph-S-S-Ph
+
base, solvent, 80 °C, 7 h
MeO
OMe
Entry
Cu salt
Base
Solvent
GC yield (%) of a
GC yield (%) of b
1b
2c
3
Cu(OAc)
K
CO
CO
Cs CO
NaOt-Bu
Et
PEG200
PEG200
PEG200
PEG200
PEG200
DMF
–
81
100
64
67
–
2
2
3
Cu(OAc)
2
K
2
3
–
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
CuI
2
2
3
36
33
100
–
4
2
5
2
2
2
2
3
N
6
K
K
K
K
K
K
K
K
K
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
91
74
63
81
94
74
75
88
–
7
2
2
2
2
2
2
2
2
1,4-dioxane
MeCN
–
8
–
9
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
–
1
1
1
0
CuCl
2
–
1d
2e
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
–
2
2
2
2
–
1 f
4g
3
–
1
–
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Synthesis
A. Rostami et al.
Paper
Table 3 (continued)
Entry
Cu salt
Base
Solvent
GC yield (%) of a
GC yield (%) of b
1
5h
1 i
1 j
Cu(OAc)
Cu(OAc)
CuS
2
K
K
K
2
2
2
CO
CO
CO
3
3
3
PEG200
PEG200
PEG200
45
100
–
55
–
6
2
7
100
a
Reactions conditions: p-methoxyphenyl acetate (1 mmol), triphenyltin chloride (0.35 mmol), sulfur (1.5 mmol), Cu salt (15 mol%), KF (3 mmol), base (3 mmol),
solvent (1.5 mL), 80 °C.
b
The reaction was performed at 60 °C.
Most effective reaction conditions.
Cu(OAc) (10 mol%) was employed.
2
KF (2.5 mmol) was used.
Sulfur (1 mmol) was employed.
Without KF.
The reaction was performed using diphenyl disulfide instead of Ph
In the absence of p-methoxyphenyl acetate.
The reaction was performed in the absence of KF and S for 13 h.
8
c
d
e
f
g
h
i
3
SnCl for 48 h.
j
In order to generalize the scope of the reaction, a series
having electron-donating groups (Table 4, entries 2–7). An-
other important aspect of this method is the successful re-
action of sterically demanding substrates to give the de-
sired products in good yields (entry 5). We have also ap-
plied this method to the reaction of 2-pyridyl esters
(acetates, triflates, and tosylates) with triphenyltin chloride
as heteroaromatic compounds (entry 10).
of structurally diverse phenolic ester was subjected to reac-
tion with triphenyltin chloride under the optimized reac-
tion conditions in PEG200 as the solvent. The reactions pro-
ceeded well to produce the corresponding phenyl aryl sul-
fides in moderate to excellent yields ranging from 79 to 94%
(
Table 4). It was observed that phenolic esters with elec-
tron-withdrawing groups show greater activity than those
a
Table 4 C–S Bond Formation of Phenolic Esters with Ph SnCl Using S Catalyzed by Cu(OAc)
3
8
2
Z
Cu(OAc)2, S8, KF
S
Ph
+
Ph3SnCl
K2CO3, PEG200, 80 °C
R
R
Z = OAc, OTs, OTf
Entry
ArZ
Product
Z = OAc
Z = OTs
Z = OTf
Time (h)
Yield (%)b
93
Time (h)
Yield (%)b
Time (h)
Yield (%)b
86
S
1
2
Z
7
3
88
83
2
8
S
MeO
Z
15
12
90
89
10
7
89
80
MeO
S
3
4
Me
Me
Z
81
80
5
6
Me
Me
S
Z
11
15
94
87
8
9
86
80
Me
S
Z
5
79
7
Me
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Paper
Table 4 (continued)
Entry
ArZ
Product
Z = OAc
Time (h)
Z = OTs
Z = OTf
Yield (%)b
92
Time (h)
Yield (%)b
88
Time (h)
Yield (%)b
94
S
6
7
O N
Z
2
0.5
1
0.1
0.5
2
O2N
S
NC
Z
3.5
92
90
86
83
80
88
81
NC
Z
S
Ph
8
9
11
6
4
Z
S
Ph
8
5
90
91
7
2
5
1
81
80
N
Z
N
S
10
80
a
Reaction conditions: phenolic ester (1 mmol), triphenyltin chloride (0.35 mmol), sulfur (1.5 mmol), Cu(OAc)
1.5 mL).
Isolated yield after column chromatographic separation.
2
2 3
(15 mol%), KF (3 mmol), K CO (3 mmol), PEG200
(
b
Based on our observations (Table 3, entries 5 and 14–
phenolic esters in the presence of S is depicted in Scheme
8
1
7) and the previously reported mechanism for C–S bond
3. Potassium disulfide, produced from the reaction of S8
with KF, reacts with Cu(OAc) to generate Cu S . Triphen-
yltin chloride reacts with copper sulfide by oxidative addi-
tion and subsequent phenyl group immigration to form in-
formation reactions in the presence of S as a sulfur
source
mechanism for the reaction of triphenyltin chloride with
8
2
2 2
13f,g
15
and Ph SnCl as a phenyl source, the proposed
3
S
Ph
Ar
ArZ
F
F
S
S
S
S
Z
S
S
PhS-Cu-Ar
S
S
S
S
5
KF
S
S
S
S
PhSCu(I)
+
2
CuII
4
K
K
Base
S
S
PhSn-Cu-S
CuII
base
–
PhSn-Cu-S
Ph-S-Cu-S-Ph
Ph-S-S-Ph
S
S
–
2 SnII
Cu
Cu
7
3
K2S2
Ph
Ph3SnCl
PhSn-Cu-Cl
S
S
6
Cl Cu
Cu SnPh Cl Cu
Cu SnPh3
S
S
Ph
1
2
Scheme 3 Proposed pathway for the synthesis of phenyl aryl sulfides via C–S bond formation reaction of phenolic ester with triphenyltin chloride using
S in the presence of Cu(OAc) as a catalyst
8
2
©
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Synthesis
A. Rostami et al.
Paper
termediate 2. Dissociation of the intermediate 2 generates
two intermediates 3 and 6. The employed base might play
an effective role upon intermediate 3. In the presence of
K CO , intermediate 3 converts into intermediate 4 and
then reacts with phenolic esters by oxidative addition to
form 5. Reductive elimination affords the diaryl sulfide to
complete the catalytic cycle. The intermediate 3 can also
Table 5 Optimization of the Reaction Conditions for the Conversion of
Phenyl Acetate into Diphenyl Sulfide Using S8a
OH
2
3
OAc
+
S
t
Cu (cat.), NaO Bu
S8
+
temp, solvent, 10 h
a
b
produce diphenyl disulfide when Et N was used instead of
3
K CO . We observed that in the absence of phenolic esters,
2
3
Entry Cu salt
Solvent
Temp
(°C)
GC yield (%) GC yield (%)
triphenyltin chloride produces diphenyl disulfide in quanti-
tative yield under similar reaction conditions within 24
hours.
It is very likely that in the absence of phenolic esters, in-
termediate 4 reverses back to intermediate 3 resulting in di-
phenyl disulfide. The intermediate 6 reacts with potassium
sulfide to give intermediate 7, which is capable of transfer-
of a
of b
1
2
3
4
5
CuI
CuI
CuI
CuI
CuI
PEG200
80
100
100
120
120
120
120
120
120
120
120
120
120
120
–
–
–
PEG200
100
DMF
89
56
13
11
DMF
46
87
DMF (anhyd)
DMF (anhyd)
MeCN (anhyd)
toluene (anhyd)
Solvent-free
DMF (anhyd)
DMF (anhyd)
DMF (anhyd)
DMF (anhyd)
DMF (anhyd)
ring to intermediate 3. When Et N is used instead of K CO ,
6b,c CuI
3
2
3
–
100
64
intermediate 3 yields diphenyl disulfide exclusively (Table
7b
8b
CuI
CuI
–
–
–
–
–
–
–
–
3, entry 5).
43
In another effort, we studied the homocoupling reac-
9b,d CuI
10b
Cu(OAc)
11
100
93
tion of phenolic esters in the presence of S to produce sym-
8
metrical diaryl sulfides. To optimize the reaction condi-
tions, phenyl acetate was employed as the starting material
2
b
CuCl2
CuI
88
(Table 5). Encouraged by the above results, we have per-
2b,e
1
1
100
79
formed the reaction in the presence of CuI, S , and NaOt-Bu
8
3b,f CuI
4b,g CuI
in PEG200 at 80 °C. Under these conditions, the reaction
failed to give the required product (Table 5, entry 1). By in-
creasing the reaction temperature to 100 °C, the complete
conversion of phenyl acetate into the phenol was observed
1
82
a
Reaction conditions: phenyl acetate (1 mmol), sulfur (0.5 mmol), CuI (5
mol%), base (4 mmol), and solvent (2 mL).
b
c
d
e
f
The reaction was performed under an inert atmosphere.
Most effective reaction conditions.
(entry 2). Using DMF as a solvent led to 11% conversion into
The reaction was carried out in the presence of Bu
(1 mmol).
4
NBr (1 mmol) for 13 h.
the desired product along with phenol (89%) (entry 3). The
GC yield was increased to 46% by increasing the tempera-
ture to 120 °C (entry 4). The complete conversion of phenyl
acetate into the desired product was achieved using anhy-
drous DMF as the solvent under an inert atmosphere within
S
8
NaOt-Bu (3 mmol).
CuI (2.5 mmol%).
g
model for the hindered phenolic esters was also converted
into the desired products in high yields (entry 5). We have
also applied this method to the reaction of 2-pyridyl ace-
tate, tosylate, and triflate with S giving 92, 76, and 87%
yield, respectively (entry 10).
A mechanism for this reaction is proposed on the basis
of our observations (Table 5, entries 6–9) and previously re-
ported mechanism.1 We believe that the synthesis of sym-
metrical diaryl sulfides proceeds through a mechanism
similar to that suggested for the synthesis unsymmetrical
10 hours (entries 5, 6). In order to expand our studies to
show the effect of the different solvents, the reaction was
conducted in toluene, MeCN, and also under solvent-free
conditions (entries 7–9). The results showed that, again,
complete conversion into the desired product was achieved
8
under solvent-free conditions in the presence of Bu NBr
4
3f
within 13 hours (entry 9). Using Cu(OAc) and CuCl instead
2
2
of CuI lower yields were obtained (entries 10, 11).
With the optimal conditions in hand, DMF as the sol-
vent, CuI as the catalyst at 120 °C (Table 5, entry 6), the gen-
erality and the applicability of this method was further ex-
amined for the synthesis of symmetrical sulfides from the
reaction of phenolic esters with S8.
As shown in Table 6, the expected products were ob-
tained in high to excellent yields. Generally, phenolic esters
with electron-withdrawing groups showed much more re-
activity than those having electron-donating groups (Table
sulfides. As shown in Scheme 4, S reacts with NaOt-Bu to
8
produce sodium disulfide.1
3f,15b
Then, the produced copper
disulfide from the reaction of sodium disulfide and CuI, re-
acts with phenolic ester via C–O bond cleavage followed by
oxidative addition to give intermediate A, which may con-
vert into intermediate B through aryl group migration. In-
termediate B can be converted into intermediate C with
NaOt-Bu and DMF.15 Then, with the addition of other phe-
nolic compound the desired product is released after reduc-
tive elimination completing the catalytic cycle.
6, entries 2–7). Interestingly, o-methylphenolic ester as the
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A. Rostami et al.
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Table 6 Reaction of Various Phenolic Esters with S for the Synthesis of Symmetrical Diaryl Sulfidesa
8
Z
S
t
CuI, NaO Bu, N2
+
S8
DMF (anhyd), 120 °C
R
R
R
Z = OAc, OTs, OTf
Entry
ArZ
Product
Z = OAc
Z = OTs
Z = OTf
Time (h)
Yield (%)b Time (h) Yield (%)b Time (h)
Yield (%)b
87
S
1
2
Z
10
90
89
5
84
80
3
9
S
MeO
Z
18
15
11
86
83
MeO
OMe
S
3
4
Me
Me
Z
88
93
8
7
79
79
6
5
Me
Me
Me
S
Me
Z
14
18
85
83
Me
Me
Z
S
5
86
12
76
9
Me
S
6
7
O N
Z
5
90
91
1
2
83
81
0.3
1
90
88
2
O2N
NC
NO2
S
NC
Z
6.5
CN
Z
S
8
9
13
90
8
80
6
86
Z
S
N
11
7
92
92
9
3
83
75
8
2
89
87
N
Z
N
S
10
a
t
Reaction conditions: phenolic ester (1 mmol), NaO Bu (4 mmol), sulfur (0.5 mmol), CuI (5 mol%), anhyd DMF (2 mL), 120 °C.
Isolated yield after column chromatographic separation.
b
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Synthesis
A. Rostami et al.
Paper
times with H O. The organic phase was dried (anhyd Na SO ) and
then evaporated under reduced pressure. Pure phenyl acetate was ob-
tained in 95% yield (120 mg) after column chromatography.
2
2
4
O
O
S
S
S
S
S
S
S
S
S
S
t
1-Naphthyl 4-Methylbenzenesulfonate; Typical Procedure
2
NaO Bu
S
S
S
S
+
4-Toluenesulfonyl chloride (2.85 g, 15 mmol) was added to a mixture
S
Ar
of 1-naphthol (1.4 g, 10 mmol) and Et N (2.8 mL, 20 mmol) in CH Cl
3
2
2
Ar
Na
Na
(50 mL) and the resulting mixture was stirred at r.t. for 24 h. To the
S
S
resulting mixture was added H O (30 mL) and the CH Cl layer was
2
2
2
separated and dried (anhyd Na SO ). Evaporation of the solvent gave
2
4
Z
2 CuI
the desired crude product. Purification of the product was performed
by crystallization from EtOH to give the pure 1-naphthyl tosylate in
ArZ
Ar-S-Cu-Ar
85% yield (253 mg).
S
Cu
Cu
Z
ArSCuII
S
Phenyl Trifluoromethanesulfonate; Typical Procedure
C
ArZ
A mixture of phenol (0.45 g, 5 mmol), trifluoromethanesulfonyl chlo-
ride (0.8 mL, 7.5 mmol) and Et N (1.4 mL, 10 mmol) in THF (30 mL)
3
DMF
Z
Cu
Ar
t
S
S
was stirred at 0 °C for 24 h. The solvent was evaporated and to the
NaO Bu
Cu
Ar
resulting residue were added H O (20 mL) and EtOAc (20 mL). The or-
2
Ar
ganic phase was decanted and dried (anhyd Na SO ). Evaporation of
2
4
S
A
Cu
the solvent and purification by column chromatography on silica gel
(hexane/EtOAc, 4:1) gave the pure triflate in 85% yield (191 mg).
Z
Cu
Cu Z
S
B
Ar
Unsymmetrical Diaryl Sulfides from Arylboronic Acid and Pheno-
lic Esters; General Procedure
Scheme 4 Proposed mechanism for the synthesis of symmetrical dia-
ryl sulfides using phenolic esters in the presence of S and CuI catalyst
8
A one-necked flask was charged with CuI (30 mg, 0.15 mmol), NaOt-Bu
(
376 mg, 4.0 mmol), S8 (47 mg, 1.5 mmol), phenolic ester (1 mmol),
In summary, we have developed new and efficient
methodologies for the synthesis of unsymmetrical diaryl
sulfides by the reaction of arylboronic acid and triphenyltin
chloride as thiolating agents with phenolic ester com-
pounds as the effective and available starting materials in
arylboronic acid (1.1 mmol), and PEG200 (2 mL). The mixture was
magnetically stirred and heated at 60–80 °C for the appropriate reac-
tion time (Table 2). After completion of the reaction, the reaction mix-
ture was cooled to r.t. H O (4 mL) was added and the product was ex-
tracted with EtOAc (3 × 4 mL) and dried (anhyd Na SO ). Evaporation
2
2
4
of the solvent and purification by column chromatography on silica
gel (n-hexane/EtOAc) gave the desired unsymmetrical diaryl sulfides
in 74–95% yields.
the presence of S and copper salts as the catalyst via C–O
bond activation. Also, the synthesis of symmetrical diaryl
sulfides was performed through homocoupling reaction of
8
The yields given below for the products from Table 2 are based on the
corresponding aryl acetates.
phenolic ester compounds in the presence of S as a sulfur
8
surrogate and CuI as a catalyst. Important features of these
procedures are as follows: (1) avoidance of unclean-smell-
ing thiols and aryl halides, which makes the methods more
easy and practical; (2) use of commercially accessible,
cheap, easy-to-handle and chemically stable starting mate-
rials, sulfur source, and catalyst; and (3) the ability to pre-
pare structurally diverse unsymmetrical and symmetrical
diaryl sulfides.
8
Diphenyl Sulfide (Table 2, entry 1)
Colorless liquid; yield: 171 mg (92%, 0.92 mmol).
1
H NMR (CDCl , 400 MHz): δ = 7.26–7.43 (10 H, m).
3
13
C NMR (CDCl , 100 MHz): δ = 135.8, 131.1, 129.3, 127.2.
3
p-Methoxyphenyl p-Tolyl Sulfide14h (Table 2, entry 4)
Yellow oil; yield: 200 mg (87%, 0.87 mmol).
1
H NMR (CDCl , 400 MHz): δ = 7.42 (2 H, d, J = 7.6 Hz), 7.16 (2 H, d, J =
3
1H NMR spectra were recorded at 400 MHz and 13CNMR were record-
8.4 Hz), 7.13 (2 H, d, J = 7.6 Hz), 6.96 (2 H, d, J = 8.4 Hz), 3.7 (3 H, s), 2.4
(3 H, s),
ed at 100 MHz in CDCl using TMS as internal standard. The reaction
3
13
monitoring was carried out by silica gel analytical sheets or by GC
analysis using a 3 m length column packed with DC-200 stationary
phase. Tosylates, triflates, and aryl acetates as phenolic compounds
were prepared in our laboratory as described in the following sec-
tions.
C NMR (CDCl , 100 MHz): δ = 159.5, 136.1, 134.4, 129.8, 129.4,
3
125.6, 114.9, 55.3, 21.0.
8
Phenyl p-Tolyl Sulfide (Table 2, entry 5)
Colorless oil; yield: 184 mg (92%, 0.92 mmol).
1
H NMR (CDCl , 400 MHz): δ = 7.0–7.3 (9 H, m), 2.5 (3 H, s).
3
Phenyl Acetate; Typical Procedure
1
3
C NMR (CDCl , 100 MHz): δ = 137.0, 133.6, 131.0, 129.4, 129.1,
3
Ac O (0.6 mL, 6 mmol) was added to a mixture of phenol (0.47 g, 5
2
1
27.7, 127.0, 126.1, 21.2.
mmol), and K CO (1.35 g, 10 mmol) in CH Cl (25 mL). The mixture
2
3
2
2
was stirred for 24 h at r.t. The resulting mixture was washed several
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A. Rostami et al.
Paper
Phenyl m-Tolyl Sulfide6g (Table 2, entry 7)
1-Naphthyl Phenyl Sulfide6d (Table 2, entry 16)
Colorless oil; 190 mg (95%, 0.95 mmol).
Colorless oil; yield: 200 mg (85%, 0.85 mmol).
1
1
H NMR (CDCl , 400 MHz): δ = 7.28–7.35 (4 H, m), 7.10–7.26 (4 H, m),
H NMR (CDCl , 400 MHz): δ = 8.36–8.39 (3 H, m), 7.92 (1 H, dd, J =
3
3
7.03–7.05 (1 H, d, J = 7 Hz), 2.26 (3 H, s).
7.2, 8 Hz), 7.58–7.63 (2 H, m), 7.56 (1 H, dd, J = 7.2, 1.2 Hz), 7.02–7.38
1
3
(5 H, m).
C NMR (CDCl , 100 MHz): δ = 139.4, 136.7, 135.8, 135.0, 131.5,
3
13
1
30.6, 128.9, 128.7, 127.8, 126.8, 21.5.
C NMR (CDCl , 100 MHz): δ = 123.7, 124.6, 126.1, 126.3, 127.0,
3
127.6, 128.7, 128.6, 129.7, 130.0, 131.8, 134.3, 135.4, 136.0. 136.5.
m-Tolyl p-Tolyl Sulfide6g (Table 2, entry 8)
1
-Naphthyl p-Tolyl Sulfide14h (Table 2, entry 17)
Colorless liquid; yield: 195 mg (91%, 0.91 mmol).
1
Colorless oil; yield: 232 mg (93%, 0.93 mmol).
H NMR (CDCl , 400 MHz): δ = 7.25–7.28 (2 H, m), 7.07–7.17 (5 H, m),
.99 (1 H, d, J = 7.5 Hz), 2.38 (3 H, s), 2.32 (3 H, s).
3
1
6
H NMR (CDCl , 400 MHz): δ = 7.87–7.95 (2 H, m), 7.53–7.57 (3 H, m),
3
1
3
7.29–7.44 (2 H, m), 6.99–7.05 (4 H, m), 2.29 (3 H, s).
C NMR (CDCl , 100 MHz): δ = 137.4, 135.4, 135.3, 134.3, 132.9,
3
13
1
29.5, 129.2, 128.9, 128.6, 126.4, 125.0, 21.1, 21.0.
C NMR (CDCl , 100 MHz): δ = 135.9, 135.4, 132.7, 131.8, 130.0,
3
129.5, 128.6, 127.9, 126.7, 124.8, 123.8, 20.9.
8
Phenyl o-Tolyl Sulfide (Table 2, entry 9)
2
-Naphthyl Phenyl Sulfide6d (Table 2, entry 18)
Colorless oil; yield: 178 mg (89%, 0.89 mmol).
1
White solid; yield: 224 mg (95%, 0.95 mmol); mp 48–49 °C.
1H NMR (CDCl
, 400 MHz): δ = 8.27–7.29 (1 H, m), 7.86–7.97 (2 H, m),
.57–7.67 (1 H, m), 7.45–7.56 (2 H, m), 7.39–7.44 (1 H, m), 7.10–7.29
H NMR (CDCl , 400 MHz): δ = 7.17–7.38 (9 H, m), 2.43 (3 H, s).
3
13
3
C NMR (CDCl , 100 MHz): δ = 140.0, 137.0, 131.1, 133.0, 131.0,
3
7
1
30.6, 129.1, 128.7, 127.0, 126.3, 20.6.
(5 H, m).
1
3
C NMR (CDCl , 100 MHz): δ = 137.3, 135.4, 134.4, 132.9, 129.5,
(
2,3-Dihydroinden-5-yl)phenyl Sulfide (Table 2, entry 10)
3
1
29.2, 128.6, 128.0, 126.4, 125.9, 124.7, 123.9.
Yellow oil; yield: 180 mg (80%, 0.80 mmol).
IR (film): 3055, 2949, 2843, 1610, 1490, 1439, 1103, 713, 472 cm–1
.
2
-Naphthyl p-Tolyl Sulfide14h (Table 2, entry 19)
1
H NMR (CDCl , 400 MHz): δ = 7.73–7.78 (2 H, m), 7.47–7.57 (5 H, m),
3
White solid; yield: 227 mg (91%, 0.91 mmol); mp 67–69 °C.
7.08–7.10 (1 H, m), 2.84–2.90 (4 H, m), 2.08–2.11 (2 H, m).
1
H NMR (CDCl , 400 MHz): δ = 7.60–7.99 (3 H, m), 7.21–7.40 (1 H, m),
3
13
C NMR (CDCl , 100 MHz): δ = 146.0, 136.2, 133.3, 132.2, 131.6,
3
7.11–7.20 (3 H, m), 7.07–7.10 (4 H, m), 2.28 (3 H, s).
128.6, 128.5, 124.9, 33.0, 31.9, 25.8.
13
C NMR (CDCl , 100 MHz): δ = 21.1, 124.7, 125.9, 126.4, 127.1, 127.9,
3
Anal. Calcd for C15H14S (226.34): C, 79.60; H, 6.23; S, 14.16. Found: C,
0.50; H, 6.73; S, 12.77.
128.6, 128.9, 129.0, 129.2, 129.3, 132.8, 135.5, 136.4, 138.3.
8
2
-Naphthyl p-Nitrophenyl Sulfide (Table 2, entry 20)
(
2,3-Dihydroinden-5-yl) p-Tolyl Sulfide (Table 2, entry 11)
Yellow solid; yield: 251 mg (91%, 0.91 mmol); mp 156–157 °C.
Yellow oil; 192 mg (80%, 0.80 mmol).
IR (film): 3016, 2950, 2844, 1607, 1490, 1436, 912, 744, 516 cm–1
1
H NMR (CDCl , 400 MHz): δ = 7.83–7.87 (2 H, d, J = 6.5 Hz), 7.63–7.77
3
.
(3 H, m), 7.52–7.55 (2 H, d, J = 6.5 Hz), 7.45–7.49 (4 H, m),
1
H NMR (CDCl , 400 MHz): δ = 7.73–7.79 (2 H, m), 7.48–7.51 (2 H, m),
13
3
C NMR (CDCl , 100 MHz): δ = 171.4, 133.3, 132.4, 132.3, 132.2,
3
7
2
.29 (2 H, d, J = 7.5 Hz), 7.11 (2 H, d, J = 7.5 Hz), 2.86–2.91 (4 H, m),
.49 (3 H, s), 2.08–2.12 (2 H, m).
131.3, 131.2, 128.6, 128.4, 126.5, 124.4, 116.2.
Anal. Calcd for C16H11NO S (281.33): C, 68.31; H, 3.94; N, 4.98; S,
2
1
3
C NMR (CDCl , 100 MHz): δ = 146.0, 141.2, 136.2, 134.9, 132.3,
3
11.40. Found: C, 68.11; H, 4.10; N, 5.12; S, 11.19.
1
32.2, 131.6, 128.5, 124.9, 33.0, 31.9, 25.8, 21.7.
Anal. Calcd for C16H16S (240.36): C, 79.95; H, 6.71; S, 13.34. Found: C,
0.70; H, 7.50; S, 11.80.
Phenyl 2-Pyridyl Sulfide14h (Table 2, entry 21)
8
Colorless oil; yield: 165 mg (88%, 0.88 mmol).
1H NMR (CDCl
m), 7.38–7.40 (4 H, m), 6.92–6.95 (1 H, m), 6.80 (1 H, d, J = 4.8 Hz).
, 400 MHz): δ = 8.50 (1 H, d, J = 4.8 Hz), 7.52–7.58 (2 H,
p-Nitrophenyl p-Tolyl Sulfide14h (Table 2, entry 13)
3
Yellow solid; yield: 225 mg (92%, 0.92 mmol); mp 81 °C.
13
C NMR (CDCl , 100 MHz): δ = 161.8, 149.4, 138.0 136.0, 129.0, 128.5,
3
1
H NMR (CDCl , 400 MHz): δ = 8.08 (2 H, d, J = 8 Hz), 7.42 (2 H, d, J = 8
3
127.1, 121.1, 119.6.
Hz), 7.25 (2 H, d, J = 7.6 Hz), 7.13 (2 H, d, J =7.6 Hz), 2.3 (3 H, s).
1
3
C NMR (CDCl , 100 MHz): δ = 146.5, 139.9, 140.2, 135.1, 130.9,
2-Pyridyl p-Tolyl Sulfide14h (Table 2, entry 22)
3
1
26.4, 126.1, 124.0, 21.3.
Colorless oil; yield: 180 mg (90%, 0.90 mmol).
1H NMR (CDCl
m), 7.42–7.44 (1 H, m), 7.39–7.51 (1 H, m), 7.21–7.30 (2 H, m), 6.94–
.99 (1 H, m), 6.85 (1 H, d, J = 4.8 Hz), 2.29 (3 H, s).
, 400 MHz): δ = 8.39 (1 H, d, J = 4.8 Hz), 7.51–7.55 (1 H,
p-Cyanophenyl p-Tolyl Sulfide14h (Table 2, entry 15)
3
White solid; yield: 200 mg (89%, 0.89 mmol); mp 95–97 °C.
6
1
H NMR (CDCl , 400 MHz): δ = 7.63–7.60 (4 H, m), 7.27 (2 H, d, J = 8.4
13
3
C NMR (CDCl , 100 MHz): δ = 162.4, 149.5, 140.1, 136.8, 135.9,
3
Hz), 7.13 (2 H, d, J = 8.4 Hz), 2.43 (3 H, s).
130.1, 127.6, 120.9, 119.9, 21.1.
13
C NMR (CDCl , 100 MHz): δ = 146.6, 140.0, 134.9, 133.9, 132.7,
3
130.7, 126.8, 118.8, 111.2, 108.3, 21.3.
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A. Rostami et al.
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4-Acetylphenyl p-Nitrophenyl Sulfide (Table 2, entry 23)
solvent and purification by column chromatography on silica gel (n-
hexane/EtOAc) gave the desired symmetrical diaryl sulfides in 75–
Yellow solid; yield: 242 mg (89%, 0.89 mmol); mp 47–48 °C.
9
3% yields.
1
H NMR (CDCl , 400 MHz): δ = 7.73–7.78 (2 H, d, J = 6.8 Hz), 7.50–7.57
3
The yields given below for the products from Table 6 are based on the
corresponding aryl acetates.
(2 H, d, J = 6.8 Hz), 7.46–7.48 (4 H, m),
13
C NMR (CDCl , 100 MHz): δ = 197.0, 171.2, 135.8, 132.3, 131.9,
3
1
29.8, 129.1, 128.4, 123.5, 26.25.
5
4
,4′-Dimethoxy Diphenyl Sulfide (Table 6, entry 2)
Anal. Calcd for C14H11NO S (273.31): C, 61.53; H, 4.06; N, 5.13; S,
3
Colorless oil; yield: 219 mg (89%, 0.89 mmol).
11.73. Found: C, 61.26; H, 4.29; N, 5.75; S, 11.19.
1
H NMR (CDCl , 400 MHz): δ = 7.30 (4 H, d, J = 6.8 Hz), 6.73 (4 H, d, J =
3
6
.8 Hz), 3.7 (6 H, s).
C–S Bond Formation by the Reaction of Triphenyltin Chloride with
Phenolic Esters; General Procedure
13
C NMR (CDCl , 100 MHz): δ = 159.7, 132.6, 128.3, 114.7, 55.4.
3
A one-necked flask was charged with Cu(OAc)2 (30 mg, 0.15 mmol),
K CO (414 mg, 3.0 mmol), S8 (48 mg, 1.5 mmol), KF (180 mg, 3
Di-p-tolyl Sulfide12d (Table 6, entry 3)
2
3
mmol), phenolic ester (1 mmol), triphenyltin chloride (0.35 mmol),
and PEG200 (1.5 mL). The mixture was magnetically stirred and heat-
ed at 80 °C for the appropriate reaction time (Table 4). After comple-
White solid; yield: 189 mg (88%, 0.88 mmol); mp 55–56 °C.
1
H NMR (CDCl , 400 MHz): δ = 7.32 (4 H, d, J = 8 Hz), 7.08 (4 H, d, J = 8
3
Hz), 2.25 (6 H, s).
tion of the reaction, the reaction mixture was cooled to r.t. H O (4 mL)
2
13
C NMR (CDCl , 100 MHz): δ = 137.4, 131.1, 129.8, 128.5, 21.0.
was added and the product was extracted with EtOAc (3 × 4 mL) and
dried (anhyd Na SO ). Evaporation of the solvent and purification by
3
2
4
column chromatography on silica gel (n-hexane/EtOAc) gave the de-
Di-m-tolyl Sulfide12d (Table 6, entry 4)
sired phenyl aryl sulfides in 79–94% yields.
Yellow liquid; yield: 199 mg (93%, 0.93 mmol).
1
H NMR (CDCl , 400 MHz): δ = 7.34–7.38 (1 H, m), 7.01–7.11 (4 H, m),
3
8
Diphenyl Sulfide (Table 4, entry 1)
6.80–6.82 (2 H, m), 2.23 (6 H, s).
Colorless liquid; yield: 173 mg (93%, 0.93 mmol).
13
C NMR (CDCl , 100 MHz): δ = 139.1, 135.7, 131.7, 129.1, 128.2,
3
1
H NMR (CDCl , 400 MHz): δ = 7.26–7.40 (10 H, m).
128.0, 21.4.
3
13
C NMR (CDCl , 100 MHz): δ = 127.1, 129.3, 131.1, 135.9.
3
Di-o-tolyl Sulfide12d (Table 6, entry 5)
8
Phenyl p-Tolyl Sulfide (Table 4, entry 3)
White solid; yield: 184 mg (86%, 0.86 mmol); mp 58–59 °C.
1
Colorless oil; yield: 178 mg (89%, 0.89 mmol).
H NMR (CDCl , 400 MHz): δ = 7.31–7.46 (2 H, m), 7.19–7.29 (2 H, m),
3
1
7.02–7.04 (4 H, m), 2.32 (6 H, s).
H NMR (CDCl , 400 MHz): δ = 7.1–7.4 (9 H, m), 2.3 (3 H, s).
3
13
13
C NMR (CDCl , 100 MHz): δ = 139.0, 134.6, 131.2, 129.6, 127.9,
C NMR (CDCl , 100 MHz): δ = 137.1. 133.7, 131.1, 129.5, 129.1,
3
3
126.8, 20.7.
1
27.7, 127.1, 126.1, 21.3.
4,4′-Dinitrodiphenyl Sulfide10
(Table 6, entry 6)
-Naphthyl Phenyl Sulfide6d (Table 4, entry 9)
2
Yellow solid; yield: 248 mg (90%, 0.90 mmol); mp 154–155 °C.
White solid; yield: 212 mg (90%, 0.9 mmol); mp 47–49 °C.
1
1
H NMR (CDCl , 400 MHz): δ = 8.11–8.16 (4 H, m), 7.38–7.47 (4 H, m).
H NMR (CDCl , 400 MHz): δ = 8.25–8.27 (1 H, m), 7.83–7.95 (2 H, m),
3
3
13
7.53–7.64 (1 H, m), 7.43–7.55 (2 H, m), 7.36–7.40 (1 H, m), 7.10–7.30
C NMR (CDCl , 100 MHz): δ = 157.9, 141.6, 130.1, 123.6.
3
(5 H, m).
13
4,4′-Dicyanodiphenyl Sulfide7b (Table 6, entry 7)
C NMR (CDCl , 100 MHz): δ = 136.8, 135.3, 134.5, 132.8, 129.7, 129.3,
3
128.8, 128.1, 126.3, 125.8.
White solid; yield: 214 mg (91%, 0.91 mmol); mp 135–136 °C.
1
H NMR (CDCl , 400 MHz): δ = 7.47–7.56 (4 H, m), 7.33–7.36 (4 H, m).
3
Phenyl 2-Pyridyl Sulfide14h (Table 4, entry 10)
13
C NMR (CDCl , 100 MHz): δ = 140.6, 133.0, 131.1, 118.2, 111.4.
3
Colorless oil; yield: 170 mg (91%, 0.91 mmol).
1
H NMR (CDCl , 400 MHz): δ = 8.40 (1 H, d, J = 4.8 Hz), 7.54−7.58 (2 H,
Di-1-naphthyl Sulfide7b (Table 6, entry 8)
3
m), 7.38–7.40 (4 H, m), 6.94–6.97 (1 H, m), 6.86 (1 H, d, J = 4.8 Hz).
White solid; yield: 257 mg (90%, 0.90 mmol); mp 109–110 °C.
13
C NMR (CDCl , 100 MHz): δ = 161.5, 149.5, 136.8, 134.9, 131.0,
3
1
H NMR (CDCl , 400 MHz): δ = 7.85–8.40 (2 H, m), 7.60–7.84 (2 H, m),
3
1
29.7, 129.1, 121.4, 119.9.
7.41–7.58 (2 H, m), 7.39–7.40 (4 H, m), 7.38 (4 H, m).
13
C NMR (CDCl , 100 MHz): δ = 135.9, 135.4, 132.7, 131.8, 130.0,
3
Symmetrical Diaryl Sulfides via Homocoupling Reaction Phenolic
Esters; General Procedure
129.5, 128.6, 127.9, 126.7, 124.8.
A one-necked flask was charged with CuI (10 mg, 0.05 mmol), NaOt-Bu
Di-2-naphthyl Sulfide7b (Table 6, entry 9)
(376 mg, 4.0 mmol), S8 (16 mg, 0.5 mmol), phenolic ester (1 mmol),
White solid; yield: 263 mg (92%, 0.92 mmol); mp 150–152 °C.
anhyd DMF (2 mL) under an inert atmosphere. The mixture was mag-
netically stirred and heated at 120 °C for the appropriate reaction
time (Table 6). After completion of the reaction, the mixture was
1
H NMR (CDCl , 400 MHz): δ = 8.27–8.30 (2 H, m), 7.80–7.83 (2 H, m),
3
7.54–7.57 (5 H, m), 7.38–7.53 (4 H, m).
cooled to r.t. H O (4 mL) was added and the product was extracted
2
with EtOAc (3 × 4 mL) and dried (anhyd Na SO ). Evaporation of the
2
4
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

M
Synthesis
A. Rostami et al.
Paper
1
3
C NMR (CDCl , 100 MHz): δ = 133.0, 132.6, 127.5, 127.2, 125.6,
(e) Faucher, A.-M.; White, P. W.; Brochu, C.; Maitre, C. G.;
Rancourt, J.; Fazal, G. J. Med. Chem. 2004, 47, 18. (f) Wang, Y.;
Chang, W.; Greenlee, V. R. Bioorg. Med. Chem. Lett. 2001, 11, 891.
(g) Nielsen, S. F.; Nielsen, E.; Olsen, G. M.; Liljefors, T.; Peters, D.
J. Med. Chem. 2000, 43, 2217.
3
1
24.9, 124.4, 123.0.
Di-2-pyridyl Sulfide12d (Table 6, entry 10)
Red solid; yield: 172 mg (92%, 0.92 mmol); mp 218–220 °C.
1
(
5) (a) Teruyuki, K.; Takeaki, M. Chem. Rev. 2000, 100, 3205.
H NMR (CDCl , 400 MHz): δ = 8.46–8.47 (2 H, m), 7.65–7.69 (2 H, m),
.49–7.51 (2 H, m), 7.22–7.29 (2 H, m).
3
(b) Bichler, P.; Love, J. A. Top. Organomet. Chem. 2010, 31, 39.
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(
c) Eichman, C. C.; Stambuli, J. P. Molecules 2011, 16, 590.
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880. (e) Bahekar, S. S.; Sarkate, A. P.; Wadhai, V. M.; Wakte, P.
13
C NMR (CDCl , 100 MHz): δ = 156.7, 150.1, 137.2, 126.0, 121.9.
3
2
S.; Shinde, D. B. Catal. Commun. 2013, 41, 123. (f) Sujatha, A.;
Thomas, A. M.; Thankachan, A. P.; Anilkumar, G. ARKIVOC 2015,
Acknowledgment
(i), 1.
We are grateful to the University of Kurdistan Research Councils for
partial support of this work and the Iran National Science Foundation
(6) (a) Zheng, N.; McWilliams, J. C.; Fleitz, F. J.; Armstrong, J. D.;
Volante, R. P. J. Org. Chem. 1998, 63, 9606. (b) Mispelaere-
Canivet, C.; Spindler, J. F.; Perrio, S.; Beslin, P. Tetrahedron 2005,
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588508.
2013, 377, 190. (g) Fernandez-Rodreguez, M. A.; Shen, Q.;
S
u
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N