Palladium Nanoparticles Immobilized on Nanosilica Triazine Dendritic Polymer (Pd np -nSTDP) as Catalyst in the Synthesis of Mono-, Di-, and Trisulfides through C-S Cross-Coupling Reactions

Article abstract of DOI:10.1055/s-0033-1340501

A wide variety of diaryl sulfides has been synthesized in excellent yields via C-S cross-couplings of aryl/heteroaryl halides with aromatic/heteroaromatic thiols in the presence of palladium nanoparticles immobilized on nanosilica triazine dendritic polymer (Pd _np -nSTDP) as a reusable catalyst under thermal conditions and microwave irradiation. Pd _np -nSTDP also showed excellent catalytic activity for the preparation of a series of di- and trisulfides with benzene, pyridine, pyrimidine, and/or 1,3,5-triazine as the central cores by one-pot multi C-S cross-coupling reactions. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1340501

LETTER
▌645
letter
Palladium Nanoparticles Immobilized on Nanosilica Triazine Dendritic Poly-
mer (Pdnp-nSTDP) as Catalyst in the Synthesis of Mono-, Di-, and Trisulfides
through C–S Cross-Coupling Reactions
Diaryl Sulfides through C–S Cross-Coupling Reactions
Amir Landarani Isfahani, Iraj Mohammadpoor-Baltork,* Valiollah Mirkhani,* Majid Moghadam,
Ahmad Reza Khosropour, Shahram Tangestaninejad, Mahboobeh Nasr-Esfahani, Hadi Amiri Rudbari
Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
Fax +98(311)6689732; E-mail: imbaltork@sci.ui.ac.ir; E-mail: mirkhani@sci.ui.ac.ir
Received: 28.10.2013; Accepted: 09.12.2013
employed as effective drugs for the treatment of inflam-
Abstract: A wide variety of diaryl sulfides has been synthesized in
mation,2 cancer,3 immunodeficiency virus (HIV),4 and
excellent yields via C–S cross-couplings of aryl/heteroaryl halides
Alzheimer’s and Parkinson’s diseases.5 Due to their im-
portance and useful properties, various methods for the
with aromatic/heteroaromatic thiols in the presence of palladium
nanoparticles immobilized on nanosilica triazine dendritic polymer
(Pdnp-nSTDP) as a reusable catalyst under thermal conditions and synthesis of diaryl sulfides have been reported. Generally,
microwave irradiation. Pdnp-nSTDP also showed excellent catalytic
activity for the preparation of a series of di- and trisulfides with ben-
zene, pyridine, pyrimidine, and/or 1,3,5-triazine as the central cores
indium-,10 rhodium-,11 platinum-,12 and iron-13based cata-
by one-pot multi C–S cross-coupling reactions.
the C–S cross-coupling reactions leading to diaryl sulfides
are catalyzed by palladium-,6 copper-,7 nickel-,8 cobalt-,9
lysts. However, some of these synthetic methods suffer
from disadvantages such as high temperature, long reac-
tion times, high loading of catalysts, low yields, and the
Key words: supported catalysis, palladium, cross-coupling, den-
drimers, thiols
use of nonreusable catalysts. Accordingly, the develop-
ment of an efficient and convenient method employing a
The synthesis of diaryl sulfides via C–S cross-coupling re-
reusable catalyst for the synthesis of diaryl sulfides is still
action is of great significance due to their abundance in
desirable.
many natural products as well as their widespread appli-
In the course of the last two decades, dendritic polymers
cations in biology and pharmacology.1 A great number of
have attracted a great interest because of their wide range
compounds containing diaryl sulfide moieties has been
of applications in macromolecular chemistry,14 nanosci-
NH2
H2N
NH2
NH2
NH2
N
N
N
H2N
NH2
NH2
NH2
N
N
N
N
N
N
N
HN
H2N
H2N
NH
H
N
N
N
H
N
N
N
N
N
N
H2N
N
N
N
N
N
N
N
NH
N
NH2
NH2
H2N
NH2
Si
EtO
O
= Pdnp
O
nanosilica
Figure 1 Palladium nanoparticles immobilized on nanosilica triazine dendritic polymer (Pdnp-nSTDP) catalyst
SYNLETT 2014, 25, 0645–0652
Advanced online publication: 14.01.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340501; Art ID: ST-2013-D1005-L
© Georg Thieme Verlag Stuttgart · New York

646
A. L. Isfahani et al.
LETTER
ence,15 gene therapy,16 drug delivery,17 and medicinal system in organic synthesis, we herein report an efficient
chemistry.18 Dendritic polymers, due to their highly and convenient method for the preparation of mono-, di-,
branched and three-dimensional structures, have also and trisulfides using Pdnp-nSTDP (Figure 1) as a recycla-
been used as molecular boxes for encapsulation of a vari- ble catalyst under thermal conditions and microwave irra-
ety of ions and molecules. One of the main applications of diation (Scheme 1). To the best of our knowledge, this is
these metal encapsulated-dendritic polymers is in the field the first report on the use of a palladium-nanoparticle-
of catalysis.19 Moreover, immobilization of these metal- based dendritic catalyst for the synthesis of mono-, di-,
containing dendrimer catalysts on various insoluble sup- and trisulfides through C–S cross-coupling reactions.
ports, especially porous materials with high surface areas,
At the outset, the coupling reaction of 4-bromoanisole (1
is of great interest from economical and environmental
mmol) with 4-methylthiophenol (1 mmol) in the presence
points of view, as they can be easily recovered and reused
of Pdnp-nSTDP catalyst was employed to screen the reac-
tion parameters including the type of base and solvent,
without significant loss of activity.15d,20
Recently, we reported palladium nanoparticles immobi- temperature, catalyst loading, and microwave power (Ta-
lized on nanosilica triazine dendritic polymer (Pdnp-nSTDP) ble 1). Various bases, such as triethylamine (Et3N), 1,8-di-
as an efficient and reusable catalyst for Suzuki–Miyaura azabicyclo[5.4.0]undec-7-ene (DBU), piperidine, sodium
cross-coupling and Heck reactions.21 In continuation of hydroxide (NaOH), potassium tert-butoxide (KOt-Bu),
our interest in exploring the use of Pdnp-nSTDP catalytic sodium carbonate (Na2CO3), and potassium carbonate
Table 1 Optimization of the C–S Cross-Coupling of 4-Bromoanisole with 4-Methylthiophenol Catalyzed by Pdnp-nSTDP
SH
S
Pdnp-nSTDP
+
solvent, base
thermal or MW
OMe
Br
OMe
Entry
Basea
Catalyst (mol% Pd) Solventa
Method
Time
Yield (%)b
1
2
Et3N
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.07
0.05
0.03
0.05
0.07
0.03
0.05
0.05
DMF
DMF
DMF
DMF
DMF
DMF
DMF
toluene
EtOH
H2O
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (80 °C)
thermal (100 °C)
thermal (80 °C)
thermal (70 °C)
thermal (80 °C)
MW (230 W, 80 °C)
MW (230 W, 80 °C)
MW (200 W, 70 °C)
MW (250 W, 90 °C)
MW (150 W, 50 °C)
24 h
20
39
25
42
37
61
95
46
40
66
95
95
70
57
96
96
75
96
60
DBU
24 h
3
piperidine
NaOH
KOt-Bu
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
24 h
4
24 h
5
24 h
6
16 h
7
10 h
8
24 h
9
24 h
10
11
12
13
14
15
16
17
18
19
24 h
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
10 h
10 h
10 h
10 h
20 min
20 min
20 min
20 min
30 min
a Reaction was performed using 1.5 mmol of base and 2 mL of solvent.
b Isolated yield.
Synlett 2014, 25, 645–652
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diaryl Sulfides through C–S Cross-Coupling Reactions
647
S
Ar1
Ar2
Ar1 SH
Ar2
or
X
mono C–S cross-coupling
or
+
Ar1
Ar1
Pdnp-nSTDP
SH
S
S
N
S
S
di C–S cross-coupling
tri C–S cross-coupling
DMF, K2CO3
80 °C or MW
Ar2
Y
Y
Y
Br
N
Br
HS
Y
SH
Y
Ar2
Ar2
Y = CH, N
X = I, Br, Cl
Y
S
Scheme 1 C–S Cross-coupling catalyzed by Pdnp-nSTDP
(K2CO3) were examined (Table 1, entries 1–7); with 2.23 A wide range of structurally diverse aryl iodides and
K2CO3 giving the highest conversion (Table 1, entry 7). bromides was reacted with various aromatic thiols in the
Different solvents such as toluene, ethanol (EtOH), water presence of Pdnp-nSTDP catalyst at 80 °C, leading to the
(H2O), and N,N-dimethylformamide (DMF) were tested corresponding diaryl sulfides in excellent yields (Table 2,
in this coupling reaction (Table 1, entries 7–10). Among entries 1–12). It is noteworthy that under Pdnp-nSTDP ca-
the solvents investigated, DMF was found to be the most talysis, aryl chlorides (both activated and nonactivated)
effective reaction medium (Table 1, entry 7). The effects underwent coupling reactions to produce the desired dia-
of temperature and amount of the catalyst were also inves- ryl sulfides in high yields (Table 2, entries 13–16).
tigated; the best yield being obtained using 0.05 mol% of
Moreover, the chemoselectivity of the present method is
palladium catalyst at 80 °C. On increasing the temperature
remarkable, since the C–S cross-coupling was performed
or the amount of the catalyst, the yield of the desired prod-
in the presence of the NH2 group with excellent selectivity
uct did not increase further (Table 1, entries 11 and 12),
(Table 2, entry 7). The C–S cross-coupling reactions were
but the yield decreased on lowering these parameters, (Ta-
also examined under microwave irradiation. As shown in
ble 1, entries 13 and 14). Based on the above results,
Table 2, a variety of aryl iodides, bromides, and chlorides
K2CO3 as the base, DMF as the solvent, together with 0.05
as reacted with aromatic thiols in the presence of Pdnp-
mol% of palladium catalyst at 80 °C were selected as the
nSTDP under the optimized microwave irradiation to af-
optimized reaction conditions (Table 1, entry 7). Under
ford the desired cross-coupling products in 77–96% yields
microwave irradiation,22 using the above-mentioned con-
within 15–45 minutes. The results indicate that micro-
ditions, the best result was obtained with an applied power
wave irradiation has the evident advantage of short reac-
tion times over the classical heating mode. The reactions
of 230 W at 80 °C (Table 1, entry 15).
To clarify the generality and efficiency of the procedure, were generally clean and no side products such as sym-
a range of halides and aromatic thiols was examined under metrical disulfides were produced; in all cases, diaryl sul-
the optimized conditions. The results are listed in Table fides were obtained as the sole products.
N
N
N
X
N
SH
Pdnp-nSTDP
DMF, K2CO3
S
S
Br
N
or
+
Or
80 °C (method A)
MW (method B)
R
X
N
SH
R
R
X = O, S
R = H, Me, OMe
O
S
O
S
N
N
S
N
N
S
N
N
OMe
3a
3b
3c
3d
A) 18 h, 80%
B) 30 min, 74%
A) 12 h, 90%
B) 20 min, 87%
A) 12 h, 90%
B) 20 min, 90%
A) 18 h, 85%
B) 30 min, 88%
O
S
S
S
S
S
S
S
N
N
N
N
OMe
OMe
3e
3g
3h
3f
A) 18 h, 82%
B) 30 min, 80%
A) 10 h, 90%
B) 20 min, 95%
A) 10 h, 85%
B) 20 min, 92%
A) 10 h, 90%
B) 20 min, 90%
Scheme 2 C–S Cross-coupling of aryl bromides and heteroaromatic thiols catalyzed by Pdnp-nSTDP. Reagents and conditions: aryl halide (1
mmol), thiol (1 mmol), K2CO3 (1.5 mmol), Pdnp-nSTDP (0.05 mol% Pd), DMF (2 mL), 80 °C or MW (230 W, 80 °C); isolated yields are given.
© Georg Thieme Verlag Stuttgart · New York
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648
A. L. Isfahani et al.
LETTER
In order to expand the scope of the reaction substrates, proceeded efficiently under thermal conditions and mi-
various heteroaromatic thiols were also examined. As re- crowave irradiation to generate excellent yields of the de-
vealed in Scheme 2, heteroaromatic thiols such as 2-mer- sired cross-coupling products.
captopyrimidine, 2-mercaptobenzoxazole, and 2-
After successful generation of diaryl sulfides via Pdnp-
mercaptobenzothiazole were coupled smoothly with aryl
nSTDP-catalyzed cross-coupling of aryl/heteroaryl ha-
bromides under thermal conditions and microwave irradi-
lides with aromatic/heteroaromatic thiols, we decided to
ation to produce the corresponding heteroaryl sulfides in
explore the potential of this catalytic system to one-pot
high yields.
multi C–S cross-couplings to produce di- and trisul-
In a further study, the activity of the Pdnp-nSDTP catalyst fides.24,25 The results are summarized in Table 3. 2,6-Di-
was evaluated in reactions involving heteroaryl halides. bromopyridine underwent twofold C–S cross-coupling
As shown in Scheme 3, the reaction of 2-bromopyridine reaction with 4-methylthiophenol, 2-mercaptobenzoxa-
with 4-methylthiophenol and/or 2-mercaptobenzothiazole zole, or 2- mercaptobenzothiazole in the presence of Pdnp-
Table 2 C–S Cross-Coupling of Aryl Halides with Aromatic Thiols Catalyzed by Pdnp-nSTDPa
X
SH
S
Pdnp-nSTDP
R2
R1
R1
R2
+
DMF, K2CO3
80 °C or MW
Entry
R1
X
R2
H
Thermal conditions
Microwave irradiation
Time (h)
Yield (%)b
Time (min)
Yield (%)b
1
2
4-Me
4-Me
4-MeO
4-Me
H
I
6
6
92
90
95
95
95
93
92
94
91
93
95
93
81
90
90
85
15
15
15
15
15
15
25
20
20
20
20
20
45
30
30
45
95
95
93
95
95
92
94
95
95
95
96
90
77
88
90
82
I
4-Me
4-Me
4-Ac
4-Me
4-Ac
4-MeO
H
3
I
5
4
I
5
5
I
6
6
4-Me
2-H2N
4-Me
H
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
8
7
12
10
10
10
10
8
8
9
4-Me
3-MeO
4-MeO
4-HOC
2-Me
4-OHC
4-Ac
H
10
11
12
13
14
15
16
4-MeO
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
24
18
18
24
a Reaction conditions: aryl halide (1 mmol), thiol (1 mmol), K2CO3 (1.5 mmol), Pdnp-nSTDP (0.05 mol% Pd), DMF (2 mL), 80 °C or MW (230
W, 80 °C).
b Isolated yield.
HS
Pdnp-nSTDP
N
+
or
or
DMF, K2CO3
80 °C or MW
S
N
S
N
S
N
Br
N
S
HS
3j
7 h, 95%
20 min, 95%
3i
thermal:
MW:
8 h, 93%
20 min, 92%
Scheme 3 C–S Cross-coupling of 2-bromopyridine with aromatic/heteroaromatic thiols catalyzed by Pdnp-nSTDP
Synlett 2014, 25, 645–652
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diaryl Sulfides through C–S Cross-Coupling Reactions
649
nSTDP catalyst under thermal conditions and microwave mides under thermal conditions and microwave irradia-
irradiation to provide the corresponding disulfides in ex- tion (Table 3, 4d–j). The structures of the products were
cellent yields (Table 3, 4a–c). Moreover, a series of trisul- characterized by IR, 1H NMR, and 13C NMR spectroscopy
fides was produced in high yields by threefold C–S cross- and elemental analysis. Furthermore, the structure of 4h
coupling reaction of benzene-1,3,5-trithiol, pyrimidine- was confirmed by X-ray crystallographic analysis (Figure
2,4,6-trithiol or 1,3,5-triazine-2,4,6-trithiol with aryl bro- 2; CCDC 948049).
Table 3 Synthesis of Di- and Trisulfides via One-Pot Multifold C–S Cross-Coupling Catalyzed by Pdnp-nSTDP
Thiol
Product
Thermal conditions
Microwave irradiation
Time (h)
Yield (%)a Time (min) Yield (%)a
4ab
4bb
4cb
14
90
86
90
30
45
30
86
90
90
SH
S
N
S
N
O
N
N
N
N
SH
SH
24
14
O
S
O
S
S
N
N
S
N
S
S
S
S
S
OMe
SH
4dc
16
88
30
92
S
MeO
HS
SH
OMe
SH
S
S
4ec
14
82
30
85
S
HS
SH
SH
N
S
S
4fc
16
85
30
84
N
N
S
HS
SH
N
OMe
S
SH
N
S
N
S
4gc
16
88
30
92
N
N
N
N
MeO
HS
SH
OMe
© Georg Thieme Verlag Stuttgart · New York
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650
A. L. Isfahani et al.
LETTER
Table 3 Synthesis of Di- and Trisulfides via One-Pot Multifold C–S Cross-Coupling Catalyzed by Pdnp-nSTDP (continued)
Thiol
Product
Thermal conditions
Microwave irradiation
Time (h)
Yield (%)a Time (min) Yield (%)a
SH
N
S
N
S
4hc
16
86
30
85
N
N
N
N
N
N
S
HS
HS
HS
SH
SH
SH
CHO
SH
N
S
4ic
16
81
30
89
N
N
S
N
S
N
OHC
CHO
SH
N
S
N
S
4jc
16
85
30
85
N
N
N
S
a Isolated yield.
b Reaction conditions: 2,6-dibromopyridine (1 mmol), thiol (2 mmol), K2CO3 (2.5 mmol), Pdnp-nSTDP (0.05 mol% Pd), DMF (3 mL), 80 °C
or MW (230 W, 80 °C).
c Reaction conditions: aryl bromide (3 mmol), thiol (1 mmol), K2CO3 (2.5 mmol), Pdnp-nSTDP (0.05 mol% Pd), DMF (3 mL), 80 °C or MW
(230 W, 80 °C).
rated by centrifugation, dried, and reused for subsequent
reactions. As shown in Table 4, the catalyst could be recy-
cled and reused at least six times without any detectable
loss of its activity. The analysis of palladium leaching
from Pdnp-nSTDP catalyst by inductively coupled plasma
(ICP) indicated that only a trace amount of palladium (less
than 2%) had been leached in the first run.
In conclusion, a highly efficient protocol for the prepara-
tion of a wide variety of diaryl sulfides by C–S cross-cou-
pling
between
aryl/heteroaryl
halides
and
aromatic/heteroaromatic thiols catalyzed by Pdnp-nSTDP
under thermal conditions and microwave irradiation is de-
scribed. Furthermore, one-pot multi C–S cross-coupling
reactions were successfully performed in the presence of
this catalyst affording the corresponding di- and trisul-
fides in high yields. The high performance as well as re-
cyclability of the catalyst make this method a valuable
contribution to the existing methodologies.
Figure 2 X-ray crystal structure of 4h
The recovery and reusability of the catalyst, which are
very important from commercial and economical points
of view, were examined in the coupling of 4-bromoan-
isole with 4-methylthiophenol. After completion of the re-
action, the mixture was cooled to room temperature and
diethyl ether (15 mL) was added. The catalyst was sepa-
Synlett 2014, 25, 645–652
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diaryl Sulfides through C–S Cross-Coupling Reactions
651
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Yield (%),b
thermal conditions
Yield (%),b
MW irradiation
1
2
3
4
5
6
7
95
93
94
94
92
94
90
96
96
95
93
94
91
92
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a Reaction conditions: 4-bromoanisole (1 mmol), 4-methylthiophenol
(1 mmol), K2CO3 (1.5 mmol), Pdnp-nSTDP (0.05 mol% Pd), DMF
(2 mL), 80 °C or MW (230 W, 80 °C).
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Acknowledgment
The authors are grateful to the Center of Excellence of Chemistry
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References and Notes
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© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 645–652

652
A. L. Isfahani et al.
LETTER
at 80 °C or irradiated with MW (230 W, 80 °C) for the
126, 10044. (c) Lim, J.; Simanek, E. E. Mol. Pharm. 2005,
2, 273.
desired time according to Table 2 and Scheme 2. The
progress of the reaction was monitored by TLC (eluent:
Et2O–EtOAc, 5:1). After completion of the reaction, the
mixture was cooled to r.t., Et2O (15 mL) was added, and the
catalyst was separated by centrifugation. The organic layer
was washed with H2O (2 × 10 mL) and dried over anhydrous
MgSO4. Filtration and evaporation of the solvent and
purification of the crude product by recrystallization from
Et2O–EtOAc (5:1) afforded the pure product.
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Bioconjugate Chem. 2000, 11, 910. (b) Sadler, K.; Tam, K.
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Haag, R. Angew. Chem. Int. Ed. 2002, 114, 1385.
(d) Grinstaff, M. W. Chem. Eur. J. 2002, 8, 2838. (e) Lee,
C.; MacKay, J. A.; Fréchet, J. M.; Szoka, F. Nat. Biotechnol.
2005, 23, 1517.
(19) Dendrimer Chemistry; Vögtle, F.; Richardt, G.; Werner, N.,
Eds.; Wiley-VCH: Weinheim, 2009.
(24) General Procedure for the Synthesis of Disulfides via
Twofold C–S Cross-Coupling Catalyzed by Pdnp-nSTDP
A mixture of 2,6-dibromopyridine (1 mmol),
(20) (a) Antebi, S.; Arya, P.; Manzer, L. E.; Alper, H. J. Org.
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K.; Yang, Y.; Sayari, A.; Alper, H. Adv. Synth. Catal. 2005,
347, 1379. (e) Zweni, P. P.; Alper, H. Adv. Synth. Catal.
2006, 348, 725. (f) Huang, W.; Kuhn, J. N.; Tsung, C.-K.;
Zhang, Y.; Habas, S. E.; Yang, P.; Somorjai, G. A. Nano
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(21) Landarani Isfahani, A.; Mohammadpoor-Baltork, I.;
Mirkhani, V.; Khosropour, A. R.; Moghadam, M.;
Tangestaninejad, S.; Kia, R. Adv. Synth. Catal. 2013, 355,
957.
(22) The microwave system used in these experiments includes
the following items: Micro-SYNTH Labstation, equipped
with a glass door, a dual magnetron system with pyramid
shaped diffuser, 1000 W delivered power, exhaust system,
magnetic stirrer, ‘quality pressure’ sensor for flammable
organic solvents, and a ATCFO fiber optic system for
automatic temperature control.
(23) General Procedure for the Synthesis of Diaryl Sulfides
via C–S Cross-Coupling Catalyzed by Pdnp-nSTDP
In a round-bottom flask equipped with a condenser and a
magnetic stirrer, a mixture of aryl halide (1 mmol),
aromatic/heteroaromatic thiol (1 mmol), K2CO3 (1.5 mmol),
and Pdnp-nSTDP (0.05 mol% Pd) in DMF (2 mL) was stirred
aromatic/heteroaromatic thiol (2 mmol), K2CO3 (2.5 mmol),
and Pdnp-nSTDP (0.05 mol% Pd) in DMF (3 mL) was stirred
at 80 °C or exposed to MW irradiation (230 W, 80 °C) for
the appropriate time as mentioned in Table 3. The reaction
progress was monitored by TLC (eluent: Et2O–EtOAc, 3:1).
After completion of the reaction, the mixture was cooled to
r.t., EtOAc (10 mL) was added, and the catalyst was
separated by centrifugation. The organic phase was washed
with H2O (2 × 10 mL), dried over anhydrous MgSO4,
filtered, and evaporated. The resulting crude product was
purified by recrystallization from EtOAc to give the pure
product.
(25) General Procedure for the Synthesis of Trisulfides via
Threefold C–S Cross-Coupling Catalyzed by Pdnp-
nSTDP
A mixture of aromatic trithiol (1 mmol), aryl bromide (3
mmol), K2CO3 (2.5 mmol), and Pdnp-nSTDP (0.05 mol% Pd)
in DMF (3 mL) was stirred at 80 °C or subjected to MW
irradiation (230 W, 80 °C) for the appropriate time
according to Table 3. The workup was performed as
mentioned for the synthesis of disulfides, and the pure
trisulfide was obtained by recrystallization of the crude
product from EtOAc.
Synlett 2014, 25, 645–652
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