Nature of the copper-oxide-mediated C-S cross-coupling reaction: Leaching of catalytically active species from the metal oxide surface

Article abstract of DOI:10.1021/acscatal.6b00337

Copper-oxide-catalyzed cross-coupling reaction is a well-known strategy in heterogeneous catalysis. A large number of applications have been developed, and catalytic cycles have been proposed based on the involvement of the copper oxide surface. In the present work, we have demonstrated that copper(I) and copper(II) oxides served as precursors in the coupling reaction between thiols and aryl halides, while catalytically active species were formed upon unusual leaching from the oxide surface. A powerful cryo-SEM technique has been utilized to characterize the solution-state catalytic system by electron microscopy. A series of different experimental methods were used to reveal the key role of copper thiolate intermediates in the studied catalytic reaction. The present study shows an example of leaching from a metal oxide surface, where the leaching process involved the formation of a metal thiolate and the release of water. A new synthetic approach was developed, and many functionalized sulfides were synthesized with yields of up to 96%, using the copper thiolate catalyst. The study suggests that metal oxides may not act as an innocent material under reaction conditions; rather, they may represent a source of reactive species for solution-state homogeneous catalysis.

Full text of DOI:10.1021/acscatal.6b00337

Research Article
pubs.acs.org/acscatalysis
Nature of the Copper-Oxide-Mediated C−S Cross-Coupling Reaction:
Leaching of Catalytically Active Species from the Metal Oxide Surface
Yulia S. Panova,† Alexey S. Kashin,‡ Maxim G. Vorobev,† Evgeniya S. Degtyareva,‡
and Valentine P. Ananikov*,†,‡
†Saint Petersburg State University, Stary Petergof, Saint Petersburg, 198504, Russia
‡N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Leninsky prospekt 47, 119991, Russia
S
* Supporting Information
ABSTRACT: Copper-oxide-catalyzed cross-coupling reaction
is a well-known strategy in heterogeneous catalysis. A large
number of applications have been developed, and catalytic
cycles have been proposed based on the involvement of the
copper oxide surface. In the present work, we have
demonstrated that copper(I) and copper(II) oxides served as
precursors in the coupling reaction between thiols and aryl
halides, while catalytically active species were formed upon
unusual leaching from the oxide surface. A powerful cryo-SEM
technique has been utilized to characterize the solution-state catalytic system by electron microscopy. A series of different
experimental methods were used to reveal the key role of copper thiolate intermediates in the studied catalytic reaction. The
present study shows an example of leaching from a metal oxide surface, where the leaching process involved the formation of a
metal thiolate and the release of water. A new synthetic approach was developed, and many functionalized sulfides were
synthesized with yields of up to 96%, using the copper thiolate catalyst. The study suggests that metal oxides may not act as an
innocent material under reaction conditions; rather, they may represent a source of reactive species for solution-state
homogeneous catalysis.
KEYWORDS: C−S cross-coupling, copper oxide, nanoparticles, catalysis, leaching, mechanism
Surprisingly, CuO and Cu2O nanoparticles showed high
catalytic activity in the cross-coupling reactions with various
sulfur-containing organic compounds.16 Supported copper-
containing nanoparticlesCuO/GO,17 CuO/Si,18 CuO/C,19
Cu/Cu2O,20 Cu/chitosan,21 and Cu/polymer22were used as
highly efficient and recyclable heterogeneous catalysts. The
mechanistic aspects of these copper-catalyzed C−S cross-
coupling reactions have raised several questions. The available
mechanistic studies have proposed copper oxide nanoparticles
as the catalytically active species.19,23−25 Note that the direct
involvement of a metal oxide surface in a cross-coupling
reaction is rather unusual and intriguing.
In the present work, we studied the C−S cross-coupling
catalytic system for the S-arylation of organic halides mediated
by copper oxide nanoparticles. Mechanistic insight was made
using cryogenic scanning electron microscopy (cryo-SEM),
field-emission scanning electron microscopy (FE-SEM),
dynamic light scattering (DLS), high-resolution electrospray
ionization mass spectroscopy (HR-ESI-MS), and nuclear
magnetic resonance (NMR) techniques. An unexpected
leaching process involving the metal oxide surface was detected.
INTRODUCTION
■
Cu-catalyzed C−S bond formation is a flexible synthetic tool
that is in high demand in research and industrial fields. A simple
protocol allows the coupling of an impressive variety of S-
nucleophiles with functionalized aryl and alkyl halides including
hindered, electron-poor, electron-rich, and heterocyclic com-
pounds.1−3 The key advantages of copper-based catalytic
systems are (i) the commercial availability and relatively low
toxicity of copper species; (ii) the high catalytic activity; and
(iii) the possibility to carry out reactions under ligand-free
conditions, often with the use of nontoxic solvents or recyclable
ionic liquids.1−6 In some cases, Cu-mediated transformations
may be superior to the well-known Pd-catalyzed reactions.7
A large number of copper compounds have been found to be
suitable catalysts for C−S cross-coupling reactions. Copper salts
promote the S-arylation and S-alkylation of a wide range of S-
nucleophiles including potassium thiocyanate,8 carbon disul-
fide,9 sulfur,10 alkyl and aryl disulfides,11 and thiourea12 under
mild conditions. Homogeneous catalytic reactions with the use
of soluble copper salts or complexes13 involving one metal
center are believed to proceed via the Cu(I)/Cu(III) oxidative
addition of aryl halide14 or the Cu(I)/Cu(II) single electron
transfer.15 Mechanistic studies suggest Cu(I) compounds as the
active catalytic species, regardless of which copper source
(Cu(0), Cu(I), or Cu(II)) was used initially.
Received: February 2, 2016
Revised: April 22, 2016
© XXXX American Chemical Society
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Leaching of metal species from the immobilized metal
complexes or metal nanoparticles is a well-known phenomen-
on; however, substitution of oxygen and leaching of metal
species from the surface of metal oxides appears rather
unusual.26 Moreover, some metal oxides are often considered
to be stable materials and are widely used as a catalyst support
in many catalytic transformations. The mechanistic studies
revealed copper thiolates as the active component that leached
into solution, and a novel catalyst was developed for an efficient
C−S cross-coupling reaction.
RESULTS AND DISCUSSION
The coupling of thiophenol with 4-iodotoluene was chosen as a
model reaction (Scheme 1). Nanosized copper(I) oxide was
■
Scheme 1. Model Catalytic C−S Cross-Coupling Reaction
between Thiophenol and 4-Iodotoluene
used as a catalyst precursor, and the reaction was carried out in
dimethyl sulfoxide (DMSO) in the presence of Cs2CO3 as a
base. The reaction mixture visually appeared as a heterogeneous
system. In order to detect and localize active copper-containing
species in solution, a cryo-SEM technique in combination with
energy-dispersive X-ray spectroscopy (EDS) was applied.
The liquid phase of the model reaction mixture was subjected
to cryo-SEM and EDS analyses. Electron microscopy revealed
complex structures consisting of round-shaped agglomerates
(2.6−24 μm) (Figure 1, point “a”) covered with crystalline
particles (Figure 1, point “b”) along the perimeter of the
agglomerates. The size of the crystalline particles varied from
85 nm to approximately 2 μm. The effect of the radiation
damage can also be observed in some sample points (Figure 1,
point “c”). Energy-dispersive X-ray spectroscopy revealed the
presence of copper in both of the described phases, which
confirmed catalyst leaching in solution. The crystalline phase
was enriched with cesium and probably contained large
amounts of cesium carbonate. On the basis of SEM-EDS
observations, a colloidal structure of the liquid phase of the
reaction mixture can be proposed. The complex structure of the
aggregates, as detected by cryo-SEM, suggests the coexistence
of active copper catalyst centers and Cs2CO3 in one colloidal
particle.
To elaborate the plausible presence of small nanoparticles in
the liquid phase, the reaction mixture was analyzed using DLS.
The precipitate was removed by centrifugation, and the liquid
phase was analyzed by DLS, which did not detect the presence
of nanosized particles in solution. Therefore, the complex
structures detected by cryo-SEM were most likely formed from
solubilized components of the reaction mixture as a result of
the partial crystallization of the vitrified solution.
Homogeneous catalysis, initiated by the transfer of the metal
species from the metal oxide surface to the solution, is a rather
unusual phenomenon. Leaching is well-known for zerovalent
metal nanoparticles and immobilized metal complexes,26
whereas oxides are usually considered as stable materials.
Moreover, metal oxides are routinely used as a catalyst support
with typically attributed innocent properties.
Figure 1. Cryo-SEM images of the vitrified reaction mixture (top) and
one spherical agglomerate at higher magnification (bottom). The
labels correspond to round-shaped agglomerates (feature “a”),
crystalline particles (feature “b”), and radiation damage (feature “c”).
The homogeneous nature of the catalytic system was
independently confirmed by a series of experiments. First of
all, a set of structurally diverse Cu2O and CuO nanoparticles
were synthesized according to the literature procedures.27−30
Synthesized copper oxides (1b−1h), as well as the control
sample of Cu2O particles from a commercial source (1a), were
analyzed using XRD (see the Supporting Information), which
confirmed the monophasic composition of all of the samples
except sample 1h, which consisted of CuO and Cu(OH)2. The
morphology of samples 1a−1h was studied using electron
microscopy. SEM characterization revealed a variety of shapes
and sizes for the synthesized and commercial copper oxides
(see Figure 2).
Copper oxides 1a−1h were tested as catalyst precursors in
the model C−S cross-coupling reaction between thiophenol
and 4-iodotoluene (Scheme 1). All of the tested copper oxides
demonstrated high catalytic activity and selectivity. The yields
of the C−S cross-coupling products were high (90%−97%)
and, surprisingly, almost the same in all cases (see entries 1−8
in Table 1), including initial reaction rate experiments (see the
Supporting Information). Neither the morphology nor the
metal oxidation state affected the observed yield of the product.
Because the morphology and the nature of the catalyst did not
influence the exhibited catalytic activity in a substantial manner,
the heterogeneous reaction pathway seems to be unlikely.
Morphology-independent catalytic activity is in a better
agreement with the leaching pathway, followed by homoge-
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microscopy showed that all the catalysts lost their initial
morphology (see the Supporting Information for details).
Modification of the catalyst surface during the reaction also
suggests the involvement of a catalyst leaching process, and,
consequently, the possibility of a homogeneous nature of the
catalytic system.
To confirm the leaching of copper during the cross-coupling
reaction, hot centrifugation and hot filtration tests were
performed.31,26 When 20%−30% conversion of thiophenol
was reached, the hot reaction mixture was separated. The
solution after separation was heated at 110 °C for 19 h. A
further increase of the thiophenol conversion (>80%) was
observed. Thus, leaching of the copper species and transfer of
the catalytically active complexes into solution occurred under
the studied reaction conditions.
To establish the composition of the leached copper species,
high-resolution electrospray ionization mass spectrometry (HR-
ESI-MS) was utilized. HR-ESI-MS analysis in negative ion
mode showed the presence of thiolate complexes [Cu(SPh)2]¯
(m/z = 280.9514) and [CuI(SPh)]¯ (m/z = 298.8446) in
solution (see the Supporting Information). It is important to
note here that a similar species was detected in the CuI/1,10-
phenanthroline-catalyzed C−S cross coupling reaction, which
did not involve copper oxide nanoparticles as precatalysts.32a
The presence of the oxidative addition product [CuIAr(SPh)2]¯
was not observed in the present study nor in the literature.32a
Thus, a soluble copper species were detected in the catalytic
reaction initiated with copper oxide nanoparticles as a
precatalyst. The copper compounds were confirmed to have a
similar nature to that of the previously studied homogeneous
catalytic system. The key role of the [Cu(SAr)2]− complex was
also recently addressed in the mechanistic study of the
photoinduced cross-coupling of an aryl thiol with an aryl
halide.32b
Finally, the reaction of copper oxide with thiophenol was
performed (in the absence of organic halide and base), and the
formation of copper thiolate was detected. The formation of
[CuSPh]n 2 in the reaction of copper(I) oxide 1a with
thiophenol was observed in 81% yield. The expected change in
the morphology of copper nanoparticles upon this trans-
formation was detected by FE-SEM (Figure 3). Rod-shaped
particles with a length of ∼5−25 μm and width of ∼100−200
nm were observed in the samples obtained in the reaction of
Cu2O (1a) with thiophenol in DMSO after heating at 110 °C
for 1.5 h (cf. Figure 2a for initial morphology). XRD (Figure 4)
Figure 2. SEM images of the copper oxide particles: (a) commercial
copper oxide 1a and (b−h) synthesized copper oxides ((b) 1b, (c) 1c,
(d) 1d, (e) 1e, (f) 1f, (g) 1g, and (h) 1h) (see Table 1 for a detailed
morphology description).
neous reaction in solution. The necessary control experiments
were carried out, and formation of the product was not
observed in the absence of the copper precatalyst or the base
(see entries 9 and 10 in Table 1).
The morphology of the solid residue isolated after
completion of the reaction provides valuable information
about the catalytic process. The catalyst isolated from the
reaction mixture was studied using FE-SEM. Electron
a
Table 1. C−S Cross-Coupling Reaction with Various Cu Oxides
b
c
entry
catalyst
Cu2O (1a)
morphology and size of the catalyst particles
yield (%)
1
2
3
4
5
6
7
8
octahedral (20−700 nm, 1−7 μm)
cubic (0.2−0.8 μm)
beveled cubic (0.5−1.5 μm)
18-facet polyhedral (0.5−2.0 μm)
octahedral (0.2−2.0 μm, rarely up to 7 μm)
97
95
94
92
90
99
94
93
0
Cu2O (1b)
Cu2O (1c)
Cu2O (1d)
Cu2O (1e)
CuO (1f)
aggregated spherical (15−80 nm, aggregates > 10 μm)
aggregated lamellar (10−15 nm thick, aggregates − 2.5−7.5 μm)
fibrillar (5−15 nm thick, up to 50 nm for bunches)
−
CuO (1g)
CuO/Cu(OH)2 (1h)
−
d
9
e
10
Cu2O (1a)
octahedral (20−700 nm, 1−7 μm)
3
a
Reaction conditions: thiophenol (1 mmol), 4-iodotoluene (1.1 mmol), base (1.5 mmol), copper oxide (1 mol %), DMSO (1 mL), Ar, 110 °C.
b
c
d
e
Determined by FE-SEM. Determined by 1H NMR. The reaction was carried out in the absence of catalyst and base. The reaction was carried out
in the absence of base.
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Scheme 2. Copper(I) Thiolate-Catalyzed C−S Cross-
a
Coupling
Figure 3. SEM images of [CuSPh]n synthesized by the treatment of
Cu2O (1a) with thiophenol in dimethyl sulfoxide (DMSO).
and elemental analysis confirmed the formation of CuSPh,
which, in the case of the nanoparticles, existed as a metal-
containing polymer [CuSPh]n.33
a
Reaction conditions: RSH (1 mmol), ArI (1.1 mmol), base (1.5
mmol), [CuSPh]n (1 mol %), DMSO (1 mL), argon, 21 h, 110 °C;
b
isolated yields are given in parentheses. Reaction was conducted in
c
d
1,4-dioxane. A quantity of 5 mol % of [CuSPh]n was used. A quantity
of 1.2 mmol of thiol was used.
efficiency as a catalyst in the C−S coupling reaction involving a
wide scope of substrates. Typically, 5−20 mol % of copper
catalyst is employed in similar reactions, and efficient synthetic
applications with <5 mol % of the catalyst are rare.4−12,16−19,34
Based on the experimental results, a plausible mechanism for
the C−S cross-coupling reaction, with copper oxides as the
catalyst precursor, can be proposed (Scheme 3).
The reaction between copper oxide nanoparticles and thiol
leads to the formation of Cu thiolate complex and release of
water.35 In the presence of thiol and base, copper precursor
Figure 4. Experimental X-ray diffraction (XRD) data for 2 (blue line)
and calculated XRD pattern for CuSPh (red line).
Scheme 3. Proposed Mechanism of C−S Cross-Coupling
Reaction with Copper Oxide Particles as a Catalyst
Precursor
Evidently, the generation of copper thiolate 2 is the first
catalyst activation step in the studied Cu2O or CuO-catalyzed
C−S cross-coupling reaction. If the mechanistic data are
correct, these findings open up a new opportunity to develop a
novel catalytic system. Easily available and air-stable [CuSPh]n
particles can be directly used as a catalyst. Thus, we have
evaluated the possibility of using [CuSPh]n as a catalyst for the
coupling of various aryl iodides with thiols (Scheme 2).
The reactions of substituted iodobenzenes and various
aromatic, heteroaromatic and aliphatic thiols were performed
with moderate to high yields (3a−3f). The developed catalyst
showed good tolerance to various functional groups (Scheme
2). In most cases, 1 mol % of the catalyst was enough to
perform the reaction (3a−3e, 3g−3j, 3m), with a few
exceptions when 5 mol % of the catalyst was employed (3f,
3k, 3l, 3n). Thus, copper thiolate [CuSPh]n demonstrated high
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dissolves with the generation of the [Cu(SR)2]¯ species (step
“A”).36 In the next step, ArI reacts with the thiolate complex,
leading to the formation of the product and the generation of
the [Cu(SR)I]¯ intermediate (step “B”). The reaction of the
[Cu(SR)I]¯ species with thiol and base regenerates the anionic
thiolate species [Cu(SR)2]¯ and the catalytic cycle repeats (step
“C”). The presence of a Cu(III) species, which may appear due
to oxidative addition or radical pathways, was not exper-
imentally confirmed. However, the involvement of a Cu(III)
intermediate cannot be ruled out, although a typical exchange
reaction (concerted or stepwise) seems to be a probable
pathway.
Thus, the catalytic system in solution (Scheme 3) can be
initiated from the copper oxide nanoparticles. Transformation
of the metal oxide to metal thiolate and leaching to solution has
been observed in the present study. The findings clearly
indicate that the metal oxide particles can undergo substantial
transformations prior to entering the catalytic cycle. The
possibility of using the coordination polymer [CuSPh]n
(instead of the copper oxide catalyst precursor) has been
successfully demonstrated in many examples (Scheme 2). In
such cases, the catalytic cycle directly started with the
generation of the active thiolate species.
patterns were recorded in the 2θ range of 5°−80° on a Bruker
D2 Phaser diffractometer with Cu Kα radiation. The
morphologies of the samples were observed on several SEM
systems: Zeiss Merlin, Zeiss Auriga Laser, and Hitachi SU8000.
Energy-dispersive X-ray spectroscopy was performed using an
Oxford Instruments X-Max 80 system. 1H and 13C spectra were
recorded on a Bruker Model Avance 400 NMR spectrometer.
Electrospray ionization mass spectrometry was performed using
a MaXis Bruker Daltonik spectrometer. Elemental analysis was
carried out on a Euro EA3028-HT elemental analyzer.
Cryogenic scanning electron microscopy (cryo-SEM) was
used to investigate the morphology and size of nanoparticles
and soluble clusters in organic solution. The samples for the
cryo-SEM studies were prepared in a controlled environment
vitrification system (CEVS) Leica EM GP. A small amount of
the sample (1.2 μL) was placed onto a carbon film on a metal
grid support and blotted with filter paper to obtain a thin liquid
film on the grid. The grid was quenched in liquid ethane at
−180 °C and transferred to liquid nitrogen (−196 °C). The
grid was subsequently mounted on a precooled cryo-SEM Leica
EM VCT100 shuttle. The shuttle was inserted into the Leica
EM BAF060 device against a counter flow of dry nitrogen gas at
−120 °C and 1 × 10−7 Pa for 60 min to remove water. The
samples were then transferred to, and examined in, a Tescan
MIRA3 LMU SEM system. All the observations were
performed at −160 °C using an accelerating voltage between
6 kV and 20 kV. Energy-dispersive X-ray spectroscopy (EDS)
was performed using an Advanced Aztec Energy (IE350)/X-
Max 80 system.
Light scattering experiments were carried out on a Nano
Partica SZ-100 (Horiba Jobin Yvon) nanoparticle analyzer. The
light source was a diode-pumped frequency-doubled laser (532
nm, 10 mW). The system determines the particle size
distribution of particles in solution with measurement capability
from 0.3 nm to 8 μm. The measurements were carried out in a
cuvette at an angle of 90° at a temperature of 24.9 0.1 °C;
after that, the position of the cuvette was changed manually,
and the measurements were repeated. The results were
analyzed according to the diffusion coefficient using the
Stokes−Einstein equation.
Synthetic Procedure for Copper Oxide-Catalyzed
Model Reaction. Copper oxide (0.01 mmol, 1.4 mg for
Cu2O or 0.8 mg for CuO), Cs2CO3 (1.5 mmol, 0.4887 g), 4-
iodotoluene (1.1 mmol, 0.2398 g), DMSO (1 mL), thiophenol
(1 mmol, 0.102 mL) were added to a vessel under inert
atmosphere. The reaction vessel was equipped with a magnetic
stirrer bar and sealed with a polytetrafluoroethylene (PTFE)-
lined cap. The mixture was stirred at 110 °C for 21 h.
CONCLUSIONS
■
In the present study, we addressed the nature of copper-oxide-
catalyzed C−S cross-coupling reaction. A set of Cu2O and CuO
particles with different morphologies was synthesized and
tested in the catalytic C−S cross coupling reaction. It was
shown that the morphology of the catalyst did not play a
significant role in the catalytic process. Indeed, all the
synthesized copper oxides demonstrated similar catalytic
activity. Cryo-SEM-EDX provided evidence of the presence
of copper species in the liquid phase, and the corresponding
[Cu(SPh)2]¯and [Cu(SPh)I]¯ intermediates were detected in
solution by HR-ESI-MS. The homogeneous pathway was
initiated by the leaching of the copper thiolate species from the
copper oxide nanoparticle precursors. Copper thiolate com-
plexes in solution, rather than copper oxide nanoparticles, were
found to be the catalytically active species.
The product of the reaction between copper oxide particles
and thiolthe coordination polymer [CuSAr]nwas synthe-
sized and studied in the C−S cross-coupling reaction as a
catalyst. The developed novel catalyst has shown high catalytic
activity and good functional group tolerance. The catalytically
active coordination polymer [CuSAr]n is a material that is
inexpensive, easy to synthesize and handle, and has good
potential areas of application.
Synthesis of [CuSPh]n (2) using Cu2O as a Starting
Reagent. Copper(I) oxide (0.1 mmol, 14 mg), DMSO (1.5
mL), and thiophenol (1 mmol, 0.102 mL) were added to a
vessel under an inert atmosphere. The reaction vessel was
equipped with a magnetic stirrer bar and sealed with a PTFE-
lined cap. The mixture was stirred at 110 °C for 1.5 h. An
insoluble yellow precipitate was formed. After cooling to room
temperature, 2 was separated by centrifugation and sequentially
washed with water (2 × 10 mL), methanol (2 × 10 mL),
diethyl ether (10 mL), and dichloromethane (DCM) (10 mL).
The residue then was dried in an oven at 105 °C overnight.
Yield: 81% (0.028 g). Elemental analysis calculated (%): C
41.72, H 2.92; found (%): C 41.73, H 2.94.
The present study provides an example of leaching from a
metal oxide surface. The leaching process involved the
formation of a metal thiolate and release of water. The findings
are of great importance in rethinking the application of metal
oxides as catalysts and catalyst supports. The possibility of
leaching from a metal oxide surface may have substantial
influence on several catalytic systems, with a key influence on
the nature of the catalytic system, stability of the catalyst and
ability to recycle.
EXPERIMENTAL SECTION
■
General Remarks. The solvents were dried and purified
according to standard procedures. The copper oxides were
synthesized using previously described methods.27−30 XRD
Synthesis of [CuSPh]n (2) Using CuO as a Starting
Reagent. A similar procedure was utilized (see above). Yield:
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73% (0.012 g). Elemental analysis calculated (%): C 41.72, H
2.92; found (%): C 41.79, H 2.76.
ACKNOWLEDGMENTS
■
We are grateful to the Saint Petersburg State University
(postdoctoral fellowship No. 12.50.1560.2013) and Russian
Foundation for Basic Research (Grant Nos. 15-33-20536 and
14-03-01005). This work was supported by research centers
“Nanotechnology Interdisciplinary Centre”, “Molecular and
Cell Technologies Centre”, “Magnetic Resonance Research
Centre”, “Centre for X-ray Diffraction Studies”, “Chemical
Analysis and Materials Research Centre”, “Centre for Optical
and Laser Materials Research” of St. Petersburg State
University. Mechanistic studies performed at Zelinsky Institute
of Organic Chemistry, Moscow were supported by a grant from
the Russian Science Foundation (RSF Grant No. 14-50-00126).
Synthetic Procedure for [CuSPh]n-Catalyzed C−S
Cross-Coupling Reaction. [CuSPh]n (0.01 mmol, 1.7 mg
for 3a−3e, 3g−3j, 3m, and 0.05 mmol, 8.5 mg for 3f, 3k, 3l,
3n), Cs2CO3 (1.5 mmol, 0.4887 g), aryl iodide (1.1 mmol),
DMSO (1 mL) or dioxane (1 mL) and thiol (1 mmol for 3a−
3j, 3l, 1.2 mmol for 3k, 3m, 3n) were added to a vessel under
an inert atmosphere. The reaction vessel was equipped with a
magnetic stir bar and sealed with a PTFE-lined cap. The
mixture was stirred at 110 °C for 21 h. The heterogeneous
mixture was cooled to room temperature, diluted with water
(20 mL) and washed with EtOAc (3 × 10 mL). The combined
organic layers were washed with water (5 × 20 mL) to remove
DMSO and then dried over Na2SO4. The mixture was filtered,
and the solvent was evaporated under reduced pressure. The
residue was purified by column chromatography (hexane or
hexane/ether or hexane/ethyl acetate) to afford the corre-
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1
sponding product. All the products were characterized by H
NMR, 13C{1H} NMR, and high-resolution mass spectroscopy.
Efficient MS ionization of sulfides was obtained by the addition
of formic acid and AgNO3 to solutions of 3a−3e, 3g−3k, 3m,
3n and 3f, 3l, correspondently.
Cryo-SEM-EDS Measurements. Copper(I) oxide (0.01
mmol, 1.4 mg), Cs2CO3 (1.5 mmol, 0.4887 g), 4-iodotoluene
(1.1 mmol, 0.2398 g), DMSO (1 mL), and thiophenol (1
mmol, 0.102 mL) were added to a vessel under inert
atmosphere. The reaction vessel was equipped with a magnetic
stir bar and sealed with a PTFE-lined cap. The mixture was
stirred at 110 °C for 3 h and then allowed to cool to room
temperature. After 2 h of residue sedimentation, the resulting
solution was characterized by cryo-SEM and cryo-SEM-EDS.
Leaching Test Using Hot Centrifugation. Copper(I)
oxide (0.01 mmol, 1.4 mg), Cs2CO3 (1.5 mmol, 0.4887 g), 4-
iodotoluene (1.1 mmol, 0.2398 g), solvent (1 mL), and
thiophenol (1 mmol, 0.102 mL) were added to a test tube
under an inert atmosphere. The mixture was stirred at 110 °C
until the 4-iodotoluene conversion level reached 20% (for 2 h).
The test tube then was covered with heat-insulating material
and centrifuged until precipitate sedimentation (for 2 min).
The solution after centrifugation was transferred into new test
tube, fresh portion of Cs2CO3 (1 mmol, 0.3258 g) was added
and mixture was heated for 19 h at 110 °C. In addition, a
standard hot filtration test was performed and similar results
were obtained.
ASSOCIATED CONTENT
■
S
* Supporting Information
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.6b00337.
Details on Cryo-SEM measurements, XRD study, FE-
SEM data, ESI-MS data, NMR data, optimization of
reaction conditions, spectral parameters, and character-
ization of products (PDF)
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: val@ioc.ac.ru.
Notes
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The authors declare no competing financial interest.
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