Cross-coupling reactions using porous multipod Cu2O microcrystals as recoverable catalyst in aqueous media

Article abstract of DOI:10.1002/aoc.3980

Porous multipod Cu₂O microcrystals were found to be an efficient, highly recyclable and eco-friendly catalyst for the cross-coupling reactions of aryl halides and terminal alkynes with high yields in aqueous media. Noteworthy, the Cu₂O catalyst can be reused for several times without significant decrease in catalytic activity.

Full text of DOI:10.1002/aoc.3980

Received: 19 May 2017
DOI: 10.1002/aoc.3980
Revised: 15 June 2017
Accepted: 20 June 2017
F U L L P A P E R
Cross‐coupling reactions using porous multipod Cu2O
microcrystals as recoverable catalyst in aqueous media
Lin Tang | Chaoting Wu | Qiyan Hu | Qian Li | Wu Zhang
Key Laboratory of Functional Molecular
Porous multipod Cu2O microcrystals were found to be an efficient, highly recy-
clable and eco‐friendly catalyst for the cross‐coupling reactions of aryl halides
and terminal alkynes with high yields in aqueous media. Noteworthy, the
Cu2O catalyst can be reused for several times without significant decrease in
catalytic activity.
Solids, Ministry of Education, Anhui
Laboratory of Molecule‐Based Materials,
College of Chemistry and Materials
Science, Anhui Normal University, Wuhu
241000, People0s Republic of China
Correspondence
Wu Zhang, Key Laboratory of Functional
Molecular Solids, Ministry of Education,
Anhui Laboratory of Molecule‐Based
Materials, College of Chemistry and
Materials Science, Anhui Normal
University, Wuhu 241000, People0s
Republic of China.
KEYWORDS
aqueous media, Cu2O microcrystals, heterogeneous catalyst, sonogashira reaction
Email: zhangwu@mail.ahnu.edu.cn
Funding information
National Natural Science Foundation of
China, Grant/Award Number: NSFC No.
21272006
1 | INTRODUCTION
Although copper‐based catalysts have been proposed
as an alternative to palladium‐based catalysts for
Transition metal catalyzed cross coupling reactions are
one of the predominant strategies for the formation of
diaryl alkynes which possess wide applications in the syn-
thesis of natural products, pharmaceuticals, polymers,
dyes and electronics.[1–6]
Sonogashira couplings, these catalyst systems generally
require high copper loadings to maintain a catalytic cycle.
Therefore, the development of an efficient reaction system
with recyclable copper catalysts is highly desirable. [22–26]
Zhang and co‐workers have reported reusable Cu2O/
PPh3/TBAB system for couplings between aryl halides
and terminal alkynes.[27] Varma group reported
Cu2O@Cu core‐shell architectures exhibit excellent cata-
lytic activity for the Sonogashira coupling reactions. How-
ever, the reaction was conducted in DMF.[28]
Organic reactions conducted in water have become
one of the most intriguing areas of research in green
chemistry as it is universal medium for all chemical reac-
tions of life.[29] Sen group have developed application of
cubic copper (I) oxide as reusable catalyst in organic syn-
thesis in aqueous medium.[30–33] Here, we wish to report
the porous multipod Cu2O microcrystals as an efficient
and reusable catalyst for the Sonogashira‐type cross cou-
pling reaction in aqueous medium. It is noteworthy that
Among these methods, Sonogashira coupling reac-
tions of terminal acetylenes with aryl halides are the most
popular.[7,8] The typical Sonogashira reactions are per-
formed with palladium (0) catalyst and copper (I) co‐cata-
lyst in organic solvents using a suitable base.[9–12]
Development of competent catalysts and reduction the
homocoupling of alkynes are the challenges faced by
Sonogashira cross‐coupling reactions. Since Miura and
co‐workers reported that CuI/PPh3 catalyzed cross‐cou-
plings of aryl iodides and terminal alkynes,[13] much
attention has been focused on the use of copper com-
plexes as the catalysts for the Sonogashira cross‐coupling
for copper is less toxic and far more economic than palla-
[14–21]
dium.
Appl Organometal Chem. 2017;e3980.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3980

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TANG ET AL.
the scope of the substrates can expand to aliphatic
acetylene.
2 | EXPERIMENTAL
2.1 | General information
All reactions were carried out in flame‐dried reaction ves-
sels. Reaction temperatures were reported as the tempera-
ture of the bath surrounding the reaction vessel. All
starting materials and reagents were commercially avail-
able and used without further purification. The prepared
catalyst was characterized by X‐ray powder diffraction
with graphite monochromatized Cu‐Kα radiation
(λ = 0.15406 nm) employing a scanning rate of 0.02 °s−1
in the 2θ range from 10° to 80°. The field‐emission scan-
ning electron microscopy (FE‐SEM) images were obtained
on S‐4800 field‐emission scanning electron microscope
with an accelerating voltage of 5 kV. All known products
gave satisfactory analytical data by NMR spectra, which
corresponding to the reported literature values. All melt-
ing points were taken on an X‐4 Digital Melting Point
FIGURE 1 XRD patterns of (a) the prepared porous multipod
Cu2O microcrystals and (b) Cu2O catalyst after third recycle
1
Apparatus without correction. H and 13C NMR spectra
were recorded on a Bruker Avance‐300 at 300 MHz for
1H NMR and at 75 MHz for 13C NMR using CDCl3 as sol-
vent and tetramethylsilane (TMS) as an internal standard.
High‐resolution mass spectra (HRMS) were recorded on
Agilent 6200 LC/MS TOF using APCI in positive mode.
Characterization data, and NMR spectra of compounds
were listed in Supporting Information.
2.2 | Preparation of porous multipod Cu2O
microcrystals
The multipod Cu2O microcrystals were prepared accord-
ing to literature procedures.[34–36] 0.180 g copper nitrate
dissolved in 24 ml C2H5OH and 6 ml H2O mixed solvents
and 2 ml of pure formic acid. Prior to the reaction, the
solution mixture was sonicated in an ultrasonic water
bath for 10 min. The reactions were carried out with a
Teflon‐lined stainless steel autoclave in an electric oven
at 150 °C for 2 h. After the reaction, the autoclave was
air cooled to room temperature. Then, the red precipitates
were obtained by centrifugation, washed with absolute
ethanol several times and dried in vacuum at 50 °C for 4 h.
2.3 | Typical procedure for Cu2O catalyzed
cross‐coupling reaction of aryl halides with
terminal alkynes.
A mixture of aryl halide 1 (0.5 mmol), alkyne 2 (0.6 mmol),
porous multipod Cu2O microcrystals (5 mol %), 1,10‐
phenanthroline (15 mol %), and K2CO3 (2 equiv) in water
FIGURE 2 (a) SEM of porous multipod Cu2O microcrystals (b)
SEM of the enlarged porous multipod Cu2O microcrystal

TANG ET AL.
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(2 ml) was heated with stirring at 100 °C in argon for 20 h.
The mixture was extracted with ethyl acetate (3 × 10 ml),
the organic layer was washed with water (2 × 10 ml), then
dried over anhydrous Na2SO4 and evaporated under
vacuum. The crude product was purified by column
chromatography on silica gel using petroleum ether/ethyl
acetate as an eluent to give the corresponding products.
3 | RESULTS AND DISCUSSION
The obtained red precipitates were characterized by X‐ray
powder diffraction analysis (XRD). Figure 1a presents a
typical XRD pattern of the as‐prepared products. All of
the detectable diffraction peaks can be indexed to (110),
(111), (200), (202), (220) and (311) reflections of the cubic
phase Cu2O by comparison with the JCPDS card file No.
5–667. The sharp and narrow diffraction peaks indicate
that the as‐obtained Cu2O crystals with good crystallinity
and large size. The morphologies of the as‐synthesized
sample were determined by field emission scanning elec-
tron microscopy (FE‐SEM), as shown in Figure 2a‐b.
Figure 2a shows a representative SEM image of the as‐
2.4 | Recycling procedure of the catalysts
The separated precipitates in the above procedure were
washed sufficiently with distilled water and ethanol three
times each and then dried under vacuum at 50 °C for 6 h,
and then the Cu2O microcrystals were recovered.
a
TABLE 1 Optimization of Cu2O catalyzed Sonagashira reaction of iodobenzene with phenylacetylene
Entry
Catalyst
Base
Ligand
Solvent
Yield (%)b
1
Cu2O
K2CO3
Phen
H2O
96
2
CuO nanoparticles
Cu2Oc
Cu2Od
Cu2O
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
Phen
Phen
Phen
PPh3
—
H2O
80
85
84
93
Trace
79
94
—
60
70
75
70
80
50
81
63
92
3
H2O
4
H2O
3
H2O
4
Cu2O
H2O
5e
6f
Cu2O
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
H2O
Cu2O
H2O
7
—
H2O
8
Cu2O
DMSO
DMF
DMF‐H2O
H2O
9
Cu2O
10
11
12
13g
15h
16i
17j
Cu2O
Cu2O
Cu2O
K3PO4
K2CO3
K3PO4
K2CO3
K2CO3
H2O
Cu2O
H2O
Cu2O
H2O
Cu2O
H2O
Cu2O
H2O
aReaction conditions: iodobenzene (0.5 mmol), phenylacetylene (0.6 mmol), catalyst (5 mol %), base (2 equiv), ligand(15 mol %), solvent (2 ml), under reflux in
argon for 20 h.
bIsolated yields.
cCu2O nanocubes.
dCu2O octahedrons.
eCu2O (1 mol %).
fCu2O(10 mol %).
gbase (1 equiv).
h80 °C.
i12 h.
j48 h.

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TANG ET AL.
prepared samples, many monodisperse porous multipod
Cu2O microcrystals can be easily found. The porous struc-
ture can be clearly seen in the enlarged multipod Cu2O
microcrystal in Figure 2b.
Temperature also plays an important role in the coupling
reaction, and the yield was dramatically decreased from
96% at 100 °C to 81% at 80 °C (entry 15). Lower yield
was obtained when the reaction time was changed from
20 h to 12 h, however, no significant increase in yield
was observed when the reaction time was extended to
48 h (entries 16–17). The optimized reaction conditions
were set to 5 mol % porous multipod Cu2O nanocrystals
in the presence of 2 equiv of K2CO3 in refluxing H2O
under argon for 20 h. Under the optimized conditions,
the desired product was obtained in 96% yield.
To demonstrate the versatility of the porous multipod
Cu2O microcrystal, a variety of aryl halides were tested with
terminal alkynes under the standard reaction conditions
(Scheme 1). It was found that aryl iodides, whether
substituted by electron‐deficient group or electron‐rich
group, all worked well with aryl alkynes in the presence of
the porous multipod Cu2O microcrystal. Several functional
groups, such as methyl, methoxy, chloro, nitro, cyano and
amino were well‐tolerated. To our delight, good results were
obtained as aliphatic alkynes such as hexyne and decyne
were tested (Scheme 1, 3f and 3 g). In addition, 2‐
iodobenzaniline and 2‐iodo‐5‐methylaniline reacted
completely with alkyne. It was found that the standard con-
ditions were also effective for the reaction of bromides to
afford the target products in moderate to good yields.
To investigate the catalytic properties of the as‐pre-
pared porous multipod Cu2O microcrystals for C–C cou-
pling reaction, the Cu2O microcrystals catalyzed
Sonogashira‐type reaction of iodobenzene (1) with
phenylacetylene (2) was chosen as a model reaction. The
effects of catalyst, solvent and ligand were investigated
and the results were summarized in Table 1. It was
observed that porous multipod Cu2O microcrystals
showed higher catalytic activity than cubic Cu2O nano-
particles and octahedral Cu2O nanoparticles in the cou-
pling reaction and no product was formed in the
absence of catalyst. It was also observed that the yield of
product was decreased to 79% by decreasing the catalyst
loading from 5 to 1 mol %, whereas no significant incre-
ment was observed using 10 mol % of catalyst. Other fac-
tors, such as ligand, temperature and reaction time were
screened for the reaction. The reaction did not proceed
well without ligand, and 1,10‐phenanthroline (phen)
proved to be the best ligand. The effect of solvents was
investigated for the model reaction at 100 °C under air.
DMF and DMSO were found less effective than H2O.
Among the base examined, K2CO3 gave the highest yield.
SCHEME 1 Study on Sonagashira
reaction of terminal acetylenes with aryl
halides catalyzed by porous multipod
Cu2O microcrystals

TANG ET AL.
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TABLE 2 Successive tests by using recycled porous multipod
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