C-S cross-coupling reaction using novel and green synthesized CuO nanoparticles assisted by Euphorbia maculata extract

Article abstract of DOI:10.1002/aoc.5144

In the present study, biosynthesis of CuO nanoparticles using a rapid, eco-friendly, cost-effective and efficient method has been reported employing aqueous Euphorbia maculata extract as mild, renewable and non-toxic reducing and capping agents without adding any surfactants. The biogenic and green method has some benefits compared to conventional physical and chemical methods. It is simple, cheap and environmentally friendly. The biosynthesized CuO NP displayed a color change pattern (from sky blue to black) on preparation and presented its respective broad peak at 365?nm, which was analyzed by UV–Vis spectroscopy. Using the FT-IR analysis, biomolecules in E. maculata extract which are responsible for bioreduction activity and synthesize of CuO NP, were identified. The XRD, EDX and FESEM results confirmed the successful synthesis of CuO nanoparticles of 18?nm sizes, with spherical and sponge crystal structure. The catalytic activity of biosynthesized CuO NPs was studied in C-S cross-coupling reaction. This method has the advantages of high yields, easy work-up, and simple reusability. The recovered CuO NP can be reused four times without any considerable loss of its catalytic activity.

Full text of DOI:10.1002/aoc.5144

Received: 16 May 2019
DOI: 10.1002/aoc.5144
Revised: 2 July 2019
Accepted: 5 July 2019
F U L L P A P E R
C‐S cross‐coupling reaction using novel and green
synthesized CuO nanoparticles assisted by Euphorbia
maculata extract
Heshmatollah Alinezhad
| Khatereh Pakzad
Faculty of Chemistry, University of
In the present study, biosynthesis of CuO nanoparticles using a rapid,
eco‐friendly, cost‐effective and efficient method has been reported employing
aqueous Euphorbia maculata extract as mild, renewable and non‐toxic reduc-
ing and capping agents without adding any surfactants. The biogenic and green
method has some benefits compared to conventional physical and chemical
methods. It is simple, cheap and environmentally friendly.
Mazandaran, Babolsar 47416‐13534, Iran
Correspondence
Iran, Mazandaran, Babolsar, University of
Mazandaran, Faculty of Chemistry, 47416‐
13534.
Email: heshmat@umz.ac.ir
Funding information
University of Mazandaran
The biosynthesized CuO NP displayed a color change pattern (from sky blue to
black) on preparation and presented its respective broad peak at 365 nm,
which was analyzed by UV–Vis spectroscopy. Using the FT‐IR analysis,
biomolecules in E. maculata extract which are responsible for bioreduction
activity and synthesize of CuO NP, were identified. The XRD, EDX and FESEM
results confirmed the successful synthesis of CuO nanoparticles of 18 nm sizes,
with spherical and sponge crystal structure.
The catalytic activity of biosynthesized CuO NPs was studied in C‐S cross‐
coupling reaction. This method has the advantages of high yields, easy
work‐up, and simple reusability. The recovered CuO NP can be reused four
times without any considerable loss of its catalytic activity.
KEYWORDS
catalyst, copper oxide nanoparticles, C‐S cross‐coupling, Euphorbia maculata, green synthesis
1 | INTRODUCTION
focused on nanotechnology.[2–4] Metal nanoparticles
(MNPs) have received significant interest regarding their
Nanotechnology is a novel scientific field that concerns
materials at the nanoscale.[1] In recent decades, many
types of research in different fields such as biotechnology,
physics, chemistry, engineering, and medicine have
considerable efficiency in catalytic reactions including
cross‐coupling, hydrogenation, multi‐component,and oxi-
dation.[5–7]
CuO NP is one of the metal nanoparticles that was
found to be very beneficial in extensive applications
regarding its singularity. CuO NPs were widely utilized
as catalysts and biological activity agents.[8,9] They also
can be used in solar cells,[10] lithium‐ion batteries and
gas sensors.[11] Copper oxide nanoparticles have been
synthesized by various methods, usually classified as
physical and chemical procedures. Although these two
Abbreviations: DMF, Dimethylformamide; DMSO, Dimethyl
Sulfoxide; EDX, Energy Dispersive X‐ray Spectrometry; FESEM, Field
Emission Scanning Electron Microscopy; FT‐IR, Fourier Transforms
Infrared
Spectroscopy;
MNPs,
Metal
Nanoparticles;
NPs,
Nanoparticles; TG‐DTA, Thermo Gravimetric‐Differential Thermal
Analysis; TLC, Thin Layer Chromatography; UV–VIS, Ultraviolet–
Visible; XRD, X‐ray Diffraction
Appl Organometal Chem. 2019;e5144.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.5144

2 of 11
ALINEZHAD AND PAKZAD
methods are widely used for the synthesis of CuO NPs,
issues such as expensive reagent, longer reaction time,
and dangerous reaction condition for separating
synthesized nanoparticles can make these methods diffi-
cult.[12] These difficulties can be solved by green
chemistry.[13]
Phytonanotechnology is a biological method for the
synthesis of highly stable and small sized metal nanopar-
ticles. Lately, this method has drawn much attention in
researches.[14,15] This synthetic method is a rapid, stable,
reliable, reproducible, and effective procedure to create
highly active copper oxide nanoparticles using plant
extracts.[16,17] The pollutant‐free solvent and eco‐friendly
reducing and capping agents are the three fundamental
elements for a perfect green synthesis technique.[18,19]
Green chemistry is a branch of chemistry based on the
production of chemical products without using or gener-
ating dangerous and toxic substances.[20,21]
Catalysts are generally classified into two types of
homogeneous and heterogeneous. Homogeneous cata-
lysts, have limited use in the industry due to the difficulties
in separating the products contaminated with residual
unstable complexes and expensive recycling process of
the catalysts.[22] Heterogeneous catalysts have the advan-
tages of superior catalytic activity, low detriment and cost,
simple recyclability, reusability, and ease of handling.[23,24]
These heterogeneous catalysts can be separated by centri-
fugation and filtration procedures for the consecutive
reuse.[25] Recently, the utilization of heterogeneous cata-
lysts, especially metal oxide nanoparticles, as catalysts in
organic reaction has attracted much attention regarding
their great surface‐to‐volume ratio, highly active surface,
and easy recovery and recyclability of the catalysts.[26–29]
Therefore, several procedures have been developed to syn-
thesize durable and reusable heterogeneous catalysts for
the organic reaction. These catalysts are very useful from
a sustainablility point of view.[30] The significance of het-
erogeneous catalysts in terms of enviro‐economical and
practical aspects for performing synthetic transformations
has caused an exponential growth in their applications in
organic reactions.[31] In green chemistry, biosynthesized
metal nanoparticles have been used in various organic
reaction especially cross‐coupling reaction as effective
and environmentally friendly catalysts.[32–36] Nowadays,
nanocatalysis is an attractive and highly demanding area
of research which involves the use of nanomaterials as
catalysts in a variety of organic transformations.[37,38]
This may be due to their unique characteristics like smaller
size, high surface area, high density of defect sites,
increased efficiency and selectivity and reusability.[39]
Biosynthesized metal nanoparticles have a combination
of the two complementary properties: the inorganic prop-
erties like mechanical/thermal/structural stability and
the properties of organic pendant moieties such as flexibil-
ity in solution (like homogeneous catalysts) and therefore,
high reactivity of the catalyst.[40] Cross‐coupling reactions
have been used as powerful and useful synthetic tools in
novel synthetic chemistry.[5,41–43] The formation of C − S
bonds is momentous in synthetic organic chemistry for
the structure of different synthetics, a large number of
drugs for diseases such as diabetes, cancer, Alzheimer's,
Parkinson's, or inflammatory HIV diseases, and natural
biologically active compounds (Figure 1).[44–46]
Recently, aryl sulfides and their derivatives have
drawn much attention in molecular precursors for the
development of this materials because of their biological,
pharmaceutical properties.[47–51] Therefore, transition‐
metal‐catalyzed C‐S bond formation has been the subject
of many studies in the last few decades.[52–55] The advan-
tages of using copper oxide nanoparticles (CuO NPs) in
the cross‐coupling reactions are the availability inexpen-
sive catalyst, recyclability, and lack of exterior ligands as
compared to the usual catalytic systems.[56–60]
In this study for the first time, we synthesized CuO NP
using aerial parts extract of Euphorbia maculata (a mem-
ber of the Euphorbiaceae family). This process is faster
than most of the existing chemical methods. We have
developed an economical, green and simple procedure
to synthesize heterogeneous catalyst for organic reaction.
In continuation of this research, a new protocol has been
presented for the procurement of CuO NPs by Euphorbia
maculata extract (new reducing/capping agents) and
Characterizations of the obtained nanoparticles were
analyzed by various standard techniques. The CuO nano-
particles as a novel heterogeneous catalyst provide
excellent catalytic activity for the synthesis of thioether
under ligand‐free conditions. In addition, the recyclability
and reusability of nanocatalyst was investigated for C‐S
cross coupling reaction at least four times without a
considerable loss of its catalytic activity.
FIGURE 1 Biologically active thioethers used as drugs

ALINEZHAD AND PAKZAD
3 of 11
adsorption–desorption of N2 using BELSORPΙΙ
instrument.
2 | MATERIAL AND METHODS
2.1 | Preparation of extract
2.4 | General procedure for aryl‐sulfur
Euphorbia maculata aerial parts were collected within
the Mazandaran region in Iran, during the month of July
2017. Healthful aerial parts were selected and separated
from the remains. Then, the collected aerial parts of
Euphorbia maculata was cleaned with distilled water fre-
quently to pick up the impurities, then were dried and
powdered these parts using a kitchen blender.
In a 250 ml flask, 10 g of powdered aerial parts of
Euphorbia maculata was added to 100 ml of double
distilled water and well stirred using a magnetic heater stir-
rer at 90 °C for 45 min to prepare the aqueous extract. The
extract was filtered and was kept at 4 °C for further use.[61]
coupling
In a round bottom flask, a mixture of aryl halide
(1.1 mmol), thiol (1 mmol), CuO nanoparticles (0.015 g),
and KOH (1.5 mmol) was well‐stirred at 110 °C under a
nitrogen atmosphere in DMSO (1 ml). The progress of
the reaction was monitored by a thin layer chromatogra-
phy (n‐hexane/ethyl acetate, 9:1). After the end of the
reaction, the reaction mixture was cooled at the room
temperature and the catalyst was separated by centrifuga-
tion and subsequently washed with ethanol (15 ml) and
used for a consecutive cycle. Then, the reaction was
diluted with 15 ml of water and was extracted with ethyl
acetate (3 × 10 ml). The organic phase was purified on a
short pad of silica gel using hexane and ethyl acetate to
give the corresponding coupling product. All organic
products were recognized easily by spectroscopy tech-
niques such as 1H NMR, 13C NMR (BRUKER
ULTRASHIELD 400 AVANCE III NMR), and FT‐IR
(Bruker model Tensor 27 spectrometer).
2.2 | Synthesis of copper oxide
nanoparticles
Capped CuO nanoparticles with Euphorbia maculata
extract were synthesized by the green method. 100 ml of
copper (II) sulfate pentahydrate (1 M, CuSO4.5H2O) was
blended in 10 ml of E. maculata aqueous extract at
50 °C for 2 hours. The reaction showed a change of color
in the solution from sky blue to black. In the following,
synthesized copper oxide nanoparticles were centrifuged
at 7000 rpm for 30 mins and washed with deionized water
(3 × 15 ml) and ethanol (3 × 15 ml). Then, these nanopar-
ticles were dried at 60 °C in an oven.[62]
3 | RESULTS AND DISCUSSION
3.1 | XRD analysis
Figure 2 displays the X‐ray diffraction patterns of the
CuO nanoparticle. The peak positions with 2θ values of
32.8°, 35.9°, 39.1°, 46.3°, 49.1°, 52.9°, 58.7°, 66.6°, 68.3°,
72.6° and 75.5°, were assigned to (−111), (002), (111),
(−112), (−202), (020), (202), (−311), (113), (311) and
2.3 | Characterization of copper oxide
nanoparticles
The optical properties and the crystalline nature of the
CuO nanoparticles were studied by UV–Visible spectros-
copy (SPEKOL 2000 Analytik Jena) and X‐ray diffractom-
eter (PHILIPS, PW1730), respectively. The particle size
and morphology of biosynthesized CuO nanoparticles
were analyzed through Field‐emission scanning electron
microscopy analysis (FESEM,TESCAN) and the composi-
tion of the elements present in CuO nanoparticles was
determined using energy dispersive spectrophotometer
(EDS, TESCAN, MIRA) attached to the Map. FT‐IR
spectra were obtained through Fourier‐transform infrared
spectrophotometer (Bruker model Tensor 27 spectrome-
ter) in the spectral region of 4000–400 cm−1 using dry KBr
pellet as a standard reference and thermogravimetric‐
differential thermal analysis (TG‐DTA) was performed
by the means of STA 1500 Rheometric Scientific. The
surface area, pore volume and pore size distribution of
the support and the catalyst were determined by
FIGURE 2 XRD powder pattern of CuO NP synthesized using
the aqueous extract of the aerial parts of Euphorbia maculata

4 of 11
ALINEZHAD AND PAKZAD
(400) planes, respectively. Therefore, the formation of
CuO nanocrystal synthesized from the E. maculata
extract was clearly demonstrated by XRD studies, which
is in agreement with previous studies.
3.2 | UV–vis analysis
UV–Vis Spectroscopy is generally used to confirm the
synthesis of the CuO nanoparticle (Figure 3). The absorp-
tion spectrum of UV–Vis spectroscopy for the CuO (NP)
was investigated in the range of 280–420 nm. The absorp-
tion peak at a wavelength of 360 nm corresponds to the
formation of the copper oxide nanoparticles.
3.3 | FT‐IR analysis
FIGURE 4 FT‐IR spectra of (a) plant extract (b) CuO NP with
plant extract
The FT‐IR analysis was performed to recognize the
biomolecules which are likely to be involved in
the biosynthesis of CuO nanoparticles. The FT‐IR analy-
sis of the Euphorbia maculata extract (Figure 4) showed
some significant peaks at 3430 and 2938, dedicated to
the OH group resulting from phenolic stretching and
the C–H stretching vibrations of the –CH2 functional
group respectively. The presence of the peaks at 1626
and 1414 are related to the carbonyl group (C = O) and
the stretching C = C aromatic ring. The peak observed
at 1218 to 1075 cm−1 corresponds to C‐O stretching
frequency of C‐OH stretching vibrations. The FT‐IR anal-
ysis confirmed the presence of phenolic compounds in
the plant extract. The FT‐IR spectrum of CuO NPs
(Figure 4) demonstrates that the 3430, 2938, 1626, 1414,
1218, and 1075 cm−1 peaks were respectively shifted to
new positions of 3462, 2935, 1637, 1359, and 1058, in
the region of 400–4000 cm−1. The existence of the peaks
at 1716 cm−1 confirmed the formation of ketone as a cap-
ping agent. The formation of CuO is characterized by
two peaks at 595 and 503 cm−1 which correspond to
the Cu‐O stretching bond. The FT‐IR results confirm
the presence of phytochemical compounds in the E.
maculata extract, which further act as reducing/capping
agents for the synthesis of CuO NPs.
3.4 | EDS and FESEM analysis
The composition of biosynthesized CuO NPs has been
analyzed by studying the energy‐dispersive X‐ray spec-
troscopy (EDS), as shown in Figure 5. The EDS spectrum
represents the existence of copper and oxygen with car-
bon, which indicates the presence of stabilizing agents,
originated from Euphorbia maculata extract (Figure 5).
Figure 6 indicates the field‐emission SEM (FESEM)
image of the biosynthesized CuO NPs. This image reveals
the spherical form of the produced CuO NP, also indi-
cates that the average size of nanoparticle by FESEM
was 18 nm. It can be considered that the green synthesis
of CuO NPs using Euphorbia maculata extract produces
spherical particles in nano sizes.
3.5 | Specific surface area and porosity
studies
The particle size, morphology, and density para-
meters depend on the specific surface area measurements
(m2.g−1). The specific surface area determined by the BET
method is 36.75 m2/g and the estimated average pore
diameter is approximately 27 nm. Also, the nitrogen
FIGURE 3 UV–vis spectrum of green synthesized CuO NP using
Euphorbia maculata

ALINEZHAD AND PAKZAD
5 of 11
FIGURE 5 (a). Energy‐dispersive X‐ray
(EDS) spectroscopy spectrum of
Euphorbia maculata extract‐
mediatedsynthesized CuO NP, (b). EDS
mapping analysis of CuO NP.

6 of 11
ALINEZHAD AND PAKZAD
FIGURE 6 FESEM images of the green synthesized CuO NPs
adsorption–desorption isotherms for CuO NPs have been
shown in Figure 7.
the presence of the remaining organic compounds and
copper in the biosynthesized CuO NPs/plant extract.
3.6 | TGA analysis
3.7 | C‐S coupling reaction
Thermogravimetric analysis of CuO NPs (Figure 8) shows
three‐step weight losses, the primary step is related to the
loss of water molecules at the temperature below 150 °C.
The second weight loss occurs at 150–300 °C and it is due
to decomposition in a part of the organic content existing
in the biosynthesized CuO NPs. The third weight loss
happens at the temperature over 300 °C, and it is due to
At first, 4‐iodobenzene, 4‐chlorothiophenol, and CuO
NPs were examined as a model reaction in order to
determine optimal reaction conditions. The effects of
different solvents, bases and different amounts of CuO
NP as a catalyst on the C‐S cross‐coupling reaction were
investigated. Several solvents were tested, and great reac-
tion yields were obtained using DMSO, toluene, and
DMF as solvents (Table 1, entries 1, 6–9). Among these
solvents, DMSO was found to be the most effective. H2O
is not a good choice for this reaction (Table 1, entry 8).
It was found that potassium hydroxide gives an excellent
FIGURE 7 N2 adsorption/desorption isotherm of capped CuO
NP by plant extract
FIGURE 8 TG‐DTA data measured for CuO NPs/plant extract

ALINEZHAD AND PAKZAD
7 of 11
TABLE 1 Optimization of reaction conditions for the C‐S cross‐coupling reaction between 4‐chlorothiophenol and iodobenzene using
biosynthesized CuO NP as the catalyst
Entry
Base
Solvent
Catalyst amount(g)
Temperature(°C)
Yield (%)
1
KOH
K2CO3
Na2CO3
Et3N
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
0.015
0.015
0.015
0.015
0.015
0.015
0.015
0.015
0.015
0.01
110
89
45
30
15
Trace
68
<5
5
2
110
3
110
4
110
5
NaOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
110
6
110
7
Toluene
H2O
110
8
Reflux
9
Ethanol
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Reflux
35
75
45
20
89
0
10
11
12
13
14
15
16
17
110
0.007
0.005
0.02
110
110
110
̶
110
0.015
0.015
0.015
80
65
0
Room temperature
130
89
General reaction conditions: 4‐cholorothiophenol (1 mmol) and iodobenzene (1.1 mmol) were mixed together with bases (1.5 mmol) and biosynthesized CuO
NP/plant extract as catalyst in various amounts in 1 ml solvent under nitrogen atmosphere. (Reaction time was 8 hrs)
reaction yield for the coupling reaction to diphenyl
thioethers (Table 1, entry1); while, by using other bases,
triethylamine, sodium carbonate, and potassium carbon-
ate the reaction yields are moderate (entries 2–4); also
using NaOH as a base gives a lower yield compared with
other bases (entry 5).
The C‐S coupling reaction was studied with various
amounts of catalyst. It should be noted that a high reac-
tion yield of 89% was achieved by using 0.015 g of CuO
NP as a catalyst. It was observed that lower catalyst
amounts decreased the reaction yield (Table 1, entry
12). However, increasing of catalyst amount to 0.02 g
did not affect the yield of reaction (entry 13). This reac-
tion without the catalyst was also investigated, but as
expected; no product was produced (entry 14).
The temperature is effective in developing the reac-
tion. When the reaction occurred at a high temperature
(110 °C), the yield of the isolated product was 89%
(Table 1, entry 1). However, increasing the temperature
could not obviously improve the reaction yield (entry
17). A good reaction yield of 65% for the product was
obtained when the reaction was performed at 80 °C
(entry 15); while at the room temperature, no desired
product was detected (entry 16). Increasing reaction time
had no effect on the reaction yields and the results
were similar.
Different catalysts were investigated in this model cross‐
coupling reaction and the results are presented in Table 2
(entries 1–9). Among these catalysts, biosynthesized CuO
TABLE 2 Screening of various catalysts for the formation of
thioether under different conditionsa
Yieldb
Entry Catalyst
Base
Solvent (%)
Reference
[63]
1
2
3
4
5
6
7
8
9
CuSO4
Cs2CO3 DMSO
Cs2CO3 DMSO
Cs2CO3 DMSO
28
22
24
[63]
[63]
[64]
[65]
[55]
[55]
[66]
Cu (OAc)2
CuO powder
CuI
K2CO3 DMSO <3
FeCl3
Cs2CO3 DMF
28
56
42
78
89
CuBr
KOH
KOH
KOH
KOH
DMF
Cu2O
DMF
CuO NP
DMSO
DMSO
Biosynthesized
CuO NP/plant
extract
This work
aReaction conditions: thiophenol (1 mmol) and iodobenzene (1.1 mmol)
were mixed together with bases (1.5 mmol) and various catalysts in 1 ml sol-
vent under nitrogen atmosphere.
bIsolated yield.

8 of 11
ALINEZHAD AND PAKZAD
NP/plant extract is an exceptionally efficient catalyst for
C‐S cross‐coupling reaction. With this catalyst, a higher
yield for the reaction is obtained compared to other
catalysts.
After optimizing the reaction conditions, various aryl
halides with different aryl and alkyl thiols were coupled
in the presence of biosynthesized CuO NP as a catalyst
(Table 3). Generally, it was observed that the C‐S
TABLE 3 C‐S cross‐coupling reaction of thiols with aryl halidesa
Entry
Aryl halide
Thiol
Product
Time (hr)
Yieldb (%)
1
8
89
2
3
4
8
7
8
88
92
85
5
6
12
10
67
70
7
8
8
80
75
11
9
8
75
75
10
14
11
14
78
12
13
12
8
79
82
14
15
16
14
14
18
10
15
_
aReaction conditions: Aryl halides (1.1 mmol), thiols (1 mmol), KOH (1.5 mmol), and biosynthesized CuO NP as catalyst (0.015 g) were mixed in DMSO (1 ml)
at 110 °C under nitrogen atmosphere.
bIsolated yield.

ALINEZHAD AND PAKZAD
9 of 11
cross‐coupling reaction was performed with good to
excellent yields. The results have indicated that the
quiddity of functional groups plays the main role
in reactivity of the coupling substrate. When
electron‐donating groups on thiols were used, the reac-
tion yield was dramatically increased to 92% (Table 3,
entries 2,3). Additionally, substrates with electron‐
donating groups in the aryl iodide were not appropriate
partners for the C‐S cross‐coupling reaction, so the
products were obtained with moderate yields (Table 3,
entries 6–11).
product complex. In the next step, the base removes the
proton of thiol so a nucleophilic attack by thiol happens
quickly. Moreover, the intermediate (a) reacts with the
thiol to form an intermediate (b). In the final step, the
release of the coupling product (c) restores the copper
(II) catalyst.
3.8 | Catalyst reusability
As expected, the reactivity of aliphatic thiol with aryl
iodide was not remarkable (entry 5). Furthermore, lower
yields were observed when 4‐iodobenzene was replaced
by 4‐bromobenzene under the same reaction condition
(entries 14,15). On the other hand, a similar coupling reac-
tion with chlorobenzenes was not successful (entry 16).
Finally, a feasible mechanism for the C‐S coupling
reaction was proposed.[67] This mechanism is described
in Scheme 1. We hypothesize that prior coordination of
the copper catalyst to the aromatic ring may provide
intermediate (a). The aryl halide then undergoes a polar-
ization that facilitates the substitution of the halide on
the ring and brings about the formation of a copper‐
Easy separation and steady reusability are two important
factors for an effective heterogeneous catalytic system.
The reusability of a catalytic system is necessary to develop
a cost‐effective and stable catalyst. Recycling capacity of
this catalyst was examined for C‐S cross‐coupling reaction
under the optimized reaction conditions of iodobenzene
with 4‐chlorothiophenol. After completion of the reaction;
the catalyst was recovered by centrifugation techniques,
washed with ethanol, dried under vacuum and then reused
in the next cycle. The catalyst could be recycled four times
with high activity and consistent activity as shown in
Figure 9. Catalytic activity was approximately the same
in the two initial cycles, but in the third cycle, the yield of
reaction reduced to 82%. The catalytic activity of the CuO
nanoparticle in the fourth cycle was also studied and an
80% yield was obtained.
We characterized the CuO NPs/plant extract heteroge-
neous catalyst by XRD and FESEM after performing the
catalytic reaction as shown in Figure 10. The average size
of the CuO NPs/plant extract after recycled four times
was found to be ~26 nm which is very close to the
18 nm, the average size of the nanoparticles before the
reaction. Therefore, the XRD, as well as FESEM analysis,
plainly indicate clearly that the size and morphology of
the CuO NPs/plant extract catalyst remain unchanged
after performing the catalytic reaction.
SCHEME 1 A plausible mechanism for the c‐s cross‐coupling
reaction using biosynthesized CuO NPs
FIGURE 9 Reusability study of
biosynthesized CuO NP/plant extract
catalyst in C‐S cross‐coupling reaction.
Reaction conditions: 4‐choloro thiophenol
(1 mmol), iodo benzene (1.1 mmol), KOH
(1.5 mmol), biosynthesized CuO NP as
catalyst (0.015 g) were mixed in DMSO
(1 ml) at 110 °C under nitrogen
atmosphere

10 of 11
ALINEZHAD AND PAKZAD
FIGURE 10 Characterization of the CuO NPs/plant extract catalyst after performing the reaction (a) XRD pattern, (b) FESEM image
The results confirm that biosynthesized CuO NP/plant
extract is a versatile and efficient heterogeneous catalyst
for the C‐S cross‐coupling reaction.
REFERENCES
[1] R. G. Saratale, G. D. Saratale, H. S. Shin, J. M. Jacob, A.
Pugazhendhi, M. Bhaisare, G. Kumar, Environ. Sci. Pollut.
Res. 2017, 25, 10164.
[2] V. D. Kulkarni, P. S. Kulkarni, Int. J. Chem. Stud. 2013, 1, 1.
4 | CONCLUSION
[3] M. Shokouhimehr, M. Shahedi Asl, B. Mazzinian, Res. Chem.
Intermed. 2018, 44, 1617.
In this study, an effective, easy, and cost‐effective method
for the biosynthesis of CuO NP by utilization the
Euphorbia maculata aerial parts extracts as a reducing
and stabilizing agent was presented. The plant extract
was employed as an efficient and economic substitute of
the chemical reagent or surfactant template, and also pro-
vided the bioprocess with the advantage of being
environment‐friendly. FESEM image of CuO NPs/plant
extract confirmed the spherical shape and the nanoparti-
cle size were found to be in the range of 18 nm. This
novel copper oxide nanoparticle which was synthesized
by the green method was used as a heterogeneous catalyst
in a C‐S cross‐coupling reaction due to its high surface to
volume ratio. The CuO NPs/plant extract was described
to be inexpensive, air‐stable, and highly efficient in C‐S
cross coupling. The cross‐coupling of different thiols with
aryl halides and their derivatives produced the coupling
products in good or excellent yields in short reaction
time. In addition, the catalyst could be easily separated
from the catalytic system and it also could be recycled
at least four times without a considerable loss of its cata-
lytic activity as a heterogeneous system.
[4] M. Shokouhimehr, Y. Piao, J. Kim, Y. Jang, T. Hyeon, Anew.
Chem. Int. Ed. 2007, 46, 7039.
[5] M. Wang, L. Wang, H. Li, W. Du, M. U. Khan, S. Zhao, C. C.
Ma, Z. Li, L. Zeng, J. Am. Chem. Soc. 2015, 137, 14027.
[6] M. Nasrollahzadeh, M. Sajjadi, M. R. Tahsili, M.
Shokouhimehr, R. S. Varm, ACS Omega. 2019, 4, 8985.
[7] S. W. Jun, M. Shokouhimehr, D. J. Lee, Y. Jang, J. Park, T.
Hyeon, Chem. Commun. 2013, 49, 7821.
[8] R. Dobrucka, J. Inorg. Organomet. Polym. Mater. 2018, 28, 812.
[9] K. Zhang, J. M. Suh, T. H. Lee, J. H. Cha, J. W. Choi, H. W.
Jang, R. S. Varma, M. Shokouhimehr, Nano Convergence
2019, 6, 1.
[10] K. Sharma, M. S. Akhtar, S. Ameen, P. Srivastava, G. Singh,
J. Alloys Compd. 2015, 632, 321.
[11] D. Li, J. Hu, R. Wu, J. G. Lu, Nanotechnology 2010, 21, 485502.
[12] A. Anantharaman, L. George, M. George, J Adv. Res. Sci. Eng.
2016, 5, 522.
[13] C. Prasad, K. Sreenivasulu, S. Gangadhara, P. Venkateswarlu,
J. Alloys Compd. 2017, 700, 252.
[14] R. Katwal, H. Kaur, G. Sharma, M. Naushad, D. Pathania,
J. Ind. Eng. Chem. 2015, 31, 173.
[15] R. Prasad, V. Kumar, K. S. Prasad, Afr. J. Biotechnol. 2014, 13,
705.
ACKNOWLEDGEMENTS
[16] H. A. Elaza, Biointerface Res Appl Chem 2018, 8, 3278.
We gratefully acknowledge the University of Mazandaran
for the support of this work. This research did not receive
any specific funding.
[17] M. Nasrollahzadeh, S. M. Sajadi, A. Rostami‐Vartooni, S.
Mamand Hussin, J. Colloid Interface Sci. 2016, 466, 113.
[18] A. Gangula, R. Podila, L. Karanam, C. Janardhana, A. M. Rao,
Langmuir 2011, 27, 15268.
[19] M. Jeyaraj, M. Rajesh, R. Arun, D. MubarakAli, G.
Sathishkumar, G. Sivanandhan, G. Kapil Deva, M.
Manickavasagama, K. Premkumar, N. Thajuddin, A.
Ganapathi, Colloids Surf. B. Biointerfaces 2013, 102, 708.
ORCID
Heshmatollah Alinezhad
7189-2961
https://orcid.org/0000-0002-
Khatereh Pakzad https://orcid.org/0000-0003-2155-7118
[20] S. Saif, A. Tahir, T. Asim, Y. Chen, Nanomaterials 2016, 6, 205.

ALINEZHAD AND PAKZAD
11 of 11
[21] M. Nasrollahzadeh, F. Ghorbannezhad, Z. Issaabadi, S. M.
[45] D. Sengupta, B. Basu, Org. Med. Chem. Lett. 2014, 4, 17.
[46] T. Kondo, T. A. Mitsudo, Chem. Rev. 2000, 100, 3205.
Sajadi, Chem. Rec. 2019, 19, 601.
[22] M. Shokouhimehr, T. Kim, S. W. Jun, K. Shin, Y. Jang, B. H.
[47] L. Rout, T. K. Sen, T. Punniyamurthy, Angew. Chem. Int. Ed.
2007, 46, 5583.
Kim, J. Kim, T. Hyeon, Appl. Catal., A 2014, 476, 133.
[23] M. Shokouhimehr, Catalysts 2015, 5, 534.
[48] D. Zhu, L. Xu, F. Wu, B. A. Wan, Tetrahedron Lett. 2006, 47,
[24] S. M. Rafiaei, A. Kim, M. Shokouhimehr, Nanosci.
Nanotechnol. Lett. 2014, 6, 309.
5781.
[49] C. G. Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman, Org.
Lett. 2004, 6, 5005.
[25] K. H. Choi, M. Shokouhimehr, Y. E. Sung, Bull. Korean Chem.
Soc. 2013, 34, 1477.
[50] Y. C. Wong, T. T. Jayanth, C. H. Cheng, Org. Lett. 2006, 8, 5613.
[26] S. Ahmed, M. Ahmad, B. L. Swami, J. Adv. Res. 2016, 7, 17.
[51] L. Liu, J. E. Stelmach, S. R. Natarajan, M. H. Chen, S. B. Singh,
C. D. Schwartz, C. E. Fitzgerald, S. J. O'Keefe, D. M. Zaller, M.
Dennis, D. M. Schmatz, J. B. Doherty, Bioorg. Med. Chem. Lett.
2003, 13, 3979.
[27] P. Kuppusamy, M. M. Yusoff, G. P. Maniam, Saudi Pharm. J.
2016, 24, 473.
[28] K. Zhang, J. M. Suh, J. Choi, H. W. Jang, M. Shokouhimehr, R.
S. Varma, ACS Omega. 2019, 4, 483.
[52] T. Itoh, T. Mase, Org. Lett. 2004, 6, 4587.
[29] M. Shokouhimehr, K. Hong, T. H. Lee, C. W. Moon, S. P. Hong,
K. Zhang, H. W. Jang, J. M. Suha, K. S. Choib, R. S. Varma, H.
W. Jang, Green Chem. 2018, 20, 3809.
[53] C. S. Lai, H. L. Kao, Y. J. Wang, C. F. Lee, Tetrahedron Lett.
2012, 53, 4365.
[54] C. H. Cho, H. S. Yun, K. Park, J. Org. Chem. 2003, 68, 3017.
[55] D. J. C. Prasad, G. Sekar, Org. Lett. 2011, 13, 1008.
[56] C. L. Sun, Z. J. Shi, Chem. Rev. 2014, 114, 9219.
[30] M. Shokouhimehr, J. E. Lee, S. I. Hana, T. Hyeon, Chem.
Commun. 2013, 49, 4779.
[31] K. Zhang, K. Hong, J. M. Suh, T. H. Lee, O. Kwon, M.
[57] C. K. Chen, Y. W. Chen, C. H. Lin, H. P. Lin, C. F. Lee, Chem.
Commun. 2010, 46, 282.
Shokouhimehr, H. W. Jang, Res. Chem. Intermed. 2019, 45, 599.
[32] M. Tajbakhsh, H. Alinezhad, M. Nasrollahzadeh, T. A. Kamali,
[58] X. Ku, H. Huang, H. Jiang, H. Liu, J. Comb. Chem. 2009, 11,
J. Colloid Interface Sci. 2016, 471, 37.
338.
[33] R. Bindig, S. Butt, I. Hartmann, M. Matthes, C. Thiel, Catalysts
2012, 2, 223.
[59] S. Jammi, S. Sakthivel, L. Rout, T. Mukherjee, S. Mandal, R.
Mitra, P. Saha, T. Punniyamurthy, J. Org. Chem. 2009, 74, 1971.
[34] A. Alshammari, V. Narayana Kalevaru, A. Martin, in Green
Nanotechnology, 1rd ed. (Ed: M. Larramendy), Intech Open
2016.
[60] E. Sperotto, G. P. M. van Klink, J. G. de Vries, G. van Koten,
J. Org. Chem. 2008, 73, 5625.
[61] M. Bordbar, N. Negahdara, M. Nasrollahzadeh, Sep. Purif.
Technol. 2018, 191, 295.
[35] P. Kasta, M. Friedricha, F. Girgsdiesa, J. Kröhnerta, D.
Teschnera, T. Lunkenbeina, M. Behrensb, R. Schlögla, Catal.
Today 2016, 260, 21.
[62] M. S. Jadhav, S. Kulkarni, P. Raikar, D. A. Barretto, S. K.
Vootla, U. S. Raikar, New J. Chem. 2018, 42, 204.
[36] A. Kim, S. M. Rafiaei, S. Abolhosseini, M. Shokouhimehr,
[63] J. Zhang, Z. Zhang, Y. Wang, X. Zheng, Z. Wang, Eur. J. Org.
Chem. 2008, 30, 5112.
Energy Environ. Focus 2015, 4, 18.
[37] K. Zhang, J. M. Suh, T. H. Lee, J. H. Cha, J. W. Choi, H. W.
Jang, R. S. Varma, M. Shokouhimehr, Nano Convergence.
2019, 6, 6.
[64] S. Ranjit, R. Lee, D. Heryadi, C. Shen, J. Wu, P. Zhang, K. W.
Huang, X. Liu, J. Org. Chem. 2011, 76, 8999.
[65] A. Correa, M. Carril, C. Bolm, Angewandte Chemie. 2008, 120,
[38] A. Ahadi, S. Rostamnia, P. Panahi, L. D. Wilson, Q. Kong, Z.
2922.
An, M. Shokouhimehr, Catalysts 2019, 9, 140.
[66] K. Harsha Vardhan Reddy, V. Prakash Reddy, J. Shankar, B.
Madhav, B. S. P. Anil Kumar, Y. V. D. Nageswar, Tetrahedron
Lett. 2011, 52, 2679.
[39] M. Shokouhimehr, K. Y. Shin, J. S. Lee, M. J. Hackett, S. W.
Jun, M. H. Oh, J. Jang, T. Hyeon, J. Mater. Chem. A 2014, 2,
7593.
[67] E. Sperotto, G. P. M. van Klink, G. van Koten, J. G. de Vries,
[40] H. Alamgholiloo, S. Zhang, A. Ahadi, S. Rostamnia, R. Banaei,
Dalton Trans. 2010, 39, 10338.
Z. Li, X. Liu, M. Shokouhimehr, Mol. Catal. 2019, 467, 30.
[41] X. Yin, X. Liu, Y. T. Pan, K. A. Walsh, H. Yang, Nano Lett.
2014, 14, 7188.
[42] L. Wang, S. Zhao, C. Liu, C. Li, X. Li, H. Li, Y. Wang, C. Ma, Z.
How to cite this article: Alinezhad H, Pakzad K.
C‐S cross‐coupling reaction using novel and green
synthesized CuO nanoparticles assisted by
Euphorbia maculata extract. Appl Organometal
Chem. 2019;e5144. https://doi.org/10.1002/aoc.5144
Li, J. Zeng, Nano Lett. 2015, 15, 2875.
[43] K. L. Dunbar, D. H. Scharf, A. Litomska, C. Hertweck, Chem.
Rev. 2017, 117, 5521.
[44] A. Z. Halimehjani, S. Shokrgozar, P. Beier, J. Org. Chem. 2018,
83, 5778.