Copper(I)–creatine complex on magnetic nanoparticles as a green catalyst for N- and O-arylation in deep eutectic solvent

Article abstract of DOI:10.1002/aoc.5447

Immobilization of copper(I) ions on magnetic nanoparticles was performed using surface modification of Fe₃O₄ with creatine. Fe₃O₄?creatine-Cu(I) magnetic catalyst was synthesized and applied in C&bond;X cross-coupling reactions with aryl halides in a deep eutectic as a green solvent. The results indicate the Fe₃O₄?creatine-Cu(I) magnetic nanoparticles showed excellent activity and high stability. In addition, it was revealed that this catalyst can be recycled five times without significant loss in catalytic activity.

Full text of DOI:10.1002/aoc.5447

Received: 19 September 2019
DOI: 10.1002/aoc.5447
Revised: 13 November 2019
Accepted: 8 December 2019
F U L L P A P E R
Copper(I)–creatine complex on magnetic nanoparticles as a
green catalyst for N- and O-arylation in deep eutectic
solvent
Sepideh Bagheri | Farzane Pazoki
| Iman Radfar
| Akbar Heydari
Department of Chemistry, Faculty of
Immobilization of copper(I) ions on magnetic nanoparticles was performed
using surface modification of Fe O4 with creatine. Fe O @creatine-Cu
Sciences, Tarbiat Modares University,
Tehran, 14117-13116, Iran
3
3 4
(I) magnetic catalyst was synthesized and applied in C&bond;X cross-
Correspondence
A. Heydari, Department of Chemistry,
Tarbiat Modares University, Tehran
coupling reactions with aryl halides in a deep eutectic as a green solvent.
The results indicate the Fe O @creatine-Cu(I) magnetic nanoparticles
3
4
14117-13116, Iran.
showed excellent activity and high stability. In addition, it was revealed
that this catalyst can be recycled five times without significant loss in cata-
lytic activity.
Email: heydar_a@modares.ac.ir
Funding information
Tarbiat Modares University
K E Y W O R D S
creatine, cross-coupling, magnetic, nanocatalyst
1
| INTRODUCTION
can react with a salicylic aldehyde for imine formation.
Then copper(I) can be bonded to the imine.
N-Arylation of various amines and alcohols affords com-
pounds that are significant building blocks in organic
synthesis as well as moieties in many biologically active
Solvents play a significant role in the natural environ-
ment. The major problems of using solvents are their vol-
atile nature, toxicity and high consumption. Several
reports of C&bond;X cross-coupling reactions have con-
[1]
molecules. Transition metal catalysts have often been
used for this purpose via C&bond;N bond formation. In
recent years, Pd, Ni and Cu complexes have been intro-
duced as being effective in C&bond;N coupling reac-
[5]
sidered the use of various solvents such as CH Cl ,
2
2
[
6]
[7]
C H Cl ,
dimethylformamide (DMF) and toluene.
2
4
2
Hence we decided to use a green solvent, a deep eutectic
solvent (DES), in this type of coupling reaction to remove
the need for toxic solvents. DESs have desirable features
including low cost, eco-friendliness, low vapor pressures
and low volatility, making them suitable for both scien-
[2]
tions. Among these, copper catalysts are preferred over
the other types of transition metal (often Pd)
catalysts from industrial, environmental and even
[3]
economic perspectives.
However, synthesis of
[
8]
copper catalysts requires various ligands like
tific and industrial applications. One of the most com-
mon methods for producing DESs is the use of mixtures
of salts (ammonium or phosphonium salts) and hydrogen
bond donors such as alcohols, carbonyl compounds (car-
boxylic acids, esters, ethers, amides), amino acids,
halides, amines, hydrated metal salts of chlorides,
2
6
-oxocyclohexanecarboxylate,
-diol and amino acids and harmful solvents. Hence it
2-aminopyrimidine-4,-
has been recognized that developing clean N-arylation is
one of the most important challenges in green chemistry.
Heterogeneous catalysts have exceptional features such
as high catalytic activity, easy separation and high selec-
tivity, making them the most promising nanomaterials
[
9]
nitrates and acetates. In the study reported here, potas-
sium carbonate and glycerol were mixed in an optimum
ratio for creating a green DES. Also, Fe O @creatine-Cu
[4]
for catalytic goals. Accordingly, with the aim of synthe-
sizing a new environmentally friendly catalytic system
for this reaction, creatine as a green, nontoxic compound
3
4
(I) as a green catalyst was used in N-arylation via various
types of amines, alcohols and aryl halides.
Appl Organometal Chem. 2020;e5447.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5447

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BAGHERI ET AL.
2
2
| EXPERIMENTAL
In the next step, 1.0 g of Fe O @creatine was dis-
persed in dry ethanol (50 ml) and then salicylaldehyde
3
4
.1 | Materials and instrumentation
(2.0 mmol) was added and the mixture was heated for
ꢀ
2
4 h at 78 C The resulting black material was separated
All commercial reagents were purchased from Merck or
Fluka. Energy-dispersive X-ray spectroscopy (EDX) was
conducted with an Oxford Instruments system and field
emission scanning electron microscopy (SEM) images
were recorded with a Zeiss-Sigma VP 500. Vibrating sam-
ple magnetometry (VSM) was carried out using a vibrat-
by magnetic decantation and washed with deionized
water (3 × 30 ml) and dried at 50 C for 24 h.
ꢀ
An amount of 1.0 g of resulting product was dispersed
in dry tetrahydrofuran (50 ml) in an ultrasonic bath for
15 min, after which CuI (0.4 mmol) was added and
ꢀ
stirred at 25 C for 24 h. Finally, the resulting black mate-
ꢀ
ing
magnetometer/alternating
gradient
force
rial was separated and dried in an oven at 60 C for 20 h
magnetometer (MD Co., Iran, www.mdk-magnetic.com).
X-ray diffraction (XRD) patterns of samples were
obtained with a Philips X-Pert 1710 diffractometer. H
(Scheme 1).
1
NMR (300 MHz) spectra were obtained using a Bruker
DRX-500 Advance spectrometer. Fourier transform infra-
red (FT-IR) spectroscopy was conducted with a Shimadzu
FT-IR-8400S spectrometer.
2.3 | General procedure for C&bond;X
cross-coupling reactions
To a mixture of phenol or amine derivative (1.2 mmol)
and aryl halide derivative (1.0 mmol) in DES (glycerin
and K CO at 1:4 mmol), 0.04 g of Fe O @creatine-Cu
2
3
3 4
ꢀ
(
I) was added at 80 C. After completion of the reaction,
2
.2 | Preparation of Fe O @creatine-Cu
the product was decanted by dilution of the residue with
water and the magnetic catalyst was separated using an
external magnet. Finally, products were isolated using
chromatography on silica gel.
3
4
(I)
Fe O @creatine-Cu(I) magnetic nanoparticles were syn-
3
4
thesized by dissolving a mixture of 2.7 g of FeCl Á6H O
3
2
(
1
10 mmol) and 1.0 g of FeCl Á4H O (5.0 mmol) salts in
2
2
30 ml of deionized water under vigorous stirring
3 | RESULTS AND DISCUSSION
3.1 | Characterization of catalyst
(
800 rpm). Then, NH OH solution (25% w/w, 11 ml) was
4
added dropwise to the stirring mixture. Afterward, crea-
tine (2 mmol) was added to this mixture. The resultant
nanoparticles were stirred for 1 h at 25 C and then the
mixture was heated for 5 h at 80 C. The resulting black
material was separated using magnetic decantation and
ꢀ
The Fe O @creatine-Cu(I) nanoparticles were character-
3
4
ꢀ
ized by using several techniques: FT-IR spectroscopy,
XRD, VSM, SEM–EDX, transmission electron microscopy
(TEM), thermogravimetric analysis (TGA) and induc-
tively coupled plasma (ICP) analysis. Figure 1 shows the
washed with deionized water (3 × 30 ml) and dried at
5
ꢀ
0 C for 24 h.
SCHEME 1 Preparation of
Fe O @creatine-Cu(I) nanoparticles
3 4

CREATINE MAGNETIC CATALYST FOR N AND O-ARYLATION IN GREEN SOLVENT
3 of 9
FIGURE 1 FT-IR spectra of
Fe
before (red) and after (blue) reaction,
Fe @creatine nanoparticles (orange)
3 4
O @creatine-Cu(I) nanoparticles
3 4
O
and creatine (black)
[
11]
FT-IR spectra of the Fe O @creatine-Cu(I) nanoparticles,
respectively (JCPDS 19-629).
These results indicate
3
4
the Fe O @creatine nanoparticles and creatine. The FT-
that Fe O @creatine-Cu(I) had been successfully
3 4
3
4
IR spectra of the Fe O @creatine-Cu(I) nanoparticles
synthesized.
SEM imaging of the nanoparticles shows
nanometer-sized particles of about 8–16 nm in diame-
ter. Figure shows the morphology of the
Fe O @creatine-Cu(I) nanoparticles, having a core–shell
structure and spherical shape. TEM images of the cata-
lyst are shown in Figure 4. The spherical shape of each
nanoparticle corresponded to the core of the catalyst
similar to SEM images which can be observed at a scale
of 50 nm. SEM and TEM images of the catalyst after
reaction are shown in Figures 3b and 4b. A comparison
of images of before and after reaction leads to the con-
clusion that there is not much difference in the shape
and the morphology of the nanoparticles before and
after reaction.
3
4
and Fe O @creatine nanoparticles shows a band at
3
4
47 cm− which can be ascribed to the vibration of
1
5
−
1
Fe&bond;O bond, while the band at 3426 cm can be
attributed to the symmetric stretching vibration of
hydroxyl groups (&bond;OH). The aromatic C&bond;H
stretching vibration band appears at about 3137 cm
and the peak at 1400 cm in the FT-IR spectrum of
Fe O @creatine is related to the C&bond;O bond, this
3
3
4
−1
−
1
3
4
peak being shifted in the FT-IR spectrum of
−
1
Fe O @creatine-Cu(I) to 1398 cm . Comparing the
3
4
vibration band in the FT-IR spectrum of Fe O @creatine
3
4
−
1
at 1619 cm
1
with that of Fe O @creatine-Cu(I) at
3 4
617 cm− demonstrates the formation of the complex.
1
Also a comparison of the spectra of Fe O @creatine-Cu
3
4
(I) before and after reaction leads to the conclusion that
To
study
the
elemental
composition
of
there is no significant difference in the catalyst structure.
The XRD pattern of Fe O @creatine-Cu(I) is shown
Fe O @creatine-Cu(I), EDX was performed (Figures 5
3
4
and 6). The EDX pattern confirms the good dispersion of
Fe O @creatine-Cu(I). Chemical characterization of the
3
4
in Figure 2. The XRD pattern of is indicative of a cubic
3
4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
structure of Fe O (2θ = 35 , 41 , 51 , 64 , 67 and 75 ).
nanoparticles showed that they were composed of iron,
nitrogen, oxygen, copper and carbon elements and this
analysis indicated the presence of 0.8% Cu in
3
4
These peaks are matched to (220), (311), (400), (422),
511) and (440) lattice planes of cubic magnetite,
(
FIGURE 2 XRD pattern of
Fe @creatine-Cu(I) nanoparticles
3 4
O

4
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BAGHERI ET AL.
FIGURE 3 SEM images of
Fe @creatine-Cu(I) nanoparticles
before reaction (a) and after reaction (b)
3 4
O
3 4
FIGURE 4 TEM images of Fe O @creatine-Cu(I) nanoparticles before reaction (a) and after reaction (b)
FIGURE 5 Weight percent of
various elements on the surface of
3 4
Fe O @creatine-Cu(I) from EDX
analysis
ꢀ
Fe O @creatine-Cu(I). ICP mass spectrometry revealed
450 C be attributed to organic moiety. Accordingly, these
3
4
ꢀ
that the loading of Cu of the Fe O @creatine-Cu
nanoparticles decomposed after 300 C.
3
4
−
1
(
I) nanoparticles was 0.2 mmol g . Also, ICP mass spec-
Magnetic hysteresis measurements of Fe O and
3
4
trometry was performed for the used catalyst, with the
amount of Cu of the Fe O @creatine-Cu(I) nanoparticles
being about 0.2 mmol g .
Fe O @creatine-Cu(I) were made in the range −10 000
to +10 000 Oe using VSM. As shown in Figure 8, the sat-
3
4
3
−
4
1
uration magnetization of Fe O @creatine-Cu(I) is around
3
4
−1
−1
TGA of Fe O and Fe O @creatine-Cu(I) was con-
53 emu g , lower than that of Fe O (63 emu g ). The
3 4
3
4
3
4
ꢀ
ducted in the range 20–700 C (Figure 7). The first mass
magnetization
curve
indicates
that
these
loss of Fe O and Fe O @creatine-Cu(I) at a temperature
Fe O @creatine-Cu(I)
nanoparticles
have
super-
3
4
3
4
3 4
ꢀ
below 180 C is due to removal of physically adsorbed
paramagnetic properties, which means the nanoparticles
can be easily separated from a reaction mixture using an
external magnet.
[12]
water . The second and most original weight loss of
Fe O @creatine-Cu(I) in the region between 300 and
3
4

CREATINE MAGNETIC CATALYST FOR N AND O-ARYLATION IN GREEN SOLVENT
5 of 9
reaction was conducted utilizing several solvents,
amounts of catalyst and temperatures to achieve the max-
imum yield (Table 1). The evaluation was initially carried
out in various solvents such as DMF, water, dioxane, dic-
hloromethane and glycerin. The results show that using
glycerin as solvent is effective in increasing the yield
Table 1, entry 8). In the next step, we investigated the
(
ꢀ
role of temperature. We found that 80 C gives the best
result for this reaction (80%).
Subsequently, we found that 0.04
g
of
Fe O @creatine-Cu(I) was enough to progress the reac-
3
4
tion which gave the desired product in 80% yield. Also,
the reaction in the presence of Fe O @creatine-Cu
3
4
FIGURE 6 EDX pattern of surface elements of functionalized
(I) without K CO and in the presence of K CO without
2 3 2 3
nanoparticles
Fe O @creatine-Cu(I) was studied. The observations
3 4
demonstrated that cooperation of Fe O @creatine-Cu
3
4
(
I) and K CO is essential for this reaction.
2
3
Various molar ratios of glycerin to potassium carbon-
ate were prepared by varying the glycerin molar ratio at a
fixed amount of potassium carbonate. The molar ratios of
:1, 1:2 and 1:3 did not lead to a DES due to the products
forming a mixture of colorless liquid and solid after
1
ꢀ
cooling to 25 C. The precipitation of solid particles in the
products indicates that the extra amount of potassium
carbonate cannot provide hydrogen bonds with the
hydrogen. Therefore, we selected a molar ratio of 1:4 for
this reaction because this form of DES afforded excellent
yield.
FIGURE 7 TGA curves of Fe
Fe @creatine-Cu(I) (red)
3
O
4
(purple) and
Indeed, the optimal reaction conditions are consid-
ered to be aniline (1.2 mmol), bromobenzene (1.0 mmol)
in DES at 80 C for 24 h.
3 4
O
ꢀ
With the optimized conditions, a series of C&bond;X
cross-coupling reactions were performed with products
afforded in good to excellent yields. The results are sum-
marized in Table 2. We investigated the catalytic effi-
ciency of Fe O @creatine-Cu(I) for coupling of aryl
3
4
halide derivatives with phenol, providing the products in
good yield (1a, 3a and 4a) but the reaction of
2,4,6-trinitrophenol (picric acid) with iodobenzene gave
moderate yield due to steric hindrance. Various aryl
halides were reacted with amine derivatives with
electron-withdrawing or electron-donating substituents
to generate the desired products in good to excellent
yields (5b–12b).
FIGURE 8 Magnetization curves of Fe
Fe @creatine-Cu(I) (red)
3 4
O (purple) and
3
O
4
A possible mechanism for the C&bond;X cross-
coupling reactions catalyzed by Fe O @creatine-Cu
3
4
3
.2 | Catalytic performance
(I) is shown in Scheme 2 which consists of three
major stages. In the first step of oxidative addition,
interaction of Fe O @creatine-Cu(I) with aryl halide
The catalytic activity of Fe O @creatine-Cu(I) was inves-
3
4
3 4
tigated in C&bond;X cross-coupling reactions for the syn-
thesis of amines and ethers. We began our study with
aniline and bromobenzene in the presence of
Fe O @creatine-Cu(I). To optimize the conditions, the
leads to increasing oxidative state and coordinate num-
ber of copper to give compound a. In the next step,
amine or phenol is deprotonated then exchange of
ligand generates compound b. Finally, the product of
3
4

6
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BAGHERI ET AL.
TABLE 1 Optimization of reaction conditions
ꢀ
d
Entry
Amount of catalyst (g)
Solvent
Base
Temperature ( C)
Yield (%)
a
1
2
3
4
5
6
7
7
8
9
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.04
0.03
0.02
0.04
DMF
Triethylamine
Triethylamine
Triethylamine
Triethylamine
100
100
100
60
75
-
a
2
H O
a
Dioxane
70
80
80
80
70
30
80
75
65
75
a
Dichloromethane
b
Glycerin
K
2
K
2
K
2
K
2
CO
CO
CO
CO
3
3
3
3
100
80
b
Glycerin
b
Glycerin
60
b
Glycerin
40
b
Glycerin
K
2
CO
3
80
b
Glycerin
K
2
K
2
K
2
CO
CO
CO
3
80
b
1
1
0
1
Glycerin
3
80
c
Glycerin
3
80
a
Reaction conditions: aniline (1.2 mmol), bromobenzene (1.0 mmol) and triethylamine (2.0 mmol) in various solvents (3.0 mml) in the presence of
Fe @creatine-Cu(I) (0.04 g) for 24 h.
Reaction conditions: aniline (1.2 mmol), bromobenzene (1.0 mmol) in DES (molar ratio of 1:4) in the presence of Fe
3 4
O
b
3
O
4
@creatine-Cu(I) (0.04 g) for 24 h.
c
3 4
Reaction conditions: aniline (1.2 mmol), bromobenzene (1.0 mmol) in DES (molar ratio of 1:5) in the presence of Fe O @creatine-Cu(I) (0.04 g) for 24 h.
d
Isolated yield.
TABLE 2 Products of the two types of C&bond;X cross-coupling reactions
a, 80% , TON/TOF: 100/4.16 h−1
a
2a, 35% , TON/TOF: 43.75/1.82 h
a
−1
3a, 85% , TON/TOF: 106.25/4.42 h
a
−1
1
a, 85% , TON/TOF: 106.25/4.42 h−1
a
4
a
−1
6
b, 80% , TON/TOF: 100/4.16 h
a
−1
5
b, 75% , TON/TOF: 93.75/3.90 h
a
−1
a
−1
8
b, 75% , TON/TOF: 93.75/3.90 h
9
b, 80% , TON/TOF: 100/4.16 h
b, 80% , TON/TOF: 100/4.16 h−1
a
7
(
Continues)

CREATINE MAGNETIC CATALYST FOR N AND O-ARYLATION IN GREEN SOLVENT
7 of 9
TABLE 2 (Continued)
a, 80% , TON/TOF: 100/4.16 h−1
a
2a, 35% , TON/TOF: 43.75/1.82 h
a
−1
3a, 85% , TON/TOF: 106.25/4.42 h
a
−1
1
0b, 85% , TON/TOF: 106.25/4.42 h−1
a
a
−1
a
−1
1
11b, 70% , TON/TOF: 87.5/3.64 h
12b, 80% , TON/TOF: 100/4.16 h
3b, 85% , TON/TOF: 106.25/4.42 h−1
a
a
−1
1
1
4b, 80% , TON/TOF: 100/4.16 h
Reaction conditions: phenol or amine derivatives (1.2 mmol), aryl halide derivatives (1.0 mmol) in DES in the presence of Fe
3
O
4
@creatine-Cu(I) (0.04 g,
ꢀ
0
.8 mol%) at 80 C for 24 h.
a
Isolated yield.
SCHEME 2 Possible mechanism for C&bond;X cross-coupling reactions

8
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BAGHERI ET AL.
FIGURE 9 Catalyst reusability in
the coupling reaction
the cross-coupled reaction is easily afforded by reduc-
tive elimination.
nanoparticles can be reused five times with no loss in
activity. Also, the magnetic nanoparticles were character-
ized using SEM, TGA, EDX, ICP analysis, FT-IR spectros-
copy, VSM, TEM and XRD.
3.3 | Catalyst recyclability
ACKNOWLEDGEMENT
Reusability is one of the significant properties of a het-
erogeneous catalyst. Hence, recyclability and reusability
of Fe O @creatine-Cu(I) were screened in the model
We gratefully acknowledge the Faculty of Chemistry of
Tarbiat Modares University for supporting this work.
3
4
reaction. The results are shown in Figure 9. These
results revealed the practical reusability and stability of
ORCID
Farzane Pazoki https://orcid.org/0000-0001-8616-5591
Iman Radfar https://orcid.org/0000-0003-4965-1982
the Fe O @creatine-Cu(I) nanoparticles. This catalyst
3
4
can be recycled efficiently five times without significant
loss in catalytic activity. Heterogeneity of the catalyst
was investigated using the hot filtration test. After 2 h
from the beginning of the reaction, the catalyst was
removed, and the reaction was continued for another
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| CONCLUSIONS
[
[
[
[
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could be easily recovered and reused owing to its good
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How to cite this article: Bagheri S, Pazoki F,
Radfar I, Heydari A. Copper(I)–creatine complex
on magnetic nanoparticles as a green catalyst for
N- and O-arylation in deep eutectic solvent. Appl
Organometal Chem. 2020;e5447. https://doi.org/10.
1002/aoc.5447
[
[
[
1
5, 2266.
11] S. Bagheri, M. J. Nejad, F. Pazoki, M. K. Miraki, A. Heydari.
ChemistrySelect, 2019, 4, 11930.
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Letters, 2019, 1.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.