Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable and Eco-friendly Catalyst for Click Chemistry from Organic Halides and Epoxides

Article abstract of DOI:10.1007/s10562-018-2523-0

Abstract: Copper(I)–caffeine complex immobilized on silica-coated magnetite nanoparticles was successfully synthesized and fully characterized by analyzing FT-IR, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, inductively couple

Full text of DOI:10.1007/s10562-018-2523-0

Catalysis Letters
https://doi.org/10.1007/s10562-018-2523-0
Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite
Nanoparticles: A Recyclable and Eco-friendly Catalyst for Click
Chemistry from Organic Halides and Epoxides
Arefe Salamatmanesh1 · Maryam Kazemi Miraki1 · Elahe Yazdani1 · Akbar Heydari1
Received: 27 February 2018 / Accepted: 9 August 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Copper(I)–caffeine complex immobilized on silica-coated magnetite nanoparticles was successfully synthesized and fully
characterized by analyzing FT-IR, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, inductively
coupled plasma, thermal gravimetric analysis and vibrating sample magnetometer data. The catalytic activity of these mag-
netically retrievable nanoparticles was evaluated for green synthesis of 1,2,3-triazoles through the three-component reaction
of various terminal alkynes with in situ generated organic azides from organic halides and epoxides in an aqueous medium
that was observed to proceed well and products were obtained in good yields. In addition to showing outstanding catalytic
activity, the magnetic catalyst is easy to synthesize and can be recycled at least five times with little loss in activity.
Graphical Abstract
Keywords Copper · NHC system · Heterogeneous catalyst · Magnetic Nanoparticles · Click chemistry
1 Introduction
This article is dedicated to memory of Yadollah Shojaee.
The concept of “click chemistry” was originally postulated by
Sharpless and colleagues [1]. Since then, a variety of transi-
tion metal catalysts (Cu, Ru, Ag, Au, Ir, Ni, Zn, Ln) have been
used for “click chemistry”, although the copper(I)-catalyzed
1,3-dipolar azide–alkyne cycloaddition (CuAAC) reaction is
still the most popular “click” reaction to produce 1,4-disubsti-
tuted 1,2,3-triazoles regioselectively [2–4]. 1,2,3-Triazoles are
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-018-2523-0) contains
supplementary material, which is available to authorized users.
* Akbar Heydari
heydar_a@modares.ac.ir
1
Chemistry Department, Tarbiat Modares University, P.O.
Box 14155-4838, Tehran, Iran
Vol.:(0123456789)
1 3

A. Salamatmanesh et al.
vital structural scaffolds found in a wide variety of biologically
active natural compounds and have extensive applications in
medicinal chemistry, pharmaceutical industry [5], biochemi-
cals [6] and materials science [7]. Even though most of the
previous studies on CuAAC reactions employed pre-isolated
organic azides [8, 9], it is difficult to prepare and handling of
toxic and potentially explosive azides [10]. To overcome this
difficulty, multicomponent one-pot CuAAC reactions using
in situ generated organic azides from organic halides and NaN3
have been developed [11, 12]. Recently, alternative one-pot
methodologies for the synthesis of 1,2,3-triazoles using aro-
matic amines [13], diazonium salts [14], and epoxides [15, 16]
as precursors of azides have been disclosed.
2 Experimental
2.1 Materials and Instrumentation
All reagents and solvents were purchased from reputable
commercial suppliers and used without further purifica-
tion. All reactions were carried out in the air. All reported
yields are isolated yields. FT-IR spectra were obtained
over the region 400–4000 cm− 1 using a Nicolet IR100
FT-IR with spectroscopic grade KBr. The X-ray diffraction
pattern was obtained at room temperature using a Philips
X-pert 1710 diffractometer with Co Kα (α = 1.78897 Å),
40 kV voltage, 40 mA current and in the range 100–900
(2θ) with a scan speed of 0.020/s. Scanning electron
microscopy (SEM; Philips XL 30 and S-4160) was uti-
lized to study the catalyst morphology and size. Magnetic
saturation of the catalyst was obtained using a vibrating
magnetometer/alternating gradient force magnetometer
(VSM/AGFM, MDK Co., Iran). Thermal gravimetric anal-
ysis (TGA) was recorded using a thermal analyzer with
a heating rate of 20 °C/min over a temperature range of
25–1100 °C under flowing nitrogen. Inductively coupled
plasma (ICP) analyse was performed using a Varlan Vista-
Pro ICP-OE spectrometer. 1H NMR and 13C NMR spectra
were recorded on a Bruker Avance (DRX 250 MHz and
DRX 500 MHz) in a pure deuterated CHCl3 solvent with
tetramethylsilane as an internal standard.
Various copper-based catalytic systems have been employed
for “click chemistry” [11, 17–19], among them copper com-
plexes bearing N-heterocyclic carbene (NHC) ligands are
prominent as they show appropriate thermal, moisture, and air
stability in metal-catalyzed transformations [20–22]. Since the
first pioneering isolation of stable free NHC by Arduengo et al.
in the last two decades [23, 24], NHCs have become ubiqui-
tous ligands with incredible activity in coordination chemistry
[25–27]. NHC–transition metal complexes with the notable
s-electron-donating abilities and the robust metal–carbon
bonds are a well-defined family of organometallic catalysts
[28–30]. The immobilization of such organometallic catalysts
and also organocatalysts on magnetic or non-magnetic nano-
particles not only facilitates catalyst separation and recovery
but also confers new levels of catalytic activity and selectiv-
ity on them [31–36]. However, Fe3O4 magnetic nanoparticles
are well known to be the most promising nanomaterials for
catalytic purposes due to their high catalytic activity and easy
separation [37–39]. In recent years, a large number of click
reactions catalyzed by various copper complex-functionalized
magnetic nanoparticles have been reported [40–43]. An effi-
cient, eco-friendly and recyclable heterogeneous catalyst for
“click chemistry” could thus be achieved by a copper–NHC
system with high activity that has been immobilized on mag-
netic nanoparticles. We herein report on the immobilization
of caffeine, a natural methylxanthine alkaloid, as NHC ligand
on the surface of silica coated magnetite nanoparticles and the
formation of a highly efficient, eco-friendly and recoverable
Fe3O4@SiO2-caffeine–Cu(I) heterogeneous catalyst for green
synthesis of 1,2,3-triazoles through aqueous multicomponent
one-pot reactions of terminal alkynes with in situ generated
organic azides from organic halides and epoxides in good
yields.
2.2 Preparation of Silica‑Coated Magnetite
Nanoparticles of Fe3O4
Magnetite nanoparticles were prepared by co-precipita-
tion method according to a previously reported procedure
[44]. Briefly, in 100 mL of deionized water, a mixture of
10 mmol FeCl3_6H2O and 5 mmol FeCl2_4H2O salts were
dissolved under vigorous stirring (800 rpm). An aqueous
ammonia solution (28% w/w, 30 mL) was then added to
the stirring mixture to reach the reaction pH about 11. The
resulting black dispersion was stirred vigorously for 1 h at
room temperature and then refluxed for 1 h. The resulting
black nanoparticles were separated magnetically from the
aqueous solution and were washed with water and etha-
nol several times before being dried in an oven at 60 °C.
In order to synthesize silica-coated Fe3O4 nanoparticles,
magnetite nanoparticles (1.0 g) were initially dispersed in
80 mL 4:1 ethanol/water solution and the pH of the solu-
tion was adjusted to 10 using concentrated aqueous ammo-
nia (1.5 mL, 28 wt%). The resulting dispersion was then
sonicated for 20 min. Then, 0.5 mL tetraethylorthosilicate
(TEOS) was added subsequently. The mixture was stirred
vigorously at 40 °C for 12 h. The resulting nanoparticles
1 3

Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable…
were collected magnetically and washed several times with
water and ethanol and dried in an oven at 80 °C.
to reflux and after 48 h, nanoparticles were magnetically
separated and washed with methanol (2×100 mL), and ace-
tone (2×100 mL). The resulting nanoparticles were dried
in an oven. In a round-bottomed flask, Fe3O4@SiO2-caf-
feine (1.0 g), CuI (0.09 g, 0.5 mmol) and KOt–Bu (0.056 g,
0.5 mmol) were suspended in dry THF (10 mL) and stirred
for 12 h at room temperature. The resulting nanoparticles
were then magnetically concentrated and washed with THF
(2×100 mL), and DCM (2×100 mL) before drying the par-
ticles overnight in an oven.
2.3 Immobilization of Caffeine on Silica‑Coated
Magnetite Nanoparticles (Fe3O4@SiO2‑Caffeine)
and Complex Preparation [Fe3O4@
SiO2‑Caffeine–Cu(I)]
The functionalized magnetic nanoparticles (Fe3O4@SiO2-
Caffeine) were prepared by treating about 1.0 g of Fe3O4@
SiO2 in 50 mL of dry chloroform with (3-chloropropyl)
triethoxysilane (3 mL). The resulting suspension was then
refluxed. After 18 h, nanoparticles were concentrated by
magnetic decantation and washed several times with tolu-
ene (2×100 mL), methanol (2×100 mL), and finally die-
thyl ether. The resulting nanoparticles were dried under Ar.
The resultant nanoparticles were dispersed in 80 mL of dry
acetone and then caffeine (0.38 g, 2 mmol) in 20 mL of
acetone was added. The resulting suspension was brought
2.4 General Procedure for Synthesis
of 1,2,3‑Triazoles
In a round-bottomed flask, an appropriate alkyl hal-
ide (1.0 mmol) or epoxide (1.0 mmol), terminal alkyne
(1.0 mmol), and sodium azide (1.1 mmol) were added in
water (5 mL). Then the suspension was magnetically stirred
at 70 °C in the presence of 25 mg (0.30 mol%) nano-Fe3O4@
1.
2.
Cl
Scheme 1 Preparation of nano-
/ Toluen
Si
(EtO)3
SiO2
H
FeCl3.6 2O
NH
TEOS/
4OH
NH
4OH
h
18
Fe3O4@SiO2-caffeine–Cu(I)
Fe3O4
Fe3O4
H
O
N
2O
EtOH,
H
FeCl2.4 2O
N
N
N
/ Aceton
48 h
O
O
N
O
N
O
N
O
SiO2
Fe3O4
N
SiO2
Fe3O4
O
O
O
KOtBu
CuI,
O
O
O
( )
( )
N
Si
N
N+
Si
3
N
3
Cl-
12 h
THF,
Cu
I
Fig. 1 The FT-IR spectra of the
Fe3O4@SiO2 (a), Fe3O4@SiO2–
Cl (b), Fe3O4@SiO2-caffeine
(c) and Fe3O4@SiO2-caffeine–
Cu(I) (d)
1 3

A. Salamatmanesh et al.
Fig. 2 a SEM and b EDX analysis of the catalyst
SiO2-caffeine–Cu(I) magnetic catalyst. The progress of the
reaction was monitored by TLC. After completion of the
reaction, the resulting mixture was decanted as much as pos-
sible followed by dilution of the residue with hot ethanol
and separation of catalyst from the mixture by an external
magnet. The solution was evaporated to afford the desired
product. The pure crystalline products were obtained by
re-crystallization from EtOH:H2O (3:1 v/v). In some cases
products had to be isolated using chromatography on silica
gel. After separation of the catalyst, it was washed with etha-
nol (2×10 mL) and dried in an oven for reuse in subsequent
reactions under the same conditions.
Fig. 3 TGA curves of Fe3O4@SiO2–Cl (a), Fe3O4@SiO2-caffeine (b)
and Fe3O4@SiO2-caffeine–Cu(I) (c)
3 Results and Discussion
The method for the synthesis of this catalyst system is shown
in Scheme 1. Silica-coated magnetite nanoparticles (Fe3O4@
SiO2) were synthesized based on literature procedures.
Fe3O4 nanoparticles were prepared according to conven-
tional co-precipitation method of ferrous and ferric ions in
alkali solution. To improve the chemical stability of Fe3O4
nanoparticles, TEOS was employed to modify the surface of
magnetic Fe3O4 with a thin layer of silica. The abundant sur-
face hydroxyl groups of Fe3O4@SiO2 provide this possibility
for grafting of 3-chloropropyltrimethoxysilane to produce
chloropropyl-functionalized magnetic nanoparticles. Sub-
sequently, the reaction of these magnetic nanoparticles with
caffeine led to the desired magnetic nanoparticle-supported
organocatalyst. Finally, treatment of caffeine functionalized
Fig. 4 The X-ray diffraction patterns of Fe3O4 (a), Fe3O4@SiO2 (b)
and Fe3O4@SiO2-caffeine–Cu(I) (c)
1 3

Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable…
magnetic nanoparticles with CuI in the presence of KOtBu
in THF for 12 h provided Fe3O4@SiO2-caffeine–Cu(I).
The catalyst was fully characterized using various tech-
niques such as FT-IR, SEM, energy-dispersive X-ray (EDX),
TGA, X-ray diffraction (XRD), ICP and vibrating sample
magnetometer (VSM). The FT-IR spectra of the magnetic
nanoparticles show the peaks that confirm the successful
synthesis of the catalyst (Fig. 1) [45]. The peaks appearing
at 590 and 1097 cm− 1 for the Fe3O4@SiO2 sample could
be associated with the presence of stretching vibrations of
Fe–O and Si–O–Si bonds, respectively (Fig. 1a). In the spec-
trum for chloropropyl-functionalized magnetic nanoparti-
cles (Fig. 1b), the additional bands around 2927 cm−1 are
related to C–H stretching vibrations that confirm grafting of
Fig. 5 Magnetization curves of Fe3O4 (a), Fe3O4@SiO2 (b) and
Fe3O4@SiO2-caffeine–Cu(I) (c)
Scheme 2 Three-component
click reaction of NaN3, phenyl
acetylene and benzyl bromide
N
Cat
Br
+ NaN3
N
N
+
Solvent/ 70°C
Table 1 Optimization of
reaction conditions for synthesis
of 1,2,3-triazole
Entries
Amount of
Copper con- Solvent
Temperature (°C)
Time (h:min)
Yield (%)a
catalyst (mg) tent (mol%)
1
2
3
4
5
6
7
8
9
None
25b
25
25
25
25
30
20
15
None
None
0.30
0.30
0.30
0.30
0.36
0.24
0.18
H2O
H2O
Acetone
CH3CN
CH3OH
H2O
H2O
H2O
H2O
70
70
Reflux
70
Reflux
70
70
70
70
24
2
NR
17
68
75
84
96
96
90
85
1:30
1:30
0:45
0:20
0:20
0:20
0:20
Reaction conditions: benzyl bromide (1.0 mmol), phenyl acetylene (1.0 mmol), sodium azide (1.2 mmol),
different values of Fe3O4@SiO2-caffeine–Cu(I) in solvent (5.0 mL)
aIsolated yields
b25 mg of Fe3O4 nanoparticles
N
0.3
Fe O
4@SiO2-Caffeine-Cu(I)
3
mol%
Br
N
N
H
70
°C
2O/
20 min
+
+
NaN3
HO
N
O
N
N
0.3
Fe O
4@SiO2-Caffeine-Cu(I)
3
mol%
H
70
°C
2O/
30 min
Scheme 3 Three-component click reaction of NaN3, phenyl acetylene and benzyl bromide/styrene oxide under optimized conditions
1 3

A. Salamatmanesh et al.
Table 2 Multicomponent synthesis of 1,2,3-triazoles from organic halides, terminal alkynes and sodium azide using Fe3O4@SiO2-caffeine–
Cu(I)
Entries Halide precursors
1
Alkynes
Products Time (min) Yielda (%) TON/TOF (h−1
)
N
20
94
313/940
l
C
N
N
N
2
3
4
5
20
20
40
20
96
94
89
92
320/960
313/940
297/445
307/920
r
B
N
N
N
r
B
N
N
r
B
r
B
N
r
B
N
N
O2N
N
O2
N
r
B
F
N
N
F
N
6
20
96
320/960
r
B
N
N
e
M
N
7
8
30
30
91
89
303/607
297/593
r
B
OH
N
N
H
O
HOOC
N
r
B
N
N
H
O
O
N
H
O
9
40
30
84
87
280/420
290/580
r
B
N
N
OH
r
B
N
10
N
N
1 3

Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable…
Table 2 (continued)
Entries Halide precursors
Alkynes
Products Time (min) Yielda (%) TON/TOF (h−1
)
O
O
11
40
89
297/445
Br
N
N
N
O
l
C
12
40
87
290/435
Br
O
Cl
N
N
N
O
N
13
O2
50
84
280/336
r
B
O
N
N
O2
N
N
Reaction conditions: benzyl/alkyl halide (1.0 mmol), alkynes (1.0 mmol), sodium azide (1.2 mmol), Fe3O4@SiO2-caffeine–Cu(I) (25 mg,
0.3 mol%) in H2O (5.0 mL), 70 °C
aIsolated yields
3-chloropropyltriethoxysilane on the surface of Fe3O4@SiO2
[46]. In the spectrum for Fe3O4@SiO2-caffeine (Fig. 1c), the
peaks appearing at 1697, 1633 and 1377 cm−1 are ascribed
to the C=O, C=N, and C–N stretching vibrations, respec-
tively. Comparing the FT-IR spectra of Fe3O4@SiO2-caf-
feine and Fe3O4@SiO2-caffeine–Cu(I) proved formation of
the complex.
desorption from the magnetite surface. As shown as Fig. 3a,
the magnetic Fe3O4@SiO2–Cl nanoparticles showed a slight
weight loss of about 4.2% in the range of 185–550 °C, and
it could be attributed to the thermal decomposition of the
organic groups. In the TGA curve of the Fe3O4@SiO2-caf-
feine (Fig. 3b), a weight loss of about 6.1% in the range
of 185–600 °C should be attributed to the evaporation and
subsequent decomposition of organic moieties grafted on the
surface of the magnetic nanoparticles. The TGA curve for
Fe3O4@SiO2-caffeine–Cu(I) (Fig. 3c), represents a weight
loss of 7% in the range of 160–600 °C corresponding to
the main decomposition of the complex. The third weight
loss could be assigned to the sublimation of iodine (melting
point of CuI: 602 °C) [47]. According to TGA analysis, the
caffeine content of Fe3O4@SiO2-caffeine–Cu(I) magnetic
nanoparticles was evaluated to be 0.33 mmol/g. By Com-
paring the TGA curves of Fe3O4@SiO2-caffeine–Cu(I) and
Fe3O4@SiO2-caffeine, the mass fraction of copper iodine on
the surface of Fe3O4@SiO2 could be deduced to be 2.39%
and the amount of adsorbed copper iodide was evaluated to
be 0.12 mmol/g. ICP analysis was also used to indicate the
0.12 mmol/Cu g loading for the catalyst.
The surface morphology of the catalyst was evaluated by
SEM. The SEM image of the catalyst shows that the mag-
netic particles obtained in the presence of caffeine–Cu(I)
have a nearly spherical shape (Fig. 2a). Also, particles of
the catalyst were observed in nano scale. EDX spectrum of
the obtained nanomaterials (Fig. 2b) confirmed the pres-
ence of the expected elements in the structure of Fe3O4@
SiO2-caffeine–Cu(I), namely iron, oxygen, silicon, and cop-
per with wt% of 6.18, 59.99, 18.87 and 3.69, respectively.
TGA was performed for quantitative determination of
inorganic and organic components in the catalyst. Curves a, b
and c at Fig. 3 represent the TGA results of Fe3O4@SiO2–Cl,
Fe3O4@SiO2-caffeine, and Fe3O4@SiO2-caffeine–Cu(I),
respectively. In the three cases, the weight loss at tempera-
tures below 200 °C can be mainly attributed to the water
1 3

A. Salamatmanesh et al.
To determine the crystalline structure of the magnetic
nanoparticles, XRD pattern was studied in a domain of
10°–90°. As shown at Fig. 4a, diffraction peaks at around
35.17°, 41.53°, 50.53°, 63.61°, 67.77°, and 74.61° corre-
sponding to (220), (311), (400), (422), (511), and (440) are
quite identical to characteristic peaks of the cubic magnetite
(JCPDS card no. 19-0629). The broad peaks at 2θ from 21°
to 30° of the XRD pattern are assigned to the silica phase,
representing the core–shell structure of the catalyst (Fig. 4b).
The appearance of the same peaks in XRD pattern after each
modification with organic groups followed by CuI shows
that the crystalline structure of magnetic nanoparticles is
maintained (Fig. 4c). Any other characteristic peaks due to
the impurities of other oxides of iron were not detected.
Magnetic hysteresis measurements of the nanoparticles
were explored in an applied magnetic field at room tempera-
ture, with the field sweeping from −10,000 to +10,000 Oe
using a VSM. As shown in Fig. 5, the saturation magnetiza-
tion (Ms( values of nanoparticles are 52.63, 29.68 and 21.83
for Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2-caffeine–Cu(I),
Table 3 Multicomponent synthesis of β-hydroxy-1,2,3-triazoles from epoxides, phenyl acetylene and sodium azide using Fe3O4@SiO2-caffeine–
Cu(I)
Entries
1
Epoxide precursors
Alkynes
Products
Time (min)
30
Yielda (%)
94
TON/TOF (h−1
313/627
)
O
N
N
N
H
O
H
O
2
3
30
30
91
90
303/607
300/600
O
O
O
N
N
N
H
O
O
O
O
N
N
N
O
N
N
4
5
30
30
90
89
300/600
297/593
H
O
H
O
N
H
O
H
O
O
N
N
N
N
N
N
H
O
6
7
8
30
40
30
88
89
83
293/587
297/445
277/553
O
N
N
H
O
O
N
N
H
O
O
N
O
O
N
Reaction conditions: epoxides (1.0 mmol), alkynes (1.0 mmol), sodium azide (1.2 mmol), Fe3O4@SiO2-caffeine–Cu(I) (25 mg, 0.3 mol%) in
H2O (5.0 mL), 70 °C
aIsolated yields
1 3

Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable…
respectively, demonstrating that the catalyst is paramag-
netic. Some decreasing of the value of Ms in compare to
pure Fe3O4 is attributed to the silica and organic layer on the
surface of Fe3O4 [48].
been prepared in high yields (Table 2, entries 2–9). When
benzyl chloride was employed in the reaction, the cor-
responding product was generated in 94% yield (Table 2,
entry 1). Allyl bromide reacted with sodium azide and
phenyl acetylene leading to the desired triazole in 87%
yield (Table 2, entry 10). When various phenacyl bro-
mides were employed in the reaction, the desired products
were obtained in good to excellent yields (Table 2, entries
11–13). Following the same procedure as described above,
when various epoxides were used in place of organic hal-
ides, the corresponding triazoles were obtained in excel-
lent yields. The results are presented in Table 3. Aliphatic
epoxides, as well as aromatic epoxides, reacted with
sodium azide and phenyl acetylene by this procedure.
Based on the above observations we proposed a plausi-
ble mechanistic pathway for this reaction (Scheme 4). In
the first step, Cu(I)–acetylidine complex (a) was generated
from the reaction of Cu(Ӏ) and aryl acetylene. Then, azide
group adds to the complex (a) and a π-complex is formed
as an intermediate product. In the next step, the distal
nitrogen of the azide attacks to the carbon (C-2) of the
Cu–acetylidine to give a six-membered metallacycle (b).
Finally, ring contraction to a Cu(I)–triazolide complex (c)
is followed by protonolysis that delivers the target product
along with regeneration of Cu(I) catalyst.
To verify the practicability of the projected route,
we selected a model reaction between phenyl acetylene
(1 mmol), benzyl bromide (1 mmol), and sodium azide
(1.2 mmol) (Scheme 2). The results are shown in Table 1.
In an initial experiment, when the mixture was heated to
70 °C for a long time in the absence of catalyst in water, no
reaction was observed (Table 1, entry 1). In the next step,
when the reaction was performed in the presence of pure
Fe3O4 in water at 70 °C, we observed the formation of a
trace amount of the desired product (Table 1, entry 2). To
examine the effect of different solvents, the model reaction
was performed in the presence of various solvents and the
results showed that experiments proceeded in acetone, ace-
tonitrile, methanol and water to afford the desired product
in good to excellent yields (Table 1, entries 3–6). Among
them, water was found to be the best solvent (Table 1, entry
6) in terms of the time and yield of desired product. Subse-
quently, we optimized the catalyst amount and according to
the obtained results (Table 1, entries 6–9) 25 mg (0.3 mol%)
of the catalyst was chosen as the best catalyst amount. As
shown in Table 1, the best result was obtained by carrying
out the reaction using 0.3 mol% Fe3O4@SiO2-caffeine–Cu(I)
at 70 °C in water (Table 1, entry 6).
In order to examine the recyclability of the catalyst in three-
component click reaction for synthesis of 1,2,3-triazoles, the
model reaction was repeated under optimized conditions. In
each cycle, after completion of the reaction, the catalyst was
magnetically concentrated and washed with ethanol several
times, dried and was used in the next cycle. We found that the
catalyst was recovered for five runs without considerable loss
of its activity, as shown in Fig. 6.
To demonstrate the generality of this method, the scope
of the reaction was investigated under the optimized con-
ditions (Scheme 3), and the results are summarized in
Tables 2 and 3. We found that the provided conditions
are useful for a wide range of organic halides, epoxides,
and alkynes. Different benzyl bromides have reacted read-
ily with a variety of alkynes and desired triazoles have
Scheme 4 Proposed mechanism
synthesis of 1,2,3-triazoles
MNPs-Caffeine-Cu(I)
SiO2
from organic halides, terminal
alkynes and sodium azide using
Fe3O4@SiO2-caffeine–Cu(I)
Fe3O4
N
R
H
N
R
N
R
[CuLn]+
N
R
N
N
Copper(I)
acetylidine (a)
(c)
R
CuLn-1
L
R
n-2Cu
+
N
R
N
-
Ln-2
Cu
N
R
R
N
N
CuLn-2
R
N
R
X
+
N
+
Copper(III) metallacycle (b)
N
N R
NaN3
1 3

A. Salamatmanesh et al.
Efficiency of the prepared nanocatalyst was compared
with previously reported catalysts in the literature for click
chemistry. It can be seen in Table 4 that the present catalyst
showed a good catalytic activity. Noticeably, this new cata-
lyst is comparable in terms of price, non-toxicity, recyclabil-
ity, commercially available materials, and easy separation.
4 Conclusions
In conclusion, we have developed a highly efficient,
recyclable and eco-friendly catalytic system, magnetic
nanoparticles-supported CuI–caffeine, for green synthe-
sis of 1,2,3-triazoles through the three-component reac-
tion of various terminal alkynes with in situ generated
organic azides from organic halides and NaN3 in an aque-
ous medium. The corresponding triazoles were prepared
with various epoxides and terminal alkynes in good yields.
In addition, recovery and reusability of the catalyst have
been investigated in three-component click reaction and
the catalyst was reused in at least five cycles without a
significant loss of activity.
Fig. 6 Recyclability of the supported catalyst
In this research, we also report amounts of copper leaching
in three-component click reaction for synthesis of 1,2,3-tria-
zoles by checking the copper loading amount before and after
recycling of the catalyst by ICP analysis. It can be seen that the
amount of copper in the fresh catalyst and the recycled catalyst
after five times recycling is 0.120 and 0.098 mmol/g, respec-
tively, which showed that the copper content of this catalyst
did not decrease appreciably after the reaction.
Table 4 Comparison of the catalytic efficiency of Fe3O4@SiO2-caffeine–Cu(I) with the previously reported catalytic systems in the click reac-
tion of benzyl chloride, phenyl acetylene, and NaN3
Entries Catalyst (mol% Cu)
Reaction conditions
Yielda (%)
1
2
3
4
5
6
7
8
9
10
Cu NPs (5)
Phenyl acetylene (0.5 mmol), benzyl chloride (0.6 mmol), NaN3 (0.6 mmol), CH3OH (2 mL), 86 [49]
r.t., 10 h
Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.1 mmol), EtOH (2.0 mL), 93 [50]
HCP-NHC–Cu (0.45)
Silica–Cu2O (5)
80 °C, 8 h
Phenyl acetylene (1.2 mmol), benzyl chloride (1.0 mmol), NaN3 (1.0 mmol), H2O (5.0 mL),
r.t., 3.5 h
96 [51]
94 [52]
97 [53]
90 [54]
3D-network polymer-sup-
ported Cu(I) (5)
MNP@SPAAm/Cu (0.5)
Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.0 mmol), H2O (3.0 mL),
100 °C, 5 min
Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.3 mmol), H2O (2.0 mL),
Na-ascorbate (10 mol%), 50 °C, 3 h
γ-Fe2O3@TiO2-EG-CuII (4) Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.2 mmol), H2O (5.0 mL),
50 °C, 15 min
MNPs@BiimCu(I) (0.85)
Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.1 mmol), H2O/EtOH (1:1) 93 [55]
(1.0 mL), r.t., 1 h
Cu2O (2)
Phenyl acetylene (2.0 mmol), benzyl azide (2.1 mmol), C6H5CO2H (2 mol%), H2O (2.0 mL), 98 [56]
r.t., 8 min
CuSO4 (110)
Alkyne (0.91 mmol), azide (0.76 mmol), H2O/THF (1:6.6) (23 mL), Na-ascorbate
97 [57]
(220 mol%), r.t., 16hb
This work (0.3)
Phenyl acetylene (1.0 mmol), benzyl chloride (1.0 mmol), NaN3 (1.2 mmol), H2O (5.0 mL),
70 °C, 20 min
94
aIsolated yields
bAlkyne and azide precursor are different from phenyl acetylene and benzyl chloride, respectively (see [57])
1 3

Copper(I)–Caffeine Complex Immobilized on Silica-Coated Magnetite Nanoparticles: A Recyclable…
17. Tavassoli M, Landarani-Isfahani A, Moghadam M, Tangestanine-
Acknowledgements We acknowledge Tarbiat Modares University for
jad S, Mirkhani V, Mohammadpoor-Baltork I (2015) Polystyrene-
supported ionic liquid copper complex: a reusable catalyst for one-
pot three-component click reaction. Appl Catal A 503:186–195
18. Sarkar SM, Rahman ML (2017) Cellulose supported
poly(amidoxime) copper complex for click reaction. J Clean
Prod 141:683–692
financial support of this work.
Compliance with Ethical Standards
Conflict of interest We declare that no conflict of interest exists.
19. Liu X, Novoa N, Manzur C, Carrillo D, Hamon J-R (2016) New
organometallic Schiff-base copper complexes as efficient “click”
reaction precatalysts. N J Chem 40(4):3308–3313
20. Tasca E, La Sorella G, Sperni L, Strukul G, Scarso A (2015)
Micellar promoted multi-component synthesis of 1,2,3-triazoles
in water at room temperature. Green Chem 17(3):1414–1422
21. Bidal YD, Leiseur M, Melaimi M, Nahra F, Cordes DB,
Arachchige AKS et al (2015) Copper(I) complexes bearing
carbenes beyond classical N-heterocyclic carbenes: synthesis
and catalytic activity in “Click Chemistry”. Adv Synth Catal
357(14-15):3155–3161
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