NHC-copper complexes immobilized on magnetic nanoparticles: Synthesis and catalytic activity in the CuAAC reactions

Article abstract of DOI:10.1016/j.jcat.2018.03.015

A series of N-heterocyclic carbene copper(I) and rare copper(II) complexes (NHCCuCl or NHCCuCl₂) were covalently immobilized directly on the surface of magnetic nanoparticles (MNPs) for the first time. The physicochemical properties were investigated by a broad range of techniques, including SEM and TEM microscopy, and TG analysis. The supported complexes exhibited excellent activity in the Huisgen cycloaddition with in situ generated azides. Unexpectedly, a direct comparison of NHCCuCl and NHCCuCl₂ complexes anchored to the magnetic nanoparticles confirmed the higher activity of the latter for the formation of 1,2,3-triazoles, also under ascorbate-free conditions.

Full text of DOI:10.1016/j.jcat.2018.03.015

Journal of Catalysis 362 (2018) 46–54
Contents lists available at ScienceDirect
Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
NHC-copper complexes immobilized on magnetic nanoparticles:
Synthesis and catalytic activity in the CuAAC reactions
a
b
a,
I. Misztalewska-Turkowicz a, , K.H. Markiewicz , M. Michalak , A.Z. Wilczewska
⇑
⇑
a University of Bialystok, Faculty of Biology and Chemistry, Institute of Chemistry, Ciolkowskiego 1K, 15-245 Bialystok, Poland
b Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of N-heterocyclic carbene copper(I) and rare copper(II) complexes (NHCCuCl or NHCCuCl2) were
covalently immobilized directly on the surface of magnetic nanoparticles (MNPs) for the first time. The
physicochemical properties were investigated by a broad range of techniques, including SEM and TEM
microscopy, and TG analysis. The supported complexes exhibited excellent activity in the Huisgen
cycloaddition with in situ generated azides. Unexpectedly, a direct comparison of NHCCuCl and
NHCCuCl2 complexes anchored to the magnetic nanoparticles confirmed the higher activity of the latter
for the formation of 1,2,3-triazoles, also under ascorbate-free conditions.
Received 4 December 2017
Revised 11 March 2018
Accepted 12 March 2018
Keywords:
N-heterocyclic carbene
Copper complexes
Magnetic nanoparticles
Click chemistry
Ó 2018 Elsevier Inc. All rights reserved.
1. Introduction
order to allow the separation and further reuse of the active cata-
lyst, which can be tedious in some cases. In this respect, the appli-
Since the first isolation and characterization of an N-heterocyclic
carbene (NHC) in 1991 by Arduengo [1] N-heterocyclic carbene
ligands revolutionized the field of modern catalysis. Many challeng-
ing CAC and C-heteroatom bond-forming processes involving these
ligands have been developed so far [2–4], including enantioselec-
tive ones [5]. Although tremendous advances in the field of the
homogenous N-heterocyclic carbene metal complex catalysis have
been made, the development of green, sustainable, and economical
processes constitutes a major challenge in modern organic and
organometallic chemistry, and is of special importance for the
transfer of academic achievements to industrial applications. For
these reasons, homogenous metal catalysis acceptable on labora-
tory scale creates many difficulties in commercial processes, associ-
ated with the environmental pollution, waste issues, atom
efficiency, and catalyst recovery. Bearing in mind these complica-
tions, heterogenization of homogenous catalysts on solid support
seems to be a natural choice which has proved useful in many pro-
cesses to date, allowing for the straightforward recovery of the cat-
alyst. Among many solid supports available, polymers, carbon,
silica or metal oxides are the most commonly used ones for the
anchoring of metal complexes. However, conventional separation
techniques such as centrifugation and filtration have to be used in
cation of magnetic nanoparticles (MNPs) offers a better platform for
recovering the metal complexes by using an external magnetic
field, which dramatically reduces the cost of the process [6–11].
Moreover, MNPs are usually non-toxic, recyclable, and allow the
covalent binding of metal complexes on the quasi-homogenous
nanoparticles surface, which is beneficial for the catalytic activity.
Among N-heterocyclic carbene metal complexes, palladium [12–
24] has garnered a lot of interest lately. Besides nickel [25], iridium
[26], platinum [27], ruthenium [12,28,29], and gold [30–33] com-
plexes supported on MNPs have been marginally reported. To the
best our knowledge, NHC-copper complexes have never been sup-
ported on magnetic nanoparticles so far. There are only some sim-
ple examples of other solid supports such as silica, cellulose, or
nanotubes [34–44]. The excellent reactivity of NHC-copper com-
plexes in many challenging transformations under homogenous
conditions [45,46], e.g. hydroboration of alkenes and alkynes,
hydrothiolation, hydroaminaton or hydroalkoxylation, CAH bond
arylation, and, last but not least, 1,2,3-triazole formation are of high
importance from the point of view of organic chemistry and further
industrial applications. For example, the widely used 1,2,3-triazoles
possess a range of biological activity such as antifungal [47],
antibacterial [48] or antiviral [49] activities, and constitute a pow-
erful linkage between disjoint chemical/biological components
such as polymers, proteins or peptides [50–53]. Despite all these
advantages, copper-catalyzed reactions suffer from several
drawbacks which limit their use in medicinal chemistry as well as
⇑
Corresponding authors.
E-mail addresses: i.misztalewska@uwb.edu.pl (I. Misztalewska-Turkowicz),
agawilcz@uwb.edu.pl (A.Z. Wilczewska).
https://doi.org/10.1016/j.jcat.2018.03.015
0021-9517/Ó 2018 Elsevier Inc. All rights reserved.

I. Misztalewska-Turkowicz et al. / Journal of Catalysis 362 (2018) 46–54
47
material science and engineering [54]. The contamination of
organic compounds with toxic copper residues usually results in
changes of cellular metabolism when used in biological systems
[55]. In contrast, NHC-copper complexes have recently found appli-
cations in medicinal chemistry due to their low cytotoxicity [56–
59]. For these reasons, the search for new efficient methods for
the immobilization of NHC-copper complexes is highly desirable.
From the angle of industrial applications, we anticipated that the
immobilization of stable NHC-copper complexes should deliver a
practical approach towards highly active, easily recoverable and
reusable copper catalysts.
Herein, we present for the first time a simple and efficient
method of immobilizing NHC-copper(I) and NHC-copper(II) com-
plexes directly on the surface of MNPs, and their successful appli-
cation in the Huisgen cycloaddition as reusable catalysts for 1,2,3-
triazole formation under aerobic conditions.
dinium intermediate [16]. The presented sequence contains well-
known reactions which were adjusted to the synthesis on the mag-
netic solid phase. After each step, the modified nanoparticles were
separated from the reaction mixture and then washed several
times with an appropriate solvent (for details, see Supporting
Information). The penultimate step of the synthesis required the
usage of an aniline derivative. The reaction with 1,6-
isopropylaniline (liquid) was carried out at 120 °C neat, whereas
the reaction with 2,6-bis(diphenylmethyl)-4-methylaniline (solid)
was performed in its saturated solution in toluene at reflux.
The preparation of the respective copper complexes was accom-
plished by the synthetic route presented in Scheme 1. First, NHC
ligands were anchored to magnetic nanoparticles consisting of iron
oxides. Magnetic nanoparticles were prepared according to a pro-
cedure published by Massart and subsequently covered by a silane
shell [60]. The synthesis of NHC salts was accomplished following a
general procedure, recently developed by us, through a formami-
dinium intermediate [16]. The presented sequence contains well-
known reactions which were adjusted to the synthesis on the mag-
netic solid phase. After each step, the modified nanoparticles were
separated from the reaction mixture and then washed several
times with an appropriate solvent (for details, see Supporting
Information). The penultimate step of the synthesis required the
usage of an aniline derivative. The reaction with 1,6-
isopropylaniline (liquid) was carried out at 120 °C neat, whereas
the reaction with 2,6-bis(diphenylmethyl)-4-methylaniline (solid)
was performed in its saturated solution in toluene at reflux.
Subsequently, the obtained MNP-supported NHC ligands were
used to prepare the corresponding copper(I) and copper(II) com-
2. Results and discussion
2.1. The preparation of immobilized NHC-copper complexes
The preparation of the respective copper complexes was accom-
plished by the synthetic route presented in Scheme 1. First, NHC
ligands were anchored to magnetic nanoparticles consisting of iron
oxides. Magnetic nanoparticles were prepared according to a pro-
cedure published by Massart and subsequently covered by a silane
shell [60]. The synthesis of NHC salts was accomplished following a
general procedure, recently developed by us, through a formami-
Scheme 1. Direct synthesis of NHC precursors on magnetic nanoparticles; APTMS – (3-Aminopropyl)-trimethoxysilane; DIPEA – Diisopropylethylamine.

48
I. Misztalewska-Turkowicz et al. / Journal of Catalysis 362 (2018) 46–54
plexes (Scheme 1). The synthesis of copper(I) complexes was
accomplished by a procedure developed by Cazin et al. [61] How-
ever, the corresponding copper(I) complexes MNP@NHC (1) and
MNP@NHC (2) appeared to be air- and moisture-sensitive. Bearing
in mind further applications from the green chemistry point of
view, we turned our attention to copper(II) complexes which we
expected to be resistant to the aerobic conditions. Indeed, applica-
tion of the above-mentioned protocol furnished cleanly the corre-
sponding copper(II) complexes MNP@NHC (3) and MNP@NHC (4)
which appeared to be stable after one week of storage in an open
flask. It should be stressed that the synthesis of NHC-copper(II)
complexes has met with limited success so far (vide infra).
The stability of higher oxidation states, namely NHC-copper(II)
is usually enhanced by the presence of a chelating arm attached to
the NHC core in the case of five-membered rings [62–68] or by
applying six-membered congeners [69]. In addition, a synthetic
approach to NHC-copper(II) halide complexes has failed, leading
to haloimidinium salts [69,70]. To the best of our knowledge,
Cazin’s method allowed to obtain the first stable NHC-copper(II)
chloride complexes. The expansion of the scope of this method is
in progress, with promising results.
were carried out at room temperature with the addition of sodium
ascorbate. After 3 h of stirring, only 30% of conversion was
observed, and after 24 h the yields reached only 39% and 32% for
catalyst 3 and 4, respectively (Table 1, entry 7 and 10). For this rea-
son, the reactions temperature was increased to the boiling point
of MeOH, and after 3 h the completion of the reactions was
observed. The model reactions catalyzed by 3 and 4 were con-
ducted with the addition of a reducing agent (sodium ascorbate).
In both cases, moderate to high yields were obtained (56% and
96%, respectively). According to the research by Zhu [73], copper
(II) species can catalyze CuAAC reactions without using a reducing
agent. Therefore, the catalytic activity of 3 and 4 was examined in
sodium ascorbate-free conditions. The product was obtained in
high yields (86% for catalyst 3, and 80% for catalyst 4), confirming
the observation made by Zhu’s group.
Additionally, the influence of catalyst loading (benzyl bromide
to catalyst ratio) on the efficiency of the model reaction was exam-
ined, and the results are presented in Fig. 1. 0.2 mmol of benzyl
bromide to 5 mg of catalyst was found to be the optimal ratio for
completion of the reaction in high yield (e.g. 96% for catalyst 4).
This ratio was used in further activity studies. The difference in
the activity of catalysts immobilized on MNPs (Fig. 1) can be
caused by various effects. Application of a high amount of the cat-
alysts (see column A, Fig. 1) can cause their agglomeration and the
decrease in their activity during the reaction. In contrast, a lower
2.2. Catalytic activity
With NHC-copper complexes in hand, their catalytic activity
and reusability was examined. At the outset of our studies, the
reaction between benzyl bromide, propargyl alcohol (1.5 equiv)
and sodium azide (2.5 equiv) was selected (Table 1). The activity
of the NHC-copper complexes was directly compared to the activ-
ity of CuCl and CuCl2 (Table 1), in order to gauge the beneficial
effect of NHC ligands.
In the case of complexes 1 and 2, THF was used as the solvent
and DIPEA as the base, analogously to the previously studied reac-
tions under inert conditions [71]. After 24 h at 40 °C, the product
was obtained in high 80% and 77% yields (for complex 1 and 2,
respectively, Table 1, entries 2 and 4). It should be mentioned that
copper(I) chloride was not active in the reaction. This observation
clearly confirms that NHC-copper complexes 1 and 2 are active cat-
alysts, and their activity is not caused by CuCl simply adsorbed on
the solid phase. In the case of complexes 3 and 4, MeOH was cho-
sen as the solvent due to the good reactivity of copper(II) catalysts
in polar solvents [72,73]. At first, the reactions catalyzed by 3 and 4
Fig. 1. Catalytic activity of MNP@NHC-Cu(3) and MNP@NHC-Cu(4) towards
propargyl alcohol and benzyl azide generated in situ in click reaction, with different
benzyl bromide to catalyst (mmol/mg) ratios with the addition of sodium
ascorbate: (A) 0.2/10; (B) 0.2/5 and (C) 0.2/2.5.
Table 1
The CuAAC reaction conditions (catalysts were used in 0.2/5 mmol/mg benzyl bromide to catalyst ratio)
.
Entry
Cat.
Solvent
Temp.
Sodium ascorbate
Basea
Time [h]
Isolated yield [%]
1
2
3
4
5
6
7
8
CuClb
1
1
2
THF
THF
MeOH
THF
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
40 °C
40 °C
Reflux
40 °C
Reflux
Reflux
rt
Reflux
Reflux
rt
–
–
–
–
–
+
+
+
–
+
+
–
DIPEA
DIPEA
DIPEA
DIPEA
24
24
3
24
3
3
24
3
0
80
49
77
62
20
39
56
86
32
96
80
2
DIPEA
b
CuCl2
–
–
–
–
–
–
–
3
3
3
4
4
4
9
3
24
3
10
11
12
Reflux
Reflux
3
The model reaction of copper-catalyzed alkyne-azide cycloaddition (CuAAC). Cu(I) catalysts were used without the addition of a reductive agent, but in the presence of a base.
In reactions catalyzed by Cu(II) complexes, sodium ascorbate was added (0.04 mmol). All four catalysts were used in 0.2/5 mmol/mg benzyl bromide to catalyst ratio. Approx.
mol% of the catalysts was 5%, 5%, 3%, and 2% for 1, 2 3 and 4 respectively (calculations based on SEM/EDX measurements, for methodology see Supporting Information).
a
2 equiv of base was used.
1 mol% of catalyst was used.
b

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49
substrate-to-catalyst ratio improves the yields (Fig. 1, column B). It
should be noted that the amount of the catalyst needs to be care-
fully calculated because, as shown in Fig. 1 (column C), the reduc-
tion of the ratio to 0.2/2.5 mmolÁmgÀ1 again decreases the yield.
activity of the four new catalysts was investigated and compared
using a variety of alkynes and benzyl azides. It was observed that
complexes 1 and 2 show low activity in this type of reactions. Even
the addition of sodium ascorbate, for oxidation prevention of the
catalyst, did not raise the yields. The results are presented in
Scheme 2. It was also proven that magnetic NHC-Cu complexes
made from CuCl2 (catalysts 3 and 4) show higher activity than
the catalysts made from CuCl (1 and 2) (Scheme 2).
2.3. The activity of catalysts 1–4 in reactions of various alkynes and
azides
In almost all studied reactions, catalyst 4 showed the best activ-
ity, as well as high stability. It should be noted that 1,2,3-triazole
Since the activity of the catalyst depends not only on its struc-
ture, but also on the reactivity of the starting material, thus, the
Scheme 2. Comparison of the activity of four different catalysts in the CuAAC reaction of various alkynes and azides. Reaction conditions: reactions were performed using 4-
bromo benzyl azide or 4-vinyl benzyl azide as starting materials, see general procedure in experimental section. Catalysts 1, 2, 3 and 4 were used in 0.2/5 mmol/mg benzyl
azide derivative to catalyst ratio, 0.04 mmol of sodium ascorbate was addedÁTHF was used as a solvent in reactions catalyzed by 1 and 2, MeOH for those catalyzed by 3 and 4.
Maximum Turnover Numbers were obtained in the synthesis of 8 and the maximum value was obtained for catalyst 3 – TON = 38, TOF = 12.5/h (for the rest of the results see
Table S1 in Supplementary Information).

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I. Misztalewska-Turkowicz et al. / Journal of Catalysis 362 (2018) 46–54
formation is generally catalyzed by copper(I) salts and correspond-
ing complexes. On the other hand, the more stable copper(II) has
been also applied in the presence of a reductant, usually sodium
ascorbate [54,74,75]. Only recently copper(II)-catalyzed reactions
under reductant-free conditions have been reported [72,73,76,77].
Mechanistic investigations and DFT calculations have proved that
the active copper(I) species is formed as a result of copper(II)-
assisted oxidation of solvents such as MeOH, EtOH or i-PrOH
[73,78,79] or homocoupling of alkynes [80,81]. Beyond many useful
copper(I) and copper(II) complexes, NHC-copper(I) complexes have
been recently applied exhibiting a remarkable activity in CuAAC
reactions [78,79,82–86]. Unfortunately, NHC-copper(II) have never
been applied in this reaction before. To our delight, we present the
first example of an NHCCu(II)-catalyzed Huisgen reaction. As men-
tioned above, NHC-copper(II) complexes showed higher activity in
the CuAAC reaction. However, the exact nature of this behavior
could not be explained without a detailed mechanistic study, due
to the complicated mechanistic scenario of the CuAAC reaction.
Recent theoretical and experimental studies have proved that
dimeric or higher order copper species are involved [81,87–90].
amount. Also, recycling without using a reducing agent was per-
formed (Fig. 2).
It appears that catalysts 3 and 4 have a good activity in metha-
nol both with and without the addition of sodium ascorbate. The
activity of catalysts 3 and 4 decreased after each reuse, indicating
their deactivation during the catalytic processes. Furthermore, the
activity of the reused catalyst with regard to the amount of the cat-
alyst was studied (Fig. 2, columns B, C, and D). It appeared that the
best yields for catalyst 3 (after the second run – 63%, after the third
run – 46%) and for catalyst 4 (72% and 46%) were obtained when
20 mg (0.2/10) of the catalyst was used (Fig. 2, column B). It was
probably caused by the presence of the catalytic centres which
did not participate in the reaction during the first run. Therefore,
they were not deactivated and could be active in the next run.
The high yields in the first run were observed even in the absence
of sodium ascorbate (Fig. 2, column A, 86% and 80% for catalysts 3
and 4, respectively). In the second and the third run, the activity of
catalysts 3 and 4 was higher when sodium ascorbate was present
(Fig. 2, column B).
These results show that the catalyst is deactivated during the
reaction cycle. The mechanism of the deactivation needs to be fur-
ther investigated in order to develop more active catalysts.
2.4. The recycling
The magnetic solid phase allows quick and easy separation of
the immobilized catalysts. Due to the highest activity of complexes
3 and 4, only the recycling of these two catalysts was investigated.
After completion of the model reactions, the catalysts were sepa-
rated from the reaction mixtures, and then washed once with
water and three times with MeOH. After purification, the solvent
was evaporated and the catalyst was reused. Fig. 2 presents the
model reaction yields after each reuse in a relation to the catalyst
3. Characterization
3.1. Copper content measurements
The copper mass content was investigated by SEM/EDX (Fig. 3).
The results show that catalyst 4 contains more copper than catalyst
3 (9 and 6 %mass, respectively). This can be assigned to stronger
complexing properties of NHC precursor 2a. The copper content
in catalysts 1 and 2 was also investigated. Surprisingly, catalysts
1 and 2 presented higher copper ion mass content (17% for both
catalysts) than catalysts 3 and 4. This fact does not correspond
with the lower activity of complexes 1 and 2. Furthermore, the
copper content after each reuse was measured and the results
are presented in Fig. 3. The graph clearly shows that copper con-
tent in catalysts 3 and 4 decreases after each reuse. The differences
are slight but they significantly influence the activity of the cata-
lysts. After the first run yields drop down by half (Fig. 2, column
C). This decrease of the activity cannot be explained only by the
leakage of copper (the drop of the yield is not directly proportional
to the copper content decrease). Deactivation of the catalyst poi-
soned by reaction by-products is an alternative explanation. Fur-
ther experiments were performed without the use of any
additional reducing agent (i.e. sodium ascorbate). Results show a
similar decrease of the activity of the tested catalysts in the second
and the third reuse.
The Cu leakage was investigated by AAS spectroscopy. Gener-
ally, after the separation of the catalyst, the reaction mixture was
washed by water. The aqueous layer was then analyzed by Atomic
Absorption Spectroscopy.
The leakage of copper from catalysts 1 (65.34 mg/ml) and 2
(256.45 mg/ml) is much higher than from 3 (7.94 mg/ml) and 4
(2.22 mg/ml), indicating lower stability of copper(I) complexes in
comparison to their copper(II) analogues.
In some cases, the activity of an immobilized catalyst can be
influenced by the engagement of a catalytically active free metal,
which can be present in the reaction mixture due to leakage [91].
In such cases, the yield is proportional to the metal ion content
in the reaction mixture after the completion of the process. In
our research no such tendency for copper ion leakage is observed.
Furthermore, the yields are not directly influenced by the free
metal ion content (high leakages of copper ions from catalysts 1
and 2 do not cause high yields).
Fig. 2. Catalytic activity of MNP@NHC (3) (up) and MNP@NHC (4) (bottom) towards
propargyl alcohol and benzyl azide generated in situ click reaction, with different
benzyl bromide to catalyst (mmol/mg) ratios: (A) 0.2/10 without sodium ascorbate;
(B), (C) and (D) - 0.2/10, 0.2/5 and 0.2/2.5, respectively, with the addition of sodium
ascorbate.

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51
Supporting Information. In the IR spectrum of 2a one can find char-
acteristic peaks which represent CAH aromatic stretch (3040 cmÀ1),
CAH aliphatic stretch (2934 cmÀ1), and vibrations of CAH present in
the imidazoline ring (1697 cmÀ1) which intensity decreased after
complexation with copper(II) (catalyst 4). This tendency appears
also in the IR spectrum of catalyst 3 (Supporting Information). In
the case of catalysts 1, 2, 3, and 4, after each reuse, no significant
changes in the IR spectra were observed (Supporting Information).
The ATR-IR spectra of all synthesized catalysts before reactions
as well as after reuse were collected and presented in Fig. 4 and in
the Supporting Information. In the IR spectrum of 2a one can find
characteristic peaks which represent CAH aromatic stretch (3040
cmÀ1), CAH aliphatic stretch (2934 cmÀ1), and vibrations of CAH
present in the imidazoline ring (1697 cmÀ1) which intensity
decreased after complexation with copper(II) (catalyst 4). This ten-
dency appears also in the IR spectrum of catalyst 3 (Supporting
Information). In the case of catalysts 1, 2, 3, and 4, after each reuse,
no significant changes in the IR spectra were observed (Supporting
Information).
3.3. TGA analyses
Thermogravimetric studies were carried out in order to investi-
gate the thermal properties of the obtained magnetic hybrids.
Fig. 5 shows TG (5A) and DTG (5B) curves of MNP@NH2, two imi-
dazolinium salts: 1a and 2a; four catalysts: 1 and 2 obtained from
copper(I) and 3 and 4 obtained from copper(II). The TG curve refers
to the temperature-dependent mass change in percent, whereas
the DTG curve refers to the rate of mass change. The TG curve of
the starting material (MNP@NH2) shows the total weight loss equal
to 10%. The increase of the total weight loss to around 21% is
observed for particles 1a and 2a containing imidazolinium salts.
This weight loss is related to the decomposition of the aminosilox-
ane shell, as well as organic imidazolinium groups which are pre-
sent on the MNP surface. After the formation of copper(I) and
copper(II) complexes, the total weight loss in all four samples is
higher (25% for 1 and 3, 31% and 24% for 2 and 4, respectively).
TG and DTG curves of the presented nanohybrids (Fig. 5A and B)
show three stages of weight loss at temperature ranges of 150–
240 °C, 250–370 °C, and 640–830 °C.
Fig. 3. The Cu %mass content in catalysts 3 and 4 before and after each reuse (SEM/
EDX investigations, signals were collected from the surface of the probe), an
example of the EDX spectrum of catalyst 3 (middle) and SEM pictures (bottom) of
catalyst 4 before (A) and after the first use (B).
3.2. IR spectra
The first two are most likely related to the decomposition of the
imidazolinium part, whereas the third one, with the maximum at
755 °C, is attributed to the degradation of the siloxane shell. In
The ATR-IR spectra of all synthesized catalysts before reactions as
well as after reuse were collected and presented in Fig. 4 and in the
Fig. 4. ATR-IR spectra of the catalyst 4 and the NHC precursor 2a.

52
I. Misztalewska-Turkowicz et al. / Journal of Catalysis 362 (2018) 46–54
Fig. 5. TG (A) and DTG (B) curves of: aminosiloxane-coated nanoparticles (MNP@NH2), imidazolinium salts: 1a and 2a, and their complexes with Cu (1–4).
the DTG curves it can be observed that the catalysts containing
copper(I) ions are less stable in comparison to those obtained from
copper(II) salt (faster decomposition of 1 and 2). The first step of
degradation starts faster in the case of catalysts 1 and 2, the max-
ima of the degradation rate are observed at 202 °C and 210 °C,
respectively.
reuse was performed. No significant changes in weight loss were
noticed (Figs. S5–S8 in Supporting Information).
4. Experimental section
4.1. Materials and methods
In the thermograms of samples 3 and 4, the rate of mass change
is different. In these cases, maxima in DTG curves are harder to dis-
tinguish. The first two degradation stages merge into one broad
peak (150–390 °C). The differences in the thermograms of nanohy-
brids indicate diverse chemical structure of the coating surround-
ing the MNPs. Additionally, TG analysis of complex 4 after first
reuse was performed. No significant changes in weight loss were
noticed (Figs. S5–S8 in Supporting Information).
In the thermograms of samples 3 and 4, the rate of mass change
is different. In these cases, maxima in DTG curves are harder to dis-
tinguish. The first two degradation stages merge into one broad
peak (150–390 °C). The differences in the thermograms of nanohy-
brids indicate diverse chemical structure of the coating surround-
ing the MNPs. Additionally, TG analysis of complex 4 after first
All reagents were purchased from Aldrich Chemical Company
and used as received. MeOH and THF were purchased from Avantor
Performance Materials Poland S.A. 3-Propargyl-penta-2,4-dione
[71], 3,3-bis-propargyl-penta-2,4-dione [92], 4-vinylbenzyl azide
and 4-bromobenzyl azide were synthesized according to a litera-
ture procedure.
The formation of magnetic nanoparticles, particle size and mor-
phology were confirmed by transmission electron microscopy
(TEM) (Tecnai G2 X-TWIN). Samples for TEM were prepared on
holey carbon copper grids. Energy-dispersive X-ray spectroscopy
(EDX – detector OctanePro) analyses were collected from samples
imaged by SEM (Inspect S50). Surface modifications were con-
firmed by FT-IR (Nicolet 6700). Thermogravimetric analysis (TGA)

I. Misztalewska-Turkowicz et al. / Journal of Catalysis 362 (2018) 46–54
53
was performed on a Mettler Toledo Star TGA/DSC unit. Differential
scanning calorimetry (DSC) was performed on a Mettler Toledo
Star DSC system. Argon was used as a purge gas (10 mLÁminÀ1).
1H NMR and 13C NMR spectra were recorded on a Bruker Avance
II spectrometer (400 MHz and 100 MHz respectively). Melting
points were measured by Mettler Toledo MP 70 Melting point Sys-
tem. Elemental Analyses were performed on VarioMicroCube (Ele-
mentar) and HRMS spectra on Accurate Mass Q-TOF LC/MS 6530
Spectrometer.
netic nanoparticles could be easily separated by external magnetic
field and reused in CuAAC reactions. In addition, the copper con-
tent was measured by Atomic Absorption Spectroscopy after each
cycle in the reaction mixture after separation of the magnetic
nanoparticles. Low levels of toxic copper residues in the case of
copper(II) complexes were detected, enabling further applications
for the synthesis of biologically relevant molecules, which are a
work in progress.
Acknowledgements
4.2. Preparation of catalysts
The project was financially supported by Polish National
Science Centre grant no. 2016/21/N/ST5/01316. The author (I.
Misztalewska-Turkowicz) is a beneficent of ETIUDA doctoral schol-
arship program financed by Polish National Science Centre, grant
no. 2017/24/T/ST5/00214. The authors are grateful to Dr. Leszek
Siergiejczyk and Dr. Jolanta Magnuszewska for NMR analyses, Dr.
Preparation of MNP@NHC copper complexes. Nanoparticles
(100 mg) with NHC-modified shell were dispersed in 40 mL of ace-
tone (30 min in ultrasonic bath) and then K2CO3 (50 mg) was
added. After 30 min of stirring, 100 mg of CuCl (or CuCl2) was
added. The mixture was stirred for 24 h at rt. Next, nanoparticles
were magnetically separated and washed once with water and
twice with MeOH, and then dried overnight at 50 °C. Formation
of the product was confirmed by FT-IR spectroscopy. The copper
mass content was investigated by EDX detector conjugated with
SEM microscope.
´
Aneta M. Tomkiel for HRMS analyses and Dr. Barbara Lesniewska
for AAS measurements. Analyses were performed in Centre of Syn-
thesis and Analysis BioNanoTechno of the University of Bialystok.
The equipment in the Centre of Synthesis and Analysis BioNano-
Techno of the University of Bialystok was funded by EU, as a part
of the Operational Program Development of Eastern Poland 2007-
2013, project: POPW.01.03.00-20-034/09-00 and POPW.01.03.00-
004/11.
4.3. CuAAC reactions
The general procedure for CuAAC reactions. The catalyst was
sonically dispersed in 4 mL of solvent. Then starting materials,
alkyne (1.5 mmol), benzyl bromide (1 mmol) and sodium azide
(2.5 mmol) were added. In the synthesis of products 6–12, previ-
ously obtained (due to known procedure [71]) appropriate azide
(1 mmol), in place of alkyl halide and sodium azide, was used. In
synthesis of 6–12 with 3 and 4 as catalyst, sodium ascorbate was
added (0.04 mmol). Mixtures were stirred for the indicated time
at given temperatures. After completion of the reaction, the cata-
lyst was separated by external magnetic field, washed several
times with THF or MeOH and dried at 50 °C. The isolated solution
was evaporated, then DCM was added and the solution was
washed once with water. The organic layer was dried over anhy-
drous Na2SO4 and the solvent was evaporated. The crude product
was purified by column chromatography (eluent–hexane, hex-
ane:AcOEt 8:2 and 7:3). The best results for copper(II) complexes
were accomplished when MeOH was used as a solvent and mixture
was stirred for 3 h at reflux. For Cu(I) complexes, the best yields
were obtained in THF at 50 °C.
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