NNN-pincer-copper complex immobilized on magnetic nanoparticles as a powerful hybrid catalyst for aerobic oxidative coupling and cycloaddition reactions in water

Article abstract of DOI:10.1016/j.molcata.2016.11.007

A simple and reliable methodology is described for preparing the first heterogeneous NNN-pincer-copper hybrid catalyst with a high control over surface composition. The strategy relies on the covalently bonding of 2-aminopyridine to cyanuric chloride-functionalized magnetic nanoparticles followed by complexation with CuI. These claims are confirmed by different characterization methods such as SEM, TEM, FT-IR, TGA, ICP, XRD, and elemental analysis. The finely engineered supported catalyst is employed in the aerobic oxidative coupling of terminal alkynes and click reaction using only 0.38 and 0.04 mol% catalyst, respectively. All reactions perform under solvent-free condition or green solvent H₂O. Also, the catalyst is readily recovered and reused for up to 8 and 6 subsequent runs in click and homocoupling reactions without significant loss of activity or leaching.

Full text of DOI:10.1016/j.molcata.2016.11.007

Accepted Manuscript
Title: NNN-Pincer-Copper Complex Immobilized on Magnetic
Nanoparticles as a Powerful Hybrid Catalyst for Aerobic
Oxidative Coupling and Cycloaddition Reactions in Water
Author: Nasrin Zohreh Mahboobeh Jahani
PII:
S1381-1169(16)30481-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.11.007
MOLCAA 10104
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
12-9-2016
28-10-2016
5-11-2016
Please cite this article as: Nasrin Zohreh, Mahboobeh Jahani, NNN-Pincer-Copper
Complex Immobilized on Magnetic Nanoparticles as a Powerful Hybrid Catalyst
for Aerobic Oxidative Coupling and Cycloaddition Reactions in Water, Journal of
Molecular Catalysis A: Chemical http://dx.doi.org/10.1016/j.molcata.2016.11.007
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

NNN-Pincer-Copper Complex Immobilized on Magnetic Nanoparticles as a Powerful
Hybrid Catalyst for Aerobic Oxidative Coupling and Cycloaddition Reactions in Water
Nasrin Zohreh,* Mahboobeh Jahani
a
Department of Chemistry, Faculty of Science, University of Qom, P. O. Box: 37185-359, Qom, Iran
1

Graphical abstract
Highlights:


Easy preparation of magnetic NNN-pincer copper catalyst as heterogeneous catalyst
-1
High loading 0.38 mmol.g of Cu(I) on heterogeneous support because of powerful pincer
ligand


Successful application of the catalyst to variety of substrates for homocoupling and click
reactions in water using 0.38 and 0.04 mol% catalyst loading
Recoverable and reusable up to 8 times without leaching and reduced activity
2

Abstract
A simple and reliable methodology is described for preparing the first heterogeneous NNN-
pincer-copper hybrid catalyst with a high control over surface composition. The strategy relies
on the covalently bonding of 2-aminopyridine to cyanuric chloride-functionalized magnetic
nanoparticles followed by complexation with CuI. These claims are confirmed by different
characterization methods such as SEM, TEM, FT-IR, TGA, ICP, XRD, and elemental analysis.
The finely engineered supported catalyst is employed in the aerobic oxidative coupling of
terminal alkynes and click reaction using only 0.38 and 0.04 mol% catalyst, respectively. All
reactions perform under solvent-free condition or green solvent H O. Also, the catalyst is readily
2
recovered and reused for up to 8 and 6 subsequent runs in click and homocoupling reactions
without significant loss of activity or leaching.
Keywords
NNN-Pincer catalyst, copper catalyst, heterogeneous catalyst, cyanuric chloride, terminal alkyne
homocoupling, click reaction
3

Introduction
Pincer ligands are extensively used in many diverse areas of chemistry primarily as a means to
direct and modulate the properties of a metal center to which it is bonded (Scheme 1).1-4 Prof.
5
Shaw, together with Dr. C.J. Moulton, were the first ones to report examples of pincer
compounds. However, the term “pincer” was first coined by van Koten in 1989 because of its
similarity to a wretch or spanner.6
An important characteristic of the pincer platforms is the fact that its three ligating sites are well
organized by the backbone of the ligand which leads to the possible formation of five- or six-
membered chelate rings in which the central metal-heteroatom bond is in common (Scheme 1).
Up to now, a multifaceted combination of donor sets has been explored that includes
combinations of, e.g., neutral, anionic, Lewis basic and acidic, arene, heteroaromatic, and
carbine donors.7-11 Moreover, in some cases, the pincer platform itself acts as a non-innocent
ligand (NIL) or provides, with its pincer-metal manifold, a system that is suitable for executing
metal-ligand cooperative (MLC) behavior in, e.g., catalytic processes.12,
13
At present,
considering the wide range of metals, the number of possibilities seems to have no limit; most
excitingly, many of these novel pincer ligand/metal combinations lead to the discovery of new
catalysts for various bond formation processes in organic synthesis,14-16 new polymerization
1
7
,18 and the activation of bonds that so far were
technologies, the chemical conversion of CO
considered as primarily unreactive.19, 20
2
Among numerous metal-EZE’ pincer catalysts, catalysts with pincer ligands of the type NNN
symmetric or unsymmetric, neutral or anionic) have been more considered because of the
(
powerful chelating property of most metals.21-25 In addition, designing a wide range of chiral
4

moiety bonded to each nitrogen atom makes metal-NNN-pincer complexes very applicable in
asymmetric synthesis.25-27
After the introduction of heterogenization concept in the realm of catalysis science, thousand
types of homogeneous catalysts have been immobilized on solid supports and applied in
chemical reactions or industrial processes.28 Recently, having considered the advantages of
heterogeneous catalyst on the one hand, and unique and effective properties of pincer catalyst on
the other hand, heterogenization of pincer catalysts has attracted much attention that could be
interesting for modifying many chemical processes. The use of MOF,29, 30 mesoporous silica,31, 32
3
3
34, 35
36
37
resins, MNP,
CNT, and SiO
2
as solid supports for immobilization of pincer catalysts,
are some examples. According to literature, there are a few reports on heterogeneous NNN-
pincer catalyst.34, 38
Given these considerations and continuing our previous works,39-41 we have investigated the
immobilization of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride, TCT)-derived copper pincer
complex onto the large surface area of highly dispersed magnetic nanoparticles. The catalytic
activity of the resulting magnetic NNN-pincer copper catalyst is studied in both of terminal
alkyne homocoupling and click reactions. To the best of our knowledge, there is no report on
heterogeneous NNN-pincer copper catalyst.
Experimental
Materials and methods
Ferric chloride hexahydrate (FeCl
3
.6H
2
O), ferrous chloride tetrahydrate (FeCl
2
.4H O), ammonia
2
(25%), tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTS), and 2,4,6-
trichloro-1,3,5-triazine (TCT) were obtained from Sigma-Aldrich without further purification.
5

N,N-Diisopropylethylamine (DIEA) was purchased from Merck and distilled before use.
Na WO . 4H O and 2-aminopyridine were purchased from Merck. Various commonly used
2
4
2
organic solvents (Merck) were dried with several different drying agents.
FT-IR spectra of samples were taken using an ABB Bomen MB-100 FT-IR spectrometer.
Thermogravimetric analysis (TGA) was acquired under a nitrogen atmosphere with a TGA Q 50
thermogravimetric analyzer. Transmission electron microscopy (TEM) images were taken with a
Philips CM30 electron microscope. Magnetization of catalyst was measured by vibrating sample
magnetometer (Meghnatis Daghigh Kavir Co., Kashan, Iran). The X-ray diffraction (XRD)
pattern was recorded on Rigaku D/Max-3c X-ray diffractometer. X-Ray fluorescence (XRF) was
taken using Phillips 1404 XRF instrument. Atomic absorption spectrometry (AAS, Shimadzu
6
80 A) or inductively coupled plasma-optical emission spectrometry (ICP-AES, Perkin-Elmer
DV 4300) were used for elemental measurements. CHN Elemental analyses were performed
using a Heraeus Elemental Analyzer CHN (Elementar-Analysesysteme). Conversions and yields
were measured using a 6890 gas chromatograph (GC) with an Agilent Technologies HP-
Innowax.
Preparation of amine functionalized magnetic nanoparticles (MNP@APTS)
Silica coated Fe
3
4
O nanoparticles (MNPs) were synthesized based on our previously reported
4
2
method. Prepared MNPs (1.0 g) were ultrasonically dispersed in 50 mL ethanol/water (4/1)
mixture. Then, APTS (5 mL) was added and the mixture was stirred at 80 °C for 24 h. The APTS
coated magnetic nanoparticles (MNP@APTS, 1.0 g) were magnetically separated and washed
several times with methanol (4 × 30 mL) and dried under vacuum at 50 °C.
6

Synthesis of APTS-functionalized TCT (compound 1)
To a 50 mL flask containing TCT (1 mmol), DIPEA (1 mmol), and super dry THF (3 mL) in ice
bath (-5 C), APTS (1 mmol) was added dropwise. The reactants were vigorously stirred for 2 h.
Then, the solvent was evaporated under vacuum at 50 °C. The crude product 1 was analyzed
1
using H NMR spectrum.
Preparation
of
pincer
ligand
TCT/Amp-functionalized
magnetic
nanoparticles
(MNP@TCT/Amp)
In a round bottom flask, MNP@APTS (1.0 g) was ultrasonically dispersed in dry THF (15 mL)
and the flask was put in an ice bath. Then, TCT (5 mmol, 1.0 g) and DIEA (7 mmol, 1.2 mL)
were added. The mixture was stirred for 2 h under N atmosphere. The product (MNP@TCT)
2
was magnetically separated and washed with THF (5×10 mL) and dried under vacuum at room
temperature. In a three necked round bottom flask, MNP@TCT (0.98 g) was dispersed in dry
CH CN (25 mL) and 2-aminopyridine (4.5 mmol, 0.42 gr) was added to flask. The flask was
3
equipped with a condenser and the mixture was refluxed for 12 h to produce MNP@TCT/Amp
ligand. The heterogeneous ligand was separated using a magnet and washed with methanol
(5×10 mL) and dried under vacuum at 50 ˚C (0.95 g).
Preparation of NNN-pincer type nanomagnetic copper catalyst (MNP@NNN-Pincer/Cu)
For complexation of MNP@TCT/Amp ligand with CuI, MNP@TCT/Amp (0.95 g) was
dispersed in CH CN (10 mL) and CuI (2 mmol, 0.38 g) was added to the mixture. The mixture
3
was stirred for 12 h at room temperature. The final catalyst (MNP@ NNN-Pincer/Cu) was
7

magnetically separated and washed with CH
3
CN (2×10 mL), water (3×10 mL) and methanol
(2×10 mL) and dried under vacuum at 50 ˚C (0.95 g).
Synthesis of 2,4,6-tri(aminopyridinyl)-1,3,5-triazine ligand (ligand A)
To a 50 mL flask containing TCT (5 mmol), DIPEA (25 mmol), and MeOH (8 mL) in ice bath (-
5
2
C), 2-aminopyridine (15 mmol) was added dropwise. The reactants were vigorously stirred for
h. Then, the temperature of the reaction was raised to 70 C and the reaction refluxed for
additional 12 h. Then, solvent was evaporated and the product A was washed with EtOH, CHCl
and Et O and dried under vacuum.
3
,
2
General procedure for aerobic oxidative homocoupling reaction of terminal alkyne
Terminal alkyne (1 mmol), morpholine (1.2 mmol), and catalyst MNP@NNN-Pincer/Cu were
loaded in a 25 mL round bottom flask. The reactants were vigorously stirred at room temperature
(or 60 C) for a defined time (the amount of catalyst loading and temperature were selected
according to Table 3). Completion of the reaction was monitored by TLC until the initial alkyne
consumed and no further product (comparing with the related known product by TLC) was
formed. After completion of the reaction, methanol was added and the catalyst was magnetically
separated, washed with methanol (3×10 mL) and dried for another run. The product mixtures
were analyzed by gas chromatography (GC). The isolated yields of products were determined
after purification of product using column chromatography (hexane/ethyl acetate as eluent).
8

General procedure for azide/alkyne cycloaddition reaction (click reaction)
Terminal alkyne (1 mmol), halide (1 mmol), NaN , H O (2 mL), and catalyst MNP@ NNN-
Pincer/Cu were loaded in a 25 mL round bottom flask. The reactants were vigorously stirred at
0 or 80 C for the defined time (the amount of azide and catalyst loading were selected
3
2
5
according to Tables 5, 6). Completion of the reaction was monitored by TLC until the initial
alkyl halide and alkyne were consumed and no further product was formed (comparing with the
related known product). Consuming of alkyl halide is not the only evidence for the completion of
the reaction because the consumption of alkyl halide may be due to the formation of alkyl azide.
Having completed the reaction, methanol (2 mL) was added and the catalyst was magnetically
separated, washed with methanol (3×10 mL) and dried for another run. The product mixtures
analyzed by gas chromatography (GC). In order to obtain isolated yield of products after
completion of the reaction, the catalyst was magnetically separated and the reaction mixture was
extracted with ethyl acetate. Solvent was evaporated and the product was recrystallized from
ethyl acetate or purified using column chromatography (hexane/ethyl acetate as eluent).
Reusability test of catalyst MNP@NNN-pincer/Cu in click reaction
Phenylacetylene (5 mmol), alkyl halide (5 mmol), NaN
3
(6.5 mmol), H O (2 mL), and catalyst
2
MNP@ NNN-Pincer/Cu (0.04 mol%, 5 mg) were loaded in a test tube. The reactants were
vigorously stirred at 50 C for a defined time. After completion of the reaction, catalyst was
carefully collected at the bottom of test tube using an external magnet and reaction mixture
decanted in another pot. The catalyst was washed with MeOH (10 mL) and utilized directly in
the next run without separation from test tube.
9

Result and discussion
Synthesis and characterization of catalyst
Continuing our previous works on magnetic catalysts, here, we report a robust, simple and
general methodology to easily get access to magnetic NNN-pincer copper catalyst. Initially, we
supposed that 1,3,5-triazinetrichloride (cyanuric chloride, TCT) could serve as a core with three
reactive sites that can bind to heterogeneous supports through substitution of one chloride and
functionalize further through substitution of the other clorides.43-45 We further took advantage of
2
-aminopyridine as a powerful ligand46, 47 while bonding to TCT. Accordingly, we designed the
magnetic NNN-pincer copper catalyst MNP@NNN-pincer/Cu easily via a few steps as visualized
in Scheme 2. First, magnetic Fe
3
4
O nanoparticles were synthesized by a co-precipitation
method48, 49 in the basic condition and covered by a silica layer to protect Fe
3
4
O from oxidative
and acidic mediums. Then the surface of MNP was modified with APTS to provide amine group
for further functionalization. Afterward, MNP@APTS was conducted to react with TCT via
substitution of one Cl with amine group in the basic condition. Due to the high reactivity of TCT,
this step was performed in ice bath using dry solvent to avoid further substitution of TCT. To
ensure successful substitution of one Cl, the reaction of TCT with APTS was also carried out
under similar condition according to Scheme 3 and the structure of product 1 was confirmed by
NMR spectrum (Scheme 3). On the other hand, compound 1 was immobilized on the surface of
MNP to confirm successful preparation of MNP@TCT (Scheme 1S and Fig. 2S). In the next
step, MNP@TCT was subjected to react with 2-aminopyridine. This is the key step and both
chlorides must be replaced with 2-aminopyridine to obtain pincer platform MNP@TCT/Amp.
Therefore the reaction was performed under reflux condition for complete substitution. The final
1
0

catalyst MNP@NNN-pincer/Cu was achieved via complexation of CuI with pincer platform in
acetonitrile as solvent at room temperature.
To verify the successful incorporation of the organic components and the maintenance of the Si-
C bonds during the catalyst preparation, FT-IR spectrum was used in each step. Fig. 1-(I) shows
the FT-IR spectra of MNP (a), MNP@APTS (b), MNP@TCT (c), MNP@TCT/Amp (d) and
-1
MNP@NNN-pincer/Cu (e). Two absorbance bands at 630 and 1090 cm in the Fig. 1a-e(I) show
stretching frequency of Fe-O and Si-O bonds of MNP that confirmed successful preparation of
-1
silica coated Fe
3
O without changing during all modifications. Region through 1200-1900 cm is
4
magnified to clarify the effect of all functionalization steps (Fig. 1-II). Functionalization of MNP
with APTS (Fig. 1b-II), was confirmed by the appearance of characteristic bands at 1410 and
-1
1
466 cm which is related to stretching vibrations of C-N bonds. The FT-IR spectrum of
MNP@TCT (Fig. 1c-II) showed strong absorption bands at 1610, 1560, and 1509 cm-1
corresponding to C=N of TCT. Stretching absorption of unreacted C-Cl is completely obscured
by the bending vibration of the Si-O-Si bond. In the IR spectrum of MNP@TCT/Amp (Fig. 1d-
II), comparing to MNP@TCT (Fig.1c-II), the C=N absorption bands shifted to 1656, 1619, and
-1
1
542 cm . This is strong evidence for the presence of several C=N bonds which is the result of
the replacement of both of Cl by 2-aminopyridine. Coordination of CuI to the pincer ligand has
no effect on the IR spectrum of MNP@NNN-pincer/Cu (Fig. 1e-II comparing to its precursor).
Thermogravimetric analysis (TGA) was performed on bare MNP, MNP@APTS, MNP@TCT,
and MNP@TCT/Amp (Fig. 2I, a-d) to investigate the organic content of each intermediate and
final catalyst. The weight losses through 100-150 ˚C were attributed to the loss of absorbed water
1
1

molecules on the surface of all samples. The TGA curve of MNP@APTS (Fig. 2Ib) showed a
weight loss at 260 ˚C, which is attributed to the degradation of amino propyl groups. From this
weight loss (3.3 wt%), the loading amount of APTS on the surface of MNP was calculated to be
-
1
0
2
.56 mmol.g . Increasing the weight loss in the TGA curve of MNP@TCT to 10.6 wt% (Fig.
Ic) showed successful incorporation of TCT to amine-functionalized MNP. The Loading
-1
amount was also calculated to be 0.48 mmol.g for APTS/TCT segment on MNP. The weight
loss increased again when MNP@TCT reacted with 2-aminopyridine (13.7 wt%) (Fig. 2I-d).
From this weight loss, the loading of NNN-pincer ligand on the surface of MNP was calculated
-1
to be 0.42 mmol.g . After complexation of CuI by pincer ligand, no significant change was
observed in the TGA carve of MNP@NNN-pincer/Cu because of inorganic identity of CuI. From
Fig.2I-d, it was found that magnetic pincer ligand is thermally stable up to 270 C. The DTG
analysis of the ligand also showed three peaks at 100, 260 and 340 C which were attributed to
loss of water molecules and organic compartments (Fig. 2II).
The XRD pattern of MNP@NNN-pincer/Cu is completely matched with the XRD pattern of the
Fe
indicated that all modifications did not change the crystalline phase of Fe
peak at 2θ=20-30 is attributed to the amorphous silica phase in the catalyst structure. The
3
O
4
standard sample (JCPDS file No. 19-0629), confirming the presence of Fe
3
4
O which
3
O
4
(Fig. 3a). The broad
electron ring diffraction pattern (RDP) of the catalyst showed the crystallinity of Fe
3
O
4
nanoparticles support (Fig. 3b).
Energy-dispersive X-ray analysis (EDX) of MNP@NNN-pincer/Cu indicated the presence of C,
O, N, Si, Fe, and impotantly Cu elements in the catalyst structure (Fig. 4). From this analysis, it
1
2

was found that the amount of Cl is very low in comparison with other element indicated
displacment of Cl with aminopyridine in high percentage (third step of catalyst preparation). This
analysis also confirms the successful immobilization of the Cu(I) on the surface of MNP by a
pincer ligand.
Magnetization property of catalyst was examined using VSM analysis. VSM curves of Fe
Fe @SiO (MNP) and catalyst MNP@NNN-pincer/Cu are shown in Fig. 5a-c, respectively.
Reasonable decrease in magnetization intensity of Fe
SiO layer on Fe
3
4
O ,
3
O
4
2
3
O
4
@SiO
2
compared to Fe
3
4
O is due to
-1
2
3
O
4
. Magnetic saturation (MS) values 54.5 emu g of catalyst showed 15.2 emu
-1
g diminution compared to MNP which is another claim for functionalization of MNP with
organic components. However, the magnetization of catalyst is still enough to respond to an
external magnetic field (Fig. 5).
The morphology, particle size, and crystallinity of Fe
nanocatalyst were determined by high resolution TEM. Fig. 6a shows the Fe
which have an average size of 7 nm. The TEM image of the MNP@NNN-pincer/Cu (Fig. 6b)
shows gray layer of SiO accompanied with organic components around Fe particles with an
average particle diameter of 17 nm.
3
O
4
support and MNP@NNN-pincer/Cu
3
O
4
dark particles
2
3
O
4
The content of Cu(I) in MNP@NNN-pincer/Cu was examined by atomic absorption spectroscopy
AAS) using standard samples. It was found that the loading amount of Cu(I) ion in the catalyst
(
-
1
structure is 0.38 mmol.g . The XRF analysis of MNP@ NNN-pincer/Cu obtained 2.27 and 4.69
-1
wt% for Cu and I which are corresponded to 0.36 and 0.37 mmol.g consisting the result of AAS
1
3

for loading of Cu(I). Also, the XRF analysis showed that no significant amount of Cl (0.15 wt%)
remained in MNP@ NNN-pincer/Cu. These results are in agreement with EDS analysis.
Table 1 shows the elemental analysis of the catalyst MNP@TCT-Amp/Cu. CHN analysis
showed that after the reaction of TCT with MNP@APTS, the weight percent of carbon and
nitrogen increased, demonstrating the successful attachment of TCT to MNP@APTS. From N
content of MNP@APTS (0.76 wt%), the loading of APTS was calculated to be 0.54 mmol.g-1
which is along with TGA data. The presence of 3.45 wt% of Cl obtained from the XRF analysis
of MNP@TCT proved that only one chloride of TCT was reacted in this step. This also gave the
-1
loading 0.50 mmol.g for MNP@TCT. The weight percent of N in MNP@TCT/Amp rose again
after the reaction of MNP@TCT with 2-aminopyridine (Entry 3). In addition, the weight percent
of Cl dramatically decreased, to 0.15 wt% confirming the complete substitution of two Cl with 2-
aminopyridine. On complexation of CuI to pincer ligand, no significant change was observed in
the %CHN of catalyst compared to its ligand.
Reactions and scopes
Elegant recent studies on metal-catalyzed oxidative coupling reactions involving terminal
alkynes,50-60 provided useful starting points for our investigations on the efficiency of
MNP@NNN-pincer/Cu. Thus, oxidative homocoupling reaction of phenylacetylene was chosen
as a model system for optimization studies (Table 2). Initially, the effect of solvent was screened
using 1.5 mol% MNP@NNN-pincer/Cu in the presence of Et N as base (entries 1-5). The
3
reaction exhibited the high activity and 85% yield of product 3a under solvent free condition.
Performing the reaction in MeCN obtained high yield of product while the leaching of Cu(I) was
also high. Evaluation of base effect on the reaction under solvent free condition (entries 6-10)
1
4

revealed that morpholine is a good base for production of more than 99% yield of product. Since
the catalyst has many nitrogen atoms on its surface, we guessed that the catalyst could be also
served as a basic catalyst and therefore the reaction could be preceded without any external base.
In effect, this claim was true and the reaction obtained relatively good yield of product in the
presence of MNP@NNN-pincer/Cu without any base, but the catalyst activity decreased in
second and third successive runs (entry 9). In the final step, the amount of catalyst loading was
explored. It was found that decreasing the catalyst loading to 0.38 mol%, did not effect on the
yield of product 3a (entries 13-17). However, using less than 0.38 mol% loading of catalyst,
even with increasing the temperature, the yield of 3a was diminished (entries 19-21). Thus,
condition of entry 17 was chosen as optimized condition. In order to comparison of catalytic
6
1
activity of the MNP@NNN-pincer/Cu to that of the free complex in solution, ligand A was
prepared and applied in the reaction. The results showed that the use of 0.38 mol% homogeneous
catalytic system A/CuI gave comparable results with heterogeneous system (entry 18).
Apparently, immobilization of pincer catalyst onto the solid support allows easy separation of
catalyst from the reaction mixture and importantly several reuse of heterogeneous systems
without loss of activity; the factors are not obtained using the homogeneous catalytic systems.
Terminal alkyne scope and product diversity were examined using various types of terminal
alkynes under optimized conditions (Table 3). As shown in Table 3, aromatic alkynes gave 92-
9
9% yield of 1,3-diynes (3a-e) at room temperature using 0.38 mol% of MNP@NNN-pincer/Cu.
1
5

Aliphatic alkynes also smoothly underwent the reaction to produce 83-92% of 3f-j, however
temperature and catalyst loading must be increased to 60 C and 0.76 mol%, due to the less
reactivity of aliphatic terminal alkynes. In the next experiments, alkyl propiolates were also
subjected to the homocoupling reaction under optimized condition. Unfortunately, any attempt
failed to produce homocoupling product 3k. In the presence of morpholine as base, enaminone 4
formed. Examination of tertiary bases resulted in mixture of products (Scheme 3).
Catalytic efficacy of the MNP@NNN-pincer/Cu was also examined in the copper catalyzed
heterogeneous three-component cycloaddition reaction of alkyl halide, azide, and alkyne, Cu-
AAC, known as click reaction.62-71 The model reaction of benzyl bromide, sodium azide, and
phenylacetylene was chosen for optimization of the reaction conditions (Table 4). Different
parameters such as solvent, catalyst loading, temperature, and sodium azide amount were tested.
As it’s evident from Table 4 (entries 1-7), solvent has a major effect on the reaction time and
product yield. Under solvent-free condition, reaction did not produce acceptable yield after 12 h.
In aprotic solvent, even polar ones, low yield of product was obtained via a long reaction time.
Instead, the reaction effectively proceeded in protic solvent, especially H
attributed to high solubility of NaN or ionic intermediates in polar protic solvents. In addition,
heterogeneous catalyst MNP@NNN-pincer/Cu is highly dispersible in H O. Water is also a green
and cheap solvent. Thus, H O was chosen as solvent for further optimization. Optimization of
catalyst loading was then examined starting from catalyst-free conditions. Mixture of 1,4- and
,5-diphenyl-1,2,3-triazoles (3:1, 75%) were obtained after 24 h under reflux condition (entry 8),
2
O. This effect could be
3
2
2
1
showing the effect of copper catalyst on selectivity and affectivity of the click reaction. From
Table 4, entries 9-15, it was found that catalyst loading, time, and temperature simultaneously
1
6

affect on the yield of 5a. Increasing the time and temperature to 2 h and 50 C has compensated
diminishing of catalyst loading from 0.38 to 0.04 mol% with almost equal yields (Compare entry
6
with 13, Table 4). It was also observed that increasing the amount of NaN
of product up to 97%, while increasing the temperature to 80 C results in a mixture of 1,5- and
,4-isomers (1:2.7, 81%, entry 15). Consecutively, the most suitable result was obtained for the
reaction in the presence of 0.04 mol% MNP@NNN-pincer/Cu and 1.3 eq. NaN in H O at 50 °C
Table 4, entry 14). Application of homogeneous copper catalytic system A/CuI was also
3
enhanced the yield
1
3
2
(
examined and its activity was compared with MNP@NNN-pincer/Cu (entries 16-17). However,
the homogeneous catalytic system was as effective as heterogeneous; it suffers from
unrecyclability and unreusability.
After finding the optimal reaction conditions, the generality and scope of the click cycloaddition
with MNP@NNN-pincer/Cu were further explored with diverse alkyl halides and terminal
alkynes. With phenylacetylene as substrate (Table 5), 81-98% of product yields were acquired
using a variety of benzyl halides (5a-f), allyl halide (5g), and alkyl halides (5h-n). However,
benzyl halides with electron donating group exhibited better reaction conditions in time and
yield. It is notable that to perform the reaction with non-benzylic halides, NaN
were increased to make substitution of azide and halide easier in H O (3k-n).
3
and temperature
2
Catalyst MNP@NNN-Pincer/Cu also showed excellent activity in cycloaddition of aliphatic
alkynes (Table 6) with sodium azide and various halides. Because of less reactivity of aliphatic
alkynes compared to phenylacetylene, the click reaction with aliphatic proceeded with 0.19
1
7

mol% catalyst and 80 C (Table 6). Again, in the cases of aliphatic halides (Table 6, 6f-g, k), the
amount of NaN must be increased to obtain good yields of product.
3
Catalytic efficacy of MNP@NNN-pincer/Cu was also evaluated using electron-deficient terminal
alkynes, which are normally difficult substrates for copper catalyzed click reaction. Good yields
of 1-benzyl-1,2,3-triazole-4-alkylcarboxylate 7a-b were obtained with 0.04 mol% Cu-catalyst at
7
2-76
5
0 C via 10-12 h (Scheme 4). This product is very interesting from synthetic point of view.
Click cycloaddition of amino acid-functionalized alkynes 8a-b with benzyl bromide and NaN
3
was also tested in the presence of pincer catalyst. As depicted in Scheme 5, good yields of amino
acid-functionalized 1,2,3-triazoles 9a-b were obtained under the optimized condition.
To investigate the highest activity of catalyst obtainable for the copper-catalyzed click reaction,
another experiment was developed considering Scheme 6. The large scale (10 mmol) reaction of
sodium azide, phenylacetylene and benzyl bromide was performed in the presence of 1 mg
MNP@PDMA-Cu (0.004 mol%). Surprisingly, excellent yield of 96% was obtained for 5a after
2
0 hours (Scheme 5). However, the time for completion of the reaction is relatively high, but
-1
calculation of the TON = 25263 and TOF = 1263 h shows that the catalyst is truly active and
effective. To the best of our knowledge, these values of TOF and TOF for a un-polymeric
heterogeneous catalyst have been rarely reported in the click reaction.77
Ensuring recyclability of the heterogeneous catalysts while maintaining the catalytic efficiency is
a prominent concern in the field of catalysis. Thus, the recyclability of MNP@NNN-pincer/Cu
1
8

was explored and evaluated in the Cu-AAC reaction of benzyl bromide, NaN , and
3
phenylacetylene under the optimized condition (Fig. 7a). The recyclability and reusability of the
MNP@NNN-pincer/Cu were verified in eight consecutive cycles; with slightly decrease in the
th
th
reactivity observed in the 7 and 8 cycles. All reactions were carried out in a test tube without
separation of catalyst. After each run, the catalyst was carefully collected at the bottom of the test
tube by applying an external magnetic field, reaction solution was decanted, and catalyst was
washed with MeOH, and utilized directly in the next cycle. Reusability of the catalyst also
examined in the aerobic oxidative homocoupling reaction of phenylacetylene (Fig. 1s). The
catalyst was recovered and reused up to 6 successive runs without significant loss of activity.
In order to gain insight into the heterogeneous nature of catalyst, the hot leaching test was carried
out. The model reaction was performed under optimized conditions and catalyst was quickly
collected from the hot solution after 1 h. According to GC analysis of the reaction mixture at
different times, as indicated in Fig. 7b, after ignition of the MNP@NNN-pincer/Cu no further
reaction took place without catalyst. After 3 h from removal of catalyst, the reaction mixture was
also analyzed using ICP to determine the content of probable leached Cu(I) in the solution. As
expected, because of high power of NNN-pincer ligand, no significant amount of Cu(I) was
found in the solution demonstrating that MNP@NNN-pincer/Cu exhibits a typical heterogeneous
catalyst nature. These results are also along with recyclability test.
1
9

Conclusion
In summary, MNP have been easily functionalized with a NNN-pincer ligand from TCT/Amp
through simple and straightforward convergent protocols. The MNP@TCT-Amp was used as a
powerful platform for the construction of nanomagnetic NNN-pincer catalyst in combination
with Cu(I) that have been immobilized in situ. The characterization of the nanocatalyst proved
-1
that it was uniformly decorated with mean diameters of 17 nm, exhibiting 0.38 mmol.g loading
of Cu(I). Investigations on the catalytic activity of MNP@NNN-pincer/Cu toward aerobic
oxidative homocoupling of terminal alkyne and click reactions showed that catalyst was the best
performer to catalyze various types of substrates. In both homocoupling and click processes,
routine substrate scope have been carried out with just 0.38 and 0.04 mol% loading, respectively,
but click reaction with only 0.004 mol% of catalyst was also possible through larger reaction
time, allowing to obtain TON of up to 25,000. This value is higher than those reported with Cu(I)
heterogeneous systems, indicating a kind of synergism among the components of the support.
Importantly, the nanocatalyst resulted to be recyclable at least 8 times in the click reaction
without remarkable loss of activity or significant leaching on Cu(I) according to AAS analysis.
Table 7 demonstrates activity and reusability of the present catalyst in comparison with the most
recent homogeneous and heterogeneous Cu catalysts in homocoupling reaction. In Table 8,
activity and reusability of MNP@NNN-pincer/Cu have been compared with recently reported
homogeneous pincer and heterogeneous copper catalysts in the click reaction.
2
0

References
1
2
3
4
5
.
.
.
.
.
M. Albrecht and G. van Koten, Angew. Chem. Int. Ed. Engl., 2001, 40, 3750-3781.
M. Asay and D. Morales-Morales, J. Chem. Soc., Dalton Trans., 2015, 44, 17432-17447.
H. Li, B. Zheng and K.-W. Huang, Coord. Chem. Rev., 2015, 293, 116-138.
K. J. Szabó, J. Mol. Catal. A: Chem., 2010, 324, 56-63.
C. J. Moulton and B. L. Shaw, J. Chem. Soc., Dalton Trans., 1976, DOI:
1
0.1039/DT9760001020, 1020-1024.
6
7
8
.
.
.
G. van Koten, Pure Appl. Chem., 1989, 61, 1681-1694.
S. Murugesan and K. Kirchner, J. Chem. Soc., Dalton Trans., 2016, 45, 416-439.
H. A. Younus, W. Su, N. Ahmad, S. Chen and F. Verpoort, Adv. Syn. Catal., 2015, 357,
2
83-330.
9
1
.
D. Yang, Y. Tang, H. Song and B. Wang, Organometallics, 2016, 35, 1392-1398.
H. Zhang, Y.-Q. Li, P. Wang, Y. Lu, X.-L. Zhao and Y. Liu, J. Mol. Catal. A: Chem.,
0.
2
016, 411, 337-343.
X. Lefèvre, G. Durieux, S. Lesturgez and D. Zargarian, J. Mol. Catal. A: Chem., 2011,
35, 1-7.
1
1.
3
1
1
1
2.
3.
4.
C. Gunanathan and D. Milstein, Chem. Rev., 2014, 114, 12024-12087.
S. Schneider, J. Meiners and B. Askevold, Eur. J. Inorg. Chem., 2012, 2012, 412-429.
S. Werkmeister, J. Neumann, K. Junge and M. Beller, Chem. Eur. J., 2015, 21, 12226-
1
2250.
1
5.
G. E. Tyson, K. Tokmic, C. S. Oian, D. Rabinovich, H. U. Valle, T. K. Hollis, J. T.
Kelly, K. A. Cuellar, L. E. McNamara and N. I. Hammer, J. Chem. Soc., Dalton Trans.,
2
015, 44, 14475-14482.
2
1

1
1
6.
7.
V. Arumugam, W. Kaminsky and D. Nallasamy, Green Chem., 2016, 18, 3295-3301.
D. E. Bellone, J. Bours, E. H. Menke and F. R. Fischer, J. Am. Chem. Soc., 2015, 137,
8
50-856.
1
1
8.
9.
G. A. Filonenko, R. van Putten, E. N. Schulpen, E. J. Hensen and E. A. Pidko,
ChemCatChem, 2014, 6, 1526-1530.
S. Murugesan, B. Stöger, E. Pittenauer, G. Allmaier, L. F. Veiros and K. Kirchner,
Angew. Chem., 2016, 128, 3097-3100.
2
2
2
2
0.
1.
2.
3.
T. Simler, P. Braunstein and A. A. Danopoulos, Chem. Commun., 2016, 52, 2717-2720.
P. M. P. Garcia, P. Ren, R. Scopelliti and X. Hu, ACS Catal., 2015, 5, 1164-1171.
S. Y. Hong, J. Kwak and S. Chang, Chem. Commun., 2016, 52, 3159-3162.
J. Shi, B. Hu, D. Gong, S. Shang, G. Hou and D. Chen, J. Chem. Soc., Dalton Trans.,
2
016, 45, 4828-4834.
2
2
4.
5.
M. J. Moure, R. SanMartin and E. Domínguez, Adv. Syn. Catal., 2014, 356, 2070-2080.
K. Herasymchuk, J. Huynh, A. J. Lough, L. Roces Fernández and R. A. Gossage,
Synthesis, 2016, 48, 2121-2129.
2
2
6.
7.
B. K. Langlotz, H. Wadepohl and L. H. Gade, Angew. Chem., 2008, 120, 4748-4752.
Q. H. Deng, C. Rettenmeier, H. Wadepohl and L. H. Gade, Chem. Eur. J., 2014, 20, 93-
9
7.
2
2
8.
9.
M. B. Gawande, P. S. Branco and R. S. Varma, Chem. Soc. Rev., 2013, 42, 3371-3393.
S. A. Burgess, A. Kassie, S. A. Baranowski, K. J. Fritzsching, K. Schmidt-Rohr, C. M.
Brown and C. R. Wade, J. Am. Chem. Soc., 2016, 138, 1780-1783.
3
0.
A. M. Rasero‐Almansa, A. Corma, M. Iglesias and F. Sánchez, ChemCatChem, 2013, 5,
3
092-3100.
2
2

3
1.
M. Rimoldi, D. Fodor, J. van Bokhoven and A. Mezzetti, Catal. Sci. Technol., 2015, 5,
575-4586.
4
3
3
2.
3.
C. del Pozo, A. Corma, M. Iglesias and F. Sanchez, Green Chem., 2011, 13, 2471-2481.
B. Tamami, M. M. Nezhad, S. Ghasemi and F. Farjadian, J. Organomet. Chem., 2013,
7
43, 10-16.
3
3
4.
5.
S. Sobhani, Z. Vahidi, Z. Zeraatkar and S. Khodadadi, RSC. Adv., 2015, 5, 36552-36559.
M. Ghotbinejad, A. R. Khosropour, I. Mohammadpoor-Baltork, M. Moghadam, S.
Tangestaninejad and V. Mirkhani, RSC. Adv., 2014, 4, 8590-8596.
3
3
6.
7.
P. Kang, S. Zhang, T. J. Meyer and M. Brookhart, Angew. Chem. Int. Ed. Engl., 2014, 53,
8
709-8713.
M. Ghotbinejad, A. R. Khosropour, I. Mohammadpoor-Baltork, M. Moghadam, S.
Tangestaninejad and V. Mirkhani, J. Mol. Catal. A: Chem., 2014, 385, 78-84.
3
3
8.
9.
Y. Zhang, X. Sun, H. Zhang and J. Zhao, Appl. Organomet. Chem., 2016, 30, 645-652.
N. Zohreh, S. H. Hosseini, A. Pourjavadi and C. Bennett, Appl. Organomet. Chem., 2016,
3
0, 73-80.
A. Pourjavadi, S. H. Hosseini, N. Zohreh and C. Bennett, RSC. Adv., 2014, 4, 46418-
6426.
N. Zohreh, S. H. Hosseini, A. Pourjavadi and C. Bennett, RSC. Adv., 2014, 4, 50047-
0055.
A. Pourjavadi, N. Safaie, S. H. Hosseini and C. Bennett, New J. Chem., 2016, 40, 1729-
736.
H. Veisi, D. Kordestani, S. Hemmati, A. R. Faraji and H. Veisi, Tetrahedron Lett., 2014,
5, 5311-5314.
4
4
4
4
0.
1.
2.
3.
4
5
1
5
2
3

4
4.
M. Nasr-Esfahani, I. Mohammadpoor-Baltork, A. R. Khosropour, M. Moghadam, V.
Mirkhani, S. Tangestaninejad and H. Amiri Rudbari, The Journal of organic chemistry,
2
014, 79, 1437-1443.
4
4
4
5.
6.
7.
N. Gupta, T. Roy, D. Ghosh, S. H. R. Abdi, R. I. Kureshy, N.-u. H. Khan and H. C. Bajaj,
RSC. Adv., 2015, 5, 17843-17850.
D. Gong, W. Liu, T. Chen, Z.-R. Chen and K.-W. Huang, J. Mol. Catal. A: Chem., 2014,
3
95, 100-107.
Y. Gartia, A. Biswas, M. Stadler, U. B. Nasini and A. Ghosh, J. Mol. Catal. A: Chem.,
012, 363–364, 322-327.
2
4
4
8.
9.
N. Zohreh, S. H. Hosseini and A. Pourjavadi, J. Ind. Eng. Chem., 2016, 39, 203-209.
A. Pourjavadi, S. H. Hosseini, F. Matloubi Moghaddam, B. Koushki Foroushani and C.
Bennett, Green Chem., 2013, 15, 2913-2919.
5
5
0.
1.
N. Barot, S. B. Patel and H. Kaur, J. Mol. Catal. A: Chem., 2016, 423, 77-84.
L. Al-Hmoud, S. Bali, S. Mahamulkar, J. Culligan and C. W. Jones, J. Mol. Catal. A:
Chem., 2014, 395, 514-522.
5
2.
B. Maaten, J. Moussa, C. Desmarets, P. Gredin, P. Beaunier, T. Kanger, K. Tõnsuaadu,
D. Villemin and M. Gruselle, J. Mol. Catal. A: Chem., 2014, 393, 112-116.
G. Cheng, H. Zhang and X. Cui, RSC. Adv., 2014, 4, 1849-1852.
5
5
3.
4.
Y. Liu, N. Gu, P. Liu, J. Xie, X. Ma, Y. Liu and B. Dai, Appl. Organomet. Chem., 2015,
2
9, 736-738.
5
5.
F.-W. Li, Q.-L. Suo, H.-L. Hong, N. Zhu, Y.-Q. Wang, L.-L. Guo and L.-M. Han, J.
Supercrit. Fluids, 2014, 92, 70-74.
2
4

5
6.
S. Biswas, K. Mullick, S.-Y. Chen, D. A. Kriz, M. Shakil, C.-H. Kuo, A. M. Angeles-
Boza, A. R. Rossi and S. L. Suib, ACS Catal., 2016, 6, 5069-5080.
5
5
5
7.
8.
9.
S. Yan, S. Pan, T. Osako and Y. Uozumi, Synlett, 2016, 27, 1232-1236.
X.-L. Shi, Q. Hu, F. Wang, W. Zhang and P. Duan, J. Catal., 2016, 337, 233-239.
M. Nasr-Esfahani, I. Mohammadpoor-Baltork, A. R. Khosropour, M. Moghadam, V.
Mirkhani, S. Tangestaninejad, V. Agabekov and H. A. Rudbari, RSC. Adv., 2014, 4,
1
4291-14296.
6
6
0.
1.
S. Li, X. Chen, J. Chen and H. Gong, Bull. Chem. Soc. Jpn., 2016, 89, 794-797.
S. Mandal, G. Bérubé, É. Asselin, I. Mohammad, V. J. Richardson, A. Gupta, S. K.
Pramanik, A. L. Williams and S. K. Mandal, Bioorg. Med. Chem. Lett., 2007, 17, 4955-
4
960.
6
6
6
6
2.
3.
4.
5.
B. Gröll, P. Schaaf, M. D. Mihovilovic and M. Schnürch, J. Mol. Catal. A: Chem., DOI:
http://dx.doi.org/10.1016/j.molcata.2016.07.013.
A. Akbari, N. Arsalani, M. Amini and E. Jabbari, J. Mol. Catal. A: Chem., 2016, 414, 47-
5
4.
D. P. Singh, B. K. Allam, K. N. Singh and V. P. Singh, J. Mol. Catal. A: Chem., 2015,
98, 158-163.
3
I. Jlalia, F. Gallier, N. Brodie-Linder, J. Uziel, J. Augé and N. Lubin-Germain, J. Mol.
Catal. A: Chem., 2014, 393, 56-61.
6
6
6.
7.
S. Gu, D. Xu and W. Chen, J. Chem. Soc., Dalton Trans., 2011, 40, 1576-1583.
S. Y. de Boer, Y. Gloaguen, M. Lutz and J. I. van der Vlugt, Inorg. Chim. Acta, 2012,
3
80, 336-342.
6
8.
T. Cheisson and A. Auffrant, J. Chem. Soc., Dalton Trans., 2014, 43, 13399-13409.
2
5

6
7
7
7
9.
0.
1.
2.
C. Wang, D. Wang, S. Yu, T. Cornilleau, J. Ruiz, L. Salmon and D. Astruc, ACS Catal.,
016, 6, 5424-5431.
X. Liu, N. Novoa, C. Manzur, D. Carrillo and J.-R. Hamon, New J. Chem., 2016, 40,
308-3313.
A. Pourjavadi, S. H. Hosseini, F. Matloubi Moghaddam and S. E. Ayati, RSC. Adv.,
015, 5, 29609-29617.
2
3
2
H. Duan, D. Arora, Y. Li, H. Setiadi, D. Xu, H.-Y. Lim and W. Wang, Bioorg. Med.
Chem., 2016, 24, 2621-2630.
7
7
3.
4.
J. Zeidler, D. Baraniak and T. Ostrowski, Eur. J. Med. Chem., 2015, 97, 409-418.
H. Cheng, J. Wan, M.-I. Lin, Y. Liu, X. Lu, J. Liu, Y. Xu, J. Chen, Z. Tu and Y.-S. E.
Cheng, J. Med. Chem., 2012, 55, 2144-2153.
7
7
5.
6.
C. W. Tornøe, S. J. Sanderson, J. C. Mottram, G. H. Coombs and M. Meldal, J. Comb.
Chem., 2004, 6, 312-324.
F. d. C. da Silva, M. C. B. V. de Souza, I. I. P. Frugulhetti, H. C. Castro, S. L. d. O.
Souza, T. M. L. de Souza, D. Q. Rodrigues, A. M. T. Souza, P. A. Abreu, F. Passamani,
C. R. Rodrigues and V. F. Ferreira, Eur. J. Med. Chem., 2009, 44, 373-383.
Y. M. A. Yamada, S. M. Sarkar and Y. Uozumi, J. Am. Chem. Soc., 2012, 134, 9285-
7
7.
9
290.
2
6

Fig. 1. FT-IR spectra of MNP (a), MNP@APTS (b), MNP@TCT (c), MNP@TCT/Amp (d) and
-1
MNP@NNN-pincer/Cu (e); (I): normal range 400-4000 cm , (II): magnified region 1200-1900
-
1
cm .
2
7

Fig. 2. (I) TGA curves of bare MNP (a), MNP@APTS (b), MNP@TCT (c), MNP@TCT/Amp
d); (II) DTG curve of MNP@TCT/Amp.
(
2
8

Fig. 3. XRD (a) and RDP (b) patterns of the MNP@NNN-pincer/Cu.
2
9