Magnetic copper-iron nanoparticles as simple heterogeneous catalysts for the azide-alkyne click reaction in water

Article abstract of DOI:10.1039/c2gc16421c

The development of a novel bimetallic copper-iron nanoparticle synthesis provides a recoverable heterogeneous catalyst for the azide-alkyne "click" reaction in water. The nanoparticles catalyze the production of a diverse range of triazoles, while separat

Full text of DOI:10.1039/c2gc16421c

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Green Chemistry
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COMMUNICATION
Magnetic copper–iron nanoparticles as simple heterogeneous catalysts for the
azide–alkyne click reaction in water†‡
Reuben Hudson, Chao-Jun Li* and Audrey Moores*
Received 9th November 2011, Accepted 25th January 2012
DOI: 10.1039/c2gc16421c
The development of a novel bimetallic copper–iron nanopar-
ticle synthesis provides a recoverable heterogeneous catalyst
for the azide–alkyne “click” reaction in water. The nanopar-
ticles catalyze the production of a diverse range of triazoles,
Scheme 1
while separation and reuse proved to be easy.
The 2002 development of Cu(I)-catalysed azide–alkyne cyclo-
addition (AAC) continues to garner much interest today.1,2 This
Table 1 Performance of a series of Cu and Fe based catalysts for the
AACa
prototypical “click” reaction offers chemists a highly efficient
means for connecting two potentially complex building blocks
under mild conditions with high tolerance to other functional
groups.3,4 This reaction has thus been extensively applied to the
synthesis of macromolecules5,6 and the functionalization of bio-
molecules.7 The catalysed AAC reaction holds several advan-
tages over the thermal version8 including regioselectivity,
increased reactivity of unactivated alkynes, and high yields even
at low concentrations in aqueous media.9
Most AAC protocols call for a homogeneous Cu(I) source –
either by direct addition of a Cu(I) salt, or in situ reduction of Cu
(II) by sodium ascorbate.2,9,10 In an effort to find more reusable
catalysts, Cu(I) AAC catalysts have been immobilized onto poly-
mers11,12 or zeolite.13 Interestingly, Cu(0) on charcoal,14 Cu(0)
nanoparticles,15–18 or microwave irradiated Cu turnings,19,20 as
well as CuO nanostructures,21 have also successfully demon-
strated activity for this reaction.
Magnetically recoverable nanoparticles (NPs) represent an
easy and environmentally benign means for catalyst recovery,22
providing catalytic properties intermediate between homo-
geneous23 and bulk heterogeneous materials.24–26 Many schemes
exist for using magnetically recoverable catalysts: anchoring
homogeneous metal complexes27–29 or organocatalysts30 to a
magnetic core, plating a catalytically active metal,31,32 or, more
simply, direct use of bare Fe(0)33–35 or iron oxide NPs.36,37
Among the strategies recently developed to produce novel mag-
netic particles, zero-valent Fe NPs (FeNPs) have been used as
precursors to seed, reduce and support another metal. By this
method, Pd NPs were deposited onto FeNPs and the resulting
Entry
Catalyst (loading)
Yield
1
2
3
4
5
6
7
8
None
<5%
<5%
96%b
99%
93%
81%
<5%
<5%c
CuFe2O4 NP (5 mol%)
CuFe2O4 NP + sodium ascorbate (5 mol%)b
CuI (5 mol%)
Cu@FeNP (5 mol%)
Cu@FeNP (1 mol%)
FeNP (5 mol%)
Cu@FeNP – supernatantc
a Reaction conditions: 1 mmol benzyl azide, 1.2 mmol phenylacetylene,
10 mL H2O, rt, 12 h. b Dissolution of nanoparticles observed.
c Supernatant obtained by subjecting particles to catalytic conditions,
removing them, and using supernatant as solvent for reaction.
hybrid NPs were proven to be active and recyclable catalysts for
Suzuki coupling.38
Herein, we present the synthesis of an active and magnetically
recyclable catalyst for the AAC in water (Scheme 1). This cata-
lyst is very simple and produced from exposure to Cu(II) salts of
reducing FeNPs seeds in a water–methanol mixture. No ligand
or extra reducer is needed.
Our initial attempts to perform AAC using magnetically reco-
verable NPs focused on the use of Cu ferrite (CuFe2O4). In
2010, Park and coworkers demonstrated that hollow structures of
CuO were active catalysts for AAC.21 However, CuFe2O4 NPs
proved inactive for this transformation (Table 1). In Cu ferrite,
Cu is present as Cu(II) in the crystal lattice, while most AAC cat-
alysts are based on Cu(I).4,10,39 Addition of sodium ascorbate to
CuFe2O4 NPs afforded the expected in situ reduction of Cu(II)
into Cu(I),39 and enabled catalysis in yields of 96%. This
activity, however, was accompanied by the complete dissolution
of the CuFe2O4 NPs – no solid material could be recovered.
These observations suggest that catalysis proceeds through a
homogeneous mechanism. To alleviate this limitation, we
needed to develop nanocatalysts featuring heterogenized Cu(I)
Center for Green Chemistry and Catalysis, Department of Chemistry,
McGill University, 801 Sherbrooke St. West, Montreal, QC, H3A 0B8,
Canada. E-mail: audrey.moores@mcgill.ca, cj.li@mcgill.ca; Fax: +1
514 398 3797
†Electronic supplementary information (ESI) available: XPS analysis.
See DOI: 10.1039/c2gc16421c
‡Dedicated to Christian Bruneau, on the occasion of his 60th birthday.
622 | Green Chem., 2012, 14, 622–624
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Table 2 Cu@Fe NP catalyzed azide–alkyne cycloadditiona
Entry
1
Product
Yield
93%
Entry
6
Product
Yield
78%
2
89%
7
84%
3
4
5
90%
88%
91%
8
9
67%
49%
a Reaction conditions: 1 mmol azide, 1.2 mmol alkyne, 5 mol% Cu@Fe NP, 10 mL H2O, rt, 12 h.
Table 3 Recycling of Cu@FeNPs catalyst for AACa
species. To this end, we explored other kinds of non-functiona-
lized, bare magnetic NPs. Following a procedure developed with
Pd,38 we plated FeNPs by galvanic reduction of CuSO4. FeNPs
are obtained by NaBH4 reduction of FeSO4,40 before being
exposed to CuSO4. The X-ray photoelectron spectroscopy
(XPS†) of the resultant nanoparticles indicated the presence of
Cu(I) and (II). These results are consistent with the reduction of
Cu(II) to Cu(I) by the core of FeNPs.41 We did not observe evi-
dence of Cu(0) by XPS.
Run
Glovebox yield (%)
Benchtop yield (%)
1
2
3
4
5
93
93
92
93
91
93
90
76
54
<5
a Reaction conditions: 1 mmol benzyl azide, 1.2 mmol phenylacetylene,
5 mol% catalyst 10 mL H2O, rt, 12 h.
These bi-metallic nanoparticles catalyzed AAC in good
yields, in most cases (Table 2). Primary and secondary aliphatic
as well as the traditional benzylic azides coupled with aliphatic
and aromatic alkynes to generate a range of triazoles. Generally,
the more electron-rich azides reacted with the highest efficiency
[benzyl (entries 1, 2 and 3) > 2° alkyl (entries 4, 5 and 6) > 1°
alkyl (entries 7, 8 and 9)]. Of the alkynes, phenylacetylene
reacted best (entries 1, 4, and 7) while simple alkyl substituted
alkynes reacted slowest (entries 3, 6 and 9). The system also
proved robust toward alcohol-substituted alkynes (entries 2, 5
and 8).
Distinguishing between true heterogeneous and homogeneous
catalysis – performed by a leached soluble species – is always
critical when using nanoparticulate catalysts.42 For this reason,
the reaction supernatant (in which no soluble copper could be
detected by an ICP-OES with a detection limit of 0.001 ppm)
was tested for catalytic activity – after the nanoparticles had been
magnetically removed and the solution filtered through Celite.
The lack of either soluble copper in the reaction mixture or
supernatant catalytic activity coupled with the reusability of the
catalyst strongly suggest a heterogeneous mechanism. In further
support of a heterogeneous mechanism, the nanoparticles could
be recovered and reused under stringent inert conditions up to
five times with no appreciable decrease in yield (Table 3).
However, when the reaction was performed on the bench top in
the presence of air, the yield quickly dropped in subsequent recy-
cling runs, most probably caused by an oxidation of Cu(I) into
Cu(II).
Conclusions
Herein, we present a bi-metallic copper–iron nanoparticle system
for catalysis of the Huigsen 1,3-dipolar, azide–alkyne cyclo-
addition in water. Interestingly, in this system, the iron(0) core
serves a three-fold role. First, it provides a means for magnetic
recoverability. Second, it serves as a source of electrons to
reduce Cu(II) into Cu(I). Third, it acts as a support for Cu(I)
species to prevent their liberation as soluble ions, enabling a het-
erogeneous mechanism. The synthesis of the catalyst proceeds
without the use of reducer, or ligand, making this reaction very
atom economical. This work represents the merger of two ubi-
quitous green chemistry themes: magnetic nanoparticles as
easily recoverable catalysts and aqueous “click chemistry”.
Ongoing studies in our group focus on further characterizing the
catalytically active Cu@FeNPs. As this manuscript was in the
publication process, another study from the group of Varma was
released, describing another highly active and magnetically reco-
verable nanocatalyst of the AAC reaction.43
Experimental section
All reactants were purchased from Sigma Aldrich and used as
received. Organic azides were synthesized from the
This journal is © The Royal Society of Chemistry 2012
Green Chem., 2012, 14, 622–624 | 623

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corresponding bromides via a previously reported procedure.20
All reactions were carried out in an oxygen-free glovebox,
except where noted, and all solvents were de-gassed for
20 minutes prior to use. FeNPs were synthesized following a
procedure similar to what had been reported before.40 In MeOH–
H2O (60 mL/140 mL), a solution of FeSO4 (4 g in 200 mL H2O)
was reduced with aqueous NaBH4 (0.8 g in 20 mL H2O added
with a syringe pump at 3 mL min−1) at pH 6 (achieved by
addition of 5 mL of 5 N NaOH). Then a CuSO4 solution (8 mg
of CuSO4 in 1 mL of H2O at a rate of 1 mL min−1) was added
dropwise to the sonicating solution of FeNPs (28 mg in 9 mL).
The resulting slurry was left to sonicate for 30 minutes after
addition of CuSO4. These nanoparticles were then washed three
times with 10 mL water before being used for catalysis. A
typical reaction consisted of resuspension of the nanoparticles in
10 mL water, followed by addition of azide (1 mmol) and alkyne
(1.2 mmol), and a magnetic stir bar. The reaction vessel was
then capped and left to stir for 12 hours. After each reaction
cycle, the nanoparticles stuck to the stir bar when stirring
stopped, the solution decanted off, the nanoparticles washed 3
times with acetone, then three times with water with no further
purification before reuse. The reaction supernatant and washings
were collected together, the solvent evaporated, and the solid
product weighed and characterized by NMR spectroscopy on a
Mercury 300. The XPS analysis was performed at Ecole Poly-
technique Montreal on a VG ESCLAB 3 MKII with a power of
206 W. A surface of 2 × 3 mm was analysed at a depth of
50–100 Å. ICP-OES was performed on a Trace Scan with a
baffled cyclonic spray chamber and mini cross flow nebulizer.
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Acknowledgements
We thank the Natural Science and Engineering Research Council
of Canada (NSERC), the Canada Foundation for Innovation
(CFI), the Canada Research Chairs (CRC), the Fonds de
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