Copper on iron: Catalyst and scavenger for azide-alkyne cycloaddition

Article abstract of DOI:10.1055/s-0032-1317697

Dipolar cycloaddition of terminal alkynes and azides catalyzed by the Cu/Fe bimetallic system is reported. In the presence of a readily accessible nanosized copper source, the cycloaddition reaction can be easily achieved at ambient temperature with high

Full text of DOI:10.1055/s-0032-1317697

3722▌
FEATURE ARTICLE
feature article
Copper on Iron: Catalyst and Scavenger for Azide–Alkyne Cycloaddition
Copper on Iron Catalyzed CuAAC
Szabolcs Kovács,a Katalin Zih-Perényi,a Ádám Révész,b Zoltán Novák*a
a
Institute of Chemistry, Eötvös Loránd University, Pázmány Péter stny. 1/a, Budapest 1117, Hungary
b
Department of Materials Physics, Institute of Physics, Eötvös Loránd University, Pázmány Péter stny. 1/a, Budapest 1117, Hungary
Fax +36(1)3722909; E-mail: novakz@elte.hu
Received: 14.09.2012; Accepted after revision: 31.10.2012
convenient and elegant procedure was developed by
Abstract: Dipolar cycloaddition of terminal alkynes and azides cat-
Veinot et al.14 Any metal ions with an appropriate reduc-
alyzed by the Cu/Fe bimetallic system is reported. In the presence
tion potential can be removed from organic products using
Fe@FexOy. For example, copper contamination of the tri-
of a readily accessible nanosized copper source, the cycloaddition
reaction can be easily achieved at ambient temperature with high ef-
ficiency. The product obtained from the reaction catalyzed by azole product that originated from a copper(II) sul-
Cu/Fe contains significantly lower copper contaminants compared
to various active homogeneous copper complexes. Iron not only be-
haves as support for copper, but acts as a redox scavenger, and re-
these excellent findings and our previous work, in which
duces the copper contamination of the organic product.
fate/ascorbate reaction could be reduced from 2026 ppm
to 4.6 ppm with the aid of this iron sequester. Inspired by
we developed and successfully applied a copper-on-iron
(Cu/Fe) catalyst for the thiolation of aromatic halides,15
Key words: alkynes, azides, copper, iron, supported catalysis
we aimed to utilize the Cu/Fe bimetallic catalyst system in
azide–alkyne cycloadditions.
Since its independent discovery by Sharpless and Meldal,1
Considering the reducing ability of iron, we supposed that
the copper-catalyzed azide–alkyne cycloaddition
our bimetallic catalyst could be highly active due to the
(CuAAC) has become a powerful tool for the rapid and re-
presence of nanosized copper particles on the surface of
gioselective formation of 1,2,3-triazoles.2 The importance
the iron, and additionally, the presence of iron support can
of this synthetic transformation3 has been shown by sev-
serve as a copper scavenger during the reaction to obtain
eral applications in organic synthesis,4 material science,5
triazoles with lower copper contamination. The synthesis
polymer chemistry,6 bioconjugation,7 or fluorescence-
of the Cu/Fe catalyst is very simple, it can be performed
based quantitative analytical determinations.8 In general,
without the use of a glove box, and it requires only a non-
Cu(I) is used as the catalyst for the transformation, which
toxic reducing agent, in contrast to other procedures de-
usually generated in situ by reduction of Cu(II) with re-
veloped for the preparation of nanosized copper
ducing agents.1b,2e Beside these homogeneous copper
catalysts.10g,16
sources,9 there are several examples of CuAAC reactions
catalyzed by heterogeneous copper catalysts10 using char-
coal,10a,i polymer,10c biopolymer,10b zeolite,10f silica gel,10k
and iron nanoparticles10m as the support. Copper nanopar-
ticles either stabilized in solution10g,11 or deposited on the
surface of charcoal10a,12 were also utilized as catalysts for
the synthesis of triazoles. In general, with few exceptions
for procedures utilizing Cu(0), relatively high tempera-
tures are required to achieve the cycloaddition compared
to the homogeneous or heterogeneous Cu(I)-catalyzed
versions.
Also, the unique structure and properties of the Cu/Fe bi-
metallic catalyst offer the possibility of easy separation
from the reaction mixture by using an external magnetic
field.
Phenylacetylene (2a) and benzyl azide (1a) were selected
as the as reactants for the model reaction, first we exam-
ined the effect of temperature on the reaction in toluene in
the presence of 5 mol% copper using 5 wt% Cu/Fe cata-
lyst. We found that the catalysts worked excellently in the
cycloaddition to give 3aa at 50 °C (Table 1, entry 1).
Moreover, we obtained complete reaction in 16 hours
even at 30 °C (entry 2), which is relatively low tempera-
ture for the transformation in the presence of the Cu/Fe
catalyst. However, the conversion of the reaction per-
formed in toluene after five hours was only 31% (entry 3).
Based on the definition of ‘click chemistry’ by Sharpless
et al.3 most CuAAC procedures are designated as click re-
actions. Although, some click syntheses do not include
chromatographic purifications to obtain the desired tri-
azole products with acceptable ‘organic purity’, the ques-
tion of copper impurities has rarely been examined.
However, removal of trace impurities is a scavenger-,
energy-, and time-consuming follow up procedure.
Next we carried out the reaction in various solvents, and
we found that the cycloaddition took place to give 3aa
slowly in polar solvents such as N,N-dimethylformamide
or ethanol. In these solvents only 5% and 8% conversion
was measured respectively (entries 4 and 5); 80% conver-
sion was observed when the reaction was conducted at 30
°C ‘on water’ and in acetonitrile after eight and five hours,
respectively (entries 6 and 7).
There are several methods for the removal of copper im-
purities from triazole products,13 but the simplest, most
SYNTHESIS 2012, 44, 3722–3730
Advanced online publication: 20.11.2012
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DOI: 10.1055/s-0032-1317697; Art ID: SS-2012-E0719-FA
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Copper on Iron Catalyzed CuAAC
3723
Further study of the reaction in dichloromethane at 30 °C ment showed (entry 12). Application of copper turnings
revealed that the cycloaddition of benzyl azide (1a) and and powder gave lower conversions (9%, 10%) after four
phenylacetylene (2a) was complete in five hours in the hours, and with these catalysts the reaction did not
presence of 5 mol% Cu (5 wt% Cu/Fe) (entry 8). Decreas- reached complete conversion even after 24 hours reaction
ing the Cu catalyst loading to 1 mol% (5 wt % Cu/Fe), the time (entries 13 and 14). However, freshly prepared mi-
reaction was also complete in five hours (entry 9). For crosized copper powder17 showed comparable activity
complete conversion with 0.1 mol% Cu catalyst (5 wt% (entry 15) to the Cu/Fe systems, indicating the importance
Cu/Fe) loading eight hours reaction time was necessary of the copper particle size in this transformation.
(entry 10); a similar result was observed when 5 mol% Cu
After proving the applicability of Cu/Fe as catalyst in the
(1 wt% Cu/Fe) was added (entry 11). Iron itself is not able
CuAAC reaction, we turned our attention to the copper
to catalyze the cycloaddition as the result of our experi-
Biographical Sketches█
Szabolcs Kovács was born Technology and Economics Zoltán Novák. His scientific
in 1985 in Hungary. He re- in 2009. He started his Ph.D. interest is mainly focused on
ceived his Master’s degree research in 2009 at the metal-catalyzed reactions
in organic chemistry at the Eötvös Loránd University and aryne chemistry.
Budapest University of under the guidance of Prof.
Katalin Zih-Perenyi stud- gree in analytical chemistry Eötvös Loránd University
ied chemistry at the Eötvös at the same university in of Sciences (Budapest,
Loránd University of Sci- 2001. Since 2004 she has Hungary).
ences (Budapest, Hungary). been an Assistant Lecturer
She received her Ph.D. de- at the Chemical Institute of
Ádám Révész undertook Prof. J. Lendvai (2000) at turned to his alma mater as
his Master’s degree in Phys- the same institution. After an Assistant Professor. Af-
ics (1996) at the Eötvös postdoctoral studies at the ter gaining his habilitation
Loránd University in Buda- Universitat Autonoma de in 2011, Ádám became an
pest. He obtained his Ph.D. Barcelona (2001–2002) and Associate Professor.
degree in materials physics at the University of Mary-
under the supervision of land (2005–2006), he re-
Zoltan Novak was born in Ph.D. in 2004. In 2004– group of Prof. Kotschy.
1974 in Budapest, Hungary. 2005 he joined the group of From September 2007 he
After completing his M.Sc. Prof. Brian M. Stoltz at Cal- started his independent re-
studies at the Eötvös Loránd ifornia Institute of Technol- search career at the Depart-
University, Budapest with ogy as
a
postdoctoral ment of Organic Chemistry,
Prof. András Kotschy in researcher. After returning Institute of Chemistry at
1999, he performed doctoral to Hungary he continued his Eötvös Loránd University
studies in the same research research at Eötvös Loránd as an Assistant Professor.
group and received his University again in the
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3722–3730

3724
S. Kovács et al.
FEATURE ARTICLE
Table 1 Solvent and Catalyst Effect on the Formation of 3aaa
pound in the laboratory (Table 2). The results of the ana-
lytical measurements showed that the copper content of
products varied from 175 ppm up to the high 2770 ppm
level depending on the type of catalyst and its loading,
while the product obtained from the reaction catalyzed by
Cu/Fe was contaminated only with 51 ppm copper. At-
tempted removal of copper impurities with disodium tet-
raethylenediaminetetraacetic acid (Na2EDTA) extraction
from product prepared using the Cu(I)/tris[(1-benzyl-1H-
1,2,3-triazol-4-yl)methyl]amine (TBTA) catalyzed reac-
tion resulted one order of magnitude lower copper content
in the triazole product (27 ppm down from 412 ppm, entry
6). After these traditional tools for the purification of or-
ganic compounds, we utilized the modified Veinot meth-
od for the removal of trace copper impurities. To achieve
this we treated the purified triazole product derived from
the 5 mol% Cu(PPh3)2NO3 catalyzed reaction twice with
iron powder in tetrahydrofuran–aqueous potassium hy-
droxide system. Comparative studies showed that the
highly efficient copper–phosphine complexes are a signif-
icant contaminant of the cycloadduct product, and the
copper content of the triazole could be reduced from 2770
ppm only to 119 ppm. Utilizing our Cu/Fe catalyst in Cu-
AAC reaction lowers the copper content of the product by
one order of magnitude (51 μg/g) relative to other methods.
catalyst
N
N
N3
+
solvent, 30 °C
N
1a
2a
3aa
Entry Catalyst
Cu
Solvent
Time Conv.b
(mol%)
(h)
(%)
1
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (5 wt%)
Cu/Fe (1 wt%)
Fe powder
5
5
toluene
toluene
toluene
DMF
16
16
5
100c
100
31
5
2
3
5
4
5
5
5
5
EtOH
5
8
6
5
H2O
8
80
82
100
100
100
97
0
7
5
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
5
8
5
5
9
1
5
10
11
12
13
14
15
0.1
5
8
4
0
4
Cu turnings
5
4
10
9
Table 2 Copper Content and Catalytic Activity of Triazole 3aa
Cu powder (~500 μm) 5
Cu powder (<100 μm) 5
4
Synthesized in Different CuAAC Reactionsa
4
82
copper catalyst
CH2Cl2, 30 °C
N
N3
+
a Reaction conditions: phenylacetylene (2a, 1.5 mmol, 1 equiv), BnN3
(1a, 1.5 mmol, 1 equiv), catalyst, solvent (900 μL), stirring, 30 °C.
b Composition of the product determined by GC.
c At 50 °C.
N
N
1a
2a
3aa
Entry Catalyst for triazole synthesisa
Copper content of
the triazoleb (μg/g)
1
2
3
5 mol% Cu(PPh3)2NO3, CH2Cl2, 30 °C 2770 (119)c
1 mol% Cu(PPh3)2NO3, CH2Cl2, 30 °C 284 ± 14
impurities in the triazole product 3aa. Regarding the cop-
per impurities in the triazole, to the best of our knowledge,
only one example of reported data14 on the expected value
of the copper content of triazoles produced in a homoge-
neous copper-catalyzed click reaction of azides and termi-
nal acetylenes is available. Due to the good coordinating
ability of the nitrogen heterocycles formed in this straight-
forward reaction, significant copper contamination of the
triazoles produced in every homogeneously catalyzed
transformation would be expected. We measured and
compared the copper impurities of triazoles synthesized
under the most frequently used reaction conditions and
catalysts for the azide–alkyne cycloaddition, such as
water–methanol mixture with 5 mol% copper(II) sul-
fate/ascorbate system, 5 mol% copper(I) iodide, 0.5–5
mol% homogeneous Cu(PPh3)2NO3, and 5 mol% of our
Cu/Fe catalyst in dichloromethane at 30 °C.
0.5 mol% Cu(PPh3)2NO3, CH2Cl2,
30 °C
175 ± 8
4
5
5 mol% CuI, CH2Cl2, 30 °C
419
5 mol% CuSO4, sodium ascorbate,
MeOH–H2O, 30 °C
1090
6
7
5 mol% CuSO4, TBTA, sodium
ascorbate, MeOH–H2O, 30 °C
412 ± 14 (27 ± 3)d
5 mol% Cu/Fe, CH2Cl2, 30 °C
51.3 ± 1.3
a Catalysts and conditions for Cu-catalyzed reaction of BnN3 (1a) and
phenylacetylene (2a).
b After column chromatography and recrystallization; Cu content was
determined by AAS measurement).
c In parentheses: Cu content after treatment (2 ×) with Fe powder us-
ing the purification method of Veinot.
To demonstrate the copper contamination effect of tradi-
tional homogeneous copper-catalyzed reactions, we de-
termined the copper content of triazoles with AAS after
recrystallization and column chromatography, as the most
frequently used purification methods of organic com-
d In parentheses: Cu content after extraction with Na2EDTA solution.
Synthesis 2012, 44, 3722–3730
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Copper on Iron Catalyzed CuAAC
3725
On the basis of these results, we can conclude that the iron ation by the triazole product, rather than the effect of
component of our Cu/Fe catalyst behaves as a scavenger catalyst surface area.20
for copper and significantly reduce the copper contamina-
tion of the triazole product. Moreover, iron serves as non-
toxic support, and taking the mass balance into
Monitoring the reaction with GC analysis, we observed
the formation of triazoles 3 only after 90 minutes when the
conversion was 5%. However, in the next 180 minutes the
consideration it is not necessary to add large amount of li-
reaction showed completion. These results confirm the
gands such as phosphines with high-molecular mass to the
presence of released copper and suggest the presence of
reaction mixture. These properties make the Cu/Fe cata-
catalytically active dissolved copper species in solution,
lyst advantageous compared to homogeneous copper cat-
which are responsible for the transformation.
alysts especially to copper–phosphine complexes.
In order to gather structural information on our Cu/Fe cat-
Next, we examined the possible of recycling the Cu/Fe
alyst we examined the physical properties of the bimetal-
catalyst using 5 mol% Cu/Fe catalyst to ensure rapid reac-
lic material with XRD and SEM. The XRD analysis
showed the presence of Cu(0), but after two runs the char-
tion and sufficient iron for redeposition of copper.18
The easy separation of organic materials from the bimetal- acteristic peak of elemental copper was not measurable by
lic system can be achieved with the aid of an external this method (see Supporting Information). The scanning
magnetic field. After washing the catalyst with dichloro- electron microscope images (Figure 2) showed the pres-
methane, the next reaction cycle can be performed in the ence of different types of microstructures in the catalyst.
same vessel with a new batch of reactants.
The major part of the Cu/Fe catalyst consist of iron
spheres with the average size of 3–6 μm covered with cop-
per layer (‘A’ type particle). The catalyst contains cloud-
like particles (‘C’ type particle), which are significantly
richer (ratio Cu/Fe 1:4) in copper than the spheres (ratio
Cu/Fe 1:15). After the second use of the catalyst the same
particle distribution was observed in the SEM images
[Figure 2, (2)]. However, minor changes in the copper/
iron ratio of each type of particles was observed. The cop-
per content of the ‘A’ type spheres decreased but the B-
type particle become richer in copper (ratio Cu/Fe 1:1).
These findings correlate well with the results of the stud-
ies focusing to the catalytic activity and the homogeneity
of the reaction. After eight uses the particle distribution
become more homodisperse regarding the type of parti-
cles, and only the spheres and its distorted variants can be
observed in various sizes on the SEM images.
We repeated the recycling process 14 times and we did not
observe a significant reduction in the rate of the reaction
during the entire study. The cycloaddition of benzyl azide
(1a) and phenylacetylene (2a) was completed in six hours
even in the 15th run at 30 °C (not shown), and the time-
conversion curve profiles (1–10 runs) showed no change
of the reaction rate (Figure 1). These exhaustive studies
show that the copper source can be used multiple times
without a significant change in the reaction rate.19
Figure 1 Catalyst recycling. Reagents and conditions: phenylacetyl-
ene (2a, 1.5 mmol, 1 equiv), BnN3 (1a, 1.5 mmol, 1 equiv), Cu/Fe
(5 mol%, 5 wt %; 96 mg, 0.075 mmol Cu), CH2Cl2 (900 μL), stirring,
30 °C.
The cycloaddition reaction has an induction period when
the Cu/Fe catalyst was used in the transformation.11 We
supposed that, in our case this phenomenon could be ex-
plained with copper leaching and possible ligand acceler-
Figure 2 SEM images of the catalysts: 1. SEM image of the unused
Cu/Fe catalyst. 2. The catalyst after 2 uses. 3. The catalyst after 8 uses.
4. The catalyst after 15 uses.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3722–3730

3726
S. Kovács et al.
FEATURE ARTICLE
Demonstrating the applicability of the Cu/Fe catalyst un- azide (1a) and in all cases the appropriate triazoles were
der the developed conditions, we synthesized several tri- isolated with good to excellent yields 3ab–ai.
azoles 3 from diverse azides 1a–j and terminal acetylenes
2a–i in CuAAC reaction (Table 3). 1-Benzyl-4-phenyl-
1,2,3-triazole (3aa) was synthesized and isolated in 98%
yield. Substituted benzyl azides 1b–d reacted smoothly
with phenylacetylene (2a) and gave the appropriate tri-
azole products 3ba–da in high isolated yields. Reaction of
bulky 1-adamantyl azide (1e) required a longer reaction
time (24 hours), but the N-adamantyl triazole 3ea was ob-
tained in 79% yield. Isopropyl-substituted aryl azide 1f
also gave the appropriate heterocycle 3fa with phenyl-
acetylene (2a). The Cu/Fe catalyst was also applicable for
the dipolar cycloaddition of alkyl azides 1g–j with termi-
nal acetylenes under our conditions. Expanding the scope
of the reaction several terminal acetylene 2b–i (aryl, heta-
ryl, alkyl, silyl) were successfully reacted with benzyl
advantages of our catalyst is that the copper contamina-
In conclusion, we successfully utilized the previously de-
veloped Cu/Fe catalyst in the copper-catalyzed azide–
alkyne cycloaddition. The easily accessible nanosized
copper pre-catalyst proved to be applicable for the con-
struction of versatile 1,4-substituted triazoles in a simple
procedure. The reaction conditions enable the easy prepa-
ration of the desired CuAAC product, and the composi-
tion of the catalysts ensures the straightforward separation
of the bimetallic system after the reaction with the appli-
cation of outer magnetic field. We demonstrated that the
Cu/Fe catalyst serves as an excellent source of highly ac-
tive homogeneous copper species for the cycloaddition re-
action, and the Cu/Fe system is reusable in 15 consecutive
reactions without a reduction in the reaction rate. Further
Table 3 Copper Content and Catalytic Activity of Triazoles Synthesized in Different CuAAC Reactionsa
R1
5 wt% Cu/Fe
CH2Cl2, 30 °C
N
N
R2
R1 N3
+
R2
N
1a–j
2a–i
3
Entry
Azide
R1
Acetyl- R2
ene
Time (h)
Product
Yieldb (%)
1
1a
1b
1c
1d
1e
1f
Bn
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2c
2f
Ph
8
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
98
94
89
98
80
98
98
80
92
93
98
97
85
95
93
92
61
95
96
2
4-IC6H4CH2
4-BrC6H4CH2
4-O2NC6H4CH2
1-adamantyl
4-i-PrC6H4
CH2SPh
Ph
8
3
Ph
12
12
24
8
4
Ph
5
Ph
6
Ph
7
1g
1h
1i
Ph
8
8
CH2CH(Me)CH2Cl
Ph
12
12
12
8
9
(CH2)4CH=CH
Ph
10
11
12
13
14
15
16
17
18
19
1j
(CH2)4CO2Et
Ph
3ja
3ab
3jc
1a
1j
Bn
3-MeC6H4
CH2OAc
2-pyridyl
(CH2)3CN
CH2OAc
Bu
(CH2)4CO2Et
12
8
1a
1a
1a
1a
1a
1a
1a
Bn
Bn
Bn
Bn
Bn
Bn
Bn
3ad
3ae
3ac
3af
3ag
3ah
3ai
12
12
16
36
12
24
2g
2h
2i
TMS
CH2OH
CMe2OH
a Reaction conditions: acetylene 2 (0.5 mmol, 1 equiv), azide 1 (0.5 mmol, 1 equiv), Cu/Fe (5 mol%, 5 w %) (32 mg, 0.025 mmol Cu), CH2Cl2
(300 μL), stirring, 30 °C.
b Isolated yields.
Synthesis 2012, 44, 3722–3730
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Copper on Iron Catalyzed CuAAC
3727
13C NMR (62.5 MHz, CDCl3): δ = 148.0, 134.6, 130.4, 128.9,
128.6, 128.5, 128.0, 127.8, 125.5, 119.5, 54.0.
MS (EI, 70 eV): m/z (%) = 235 (8, [M+]), 206 (24), 180 (8), 130 (9),
116 (100), 104 (24), 91 (97), 65 (25).
tion of the product is significantly lower than the triazoles
synthesized under homogeneous conditions, showing that
iron not only behaves as a support for copper, but acts as
a redox scavenger, and reduces the copper contamination
of the organic products. Additionally, we indicate the im-
portance and necessary determination of copper impuri-
ties in triazole compounds prepared via CuAAC.
1-(4-Iodobenzyl)-4-phenyl-1H-1,2,3-triazole (3ba)9a
Following the general procedure; time: 8 h; white crystals; yield:
169 mg (0.47 mmol, 94%); mp 153–156 °C; Rf = 0.40 (hexane–
EtOAc, 3:1).
1H NMR (250 MHz, CDCl3): δ = 7.81–7.78 (m, 2 H), 7.72–7.67 (m,
3 H), 7.44–7.29 (m, 3 H), 7.04 (d, J = 8.21 Hz, 2 H), 5.51 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 146.6, 138.2, 134.3, 130.3,
129.7, 128.8, 128.2, 125.6, 119.4, 94.5, 52.4.
MS (EI, 70 eV): m/z (%) = 361 (5, [M+]), 332 (5), 230 (4), 217 (9),
Unless otherwise indicated, all starting materials were obtained
from commercial suppliers, and were used without further purifica-
tion. Analytical TLC was performed on Merck DC precoated TLC
plates with 0.25-mm Kieselgel 60 F254. Visualization was per-
formed with a 254-nm UV lamp. 1 H and 13C NMR spectra were re-
corded on a Bruker Avance-250 spectrometer in CDCl3 with
residual solvent protons as internal standards [δ = 7.26 (1H), 77.0
(13C)]. Combination GC and LR-MS was obtained on an Agilent
6890N gas chromatograph (30 m × 0.25 mm column with 0.25-μm
HP-5MS coating, He carrier gas) and Agilent 5973 mass spectrom-
eter (ion source: EI+, 70 eV, 230 °C; interface: 300 °C). IR spectra
were obtained on a Bruker IFS55 spectrophotometer on a single-re-
flection diamond ATR unit. All melting points were measured on
Büchi 501 apparatus and are uncorrected. HRMS were recorded on
an Agilent Technologies 6210 TOFMS. Microstructure of the pow-
ders was examined by powder X-ray diffraction (XRD) on a Philips
Xpert diffractometer using Cu-Kα radiation in the range of 30–130°
with a step width of 0.02° in θ–2θ geometry. The instrumental pat-
tern was measured on a NIST SRM660a LaB6 peak profile standard
material. Morphology studies were performed on a FEI Quanta
dual-beam scanning electron microscope (SEM) in backscattered
electron (BSE) mode. Compositional changes were quantitatively
determined by energy dispersive X-ray (EDX) analysis with a rela-
tive accuracy of 3%.
206 (12), 116 (100), 89 (43).
1-(4-Bromobenzyl)-4-phenyl-1H-1,2,3-triazole (3ca)10i
Following the general procedure; time: 12 h; white crystals; yield:
140 mg (0.44 mmol, 89%); mp 150–152 °C; Rf = 0.35 (hexane–
EtOAc, 3:1).
1H NMR (250 MHz, CDCl3): δ = 7.80 (d, J = 7.1 Hz, 2 H), 7.69 (s,
1 H), 7.50 (d, J = 8.3 Hz, 2 H), 7.43–7.32 (m, 3 H), 7.16 (d, J = 8.2
Hz, 2 H), 5.51 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 133.6, 132.2, 129.6, 128.8,
128.2, 125.6, 122.8, 53.4.
MS (EI, 70 eV): m/z (%) = 315 (4, [M+]), 286 (6), 284 (7), 206 (10),
169 (14), 171 (16), 116 (100), 89 (35).
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (3da)21
Following the general procedure; time: 12 h; white solid; yield: 138
mg (0.49 mmol, 98%); mp 151–153 °C; Rf = 0.59 (hexane–EtOAc,
1:1).
1H NMR (250 MHz, CDCl3): δ = 8.21 (d, J = 8.5 Hz, 2 H), 7.81–
7.77 (m, 2 H), 7.45–7.30 (m, 6 H), 5.68 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 141.7, 130.0, 128.9, 128.5,
128.4, 125.7, 124.3, 119.7, 53.1.
MS (EI, 70 eV): m/z (%) = 280 (4, [M+]), 251 (4), 205 (4), 116
(100), 106 (10), 89 (31).
Triazoles were recrystallized from EtOH. The copper contents were
measured with AAS. The sample (ca. 10 mg) was dissolved in
concd HNO3 (0.5 mL) and diluted to 10 mL with MeOH/distilled
H2O (1:1). The soln was analyzed by FAAS and GFAAS using a
Perkin Elmer AAnalyst 800 atomic absorption spectrometer. Exter-
nal calibration with matrix-matched standards were used. The re-
coveries were between 90–106%, the reproducibility of the
sampling was below 5%.
1-(1-Adamantyl)-4-phenyl-1H-1,2,3-triazole (3ea)22
Following the general procedure; time: 24 h; white solid; yield: 112
mg (0.40 mmol, 80%); mp 193–195 °C; Rf = 0.65 (hexane–EtOAc,
3:1).
1H NMR (250 MHz, CDCl3): δ = 7.79–7.75 (m, 3 H), 7.37–7.20 (m,
3 H), 2.21 (br s, 9 H), 1.72 (br s, 6 H).
13C NMR (62.5 MHz, CDCl3): δ = 146.7, 131.0, 128.7, 127.7,
125.5, 116.0, 59.5, 43.0, 35.8, 29.3.
MS (EI, 70 eV): m/z (%) = 279 (4, [M+]), 223 (4), 181 (5), 135
Preparation of the Cu/Fe Catalyst
A round-bottom flask was charged with Fe powder (5 g, 89.5 mmol)
and H2O (deoxygenated with argon) (50 mL). The mixture was
stirred vigorously with a mechanical stirrer and a soln of CuSO4
(125.6 mg, 0.79 mmol) in H2O (50 mL) was added dropwise under
an argon atmosphere over 1 h, and stirring was continued for 3 h.
The catalyst was separated with a magnet and washed with deoxy-
genated H2O (5 × 20 mL) then acetone (3 × 20 mL) and dried under
reduced pressure.
(100), 116 (13), 107 (15), 93 (30), 79 (37), 67 (15).
Cu/Fe Catalyzed CuAAC Reaction; General Procedure
A mixture of terminal acetylene (0.5 mmol, 1 equiv), azide (0.5
mmol, 1 equiv), Cu/Fe (5 mol%, 5 w/w%) (32 mg, 0.025 mmol Cu)
and CH2Cl2 (200 μL) was heated for 8–24 h at 30 °C. After the ap-
propriate time the mixture was diluted with CH2Cl2 (5 mL). The cat-
alyst was separated with a magnet and washed with CH2Cl2 (4 × 5
mL). The organic phase was separated, dried (MgSO4), and filtered,
and the solvent was removed under vacuum. The residue was puri-
fied by chromatography (silica gel) to give desired triazole.
1-(4-Isopropylphenyl)-4-phenyl-1H-1,2,3-triazole (3fa)
Following the general procedure; time: 8 h; slightly yellow solid;
yield: 130 mg (0.49 mmol, 98%); mp 53–55 °C; Rf = 0.75 (hexane–
EtOAc, 3:1).
IR (ATR): 3121, 3052, 2973, 2860, 1519, 1455, 1229, 1039 cm–1.
1H NMR (250 MHz, CDCl3): δ = 8.18 (s, 1 H), 7.91 (d, J = 7.0 Hz,
2 H), 7.70 (d, J = 8.5 Hz, 2 H), 7.48–36 (m, 5 H), 2.99 (q, 1 H), 1.29
(d, J = 7.0 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): δ = 149.7, 148.1, 134.9, 130.3,
128.8, 128.3, 127.6, 125.7, 120.5, 117.6, 33.8, 23.8.
MS (EI, 70 eV): m/z (%) = 263 (2, [M+]), 235 (43), 220 (100), 204
(13), 193 (91), 165 (22), 110 (75), 103 (32), 89 (38), 77 (34).
1-Benzyl-4-phenyl-1H-1,2,3-triazole (3aa)10f
Following the general procedure; time: 8 h; white solid; yield: 115
mg (0.49 mmol, 98%); mp 128–130 °C; Rf = 0.48 (hexane–EtOAc,
3:1).
1H NMR (250 MHz, CDCl3): δ = 7.81 (d, J = 6.75 Hz, 2 H), 7.69 (s,
1 H), 7.42–7.27 (m, 8 H), 5.53 (s, 2 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3722–3730

3728
S. Kovács et al.
FEATURE ARTICLE
HRMS: m/z [M + H]+ calcd for C17H18N3: 264.1495; found:
264.1501.
Ethyl 5-[4-(Acetoxymethyl)-1H-1,2,3-triazol-1-yl]pentanoate
(3jc)9a
Following the general procedure; time: 12 h; colorless oil; yield:
130 mg (0.48 mmol, 97%); Rf = 0.61 (hexane–EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.57 (s, 1 H), 5.12 (s, 2 H), 4.31
(t, J = 7.1 Hz, 2 H), 4.05 (q, J = 7.1 Hz, 2 H), 2.27 (t, J = 7.1 Hz, 2
H), 2.00 (s, 3 H), 1.96–1.84 (m, 2 H), 1.64–1.52 (m, 2 H), 1.17 (t,
J = 7.1 Hz, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 172.7, 170.7, 60.3, 57.4, 49.8,
33.2, 29.3, 21.5, 20.7, 14.0.
MS (EI, 70 eV): m/z (%) = 269 (2, [M+]), 226 (10), 199 (12), 154
(20), 136 (20), 108 (30), 101 (48), 84 (69), 55 (100).
4-Phenyl-1-[(phenylthio)methyl]-1H-1,2,3-triazole (3ga)9a
Following the general procedure; time: 8 h; white crystals; yield:
131 mg (0.49 mmol, 98%); mp 92–94 °C; Rf = 0.50 (hexane–
EtOAc, 3:1).
1H NMR (250 MHz, CDCl3): δ = 7.81–7.78 (m, 3 H), 7.45–7.30 (m,
8 H), 5.65 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 148.1, 132.2, 131.7, 130.2,
129.4, 128.8, 128.6, 128.2, 125.6, 119.0, 53.8.
MS (EI, 70 eV): m/z (%) = 267 (4, [M+]), 238 (13), 130 (100), 123
(18), 116 (17), 103 (61), 77 (43), 51 (18).
1-Benzyl-4-(2-pyridyl)-1H-1,2,3-triazole (3ad)23
Following the general procedure; time: 8 h; light brown crystals;
yield: 100 mg (0.42 mmol, 85%); mp 113–115 °C; Rf = 0.32
(hexane–EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 8.51 (d, J = 4.6 Hz, 1 H), 8.15 (d,
J = 7.9 Hz, 1 H), 8.03 (s, 1 H), 7.73 (td, J1 = 7.8 Hz , J2 = 1.8 Hz, 1
H), 7.36–7.29 (m, 5 H), 7.20–7.15 (m, 1 H), 5.55 (s, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 150.2, 149.3, 148.6, 136.8,
134.3, 129.1, 128.7, 128.2, 122.7, 121.8, 120.1, 54.3.
MS (EI, 70 eV): m/z (%) = 236 (5, [M+]), 207 (47), 180 (10), 117
(51), 91 (100), 65 (23).
1-(3-Chloro-2-methylpropyl)-4-phenyl-1H-1,2,3-triazole
(3ha)9a
Following the general procedure; time: 12 h; white crystals; yield:
94 mg (0.40 mmol, 80%); mp 50–51 °C; Rf = 0.40 (hexane–EtOAc,
3:1).
1H NMR (250 MHz, CDCl3): δ = 7.85–7.80 (m, 3 H), 7.45–7.29 (m,
3 H), 4.49–4.32 (m, 2 H), 3.45 (d, J = 5.1 Hz, 2 H), 2.63–2.51 (m, 1
H), 1.09 (2, J = 6.8 Hz, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 130.3, 128.8, 128.1, 125.6,
120.4, 52.4, 47.3, 36.1, 15.4.
MS (EI, 70 eV): m/z (%) = 235 (9, [M+]), 172 (14), 158 (11), 145
(6), 130 (45), 117 (100), 103 (35), 89 (21), 77 (16), 63 (16), 55 (31).
4-(1-Benzyl-1H-1,2,3-triazol-4-yl)butanenitrile (3ae)9a
Following the general procedure; time: 12 h; white solid; yield: 108
mg (0.48 mmol, 95%); mp 64–66 °C; Rf = 0.20 (hexane–EtOAc,
1:1).
1H NMR (250 MHz, CDCl3): δ = 7.31–7.29 (m, 3 H), 7.22–7.18 (m,
3 H), 5.43 (s, 2 H), 2.77 (t, J = 7.0 Hz, 2 H), 2.34 (t, J = 7.25 Hz, 2
H), 1.98 (p, J = 7.0 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 145.9, 134.5, 129.0, 128.6,
127.9, 121.1, 119.3, 54.0, 24.7, 24.1, 16.4.
MS (EI, 70 eV): m/z (%) = 226 (3, [M+]), 197 (4), 144 (4), 130 (4),
104 (4), 91 (100), 65 (12).
1-(Hex-5-enyl)-4-phenyl-1H-1,2,3-triazole (3ia)9a
Following the general procedure; time: 12 h; white crystals; yield:
104 mg (0.46 mmol, 92%); mp 52–53 °C; Rf = 0.48 (hexane–
EtOAc, 3:1).
1H NMR (250 MHz, CDCl3): δ = 7.83 (d, J = 8.0 Hz, 2 H), 7.74 (s,
1 H), 7.44–7.31 (m, 3 H), 5.83–5.67 (m, 1 H), 5.04–4.95 (m, 2 H),
4.37 (t, J = 7.1 Hz, 2 H), 2.13–2.05 (m, 2 H), 2.00–1.88 (m, 2 H),
1.50–1.38 (m, 2 H).
13C NMR (62.5 MHz, CDCl3): δ = 137.6, 130.6, 128.7, 128.0,
125.4, 119.4, 115.2, 50.1, 32.9, 29.6, 25.5.
MS (EI, 70 eV): m/z (%) = 227 (18, [M+]), 198 (26), 156 (32), 117
(100), 102 (35), 89 (42), 55 (69).
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl Acetate (3ac)9a
Following the general procedure; time: 12 h; slightly yellow crys-
tals; yield: 108 mg (0.47 mmol, 93%); mp 55–56 °C; Rf = 0.50
(hexane–EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 7.51 (s, 1 H), 7.32–7.21 (m, 5 H),
5.46 (s, 2 H), 5.11 (s, 2 H), 1.98 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 170.6, 142.9, 134.2, 128.9,
128.6, 127.9, 123.5, 57.3, 53.9, 20.6.
MS (EI, 70 eV): m/z (%) = 231 (1, [M+]), 188 (6), 161 (5), 91 (100),
65 (14).
Ethyl 5-(4-Phenyl-1H-1,2,3-triazol-1-yl)pentanoate (3ja)9a
Following the general procedure; time: 12 h; white crystals; yield:
127 mg (0.46 mmol, 93%); mp 50–53 °C; Rf = 0.57 (hexane–
EtOAc, 1:1).
1H NMR (MHz, CDCl3): δ = 7.78 (t, J = 8.2 Hz, 3 H), 7.41–7.29 (m,
3 H), 4.37 (t, J = 7.0 Hz, 2 H), 4.13–4.05 (m, 2 H), 2.32 (t, J = 7.1
Hz, 2 H), 2.02–1.91 (m, 2 H), 1.71–1.59 (m, 2 H), 1.21 (t, J = 7.1
Hz, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 172.8, 130.5, 128.7, 128.0,
125.6, 119.5, 60.4, 49.9, 33.3, 29.5, 21.7, 14.1.
MS (EI, 70 eV): m/z (%) = 273 (9, [M+]), 228 (4), 200 (43), 144
(30), 129 (57), 116 (60), 101 (73), 83 (50), 55 (100).
1-Benzyl-4-butyl-1H-1,2,3-triazole (3af)24
Following the general procedure; time: 16 h; white crystals; yield:
99 mg (0.46 mmol, 92%); mp 57–59 °C; Rf = 0.35 (hexane–EtOAc,
3:1).
1H NMR (250 MHz, CDCl3): δ = 7.34–7.32 (m, 3 H), 7.24–7.18 (m,
3 H), 5.46 (s, 2 H), 2.66 (t, J = 7.5 Hz, 2 H), 1.65–1.54 (m, 2 H),
1.40–1.25 (m, 2 H), 0.88 (t, J = 7.25 Hz, 3 H).
1-Benzyl-4-m-tolyl-1H-1,2,3-triazole (3ab)9a
Following the general procedure; time: 8 h; white crystals; yield:
122 mg (0.49 mmol, 98%); mp 147–149 °C; Rf = 0.45 (hexane–
EtOAc, 3:1).
13C NMR (62.5 MHz, CDCl3): δ = 134.9, 128.9, 128.4, 127.8, 53.8,
31.4, 25.3, 22.2, 13.7.
MS (EI, 70 eV): m/z (%) = 215 (1, [M+]), 173 (5), 144 (3), 104 (5),
91 (100), 65 (10).
1H NMR (250 MHz, CDCl3): δ = 7.66 (s, 2 H), 7.58 (d, J = 7.5 Hz,
1 H), 7.38–7.25 (m, 6 H), 7.13 (d, J = 7.5 Hz, 1 H), 5.55 (s, 2 H),
2.38 (s, 3 H).
13C NMR (62.5 MHz, CDCl3): δ = 148.2, 138.4, 134.6, 130.3,
129.0, 128.8, 128.63, 128.60, 127.9, 126.2, 122.7, 119.4, 54.1, 21.3.
MS (EI, 70 eV): m/z (%) = 249 (8, [M+]), 220 (25), 179 (10), 130
(100), 103 (17), 91 (83), 77 (18).
1-Benzyl-4-(trimethylsilyl)-1H-1,2,3-triazole (3ag)25
Following the general procedure; time: 36 h; white solid; yield: 71
mg (0.31 mmol, 61%); mp 53–55 °C; Rf = 0.43 (hexane–EtOAc,
3:1).
Synthesis 2012, 44, 3722–3730
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Copper on Iron Catalyzed CuAAC
3729
1H NMR (250 MHz, CDCl3): δ = 7.43 (s, 1 H), 7.37–7.24 (m, 5 H),
5.54 (s, 2 H), 0.29 (s, 9 H).
13C NMR (62.5 MHz, CDCl3): δ = = 148.2, 136.1, 130.20, 130.15,
129.7, 129.2, 129.1, 54.5, 0.0.
MS (EI, 70 eV): m/z (%) = 216 (2, [M+]), 173 (48), 144 (8), 104 (4),
91 (100), 65 (10), 58 (13).
Discovery Today 2003, 8, 1128. (d) Sharma, P.; Ritson, D.
J.; Burnley, J.; Moses, J. E. Tetrahedron 2012, 68, 197.
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(f) Morrhouse, A. D.; Moses, J. E. Synlett 2008, 2089.
(5) Hawker, C. J.; Wooley, K. L. Science 2005, 309, 1200.
(6) (a) Cavalli, S.; Tipton, A. R.; Overhand, M.; Kros, A. Chem.
Commun. 2006, 3193. (b) O’Reilly, R. K.; Joralemon, M. J.;
Hawker, C. J.; Wooley, K. L. Chem.–Eur. J. 2006, 12, 6776.
(c) White, M. A.; Johnson, J. A.; Koberstein, J. T.; Turro, N.
J. J. Am. Chem. Soc. 2006, 128, 11356. (d) Chernykh, A.;
Agag, T.; Ishida, H. Polymer 2009, 50, 382.
1-Benzyl-1H-1,2,3-triazole-4-methanol (3ah)25
Following the general procedure; time: 12 h; white solid; yield: 89
mg (0.48 mmol, 95%); mp 52–53 °C; Rf = 0.09 (hexane–EtOAc,
1:1).
(7) (a) Berndl, S.; Herzig, N.; Kele, P.; Lachmann, D.; Li, X.;
Wolfbeis, O. S.; Wagenknecht, H.-A. Bioconjugate Chem.
2009, 20, 558. (b) Dirks, A. J.; van Berkel, S. S.; Hatzakis,
N. S.; Opsten, J. A.; van Delft, F. L.; Cornellissen, J. J. L. M.;
Rowan, A. E.; van Hest, J. C. M.; Rutjes, F. P. J. T.; Nolte,
R. J. M. Chem. Commun. 2005, 4172. (c) Agard, N. J.;
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15046. (d) Link, A. J.; Vink, M. K. S.; Tirrell, D. A. J. Am.
Chem. Soc. 2004, 126, 10598.
1H NMR (250 MHz, CDCl3): δ = 7.38 (s, 1 H), 7.28–7.14 (m, 5 H),
5.38 (s, 2 H), 4.63 (s, 2 H), 4.10 (br s, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = 148.2, 134.4, 129.0, 128.6,
128.0, 121.8, 55.9, 54.0.
MS (EI, 70 eV): m/z (%) = 187 (2, [M+]), 158 (30), 130 (23), 104
(8), 91 (100), 77 (8), 65 (21).
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3ai)21
Following the general procedure; time: 24 h; white solid; yield: 104
mg (0.48 mmol, 96%); mp 78–80 °C; Rf = 0.18 (hexane–EtOAc,
1:1).
(8) (a) Wolfbeis, O. S. Angew. Chem. Int. Ed. 2007, 46, 2980.
(b) Kele, P.; Mező, G.; Achatz, D.; Wolfbeis, O. S. Angew.
Chem. Int. Ed. 2009, 48, 344.
1H NMR (250 MHz, CDCl3): δ = 7.36–7.23 (m, 6 H), 5.46 (s, 1 H),
3.13 (br s, 1 H), 1.58 (s, 6 H).
13C NMR (62.5 MHz, CDCl3): δ = 156.0, 134.5, 129.0, 128.6,
128.0, 119.0, 68.4, 54.0, 30.3.
MS (EI, 70 eV): m/z (%) = 217 (1, [M+]), 202 (18), 170 (4), 104 (4),
91 (100), 65 (13).
(9) (a) Gonda, Zs.; Novák, Z. Dalton Trans. 2010, 39, 726.
(b) Diez-González, S.; Stevens, E. D.; Nolan, S. P. Chem.
Commun. 2008, 4747. (c) Diez-González, S.; Escudero-
Adán, E. C.; Benet-Buchholz, J.; Stevens, E. D.; Slawinc, A.
M. Z.; Nolan, S. P. Dalton Trans. 2010, 39, 7595. (d) Lal, S.;
Díez-González, S. J. Org. Chem. 2011, 76, 2367. (e) Lal, S.;
McNally, J.; White, A. J. P.; Díez-González, S.
Organometallics 2011, 30, 6225.
(10) (a) Lipshutz, B.; Taft, B. R. Angew. Chem. Int. Ed. 2006, 45,
8235. (b) Chtchigrovsky, M.; Pirmo, A.; Gonzalez, P.;
Molvinger, K.; Robitzer, M.; Quignard, F.; Taran, F. Angew.
Chem. Int. Ed. 2009, 48, 5916. (c) Girard, C.; Onen, E.;
Aufort, M.; Beauvire, S.; Samson, E.; Erscovici, J. Org. Lett.
2006, 8, 1689. (d) Chassing, S.; Kumarraja, M.; Sido, A. S.
S.; Pale, P.; Sommer, J. Org. Lett. 2007, 9, 883. (e) Miao,
T.; Wang, L. Synthesis 2008, 363. (f) Park, I. S.; Kwon, M.
S.; Kim, Y.; Lee, J. S.; Park, J. Org. Lett. 2008, 10, 497.
(g) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M.
Acknowledgment
The authors thank for the generous research support and Graduate
Scholarship for Sz. K. to Sanofi. The help of Prof. K. Torkos, Dr Zs.
Eke, Mr Sz. Nász for providing the necessary analytical background
are gratefully acknowledged. This project was supported by the
János Bolyai Research Scholarship of the Hungarian Academy of
Sciences and OTKA-NKTH (CK 80763) and TÉT-10-1-2011-
0245. The European Union and the European Social Fund have pro-
vided financial support to the project under the Grant agreement no.
TÁMOP 4.2.1./B-09/KMR-2010-0003.
Tetrahedron Lett. 2009, 50, 2358. (h) Cravotto, G.; Fokin,
V. V.; Garella, D.; Binello, A.; Boffa, L.; Barge, A. J. Comb.
Chem. 2010, 12, 13. (i) Sharghi, H.; Khalifeh, R.;
Doroodmand, M. M. Adv. Synth. Catal. 2009, 351, 207.
(j) Zhang, Z.; Dong, C.; Yang, C.; Hu, D.; Long, J.; Wang,
L.; Li, H.; Chen, Y.; Kong, D. Adv. Synth. Catal. 2010, 352,
1600. (k) Megia-Fernandez, A.; Ortega-Muñoz, M.; Lopez-
Jaramillo, J.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F.
Adv. Synth. Catal. 2010, 352, 3306. (l) Wang, Y.; Liu, J.;
Xia, C. Adv. Synth. Catal. 2011, 353, 1534. (m) Hudson, R.;
Li, C.-J.; Moores, A. Green Chem. 2012, 14, 622.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3722–3730

3730
S. Kovács et al.
FEATURE ARTICLE
(18) Examination of heterogeneity showed some copper leaching
from the surface of iron during the reaction, see the
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(19) During the recycling process some part of the copper was
leached from the iron support (for AAS results, see ESI), but
it does not contaminate the triazole product. When 1 w/w%
Cu/Fe was recycled and reused, significant loss of activity
was found in the second run. When we started from 5 wt%
Cu/Fe catalyst we reached 0.8 wt% copper content after 8
runs, and interestingly the catalyst could be reused additional
7 times without loss of activity. We suppose that significant
structural changes of the catalyst occur during the recycling,
and more stable catalyst was formed.
Synthesis 2012, 44, 3722–3730
© Georg Thieme Verlag Stuttgart · New York