Insights into supported copper(II)-catalyzed azide-alkyne cycloaddition in water

Article abstract of DOI:10.1002/adsc.201000868

Cross-linked polymeric ionic liquid material-supported copper (Cu-CPSIL), imidazolium-loaded Merrifield resin-supported copper (Cu-PSIL) and silica dispersed CuO (CuO/SiO₂), were prepared and proved to be efficient catalysts for the one-pot synthesis of 1,4-disubsituted-1,2,3-triazoles by the reaction of alkyl halides with sodium azide and terminal alkynes in water at room temperature. Moreover, these supported copper catalysts were recovered quantitatively from the reaction mixture by simple filtration and reused for five consecutive recycles without significant loss of catalytic activity. Among the three immobilized copper catalysts, Cu-CPSIL exhibited excellent catalytic activity for the reaction of aliphatic bromides, sodium azide and terminal alkynes. The differences in the catalytic performances of the catalysts could be ascribed to the copper dispersion and the interaction between copper and the supports. In addition, water was used as the reaction media and the proton provider, the latter was found to be very important for the reaction. The XPS results suggested that the supported Cu(II) catalysts were reduced to catalytic Cu(I) species via alkynes homocoupling reaction. By means of IR and ESI-MS studies, a possible mechanism of cycloaddition based on the reduction of Cu(II) to Cu(I) species was proposed. Copyright

Full text of DOI:10.1002/adsc.201000868

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DOI: 10.1002/adsc.201000868
Insights into Supported Copper(II)-Catalyzed Azide-Alkyne
Cycloaddition in Water
Yan Wang,a,b Jianhua Liu,a,* and Chungu Xiaa,*
a
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences, No. 18 Tianshui Middle Road, Lanzhou 730000, Peopleꢀs Republic of China
Fax : (+86)-931-827-7088; e-mail: jhliu@licp.cas.cn or cgxia@licp.cas.cn
Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences
b
No. 19 Yuquan Road, Beijing 100049, Peopleꢀs Republic of China
Received: November 18, 2010; Revised: March 22, 2011; Published online: June 16, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000868.
Abstract: Cross-linked polymeric ionic liquid materi- of the catalysts could be ascribed to the copper dis-
al-supported copper (Cu-CPSIL), imidazolium- persion and the interaction between copper and the
loaded Merrifield resin-supported copper (Cu-PSIL) supports. In addition, water was used as the reaction
and silica dispersed CuO (CuO/SiO2), were prepared media and the proton provider, the latter was found
and proved to be efficient catalysts for the one-pot to be very important for the reaction. The XPS re-
synthesis of 1,4-disubsituted-1,2,3-triazoles by the re- sults suggested that the supported Cu(II) catalysts
action of alkyl halides with sodium azide and termi- were reduced to catalytic Cu(I) species via alkynes
nal alkynes in water at room temperature. Moreover, homocoupling reaction. By means of IR and ESI-MS
these supported copper catalysts were recovered studies, a possible mechanism of cycloaddition based
quantitatively from the reaction mixture by simple on the reduction of Cu(II) to Cu(I) species was pro-
filtration and reused for five consecutive recycles posed.
without significant loss of catalytic activity. Among
the three immobilized copper catalysts, Cu-CPSIL
exhibited excellent catalytic activity for the reaction Keywords: azide-alkyne cycloaddition; click chemis-
of aliphatic bromides, sodium azide and terminal al- try; reaction mechanism; recyclability; supported
kynes. The differences in the catalytic performances copper(II) catalysts; water
Introduction
copper N-heterocyclic carbene complexes[9] have also
been reported. Nonetheless, these catalysts are homo-
The copper-catalyzed azide-alkyne cycloaddition reac- geneous systems, suffering from the problem of sepa-
tion, as introduced independently by Meldal[1] and the ration of catalyst/product(s) and/or the requirement
Sharpless et al.,[2] is a representative example of click of adding reducing agents and stabilizing ligands.
chemistry, which proceeds with high regioselectivity
when terminal alkynes are used, providing 1,2,3-tri- and facile separation of products, immobilized cata-
ACHTUNGTRENNUNGazoles with 100% atom efficiency. This important re- lysts have attracted much attention in economical and
In recent years, due to their efficient recyclability
action has attracted a considerable amount of atten- environmentally benign chemical processes. A variety
tion in organic synthesis, medicinal chemistry, surface of supports such as polymer,[10] aluminum oxyhydrox-
and polymer chemistry, as well as bioconjugation ap- ide nanofibers,[11] activated charcoal,[12] zeolites,[13] hy-
plications.[3–5] Compared with other metals, the use of drotalcite[14]and magnetic material[15] supported Cu(I)
Cu(I) presents the major advantages of being inex- catalysts have been attempted for the azide-alkyne cy-
pensive and easy to handle.[6] Generally, the active cloaddition reaction. Nevertheless, the Cu(I) species
Cu(I) species could be obtained directly from Cu(I) in these catalysts is unstable and can be easily oxi-
salts (such as CuI chelated with protecting ligand)[7] dized to Cu(II) or disproportionate to Cu(0) and
or from in situ reduction of Cu(II) salts with organic Cu(II), which limited their utilization in practical pro-
agents[8] or from in situ oxidation of Cu(0) clusters. In cesses. More recently, Kamata et al. demonstrated
addition, some other new catalytic systems, such as that Cu(II) species could be reduced to Cu(I) species
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Insights into Supported Copper(II)-Catalyzed Azide-Alkyne Cycloaddition in Water
by alkyne during homocoupling reaction,[16] and they
successfully applied several immobilized Cu(II) cata-
lysts in the azide-alkyne cycloaddition reaction.[17]
High TOFs were obtained and an in-situ generated
Cu(I) species-catalyzed 1,3-dipolar cycloaddition
mechanism was also demonstrated by them. Nonethe-
less, organic solvents were generally required for
these catalyst systems to achieve high reactivity and
the reaction needs to be handled in an inert atmos-
phere. Furthermore, the theory that a Cu(I) species
was the catalytic active species was lacking detailed
characterizations for support in all the above reports.
Therefore, it is highly desirable to develop efficient
heterogeneous systems with high stability in a much
cleaner catalytic system and get more clear insights
into the catalytic mechanisms of the azide-alkyne cy-
cloaddition reaction.
Scheme 1. Synthesis of Cu-CPSIL from cross-linked poly-
mer.
In the present work, we have developed two sup-
ported Cu(II) catalysts [cross-linked polymeric ionic
liquid material-supported copper (Cu-CPSIL) and
imidazolium-loaded
Merrifield
resin-supported
copper (Cu-PSIL)] and applied them in the one-pot
synthesis of 1,2,3-triazoles via a three-component re-
action of benzyl or alkyl halides, sodium azide and
terminal alkynes under mild conditions without a re-
ducing agent. This reaction procedure avoids the han-
Scheme 2. Synthesis of Cu-PSIL from polymer-supported IL.
dling of organic azides, as they are generated in situ, Cu catalyst Cu-CPSIL was easily prepared with CuI
making this already powerful click process even more by a one-pot procedure similar to the synthesis of
user-friendly and safe.[19] High yields of 1,2,3-triazoles copper N-heterocyclic carbene complexes.[7a] The Cu
were cleanly synthesized in water at room tempera- content of Cu-CPSIL was calculated to be 6.4 wt% by
ture by both catalysts and the catalysts could be recy- the analysis with AAS (atomic absorption spectrosco-
cled for several times without significant loss of activi- py).
ty. For comparison, we also investigated the catalytic
As depicted in Scheme 2, imidazolium-loaded Mer-
performance of the heterogeneous CuO/SiO2 catalyst rifield resin-supported copper (Cu-PSIL) was derived
prepared by a precipitation-gel method. The effects of from CuI and imidazolium-loaded polymeric support
solvents and supports on the catalytic performances PSIL. The support was prepared in a typical proce-
were studied and discussed. Finally, a possible catalyt- dure from commercially available chloromethylpoly-
ic mechanism of supported copper(II)-catalyzed
ACHTUNGTRENsNGNU tyrene resin (1.0% cross-linked with DVB, spherical
azide-alkyne cycloaddition reaction was proposed beads, 100–200 mesh) with 1-methylimidazole in a
based on the detailed characterizations of the cata- typical procedure.[20] The Cu content of Cu-PSIL was
lysts by X-ray photoelectron spectra (XPS) and infra- calculated to be 8.0 wt% by the analysis with AAS.
red (IR) and the analysis of the reaction liquid by
electrospray ionization mass spectrometry (ESI-MS).
Silica-dispersed CuO (CuO/SiO2) was prepared
with the precipitation-gel method,[21] and the Cu con-
tent was 8.0 wt% (10.0 wt% CuO).
Results
Catalytic Performance of Click Reaction
Synthesis of Immobilized Copper Catalysts
In order to test the ability of our catalysts, we initial-
The synthesis of cross-linked polymeric ionic liquid ized the copper-catalyzed optimum azide-alkyne cy-
material-supported copper (Cu-CPSIL) is illustrated cloaddition conditions using sodium azide with benzyl
in Scheme 1. Starting with 1-vinylimidazole and 1-io- bromide (1a) and phenylacetylene (2a) as the bench-
dobutane, the monomer 3-butyl-1-vinylimidazolium mark substrates, as shown in Table 1. First, the effect
iodide ([VBIM]I) was prepared. Radical polymeri- of solvents on the Cu-CPSIL-catalyzed three-compo-
zation of [VBIM]I and divinylbenzene (DVB) using nent coupling reaction was examined. All cycloaddi-
azobis(isobutyronitrile) (AIBN) as the initiator af- tion reactions were carried out under an air atmos-
forded the cross-linked polymer,[19] from which the phere at room temperature. Among the solvents ex-
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Table 1. Effects of catalysts and solvent on reaction yield
after 48 h at room temperature.[a]
Scheme 3. Cu-PSIL-catalyzed reaction of n-octyl azide with
phenylacetylene.
Entry
Catalyst
Cu loading
Solvent
Yield[b] [%]
CPSIL as the catalyst, other aliphatic bromides (1b,
1c) also reacted easily with sodium azide and alkyne
affording 3ba, 3bc, 3bd, 3cc, 3ca in high yields. Un-
fortunately, aliphatic bromide such as 1b and 1c could
not offer 1,2,3-triazoles by reacting them with sodium
azide and alkyne directly in the reactions catalyzed by
Cu-PSIL and CuO/SiO2 (Table 2, entries 6–10).
Surprisingly, n-octyl azide, the product of nucleo-
philic substitution of n-octyl bromide with NaN3, pro-
vided 1-n-octyl-4-phenyl-1H-1,2,3-triazole 3ca in 97%
isolated yield when reacted with 2a in presence of
1.0 mol% Cu-PSIL in water, by stirring for 48 h at
room temperature. The result revealed that in Cu-
PSIL and CuO/SiO2 catalytic system, the nucleophilic
substitution of aliphatic bromide with azide was re-
strained (Scheme 3).
1
2
3
4
5
6
7
8
Cu-CPSIL
Cu-CPSIL
Cu-CPSIL
Cu-CPSIL
Cu-CPSIL
Cu-PSIL
CuO/SiO2
CuO/SiO2
CuO/SiO2
CuO/SiO2
CuO/SiO2
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
1.0 mol%
5.0 mol%
10.0 mol%
H2O
98
56
36
88
–
98
14
11
36
52
98
CH3OH
PhCH3
CH3CN
THF
H2O
CH3OH
CH3CN
H2O
H2O
H2O
9
10
11
[a]
Reaction conditions: NaN3 1.0 mmol, 1a 1.0 mmol, 2a
1.2 mmol, solvent 1.0 mL, room temperature, 48 h.
Isolated yield.
[b]
amined, water was the best solvent and gave a quanti-
tative yield of 1-benzyl-4-phenyl-1H-1,2,3-triazole
(3aa) (Table 1, entry 1). On further optimization of Recycle of the Three Supported Catalysts
the solvent conditions, methanol and toluene only
give poor isolated yields (Table 1, entries 2 and 3). The key property of supported catalysts is their ability
Replacement of H2O by acetonitrile gave a decreased for recovery and reuse, an essential perspective for
yield (88%) (Table 1, entry 4) and no triazole product green chemistry involving both ecological and eco-
was obtained in THF. Under the same optimal reac- nomic considerations. Thus, we evaluated the recycla-
tion conditions, the Cu-PSIL-catalyzed three-compo- bility of Cu-CPSIL, Cu-PSIL and CuO/SiO2 catalysts
nent coupling reaction also worked well and afforded in the three-component coupling reaction of sodium
3aa in 98% yield (Table 1, entry 6). For the inorganic azide with 1a and 2a in water at room temperature by
material supported catalyst system, the cycloaddition
of sodium azide with 1a and 2a catalyzed by
1.0 mol% CuO/SiO2 at room temperature by stirring
for 48 h proceeded sluggishly, a large decrease of
yield was observed under various solvent conditions
(Table 1, entries 7–9). The yield of product could be
remarkably improved merely by increasing the cata-
lyst loading (Table 1, entries 10 and 11).
With the optimal reaction conditions in hand, the
scope of the supported copper-catalyzed synthesis of
1,2,3-triazole was explored. Alkyl halides and termi-
nal arylalkynes were investigated at room tempera-
ture in H2O with 1.0 mol% Cu-CPSIL, 1.0 mol% Cu-
PSIL and 10.0 mol% CuO/SiO2 (Table 2). Benzyl bro-
mide 1a and benzyl chloride 1a’ could react with vari-
ous substituted phenylaceylenes 2a–2e providing 1,4-
disubstituded-1,2,3-triazoles 3 in over 90% yields in
the three copper-catalyzed systems (Table 2, en-
tries 1–5). However, the reaction rate of benzyl chlo-
ride 1a’ was slower than that of benzyl bromide 1a, so
Figure 1. The reusability of the Cu catalysts. Reaction condi-
tions: NaN3 1.0 mmol, 1a 1.0 mmol, 2a 1.2 mmol, distilled
water 1.0 mL, room temperature, 48 h, with 1.0 mol% Cu-
CPSIL, 1.0 mol% Cu-PSIL, or 10.0 mol% CuO/SiO2, The
that the reaction time must be enhanced to 72 h for
an equivalent transformation. Furthermore, with Cu- reaction time of the 5th recycle was enhanced to 72 h.
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Insights into Supported Copper(II)-Catalyzed Azide-Alkyne Cycloaddition in Water
Table 2. Supported copper-catalyzed azide-alkyne cycloaddition in water.[a]
Entry
R1X
R2
Product
Isolated yield [%]
Cu-CPSIL[c] Cu-PSIL[d] CuO/SiO2
[e]
1
2
3
4
5
1a
2a Ph
3aa
3ab
3ac
98
98
98
80
86
52
90
1a’
1a
96[b]
94[b]
2b 4-CH3-C6H4-
2c 4-C2H5-C6H4-
98
89
1a’
1a
95[b]
94
90[b]
98
1a’
1a
95[b]
92[b]
2d 4-CH3O-C6H4- 3ad
87
92
1a’
1a
80[b]
94
93[b]
98
2e 4-t-Bu-C6H4-
3ae
1a’
1b
93[b]
95[b]
6
7
8
2a
2c
2d
3ba
3bc
3bd
86
–
–
–
–
1b
1b
94
97
–
–
9
1c
1c
2e
2a
3cc
3ca
80
93
–
–
–
–
10
[a]
Reaction conditions: NaN3 1.0 mmol, 1a 1.0 mmol, 2a 1.2 mmol, distilled water 1.0 mL, room temperature, 48 h.
Reaction time is 72 h.
1.0 mol% copper loading.
1.0 mol% copper loading.
10.0 mol% copper loading.
[b]
[c]
[d]
[e]
stirring for 48 h. The catalysts could be separated by Discussion
simple centrifugation from the reaction. The results
obtained are presented in Figure 1. Obviously, the Procedure Study
three supported copper catalysts could be reused for
five consecutive trials without significant loss of cata- XPS Characterizations of Catalysts in the Catalytic
lytic activity in the reaction. It should be noted that Process
the color of all the catalysts changed from grey to
light yellow after the 1st run, which suggested that the To further study the procedure of this catalytic
valence state of copper in the three supported copper- system, the XPS (X-ray photoelectron spectra) char-
based catalysts had changed. After the 5th run, the acterization was employed to investigate the variation
copper contents in these supported complexes were of binding energy (BE) of Cu 2p3/2 in the three sup-
3.4 wt% (Cu-CPSIL), 4.7 wt% (Cu-PSIL) and ported catalytic systems and the transformation of the
5.6 wt% (CuO/SiO2) as determined by AAS, respec- valence state in the reaction process. We start our
tively. This indicated that the catalysts were very XPS study with Cu-CPSIL. The shift of BE of Cu
active, but unstable.
2p3/2 in the Cu-CPSIL system is shown in Figure 2.
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Figure 3. XPS analysis on Cu 2p3/2 of Cu-PSIL: (a) fresh cat-
alyst; (b) catalyst after reaction with 2a in water; (c) catalyst
after 1st reaction cycle; (d) CuI.
Figure 2. XPS analysis on Cu 2p3/2 of Cu-CPSIL: (a) fresh
catalyst; (b) catalyst after stirring with water; (c) catalyst
after reaction with alkyne 2a in water; (d) catalyst after 1st
reaction cycle; (e) catalyst after 5th reaction recycle; (f) CuI.
PSIL was reduced to Cu(I) in the reaction with
The BE of Cu 2p3/2 was located at 936.0 eV (Figure 2, alkyne and azide, what is more, different from the
a) corresponding to Cu(II) for fresh Cu-CPSIL cata- Cu-CPSIL system, the Cu species did not have the
lyst. The BE of the Cu 2p3/2 remained unchanged same presumed interaction with the polymer support,
after Cu-CPSIL had been stirred with water for 48 h and might be only a physical adsorption over the sur-
(Figure 2, b). Then, after Cu-CPSIL had reacted with face of PSIL.
2a in water, the BE of Cu 2p3/2 was detected at
For supported copper on inorganic material, similar
934.6 eV (Figure 2, c), along with the the detection of results could also be obtained from the XPS analysis
a diyne product by GC-MS, it could be proposed that of CuO/SiO2 in the catalytic process (Figure 4). The
the Cu(II) ions were reduced partly via phenylacety- BE of 2p3/2 of CuO species was 934.1 eV, thus the rel-
lene homocoupling. After a reaction cycle under the atively large BE shift of the Cu 2p3/2 core level for the
the standard conditions, the BE of Cu 2p3/2 of the Cu- catalyst was indicative of a charge transfer from the
CPSIL was located at 933.6 eV (Figure 2, d). It corre- copper ions toward the SiO2 support, that is, a strong
sponded to the Cu(I) state according with the interaction between copper and SiO2. A large Cu 2p3/2
CuLMM Augur kinetic energy peak (about 914.8 eV BE was observed when CuO/SiO2 reacted with 2a in
as shown in Figure 5, a). The BE of Cu 2p3/2 of Cu- water. After a one-pot reaction cycle, the BE of Cu
CPSIL after the 5th use remained unchanged com- 2p3/2 core levels was reduced to 932.8 eV correspond-
pared with that of Cu-CPSIL after the 1st use. In addi- ing to Cu(I) (CuLMM Augur kinetic energy peak
tion, compared with the BE of Cu 2p3/2 of CuI center was about 915.1 eV as shown in Figure 5, c),
(932.8 eV, Figure 2, f), the relatively large negative
BE shift of Cu(I) indicated that Cu-CPSIL catalyst
was not a simple physical adsorption of CuI on the
cross-linked polymer. Thus we speculated that the
cross-linked polymer supports may act as a ligand sta-
bilizing the Cu species with a strong interaction.
The XPS study on Cu-PSIL was also investigated in
the general procedure as Cu-CPSIL, and similar re-
sults were obtained. As shown in Figure 3, the BE of
Cu 2p3/2 of fresh Cu-PSIL, the catalyst reacted with 2a
and the reused catalyst after a successive reaction re-
cycle were detected at 936.2 eV, 933.7 eV and
933.0 eV, respectively (Figure 3, a, b, c). The BE of
Cu 2p3/2 of Cu-PSIL after reaction was as same as that
of CuI (932.8 eV, Figure 3, d), and corresponded to
the Cu(I) state obtained by XPS analysis of the
CuLMM Augur kinetic energy peak of the Cu-PSIL
catalyst after click reaction (about 914.7 eV,
Figure 4. XPS analysis on Cu 2p3/2 of CuO/SiO2: (a) fresh
catalyst; (b) catalyst after stirring with 2a in water; (c) cata-
a
Figure 5, b). The results illustrated that Cu(II) of Cu- lyst after 1st reaction cycle.
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Insights into Supported Copper(II)-Catalyzed Azide-Alkyne Cycloaddition in Water
different from the BE of Cu2O (932.5 eV). In summa-
ry, large BE shifts of the Cu 2p3/2 core level for the
three catalysts were observed when the supported cat-
alysts reacted with 2a. The alkyne-alkyne homocou-
pling may proceed on the Cu(II)I site to form the cor-
responding diyne and the catalytically active Cu(I)
species on either the organic material or inorganic
material (Scheme 4).
Mechanism Study
By analogy with previous reports,[13a,16a,22] the pro-
posed mechanism for this transformation is depicted
in Figure 6. Firstly, the alkyne-alkyne homocoupling
proceeds on the Cu(II)I site to form the catalytically
active Cu(I) species. After the Cu(I) species has been
generated, the cycloaddition likely proceeds via the
reaction mechanism proposed by Sharpless and co-
workers.[22]
Figure 5. XPS analysis of CuLMM Augur kinetic energy
peaks: (a) Cu-CPSIL catalyst after 1st reaction cycle; (b)
Cu-PSIL catalyst after 1st reaction cycle; (c) CuO/SiO2 cata-
lyst after 1st reaction cycle.
To get a deeper insight into the mechanism of the
supported-Cu-catalyzed reaction, IR characterization
was performed and the results are illustrated in
Figure 7. Compared with the fresh Cu-CPSIL, new
bands appeared at 2361 cmÀ1 and 3140 cmÀ1 after the
1st reaction cycle, which were assigned to the C C
Scheme 4. Formation of Cu(I) via alkyne homocoupling.
ꢀ
Figure 6. Proposed reaction mechanism for the Cu(II)-catalyzed click reaction.
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Yan Wang et al.
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firmed that water played the role as a proton provid-
er.
Additionally, the catalytic system is a two-phase
system when water is used as the solvent, so that the
intermediate NaBr could dissolve in H2O and be sep-
arated conveniently from the reaction mixture. There-
fore, such a two-phase system could promote the
yield of triazoles as a result.[24]
Besides the role of solvents, the effect of different
copper catalysts on the catalytic activity was also in-
vestigated under the same conditions (room tempera-
ture, water as solvent, air atmosphere). In the forma-
tion of 3 from 1, 2 and sodium azide, the Cu loadings
of Cu-CPSIL, Cu-PSIL catalyst and the CuO/SiO2
catalyst had to be 1.0 mol%, 1.0 mol% and
10.0 mol% to achieve equivalent transformations, re-
spectively. From the TEM micrographs of the three
catalysts (Supporting Information, Figure S3), it is
clearly observed that Cu species are dispersed granu-
larly and uniformly on the surface of Cu-CPSIL and
Cu-PSIL, the average size of the Cu nanoparticles is
Figure 7. IR analysis of Cu-CPSIL and the catalyst after 1st
cycle: (a) fresh Cu-CPSIL; (b) Cu-CPSIL catalyst after 1st
reaction cycle.
À
stretch vibration and the C H stretch vibration of the about 1-2 nm, while the apparent lumpy Cu conglom-
Cu(I) acetylide complex. According to this result, we eration on SiO2 appeared as shown in Supporting In-
can propose that the Cu-catalyzed cycloaddition reac- formation, Figure S3c. Hence, in the solid-liquid
tion relies on the intermediate formation of copper phase reaction system, Cu species on CPSIL and
acetylides (A, B in Figure 6). The ligand exchange PSIL had more chances to contact with reactants than
process of p-alkyne copper deprotonated in an aque- those over SiO2 did. In addition, the Cu-CPSIL cata-
ous medium forming s-alkyne copper is nearly ther- lyst was superior to the other two copper catalysts in
moneutral computationally.[23] To study this hypothe- the reaction with aliphatic bromides. This was attrib-
sis further, we examined the liquid phase of the reac- uted to the following two reasons: firstly, the copper
tion mixture after the reaction cycle of 1a, 2a and species on the CPSIL showed high dispersion; second-
sodium azide by ESI-MS (Supporting Information, ly, the interaction between Cu species and CPSIL was
Figure S1), which were catalyzed by the three immo- different from that of the Cu-PSIL and CuO/SiO2 sys-
bilized copper catalysts.
tems which was confirmed by the XPS analysis above.
Triazole molecular cationic species [Triazo- More specifically, a metal-carbon bond such as car-
lePhCH2]+ and copper anionic species [CuBr2]À were bene may be formed in the presence of the strong in-
detected in solution. The copper anionic species des- teraction between copper and the cross-linked poly-
orbed from the supports so we can propose the occur- mer CPSIL. The NHC ligand on the copper center
rence of an H/Cu exchange process and explain the acted as a base and deprotonated the starting alkyne
loss of copper from the supported catalysts to a cer- to initiate the catalytic cycle[25] and such a structure
tain extent. Therefore, the mechanism involves the with a metal-carbon bond promoted the nucleophilic
formation of Cu(I) species by reduction of Cu(II) and substitution of aliphatic halides with sodium azide.
copper acetylides in the reaction recycle.
That the catalytic results occur only when water is
used as the solvent, supports the idea that copper cat- Conclusions
alysts can lead to an equivalent transformation in the
three-component reaction for the direct synthesis of In summary, Cu-CPSIL, Cu-PSIL and CuO/SiO2 cata-
1,2,3-triazoles at room temperature. Hence, it is nec- lysts were prepared using straightforward procedures
essary to investigate the promotion effect of water in and their catalytic activity in the one-pot synthesis of
the reaction. We applied deuterated water (D2O) as triazoles was investigated. Water proved to be the
the solvent in the reaction of benzyl bromide, sodium most suitable solvent in the one-pot synthetic reaction
azide and phenylaceylene with 1.0 mol% Cu-CPSIL due to its proton providing ability. All the supported
at room temperature. The product 3aa was analyzed catalysts exhibited high activity towards the formation
by NMR spectrometry after chromatographic purifi- of 1,4-disubstituted-1,2,3-triazoles from benzyl halides
1
cation. From the H NMR shown in the Supporting in water at room temperature. This is attributed to
Information, Figure S2, 84% of the olefinic hydrogen the fact that the valence state of Cu species changed
was replaced by deuterium from D2O. This result con- from Cu(II) to Cu(I) by reductive elimination via
1540
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 1534 – 1542

Insights into Supported Copper(II)-Catalyzed Azide-Alkyne Cycloaddition in Water
5686; c) Y. Xia, W. Li, F. Qu, Z. Fan, X. Liu, C. Berro,
alkyne-alkyne homocoupling. Whatꢀs more important,
the Cu-CPSIL system promoted the one-pot reaction
with aliphatic bromides giving excellent isolated
yields for the strong interaction between copper spe-
cies and cross-linked polymer. The recyclability tests
of catalysts showed high catalytic activity over each
subsequent cycle. This indicated that the three sup-
ports acted as ligands stabilizing the copper particles.
Based on XPS, IR and ESI-MS characterizations, a
mechanism was proposed as follows: the alkyne-
alkyne homocoupling proceed on the Cu(II) site to
form the catalytically active Cu(I) species, and the cy-
cloaddition proceeded over the active Cu(I) species
generated.[22] We believe that the excellent nature of
these immobilized, supported copper catalysts will
help in a better understanding of heterogeneous
Cu(II) catalysts in click reactions.
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General Procedure for the One-Pot Direct Synthesis
of 1,2,3-Triazoles
A 10-mL flask fitted with a magnetic stirred, the catalyst,
sodium azide (1.0 mmol, 65 mg), alkyl halide 1 (1.0 mmol)
and arylalkyne 2 (1.2 mmol) were added and stirred in the
desired solvent (1.0 mL) at room temperature for 48–72 h.
The reaction mixture was diluted with ethyl acetate and
then analyzed by GC-MS. The organic phase was worked up
by removing the solvent under vacuum and the residue was
purified by chromatography on silica gel (ethyl acetate:
petroleum ether=1:10). For the reuse process, in each cycle,
the catalyst was separated by centrifugation after reaction
and dried under vacuum before the next cycle.
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This work was financially supported by the National Natural
Science Foundation of China (No. 20625308, 21073209).
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