SiO2-NHC-Cu(I): an efficient and reusable catalyst for [3+2] cycloaddition of organic azides and terminal alkynes under solvent-free reaction conditions at room temperature

Article abstract of DOI:10.1016/j.tet.2008.09.021

A novel SiO₂-NHC-Cu(I) 3b was developed and used as a highly efficient catalyst for [3+2] cycloaddition of organic azides and terminal alkynes. In the presence of SiO₂-NHC-Cu(I) 3b (1 mol %), the reactions of terminal alkynes with or

Full text of DOI:10.1016/j.tet.2008.09.021

Tetrahedron 64 (2008) 10825–10830
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
SiO2–NHC–Cu(I): an efficient and reusable catalyst for [3þ2]
cycloaddition of organic azides and terminal alkynes under
solvent-free reaction conditions at room temperature
,
b
,
a
Pinhua Li a, Lei Wang a , Yicheng Zhang
*
a Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 June 2008
Received in revised form 23 August 2008
Accepted 5 September 2008
Available online 17 September 2008
A novel SiO2–NHC–Cu(I) 3b was developed and used as a highly efficient catalyst for [3þ2] cycloaddition
of organic azides and terminal alkynes. In the presence of SiO2–NHC–Cu(I) 3b (1 mol %), the reactions of
terminal alkynes with organic azides underwent smoothly to generate the corresponding regiospecific
1,4-disubstituted 1,2,3-triazoles in excellent yields under solvent-free reaction conditions at room
temperature. Furthermore, catalyst 3b was quantitatively recovered from the reaction mixture by
a simple filtration and reused for 10 cycles without loss of its activity.
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
SiO2–NHC–Cu(I)
[3þ2] Cycloaddition
Recyclable
Organic azides
Alkynes
Solvent-free
1. Introduction
regioselectivity, wide substrate scope, mild reaction conditions,
effective catalysis system and high yields have made it the method
1,2,3-Triazoles have been widely used in synthetic intermediates
and industrial applications, such as dyes, anticorrosive agents,
photostabilizers, photographic materials, and agrochemicals.1 Al-
though the 1,2,3-triazole structural moiety does not occur in na-
ture, it may display biological activities and there are numerous
examples in the literature including anti-HIV activity,2 anti-mi-
crobial activity against Gram positive bacteria,3 anti-allergic,4 anti-
of choice for making permanent connections by means of 1,4-di-
substituted 1,2,3-triazoles in the presence of copper catalyst. The
catalyst can be introduced as a Cu(I) salt generated in situ by re-
duction of Cu(II) salts,12 comproportionation of Cu(0) and Cu(II),13
Cu(0) nanosize cluster,14 and Cu(II) salt.15 However, little attention
has been paid to cuprous salts due to their inherent thermody-
namic instability and the formation of undesired alkyne–alkyne
homo-coupling products observed in their presence.11b On the
other hand, a Ru(II) complex was used for the reaction only to give
the corresponding 1,5-disubstituted 1,2,3-triazoles with complete
conversion.16 It should be noted that the high cost of transition
metal catalysts coupled with the toxic effects associated with many
transition metals has led to an increasing interest in immobilizing
catalysts onto a support. This class of supported reagent can
facilitate both the isolation and recycling of the catalyst by filtra-
tion, thus providing environmentally cleaner processes.17
convulsant,5
b b3 adrenergic re-
-lactamase inhibitory,6 selective
ceptor agonism,7 et al.8
Numerous synthetic methods for the preparation of 1,2,3-tri-
azole derivatives have been developed. Among them, Huisgen 1,3-
dipolar cycloaddition between an alkyne and an azide is the clas-
sical and extensively used method.9 However, the regioselectivity
of this cycloaddition reaction is generally low and the reaction
usually leads to a mixture of 1,4- and 1,5-regioisomer.10 Cu(I)-cat-
alyzed ligation (click chemistry) of organic azides and terminal
alkynes has enjoyed much use since its discovery independently by
the groups of Sharpless and Meldal in 2002.11 Exclusive
N-Heterocyclic carbenes (NHCs) are widely used as ligands in
inorganic and organometallic chemistry since Arduengo and co-
workers isolated the first stable N-heterocyclic carbene.18 NHCs
were first considered as simple phosphine mimics in organome-
tallic chemistry.19 However, increasing experimental data clearly
show that NHC–metal catalysts can surpass their phosphine-based
* Corresponding author. Tel.: þ86 561 380 2069; fax: þ86 561 309 0518.
E-mail address: leiwang@hbcnc.edu.cn (L. Wang).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.021

10826
P. Li et al. / Tetrahedron 64 (2008) 10825–10830
counterparts in both activity and scope.20 NHCs are stronger
-donors and weaker -acceptors, making the properties of NHC–
a model [3þ2] cycloaddition reaction of benzyl azide and phenyl-
acetylene at room temperature in C2H5OH. The results are listed in
Table 1. The influence of a substituted group of imidazolium salts in
3a–3d on their catalytic activity for [3þ2] cycloaddition is
C6H5CH2>C6H5>t-C4H9>CH3. It is obvious that when 3a–3d were
used in the Huisgen [3þ2] cycloaddition, however, several catalysts
gave quite similar yields (65, 81, 77, 72%) according to the results
from Table 1, entries 1–4.
The effect of solvent on [3þ2] cycloaddition of benzyl azide and
phenylacetylene using 3b as catalyst was investigated (Table 1,
entries 5–14). Among the solvents tested in Table 1, acetone, DMSO,
DMF, CH3OH, C2H5OH and CH2Cl2 were the most suitable reaction
media for [3þ2] cycloaddition (Table 1, entries 5–9). CH3CN,
C2H5OC2H5 and H2O were inferior and generated the corresponding
products in 71–79% yields (Table 1, entries 10–12), whereas toluene
and THF afforded moderate yields of desired products (Table 1,
entries 13 and 14). Surprisingly, 93% yield of the desired product
was isolated when the reaction was carried out under neat reaction
conditions (Table 1, entry 15). To avoid the use of volatile solvents
and reduce the environmental pollution, all [3þ2] cycloaddition
reactions were performed under solvent-free reaction conditions.
The optimized reaction conditions for this [3þ2] cycloaddition re-
action are SiO2–NHC–Cu(I) catalyst 3b (1 mol %) under neat re-
action conditions at room temperature for 0.5 h.
s
p
metal complexes notably different from a corresponding phosphine
complex. Because of their specific coordination chemistry, NHCs
both stabilize and activate metal centres in quite different key
catalytic steps of organic syntheses, such as, C–C, C–H, C–O, C–N
bond formations and cycloaddition.21 To avoid catalyst leaching,
polymer-, PEG- or silica-supported NHC–metal complexes were
synthesized and applied successfully to organic reactions.22
We herein report an efficient SiO2–NHC–Cu(I) 3b heterogeneous
catalyst for [3þ2] cycloaddition of organic azides and terminal al-
kynes. In the presence of 3b (1 mol %), the reactions of terminal
alkynes with organic azides underwent smoothly to generate the
corresponding regiospecific 1,4-disubstituted 1,2,3-triazoles in ex-
cellent yields under solvent-free reaction conditions at room
temperature. Furthermore, 3b catalyst was quantitatively re-
covered from the reaction mixture by a simple filtration and reused
for 10 cycles without loss of its activity (Scheme 1).
Cl3Si
CH2Cl
CH2Cl
OH
Toluene, 120 °C
SiO2
SiO2
1
To examine the scope of the Huisgen [3þ2] cycloaddition of or-
ganic azides and alkynes, a variety of organic azides reacted with
terminal alkynes smoothly and generated the corresponding 1,4-
disubstituted 1,2,3-triazoles in good yields in a short reaction time
underoptimized reaction conditions. Theresults are listed inTable 2.
At the beginning of the search for the organic azides substrate scope,
different azides with phenylacetylene used as a model substrate
were examined (Table 2, entries 1–11). The results indicated that the
reactions of benzyl azide and its analogues (Table 2, entries 1–3), as
well as phenyl azides and its derivatives (Table 2, entries 4–6), with
phenylacetylene proceeded smoothly to complete within 0.5 h, and
the corresponding 1,4-disubstituted 1,2,3-triazoles were isolated in
excellent yields and high purity after simple filtration or extraction.
N
N
R
Toluene, 80 °C
CuI, t-BuOK
N
THF, r.t.
N
SiO2
SiO2
Cl
N
R
Cu
N
R
I
2
a: R = CH3
b: R = C6H5CH2
c: R = C6H5
3
_
_
SiO2 NHC Cu(I)
d: R = t-C4H9
R1
N
SiO2-NHC-Cu(I) (1 mol%)
neat
N
N
R1 N3
R2
R3
+
Table 1
R1 = Aromatic, Aliphatic
Effect of catalyst and solvent on Huisgen [3þ2] cycloadditiona
R2
R3
R
R
2 = Aromatic, Aliphatic
3 = H or Aromatic
N
[Cu] catal.
+
N3
N
N
Ph
Ph
Ph
solvent, RT
Scheme 1.
Ph
Entry
Catalyst
Solvent
Yieldb(%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3a
3c
3d
3b
C2H5OH
C2H5OH
C2H5OH
C2H5OH
CH3COCH3
DMSO
DMF
CH3OH
CH2Cl2
CH3CN
C2H5OC2H5
H2O
Toluene
THF
Neat
Neat
Neat
65
81
77
72
89
88
85
84
83
79
78
71
68
63
93
76
88
81
61c
2. Results and discussion
The synthesis of a number of SiO2–NHC–Cu(I) catalysts was
shown in Scheme 1. They were readily prepared in good yields
through a straightforward three-step procedure from commercially
available starting materials and reagents. The activated silica
reacted with trichloro[4-(chloromethyl)phenyl]silane in dry tolu-
ene at 120 ꢀC under an inert atmosphere for 24 h to afford the
benzyl chloride functionalized silica 1. The obtained 1 was then
reacted with N-substituted imidazoles in toluene at 80 ꢀC for 24 h
to generate the corresponding silica supported ionic liquids 2a–2d,
respectively. Then, the ionic liquids 2a–2d reacted with freshly
prepared CuI in the presence of t-BuOK in dry THF at room tem-
perature for 6 h under an inert atmosphere and the corresponding
SiO2–NHC–Cu(I) catalysts 3a–3d, as a grey-green powders, were
obtained. The copper metal amounts of 3a–3d were found to be
0.86, 0.87, 0.85 and 0.82 mmol gꢁ1, respectively, based on in-
ductively coupled plasma (ICP) analysis.
9
10
11
12
13
14
15
16
17
18
19
Neat
Neat
a
Reaction conditions: benzyl azide (1.0 mmol), phenylacetylene (1.0 mmol),
SiO2–NHC–Cu(I) (1 mol %), solvent (0.5 mL), nitrogen atmosphere at room temper-
ature for 0.5 h.
b
Our initial investigation was focused on the catalytic activity of
SiO2–NHC–Cu(I) catalysts 3a–3d. The above catalysts were used in
Isolated yields.
c
Using 0.5 mol % of 3b.

P. Li et al. / Tetrahedron 64 (2008) 10825–10830
10827
Table 2
Table 3
[3þ2] Cycloaddition of azides and alkynes catalyzed by 3ba
Successive trials using recoverable 3b as catalysta
R1
Reused 3b
neat, r. t.
N
N
3b (1.0 mol %)
R1 N3
Ph
N3
+
Ph
N
N
R2
R3
Ph
N
N
+
neat
R2
R3
Ph
Yieldb (%)
Cycle
Yieldb (%)
Cycle
Yieldb (%)
Entry
Organic azide
Alkyne
T (h)
1
2
3
4
5
93
93
91
92
89
6
7
8
9
10
92
90
90
88
87
1
2
3
4
5
6
7
8
9
C6H5CH2N3
p-CH3C6H4CH2N3
p-NO2C6H4CH2N3
C6H5N3
p-CH3C6H4N3
p-ClC6H4N3
n-C6H13N3
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
C6H5C^CH
0.5
0.5
0.5
0.5
0.5
0.5
3
93
95
97
90
88
89
87
90
86
a
Reaction conditions: benzyl azide (1.0 mmol), phenylacetylene (1.0 mmol),
reused SiO2–NHC–Cu(I) 3b (1 mol %), nitrogen atmosphere under neat reaction
conditions at room temperature for 0.5 h.
n-C8H17N3
n-C10H21N3
3
3
b
Isolated yields.
N3
10
C6H5C^CH
3
3
91
N
H
reaction by adding substrates to a filtrate obtained from the fil-
tration of the supported catalyst after the reaction.
N3
11
C6H5C^CH
90
OH
C6H5CH2N3
C6H5CH2N3
C6H5CH2N3
C6H5CH2N3
C6H5CH2N3
C6H5CH2N3
C6H5CH2N3
12
13
14
15
16
17
18
p-CH3C6H4C^CH
p-ClC6H4C^CH
p-BrC6H4C^CH
n-C6H13C^CH
C2H5O2CC^CH
HOCH2C^CH
0.5
0.5
0.5
3
3
3
96
98
95
82
97
91
3. Conclusion
In conclusion, we have successfully developed a versatile, highly
efficient and environmentally friendly catalytic system for the
Huisgen [3þ2] cycloaddition of organic azides and alkynes by using
SiO2–NHC–Cu(I) 3b as catalyst (1 mol %) at room temperature un-
der solventless reaction conditions. The reactions generated the
corresponding 1,4-disubstituted 1,2,3-triazoles in high yields and
were applicable to aromatic and aliphatic organic azides and
alkynes. In addition, this methodology offers the competitive of
recyclability of the catalyst without significant loss of its activity,
and the catalyst could be readily recovered and reused for 10 cycles,
thus making this procedure more environmentally acceptable
whilst no catalyst leaching was observed. Further investigation on
the application of this kind of supported catalysts in organic syn-
thesis, as well as in asymmetric organic reaction is still underway in
our laboratory.
C6H5C^CC6H5
24
54c
a
Reaction conditions: organic azide (1.0 mmol), alkyne (1.0 mmol), SiO2–NHC–
Cu(I) 3b (1 mol %), nitrogen atmosphere under neat reaction conditions at room
temperature for 0.5–3 h.
b
Isolated yields.
At 80 ꢀC for 24 h.
c
As is evident from the above results, electron-donating group (such
as CH3) or electron-withdrawing groups (such as NO2 and Cl) and
theirlocations on the aromatic ring had little effect on the reaction. It
is interesting to note that the reactions of alkyl azides, except
benzylic ones, with phenylacetylene led to slower reactions and
generated the products in high yields within 3 h (Table 2, entries
7–11). Subsequently, a variety of alkynes were also examined for the
Huisgen[3þ2] cycloaddition byusing benzyl azide-terminal alkynes
combination (Table 2, entries12–17). As canbe seenfromtheTable 2,
both of the reactivity of aliphatic and aromatic alkynes was ob-
served, in which aromatic alkynes were often much more reactive
than aliphatic alkynes. Aromatic alkynes, such as phenylacetylene,
p-methylphenylacetylene, p-chlorophenylacetylene and p-bromo-
phenylacetylene were able to undergo ‘click reaction’ smoothly and
generated the corresponding products in excellent yields within
0.5 h (Table 2, entries 1 and 12–14). On the other hand, the reactions
involving aliphatic alkynes also gave both higher conversions
and isolated yields, leading to the corresponding 1,4-disubstituted
1,2,3-triazoles in greater yields after 3 h (Table 2, entries 15–17).
However, disubstituted acetylene, such as diphenylacetylene could
not react with benzyl azide under the optimized reaction conditions
at room temperature, and 54% yield of the desired product was
isolated after 24 h at 80 ꢀC (Table 2, entry 18).
The recyclability of SiO2–NHC–Cu(I) catalyst 3b was also in-
vestigated. After the reaction, the catalyst 3b was separated by
simple filtration and washed with acetone. After being dried, it
could be reused directly without further purification. The recovered
catalyst was used in the next run and almost consistent activity was
observed for 10 consecutive cycles (Table 3, entries 1–10). Mean-
while, copper leaching in 3b was determined. Inductively coupled
plasma (ICP) analyses of the clear filtrates obtained by filtration
after the reaction indicated that Cu content is <0.1 ppm. However,
only trace amount of the desired product was isolated for the model
4. Experimental
4.1. Physical measurements and materials
All 1H NMR spectra were recorded at 300 MHz MHz by Bruker
FT-NMR spectrometers. Chemical shift are given as
d value with
reference to tetramethylsilane (TMS) as internal standard. IR spectra
were obtained by using a Nicolet NEXUS 470 spectrophotometer.
The CHN analysis was performed on a Vario El III elementar. The Cu
content was determined by a Jarrell-Ash 1100 ICP analysis. Specific
surface areas and pore volumes of the samples were determined in
a Micromeritics ASAP-2000 automated nitrogen physisorption
apparatus and calculated according to the BET method. Products
were purified by flash chromatography on 230–400 mesh silica
gel, SiO2.
The chemicals were purchased from commercial suppliers
(Aldrich, USA and Shanghai Chemical Company, China) and were
used without purification prior to use.
4.2. Preparation of benzyl chloride functionalized silica 1
Into a 100 mL of round-bottomed flask, were introduced suc-
cessively 30 mL of anhydrous toluene, 5.0 g of activated silica, and
2.0 g of trichloro[4-(chloromethyl)phenyl]silane. The solution was
refluxed for 24 h at 120 ꢀC under an inert atmosphere. The solution
was filtered and the solid was washed subsequently with toluene,
dichloromethane and methanol, and dried under reduced pressure

10828
P. Li et al. / Tetrahedron 64 (2008) 10825–10830
at 80 ꢀC for 10 h. The benzyl chloride functionalized silica 1 was
obtained (5.81 g).17i The loading of the modified silica was readily
quantified via CHN microanalysis and found to be 1.12 mmol gꢁ1
based on C percentage. The surface area and pore volume of the
4.7. Preparation of SiO2–NHC–Cu(I) catalyst 3a
In an oven-dried Schlenk flask, freshly prepared CuI (0.190 g,
1.0 mmol), NaO-t-Bu (0.096 g, 1.0 mmol), 2a (1.1 g) and THF (5 mL)
were added. The resulting suspension was stirred at room tem-
perature for 6 h under an inert atmosphere. Then the solution was
filtered and the solid was washed with water, methanol, acetone,
respectively, and dried under vacuum at 60 ꢀC for 12 h. The SiO2–
NHC–Cu(I) catalyst 3a was obtained as a grey-green powder
(1.14 g).23 The copper metal amount of 3a was found to be
0.86 mmol gꢁ1 based on ICP analysis. The surface area and pore
volume of 3a were found to be 235 m2 gꢁ1 and 0.32 cm3 gꢁ1, re-
modified silica were found to be 433 m2 gꢁ1 and 0.53 cm3 gꢁ1
,
respectively.
4.3. Preparation of silica supported ionic liquid 2a
Under nitrogen atmosphere, N-methylimidazole (0.41 g,
5.0 mmol) and benzyl chloride functionalized silica 1 (2.0 g, loading
1.12 mmol gꢁ1) were mixed in toluene (15 mL) in a round-bottomed
flask. The reaction was carried out at 80 ꢀC for 24 h. Then the so-
lution was filtered and the solid was washed with chloroform,
methanol and ethyl acetate, respectively, and dried under vacuum
at 60 ꢀC; 2.08 g of a pale powder 2a was obtained.17e The loading of
2a was quantified via CHN microanalysis and found to be
0.96 mmol gꢁ1 based on N percentage. The surface area and pore
volume of 2a were found to be 319 m2 gꢁ1 and 0.43 cm3 gꢁ1, re-
spectively. 29Si NMR (solid):
d
¼ꢁ78.7 (br, SiC), ꢁ111.5 (br,
SiO2) ppm. IR (KBr):
n
¼1668, 1553, 1457, 1097 cmꢁ1
.
4.8. Preparation of SiO2–NHC–Cu(I) catalyst 3b
In an oven-dried Schlenk flask, freshly prepared CuI (0.190 g,
1.0 mmol), t-BuONa (0.096 g, 1.0 mmol), 2b (1.1 g) and THF (5 mL)
were added. The resulting suspension was stirred at room tem-
perature under an inert atmosphere for 6 h. Then the solution was
filtered, and the solid was washed with water, methanol, acetone
and dried under vacuum at 60 ꢀC for 12 h. The SiO2–NHC–Cu(I)
catalyst 3b was obtained as a grey-green powder (1.15 g). The
copper content of 3b was found to be 0.87 mmol gꢁ1 based on ICP
analysis. The surface area and pore volume of 3b were found to be
spectively. 29Si NMR (solid):
d
¼ꢁ79.4 (br, SiC), ꢁ111.5 (br,
SiO2) ppm. IR (KBr):
n
¼1643, 1513, 1438, 1089 cmꢁ1
.
4.4. Preparation of silica supported ionic liquid 2b
Under nitrogen atmosphere, N-benzylimidazole (0.790 g,
5.0 mmol) and benzyl chloride functionalized silica 1 (2.0 g, loading
1.12 mmol gꢁ1) were mixed in toluene (15 mL) in a round-bottomed
flask. The reaction was carried out at 80 ꢀC for 24 h. Then the so-
lution was filtered, and the solid was washed with toluene, meth-
anol and ethyl acetate, and dried under vacuum at 60 ꢀC to yield
2.20 g of silica supported ionic liquid 2b as a pale powder, and its
loading was quantified by CHN microanalysis and found to be
0.97 mmol gꢁ1 based on the N content. The surface area and pore
volume of 2b were found to be 321 m2 gꢁ1 and 0.45 cm3 gꢁ1, re-
238 m2 gꢁ1 and 0.34 cm3 gꢁ1
¼ꢁ78.5 (br, SiC), ꢁ111.5 (br, SiO2) ppm. IR (KBr):
1209 cmꢁ1
,
respectively. 29Si NMR (solid):
d
n
¼1666, 1498,
.
4.9. Preparation of SiO2–NHC–Cu(I) catalyst 3c
In an oven-dried Schlenk flask, freshly prepared CuI (0.190 g,
1.0 mmol), t-BuONa (0.096 g, 1.0 mmol), 2c (1.1 g) and THF (5 mL)
were added. The resulting suspension was stirred at room tem-
perature under an inert atmosphere for 6 h. Then the solution was
filtered, and the solid was washed with water, methanol, acetone
and dried under vacuum at 60 ꢀC for 12 h. The SiO2–NHC–Cu(I)
catalyst 3c was obtained as a grey-green powder (1.13 g). The
copper content of 3c was found to be 0.85 mmol gꢁ1 based on ICP
analysis. The surface area and pore volume of 3c was found to be
spectively. 29Si NMR (solid):
d
¼ꢁ79.2 (br, SiC), ꢁ111.5 (br,
SiO2) ppm. IR (KBr):
n
¼1640, 1453, 1147 cmꢁ1
.
4.5. Preparation of silica supported ionic liquid 2c
Under nitrogen atmosphere, N-phenylimidazole (0.720 g,
5.0 mmol) and benzyl chloride functionalized silica 1 (2.0 g, loading
1.12 mmol gꢁ1) were mixed in toluene (15 mL) in a round-bottomed
flask. The reaction was carried out at 80 ꢀC for 24 h. Then the so-
lution was filtered, and the solid was washed with toluene, meth-
anol and ethyl acetate, and dried under vacuum at 60 ꢀC to yield
2.18 g of silica supported ionic liquid 2c as a pale powder, and its
loading was quantified by CHN microanalysis and found to be
0.95 mmol gꢁ1 based on the N content. The surface area and pore
volume of 2c were found to be 316 m2 gꢁ1 and 0.44 cm3 gꢁ1, re-
231 m2 gꢁ1 and 0.32 cm3 gꢁ1
¼ꢁ78.3 (br, SiC), ꢁ111.5 (br, SiO2) ppm. IR (KBr):
1551, 1123 cmꢁ1
,
respectively. 29Si NMR (solid):
d
n
¼1671, 1603,
.
4.10. Preparation of SiO2–NHC–Cu(I) catalyst 3d
In an oven-dried Schlenk flask, freshly prepared CuI (0.190 g,
1.0 mmol), t-BuONa (0.096 g, 1.0 mmol), 2d (1.1 g) and THF (5 mL)
were added. The resulting suspension was stirred at room tem-
perature under an inert gas for 6 h. Then the solution was filtered,
and the solid was washed with water, methanol, acetone and dried
under vacuum at 60 ꢀC for 12 h. The SiO2–NHC–Cu(I) catalyst 3d
was obtained as a grey-green powder (1.12 g). The copper content
of 3d was found to be 0.82 mmol gꢁ1 based on ICP analysis. The
surface area and pore volume of 3d were found to be 227 m2 gꢁ1
spectively. 29Si NMR (solid):
d
¼ꢁ79.0 (br, SiC), ꢁ111.5 (br,
SiO2) ppm. IR (KBr):
n
¼1636, 1555, 1497, 1098 cmꢁ1
.
4.6. Preparation of silica supported ionic liquid 2d
Under nitrogen atmosphere, N-tert-butylimidazole (0.620 g,
5.0 mmol) and benzyl chloride functionalized silica 1 (2.0 g, loading
1.12 mmol gꢁ1) were mixed in toluene (15 mL) in a round-bottomed
flask. The reaction was carried out at 80 ꢀC for 24 h. Then the so-
lution was filtered, and the solid was washed with toluene, meth-
anol and ethyl acetate, and dried under vacuum at 60 ꢀC to yield
2.17 g of silica supported ionic liquid 2d as a pale powder, and its
loading was quantified by CHN microanalysis and found to be
0.92 mmol gꢁ1 based on the N content. The surface area and pore
volume of 2d were found to be 317 m2 gꢁ1 and 0.43 cm3 gꢁ1, re-
and 0.31 cm3 gꢁ1, respectively. 29Si NMR (solid):
d
¼ꢁ78.4 (br, SiC),
ꢁ111.5 (br, SiO2) ppm. IR (KBr):
n
¼1647, 1562, 1402, 1094 cmꢁ1
.
4.11. Typical procedure for [3D2] cycloaddition of
phenylacetylene and benzyl azide catalyzed by 3b
In a 5 mL Schlenk flask, 3b (12 mg, contains 0.01 mmol of Cu),
phenylacetylene (102 mg, 1.0 mmol), benzyl azide (133 mg,
1.0 mmol) were added. The mixture was stirred at room tempera-
ture for 30 min. After the reaction was completed, ethyl acetate
spectively. 29Si NMR (solid):
d
¼ꢁ79.1 (br, SiC), ꢁ111.5 (br,
SiO2) ppm. IR (KBr):
n
¼1633, 1553, 1383, 1083 cmꢁ1
.

P. Li et al. / Tetrahedron 64 (2008) 10825–10830
10829
(3 mLꢂ2) was added, and the slurry was stirred, and then filtered
4.20. 1-Decyl-4-phenyl-1H-1,2,3-triazole17c
1H NMR (300 MHz, CDCl3):
using a sintered-glass funnel. The residue was washed with ethyl
acetate to ensure removal of the product from the surface of the
catalyst. The combined organic layers were washed with water and
brine, dried with MgSO4 and evaporated under reduced pressure.
The residue was finally purified by flash chromatography on silica
gel (eluant: hexane/ethyl acetate, 3:1, v/v) to give the correspond-
ing [3þ2] cycloaddition product 1-benzyl-4-phenyl-1H-1,2,3-tri-
azole as a colourless crystal (219 mg, 93% yield).
d
¼7.84–7.80 (m, 2H), 7.76 (s, 1H),
7.43–7.38 (m, 2H), 7.34–7.25 (m, 1H), 4.37 (t, J¼7.2 Hz, 2H), 1.94–
1.88 (m, 2H), 1.32–1.25 (m, 14H), 0.87 (t, J¼6.8 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
29.0, 26.6, 22.7, 14.2.
d
¼147.7, 130.7, 128.7, 125.6, 119.4, 50.5, 31.7, 30.6,
4.21. 4-Phenyl-1-(((S)-pyrrolidin-2-yl)methyl)-1H-1,2,3-
triazole25
4.12. 1-Benzyl-4-phenyl-1H-1,2,3-triazole12b
1H NMR (300 MHz, CDCl3):
7.36–7.24 (m, 3H), 4.46–4.35 (m, 1H), 4.23–4.12 (m, 1H), 3.65–3.53
d
¼7.89 (s, 1H), 7.79 (t, J¼7.2 Hz, 2H),
1H NMR (300 MHz, CDCl3):
d
¼7.80 (d, J¼7.1 Hz, 2H), 7.67 (s, 1H),
7.42–7.27 (m, 8H), 5.54 (s, 2H). 13C NMR (75 MHz, CDCl3):
134.2, 130.0, 126.1, 125.5, 124.7, 119.1, 53.7.
d
¼147.7,
(m, 1H), 2.91 (t, J¼6.6 Hz, 2H), 2.03 (s, 1H), 2.01–1.87 (m, 1H), 1.80–
1.60 (m, 2H), 1.52–1.37 (m, 1H). 13C NMR (75 MHz, CDCl3):
130.9, 129.1, 128.2, 125.8, 120.7, 58.1, 55.7, 46.7, 29.3, 25.9.
d
¼147.7,
4.13. 1-(4-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole17c
4.22. 2-(4-Phenyl-(1,2,3-triazol-1-yl))-cyclohexanol11a
1H NMR (300 MHz, CDCl3):
7.42–7.30 (m, 3H), 7.21–7.18 (m, 4H), 5.51 (s, 2H), 2.35 (s, 3H). 13C
d
¼7.81–7.78 (m, 2H), 7.65 (s, 1H),
1H NMR (300 MHz, DMSO-d6):
7.49–7.27 (m, 3H), 4.89–4.83 (m, 1H), 4.31–4.18 (m, 1H), 3.92–3.75
d
¼8.02 (s, 1H), 7.85–7.79 (m, 2H),
NMR (75 MHz, CDCl3):
125.5, 119.4, 53.9, 21.1.
d¼148.0, 138.6, 131.5, 129.7, 128.7, 128.0,
(m, 1H), 2.28–1.89 (m, 5H), 1.58–1.30 (m, 3H). 13C NMR (75 MHz,
DMSO-d6):
32.1, 25.0, 24.2.
d
¼146.1, 131.3, 128.9, 127.8, 125.4, 120.4, 71.9, 66.8, 35.0,
4.14. 1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole12b
1H NMR (300 MHz, CDCl3):
d
¼8.17–8.15 (m, 2H), 7.74–7.67 (m,
4.23. 1-Benzyl-4-(4-tolyl)-1H-1,2,3-triazole17c
3H), 7.38–7.19 (m, 5H), 5.63 (s, 2H). 13C NMR (75 MHz, CDCl3):
d
¼148.0, 142.6, 141.7, 130.1, 128.7, 128.6, 125.7, 124.4, 123.9, 119.9,
1H NMR (300 MHz, CDCl3):
7.37–7.26 (m, 5H), 7.21–7.18 (m, 2H), 5.57 (s, 2H), 2.35 (s, 3H). 13C
NMR (75 MHz, CDCl3):
d
¼7.71 (d, J¼7.8 Hz, 2H), 7.63 (s, 1H),
53.6.
d
¼148.2, 138.0, 134.6, 129.4, 128.7, 127.5,
4.15. 1,4-Diphenyl-1H-1,2,3-triazole24
126.1, 125.6, 119.2, 54.2, 21.2.
1H NMR (300 MHz, CDCl3):
d
¼8.16 (s, 1H), 7.93 (d, J¼6.0 Hz, 2H),
7.75 (d, J¼6.3 Hz, 2H), 7.50 (t, J¼5.7 Hz, 2H), 7.42–7.39 (m, 3H), 7.33–
4.24. 1-Benzyl-4-(4-chlorophenyl)-1H-1,2,3-triazole17c
7.26 (m, 1H). 13C NMR (75 MHz, CDCl3):
128.6, 127.9, 126.0, 125.3, 120.2, 117.7.
d
¼148.7, 137.4, 130.7, 129.9,
1H NMR (300 MHz, CDCl3):
7.39–7.36 (m, 5H), 7.33–7.29 (m, 2H), 5.57 (s, 2H). 13C NMR (75 MHz,
CDCl3):
¼147.0, 134.4, 133.9, 129.1, 128.9, 128.0, 126.9, 119.6, 54.3.
d¼7.73 (d, J¼9.0 Hz, 2H), 7.66 (s, 1H),
4.16. 1-(4-Tolyl)-4-phenyl-1H-1,2,3-triazole24
1H NMR (300 MHz, CDCl3):
d
4.25. 1-Benzyl-4-(4-bromophenyl)-1H-1,2,3-triazole17c
d
¼8.17 (s, 1H), 7.90 (d, J¼7.2 Hz, 2H),
7.67 (d, J¼8.1 Hz, 2H), 7.47 (t, J¼7.2 Hz, 2H), 7.40–7.31 (m, 3H), 2.40
(s, 3H). 13C NMR (75 MHz, CDCl3):
d¼148.4, 139.0, 134.9, 130.4,
1H NMR (300 MHz, CDCl3):
d
¼7.70–7.66 (m, 3H), 7.54–7.50 (m,
129.0, 128.8, 128.5, 126.0, 120.6, 117.9, 21.3.
2H), 7.42–7.40 (m, 2H), 7.33–7.30 (m, 2H), 7.25 (s, 1H), 5.57 (s, 2H).
13C NMR (75 MHz, CDCl3):
126.1, 119.4, 54.2.
d¼147.1, 134.9, 134.0, 129.4, 129.0, 128.2,
4.17. 1-(4-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole24
1H NMR (300 MHz, CDCl3):
d
¼8.18 (s, 1H), 7.93 (d, J¼8.4 Hz, 2H),
4.26. 1-Benzyl-4-hexyl-1H-1,2,3-triazole17c
1H NMR (300 MHz, CDCl3):
7.77 (d, J¼8.7 Hz, 2H), 7.54–7.38 (m, 5H). 13C NMR (75 MHz, CDCl3):
d
¼130.8, 130.5, 130.2, 129.8, 129.1, 128.0, 126.5, 122.9, 122.7.
d¼7.38–7.19 (m, 6H), 5.47 (s, 2H),
2.69 (t, J¼7.8 Hz, 2H), 1.68–1.59 (m, 2H), 1.32–1.29 (m, 6H), 0.87 (t,
4.18. 1-Hexyl-4-phenyl-1H-1,2,3-triazole17c
J¼6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3):
¼148.9, 135.0, 129.0,
d
127.9, 120.4, 53.9, 31.5, 28.9, 25.7, 22.5, 14.0.
1H NMR (300 MHz, CDCl3):
d
¼7.81 (t, J¼3.6 Hz, 2H), 7.73 (s, 1H),
7.43–7.38 (m, 2H), 7.34–7.26 (m, 1H), 4.36 (t, J¼7.2 Hz, 2H), 1.97–
4.27. Ethyl-1-benzyl-1H-1,2,3-triazole-4-carboxylate11a
1.87 (m, 2H), 1.35–1.24 (m, 6H), 0.85 (t, J¼6.8 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
26.1, 22.3, 13.9.
d
¼147.6, 130.6, 128.0, 125.6, 119.5, 50.5, 31.1, 30.2,
1H NMR (300 MHz, CDCl3):
d
¼7.91 (s, 1H), 7.42–7.23 (m, 5H),
5.56 (s, 2H), 4.36 (q, J¼7.2 Hz, 2H), 1.34 (t, J¼6.9 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
d¼158.8, 137.7, 134.8, 128.3, 127.9, 127.6, 60.8, 13.7.
4.19. 1-Octyl-4-phenyl-1H-1,2,3-triazole17c
1H NMR (300 MHz, CDCl3):
d
¼7.81 (t, J¼4.2 Hz, 2H), 7.72 (s, 1H),
4.28. (1-Benzyl-1H-1,2,3-triazol-4-yl)methanol17c
7.43–7.37 (m, 2H), 7.33–7.24 (m, 1H), 4.36 (t, J¼7.2 Hz, 2H), 1.96–
1.87 (m, 2H), 1.32–1.24 (m, 10H), 0.85 (t, J¼6.8 Hz, 3H). 13C NMR
1H NMR (300 MHz, CDCl3):
d
¼7.81 (s, 1H), 7.42–7.19 (m, 5H),
(75 MHz, CDCl3):
28.9, 26.4, 22.5, 14.0.
d
¼147.6, 130.6, 128.0, 125.6, 119.4, 50.4, 31.6, 30.3,
5.47 (s, 2H), 4.71 (s, 2H), 4.10 (br s, 1H). 13C NMR (75 MHz, CDCl3):
¼146.5, 135.7, 129.5, 128.7, 127.4, 122.1, 55.1, 52.4.
d

10830
P. Li et al. / Tetrahedron 64 (2008) 10825–10830
4.29. 1-Benzyl-4,5-diphenyl-1H-1,2,3-triazole26
13. (a) Wang, Q.; Chan, T. R.; Hilgraf, R.; Fokin, V. V.; Sharpless, K. B.; Finn, M. G.
J. Am. Chem. Soc. 2003, 125, 3192–3193; (b) Himo, F.; Lovell, T.; Hilgraf, R.;
Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc.
2005, 127, 210–216.
1H NMR (300 MHz, CDCl3):
3H), 7.29–7.22 (m, 6H), 7.17–7.13 (m, 2H), 7.05–7.01 (m, 2H), 5.42 (s,
2H). 13C NMR (75 MHz, CDCl3):
d
¼7.60–7.49 (m, 2H), 7.46–7.39 (m,
14. Pacho´ n, L. D.; Maarseveen, J. H.; Rothenberg, G. Adv. Synth. Catal. 2005, 347,
811–815.
15. Reddy, K. R.; Rajgopal, K.; Kantam, M. L. Synlett 2006, 957–959.
16. Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B.; Fokin,
V. V.; Jia, G. J. Am. Chem. Soc. 2005, 127, 15998–15999.
d
¼144.9, 135.6, 134.1, 131.1, 129.7,
128.9, 128.6, 128.2, 128.0, 127.8, 127.6, 126.7, 52.3.
17. (a) Kirschnig, A.; Monenschein, H.; Wittenberg, R. Angew. Chem., Int. Ed. 2001,
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Acknowledgements
We gratefully acknowledge financial support by the National
Natural Science Foundation of China (No. 20772043, 20572031) and
the Key Project of Science and Technology of the Department of
Education, Anhui Province, China (No. ZD2007005-1).
P.; Wang, L. Tetrahedron 2007, 63, 5455–5459; (j) Miao, T.; Wang, L. T
etrahedron
Lett. 2007, 48, 95–99; (k) Li, H.; Wang, L. Synthesis 2007, 1635–1642; (l) Zhang,
L.; Li, P.; Wang, L. Lett. Org. Chem. 2006, 3, 282–285; (m) Li, P.; Wang, L. Adv.
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