Cu(OAc)2·H2O/NH2NH 2·H2O: An efficient catalyst system that in situ generates Cu2O nanoparticles and HOAc for Huisgen click reactions

Article abstract of DOI:10.1039/c3ra45437a

A combination of Cu(OAc)₂·H₂O and NH ₂NH₂·H₂O, which in situ generates Cu₂O-NPs and HOAc in water at room temperature, has been developed as a highly efficient catalytic system for Huisgen

Full text of DOI:10.1039/c3ra45437a

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Cu(OAc)2$H2O/NH2NH2$H2O: an efficient catalyst
system that in situ generates Cu2O nanoparticles
and HOAc for Huisgen click reactions†
Cite this: RSC Adv., 2014, 4, 1010
Received 27th September 2013
Accepted 3rd October 2013
*
*
Yuqin Jiang, Duanyang Kong, Jinglin Zhao, Qinghua Qi, Wei Li and Guiqing Xu
DOI: 10.1039/c3ra45437a
www.rsc.org/advances
A combination of Cu(OAc)2$H2O and NH2NH2$H2O, which in situ Huisgen click reactions in water at physiological temperatures
generates Cu2O-NPs and HOAc in water at room temperature, has (37 ꢀC). The results in this paper indicated that Cu2O-NPs were
been developed as a highly efficient catalytic system for Huisgen click more efficient and less toxic than the commonly used CuSO4/
reactions. Our results indicate that the in situ generated Cu2O-NPs and reductant catalyst systems. Hu et al.10 have established a prac-
HOAc play important roles in the Huisgen click reaction.
tical and effective catalytic method using PhCO2H as an addi-
tive. More recently, heterogeneous Cu2O-NPs catalysts using
charcoal,11 and melamine–formaldehyde resin12 as supports
were prepared and applied in CuAAC reactions.
Hydrazine monohydrate14 is an attractive reductant for
reducing Cu(II) salts due to its strong reducibility and environ-
mentally friendly by-products (nitrogen gas and water) and has
been successfully used in CuAAC reactions.15–17 Recently,
Pathigoolla16 and Kumar17 prepared copper nanoparticles from
a CuSO4$5H2O/NH2NH2$H2O catalyst system, which efficiently
catalyzed the CuAAC reaction under ambient, open-air condi-
tions. Unfortunately, the amount of NH2NH2$H2O required
was more than 10 times the stoichiometric amount, which is
harmful to the environment because of the high toxicity of
hydrazine itself. Thus, controlling the amount of the hydrazine
is essential in order to be more environmentally conscious. In
Introduction
The azide–alkyne Huisgen cycloaddition, a 1,3-dipolar cyclo-
addition between an azide and a terminal or internal alkyne to
give a 1,4- or 1,5-disubstituted 1,2,3-triazole, was developed by
Rolf Huisgen.1 The drawbacks of the classical Huisgen cyclo-
addition reaction are the requirement of high reaction
temperatures and a lack of regioselectivity. Since Sharpless2 and
Meldal3 independently discovered that copper(I) catalysts could
facilitate the Huisgen azide–alkyne cycloaddition in a regio-
specic manner to give only 1,4-disubstituted triazoles, cop-
per(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions
have attracted signicant attention due to their application in
the synthesis of pharmaceuticals, agrochemicals, dyes, corro-
sion inhibitors, biochemicals, polymers and functional mate-
rials.4 The usual sources of the copper(I) catalyst for CuAAC
reactions are Cu(I) salts or their complexes,5 Cu(II) salts
combined with a reducing agent (sodium ascorbate, metallic
copper, hydrazine monohydrate, etc.)2,6 and different sizes of
metallic copper.7
Cu2O is also a source of catalytic Cu(I) for CuAAC reactions.
Using Cu2O powder directly in a CuAAC reaction usually results
in incomplete conversion, poor yields and long reaction times.8
Recently, efforts have been made to enhance the catalytic effi-
ciency of Cu2O.9–13 In 2010, Kong et al.9 reported poly-
vinylpyrrolidone-coated Cu2O nanoparticles as a catalyst for
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang
453007, Henan, P. R. China. E-mail: jiangyuqin@htu.cn; guiqingxu@163.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra45437a
Fig. 1 Effect of the ratio of NH2NH2$H2O to Cu(OAc)2$H2O on the
yield and pH value.
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the work described in this paper, Cu(OAc)2$H2O was selected as at room temperature. As shown in Fig. 2, the higher the amount
the Cu(II) salt and a stoichiometric amount [Cu(II) to Cu(I)] of of water, the higher the pH value and the lower the yield, which
hydrazine was used as the reducing agent. It is well known that is consistent with the results mentioned above. Another exper-
[(CuOAc)2]n is unstable in water and will immediately decom- iment, using separate Cu2O-NPs (1 mol%) and HOAc (4 mol%)
pose to Cu2O and HOAc,18 which could act as the catalyst for the as the catalyst for the model reaction, was carried out in water
CuAAC reaction. To the best of our knowledge, there have been (1 mL) at room temperature. Unfortunately, the product yield
no CuAAC reactions in water catalyzed by in situ generated Cu2O was only 21% aer 20 min, while the pH value was 3.84 and it
and HOAc, which should show better catalytic efficiency than took 110 min to nish the model reaction. The above result
that of isolated Cu2O combined with HOAc.
indicated that the catalytic activity of Cu2O-NPs generated
in situ was higher than that of separate Cu2O-NPs. The reason
for this is probably that the chemical equilibrium between
the in situ generated Cu2O-NPs and HOAc is shied more to
the side of CuOAc.19–21 Therefore, the optimum amount of water
is 1 mL.
Results and discussion
NH2NH2$H2O (0.1 mmol) was added to
a solution of
Cu(OAc)2$H2O (0.2 mmol) in water (10 mL) with vigorous stir-
ring. The solution turned into a dark yellow colored suspension
instantaneously (see ESI†). The suspension did not subside for a
long time. Aer ltration, the precipitate was dried for three
days under high vacuum at room temperature. The reduced
product was characterized by X-ray powder diffraction (XRD),
scanning electron microscopy (SEM) and transmission electron
microscopy (TEM) (see ESI†), which showed the product to be
hollow spherical Cu2O-NPs with sizes of 400–500 nm.
The reaction between propargyl phenyl ether and ethyl azi-
doacetate was selected as a model reaction. The reaction
conditions were chosen as follows: propargyl phenyl ether
(1 mmol), ethyl azidoacetate (1 mmol), Cu(OAc)2$H2O (2 mol%)
and water (1 mL). The inuence of the ratio of NH2NH2$H2O to
Cu(OAc)2$H2O on the isolated yields of the model reaction
(Scheme 1) were investigated.
As shown in Fig. 1 (line a), the yield increased signicantly
over the ratio range of 0 : 1 to 1 : 2, from 0 to 92%, and then
decreased over the ratio range of 1 : 2 to 3 : 1, from 92% to 24%.
Meanwhile, the pH value of the reaction mixture without adding
the model substrates (as shown in Fig. 1, line b) decreased from
5.55 to 4.61, over the ratio range of 0 : 1 to 1 : 2, which can be
attributed to the generation of HOAc in the solution. In addi-
tion, the pH value increased from 4.61 to 6.24, between the ratio
range of 1 : 2 to 3 : 1, which can be attributed to neutralization
of the generated HOAc and excess hydrazine. The relationship
between the yield and the pH value indicates that the in situ
generated HOAc is critical for the catalytic efficiency of Cu2O-
NPs. Thus, the optimum ratio of NH2NH2$H2O to
Cu(OAc)2$H2O is 1 : 2, at which ratio the generated amount of
HOAc reaches its peak while hydrazine has been completely
consumed.
Reactions involving a wide range of diversely substituted
terminal alkynes and azides were carried out using the opti-
mized conditions. As shown in Table 1, the reaction works well
not only with alkyl azides, but also with aryl azides. All of the
reactions were highly regioselective towards the 1,4-disubsti-
tuted triazoles within 30 min.
The proposed mechanism (Scheme 2) for the reaction is the
same as the established mechanism shown in earlier reports.22
The in situ generated HOAc plays many important roles in the
reaction:10,19–21 (a) HOAc breaks the crystal structure of Cu2O to
allow the formation of copper(I) carboxylates, which are highly
efficient catalysts for the CuAAC reaction; (b) the acidity of
HOAc is also necessary for the success of this conversion; (c)
AcOÀ acts as a bidentate ligand coordinated to the Cu(I) species
of the monomer to promote the formation of dinuclear alkynyl–
copper(I) intermediate (3) (see step 2); (d) it has an active effect
on the cycloaddition (step 3) and protonation of the C–Cu bond
(step 4).
In order to verify the relationship between the yield and the
pH value again, the model reaction was carried out separately
in varying amounts of water using NH2NH2$H2O (1 mol
%)/Cu(OAc)2$H2O (2 mol%) (molar ratio of 1 : 2) as the catalyst Fig. 2 Effect of the amount of H2O on the model reaction.
Scheme 1 Model reaction for selecting the ratio of NH2NH2$H2O to Cu(OAc)2$H2O.
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Table 1 Synthesis of triazoles using the Cu(OAc)2$H2O/NH2NH2$H2O system
Entry
1
Azide
Alkyne
Producta
Time (min)
20
Yieldb (%)
92
N3CH2COOEt
2
3
15
10
93
93
4
5
6
12
8
92
94
92
N3CH2COOEt
10
7
9
90
8
12
18
25
91
93
92
9
10
11
12
13
14
20
22
18
20
90
90
89
86
15
10
94
16
17
18
16
25
22
92
91
90
N3CH2COOEt
19
28
89
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Table 1 (Contd.)
Entry
Azide
Alkyne
Producta
Time (min)
12
Yieldb (%)
91
20
a
Reaction conditions: terminal alkyne (1 mmol), azide (1 mmol), NH2NH2$H2O (1 mol%), Cu(OAc)2$H2O (2 mol%), H2O (1 mL), at room
temperature. b Isolated yield.
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In summary, we have presented a novel and high yielding
Cu(OAc)2$H2O/NH2NH2$H2O catalyst system, which could in
situ generate Cu2O-NPs and HOAc to catalyze Huisgen click
cycloadditions in water at room temperature with relatively
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This work was supported nancially by the Natural Science
Foundation of China (No. 21172058) and Scientic Research
Foundation for Doctors (No. 01036500508) and the Youth
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