Claycop/hydrazine: A new and highly efficient recyclable/reusable catalytic system for 1,4-disubstituted-1,2,3-triazole synthesis under solvent-free conditions

Article abstract of DOI:10.1002/aoc.3931

Clay-supported copper(II) nitrate (claycop) has been used as an efficient catalyst for azide–alkyne cycloaddition reactions leading to 1,4-disubstituted 1,2,3-triazoles. The highly efficient claycop/hydrazine hydrate catalytic system affords triazoles in a few minutes (1–20?min) at room temperature, under mild and solvent-free conditions. High regioselectivity, excellent yields, ease of claycop synthesis and recyclability/reusability of the catalyst are considered as practical merits of the protocol.

Full text of DOI:10.1002/aoc.3931

Received: 20 March 2017
DOI: 10.1002/aoc.3931
Revised: 3 May 2017
Accepted: 20 May 2017
C O M M U N I C A T I O N
Claycop/hydrazine: A new and highly efficient recyclable/reusable
catalytic system for 1,4‐disubstituted‐1,2,3‐triazole synthesis under
solvent‐free conditions
Hanan M. F. Elnagdy1 | Kongkona Gogoi2 | Abdul A. Ali1 | Diganta Sarma1
1 Department of Chemistry, Dibrugarh
University, Dibrugarh 786004Assam, India
Clay‐supported copper(II) nitrate (claycop) has been used as an efficient catalyst for
2 Analytical Chemistry Group, Chemical
Science and Technology Division, CSIR‐
North East Institute of Science and
Technology, Jorhat 785006, India
azide–alkyne cycloaddition reactions leading to 1,4‐disubstituted 1,2,3‐triazoles.
The highly efficient claycop/hydrazine hydrate catalytic system affords triazoles in
a few minutes (1–20 min) at room temperature, under mild and solvent‐free
conditions. High regioselectivity, excellent yields, ease of claycop synthesis and
recyclability/reusability of the catalyst are considered as practical merits of the
protocol.
Correspondence
Diganta Sarma, Department of Chemistry,
Dibrugarh University, Dibrugarh 786004,
Assam, India.
KEYWORDS
Email: dsarma22@gmail.com;
dsarma22@dibru.ac.in
1,2,3‐triazoles, alkyne, azide, claycop/hydrazine hydrate, heterogeneous
Funding information
CSIR, New Delhi, Grant/Award Number: 02
(0154)/13/EMR‐II
The 1,3‐dipolar cycloaddition reaction between azide and
alkyne leading to the formation of disubstituted 1,2,3‐triazoles
has attracted tremendous interest during the last few decades.
Compounds containing the 1,2,3‐triazole unit find various
applications in medicinal chemistry, organic synthesis,
biology and material sciences.[1–4] Some of the important
properties that the 1,2,3‐triazole unit possesses are high
chemical stability, generally inert to severe hydrolytic,
oxidizing and reducing conditions, even at high temperature,
strong dipole moment (4.8–5.6 Debye), aromatic character
and hydrogen bond accepting ability.[5]
Various synthetic protocols have been developed for the
synthesis of 1,2,3‐triazole derivatives. Among these
methods, the Cu‐catalysed azide–alkyne cycloaddition
(CuAAC) reaction, discovered independently by the groups
of Meldal and Sharpless, is undoubtedly one of the most
prominent strategies.[6,7] There have been many literature
reports of using copper(I) source in regioselective azide–
alkyne cycloaddition.[8] The copper(I) species is either gener-
ated from copper(II) salts with reducing agents (e.g. sodium
ascorbate) or added directly as cuprous salts, usually with
stabilizing ligands.[9] Metallic copper or clusters are also
employed, but these catalytic systems sometimes require
oxidative agents.[10] The disadvantages of such systems are
that the reaction kinetics is relatively slow and a significant
amount of catalyst is required. There are also reports indicat-
ing the formation of diacetylenes and bistriazoles.[11]
In order to overcome the drawbacks associated with homo-
geneous systems, heterogeneous catalysts have been devel-
oped. Along with many other advantages, recyclability and
reusability are the key features that heterogeneous catalysts
have for application in synthetic chemistry.[12] Heterogeneous
catalyst systems with Cu catalysts have been successfully used
in click reactions. Cu(I) catalysts immobilized on polymers,
silica or zeolite, Cu(0) on charcoal, CuO nanostructures, etc.,
are some examples of heterogeneous systems used in azide–
alkyne cycloaddition.[13]
To continue our study of 1,2,3‐triazole synthesis,[14] in
the work reported herein we developed a very efficient
heterogeneous catalytic system for azide–alkyne cycloaddition
reaction. Copper(II) nitrate immobilized on montmorillonite
clay (claycop) was used as catalyst and for some substrates the
reactions proceeded within 1–5 min affording almost quantita-
tive yields of the desired 1,2,3‐triazoles. The highlighting
Appl Organometal Chem. 2017;e3931.
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https://doi.org/10.1002/aoc.3931

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ELNAGDY ET AL.
factors of this novel protocol are that it is a solvent‐free
approach and the catalytic system is recyclable and reusable.
The reaction of benzyl azide with phenylacetylene in the
presence of 50 mg of claycop and 50 μl of hydrazine hydrate
proceeded in less than 1 min affording almost quantitative
yield of the desired product. The high activity of the catalyst
system is demonstrated by the results in Table 1 (entries 1–5).
The yields of desired products of the optimized cycloaddition
reaction with different loadings of claycop/hydrazine hydrate
catalyst (5–50 mg claycop; 5–50 μl hydrazine hydrate) are
between 79 and 98%. The significant acceleration of click
reaction using claycop/hydrazine hydrate is related to the
reduction of Cu(II) in claycop by hydrazine hydrate.
Hydrazine hydrate produces exothermic heating, once it is
added to claycop. This heat energy is believed to be the
key factor for speeding up the reduction of Cu(II) to Cu
(I), as well as the acceleration of the dipolar cycloaddition
reaction.
The reaction of benzyl azide and phenylacetylene in the
presence of 50 mg of claycop and 50 μl of hydrazine hydrate
proceeded very fast affording triazole instantaneously
(Table 1, entry 1). After a set of experiments (Table 1, entries
1–5), the use of 20 mg of claycop and 10 μl of hydrazine
hydrate (Table 1, entry 4) was chosen as the optimized
reaction conditions for azide–alkyne cycloaddition reaction.
In the absence of hydrazine hydrate, the reaction requires
more than 12 h with the formation of both 1,5‐ and 1,4‐disub-
stituted 1,2,3‐triazoles.
1 | RESULTS AND DISCUSSION
Claycop was synthesized following a literature procedure.[15]
Briefly, it was prepared by adding K10 clay (20 g) to a solu-
tion of copper(II) nitrate trihydrate (10 g) in acetone
(250 ml). The resulting suspension was placed in a rotary
vacuum evaporator and the solvent evaporated under reduced
pressure giving claycop as a light blue, free‐flowing powder.
Powder X‐ray diffraction data (Figure 1) indicate the
presence of copper in claycop. Brunauer–Emmett–Teller
surface area measurements were done to compare the surface
area of unmodified K10 clay with that of claycop. Unmodi-
fied clay has a surface area of 220 m2 g−1 whereas the surface
area for claycop is found to be 57 m2 g−1 indicating the
impregnation of copper on the clay surface.
After optimizing the reaction conditions, the optimal cat-
alytic system for one‐pot CuAAC was examined using a
series of different azides and alkynes at room temperature
under solvent‐free conditions.[16] The results are summarized
in Table 2 (entries 1–13). All reactions proceeded smoothly
giving excellent isolated yields of the corresponding
triazoles. Both electron‐rich and electron‐deficient aryl
azides showed excellent reactivity and furnished products in
excellent yields in short reaction times (Table 2, entries 4,
5, 8–11) at room temperature. Aromatic alkynes show
slightly better reactivity towards benzyl or aryl azides as
compared to aliphatic alkyne (Table 2, entry 13).
FIGURE 1 Powder X‐ray diffraction pattern for claycop
TABLE 1 Optimization of click reaction with various loadings of catalyst (claycop/hydrazine hydrate)a
Entry
Claycop (mg)
NH2NH2·H2O (μl)
50 (1 mmol)
Time (min)
Yield (%)b
1
2
3
4
5
50
50
20
20
5
1
5
95
86
98
98
79
30 (0.6 mmol)
50 (1 mmol)
5
10 (0.2 mmol)
5 (0.1 mmol)
5
10
aReagents and reaction conditions: 1a (1 mmol), 2a (1.2 mmol), claycop 5–50 mg, hydrazine hydrate (5–50 μl).
bIsolated yields.

ELNAGDY ET AL.
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TABLE 2 Catalytic system (claycop/hydrazine hydrate) investigated with various azides and alkynes at room temperature under mild conditionsa
Entry
Azide
Alkyne
Product
3a
Time (min)
Yield (%)b
1
5
98
2
3
3b
3c
5
98
92
10
4
5
3d
3e
20
30
92
97
6
7
3f
20
10
98
98
3g
8
9
3h
3i
20
10
97
98
10
11
3j
20
20
90
92
3k
12
13
3l
40
50
85
81
3m
aAll reactions were carried out using azide (1 mmol), alkyne (1.2 mmol) claycop (20 mg) and hydrazine hydrate (10 μl, 0.2 mmol) under solvent‐free conditions at room
temperature.
bIsolated yields.

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ELNAGDY ET AL.
TABLE 3 Recyclability of claycop catalytic systema
hydrate under solvent‐free conditions (Table 3, entry 1).
After the completion of the first cycle, the product was
extracted by addition of ethyl acetate and the catalyst system
consisting of claycop/hydrazine was precipitated from the
reaction mixture and separated using a centrifugation system,
followed by washing with ethyl acetate three to four times
ensuring that no residual product was left with the catalytic
system. The catalyst was dried and used for subsequent runs
(Table 3, entries 2–4). The experimental results indicate that
it is possible to recycle and reuse our catalytic system up to
the fourth cycle without loss of any catalytic activity.
The mechanism of CuAAC reaction has been the subject
of extensive study and, based on that, a plausible mechanism
of the claycop/hydrazine‐catalysed azide–alkyne cycloaddi-
tion reaction is depicted in Figure 2.
Entry
Run
Time
5
Yield (%)b
1
2
3
4
First
98
95
92
90
Second
Third
10
20
Fourth
20
aReagents and reaction conditions: 1a (1 mmol), 2a (1.2 mmol) and claycop cat-
alyst (20 mg), hydrazine hydrate (10 μl, 0.2 mmol) under solvent‐free conditions
and stirred at room temperature.
bIsolated yields.
To show the convenient utility of our catalytic system
we compare the procedure developed by us with proce-
dures reported earlier for the same purpose. The results
are summarized in Table 4. The ease of preparation of
the catalyst, easier separation from the reaction mixture
and operational simplicity make our protocol superior and
easily acceptable.
2 | CONCLUSIONS
We have developed a mild and very efficient methodology for
azide–alkyne cycloaddition reactions. The clay‐supported
copper(II) nitrate/hydrazine hydrate catalytic system for the
synthesis of 1,4‐disubstituted 1,2,3‐triazoles is very easy to
prepare and has tolerance for a range of azides and alkynes.
The CuAAC reactions proceeded very fast under solvent‐free
conditions at room temperature. This mild methodology is
expected to have wide applications.
FIGURE 2 Plausible mechanism of formation of 1,2,3‐triazoles
In order to demonstrate the practical importance and wide
application of this new heterogeneous catalytic system, it is
desirable to show that the catalyst is recyclable and reusable.
The recycling experiment was performed using the standard
reaction of phenylacetylene and benzyl azide in the presence
of 20 mg of claycop and 10 μl (0.2 mmol) of hydrazine
ACKNOWLEDGEMENTS
The authors acknowledge financial support from CSIR, New
Delhi (research grant no. 02(0154)/13/EMR‐II). DST and
UGC, New Delhi are gratefully acknowledged for financial
TABLE 4 Comparison of catalytic efficiency of claycop/hydrazine hydrate system with earlier reported catalysts for synthesis of 3a
Entry
Catalyst
Cell‐CuI NPs 100 mg
Cu‐Al2O3 NPs, 10 mg
CuI–zeolite (CuI‐USY),10 mol%
Cu NPs on charcoal (1 mol%)
Silica‐immobilized NHC‐cu(I), 0.5 mol% cu
CuFe2O4 NPs, 5 mol%
Conditions
70 °C, H2O
r.t., H2O
Time(h)
Yield (%)
Ref.
[17]
1
2
3
4
5
6
7
2
3
96
92
90
91
98
93
98
[18]
[19]
[20]
[21]
[22]
90 °C, H2O
100 °C, H2O
80 °C, H2O
70 °C, H2O
Solvent free, r.t.
15
0.6
6
3
Clay–Cu(II)/NH2NH2·H2O, 20 mg
0.08
This work

ELNAGDY ET AL.
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[16] Typical procedure: A mixture of azide (1 mmol), acetylene (1.2
mmol), hydrazine hydrate (10 μl, 0.20 mmol) and catalyst claycop
(20 mg) was stirred at room temperature for the given time period
as mentioned in table 2. The progress of the reaction was monitored
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EtOAc (2 × 20 ml), washed with brine and dried over anhydrous
sodium sulfate. The organic phases were combined and concen-
trated under vacuum to give the crude product and purified
through silica gel column chromatography (10–20% EtOAc–-
hexanes) to afford the desired product. The products were
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How to cite this article: Elnagdy HMF, Gogoi K, Ali
AA, Sarma D. Claycop/hydrazine: A new and highly
efficient recyclable/reusable catalytic system for 1,4‐
disubstituted‐1,2,3‐triazole synthesis under solvent‐
free conditions. Appl Organometal Chem. 2017;
e3931. https://doi.org/10.1002/aoc.3931