Copper on chitosan: An efficient and easily recoverable heterogeneous catalyst for one pot synthesis of 1,2,3-triazoles from aryl boronic acids in water at room temperature

Article abstract of DOI:10.1016/j.tetlet.2015.02.107

Abstract A facile, efficient, and environmentally-friendly one pot protocol has been developed for the synthesis of 1,4-diaryl-1,2,3-triazoles from boronic acids, sodium azide, and acetylenes using copper sulfate immobilized on chitosan as a recyclable he

Full text of DOI:10.1016/j.tetlet.2015.02.107

Accepted Manuscript
Copper on chitosan: an efficient and easily recoverable heterogeneous catalyst
for one pot synthesis of 1,2,3-triazoles from aryl boronic acids in water at room
temperature
B.S.P. Anil Kumar, K. Harsha Vardhan Reddy, K. Karnakar, G. Satish, Y.V.D.
Nageswar
PII:
S0040-4039(15)00388-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.02.107
TETL 45977
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
20 December 2014
18 February 2015
19 February 2015
Please cite this article as: Anil Kumar, B.S.P., Harsha Vardhan Reddy, K., Karnakar, K., Satish, G., Nageswar,
Y.V.D., Copper on chitosan: an efficient and easily recoverable heterogeneous catalyst for one pot synthesis of
1,2,3-triazoles from aryl boronic acids in water at room temperature, Tetrahedron Letters (2015), doi: http://
dx.doi.org/10.1016/j.tetlet.2015.02.107
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Copper on chitosan: an efficient and easily recoverable heterogeneous catalyst for one pot
synthesis of 1,2,3-triazoles from aryl boronic acids in water at room temperature
B. S. P. Anil Kumar, K. Harsha Vardhan Reddy, K. Karnakar, G. Satish and Y. V. D. Nageswar*

Tetrahedron Letters
1
Copper on chitosan: an efficient and easily recoverable
heterogeneous catalyst for one pot synthesis of 1,2,3-triazoles from
aryl boronic acids in water at room temperature
B. S. P. Anil Kumar, K. Harsha Vardhan Reddy, K. Karnakar, G. Satish and Y. V. D. Nageswar*
MCP Division, Indian Institute of Chemical Technology, Hyderabad 500607, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
A facile, efficient and environmentally-friendly one pot protocol has been
developed for the synthesis of 1,4-diaryl-1,2,3-triazoles from boronic acids,
sodium azide, and acetylenes using copper sulphate immobilized on
chitosan as a recyclable heterogeneous catalyst. This green synthetic three
component protocol avoids handling of hazardous and toxic azides
involving its insitu generation. The use of aqueous medium at room
temperature and the easy recovery of the catalyst are other remarkable
features of this procedure.
Received in revised form
Accepted
Available online
Keywords:
copper on chitosan (CS)
recyclability
boronic acids
1,2,3-triazoles
Click reaction
Copper-mediated 1,3-dipolar cycloaddition1 (click
number of chitosan-supported (CS) metal complexes such
as CS-supported Pd catalyst,11 CS-supported Cu catalyst,12
CS-supported Rh catalyst13 and CS-supported Ti catalyst,14
have been reported recently.
reaction) to give 1,2,3-triazoles has gained prominent
attention in green chemistry domain due to the mild reaction
conditions and high efficiency involved. These compounds
are useful as pharmaceutical agents, agrochemicals, dyes,
corrosion inhibitors, photo stabilizers and photographic
materials.2 Efforts have been placed towards the
development of novel copper based catalytic systems which
minimize pollution in different synthetic protocols.3
Although Cu(I)-catalyzed click reaction has provided
excellent yields and good regioselectivity, thermodynamic
instability and initiation of undesired alkyne–alkyne
coupling restricted the use of Cu(I) catalysts.4 Instead
Cu(0)/Cu(II) salts with various additives and ligands have
been investigated.5 However, most of them are
homogeneous and involved 1,3-dipolar cycloaddition of
organic azides with alkynes.6
Figure 1: Chitosan
Chitosan (CS) (Fig 1) is a biodegradable, non-toxic
polymer which can be obtained by deacetylation of chitin
from the cell walls of algae.15 The amino and hydroxyl
groups of chitosan form stable complex with Cu metal and
the resulting chitosan supported copper complex is
recyclable and inexpensive catalyst.12
The major limitations of existing protocols can be
realized as handling of unstable, toxic organic azides and
using homogeneous catalysts which cannot be separated
easily from the reaction system. In view of this, it is
desirable to use heterogeneous catalysts, which have several
advantages, such as faster and simpler isolation of the
catalyst from reaction products by filtration, as well as easy
recovery and recyclability. For this reason, immobilization
of transition metals on various supports such as alumina,7
Amberlyst8 and zeolites9 as well as copper nanoparticles on
charcoal10 have generated remarkable attention because of
their green and efficient roles in catalyzed reactions. A
In continuation of our research in the field of
novel environ friendly approaches16, 17 in synthetic organic
chemistry, we describe here in a CS- supported copper
catalyzed synthesis of 1,2,3 triazoles in aqueous medium
from boronic acids, NaN3 and alkynes in one pot. Initially
chitosan supported copper complex was prepared by
suspending chitosan in an aqueous solution of CuSO4 or
Cu(OAC)2 or CuI for 3 hr under neutral conditions. After
the copper adsorption, the copper complex was separated
by decantation and washed thoroughly with water several

2
Tetrahedron Letters
times to remove excess of copper salt, and was dried under
vacuum at 60 °C for 12 hr to give the chitosan@copper
catalyst (prepared according to the previously reported
method12)
chitosan@CuSO4 in water was found to be excellent for
this tandem reaction giving the desired 1,2,3-triazole (Table
1, entry 6). Other protic solvents such as methanol, ethanol
and the mixture of water and methanol are proved to be less
suitable for the reaction (Table 1, entries 1, 3, 5, 10 and
12). On the other hand aprotic solvents like DMSO, DMF,
acetone, THF and DCM were ineffective (Table 1, entries
7, 8, 11, 13 and 14).
The present protocol offers an improvement over
the recent report of R. B. Nasir Baig18 as we replaced the
aryl azides with aryl boronic acids because of their
stability, low toxicity and commercial availability. The
insitu preparation of the organic azide as the main reactant
reduces the number of steps and time involved in the
reaction strategy. The advantages of the present approach
are avoiding the isolation and handling of the hazardous
and unstable organic azides, the use of aqueous medium
and recyclability of the catalyst.
Having identified chitosan@CuSO4 in water as
the optimized reaction medium, catalyst loading was next
investigated for the representative phenyl boronic acid,
sodium azide and phenyl acetylene reaction (Table 2). The
highest yield was obtained with 10 mol% of catalyst and
1.2 m.mol of NaN3 (Table 2, entry 3).
Table 2: Copper-catalyzed azide-alkyne cycloaddition with
a
different loadings of NaN3 and chitosan@CuSO4
N
N
NaN3 , Chitosan@Cu Salt
Solvent, rt, 6 hr
B(OH)2
N
Yieldb(%)
1a
2a
3a
Entry Catalyst (mol%) NaN3 (m.mol)
Scheme 1: Optimisation of reaction conditions for the synthesis of 1,2,3-
triazoles
2
5
1
2
3
4
1.2
1.2
1.2
48
64
90
90
10
20
Table 1 Screening of Chitosan@copper salts as catalysts
for Phenyl boronicacid and Phenyl acetylene cyclo
additiona
1.2
1.0
1.5
5
6
10
10
75
90
Yieldb(%)
Entry
Catalyst
Solvent
aReaction conditions: Phnyl Acetylene (1 mmol), Phenyl boronic acid
(1 mmol), NaN3 (1.0 to 1.2 mmol), chitosan@CuSO4 (2to 20 mol%)
in H2O (2mL) at rt for 6 hr. bIsolated yield
1
2
3
4
Chit-CuI
Chit-CuI
MeOH
H2O
72
81
63
68
MeOH
Chit-Cu(OAc)2
H2O
MeOH
H2O
Chit-Cu(OAc)2
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
The scope of this methodology has been extended
using a variety of phenyl boronic acids and alkynes
(scheme 2). As illustrated in Table 3, it was found that both
the electron donating substituents (4-methoxyphenyl-
boronic acid and 4-methyl phenyl boronic acid) and
electron withdrawing substituents (4-chlorophenyl boronic
acid and 4-fluoro phenyl boronic acid) could be efficiently
converted to the desired products in high yields (Table 3,
entries 2, 4, 13 and 14). In the case of para and meta fluoro
boronic acids, both have participated well in click
cyclisation reaction (Table 3, entries 14 and 15).
5
6
84
90
DMSO
DMF
7
Trace
28
8
CH3CN
9
30
10
11
12
13
14
67
EtOH
29
Acetone
Chit-CuSO4
Chit-CuSO4
Chit-CuSO4
78
MeOH:H2O (1:1)
THF
Trace
Trace
DCM
aReaction conditions: Phenyl acetylene (1 mmol), Phenyl boronic acid
(1 mmol), NaN3 (1.2 mmol), chitosan@copper salts (10 mol%)
in H2O (2 mL) at rt for 6 hr. bIsolated yield
Furthermore,
a
disubstituted 4-fluoro-3-methylphenyl
boronic acid successfully converted to triazole giving a
little low yield (Table 3, entry 5). In addition to the phenyl
boronic acids other aromatic substrates such as quinolin-8-
ylboronic acid has reacted sluggishly giving rise to the
expected triazole in 71% isolated yield (Table 3, entry 6).
Initially the reaction between phenyl boronic acid
with phenyl acetylene was selected as a model reaction for
optimizing the reaction conditions such as various copper
sources and solvents (scheme 1), the results of which were
represented in Table 1. The insitu generated azide from the
reaction mixture of phenyl boronic acid and NaN3 reacted
well with phenyl acetylene and desired triazole was
obtained in one pot. It was observed that the click reaction
occurred smoothly in the presence of several deferent
Chitosan supported Cu salts including Cu(OAc)2, CuI and
Scheme 2: Synthesis of 1,2,3-triazoles by using chitosan@CuSO4 catalyst
CuSO4.
Among
the
copper
salts
screened,

Tetrahedron Letters
3
In the case of substituted alkynes, methyl and tertiary butyl
substituents on para position of phenyl acetylenes and meta
flouro phenyl acetylene proceeded smoothly and the
products were isolated in good yields (Table 3, entries 7-
19).
Table 3. Synthesis of 1,4-disubstituted-1,2,3-triazoles
using chitosan@CuSO4 as catalyst in watera
Scheme 3: Model reaction to check the recyclability of the catalyst
Important features of the supported catalysts are
reusability, recyclability and selectivity, which make them
green catalysts especially considering from an
environmental point of view. In this regard, the life time as
well as reusability of the catalyst is verified. The
recyclability of the CS-CuSO4 catalyst was checked by
conducting a model reaction by using phenyl boronic acid,
NaN3, phenyl acetylene (scheme 3). After each cycle, the
catalyst was recovered by decantation and dried for 3hr at
60 0C (Figure 2).
Figure 2: Reaction mixture before and after the reaction
Figure 3. Recyclability of chitosan@CuSO4 catalyst
The recovered catalyst was reused directly in the
next cycle. The catalyst was found to be recyclable without
significant loss of catalytic activity up to five cycles.
(Figure 3). SEM analysis showed that the size and shape of

4
Tetrahedron Letters
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In conclusion, the present protocol involves a
shorter reaction pathway which helps in the reduction of
reaction steps as well as workup and avoids the isolation of
unstable azides with the use of recyclable and reusable
chitosan@CuSO4 catalyst in water as a green solvent to
synthesize 1,4-disubstituted-1,2,3-triazoles with high
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Y. V. D. Tetrahedron Lett. 2011, 52, 2862; (b) Anil Kumar, B. S.
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Acknowledgement
17. (a) Reddy, K. H. V.; Reddy, V. P.; Shankar, J.; Madhav, B.;
Kumar, B. S. P. A.; Nageswar, Y. V. D. Tetrahedron Lett. 2011,
52, 2679; (b) Reddy, K. H. V.; Reddy, V. P.; Shankar, J.;
Nageswar, Y. V. D. Synlett. 2011, 9, 1268; (c) Reddy, K. H. V.;
Kumar, A. A.; Kranthi, G.; Nageswar, Y. V. D. Beilstein J. Org.
Chem. 2011, 7, 886; (d) Satish, G.; Reddy, K. H. V.; Ramesh, K.;
Karnakar, K. Tetrahedron Lett. 2012, 53, 2518; (e) Reddy, K. H.
V.; Satish, G.; Ramesh, K.; Karnakar, K.; Nageswar, Y. V. D.
Chem. Lett. 2012, 41, 585; (f) Madhav, B.; Narayana Murthy, S.;
Anil Kumar, B.S.P.; Ramesh, K.; Nageswar, Y.V.D. Tetrahedron
Lett. 2012, 53, 3835; (g) Ramesh, K.; Karnakar, K.; Satish, G.;
Anil Kumar, B. S. P.; Nageswar, Y. V. D. Tetrahedron Lett. 2012,
53, 6936; (h) Harsha Vardhan Reddy, K.; Satish, G.; Prakash
Reddy, V.; Anil Kumar, B. S. P.; Nageswar Y. V. D. RSC Adv.
2012, 2, 11084; (i) Satish, G.; Reddy, K. H. V.; Ramesh, K.; Anil
kumar, B. S. P.; Nageswar Y. V. D. Tetrahedron Lett. 2014, 55,
2596; (j) Reddy, K. H. V.; Satish, G.; Ramesh, K.; Karnakar, K.;
Nageswar, Y. V. D. Tetrahedron Lett. 2012, 53, 3061; (k) Satish,
G.; Reddy, K. H. V.; Anil kumar, B. S. P.; Shankar, J.; Uday
kumar, R.; Nageswar Y. V. D. Tetrahedron Lett., 2014, 55, 5533;
(l) Harsha Vardhan Reddy, K.; Anil Kumar, B. S. P.; Prakash
Reddy, V.; Uday kumar, R.; Nageswar Y. V. D. RSC Adv. 2014,
4, 45579; (m) Swapna, K.; Murthy, S. N.; Jyothi, M. T.;
Nageswar, Y. V. D. Org. Bio. Chem. 2011, 9, 5989.
The authors thank the Council of Scientific and
Industrial Research (CSIR), New Delhi for financial
assistance.
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18. Nasir Baig R. B.; Varma, R. S. Green Chem. 2013, 15, 1839.
19. Preparation of Chitosan@copper catalyst:The catalyst was
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Chitosan was suspended in a 250 ml beaker containing 100 ml of
water. 1 gm of copper salt was added to this suspension with
stirring. After 3 hr the catalyst was separated by decantation,
washed with water several times to remove excess of copper salt,
and was dried under vacuum at 60 °C for 12 hr to give the
chitosan@copper catalyst.
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20. Procedure for the synthesis of 1,4-disubstituted 1, 2, 3-triazoles:
Aryl boronic acid (1 mmol), phenyl acetylene (1 mmol) and NaN3
(1.2 mmol) in H2O (2 mL) were placed in a 10 ml RB flask to
which 10 mol% chitosan@CuSO4catalyst was added. The reaction
mixture was stirred at room temperature and monitored by TLC
until total conversion of the starting materials. After completion
of the reaction, water (20 mL) was added to the resulting reaction
mixture followed by extraction with EtOAc (4x10 mL). Catalyst
was separated by simple decantation and dried for 3 hr at 60 °C

Tetrahedron Letters
5
temperature. The recovered catalyst was used directly in the next
cycle. The organic phase was washed with water and dried with
Na2SO4. Solvent was removed under vacuum and the crude
product was purified by column chromatography to obtain the
corresponding triazole compound.
21. Data of representative example: 1,4-diphenyl-1H-1,2,3-triazole
(Table 3, entry 1): 1H NMR (300 MHz, CDCl3): δ 7.31-7.62 (m, 6H),
7.73-7.81 (d, J = 8.1Hz, 2H), 7.87-7.96 (d, J = 6.9Hz, 2H), 8.20 (s,
1H); 13C NMR (75 MHz, CDCl3): δ 115.39, 117.57, 120.51, 125.84,
128.41, 128.89, 129.75, 137.05, 148.39; ESI-MS: m/z 222 (M+H)+.
HRMS calctd. For 222.1026 found 222.1024. C14H12N3.