Click synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by CuO-CeO2 nanocomposite in the presence of amberlite-supported azide

Article abstract of DOI:10.1007/s12039-013-0537-0

A CuO-CeO₂ nanocomposite in the presence of amberlite-supported azide has been used for the click synthesis of 1,4-disubstituted-1,2,3-triazoles in good yields. This catalyst can be reused several times without any significant decrease in the c

Full text of DOI:10.1007/s12039-013-0537-0

c
J. Chem. Sci. Vol. 126, No. 1, January 2014, pp. 147–150. ꢀ Indian Academy of Sciences.
Click synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by
CuO–CeO2 nanocomposite in the presence of amberlite-supported azide
JALAL ALBADIa,∗, JAFAR ABBASI SHIRANb and AZAM MANSOURNEZHADc
aBehbahan Khatam Alanbia University of Technology, Behbahan 6361647189, Iran
bFaculty of Science, Department of Chemistry, Guilan University, Rasht 413351914, Iran
cDepartment of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran 7581863886, Iran
e-mail: Chemalbadi@gmail.com
MS received 26 June 2013; revised 17 September 2013; accepted 19 September 2013
Abstract. A CuO–CeO2 nanocomposite in the presence of amberlite-supported azide has been used for the
click synthesis of 1,4-disubstituted-1,2,3-triazoles in good yields. This catalyst can be reused several times
without any significant decrease in the catalytic activity.
Keywords. Click chemistry; CuO–CeO2 nanocomposite; amberlite-supported azide;
1,4-disubstituted-1,2,3-triazoles.
1. Introduction
membranes. The use of excess sodium azide during
nucleophilic substitution reactions in organic processes
pollutes the environment since it is not usually recov-
ered from reaction medium. Such drawbacks could be
obviated using the supported azide anion. Recently,
we have reported multicomponent synthesis of tria-
zole derivatives with amberlite-supported azide as the
source of azide ion.13 amberlite-supported azide was
easily prepared from its corresponding chloride form
via ion exchange using 10% NaN3 aqueous solu-
tion (scheme 1).
In general, as a catalyst, a Cu(I) salt is directly
used, or Cu(II) after reduction.14–17 The Cu(II)-
catalysed azide-alkyne cycloaddition (CuAAC) reac-
tions18,19 have also been reported. In previous studies,
we reported the preparation of copper iodide nanopar-
ticles supported on poly(4-vinylpyridine) (P4VPy-CuI)
and their application in click synthesis of triazoles.20,21
In continuation of these studies, herein we report a
green recyclable catalyst for regioselective click syn-
thesis of 1,4-disubstituted-1,2,3-triazoles from α-halo
ketones or benzyl halides and terminal alkynes in the
presence of amberlite-supported azide (scheme 2).
Nanocrystalline oxides have proved to be useful to
chemists in the laboratory and in industry due to the
good activation of adsorbed compounds and reaction
rate enhancement, selectivity, easier work-up, recy-
clability of the supports and eco-friendly reaction
conditions.1–5 Also, practical applications of nanocom-
posite metal oxides as catalysts in organic synthe-
sis have increased due to their high catalytic activity
resulting from their large surface area.6,7 Recently, we
have reported the preparation of CuO–CeO2 nanocom-
posite and its catalytic activity for the synthesis of
aryl-14H-dibenzo[a-j]xanthenes.8 This catalyst is safe,
easy to handle, environmentally benign and has shown
very good catalytic activity. Therefore, we decided
to study of click synthesis of 1,4-disubstituted-1,2,3-
triazoles in the presence of this catalyst. Owing to
the diversity in pharmacological activities, the syn-
thesis of 1,2,3-triazoles has received significant atten-
tion.9,10 The main method for the synthesis of these
compounds is the Huisgen 1,3-dipolar cycloaddition
reaction of azides with alkynes, which has become the
model for click reactions.11 1,3-dipolar cycloadditions
have been used in drug discovery, chemical biology
and medicinal chemistry as well as in materials science
and solid phase organic synthesis.12 Sodium azide is a
potent toxin and can be absorbed through the mucous
-
-
N3
+
Cl
+
NaN3/ H2O
25°
N(CH3)2CH2OH
N(CH3)2CH2OH
C/ 6 h
∗For correspondence
Scheme 1. Preparation of amberlite-supported azide.
147

148
Jalal Albadi, Jafar Abbasi Shiran and Azam Mansournezhad
O
N
O
N
2. Experimental
N
Br
R
R
CuO−CeO2
Amberlite-supported azide
R'
Chemicals were purchased from Fluka and Merck
chemical companies. Products were characterized by
comparison of their spectroscopic data (NMR, IR) and
physical properties with those reported in the literature.
Yields refer to isolated pure products.
R'
+
N
EtOH, reflux
N
N
Br
R'
Scheme 2. CuO–CeO2 nanocomposite-catalysed click
synthesis of 1,4-disubstituted-1,2,3-triazoles.
Table 1. CuO–CeO2 nanocomposite-catalysed synthesis of triazole derivatives.
Time Yield
(min) (%)a
M.P.
Entry
1
Substrate
Alkyne
Product
(◦C)b
N
N
N
N
N
CH2Br
65
60
91
90
128–130
108–110
N
CH2Br
2
H3C
H3CO
Cl
CH3
N
N
N
3
4
45
60
90
89
117–118
148–150
CH2Br
H3CO
N
N
N
CH2Br
Cl
Cl
Cl
N
N
N
O2N
CH2Br
5
6
7
8
75
70
91
89
139–140
136–138
O2N
N
N
H2N
H2N
N
NH2
CH2Br
N
N
N
NH2
60
92
91
139–141
188–189
H3CO
CH2Br
CH2Br
H3CO
Cl
N
N
N
N
N
Cl
N
Cl
120
Cl
Cl
Cl
O
O
N
N
N
Br
9
60
45
92
92
145–147
141–143
O
N
N
O
N
Br
10
MeO
MeO

CuO–CeO2 nanocomposite-catalysed synthesis of triazoles
149
Table 1. (Continued).
Time Yield
(min)
M.P.
Entry
11
Substrate
O
Alkyne
Product
(%)a
(◦C)b
N
N
N
O
C2H5O
O
90
90
88
89
89
110–112
144–146
299–300
Br
C2H5O
N
N
N
O
O
H2N
NH2
O
Br
12
O
N
N
N
N
N
N
Br
13
120
aIsolated yield.
bProducts were characterized by comparison of their spectroscopic data (NMR and IR) and melting points with those reported
in the literature.23–25
2.1 Catalyst preparation
through the amberlite-supported azide packed in a col-
umn. The amount of sodium salt of the nucleophile in
the eluent was then titrated with 0.01 M hydrochloric
acid using methyl orange as an indicator. The exchange
capacity of the amberlite-supported nucleophile was
calculated to be 3.5 mmol/g of N−3 .
CuO–CeO2 nanocomposite was prepared by co-
precipitation method using aqueous solution of cerium
and copper nitrates and drop-wise KOH as precipitant
agent under vigorous mixing while temperature and
pH was fixed at unique values. Then, acquired sample
was filtered, washed and calcined to obtain final cata-
lyst for using in the synthesis of 1,4-disubstituted-1,2,3-
triazoles.
3. Results and discussion
The catalyst was synthesized by co-precipitation
method and characterized by XRD, BET specific sur-
face area, ESEM and EDS analysis.8 To optimize
the reaction conditions, the reaction of benzyl bro-
mide, phenylacetylene and amberlite-supported azide
was chosen as a model and its behaviour was studied
under a variety of conditions (table 2).
The best result was achieved by carrying out
the reaction of benzyl bromide and phenylacetylene
(1:1 mol/ratio) in the presence of 0.1 g of CuO–
CeO2 nanocomposite and 1 g of amberlite-supported
azide under reflux conditions in ethanol as the solvent
2.2 General procedure
Benzyl bromide (1 mmol) and phenyl acetylene
(1 mmol) were added to round-bottom flask containing
10 mL of EtOH, CuO–CeO2 nanocomposite (0.1 g) and
amberlite-supported azide (1 g) were added at once to
the mixture. The suspension was stirred under reflux
conditions for appropriate number of times (table 1).
After completion of the reaction as followed by TLC,
the catalyst and resin were filtered and washed with
hot acetone (2 × 5 mL). The filtrate was evaporated
to dryness, and the solid residue recrystallized from
EtOH/H2O (1:3 v/v) to gave crystalline pure product.
Table 2. Optimization of the reaction conditions.
Entry
Conditionsa
Time (min)
Yield (%)b
1
2
3
4
5
CH3CN
CH2Cl2
H2O
CH3OH
CH3CH2OH
120
120
90
60
65
75
45
72
88
91
2.3 Reusing of the catalyst and reagent
The filtered mixture of resin and catalyst were washed
with 25 mL of distilled water and stirred for 6 h in
50 mL of 10% NaN3 aqueous solution and dried under
vacuum at 50◦C before the next run. The exchange
capacity of the amberlite-supported azide was deter-
mined by passing sodium chloride solution (1M)
aThe reaction was performed in the presence of 0.1 g of
CuO–CeO2 and 1 g of amberlite-supported azide under reflux
conditions.
bIsolated yield

150
Jalal Albadi, Jafar Abbasi Shiran and Azam Mansournezhad
carbon–heteroatom bond forming reactions are under-
way in our laboratory.
Table 3. Recyclability study of CuO–CeO2.
Run
1
2
3
4
5
Time (min)
Yield (%)a
65
91
65
90
70
90
75
88
75
88
Supplementary information
The spectra of compounds that synthesized in the
presence of CuO–CeO2 nanocomposite can be seen at
www.ias.ac.in/chemsci.
aIsolated yield
(table 1, entry 1). Using these optimized conditions, the
reaction of various terminal alkynes, benzyl halides and
α-halo ketones were explored. All the products were
easily isolated by straightforward filtration and evapo-
ration of the solvent. A simple purification technique
is one of the key characteristics of click reactions. The
solid products were recrystallized from a mixture of
ethanol/water (1:3 v/v), or in some cases, from hot
ethanol. It is very important to note that the correspond-
ing triazoles were obtained in high yields and good
regioselectivities.
Acknowledgement
We are thankful to research council of Behbahan
Khatam Alanbia University of Technology, for partial
financial support to carry out this work.
References
1. Sharghi H and Hosseini M 2002 Synthesis 1057
2. Hosseini S M and Sharghi H 2004 J. Org. Chem. 69 6953
3. Yin S F, Xu B Q, Wang S J, Ng C F and Au C T 2004
Catal. Lett. 96 113
Click cyclizations were confirmed by the appearance
of a singlet in the region of 8–8.5 ppm for the triazole
derivate from α-halo ketones and 7.8–8.5 ppm for the
trizole derivate from benzyl halides in 1H-NMR spectra
which corresponds to the hydrogen on 5-position of tri-
azole ring and confirms the regioselective synthesis of
1,4-disubstituted triazole regioisomers.22 Moreover, the
recyclability of the catalyst is also important. To inves-
tigate these properties, the reaction of benzyl bromide
with phenyl acetylene was selected again as a model
(table 3). After the completion of reaction, the catalyst
and resin were filtered and washed with distilled water,
then treated with aqueous NaN3 solution to reload the
amberlite-supported azide. Then, the catalyst and resin
were dried and stored for another consecutive run. This
process was repeated for four runs and no appreciable
decrease in the yield was observed.
4. Drexler M T and Amiridis M D 2002 Catal. Lett. 79 175
5. Varma R S 1999 Green Chem. 1 43
6. Samantaray S, Pradhan D K, Hota G and Mishra B G
2012 Chem. Eng. J. 193 1
7. Li S, Zhang W, So M H, Che C M, Wang R and Chen R
2012 J. Mol. Catal. A: Chem. 359 81
8. Albadi J, Razeghi A, Mansournezhad A and Abbaszadeh
H 2013 J. Nanoparticles 1
9. Buckle D R, Outred D J, Rockell C J M, Smith H and
Spicer B A 1983 J. Med. Chem. 26 251
10. Xia Y, Fan Zm Yao J, Liao Q, Li W, Qu F and Peng L
2006 Bioorg. Med. Chem. Lett. 16 2693
11. Huisgen R 1989 Pure Appl. Chem. 61 613
12. Rostovtest V V, Green L G, Fokin V V and Sharpless
K B 2002 Angew. Chem. Int. Ed. 41 2596
13. Albadi J and Keshavarz M 2013 Synth. Commun. 43
2019
14. Wang D, Li N, Zhao M, Shi W, Ma C and Chen B 2010
Green. Chem. 12 2120
15. Lee L V, Michaell L, Huang S J, Fokin V V, Sharpless
K B and Wong C H 2003 J. Am. Chem. Soc. 125 9588
16. Appukkuttan P, Dehaen W, Fokin V V and Eycken V
2004 Org. Lett. 6 4223
17. Feldman A K, Colasson B and Fokin V V 2004 Org.
Lett. 6 3897
4. Conclusion
In conclusion, we have described the CuO–CeO2
nanocomposite as a green and efficient catalyst in
the presence of amberlite-supported azide catalysed
click synthesis of 1,4-disubstituted-1,2,3-triazoles under
reflux conditions in ethanol as the solvent. This cat-
alyst and reagent can be reused at least four times
without significant decrease of catalytic activity. More-
over, high yields of products, short reaction times, ease
of work-up and clean procedures, should make the
present method a useful and important addition for
the synthesis of triazole derivatives. Studies on other
applications of this catalyst for carbon–carbon and
18. Kim J Y, Park J C, Kang H, Song H and Park K H 2010
Chem. Commun. 46 439
19. Mohammad S, Padala A K, Dar B A, Singh B, Sreedhar
B, Vishwakarma R A and Bharate S B 2012 Tetrahedron
68 8156
20. Albadi J, Keshavarz M, Abedini M and Vafaie-nezhad
M 2012 Chin. Chem. Lett. 23 797
21. Albadi J, Keshavarz M, Shirini F and Vafaie-nezhad M
2012 Catal. Commun. 27 17
22. Keshavarz M and Badri R 2011 Mol. Divers. 15 957
23. Sharghi H, Khalifeh R and Doroodmand M M 2009 Adv.
Synth. Catal. 351 207
24. Shamim T and Paul S 2010 Catal. Lett. 136 260
25. Gonda Z and Novak Z 2010 Dalton Trans. 39 726