[Bmim]OH mediated Cu-catalyzed azide–alkyne cycloaddition reaction: A potential green route to 1,4-disubstituted 1,2,3-triazoles

Article abstract of DOI:10.1016/j.tetlet.2016.11.014

In this work, a task-specific ionic liquid 1-methyl-3-butylimidazolium hydroxide [Bmim]OH has been used as a potential greener solvent for Cu-catalyzed azide–alkyne cycloaddition reaction (CuAAC) and provides a simple way to access 1,4-disubstituted 1,2,3

Full text of DOI:10.1016/j.tetlet.2016.11.014

Accepted Manuscript
[Bmim]OH mediated Cu- catalyzed azide–alkyne cycloaddition reaction: A po-
tential green route to 1,4-disubstituted 1,2,3-triazoles
Abdul Aziz Ali, Manashjyoti Konwar, Mitali Chetia, Diganta Sarma
PII:
S0040-4039(16)31470-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.014
TETL 48300
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
2 September 2016
31 October 2016
3 November 2016
Please cite this article as: Aziz Ali, A., Konwar, M., Chetia, M., Sarma, D., [Bmim]OH mediated Cu- catalyzed
azide–alkyne cycloaddition reaction: A potential green route to 1,4-disubstituted 1,2,3-triazoles, Tetrahedron
Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.014
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2
Graphical Abstract
To create your abstract, type over the instructions in the template box below
Fonts or abstract dimensions should not be changed or altered.
[Bmim]OH mediated Cu- catalyzed azide–
alkyne cycloaddition reaction: A potential
green route to 1,4-disubstituted 1,2,3-triazoles
Leave this area blank for abstract info.
Abdul Aziz Ali, Manashjyoti Konwar, Mitali Chetia, and Diganta Sarma*
Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India.

1
Tetrahedron Letters
[Bmim]OH mediated Cu- catalyzed azide–alkyne cycloaddition reaction: A potential
green route to 1,4-disubstituted 1,2,3-triazoles
Abdul Aziz Ali, Manashjyoti Konwar, Mitali Chetia, and Diganta Sarma*
Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
In this work, a task-specific ionic liquid 1-methyl-3-butylimidazolium hydroxide [Bmim]OH has
been used as a potential greener solvent for Cu- catalyzed azide–alkyne cycloaddition reaction
(CuAAC) and provides a simple way to access 1,4-disubstituted 1,2,3-triazoles regioselectively
with excellent yields, without requiring bases, reducing agents, ligands or inert atmosphere.
Moreover, a one-pot three component CuAAC reaction was developed using alkyl bromide,
sodium azide, and terminal alkyne affording 1,2,3-triazoles in high yields.
Available online
Keywords:
[Bmim]OH
Azide
2009 Elsevier Ltd. All rights reserved.
Alkyne
1,2,3- triazoles
Green Chemistry
Introduction
Nowadays, environmental consciousness is one of the most
significant topics across the academia and the industry.
Following the 12 principles of green chemistry the development
of sustainable and efficient processes to convert molecules into
products of interest, by using clean methodology is a global
effort.1 Much attention has been paid to replace harmful organic
solvents by environmental benign reaction media, especially by
water, ionic-liquids, supercritical fluids, solventless processes,
and fluorous techniques.2 In this context ionic liquids (ILs) have
gained a great deal of interest, extensively used in material
science,3 electrochemistry,4 and organic synthesis5 due to their
unique properties, such as negligible vapor pressure,
nonvolatility, nonflammability, electrochemical and thermal
stability and high conductivity.6 Additionally, ILs enjoy
physicochemical properties that make them superior media able
to increase reactivity, selectivity, catalyst recyclability, and so
on.7
Markovnikov Addition,14 amidation of azides and aldehydes,15
Gewald Reaction,16 Heterocyclization,17 Henry Reaction,18
synthesis of spirooxindole derivatives,19 Alkaline electrolyte
membrane,20 Cycloaddition of Carbon Dioxide,21 synthesis of
oximes,22 multi-component reaction,23 Mannich-type reaction,24
and Knoevenagel Condensation.25
1,2,3-triazoles are important structural motifs increasingly
found in a wide array of applications including medicinal
chemistry, chemical biology and materials science.26 As a result,
there is extensive interest in developing synthetic methods for
their facile construction. The conventional way to synthesize
1,2,3-triazole is the Huisgen 1,3-dipolar cycloaddition of alkynes
with organic azides.27 However, due to the high activation
energy, these cycloadditions normally require elevated
temperature and long reaction times and typically afford a
mixture of the 1,4- and 1,5-regioisomers. One of the most
popular “click chemistry” reactions, the copper-catalyzed
cycloaddition of azides with terminal alkynes (CuAAC),
developed by Sharpless and co-workers,28 and independently by
Meldal and co-workers29 is a powerful method for the synthesis
of 1,2,3-triazoles. This transformation leads to the enormously
efficient formation of the corresponding 1,4-disubstituted 1,2,3-
Nevertheless, to exploit the advantages from using these new
solvents, functionalized ILs (usually, defined task-specific ILs,
TSILs) have been developed and characterized by the presence of
functional groups able to impart a particular reactivity, enhancing
the capability for inter action with specific solutes (acids, bases,
metals, nanoparticles etc.).8 TSILs have shown improved
performance with respect to molecular solvents used in well
known reactions.9 Especially, basic ionic liquids have attracted
unprecedented interest because they exhibit more advantages
such as catalytic efficiency and recycling of the ionic liquid than
the combination of inorganic base and ionic liquid for some base-
catalyzed processes.10 A basic ionic liquid [Bmim]OH first
reported by Ranu and coworkers11 in 2005 has been successfully
applied to catalyze Michael addition,12 transesterification,13
triazoles as
a sole regioisomer. Furthermore, numerous
successful examples have been reported in the literature for the
preparation of 1,2,3-triazoles regarding the green aspect of the
method including water as a green solvent,30 the limited solubility
of the less polar reactants can create a serious complication in a
reaction step.31 In contrast, less attention has been paid to
investigate the cycloaddition reactions of azides with alkynes in
ionic liquids.9,31-32Therefore, to go even further and also ensure
high catalytic activity and stability, the development new
synthetic strategy in ionic liquids is one of the most interesting
topics in green chemistry. In continuation of our interest to
develop straightforward, efficient and green methodology for the
*Corresponding author. Tel.: +91 373-2370210
E-mail address: dsarma22@gmail.com; dsarma22@dibru.ac.in

2
synthesis of 1,2,3-triazoles,33 herein we report that 1-methyl-3-
butylimidazolium hydroxide [Bmim]OH could efficiently be
used as a solvent in copper-catalyzed azide -alkyne cycloaddition
reaction without need of bases, reducing agents, ligands or inert
atmosphere, producing a series of 1,4-disubstituted 1,2,3-
triazoles in excellent yields.
the substrates could undergo the cycloaddtion producing
corresponding 1,2,3-triazoles in good to excellent yields. The
reaction of benzyl azides with aromatic acetylene afforded 1,4-
disubstituted 1,2,3-triazoles in excellent yields (Table 2, entries
1-4,13-16). Reactions of phenethyl azide with alkyne such as
phenyl acetylene produced excellent yields of corresponding 1,4-
disubstituted-1,2,3-triazole (Table 2, entry 17), respectively.
Aliphatic azide such as octyl azide shows relatively slower
reaction kinetics and the desired cycloaddition products were
obtained in good yields when the time was increased from 1h to
3h (Table 2, entry 12). Interestingly, aryl azides which contain
functional groups, such as, CN, halogen, and OMe, at different
positions of the aromatic ring, delivered the expected product in
excellent yields within 1h (Table 2, entries 5-11). The reactions
also worked on aliphatic alkynes, however, they showed lesser
activity than the aromatic substrates (Table 2, entries 15-17).34 In
addition, propargyl benzoate also reacted readily to give the
desired triazole product in 95% yields within 0.5h (Table 2, entry
19).35
Results and discussion
We initiated our research on the model reaction of benzyl
azide (1a) with phenyl acetylene (2a) under different reaction
conditions (Table 1). This reaction did not proceed without
catalyst (Table 1, entry 1). To our delight, the hydroxide-based
ILs with different cations were effective for catalyzing this
reaction (Table 1, entries 2−4). Especially, [Bmim]OH showed
the best activity, affording the sole reaction product 1,4-
disubstituted 1,2,3-triazole 3a in quantitative yields under the
experimental conditions (Table 1, entry 2). Among the copper
catalysts, CuI was found to be the most effective (Table 1, entry
2 vs. entries 5-8). Having [Bmim]OH as the best solvent for the
reaction, we next investigated catalyst loading and we found that
decreasing the catalyst loading lead to a significant drop in the
conversion (Table 1,entries 9-10). Notably, under these
optimized conditions, no undesirable by-product was detected.
However replacing the anion of the ionic liquid [Bmim]OH
showed no progress in product yield (Table 1, entries 11-13), The
differences in the reactivity of the tested Bmim based ILs may
result from the influences of their anions, suggesting that the
anions of the ILs had effects on the reaction. The unique role of
the [Bmim]OH in the reaction is to promote the formation of
reactive Cu(I) acetylide complex by rapid deprotonation of the
alkyne.
Table 2. Substrate scope of the CuAAC Reaction to Form 1,4-
disubstituted 1,2,3-Triazoles in [Bmim]OHa
R
CuI, [Bmim]OH
rt
N
N
N
R N3
R'
R'
Entry
Azide
Alkyne
Product
Time
1h
yieldb(%)
99
N
N
N
N3
1
2
3
4
5
6
N
N
N
N
N3
1h
1h
1h
1h
1h
95
92
94
96
93
Table 1. Optimization of reaction conditions.a
O2N
O2N
N
Bn
[Cu], Ionic liquids
rt, 1h
N3
N
N
N
N
N3
Cl
Ph
Cl
3a
2a
1a
N
N
N
N3
Br
Entry
[Cu]
-
CuI
CuI
CuI
CuBr
CuCl
Ionic liquid
[Bmim]OH
[Bmim]OH
[Emim]OH
[Omim]OH
[Bmim]OH
[Bmim]OH
[Bmim]OH
yieldb(%)
Br
1
2
0
N3
N
99
85
90
90
86
88
Cl
N
N
3c
4d
5
Cl
N3
N
N
N
6
7e
Cu(OAc)2.H2O+ Na
ascorbate
CuSO4.5H2O + Na
Cl
N3
8e
[Bmim]OH
90
N
7
1h
1h
1h
1h
1h
94
94
95
97
96
N
N
ascorbate
CuI
9f
[Bmim]OH
[Bmim]OH
[Bmim]Br
[Bmim]OAc
[Bmim]PF6
75
55
40
42
40
Cl
10g
11h
12i
13j
CuI
CuI
CuI
CuI
F
N3
N
8
9
N
N
F
N3
aReaction conditions: Benzyl azide 1a (1mmol), phenyl acetylene 2a (1.2
mmol), IL (2 ml) in the presence of 1 mol % of [Cu], bIsolated yield of pure
product based on 1a, c[Emim]OH,1-methyl-3-ethylimidazolium hydroxide,
Br
N
N
N
d[Omim]OH,1-methyl-3-octylimidazolium hydroxide, 5 mol% Na ascorbate,
e
Br
MeO
N3
f0.5mol% CuI, g0.1mol% CuI, h[Bmim]Br, 1-Butyl-3-methylimidazolium
N
10
11
N
N
bromide, i[Bmim]OAc, 1-Butyl-3-methylimidazolium acetate, [Bmim]PF6, 1-
j
Butyl-3-methylimidazolium hexafluorophosphate.
OMe
N3
NC
N
N
N
Using our optimized experimental conditions, the scope of the
formation of 1,4-disubstituted 1,2,3-triazoles in [Bmim]OH was
examined with a range of different azides and alkynes. The
results are summarized in Table 2. It was worth noting that all
CN

3
aAll reactions were carried out using bromide (1 mmol), NaN3 (1.2 mmol),
N
N
N
12
13
14
3h
1h
85
92
alkynes (1.2 mmol), CuI (1 mol %), in [Bmim]OH (2 mL) at room
temperature.
N3
7
N
N
N
b Reported yields are for the isolated products.
N3
Conclusion
N
N
N
In summary, a simple and practical method was developed for
the generation of diverse 1,4-disubstituted 1,2,3-triazoles in
excellent yields under very mild conditions. The CuAAC
reactions of azides with various alkynes were performed well in
the basic ionic liquid [Bmim]OH without using any bases,
reducing agent and additives. Specifically, one-pot three-
component cycloaddition process starting from bromide
substrates, sodium azide, and alkynes was also effective in this
facile and environmentally friendly alternative protocol.
1h
94
N3
OMe
OMe
N
N
N
N
3h
3h
84
85
30
90
95
N3
15
16
N
N
N3
Acknowledgement
N3
17
18
19
10h
1h
7
We gratefully acknowledge financial support of this work by
CSIR, New Delhi [research grant No. 02(0154)/13/EMR-II].
A.A.A is thankful to CSIR, New Delhi for SRF. DST and UGC,
New Delhi are favourably acknowledged for financial assistance
to the Department of Chemistry, Dibrugarh University.
N
N
N
N3
O
N
N
0.5 h
N
N3
O
O
References and notes:
O
aAll reactions were carried out using azide (1 mmol), alkynes (1.2 mmol),
CuI (1 mol %), in [Bmim]OH (2 mL) at room temperature
1.
(a) Gu, Y.; Jerome, F. Chem. Soc. Rev. 2013, 42, 9550. (b)
Gauchot, V.; Schmitzer, A. R. J. Org. Chem. 2012, 77,4917. (c)
Anastas, P. T.; Warner, J. C. in Green Chemistry: Theory and
Practice (Ed.: Oxford University Press, Oxford), UK, 2000. (d)
Horv´ath, I. T.; Anastas, P. T. Chem. Rev. 2007, 107, 2167.
(a) Polshettiwar, V.; Varma, R. Chem. Soc. Rev. 2008, 37, 1546.
(b) Polshettiwar, V.; Decottignies, A.; Len, C.; Fihri, A.
ChemSusChem, 2010, 3, 502. (c) Horv´ath, I.T.; Anastas, P. T.
Chem. Rev. 2007, 107, 2169.
(a) Susan, M. A. B. H.; Kaneko, T.; Noda, A.; Watanabe, M. J.
Am. Chem. Soc. 2005, 127, 4976. (b) Rogers, R. D. Nature 2007,
447, 917. (c) Torimoto, T.; Tsuda, T.; Okazaki, K.; Kuwabata, S.
Adv. Mater. 2010, 22, 1196.
(a) MacFarlane, D. R.; Forsyth, M.; Howlett, P.C.; Pringle, J. M.;
Sun, J.; Annat, G.; Neil, W.; Izgorodina, E. I. Acc. Chem. Res.
2007, 40 , 1165. (b) Liu, H.; Liu, Y.; Li, J. Phys. Chem. Chem.
Phys. 2010, 12, 1685.
(a) Chauhan, S.; Chauhan, S. M. Tetrahedron 2005, 61, 1015. (b)
Miao, W.; Chan, T.H. Org. Lett. 2003, 5, 5003. (c) Ruß, C.;
König, B. Green Chem. 2012, 14, 2969.
(a) Chiappe, C.; Melai, B.; Sanzone, A.; Valentini, G. Pure Appl.
Chem. 2009, 81, 2035. (b) Amarasekara, A. S. Chem. Rev. 2016,
116, 6133.
(a) Welton, T.; Wasserscheid, P. in Ionic Liquids in Synthesis,
Wiley-VCH, Weinheim, 2007. (b) Hallett, J. P.; Welton, T. Chem.
Rev. 2011, 111, 3508.
Fei, Z.; Geldbach, T. J.; Zhao, D.; Dyson, P. J. Chem.-Eur. J.
2006, 12, 2122.
Chiappe, C.; Mennucci, B.; Pomelli, C. S.; Sanzonea, A.; Marra,
A. Phys. Chem. Chem. Phys. 2010, 12, 1958.
b Reported yields are for the isolated products.
Besides, organic azides are generally safe and stable toward
water and oxygen, those of low molecular weight can be mostly
dangerous and difficult to handle.36 Notably, numerous
methodologies can be found in the literature in order to avoid the
handling and isolation of organic azides for CuAAC reaction. To
2.
3.
4.
demonstrate the generality of CuAAC reaction,
a novel
sequential one-pot procedure involving the formation of the
organic azide in situ from the corresponding bromide with
sodium azide was investigated. When carrying out the
multicomponent model reaction of benzyl bromide, NaN3, and
phenylacetylene under the above-mentioned reaction conditions,
we were delighted to notice that the desired triazole product
formed in excellent yields within 1h (Table 3, entry1). Thus, 1,4-
disubstituted-1,2,3-triazoles could be obtained directly from
different bromides (Table 3, entries 2-4 ).37
5.
6.
7.
Table 3. One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
from Bromidesa
R
N
NaN3, CuI, [Bmim]OH
rt
8.
9.
N
N
R Br
R'
R'
10. Hajipour, A. R.; Rafiee, F. J. Iran. Chem. Soc. 2009, 6, 647.
11. Ranu, B. C.; Banerjee, S. Org. Lett. 2005, 7, 3049.
12. (a) Xu, J.-M.; Qian, C.; Liu, B.-K.; Wu, Q.; Lin, X.-F.
Tetrahedron 2007, 63, 986. (b) Ranu, B. C.; Banerjee, S.; Jana, R.
Tetrahedron 2007, 63, 776.
Entry
1
Bromide
Alkyne
Product
Time
1h
yieldb(%)
94
N
N
N
Br
13. Han, S.; Luo, M.; Zhou, X.; He, Z.; Xiong, L. Ind. Eng. Chem.
Res. 2012, 51, 5433.
14. Xu, J.-M. ; Liu, B.-K.; Wu, W.-B.; Qian, C.; Wu, Q.; Lin, X.F. J.
Org. Chem. 2006, 71, 3991.
15. Gu, L.; Wang, W.; Liu, J.; Lia, G.; Yuan, M. Green Chem.
2016, 18, 2604.
16. Kaki, V. R.; Akkinepalli, R. R.; Deb, P. K.; Pichika, M.R. Synth.
Commun. 2015, 45, 119.
17. Siddiqui, I. R.; Waseem, M. A.; Shamim, S.; Shireen; Srivastava,
A. ; Srivastava, A. Tetrahedron Lett. 2013, 54, 4154.
18. Wu, H.; Zhang, F.; Wan, Y.; Ye, L. Lett.Org.Chem. 2016, 5, 209.
19. Swapnil, A. P.; Tayade, Y. A.; Wagh, Y. B.; Dalal, D.S. Chin.
Chem. Lett. 2016, 27, 714.
N
N
N
Br
2
3
1h
1h
1h
92
90
93
O2N
O2N
N
N
N
Br
Cl
Cl
N
N
N
Br
4
Br
Br

4
20. Zhu, X.; Wang, B.; Wang, H. Polym. Bull. 2010, 65,719.
21. Zhang, X. L.; Wang, D. F. Adv. Mat. Res. 2014, 989-994, 676.
22. Zang, H.; Wang, M.; Cheng, B.-W.; Song, J. Ultrasound.
Sonochem. 2009, 16, 301.
23. Khurana, J. M.; Chaudhary, A. Green Chem. lett. rev. 2012, 5,
633.
24. Gong, K.; Fang, D.; Wang, H. -L.; Liu, Z.-L. Monatsh. Chem.
2007, 138, 1195.
25. Ranu, B.C.; Jana, R. Eur. J. Org. Chem. 2006, 3767.
26. (a) Agalave, S. G.; Maujan, S. R.; Pore, V. S. Chem. Asian J.
2011, 6, 2696. (b) Tron, G. C.; Pirali, T.; Billington, R. A.;
Canonico, P. L.; Sorba, G.; Genazzani, A. A. Med. Res. Rev.
2008, 28, 278. (c) Kolb, H. C.; Sharpless, K. B. Drug Discovery
Today, 2003, 8, 1128. (d) Tam, A.; Arnold, U.; Soellner, M.B.;
Raines, R.T. J. Am. Chem. Soc. 2007, 129, 12670. (e) Lutz, J.-F.
Angew. Chem. Int. Ed. 2007, 46, 1018.
27. Huisgen, R. in 1,3-Dipolar Cycloaddition Chemistry (Ed.: A.
Padwa), Wiley, New York, 1984, p. 1-176.
28. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596.
29. Tornøe, C.W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002,
67, 3057.
30. Shin, J.A.; Lim, Y.-G.; Lee, K.-H. J. Org. Chem. 2012, 77, 4117.
31. Marra, A.; Vecchi, A.; Chiappe, C.; Melai, B.; Dondoni, A. J.
Org. Chem. 2008, 73, 2458.
32. (a) Zhao, Y.-B.; Yan, Z.-Y.; Liang Y.-M. Tetrahedron Lett. 2006,
47, 1545. (b) Ahmady, A. Z.; Heidarizadeh, F.; Keshavarz, M.
Synth. Commun. 2013, 43, 2100. (c) Mohan, B.; Kang, H.; Park,
K. H. Inorg. Chem. Commun. 2013, 35, 239. (d) Javaherian, M.;
Kazemi, F.; Ghaemi, M. Chin. Chem. Lett. 2014, 25, 1643. (e)
Artyushin, O. I.; Vorob'eva, D. V.; Vasil'eva, T. P.; Osipov, S. N.;
Röschenthaler, G.-V.; Odinets, I. L. Heteroatom Chem. 2008, 19,
293. (f) Yana, J.; Wang, L. Synthesis 2010, 3, 447.(g) Raut, D.;
Wankhede, K.; Vaidya V.; Bhilare, S.; Darwatkar, N.;
Deorukhkar, A.; Trivedi, G.; Salunkhe, M. Catal. Commun. 2009,
10, 1240. (h) Valizadeh, H.; Amiri, M.; Khalili, E. Mol Divers.
2012, 16, 319. (i) Zhong, P.; Guo, S.-R. Chin. J. Chem. 2004, 22,
1183.
33. (a) Ali, A. A.; Chetia, M.; Saikia, P. J.; Sarma, D. RSC Adv. 2014,
4, 64388. (b) Chetia, M.; Ali, A. A.; Bhuyan, D.; Saikia, L.;
Sarma, D. New J. Chem. 2015, 39, 5902. (c) Ali, A. A., Chetia,
M., Saikia, B., Saikia, P.J., Sarma, D. Tetrahedron Lett. 2015, 56,
5892. (d) Ali, A. A.; Chetia, M.; Sarma, D. Tetrahedron Lett.
2016, 57, 1711.(e) Konwar, M., Ali, A.A., Chetia, M., Saikia, P.J.,
Sarma, D. Tetrahedron Lett. 2016, 57, 4473.
34. (a) rasi ski, A.; Fokin V. V.; Sharpless, K. B. Org. Lett. 2004, 6
,1237. (b) Meng, X.; Xu, X.; Gao, T.; Chen B. Eur. J. Org. Chem.
2010, 5409.
35. General procedure for for the [3+2] Cycloaddition of Azides and
Terminal Alkynes: To a mixture of azide (1 mmol, 1 equiv.) and
acetylene (1.2 mmol, 1.2 equiv.) in [Bmim]OH ( 2 mL), catalyst
CuI (1 mol%) was consecutively added and the mixture was
allowed to proceed at room temperature for the given time period
as mentioned in Table 2. The progress of the reaction was
monitored by TLC. After completion of the reaction it was
extracted with EtOAc (2x20 mL), washed with brine, dried over
anhydrous sodium sulfate. The solvent was removed under
reduced pressure to give the crude product and purified through
silica gel column chromatography (10–20% EtOAc/hexanes) to
afford the desired product. The products are characterized by 1H
and 13C NMR spectroscopic data.
36. al, . e - on le . J. Org. Chem. 2011, 76, 2367.
37. General Procedure for the [3+2] Cycloaddition of Using Benzyl
Bromide Derivatives, sodium azide and Terminal Alkynes: To a
mixture of benzyl bromide derivatives (1 mmol), NaN3 (1.2
mmol), and an alkyne (1.2 mmol) in [Bmim]OH ( 2 mL) was
added CuI (1 mol%) and the resulting mixture was stirred at room
temperature for the given time period as mentioned in Table 3.
The progress of the reaction was monitored by TLC. After
completion of the reaction it was extracted with EtOAc (2x20
mL), washed with brine, dried over anhydrous sodium sulfate. The
solvent was removed under reduced pressure to give the crude
product and purified through silica gel column chromatography
(10–20% EtOAc/hexanes) to afford the desired product. The
products are characterized by 1H and 13C NMR spectroscopic data.

5
HIGHLIGHTS
. Basic ionic liquid catalyzed organic solvent free approach for 1,2,3-triazole synthesis
. No requirement of reducing agent, external base, promoter and ligand
. Inert condition is not necessary
. Development of three component one pot synthesis of 1,2,3-triazole in ionic liquid
. Environment friendly protocol