A copper-based ionic liquid as inexpensive and efficient catalyst for the [3 + 2] cycloaddition of azides and terminal alkynes

Article abstract of DOI:10.1016/j.inoche.2013.06.045

A fast and single-step synthesis of the octahedral Cu[(OHCH ₂CH₂)₂NH]₆[CF₃SO ₃]₂ ionic liquid is presented for use in click chemistry. The ionic liquid effectively catalyzes the

Full text of DOI:10.1016/j.inoche.2013.06.045

A copper-based ionic liquid as inexpensive and efficient catalyst for the [3+2]
cycloaddition of azides and terminal alkynes
Balaji Mohan, Hyuntae Kang, Kang Hyun Park
PII:
DOI:
Reference:
S1387-7003(13)00288-8
doi: 10.1016/j.inoche.2013.06.045
INOCHE 5151
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Inorganic Chemistry Communications
Received date:
Accepted date:
8 May 2013
27 June 2013
Please cite this article as: Balaji Mohan, Hyuntae Kang, Kang Hyun Park, A
copper-based ionic liquid as inexpensive and efficient catalyst for the [3+2] cycload-
dition of azides and terminal alkynes, Inorganic Chemistry Communications (2013), doi:
1
0.1016/j.inoche.2013.06.045
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ACCEPTED MANUSCRIPT
A copper-based ionic liquid as inexpensive and efficient catalyst for
the [3+2] cycloaddition of azides and terminal alkynes
*
Balaji Mohan, Hyuntae Kang and Kang Hyun Park
Department of Chemistry and Chemistry Institute for Functional Materials,
Pusan National University, Busan 609-735, Korea.
Corresponding author: Tel.: 82-51-510-2238
E-mail address: chemistry@pusan.ac.kr
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Abstract
A fast and single-step synthesis of the octahedral Cu[(OHCH CH ) NH] [CF SO ] ionic liquid is presented for
2
2 2
6
3
3 2
use in click chemistry. The ionic liquid effectively catalyzes the [3+2] cycloaddition of azides and terminal alkynes to
give 1,4-disubstituted 1,2,3-triazoles regioselectively with high yields, without requiring bases, reducing agents, or
inert atmospheres. The scope and catalytic activity of this ionic liquid are described herein for the first time. In
addition, the present cost effective catalytic system is impressive even under stirring free conditions.
Key Words: Alkynes; Copper; Cycloaddition; Homogeneous catalysis; Ionic Liquid.
The term “click chemistry” was coined by Sharpless [1] in 2001. Click chemistry refers to the synthesis of
complex compounds from a small set of modular building blocks and reactions and has applications in various fields
[
2]. For example, the copper(I)-catalyzed azide–alkyne cycloaddition regioselectively produces 1,2,3-triazoles with
high yields. This cycloaddition is generally achieved by in situ reduction of cupric salts [3], direct usage of cuprous
salts with phosphane [4] or polytriazoles [5] as ligands, N-heterocyclic carbene complexes [6] or comproportionation
0
II
I
of Cu /Cu couples [7]. Recently, many heterogeneous catalysts [8] such as Cu species immobilized on solid supports
like silica, activated charcoal, dendrimers, and zeolites were reported. Nevertheless, these heterogeneous catalytic
I
II
systems often suffer from aerial oxidation of Cu to Cu . Hence, these catalysts require an inert atmosphere and
anhydrous conditions to remain active, be recyclable, and give high yields of 1,4-regioisomers.
II
Furthermore, there are some reports of click chemistry catalyzed by Cu supported on heterogeneous systems [9],
which usually requires high temperatures, long reaction times, an inert atmosphere, and pretreatment of the catalysts.
In contrast, homogeneous catalysts [10] have also been employed, which generally demand microwave irradiation,
mixture of solvents, prolonged maintenance, reducing agents, additives, etc. In view of these drawbacks, the use of
metal nanoparticles has been increasingly explored to reduce both catalyst quantity and reaction time. Regardless of
the fascinating properties associated with copper nanoparticles (CuNPs) [11], there are some drawbacks preventing
their application, scope, competitiveness, and general acceptance that need to be overcome. For instance, most of the
methods to synthesize CuNPs require a long reaction time, base, high temperature, and an inert atmosphere. In
addition, the presence of stabilizing agents or surfactants is essential to circumvent the agglomeration of NPs and the
I
II
oxidation of Cu to Cu in most of the cases.
Metal nanoparticles immobilized on ionic liquids have been used as catalysts in various organic transformations.
For instance, Salunkhe et al. showed that CuNPs [12] immobilized in imidazolium ionic liquids were active catalysts
for the effective synthesis of triazoles under mild conditions. Although this catalyst is very active, it requires an excess
of reducing agents and two steps for the click reaction: synthesis of CuNPs protected by PVP (Polyvinylpyrrolidone),
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followed by immobilization of CuNPs in imidazolium ionic liquids.
To our knowledge, copper-based ionic liquids have not extensively been studied as catalysts [13] in organic
synthesis in the context of click chemistry, as opposed to in the context of immobilized ionic liquids [14]. Anderson
etal. [15] reported the simple synthesis of copper-, manganese-, iron-, and zinc-based ionic liquids well characterized
by various techniques, including IR, CV, TGA, and magnetic susceptibility measurements. Among these, we have
chosen the copper-based ionic liquid to study its catalytic activity in cycloadditions of azides and terminal alkynes.
Remarkably, this ionic liquid shows excellent catalytic activity with fast and complete consumption of azides under
very mild conditions in the absence of additives, stabilizers, and reducing agents. Thus, based on the above report,
[
15]we synthesized the copper ionic liquid by mixing copper trifluoromethanesulfonate and diethanolamine (DEA) at
elevated temperature and employed it as the catalyst for the azide–alkyne cycloaddition under aerobic conditions. Our
results demonstrate that this copper ionic liquid is an indispensable, environmentally friendly homogeneous catalytic
system that can convert both activated and non-activated substrates into the corresponding 1,4-disubstituted 1,2,3-
triazoles with excellent yields.
Reagents were purchased from Aldrich Chemical Co., TCI and Strem Chemical Co. and used as received.
1
13
Reaction products were analyzed by H and C-NMR (Varian Mercury Plus, 300 MHz). Chemical shift values were
recorded as parts per million relative to tetramethylsilane as an internal standard, unless otherwise indicated, and
coupling constants in Hertz. Reaction products were assigned by comparison with the literature value of known
compounds. A copper-based ionic liquid [Cu-IL] catalyst was synthesised [see Supplementary data] from Anderson’s
procedure [15]. All substituted triazoles (Table 2, entries 1-10) are synthesized at the reaction temperature of 50℃ in
order to get good
yields.
A 25mL Schlenk tube was flame dried under vacuum and cooled to room temperature. The flask was charged with
Cu-IL(10mol%), azide (200mg,1.503mmol), acetylene (184mg, 1.803mmol) were charged along with 2mL of DMF
and kept it in a preheated 50°C water bath under vigorous stirring. Reaction progress was monitored by TLC (10%
Ethyl Acetate : Hexane) from the consumption of azide. After the complete consumption of azide, reaction mass was
cooled to RT and poured into a beaker contains 10mL of water, stirred well and extracted with dichloromethane or
diethyl ether. Combined organic layers were separated and washed with water until complete copper ionic liquid goes
off into aqueous layer. The separated organic layer was dried with anhydrous sodium sulfate, filtered and concentrated
1
13
in a rotary evaporator until to remove solvent completely. The crude solid product was analyzed by H & C – NMR.
First, the cycloaddition of benzyl azide and phenylacetylene was carried out under various experimental
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conditions (see Table 1). The solvent screening revealed that dimethylformamide (DMF) gave excellent yield within a
short time (Table 1, entry 10) under very mild conditions. Other solvents such as t-butanol and t-butanol:water (Table
1
, entries 3 and 4) also gave quantitative yields of 3aa at slightly higher temperatures. Moderate yields were obtained
with water, toluene, and tetrahydrofuran (THF) (Table 1, entries 1, 2, 5, and 7). The reactions were also performed
with copper triflate alone and copper triflate combined with diethanolamine (Table 1, entries 13, 11, and 12). The
former isolates only the starting materials, whereas the latter exhibits low conversions due to incomplete ionic-liquid
formation at low temperature. Furthermore, the reaction in acetonitrile and without solvent (Table 1, entries 6 and 8)
took a long time.
Because the catalytic system is homogeneous, we compared its catalytic activity with and without stirring.
Surprisingly, the present catalytic system showed outstanding consumption of benzyl azide within 2 h (Scheme 1)
under mild conditions without stirring. We examined the catalytic activity of other copper (I) sources such as CuI,
[
Cu(OTf) ].C H , [Cu(NCCH ) ][PF ] shows 39, 83, 99% yields respectively. Among above, expensive
2 6 6 3 4 6
[
Cu(NCCH ) ][PF ] claims highest yield and almost equal to our copper (II) coordinated ionic liquid. We also
3
4
6
investigated whether Glaser homocoupling occurred in the absence of azides. Surprisingly, the catalytic system
showed no homocoupling products even under long-time stirring and heating (Scheme 2).
The scope of the present 1,3-dipolar cycloaddition of azides and terminal alkynes catalyzed by a copper ionic
liquid is rather broad, as illustrated in Table 2. All reactions showed excellent yields of 1,4-disubstituted 1,2,3-
triazole derivatives in the presence of air and in the absence of additives, bases, reducing agents, and expensive
ligands. NMR analyses revealed that the obtained products are exclusively 1,4-regioisomers (Table 2, entries 1–10).
In conclusion, the reported copper ionic liquid could act as an efficient, inexpensive homogeneous catalyst for the
1
,3-dipolar cycloaddition of azides and terminal alkynes. To improve the stability and recyclability of the catalyst,
work focusing on immobilizing the copper ionic liquid on a supporting material is underway.
Acknowledgments
This work was supported by Basic Science Research Program (2010-0026167), and the Ministry of Education,
Science Technology (MEST) and National Research Foundation of Korea(NRF) through the Human Resource
Training Project for Regional Innovation.
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Table 1. Click reaction under various experimental conditions
˚
T ( C) Conv.(%)a
Entry
Catalyst
10 mol%
10 mol%
Time
30mts
1hr
Solvent
H2O
1
2
50
50
46
100
H2O
3
4
5
6
7
8
9
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
30mts
30mts
30mts
30mts
30mts
30mts
30mts
15mts
30mts
50
50
50
50
50
50
30
30
50
96
100
71
32
72
53
67
96
23
t-BuOH:H O (1:1)
2
t-BuOH
Toluene
Acetonitrile
THF
Neat
t-BuOH
DMF
1
0
11
Cu(OTf) + DEA
t-BuOH
2
1
2
Cu(OTf) + DEA
30mts
30mts
50
50
37
0
DMF
DMF
2
13
Cu(OTf)2
a
1
Determined by H NMR from the amount of benzyl azide used.
Scheme 1. Catalytic activity of copper ionic liquid with and without stirring conditions
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Scheme 2. An inert catalytic system for Glaser homo coupling reaction
Table 2. Copper ionic liquid assisted 1,3-dipolar cycloaddition
a
Entry
Azide
Alkyne
Product
Time(min)
Conv.(%)
1
120
100 (100)
2
3
60
30
100 (100)
100 (100)
4
5
30
60
100 (100)
100 (100)
6
7
8
4
5
100 (100)
100 (100)
30
1
20
100 (98)
99 (100)
9
6
0
10
30
91 (100)
a
1
13
Determined by H & C NMR spectra.
Yield in parenthesis determined by GC-MS.
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Graphical Abstract
Cu-IL
Cu-IL
A fast single-step synthesis of the octahedral Cu[(OHCH CH ) NH] [CF SO ] ionic liquid is presented for use in
2
2 2
6
3
3 2
click chemistry. The ionic liquid effectively catalyzes the [3+2] cycloaddition of azides and terminal alkynes to
give1,4-disubstituted 1,2,3-triazoles regioselectively with high yields, without requiring bases, reducing agents, or
inert atmospheres.
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Highlights


A fast and Single step synthesis of copper-based ionic liquid
The catalytic activity of copper coordinated ionic liquid to synthesize triazoles through click chemistry


High regioselectivity with various substituted triazoles were reported
Stirring free conditions and no side products
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