Application of two magnetic nanoparticle-supported copper(I) catalysts for the synthesis of triazole derivatives

Article abstract of DOI:10.1007/s11164-019-03864-7

Catalytic performance of two magnetically recoverable copper(I) complexes is reported for the synthesis of 1,2,3-triazole derivatives. Boronic acids and alkyl halides, in the presence of either catalyst, react with terminal alkynes and NaN₃, fo

Full text of DOI:10.1007/s11164-019-03864-7

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03864-7
Application of two magnetic nanoparticle‑supported
copper(I) catalysts for the synthesis of triazole derivatives
Leila Mohammadi1,2 · Mohammad Ali Zolifgol1 · Meysam Yarie1 ·
Mahsa Ebrahiminia2 · Kenneth P. Roberts2 · Syed R. Hussaini2
Received: 8 April 2019 / Accepted: 15 May 2019
© Springer Nature B.V. 2019
Abstract
Catalytic performance of two magnetically recoverable copper(I) complexes is
reported for the synthesis of 1,2,3-triazole derivatives. Boronic acids and alkyl hal-
ides, in the presence of either catalyst, react with terminal alkynes and NaN3, form-
ing 1,2,3-triazole derivatives in good yields. Both catalysts are easily recoverable
and show a high potential of reusability.
Keywords 1,2,3-Triazole · Click reaction · Nanomagnet · Copper(I)
Introduction
Currently, one important feld of catalysis is the design, synthesis and applica-
tion of nanomagnetic catalysts in organic transformations. From the perspective
of green chemistry principles, nanomagnetic catalysts are ideal selections as they
enable environmentally friendly and sustainable catalytic processes [1–4]. Further-
more, functionalization of magnetically recoverable nanomaterials provides a bridge
between heterogeneous and homogeneous catalysis. These magnetic nanoparticle-
supported catalysts have features of both homogeneous and heterogeneous catalysts.
For example, they have high activity and selectivity, and they are easy to separate,
recover and reuse [5–9].
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03864-7) contains supplementary material, which is available to authorized users.
* Mohammad Ali Zolifgol
zolf@basu.ac.ir
* Syed R. Hussaini
syed-hussaini@utulsa.edu
1
Faulty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
2
Department of Chemistry & Biochemistry, The University of Tulsa, 800 S. Tucker Dr., Tulsa,
OK 74104, USA
Vol.:(0123456789)
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L. Mohammadi et al.
Among the metal-based catalytic systems, copper catalysis has received sig-
nificant attention due to the appealing features of copper such as low cost and
low toxicity [10]. As Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states are eas-
ily accessible, both radical and two-electron bond-forming pathways are pos-
sible through copper catalysis [11]. Because of these qualities, copper catal-
ysis is frequently used to enhance the ease and practicality of the synthetic
processes. Copper catalysts have shown great performance in varied organic
transformations including C–N, C–O, C–S, and C–C bond forming reactions
[10], asymmetric coupling reactions [12], C–H functionalization [13], syn-
thesis of N-heterocyclic compounds [14], and aerobic organic reactions [11].
Compared with other catalysts based on Ru, Ag, Ir, Ni, Zn, and Ln metals,
Cu(I) catalysts are the ones most used in promoting the azide-alkyne cycload-
dition reaction [15, 16].
Formation of 1,2,3-triazoles through Cu(I)-catalyzed azide-alkyne cycload-
dition (CuAAC) has attracted much attention in recent years. This reaction
between organic azides and terminal alkynes enables the construction of 1,4-dis-
ubstituted triazoles and is classifed as a ‘click reaction’. The reaction has vari-
ous advantages. These include no or mild heating requirements, a wide substrate
scope, benign reaction conditions and easy workup and purifcation procedures
that give high yields of products [17].
The 1,2,3-triazole derivatives are commonly utilized in drug development and
in the preparation of functional materials [14, 18]. These versatile heterocycles
are used as antibacterial and antiviral agents, and as a ligation tool in polymer
and materials science [18–27]. Due to this importance, the synthesis and chem-
istry of 1,2,3-triazole are well-documented [28–40].
We are interested in the design, synthesis and applications of nanomagnetic
catalysts [41–43]. Because of the abovementioned merits of Cu(I)-catalysis in
organic transformations and the importance of 1,2,3-triazoles, we were inter-
ested to test nanomagnetic catalysts in the synthesis of 1,2,3-triazoles. Although
many copper catalysts have been used in the synthesis of 1,2,3-triazoles, genu-
ine Cu(I) catalysts are more reactive. The copper component may be a prob-
lem if traces remain under physiological conditions [44]. Copper(I)-complexed
magnetic nanoparticle catalysts provide a solution to this problem as these cata-
lysts can provide stable Cu(I)-catalysts which can be easily removed from the
reaction mixture and reused. Furthermore, nanocatalysts exhibit higher catalytic
activity than conventional catalysts, due to enhanced surface area [16]. This is
one reason why application of nanomagnetic catalysts in the preparation of tri-
azoles have become an active area of research [29, 31, 36, 45–47]. Here, we
report the performance of two highly efcient Cu(I)-nanomagnetic catalysts in
the synthesis of 1,2,3-triazoles. These catalysts were tested in two very direct
methods (both one pot) of making 1,2,3-traizoles—the reaction between NaN3,
alkynes and boronic acids, and the reaction between NaN3, alkynes and alkyl
halides. The structures of the two catalysts are shown in Fig. 1. We have previ-
ously reported the synthesis and characterization of these two catalysts [42, 43].
1 3

Application of two magnetic nanoparticle-supported copper(I)…
Fig. 1 The structures of Cu(I)-complexed magnetic nanoparticle catalysts 1 and 2
Experimental
General Method A. Synthesis of 3a–3i
Catalyst 1 or 2 (20 mg) was added to a mixture of alkyne (1.0 mmol), NaN3
(3.0 mmol) and arylboronic acid (1.0 mmol) in 2.0 mL of EtOH/H2O. The resulting
mixture was stirred at room temperature for the specifed period of time (Table 2).
The catalyst was separated from the reaction mixture with a permanent magnet. The
catalyst was washed with distilled water (15 mL×5) and MeOH (15 mL×5) for
future use. The reaction mixture was evaporated. The residue was dissolved in ethyl
acetate (30 mL) and washed with water (10 mL). The organic layer was separated,
dried over anhydrous Na2SO4, and concentrated under reduced pressure to give
crude 3. Crude 3 was purifed by column chromatography.
General method B. Synthesis of 4a–4h
Similar to general method A with the following modifcations. Amount of catalyst 2
used in the reaction was 50.0 mg. The reaction was stirred for the time specifed in
Table 4. After the catalyst was removed, water (5.0 mL) was added and the reaction
mixture was extracted with EtOAc (2.0×10 mL). The organic layer was dried over
anhydrous Na2SO4 and the solvent was evaporated under reduced pressure to give
crude 4. Crude 4 was recrystallized from CH2Cl2, n-hexane, to yield the purifed
product.
3‑(1‑(4‑(tert‑Butyl)phenyl)‑1H‑1,2,3‑triazol‑4‑yl)propan‑1‑ol (3b)
General method A was used for the preparation of 3b. Column chromatography
was carried out using 60% ethyl acetate in dichloromethane. Isolated yield: 43%;
1
m.p.=83–85 °C; H NMR (400 MHz, CDCl3) δ: 7.65–7.51 (m, 5H), 3.80 (s, br,
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L. Mohammadi et al.
2H), 2.93 (s, br, 2H), 2.10–2.03 (m, 3H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3)
δ: 152.1, 133.8, 126.8, 124.9, 120.4, 62.1, 34.9, 31.9, 29.8; HRMS (ESI+) m/z
(M+H)+ calcd for C15H22N3O, 260.1759; measured, 260.1761.
4‑Phenyl‑1‑(phenyl‑1‑(p‑tolyl)‑1H‑1,2,3‑triazole (3h) [48, 49]
General method A was used for the preparation of 3h. Column chromatography
was carried out using 60% ethyl acetate in petroleum ether. Isolated yield: 81%;
1
m.p.=158–160 °C; H NMR (300 MHz, DMSO-d6) δ: 9.24 (s, br, 1H), 8.05–7.71
(m, 4H), 7.60–7.30 (m, 5H), 2.37 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 148.2,
139.3, 131.2, 130.0, 129.1, 126.6, 120.8, 120.4, 21.5.
Results and discussion
We selected the reaction of phenylboronic acid, NaN3 and phenylacetylene to fnd
the best reaction conditions for the synthesis of 1,2,3-triazoles. In light of previ-
ous results [42, 43] selected amounts of catalysts and solvents were screened at
room temperature (Table 1). Both catalysts 1 and 2 successfully formed 3a. The
best conditions are when the reaction (1 mmol scale) is performed in the solvent
mixture of EtOH and water (1:1) with 20 mg of catalysts. In the case of catalyst
Table 1 Screening for optimal reaction conditions for the synthesis of 3aa
Entry
Catalyst (mg)
Solvent
Catalyst 1
Catalyst 2
Time (h)
Yield (%)b
Time (h)
Yield (%)b
1
2
3
4
20
20
20
10
H2O
EtOH
EtOH/H2O (1:1)
EtOH/H2O (1:1)
4
4
4
4
90
60
95
60
10
10
10
10
70
70
98
60
aReaction conditions: Phenylboronic acid (1.00 mmol, 0.122 g), NaN3 (3.00 mmol, 0.195 g), phenyla-
cetylene (1.00 mmol, 0.102 g), solvent: 2.00 mL. rt
bIsolated yield
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Application of two magnetic nanoparticle-supported copper(I)…
1, the reaction completes in 4 h and in the case of catalyst 2, the model reaction
completes in 10 h.
We used the optimized reaction conditions to study the scope and limitations of
these catalysts. Various 1,2,3-triazole derivatives were prepared via the three-com-
ponent cross-coupling click reaction between arylboronic acids, NaN3 and alkynes
in the presence of nanomagnetic catalysts 1 and 2 (Table 2). The reaction was suc-
cessful with both electron donating (Table 2, entries 2, 6 and 8–9) and electron with-
drawing groups (Table 2, entry 7) on arylboronic acids. Both aromatic (Table 2,
entries 1, 3–9) and aliphatic (Table 2, entry 2) alkynes can be transformed into
3. The presence of unprotected alcohol or the fuorine atom on alkynes (Table 2,
entries 2–4) afected the performance of catalyst 2. However, even in these cases,
catalyst 1 still gave high yields of cycloadducts 3.
Next, we decided to compare the two catalysts in the preparation of 1,2,3-tria-
zoles from aryl halides, NaN3 and alkynes. Reaction optimization and substrate
scope have already been reported with catalyst 1 [42]. We carried out same reaction
optimization strategy with catalyst 2 (Table 3). The best results were obtained when
the reaction (1 mmol scale) was performed in the presence of 50 mg of the catalyst
and using water as the green solvent (Table 3, entry 3).
We tested the scope and versatility of the method towards the synthesis of
1,2,3-triazoles. Yields of 4 obtained from catalyst 2 were compared with our previ-
ously reported yields of 4 while using catalyst 1 (Table 4) [42]. The reaction was
successful with aromatic (Table 4, entries 1–7) and aliphatic (Table 4, entry 8) alkyl
halides. The reaction gave product 4 with aromatic (Table 4, entries 1, 3–5 and 8)
and aliphatic alkynes (Table 4, entries 2 and 6–7) and tolerated both electron donat-
ing (Table 4, entries 3 and 5) and electron withdrawing alkynes (Table 4, entry 7).
All products were obtained in high yields.
We explored the recovery and reusability of catalysts 1 and 2 in the synthesis of
3a and 4a (Table 5). After each run, the nanomagnetic catalysts were separated from
the reaction mixture via an external magnet. The catalysts were thoroughly washed
with H2O and MeOH. After drying, the catalysts were used in the next run. Even
after fve cycles, both catalysts were able to catalyze the formation of 3a and 4a and
the products were obtained in high yields. Therefore, we conclude that both catalysts
have good recyclability in the formation of 1,2,3-triazoles from either arylboronic
acids or alkyl halides.
The expected mechanism operative here involves formation of aryl azides from
arylboronic acids and alkyl halides. Although the conversion of arylboronic acids to
aryl azides via a Cu(I)-catalyzed process in the presence of sodium azide is known
[50, 51], the mechanistic details are unknown [49, 52, 53] The conversion of alkyl
halides to alkyl azides is an SN2 process [50]. Once formed, aryl or alkyl azides
undergo the usual Cu(I)-catalyzed cycloaddition, giving products 3 and 4 [54].
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L. Mohammadi et al.
Table 2 Synthesis of 1,2,3-triazoles from arylboronic acids in the presence of catalysts 1 and 2a
Catalyst Catalyst
1
2
Arylboronic
acid
Time
(h)/
Time
Entry
Alkyne
Product
(h)/
Yield
Yield(%)b
(%)b
1
4/95
10/98
2
4/85
7/43
3
4
4/82
5/81
10/78
12/50
5
3/93
12/90
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Application of two magnetic nanoparticle-supported copper(I)…
Table 2 (continued)
Catalyst Catalyst
1
2
Arylboronic
Time
(h)/
Time
Entry
Alkyne
Product
acid
(h)/
Yield
Yield(%)b
(%)b
6
2/90
10/92
7
3/93
10/85
8
4/92
8/81
9
3/90
6/83
aReaction conditions: Boronic acids (1.00 mmol), NaN3 (3.00 mmol, 0.195 g), alkynes (1.00 mmol), sol-
vent: 2.00 mL. 20 mg catalyst 1 or 2, rt
bIsolated yield
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L. Mohammadi et al.
Table 3 Screening for optimal reaction conditions for the synthesis of 4aa
Entry
Catalyst (mg)
Solvent
Catalyst 2
Time (h)
Yield (%)b
1
2
3
4
5
6
7
10
50
20
50
10
10
20
–
–
5
5
5
5
5
5
5
5
5
H2O
H2O
EtOH
MeOH
CH3CN
60
90
20
25
10
aReaction conditions: Benzyl bromide (1.00 mmol, 0.171 g), NaN3 (3.00 mmol, 0.195 g), phenylacety-
lene (1.00 mmol, 0.102 g), solvent: 2.00 mL. rt
bIsolated yield
Conclusions
In summary, catalytic performance of two magnetically recoverable copper(I) com-
plexes was investigated in the synthesis of 1,2,3-triazoles via reactions between
arylboronic acids or alkyl halides, terminal alkynes and NaN3. Both catalysts show
excellent catalytic activity and recyclability. All desired compounds, prepared
through benign reaction conditions, were obtained in high yields.
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Application of two magnetic nanoparticle-supported copper(I)…
Table 4 Synthesis of 1,2,3-triazoles from aryl halides in the presence of catalysts 1 and 2a
Catalyst Catalyst
1
2
Time
(h)/
Time
Entry
Alkyl halide
Alkyne
Product
(h)/
Yield
Yield(%)c
(%)b
1
0.5/92
5/90
2
1/90
5/90
3
1/90
5/93
4
5
0.5/90
0.5/85
5/86
5/92
6
1.5/92
5/91
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L. Mohammadi et al.
Table 4 (continued)
Catalyst Catalyst
1
2
Time
(h)/
Time
Entry
Alkyl halide
Alkyne
Product
(h)/
Yield
Yield(%)c
(%)b
7
8
1.5/89
1/89
5/88
5/88
aReaction conditions: Alkyl halides (1.00 mmol), NaN3 (3.00 mmol, 0.195 g), alkynes (1.00 mmol), sol-
vent: 2.00 mL. 50.0 mg catalyst 2, rt
bIsolated yield
cPreviously reported yields [42]
Table 5 Recyclability of catalysts 1 and 2 in the preparation of 3a and 4a
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Cycle 5
3a
4a
Yield (%)a catalyst 1/2
Time (h) catalyst 1/2
Yield (%)a catalyst 1/2
Time (h) catalyst 1/2
95/98
4/10
92/90
91/93
4/10
89/87
87/90
4/10
85/85
85/82
6/11
84/85
85/82
6/11
82/80
0.5/5
0.5/5
0.5/5
0.75/7
0.75/7
aIsolated yields
Acknowledgements This work was supported by The University of Tulsa; The National Science Founda-
tion under Grant [CHE-1048784]; the Ministry of Science, Iran; Bu-Ali Sina University; the Iran National
Science Foundation [Grant No. 940124]; and the National Elites Foundation.
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