Cu(BTC)-MOF catalyzed multicomponent reaction to construct 1,4-disubstituted-1,2,3-triazoles

Article abstract of DOI:10.1016/j.poly.2018.05.058

Cu(BTC)-MOF catalyzed one-pot, three-component reaction of terminal alkynes, halides and sodium azide to form 1,4-disubstituted-1,2,3-triazoles was investigated. It was conducted in methanol under room temperature with good to excellent product yields. Th

Full text of DOI:10.1016/j.poly.2018.05.058

Polyhedron 151 (2018) 515–519
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Cu(BTC)-MOF catalyzed multicomponent reaction to construct
1,4-disubstituted-1,2,3-triazoles
⇑
Xiangru Jia, Guangli Xu, Zhengyin Du , Ying Fu
Key Laboratory of Eco-Environment Related Polymer Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Northwest Normal University,
Lanzhou 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Cu(BTC)-MOF catalyzed one-pot, three-component reaction of terminal alkynes, halides and sodium
azide to form 1,4-disubstituted-1,2,3-triazoles was investigated. It was conducted in methanol under
room temperature with good to excellent product yields. The Cu(BTC)-MOF catalyst could be easily
recovered by filtration and be reused at least three recycles with no significant decrease in the yield.
The method was demonstrated to be a truly green process with sustainability and economics.
Ó 2018 Elsevier Ltd. All rights reserved.
Received 23 March 2018
Accepted 30 May 2018
Available online 7 June 2018
Keywords:
Cu(BTC)-MOF
Triazoles
Multicomponent reaction
One-pot reaction
Click reaction
1. Introduction
(CuAAC) [10]. In the past decades, CuAAC has been investigated
and applied in wide fields [11–14].
The 1,2,3-triazole group is an important structural element in a
broad range of organic molecules utilized in medicinal chemistry,
biological science, and material science [1]. Compounds-containing
1,2,3-triazole unit have been found widespread uses in pharma-
ceuticals and agrochemicals. 1,4-Disubstituted-1,2,3-triazoles are
known to possess many biological activities, for instance, anti
microbial, anti-HIV, anti-inflammatory, anti-cancer, fluorescent
activity, inhibitors of kinase-3b and other enzyme inhibitors
[2–5]. In addition, 1,2,3-triazole compounds have different applica-
tions in industry as dyes, corrosion inhibitors, photostabilizers,
photographic materials, and agrochemicals [6].
In the context of triazole assembly, regioselectivity control has
attracted extensive attention from the organic chemistry commu-
nity [7]. Classic thermal 1,3-dipolar cycloadditions of alkynes and
azides required high temperatures and resulted in triazoles with
low levels of regioselectivity control [8]. The synthesis of substi-
tuted 1,2,3-triazoles strongly relies on Huisgen’s 1,3-dipolar
cycloaddition between organic azides and substituted alkynes
[9]. Later, Sharpless and colleagues in 2002 developed the copper
catalyzed version of azide-alkyne cycloaddition with the formation
of regioselective product 1,4-disustituted-1H-1,2,3-triazole and
they named the reaction as the Click reaction, which is also
referred as the Cu-catalyzed azide-alkyne cycloaddition reaction
Nowadays, environmental consciousness encourages the chem-
ical community to search for more environmentally sustainable
chemical processes for chemical syntheses. For these purposes,
development of new heterogeneous recyclable catalysts and the
use of less toxic materials as solvents and reagents are two impor-
tant challenges.
The key role played by transition metal catalysts in chemical
reactions led to their integration into a wide array of more complex
structures [15,16]. In truth, several types of macro-molecular
metal catalysts have been developed to increase catalyst selectiv-
ity, stability, and recyclability. For example, metal–organic frame-
works (MOFs) are heterogeneous lattices in which the metal is
integral to the three-dimensional structure [17]. MOFs as a new
type of organic/inorganic hybrid materials have attracted great
focus of scientists in recent years [18]. It is composed of organic
ligands and inorganic metal units and generally has a varied topo-
logical structure and unique physical/chemical properties. Due to
its porous frame structure, large specific surface area and great
variety, MOFs are widely used in functional materials, gas adsorp-
tion, drug sustained release, catalysis and organic synthesis [19].
Furthermore, multicomponent reactions (MCRs) represent one
of the growing synthetic approaches due to the fact that they pro-
vide useful products through the expeditious creation of multiple
bonds in a one-pot reaction [20]. Under this concept, many
reagents are added in only one step and they react to give only
one product selectively [21]. This method has been successfully
applied in the organic chemistry field [22–24].
⇑
Corresponding author.
E-mail address: clinton_du@126.com (X. Jia).
https://doi.org/10.1016/j.poly.2018.05.058
0277-5387/Ó 2018 Elsevier Ltd. All rights reserved.

516
X. Jia et al. / Polyhedron 151 (2018) 515–519
So far, no literature was involved in MOFs catalyzed three-com-
reaction. The impact of different reaction conditions was tested.
The results are shown in Table 1.
ponent Click reaction. At this point, we report herein a simple and
efficient one-pot, three-component cycloaddition of terminal alky-
nes, halides, and sodium azide to get 1,4-disubstituted-1,2,3-tria-
zoles catalyzed by Cu(BTC)-MOF under mild reaction conditions.
In our initial study, the reaction solvent was screened (Table 1,
entries 1–4). It was observed that the reaction was effective in
CH3OH to form the product in 66% yield, whereas no product
was observed in DMF and THF. So methanol was chosen as the sol-
vent for further study of the synthesis of triazoles. The effect of
mole ratio of benzeneacetylene, benzyl chloride, and sodium azide
was also investigated. From the results shown in Table 1, entries 1,
5–8, the better mole ratio of benzeneacetylene, benzyl chloride,
and sodium azide was 1:1.6:2 and 83% product yield was obtained
(entry 8). Then we studied the effect of the temperature on the
reaction. In accordance with expectation, with increase the reac-
tion temperature to 50 °C, the yield of the product decreased
slightly (Table 1, entry 9). To further improve the yield, the amount
of the catalyst was increased and the results show that 0.0100 g of
Cu(BTC)-MOF was the optimized dosage (Table 1, entries 8, 10 and
11).
2. Results and discussion
A preliminary survey of reaction conditions was conducted with
phenylacetylene, benzyl chloride, and sodium azide as a model
Table 1
Screening of the reaction conditions for the three-component click reaction.a
N
N
N
l
C
NaN3, Cu(BTC)-MOF
+
Subsequently, we studied the scope of phenylacetylenes and
benzyl halides in this reaction under optimized conditions. The
results indicated that reactions of various substituted pheny-
lacetylenes, benzyl halides and sodium azide proceeded well, and
desire products were obtained in good to excellent isolated yields
as shown in Table 2. Electron-donating and electron-withdrawing
groups attaching on benzene ring of phenylacetylenes and benzyl
halides have no significant effect on the reaction. Nevertheless,
when electron-rich 4-methylphenylacetylene and electron-defi-
cient 4-fluorobenzyl halide were used in this reaction, the corre-
sponding 1,2,3-triazole with an alkynyl substituent at 5-position
was obtained in 76% yield (Table 2, entry 6). Moreover, when
1-hexyne was used instead of phenylacetylene in this reaction,
the corresponding 5-alkynyl substituted 1,2,3-triazole was
obtained in 54% yield (Table 2, entry 11). These results are consis-
tent with the reported literatures [11,25].
Entry
Mole ratio
Cu(BTC)-MOF (g)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.6
1:1.6:1.2
1:1.6:1.6
1:1.6:2
0.0050
0.0050
0.0050
0.0050
0.0050
0.0050
0.0050
0.0050
0.0050
0.0075
0.0100
CH3OH
DMF
CH3CN
THF
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
66
–
<5
–
72
78
82
83
81
87
88
9c
10
11
1:1.6:2
1:1.6:2
1:1.6:2
a
Reaction conditions: Solvent (2 mL), r.t., 16 h. Mole ratio is n(benzeneacetylene)
n(benzyl chloride):n(sodium
:
In addition, all kinds of alkyl bromides were subjected to the
same reaction conditions to furnish the corresponding 1,4-disub-
stituted-1,2,3-triazoles and the results are given in Table 3. The
.
azide)
b
Isolated yield.
Temperature is 50 °C.
c
Table 2
Cu(BTC)-MOF catalyzed cycloaddition of substituted alkynes, benzyl halides, and sodium azide.a
Entry
1
Alkyne
Benzyl halide
Product
Yield (%)b
88
N
N
N
N
Cl
2
3
4
5
6
N
91
89
78
83
76
N
Br
Br
Br
N
N
Me
F
N
Me
F
N
N
N
N
N
F
F
N
Cl
Cl
F
Me
F
Me
N
N
N
Me

X. Jia et al. / Polyhedron 151 (2018) 515–519
517
Table 2 (continued)
Entry
7
Alkyne
Benzyl halide
Product
Yield (%)b
N
N
N
67
F
F
N
Cl
F
F
8
N
90
Me
N
Cl
Me
N
N
9
82
80
Me
F
Me
Me
N
Cl
Me
Me
F
N
N
10
N
Cl
e
M
11
54
Br
N
N
N
a
Reaction conditions: alkynes (0.5 mmol), benzyl halides (0.8 mmol), sodium azide (1.0 mmol), Cu(BTC)-MOF (0.0100 g), methanol (2 mL), r.t., 16 h.
Isolated yield.
b
Table 3
Cu(BTC)-MOF catalyzed cycloaddition of substituted phenylacetylenes, alkyl bromides and sodium azide.a
Entry
1
Alkyne
Alkyl bromide
Product
Yield (%)b
64
N
N
Br
N
N
N
2
3
4
51
50
57
Me
F
Br
N
Me
F
N
N
Br
N
Br
N
N
N
N
N
5
6
65
52
Br
Me
Me
N
Me
Me
N
N
Br
Br
N
N
N
7
57
56
58
61
83
N
N
N
8
Br
Br
N
N
N
9
Me
F
N
Me
F
N
N
10
11
Br
N
N
N
Br
N
a
Reaction conditions: substituted benzeneacetylene (0.5 mmol), alkyl bromides (0.8 mmol), sodium azide (1.0 mmol), Cu(BTC)-MOF (0.0100 g), methanol (2 mL), 16 h, r.t.
Isolated yield.
b

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X. Jia et al. / Polyhedron 151 (2018) 515–519
Table 4
4.2. Preparation and characterization of Cu(BTC)-MOF
Reusability of Cu(BTC)-MOF.a
We prepared the Cu(BTC)-MOF catalyst according to the previ-
ous literature [26,27]. A mixture of Cu(NO3)2Á3H2O (3.0 mmol,
0.725 g), benzene-1,3,5-tricarboxylic acid (H3BTC, 1.0 mmol,
0.210 g), DMF (5.0 mL) and distilled water (5.0 mL) were placed
in a Teflonlined stainless autoclave to react at 100 °C for 10 h, then
cooled to room temperature, washed with deionized water and
anhydrous ethanol for 3–5 times and dried at 80 °C to give a blue
powder.
Entry
Cycle
Yield b(%)
1
2
3
4
Fresh
91
89
87
87
1st recycle
2nd recycle
3rd recycle
a
Reaction conditions: phenylacetylene (0.5 mmol), benzyl bromide (0.8 mmol),
sodium azide (1.0 mmol), Cu(BTC)-MOF (0.0100 g), methanol (2 mL), r.t., 16 h.
b
Isolated yield.
The characterization of fresh and recycled Cu(BTC)-MOF was
conducted by FT-IR spectra and comparison study with reported
literatures [26,27].
yields of products were moderate in general. The length of alkyl
chain didn’t evidently affect yields of products. When bulky tert-
butyl bromide was used in this reaction, satisfied yields of 50–
64% were obtained (Table 3, entries 1–3). This indicates that steric
hindrance of alkyl bromides has also no obvious effect on the
reaction.
4.3. General procedure for one-pot synthesis of 1,4-disubstituted-
1,2,3-triazoles
In a 10 mL round bottom flask fitted with a magnetic stirrer, the
catalyst (0.0100 g), alkyne (0.5 mmol), sodium azide (0.8 mmol)
and halide (1.0 mmol) were stirred in CH3OH (2.0 mL) at room
temperature and the progress of the reaction was monitored using
TLC. After completion of the reaction, the solution was filtered by
suction and the solvent was evaporated in vacuo to give the crude
product. The obtained crude product was purified by column chro-
matography on silica gel to give the desired 1,4-disubstituted-
1,2,3-triazoles using petroleum ether/ethyl acetate (8:1 v/v) as
eluting solvents to yield the pure product as colorless solid.
Finally, we have investigated the possibility of recycling of the
catalyst. The reusability of Cu(BTC)-MOF was explored by model
reaction of phenylacetylene, benzyl bromide and sodium azide
and the results are shown in Table 4. The performance of the recy-
cled catalyst was tested up to three successive runs without signif-
icant yield loss of the reaction. It can be showed that the product
yield was still up to 87%, which indicates that Cu(BTC)-MOF have
high catalytic activity and stability under our experimental condi-
tions (Table 4). The result of hot filtration experiment of the cata-
lyst shows that Cu(BTC)-MOF was the efficient heterogeneous
catalyst and no copper ion was found in the filtrate. The compar-
ison of IR spectra of Cu(BTC)-MOF before and after reaction also
manifests that the structure of Cu(BTC)-MOF had no obvious
changes (see Supplementary Materials).
Acknowledgment
We gratefully acknowledge the National Natural Science
Foundation of China (21262028, 21762039) for financial support.
3. Conclusions
Appendix A. Supplementary data
In conclusion, a simple protocol for the synthesis of 1,4-disub-
stituted-1,2,3-triazoles through the one pot, three-component
reaction of halides, sodium azide and terminal alkynes was estab-
lished. The reaction was performed in methanol at room tempera-
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.poly.2018.05.058.
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substrates, cleaner process and good to excellent yields of
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