Cu(ii) PBS-bridged PMOs catalyzed one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles in water through click chemistry

Article abstract of DOI:10.1039/c4ra04093g

A series of PBS-HPMO and Cu(ii)-PBS-HPMO were synthesized from the self-assembly of 1,2-bis(triethoxysilyl)ethane and porphyrin-bridged silsesquioxane (PBS). These synthesized PBS-HPMO and Cu(ii)-PBS-HPMO were characterized using different spectroscopic and non-spectroscopic techniques, namely, XRD, FT-IR spectroscopy, nitrogen adsorption-desorption isotherms, and UV-visible and EPR spectroscopies. Among these, the porphyrin-bridged PMOs, specifically Cu(ii)-PBS-HPMO, were found to be proficient catalysts for the multicomponent reaction of benzyl halides with sodium azide and terminal alkynes. This catalyst allowed for the high regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles through a one-step and atom economic tandem reaction with water as the solvent. Note that no additional base or ligand or reducing agent is required. Moreover, in addition to benzyl halides, hetero benzyl halides have also been achieved in remarkable yields and in a completely regioselective manner. A series of structurally diverse 1,2,3-triazoles were also prepared in good to excellent yields from easily accessible starting materials by employing this protocol. Furthermore, this process is purely heterogeneous and the cascade reactions were performed in water, and the efficient catalyst recyclability makes such a synthesis a truly green process.

Full text of DOI:10.1039/c4ra04093g

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Cu(II) PBS-bridged PMOs catalyzed one-pot
synthesis of 1,4-disubstituted 1,2,3-triazoles in
Cite this: RSC Adv., 2014, 4, 29772
water through click chemistry†
a
b
b
Avvari N. Prasad,ab Benjaram M. Reddy, Eun-Young Jeong and Sang-Eon Park
*
*
A
series of PBS-HPMO and Cu(II)-PBS-HPMO were synthesized from the self-assembly of 1,2-
bis(triethoxysilyl)ethane and porphyrin-bridged silsesquioxane (PBS). These synthesized PBS-HPMO and
Cu(II)-PBS-HPMO were characterized using different spectroscopic and non-spectroscopic techniques,
namely, XRD, FT-IR spectroscopy, nitrogen adsorption–desorption isotherms, and UV-visible and EPR
spectroscopies. Among these, the porphyrin-bridged PMOs, specifically Cu(II)-PBS-HPMO, were found to
be proficient catalysts for the multicomponent reaction of benzyl halides with sodium azide and terminal
alkynes. This catalyst allowed for the high regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles
through a one-step and atom economic tandem reaction with water as the solvent. Note that no
additional base or ligand or reducing agent is required. Moreover, in addition to benzyl halides, hetero
benzyl halides have also been achieved in remarkable yields and in a completely regioselective manner.
A series of structurally diverse 1,2,3-triazoles were also prepared in good to excellent yields from easily
accessible starting materials by employing this protocol. Furthermore, this process is purely
heterogeneous and the cascade reactions were performed in water, and the efficient catalyst
recyclability makes such a synthesis a truly green process.
Received 4th May 2014
Accepted 11th June 2014
DOI: 10.1039/c4ra04093g
www.rsc.org/advances
materials and permit savings on solvents as well as reagents. In
addition, MCRs are the most potent tools for the creation of
intricate structures in a single step.1,2 Hence, we have been
working on MCRs, employing a new class of ecofriendly
heterogeneous catalysts, which are easy to prepare, handle, and
recycle.
1 Introduction
In the context of green chemistry, the search for alternative
safer, cleaner, and ecofriendly technologies plays a vital role in
synthetic organic chemistry. With this objective, chemists are
facing major challenges to develop organic chemistry processes
using new catalysts and catalytic systems that result in less
waste and generate fewer hazardous substances. Catalysis, in
particular, heterogeneous catalysis is one of the fundamental
aspects of green chemistry. Multicomponent reactions (MCRs)
have proven to be very prominent and effective bond-forming
tools in synthetic organic chemistry along with medicinal and
combinatorial chemistry, in recent years. MCRs are convergent
chemical synthesis processes, in which three or more starting
materials are involved in a single synthetic operation without
any isolation of any intermediate. These approaches have
multiple advantages such as the elimination of complicated
purication operations, use of readily available starting
Since 2001, the click reaction of azides and terminal alkynes,
which was pioneered by Sharpless and co-investigators, has
received prominent attention.3 Huisgen 1,3-dipolar azide–
alkyne cycloaddition4 has been recognized as one of the most
noteworthy synthetic tools because of the expedient and reliable
assembly of 1,2,3-triazole moieties, which exhibit a wide spectra
of biological activities and are thus oen found to be the vital
nuclei of biologically active molecules.5 Moreover, the cycload-
dition of azides with alkynes has emerged as an archetypical
example of “click chemistry,” and it is a key step in the rst
series of click backbone amide linkers.6 The obtained 1,2,3-tri-
azole scaffolds possess interesting properties and have led to a
substantial growth in click chemistry research. The wide scope
of azide–alkyne cycloaddition is demonstrated by its use in
numerous areas of life and material sciences, including drug
discovery,7 bioconjugation chemistry,8 supramolecular chem-
istry,9 solid phase reactions,10 DNA labelling,11 drug-like mole-
cules with signicant biological properties comprising anti-HIV
activity,12 as well as antimicrobial activity against Gram-positive
bacteria, the assembly of glycoclusters13 and glycodendrimers,14
and for stationary phases in functionalized HPLC columns.15
aInorganic and Physical Chemistry Division, CSIR–Indian Institute of Chemical
Technology, Hyderabad – 500007, India. E-mail: bmreddy@iict.res.in; Tel: +91 40
27193510
bLaboratory of Nano-Green Catalysis, Department of Chemistry, Inha University, 253
Yonghyun-dong, Incheon 402-751, Republic of Korea. E-mail: separk@inha.ac.kr;
Tel: +82 32 860 7675
† Electronic supplementary information (ESI) available: 1H NMR and 13C NMR
data and spectras of isolated compounds. See DOI: 10.1039/c4ra04093g
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In heterocyclic chemistry, the triazole moiety is treated as a covalent attachment of the catalytic active metal centres at the
robust keystone in complex molecular architectures.16 Recently, mesopore surface.42
several groups have reported triazole moieties acting as donors
We herein report the synthesis of a series of PBS-HPMO and
in metal complexes, including in applications in catalysis17 such Cu(II)-PBS-HPMO as novel catalysts, and their use for the
as the tris-(triazole) ligands,18 and as very procient catalysts for synthesis of 1,4-disubstituted 1,2,3-triazoles as MCRs with
the azide–alkyne cycloaddition reaction. Further, tri- readily available starting materials and water as the solvent. To
azolylmethyl phosphines and tetradentate bis-(triazolylamines) the best of our knowledge, in only very few instances, has Cu(II)
have been used for Pd-catalyzed allylic alkylation reactions19 (as Cu(II)-hydrotalcite, Cu(II) acetate) been used for the regio-
and Mn-catalyzed epoxidation reactions,20 respectively. In selective synthesis of 1,4-disubstituted 1,2,3-triazoles.36 It is
addition, 1,2,3-triazole scaffolds are smart linking units due to worth mentioning here that the Cu(II)-PBS-HPMO has been
their capability of hydrogen bonding; moreover, they are stable employed for the rst time in the eld of azide–alkyne cyclo-
to metabolic degradation, which is responsible for binding the addition MCR and has achieved a high product yield.
biomolecular targets and can improve the solubility of the
compounds. The triazole moieties also display a number of
chemotherapeutic properties along with signicant anticon-
vulsant properties.21
2 Experimental section
2.1 Reagents and materials
All chemicals for the synthesis of materials and catalytic activity
testing were purchased from Sigma-Aldrich Corporation, St.
Louis, MO (U.S.A.) and directly used without further purication.
The Cu(I) catalyzed cycloaddition of azides with alkynes has
gained signicant attention since its discovery by Sharpless and
co-workers,3,22 as well as independently by Meldal et al.,23 in
which copper(I) catalysts showed a dramatic rate acceleration of
up to 107 times.24 Generally, the sources of copper(I) include the
oxidation of copper metal turnings,25 the direct addition of
cuprous salts (CuI, CuBr) with methyl(phenyl)sulfane,26 imino-
pyridine,27 mono- (or) polydentate nitrogen ligands,18,28 N-
heterocyclic copper carbene complexes,22b and the compro-
portionation of copper(0)/copper(II), which is usually limited to
special applications (e.g., biological systems).29 Recently, copper
catalysts immobilized on various supports have been explored
for the Huisgen cyclization of azides to alkynes, namely, amine-
2.2 Synthesis of tetrakis(4-carboxyphenyl)porphyrin
(TCPP)43
Pyrrole (10 mmol) and 4-carboxybenzaldehyde (10 mmol) were
added to reagent grade propionic acid (100 mL). The mixture
was reuxed for 1 h, and the resultant crude product was
allowed to cool to room temperature, and then methanol (100
mL) was added and the solution was further chilled in an ice
bath with stirring. Then, the resultant solid was removed by
ltration and thoroughly washed with methanol and hot water,
and then the porphyrin was puried. The observed atomic ratio
of C/N was 12.35. The theoretical atomic ratio of C/N for
bound silica,30 superparamagnetic mesoporous silica,31
a
ligand-bound organic polymer,32 activated charcoal,33 poly-
saccharide,34 zeolites,35 hydrotalcite,36 and AlO(OH).37
Conversely, most of these catalysts with Cu(I) species oen less
advised due to their thermodynamic instability, and due to the
formation of an alkyne–alkyne coupling product and other
undesired by-products. In addition, many of these reports
involved reactions that were homogeneous in nature, and
required an inert atmosphere as well as anhydrous solvents.36a
Periodic mesoporous organosilicas (PMOs) have gained
signicant attention due to their large surface area and struc-
tural diversity of the organosilica frameworks. PMOs are an
innovative type of organic–inorganic hybrid materials, synthe-
sized from up to 100% organic-bridged alkoxysilane precursors
(R–[Si(OR0)3]n, n $ 2, R ¼ organic group, R0 ¼ –CH3, –C2H5.), in
which these organic groups are densely and covalently
embedded within the silica framework.38 Moreover, in PMOs
the organic groups are not only distributed uniformly inside the
framework but also do not affect the pore, which is more
favorable for guest molecule diffusion.39 PMOs with dissimilar
bridging organic groups could be potentially applied in various
elds, namely, adsorption, catalysis, drug delivery, metal ion
detection, and optics.40 Specically, PMOs are well suited for
use as catalysts because of the numerous advantages they offer,
including easy accessibility, rapid diffusion, and favorable mass
1
{C48H30N4O8} is 12. The spectral data are as follows: H NMR
(d6-DMSO): 8.85 ppm (s, 8H), 8.39–8.33 ppm (m, 16H). m/z 791
([M + H]+ calcd for 790.77). FT-IR spectrum: 1299 cmꢀ1 (C–O
stretch of carboxylic acid), 1693 cmꢀ1 (C]O in carboxylic acid),
2500 cmꢀ1 ꢁ3300 cmꢀ1 (broad, (–OH) in acid).
2.3 Synthesis of porphyrin bridged silsesquioxane (PBS)
A mixture of TCPP (1 mmol), 3-aminopropyltriethoxysilane (4
mmol) and dicyclohexyl carbodiimide (4 mmol), THF (50 mL) were
stirred at 80 ꢂC for 12 h under a nitrogen atmosphere. The mixture
was allowed to cool to room temperature. The reaction mixture
was ltered and washed with THF and petroleum ether several
times.43b The observed C/N was 9.82, and the theoretical atomic
ratio of C/N for {C84H114N8O16Si4} is 10.5. The spectral data are as
follows: 13C CPTOSS NMR: 10.46, 22.0, 31.12 and 42.02 ppm (C in
propyl groups of silane and terminal CH3 of ethoxy group), 116,
127,134 and 143 ppm (aromatic and pyrrole C) and 173 ppm (C]
O in amide) FT-IR spectrum: 950–1250 cmꢀ1 (Si–O–C), 1664 cmꢀ1
(C]O in amide), 1528, 3276 cmꢀ1 (N–H bond).
2.4 PBS bridged hybrid periodic mesoporous organosilica
(PBS-HPMO)
transfer for substrates into and out of the mesopores.41 Hence, A series of PBS-HPMO were prepared by considering various
PMOs are promising candidates for heterogeneous catalysis, molar percentages of PBS precursors. For this procedure, hex-
and they also offer good reusability owing to their strong adecyltrimethylammonium bromide (CTAB, 0.47 g) was added
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Table 1 Parameters for hybrid mesoporous organosilica synthesis
using PBS and BTEE
2.7 Synthesis of 1,4-disubstituted 1,2,3-triazoles
All chemicals employed in this study were commercially avail-
able and used without further purication. A mixture of benzyl
halide (1 mmol), sodium azide (1.2 mmol), terminal alkyne (1.1
mmol) and a catalytic amount of Cu(II)-PBS-HPMO-2 (10 mg) in
Catalyst
CTAB (g) PBS (g) BTEE (g) Ammonia water–H2O
PBS-HPMO-1 0.47
PBS-HPMO-2 0.47
0.02
0.08
0.9
0.9
4.45/8.85
4.45/8.85
ꢂ
water (1.5 mL) were stirred at 100 C for an appropriate time.
Aer completion of the reaction, as conrmed by thin layer
chromatography (TLC), the reaction mixture was ltered off and
washed with ethyl acetate (3 ꢃ 5 mL). The combined layers were
dried over anhydrous Na2SO4, concentrated in vacuum and
puried by column chromatography on 60–120 mesh silica gel
using ethyl acetate and hexane as the eluent (1 : 9) to afford the
pure 1,4-disubstituted 1,2,3-triazoles. All products were identi-
ed by comparing their spectral data with the literature.
Moreover, the solid catalyst was conveniently separated by
centrifugation from the reaction mixture, and its activity was
examined in the subsequent experiments.
to distilled water (8.85 g)–NH3H2O (4.45 g), and the mixture was
vigorously stirred to obtain a clear solution (Table 1). Then, PBS
and 1,2-bis(triethoxysilyl)ethane (BTEE) were added to the CTAB
solution according to the desired ratio and the mixture was
stirred for 24 h at room temperature. The resultant precipitate
was collected byꢂltration, extracted with ethanol–HCl solution
and dried at 60 C.
2.5 Metalation of PBS-HPMO with copper
PBS-HPMOs (0.5 g) and copper acetate monohydrate (0.25 g)
were added to methanol (30 mL), and the mixture was stirred for
12 h at 80 C. The resultant precipitate was collected by ltra-
3 Results and discussion
ꢂ
The low-angle powder XRD patterns of the synthesized PBS-
HPMO-n and Cu(II)-PBS-HPMO-n catalysts are presented in
Fig. 1. As shown in Fig. 1, the well-resolved diffraction peaks at
2q ¼ 1.4–2ꢂ reect the (100) planes of the ordered and textural
uniformity of the MCM-41 type mesoporous materials. The N2
adsorption–desorption isotherms of PBS-HPMO-n are shown in
Fig. 2. The isotherms can be classied as type IV isotherms,
which correspond to the presence of ordered mesoporous
materials.41,43 The textural properties, including the surface
tion, washed with methanol and water several times, and dried
at 60 ꢂC (Scheme 1). The synthesized Cu-PBS-HPMOs were
characterized by UV-Vis spectroscopy and electron para-
magnetic resonance (EPR) spectroscopy.
2.6 Characterization techniques
The X-ray diffraction (XRD) patterns were recorded on a Rigaku
Multiex diffractometer with a monochromated high-intensity
˚
Cu Ka radiation (l ¼ 1.54 A). All samples were scanned under
the ambient conditions over the 2q range of 0.7–5ꢂ at a rate of
0.5ꢂ minꢀ1 (40 kV, 30 mA). Solid-state NMR spectra were
collected through a DSX Bruker NMR 600 MHz. The N2
adsorption–desorption isotherms and pore-size distribution
were achieved by using a Micromeritics tristar apparatus at
liquid N2 temperature. The specic surface area is obtained
from a nitrogen adsorption isotherm by using the BET equa-
tion. The pore diameter was calculated by using the Barrett–
Joyner–Halenda (BJH) method using the desorption branch of
the adsorption–desorption isotherms. Cu(II)-PBS-PMOs were
analysed and characterized by UV-visible and EPR spectroscopy
by using Solidspec-3700 and JEOL FA200 instruments, respec-
tively. FT-IR spectra were obtained by a VERTEX 80V FT-IR
vacuum spectrometer using KBr pellets.
Fig. 1 Powder XRD patterns of PBS-HPMO-1 (a), PBS-HPMO-2 and
Cu-PBS-HPMO-2 (b).
Fig. 2 Nitrogen adsorption–desorption isotherms (a) and pore-size
distribution (b) of PBS HPMO-n.
Scheme 1 Typical synthetic route of Cu(II)-PBS-HPMOs.
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Table 2 The textural properties of synthesized PBS-HPMO-n
BET surface area
Pore diameter
(nm)
Total pore volume
Catalyst
BTE (mmol)
PBS (mmol)
(m2 gꢀ1
)
(cm3 gꢀ1
)
PBS amounta
PBS-HPMO-1
PBS-HPMO-2
2.5
2.5
0.01
0.04
706
477
2.25
2.40
0.53
0.43
0.01 mmol
0.03 mmol
a
Calculated by TGA analysis.
area, and pore diameter, are shown in Table 2. As the PBS PBS unit in the bridged mesoporous organosilica (Table 3).
content increases, the pore diameter curve shis from 2.25 to Moreover, the change in the Q band region (fewer bands) on
2.40 nm. The tendency of mesopore shrinkage with increasing metalation is because of the changed symmetry of the free-base
PBS loading is also revealed by the changes in the surface area porphyrin.44
and total pore volume.
The typical FT-IR spectra of synthesized PBS-HPMO-n and
From UV-vis spectroscopy, the spectra of the PBS-HPMO-1 Cu(II)-PBS-HPMO-n catalysts are presented in Fig. 4. The FT-IR
and PBS-HPMO-2 show one Soret band at 419 and 418.5 nm, spectra display a strong absorbance in the range of 1200–1000
along with four Q bands at 516, 555, 597, 660 and 517, 553, 594, cmꢀ1 that reveal the stretching of the Si–O–Si bond, and the
647 nm. Moreover, Cu(II)-PBS-HPMO-1 and Cu(II)-PBS-HPMO-2 bands related to Si–O–C and Si–C overlap with the strong
exhibit Soret bands at 410 and 409 nm and are accompanied absorption bands of the Si–O–Si vibration modes in this
with Q bands at 541 and 581 nm, respectively (Fig. 3). These region.45 All samples also show bands at 1644 cmꢀ1 and 3443
obtained results revealed that the synthesized catalysts have the cmꢀ1, which are caused by the PBS moiety.
Synthesized PBS-HPMOs and Cu(II)-PBS-HPMOs were char-
acterized by means of EPR spectroscopy to conrm the presence
of Cu(II) ions inside the PBS-HPMOs aer metalation (Fig. 5).
From Fig. 5, the EPR spectrum reveals the presence of Cu(II) ions
Fig. 3 UV-vis spectra of PBS (a) and PBS-PMO-n (b), and Cu-PBS-
PMO-n (c).
Table 3 UV-vis absorption bands of synthesized catalysts
Catalyst
Soret band (nm)
Q bands (nm)
PBS-HPMO-1
PBS-HPMO-2
Cu PBS-HPMO-1
CuPBS-HPMO-2
419
418.5
410
516, 555, 597, 660
517, 553, 594, 647
541
409
541, 581
Fig. 4 FT-IR spectra of PBS-PMO-n (a) and Cu-PBS-PMO-n (b).
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Scheme 2 Synthesis of 1,4-disubstituted 1,2,3-triazoles with different
benzyl halides, sodium azide and various terminal alkynes by using
Cu(II)-PBS-HPMO-2 catalyst.
as T2 [SiR(OH)(OSi)2] and T3 [SiR(OSi)3] and are shown in Fig. 6,
where R is the PBS moiety and BTEE, respectively. All charac-
terization techniques revealed the formation of PBS-HPMOs
and Cu(II)-PBS-HPMOs materials.
As part of our ongoing research, we have been working on
porphyrin-bridged PMOs having a regular porous structure,
large surface area and tunable surface properties, as these play
vital roles in the eld of catalysis and are preferable for specic
and selective catalysis. Very recently, we have successfully
employed PMO catalysts for the Baeyer–Villiger oxidation reac-
tion with cyclic ketones as the starting materials.41 We wish to
extend our work to MCRs by using these PMOs; thus, we report
herein a novel Cu(II)-PBS-bridged PMOs for MCRs using readily
available starting materials such as benzyl halides, sodium
azide, and terminal alkynes for the synthesis of 1,4-disubsti-
tuted 1,2,3-triazoles (Scheme 2). The MCR consists of a one-pot,
two-step synthesis of 1,4-disubstituted 1,2,3-triazoles proceeded
by a click reaction through the formation of benzyl azides from
sodium azide and benzyl halides. In click chemistry, the
formation of organic azide [R-N3] is the crucial step, and these
azides made a eeting appearance in organic synthesis. The
benzyl azides are formed easily within a short reaction time and
Fig. 5 EPR spectra of PBS-PMO-n (a) and Cu-PBS-PMO-n (b).
in the synthesized materials, and the Cu(II)-PBS-HPMO-2
sample exhibits a higher intensity of signal than the Cu(II)-PBS-
HPMO-1 due to smaller amount of Cu(II) ions inside the
porphyrin-bridged PMO. The EPR spectrum of Cu(II)-PBS-
HPMO-2 containing adsorbed Cu(II) ions shows the g parame-
ters at g ꢁ 2.20 and gt ꢁ 2.06, which indicates that the Cu(II)
k
are conrmed by the observation of the characteristic azido
ions are linked to nitrogen ligands in the PBS. Solid-state 29Si
NMR experiments oen afford expedient information regarding
the chemical environment around the Si nuclei with the pres-
ence of organic functional moieties in the hybrid matrices.
From the 29Si NMR spectra, the downeld chemical shis at
ꢀ64 and ꢀ57 ppm resemble different Si states (T2 and T3) such
36b
stretching frequency at ꢁ2100 cmꢀ1
.
Remarkably, the
construction of heterocyclic frameworks with a nitrogen atom
Table 4 Optimization of the reaction conditions for the synthesis of
1,4-disubstituted 1,2,3-triazolesa
Temp.
(ꢂC)
Time
(h)
Yieldb
(%)
Entry
Catalyst
Solvent
1
2
3
4
5
6
7
8
PBS-HPMO-1
PBS-HPMO-2
Cu-PBS-HPMO-1
Cu-PBS-HPMO-2
—
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Cu-PBS-HPMO-2
Water
Water
Water
Water
Water
—
Water
Toluene
Methanol
DCM
100
100
100
100
100
100
RT
110
65
40
120
80
65
80
7
7
4
3.5
10
6
10
3.5
3.5
3.5
3.5
3.5
3.5
3.5
45
60
81
96
c
—
72
d
—
27
70
15
65
32
64
73
9
10
11
12
13
14
DMF
Benzene
THF
Acetonitrile
a
Reagents and reaction conditions: benzyl bromide (1 mmol), sodium
azide (1.2 mmol), phenylacetylene (1.1 mmol), catalyst (10 mg), and
b
solvent (1.5 mL); unless mentioned otherwise. Yields of isolated
products. Without catalyst. Undesired products, including starting
materials.
c
d
Fig. 6 Solid-state 29Si NMR spectra of PBS-HPMO-2.
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Table 5 Synthesis of 1,4-disubstituted 1,2,3-triazoles from various benzyl halides, sodium azide, and terminal alkynesa
Entry
Halide
Alkyne
Product
Time (h)
Yieldb (%)
93
1
4
2
3
3.5
5
96
89
4
5
6
6
91
81
6
7
4
4
93
94
8
9
6
86
92
4.5
10
11
12
4
90
86
82
1-Octyne
7
7.5
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Table 5 (Contd.)
Entry
Halide
Alkyne
Product
Time (h)
Yieldb (%)
13
14
15
9
79
6
7
88
85
16
17
1-Octyne
6
8
83
81
18
19
20
5.5
86
86
91
90
7
5
21
22
6
1-Octyne
1-Octyne
10
9
82
84
23
a
Reagents and reaction conditions: Halide (1 mmol), sodium azide (1.2 mmol), terminal alkyne (1.1 mmol), catalyst (10 mg), and solvent (1.5 mL).
Yields of isolated products.
b
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plays a vital role in organic synthesis, as well as in medicinal
chemistry, because of their existence in many natural products
and biologically active molecules.46
In order to determine the best catalytic system suited for the
synthesis of 1,4-disubstituted 1,2,3-triazoles, we examined
typical reaction parameters. For instance, benzyl bromide (1
mmol), sodium azide (1.2 mmol), and phenylacetylene (1.1
mmol) were used as model substrates with a series of synthe-
sized PBS-HPMO, Cu(II)-PBS-HPMO catalysts in various
solvents. These results are illustrated in Table 4. The prelimi-
nary results revealed that the Cu(II)-PBS-HPMO-2 catalyst
exhibits promising catalytic activity in the presence of water
under reux conditions with enhanced regioselectivity towards
the desired 1,4-disubstituted 1,2,3-triazole product (Table 4,
Entry 4). The Cu(II)-PBS-HPMO-1 also showed good catalytic
activity in comparison to copper-free PBS-HPMO catalyst (Table
4, Entry 3). Nevertheless, the yields were lower than that of the
Cu(II)-PBS-HPMO-2 catalyst. The CuII species present in the
frameworks of PMOs exhibited remarkable activity in the
absence of an inert atmosphere and without the addition of any
sacricial ligands and additives. Trace amounts of products,
including some by-products, and longer reaction times were
noted in the absence of the catalyst (Table 4, Entry 5), and we
also observed different spots in the TLC in the presence of
catalyst under room temperature conditions (Table 4, Entry 7).
Aer selection of the most efficient catalyst, we further
screened with different solvents to adjust the reaction conditions.
Among all the solvents, the reaction proceeded well in water,
which was found to be the most appropriate solvent for the
synthesis of desired 1,4-disubstituted 1,2,3-triazoles with excel-
lent yields. The enriched product yields are partly due to the
hydrophobic nature of the organic reactants, since their repul-
sion from water enhances the number of collisions between the
organic molecules and increases their ground-state energies,
leading to an increase in the reaction rate.47 In recent years, water
has been considered as an excellent reaction medium in
synthetic organic chemistry with many promising advantages.
Moreover, we have observed that several reactions frequently
progress optimally in pure water. Although, the rate acceleration
is trivial, the use of water as the only reaction medium has
additional benets, such as ease of product isolation and safety,
due to its high heat capacity and unique redox stability.48
Nonpolar solvents, such as toluene and benzene, are not suitable
for synthesis of 1,2,3-triazoles with this catalyst (Table 4, Entries 8
and 12). The polar solvents, namely, methanol, DMF, THF, and
acetonitrile, yielded the products in moderate yields (Table 4,
Entries 9, 11, 13 and 14). However, the DCM yield was very low in
comparison to other solvents (Table 4, Entry 10). This is probably
due to interference of the solvents with the surface active sites of
the catalyst. Interestingly, good yields were observed under
solvent-free conditions (Table 4, Entry 6).
Scheme 3 Plausible reaction mechanism for 1,4-disubstituted 1,2,3-
triazole formation with Cu(II)-PBS-HPMO catalyst.
Likewise, reactions of most of the substrates with several benzyl
halides and terminal alkynes bearing electron neutral and
electron-donating as well as electron-withdrawing groups were
accomplished smoothly and the corresponding 1,2,3-triazoles
are attained in good to excellent yields. Note that the benzyl
halides generated moderate to excellent yields with aliphatic to
aromatic terminal alkynes, respectively. Interestingly, a hetero
benzyl halide, namely, 2-picolyl chloride, exhibited an excellent
yield with diverse terminal alkynes (Table 5, Entries 3–5). The
benzyl halides offered good yields with aromatic terminal
alkynes; however, lower yields were observed with aliphatic
terminal alkynes (Table 5). The benzyl halide having a strong
withdrawing group (–NO2) delivered moderate yields aer a
long time (Table 5, Entries 13, 17, 22). We also conducted this
reaction on a large scale (with benzyl bromide (10 mmol),
sodium azide and phenylacetylene as the model reaction) to
further advance the industrial utility of the catalytic formula-
tions. Remarkably, we found signicant regioselectivity and
high yields of the desired products.
By analogy with our investigation and earlier reports, the
plausible mechanistic pathways for the synthesis of 1,4-disub-
stituted 1,2,3-triazoles with Cu(II)-PBS-HPMO catalyst are shown
in Scheme 3. The one-pot multicomponent click reaction involves
rst the formation of in situ generated organic azide within a
short reaction time and a marginal increase in polarity by benzyl
substitution of the azide.29 The role of the Cu species in the
porphyrin-bridged PMOs is to facilitate the formation of the
Cu(II)–acetylide complex and the activation of the azide function
towards nucleophilic attack by reducing the electron density of
the alkyne. Finally, the porphyrinatocopper catalyst is regen-
erated by protonolysis of the intermediate to give the corre-
sponding 1,2,3-triazoles. Interestingly, the used Cu(II)-PBS-HPMO
catalyst did not exhibit any signicant loss of product yield, and
the catalyst could be recycled successively for ve runs.
With this optimized reaction condition (catalyst, solvent,
temperature, and additive-free) in hand, we sought to extend
our studies through the synthesis a variety of benzyl halides
with sodium azide, followed by [3 + 2] cycloaddition with
4 Conclusions
dissimilar terminal alkynes by using the novel Cu(II) catalyzed In summary, an efficient, straightforward, and atom-econom-
process, and the results obtained are shown in Table 5. ical one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles is
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reported for the rst time using Cu(II)-PBS-HPMO as a hetero-
geneous catalyst. This simple and environmentally benign
catalysis proceeds under mild conditions without any reducing
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Acknowledgements
ANP thanks the Korean Embassy in India for their support of his
stay in South Korea under IKRI Program Fellowship. This work
was supported by the National Research Foundation of Korea
¨
9152; (c) S. Ozçubukçu, E. Ozkal, C. Jimeno and
`
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[NRF] grant funded by the Korea Government [MSIP] [no. 19 R. J. Detz, S. A. Heras, R. de Gelder, P. W. N. M. van Leeuwen,
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