One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via Huisgen 1,3-dipolar cycloaddition catalysed by SiO2-Cu(I) oxide and single crystal X-ray analysis of 1-benzyl-4-phenyl-1H-1,2,3-triazole

Article abstract of DOI:10.1007/s00706-014-1285-7

A one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via Huisgen 1,3-dipolar cycloaddition reaction between terminal alkynes, benzyl/allyl/alkyl halides, and NaN3 in water at room temperature using silica-supported copper(I) oxide (SiO₂-Cu₂O) has been developed. Various supported copper(I) oxide catalysts have been tested for this reaction where silica-supported copper(I) oxide works well in this reaction. The catalyst being heterogeneous can be easily recovered at the end of reaction and can be reused making the process completely economical. A single crystal X-ray analysis of 1-benzyl-4-phenyl-1H-1,2,3-triazole has revealed that the compound crystallizes in the monoclinic space group P21.

Full text of DOI:10.1007/s00706-014-1285-7

Monatsh Chem (2015) 146:143–148
DOI 10.1007/s00706-014-1285-7
ORIGINAL PAPER
One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via Huisgen
1,3-dipolar cycloaddition catalysed by SiO2–Cu(I) oxide
and single crystal X-ray analysis of 1-benzyl-4-phenyl-1H-1,2,3-
triazole
•
Manjulla Gupta Monika Gupta Satya Paul
•
•
•
Rajni Kant Vivek K. Gupta
Received: 8 June 2014 / Accepted: 21 July 2014 / Published online: 4 September 2014
Ó Springer-Verlag Wien 2014
Abstract A one-pot synthesis of 1,4-disubstituted 1,2,3-
triazoles via Huisgen 1,3-dipolar cycloaddition reaction
between terminal alkynes, benzyl/allyl/alkyl halides, and
NaN3 in water at room temperature using silica-supported
copper(I) oxide (SiO2–Cu2O) has been developed. Various
supported copper(I) oxide catalysts have been tested for
this reaction where silica-supported copper(I) oxide works
well in this reaction. The catalyst being heterogeneous can
be easily recovered at the end of reaction and can be reused
making the process completely economical. A single
crystal X-ray analysis of 1-benzyl-4-phenyl-1H-1,2,3-tria-
zole has revealed that the compound crystallizes in the
monoclinic space group P21.
This catalytic species further improves both the rate and
regioselectivity of the reaction due to its quantitative, very
robust, general, and insensitive nature [3]. Various copper
species were used as a copper source for this azide/alkyne-
‘‘click’’-reaction or CuAAC-reaction such as Cu(0)/oxi-
dizing agent, Cu(0) on charcoal, Cu(0) nano particles [3],
Cu(0) catalyst [4], Cu(II)-TD@nSiO2 [5], Cu(I)/auxiliary
ligand [3], and the use of Cu(I) species alone [3].
Although various catalytic systems, both homogenous as
well as heterogeneous, have been explored heterogeneous
catalysis in organic reactions is of great interest to organic
chemists because of their synthetic utility [6], easy isolation
of product, simple work-up procedure, recovery and reus-
ability of the catalyst, thus making the process green and
economical [7]. The use of silica as a support for hetero-
geneous catalyst takes the advantage due to its excellent
stability (both chemical and thermal), high surface area,
good accessibility, and also because organic groups can be
robustly anchored to the surface [8–15]. Further, water
provides an excellent medium for this CuAAC-reaction due
to its non-toxic, non-flammable, abundant, inexpensive
nature, and rate enhancement property. Further, silica sup-
ported heterogeneous catalysts have been successfully used
in the aqueous medium [16, 17].
Keywords Crystal structure ꢀ Heterogeneous catalysis ꢀ
One-pot synthesis ꢀ Transition metal compounds ꢀ
SiO2–Cu2O
Introduction
The introduction of Cu(I) catalysis in 2001 for the Huisgen
1,3-dipolar cycloaddition reaction of organic azides and
alkynes [1] has gained much attention in recent years [2].
The multicomponent reaction of alkynes and azides
yielding 1,2,3-triazoles is a powerful one-pot three-com-
ponent click reaction as the afforded triazoles show anti-
allergical [18], anti-infective [19], anti-malarial [20], anti-
HIV [21], and anti-bacterial biological activities[22]. The
low-molecular-weight organic azides are difficult to handle
due to their explosive nature. Therefore, a method which
involves the in situ formation of organic azides from the
starting materials in the reaction medium will be advan-
tageous. Further, avoiding the use of any base makes the
process more useful.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-014-1285-7) contains supplementary
material, which is available to authorized users.
M. Gupta ꢀ M. Gupta (&) ꢀ S. Paul
Department of Chemistry, University of
Jammu, Jammu 180 006, India
e-mail: monika.gupta77@rediffmail.com
R. Kant ꢀ V. K. Gupta
Post-Graduate Department of Physics and Electronics,
University of Jammu, Jammu Tawi 180 006, India
123

144
M. Gupta et al.
Catalyst testing for the azide/alkyne-‘‘click’’-reaction
Herein, we report a silica-supported copper(I) oxide
or CuAAC-reaction
catalysed one-pot synthesis of 1,4-disubstituted 1,2,3-tri-
azoles from terminal alkynes, benzyl/allyl/alkyl halides,
and NaN3 in water at room temperature (Scheme 1). The
catalyst is easy to prepare, inexpensive, and can be reused
for five times without significant loss of catalytic activity.
Use of additional base for this CuAAC reaction is
avoided.
To optimise the reaction conditions for this CuACC reac-
tion, phenylacetylene, benzyl chloride, and sodium azide
were selected as a test substrate to examine the catalytic
effect of supported copper(I) oxide.
To select the most appropriate heterogeneous solid
supported copper(I) oxide catalyst, Huisgen 1,3-dipolar
cycloaddition reaction was carried out using different
supported copper(I) oxide catalysts (1–4) at room tem-
perature in aqueous medium. The results are summarised
in Table 1. It has been seen that silica-supported cop-
per(I) oxide gave good yields whereas for basic alumina
supported copper(I) oxide, yield is quite low. After car-
rying out series of reactions, 5 mol% of Cu in SiO2–Cu2O
was found to be sufficient to carry out the reaction in good
to excellent yields. Further, the use of different solvents
(water, ethanol, acetonitrile) has been investigated using
the test substrates (phenylacetylene, benzyl chloride, and
sodium azide). The results are evaluated through TLC
(Table 2). It has been assumed that water proves to be an
activator for Cu2O catalyst. The product, i.e. 1-benzyl-4-
phenyl-1H-1,2,3-triazole obtained from the reaction has
been subjected to single crystal X-ray studies. It is
important to note that the reaction proceeds under neat
conditions but the yield is very poor, i.e. 60 % in 20 h at
Results and discussion
Preparation and characterization of SiO2–Cu2O
All the supported copper(I) oxide catalysts such as SiO2–
Cu2O (1), HAP/Cu2O (2), basic Al2O3/Cu2O (3), and cel-
lulose/Cu2O (4) have been prepared following the earlier
reported procedure [23] as shown in Scheme 2. Among the
various supported copper(I) oxide catalysts, SiO2–Cu2O
was found to be most active and was further characterized
by FTIR, thermogravimetric analysis (TGA), X-ray dif-
fractometry (XRD), X-ray photoelectron spectroscopy
(XPS), scanning electron microscopy (SEM), transmission
electron microscopy (TEM), and atomic absorption spec-
troscopic analysis (AAS). Complete characterization of the
catalyst has been reported [23] (see Supplementary
Material).
Table 1 Effect of different supported catalysts for CuACC reaction
S. no.
Support
Time/h
Yieldb/%
Scheme 1
1
2
3
4
Silica–Cu2O
3.5
3.5
3.5
3.5
96
90
75
70
R
R'
SiO2-Cu2O
water, r.t.
N
R'
+ NaN3
RX
C
CH
+
Hydroxyapaptite–Cu2O
Cellulose–Cu2O
N
N
1
2
3
Basic alumina–Cu2O
Reaction conditions: phenylacetylene (1.2 mmol), benzyl chloride
(1 mmol), NaN3 (1 mmol), 0.2 g catalyst (5 mol% Cu), and 5 cm3
water by stirring at room temperature
a
Yields refer to column chromatography yield
Scheme 2
Cu2O Cu2O
Glucose
+
Fehling solution
100 o
Table 2 Effect of different solvents for CuACC reaction
C,
reflux, 24 h
Solid Support
S. no.
Solvent
Time/h
Yieldb/%
Solid
Support
1
2
3
Toulene
Acetonitrile
Water
3.5
3.5
3.5
70
82
96
Cu2O
Cu2O
OH OH
OH
OH
Glucose
+
Reaction conditions: phenylacetylene (1.2 mmol), benzyl chloride
(1 mmol), NaN3 (1 mmol), 0.2 g SiO2–Cu2O (5 mol% Cu), and
5 cm3 solvent by stirring at room temperature
Fehling solution
SiO
SiO2
OH
OH
100 oC,
2
reflux, 24 h
SiO2-Cu2O
a
Yields refer to column chromatography yield
123

One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
145
Table 3 SiO2–Cu2O catalyzed azide alkyne cycloaddition at room temperature in aqueous medium
Comp.a
RX
Alkyne R0
Time/h
4
Yieldb/%
M.p. (lit. m.p.)/°C
3a
C6H5–
95
128–130 (128–129 [29])
128–130 (128–129 [29])
126–127 (127–129 [30])
3b
3c
C6H5–
3.5
3.5
96
97
C6H5–
3d
3e
3f
C6H5–
C6H5–
C6H5–
2
92
92
91
40–41 (40–42 [31])
59–60 (61–62 [32])
45–46 (46–47 [29])
6.5
8
C2H5I
Br
3g
3h
C6H5–
8
92
95
45–46 (46–47 [29])
75–76 (76–77 [33])
HOCH2–
4.5
3i
HOCH2–
HOCH2–
4.5
96
92
75–76 (76–77 [33])
44–45 (43–45 [31])
3j
3
a
Optimized reaction conditions: alkyne (1.2 mmol), halide (1 mmol), NaN3 (1 mmol), 0.2 g SiO2–Cu2O (5 mol% Cu), and 5 cm3 water by
stirring at room temperature
b
Yields refer to column chromatography yield
Crystal and molecular structure of 3b
room temperature. To study the generality of the devel-
oped protocol, various benzyl/allyl/alkyl halides with
phenylacetylene or propargyl alcohol were chosen and
results are presented in Table 3. It has been observed that
benzyl halides provide the best results, whereas alkyl
halides take much time for the reaction to proceed to
completion.
An ORTEP view of the title compound with atomic
labelling is shown in Fig. 1 [24]. The geometry of the
molecule was calculated using PLATON [25] and PARST
[26] software. The selected bond lengths and bond angles
are given in Table 4.
123

146
M. Gupta et al.
Fig. 1 ORTEP view of the molecule with displacement ellipsoids
drawn at 40 %
˚
Table 4 Selected bond lengths/A and bond angles/°
N1–C5
1.332(2)
1.346(2)
1.462(3)
1.320(2)
1.351(2)
1.371(3)
1.470(3)
1.506(3)
1.380(3)
1.387(3)
1.377(3)
1.378(3)
1.367(3)
1.377(3)
1.383(3)
1.387(3)
1.375(3)
1.374(3)
1.377(3)
1.374(3)
121.33(1)
120.6(2)
120.3(2)
C5–N1–N2
110.38(17)
128.99(18)
120.57(17)
106.83(16)
109.42(17)
107.33(17)
122.89(17)
129.77(19)
106.03(18)
111.34(15)
118.48(18)
120.9(2)
N1–N2
C5–N1–C6
N1–C6
N2–N1–C6
Fig. 2 The packing arrangement of molecules viewed down the b-
axis
N2–N3
N3–N2–N1
N2–N3–C4
N3–C4
C4–C5
N3–C4–C5
C4–C13
C6–C7
N3–C4–C13
C5–C4–C13
N1–C5–C4
100
80
60
40
20
0
C7–C8
C7–C12
C8–C9
N1–C6–C7
C8–C7–C12
C8–C7–C6
C9–C10
C10–C11
C11–C12
C13–C18
C13–C14
C14–C15
C15–C16
C16–C17
C17–C18
C14–C13–C4
C16–C15–C14
C18–C17–C16
C12–C7–C6
C9–C8–C7
120.57(18)
120.6(2)
C8–C9–C10
C11–C10–C9
C10–C11–C12
C11–C12–C7
C18–C13–C14
C18–C13–C4
C15–C14–C13
C15–C16–C17
C17–C18–C13
120.4(2)
119.5(2)
120.3(2)
120.70(19)
118.23(19)
120.44(18)
120.7(2)
1
2
3
4
5
No. of runs
Fig. 3 Recyclability of the SiO2–Cu2O for CuACC reaction
119.3(2)
121.0(2)
Recyclability of SiO2–Cu2O for CuAAC-reaction
The title molecule comprises of a triazole ring and two
phenyl rings (Fig. 1). Bond lengths and angles of the title
molecules are within normal ranges [27]. Triazole ring
(N1/N2/N3/C4/C5) makes a dihedral angle of 79.02(7)°
and 9.63(7)° with phenyl rings (C7–C12) and (C13–C18),
respectively. Dihedral angle between the phenyl rings is
77.67(7)°. Packing view of the molecules in the unit cell
viewed down the b axis is shown in Fig. 2.
For heterogeneous catalyst, recyclability is an important
factor which made the process cost effective and greener.
A series of five consecutive runs were carried out in case of
compound 3b. It was found that there is almost no change
in the activity of catalyst up to fifth use: yields were 96, 95,
94, 94, and 92 %, respectively (Fig. 3). The catalyst after
fifth use showed the presence of Cu(II), as indicated by
magnetic moment measurements.
123

One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
147
Conclusion
Table 5 Crystal and experimental data
Crystal description
Crystal colour
Crystal size/mm3
Empirical formula
Formula weight
Block-shaped
In conclusion, we have presented a simple, efficient, and
greener method for the synthesis of 1,4-disubstituted 1,2,3-
triazoles via azide/alkyne-‘‘click’’-reaction or CuAAC-
reaction using recyclable SiO2–Cu2O. This simple proce-
dure afforded the products in good to excellent yields. The
catalyst is selective and heterogeneous and therefore its
practical use in this reaction makes the process more
advantageous. Further, the reaction proceeds in the absence
of any ligand and base. The use of water as a solvent in the
reaction makes the process environment-friendly.
White
0.3 9 0.2 9 0.2
C
15H13N3
235.28
˚
Radiation, wavelength/A
MoKa, 0.71073
˚
Unit cell dimensions/A/°
a = 7.9749(6), b = 5.7607 (4)
c = 13.7668(9)
b = 100.361(7)
Monoclinic
P21
Crystal system
Space group
3
˚
Unit cell volume/A
622.15(8)
2
Experimental
No. of molecules per unit cell,
Z
Silica gel was purchased from ACROSS Organics and all
other chemicals were purchased from Merck and Sigma
Aldrich and were used without further purification. IR
spectra of the catalyst and the synthesized compounds were
recorded in the range of 4,000–300 cm-1 on a Shimadzu
Prestige-21 spectrophotometer. TGA of the catalyst was
obtained on a Linesis Thermal Analyser. X-ray diffracto-
grams were recorded in 2h range of 10°–80° on a Panalyticals
X’pert Pro X-ray diffraction spectrometer using CuKa radi-
ation. XPS spectra of the catalyst were recorded on KRATOS
ESCA model AXIS 165 (Resolution). SEM was recorded on
JSM-6100 (JEOL) and TEM was recorded on Hitachi (H-
7500) 120 kV with CCD camera. The atomic absorption
spectrometric analysis (AAS) was done on Avanta-M atomic
Temperature/K
Absorption coefficient/mm-1
F(000)
293(2)
0.077
248
Scan mode
x scan
h range for entire data
collection/°
Range of indices
3.60 \ h \ 26.00
h = –9 to 9, k = -7 to 7,
l = –16 to 16
Reflections collected/unique
21,166/2,427
1,891
Reflections observed
(I [ 2r(I))
Rint
0.0639
Rsigma
0.0419
Structure determination
Refinement
Direct methods
Full-matrix least-squares on F2
1
absorption spectrometer. H NMR and 13C NMR of the
No. of parameters refined
Final R
wR(F2)
163
compounds were obtained on Bruker Avance III (400 MHz)
spectrometer. Mass spectra of the products were obtained on
a Bruker Daltonics Esquire 3000 spectrometer.
0.0429
0.0843
1/[r2(F ) ?
2
o
Weight
(0.0434P)2 ? 0.0000P],
General procedure for azide/alkyne-‘‘click’’-reaction
or CuAAC-reaction using SiO2–Cu2O
2
o
2
c
where P = [F ? 2F ]/3
Goodness-of-fit
1.025
0.001 (for U22 N1)
In a round-bottom flask (25 cm3), a mixture of alkyne 1
(1.2 mmol), halide 2 (1 mmol), NaN3 (1 mmol), and 0.2 g
SiO2–Cu2O (5 mol% Cu) in 5 cm3 water was stirred at
room temperature for an appropriate time. On completion
(monitored by TLC), the reaction was cooled to room
temperature and filtered. The residue was washed with
water followed by EtOAc (3 9 10 cm3). The product was
obtained after the removal of solvent under reduced pres-
sure followed by crystallization from petroleum ether or
EtOAc: petroleum ether or passing through column of
silica and elution with EtOAc: petroleum ether.
(D/r)max
Final residual electron density/ -0.133 \ Dq \ 0.099
A
-3
˚
Measurement
X’calibur system, Oxford
diffraction, UK
Software for structure solution SHELXS97 [28]
Software for refinement:
SHELXL97 [28]
ORTEP-3 [24]
PLATON [25]
PLATON [25]
PARST [26]
Software for molecular
plotting:
Software for geometrical
calculation
Crystal structure determination and refinement
diffractometer equipped with graphite monochromated
˚
X-ray intensity data of 21,166 reflections (of which 2,427
unique) were collected on X’calibur CCD area-detector
MoKa radiation (k = 0.71073 A). The crystal used for data
collection was of dimensions 0.30 9 0.20 9 0.20 mm. The
123

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M. Gupta et al.
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cell dimensions were determined by least-squares fit of
angular settings of 8,109 reflections in the h range 3.53°–
29.10°. The intensities were measured by x scan mode for h
ranges 3.60°–26.00°. 1,891 reflections were treated as
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solved by direct methods using SHELXS97 [28]. All non-
hydrogen atoms of the molecule were located in the best
E-map. All the hydrogen atoms were geometrically fixed
and allowed to ride on the corresponding non-hydrogen
˚
atoms with C–H = 0.93–0.97 A. Full-matrix least-squares
refinement was carried out using SHELXL97 [28]. The final
refinement cycles converged to an R = 0.0429 and
wR(F2) = 0.0843 for the observed data. Residual electron
densities ranged from -0.133 to 0.099 eA-3. Atomic scat-
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Crystallography (1992, Vol. C, Tables 4.2.6.8 and 6.1.1.4).
The crystallographic data are summarized in Table 5.
CCDC-940362 contains the supplementary crystallo-
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of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Acknowledgments We are grateful to Director, SAIF, Punjab
University, Chandigarh, for SEM, TEM, and XRD. We also extend
our sincere thanks to UGC, New Delhi, for financial support to pur-
chase FTIR and for awarding Major Research Project (F 41-281/2012
(SR)), and Prof. R. K. Bamezai, Department of Chemistry, University
of Jammu, for recording TGA. We are also thankful to Prof. Rajni
Kant for the single crystal X-ray diffractometer sanctioned as a
National Facility under project No. SR/S2/CMP-47/2003 by Depart-
ment of Science and Technology.
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