Ultrasound promoted facile one pot synthesis of triazole derivatives catalyzed by functionalized graphene oxide Cu(I) complex under mild conditions

Article abstract of DOI:10.1016/j.ultsonch.2016.05.043

A facile one pot three component reaction of alkyl halides, sodium azide with terminal alkynes can be catalyzed by functionalized graphene oxide copper (I) complex under ultrasonic irradiation at room temperature. In this protocol, the 1,4-disubstituted 1,2,3-triazoles were afforded as target pure products in excellent yields and short reaction times. The prepared catalyst has been characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), Energy Dispersive X-ray (EDX) and field emission scanning electron microscopy (FE-SEM) techniques. Also, the catalyst is chemoselective and stable and can be reused several times without any appreciable loss of its catalytic activity.

Full text of DOI:10.1016/j.ultsonch.2016.05.043

Accepted Manuscript
Ultrasound promoted facile one pot synthesis of triazole derivatives catalyzed
by functionalized graphene oxide Cu(I) complex under mild conditions
Hossein Naeimi, Rahele Shaabani
PII:
S1350-4177(16)30186-9
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2016.05.043
ULTSON 3253
Reference:
Ultrasonics Sonochemistry
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26 May 2016
Please cite this article as: H. Naeimi, R. Shaabani, Ultrasound promoted facile one pot synthesis of triazole
derivatives catalyzed by functionalized graphene oxide Cu(I) complex under mild conditions, Ultrasonics
Sonochemistry (2016), doi: http://dx.doi.org/10.1016/j.ultsonch.2016.05.043
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Ultrasound promoted facile one pot synthesis of triazole
derivatives catalyzed by functionalized graphene oxide Cu(I)
complex under mild conditions
Hossein Naeimi*, Rahele Shaabani
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
87317-51167, I.R. Iran;
Tel: 983155912388; Fax: 983155912397; E-mail: naeimi@kashanu.ac.ir
Abstract
A facile one pot three component reaction of alkyl halides, sodium azide with terminal
alkynes can be catalyzed by functionalized graphene oxide copper (I) complex under
ultrasonic irradiation at room temperature. In this protocol, the 1,4-disubstituted 1,2,3-
triazoles were afforded as target pure products in excellent yields and short reaction times.
The prepared catalyst has been characterized by Fourier transform infrared spectroscopy (FT-
IR), X-ray diffraction spectroscopy (XRD), Energy Dispersive X-ray (EDX) and field
emission scanning electron microscopy (FE-SEM) techniques. Also, the catalyst is
chemoselective and stable and can be reused several times without any appreciable loss of its
catalytic activity.
Keywords: Ultrasound, 1,2,3-Triazole, Graphene oxide, Ultrasound, One pot, Three
component.
Introduction
The triazole rings has been widely used in pharmaceuticals, agro chemicals, dyes,
photographic materials, corrosion inhibition [1]. 1,2,3-Triazoles are also associated with a
1

wide range of biological properties such as antiviral (I) [2], antiepileptic, antiallergic [3],
anticancer (II) [4-6] and anti HIV (III, IV) [7] (Fig. 1).
<Figure 1>
These heterocyclic compounds were readily prepared from Cu (I)-catalyzed azide–
alkyne 1,3-dipolar cycloaddition (CuAAC) [8,9]. The required copper (I) catalysts are usually
prepared by in situ reduction of copper (II) salts with ascorbate [10,11], or by
comproportionation of copper (0) and copper (II) [12,13]. In recent studies, the CuAAC has
been proven to be accelerated by Cu(I) species supported by nitrogen [14], sulfur [15], TiO2-
nanotube/Ti plates loaded Cu2O nanoparticles [16], Copper/Graphene/Clay Nanohybrid [17],
chitosan-stabilised copper–iron oxide nanocomposite [18] and polydentate ligands [19], since
those serve both to protect the copper (I) center from oxidation or disproportionation and to
enhance its catalytic activity. Moreover, a number of heterogeneous catalysts for this reaction
are also reported such as: magnetic starch immobilized by copper ions [20], copper (I)
confined in interlayer space of montmorillonite [21] and copper (I) iodide nanoparticles on
polyaniline [22].
Although organic azides are generally safe compounds, those of low molecular weight
can be unstable and, therefore, difficult to handle [23]. Thus, a method that avoids isolation
of organic azides is desirable. In situ generation of organic azides from suitable precursors
followed by addition of alkyne in one-pot, to form the corresponding 1,2,3-triazole would
avoid the difficulties associated with the explosive nature of azides. Already, the one-pot
synthesis of 1,2,3-triazoles from alkyl halides, alkynes and sodium azides in the presence of
copper (I) as a catalyst have been reported [24].
Graphene a single two-dimensional (2D) large of carbon atoms, has attached much
attention in recent years [25]. Graphene and graphene oxide (GO) have fantastic physical,
2

optical, and mechanical properties [26, 27]. Recently, graphene oxide (GO), the precursor of
graphene, which has a wide range of oxygen functional groups had been directly used as a
catalyst for many reactions [28].
Ultrasound-assisted organic synthesis, as a synthetic approach, is a powerful
technique that is used to accelerate organic reactions. The notable features of the ultrasound
approach are enhanced reaction rates, formation of pure products in high yields, and easier
manipulation [29, 30]. Ultrasound has been recognized as an important technique for green
and sustainable synthetic processes [31-33].
In 1984, Priebe [34] described the synthesis of organic azides from the corresponding
activated primary halides and aqueous sodium azide under ultrasonic irradiation. Also, the
acceleration of the reaction rate of Huisgen reaction by ultrasonic irradiation has already been
reported by other groups [35-37].
In continuation of our work on going toward usage of ultrasonic irradiation in organic
synthesis [38, 39], we hope to report a simple synthetic sonochemical preparation of 1-H-
1,2,3-triazoles in the presence of Cu(I) functionalized graphene oxide as heterogeneous
catalyst at room temperature.
2. Experimental
2.1. Materials
High-purity chemicals were purchased from Merck, Fluka, and Aldrich. All materials
were of commercial reagent grade. Alkyl halides and solvents were purified by using of
standard procedures.
3

2.2. Apparatus
IR spectra were recorded as KBr pellets on a Perkin–Elmer 781 spectrophotometer
1
and an Impact 400 Nicolet FT-IR spectrophotometer. H NMR and 13C NMR spectra were
recorded in DMSO-d6 or CDCl3 as solvents on a Bruker DRX-400 spectrometer, with
tetramethyl silane as internal reference. A Bandelin ultrasonic HD 3200 with 6 mm diameter
model KE 76 probe was used to generate ultrasonic irradiation and homogenize the reaction
mixture. The piezoelectric crystals in this kind of probe normally work at approximately 700
kHz; by use of appropriate clamps. However, the output frequency of piezoelectric crystals
was controlled and reduced to 20 kHz in the reaction mixture. X-ray diffraction patterns of
samples were taken on a Philips Xpert X-ray powder diffraction diffractometer (CuK,
radiation, k=0.154056 nm). FE-SEM and elemental analysis were carried out using a Jeol
SEM instrument (model- VESCAN) combined with an INCA instrument for energy
dispersive X-ray scanning electron microscopy (EDX-SEM), Field emission scanning
electron microscopy (FE SEM) images were obtained by HITACHI S-4160. Melting points
obtained with a Thermo scientific 9300 melting point apparatus. Determination of the
substrate purity and monitoring of reactions were accomplished by use of thin-layer
chromatography (TLC) on Polygram SILG/UV 254 silica gel plates (Merck).
2.3. General procedure for the synthesis of functionalized graphene oxide Cu(I) complex
(GO-NH-IA-Cu(I))
2.3.1. Synthesis of graphene oxide (GO)
Graphene oxide was prepared using a modification of Hummers and Offeman’s
method [34]. Briefly in a typical reaction, 2 g graphite, 1 g NaNO3, and 46 mL H2SO4 were
stirred together in an ice bath. KMnO4 (6 g) was slowly added while stirring, and the rate of
addition was controlled to prevent the mixture temperature from exceeding 5oC. The mixture
was then transferred to a 35 oC water bath and stirred for about 30 min, forming a thick paste.
4

Subsequently, 100 mL de-ionized water was added gradually and the temperature was raised
to 98 oC. The mixture was further treated with 500 mL deionized water and 15 mL 30% H2O2
o
solution. The warm solution was then filtered and dried at 65 C under vacuum. Finally, the
precipitate was dispersed in water by sonication.
2.3.2. Synthesis of GO–COCl
In this step, GO (0.5 g) was suspended in SOCl2 (30 mL) and 10 mL of DMF was
o
added and refluxed at 70 C for 24 h. The resultant solution was filtered and washed with
anhydrous tetrahydrofuran (THF) and dried under vacuum, the GO-COCl was obtained.
2.3.3. Synthesis of amino-functionalized grapheme oxide (GO-CO-NH2)
The GO–COCl (0.4 g) was suspended in 1,7-heptandiamine and 25 mL DMF was
o
added and refluxed at 70 C for 24 h. The resultant solution was filtered and washed with
ethanol to ensure that the excess diamine was completely removed. Finally, the products were
dried at 70 oC under vacuum.
2.3.4. Synthesis of functionalized graphene oxide with isotoic anhydride (GO-CO-NH-IA)
In continuation of the catalyst preparation, GO-CO-NH2 (0.36 g) and isotoic
anhydride (0.36 g) was suspended in 30 mL ethanol was added and refluxed at 60 oC for 24 h.
The resultant solution was filtered and washed with ethanol to ensure that the excess isotoic
anhydride was completely removed. Finally, the products were dried at 70 oC under vacuum.
2.3.5. Synthesis of functionalized graphene oxide with copper iodide complex (GO-CO-
NH-IA-Cu (I))
5

In the final step, the GO-CO-NH-IA (0.35 g) and copper iodide (0.35 g) was
o
suspended in 30 mL acetonitrile was added and refluxed at 60 C for 18 h. The resultant
solution was filtered and washed with acetonitrile to ensure that the excess copper iodide was
o
completely removed. Finally, the products were dried at 70 C under vacuum, the pure
complex was obtained.
2.4. A typical procedure for the sonication synthesis of 1,2,3-triazoles
A mixture of alkyne (1mmol), alkyl halide (1 mmol), NaN3 (1.2 mmol) and
functionalized graphene oxide Cu (I) complex (0.005 g) as a catalyst were added to a mixture
of water and EtOH (1:1) (6 mL) as solvent and the reaction mixture was soncated in
ultrasonic apparatus with 70 Watt power. The progress of the reaction was monitored by
TLC. After completion of the reaction, the reaction mixture was filtered through celite and
the isolated catalyst was washed three times with ethanol (3× 10 mL). The organic layer was
separated and dried by rotary evaporator until the solid product precipitated. In order to
further purification, recrystallization of the product was performed at 5:1 EtOAc:MeOH to
yield the pure desired products. The products were characterized by 1H NMR, 13C NMR, FT-
IR and melting points and the spectral data of synthesized compounds were compared with
authentic samples as followed;
1-Benzyl-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 1); White solid, m.p = 125-127 oC (Lit.
o
[41]. 128-130 C); IR (KBr) ν (cm-1): 3139 (C=C-H), 2924 (-C-H), 1607 (C=C), 1456, 1353
(C-N), 1218, 1073, 1046; 1H NMR (CDCl3, 400 MHz) δ (ppm): 5.58 (s, 2H, CH2), 7.32 (m,
3H, Haromatic), 7.40 (m, 5H, Haromatic), 7.67 (s, 1H, Htriazole), 7.80 (d, J=8.0 Hz, 2H, Haromatic);
13C NMR (CDCl3, 100 MHz) δ (ppm): 54.21, 119.57, 125.71, 128.06, 128.17, 128.78,
128.82, 129.16, 130.58, 134.74, 148.22.
6

4-Bromobenzyl-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 2); Colorless solid, m.p = 148-
o
o
152 C (Lit. [41]. 151-152 C); IR (KBr) ν (cm-1): 3123 (C=C-H), 2924 (-C-H), 2850, 1623
(C=Caromatic), 1482, 1462 (CH2, bending), 1352 (C-N, stretching), 1072, 1017, 761 (C-Br),
694; 1H NMR (DMSO-d6, 400 MHz) δ (ppm): 5.67 (s, 2H, CH2), 7.35-7.38 (m, 5H, Haromatic),
7.40-7.58 (m, 2H, Haromatic), 7.88 (s, 2H, Haromatic), 8.39 (s, 1H, Htriazole); 13C NMR (DMSO,
100 MHz) δ (ppm): 52.79, 121.95, 122.09, 125.67, 128.37, 129.34, 130.62, 131.09, 132.17,
135.81, 147.21.
1-(3-Chlorobenzyl)-4-phenyl-1H-1,2,3-triazole; (Table 4, entry 3); Colorless solid, m.p =
o
o
88-91 C (Lit. [42]. 87-89 C); IR (KBr) ν (cm-1): 3082 (C=C-H), 2925 (-C-H), 1725, 1574
(C=Caromatic), 1465 (CH2, bending), 1432, 1344 (C-N, stretching), 1221, 1076, 756 (C-Cl),
1
692; H NMR (Acetone-d6, 400 MHz) δ (ppm): 5.71 (s, 2H, CH2), 7.41-7.44 (m, 7H,
Haromatic), 7.89 (s, 2H, Haromatic), 8.44 (s,1H, Htriazole); 13C NMR (DMSO-d6, 100 MHz) δ
(ppm): 52.76, 122.15, 125.68, 127.08, 128.33, 128.62, 129.33, 131.14, 131.49, 133.85,
138.85, 147.52.
1-(2-Chlorobenzyl)-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 4); Colorless solid, m.p =
o
o
93-95 C (Lit. [43] 96-97 C); IR (KBr) ν(cm-1): 3123 (C=C-H), 2925 (-C-H), 1572
(C=Caromatic), 1466, 1438 (CH2, bending), 1444, 1359 (C-N, stretching), 1272, 1221, 1126,
1
1079, 1042, 977, 753 (C-Cl), 692; H NMR (CDCl3, 400 MHz) δ (ppm): 5.85 (s, 2H, CH2),
7.06 (d, J=8.0 Hz, 1H, H aromatic), 7.22-7.27 (t, 1H), 7.41-7.45 (m, 3H), 7.47-7.49 (m, 3H),
8.24 (d, J=8.0 Hz, 2H, Haromatic, Htriazole); 13C NMR (CDCl3, 100 MHz) δ (ppm): 51.69,
121.37, 126.24, 127.39, 128.23, 128.67, 129.07, 129.67, 130.185, 131.59, 132.6, 132.86,
148.01.
1-(2-Chloro-6-fluorobenzyl)-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 5); Colorless solid,
o
o
m.p = 102-105 C (Lit.[44] 106-108 C); IR (KBr) ν (cm-1): 3128 (C=C-H), 2924 (-C-H),
7

1643, 1606 (C=Caromatic), 1577, 1457(C-F), 1353 (C-N, stretching), 762 (C-Cl), 693; 1H NMR
(DMSO-d6, 400 MHz) δ (ppm): 5.86 (s, 2H, CH2), 7.33-7.62 (m, 7H, Haromatic), 8.08 (s, 2H,
Haromatic, Htriazole); 13C NMR (CDCl3, 100 MHz) δ (ppm): 49.32, 114.95, 116.04, 118.65,
125.40, 127.10, 127.59, 128.99, 130.07, 133.02, 133.54, 135.08, 143.01, 152.82.
1-(2,4-Dinitrobenzyl)-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 6); Pale yellow solid, m.p=
211-214 oC (Lit.[44] 214-215 oC); IR (KBr) ν (cm-1): 3124 (C=C-H), 1610 (C=Caromatic), 1535
and 1348 (-NO2), 1463 (CH2, stretching), 1402, 1205, 1152, 1072; 1H NMR (Acetone-d6, 400
MHz) δ (ppm): 6.16 (s, 2H, CH2), 7.2-7.36 (m, 2H, Haromatic), 7.43-7.47 (t, J=7.2 Hz, 2H,
Haromatic), 7.84 (d, J=8.0 Hz, 2H, Haromatic), 8.53(d, J=12.0 Hz, 1H, Htriazole), 8.64(s, 1H,
Haromatic), 8.84(s, 1H, Haromatic); 13C NMR (CDCl3, 100 MHz) d (ppm): 50.47, 122.57, 125.40,
128.55, 129.02, 129.92, 131.02, 132.07, 138.34, 143.39, 146.18, 147.51.
1-Benzyl-4-(4-methylphenyl)-1H-1,2,3-triazol; (Table 5, entry 7); Pale yellow solid, m.p
o
o
=150-152 C (Lit.[45] 150 C); IR (KBr) ν (cm-1): 3141 (C=C-H), 2921 (-C-H), 1605
(C=Caromatic), 1496, 1455, 1350 (C-N, stretching), 1221, 1006; 1H NMR (CDCl3, 400 MHz) δ
(ppm): 2.159 (s, 3H, CH3), 5.36 (s, 2H, CH2), 7.17-7.47(m, 8H, Haromatic), 7.88 (s, 2H,
Haromatic, Htriazole).
1-(4-Bromobenzyl)-4-(4-methylphenyl)-1H-1,2,3-triazole; (Table 5, entry 8); Pale yellow
o
o
solid, m.p = 201–203 C (Lit.[44] 202-204 C); IR (KBr) ν (cm-1): 3029 (C=C-H), 1623
(C=Caromatic), 1592, 1521, 1487 (CH3), 1442, 1341 (C-N, stretching), 1224, 1071, 1010,
824(C-Br), 741. 1H NMR (Acetone-d6, 400 MHz) δ (ppm): 2.33 (s, 3H, CH3), 5 (d, J=16.0 Hz
1H), 5.2 (d, 1H), 6.82(d, J=8.0 Hz, 2H, Haromatic), 7.01-7.03(s, 2H, Haromatic), 7.18-7.23(m, 5H,
Haromatic, Htriazole); 13C NMR (CDCl3, 100 MHz) δ (ppm): 21.34, 52.02, 119.37, 123.02,
125.67, 126.19, 129.65, 129.76, 131.87, 139.26, 140.02, 148.16.
8

o
1-methyl-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 9); Pale yellow solid m.p= 112-115 C
(Lit.[46] 111-113oC); IR (KBr) ν (cm-1): 2925 (C=C-H), 1609 (C=Caromatic), 1449(CH3), 1221
(C-N, stretching), 1237 (C-C), 1190, 1078; 1H NMR (Acetone-d6, 400 MHz) δ (ppm): 4.13(s,
3H, CH3), 7.29-7.8 (m, 5H, Htriazole), 8.26 (s, 1H).
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 10); Pale yellow solid, m.p =
o
140–142 C (Lit.[41]. 140-141 oC); IR (KBr) ν (cm-1): 3081 (C=C-H), 1604 (C=C), 1348 and
1
1518 (-NO2), 1466 (-CH2, bending), 1220 (C-N), 1109, 1077, 1044; H NMR (DMSO-d6,
400 MHz) δ (ppm): 5.702 (s, 2H, CH2), 7.36-7.43 (m, 5H, Haromatic), 7.76-7.82 (m, 3H,
Haromatic, Htriazole), 8.24(s, 2H, Haromatic); 13C NMR (CDCl3, 100 MHz) δ (ppm): 53.16, 119.82,
124.31, 125.74, 128.56, 128.93, 130.11, 141.82, 148.03, 148.66.
1-(4-Nitrobenzyl)-4-(4-methylphenyl)-1H-1,2,3-triazole; (Table 5, entry 11); Green solid,
o
m.p = 242–245 C (Lit.[44] 242-243); IR (KBr) ν (cm-1): 2924 (C=C-H), 1607 (C=C), 1346
and 1522(-NO2), 1446(CH3), 1220 (C-N); 1H NMR (CDCl3, 400 MHz) δ (ppm): 2.24 (s, 3H,
CH3), 4.8 (s, 1H), 5.10 (s, 1H), 6.96 (s, 4H, Haromatic), 7.24 (s, 3H, Haromatic, Htriazole), 7.85 (s,
2H, Haromatic).
1-Benzyl-4-propyl-1H-1,2,3-triazole; (Table 5, entry 12); green oil(Lit.[43, 45]); IR (KBr) ν
(cm-1): 2925 (C=C-H), 1626 (C=Caromatic), 1449 (CH3), 1237 (C-N, stretching), 1237 (C-C),
1
1158, 1084; H NMR (CDCl3, 400 MHz) δ (ppm): 0.95 (d, 3H, CH3), 1.26 (s, 2H, -CH2),
2.26 (s, 2H, -CH2), 5.7 (s, 2H, -CH2), 7.27-7.56 (m, 6H, Haromatic, Htriazole); 13C NMR (CDCl3,
100 MHz) δ (ppm): 13.69, 22.01, 27.33, 53.92, 120.54, 127.83, 128.19, 128.75, 135.03,
150.09.
1-Cinnamyl-4-phenyl-1H-1,2,3-triazole; (Table 5, entry 13); Pale yellow solid, m.p= 128-
130 ̊
C (Lit.[47] 134 oC); IR (KBr) ν (cm-1): 3130, 3028, 1606 (C=Caromatic), 1461, 1074, 977,
9

1
760; H NMR (CDCl3, 400 MHz) δ (ppm): 5.25 (d, J=4.0 Hz, 2H), 6.57-6.59 (m, 1H), 6.61
(d, J=4.0 Hz, 1H), 7.3-7.43 (m, 8H), 7.8(d, J=7.2 Hz, 2H), 8.41 (s, 1H).
3. Results and discussion
3.1 Preparation and characterization of the catalyst
A synthetic strategy of functionalized graphene oxide is shown in the Scheme 1. At
first, graphene oxide was prepared according to the modified Hummer's method. The
obtained GO was treated with thionyl chloride in DMF at reflux temperature for 24 hours to
generate GO–COCl and subsequently reacted 1,7-heptandiamin to yield amino-modified
graphene oxide (GO-CO-NH2). The obtained amino-modified graphene oxide were then
treated with isotoic anhydride in ethanol at reflux temperature for 24 hours to generate (GO-
CO-NH-IA) Finally, the GO-CO-NH-IA was treated with CuI in acetonitrile at reflux
temperature for 18 hours. The catalyst was characterized using various methods.
<Scheme 1>
Fig. 2 shows the FT-IR spectra of GO, GO–COCl, GO-NH2, GO-NH-IA. In the FT-
IR spectrum of GO the peaks at 3349, 1719, 1580, 1064 cm-1 correspond to the O–H, C=O,
C=C and C–O stretching vibration. In the FT-IR spectrum of GO–COCl (Fig. 2b), the C=O
stretching vibration of the –COCl group was appeared at 1730 cm-1 with a low relative
intensity of related peak. The low concentration of C=O functional groups to the highly
amount of GO can be cause the desired peak appear in low absorption and high transmittance
in the FT-IR spectra.
<Figure 2>
Fig. 3 shows XRD patterns of GO and GO-NH-IA -Cu (I). The XRD pattern of GO
(Fig. 3 a) shows an intense and sharp peak centered at 11.99° which corresponds to an
10

interplanar distance of 0.78 nm. After the functionalization, in the XRD patterns of GO-NH-
o
IA-Cu (I), the peak at about 2Ө= 23.7 was broad peak. Diffraction peak at 2Ө= 42o
indicates a short range order in stacked graphene oxide layers. The reasons of this matter can
be due to the covalent functionalization.
<Figure 3>
The successful covalent grafting of NH-IA-Cu (I) onto the surface of graphene oxide
was further confirmed by EDX analysis. The EDX spectra of functionalized graphene oxide-
Cu (I) shown in Fig. 4 that was confirmed the presence of copper, iodide and nitrogen
elements in the complex.
<Figure 4>
The FE-SEM images of GO and GO-NH-IA-Cu (I) are shown in Fig. 5. As can be
clearly seen in this Figure, the GO has layered structures with sheets crumpled. Fig. 5b is
indicated the SEM image of GO-NH-IA-Cu (I) revealing that the layered structure can be
maintained in the functionalized graphene oxide after the treatments.
<Figure 5>
3.2. Investigation of catalyst activity
This three-component reaction proceeds via in-situ formation of an alkyl azide from
an alkyl halide and sodium azide. The alkyl azide then undergoes 1,3-dipolar cycloaddition
reaction with terminal alkynes to give 1,4-disubstituted 1,2,3-triazoles in good to excellent
yields. Here we describe a process in which GO-NH-IA-Cu (I) efficiently catalyzes azide–
alkyne cycloaddition under ultrasonic irradiation (Scheme 2).
< Scheme 2>
11

In order to optimization of the reaction conditions, the reaction of alkyne (1 mmol),
alkyl halide (1 mmol) and NaN3 (1.1 mmol) were studied as a simple model. The reaction
was carried out in the presence of different quantities of the catalyst in water-ethanol solvent
(Table 1). It was found that the best result was obtained when the reaction was carried out in
the presence of 0.005 g of catalyst (Table 1, entry 3).
<Table 1>
In continuation of this research, to investigate the effects of ultrasonic irradiation and
to evaluate and compare conventional heating with ultrasound assisted method, we focused
our efforts under different conditions. The results were listed in Table 2. As can be seen,
when the catalyst was tried for the model reaction without sonication at room temperature for
2 h, was obtained any triazole as product. Also, the reaction at 80 °C temperature and without
sonication for 90 min the yield of the obtained triazole was found to be only 35% (Table 2,
entries 1,2). Moreover, the effect of ultrasonic irradiation of different powers was
investigated. It was observed that reaction in the presence of GO-NH-IA-Cu (I) and
ultrasonic irradiation power of 70 W afforded the best yield of product, with 92 % isolated
yield after 7 min (Table 2, entry 5).
It was found that the ultrasound can be raised the rate of reaction and therefore
reduced the energy consumption. The chemical and physical effects of ultrasound derive
primarily from sonic cavitation, which includes formation, growth and collapse of the hole.
The motive force for the increased efficiency of 1,4-disubstituted 1,2,3-triazoles formation by
ultrasound is due to the increase of temperature related to the formation of hot spots; and due
to the increase of reactant impact surface area through cavitation events.
<Table 2>
12

In an effort to seek improved yields and a more effective solvent, various solvents
were screened in the reaction of phenylacetylene, benzyl chloride and NaN3 in the catalytic
amount of GO-NH-IA-Cu (I) as a simple reaction. With attention to the results in Table 3, in
H2O-EtOH provided excellent yields and proved to be the solvent of choice.
<Table 3>
To ascertain the scope and limitation of this reaction, some aryl halides and
phenylacetylenes were reacted with sodium azide in the presence of the optimum amount of
GO-NH-IA-Cu(I) under ultrasonic irradiation (Table 4). The desired 1,4-disubstituted 1,2,3-
triazole derivatives were synthesized, and then characterized by spectroscopic methods. As
shown in Table 4, the corresponding products were obtained in excellent yields and short
reaction times under ultrasonic conditions. Moreover, the effect of various benzyl halides in
this method was examined and the obtained results were provided and added to the Table 4,
entries 14 and 15.
<Table 4>
A comparison of the present method with previously reported works [27, 38, 40] is reported
in Table 5. As shown in this Table, the reaction of alkyne (1mmol), alkyl halide (1 mmol),
NaN3 (1.2 mmol) and GO-NH-IA-Cu(I) as catalyst the excellent yields of related products
were achieved in shorter reaction times (Table 5, entries 1,3,5,7). While, in the previously
reported works, the similar reaction in the presence of other catalysts afforded the
corresponding products in lower yields and longer reaction times (Table 5, entries 2,4,6,8).
<Table 5>
13

3.3. Recycling of the catalyst
For practical applications of such heterogeneous system, the reusability is one of the
important properties of the catalyst. The reusability of used catalyst was investigated using
the reaction of benzyl chloride, phenylacetylene, NaN3 and water-ethanol in the presence of
GO-NH-IA-Cu (I) as a catalyst under microwave condition. The catalyst was isolated by
simple filtration, washed exhaustively with water-acetone and dried. The catalyst can be
reused for six runs without any treatment in its catalytic activity.
<Fig. 6>
4. Conclusion
In this study, we synthesized 1,4-disubstituted 1,2,3-triazole derivatives by reaction of
a variety of alkyl halides with acetylene compounds, under the action of ultrasonic
irradiation, in the presence of GO-NH-IA-Cu (I) as novel catalyst, in a 1:1 mixture of water
and ethanol at room temperature. The corresponding products were obtained in excellent
yields and high purity after short reaction times. The advantages of catalyst are inexpensive
nature of the catalyst, reusability and stability.
Acknowledgments
The authors are grateful to the University of Kashan for supporting this work (grant no.
159148/69).
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20

O
O
N
OCH3
N
COOMe
N
N
N
N
N
N
NH
2
1
N
N
N
OTBS
R
O
H2N
OTBS
O
S
O
O
3
4
R= CH(OCH2CH3)3
R=CO2CH3
Figure 1. Some examples of bioactive 1,2,3-triazoles
21

O
Cl
O
OH
C
C
O
O
SO2Cl
O
C
O
OH
C
OH
Cl
OH
NH2
H2N
N
H
NH2
O
O
C
NH2
N
H
O
O
O
C
O
N
H
O
O
C
O
O
OH
C
H
N
OH
NH2
HN
N
H
H2N
CuI
N
H
NH2
O
C
O
O
C
O
OH
H
N
N
H
H2N
I Cu
Scheme 1. Preparation routes of functionalized graphene oxide
22

Figure 2. FT-IR spectra of a) GO, b) GO-CO-Cl c) GO-NH2 d) GO-NH-IA
23

Figure3. XRD patterns of (a) GO, (b) GO-NH-IA-Cu (I)
24

Figure 4. EDX spectra of GO-NH-IA-Cu (I)
25

Figure 5. FE- SEM of a) GO, b) GO-NH-IA-Cu (I)
26

R2
N
GO-CO-NH-IA-Cu(I)
NaN3
N
R2
+
X
+
R1
)))), r.t.
N
X= Cl, Br, I
EtOH:H2O
R1
R1= Alkyl, Benzyl, Cinamyl
R2 = Ph, CH3-Ph,CH3-CH2-CH2-
Scheme 2. Synthesis of 1,4-disubstituted 1,2,3-triazoles
27

Table 1. Optimization of catalyst amount for synthesis of 1,2,3-triazolea
Time
(min)
Entry
Catalyst amount (g)
Yield (%)b
1
2
-
60
0
0.002
10
86
3
4
0.005
0.010
7
7
92
89
5
0.015
8
88
aReaction conditions: phenylacetylene (1 mmol), benzyl chloride (1
mmol), NaN3 (1.2 mmol) and GO-NH-IA-Cu(I) catalyst were added to the
EtOH:H2O (1:1) as solvent (6 mL) under ultrasonic irradiation (70 W) at
room temperature
bIsolated yields
28

Table 2. Survey the effect of ultrasonic irradiation on the synthesis of 1,2,3-triazole
Yield (%)a
Entry
Power (W)
without sonication (r.t.)
Time (min)
1
2
3
4
5
6
120
90
12
10
7
-
35
88
87
92
89
without sonication (80oC)
40
60
70
80
8
Reaction conditions: 1 mmolphenylacetylene, 1 mmol benzyl chloride, 1.2 mmol NaN3, and
(0.005 gr) GO-NH-IA-Cu(I) were added to the 1:1 mixture solvent of EtOH:H2O as solvent
(6 mL) under various ultrasound irradiation power at room temperature
aIsolated yields
29