Uniform copper nanoparticles as an inexpensive and efficient catalyst for synthesis of novel β-carbonyl-1, 2, 3-triazoles in water medium

Article abstract of DOI:10.1007/s11164-019-03773-9

Copper nanoparticles as an efficient, inexpensive catalyst were prepared via ball milling for synthesis of β-carbonyl 1, 2, 3-triazoles from azido alcohol by click reaction in water. An extensive range of raw materials such as sodium azide, phenacyl bromi

Full text of DOI:10.1007/s11164-019-03773-9

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03773-9
Uniform copper nanoparticles as an inexpensive
and efcient catalyst for synthesis of novel β‑carbonyl‑1, 2,
3‑triazoles in water medium
Hadi Esmaeili‑Shahri1 · Hossein Eshghi2 · Jalil Lari1 · Seyyed Amin Rounaghi3 ·
Efat Esmaeili‑Shahri1
Received: 9 September 2018 / Accepted: 12 February 2019
© Springer Nature B.V. 2019
Abstract
Copper nanoparticles as an efcient, inexpensive catalyst were prepared via ball
milling for synthesis of β-carbonyl 1, 2, 3-triazoles from azido alcohol by click reac-
tion in water. An extensive range of raw materials such as sodium azide, phenacyl
bromide, epichlorohydrin, and terminal alkynes were used. Complete reduction of
CuO in presence of NaBH4 was done via ball milling with a ball-to-powder weight
ratio of 50:1 under air atmosphere at room temperature. The fnal copper nanopar-
ticles (Cu NPs) were characterized by SEM, EDX, XRD and FT-IR. The Cu NPs
catalyzed one-pot three component synthesis of β-carbonyl 1, 2, 3-triazoles at room
temperature with short reaction time and high product yields. The catalyst could be
easily recovered and reused in several successive runs.
Keywords Click chemistry · Copper nanoparticles · β-carbonyl-1, 2, 3-triazoles ·
Green solvent
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03773-9) contains supplementary material, which is available to authorized users.
*
Hossein Eshghi
heshghi@um.ac.ir
1
Department of Chemistry, Faculty of Science, Payame Noor University, PO Box 19395-3697,
Tehran, Iran
2
3
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
Department of Materials Engineering, Birjand University of Technology, 9719866981 Birjand,
Iran
Vol.:(0123456789)
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H. Esmaeili-Shahri et al.
Introduction
The growing demand for novel pharmaceuticals has led researchers to use fac-
ile, high-yield and biologically oriented synthetic methods. In recent years, the
advent of click chemistry has propelled the feld of synthetic methodologies
[1–4]. The Huisgen reaction is a common click reaction, which proceeds via a
thermal 1, 3-dipolar cycloaddition reaction of azides and alkynes. The Huisgen
reaction was promoted by using copper-based catalysts in azide-alkyne cycload-
dition (CuAAC) reaction for production of a wide range of fve-membered hetero-
cycles [5–10]. 1, 2, 3-Triazoles are a signifcant class of heterocyclic compounds
with an extensive range of industrial use such as optical brighteners, solar cells,
herbicides and fungicides. Additionally, the 1, 2, 3-triazole family is found in new
synthetic drugs for many diseases, such as cancer and HIV (Fig. 1) [8–14]. Sub-
stitution on the 1, 2, 3-triazole ring, such as carbonyl groups, increases the ef-
ciency of these structures.
The placement of substrates in 1, 4-disubstituted 1, 2, 3-triazole rings also afects
the pharmaceutical and biological activity of these substances. It is very important
to make 1, 2, 3-triazoles from available low-cost raw materials. Based on research
literature, reaction of sodium azide, terminal alkenes, and alpha halo ketones was
used for synthesis of 1, 4-disubstituted 1, 2, 3-triazoles [2–4, 6, 7, 12, 15, 16].
Heterogeneous catalysts with recyclable properties are widely used in chemi-
cal synthesis [2–4, 12]. An important branch of heterogeneous catalysts is metal-
lic nanocatalysts that provide the high surface-to-volume ratios for catalytic per-
formances [11, 12].
The possibility of producing nanocatalysts on large scales is a key point [2–4].
From among heterogeneous catalysts, heterogeneous copper catalysts are very
important in the synthesis of heterocyclic compounds, because of minimized
product contamination and high purity of the product in copper catalyzed pro-
cesses. Copper nanostructure catalyzes 1, 4-disubstituted 1, 2, 3-triazole and 1,
5-disubstituted 1, 2, 3-triazole cyclization reaction in short reaction time and high
yields [2–4, 6, 12, 18]. Representatively, 1, 2, 3-triazoles have been synthesized
in metal-free and azide-free conditions [19–27].
In this work, Cu nanoparticles (Cu NPs) were prepared via ball milling, and
after full characterization were used for the synthesis of novel β-carbonyl -l, 2,
3-triazoles and triazole azido alcohols. Cu NPs have very useful properties, such
as heterogeneity, possibility of being produced on a large scale and reusability
without any structural changes.
The frst step in realization of this goal was the synthesis of the diferent ter-
minal alkynes via reaction of phenol and its derivatives with propargyl bromide
(Scheme 1a). Then, novel β-carbonyl -l, 2, 3-triazoles were synthesized via Cu
NPs catalyzed cyclization reaction of sodium azide, terminal alkynes and halo
ketones in water at room temperature (Scheme 1b). The performance of this cata-
lytic system in producing nearly pure products at high yield was excellent.
In the following, a multi-stage synthesis was planned by using the same cata-
lyst (Cu NPs) for the synthesis of triazole azido alcohol to design drugs. This
1 3

Uniform copper nanoparticles as an inexpensive and efcient…
Fig. 1 Some derivatives of 1,
2, 3-triazole with a biological
application
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H. Esmaeili-Shahri et al.
(a)
(b)
Scheme 1 a The synthesis of terminal alkynes of phenol. b Multicomponent synthesis of β-carbonyl -1,
2, 3-triazoles from halo ketone
azidotriazole alcohol was synthesized through the simplest raw materials, such as
sodium azide alkyne and α-halocton (as well as in some cases instead of α-halate
ketone, epichlorohydrin). We intend to react with triazole azido alcohol with
nitrile to make important polycyclic compounds. At this stage, the same catalyst
(Cu NPs) is used, but because there were no facilities for product purifcation,
work on this part is still in progress [17, 30, 31] (Scheme 2).
In order to increase the scope of work, the reaction was carried out with ethyl-
2-bromoacetate and 1-chloropropan-2-one as another alkylating agents, which did
not produce signifcant results due to instability of these reagents in water. We are
also reminded that our previous work was devoted to this reaction with epoxides
in the presence of diferent catalyst [2].
Scheme 2 Multicomponent synthesis of triazole azido alcohol from epichlorohydrin
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Uniform copper nanoparticles as an inexpensive and efcient…
Experimental
Instruments and reagents
All reagents were purchased from Merck and Sigma-Aldrich Company and used
in the same situation without purifcation. Electrothermal Type 9100 was used to
measure the melting point. By using DMSO-d6 or CDCl3 as a deuterat solvent, the
1H and 13C NMR spectra were obtained on a Bruker DRX 300 MHz Avance spec-
trometer at 300 and 75 MHz. Chemical shifts are presented in ppm downfeld from
TMS as internal standard; coupling constants J are given in Hertz. Microstructure,
phase characterization of the catalyst were recorded using a Philips X’Pert X-ray
difractometer (XRD) with Cu Kα radiation (λ=0.154056 nm), and the difrac-
tion data were collected over a 2θ range of 5–95° with a step width of 0.02°. FT-IR
spectra were prepared at room temperature by a Thermo Nicolet Avatar 370 infra-
red spectrometer, using KBr pellets (USA). Using a Tescan Mira 3 scanning elec-
tron microscope (SEM) that operated at 20 kV, the powder morphology was studied
and elemental contained were curtained by using an Ansamx EDS instrument with
15.00 eV resolution.
The synthesis of Cu NPs from CuO
At the start of construction operations, CuO (2.43 g) was combined with NaBH4
(0.57 g) to create a CuO/NaBH4 molar ratio of 2 [2–4]. The above mixture was
placed in a hardened steel vial flled with steel balls (10 mm diameter), and a weight
ratio of 50:1 was used between ball-to-powder. The 70-min milling procedure was
operated with a rotating speed of 250 rpm in ambient atmosphere at high energy.
Before using the catalyst for synthesis, purifcation was done, and the mixture was
cleaned with distilled water/methanol (3:1) (2×10 mL) to remove NaBH4 and boron
oxides [2–4].
The synthesis of terminal alkynes (1a–1h)
K2CO3 (10 mmol) 1.38 g and phenols (10 mmol) in dry acetone (15 mL) at 0 °C
were stirred, then propargyl bromide 1.19 g (10 mmol) was added to this mixture.
The mixture was allowed to reach room temperature. Under these conditions, it was
stirred for 17 h. After evaporation of the solvent, the product was extracted with
ethyl acetate (3×10 mL). The organic phase was washed with water, cold NaOH
(5%) and saturated brine and fnally dried with anhydrous MgSO4 . The organic
phase was evaporated, and terminal alkynes 1a–1h were obtained in 85–60% yield
[18].
General procedure for the synthesis of β‑carbonyl 1, 2, 3‑triazoles (2a–2l)
The terminal alkynes (1.0 mmol), phenacyl bromide 0.199 g (1.0 mmol), sodium
azide 0.078 g (1.2 mmol) and Cu NPs (0.01 g) were stirred in water (5 mL) as a
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H. Esmaeili-Shahri et al.
solvent. Progress of the reaction was monitored using TLC in n-hexane/ethyl ace-
tate (4:1). After completion of the reaction, to separate the heterogeneous catalyst,
the total reaction mixture was centrifuged. In this way the catalyst was separated
from the mixture. The upper phase was diluted with H2O (5 mL), and extracted with
ethyl acetate (3×10 mL). Saturated brine was used twice for washing the organic
phase and this phase was dried with anhydrous MgSO4. β-carbonyl-1, 2, 3-tria-
zoles were obtained after the solvent evaporation in vacuum. Although the obtained
β-carbonyl-1, 2, 3-triazoles are almost pure, in order to increase their purity, column
chromatography from a silica gel column and ethyl acetate-hexane as eluent was
used. Finally, the used heterogeneous catalyst was washed with methanol three times
and dried in room temperature.
Spectral data of representative compounds
2.5a Phenyl-2-(4-phenyl-1,2,3 triazol-1-yl)ethanone (2a)[18, 28, 29, 35, 41]: Light
yellow solid, yield: 75%, C16H13N3O, M.p.: 143 °C, 1H NMR (CDCl3, 300 MHz): δ
8.05 (d, 2H, Ar, J=6 Hz), 7.99 (s, 1H, CH), 7.90 (d, 1H, Ar, J=6 Hz), 7.71 (t, 1H,
Ar, J=6 Hz), 7.58 (t, 2H, Ar, J=8.5 Hz), 7.47 (t, 2H, Ar, J=8.5 Hz), 7.38 (t, 2H,
Ar, J=8.5 Hz), 5.92 (s, 2H, CH2) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.3, 134.6,
133.9, 132.5, 130.49, 129.2, 128.8, 128.4, 128.2, 125.8, 121.5, 99.96, 55.51 ppm.
2.5b 2-(4-Hydroxymethyl-1,2,3 triazol-1-yl)-1-phenyl-ethanone (2b)[18, 37–39]:
1
Light yellow solid, yield: 72%, C11H11N3O2, M.p.: 106 °C, H NMR (CDCl3,
300 MHz): δ 8.04 (dd, 2H, Ar, J1 =8.4 Hz, J2 =1.5 Hz), 7.74 (s, 1H, CH), 7.71 (td,
1H, Ar, J1 =7.5 Hz, J2 =1.5 Hz), 7.59 (t, 2H, Ar, J=7.5 Hz), 5.90 (s, 2H, CH2), 4.89
(s, 2H, CH2), 2.40 (b, 1H, OH) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.2, 134.7,
133.9, 129.2, 128.1, 123.5, 56.76, 55.44 ppm. FT-IR (KBr): νmax: 3306, 1691 and
1229 cm−1.
2.5c 2-(4-(phenoxy methyl)-1H-1,2,3-triazol-1-yl)-1-phenyl-ethanone (2c)[40]:
Dark green solid, yield: 68%; C17H15N3O2, 1H NMR (CDCl3, 300 MHz): δ 8.03 (d,
2H, Ar, J=7.5 Hz), 7.82 (s, 1H, CH), 7.70 (t, 1H, Ar, J=7.5 Hz), 7.57 (t, 2H, Ar,
J=7.5 Hz), 7.33 (t, 2H, Ar, J=7.8 Hz), 7.05–6.98 (m, 3H, Ar), 5.88 (s, 2H, CH2),
5.28 (s, 2H, CH2) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.2, 158.2, 144.5, 139.4,
134.7, 133.9, 129.2, 128.1, 127.4, 127.1, 125.8, 124.6, 123.5, 116.8, 115.9, 56.7,
55.4 ppm.
2.5d
2-(4-((4-chlorophenoxy)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylethanone
1
(2d): Dark solid; yield: 61%; C17H14N3O2Cl, H NMR (CDCl3, 300 MHz): δ 8.02
(d, 2H, Ar, J=7.8 Hz), 7.83 (s, 1H, CH), 7.70 (t, 1H, Ar, J=7.2 Hz), 7.56 (t, 2H,
Ar, J=7.8 Hz), 7.27 (d, 2H, Ar, J=8.7 Hz), 6.95 (d, 2H, Ar, J=8.7 Hz), 5.89 (s,
2H, CH2), 5.23 (s, 2H, CH2) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.2, 156.8,
155.2, 139.4, 134.7, 134.0, 133.8, 129.3, 128.5, 128.0, 127.8, 127.3, 126.1, 124.6,
116.8, 115.9, 62.1, 55.5 ppm.
2.5e 1-phenyl-2-(4-((o-tolyloxy) methyl)-1H-1,2,3-triazol-1-yl)ethanone (2e):
1
Black oily compound; yield: 74%; C18H17N3O2, H NMR (CDCl3, 300 MHz): δ
8.04 (d, 2H, Ar, J = 7.5 Hz), 7.81 (s, 1H, CH), 7.71 (t, 1H, Ar, J1 = 7.5 Hz), 7.58
(t, 2H, Ar, J = 6 Hz), 7.20 (dd, 2H, Ar, J1 = 9 Hz, J2 = 9 Hz), 7.05 (d, 1H, Ar),
1 3

Uniform copper nanoparticles as an inexpensive and efcient…
5.88 (s, 2H, CH2), 5.30 (s, 2H, CH2), 2.29 (3H, CH3) ppm; 13C NMR (CDCl3,
75 MHz): δ 190.2, 158.2, 144.7, 138.6, 134.6, 133.9, 129.3, 129.3, 129.2, 128.1,
124.7, 122.1, 115.7, 112.4, 111.6, 61.9, 55.44, 21.5 ppm; FT-IR (KBr): νmax
:
3096, 1702, 1496, 1226 cm−1. Molecular Weight: 307.0.
2.5f
1-phenyl-2-(4-((m-tolyloxy)methyl)-1H-1,2,3-triazol-1-yl)ethanone
(2f)[36]: Yellow crystal clear; yield: 84%; C18H17N3O2, 1H NMR (CDCl3,
300 MHz): δ = 8.04 (d, 2H, Ar, J = 9 Hz), 7.81 (s, 1H, CH), 7.71 (t, 1H, Ar,
J = 6 Hz), 7.57 (t, 2H, Ar, J = 9 Hz), 7.21 (t, 1H, Ar, J = 9 Hz), 6.85 (m, 3H, Ar),
5.87 (s, 2H, CH2), 5.27 (s, 2H, CH2), 2.36 (3H, CH3) ppm; 13C NMR (CDCl3,
75.6 MHz): δ = 190.2, 156.4, 145.0, 134.6, 133.9, 130.9, 130.7, 129.2, 129.1,
128.1, 127.0, 126.7, 124.4, 120.9, 114.9, 62.3, 55.49, 16.2 ppm; FT-IR (KBr):
νmax: 3141, 1702, 1595, 1223 cm−1. Molecular Weight: 307.0.
2.5g 1-phenyl-2-(4-((p-tolyloxy)methyl)-1H-1,2,3-triazol-1-yl)ethanone (2g):
1
White crystal clear; yield: 77%; C18H17N3O2, M.p.: 136 °C, H NMR (CDCl3,
300 MHz): δ 8.02 (d, 2H, Ar, J = 7.5 Hz), 7.80 (s, 1H, CH), 7.70 (t, 1H, Ar,
J = 7.5 Hz), 7.56 (t, 2H, Ar, J = 7.8 Hz), 7.11 (d, 2H, Ar, J = 8.4 Hz), 6.92 (d,
2H, Ar, J = 8.4 Hz), 5.86 (s, 2H, CH2), 5.24 (s, 2H, CH2), 2.31 (3H, CH3) ppm;
13C NMR (CDCl3, 75 MHz): δ 190.2, 156.1, 144.8, 134.6, 133.9, 130.5, 130.0,
129.2, 129.1, 128.1, 127.0, 126.7, 124.6, 120.8, 114.7, 62.1, 55.4, 20.5 ppm.
Molecular Weight: 307.0.
2.5h 2-(4-((4-nitrophenoxy)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylethanone
1
(2h): Orange oily compound; yield: 60%; C17H14N4O4, M.p.: 115 °C, H NMR
(CDCl3, 300 MHz): δ 8.04 (d, 2H, Ar, J = 7 Hz), 7.88 (s, 1H, CH), 7.71 (t, 1H,
Ar, J = 7.2 Hz), 7.53 (t, 2H, Ar, J = 7.8 Hz), 7.14-7.079 (m, 4H, Ar), 5.40 (s,
2H, CH2), 4.50 (s, 2H, CH2) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.2, 165.7,
142.2, 141.3, 134.4, 134.2, 133.9, 133.2, 129.0, 128.6, 127.1, 125.9, 122.9,
116.1, 115.2, 62.7, 55.71 ppm, FT-IR (KBr): νmax: 3261, 1697, 1592, 1510 and
1341 cm−1
.
2.5k 4-((1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl)methoxy)benzonitrile
1
(2k): Light yellow crystal; yield: 62%; C18H14N4O2. M.p.: 138 °C, H NMR
(CDCl3, 300 MHz): δ 8.0 (d, 2H, Ar, J = 7.2 Hz), 7.87 (s, 1H, CH), 7.68 (t,
1H, Ar, J = 9 Hz), 7.64–7.52 (m, 4H, Ar), 7.11–7.05 (m, 2H, Ar), 5.92 (s, 2H,
CH2), 5.32 (s, 2H, CH2) ppm; 13C NMR (CDCl3, 75 MHz): 190.1, 161.4, 143.3,
134.7, 134.0, 133.9, 133.7, 129.2, 129.0, 128.5, 128.1, 127.9, 125.1, 119.1,
115.6, 104.5, 62.3, 55.9 ppm. FT-IR (KBr): νmax: 3141, 2227, 1696, 1608 and
1228 cm−1
.
2.5l 2-(4-((2-chloro-5-methylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)-1-phe-
nylethanone (2l): White must blanket crystal; yield: 70%; C18H16N3O2Cl, M.p.:
1
113.5 °C, H NMR (CDCl3, 300 MHz): δ 8.04 (d, 2H, Ar, J = 9 Hz), 7.87 (s,
1H, CH), 7.68 (t, 1H, Ar, J = 6 Hz), 7.54 (t, 2H, Ar, J = 6 Hz), 7.23 (d, 2H, Ar,
J = 9 Hz), 6.94 (s, 1H, Ar), 6.75 (d, 2H, Ar, J = 6 Hz), 5.88 (s, 2H, CH2), 5.32
(s, 2H, CH2), 2.34 (3H, CH3) ppm; 13C NMR (CDCl3, 75 MHz): δ 190.2, 153.4,
138.1, 134.6, 133.8, 129.8, 129.1, 129.0, 128.1, 124.9, 124.7, 122.8, 119.9,
119.8, 115.2, 62.3, 55.59, 21.36 ppm.
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H. Esmaeili-Shahri et al.
General procedure for the synthesis of triazole azido alcohol (3 m)
Phenyl acetylene (1 mmol) 1.2 g, NaN3 (4 mmol) 0.268 g and epichlorohydrin
(2 mmol) was stirred in water (8.0 mL) in the presence of the Cu NPs (0.01 g) at
room temperature for 5 h. After completion of the reaction (monitored by TLC) the
mixture was diluted with ethyl acetate (5 mL). In the following, the Cu NPs catalyst
was separated by centrifuging. Then 5 mL water was added to the reaction mix-
ture and extracted with EtOAc (3×10 mL). By saturated brine, organic phases was
washed and dried with anhydrous MgSO4. Solvent was evaporated in vacuum and
triazole azido alcohol was obtained in 45% yield. The column chromatography from
silica gel column and ethyl acetate-hexane as eluent was used to increase purity of
products.
2.6a 1-azido-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-ol (3m) [10, 30]:
1
C11H12N6O, H NMR (CDCl3, 300 MHz): δ 7.67 (d, 2H, Ar, J=12.9 Hz), 7.60 (s,
1H, CH), 7.71 (m, 3H, Ar, J=7.2 Hz),4.83 (b, 1H, OH), 4.21 (m, 2H, CH2), 3.69
(m, 1H, CH), 3.39 (m, 2H) ppm.
Results and discussion
Characterization of catalyst
Based on our previously reported method for synthesis of Cu nanostructures (NSs),
[2–4] the molar ratio of CuO/NaBH4 is an important factor in crystalline structure
of obtained Cu nanoparticles. With a CuO/NaBH4 molar ratio of 4, the ratio of Cu
NPs to CuO and Cu2O NSs was low [2–4]. Therefore, a modifed method was used
for the synthesis of Cu NPs. In this modifed method, the molar ratio of CuO/NaBH4
was 2. The Cu NPs were synthesized via ball mill reduction with very high purity,
which was further investigated with SEM, EDS, FT-IR and XRD analyses.
As shown in Fig. 2a, SEM image of catalyst revealed that Cu nanoparticles are
spherical. The particles of the catalyst are in the size of the nanoparticles. Also, the
EDS result indicated that the elemental composition of the catalyst is Cu and O,
which can be attributed to the existence of CuO nanoparticles (Fig. 2b).
The peaks at 567 cm−1 and 621 cm−1 in the FT-IR spectrum of the catalyst can
be attributed to the stretching vibrations of a Cu–O bond. Also, the peak located at
721 cm−1 was attributed to Cu2O species, which were produced from surface oxida-
tion of Cu NPs. Specifed peaks appeared in the range of 1008–1333 cm−1 related
to the combination of B and O, which are unwittingly produced in the production
process [32, 33] (Fig. 3).
The crystalline structure of catalyst was studied with XRD analysis, as shown in
Fig. 4. It is clear that CuO was reduced to Cu NPs. Characteristic difraction peaks
of Cu nanoparticle were observed in the XRD pattern.[2–4, 35] Weak peaks at 2θ
36.5°, 39° and 2θ 36.5° in XRD pattern are related to CuO, Cu2O, respectively [2–4,
34, 35]. The appearance of these compounds is probably due to the surface oxida-
tion of the sample. Also, no difraction peaks were observed for boron species in
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Uniform copper nanoparticles as an inexpensive and efcient…
Fig. 2 a SEM image of synthesized Cu nanocatalyst, b EDS analysis of synthesized Cu nanocatalyst
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H. Esmaeili-Shahri et al.
B-O
3900
3400
2900
2400
1900
1400
900
400
Wavenumbers
Fig. 3 FT- IR spectrum of synthesized Cu nanocatalyst
Fig. 4 XRD pattern of synthe-
sized Cu nanocatalyst
the XRD spectrum of catalyst, which indicates the non-crystalline structure of these
compounds and purity of catalyst.
Catalytic activity of Cu nanocatalyst in synthesis of β‑carbonyl‑1, 2, 3‑triazoles
with diferent terminal alkynes
At the beginning, the desired terminal alkynes were synthesized from reaction of
phenol derivatives and propargyl bromide in high yields (Table 1). In continua-
tion, reaction of sodium azide, phenyl acetylene and phenacylbromide (2-bromo-
1-phenylethanone) was selected as a model reaction. In toluene as a solvent at room
temperature without any catalyst no cyclic products were obtained even after 36 h
(Table 2, entry 1). In the presence of a catalyst, diferent solvents were tested for
model reaction (Table 2, entries 4–7). It was concluded that the polar solvents were
more efective in this reaction. By increasing the catalyst amount from 0.01 to 0.1 g,
no signifcant increase was observed in the reaction yield. Also, diferent tempera-
tures (25, 50, 75 °C) were tested for model reaction with 0.01 g of catalyst. Based
on these results, 0.01 g of catalyst in water and room temperature was selected as
optimized reaction condition.
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Uniform copper nanoparticles as an inexpensive and efcient…
Table 1 The synthesis of terminal alkynes (1a–h)
Yield%
75
Phenol
Products
1
4
5
6
60
82
85
7
80
8
65
60
74
9
10
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H. Esmaeili-Shahri et al.
Table 2 Optimization of the reaction condition
Entry
Solvent
Temperature (°C)
Catalyst loading (g)
Yield (%)
1
2
3
4
5
6
7
Toluene
DMF
25
25
25
25
25
25
25
0
0
65
63
80
81
80
82
0.010
0.010
0.010
0.020
0.025
0.100
Ethanol
Water
Water
Water
Water
Subsequently, diferent types of terminal alkynes with electron-withdrawing
group and electron-donating groups have been used in described conditions
in the click reaction. All products with high yields and purity were obtained
(Table 3).
For the recyclability study of the catalyst, phenacyl bromide, phenyl acety-
lene, and sodium azide were selected as model reaction. For this purpose, at
the end of the reaction, heterogeneous catalyst was separated by centrifuging.
The heterogeneous catalyst was washed three times with methanol and dried at
room temperature for 2 h. Without an extreme change in yields, the catalyst was
reused for three times with 85, 75, and 70% of yields for runs 1-3, respectively.
The performance of the catalyst was compared with other catalytic systems.
Various catalysts have been used in the synthesis of triazoles. Some of these
catalysts produce 1, 4-disubstituted 1, 2, 3-triazoles and some other 1, 5-dis-
ubstituted 1, 2, 3-triazoles. Diferent catalysts were compared in terms of ef-
ciency and type of substitution product in reaction model (phenacyl bromide,
sodium azide and phenyl acetylene in a 1:1:1 molar ratio). Cu NPs (this work),
were used in the absence of any toxic co-catalyst which promote the reaction at
room temperature in water as a green solvent. The diferent catalysts (efciency
and type of substitution product in synthesis of β- carbonyl 1, 2, 3-triazole) was
compared with the other same research (Table 4).
1
For the chemical structure study of products, the H- NMR NOESY spectrum
was obtained from product 2 g. The NOESY efects between both methylene
hydrogen and triazole proton confrm the 1, 4-disubstituted-1, 2, 3-triazole prod-
uct in comparison with 1,5-disubstituted 1,2,3-triazole (Figs. 5, 6).
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Uniform copper nanoparticles as an inexpensive and efcient…
Table 3 Synthesis of β-carbonyl - 1, 2, 3-triazoles
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H. Esmaeili-Shahri et al.
Table 3 (continued)
Table 4 Comparison of diferent catalysts (efciency and type of substitution product in synthesis of
β-carbonyl 1, 2, 3-triazoles) (3a)
Entry
Catalyst
Yield (%)
Time (h)
Temperature(°C)
References
1
2
3
4
5
Cu(I)-Catalyzed
Cp*RuCl(PPh3)2
[Cp*RuCl2]2
Cp2Ni/Xantphos
Cu nanoparticle
87
–
–
83
75
24
0.8
2
8
2
100
r.t
r.t
r.t
r.t
[34]
[36]
[36]
[35]
This work
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Uniform copper nanoparticles as an inexpensive and efcient…
Fig. 5 1H- NMR NOESY spectrum 1,4-Disubstituted-1,2,3-triazoles (2g)
Fig. 6 1,5-disubstituted-1,2,3-triazoles (a) 1,4-Disubstituted-1,2,3-triazoles (b)
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H. Esmaeili-Shahri et al.
Scheme 3 Suggested mechanism
Finally, we suggested a mechanism which Cu (I) in the surface of Cu nano-
particles is responsible for this click reaction as outlined in Scheme 3 [9].
Conclusion
We have presented a simple and efective method for synthesis of β-carbonyl-1, 2,
3-triazoles through a multicomponent reaction of terminal alkyne, sodium azide and
phenacyl bromide (or epichlorohydrin). The Cu NPs were synthesized as a recy-
clable catalyst for room temperature synthesis of triazoles in water, without using
any toxic solvent or co-catalysts. This protocol can be applied to provide a wide
range of β-carbonyl-1, 2, 3-triazoles with high purity. Some of these β-carbonyl-1,
2, 3-triazoles are new, and for the frst time have been reported. Also, this protocol
can be used for production of triazole azido alcohol, as they are very useful precur-
sor in the synthesis of pharmaceutical derivatives. In addition, simplicity in catalyst
preparation and its reusability without signifcant change in catalytic activity are the
advantages of this method.
Acknowledgements The authors are thankful to the Department of Chemistry, Faculty of Science, Fer-
dowsi University of Mashhad and Department of Chemistry, Faculty of Science, Payame Noor University.
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Uniform copper nanoparticles as an inexpensive and efcient…
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