Preparation, characterization and application of MgFe2O4/Cu nanocomposite as a new magnetic catalyst for one-pot regioselective synthesis of β-thiol-1,4-disubstituted-1,2,3-triazoles

Article abstract of DOI:10.1039/d1ra01588e

Magnesium ferrite magnetic nanoparticles were synthesized by a solid-state reaction of magnesium nitrate, hydrated iron(iii) nitrate, NaOH and NaCl salts and then calcined at high temperatures. In order to prevent oxidation and aggregation of magnesium ferrite particles, and also for preparing a new catalyst of supported copper on the magnetic surface, the MgFe₂O₄was covered by copper nanoparticles in alkaline medium. Magnetic nanoparticles of MgFe₂O₄/Cu were successfully obtained. The structure of the synthesized magnetic nanoparticles was identified using XRD, TEM, EDS, FT-IR, FESEM and VSM techniques. The prepared catalyst was used in the three component one-pot regioselective synthesis of 1,2,3-triazoles in water. The various thiiranes bearing alkyl, allyl and aryl groups with terminal alkynes, and sodium azide in the presence of the MgFe₂O₄/Cu nanocatalyst were converted to the corresponding β-thiolo/benzyl-1,2,3-triazoles as new triazole derivatives. The effects of different factors such as time, temperature, solvent, and catalyst amount were investigated, and performing the reaction using 0.02 g of catalyst in water at 60 °C was chosen as the optimum conditions. The recovered catalyst was used several times without any significant change in catalytic activity or magnetic property.

Full text of DOI:10.1039/d1ra01588e

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Preparation, characterization and application of
MgFe2O4/Cu nanocomposite as a new magnetic
catalyst for one-pot regioselective synthesis of b-
thiol-1,4-disubstituted-1,2,3-triazoles†
Cite this: RSC Adv., 2021, 11, 13061
*
Ronak Eisavi
and Kazhal Naseri
Magnesium ferrite magnetic nanoparticles were synthesized by a solid-state reaction of magnesium nitrate,
hydrated iron(III) nitrate, NaOH and NaCl salts and then calcined at high temperatures. In order to prevent
oxidation and aggregation of magnesium ferrite particles, and also for preparing a new catalyst of supported
copper on the magnetic surface, the MgFe2O4 was covered by copper nanoparticles in alkaline medium.
Magnetic nanoparticles of MgFe2O4/Cu were successfully obtained. The structure of the synthesized
magnetic nanoparticles was identified using XRD, TEM, EDS, FT-IR, FESEM and VSM techniques. The
prepared catalyst was used in the three component one-pot regioselective synthesis of 1,2,3-triazoles in
water. The various thiiranes bearing alkyl, allyl and aryl groups with terminal alkynes, and sodium azide in
the presence of the MgFe2O4/Cu nanocatalyst were converted to the corresponding b-thiolo/benzyl-
1,2,3-triazoles as new triazole derivatives. The effects of different factors such as time, temperature,
solvent, and catalyst amount were investigated, and performing the reaction using 0.02 g of catalyst in
water at 60 ꢀC was chosen as the optimum conditions. The recovered catalyst was used several times
without any significant change in catalytic activity or magnetic property.
Received 27th February 2021
Accepted 30th March 2021
DOI: 10.1039/d1ra01588e
rsc.li/rsc-advances
Multi-component reactions (MCRs) are reactions in which
three or more reactants react to generate only one product.
1. Introduction
MCRs present a convenient synthetic procedure for producing
complex molecules with structural variety and molecular intri-
cacy.32 These kinds of reactions provide major benets like
environmental compatibility, high efficiency, quick and plain
performance, and reducing the reaction time and saving energy.
Compared to conventional methods, these reactions require
fewer steps to achieve the nal product and can be performed in
one-pot. Therefore, MCRs play signicant roles in different
research elds such as biomedical, synthetic organic, gener-
ating libraries of bioactive compounds, pharmaceutical and
drug discovery research, industrial chemistry etc.33–36 An ideal
multicomponent reaction permits the concurrent addition of all
reactants, reagents and catalysts under the same reaction
conditions. One-pot reactions show an efficient strategy in
modern synthetic chemistry.37 Minimizing the number of
synthetic steps in obtaining products from starting reactants is
highly favorable in organic synthesis. The perfect regiose-
lectivity and high purity of desired products, and excellent
yields are among the other remarkable advantages of multi-
component one-pot reactions.
In recent decades, 1,2,3-triazoles have attracted considerable
attention due to their important biological and pharmacolog-
ical activities such as analgesic,1 local anaesthetic,2 antimicro-
bial,3,4 anti HIV,5 anticancer,6 antiallergic,7 anticonvulsant,8
antiproliferative,9 antiviral, antitubercular,10 antifungal,11 anti-
bacterial,12
antioxidants,13
antimalarial,14
and
anti-
inammatory activities.15
Huisgen 1,3-dipolar cycloaddition between an azide and
alkyne has rapidly gained importance for its potential to
manufacture drug targets with different biological signicance.6
Recently, one-pot synthesis of b-hydroxy-1,2,3-triazoles has
been reported through the click reaction of azides, alkynes and
epoxides catalyzed by various copper catalysts.16–31 Although
nucleophilic ring opening of strained three-membered hetero-
cycles such as epoxides and aziridines is easily carried out using
different nucleophiles such as azides and amines, no cases have
been reported yet for 1,3-dipolar cycloaddition between azide,
alkyne and thiiranes.
Ferrite nanoparticles due to their magnetic property are
easily separable. Recently, they have received great attention in
biomedicine,38–40 and organic synthesis.41–44 Nevertheless, the
nano-ferrites have hydrophobic surfaces with a large surface to
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran.
E-mail: roonak.isavi@gmail.com
† Electronic supplementary information (ESI) available: FT-IR, 1H NMR and 13C
NMR
spectra
of
b-thiol-1,4-disubstituted-1,2,3-triazoles.
See
DOI:
10.1039/d1ra01588e
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volume ratio and strong magnetic dipole–dipole attractions, carried out in the electron impact mode (EI) at 70 eV. The Cu
and they always suffer from adsorption problems because of content on the catalyst was determined by Perkin Elmer Optima
their intense tendency of self-aggregation and low quantity of 7300DV ICP-OES analyzer.
functional groups.45,46 To prevent agglomeration of magnetic
nanoparticles (MNPs) and improve their efficiency, surface
2.2. Synthesis of MgFe2O4 nanoparticles
coating of the MNPs is required.47 Aqueous MNP dispersions
MgFe2O4 nanoparticles were synthesized by a solid-state
procedure according to our reported investigation.48 Briey, in
a mortar, Mg(NO3)2$6H2O (0.512 g, 2 mmol), Fe(NO3)3$9H2O
(1.61 g, 4 mmol), NaOH (0.64 g, 16 mmol), and NaCl (0.232 g, 4
can be achieved by surface coating with copper nanoparticles.
In continuation of pioneering works on nano-ferrites,48–54
herein, we wish to report an efficient, three-component click
reaction protocol for synthesis of b-thiol-1,4-disubstituted-1,2,3-
mmol) were mixed in a molar ratio of 1 : 2 : 8 : 2 and ground
triazoles as new triazole derivatives from sodium azide, thiir-
together for 55 min. The reaction was carried out with the
anes, and terminal alkynes in the presence of MgFe2O4/Cu
release of heat. Aer 5 minutes of grinding, the mixture became
pasty and its color changed to dark brown. For removing the
additional salts, the obtained mixture was washed with double-
distilled water for several times. The produced mixture was
dried at 80 ꢀC for 2 h and it was then calcined at 900 ꢀC for 2 h to
magnetic nanoparticles as a novel and environmentally friendly
heterogeneous catalyst in water (Scheme 1).
2. Experimental
2.1. Instruments and materials
obtain the MgFe2O4 nanoparticles as a dark brown powder.
All materials were purchased from the Merck and Aldrich
Chemical Companies with the best quality and they were used
2.3. Preparation of MgFe2O4/Cu nanocomposite
In a round-bottom ask, a solution of CuCl2$2H2O (0.68 g, 4
mmol) in distilled water (50 mL) was prepared and then
MgFe2O4 (1 g) was added. The mixture was stirred vigorously for
30 min and followed by gradually addition of KBH4 powder (0.1
g) in order to reduce Cu2+ cations to copper nanoparticles. The
stirring of mixture was continued at room temperature for 1 h.
The black MgFe2O4/Cu nanocomposite was separated using
a magnet, washed with distilled water and then dried under air
atmosphere.
1
without further purication. IR and H/13C NMR spectra were
recorded on Thermo Nicolet Nexus 670 FT-IR and 500 MHz
Bruker Avance spectrometers, respectively. Melting points were
measured on an Electrothermal IA9100 microscopic digital
melting point apparatus. The synthesized nanocatalyst was
characterized by XRD on a Bruker D8-Advanced diffractometer
with graphite-monochromatized Cu Ka radiation (l ¼ 1.54056
˚
A) at room temperature. TEM image was recorded using an
EM10C-100 kV series microscope from the Zeiss Company,
Germany. FESEM images were determined using FESEM-
TESCAN. The energy dispersive X-ray spectrometer (EDS) anal-
ysis was taken on a MIRA3 FE-SEM microscope (TESCAN, Czech
2.4. Solvent-free synthesis of thiiranes from epoxides:
general procedure
Republic) equipped with an EDS detector (Oxford Instruments, The various thiiranes were prepared using a solvent-free
UK). Magnetic property of synthesized nanocatalyst was method reported in our previous research.55 Briey, a mixture
measured using a VSM (Meghnatis Daghigh Kavir Co., Kashan of epoxide (1 mmol) and alumina immobilized thiourea
Kavir, Iran) at room temperature. HRMS analyses were also (0.752 g, 25% w/w) was ground in a mortar for an appropriate
Scheme 1 Synthesis of b-thiol-1,4-disubstituted-1,2,3-triazoles from thiiranes catalyzed by MgFe2O4/Cu.
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Scheme 2 Synthesis of MgFe2O4 nanoparticles.
time at room temperature. The progress of the reaction was
monitored by TLC using n-hexane : EtOAc (5 : 2) as an eluent.
Aer completion of the reaction, the mixture was washed with
EtOAc (3 ꢁ 5 mL). The combined washing solvents were evap-
orated under reduced pressure to give the crude thiirane for
further purication by a short-column chromatography over
silica gel.
2.5.1. Characterization of b-thiol-1,4-disubstituted-1,2,3-
triazoles
2.5.1.1. 2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-ethane-1-
thiol (1b).
2.5. One-pot synthesis of b-thiol-1,4-disubstituted-1,2,3-
triazoles from thiiranes catalyzed by MgFe2O4/Cu in water:
a general procedure
White solid: mp 122–124 ꢀC, FT-IR (KBr): n/cmꢂ1 3371, 3085,
3026, 2927, 2365, 1584, 1450, 1270, 1029, 762, 695; 1H NMR (500
MHz, CDCl3) d 7.78–7.71 (m, 2H, Ar-H), 7.44–7.23 (m, 9H, Ar-H)
5.69 (dd, J ¼ 7, 4.5 Hz, 1H, CHN), 4.63 (dd, J ¼ 12.5, 5 Hz, 1H,
CH2), 4.23 (dd, J ¼ 15, 5 Hz, 1H, CH2), 3.63 (bs, 1H, SH); 13C
NMR (125 MHz, CDCl3) d 146.7 (]CN), 135.0 (NCH]), 128.1,
127.8, 127.2, 126.1, 124.7, 119.5 (10 ꢁ ArC), 66.2 (CHCH2), 28.6
(CH2). HRMS (EI) m/z calcd for C16H15N3S 281.0987, found
281.0985.
In a round-bottomed ask equipped with a magnetic stirrer and
condenser, a solution of the thiirane (1 mmol), alkyne (1 mmol)
and sodium azide (0.078 g, 1.2 mmol) in H2O (5 mL) was
prepared. MgFe2O4/Cu nanocomposite (0.02 g) was then added
to the solution and the resulting mixture was stirred magneti-
cally for 2–4 h at 60 ꢀC. The progress of the reaction was
monitored by TLC using n-hexane : EtOAc (10 : 2) as an eluent.
Aer completion of the reaction, the magnetic nanocatalyst was
separated using an external magnet and collected for the next
run. The reaction mixture was extracted with ethyl acetate and
then dried over anhydrous Na2SO4. Aer evaporating the
organic solvent, the crude b-thiol-1,4-disubstituted-1,2,3-
triazoles were obtained. Removal of the solvent under
vacuum, followed by recrystallization with EtOH/H2O (1 : 1)
afforded the pure b-thiol-1,4-disubstituted-1,2,3-triazoles
derivatives in 80–96% yield (Table 2). All products are new
compounds and were characterized by HRMS (EI), FT-IR, 1H
NMR and 13C NMR spectra. The spectra of the products are
given in the ESI.†
2.5.1.2. 1-Phenoxy-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propane-
2-thiol (2b).
Milky solid: mp 113–114 ꢀC, FT-IR (KBr): n/cmꢂ1 3302, 3086,
2919, 2873, 2365, 1587, 1638, 1599, 1497, 1474, 1466, 1303,
1
1044, 764, 752, 712, 691; H NMR (500 MHz, CDCl3) d 7.86 (s,
1H, NCH]C), 7.67–7.65 (m, 2H, Ar-Ho), 7.35–7.31 (m, 2H, OAr-
Hm), 7.29–7.26 (m, 3H, Ar-Hm,p), 7.00–6.87 (m, 3H, OAr-Ho,p),
Scheme 3 Synthesis of MgFe2O4/Cu nanocomposite.
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Fig. 1 Magnetization curves of (a) MgFe2O4 (b) MgFe2O4/Cu nanoparticles.
4.96 (bs, 1H, SH), 4.67 (dd, J ¼ 13, 5 Hz, 1H, CH2O), 4.52 (dd, J ¼ SH); 13C NMR (125 MHz, CDCl3) d 148.0 (]CN), 130.1 (ArC,
13, 5 Hz, 1H, CH2O), 4.47 (dd, 1H, J ¼ 12.5, 5 Hz, CH2N), 4.08 NCH]), 128.9, 128.4, 125.7, 117.6 (5 ꢁ ArCH), 55.9 (CH2N), 34.4
(dd, 1H, J ¼ 12.5, 5 Hz, CH2N), 4.05–3.72 (m, 1H, CHS); 13C NMR (CH2Cl), 29.6 (CHS). HRMS (EI) m/z calcd for C11H12ClN3S
(125 MHz, CDCl3) d 157.1 (]CN), 146.53, 129.1 (2 ꢁ ArC), 128.6, 253.0441, found 253.0442.
128.5, 127.8, 127.1, 124.6, 120.5, 120.4 (10 ꢁ ArCH), 113.5
(NCH]), 67.8 (CH2O), 52.2 (CH2N), 28.6 (CHS). HRMS (EI) m/z
calcd for C17H17N3OS 311.1092, found 311.1092.
2.5.1.3. 1-Chloro-3-(5-phenyl-1H-1,2,3-triazol-1-yl)propane-2-
thiol (3b).
2.5.1.4. 1-(4-Phenyl-1H-1,2,3-triazol-1-yl)butane-2-thiol (4b).
White solid: mp 104–106 ꢀC, FT-IR (KBr): n/cmꢂ1 3692, 3139,
2958, 2873, 2366, 2345, 1585, 1439, 1230, 1072, 765, 694; 1H
NMR (500 MHz, CDCl3) d 7.83 (s, 1H, NCH]C), 7.68–7.23 (m,
5H, Ar-H), 4.49 (dd, J ¼ 14, 5 Hz, 1H, CH2N), 4.24 (dd, J ¼ 14,
8 Hz, 1H, CH2N), 4.09–4.04 (m, 1H, CHS), 3.43 (bs, 1H, SH),
1.61–1.55 (m, 2H, CH2), 1.06 (t, J ¼ 7.5 Hz, 3H, CH3); 13C NMR
(125 MHz, CDCl3) d 147.3 (]CN), 130.3 (NCH]), 128.7, 128.0,
125.5, 121.1 (6 ꢁ ArC), 71.7 (CH2N), 55.9 (CHS), 27.4 (CH2), 9.8
Mint white solid: mp 154–157 ꢀC FT-IR (KBr): n/cmꢂ1 3690,
3100, 2920, 2363, 2344, 1561, 1441, 1364, 1045, 764, 692, 668. 1H
NMR (500 MHz, CDCl3) d 7.93 (s, 1H, NCH]C), 7.88–7.23 (m,
5H, Ar-H), 4.61–4.41 (m, 2H, CH2N), 4.39–4.31 (m, 1H, CH2Cl),
4.00–3.94 (m, 1H, CH2Cl), 3.90–3.37 (m, 1H, CHS), 2.07 (bs, 1H,
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Fig. 2 FT-IR (KBr) spectrum of MgFe2O4/Cu nanoparticles.
Fig. 3 The X-ray diffraction patterns of (a) nano-Cu, (b) nano-MgFe2O4 and (c) MgFe2O4/Cu nanocomposite.
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Fig. 4 TEM images of MgFe2O4/Cu.
(CH3). HRMS (EI) m/z calcd for C12H15N3S 233.0987, found
233.0986.
2.5.1.5. 1-Isopropoxy-3-(4-phenyl-1H-1,2,3-triazol-1-yl)
propane-2-thiol (5b).
Yellow solid: mp 74–75 ꢀC, FT-IR (KBr): n/cmꢂ1 3177, 2968, 2875,
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Fig. 5 FESEM images of MgFe2O4/Cu.
2369, 2345, 1583, 1460, 1444, 1366, 1071, 767, 702; 1H NMR (500
MHz, CDCl3) d 7.86 (s, 1H, NCH]C), 7.67–7.65 (m, 2H, Ar-H),
7.33–7.23 (m, 3H, Ar-H), 4.53 (dd, J ¼ 14, 4 Hz, 1H, CH2N),
4.34 (dd, J ¼ 14, 7.5 Hz, 1H, CH2N), 4.21–4.16 (m, 2H, OCH2),
3.58–3.51 (m, 1H, CHO), 3.46–3.35 (m, 2H, CHS overlapped with
SH), 1.11 (d, J ¼ 5 Hz, 6H, 2CH3); 13C NMR (125 MHz, CDCl3)
d 147.9 (]CN), 130.3 (NCH]), 128.7, 128.0, 125.5, 121.4 (6 ꢁ
ArC), 72.3 (CHO), 69.2 (OCH2), 69.1 (CH2N), 53.4 (CHS), 21.9 (2
ꢁ CH3). HRMS (EI) m/z calcd for C14H19N3OS 277.1249, found
277.1247.
Pale green solid: mp 156–159 ꢀC, FT-IR (KBr): n/cmꢂ1 3305,
3094, 2936, 2853, 2364, 1586, 1440, 1236, 1055, 766, 698; 1H
NMR (500 MHz, CDCl3) d 7.83 (s, 1H, NCH]C), 7.63–7.25 (m,
5H, Ar-H), 4.12–4.04 (m, 1H, CHN), 3.57–2.94 (m, 1H, CHS),
2.04–1.22 (m, 4 ꢁ CH2 overlapped with 1H, SH); 13C NMR (125
MHz, CDCl3) d 146.6 (]CN), 132.4 (NCH]), 130.2, 128.6, 127.9,
125.4, 119.8 (6 ꢁ ArC), 72.5 (CHN), 67.2 (CHS), 28.6 (CHS), 33.8,
2.5.1.6. 2-(4-Phenyl-1H-1,2,3-triazol-1-yl)cyclohexane-1-thiol
(6b).
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Fig. 6 EDS of MgFe2O4/Cu.
31.5, 24.8, 24.0 (4 ꢁ CH2). HRMS (EI) m/z calcd for C14H17N3S 2872, 2366, 1590, 1438, 1350, 1230, 1000, 767, 696; 1H NMR (500
259.1143, found 259.1143.
MHz, CDCl3) d 7.85 (s, 1H, NCH]C), 7.55–7.23 (m, 5H, Ar-H),
2.5.1.7. 1-(Allyloxy)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propane- 5.80–5.87 (m, 1H, ]CH), 5.22 (dt, J ¼ 17, 1.2 Hz, 1H, C]
2-thiol (7b).
CH2), 5.14 (dt, J ¼ 10, 1.2 Hz, 1H, C]CH2), 4.55–4.50 (m, 2H,
CH2O), 4.35 (dd, J ¼ 15, 7 Hz, 1H, CH2N), 4.26–4.23 (m, 1H,
CH2N), 4.00–3.88 (m, 2H, OCH2), 348–3.41 (m, 1H, CHS), 2.91
(bs, 1H, SH); 13C NMR (125 MHz, CDCl3) d 147.1 (]CN), 134.2
(NCH]), 130.2 (]CH), 128.7, 128.0, 125.5, 121.5 (6 ꢁ ArC),
117.4 (]CH2), 72.3 (OCH2), 71.2 (CH2O), 69.0 (CH2N), 53.4
(CHS). HRMS (EI) m/z calcd for C14H17N3OS 275.1092, found
275.1094.
ꢂ1
ꢀ
Cream solid: mp 70 C, FT-IR (KBr): n/cm 3233, 3141, 2930,
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Table 1 Nano-MgFe2O4/Cu-catalysed reaction of styrene episulfide
with phenylacetylene and sodium azide under different conditionsa
White solid: mp 125–128 ꢀC, FT-IR (KBr): n/cmꢂ1 3233, 3117,
3061, 2923, 2849, 1448, 1067, 889, 756, 697; 1H NMR (500 MHz,
CDCl3): d 7.60 (s, 1H, NCH]C), 7.42–7.26 (m, 5H, Ar-H), 5.68
(dd, J ¼ 8.7, 4.8 Hz, 1H, NCHCH2), 4.40–4.28, 4.15–4.03 (2 m,
2H, CH2S), 3.32 (t, J ¼ 5.9 Hz, 1H, SH), 2.76–2.68 (m, 1H, CH2-
CHCH2), 1.76–1.65 (m, 4H, 2 ꢁ CH2CH2CH), 1.43–1.36 (m, 4H,
2 ꢁ CH2CH2CH), 1.27–1.18 [m, 2H, (CH2)2CH2(CH2)2]. 13C NMR
(125 MHz, CDCl3): d ¼ 153.9 (NCCH), 138.5 (ArC), 129.7, 129.3,
128.1 (5 ꢁ ArCH), 120.9 (NCCH), 64.7 (NCHCH2), 53.3 (CH2S),
36.1 (CH2CHCH2), 33.8, 26.9, 26.8 [(CH2)5]; HRMS (EI) m/z calcd
for C16H21N3S 287.1456, found 287.1455.
MgFe2O4/Cu
Entry (g)
Temperature
Time (h) (ꢀC)
Solvent
Yieldb (%)
1
—
H2O
H2O
H2O
H2O
11
5
60
60
60
60
60
82
78
65
77
100
60
68
77
25
45
60
60
0
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16c
17d
0.005
0.01
0.02
0.03
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
40
75
96
96
50
60
60
65
55
0
5
2.5
2.4
3
H2O
CH3CN
EtOH
MeOH
EtOAc
DMF
THF
2.5.1.10. (1-(2-Mercapto-1-phenylethyl)-1H-1,2,3-triazol-4-yl)
methanol (10b).
3
3
3
3
20
n-Hexane 20
0
0
CCl4
H2O
H2O
H2O
H2O
20
10
6
4
3
45
70
Trace
92
Colorless solid: mp 101–105 ꢀC, FT-IR (KBr): n/cmꢂ1 3340,
3167, 2932, 2893, 1454, 1234, 1119, 1084, 1011, 849, 795, 702.
1H NMR (500 MHz, CDCl3): d 7.62 (s, 1H, NCH]C), 7.37–7.28
(m, 5H, Ar-H), 5.68 (dd, J ¼ 8.7, 4.8 Hz, 1H, NCHCH2), 4.52 (s,
2H, CH2O), 4.38–4.30, 4.13–4.02 (2 m, 2H, CH2S), 3.76 (bs,
1H, OH), 3.32 (t, J ¼ 5.9 Hz, 1H, SH), 13C NMR (125 MHz,
CDCl3): d ¼ 147.1 (]CN), 130.1 (ArC), 128.5, 128.0, 125.7 (5 ꢁ
ArCH), 121.3 (]CHN), 71.8 (CHN), 55.7 (CH2O), 27.3 (CH2S).
HRMS (EI) m/z calcd for C11H13N3OS 235.0779, found
235.0781.
a
All reactions were carried out with styrene episulde (1 mmol),
b
phenylacetylene (1 mmol) and sodium azide (1.2 mmol). Isolated
yields. c Catalysed by MgFe2O4. d Catalysed by Cu nanoparticles.
2.5.1.8. 2-Mercapto-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl
methacrylate (8b).
2.5.1.11. 2-(4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl)-2-
phenylethane-1-thiol (11b).
Milky solid: mp 86–92 ꢀC, FT-IR (KBr): n/cmꢂ1 3000, 2925,
2367, 1719, 1593, 1438, 1294, 1097, 762, 695; 1H NMR (300
MHz, CDCl3): d 7.86 (s, 1H, NCH]C), 7.66–7.64 (m, 2H, Ar-
H), 7.34–7.25 (m, 3H, Ar-H), 6.10 (d, J ¼ 10 Hz, 1H, ]CH2),
5.93 (d, J ¼ 10 Hz, 1H, ]CH2), 4.48–4.12 (m, 2H, OCH2), 3.57
(m, 2H, CH2N), 3.66 (bs, 1H, SH), 3.33–3.32 (m, 1H, CSH),
2.05 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3): d ¼ 161.6 (C]
O), 147.3 (]CN), 135.7 (C]), 128.9 (NCH]), 128.8, 128.2,
125.5, 121.6 (6 ꢁ ArC), 70.6 (OCH2), 63.6 (CH2N), 53.0 (CHS),
18.3 (CH3). HRMS (EI) m/z calcd for C15H17N3O2S 303.1042,
found 303.1045.
ꢂ1
ꢀ
White solid: mp 130–132 C, FT-IR (KBr): n/cm 3371, 3085,
3026, 2927, 2365, 1584, 1450, 1270, 1074, 1041, 1029, 762,
695; 1H NMR (500 MHz, CDCl3) d 7.76–7.71 (m, 3H, Ar-H),
7.44–7.21 (m, 7H, Ar-H) 5.71 (dd, J ¼ 7, 4.5 Hz, 1H, CHN),
4.15 (s, 3H, OCH3), 3.76 (dd, J ¼ 12.5, 5 Hz, 1H, CH2), 3.37 (dd,
J ¼ 15, 5 Hz, 1H, CH2), 2.75 (bs, 1H, SH); 13C NMR (125 MHz,
CDCl3) d 146.6 (]CN), 135.0 (NCH]), 128.1, 127.7, 127.2,
126.1, 124.7, 119.1 (10 ꢁ ArC), 66.2 (CHN), 58.26 (OCH3), 28.6
(CH2S). HRMS (EI) m/z calcd for C17H17N3OS 311.1092, found
311.1095.
2.5.1.9. 2-(4-Cyclohexyl-1H-1,2,3-triazol-1-yl)-2-phenylethane-1-
thiol (9b).
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Table 2 One-pot synthesis of b-Thiol-1,4-disubstituted-1,2,3-triazoles from thiiranes catalyzed by nano-MgFe2O4/Cua
Entry
1
Thiirane (a)
Alkyne
Triazole (b)
Time (h)
Yieldb (%)
2.5
96
2
2
91
3
4
2.5
4
80
95
5
3
90
6
7
8
2
94
90
80
2.5
2
9
3
92
90
10
3.5
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Table 2 (Contd.)
Entry
Thiirane (a)
Alkyne
Triazole (b)
Time (h)
Yieldb (%)
11
2.5
95
a
All reactions were carried out with 1 mmol of thiirane in the presence of alkyne (1 mmol), sodium azide (1.2 mmol) and nano-MgFe2O4/Cu (0.02 g)
in water at 60 ꢀC. b Yields refer to isolated pure products.
contact surface, it tends to aggregate so as to minimize the
surface energies. Moreover, the naked magnesium ferrite
nanoparticles have high chemical activity, and are easily
oxidized in air, generally resulting in loss of magnetic property
and dispersibility. Therefore, it is signicant to provide appro-
priate surface coating to keep the stability of MgFe2O4 particles.
Coating with an inorganic layer, such as silica, metal or
nonmetal elementary substance and metal oxide is important
because the protecting shells not only reduces the aggregation
of the nanoparticles in the solution and stabilize the magnetic
nano-ferrite, but can also be used for further functionalization
2.6. Recycling of MgFe2O4/Cu nanocatalyst
The MgFe2O4/Cu nanoparticles were recovered with an external
magnet, washed several times with ethyl acetate and distilled
water, and used for the subsequent cycles aer drying under air
atmosphere.
3. Results and discussion
3.1. Synthesis and characterization of MgFe2O4/Cu
nanocatalyst
Although, MgFe2O4 has a large surface to volume ratio and and improves the efficiency of the catalyst.56 Ferrites are highly
therefore possesses high catalytic capability due to its wide valuable catalyst supports because they take advantage of
Fig. 7 Recycling of nano-MgFe2O4/Cu in the synthesis of 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethane-1-thiol.
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Fig. 8 (a) Magnetization curve, (b) FESEM, (c) XRD pattern and (d) TEM image of MgFe2O4/Cu after five runs in the synthesis of 2-phenyl-2-(4-
phenyl-1H-1,2,3-triazol-1-yl)ethane-1-thiol.
Scheme 4 The mechanism proposed for the one-pot synthesis of b-thiol-1,4-disubstituted-1,2,3-triazole catalyzed by MgFe2O4/Cu.
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magnetic property and can provide unique features such as easy MgFe2O4/Cu nanoparticles is calculated using the Scherrer's
separation, recoverability and reusability for the new synthe- formula (46 nm).
sized MgFe2O4/Cu nanocatalyst.
3.1.4. TEM, FESEM and EDS of MgFe2O4/Cu. The
The nanoparticles of MgFe2O4/Cu were synthesized in a two- morphology and size distribution of the synthesized nano-
step procedure. MgFe2O4 was prepared using solid-state reac- catalyst have been studied by TEM and FESEM techniques. TEM
tion of Mg(NO3)2$6H2O, Fe(NO3)3$9H2O, NaOH, and NaCl in images of the MgFe2O4/Cu nanocomposite are shown in Fig. 4.
a mortar (Scheme 2). Aer calcination of crude powder at As can be seen from the images, two sizes of particles are clearly
900 ꢀC, the MgFe2O4 nanoparticles were obtained with high distinguishable, with differences in their colour and
crystallinity and phase purity. Then, MgFe2O4 nanoparticles morphology. The larger grey spots with cubic shape were
were added to an aqueous solution of CuCl2$2H2O and followed attributed to the MgFe2O4 particles which coated with the small
by gradually addition of KBH4 powder under intense stirring. black segments of copper nanoparticles.
Finally, the black precipitate was collected through magnetic
Fig. 5 shows FESEM images of MgFe2O4/Cu nanocomposite
separation, washed with deionized water, and dried at room that conrm the presence of nanoparticles with diameters
temperature (Scheme 3). The prepared MgFe2O4/Cu nano- ranging from 29 to 43 nm. The obtained results are in good
catalyst was characterized by various techniques such as FT-IR, agreement with TEM and XRD data.
vibration sample magnetometer (VSM), X-ray diffraction (XRD),
The chemical composition of MgFe2O4/Cu nanocomposite
transmission electron microscopy (TEM), eld emission scan- was conrmed with EDS data. In this analysis, Cu, Mg, Fe, and
ning electron microscope (FESEM), energy dispersive X-ray O signals are observable (Fig. 6). Additionally, the exact
spectrometer (EDS), and inductively coupled plasma optical concentration of Mg, Fe and Cu was determined by ICP-OES and
emission spectrometry (ICP-OES) analyses.
the obtained values were 10.2, 33.35 and 31.68 wt% respectively,
3.1.1. Vibration sample magnetometer (VSM). The hyster- which are in good agreement with EDS data.
esis loops, saturation magnetization (Ms) and switching eld
(Hc) of MgFe2O4 and MgFe2O4/Cu nanoparticles are shown in
Fig. 1. MgFe2O4/Cu nanoparticles show lower magnetization
saturation (27 emu gꢂ1) than the uncoated magnesium ferrite
3.2. Catalytic activity of MgFe2O4/Cu for the synthesis of b-
thiol-1,4-disubstituted-1,2,3-triazoles
nanoparticles (48 emu gꢂ1). This is owing to the effect of copper In order to optimize the reaction conditions, we investigated the
shell coating where each ferrite particle was separated from its one-pot click synthesis of 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-
neighbors by the coated layer leading to diminish the magne- 1-yl)ethane-1-thiol from styrene episulde, sodium azide and
tostatic coupling between the particles. The samples exhibit phenyl acetylene under various reaction conditions. Initially,
typical ferromagnetic behavior at room temperature. The temperature, solvents, reaction time and the amounts of cata-
narrow cycles and the hysteresis loops show the behavior of so lyst and reactants were studied as experimental factors, and
magnetic materials with low coercivity.
then the results were summarized in Table 1. The favorable
3.1.2. Fourier transform infra-red (FT-IR) spectrum. Fig. 2 outcome was obtained using styrene episulde (1 mmol),
shows the FT-IR spectrum of MgFe2O4/Cu nanocatalyst. The sodium azide (1.2 mmol) and phenylacetylene (1 mmol) in the
absorption band at 577 cmꢂ1 is related to the vibration of metal presence of nano-MgFe2O4/Cu (0.02 g) as catalyst in water at
ꢀ
oxide bonds (Fe–O and Mg–O) which conrms the formation of 60 C (Table 1, entry 4). It is noteworthy that the presence of
MgFe2O4 nanoparticles. The absorption peaks at 3314 and catalyst was necessary to perform the reaction and in the
3449 cmꢂ1 are assigned to the stretching vibration of H2O absence of nanocomposite, the reaction did not proceed even
molecules and indicates the OH groups on the surface of the aer 11 h (entry 1). The quantity of catalyst was optimized using
magnetic nanoparticles. The band around 1637 cmꢂ1 corre- various amounts of nano-MgFe2O4/Cu (0.005, 0.01, 0.02 and
sponds to the bending mode of H2O molecules.51
0.03 g), and the best result was obtained with 0.02 g of catalyst.
3.1.3. X-ray diffraction (XRD). Fig. 3 shows the X-ray The catalyst concentration plays a signicant role in the opti-
diffraction (XRD) patterns of MgFe2O4/Cu, MgFe2O4 and mization of the product yield. An increase in the amount of
copper nanoparticles. In the XRD pattern of MgFe2O4/Cu, all the catalyst from 0.01 to 0.02 g not only increased the triazole yield
peaks of MgFe2O4 and Cu nanoparticles are traceable. The lines but also accelerated the rate of reaction (entries 2–4). Using the
(220), (311), (400), (422), (511), (440), (620) and (533) related to more amounts of nanocatalyst did not improve the product
2q ¼ 30.22ꢀ, 35.60ꢀ, 37.18ꢀ, 43.27ꢀ, 57.09ꢀ, 62.68ꢀ, 74.38ꢀ and yield (entry 5).
75.39ꢀ respectively, are assigned to the diffraction of MgFe2O4
In order to study of solvent effect, the cyclization reaction
crystals and indicate that the synthesized MgFe2O4 nano- was tested in the various solvents. The results showed that the
particles are pure and high crystalline. These peaks are polar solvents such as water, acetonitrile, ethanol, methanol,
compatible with the standard data (JCPDS: 01-036-0398).51 The ethyl acetate and dimethylformamide were effective and utiliz-
characteristic diffraction peaks of copper located at 2q ¼ 43.7ꢀ, able whereas non-polar solvents were not suitable for this
50.7ꢀ, and 74.3ꢀ which correspond to the (111), (200), and (220) purpose (entries 6–13). The reaction was carried out success-
planes of the fcc structure, respectively and they are in good fully in H2O and it was selected as the best option because in
agreement with copper standard (JCPDS: 04-0836).57 The peaks comparison with water, the product yields were lower in all
at 43.7ꢀ and 74.3ꢀ for copper overlap with the 43.27ꢀ and 74.38ꢀ other solvents and also water is a green and eco-friendly solvent
peaks of MgFe2O4, respectively. The average crystallite size of (entry 4).
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The effect of temperature was also investigated and the poisoned and inactivated MgFe2O4/Cu heterogeneous catalyst
reaction was tested at different temperatures (25, 45 and 60 ꢀC). through amalgamating the metal catalyst or adsorbing on its
The product yield was not satisfactory at room temperature (25 surface and no product was obtained aer 3 h.
ꢀC) aer 10 h (entry 14). Increasing the temperature simulta-
neously increased the reaction rate and product yield, and the
3.5. The proposed mechanism for synthesis of b-thiol-1,4-
desired triazole was synthesized in 70% yield aer 6 h at 45 ꢀC
disubstituted-1,2,3-triazoles catalyzed by MgFe2O4/Cu
ꢀ
(entry 15). Further increase of temperature up to 60 C led to
produce the product with excellent yield at short reaction time The designed mechanism for the synthesis of b-thiol-1,4-
(entry 4). The reaction was tested in the presence of bare disubstituted-1,2,3-triazole may comprise two possible path-
MgFe2O4 and Cu nanoparticles separately under the optimized ways (A and B). MgFe2O4/Cu nanoparticles catalyze both
conditions and results showed that although magnesium ferrite cleavage of the thiirane ring and 1,3-dipolar cycloaddition
nanoparticles improve and enhance the catalytic activity of leading to the formation of triazoles.27,28 First, as a result of non-
nanocomposite, copper particles play an essential role for covalent interaction a bond is formed between metal and azide,
proceeding the reaction and their presence is vital in triazole followed by activation of thiirane ring with MgFe2O4/Cu cata-
cyclization (entries 16 and 17).
lyst. Then, ring opening of thiirane is accomplished through
The generality of the presented procedure was established by azide transference from the catalyst which leads to the forma-
reaction of various thiiranes bearing either electron-donating or tion of 2-azido-2-arylethanethiol (pathway A). The thiirane rings
withdrawing substituents, and cyclic thiiranes with phenyl- carrying aryl groups due to the stability of benzyl carbocation
acetylene and sodium azide in the presence of MgFe2O4/Cu prefer to be opened from the more hindered position via SN1
nanocomposite under the optimized conditions. The results are type of mechanism (a-cleavage); nevertheless, the regioselective
summarized in Table 2. In addition, the reaction of other ring opening of thiiranes bearing alkyl and allyl substituents by
alkynes such as aliphatic terminal alkynes and 4-methox- azide is powerfully preferred from less hindered carbon of the
yphenyl acetylene with styrene episulde was also considered thiirane via SN2 type of mechanism (b-cleavage). In order to
under mentioned conditions (entries 9–11). All reactions were accredit the catalytic role of MgFe2O4/Cu in the pathway A, the
carried out successfully within 2–4 h to give triazoles in 80–96% styrene episulde and sodium azide were reacted in the absence
yields.
of catalyst, and it was found that, only a trace amount of 2-azido-
2-arylethanethiol had been generated. For pathway A,
consumption of styrene episulde and sodium azide and also
the generation of 2-azido-2-phenylethanethiol intermediate
were monitored by gas chromatography (GC) analysis and thin
layer chromatography (TLC) runs of the reaction mixture, and
we found that 2-azido-2-arylethanethiol is formed easily (within
the rst 30 min of the reaction) and the rate determining step
(RDS) was found to be the 1,3-dipolar cycloaddition step. 2-
Azido-2-arylethanethiol was characterized by FT-IR spectrum
and stretching frequency of 2097 cmꢂ1 related to the azide (the
FT-IR spectrum of 2-azido-2-phenylethanethiol has been
provided in ESI Section†).
3.3. Recycling of nano-MgFe2O4/Cu
The recycling of the green nanocatalyst was investigated under
the optimized reaction conditions (Table 2, entry 1). The
nanoparticles were easily accumulated by applying an external
magnetic eld, washed with ethyl acetate and distilled water
and, aer drying, reused several times without any signicant
loss of activity (Fig. 7). The structure of the recovered catalyst
was conrmed using VSM, FESEM, XRD and TEM analyses aer
ve runs (Fig. 8).
The extent of Mg, Fe and Cu leaching during catalytic reac-
tion was studied by ICP-OES analysis of the supernatant liquid
aer removal of catalyst and the result showed no presence of
Mg, Fe and Cu in supernatant liquid.
The pathway B shows the insertion of copper to the C–H
bond of phenylacetylene and generation of the intermediate(I),
which accelerates the [3+2] cycloaddition between azide and
carbon–carbon triple bond of in situ produced intermediate(II),
to afford the Cu–C-triazole(IV). The phenylacetylene consump-
3.4. Mercury poisoning and hot ltration tests
In order to conrm the heterogeneity of the catalyst, both hot tion and also the disappearance of the 2-azido-2-arylethanethiol
ltration and mercury poisoning tests were performed. intermediate, were monitored by GC analysis and TLC runs of
Accordingly, the ltration of the catalyst was carried out aer the reaction mixture. Eventually, proteolysis of the Cu–C bond
ꢀ
30 min at 100 C and the ltrate was allowed to react for addi- of intermediate(IV) by aqueous media gives the corresponding b-
tional 2 hours, but the reaction due to the absence of copper did thiol-1,4-disubstituted-1,2,3-triazole(V) (Scheme 4).
not take place, and no cyclization reaction was occurred.
In order to evaluate the accuracy of reaction RDS, 2-azido-2-
The Hg poisoning test was conducted for the model reaction phenylethanethiol was separately reacted with phenylacetylene
under the optimum conditions as follows: the one-pot reaction in the presence of MgFe2O4/Cu nanocatalyst. The formation of
of styrene episulde (1 mmol), phenyl acetylene (1 mmol), corresponding 1,2,3-triazole was monitored via GC analysis and
sodium azide (1.2 mmol) and MgFe2O4/Cu nanocatalyst (0.02 g) TLC runs. It was observed that the reaction was carried out
was carried out in the presence of Hg(0) excess (1.89 g, within 2 h. This result demonstrated that the pathway B
9.43 mmol, 277 equiv.) under intense stirring conditions at determines the reaction rate.
60 ꢀC for 3 h in water. The suppression of catalysis by mercury is
evidence for a heterogeneous catalyst.58 The added Hg(0) nylacetylene and MgFe2O4/Cu nanocatalyst were mixed in
To conrm the formation of acetylide intermediate(I), phe-
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a separate experiment in aqueous media, and pH of water as
a solvent was investigated. A 0.6 unit decrease in pH aer
20 min was detected, indicative of terminal proton release to the
9 S. Manfredini, C. B. Vicentini, M. Manfrini, N. Bianchi,
C. Rustigliano, C. Mischiati and R. Gambari, Bioorg. Med.
Chem., 2000, 8, 2343.
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copper to form acetylide intermediate(I).
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Pharma Chem., 2014, 6, 223.
4. Conclusions
In summary, in this research, the magnetic nanocomposite of
MgFe2O4/Cu has been easily manufactured through a solid-
state procedure and it was then characterized by different
techniques such as VSM, FESEM, TEM, XRD, EDS and FT-IR.
This novel composite has been utilized as an efficient catalyst
for one-pot synthesis of b-thiol-1,4-disubstituted-1,2,3-triazoles
as new products via three component reactions of sodium
azide, terminal alkynes, and various thiiranes in water. The
method reported is completely new due to the novelty of both
the catalyst and the triazole products. Furthermore, perfect
regioselectivity, the simple process, high product yields, short
reaction times, the use of eco-friendly solvent, easy separation
and recycling of catalyst are signicant advantages of this
proposed procedure.
13 M. F. Mady, G. E. A. Awad and K. B. Jørgensen, Eur. J. Med.
Chem., 2014, 84, 433.
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Conflicts of interest
There are no conicts to declare.
22 B. S. P. Anil Kumar, K. Harsha Vardhan Reddy, G. Satish,
R. Uday Kumar and Y. V. D. Nageswar, RSC Adv., 2014, 4,
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23 H. Naeimi and V. Nejadshaee, New J. Chem., 2014, 38, 5429.
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M. Lakshmi Kantam, Synth. Commun., 2008, 38, 2158.
25 H. Esmaeili-Shahri, H. Eshghi, J. Lari and S. A. Rounaghi,
Appl. Organomet. Chem., 2018, 32, e3947.
Acknowledgements
The nancial support of this work by the Research Council of
Payame Noor University is gratefully acknowledged.
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