Magnetically Recoverable Cu0/Fe3O4-Catalysed One-Pot Tandem Synthesis of Sulfur-Containing Triazoles from Alkynes and Azide: DMSO Acts as an Alkylating Agent

Article abstract of DOI:10.1002/ejoc.201600740

An efficient one-pot tandem nano Cu⁰/Fe₃O₄-catalysed synthesis of sulfur-containing triazoles from alkynes and azide has been developed. In this newly developed method, the readily available TMS-azide and dimethyl sulfoxide act as nitrogen and sulfur sources, respectively. The catalyst was magnetically recovered and reused six times without any significant loss of activity.

Full text of DOI:10.1002/ejoc.201600740

DOI: 10.1002/ejoc.201600740
Full Paper
Alkyne–Azide Cycloaddition
Magnetically Recoverable Cu0/Fe3O4-Catalysed One-Pot Tandem
Synthesis of Sulfur-Containing Triazoles from Alkynes and
Azide: DMSO Acts as an Alkylating Agent
Mandalaparthi Phanindrudu,[a,b] Dipak Kumar Tiwari,[a,b] Vinod Kumar Aravilli,[a]
Kishor Chandra Bhardwaj,[c] Gokulnath Sabapathi,[d] Pravin R. Likhar,[a,b] and
Dharmendra Kumar Tiwari*[a,b]
Abstract: An efficient one-pot tandem nano Cu0/Fe3O4-cata- nitrogen and sulfur sources, respectively. The catalyst was mag-
lysed synthesis of sulfur-containing triazoles from alkynes and
azide has been developed. In this newly developed method,
the readily available TMS-azide and dimethyl sulfoxide act as
netically recovered and reused six times without any significant
loss of activity.
more, the recovery and reusability of the catalyst is probably
one of the great challenges associated with these methods.
Therefore, the development of a new catalytic system to over-
come these shortcomings and fulfil the criteria of a mild, effi-
cient, and environmentally benign protocol for the synthesis of
substituted triazoles would be highly desirable.
Introduction
1,2,3-Triazoles and their derivatives are some of the most well-
known five-membered nitrogen-containing heterocycles by vir-
tue of their frequent appearance in a large number of biologi-
cally and pharmaceutically relevant molecules, agrochemicals,
and functional materials.[1] The fact that several of these mol-
ecules have been found to show different potent biological ac-
tivities, such as anti-HIV,[2] anticancer,[3] antimicrobial,[4] and b3-
adrenergic receptor agonist[5] activities, has aroused substantial
interest among medicinal chemists. In the recent past, sulfur-
containing triazoles in particular have also gained huge mo-
mentum, due to their presence in a wide variety of therapeuti-
cally interesting drug candidates, such as mPGES-1 and anti-
inflammatory agents.[6] Despite their being an integral part of
life-saving drugs, surprisingly, the synthesis of sulfur-containing
triazoles remains rather underexplored.[7] The methods avail-
able in the literature have various disadvantages, such as harsh
reaction conditions, expensive starting materials, long reaction
times, and laborious and complex work-up procedures. Further-
In recent years, heterogeneous catalysts, particularly magnet-
ite-supported copper nanoparticles, are increasingly being used
for various functional-group transformations in organic reac-
tions.[8] Such catalysts have high thermal and mechanical stabil-
ity along with a high surface area to increase the number of
catalytic active sites.[9] Furthermore, their unique paramagnetic
nature and inherent insolubility in most reaction solvents allows
them to be simply and efficiently separated from reaction mix-
tures using an external magnet, in an economical, practical, and
environmentally benign way.[10] Recently, our group have pre-
pared Cu0/Al2O3 and magnetically separable Cu0/Fe3O4 nano-
catalysts, and successfully demonstrated their catalytic activities
in alkyne–isocyanide cycloaddition reactions to give syntheti-
cally challenging 2,4-disubstitiuted pyrroles and 2,3,4 trisubstiti-
uted pyrroles, respectively.[11,12] In a continuation of this re-
search programme, we report in this paper our new findings
on the synthesis of sulfur-containing triazoles from terminal alk-
ynes and azide in the presence of a magnetically separable and
reusable nano Cu0/Fe3O4 catalyst (Figure 1).
[a] Inorganic and Physical Division, CSIR – Indian Institute of Chemical
Technology,
Uppal road, Tarnaka, Hyderabad 500607, India
E-mail: dktiwari@iict.res.in
dkt80.org@gmail.com
[b] Academy of Scientific & Innovative Research (AcSIR),
New Delhi 110001, India
http://www.iictindia.org/
[c] Department of Chemistry, Faculty of Science, Banaras Hindu University,
Varanasi 221005, India
[d] School of Chemistry Indian Institute of Science Education and Research
(IISER), CET Campus,
Thiruvananthapuram 695016, Kerala, India
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600740.
Figure 1. Cu0/Fe3O4-catalysed alkyne–azide click reaction.
1 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Results and Discussion
Table 1. Optimisation of the reaction conditions.[a]
We chose phenylacetylene (1a) and TMSN3 (TMS = trimethyl-
silyl) as model substrates to start our study. When a mixture of
phenylacetylene (1a; 1.0 mmol), TMSN3 (1.10 mmol), and freshly
prepared Cu0/Fe3O4 (90 mg) in DMSO (2.0 mL) was heated at
100 °C for 4 h under a nitrogen atmosphere, the corresponding
sulfur-containing 1,2,3-triazole (i.e., 3a) was obtained in 70 %
yield, along with partially oxidised product 3a′ in 22 % yield
(Scheme 1). It is worth noting that under these catalytic condi-
tions, the expected 4-phenyl-1H-1,2,3-triazole (2a) was not de-
tected, even in a trace amount. At this stage, the structure of
the unexpected product (i.e., 3a) was well characterised using
all spectroscopic techniques, and the ultimate structural proof
of 3a was obtained by single-crystal X-ray diffraction analysis
(Figure 2). Since this reaction represents an efficient and mild
route to pharmaceutically valuable sulfur-containing triazoles,
we systematically carried out an extensive optimisation of the
reaction conditions (Table 1).
Entry
Catalyst (mg)
T [°C]
Time [h]
Isolated yield [%][d]
2a
3a
3a′
1
2
3
4
5
6
7
8
Cu0/Fe3O4 (90)
Cu0/Fe3O4 (60)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
Cu0/Fe2O3 (30)
Cu0/Al2O3 (30)
Cu0/(rGO) (30)
Cu0/polymer(30)
Cu0/Fe3O4 (30)
Cu0/Fe3O4 (30)
100
100
100
120
80
60
80
80
80
80
80
80
80
80
80
4
4
4
4
4
4
2
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
n.o.
n.o.
n.o.
n.o.
n.o.
n.o.
n.o.
n.o.
n.o.
10
70
75
75
65
76
53
85
90
96
65
n.o.
10
8
22
15
15
27
20
20
10
trace
n.o.
n.o.
n.o.
n.o.
n.o.
n.o.[b]
n.o.[c]
9
10
11
12
13
14
15
70
58
67
86
no
61
n.o.
[a] Reaction was carried out using phenylacetylene (1a; 1.0 mmol), TMSN3
(1.10 mmol) and Cu0/Fe3O4 (30 mg) in DMSO (2.0 mL) at 80 °C for 0.5 h under
nitrogen. [b] NaN3 was used as an azide source. [c] DPPA (diphenylphosphoryl
azide) was used as an azide source. [d] Isolated yields; n.o.: not obtained.
perature was decreased to 80 °C, the desired product (i.e., 3a)
was obtained in 76 % yield, along with 3a′ in in 20 % yield
(Table 1, entry 5). Further decreasing the temperature (60 °C)
produced 3a and 3a′ in lower yields (Table 1 entry 6). In con-
trast, when the reaction time was decreased to 2 h from 4 h,
we surprisingly obtained the desired product (i.e., 3a) in 85 %
yield, along with 3a′ in 10 % yield (Table 1, entry 7). Further
decreasing the reaction time (1 h) gave 3a′ in 90 % yield, along
with a trace amount of the undesired 3a′ (Table 1, entry 8). To
our delight, when the reaction was quenched after 0.5 h, the
desired product (i.e., 3a) was obtained as the sole product in
96 % yield (Table 1, entry 9).
Scheme 1. Cu0/Fe3O4-catalysed unexpected formation of 3a from phenylacet-
ylene (1a) and TMSN3 in DMSO at 100 °C under nitrogen.
In order to minimise the formation of the undesired product
(i.e., 3a′), we initially decreased the catalyst loading (to 60 from
90 mg). However, under these conditions, 3a and 3a′ were ob-
tained in 75 and 15 % yields, respectively (Table 1, entry 2).
Further decreasing the catalyst loading (to 30 mg) did not help
much, and 3a and 3a′ were produced in a similar ratio (Table 1,
entry 3). Increasing the reaction temperature was also found to
be less effective, and produced a poor yield of the desired prod-
We screened various copper nanocatalysts for this reaction,
uct (i.e., 3a; Table 1, entry 4). However, when the reaction tem- including Cu0/Fe2O3, Cu0/Al2O3, Cu0/graphene oxide, and Cu0/
Figure 2. ORTEP diagram of 3a with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30 % probability level, and hydrogen atoms are
shown as small spheres of arbitrary radius.[14]
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polymer. Most of them were found to be less efficient, and pro- give the corresponding product (i.e., 3i) in 91 % yield. Various
duced undesired product 2a in very high yields, except for Cu0/ heteroaromatic alkynes, including thienyl (1j), 2-pyridyl (1k),
Fe2O3, which gave the desired product (i.e., 3a) in 65 % yield and pyrrole (1l) derivatives, reacted smoothly with TMSN3 to
(Table 1 entries 10–13). The bimetallic nature of the Cu/iron- give the corresponding sulfur-containing triazoles (i.e., 3j–3l)
oxide catalyst could be responsible for the formation of unex- in very good yields. Furthermore, various polycyclic aromatic
pected sulfur-containing triazole 3a under these catalytic con- alkynes, including 6-methoxy-2-ethynylnaphthalene (1m), 9-
ditions.[13] It is also important to note that, the reaction was ethynylphenanthrene (1n), and pyrene (1o), reacted effectively
completely shut down when NaN3 was used as the source of with TMSN3 under the optimised reaction conditions, and gave
azide (Table 1 entry 14). However, a 61 % yield of the desired comparable yields of the desired products (i.e., 3m–3o). Nota-
product (i.e., 3a) was obtained when DPPA (diphenylphosphoryl bly, aliphatic alkynes 1p–1s were also found to be suitable sub-
azide) was used as the azide source (Table 1, entry 15).
Having optimised the reaction conditions (Table 1 entry 9),
we evaluated the substrate scope of this reaction with respect
strates for this reaction, although lower yields of the corre-
sponding triazoles (i.e., 3p–3s) was obtained.
To demonstrate the synthetic utility of our strategy, a gram-
to various alkyl/aryl alkynes. The results are summarised in scale synthesis of 3m was carried out under the standard condi-
Table 2. We were pleased to see that various aromatic alkynes tions. Pleasingly, sulfur-containing triazole 3m was obtained in
bearing both electron-donating and -withdrawing groups un- a satisfactory yield (86 %) when the reaction was carried out on
derwent the azide–alkyne cycloaddition to give the correspond- a 10.0 mmol scale (Scheme 2). This result indicates that there is
ing sulfur-containing triazole products in good yields (62–96 %). also potential for industrial application.
A wide range of arylacetylenes bearing alkyl (methyl, ethyl,
propyl, tert-butyl and pentyl; 1b–1f), alkoxy (1g–1h), and tri-
fluoromethyl (1i) groups gave the corresponding sulfur-contain-
ing triazoles (i.e., 3b–3l) in very high yields. It is important to
note that the presence of bulky groups such as isopropyl (1f)
and tert-butyl (1g) on the phenyl ring did not affect the out-
come of the reaction, and excellent yields of the desired prod-
ucts were obtained. m-Trifluoromethylphenylacetylene (1i) re-
Scheme 2. Synthesis of 3m on a gram scale.
acted with TMSN3 under the optimised reaction conditions to
Next, we investigated the recovery and reusability of the cat-
alyst. After completion of the reaction, the stirring was stopped,
and the catalyst was separated magnetically. The recovered cat-
alyst was washed thoroughly with diethyl ether, and dried at
Table 2. Substrate scope.[a]
120 °C for 12 h. A new reaction was then carried out with fresh
reactants, under the optimised reaction conditions. We found
that Cu0/Fe3O4 could be reused in up to six consecutive cata-
lytic runs without any significant change in activity (Figure 3).
Figure 3. Recycling of the Cu0/Fe3O4 catalyst for the preparation of sulfur-
containing trazoles. Reaction conditions: 1a (1.0 mmol), TMSN3 (1.0 mmol),
cat. (Cu 8 wt.-%, 30 mg), DMSO (2.0 mmol), 80 °C, 0.5 h.
Based on our findings and on literature reports,[7c,15] a plausi-
ble mechanism for the synthesis of sulfur-containing triazoles
from alkynes and TMSN3 is shown in Scheme 3. Initially, the
oxygen of the polarised DMSO attacks TMSN3, leading to the
formation of intermediate A along with release of azide ion.
Intermediate A loses a proton to give thionium ion B, which
undergoes nucleophilic substitution with azide ion to give in-
termediate C. Intermediate C then undergoes a click reaction
[a] Reaction conditions: Phenylacetylene (1a; 1.0 mmol), TMSN3 (1.10 mmol),
Cu0/Fe3O4 (30 mg), DMSO (2.0 mL), at 80 °C for 0.5 h under nitrogen.
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was washed with brine (10.0 mL), and dried with anhydrous sodium
sulfate. The solvent was then removed under reduced pressure. The
residue was purified by column chromatography using 100–
200 mesh silica gel to give sulfur-containing triazole 3a–3s.
with copper acetylide (1a′) to produce intermediate D, and this
finally loses Cu to give the desired product (i.e., 3a).
1-[(Methylthio)methyl]-4-phenyl-1H-1,2,3-triazole (3a): White
1
solid (96 %), m.p. 75 –77 °C. H NMR (400 MHz, CDCl3): δ = 7.99 (s,
1 H), 7.86–7.83 (m, 2 H), 7.46–7.42 (m, 2 H), 7.38–7.32 (m, 1 H), 5.38
(s, 2 H), 2.17 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 128.91,
128.38, 125.77, 118.88, 52.75, 14.84 ppm. HRMS (ESI, Orbitrap):
calcd. for C10H12N3S [M + H]+ 206.07464; found 206.07472.
1-[(Methylthio)methyl]-4-(m-tolyl)-1H-1,2,3-triazole (3b): Sticky
white solid (94 %). H NMR (400 MHz, CDCl3): δ = 7.98 (s, 1 H), 7.70
1
Scheme 3. Proposed reaction mechanism.
(s, 1 H), 7.62 (d, J = 7.7 Hz, 1 H), 7.32 (t, J = 7.6 Hz, 1 H), 7.16 (d, J =
7.5 Hz, 1 H), 5.37 (s, 2 H), 2.41 (s, 3 H), 2.16 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 148.82, 138.61, 129.16, 128.80, 126.46, 122.88,
118.87, 77.31, 77.06, 76.80, 52.74, 21.46, 14.82 ppm. HRMS (ESI, Orbi-
trap): calcd. for C11H14N3S [M + H]+ 220.09029; found 220.09035.
Conclusions
In summary, we have developed an efficient method to access
medicinally important sulfur-containing triazoles from alkynes
and azide in the presence of magnetically separable copper
nanocatalyst (Cu0/Fe3O4). The reaction is compatible with vari-
ous alkynes, including aromatic, aliphatic, heteroaromatic, and
polyaromatic examples, and as a result, a series of 19 sulfur-
containing triazoles was prepared. Considering, the ready avail-
ability of the starting materials, the broad substrate scope, the
operational simplicity, and the highly functionalised nature of
the reaction products, this method provides an attractive and
convenient protocol for the synthesis of sulfur-containing tri-
azoles.
4-(4-Ethylphenyl)-1-[(methylthio)methyl]-1H-1,2,3-triazole (3c):
White solid (93 %), m.p. 72–75 °C. 1H NMR (500 MHz, CDCl3): δ =
7.96 (s, 1 H), 7.76 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H), 2.68
(q, J = 7.6 Hz, 2 H), 2.15 (s, 3 H), 1.26 (t, J = 7.6 Hz, 3 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 144.64, 128.39, 127.80, 125.77, 77.30,
77.05, 76.79, 52.70, 28.71, 15.53, 14.81 ppm. HRMS (ESI, Orbitrap):
calcd. for C12H16N3S [M + H]+ 234.10594; found 234.10586.
1-[(Methylthio)methyl]-4-(4-propylphenyl)-1H-1,2,3-triazole
1
(3d): White solid (95 %), m.p. 62–64 °C. H NMR (400 MHz, CDCl3):
δ = 7.95 (s, 1 H), 7.75 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 2 H),
5.37 (s, 2 H), 2.61 (t, J = 7.6 Hz, 2 H), 2.15 (s, 3 H), 1.67 (dq, J = 14.7,
7.4 Hz, 2 H), 0.95 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 143.09, 129.02, 127.80, 125.86, 125.70, 52.78, 37.85, 24.49, 14.84,
13.81 ppm. HRMS (ESI, Orbitrap): calcd. for C13H18N3S [M + H]+
248.12159; found 248.12181.
Experimental Section
General Remarks: The reagents, chemicals, and solvents were ei-
ther purchased from commercial suppliers or prepared and purified
by standard techniques. Column chromatography was carried out
using silica gel 100–200 mesh. Infrared spectra were recorded using
1-[(Methylthio)methyl]-4-(4-pentylphenyl)-1H-1,2,3-triazole
(3e): White solid (96 %). 1H NMR (400 MHz, CDCl3): δ = 7.95 (s, 1
H), 7.75 (d, J = 8.1 Hz, 2 H), 7.29 (d, J = 8.1 Hz, 2 H), 5.37 (s, 2 H),
2.64 (t, J = 7.3 Hz, 2 H), 2.16 (s, 3 H), 1.64 (dt, J = 15.0, 7.5 Hz, 2 H),
1.38–1.22 (m, 4 H), 0.90 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 143.35, 128.95, 127.76, 125.69, 118.56, 52.70, 35.75,
31.49, 31.10, 22.57, 14.79, 14.06 ppm. HRMS (ESI, Orbitrap): calcd.
for C15H22N3S [M + H]+ 276.15289; found 276.15293.
an FTIR spectrophotometer, and values are reported in cm–1 1H
.
and 13C NMR spectra were recorded with 300 and 500 MHz NMR
instruments, using tetramethylsilane as an internal standard. High-
resolution mass spectra (ESI-HRMS) were recorded with an ESI-QTOF
mass spectrometer. X-ray powder diffraction (XRD) data were col-
lected with a Simens/D-5000 diffractometer using Cu-Kα radiation.
XPS spectra were recorded with a Kratos AXIS 165 apparatus with
a dual anode (Mg and Al) using the Mg-Kα anode. The pressure in
the spectrometer was about 10–9 Torr. The particle size and external
morphology of the samples were observed with a JEOL JEM-2100
high-resolution transmission electron microscope (HRTEM). Auger
electron spectroscopic (AES) analysis was carried out at a base pres-
sure of 10–10 Torr, within a kinetic energy range of 110–700 eV
(beam voltage of 3 kV, eV/step 1 eV, time/step 50 ms). X-ray absorp-
tion spectra were recorded using a Rigaku spectrometer with a ro-
tating anode X-ray generator (Ru-200B, Rigaku, Japan).
4-[4-(tert-Butyl)phenyl]-1-[(methylthio)methyl]-1H-1,2,3-tri-
azole (3f): White solid (92 %), m.p. 80–82 °C 1H NMR (500 MHz,
CDCl3): δ = 7.96 (s, 1 H), 7.78 (d, J = 8.2 Hz, 2 H), 7.46 (d, J = 8.1 Hz,
2 H), 5.37 (s, 2 H), 2.15 (s, 3 H), 1.35 (s, 9 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 151.50, 127.50, 125.80, 125.49, 118.05, 52.68, 34.71,
31.30, 14.77 ppm. HRMS (ESI, Orbitrap): calcd. for C14H20N3S [M +
H]+ 262.13724; found 262.13742.
4-(4-Methoxyphenyl)-1-[(methylthio)methyl]-1H-1,2,3-triazole
(3g): White solid (89 %), m.p. 98–100 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.91 (s, 1 H), 7.78 (d, J = 8.8 Hz, 2 H), 6.97 (d, J = 8.8 Hz, 2 H),
5.36 (s, 2 H), 3.85 (s, 3 H), 2.16 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.74, 131.87, 127.06, 123.08, 114.29, 55.35, 52.68,
14.80 ppm. HRMS (ESI, Orbitrap): calcd. for C11H14N3OS [M + H]+
236.08521; found 236.08525.
General Experimental Procedure for the Synthesis of Sulfur-
Containing Triazoles 3a–3s: Freshly prepared Cu0/Fe3O4 was
added to a mixture of alkyne 1a–1s (1.0 mmol) and TMSN3
(1.10 mmol) in DMSO (2.0 mL), and the reaction mixture was heated
at 70 °C for 30 min under a nitrogen atmosphere. Stirring was then
1-[(Methylthio)methyl]-4-[4-(pentyloxy)phenyl]-1H-1,2,3-tri-
azole (3h): White solid (87 %), m.p. 80–82 °C. 1H NMR (500 MHz,
stopped, and the mixture was allowed to cool to room temperature. CDCl3): δ = 7.91 (s, 1 H), 7.76 (d, J = 8.0 Hz, 2 H), 6.96 (d, J = 8.1 Hz,
The catalyst was separated using an external magnet, and water
(5.0 mL) was added to the reaction mixture. The aqueous layer was
further washed with ethyl acetate (3 × 10 mL). The organic layer
2 H), 5.36 (s, 2 H), 3.99 (t, J = 6.6 Hz, 3 H), 2.16 (s, 3 H), 1.82–1.77
(m, 2 H), 1.50–1.43 (m, 2 H), 1.41–1.37 (m, 2 H), 0.94 (t, J = 7.1 Hz,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.36, 130.94, 128.87,
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127.03, 122.93, 114.89, 68.13, 52.79, 28.98, 28.23, 22.50, 14.83,
14.06 ppm. HRMS (ESI, Orbitrap): calcd. for C15H22N3OS [M + H]+
292.14781; found 292.14801.
4-Isopropyl-1-[(methylthio)methyl]-1H-1,2,3-triazole (3p): White
gummy solid (66 %). 1H NMR (400 MHz, CDCl3): δ = 7.50 (s, 1 H),
5.30 (s, 2 H), 3.14 (dq, J = 20.6, 7.0 Hz, 2 H), 2.13 (s, 3 H), 1.34 (d,
J = 6.9 Hz, 3 H), 1.32 (d, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 118.72, 52.56, 25.94, 22.51, 22.48, 14.88 ppm. HRMS (ESI,
Orbitrap): calcd. for C7H14N3S [M + H]+ 172.09029; found 172.09041.
1-[(Methylthio)methyl]-4-[3-(trifluoromethyl)phenyl]-1H-1,2,3-
triazole (3i): White gummy solid (91 %). 1H NMR (500 MHz, CDCl3):
δ = 8.00 (s, 1 H), 7.77 (d, J = 7.9 Hz, 1 H), 7.72–7.62 (m, 2 H), 7.50
(dd, J = 7.8, 6.9 Hz, 2 H), 5.40 (s, 2 H), 2.16 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 145.03, 132.05, 131.67, 128.43, 126.20, 126.14,
122.36, 122.31, 52.79, 14.75 ppm. HRMS (ESI, Orbitrap): calcd. for
C11H11N3S [M + H]+ 274.06203; found 274.06215.
4-Butyl-1-[(methylthio)methyl]-1H-1,2,3-triazole (3q): Sticky
1
solid (62 %). H NMR (500 MHz, CDCl3): δ = 7.48 (s, 1 H), 5.28 (s, 2
H), 2.72 (t, J = 7.1 Hz, 2 H), 2.10 (s, 3 H), 1.68–1.62 (m, 2 H), 1.36–
1.28 (m, 2 H), 0.87 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 149.30, 119.95, 52.33, 31.78, 29.30, 29.26, 29.19, 29.15,
25.68, 22.60, 14.71, 14.05 ppm. HRMS (ESI, Orbitrap): calcd. for
C8H16N3S [M + H]+ 186.10594; found 186.10602.
1-[(Methylthio)methyl]-4-(thiophen-2-yl)-1H-1,2,3-triazole (3j):
1
White solid (87 %), m.p. 100–102 °C. H NMR (500 MHz, CDCl3): δ =
7.91 (s, 1 H), 7.73 (dd, J = 2.8, 0.9 Hz, 1 H), 7.53–7.47 (m, 1 H), 7.42
(dd, J = 5.0, 3.0 Hz, 1 H), 5.39 (s, 2 H), 2.18 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 144.87, 131.62, 126.44, 125.77, 121.36, 118.63,
52.69, 14.78 ppm. HRMS (ESI, Orbitrap): calcd. for C8H10N3S2 [M +
H]+ 212.03107; found 212.03127.
1-[(Methylthio)methyl]-4-octyl-1H-1,2,3-triazole (3r): White solid
1
(65 %), m.p. 68–70 °C. H NMR (400 MHz, CDCl3): δ = 7.50 (s, 1 H),
5.28 (s, 2 H), 2.71 (t, J = 7.0 Hz, 2 H), 2.11 (s, 3 H), 1.71–1.64 (m, 2
H), 1.38–1.22 (m, 10 H), 0.87 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 149.30, 119.95, 52.33, 31.78, 29.30, 29.26,
29.19, 29.15, 25.68, 22.60, 14.71, 14.05 ppm. HRMS (ESI, Orbitrap):
calcd. for C12H24N3S [M + H]+ 242.16854; found 242.16868.
3-{1-[(Methylthio)methyl]-1H-1,2,3-triazol-4-yl}pyridine (3k):
White solid (86 %), m.p. 70–72 °C. 1H NMR (400 MHz, CDCl3): δ =
8.62 (d, J = 3.9 Hz, 1 H), 8.54 (s, 1 H), 8.24 (d, J = 7.9 Hz, 1 H), 7.86
(t, J = 7.7 Hz, 1 H), 7.38–7.27 (m, 1 H), 5.41 (s, 2 H), 2.19 (s, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = δ = 148.52, 137.89, 123.20,
122.11, 120.68, 53.02, 15.01 ppm. HRMS (ESI, Orbitrap): calcd. for
C9H11N4S [M + H]+ 207.06989; found 207.06101.
4-Cyclohexyl-1-[(methylthio)methyl]-1H-1,2,3-triazole (3s):
White solid (63 %), m.p. 82–84 °C. 1H NMR (500 MHz, CDCl3): δ =
7.47 (s, 1 H), 5.29 (s, 2 H), 2.79 (tt, J = 7.5, 3.7 Hz, 1 H), 2.12 (s, 3 H),
2.10–2.02 (m, 2 H), 1.84–1.77 (m, 2 H), 1.77–1.69 (m, 2 H), 1.44–1.36
(m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 154.70, 118.70, 52.48,
35.32, 32.97, 32.85, 32.02, 26.11, 26.02, 14.83 ppm. HRMS (ESI, Orbi-
trap): calcd. for C12H24N3S [M + H]+ 242.16854; found 242.16868.
1-[(Methylthio)methyl]-4-(1-tosyl-1H-pyrrol-3-yl)-1H-1,2,3-tri-
azole (3l): White solid (94 %), m.p. 76–78 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.13 (s, 1 H), 7.45 (dd, J = 3.3, 1.8 Hz, 1 H), 7.43 (d, J =
8.4 Hz, 2 H), 7.16 (d, J = 8.1 Hz, 2 H), 6.67 (dd, J = 3.4, 1.8 Hz, 1 H),
6.37 (t, J = 3.4 Hz, 1 H), 5.38 (s, 2 H), 2.34 (s, 3 H), 2.18 (s, 3 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 145.18, 139.11, 135.33, 129.85,
127.12, 126.93, 124.83, 124.75, 123.55, 117.33, 112.49, 52.82, 21.62,
14.97 ppm. HRMS (ESI, Orbitrap): calcd. for C15H17N4O2S2 [M + H]+
349.07874; found 349.08001.
Acknowledgments
The authors thank the Department of Science and Technology
(DST), New Delhi, India, for financial support in the form of an
INSPIRE Faculty grant and a Startup Research Grant for young
researchers (GAP 0414 and GAP 0512). M. P. thanks the Univer-
sity Grants Commission (UGC), New Delhi for a research fellow-
ship. M. P. and D. K. T. greatly acknowledge the Academy of
Scientific and Innovative Research (AcSIR) for PhD registration.
The authors are grateful to the Director, CSIR-IICT, for providing
the necessary infrastructure.
4-(6-Methoxynaphthalen-2-yl)-1-[(methylthio)methyl]-1H-1,2,3-
triazole (3m): White solid (92 %), m.p. 125–127 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.29 (s, 1 H), 8.07 (s, 1 H), 7.91 (d, J = 8.5 Hz,
1 H), 7.80 (dd, J = 8.6, 4.4 Hz, 2 H), 7.20–7.14 (m, 2 H), 5.41 (s, 2 H),
3.94 (s, 3 H), 2.19 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
158.03, 148.91, 134.48, 129.75, 128.99, 127.44, 125.61, 124.45,
124.36, 119.38, 118.80, 105.84, 77.32, 77.07, 76.81, 55.37, 52.78,
14.87 ppm. HRMS (ESI, Orbitrap): calcd. for C9H11N4S [M + H]+
207.06989; found 207.06989.
Keywords: Alkynes · / Cycloaddition · Click chemistry ·
Nanoparticles · Nitrogen heterocycles · Magnetic properties
1-[(Methylthio)methyl]-4-(phenanthren-9-yl)-1H-1,2,3-triazole
(3n): White solid (89 %), m.p. 135–137 °C. 1H NMR (400 MHz, CDCl3):
δ = 8.78 (d, J = 7.9 Hz, 1 H), 8.72 (d, J = 8.2 Hz, 1 H), 8.39 (dd, J =
8.2, 1.0 Hz, 1 H), 8.10 (s, 1 H), 8.03 (s, 1 H), 7.93 (dd, J = 7.8, 1.1 Hz,
1 H), 7.73–7.67 (m, 2 H), 7.66–7.60 (m, 2 H), 5.49 (s, 2 H), 2.26 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 131.30, 130.77, 130.50,
130.07, 128.94, 128.55, 127.24, 127.01, 126.96, 126.79, 126.57,
126.09, 123.08, 122.61, 122.17, 52.91, 15.11 ppm. HRMS (ESI, Orbi-
trap): calcd. for C18H16N3S [M + H]+ 306.10594; found 306.10518.
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Published Online: ■
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Alkyne–Azide Cycloaddition
M. Phanindrudu, D. K. Tiwari,
V. K. Aravilli, K. C. Bhardwaj,
G. Sabapathi, P. R. Likhar,
D. K. Tiwari* ......................................... 1–7
Magnetically
Recoverable
Cu0/
An efficient one-pot tandem nano as the nitrogen and sulfur sources, re-
Fe3O4-Catalysed One-Pot Tandem
Synthesis of Sulfur-Containing Tri-
azoles from Alkynes and Azide:
DMSO Acts as an Alkylating Agent
Cu0/Fe3O4-catalysed
synthesis
of spectively. The catalyst can be recov-
sulfur-containing triazoles from alk- ered magnetically and reused six times
ynes and azide has been developed. without any significant loss of activity.
TMS-Azide and dimethyl sulfoxide act
DOI: 10.1002/ejoc.201600740
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