Selenium compounds in Click Chemistry: Copper catalyzed 1,3-dipolar cycloaddition of azidomethyl arylselenides and alkynes

Article abstract of DOI:10.1016/j.tet.2012.07.019

We described herein the use of selenium compounds in Click Chemistry by copper catalyzed 1,3-dipolar cycloaddition of azidomethyl arylselenides with alkynes. The reactions were performed under mild conditions reacting azidomethyl arylselenides with a rang

Full text of DOI:10.1016/j.tet.2012.07.019

Tetrahedron 68 (2012) 10419e10425
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Selenium compounds in Click Chemistry: copper catalyzed 1,3-dipolar
cycloaddition of azidomethyl arylselenides and alkynes
a
a
b
a
a,
*
ꢀ
Natalia Seus , Maiara T. Saraiva , Eduardo E. Alberto , Lucielli Savegnago , Diego Alves
a LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
b Chemistry Department, The State University of New York at Buffalo, Buffalo, NY, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
We described herein the use of selenium compounds in Click Chemistry by copper catalyzed 1,3-dipolar
cycloaddition of azidomethyl arylselenides with alkynes. The reactions were performed under mild
conditions reacting azidomethyl arylselenides with a range of terminal alkynes using catalytic amount of
Cu(OAc)2.H2O/sodium ascorbate and the corresponding 1-(arylseleno-methyl)-1,2,3-triazoles were
obtained in high yields. The reaction time of these reactions could be reduced to a few minutes using
microwave irradiation.
Received 2 March 2012
Received in revised form 5 July 2012
Accepted 9 July 2012
Available online 15 July 2012
Keywords:
Organoselenium compounds
Azides
Ó 2012 Elsevier Ltd. All rights reserved.
Click Chemistry
1,2,3-Triazoles
Copper catalysis
1. Introduction
special interest. Thisclassofmolecules havebeenemployedinvarious
organic transformations, for instance, in asymmetric synthesis.10b,13
1,2,3-Triazoles, classic nitrogen heterocyclic compounds, are an
important class of molecules, which display a broad spectrum of
biological activities.1 These compounds are also widely employed in
various fields of chemistry, such as in the research and modulation
of drug candidates,2 development of new materials,3 design of new
catalysts,4 among others.5 There is a variety of methods available in
the literature for the preparation of 1,2,3-triazoles. The most at-
tractive way to prepare these compounds involves the thermal 1,3-
dipolar cycloaddition of azides with alkynes, pioneered by Huis-
gen.6 Independently, Sharpless7 and Meldal8 not only popularized
this reaction but also discovered a copper-catalyzed version for this
useful transformation. The development of the copper-catalyzed
azideealkyne cycloaddition (CuAAC) process was a definitive ad-
vance in triazole synthesis, and represents the most effective re-
action of ‘Click Chemistry’.9
Consequently, the search for new and efficient methods for the syn-
thesis of nitrogen-functionalized organoselenium compounds, more
specificallyorganoseleniumetriazoles, remains a challengeinorganic
chemistry. A number of examples for the synthesis of selenium-
containing 1,2,3-triazole compounds has been reported,16 and re-
cently, a CuAAC protocol was published for the synthesis of arylse-
leno-1,2,3-triazolesinexcellentyields undermild reactionconditions,
starting from azido arylselenides (Scheme 1).16d
On the other hand, organoselenium compounds are attractive
synthetic targets. They can promote transformations with high levels
of selectivity,10,11 can be used as ionic liquids,12 in asymmetric reac-
tions,10b,13 exhibit fluorescent properties14 and are often linked to
interesting biological activities.15 The versatility and applicability of
organoselenium compounds in organic chemistry is well described in
a great number of reviews10 and books.11 Among organoselenium
compounds, those containing nitrogen atoms in their structure are of
Scheme 1. CuAAC synthesis of arylseleno-1,2,3-triazoles.
However, to the best of our knowledge, methodologies involving
CuAAC for the synthesis of organoseleniumetriazoles are
scarce and have not been well explored. In this sense, and due to
our interest correlated to CuAAC protocol for the synthesis
* Corresponding author. E-mail address: diego.alves@ufpel.edu.br (D. Alves).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.019

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N. Seus et al. / Tetrahedron 68 (2012) 10419e10425
Table 1
organoseleniumetriazoles, we describe herein the copper cata-
lyzed 1,3-dipolar cycloaddition of azidomethyl arylselenides 1 with
terminal alkynes to obtain 1-(arylseleno-methyl)-1,2,3-triazoles 3
(Scheme 2).
Study of the solvent effect on CuAAC of azidomethyl arylselenide 1a
Entry
Solvent (Ratio)
Isolated yield 3a (%)
1
2
3
4
5
6
7
8
9
MeOH/H2O (1:1)
t-BuOH/H2O (1:1)
CH2Cl2/H2O/ (1:1)
Et2O/H2O (1:1)
acetone/H2O (1:1)
THF/H2O (1:1)
THF/H2O (1:0.5)
THF
80
83
77
82
79
88
47
Traces
nd
Scheme 2. Synthesis of 1-(arylseleno-methyl)-1,2,3-triazoles 3.
2. Results and discussion
H2O
10
THF/H2O (1:1)a
86
Initially, our studies were focused on the synthesis of azido-
methyl arylselenides 1, the starting materials for the synthesis of
the selenium-triazoles 3. Thus, phenylselenolate, generated in situ
by the reaction of diphenyl diselenide 4a with NaBH4/EtOH, reacted
with methylene chloride at reflux, affording chloromethyl phe-
nylselenide 5a in satisfactory yield (Scheme 3).17 This compound
was easily converted to azidomethyl phenylselenide 1a in excellent
yield after reaction with sodium azide and 18-crown-6 in CH3CN at
room temperature.18 This protocol was extended to the chloro- and
methylearylselenide 5b and 5c, giving the products 1b and 1c in
87% and 92% yield, respectively (Scheme 3).
a
Reaction under argon atmosphere.
was not observed (Table 1, entry 9). It is important to note that the
reactions are not air sensitive, allowing the preparation of the re-
spective triazole 3a in an open atmosphere (Table 1, entry 10).
We observed that the nature of the copper salt and its amount
were critical for the success of the reaction. As shown in Table 2,
different copper salts, such as CuSO4$5H2O, CuBr2, Cu(OTf)2,
Cu(OAc)2$H2O, and CuO nanoparticles, exhibited a moderate to
good catalytic activity (Table 1, entries 1e5). Among the conditions
tested, the best result was obtained using Cu(OAc)2.H2O (5 mol %),
which gave the product 3a in excellent yield (Table 2, entry 5). It is
significant to note that when the amount of catalyst was reduced
from 5 mol % to 1 mol %, a decrease in the yield was observed (Table
1, entries 5e7). The analysis of the obtained results indicated that
the best reaction conditions were found to be use azidomethyl
phenylselenide 1a (0.3 mmol), phenylacetylene 2a (0.3 mmol) in
presence of CuSO4.5H2O (5 mol %), sodium ascorbate (10 mol %) in
a mixture of THF/H2O (1:1, 2 mL) at room temperature under air
atmosphere for 8 h.
Scheme 3. Synthesis of azidomethyl arylselenides 1.
Azidomethyl arylselenides 1aec obtained as described above
appear to be highly promising substrates for the CuAAC protocol to
obtain seleniumetriazol derivatives. This class of compounds16b,19a
has a large synthetic importance since they combine the well
known reactivity of the azido group20 with that of the selenium-
containing group.10,11
Table 2
Influence of copper salt in the CuAAC of azidomethyl arylselenide 1a and phenyl-
acetylene 2a
After that, we turned out our attention to the application of the
obtained azidomethyl arylselenides 1aec in the synthesis of 1-
(arylseleno-methyl)-1,2,3-triazoles 3, using a copper-catalyzed 1,3-
dipolar cycloaddition reaction. Generally, these reactions require
the generation of Cu(I) species in situ starting from CuSO4$5H2O
and sodium ascorbate in aqueous medium.7a In view of this, firstly
we studied the reaction of azidomethyl phenylselenide 1a
(0.3 mmol) with phenylacetylene 2a (0.3 mmol) in the presence of
CuSO4.5H2O (5 mol %) and sodium ascorbate (10 mol %) in a mixture
of different solvents (2 mL) (Table 1).
Entry
Copper salt (mol %)
Isolated yield 3a (%)
1
2
3
4
5
6
7
CuSO4$5H2O (5%)
CuBr2 (5%)
Cu(OTf)2 (5%)
88
70
65
75
94
87
80
CuO$NPs (5%)
Cu(OAc)2$H2O (5%)
Cu(OAc)2$H2O (3%)a
Cu(OAc)2$H2O (1%)b
Checking the Table 1, it is possible to verify that the reaction
afforded the selenium-triazole 3a in good yields using a variety of
organic solvents in combination with H2O. When we used mixtures
of MeOH/H2O, t-BuOH/H2O, CH2Cl2/H2O, Et2O/H2O, acetone/H2O
and THF/H2O, good yields were obtained of the desired product 3a
(Table 1, entries 1e6). Optimal result was achieved using a mixture
of THF/H2O (1:1) as solvent (Table 1, entry 6). A remarkable feature
of this reaction was the H2O dependence in the selenium-triazole
synthesis. Reactions using a mixture of THF/H2O (1:0.5) or just
THF, gave poor yields of the desired product 3a (Table 1, entries
7e8). This may be due to the increased solubility of sodium
ascorbate and copper salt in this solvent.16d However, when the
reaction was performed only in H2O, the formation of product 3a
a
6 mol % of sodium ascorbate was used.
2 mol % of sodium ascorbate was used.
b
To extend the scope of the reaction, a range of terminal alkynes
were reacted with azidomethyl phenylselenide 1a under the opti-
mized reaction conditions. Thus, terminal alkynes with a variety of
substituents, including aryl, alkyl, vinyl, alcohol, and ester were
successfully employed in these reactions and the corresponding
products were obtained in high yields (Table 3, entries 1e11). Good
results were achieved when dialkyne 2l was reacted with two dif-
ferent amounts of azidomethyl phenylselenide 1a. When we used
0.3 mmol of compound 1a, the respective alkynyl seleniumetriazole
3l (Table 3, entry 12) was obtained in 68% yield with traces of bis-

N. Seus et al. / Tetrahedron 68 (2012) 10419e10425
10421
Table 3
Scope and variability of CuAAC of azidomethyl arylselenidesa
Entry
Selenoazide
Alkyne
Product
Isolated Yield (%)c
H
1
94 (93)
2a
1a
3a
3b
2
1a
80 (94)
2b
2c
3
4
5
1a
1a
1a
75
3c
87
2d
2e
2f
3d
91 (97)
3e
3f
6
7
1a
1a
85
78
77
2g
3g
8
9
1a
1a
2h
2i
3h
3i
91 (90)
(continued on next page)

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N. Seus et al. / Tetrahedron 68 (2012) 10419e10425
Table 3 (continued )
Entry
Selenoazide
Alkyne
Product
Isolated Yield (%)c
10
11
12
1a
90 (98)
2j
3j
1a
85 (86)
2k
3k
1a
68
2l
2l
3l
13b
1a
78
3m
3n
14
2a
91
1b
1c
15
2a
89
3o
a
Reactions were performed with azidomethyl arylselenides 1 (0.3 mmol), terminal alkynes 2 (0.3 mmol), Cu(OAc)2$H2O (5 mol %), sodium ascorbate (10 mol %) in a mixture
of THF/H2O (1:1) (2 mL) at room temperature under air atmosphere for 8 h.
b
Reaction was performed with 0.6 mmol of azidomethyl phenylselenide 1a.
Yields in parenthesis correspond to reactions performed in a microwave reactor at 50 ꢀC for 10 min.
c
selenium-triazole 3m. When we used 0.6 mmol of azidomethyl
phenylselenide 1a the corresponding bis-selenium-triazole 3m was
obtained as the sole product (Table 3, entry 13). Additionally, phe-
nylacetylene 2a reacted smoothly with azidomethyl arylselenides
1b and 1c yielding the corresponding products 3n and 3o in 91% and
89%, respectively (Table 3, entries 14e15).
other terminal alkynes were reacted with azidomethyl phenyl-
selenide 1a under MW irradiation and the desired selenium-
triazoles were obtained in excellent yields in a short reaction
time (Table 3, entries 1e2, 5, 9e11).
3. Conclusion
In order to obtain an efficient protocol in terms of energy
economy, we performed these 1,3-dipolar cycloaddition reactions
under microwave irradiation.21 Thus, the mixture of azidomethyl
phenylselenide 1a and phenylacetylene 2a in the presence of
CuSO4.5H2O (5 mol %) and sodium ascorbate (10 mol %) in a solvent
system of THF/H2O (1:1) was irradiated under stirring and fortu-
nately, after 10 min at 50 ꢀC, seleniumetriazole 3a was obtained in
93% yield (Table 3). To extend the scope of the microwave protocol,
In conclusion, we have demonstrated the use of selenium com-
pounds in Click Chemistry by copper catalyzed 1,3-dipolar cyclo-
addition of azidomethyl arylselenides with alkynes. The
corresponding seleniumetriazoles were selectively prepared in high
yields under mild conditions via reaction of azidomethyl arylsele-
nides with a range of terminal alkynes. This click protocol minimizes
the energy demand, as well the reaction time could be reduced from

N. Seus et al. / Tetrahedron 68 (2012) 10419e10425
10423
several hours to few minutes using MW irradiation. This method-
ology is efficient to synthesize new selenium-containing triazoles
with potential application in biological studies.
156 (81), 154 (42), 139 (12), 114 (18), 112 (48), 77 (20), 75 (47), 63
(20), 50 (30). HRMS: Calculated mass to C7H6ClN3Se: 246.9415,
found: 246.9420.
4. Experimental section
4.1. General remarks
4.3. General procedure for the synthesis of 1-(arylselanyl-
methyl)-1,2,3-triazoles 3aeo
To a solution of azidomethyl arylselenide (0.3 mmol) in THF
(1.0 mL), alkyne (0.3 mmol), and distilled water (0.5 mL) were
added. Then a fresh solution of sodium ascorbate (0.0012 g,
10 mol %) and Cu(OAc)2$H2O (0.0006 g, 5 mol %) in distilled water
(0.5 mL) was added and the mixture was stirred under air for 8 h.
Brine solution (3 mL) was added and the mixture was extracted
with methylene chloride (3ꢁ5 mL). The organic layers were com-
bined, washed with brine (3 mL) and dried with MgSO4. The solvent
was removed under vacuum and the product was isolated by col-
umn chromatography using hexane/ethyl acetate as eluent. Spec-
tral data of the products prepared are listed below.
Proton nuclear magnetic resonance spectra (1H NMR) were
obtained at 300 MHz on a Varian Gemini NMR spectrometer.
Spectra were recorded in CDCl3 solutions. Chemical shifts are re-
ported in parts per million, referenced to tetramethylsilane (TMS)
as the external reference. Data are reported as follows: chemical
shift (d), multiplicity, coupling constant (J) in Hertz and integrated
intensity. Carbon-13 nuclear magnetic resonance spectra (13C NMR)
were obtained at 75 MHz on a Varian Gemini NMR spectrometer.
Spectra were recorded in CDCl3 solutions. Chemical shifts are re-
ported in ppm, referenced to the solvent peak of CDCl3. Abbrevia-
tions to denote the multiplicity of a particular signal are s (singlet),
d (doublet), t (triplet), qua (quartet), qui (quintet), td (triple dou-
blet), bs (broad singlet) and m (multiplet). Mass spectra (MS) were
measured on a Shimadzu GC-MS-QP2010 mass spectrometer. High
resolution mass spectra were recorded on a Bruker Micro TOF-QII
spectrometer. Column chromatography was performed using
Merck Silica Gel (230e400 mesh). Thin layer chromatography (TLC)
was performed using Merck Silica Gel GF254, 0.25 mm thickness. For
visualization, TLC plates were either placed under ultraviolet light,
or stained with iodine vapor, or acidic vanillin. All solvents were
used as purchased unless otherwise noted. Microwave reactions
were conducted using a CEM Discover, mode operating systems
working at 2.45 GHz, with a power programmable from 1 to 300 W.
4.3.1. 4-Phenyl-1-(phenylselanylmethyl)-1,2,3-triazole (3a). Yield:
0.089 g (94%); white solid; mp 73e74 ꢀC. 1H NMR (CDCl3, 300 MHz)
d
¼7.78e7.75 (m, 2H), 7.64 (s, 1H), 7.52e7.49 (m, 2H), 7.43e7.29 (m,
6H), 5.72 (s, 2H). 13C NMR (CDCl3, 75 MHz)
d
¼148.09,134.74,130.23,
129.52, 128.92, 128.76, 128.19, 127.28, 125.61, 119.28, 44.69. MS
(relative intensity) m/z: 315 (3), 286 (15), 157 (13), 130 (100), 103
(92), 77 (50), 51 (10), 40 (29). Calculated mass to C15H13N3SeþHþ:
316.0353, found: 316.0356.
4.3.2. 4-Pentyl-1-(phenylselanylmethyl)-1,2,3-triazole (3b). Yield:
0.074 g (80%); white solid; mp 55e56 ꢀC. 1H NMR (CDCl3, 300 MHz)
d
¼7.48e7.45 (m, 2H), 7.35e7.29 (m, 3H), 7.17 (s, 1H), 5.65 (s, 2H),
2.66 (t, J¼7.7 Hz, 2H), 1.62 (qui, J¼7.7 Hz, 2H), 1.33e1.30 (m, 4H),
4.2. General procedure for the synthesis of azidomethyl
arylselenides 1aec
0.89 (t, J¼7.7 Hz, 3H). 13C NMR (CDCl3, 75 MHz)
¼148.92, 134.68,
d
129.42, 128.78, 127.38, 120.37, 44.47, 31.23, 28.94, 25.50, 22.33,
13.96. MS (relative intensity) m/z: 310 (2), 215 (2), 171 (8), 157 (12),
152 (20), 124 (19), 109 (6), 95 (33), 91 (28), 82 (40), 77 (20), 68 (79),
55 (64), 41 (100). HRMS: Calculated mass to C14H19N3SeþNaþ:
332.0642, found: 332.0645.
To a solution of chloromethyl arylselenide 5 (1 mmol) in CH3CN
(1.5 mL), sodium azide (1.5 mmol) followed by 18-crown-6
(0.20 mmol) were added at room temperature. Then the mixture
was stirred at this temperature for 48 h under nitrogen atmo-
sphere. After this time, the solution was diluted with H2O (10 mL),
and washed with CH2Cl2 (3ꢁ10 mL). The organic layers were
combined, dried over MgSO4, and concentrated under vacuum. The
residue was purified by flash chromatography on silica gel using
hexanes as the eluent. Spectral data of the products prepared are
listed below.
4.3.3. 4-Octyl-1-(phenylselanylmethyl)-1,2,3-triazole
0.079 g (75%); white solid; mp 43e44 ꢀC. 1H NMR (CDCl3, 300 MHz)
¼7.48e7.45 (m, 2H), 7.35e7.27 (m, 3H), 7.17 (s, 1H), 5.65 (s, 2H),
(3c). Yield:
d
2.66 (t, J¼7.7 Hz, 2H), 1.63e1.59 (m, 2H), 1.30e1.26 (m, 10H), 0.88 (t,
J¼7.7 Hz, 3H). 13C NMR (CDCl3, 75 MHz)
¼149.01, 134.71, 129.45,
d
128.81,127.44,120.37, 44.49, 31.85, 29.56, 29.52, 29.29, 29.12, 25.59,
22.64, 14.09. MS (relative intensity) m/z: 285 (5), 194 (54), 110 (14),
96 (69), 82 (70), 77 (17), 68 (100). HRMS: Calculated mass to
C17H25N3SeþHþ: 352.1292, found: 352.1298.
4.2.1. Azidomethyl phenylselenide (1a). Yield: 0.193 g (91%); yellow
oil; 1H NMR (CDCl3, 300 MHz)
d
¼7.64e7.62 (m, 2H); 7.33e7.30 (m,
3H); 4.62 (s, 2H). 13C NMR (CDCl3, 75 MHz)
d
¼133.97,129.33,129.15,
127.69, 48.71. MS (relative intensity) m/z: 187 (6), 185 (40), 158 (26),
157 (100), 154 (54), 117 (13), 78 (56), 77 (86), 51 (40). HRMS: Cal-
culated mass to C7H7N3Se: 212.9805, found: 212.9807.
4.3.4. 1-(Phenylselanylmethyl)-4-(prop-1-en-2-yl)-1,2,3-triazole
(3d). Yield: 0.073 g (87%); white solid; mp 67e68 ꢀC. 1H NMR
(CDCl3, 300 MHz)
5.70e5.64 (m, 3H), 5.09e5.08 (m, 1H), 2.07e2.06 (m, 3H). 13C NMR
(CDCl3, 75 MHz)
d¼7.50e7.47 (m, 2H), 7.38e7.27 (m, 4H),
4.2.2. Azidomethyl 4-methylphenylselenide (1b). Yield: 0.197
g
d
¼149.06, 134.71, 133.14, 129.47, 128.85, 127.34,
(87%); yellow oil; 1H NMR (CDCl3, 300 MHz)
d
¼7.51 (d, J¼8.1 Hz,
119.28, 112.68, 44.54, 20.49. MS (relative intensity) m/z: 279 (5), 171
(5), 157 (7), 122 (28), 94 (100), 77 (19), 67 (98), 65 (35), 54 (49).
HRMS: Calculated mass to C12H13N3SeþNaþ: 302.0172, found:
302.0176.
2H); 7.11(d, J¼8.1 Hz, 2H); 4.54 (s, 2H); 2.33 (s, 3H). 13C NMR (CDCl3,
75 MHz)
d
¼138.34, 134.40, 130.11, 124.54, 48.90, 21.10. MS (relative
intensity) m/z: 199 (24), 171 (49), 169 (31), 92 (18), 91 (100), 89 (18),
77 (6), 65 (16). HRMS: Calculated mass to C8H9N3Se: 226.9962,
found: 226.9969.
4.3.5. 4-Cyclohexenyl-1-(phenylselanylmethyl)-1,2,3-triazole (3e).
Yield: 0.087 g (91%); white solid; mp 49e50 ꢀC. 1H NMR (CDCl3,
4.2.3. Azidomethyl 4-chlorophenylselenide (1c). Yield: 0.226
g
300 MHz)
1H), 5.65 (s, 2H), 2.33e2.28 (m, 2H), 2.21e2.18 (m, 2H), 1.79e1.64
(m, 4H). 13C NMR (CDCl3, 75 MHz)
127.49, 126.92, 125.25, 117.90, 44.58, 26.19, 25.17, 22.31, 22.06. MS
(relative intensity) m/z: 319 (3),194 (4),163 (100),133 (12),104 (31),
d
¼7.49e7.46 (m, 2H), 7.35e7.27 (m, 4H), 6.51e6.47 (m,
(92%); yellow oil; 1H NMR (CDCl3, 300 MHz)
d
¼7.54 (d, J¼8.5 Hz,
2H); 7.28(d, J¼8.5 Hz, 2H); 4.58 (s, 2H). 13C NMR (CDCl3, 75 MHz)
d¼149.86, 134.61, 129.44, 128.76,
d
¼135.41, 134.18, 129.56, 126.51, 48.94. MS (relative intensity) m/z:
220 (19), 219 (42), 217 (20), 193 (44), 192 (21), 191 (100), 189 (51),

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N. Seus et al. / Tetrahedron 68 (2012) 10419e10425
77 (40), 57 (13), 44 (38). HRMS: Calculated mass to
(9), 118 (19), 91 (97), 80 (65), 77 (100), 65 (29), 41 (39). HRMS:
C15H17N3SeþHþ: 320.0666, found: 320.6670.
Calculated mass to C14H15N3SeþNaþ: 328.0329, found: 328.0331.
4.3.6. (1-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)methanol
Yield: 0.069 g (85%); yellow oil. 1H NMR (CDCl3, 300 MHz)
¼7.40e7.37 (m, 3H), 7.24e7.19 (m, 3H), 5.57 (s, 2H), 4.60 (s, 2H),
3.47 (bs, 1H). 13C NMR (CDCl3, 75 MHz)
128.78, 127.43, 121.62, 56.09, 44.55. MS (relative intensity) m/z: 269
(4),175 (13),149 (10),112 (100),110 (23), 91 (21), 77 (33), 57 (35), 43
(83), 42 (87). HRMS: Calculated mass to C10H11N3OSeþNaþ:
291.9965, found: 291.9970.
(3f).
4.3.13. 1,3-bis(1-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)propane
(3m). Yield: 0.121 g (78%); white solid; mp 88e90 ꢀC. 1H NMR
d
(CDCl3, 300 MHz)
d
¼7.48e7.45 (m, 4H), 7.37e7.22 (m, 8H), 5.65 (s,
d
¼148.34, 134.46, 129.49,
4H), 2.69 (t, J¼7.5 Hz, 4H), 1.97 (qui, J¼7.5 Hz, 4H). 13C NMR (CDCl3,
75 MHz)
d¼148.25, 134.96, 129.82, 129.16, 127.70, 121.07, 44.82,
29.12, 25.07. MS (relative intensity) m/z: 518 (1), 333 (4), 266 (15),
173 (11), 171 (61), 169 (31), 157 (10), 147 (13), 93 (26), 91 (100), 80
(20), 77 (22), 41 (26). HRMS: Calculated mass to C21H22N6Se2þHþ:
519.0315, found: 519.0320.
4.3.7. (2-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)ethanol
(3g).
Yield: 0.066 g (78%); yellow oil. 1H NMR (CDCl3, 300 MHz)
4.3.14. 4-Phenyl-1-(4-tolylselanylmethyl)-1,2,3-triazole (3n). Yield:
0.090 g (91%); white solid; mp 77e79 ꢀC. 1H NMR (CDCl3, 300 MHz)
d
¼7.40e7.37 (m, 2H), 7.27e7.21 (m, 4H), 5.58 (s, 2H), 3.79 (t,
J¼6.0 Hz, 2H), 3.53 (bs, 1H), 2.81 (t, J¼6.0 Hz, 2H). 13C NMR (CDCl3,
d
¼7.76 (d, J¼7.9 Hz, 2H), 7.63 (s, 1H), 7.41e7.29 (m, 5H), 7.10 (d,
75 MHz)
d¼145.78, 134.59, 129.46, 128.84, 127.27, 121.61, 61.24,
J¼7.9 Hz, 2H), 5.67 (s, 2H), 2.33 (s, 3H). 13C NMR (CDCl3, 75 MHz)
44.56, 28.56. MS (relative intensity) m/z: 283 (3), 189 (6), 157 (14),
126 (77), 91 (31), 77 (30), 69 (82), 55 (100). HRMS: Calculated mass
to C11H13N3OSeþNaþ: 306.0122, found: 306.0124.
d¼148.30, 139.31, 135.11, 130.63, 130.43, 128.82, 128.22, 125.84,
123.88, 119.27, 44.88, 21.13. MS (relative intensity) m/z: 329 (7), 300
(16), 130 (100), 103 (76), 91 (22), 77 (35), 57 (39), 43 (30). HRMS:
Calculated mass to C16H15N3SeþHþ: 330.0509, found: 330.0511.
4.3.8. (3-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)propanol
Yield: 0.069 g (77%); yellow oil. 1H NMR (CDCl3, 300 MHz)
¼7.40e7.37 (m, 2H), 7.28e7.22 (m, 3H), 7.16 (s, 1H), 5.57 (s, 2H),
3.58 (t, J¼6.1 Hz, 2H), 2.70 (t, J¼6.1 Hz, 2H), 1.80 (t, J¼6.1 Hz, 2H),
1.18 (s, 1H). 13C NMR (CDCl3, 75 MHz)
(3h).
4.3.15. 4-Phenyl-1-(4-chlorophenylselanylmethyl)-1,2,3-triazole
d
(3o). Yield: 0.093 g (89%); white solid; mp 82e83 ꢀC. 1H NMR
(CDCl3, 300 MHz)
d
¼7.78 (d, J¼8.0 Hz, 2H), 7.72 (s, 1H), 7.44e7.33
d¼148.02, 134.67, 130.23,
(m, 5H), 7.27 (d, J¼8.0 Hz, 2H), 5.70 (s, 2H). 13C NMR (CDCl3,
129.48, 128.86, 127.29, 120.83, 61.69, 44.53, 31.84, 21.87. MS (rela-
tive intensity) m/z: 298 (1), 203 (2), 171 (7), 157 (12), 140 (33), 112
(7), 94 (21), 91 (26), 84 (27), 82 (31), 77 (25), 67 (45), 55 (33), 41
(100). HRMS: Calculated mass to C12H15N3OSeþNaþ: 320.0278,
found: 320.0282.
75 MHz)
d¼148.39, 136.20, 135.57, 130.12, 129.77, 128.86, 128.37,
125.69, 125.24, 119.19, 44.79. MS (relative intensity) m/z: 349 (4),
320 (7), 240 (5), 131 (11), 130 (100), 103 (57), 102 (20), 77 (26), 57
(24), 43 (19). HRMS: Calculated mass to C15H12ClN3SeþHþ:
349.9963, found: 349.9968.
4.3.9. (2-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)propan-2-ol (3i).
4.4. General procedure for the microwave synthesis of 1-(ar-
ylselanyl-methyl)-1,2,3-triazoles
Yield: 0.081 g (91%); yellow oil. 1H NMR (CDCl3, 300 MHz)
d
¼7.40e7.37 (m, 2H), 7.27e7.17 (m, 4H), 5.56 (s, 2H), 1.98 (bs, 1H),
1.49 (s, 6H). 13C NMR (CDCl3, 75 MHz)
d
¼155.93, 134.72, 129.42,
In a 10 mL glass vial equipped with a small magnetic stirring bar,
containing a solution of azidomethyl phenylselenide 1a (0.3 mmol)
and the appropriate alkyne 2 (0.3 mmol) in THF (1.0 mL), the fresh
aforementioned aqueous solution of sodium ascorbate and
Cu(OAc)2$H2O was added. The vial was tightly sealed with an alu-
minum/Teflon crimp top and the mixture was then irradiated in
a focused microwaves reactor (CEM) at 50 ꢀC, using an irradiation
power of 50 W and pressure of 50 psi. After stirring for 10 min, the
products were isolated as described above.
128.84, 127.22, 119.21, 68.13, 44.50, 30.16. MS (relative intensity) m/
z: 250 (6), 171 (8), 122 (18), 94 (100), 77 (25), 67 (81), 65 (30), 54
(31), 43 (26). HRMS: Calculated mass to C12H15N3OSeþNaþ:
320.0278, found: 320.0283.
4.3.10. (1-(Phenylselanylmethyl)-1,2,3-triazol-4-yl)cyclohexanol
(3j). Yield: 0.091 g (90%); white solid; mp 45e47 ꢀC. 1H NMR
(CDCl3, 300 MHz)
d
¼7.49e7.46 (m, 2H), 7.38e7.27 (m, 4H), 5.65 (s,
2H), 2.66 (bs, 1H), 2.90e1.78 (m, 10H). 13C NMR (CDCl3, 75 MHz)
d
¼154.62, 134.74, 129.49, 128.88, 127.33, 119.59, 78.75, 44.52, 41.09,
Acknowledgements
23.49. MS (relative intensity) m/z: 337 (3), 276 (5), 197 (11), 166
(26), 120 (71), 110 (53), 96 (61), 91 (100), 77 (68), 41 (48). HRMS:
Calculated mass to C15H19N3OSeþNaþ: 360.0591, found: 360.0593.
We are grateful to CAPES, CNPq (Grant 473734/2010-9),
FINEP and FAPERGS (ARD 10/0130-3) for the financial support.
Prof. Diogo O. Silva from Group of Bioorganic and Bio-
analyticsdGBBdUNIFESPdDiadema-SP is acknowledged for the
HRMS analysis.
4.3.11. Ethyl 1-(phenylselanylmethyl)-1,2,3-triazole-4-carboxylate
(3k). Yield: 0.079 g (85%); white solid; mp 70e72 ꢀC. 1H NMR
(CDCl3, 300 MHz)
d¼8.00 (s, 1H), 7.48e7.45 (m, 2H), 7.38e7.29 (m,
3H), 5.71 (s, 2H), 4.41 (qua, J¼7.1 Hz, 2H), 1.40 (t, J¼7.1 Hz, 3H). 13C
Supplementary data
NMR (CDCl3, 75 MHz)
d¼160.46, 140.58, 134.81, 129.74, 129.27,
127.16, 126.68, 61.37, 44.84, 14.26. MS (relative intensity) m/z: 266
(5), 217 (6), 157 (13), 154 (100), 77 (27), 54 (27), 51 (12). HRMS:
Calculated mass to C12H13N3O2SeþNaþ: 334.0071, found: 334.0073.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.07.019.
References and notes
4.3.12. 4-(Pent-4-ynyl)-1-(phenylselanylmethyl)-1,2,3-triazole (3l).
Yield: 0.062 g (68%); yellow oil. 1H NMR (CDCl3, 400 MHz)
1. Grimett, M. R. In Comprehensive Organic Chemistry; Barton, D., Ollis, D., Eds.;
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d
¼7.49e7.46 (m, 2H), 7.39e7.27 (m, 3H), 7.23 (s, 1H), 5.66 (s, 1H),
2. (a) Tron, G. C.; Pirali, T.; Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani, A.
A. Med. Res. Rev. 2008, 28, 278; (b) Hein, C. D.; Liu, X. eM.; Wang, D. Pharm. Res.
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d
134.72, 129.51, 128.89, 127.28, 120.88, 104.66, 83.60, 68.93, 44.56,
27.76, 24.23, 17.65. MS (relative intensity) m/z: 224 (6), 196 (4), 157

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