Synthesis of arylselanyl-1H-1,2,3-triazole-4-carboxylates by organocatalytic cycloaddition of azidophenyl arylselenides with β-keto-esters

Article abstract of DOI:10.1016/j.tet.2012.10.007

The β-enaminone-azide cycloaddition has been used for the synthesis of arylselanyl-1H-1,2,3-triazole-4-carboxylates by reaction of azidophenyl arylselenides with β-keto-esters. The cycloaddition reactions were performed under mild conditions, reacting var

Full text of DOI:10.1016/j.tet.2012.10.007

Tetrahedron 68 (2012) 10456e10463
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Synthesis of arylselanyl-1H-1,2,3-triazole-4-carboxylates by organocatalytic
cycloaddition of azidophenyl arylselenides with
b
-keto-esters
a
a
b
c
a,
*
ꢀ
Natalia Seus , Loren C. Gonc¸ alves , Anna M. Deobald , Lucielli Savegnago , Diego Alves
,
b,
*
ꢀ
~
Marcio W. Paixao
Laboratorio de Síntese Organica LimpadLASOLdCCQFAdUniversidade Federal de PelotasdUFPel, Pelotas, RS, Brazil
ˇ
a
ꢀ
b
ꢀ
~
~
Laboratorio de Síntese de Produtos Naturais, Universidade Federal de Sao Carlos, Sao Carlos 13565-905, SP, Brazil
c Grupo de Pesquisa em NeurobiotecnologiadGPN, CDTec, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2012
Received in revised form 27 September 2012
Accepted 2 October 2012
Available online 9 October 2012
The
carboxylates by reaction of azidophenyl arylselenides with
were performed under mild conditions, reacting various azidophenyl arylselenides and
using catalytic amount of Et2NH (1 mol %) and the corresponding products were obtained in good to
excellent yields. Reactions using focused microwave irradiation reduced considerably the reaction time
of this organocatalytic protocol from hours to few minutes, which makes this protocol useful and an
attractive approach for the synthesis of high-functionalized 1,2,3-triazoles.
b
-enaminoneeazide cycloaddition has been used for the synthesis of arylselanyl-1H-1,2,3-triazole-4-
-keto-esters. The cycloaddition reactions
-keto-esters
b
b
Keywords:
Organocatalysis
Cycloaddition
Azides
Ó 2012 Elsevier Ltd. All rights reserved.
1,2,3-Triazoles
Organoselenium compounds
1. Introduction
elegant modification of Sakai reaction, by the combination of an
amine and
a,a-dichlorotosylhydrazones has been reported as
1,2,3-Triazoles are an interesting class of heterocyclic1 unit
widely used in the discovery and modulation of drug candidates,2
development of new materials,3 supramolecular chemistry,4 de-
sign of new supported organocatalysts,5 and biotechnology area.6
Therefore, several elegant methods for the synthesis of this classic
nitrogen heterocyclic compounds have been reported by 1,3-dipolar
cycloaddition of azides with alkynes under thermal7 conditions as
well as copper or ruthenium catalysis.8 However, the requirement of
transition metals has restricted the application of this technology in
chemical biology,9 since they could induce damages in some bi-
ological system (e.g., virus and oligonucleotides).10 This limitation
can be easily overcome through the application of an organocatalytic
approach.11 In this sense, Fokin et al. described the transition-metal-
free synthesis of 1,5-diaryl-1,2,3-triazoles.12 The Fokin approach
relies on the condensation of organic azides with terminal alkynes in
the presence of catalytic amount of tetramethylammonium hy-
droxide. Furthermore, an amine-catalyzed strategy has been utilized
to promote the [3þ2]-Huisgen cycloaddition between a wide range
of carbonyl compounds and azides, which permit the assembly of
a library of highly substituted 1,2,3-triazoles.13 More recently, an
a powerful strategy in metal-free triazole synthesis.14 Nevertheless,
remains the necessity for a deep study on the combinations of
substrates for the synthesis of more functionalized and complexes
1,2,3-triazoles.
On the other hand, organoselenides are valuable compounds in
organic synthesis since these scaffolds are important units in bi-
ological/pharmaceutical15 and also served as versatile building
blocks.16 Among them, those containing nitrogen atoms in their
structure are a special class of molecules and have been used in
several organic transformations,17 e.g., in asymmetric synthesis,18
supramolecular chemistry19 and as new molecular materials.20
Therefore, the development of new and efficient protocols for the
synthesis of highly functionalized nitrogen-containing organo-
selenide compounds, remains an important challenge in synthetic
organic chemistry.
In this context, selenium-containing 1,2,3-triazole compounds,
are an interesting class of molecules and have a larger synthetic
importance since they combine the well known activity of the
1,2,3-triazole core21 with that of the selenium-containing group.15
A number of reports for the synthesis of selenium-containing
1,2,3-triazole compounds have been published using different
methodologies (Fig. 1).22 In some examples, these methods furnish
the selenium-containing 1,2,3-triazoles in moderate yields and low
~
* Corresponding authors. E-mail address: mwpaixao@ufscar.br (M.W. Paixao).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.007

N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
10457
Table 1
Optimization studies of organocatalytic cycloaddition of azidophenyl arylselenide
1a with
b
-keto-ester 2aa
Entry Catalyst (mol %)
Solvent/temperature Timeb (h) Yield 3ac (%)
1
2
3
4
5
6
7
8
Et2NH (10%)
Et2NH (10%)
Et2NH (10%)
Glycine (10%)
L-Proline (10%)
Pyrrolidine (10%)
Piperidine (10%)
DMSO/70 ꢀ
DMSO/50 ꢀ
DMSO/rt
DMSO/rt
DMSO/rt
DMSO/rt
DMSO/rt
C
C
2
3
3
98
95
95
Traces
65
70
70
68
25
75
Traces
95
84
95
Fig. 1. Examples of organylselanyl-1,2,3-triazoles in literature.
48
48
48
48
48
48
48
48
5
5
4
8
48
regioselectivity. Recently, a copper-catalyzed azide-alkyne cyclo-
addition (CuAAC) of selenium-containing azides or alkynyl sele-
nides, notably provide a convergent and regiospecific protocol to
this molecular architecture.23
Morpholine (10%) DMSO/rt
9
Et3N (10%)
Et2NH (10%)
Et2NH (10%)
Et2NH (5%)
Et2NH (1%)
Et2NH (1%)
Et2NH (1%)
d
DMSO/rt
DMF/rt
10
11
12
13
14d
15e
16
However, to the best of our knowledge, an organocatalytic
Toluene/rt
DMSO/rt
DMSO/rt
DMSO/rt
DMSO/rt
DMSO/rt
methodology to synthesize organylselanyl-1,2,3-triazoles via
b-
enaminoneeazide cycloaddition has not been explored. In this
sense, we describe herein our contribution to the application of
85
d
organocatalytic
b-enaminoneseazide cycloaddition for the synthe-
sis of 1,2,3-triazoles bearing an organoselenium moiety (Scheme 1).
a
Reactions were performed using azidophenyl arylselenide1a (0.25 mmol) and
-keto-ester 2a (0.25 mmol), in 0.25 mL of solvent under air atmosphere.
Most reactions were monitored by TLC for disappearance of starting materials.
Yields are given for isolated products.
Reaction was performed using 0.275 mmol of azidophenyl arylselenide 1a and
b
b
c
d
0.25 mmol of
b
-keto-ester 2a.
Reaction was performed using 0.275 mmol of
azidophenyl arylselenide 1a.
e
b
-keto-ester 2a and 0.25 mmol of
Analyzing Table 1, the best reaction conditions to obtain
selenium-triazole-carboxylate 3a were found using azidophenyl
Scheme 1. Organocatalytic cycloaddition of azidophenyl arylselenides 1 with
esters 2.
b-keto-
arylselenide 1a (0.275 mmol), b-keto-ester 2a (0.25 mmol), Et2NH
2. Results and discussion
(1 mol %) as organocatalyst, DMSO as solvent at room temperature
under air atmosphere. Having in hand a general and efficient pro-
tocol for the organo-catalytic cycloaddition reaction, we focused
our attention to extend the scope of this methodology by using (2-
To establish the appropriate reaction conditions for the organo-
catalytic -enaminoneeazide cycloaddition, a set of experiments
were undertaken with the azidophenyl arylselenides 1 and -keto-
b
b
azidophenyl)(phenyl)selenide 1a as
a number of -keto-esters under the optimized reaction conditions.
The results depicted in Table 2 disclose that our protocol worked
well for a range of substituted -keto-esters, affording high yields of
the desired products. Therefore, -keto-acetates containing alkyl
a selenium partner with
esters 2 in the presence of an organocatalyst (Table 1). In the
first experiment, we tested (2-azidophenyl)(phenyl)selenide 1a
(0.25 mmol) with ethyl acetoacetate 2a (0.25 mmol) in DMSO
(0.25 mL) using 10 mol % of Et2NH at 70 ꢀC (Table 1, entry 1). Under
these reaction conditions the desired product 3a was obtained in
excellent yield after only 2 h (Table 1, entry 1, 98%). To our delight,
high yields of compound 3a were also achieved when the reaction
temperature was decreased to, 50 ꢀC and room temperature (Table
1, entries 2 and 3, 95% in both cases). Inspired by these promising
results the nature of organocatalyst was further evaluated. A mod-
erate and poor yield of product 3a was obtained using other orga-
b
b
b
(Et, t-Bu and Oct), benzyl and propargyl groups delivered the de-
sired selenium-triazoles 3aee in good to excellent yields (Table 2,
entries 1e5). When the reactions were performed using ethyl
benzoylacetate 2f, benzyl benzoylacetate 2g and ethyl 4,4,4-
trifluoroacetoacetate 2h, the corresponding selenium-triazole-
carboxylates 3feh were obtained in 91%, 87% and 85% yields, re-
spectively (Table 2, entries 6e8).
nocatalysts, such as, glycine,
L-proline, pyrrolidine, piperidine,
Under similar reaction conditions, we next evaluated the re-
morpholine and Et3N (Table 1, entries 4e9). Furthermore, by using
DMF or toluene as solvent, the desired product 3a was obtained in
75% or in traces, respectively (Table 1, entries 10 and 11). Decreasing
the organocatalyst loading from 10 to 1 mol %, a slight decrease in
the yield of compound 3a was observed (Table 1, entry 13). To our
satisfaction excellent yield of the product could be obtained even at
low loading of optimal organocatalyst by simply increasing the
amount of the azide. Therefore, when we used 1 mol % of Et2NH and
an excess of 10% of azidophenyl arylselenide 1a (0.275 mmol) the
desired product 3a was obtained in 95% yield after 4 h (Table 1, entry
activity of
phenyl arylselenides. Besides, 4-(azidophenyl)(phenyl)-selenide 1b
reacted smoothly with -keto-esters 2a, 2f and 2h yielding the
b-keto-esters towards different functionalized azido-
b
corresponding selenium-triazole-carboxylates 3iek in good yields
(Table 2, entries 9e11). Substituted 2-azidophenyl arylselenides
were also cyclized with ethyl acetoacetate 2a. In a general, the re-
actions are not sensitive to the electronic effect of the aromatic ring
in the arylselanyl moiety. Consequently, azidophenyl arylselenides
containing electron-donating group (2-Me and 4-Me) and electron-
withdrawing group (2-Cl, 4-Cl and 3,5-CF3) at the aromatic ring
gave excellent yields of selenium-triazole-carboxylates 3leo (Table
2, entries 12e15).
14). Unfortunately, using an excess of b-keto-ester 2a the desired
product 3a was obtained in lower yield comparing reaction using an
excess of starting material 1a (Table 1, entry15 vs 14). In the absence
of an organocatalyst the reaction does not occur (Table 1, entry 16).
To our delight, ketone 2i with a cyano-group in the
a-position
efficiently reacted with azidophenyl arylselenide 1a to generate

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N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
Table 2
Scope of substrates: variation of the azidophenyl arylselenides and b
-keto-estersa
Entry
Azidophenyl
arylselenide
b
-keto-ester
Time (h)
Product
Isolated yield (%)
1
4
95
2a
1a
1a
1a
1a
1a
1a
3a
3b
3c
3d
3e
3f
2
3
4
5
6
24
89
84
89
90
91
2b
7
2c
3
2d
4
2e
3
2f
7
8
87
1a
2g
3g

N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
10459
Table 2 (continued )
Entry
Azidophenyl
arylselenide
b
-keto-ester
Time (h)
Product
Isolated yield (%)
8
4
85
85
82
78
2h
1a
1b
1b
1b
3h
9
5
6
6
2a
3i
10
2f
3j
11
2h
3k
12
8
92
2a
1c
3l
13
8
90
2a
1d
3m
14
6
98
2a
1e
3n
(continued on next page)

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N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
Table 2 (continued )
Entry
Azidophenyl
arylselenide
b
-keto-ester
Time (h)
Product
Isolated yield (%)
15
5
91
2a
1f
3o
a
Reactions conditions: azidophenyl arylselenides 1aef (0.275 mmol), b-keto-esters 2aeh (0.25 mmol), EtN2H (0.0025 mmol) in DMSO (0.25 mL) at room temperature
under air atmosphere.
selenium-triazole-carbonitrile 3p in acceptable chemical yield,
however using 10 mol % of organocatalyst (Scheme 2).
an elimination reaction to regenerate Et2NH for the next catalytic
cycle and produce the desired product 3 (Scheme 3).
Recently, it has been shown that organocatalytic and cycload-
dition reactions can be influenced also by microwave irradiation
(polar transition states).24 In all these cases, the authors demon-
strated that the use of microwave irradiation can dramatically re-
duce the reaction time often accompanied with increased chemical
outcome.25 Therefore, the copper-free
b-enaminoneeazide cyclo-
addition reaction was evaluated under focused microwave irradi-
ation. To this end, a mixture of (2-azidophenyl)(phenyl)-selenide 1a
(0.275 mmol), ethyl acetoacetate 2a (0.25 mmol), Et2NH (1 mol %)
in DMSO (0.25 mL) were reacted using different temperatures and
times under microwave irradiation. High levels of conversion were
observed in this set of experiments and the best result was ach-
ieved after microwave irradiation at 70 ꢀC for 10 min, giving the
corresponding product 3a in 94% isolated yield (Scheme 4).
Scheme 2. Synthesis of selenium-triazole-carbonitrile 3p.
Based on the obtained results and according to the previous re-
ports on the organocatalytic synthesis of 1,2,3-triazoles,13 a plausi-
ble mechanism for the synthesis of selenium-triazole-carboxylates
3 can be proposed. Therefore, this reaction may occur via b-enam-
inoneeazide cycloaddition pathway catalyzed by Et2NH (Scheme 3).
Scheme 4. Microwave assisted synthesis of arylselanyl-1H-1,2,3-triazole-4-
carboxylates 3.
The protocol using microwave irradiation was extended to
synthesis of selenium-triazole-carboxylates 3b and 3e, and the
desired products were obtained in excellent yields after a short
reaction time (Scheme 4).
Scheme 3. proposed mechanism for the organocatalytic synthesis of arylselanyl-1H-
1,2,3-triazole-4-carboxylates.
3. Conclusion
In conclusion, we have described the organocatalytic
b-enami-
Firstly, the
condensation of Et2NH with the
cycloaddition of -enaminones (A) with the azidophenyl arylsele-
nide 1 gave the triazoline intermediate (B), which suffers a 1,3-
hydride shift, affording the triazoline intermediate (C). Finally, the
zwitterionic form of (C), represented as intermediate (D) undergoes
b
-enaminones intermediate (A) was formed by the
noneseazide cycloaddition of azidophenyl arylselenides with b-
b-ketoester 2. Then, the 1,3-dipolar
keto-esters using catalytic amount of Et2NH in DMSO as solvent. As
an application of this approach, a range of corresponding arylse-
lanyl-1H-1,2,3-triazole-4-carboxylates were exclusively obtained in
good to excellent yields under mild reaction conditions. Microwave
experiments reduced considerably the time of these reactions to
b

N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
10461
few minutes, which makes this protocol useful attractive approach
for the diversity-oriented synthesis of high-functionalized 1,2,3-
triazoles. This organocatalytic methodology showed to be an effi-
cient methodology for combinatorial synthesis of new selenium-
containing triazoles molecules. The application of aliphatic and
other non-aryl azides as well as the toxicological and pharmaco-
logical evaluations of these compounds are under studies in our
laboratories.
71 (30); 57 (84); 56 (56); 44 (41); 43 (81); 41 (100). HRMS: calculated
to C20H21N3O2Se [MþK]þ 454.0436, found 454.0432.
4.2.3. Octyl 5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-
4-carboxylate (3c). Yield: 0.099 g (84%); yellow oil. 1H NMR (CDCl3,
400 MHz)
d
¼7.49e7.46 (m, 2H), 7.42e7.27 (m, 7H), 4.40 (t, J¼7 Hz,
2H), 2.44 (s, 3H),1.83 (qui, J¼7 Hz, 2H),1.50e1.43 (m, 2H),1.38e1.25
(m, 8H), 0.88 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
¼161.83,
d
139.91, 136.25, 135.31, 134.92, 133.05, 131.31, 129.71, 128.66, 127.90,
127.84, 127.72, 65.23, 31.78, 29.25, 29.17, 28.74, 25.97, 22.63, 14.09,
9.63. MS (relative intensity) m/z: 472 (3); 471 (Mþ, 12); 470 (6); 366
(100); 364 (51); 362 (19); 286 (29); 270 (13); 253 (66); 231 (18);
207 (34); 206 (34); 157 (26); 152 (27); 103 (11); 77 (29); 57 (35); 43
(71); 41 (53). HRMS: calculated to C24H29N3O2Se [MþH]þ 472.1503,
found 472.1520.
4. Experimental section
4.1. General remarks
Proton nuclear magnetic resonance spectra (1H NMR) were
obtained at 400 MHz on a Bruker ARX-400NMR 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
4.2.4. Benzyl 5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-
triazole-4-carboxylate (3d). Yield: 0.100 g (89%); yellow solid; mp
shift (
d), multiplicity, coupling constant (J) in hertz and integrated
107e108 C. 1H NMR (CDCl3, 400 MHz)
d
¼7.51 (d, J¼7 Hz, 2H), 7.45 (d,
intensity. Carbon-13 nuclear magnetic resonance spectra (13C NMR)
were obtained at 100 MHz on a Bruker ARX-400 NMR spectrome-
ter. Spectra were recorded in CDCl3 solutions. Chemical shifts are
reported in parts per million, referenced to the solvent peak of
CDCl3. Mass spectra (MS) were measured on a Shimadzu GCMS-
QP2010 mass spectrometer. Column chromatography was per-
formed using Merck Silica Gel (230e400 mesh). Thin layer chro-
J¼7 Hz, 2H), 7.40e7.25 (m, 10H), 5.45 (s, 2H), 2.41 (s, 3H). 13C NMR
(CDCl3, 100 MHz)
d¼161.53, 140.23, 135.98, 135.77, 135.39, 135.29,
134.90, 133.12, 133.01, 131.36, 129.72, 128.88, 128.61, 128.56, 128.37,
127.91,127.71, 66.65, 9.69. MS (relative intensity) m/z: 449 (Mþ, 2); 447
(1); 344 (15); 342 (8); 152 (11); 91 (100); 77 (15); 65 (17); 51 (6). HRMS:
calculated to C23H19N3O2Se [MþH]þ 450.0721, found 450.0723.
matography (TLC) was performed using Merck Silica Gel GF254
,
4.2.5. Prop-2-ynyl 5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-
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 pro-
grammable from 1 to 300 W. Azidophenyl arylselenides 1aef were
synthesized according procedure described by Braga.26
triazole-4-carboxylate (3e). Yield: 0.089 g (90%); yellow oil. 1H
NMR (CDCl3, 400 MHz)
d
¼7.48e7.45 (m, 2H), 7.43e7.28 (m, 7H),
5.00 (d, J¼2 Hz, 2H), 2.54 (t, J¼2 Hz, 1H), 2.46 (s, 3H). 13C NMR
(CDCl3, 100 MHz)
d¼160.83, 140.64, 135.39, 135.27, 134.81, 133.16,
132.95, 131.43, 129.74, 128.91, 127.94, 127.90, 127.65, 75.32, 52.32,
9.65. MS (relative intensity) m/z: 398 (6); 397 (Mþ, 26); 396 (3); 291
(20); 270 (25); 250 (35); 248 (19); 231 (32); 212 (100); 206 (25); 167
(34); 157 (21); 152 (65); 115 (26); 77 (50); 51 (27); 43 (13). HRMS:
calculated to C19H15N3O2Se [MþH]þ 398.0408, found 398.0400.
4.2. General procedure for the synthesis of arylselanyl-1H-
1,2,3-triazole-4-carboxylates 3aeo
4.2.6. Ethyl 5-phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-
To a solution of azidophenyl arylselenides 1aef (0.275 mmol) in
4-carboxylate (3f). Yield: 0.102 g (91%); yellow oil. 1H NMR (CDCl3,
DMSO (0.25 mL), was firstly added the
b
-keto-esters 2aeh
400 MHz)
d
¼7.32e7.21 (m, 8H), 7.19e7.11 (m, 6H), 4.31 (q, J¼7 Hz,
(0.25 mmol) and then the catalyst diethylamine (0.0025 mmol). The
reaction mixture was stirred in an open vial for the time indicated in
Table 2. After completion of the reaction, the crude product was
purified by column chromatography on silica gel using a mixture of
hexane/ethyl acetate (5:1) as eluent to afford the desired products
3aeo. Spectral data of the products prepared are listed below.
2H), 1.26 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
d
¼161.07,
142.09, 136.36, 135.52, 134.85, 133.31, 132.89, 130.97, 130.39, 129.90,
129.63, 128.71, 128.58, 128.28, 128.09, 127.54, 125.31, 61.25, 14.20.
MS (relative intensity) m/z: 450 (4); 449 (Mþ, 16); 447 (8); 348 (30);
344 (78); 271 (55); 269 (49); 236 (100); 298 (30); 190 (37); 165
(68); 152 (58); 105 (35); 89 (30); 77 (47); 63 (13); 51 (18). HRMS:
calculated to C23H19N3O2Se [MþH]þ 450.0721, found 450.0743.
4.2.1. Ethyl 5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-
4-carboxylate (3a). Yield: 0.091 g (95%); white solid; mp 51e53 C.
4.2.7. Benzyl 5-phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-
1H NMR (CDCl3, 400 MHz)
d
¼7.47 (d, J¼7 Hz, 2H), 7.42e7.27 (m,
triazole-4-carboxylate (3g). Yield: 0.111 g (87%); yellow oil. 1H
7H), 4.47 (q, J¼7 Hz, 2H), 2.45 (s, 3H), 1.46 (t, J¼7 Hz, 3H). 13C NMR
NMR (CDCl3, 400 MHz)
(CDCl3, 100 MHz)
d
¼7.31e7.12 (m, 19H), 5.29 (s, 2H). 13C NMR
(CDCl3, 100 MHz)
d
¼161.72, 140.00, 136.19, 135.29, 134.88, 133.04,
d
¼160.85, 142.10, 136.20, 135.50, 134.85, 133.33,
131.34, 129.71, 128.86, 127.87, 127.69, 61.06, 14.39, 9.60. MS (relative
intensity) m/z: 388 (5); 387 (Mþ, 22); 386 (3); 286 (22); 282 (100);
280 (49); 271 (24); 253 (29); 231 (27); 207 (44); 206 (39); 157 (21);
152 (53); 128 (19); 77 (47); 51 (21); 43 (13). HRMS: calculated to
C18H17N3O2Se [MþH]þ 388.0564, found 388.0543.
132.92, 130.96, 130.37, 129.86, 129.62, 128.73, 128.57, 128.47, 128.37,
128.28, 128.21, 128.14, 128.09, 127.51, 66.74. MS (relative intensity)
m/z: 512 (7); 511 (Mþ, 15); 510 (3); 450 (17); 387 (36); 344 (64); 307
(38); 271 (55); 265 (17); 241 (33); 234 (100); 182 (13); 152 (40); 89
(35); 77 (37); 51 (28); 50 (33); 43 (32). HRMS: calculated to
C28H21N3O2Se [MþH]þ 512.0877, found 512.0879.
4.2.2. tert-Butyl 5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-
triazole-4-carboxylate (3b). Yield: 0.092 g (89%); white solid; mp
4.2.8. Ethyl
1-(2-(phenylselanyl)phenyl)-5-(trifluoromethyl)-1H-
123e125 C. 1H NMR (CDCl3, 400 MHz)
d
¼7.41e7.39 (m, 2H),
1,2,3-triazole-4-carboxylate (3h). Yield: 0.094 g (85%); red oil. 1H
7.32e7.16 (m, 7H), 2.33 (s, 3H),1.58 (s, 9H).13C NMR (CDCl3,100 MHz)
NMR (CDCl3, 400 MHz)
d¼7.47e7.40 (m, 5H), 7.38e7.27 (m, 4H),
d
¼159.95,138.31,136.28,134.35,133.93,132.12,131.89,130.20,128.67,
4.52 (q, J¼7 Hz, 2H), 1.46 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
127.81, 126.84, 126.73, 81.07, 27.32, 8.68. MS (relative intensity) m/z:
416 (1); 415 (Mþ, 4); 413 (2);359(6);354(38); 208 (28); 207 (66);206
(36); 157 (14); 152 (27); 130 (19); 103 (12); 85 (19); 83 (15); 77 (36);
d
¼158.95, 138.90, 135.76, 134.86, 133.97, 132.53, 131.93, 129.71,
128.79, 128.16, 127.95, 127.38, 120.11, 117.40, 62.37, 14.07. MS (rela-
tive intensity) m/z: 444 (3); 442 (1); 441 (Mþ, 5); 412 (32); 339 (37);

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N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
337 (36); 335 (100); 333 (49); 307 (38); 270 (30); 260 (55); 182
(13); 156 (37); 152 (45); 78 (12); 77 (70); 50 (34). HRMS: calculated
to C18H14F3N3O2Se [MþH]þ 442.0282, found 442.0277.
7.32e7.30 (m, 1H), 7.27 (d, J¼8 Hz, 2H), 4.47 (q, J¼7 Hz, 2H), 2.45 (s,
3H), 1.46 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
d
¼161.64,
139.91, 136.42, 136.24, 135.23, 135.06, 133.28, 132.33, 131.47, 129.89,
128.26,127.96,126.07, 61.09,14.39, 9.63. MS (relative intensity) m/z:
423 (7); 421 (Mþ, 15); 285 (26); 282 (100); 280 (49); 254 (31); 252
(47); 207 (39); 204 (25); 130 (16); 77 (22); 75 (15); 43 (13). HRMS:
calculated to C18H16ClN3O2Se [MþH]þ 422.0175, found 422.0147.
4.2.9. Ethyl 5-methyl-1-(4-(phenylselanyl)phenyl)-1H-1,2,3-triazole-
4-carboxylate (3i). Yield: 0.082 g (85%); yellow oil. 1H NMR (CDCl3,
400 MHz)
d
¼7.60e7.58 (m, 2H), 7.54e7.51 (m, 2H), 7.38e7. 34 (m,
3H), 7.33e7.28 (m, 2H), 4.45 (q, J¼7 Hz, 2H), 2.58 (s, 3H), 1.44 (t,
J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
d
¼161.69, 138.80, 136.79,
4.2.15. Ethyl 1-(2-(3,5-bis(trifluoromethyl)phenylselanyl)phenyl)-5-
methyl-1H-1,2,3-triazole-4-carboxylate (3o). Yield: 0.119 g (91%);
135.54, 134.68, 133.87, 132.21, 129.77, 128.92, 128.55, 125.89, 61.11,
14.39, 10.02. MS (relative intensity) m/z: 388 (7); 387 (Mþ, 35); 385
(17); 286 (62); 284 (36); 279 (52); 251 (27); 232 (65); 230 (32); 206
(100); 157 (73); 156 (48); 152 (90); 130 (34); 83 (77); 77 (68); 51
(28); 43 (32). HRMS: calculated to C18H17N3O2Se [MþH]þ 388.0564,
found 388.0547.
yellow oil. 1H NMR (CDCl3, 400 MHz)
d
¼7.67 (s, 1H), 7.61e7.57 (m,
2H), 7.52e7.45 (m, 3H), 7.42 (t, J¼8 Hz, 1H), 7.36e3.34 (m, 1H), 4.47
(q, J¼7 Hz, 2H), 2.44 (s, 3H), 1.46 (t, J¼7 Hz, 3H). 13C NMR (CDCl3,
100 MHz)
d
¼161.59, 139.88, 137.80, 136.24, 135.64, 134.11, 131.61,
131.27, 130.85, 130.81, 130.01, 129.46, 128.86, 128.16, 125.37, 124.75,
122.04, 61.08, 14.33, 9.58. MS (relative intensity) m/z: 455 (Mþ, 11);
453 (6); 284 (19); 282 (100); 280 (50); 254 (31); 232 (18); 208 (43);
206 (23); 152 (24); 77 (20); 43 (15). HRMS: calculated to
C20H15F6N3O2Se [MþH]þ 524.0312, found 524.1660.
4.2.10. Ethyl 5-phenyl-1-(4-(phenylselanyl)phenyl)-1H-1,2,3-
triazole-4-carboxylate (3j). Yield: 0.092 g (82%); yellow solid; mp
108e110 C. 1H NMR (CDCl3, 400 MHz)
d
¼7.51e7.49 (m, 2H),
7.44e7.28 (m, 10H), 7.13 (d, J¼8 Hz, 2H), 4.34 (q, J¼7 Hz, 2H), 1.30 (t,
J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
¼160.88, 140.74, 137.03,
d
4.3. General procedure for the synthesis of 5-phenyl-1-(2-
(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile 3p
134.70,134.44,134.35,132.22,131.94,130.26,130.04,129.70,129.00,
128.44, 125.73, 125.65, 61.21, 14.17. MS (relative intensity) m/z: 450
(3); 449 (Mþ, 6); 447 (3); 269 (26); 236 (57); 220 (25); 190 (18); 152
(20); 105 (27); 89 (100); 77 (28); 63 (14). HRMS: calculated to
C23H19N3O2Se [MþH]þ 450.0721, found 450.0730.
To
a
solution of (2-azidophenyl)(phenyl)selenide 1a
(0.275 mmol) in DMSO (0.25 mL), was firstly added the benzoyla-
cetonitrile 2i (0.25 mmol) and then the catalyst diethylamine
(0.025 mmol). The reaction mixture was stirred in an open vial for
18 h. After that, the crude product was purified by column chro-
matography on silica gel using a mixture of hexane/ethyl acetate
(5:1) as eluent to afford the desired product.
4.2.11. Ethyl
1,2,3-triazole-4-carboxylate (3k). Yield: 0.086 g (78%); red oil. 1H
NMR (CDCl3, 400 MHz)
¼7.63e7.61 (m, 2H), 7.50e7.47 (m, 2H),
1-(4-(phenylselanyl)phenyl)-5-(trifluoromethyl)-1H-
d
7.41e7.35 (m, 3H), 7.31 (d, J¼8 Hz, 2H), 4.49 (q, J¼7 Hz, 2H), 1.44 (t,
J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
¼158.97, 139.48, 137.60,
d
4.3.1. 5-Phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-
carbonitrile (3p). Yield: 0.091 g (91%); yellow solid; mp 94e96 C.
135.13, 133.62, 131.38, 129.88, 128.83, 128.31, 126.22, 120.16, 117.46,
62.42, 14.04. MS (relative intensity) m/z: 442 (4); 441 (Mþ, 20); 439
(10); 289 (25); 274 (35); 265 (17); 261 (100); 241 (33); 156 (32); 155
(17); 152 (32); 77 (34); 51 (18); 40 (15). HRMS: calculated to
C18H14F3N3O2Se [MþH]þ 442.0282, found 442.0276.
1H NMR (CDCl3, 400 MHz)
d
¼7.49e7.23 (m, 14H). 13C NMR (CDCl3,
100 MHz)
d¼142.69, 133.65, 133.32, 132.39, 130.94, 130.10, 129.56,
128.22, 127.81, 127.32, 127.25, 126.67, 126.62, 121.73, 118.21, 110.79.
MS (relative intensity) m/z: 403 (6); 402 (Mþ, 22); 400 (12);
297 (48); 294 (100); 293 (40); 217 (53); 190 (60); 77 (41); 51
(26). HRMS: calculated to C21H14N4Se [MþH]þ 403.0462, found
403.0470.
4.2.12. Ethyl 5-methyl-1-(2-(p-tolylselanyl)phenyl)-1H-1,2,3-
triazole-4-carboxylate (3l). Yield: 0.092 g (92%); white solid; mp
100e102 C. 1H NMR (CDCl3, 400 MHz)
d¼7.40e7.32 (m, 4H),
7.30e7.25 (m, 2H), 7.13 (d, J¼8 Hz, 2H), 4.48 (q, J¼7 Hz, 2H), 2.46 (s,
4.4. General procedure for the microwave synthesis of ar-
ylseleno-1H-1,2,3-triazole-4-carboxylates
3H), 2.35 (s, 3H), 1.47 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
d
¼161.76, 140.01, 139.28, 135.82, 134.46, 133.75, 132.33, 131.24,
130.58, 129.23, 127.80, 127.45, 123.62, 61.06, 21.25, 14.40, 9.61. MS
(relative intensity) m/z: 401 (Mþ, 21); 399 (11); 300 (30); 285 (31);
282 (100); 280 (44); 253 (38); 231 (21); 207 (57); 165 (33); 152
(42); 91 (63); 77 (32); 65 (24); 43 (13). HRMS: calculated to
C19H19N3O2Se [MþH]þ 402.0721, found 402.0730.
In a 10 mL glass vial equipped with a small magnetic stirring bar,
containing azidophenyl arylselenide 1a (0.275 mmol), an appro-
priated b-keto-ester (0.25 mmol) in DMSO (0.25 mL), diethylamine
(0.0025 mmol). The vial was tightly sealed with an aluminum/
Teflon crimp top and the mixture was then irradiated in a focused
microwaves reactor (CEM) at 70 ꢀ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.
4.2.13. Ethyl 5-methyl-1-(2-(o-tolylselanyl)phenyl)-1H-1,2,3-
triazole-4-carboxylate (3m). Yield: 0.090 g (90%); white solid; mp
106e108 C. 1H NMR (CDCl3, 400 MHz)
d
¼7.48 (d, J¼7 Hz, 1H),
7.40e7.26 (m, 5H), 7.16e7.10 (m, 2H), 4.47 (q, J¼7 Hz, 2H), 2.47 (s,
3H), 2.30 (s, 3H), 1.46 (t, J¼7 Hz, 3H). 13C NMR (CDCl3, 100 MHz)
Acknowledgements
d¼161.73, 141.88, 139.97, 136.73, 136.21, 134.67, 132.83, 131.91,
The authors are indebted to FAPESP (09/07281-0 to M.W.P.),
CNPq (305272/2010-1; 470695/2011-0, to D.A. and M.W.P., re-
spectively) for financial support. A.M.D., N.S. and L.C.G. thank
FAPESP and CAPES for their Ph.D. fellowships. We are also grateful
to Prof. Dr. E.R. Filho and M.A. Trapp (UFSCar), for HRMS analyses.
131.34, 130.69, 129.62, 128.13, 127.96, 127.47, 127.10, 61.05, 22.65,
14.40, 9.54. MS (relative intensity) m/z: 401 (Mþ, 27); 402 (6); 403
(6); 399 (14); 292 (13); 284 (26); 282 (100); 280 (48); 278 (18); 272
(23); 253 (36); 251 (17); 219 (31); 218 (33); 207 (52); 204 (42); 165
(46); 130 (22); 91 (68); 77 (32); 65 (34). HRMS: calculated to
C19H19N3O2Se [MþH]þ 402.0721, found 402.0728.
Supplementary data
4.2.14. Ethyl
1,2,3-triazole-4-carboxylate (3n). Yield: 0.103 g (98%); white solid;
mp 121e123 C. 1H NMR (CDCl3, 400 MHz)
¼7.46e7.36 (m, 5H),
1-(2-(4-chlorophenylselanyl)phenyl)-5-methyl-1H-
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.10.007.
d

N. Seus et al. / Tetrahedron 68 (2012) 10456e10463
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