Organocatalytic synthesis of (Arylselanyl)phenyl-1H-1,2,3-triazole-4- carboxamides by cycloaddition between azidophenyl arylselenides and β-oxo-amides

Article abstract of DOI:10.1002/ejoc.201301547

We describe the use of β-oxo-amides in organocatalytic cycloaddition with aryl azidophenyl selenides. The cycloaddition reactions were performed under mild conditions, with β-oxo-amides and aryl azidophenyl selenides in the presence of a catalytic amount of Et₂NH (5 mol-%), and the corresponding products were obtained in good to excellent yields. This organocatalytic methodology tolerated a range of substituents either in the β-oxo-amides or in the aryl azidophenyl selenides and proved to be an efficient methodology for the combinatorial synthesis of new selenium-containing triazole compounds. The use of β-oxo-amides in organocatalytic cycloaddition with aryl azidophenyl selenides has been developed, with the corresponding (arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides being obtained in good to excellent yields. This organocatalytic protocol proved to be an efficient methodology for the combinatorial synthesis of new selenium-containing triazole compounds. Copyright

Full text of DOI:10.1002/ejoc.201301547

FULL PAPER
DOI: 10.1002/ejoc.201301547
Organocatalytic Synthesis of (Arylselanyl)phenyl-1H-1,2,3-triazole-
4-carboxamides by Cycloaddition between Azidophenyl Arylselenides and
β-Oxo-amides
Natália Seus,[a] Bruna Goldani,[a] Eder J. Lenardão,[a] Lucielli Savegnago,[b]
Márcio W. Paixão,[c] and Diego Alves*[a]
Keywords: Organoselenium compounds / Selenium / Organocatalysis / Cycloaddition / 1,2,3-Triazoles / β-Oxoamides
We describe the use of β-oxo-amides in organocatalytic cy-
cloaddition with aryl azidophenyl selenides. The cycload-
dition reactions were performed under mild conditions, with
β-oxo-amides and aryl azidophenyl selenides in the presence
of a catalytic amount of Et2NH (5 mol-%), and the corre-
sponding products were obtained in good to excellent yields.
This organocatalytic methodology tolerated a range of sub-
stituents either in the β-oxo-amides or in the aryl azido-
phenyl selenides and proved to be an efficient methodology
for the combinatorial synthesis of new selenium-containing
triazole compounds.
Introduction
1,2,3-triazoles through cascade [3+2] cycloaddition/hydrol-
ysis with Hagemann esters and p-toluenesulfonyl azide
(TsN3) in the presence of proline as a catalyst.[12a] More
recently, our research group described the application of the
organocatalytic enamide–azide cycloaddition for the syn-
thesis of 1,2,3-triazoles bearing organoselenium moieties.[13]
In this sense, organoselenides are valuable compounds in
organic synthesis, because these scaffolds are important
units in biological sciences[14] and also serve as versatile
building blocks.[15] Among them, those containing nitrogen
atoms in their structures are a special class of molecules
and have been used for several purposes.[16] In addition, sel-
enium-containing 1,2,3-triazole compounds are an interest-
ing and as yet unexplored class of molecules that might
have broader biological applications, because they combine
the well-known activity of the 1,2,3-triazole core[1,17] with
that of the selenium-containing group.[14–16] The develop-
ment of new and efficient protocols for the synthesis of
highly functionalized nitrogen-containing organoselenium
compounds therefore remains an important challenge in
synthetic organic chemistry.
In the context of functionalized nitrogen compounds, β-
oxo-amides and their derivatives showed attractive struc-
tural features as versatile organic intermediates. Several mo-
lecules containing these units display biological activities,[18]
and they are found in natural products (e.g., pestal-
amides A, B and C, aspernigrin A and carboranone A, Fig-
ure 1).[19] Consequently, several robust approaches using β-
oxo-amides have been reported for the production of a
plethora of heterocycles such as 2- and 4-pyridones,[20] di-
hydropyranones,[21] dihydropyrimidones,[22] 3-acyloxind-
oles,[23] isoxazoles,[24] and nicotinamides,[25] among
others.[26] More recently, iron-catalyzed Wolff cycloconden-
Heterocycles represent the most general structural units
in several natural and synthetic bioactive compounds.[1] In
particular, 1,2,3-triazoles[2] are an interesting class of nitro-
gen-based heterocycles widely used in the discovery and
modulation of drug candidates,[3] the development of new
materials,[4] supramolecular chemistry,[5] the design of new
supported catalysts,[6] and the biotechnology area.[7] Several
methodologies for the synthesis of the 1,2,3-triazole scaffold
based on 1,3-dipolar cycloaddition between azides and alk-
ynes have therefore already been reported.[8,9] However, the
necessity of transition metals has restricted the application
of these methodologies in chemical biology,[10] because
some transition metals can induce damage in different bio-
logical systems such as bacterial or mammalian cells or oli-
gonucleotides.[11]
To overcome this limitation, an organocatalytic approach
has been utilized to promote the synthesis of functionalized
1,2,3-triazoles through enamide–azide cycloaddition be-
tween a range of carbonyl compounds and organic az-
ides.[12] Ramachary and co-workers, for example, described
a practical and environmentally friendly amino-acid-cata-
lyzed cascade process for the synthesis of highly substituted
[a] Laboratório de Síntese Orgânica Limpa – LASOL – CCQFA –
Universidade Federal de Pelotas – UFPel,
Pelotas, RS, Brazil
E-mail: diego.alves@ufpel.edu.br
http://wp.ufpel.edu.br/lasol
[b] Grupo de Pesquisa em Neurobiotecnologia – GPN, CDTec,
Universidade Federal de Pelotas, UFPel,
Pelotas, RS, Brazil
[c] Laboratório de Síntese de Produtos Naturais, Universidade
Federal de São Carlos,
São Carlos, 13565-905 SP, Brazil
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301547.
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D. Alves et al.
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sation between α-diazo-β-oxo-amides and aromatic or ali- reaction conditions the desired product 3a was obtained in
phatic amines, described by Dong and co-workers, has excellent yield after only 4 h (Table 1, Entry 1, 90%). On
come to represent a powerful approach to the synthesis of changing the organocatalyst to l-proline (10 mol-%) no
a range of 1,2,3-triazole-4-carboxamides.[27] Furthermore, product 3a was obtained (Table 1, Entry 2). To our delight,
1,2,3-triazole-4-carboxamide derivatives potently inhibited however, a small improvement in the chemical yield of com-
the replication of various H3N2 and H1N1 influenza A pound 3a was achieved on replacement of the organocata-
virus strains.[28]
lyst with Et2NH (10 mol-%, Table 1, Entry 3).
Table 1. Optimization of organocatalytic cycloaddition of β-oxo-
amide 1a and aryl azidophenyl selenide 2a.[a]
Entry Organocatalyst
([mol-%])
DMSO [mL]/
temperature [°C]
Time Yield 3a
[%][b]
Figure 1. Natural products containing β-oxo-amide units.
[h]
1
2
3
4
5
6
7
8
9
10
11
12
13
pyrrolidine (10)
l-proline (10)
Et2NH (10)
Et2NH (10)
Et2NH (10)
pyrrolidine (10)
Et2NH (10)
Et2NH (5)
Et2NH (1)
Et2NH (5)
Et2NH (1)
–
0.6/70
0.6/70
0.6/70
4
48
2
2
2
4
2
2
2
90
n.d.
93
84
85
69
87
78
To the best of our knowledge, however, the direct use
of β-oxo-amides to synthesize highly functionalized 1,2,3-
triazoles through organocatalytic enamide–azide cycload-
dition with organic azides has not been explored. In this
context and in continuation of our interest in the synthesis
of 1,2,3-triazoles bearing organoselenium moieties, here we
describe the application of β-oxo-amides in organocatalytic
enamide–azide cycloaddition for the synthesis of a range of
(arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides
(Scheme 1).
0.6/room temp.
0.3/room temp.
0.3/room temp.
0.3/70
0.3/70
0.3/70
0.3/room temp.
0.3/room temp.
0.3/room temp.
0.3/70
65
2
83[c]
72
12
48
48
n.d.
n.d.
–
[a] Reactions were performed with 3-oxo-N-phenylbutanamide (1a,
0.3 mmol) and aryl azidophenyl selenide 2a (0.3 mmol) in DMSO
as solvent under air and were monitored by TLC until total disap-
pearance of the starting materials. [b] Yields are given for isolated
products. [c] When the reaction was performed under N2 the same
yield was obtained.
Inspired by this result, we performed additional experi-
ments with Et2NH as organocatalyst. Reactions performed
in the presence of 10 mol-% of catalyst at room temperature
gave good yields of the desired product 3a at both 0.5 and
1.0 m concentrations (Table 1, Entries 4 and 5). When the
reaction was performed with Et2NH (10 mol-%) and
0.3 mL of DMSO at 70 °C a good yield of product 3a was
also obtained (Table 1, Entry 7). On decreasing the organo-
catalyst loading from 10 to 1 mol-% in reactions in the pres-
ence of 0.3 or 0.6 mL of DMSO and at 70 °C or room tem-
Scheme 1. Synthesis of (arylselanyl)phenyl-1H-1,2,3-triazole-4-
carboxamides 3.
Results and Discussion
To identify appropriate reaction conditions for this or- perature, slight decreases in the reaction yields were ob-
ganocatalytic enamide–azide cycloaddition, a set of experi- served (Table 1, Entries 8–11). In the absence of an organo-
ments was performed with the β-oxo-amide 1a and aryl az- catalyst no reaction had taken place even after 48 h
idophenyl selenide 2a as standard substrates (Table 1). We (Table 1, Entries 12 and 13).
started the reaction screening with 3-oxo-N-phenylbutan-
Analyzing the results shown in Table 1, we judged that
amide (1a, 0.3 mmol) and 2-azidophenyl phenyl selenide the best reaction conditions to afford selenium-containing
(2a, 0.3 mmol) in DMSO (0.6 mL) together with 10 mol- triazole-carboxamide 3a are those in Entry 10, with 3-oxo-
% of pyrrolidine at 70 °C (Table 1, Entry 1). Under these N-phenylbutanamide (1a, 0.3 mmol), aryl azidophenyl sele-
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(Arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides
Table 2. Scope and generality of the cycloaddition reaction.
nide 2a (0.3 mmol), Et2NH (5 mol-%) as organocatalyst,
and DMSO (0.3 mL) as solvent at room temperature under
air (Table 1, Entry 10). After that, we focused our attention
on extending the scope of this methodology by using 2-
azidophenyl phenyl selenide (2a) as selenium partner with
a number of β-oxo-amides under the optimized reaction
conditions.
The results shown in Table 2 reveal that our protocol
worked well for a range of substituted β-oxo-amides, afford-
ing suitable yields of the desired products. In a general way,
the reactions are sensitive to the electronic conditions at the
oxo group in the β-oxo-amides. β-Oxo-amide 1c, containing
an electron-withdrawing group (–CF3) adjacent to the oxo
group, for example, gave a lower yield than β-oxo-amides
2a and 2b (Table 2, Entries 1 and 2 vs. 3). Furthermore,
β-oxo-amides containing either an electron-donating group
(EDG) or an electron-withdrawing group (EWG) on the
amide aromatic ring delivered the desired selenium-contain-
ing triazole-carboxamides 3d–j in good isolated yields
(Table 2, Entries 4–10). However, when the reaction was
performed with β-oxo-amide 1k, containing a strongly elec-
tron-withdrawing group (NO2), the corresponding product
3k was obtained in only 59% isolated yield (Table 2, En-
try 11).
We next evaluated the reactivity of 3-oxo-N-phenylbut-
anamide (1a) with the different functionalized aryl azido-
phenyl selenides 2b–d (Scheme 2) under the same reaction
conditions. Substituted aryl 2-azidophenyl selenides 2b and
2c efficiently cyclized with 3-oxo-N-phenylbutanamide (1a),
and the reactions are sensitive to electronic effects in the
aromatic ring in the arylselanyl moiety. Aryl azidophenyl
selenide 2b, containing an EDG (4-Me) in the aromatic
ring, gave a lower yield than the aryl azidophenyl selenide
2c, containing an EWG (4-Cl). In addition, 4-azidophenyl
phenyl selenide (2d) was treated with β-oxo-amide 1a to
afford the desired product in 93% yield as a mixture of
regioisomers (6:1).
It is possible to propose a possible mechanism for the
synthesis of selenium-containing triazole-carboxamides 3
based on recently published reports on organocatalytic en-
amide–azide cycloadditions[12] involving organic azides
(Figure 2). We believe that the enamine intermediate A
should be formed first, after condensation of Et2NH with
the β-oxo-amide 1. After that, 1,3-dipolar cycloaddition be-
tween enamine A and the aryl azidophenyl selenide 2 would
give the triazoline intermediate B, which after a possible
1,3-hydride shift could afford the triazoline intermediate C.
Finally, the zwitterionic form of C, represented as interme-
diate D, could undergo an elimination reaction to regener-
ate Et2NH in the next catalytic cycle and produce the de-
sired product 3 (Figure 2). The excellent reactivity and high
regioselectivity observed with the aryl azidophenyl selenide
2 is probably explained on the basis of the major contribut-
ing mesomeric structure represented in 2, according to the
electronic effects of the arylselanyl moiety.[12f,29] The reac-
tion between mesomeric structure 2 and enamine intermedi-
ate A would selectively furnish the adduct B through a con-
certed 1,3-dipolar cycloaddition.
[a] Yields are given for isolated products. [b] Reaction was per-
formed at 70 °C.
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D. Alves et al.
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Scheme 2. Cycloaddition reaction of 1a with different aryl azidophenyl selenides.
Figure 2. Proposed mechanism.
ternal reference. Data are reported as follows: chemical shift (δ),
multiplicity, coupling constant (J) in Hertz, and integrated inten-
sity. Carbon-13 nuclear magnetic resonance (13C NMR) spectra
Conclusions
We describe the use of β-oxo-amides in organocatalytic
cycloadditions with aryl azidophenyl selenides. Under opti- were obtained at 100 MHz with a Bruker ARX 400 NMR spec-
trometer. Spectra were recorded in CDCl3. Chemical shifts are re-
ported in ppm, referenced to the solvent peak of CDCl3. Mass
spectra (MS) were measured with a Shimadzu GC–MS-QP2010
mass spectrometer. High-resolution mass spectra (HRMS) were re-
corded with a Bruker Micro TOF-QII spectrometer 10416. Column
chromatography was performed with Merck silica gel (230–
400 mesh). Thin layer chromatography (TLC) was performed with
Merck GF254 silica gel (0.25 mm thickness). For visualization, TLC
plates were either placed under ultraviolet light or stained with io-
dine vapor or acidic vanillin.
mized mild reaction conditions, a range of (arylselanyl)-
phenyl-1H-1,2,3-triazole-4-carboxamides were synthesized
in high yields with use of catalytic amounts of Et2NH in
DMSO as solvent. This organocatalytic methodology toler-
ated a range of substituents in the β-oxo-amides or aryl
azidophenyl selenides and proved to be an efficient method-
ology for combinatorial synthesis of new selenium-contain-
ing triazole compounds.
General Procedure for the Synthesis of (Arylselanyl)phenyl-1H-
1,2,3-triazole-4-carboxamides 3a–n: The appropriate β-oxo-amide
(out of 1a–k, 0.3 mmol) was first added to a solution of the appro-
priate arylselanyl azide (out of 2a–d, 0.3 mmol) in DMSO (0.3 mL),
followed by diethylamine (0.015 mmol) as catalyst. The reaction
mixture was stirred in an open vial for the time indicated in Table 2
Experimental Section
General Remarks: Proton nuclear magnetic resonance (1H NMR)
spectra were obtained at 400 MHz with a Bruker ARX 400 NMR
spectrometer. Spectra were recorded in CDCl3. Chemical shifts are
reported in ppm, referenced to tetramethylsilane (TMS) as the ex- and Scheme 2. After completion of the reaction, the crude product
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(Arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides
was purified by column chromatography on silica gel with a mix-
ture of hexane/ethyl acetate (5:1) as eluent to afford the desired
product (3a–n). Spectral data for the products prepared are listed
below.
2 H), 7.50–7.31 (m, 9 H), 6.93 (d, J = 8.9 Hz, 2 H), 3.82 (s, 3 H),
2.52 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 158.93,
156.38, 138.25, 138.11, 135.16, 134.97, 133.08, 132.93, 131.21,
130.82, 129.61, 128.76, 127.77, 127.74, 121.48, 114.19, 55.41,
9.26 ppm. MS: m/z (%) = 466 (22), 464 (100), 462 (54), 314 (20),
251 (25), 207 (25), 198 (84), 196 (43), 157 (29), 152 (37), 146 (68),
122 (35), 77 (35), 51 (11). HRMS: calcd. for C23H21N4O2Se [M +
H]+ 465.0830; found 465.0850.
5-Methyl-N-phenyl-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-triazole-
4-carboxamide (3a): Yield: 0.108 g (83 %); orange oil. 1H NMR
(CDCl3, 400 MHz): δ = 9.12 (s, 1 H), 7.72 (d, J = 8.1 Hz, 2 H),
7.47 (d, J = 8.2 Hz, 2 H), 7.41–7.25 (m, 9 H), 7.13 (t, J = 7.4 Hz,
1 H), 2.52 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.07,
138.43, 138.01, 137.66, 135.09, 134.92, 133.10, 132.85, 131.20,
129.58, 128.94, 128.72, 127.78, 127.71, 127.69, 124.17, 119.73,
9.26 ppm. MS: m/z (%) = 435 (12), 434 (47), 431 (23), 328 (14), 314
(37), 312 (20), 249 (100), 234 (26), 232 (28), 207 (37), 206 (33),
157 (25), 152 (50), 129 (19), 77 (64), 51 (20). HRMS: calcd. for
C22H19N4OSe [M + H]+ 435.0724; found 435.0744.
N-(2-Methoxyphenyl)-5-methyl-1-[2-(phenylselanyl)phenyl]-1H-
1,2,3-triazole-4-carboxamide (3g): Yield: 0.116 g (83%); white solid;
1
m.p. 111–112 °C. H NMR (CDCl3, 400 MHz): δ = 9.71 (s, 1 H),
8.53 (d, J = 7.9 Hz, 1 H), 7.47 (d, J = 8.1 Hz, 2 H), 7.39–7.25 (m,
7 H), 7.08–6.92 (m, 3 H), 3.94 (s, 3 H), 2.52 (s, 3 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 159.03, 148.38, 138.42, 138.22,
135.14, 134.99, 133.04, 132.93, 131.13, 129.58, 128.71, 127.75,
127.74, 127.72, 127.51, 123.74, 120.82, 119.62, 110.05, 55.69,
9.27 ppm. MS: m/z (%) = 466 (2), 464 (8), 434 (25), 433 (100), 431
(52), 342 (2), 316 (3), 314 (14), 286 (6), 279 (9), 271 (7), 264 (8),
248 (5), 235 (7), 232 (13), 207 (15), 198 (10), 169 (5), 157 (15), 152
(18), 77 (20), 55 (10). HRMS: calcd. for C23H21N4O2Se [M + H]+
465.0830; found 465.0855.
N,5-Diphenyl-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-triazole-4-carb-
oxamide (3b): Yield: 0.127 g (85%); yellow solid; m.p. 133–134 °C.
1H NMR (CDCl3, 400 MHz): δ = 9.26 (s, 1 H), 7.70 (d, J = 8.1 Hz,
2 H), 7.40 (d, J = 8.1 Hz, 2 H), 7.35–7.23 (m, 14 H), 7.10 (t, J =
7.4 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 158.05,
140.65, 138.16, 137.66, 135.59, 134.76, 133.26, 132.76, 130.84,
130.49, 129.75, 129.53, 128.90, 128.58, 128.50, 128.16, 127.98,
127.46, 125.04, 124.18, 119.84 ppm. MS: m/z (%) = 498 (8), 496
(37), 391 (27), 376 (39), 374 (20), 348 (54), 311 (100), 267 (48), 219
(18), 190 (27), 165 (44), 152 (39), 77 (40), 51 (13). HRMS: calcd.
for C27H21N4OSe [M + H]+ 497.0881; found 497.0993.
N-(4-Chlorophenyl)-5-methyl-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-
triazole-4-carboxamide (3h): Yield: 0.122 g (87 %); yellow solid;
1
m.p. 121–122 °C. H NMR (CDCl3, 400 MHz): δ = 9.10 (s, 1 H),
7.68 (d, J = 8.8 Hz, 2 H), 7.47 (d, J = 8.2 Hz, 2 H), 7.39–7.29 (m,
9 H), 2.52 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.12,
138.66, 137.88, 136.34, 135.19, 134.94, 133.21, 132.97, 131.34,
129.68, 129.22, 129.06, 128.84, 127.87, 127.77, 127.73, 120.98,
9.33 ppm. MS: m/z (%) = 470 (32), 469 (19), 468 (68), 466 (35), 314
(77), 312 (19), 286 (31), 285 (40), 283 (100), 274 (25), 271 (30), 268
(22), 248 (20), 232 (44), 219 (29), 206 (68), 198 (42), 169 (20), 152
(91), 129 (43), 102 (29), 91 (21), 77 (84), 67 (23), 55 (27), 44 (30).
HRMS: calcd. for C22H18ClN4OSe [M + H]+ 469.0334; found
469.0371.
N-Phenyl-1-[2-(phenylselanyl)phenyl]-5-(trifluoromethyl)-1H-1,2,3-
triazole-4-carboxamide (3c): Yield: 0.095 g (65%); yellow oil. 1H
NMR (CDCl3, 400 MHz): δ = 9.13 (s, 1 H), 7.74 (d, J = 8.3 Hz, 2
H), 7.46–7.26 (m, 11 H), 7.17 (t, J = 7.4 Hz, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 155.44, 141.37, 137.11, 135.95, 134.66,
133.99, 132.26, 131.86, 129.62, 129.06, 128.68, 128.12, 127.94,
127.29, 124.86, 119.94, 118.33 (q, J = 271.4 Hz) ppm. MS: m/z (%)
= 488 (6), 368 (39), 366 (21), 314 (14), 303 (100), 261 (30), 234 (14),
157 (17), 152 (20), 77 (55), 365 (15), 51 (14). HRMS: calcd. for
C22H16F3N4OSe [M + H]+ 489.0441; found 489.0495.
N-(2-Chlorophenyl)-5-methyl-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-
1
triazole-4-carboxamide (3i): Yield: 0.111 g (79%); yellow oil. H
NMR (CDCl3, 400 MHz): δ = 9.69 (s, 1 H), 8.55 (d, J = 9.2 Hz, 1
H), 7.48–7.27 (m, 11 H), 7.07 (t, J = 8.7 Hz, 1 H), 2.52 (s, 3 H)
ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.09, 138.59, 137.91,
135.07, 134.89, 134.56, 133.11, 132.82, 131.21, 129.57, 129.10,
128.72, 127.79, 127.71, 127.69, 127.47, 124.47, 123.22, 121.21,
9.25 ppm. MS: m/z (%) = 470 (19), 468 (37), 433 (100), 363 (23),
314 (43), 312 (23), 283 (55), 248 (28), 207 (57), 206 (45), 157 (37),
152 (67), 129 (29), 77 (52), 51 (19). HRMS: calcd. for
C22H18ClN4OSe [M + H]+ 469.0334; found 469.0347.
5-Methyl-1-[2-(phenylselanyl)phenyl]-N-p-tolyl-1H-1,2,3-triazole-
4-carboxamide (3d): Yield: 0.105 g (78%); yellow solid; m.p. 48–
49 °C. 1H NMR (CDCl3, 400 MHz): δ = 9.05 (s, 1 H), 7.60 (d, J =
8.2 Hz, 2 H), 7.46 (d, J = 7.0 Hz, 2 H), 7.37–7.28 (m, 7 H), 7.17
(d, J = 8.2 Hz, 2 H), 2.51 (s, 3 H), 2.33 (s, 3 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 158.97, 138.31, 138.10, 135.18, 135.12,
135.06, 134.96, 133.77, 133.09, 132.89, 131.19, 129.59, 129.45,
128.73, 127.77, 127.73, 119.76, 20.79, 9.26 ppm. MS: m/z (%) = 448
(1), 446 (1), 77 (3), 44 (23), 42 (13), 40 (100). HRMS: calcd. for
C23H21N4OSe [M + H]+ 449.0881; found 449.0905.
N-(4-Fluorophenyl)-5-methyl-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-
1
triazole-4-carboxamide (3j): Yield: 0.096 g (71%); yellow oil. H
5-Methyl-1-[2-(phenylselanyl)phenyl]-N-o-tolyl-1H-1,2,3-triazole-
4-carboxamide (3e): Yield: 0.097 g (72 %); yellow oil. 1H NMR
(CDCl3, 400 MHz): δ = 9.04 (s, 1 H), 8.14 (d, J = 7.9 Hz, 1 H),
7.49–7.47 (m, 2 H), 7.38–7.22 (m, 9 H), 7.09 (d, J = 7.4 Hz, 1 H),
2.52 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ
= 159.08, 138.33, 138.23, 135.60, 135.17, 134.97, 133.07, 132.94,
131.20, 130.42, 129.61, 128.76, 128.41, 127.77, 127.74, 126.67,
124.68, 121.96, 53.35, 17.67, 9.27 ppm. MS: m/z (%) = 450 (9), 448
(39), 446 (22), 420 (92), 418 (52), 314 (38), 274 (21), 271 (26), 263
(100), 248 (50), 235 (19), 232 (45), 207 (59), 198 (44), 196 (24), 169
(38), 157 (48), 152 (79), 129 (35), 91 (57), 77 (85), 51 (25). HRMS:
calcd. for C22H19N4OSe [M + H]+ 449.0881; found 449.0902.
NMR (CDCl3, 400 MHz): δ = 9.10 (s, 1 H), 7.68 (dd, J = 9.0,
4.8 Hz, 2 H), 7.49–7.46 (m, 2 H), 7.40–7.28 (m, 7 H), 7.06 (t, J =
8.8 Hz, 2 H), 2.52 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ
= 159.32 (d, J = 242.0 Hz), 159.07, 138.51, 137.89, 135.15, 134.92,
133.71 (d, J = 2.8 Hz), 133.14, 132.92, 131.27, 129.63, 128.79,
127.77 (d, J = 8.0 Hz), 127.71, 121.56, 121.48, 115.61 (d, J =
22.5 Hz), 9.27 ppm. MS: m/z (%) = 454 (19), 452 (89), 450 (48),
347 (32), 314 (71), 312 (37), 274 (25), 271 (28), 267 (100), 239 (28),
232 (44), 230 (22), 207 (56), 198 (40), 196 (20), 157 (47), 152 (76),
129 (32), 95 (21), 77 (60), 51 (24). HRMS: calcd. for
C22H18FN4OSe [M + H]+ 453.0630; found 453.0647.
5-Methyl-N-(4-nitrophenyl)-1-[2-(phenylselanyl)phenyl]-1H-1,2,3-tri-
azole-4-carboxamide (3k): Yield: 0.085 g (59%); white solid; m.p.
N-(4-Methoxyphenyl)-5-methyl-1-[2-(phenylselanyl)phenyl]-1H-
1,2,3-triazole-4-carboxamide (3f): Yield: 0.100 g (72%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 9.03 (s, 1 H), 7.64 (d, J = 8.9 Hz,
1
176–177 °C. H NMR (CDCl3, 400 MHz): δ = 9.46 (s, 1 H), 8.25
(d, J = 9.1 Hz, 2 H), 7.91 (d, J = 9.1 Hz, 2 H), 7.48–7.30 (m, 9 H),
Eur. J. Org. Chem. 2014, 1059–1065
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. Alves et al.
FULL PAPER
2.53 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.29,
143.58, 143.50, 139.27, 137.43, 135.10, 134.74, 133.25, 132.83,
131.46, 129.68, 128.85, 127.93, 127.71, 127.61, 125.08, 119.08,
9.33 ppm. MS: m/z (%) = 481 (23), 480 (26), 479 (100), 477 (55),
374 (53), 372 (27), 359 (25), 357 (14), 314 (37), 312 (21), 294 (92),
286 (29), 270 (31), 231 (44), 220 (20), 207 (68), 206 (60), 198 (23),
179 (10), 157 (47), 117 (14), 105 (18), 103 (20), 102 (19), 77 (56),
76 (17), 67 (14), 55 (13). HRMS: calcd. for C22H18N5O3Se [M +
H]+ 480.0575; found 480.0570.
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[2]
[3]
5-Methyl-N-phenyl-1-[2-(p-tolylselanyl)phenyl]-1H-1,2,3-triazole-
4-carboxamide (3l): Yield: 0.090 g (67%); white solid; m.p. 113–
1
114 °C. H NMR (CDCl3, 400 MHz): δ = 9.12 (s, 1 H), 7.72 (d, J
= 7.7 Hz, 2 H), 7.39–7.25 (m, 8 H), 7.13 (t, J = 9.5 Hz, 3 H), 2.53
(s, 3 H), 2.33 (s, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
159.06, 139.13, 138.40, 138.01, 137.66, 135.60, 134.47, 133.55,
132.36, 131.10, 130.44, 128.92, 127.60, 127.36, 124.13, 123.60,
119.70, 21.10, 9.26 ppm. MS: m/z (%) = 450 (12), 448 (54), 328
(37), 285 (20), 249 (100), 234 (22), 221 (48), 204 (16), 152 (27), 129
(16), 91 (35), 77 (37), 65 (22). HRMS: calcd. for C23H21N4OSe [M
+ H]+ 449.0881; found 449.0897.
[4]
[5]
1-[2-(4-Chlorophenylselanyl)phenyl]-5-methyl-N-phenyl-1H-1,2,3-tri-
azole-4-carboxamide (3m): Yield: 0.114 g (81%); white solid; m.p.
1
72–73 °C. H NMR (CDCl3, 400 MHz): δ = 9.11 (s, 1 H), 7.72 (d,
J = 8.1 Hz, 2 H), 7.43–7.31 (m, 8 H), 7.25 (d, J = 8.4 Hz, 2 H),
7.14 (t, J = 7.4 Hz, 1 H), 2.53 (s, 3 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 158.98, 138.36, 138.07, 137.60, 136.22, 135.15,
135.06, 133.22, 132.22, 131.33, 129.78, 128.93, 128.12, 127.78,
126.02, 124.19, 119.72, 9.29 ppm. MS: m/z (%) = 470 (21), 468 (44),
348 (18), 249 (75), 241 (23), 232 (18), 157 (19), 152 (32), 97 (35),
85 (50), 77 (34), 71 (67), 57 (100), 43 (60). HRMS: calcd. for
C22H18ClN4OSe [M + H]+ 469.0334; found 469.0338.
[6]
[7]
5-Methyl-N-phenyl-1-[4-(phenylselanyl)phenyl]-1H-1,2,3-triazole-
4-carboxamide (3n): The mixture of regioisomers was obtained in
a 6:1 ratio, as determined by 1H NMR analysis. Yield: 0.121 g
(93 %); pale yellow solid; m.p. 147–148 °C. 1H NMR (CDCl3,
400 MHz): δ = 9.06 (s, 1, H), 7.70 (d, J = 7.6 Hz, 2, H), 7.62–7.59
(m, 2, H), 7.53 (d, J = 8.5 Hz, 2, H), 7.39–7.31 (m, 7, H), 7.14 (t,
J = 7.4 Hz, 1, H), 2.66 (s, 3, H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 159.04, 138.86, 137.55, 135.56, 134.69, 133.79, 132.05, 129.72,
129.02, 128.77, 128.52, 126.69, 125.70, 124.28, 119.72, 9.80 ppm.
MS: m/z (%) = 434 (37), 432 (19), 314 (35), 287 (14), 286 (26), 284
(17), 249 (20), 234 (18), 133 (27), 232 (41), 220 (20), 221 (15), 207
(100), 206 (31), 169 (25), 157 (29), 153 (18), 152 (41), 130 (19), 77
(52), 65 (11), 51 (19), 44 (34), 40 (24). HRMS: calcd. for
C22H19N4OSe [M + H]+ 435.0724; found 435.0728.
[8]
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Acknowledgments
[10]
We are grateful to Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior (CAPES), Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq) (Grant 473165/2012-0), Fun-
dação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
(09/07281-0), and Fundação de Amparo à Pesquisa do Estado do
Rio Grande do Sul (FAPERGS) for financial support. Prof. Sidnei
Moura e Silva of the Biotechnology Laboratory of Natural and
Synthetic Products, Biotechnology Institute – UCS – Caxias do
Sul – RS, is acknowledged for the HRMS analysis.
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Received: October 11, 2013
Published Online: December 6, 2013
Eur. J. Org. Chem. 2014, 1059–1065
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