Synthesis of [(arylselanyl)alkyl]-1,2,3-triazoles by copper-catalyzed 1,3-dipolar cycloaddition of (arylselanyl)alkynes with benzyl azides

Article abstract of DOI:10.1055/s-0031-1291135

In the presence of catalytic amounts of copper salts and sodium ascorbate, various (arylselanyl)alkynes underwent click-type 1,3-dipolar cycloaddition reactions with a range of benzyl azides bearing electron-withdrawing or electron-donating groups to give a series of novel [(arylselanyl)alkyl]-1,2,3- triazoles. This click chemistry protocol is an efficient method for synthesizing new selenium-nitrogen compounds that are potentially useful in biological studies. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0031-1291135

PAPER
▌1997
paper
Synthesis of [(Arylselanyl)alkyl]-1,2,3-triazoles by Copper-Catalyzed
1,3-Dipolar Cycloaddition of (Arylselanyl)alkynes with Benzyl Azides
Maiara T. Saraiva,a Natália Seus,a Diego de Souza,b Oscar E. D. Rodrigues,*b Márcio W. Paixão,c
Raquel G. Jacob,a Eder J. Lenardão,a Gelson Perin,a Diego Alves*a
a
LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, 96010-900 Pelotas, RS, Brazil
b
Labselen-NanoBio, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
E-mail: rodriguesoed@smail.ufsm.br
c
Laboratório de Síntese de Produtos Naturais, Universidade Federal de São Carlos, São Carlos, SP, Brazil
Fax +55(53)32757533; E-mail: diego.alves@ufpel.edu.br
Received: 21.12.2011; Accepted after revision: 16.04.2012
triazole synthesis and is the most effective reaction of the
type known as click chemistry.15 There remains, however,
a need for an in-depth study of various combinations of
substrates for the synthesis of more highly functionalized
Abstract: In the presence of catalytic amounts of copper salts and
sodium ascorbate, various (arylselanyl)alkynes underwent click-
type 1,3-dipolar cycloaddition reactions with a range of benzyl
azides bearing electron-withdrawing or electron-donating groups to
give a series of novel [(arylselanyl)alkyl]-1,2,3-triazoles. This click and complex 1,2,3-triazoles. Although sulfur-functional-
chemistry protocol is an efficient method for synthesizing new se-
lenium–nitrogen compounds that are potentially useful in biological
studies.
ized 1,2,3-triazoles have been synthesized in high yields
by CuAAC reactions of alkynyl sulfides as the alkyne pre-
cursors,16 the use of alkynyl selenides as substrates in
Key words: heterocycles, azides, alkynes, click reactions, seleni-
um, cycloadditions, catalysis, copper
CuAAC-based syntheses of selenium-containing 1,2,3-
triazoles has not been previously described. Alkynyl sele-
nides have, however, been widely used in many reactions,
such as syntheses of functionalized heterocycles17 or al-
kenes.18
The versatility and usefulness of organoselenium com-
pounds in organic chemistry is well described in many
reviews1 and books.2 Organoselenium compounds are at-
tractive synthetic targets because of their use as ionic liq-
uids,3 their applications in asymmetric catalysis,1b,e,4 their
fluorescence properties,5 and their interesting biological
activities.6 Nitrogen-containing organoselenium com-
pounds form a particular class of molecules that have been
used in various organic transformations, particularly in
asymmetric synthesis.1b,e,4 Consequently, the search for
new and efficient protocols for the synthesis of nitrogen-
functionalized organoselenium compounds, especially
selenium-containing heterocycles, remains an interesting
challenge in organic chemistry.
Many selenium-containing 1,2,3-triazoles have been
synthesized17a,19 and, very recently, a CuAAC protocol
was reported for the synthesis of arylseleno-1,2,3-tri-
azoles in excellent yields under mild conditions from the
corresponding azido aryl selenides.19c However, few
methods based on CuAAC have been reported for the syn-
thesis of organoselenium-functionalized triazoles and this
type of reaction has not been explored in detail. With this
background, and with our interest in applying the CuAAC
protocol for the synthesis of organoselenium-functional-
ized triazoles, we examined the copper-catalyzed 1,3-di-
polar cycloaddition reactions of alkynylselenium
compounds 1 with benzyl azides 2 to give the correspond-
ing [(arylselanyl)alkyl]-1,2,3-triazoles 3 (Scheme 1).
Functionalized 1,2,3-triazoles are an important category
of molecules that display a wide spectrum of biological
activities7 and that are widely used in various fields of
chemistry, for example, in the discovery and modulation
of drug candidates,8 in the development of new materials,9
and in the design of new catalysts,10 among others.11 Var-
ious methods are available for the preparation of 1,2,3-tri-
azoles, the most attractive of which involves a thermal
1,3-dipolar cycloaddition of an azide with an alkyne. This
reaction was pioneered by Huisgen12 and was popular-
ized, independently, by Sharpless13 and by Meldal,14 who
discovered a copper-catalyzed protocol for the reaction.
The development of the copper-catalyzed azide–alkyne
cycloaddition (CuAAC) represents a definitive advance in
The normal experimental procedures for reactions of this
type require the generation in situ of copper(I) species
from copper(II) sulfate pentahydrate and sodium ascor-
bate in a 1:2 mixture of tert-butyl alcohol and water.13a For
this reason, we began by studying the reaction of (prop-2-
yn-1-ylselanyl)benzene (1a; 0.3 mmol) with benzyl azide
(2a; 0.3 mmol) in the presence of copper(II) sulfate pen-
tahydrate (1 mol%) and sodium ascorbate (2 mol%) in 1:2
tert-butyl alcohol–water at room temperature. Under
these standard conditions, the desired 1,2,3-triazole 3a
was obtained in 35% yield after 12 hours (Table 1; entry
1). In an attempt to improve the yield of product 3a, we
examined the effects of various copper salts and solvent
systems on the reaction of alkyne 1a, azide 2a, and sodi-
um ascorbate under air for 12 hours (Table 1). We ob-
tained triazole 3a in 89% by using 3 mol% of copper(II)
acetate monohydrate in a 1:1 mixture of tert-butyl alcohol
SYNTHESIS 2012, 44, 1997–2004
Advanced online publication: 25.05.2012
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DOI: 10.1055/s-0031-1291135; Art ID: SS-2011-M1171-OP
© Georg Thieme Verlag Stuttgart · New York

1998
M. T. Saraiva et al.
PAPER
R1
N3
2
H
RSe
R1
n
Cu(OAc)2⋅H2O (3 mol%)
RSe
sodium ascorbate (6 mol%)
H
N
N
n
CH2Cl2/H2O (1:1)
12 h, r.t., air
N
1
3
R = aryl, heteroaryl
1 = H, Me, OMe, Cl, CF3
n = 0, 1, 2, 3
R
Scheme 1 General scheme for the reaction
and water (entry 5), and when we used the same catalyst precursor of triazoles, we examined its reactions with sev-
in a 1:1 mixture of dichloromethane and water,20 we ob- eral substituted benzyl azides under the optimized reac-
tained triazole 3a in 94% yield (entry 7).
tion conditions (Table 2). We found that our protocol
worked well for a wide variety of substituted benzylic and
alkyl azides, giving excellent yields of the desired tri-
azoles.
Table 1 Optimization of the Conditions for the Reaction of Alkyne
1a and Azide 2a
In general, the reactions were insensitive to electronic ef-
fects in the aromatic ring of the azide partner. Benzylic
azides containing electron-donating groups (Me or OMe)
or electron-withdrawing groups (Cl or CF3) on the aro-
matic ring gave excellent yields of the corresponding tri-
azoles 3b–h (Table 2, entries 2–8). When the reaction was
performed with 2-(azidomethyl)naphthalene (2i), the cor-
responding product 3i was obtained in 86% yield (entry
9). Furthermore, selenide 1a reacted smoothly with azido-
methyl phenyl selenide (2j) to give 1,4-bis[(phenylsela-
nyl)methyl]-1H-1,2,3-triazole (3j) in 80% yield (entry
10). Octyl azide and dodecyl azide also reacted efficiently
with selenide 1a to give good yields of the corresponding
triazoles 3k and 3l (entries 11 and 12).
N3
H
Se
2a
copper salt
Se
N
N
sodium ascorbate
H
N
solvent
12 h, r.t., air
3a
1a
Entrya Catalyst (mol%)
Solvent
Yield (%)
1
CuSO4·5H2O (1%)
CuSO4·5H2O (1%)
CuSO4·5H2O (3%)
Cu(OTf)2 (3%)
t-BuOH–H2O (1:2)
t-BuOH–H2O (1:1)
t-BuOH–H2O (1:1)
t-BuOH–H2O (1:1)
t-BuOH–H2O (1:1)
THF–H2O (1:1)
35
55
64
51
89
70
94
75
2
3b
4b
5b
6b
7b
8
We also examined the possibility of performing the reac-
tion with benzyl azide (2a) and various alkynes (Table 3).
(Ethynylselanyl)benzene (1b) reacted efficiently with
azide 2a to give triazole 3m in 84% yield (Table 3; entry
1). When the reaction was performed with the homo-
propargylic selenide 1c or its homologue 1d, the corre-
sponding products 3n and 3o were each obtained in 90%
yield (entries 2 and 3). High yields of the substituted [(ar-
ylselanyl)methyl]-1,2,3-triazoles 3p–s were obtained
from the corresponding substituted aryl propargyl sele-
nides 1e–h (entries 4–7).
Cu(OAc)2·H2O (3%)
Cu(OAc)2·H2O (3%)
Cu(OAc)2·H2O (3%)
Cu(OAc)2·H2O (1%)
CH2Cl2–H2O (1:1)
CH2Cl2–H2O (1:1)
a Reaction conditions: alkyne 1a (0.3 mmol), BnN3 (2a; 0.3 mmol),
sodium ascorbate (2 mol%), mixed solvent (2 mL), r.t., under air, 12
h.
b 6 mol% of sodium ascorbate was used.
In conclusion, we have demonstrated that (arylselanyl)al-
kynes undergo a copper-catalyzed 1,3-dipolar click cyclo-
addition reaction with benzyl azides to give a novel series
of arylselanyl-containing 1,2,3-triazoles selectively and in
high yields under mild conditions. This atom-economic
method provides an efficient way of synthesizing new se-
lenium-containing triazoles, the biological proprieties of
which we are currently evaluating.
An analysis of our results indicated that the best yield of
product 3a was obtained in the presence of copper(II)
acetate (3 mol%) and sodium ascorbate (6 mol%) in a 1:1
mixture of dichloromethane and water at room tempera-
ture under air for 12 hours. To extend the scope of the re-
action of (prop-2-yn-1-ylselanyl)benzene (1a) as a
Synthesis 2012, 44, 1997–2004
© Georg Thieme Verlag Stuttgart · New York

PAPER
[(Arylselanyl)alkyl]-1,2,3-triazoles
1999
Table 3 Syntheses of Triazoles 3m–s
N3
2a
H
RSe
n
Cu(OAc)2⋅H2O (3 mol%)
RSe
sodium ascorbate (6 mol%)
H
n
N
N
CH2Cl2/H2O (1:1)
12 h, r.t., air
N
1b–h
3m–s
Entry
1a
Alkyne
Product (yield)
Se
Se
H
N
N
N
1b
3m (84%)
Se
2
3
Se
H
N
N
N
1c
3n (90%)
Se
Se
H
N
N
N
1d
3o (90%)
4
5
Se
Se
H
N
N
N
1e
3p (88%)
MeO
MeO
Se
Se
H
N
N
N
1f
3q (89%)
Cl
Cl
6
7
Se
Se
H
N
N
N
1g
3r (85%)
S
S
Se
Se
N
H
N
N
1h
3s (81%)
a Reaction conditions: alkynes 1a–h (0.3 mmol), BnN3 (2a; 0.3 mmol), Cu(OAc)2·H2O (3 mol%), sodium ascorbate (6 mol%), (1:1)
CH2Cl2/H2O (2 mL), r.t., under air, 12 h.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1997–2004

2000
M. T. Saraiva et al.
PAPER
Table 2 Syntheses of 1-Benzyl-4-(phenylselanylmethyl)-1H-1,2,3-triazoles 3a–j
R
N3
2a–j
H
Se
Cu(OAc)2⋅H2O (3 mol%)
sodium ascorbate (6 mol%)
R
Se
H
N
N
CH2Cl2/H2O (1:1)
12 h, r.t., air
N
1a
3a–j
Entrya
Azide
Product (yield)
N3
Se
1b
N
N
N
2a
3a (94%)
N3
Se
2
N
N
N
2b
3b (96%)
N3
Se
3
4
N
N
N
2c
3c (94%)
N3
Se
N
N
N
2d
3d (91%)
OMe
N3
Se
5
MeO
N
N
N
2e
3e (95%)
Cl
N3
Se
6
7
Cl
N
N
N
N
N
N
2f
3f (92%)
N3
Se
Cl
Cl
2g
3g (91%)
Synthesis 2012, 44, 1997–2004
© Georg Thieme Verlag Stuttgart · New York

PAPER
[(Arylselanyl)alkyl]-1,2,3-triazoles
2001
Table 2 Syntheses of 1-Benzyl-4-(phenylselanylmethyl)-1H-1,2,3-triazoles 3a–j (continued)
R
N3
2a–j
H
Se
Cu(OAc)2⋅H2O (3 mol%)
sodium ascorbate (6 mol%)
R
Se
H
N
N
CH2Cl2/H2O (1:1)
12 h, r.t., air
N
1a
3a–j
Entrya
Azide
Product (yield)
F3C
CF3
N3
Se
8
N
N
N
2h
2i
3h (85%)
N3
Se
9
N
N
N
3i (86%)
Se
Se
10
Se
N3
N
N
N
N
N
N
N
N
N
2j
3j (80%)
Se
Me(CH2)7N3
2k
11
12
(CH2)7Me
3k (77%)
Se
Me(CH2)11N3
2l
(CH2)11Me
3l (74%)
a Reaction conditions: alkyne 1a (0.3 mmol), azide 2a–l (0.3 mmol), Cu(OAc)2·H2O (3 mol%), sodium ascorbate (6 mol%), 1:1 CH2Cl2–H2O
(2 mL), r.t., under air, 12 h.
b At the 5-mmol scale, this reaction gave 3a in 90% yield.
4-[(Arylselanyl)alkyl]-1-benzyl-1,2,3-triazoles 3a–s; General
1H NMR spectra were recorded in CDCl3 at 400 MHz on a Bruker
DPX-400 NMR spectrometer. Chemical shifts are reported in ppm
relative to TMS as an external standard. 13C NMR spectra were re-
corded in CDCl3 at 100 MHz on a Bruker DPX-400 NMR spec-
trometer. Chemical shifts are reported in ppm relative to the solvent
peak of CDCl3. Mass spectra were recorded on a Shimadzu GCMS-
QP2010 mass spectrometer. Column chromatography was per-
formed on Merck silica gel (230–400 mesh). TLC was performed
on Merck silica gel GF254 (0.25 mm thickness) and the plates were
visualized by UV radiation or by staining with I2 vapor or acidic
vanillin. All solvents were used as purchased unless otherwise not-
ed. Arylselanyl alkynes17b,21 and organic azides22 were prepared ac-
cording to the methods reported in the literature.
Method
Azide 2 (0.3 mmol) and H2O (0.5 mL) were added to a soln of al-
kyne 1 (0.3 mmol) in CH2Cl2 (1.0 mL). A fresh soln of sodium
ascorbate (6 mol%) and Cu(OAc)2·H2O (3 mol%) in H2O (0.5 mL)
was added and the mixture was stirred under air for 12 h. Brine (3
mL) was then added and the mixture was extracted with CH2Cl2
(3 × 5 mL). The organic layers were combined, washed with brine
(3 mL), and dried (MgSO4). The solvent was removed under vacu-
um and the product was isolated by column chromatography (silica
gel, hexane–EtOAc).
1-Benzyl-4-[(phenylselanyl)methyl]-1H-1,2,3-triazole (3a)
Yield: 0.093 g (94%); pale yellow solid; mp 35–36 °C.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 2 H), 7.36–7.32 (m,
3 H), 7.20–7.14 (m, 5 H), 7.08 (s, 1 H), 5.41 (s, 2 H), 4.12 (s, 2 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1997–2004

2002
M. T. Saraiva et al.
PAPER
13C NMR (100 MHz, CDCl3): δ = 145.88, 134.63, 133.43, 129.65,
128.98 (2 C), 128.59, 127.87, 127.35, 121.64, 53.99, 20.66.
1-(4-Chlorobenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3f)
Yield: 0.100 g (92%); pale gray solid; mp 43–44 °C.
MS: m/z (%) = 329 (7), 157 (3), 144 (38), 117 (8), 104 (10), 91
(100), 77 (10), 65 (13).
1H NMR (400 MHz, CDCl3): δ = 7.41–7.40 (m, 2 H), 7.29 (d,
J = 8.2 Hz, 2 H), 7.20–7.15 (m, 3 H), 7.09–7.07 (m, 3 H), 5.36 (s, 2
H), 4.12 (s, 2 H).
Anal. Calcd for C16H15N3Se: C, 58.54; H, 4.61; N, 12.80. Found: C,
58.94; H, 4.59; N, 12.54.
13C NMR (100 MHz, CDCl3): δ = 146.00, 134.60, 133.32, 133.17,
1-(4-Methylbenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3b)
129.61, 129.13 (2C), 128.94, 127.31, 121.60, 53.15, 20.49.
MS: m/z (%) = 365 (6), 363 (13), 180 (12), 178 (34), 157 (5), 143
(16), 127 (33), 125 (100), 115 (9), 89 (16), 85 (9), 77 (10), 57 (17).
Yield: 0.099 g (96%); white solid; mp 43–44 °C.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 2 H), 7.19–7.12 (m,
5 H), 7.07–7.05 (m, 3 H), 5.35 (s, 2 H), 4.11 (s, 2 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.82, 138.51, 133.43, 131.75,
129.65, 129.67, 128.97, 127.96, 127.29, 121.53, 53.85, 20.99,
20.74.
Anal. Calcd for C16H14ClN3Se: C, 52.98; H, 3.89; N, 11.58. Found:
C, 52.36; H, 3.96; N, 11.80.
1-(2-Chlorobenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3g)
Yield: 0.099 g (91%); pale gray solid; mp 41–43 °C.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.39 (m, 3 H), 7.30–7.17 (m,
6 H), 7.06 (d, J = 7.3 Hz, 1 H), 5.55 (s, 2 H), 4.14 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 145.90, 133.53, 133.43, 132.59,
130.17, 130.06, 129.85, 129.76, 129.00, 127.50, 127.39, 121.96,
51.26, 20.67.
MS: m/z (%) = 343 (10), 341 (5), 158 (35), 105 (100), 79 (9), 77
(13), 51 (3), 43 (2).
Anal. Calcd for C17H17N3Se: C, 59.65; H, 5.01; N, 12.28. Found: C,
59.90; H, 5.03; N, 12.17.
1-(3-Methylbenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3c)
Yield: 0.097 g (94%); white solid; mp 41–43 °C.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 2 H), 7.26–7.14 (m,
5 H), 7.08 (s, 1 H), 7.00 (s, 1 H), 6.97 (d, J = 7.5 Hz, 1 H), 5.37 (s,
2 H), 4.13 (s, 2 H), 2.33 (s, 3 H).
MS: m/z (%) = 365 (6), 363 (14), 180 (15), 178 (45), 157 (6), 143
(18), 127 (32), 125 (100), 115 (12), 89 (19), 77 (11).
Anal. Calcd for C16H14ClN3Se: C, 52.98; H, 3.89; N, 11.58. Found:
C, 52.96; H, 3.69; N, 11.52.
13C NMR (100 MHz, CDCl3): δ = 145.79, 138.79, 134.49, 133.36,
129.69, 129.33, 128.96, 128.86, 128.61, 127.31, 124.96, 121.62,
53.99, 21.23, 20.67.
4-[(Phenylselanyl)methyl]-1-[3-(trifluoromethyl)benzyl]-1H-
1,2,3-triazole (3h)
Yield: 0.101 g (85%); white solid; mp 58–60 °C.
1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 7.8 Hz, 1 H), 7.52–
7.32 (m, 5 H), 7.22–7.13 (m, 3 H), 7.10 (s, 1 H), 5.48 (s, 2 H), 4.15
(s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 146.33, 135.71, 133.48, 131.49
(q, J = 32.5 Hz), 131.15, 129.67, 129.51, 129.01, 127.46, 125.53 (q,
J = 3.7 Hz), 124.57 (q, J = 3.7 Hz), 123.66 (q, J = 272.5 Hz),
121.68, 53.37, 20.54.
MS: m/z (%) = 343 (11), 341 (6), 158 (46), 143 (7), 131 (6), 106 (9),
105 (100), 91 (9), 79 (12), 77 (16).
Anal. Calcd for C17H17N3Se: C, 59.65; H, 5.01; N, 12.28. Found: C,
59.54; H, 5.18; N, 12.58.
1-(2-Methylbenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3d)
Yield: 0.094 g (91%); white solid; mp 32–34 °C.
1H NMR (400 MHz, CDCl3): δ = 7.41–7.39 (m, 2 H), 7.28–7.25 (m,
1 H), 7.20–7.14 (m, 5 H), 7.02 (d, J = 7.6 Hz, 1 H), 6.95 (s, 1 H),
5.41 (s, 2 H), 4.11 (s, 2 H), 2.20 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.61, 136.73, 133.39, 132.45,
130.89, 129.62, 129.20, 128.95 (2 C), 127.32, 126.52, 121.44,
52.17, 20.66, 18.81.
MS: m/z (%) = 397 (19), 395 (10), 212 (62), 172 (22), 159 (100),
119 (6), 109 (19), 77 (13), 66 (1), 51 (5), 41 (3).
Anal. Calcd for C17H14F3N3Se: C, 51.53; H, 3.56; N, 10.60. Found:
C, 51.49; H, 3.97; N, 11.32.
1-(2-Naphthylmethyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3i)
Yield: 0.098 g (86%); pale yellow solid; mp 82–84 °C.
1H NMR (400 MHz, CDCl3): δ = 7.91–7.86 (m, 3 H), 7.53–7.47 (m,
2 H), 7.42 (dd, J = 8.2, 7.1 Hz, 1 H), 7.30–7.28 (m, 3 H), 7.11–7.07
(m, 1 H), 7.03–7.01 (m, 2 H), 6.91 (s, 1 H), 5.85 (s, 2 H), 4.05 (s, 2
H).
MS: m/z (%) = 343 (10), 341 (5), 158 (39), 118 (8), 105 (100), 91
(7), 79 (12), 77 (16), 65 (3), 51 (4).
Anal. Calcd for C17H17N3Se: C, 59.65; H, 5.01; N, 12.28. Found: C,
59.62; H, 5.21; N, 12.34.
1-(4-Methoxybenzyl)-4-[(phenylselanyl)methyl]-1H-1,2,3-tri-
azole (3e)
Yield: 0.102 g (95%); white solid; mp 61–63 °C.
13C NMR (100 MHz, CDCl3): δ = 145.73, 133.98, 133.53, 131.21,
129.93, 129.86, 129.59, 128.86, 128.84, 127.62, 127.28, 127.20,
126.34, 125.26, 122.83, 121.58, 52.14, 20.74.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 2 H), 7.21–7.15 (m,
3 H), 7.13 (d, J = 8.6 Hz, 2 H), 7.05 (s, 1 H), 6.87 (d, J = 8.6 Hz, 2
H), 5.35 (s, 2 H), 4.12 (s, 2 H), 3.80 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.88, 145.75, 133.37, 129.76,
129.46, 128.99, 127.32, 126.62, 121.42, 114.42, 55.30, 53.56,
20.69.
MS: m/z (%) = 380 (3), 379 (11), 377 (6), 194 (29), 141 (100), 115
(19), 77 (4), 66 (2), 51 (2).
Anal. Calcd for C20H17N3Se: C, 63.49; H, 4.53; N, 11.11. Found: C,
63.07; H, 4.51; N, 10.85.
1,4-Bis[(phenylselanyl)methyl]-1H-1,2,3-triazole (3j)
Yield: 0.098 g (80%); pale yellow solid; mp 45–47 °C.
1H NMR (400 MHz, CDCl3): δ = 7.46–7.43 (m, 2 H), 7.41–7.38 (m,
2 H), 7.33–7.29 (m, 1 H), 7.26–7.21 (m, 5 H), 7.19 (s, 1 H), 5.57 (s,
2 H), 4.11 (s, 2 H).
MS: m/z (%) = 359 (4), 174 (11), 121 (100), 91 (5), 78 (6), 77 (9),
65 (2), 57 (3), 43 (4).
Anal. Calcd for C17H17N3OSe: C, 56.99; H, 4.78; N, 11.73. Found:
C, 56.98; H, 5.18; N, 11.79.
13C NMR (100 MHz, CDCl3): δ = 146.24, 134.57, 133.10, 129.95,
129.51, 129.09, 128.80, 127.47, 127.32, 121.55, 44.50, 20.50.
Synthesis 2012, 44, 1997–2004
© Georg Thieme Verlag Stuttgart · New York

PAPER
[(Arylselanyl)alkyl]-1,2,3-triazoles
2003
MS: m/z (%) = 410 (7), 409 (22), 408 (5), 407 (21), 224 (16), 197
(12), 195 (40), 171 (15), 157 (88), 155 (46), 144 (28), 143 (28), 116
(30), 115 (33), 91 (69), 77 (61), 67 (66), 66 (100), 65 (12), 51 (23),
41 (29).
13C NMR (100 MHz, CDCl3): δ = 147.41, 134.81, 132.52, 130.09,
129.03, 128.99, 128.61, 127.92, 126.74, 120.76, 53.95, 29.61,
27.04, 25.46.
MS: m/z (%) = 357 (5), 200 (25), 173 (21), 91 (100), 77 (5), 65 (9),
Anal. Calcd for C16H15N3Se2: C, 47.19; H, 3.71; N, 10.32. Found:
C, 46.83; H, 3.57; N, 10.48.
53 (3).
Anal. Calcd for C18H19N3Se: C, 60.67; H, 5.37; N, 11.79. Found: C,
60.99; H, 5.73; N, 11.95.
1-Octyl-4-[(phenylselanyl)methyl]-1H-1,2,3-triazole (3k)
Yield: 0.081 g (77%); white solid; mp 40–42 °C.
1-Benzyl-4-[(4-tolylselanyl)methyl]-1H-1,2,3-triazole (3p)
Yield: 0.091 g (88%); pale yellow solid; mp 65–67 °C.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.16 (m, 7 H), 7.04–6.95 (m,
3 H), 5.42 (s, 2 H), 4.08 (s, 2 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.97, 137.47, 134.63, 133.93,
129.77, 128.95, 128.56, 127.86, 125.72, 121.60, 53.95, 21.02,
20.91.
1H NMR (400 MHz, CDCl3): δ = 7.49–7.46 (m, 2 H), 7.26–7.24 (m,
3 H), 7.17 (s, 1 H), 4.24 (t, J = 7.2 Hz, 2 H), 4.17 (s, 2 H), 1.81 (quin,
J = 7.2 Hz, 2 H), 1.31–1.26 (m, 10 H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.14, 132.97, 129.63, 128.75,
127.04, 121.18, 49.95, 31.36, 29.90, 28.68, 28.60, 26.09, 22.25,
20.37, 13.69.
MS: m/z (%) = 352 (28), 351 (62), 349 (35), 166 (100), 157 (22),
155 (12), 126 (11), 110 (10).
MS: m/z (%) = 343 (9), 172 (5), 144 (37), 117 (9), 92 (11), 91 (100),
85 (13), 71 (20), 57 (27).
Anal. Calcd for C17H25N3Se: C, 58.28; H, 7.19; N, 11.99. Found: C,
58.93; H, 7.55; N, 12.19.
Anal. Calcd for C17H17N3Se: C, 59.65; H, 5.01; N, 12.28. Found: C,
59.31; H, 5.65; N, 12.40.
1-Dodecyl-4-[(phenylselanyl)methyl]-1H-1,2,3-triazole (3l)
1-Benzyl-4-{[(4-methoxyphenyl)selanyl]methyl}-1H-1,2,3-tri-
azole (3q)
Yield: 0.091 g (74%); white solid; mp 52–53 °C.
1H NMR (400 MHz, CDCl3): δ = 7.49–7.46 (m, 2 H), 7.26–7.24 (m,
3 H), 7.17 (s, 1 H), 4.24 (t, J = 7.2 Hz, 2 H), 4.17 (s, 2 H), 1.81 (quin,
J = 7.2 Hz, 2 H), 1.32–1.26 (m, 18 H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.46, 133.30, 129.96, 129.08,
127.36, 121.51, 50.28, 31.89, 30.23, 29.58 (2 C), 29.50, 29.36,
29.31, 28.97, 26.43, 22.66, 20.70, 14.07.
Yield: 0.096 g (89%); white solid; mp 70–72 °C.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.29 (m, 5 H), 7.19–7.15 (m,
2 H), 7.00 (s, 1 H), 6.69 (d, J = 8.7 Hz, 2 H), 5.42 (s, 2 H), 4.03 (s,
2 H), 3.75 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.54, 145.90, 136.30, 134.63,
128.90, 128.50, 127.79, 121.52, 119.31, 114.61, 55.11, 53.87,
21.43.
MS: m/z (%) = 407 (39), 406 (16), 405 (24), 182 (6), 223 (17), 222
(100), 158 (10), 157 (16), 110 (12).
MS: m/z (%) = 359 (15), 149 (17), 144 (46), 127 (10), 108 (13), 97
(15), 91 (100), 83 (16), 77 (6), 57 (66).
Anal. Calcd for C21H33N3Se: C, 62.05; H, 8.18; N, 10.34. Found: C,
62.22; H, 8.27; N, 10.34.
Anal. Calcd for C17H17N3OSe: C, 56.99; H, 4.78; N, 11.73. Found:
C, 56.56; H, 5.69; N, 11.69.
1-Benzyl-4-(phenylselanyl)-1H-1,2,3-triazole (3m)
Yield: 0.079 g (84%); yellow solid; mp 56–58 °C.
1H NMR (400 MHz, CDCl3): δ = 7.52 (s, 1 H), 7.44–7.41 (m, 2 H),
7.36–7.32 (m, 3 H), 7.25–7.22 (m, 2 H), 7.20–7.17 (m, 3 H), 5.50
(s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 134.39, 132.71, 131.59, 130.70,
129.22, 129.17, 128.86, 128.26, 128.09, 127.21, 54.34.
1-Benzyl-4-{[(4-chlorophenyl)selanyl]methyl}-1H-1,2,3-tri-
azole (3r)
Yield: 0.093 g (85%); white solid; mp 68–70 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.30 (m, 5 H), 7.21–7.10 (m,
4 H), 7.07 (s, 1 H), 5.44 (s, 2 H), 4.11 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 145.57, 135.01, 134.49, 133.77,
129.16, 129.08, 128.75, 127.94, 127.52, 121.60, 54.08, 20.92.
MS: m/z (%) = 315 (8), 286 (23), 284 (13), 206 (14), 169 (13), 130
(29), 103 (20), 91 (100), 77 (21), 65 (27), 51 (13).
MS: m/z (%) = 365 (3), 363 (8), 144 (54), 117 (9), 104 (10), 91
(100), 77 (4), 65 (11).
Anal. Calcd for C15H13N3Se: C, 57.33; H, 4.17; N, 13.37. Found: C,
57.58; H, 4.26; N, 13.19.
Anal. Calcd for C16H14ClN3Se: C, 52.98; H, 3.89; N, 11.58. Found:
C, 53.50; H, 3.94; N, 11.81.
1-Benzyl-4-[2-(phenylselanyl)ethyl]-1H-1,2,3-triazole (3n)
Yield: 0.093 g (90%); white solid; mp 64–65 °C.
1-Benzyl-4-[(2-thienylselanyl)methyl]-1H-1,2,3-triazole (3s)
Yield: 0.081 g (81%); pale yellow solid; mp 63–65 °C.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.34 (m, 3 H), 7.29–7.18 (m,
3 H), 6.98–6.94 (m, 2 H), 6.82 (dd, J = 5.3, 3.5 Hz, 1 H), 5.43 (s, 2
H), 4.01 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 145.05, 136.35, 134.54, 131.25,
128.88, 128.51, 127.88, 127.85, 122.84, 121.62, 53.88, 23.87.
1H NMR (400 MHz, CDCl3): δ = 7.46–7.44 (m, 2 H), 7.37–7.32 (m,
3 H), 7.23–7.20 (m, 6 H), 5.45 (s, 2 H), 3.18 (t, J = 7.4 Hz, 2 H),
3.08 (t, J = 7.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 146.97, 134.78, 132.70, 129.69,
128.99, 128.97, 128.54, 127.87, 126.88, 121.01, 53.91, 26.72,
26.63.
MS: m/z (%) = 343 (6), 263 (8), 262 (38), 91 (100), 83 (6), 83 (6),
71 (11), 65 (11), 57 (8), 43 (9).
MS: m/z (%) = 335 (5), 256 (3), 172 (13), 144 (48), 117 (9), 104 (9),
99 (12), 91 (100), 85 (27), 71 (85), 69 (17), 57 (58).
Anal. Calcd for C17H17N3Se: C, 59.65; H, 5.01; N, 12.28. Found: C,
58.96; H, 4.60; N, 12.68.
Anal. Calcd for C14H13N3SSe: C, 50.30; H, 3.92; N, 12.57, S 9.59.
Found: C, 49.84; H, 3.65; N, 12.87, S 9.98.
1-Benzyl-4-[3-(phenylselanyl)propyl]-1H-1,2,3-triazole (3o)
Yield: 0.096 g (90%); white solid; mp 69–70 °C.
Acknowledgment
1H NMR (400 MHz, CDCl3): δ = 7.48–7.43 (m, 2 H), 7.40–7.33 (m,
3 H), 7.26–7.20 (m, 5 H), 7.12 (s, 1 H), 5.47 (s, 2 H), 2.92 (t, J = 7.4
Hz, 2 H), 2.81 (t, J = 7.4 Hz, 2 H), 2.05 (quin, J = 7.4 Hz, 2 H).
We are grateful to CAPES, CNPq (473734/2010-9), FINEP, FAPESP
(09/07281-0), and FAPERGS (ARD 10/0130-3) for their financial
support.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1997–2004

2004
M. T. Saraiva et al.
PAPER
585. (e) Parrish, B.; Emrick, T. Bioconjugate Chem. 2007,
18, 263.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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Synthesis 2012, 44, 1997–2004
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