Four-component, one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles bearing 1-(2-phenylselenocyclohexyl) group

Article abstract of DOI:10.1002/jhet.1972

An efficient, one-pot, three-step, regioselective synthesis of 4-substituted 1-(2-phenylselenocyclohexyl)-1,2,3-triazoles, involving in situ generation of l-azido-2-phenylselenocyclohexane has been developed via four-component reaction of phenylselenenyl

Full text of DOI:10.1002/jhet.1972

E222
Four-Component, One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
Bearing 1-(2-Phenylselenocyclohexyl) Group
Vol 51
*
Wusheng Sheng, Shouri Sheng, Jiangbo Zeng, Zhenzhong Huang, and Mingzhong Cai
Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi Normal University,
JiangxiNanchang 330022, People’s Republic of China
*
E-mail: shengsr@jxnu.edu.cn
Received August 23, 2012
DOI 10.1002/jhet.1972
Published online 25 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
An efficient, one-pot, three-step, regioselective synthesis of 4-substituted 1-(2-phenylselenocyclohexyl)-
1,2,3-triazoles, involving in situ generation of l-azido-2-phenylselenocyclohexane has been developed via
four-component reaction of phenylselenenyl bromide, cyclohexene, sodium azide and terminal alkynes
catalyzed by copper iodide in a mixture of DMF/THF (1:1) at room temperature under mild conditions with
simple workup and good yields.
J. Heterocyclic Chem., 51, E222 (2014).
INTRODUCTION
in situ generation of l-azido-2-phenylselenocyclohexane (2)
via reaction of phenylselenenyl bromide and cyclohexene,
subsequent with sodium azide, followed by coupling with
a terminal alkyne, as shown in Scheme 1. These 1,4-
disubstituted 1,2,3-triazoles are not reported in the literature.
1,2,3-Triazoles are one of the most useful heterocycles
[1] and have been widely used in many research fields such
as materials, chemical, and biological sciences [2]. Because
Meldal and Sharpless developed the copper-catalyzed
Huisgen’s 1,3-dipolar cycloaddition reaction of azides with
alkynes [3], “click chemistry” has received growing interest
in the regioselective synthesis of 1,4-disubstituted 1,2,3-
triazoles [4]. Multicomponent reactions (MCRs) are one
of the most useful synthetic methods because they allow
rapid and convergent construction of complex molecules
without the isolation of intermediates [5–7]. Moreover,
this process is especially useful when the reaction inter-
mediates are unstable and difficult to isolate. Therefore,
the development and optimization of new, MCRs to
construct efficiently 1,2,3-triazole libraries from readily
available, diverse and functional starting materials is of
importance in synthesizing new compounds that might
deliver future lead compounds for the pharmaceutical
community. The organoselenium chemistry has played
an important role in organic synthesis [8,9], and the
organoselenium reagents have been increasingly used to
introduce functional groups into organic substrates under
extremely mild conditions. So, the introduction of an
organoselenium moiety into the triazole framework will
be of interest and might be an effective way for the
development of new biological and pharmacological
molecules. Although many MCRs have been recent
explored for the synthesis of 1,2,3-triazoles [10], to our
knowledge, there have been no reports on the synthesis
of 1,2,3-triazole molecules containing an organoselenium
moiety through MCRs method. We report herein a new
and sequential one-pot synthesis of 4-substituted 1-(2-
phenylselenocyclohexyl)-1,2,3-triazoles (4), which involves
RESULTS AND DISCUSSION
Apparently, the formation of l-azido-2-phenylseleno-
cyclohexane (2) in situ is the key for the success of this
protocol. Previously, compound 2 [11] was prepared in
79% yield by stirring a mixture of the cyclohexene with
(diacetoxyiodo)benzene, diphenyl diselenide, and sodium
azide in methylene chloride at RT. However, apart from
the yield of 2 was not high, an excess of (diacetoxyiodo)
benzene and diphenyl diselenide was necessary, which is
problematic in the latter isolation and purification
procedure. Additionally, compound 2 is solvolytically
unstable in solvents such as acetic acid and alcohols [12].
Consequently, its in situ formation is advantageous to
handle it safely and conveniently.
On the basis of these results, together with the literature
report on the electrophilic addition reaction of phenylselenenyl
bromide to cyclohexene [12], as well as varying the reaction
conditions, the best result for the in situ generation of L-
azido-2-phenylselenocyclohexane (2) was conveniently
achieved in 93% yield by simply adding anhydrous
sodium azide and a small amount of sodium iodide to a
solution of phenylselenenyl bromide and cyclohexene in
DMF at RT. In the experiment, an immediate electrophilic
addition of phenylselenenyl bromide to cyclohexene and
subsequent substitution reaction occurred, and the
mixture turned a pale yellow white. Other solvents such
as DMSO, MeCN, and THF, and their combination are
also applicable for this conversion. However, a decrease
© 2014 HeteroCorporation

August 2014
One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
E223
Scheme 1. One-pot synthesis of 4-substituted 1-(2-phenylselenocyclohexyl)-1,2,3-triazoles.
in the product yield of 2 was tested using CH2Cl2 even if the
reaction time was prolonged or at refluxing temperature.
Following successful formation of l-azido-2-phenylseleno-
cyclohexane (2) in situ, one-pot four-component reactions of
phenylselenenyl bromide, cyclohexene, sodium azide, and
terminal alkynes (3) were investigated (Scheme 1). To find
the most suitable conditions for our purpose, we examined a
template reaction involving phenylselenenyl bromide,
cyclohexene, sodium azide, and phenylacetylene (3a) in
various solvents such as DMF, DMSO, THF, MeCN, and
their co-solvents in the presence of copper(I)-catalyst and
organic bases such as triethylamine (Et3N) and diisopropy-
lethylamine (DIPEA) at RT, and the results are summarized
in Table 1.
As can be seen from Table 1, DMF/THF (1:1) mixed
solvent gave best result in the model reaction (Table 1,
entry 5). Thus, DMF/THF was chosen as the typical
solvent in subsequent experiments. It should be pointed
out that organic bases could promote the “click reaction”
(Table 1, entries 6 and 7), which is in accordance with
the reported results [3b]. Especially, DIPEA was found to
be better base to promote the reaction. It was found that
10 mol% of CuI gave best result (Table 1, entry 7). When
15 mol% of CuI was used, the yield of the product 4a was
not improved significantly (Table 1, entry 8). Whereas reduc-
ing the amount of the catalyst CuI to 5 mol% led to a drop of
product 4a to 68% (Table 1, entry 9). In addition, other Cu(I)
catalysts such as CuBr, CuCl, and CuSO4 Á 5H2O/Na
ascorbate were also examined, which showed a significant
decrease in the product yield (Table 1, entries 10 and 12).
Under these optimized conditions, reaction of phenylse-
lenenyl bromide (1.0 equiv) and cyclohexene (1.2 equiv) in
DMF/THF, and subsequently treated with anhydrous
sodium azide (1.2 equiv) and NaI (0.2 equiv) at RT for
1 h, followed by the addition of 3a (1.2 equiv), CuI
(10 mol%), and DIPEA (40 mol%), after stirring at RT for
12h, 1-(2-phenylselenocyclohexyl)-4-phenyl-1,2,3-triazole
(4a) was isolated in 88% yield as an exclusive product in
one-pot, three-step (Table 1, entry 7). The structure of 4a
was confirmed unambiguously by NMR spectroscopy and
from elemental analysis data. The trans stereochemistry in
4a was indicated by two similar doublets of doublets of
doublets with coupling constants of 12.0, 11.2, and 4 Hz,
and 11.2, 11.2, and 4 Hz indicative of equatorial substituents
at CH—Se and CH-triazolyl, respectively. The correlated
13C spectrum indicates the CH—Se absorption at 47.36 ppm
with the corresponding H absorbing at 3.56 ppm, whereas
the CH-triazolyl absorbed at 65.14 ppm and the H at
1
Table 1
4.45 ppm. Besides, the H-NMR spectrum of 4a exhibited a
characteristic singlet at d = 7.67 ppm because of the triazolyl
C5—H proton.
Optimisation of experimental conditions for one-pot process.a
b
Entry
Solvent
Cu(I)
Base
Yield (%)
Finally, the scope of this one-pot method was further
examined using various terminal alkynes. A variety of
terminal alkynes including aryl-, aryloxymethyl-, and n-
butylacetylenes were then subjected to the reaction system
under the aforementioned optimized reaction conditions, to
afford the corresponding 1,4-disubstituted 1,2,3-triazoles
(4a–4k) in good yields (Table 2). As seen from Table 2,
both aromatic and aliphatic acetylenes underwent the
reaction smoothly to give satisfactory results. Moreover,
the transrelationship of the two substituents at CH—Se
and CH-triazolyl was established on the basis of the
coupling constant measured for the anomeric proton.
c
1
2
3
4
5
6
7
8
MeCN
THF
DMSO
DMF
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
DMF/THF (1:1)
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
–
–
–
–
70
70
72
75
80
85
88
89d
68e
78
76
74
c
c
c
c
–
Et3N
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
9
CuI
10
11
12
CuBr
CuCl
CuSO4/Vcf
DIPEA, diisopropylethylamine.
aPhenylselenenyl bromide (1.0 mmol), cyclohexene (1.2 mmol), sodium
azide (1.2 mmol), 3a (1.2 mmol), base (40 mol%), Cu(I) (10 mol%),
solvent (5 mL), RT, 12–15 h.
CONCLUSIONS
bIsolated yield based on phenylselenenyl bromide.
cNo base was used.
In summary, a convenient, one-pot, three-step protocol
has been developed for the preparation of 1,4-disubstituted-
1,2,3-triazoles bearing functional phenylseleno group involving
dCuI (15 mol%) was used.
eCuI (5 mol%) was used.
fVc = Na ascorbate
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E224
W. Sheng, S. Sheng, J. Zeng, Z. Huang, and M. Cai
Vol 51
Table 2
Yields of 4-substituted 1-(2-phenylselenocyclohexyl)-1,2,3-triazoles (4a–4k).
the solvent was removed under reduced pressure. The crude product
was purified by column chromatography on silica gel using (hexane–
ethyl acetate) to afford pure product 4a–4k.
Entry
R
Product
Yield (%)a
1-(2-Phenylselenocyclohexyl)-4-phenyl-1,2,3-triazole (4a).
Pale yellow solid, mp 128–129ꢀC; 1H-NMR: d = 7.79 (d,
J = 7.2 Hz, 2 H), 7.67 (s, 1H), 7.42–7.38 (m, 4H), 7.32–7.28 (m,
1H), 7.20–7.12 (m, 3H), 4.45 (ddd, J = 11.2, 11.2, 4.0 Hz, 1H),
3.56 (ddd, J = 12.0, 11.2, 4.0 Hz, 1H), 2.39 (d, J = 13.6 Hz, 1H),
2.22 (d, J = 13.6 Hz, 1H), 1.99–1.92 (m, 1H), 1.93–1.87 (m,
1H), 1.79–1.77 (m, 1H), 1.64–1.58 (m, 1H), 1.42–1.32 (m, 2H);
13C-NMR: d = 147.16, 135.90, 130.86, 128.88, 128.72, 128.13,
127.94, 126.87, 125.75, 118.80, 65.14, 47.36, 34.93, 34.34,
26.53, 25.02; IR (KBr): n = 3131, 3057, 2936, 2858, 1610,
1578, 1477, 1436, 1371, 1228, 1183, 1075, 1045, 1022, 985,
910, 814, 764, 741, 694 cm–1; Anal. Calcd for C20H21N3Se: C,
62.82; H, 5.54; N, 10.99. Found: C, 62.90; H, 5.60; N, 10.95.
1-(2-Phenylselenocyclohexyl)-4-(4-ethylphenyl)-1,2,3-triazole
(4b). Pale yellow solid, mp 104–105ꢀC; 1H-NMR: d = 7.72 (d,
J = 7.6 Hz, 2H), 7.70 (s, 1H), 7.39–7.38 (m, 2H), 7.23 (d,
J = 8.0 Hz, 2H), 7.17–7.11 (m, 3H), 4.45 (ddd, J = 11.2, 11.2,
4.0 Hz, 1H), 3.55 (ddd, J = 12.0, 11.6, 4.0 Hz, 1H), 2.68 (q,
J = 7.6 Hz, 2H), 2.35 (d, J = 13.6 Hz, 1H), 2.16 (d, J = 10.8 Hz,
1H), 1.98–1.92 (m, 1H), 1.84–1.81 (m, 1H), 1.74–1.68 (m, 1H),
1.57–1.51 (m, 1H), 1.43–1.32 (m, 2H), 1.23 (t, J = 7.6 Hz, 3H);
13C-NMR: d = 147.24, 144.08, 135.99, 128.87, 128.30, 128.21,
128.13, 126.85, 125.77, 118.59, 64.97, 47.32, 34.90, 34.38,
28.69, 26.51, 25.00, 15.57; IR (KBr): n = 3134, 3055, 2934,
2858, 1578, 1498, 1476, 1447, 1416, 1371, 1264, 1225, 1184,
1117, 1075, 1045, 1022, 986, 840, 741, 694 cm–1; Anal. Calcd
for C22H25N3Se: C, 64.38; H, 6.14; N, 10.24. Found: C, 64.45;
H, 6.22; N, 10.30.
1
2
3
4
5
6
7
8
C6H5
4a
4b
4c
4d
4e
4f
4g
4h
4i
88
90
85
86
85
87
88
85
83
84
86
4-EtC6H4
3-FC6H4
C6H5OCH2
2-MeC6H4OCH2
3-MeC6H4OCH2
4-MeC6H4OCH2
4-NO2C6H4OCH2
2-Naphthoxymethyl
2-Cinnamoylphenoxymethyl
n-C4H9
9
10
11
4j
4k
aIsolated yield based on phenylselenenyl bromide.
four-component reaction of phenylselenenyl bromide with
cyclohexene, followed by sodium azide to generate in situ L-
azido-2-phenylselenocyclohexane, which immediately reacted
with terminal alkynes regioselectively in DMF/THF in the
presence of a mixture of DIPEA/CuI. This new one-pot,
three-step process will make it possible to rapidly prepare
compound libraries for drug discovery programs, as it avoids
time-consuming and costly purification protocols of synthetic
intermediates. Further investigations based on these new
functional 1,4-disubstituted-1,2,3-triazoles with phenylseleno
group are now in progress.
1-(2-Phenylselenocyclohexyl)-4-(3-fluorophenyl)-1,2,3-triazole
(4c). Pale yellow solid, mp 103–104ꢀC; 1H-NMR: d = 7.64
(s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 9.6 Hz, 1H),
7.38–7.34 (m, 3H), 7.21–7.10 (m, 3H), 7.03 (t, J = 7.6 Hz,
1H), 4.47 (ddd, J = 10.8, 11.2, 4.0 Hz, 1H), 3.57 (ddd,
J = 11.6, 11.6, 4.0 Hz, 1H), 2.43 (d, J = 13.6 Hz, 1H), 2.25 (d,
J = 13.2 Hz, 1H), 2.02–1.91 (m, 2H), 1.84–1.81 (m, 1H),
1.67–1.58 (m, 1H), 1.51–1.37 (m, 2H); 13C-NMR: d = 164.37,
146.09, 135.74, 133.05, 130.31, 128.89, 128.13, 126.89,
121.35, 119.14, 114.82, 112.76, 65.44, 47.37, 34.93, 34.29,
26.55, 25.03; IR (KBr): n = 3133, 3071, 2936, 2858, 1619,
1589, 1477, 1438, 1371, 1229, 1199, 1154, 1081, 1044,
1022, 979, 963, 785, 741, 689 cm–1; Anal. Calcd for
C20H20FN3Se: C, 60.00; H, 5.04; N, 10.50. Found: C, 60.07;
H, 5.10; N, 10.56.
1-(2-Phenylselenocyclohexyl)-4-phenoxymethyl-1,2,3-triazole
(4d). Yellow oil; 1H-NMR: d = 7.53 (s, 1H), 7.40–7.37 (m, 2H),
7.32–7.23 (m, 3H), 7.20–7.18 (m, 2H), 7.00–6.95 (m, 3H), 5.13 (s,
2H), 4.40 (ddd, J = 11.6, 11.6, 4.0 Hz, 1H), 3.53 (ddd, J = 12.0,
11.6, 4.0Hz, 1H), 2.39–2.37 (m, 1H), 2.20–2.17 (m, 1H), 1.98–
1.88 (m, 2H), 1.80–1.78 (m, 1H), 1.67–1.54 (m, 1H), 1.43–1.32
(m, 2H); 13C-NMR: d = 158.31, 143.62, 135.82, 129.55, 128.88,
128.10, 126.85, 121.79, 121.22, 114.81, 65.21, 62.17, 47.36,
34.82, 34.29, 26.51, 24.99; IR (film): n = 3057, 2935, 2858,
1599, 1495, 1241, 1174, 1079, 1034, 855, 753, 692 cm–1; Anal.
Calcd for C21H23N3OSe: C, 61.16; H, 5.62; N, 10.19. Found: C,
61.23; H, 5.67; N, 10.23.
EXPERIMENTAL
1H-NMR (400 MHz) and 13C-NMR (100 MHz) spectra were
recorded on a Bruker Avance (400 MHz) spectrometer (Bruker
Corp., Billerica, MA), using CDCl3 as the solvent and TMS as
an internal standard. FTIR spectra were taken on a Perkin-Elmer
SP One FTIR spectrophotometer (PerkinElmer, Inc., Waltham,
MA). Microanalyses were performed with a Carlo Erba 1106
Elemental Analyzer (Milan, Italy). Phenylselenenyl bromide [13]
was prepared according to procedures in literature. Terminal
alkynes (3e–3m) were prepared by alkylation of the corresponding
phenols with propargyl bromide in the presence of K2CO3 in
acetone under refluxing conditions using similar method described
in the literature [14]. The other terminal alkynes were obtained from
commercial suppliers (Aldrich, USA and Shanghai Chemical
Company, China) and used without purification prior to use. All
organic solvents were dried by standard methods.
General procedure for the one-pot preparation of 4-
substituted 1-(2-phenylselenocyclohexyl)-1,2,3-triazoles (4a–4k).
To a stirred solution of phenylselenenyl bromide (1.0 mmol) in DMF/
THF (5 mL, 1:1, v/v) was added cyclohexene (1.2 mmol), followed by
the addition of anhydrous sodium azide (1.2 mmol) and NaI
(0.2 mmol). An immediate exothermic reaction occurred, and the
mixture turned a pale yellow white. After stirring for 1 h, terminal
alkyne (1.2 mmol), CuI (10 mol%), and DIPEA (0.052 mL,
0.4 mmol) were added, and the reaction mixture was stirred at RT for
12 h. After completion of the reaction (as monitored by TLC), the
reaction mixture was filtered through a short pad of Celite 545, and
1-(2-Phenylselenocyclohexyl)-4-(2-methylphenoxymethyl)-
1,2,3-triazole (4e).
Yellow oil; 1H-NMR: d = 7.71 (s, 1H),
7.56–7.50 (m, 2H), 7.41–7.37 (m, 2H), 7.20–7.14 (m, 3H),
6.95–6.87 (m, 2H), 5.15 (s, 2H), 4.37 (ddd, J = 11.6, 11.6,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

August 2014
One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
E225
4.0 Hz, 1H), 3.54 (ddd, J = 12.0, 11.6, 4.0 Hz, 1H), 2.40 (d,
J = 13.4 Hz, 1H), 2.24 (s, 3H), 2.20 (d, J = 13.4 Hz, 1H),
2.00–1.88 (m, 3H), 1.81–1.78 (m, 1H), 1.69–1.58 (m, 1H),
1.46–1.37 (m, 2H); 13C-NMR: d = 167.72, 156.24, 143.34,
135.65, 132.41, 130.95, 128.82, 128.18, 126.87, 122.48,
121.13, 111.62, 65.55, 61.90, 47.15, 34.67, 34.16, 26.40,
24.91, 19.26; IR (film): n = 3058, 2957, 2862, 1600, 1494,
1462, 1383, 1287, 1244, 1122, 1073, 744, 694 cm–1; Anal.
Calcd for C22H25N3OSe: C, 61.97; H, 5.91; N, 9.85.
Found: C, 61.94; H, 5.85; N, 9.90.
1358, 1257, 1215, 1179, 914, 839, 812, 743, 693 cm–1; Anal.
Calcd for C25H25N3OSe: C, 64.93; H, 5.45; N, 9.09. Found: C,
64.88; H, 5.52; N, 9.14.
1-(2-Phenylselenocyclohexyl)-4-(2-cinnamoylphenoxymethyl)-
1,2,3-triazole (4j). Yellow oil; 1H-NMR: d = 7.68–7.66 (m, 2H),
7.63 (s, 1H), 7.56–7.48 (m, 5H), 7.44 (s, 1H), 7.40–7.37 (m, 5H),
7.31–7.29 (m, 3H), 5.22 (s, 2H), 4.10 (ddd, J = 11.6, 11.6, 4.0 Hz,
1H), 3.19 (ddd, J = 12.0, 11.2, 4.0 Hz, 1H), 2.27–1.84 (m, 3H),
174–1.70 (m, 1H), 1.57–1.38 (m, 3H); 13C-NMR: d = 192.62,
156.85, 143.29, 142.36, 135.83, 135.00, 133.23, 130.60, 130.30,
129.75, 129.06, 128.81, 128.44, 128.03, 127.37, 126.75, 121.54,
121.38, 112.97, 64.94, 63.36, 47.04, 34.52, 34.14, 26.31, 24.86;
IR (film): n = 3058, 2936, 2859, 1723, 1658, 1602, 1482, 1450,
1333, 1290, 1240, 1205, 1115, 756, 696 cm–1; Anal. Calcd for
C30H29N3O2Se: C, 66.42; H, 5.39; N, 7.75. Found: C, 66.47; H,
5.46; N, 7.80.
1-(2-Phenylselenocyclohexyl)-4-(3-methylphenoxymethyl)-
1,2,3-triazole (4f).
Yellow oil; 1H-NMR: d = 7.52 (s, 1H),
7.37 (d, J = 7.2 Hz, 2H), 7.26–7.15 (m, 4H), 6.80–6.77 (m,
3H), 5.11 (s, 2H), 4.39 (ddd, J = 11.6, 11.2, 4.0 Hz, 1H), 3.52
(ddd, J = 12.0, 11.6, 4.0 Hz, 1H), 2.38–3.27 (m, 4H), 2.18–
2.15 (m, 1H), 1.99–1.86 (m, 2H), 1.79–1.73 (m, 1H), 1.62–
1.52 (m, 1H), 1.43–1.34 (m, 2H); 13C-NMR: d = 158.33,
143.70, 139.60, 135.86, 129.30, 128.90, 128.12, 126.81,
122.09, 121.88, 115.68, 111.68, 65.22, 62.10, 47.34, 34.81,
34.28, 26.50, 24.98, 21.59; IR (film): n = 3054, 2936, 2858,
1599, 1586, 1489, 1447, 1289, 1259, 1156, 1043, 1022, 778,
742, 691 cm–1; Anal. Calcd for C22H25N3OSe: C, 61.97; H,
5.91; N, 9.85. Found: C, 61.92; H, 5.96; N, 9.91.
1-(2-Phenylselenocyclohexyl)-4-(n-butyl)-1,2,3-triazole (4k).
1
Yellow oil; H-NMR: d = 7.75 (s, 1H), 7.63–7.58 (m, 2H), 7.35–
7.26 (m, 3H), 4.38–4.21 (m, 1H), 3.36 (ddd, J= 9.6, 9.6, 4.0 Hz,
1H), 2.99–2.87 (m, 2H), 2.66–2.63 (m, 1H), 2.42–2.41 (m, 1H),
2.20–2.08 (m, 2H), 176–1.61 (m, 3H), 1.50–1.28 (m, 5H),
0.96 (t, J = 7.6 Hz, 3H); 13C-NMR: d = 147.93, 135.28, 128.88,
127.92, 127.23, 118.86, 65.09, 47.43, 34.88, 34.33, 31.90,
26.54, 25.67, 25.01, 22.58, 14.01; IR (film): n = 3070, 2933,
2858, 1580, 1476, 1438, 1381, 1255, 1188, 1115, 1068, 1035,
961, 865, 742, 695 cm–1; Anal. Calcd for C18H25N3Se: C,
59.66; H, 6.95; N, 11.60. Found: C, 59.72; H, 6.98; N, 11.64.
1-(2-Phenylselenocyclohexyl)-4-(4-methylphenoxymethyl)-
1,2,3-triazole (4g).
Yellow oil; 1H-NMR: d = 7.51 (s, 1H),
7.37 (d, J = 8.0 Hz, 2H), 7.27–7.17 (m, 3H), 7.09 (d,
J = 8.0 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 5.10 (s, 2H), 4.38
(ddd, J = 11.6, 11.6, 4.0 Hz, 1H), 3.50 (ddd, J = 12.0, 11.6,
4.0 Hz, 1H), 2.40–3.37 (m, 1H), 2.27 (s, 3H), 2.18–2.15 (m, 1H),
1.90–1.84 (m, 2H), 1.75–1.68 (m, 1H), 1.60–1.56 (m, 1H),
1.45–1.30 (m, 2H); 13C-NMR: d = 167.70, 156.17, 143.53,
135.77, 130.98, 128.83, 128.10, 126.85, 122.11, 114.75,
65.45, 62.16, 47.24, 34.76, 34.24, 26.45, 24.94, 20.48; IR
(film): n = 3056, 2934, 2859, 1585, 1510, 1448, 1289, 1241,
1177, 1121, 1073, 1047, 1022, 817, 742, 693 cm–1; Anal.
Calcd for C22H25N3OSe: C, 61.97; H, 5.91; N, 9.85. Found:
C, 61.93; H, 5.95; N, 9.89.
Acknowledgments. The authors thank the financial support from
the Natural Science Foundation of China (No. 21062007), and the
Research Program of Jiangxi Province Department of Education
(Nos. GJJ10385, GJJ11380, GJJ12201).
REFERENCES AND NOTES
1-(2-Phenylselenocyclohexyl)-4-(4-nitrophenoxymethyl)-
1,2,3-triazole (4h).
Yellow oil; 1H-NMR: d = 8.18 (d,
[1] Fan, W. Q.; Katritzky, A. R. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, C. W. V., Eds.;
Elsevier: Oxford, 1996.
[2] (a) Krasiski, A.; Radi, Z.; Manetsch, R.; Raushel, J.; Taylor,
P.; Sharpless, K. B.; Kolb, H. C. J Am Chem Soc 2005, 127, 6686; (b)
Binder, W. H.; Kluger, C. Curr Org Chem 2006, 10, 1791; (c)
Suijkerbuijk, B. M. J. M.; Aerts, B. N. H.; Dijkstra, H. P.; Lutz, M.;
Spek, A. L.; Koten, G. V.; Gebbink, R. J. M. K. Dalton Trans 2007,
1273.
J = 9.2 Hz, 2H), 7.75–6.70 (m, 1H), 7.52 (s, 1H), 7.36 (d,
J = 6.4 Hz, 2H), 7.21–7.17 (m, 2H), 7.08 (d, J = 9.2 Hz, 2H),
5.25–5.18 (m, 2H), 4.42 (ddd, J = 11.0, 11.2, 4.0 Hz, 1H),
3.53 (ddd, J = 11.6, 11.2, 4.0 Hz, 1H), 2.39–2.36 (m, 1H),
2.21–2.18 (m, 1H), 2.00–1.81 (m, 2H), 1.79–1.74 (m, 1H),
1.72–1.66 (m, 2H), 1.60–1.50 (m, 1H); 13C-NMR:
d = 167.73, 163.25, 141.73, 135.62, 130.92, 128.80, 128.05,
125.87, 122.36, 114.88, 65.52, 62.54, 47.31, 34.76, 34.25,
26.45, 24.93; IR (film): n = 3074, 2958, 2935, 2861, 1593,
1515, 1496, 1342, 1258, 1175, 1113, 1074, 999, 846, 743,
692 cm–1; Anal. Calcd for C21H22N4O3Se: C, 55.15; H,
4.85; N, 12.25. Found: C, 55.19; H, 4.89; N, 12.31.
[3] (a) Tornøe, C.; Christensen, M. Meldal, J Org Chem 2002, 67,
3057; (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew Chem Int Ed 2002, 41, 2596.
[4] For recent reviews, see: (a) Bock, V. D.; Hiemstra, H.; van
Maarseveen, J. H. Eur J Org Chem 2006, 51; (b) Gil, M. V.; Arevalo,
M. G.; Lopez, O. Synthesis 2007, 1589; (c) Moses, J. E.; Moorhouse,
A. D. Chem Soc Rev 2007, 36, 1249; (d) Meldal, M.; Tornøe, C. W.
Chem Rev 2008, 108, 2952; (e) Amblard, F.; Cho, J. H.; Schinazi, R. F.
Chem Rev 2009, 109, 4207; (f) Kappe, C. O.; Van der Eycken, E. Chem
Soc Rev 2010, 39, 1280; (g) Hein, J. E.; Fokin, V. V. Chem Soc Rev
2010, 39, 1302.
[5] For reviews on MCR, see: (a) Armstrong, R. W.; Combs, A.
P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc Chem Res 1996,
29, 123; (b) Ramon, D. J.; Miguel, Y. Angew Chem Int Ed 2005, 44,
1602; (c) Döling, A. Chem Rev 2006, 106, 17; (d) Ganem, B. Acc Chem
Res 2009, 42, 463; (e) Wessjohann, L. A.; Rivera, D. G.; Vercillo, O. E.
Chem Rev 2009, 109, 796; (f) Dotz, K. H.; Stendel, J., Jr. Chem Rev
2009, 109, 3227; (g) Toure, B. B.; Hall, D. G. Chem Rev 2009, 109,
1-(2-Phenylselenocyclohexyl)-4-(2-naphthoxymethyl)-1,2,3-
triazole (4i).
Yellow oil; 1H-NMR: d = 7.76–7.72 (m, 2H),
7.60–7.58 (m, 2H), 7.52 (s, 1H), 7.44–7.40 (m, 1H), 7.36–7.29
(m, 2H), 7.25–7.14 (m, 5H), 5.23 (s, 2H), 4.37 (ddd, J = 11.6,
11.6, 4.0 Hz, 1H), 3.50 (ddd, J = 11.6, 11.2, 4.0 Hz, 1H), 2.35–
2.32 (m, 1H), 2.16–2.12 (m, 1H), 1.98–1.73 (m, 3H), 1.60–
1.50 (m, 1H), 1.43–1.31 (m, 2H); 13C-NMR: d = 156.31,
143.41, 135.85, 134.50, 129.58, 129.35, 129.18, 128.92,
128.12, 127.69, 126.99, 126.52, 123.92, 121.99, 118.90,
107.31, 65.16, 62.24, 47.39, 34.81, 34.30, 26.49, 24.97; IR
(film): n = 3056, 2936, 2858, 1628, 1600, 1510, 1470, 1389,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E226
W. Sheng, S. Sheng, J. Zeng, Z. Huang, and M. Cai
Vol 51
4439; (h) Bonne, D.; Coquerel, Y.; Constantieux, T.; Rodriguez, J.
Tetrahedron Asymmetry 2010, 21, 1085; (i) Eelco, R.; Rachel, S.;
Romano, V. A. O. Angew Chem Int Ed 2011, 50, 6234.
[6] Zhu, J., Bienaymé, H., Eds. Multicomponent Reactions;
Wiley: Weinheim, 2005.
[7] (a) Burke, M. D.; Schreiber, S. L. Angew Chem Int Ed 2004,
43, 46; (b) Spandl, R. J.; Spring, D. R. Org Biomol Chem 2008, 6, 1149.
[8] Paulmier, C., Ed. Selenium Reagents and Intermediates in
Organic Synthesis; Pergamon Press: Oxford, 1986.
Jewell, R.; Perry, M. W. D.; Stocks, M. J.; Stonehouse, J. P. Synlett
2009, 1391; (b) Kumar, D.; Reddy, V. B. Synthesis 2010, 1687; (c) Doak,
B. C.; Scanlon, M. J.; Simpson, J. S. Org Lett 2011, 13, 537; (d)
Bahulayan, D.; Arun, S. Tetrahedron Lett 2012, 53, 2850; (e) Hwang,
S.; Bae, H.; Kim, S.; Kim, S. Tetrahedron 2012, 68, 1460.
[11] Tingoli, M.; Tiecco, M.; Chianelli, D.; Balducci, R.;
Temperini, A. J Org Chem 1991, 56, 6809.
[12] Sharpless, K. B.; Lauer, R. F. J Org Chem 1974, 39, 429.
[13] Reich, H. J.; Renga, J. M.; Reich, I. L. J Am Chem Soc 1975,
97, 5434.
[9] Reich, H. J. Acc Chem Res 1979, 12, 22.
[14] Pérez-Serrano, L.; Blanco-Urgoiti, J.; Casarrubios, L.;
Domínguez, G.; Pérez-Castells, J. J Org Chem 2000, 65, 3513.
[10] For recent selective one-pot, multi-component processes for
1,4-disubstituted 1,2,3-triazoles, see: (a) Smith, N. M.; Greaves, M. J.;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet