Copper immobilized on Nanosilica Triazine Dendrimer (Cu(II)-TD@nSiO 2)-catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles and bis- and tris-triazoles via a one-pot multicomponent click reaction

Article abstract of DOI:10.1021/jo402170n

An efficient, atom-economical, and regioselective synthesis of a wide range of 1,4-disubstituted 1,2,3-triazoles in excellent yields has been achieved via a one-pot three-component reaction of alkynes and sodium azide with organic halides or α-bromo keton

Full text of DOI:10.1021/jo402170n

Note
pubs.acs.org/joc
Copper Immobilized on Nanosilica Triazine Dendrimer (Cu(II)-
TD@nSiO2)‑Catalyzed Regioselective Synthesis of 1,4-Disubstituted
1,2,3-Triazoles and Bis- and Tris-Triazoles via a One-Pot
Multicomponent Click Reaction
Mahboobeh Nasr-Esfahani, Iraj Mohammadpoor-Baltork,* Ahmad R. Khosropour,* Majid Moghadam,
Valiollah Mirkhani, Shahram Tangestaninejad, and Hadi Amiri Rudbari
Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
S
* Supporting Information
ABSTRACT: An efficient, atom-economical, and regioselec-
tive synthesis of a wide range of 1,4-disubstituted 1,2,3-
triazoles in excellent yields has been achieved via a one-pot
three-component reaction of alkynes and sodium azide with
organic halides or α-bromo ketones catalyzed by Cu(II)-TD@
nSiO2/sodium ascorbate at room temperature. This catalytic
system also showed excellent activity in the synthesis of bis-
and tris-1,4-substituted 1,2,3-triazoles. Moreover, the catalyst
could be recycled and reused for seven cycles without any loss
in its catalytic activity.
lick chemistry, which has been applied for the copper-
Ccatalyzed alkyne−azide cycloaddition (CuAAC) to give
1,2,3-triazoles, has emerged as a prominent organic trans-
formation.1 On the other hand, the development of new
synthetic protocols has attracted the interest of chemists
because of the significance of these heterocycles in the fields of
bioconjugation,2 pharmaceutical science,3 dendrimers,4 and
materials science.5 For instance, some 1,2,3-triazoles exhibit
crucial biological activities such as anti-HIV,6 antibacterial,7 and
antiallergic8 properties. One of the most widely used methods
for the synthesis of 1,2,3-triazoles is Huisgen [3 + 2]
cycloaddition of organic azides and terminal alkynes in the
presence of copper catalysts.9 In the first report of this reaction,
Figure 1. Structure of copper immobilized on nanosilica triazine
dendrimer (Cu(II)-TD@nSiO2).
the active Cu(I) species were directly formed from Cu(I) salts
in the presence of ligands.1a,10 However, because of the
catalyst, herein we describe a convenient and efficient one-pot
synthesis of 1,4-disubstituted 1,2,3-triazoles and bis- and tris-
triazoles catalyzed by Cu(II)-TD@nSiO2/sodium ascorbate at
room temperature (Scheme 1).
The Cu(II)-TD@nSiO2 catalyst was prepared according to
our previously reported procedure.15 Briefly, the reaction of
aminopropylated nanosilica (AP-nSiO2) with cyanuric chloride
(CC) and then with bis(3-aminopropyl)amine was carried out
in the presence of diisopropylethylamine (DIPEA) in a
stepwise manner to afford the second generation of nano-
silica-supported dendrimer (G2 or TD@nSiO2). The resulting
dendrimer with NH2 groups on its periphery was used suitably
for encapsulation of Cu(II). The encapsulation was carried out
instability of Cu(I) salts, usually Cu(I) is prepared in situ via
reduction of Cu(II) with ascorbate11 or by comproportionation
of Cu metal and Cu(II) salts.12 By the way, because of the
explosive property and difficulty of handling some of the low-
molecular-weight azides, various procedures for the preparation
of 1,4-disubstituted 1,2,3-triazoles through the in situ
generation of organic azides have been developed.13 In
comparison with alkyl- or benzyl-substituted 1,2,3-triazoles,
little attention has been paid to the synthesis of β-keto-1,2,3-
triazoles, and only a few reports are available dealing with the
synthesis of these compounds from α-bromo or α-azido
ketones.14
Very recently, we reported Cu(II)-TD@nSiO2 (Figure 1) as
a recyclable catalyst for the synthesis of benzimidazoles,
benzothiazoles, bis(benzimidazole)s, and bis(benzothiazole)s.15
In continuation of our research on the application of this
Received: October 1, 2013
© XXXX American Chemical Society
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Scheme 1. Synthesis of 1,2,3-Triazoles and Bis- and Tris-
Triazoles Catalyzed by Cu(II)-TD@nSiO2/Sodium
Ascorbate
Table 1. Screening of the Experimental Conditions for the
Synthesis of 3aa
a
b
entry
mol % [Cu]
solvent
yield (%)
c
1
−
0.3
H2O/MeOH (2:1)
H2O/MeOH (2:1)
CH3CN
−
c
2
45
10
10
10
55
30
35
80
85
98
99
65
85
99
32
45
68
40
3
4
0.3
0.3
DMF
5
0.3
EtOAC
6
0.3
H2O
7
0.3
MeOH
8
0.3
EtOH
9
0.3
H2O/MeOH (1:1)
H2O/EtOH (1:1)
H2O/MeOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
H2O/EtOH (2:1)
10
11
12
13
14
0.3
0.3
0.3
by the reaction of G2 with CuCl2·2H2O to afford Cu(II)-TD@
nSiO2. The synthesized catalyst was characterized by several
instrumental methods.15 Thermogravimetric analysis (TGA)
indicated that the total amount of organic moieties on
nanosilica was about 0.76 mmol/g. The copper content of
Cu(II)-TD@nSiO2 was found to be 0.34 mmol of Cu(II) per
gram of the catalyst as measured by ICP-OES analysis. The
morphology of the catalyst surface, studied by field emission
scanning electron microscopy (FE-SEM), showed that the
Cu(II)-TD@nSiO2 particles are spherical. Energy-dispersive X-
ray (EDX) results obtained from SEM analysis of Cu(II)-TD@
nSiO2 revealed that Cu(II) particles had been introduced into
the nanosilica-supported dendrimer. A transmission electron
microscopy (TEM) image of Cu(II)-TD@nSiO2 revealed dark-
colored regions or black spots and colorless parts that
correspond to the copper species and nanosilica, respectively.
The size distribution histogram demonstrated that the average
diameter of the matrix was about 20−30 nm.
Initially, for screening experiments, the three-component
reaction between phenylacetylene (1 mmol), 4-bromobenzyl
bromide (1 mmol), and sodium azide (1.1 mmol) was chosen
as a model reaction (Table 1). The model reaction was first
carried out in the absence of sodium ascorbate and catalyst, and
no product was formed under these conditions (Table 1, entry
1). In the presence of Cu(II)-TD@nSiO2 (0.3 mol %, 10 mg)
without sodium ascorbate, the desired product was obtained in
45% yield (Table 1, entry 2). Then, the same reaction was
performed in the presence of Cu(II)-TD@nSiO2 (0.3 mol %,
10 mg) and sodium ascorbate (5 mol %, 10 mg) in different
single and mixed solvents at room temperature (Table 1,
entries 3−12). As can be seen, the maximum yields were
obtained in both H2O/MeOH (2:1) and H2O/EtOH (2:1)
mixed solvent systems (Table 1, entries 11 and 12). However,
H2O/EtOH (Table 1, entry 12) was preferred because of safety
problems. Next, we examined the catalyst loading (0.1−0.4 mol
%), and 0.3 mol % was found to be the optimum catalyst
loading for completion of this reaction (Table 1, entries 12−
15). When a catalyst loading of 0.4 mol % was used, the yield of
the product was still 99%, but the reaction rate increased, so
that the reaction was complete within 17 min (Table 1, entry
15). The model reaction was also carried out in the presence of
a 0.3 mol % loading of conventional copper salts such as CuI,
CuCl, CuCl2·2H2O/sodium ascorbate, and CuSO4·5H2O/
sodium ascorbate (Table 1, entries 16−19). Under these
0.1
0.2
d
15
0.4
16
17
CuI, 0.3
CuCl, 0.3
e
18
CuCl2·2H2O, 0.3
CuSO4·5H2O, 0.3
e
19
a
Unless otherwise noted, [Cu] = Cu(II)-TD@nSiO2 containing 0. 34
mmol of Cu(II) per gram of catalyst as determined by ICP-OES
b
c
d
analysis. Isolated yields. Without sodium ascorbate at rt. The
reaction was complete after 17 min. With sodium ascorbate.
e
conditions, the desired product was obtained in lower yields
(32−68%) compared with that using Cu(II)-TD@nSiO2.
Under the optimized reaction conditions, the efficiency of
this protocol for the synthesis of various 1,4-disubstituted 1,2,3-
triazoles was studied, and the results are summarized in Scheme
2. Aryl acetylenes such as phenylacetylene (1a), 3-methox-
yphenylacetylene (1b), and 4-chlorophenylacetylene (1c) as
well as alkyl acetylenes such as 1-hexyne (1d) reacted rapidly
and smoothly with benzyl bromides 2a−d and sodium azide in
the presence of Cu(II)-TD@nSiO2/sodium ascorbate at room
temperature to afford the corresponding 1,4-disubstituted 1,2,3-
triazoles 3aa−dc in excellent yields (97−99%). Under the same
conditions, the reactions of 1a with butyl bromide (2e) and 4-
nitrobenzyl chloride (2f) proceeded efficiently to provide the
desired 1,4-disubstituted 1,2,3-triazoles 3ae and 3af in 96% and
94% yield, respectively. It is noteworthy that the reactions were
completed within 10−40 min at room temperature, and the
products were obtained in excellent yields with high purity and
excellent regioselectivity, in which only 1,4-regioisomeric
products were formed.
Encouraged by the excellent results obtained with alkyl/
benzyl halides, we then examined the activity of this catalytic
system for the preparation of 1,4-disubstituted 1,2,3-triazoles
using α-bromo ketones. As shown in Scheme 3, various α-
bromo ketones 4a−i having different functionalities on the
aromatic ring reacted smoothly with terminal alkynes 1a, 1b,
1d, and 1e and sodium azide in the presence of Cu(II)-TD@
nSiO2/sodium ascorbate at room temperature to give the
corresponding β-keto-1,2,3-triazoles 5aa−ei in 88−99% yield
within 10−30 min. The heterocyclic α-bromo ketone 2-bromo-
1-(furan-2-yl)ethanone (4j) also participated well in this
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reaction under similar conditions to provide the desired
product 5aj in 90% yield after 30 min.
To further widen the applicability of the present method-
ology and because of the various applications of bis- and tris-
triazoles in the field of organic semiconductors,16 as precursors
of ionic liquids,17 and as ligands in chemistry,18 their synthesis
was also examined. As shown in Scheme 4, the reactions of 1,4-
Scheme 2. Cu(II)-TD@nSiO2-Catalyzed Three-Component
Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Alkyl/
Benzyl Halides
a
Scheme 4. Cu(II)-TD@nSiO2 Catalyzed Synthesis of Bis-
a
and Tris-Triazoles
a
a
Isolated yields are shown.
Isolated yields are shown.
Scheme 3. Cu(II)-TD@nSiO2-Catalyzed Three-Component
Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from α-Bromo
Ketones
bis(bromomethyl)benzene (6a), 1,3,5-tris(bromomethyl)-
benzene (6b), and 1,3,5-tris(bromomethyl)-2,4,6-trimethylben-
zene (6c) with terminal alkynes 1a, 1b, and 1d and sodium
azide proceeded efficiently in the presence of Cu(II)-TD@
nSiO2/sodium ascorbate at room temperature, and the
corresponding bis- and tris-triazoles 7aa−db were obtained in
90−96% yield within 1 h. It is noteworthy that the synthesis of
bis- and tris-triazoles through such a one-pot multicomponent
reaction has not been previously reported. This method also
offers several advantages such as high product yields, short
reaction times, mild reaction conditions, excellent regioselec-
tivity, cleaner reaction profiles, and operational simplicity.
Therefore, this synthetic methodology can be considered as a
useful practical achievement in the preparation of these
important heterocyclic compounds.
a
The possibility of recycling and reusing the catalyst was
examined in the three-component reaction between phenyl-
acetylene, 4-bromobenzyl bromide, and sodium azide (Table
2). When the reaction was completed, the mixture was diluted
with water and EtOAc. The catalyst was separated by simple
Table 2. Reusability of the Cu(II)-TD@nSiO2 Catalyst in the
a
Synthesis of 3aa
run
1
2
3
4
5
6
7
8
b
yield (%)
99
99
97
98
97
96
95
95
a
Reaction conditions: phenylacetylene (1 mmol), 4-bromobenzyl
bromide (1 mmol), sodium azide (1.1 mmol), Cu(II)-TD@nSiO2 (0.3
mol %, 10 mg), sodium ascorbate (5 mol %, 10 mg), rt, 20 min.
Isolated yields.
a
b
Isolated yields are shown.
C
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mixture was diluted with water and EtOAc and filtered. The organic
layer was separated, and the aqueous layer was extracted with EtOAc
(2 × 5 mL). The combined organic layers were dried over MgSO4 and
evaporated to afford the pure 1,4-disubstituted 1,2,3-triazole in most
cases. If necessary, the product was purified by recrystallization from n-
hexane/EtOAc.
General Procedure for the One-Pot Synthesis of 1,4-
Disubstituted 1,2,3-Triazoles from α-Bromo Ketones Cata-
lyzed by Cu(II)-TD@nSiO2 (Scheme 3). A mixture of sodium
ascorbate (5 mol %, 10 mg) and Cu(II)-TD@nSiO2 (0.3 mol %, 10
mg) in 3 mL of H2O/EtOH (2:1) was stirred for 1 min. Then the
alkyne (1 mmol), the α-bromo ketone (1 mmol), and sodium azide
(1.1 mmol) were added, and the resulting mixture was stirred at room
temperature for 10−30 min. The progress of the reaction was
monitored by TLC (eluting with n-hexane/ethyl acetate, 1:1). After
completion of the reaction, the mixture was diluted with water and
EtOAc and filtered. The organic layer was separated, and the aqueous
layer was extracted with EtOAc (2 × 5 mL). The combined organic
layers were dried over MgSO4 and evaporated to afford the pure
triazole in most cases. If necessary, the product was purified by
recrystallization from n-hexane/EtOAc.
filtration, dried, and used for subsequent runs. The
experimental results indicated that the catalyst can be reused
at least seven times without considerable loss of activity and
product yield (95−99%). Furthermore, the leaching of copper
from the Cu(II)-TD@nSiO2 catalyst was measured by ICP-
OES, and it was found that only very limited leaching of copper
(less than 0.1 ppm) occurred during the reaction. This clearly
revealed that the catalyst is stable under the reaction conditions
and can be recovered and reused.
The structure of the products was identified by IR, MS, and
1H and 13C NMR spectra and elemental analysis. Furthermore,
the structure of 3ad was confirmed by X-ray crystallographic
analysis (Figure 2; CCDC 948081).
General Procedure for the One-Pot Synthesis of Bis- and
Tris-Triazoles Catalyzed by Cu(II)-TD@nSiO2 (Scheme 4). A
mixture of sodium ascorbate (5 mol %, 20−30 mg) and Cu(II)-TD@
nSiO2 (0.3 mol %, 20−30 mg) in 4−6 mL of H2O/EtOH (2:1) was
stirred for 1 min. Then 1,4-bis(bromomethyl)benzene, 1,3,5-tris-
(bromomethyl)benzene, or 1,3,5-tris(bromomethyl)-2,4,6-trimethyl-
benzene (1 mmol), the alkyne (2−3 mmol), and sodium azide (2.2−
3.3 mmol) were added, and the resulting mixture was stirred at room
temperature for 1 h. The progress of the reaction was monitored by
TLC (eluting with n-hexane/ethyl acetate, 1:1). The workup was
performed as in the general procedure for one-pot synthesis of 1,4-
disubstituted 1,2,3-triazoles, and the pure product was obtained by
recrystallization of the crude product from n-hexane/EtOAc.
1-(4-Bromobenzyl)-4-phenyl-1H-1,2,3-triazole (Scheme 2,
Figure 2. X-ray crystal structure of 3ad.
In conclusion, we have demonstrated a novel and efficient
strategy for the regioselective synthesis of a variety of 1,4-
disubstituted 1,2,3-triazoles via a one-pot three-component
reaction of terminal alkynes, organic halides or α-bromo
ketones, and sodium azide in the presence of catalytic amounts
of Cu(II)-TD@nSiO2/sodium ascorbate at room temperature.
Also, this catalytic system exhibited excellent activity in the
synthesis of bis- and tris-triazoles. The noteworthy features of
the present method are excellent regioselectivity, short reaction
times, excellent yields, very mild reaction conditions, opera-
tional simplicity, avoidance of isolation and handling of
potentially unstable small organic azides, stability and
reusability of the catalyst, and use of a green solvent system,
making it a useful and attractive process for the synthesis of 1,4-
disubstituted 1,2,3-triazoles and bis- and tris-triazoles in a
single-step operation.
3aa).9i Yield: 99% (310 mg). Mp: 148−150 °C. IR (KBr): νmax
=
1
3109, 3082, 1579, 1485, 1220, 1076, 764, 689, 484 cm−1. H NMR
(400 MHz, CDCl3): δ 7.82 (d, J = 7.6 Hz, 2H), 7.77 (s, 1H), 7.52 (d, J
= 7.6 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.20
(d, J = 7.6 Hz, 2H), 5.54 (s, 2H). 13C NMR (100 MHz, CDCl3): δ
133.7, 132.4, 130.4, 129.7, 128.9, 128.3, 125.7, 123.0, 119.4, 53.6. MS:
m/z (%) 315.99 ([M + 1]+, 15.59), 314.98 ([M]+, 60.39), 286.00
(65.88), 206.17 (78.82), 168.91 (100.00), 130.14 (47.84), 115.83
(100.00), 102.21 (98.04), 89.51 (100.00), 77.11 (70.20), 63.09
(100.00), 43.21 (19.51). Anal. Calcd for C15H12N3Br: C, 57.34; H,
3.85, N, 13.37. Found: C, 57.14; H, 3.89; N, 13.29.
1-(3,5-Dimethylbenzyl)-4-phenyl-1H-1,2,3-triazole (Scheme
2, 3ad). Yield: 98% (257 mg). Mp: 114−115 °C. IR (KBr): νmax
=
1
3082, 3028, 1609, 1461, 1347, 1215, 1082, 857, 763, 515 cm−1. H
NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4 Hz, 2H), 7.68 (s, 1H),
7.44 (t, J = 7.2 Hz, 2H), 7.35 (tt, 1J = 7.6 Hz, 2J = 1.6 Hz, 1H), 7.02 (s,
1H), 6.94 (s, 2H), 5.52 (s, 2H), 2.35 (s, 6H). 13C NMR (100 MHz,
CDCl3): δ 148.2, 138.9, 134.5, 130.7, 130.4, 128.8, 128.1, 125.9, 125.7,
119.5, 54.2, 21.2. MS: m/z (%) 265.18 ([M + 2]+, 3.37), 263.17
([M]+, 72.35), 220.15 (77.42), 193.19 (32.72), 158.18 (23.27), 132.14
(70.05), 119.12 (93.55), 116.09 (100.00), 91.08 (80.18), 77.10
(76.50), 55.15 (46.08), 43.18 (49.77). Anal. Calcd for C17H17N3: C,
77.54; H, 6.51; N, 15.96. Found: C, 77.37; H, 6.55; N, 15.89.
1-(4-Bromobenzyl)-4-(3-methoxyphenyl)-1H-1,2,3-triazole
(Scheme 2, 3ba). Yield: 98% (337 mg). Mp: 82−84 °C. IR (KBr):
νmax = 3113, 3077, 2936, 1616, 1583, 1450, 1222, 1041, 784 cm−1. 1H
NMR (400 MHz, CDCl3): δ 7.67 (s, 1H), 7.55 (d, J = 8.4 Hz, 2H),
7.44 (s, 1H), 7.34 (d, J = 6.0 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.91−
6.88 (m, 1H), 5.55 (s, 2H), 3.88 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 160.0, 148.3, 133.7, 132.4, 131.7, 129.9, 129.7, 123.0, 119.6,
118.1, 114.4, 110.7, 55.4, 53.6. MS: m/z (%) 344.06 ([M]+, 16.73),
314.27 (11.80), 171.06 (62.68), 146.16 (100.00), 119.16 (23.24),
90.17 (78.17), 76.15 (70.42), 63.16 (71.83), 55.20 (31.69), 43.22
(56.34). Anal. Calcd for C16H14BrN3O: C, 55.83; H, 4.10; N, 12.21.
Found: C, 55.69; H, 4.13; N, 12.14.
EXPERIMENTAL SECTION
■
Melting points were determined with a Stuart Scientific SMP2
apparatus. FT-IR spectra were recorded on a Nicolet Impact 400D
instrument in the range of 400−4000 cm−1. 1H and 13C NMR spectra
(400 and 100 MHz) were recorded on a Bruker Avance 400
spectrometer using CDCl3 as the solvent. Mass spectra were recorded
on a Micromass Platform II spectrometer in EI mode at 70 eV.
Elemental analysis was done on a LECO CHNS-932 analyzer. The α-
bromo ketones were prepared as described previously.19
General Procedure for the One-Pot Synthesis of 1,4-
Disubstituted 1,2,3-Triazoles from Alkyl/Benzyl Halides Cata-
lyzed by Cu(II)-TD@nSiO2 (Scheme 2). A mixture of sodium
ascorbate (5 mol %, 10 mg) and Cu(II)-TD@nSiO2 (0.3 mol %, 10
mg) in 3 mL of H2O/EtOH (2:1) was stirred for 1 min. Then the
alkyne (1 mmol), the alkyl/benzyl halide (1 mmol), and sodium azide
(1.1 mmol) were added, and the mixture was stirred at room
temperature for 10−40 min, during which the desired 1,4-disubstituted
1,2,3-triazole precipitated out. After completion of the reaction (as
monitored by TLC, eluting with n-hexane/ethyl acetate, 2:1), the
D
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4-(3-Methoxyphenyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole
(Scheme 2, 3bc). Yield: 99% (306 mg). Mp: 136−138 °C. IR (KBr):
νmax = 3113, 3086, 1616, 1583, 1521, 1487, 1348, 1168, 1043, 837,
MS: m/z (%) 281.14 ([M + 1]+, 7.11), 280.14 ([M]+, 37.62), 251.16
(30.48), 205.19 (51.43), 178.20 (22.38), 136.17 (41.90), 121.16
(63.33), 116.13 (100.00), 106.17 (59.05), 102.15 (63.81), 91.18
(34.29), 78.17 (73.33), 63.16 (68.10), 51.20 (55.24), 43.26 (21.31).
Anal. Calcd for C15H12N4O2: C, 64.28; H, 4.32; N, 19.99. Found: C,
64.42; H, 4.36; N, 19.90.
1
780, 568 cm−1. H NMR (400 MHz, CDCl3): δ 8.27 (d, J = 8.8 Hz,
2H), 7.76 (s, 1H), 7.47 (d, J = 8.4 Hz, 3H), 7.36 (d, J = 7.2 Hz, 2H),
6.92−6.89 (m, 1H), 5.71 (s, 2H), 3.88 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 160.1, 148.6, 148.1, 141.7, 131.4, 129.9, 128.6, 124.4, 119.9,
118.1, 114.5, 110.9, 55.4, 53.2. MS: m/z (%) 311.08 ([M + 1]+, 34.51),
310.07 ([M]+, 74.90), 281.10 (59.61), 251.13 (41.57), 235.17 (48.24),
165.17 (36.47), 145.90 (100.00), 119.14 (66.67), 90.11 (71.37), 77.14
(55.29), 51.13 (59.22), 43.20 (22.90). Anal. Calcd for C16H14N4O3: C,
61.93; H, 4.55; N, 18.06. Found: C, 61.84; H, 4.60; N, 17.99.
4-(4-Chlorophenyl)-1-(4-iodobenzyl)-1H-1,2,3-triazole
(Scheme 2, 3cb). Yield: 99% (390 mg). Mp: 90−92 °C. IR (KBr):
1-(4-Bromophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-
ethanone (Scheme 3, 5aa).14d Yield: 99% (338 mg). Mp: 178−180
°C. IR (KBr): νmax = 3142, 2936, 1709, 1582, 1229, 847, 762, 562
1
cm−1. H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H), 7.92 (t, J = 7.6
Hz, 4H), 7.73 (d, J = 8.0 Hz, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.39 (t, J =
7.2 Hz, 1H), 5.88 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 189.5,
148.3, 132.6, 130.4, 130.2, 129.6, 128.9, 128.3, 125.8, 121.4, 55.4. MS:
m/z (%) 343.00 ([M + 1]+, 0.51), 341.98 ([M]+, 1.42), 340.98 (0.61),
314.01 (0.38), 286.04 (1.01), 182.99 (19.48), 154.98 (20.29), 130.09
(48.70), 116.08 (18.83), 102.08 (100.00), 76.07 (85.71), 41.15
(13.80). Anal. Calcd for C16H12BrN3O: C, 56.16; H, 3.53; N, 12.28.
Found: C, 56.02; H, 3.56; N, 12.39.
1
νmax = 3126, 3084, 2923, 1605, 1565, 1455, 1095, 812, 728 cm−1. H
NMR (400 MHz, CDCl3): δ 7.68 (d, J = 7.6 Hz, 4H), 7.60 (s, 2H),
7.32 (d, J = 7.6 Hz, 2H), 7.07 (t, J = 8.0 Hz, 1H), 5.44 (s, 2H). 13C
NMR (100 MHz, CDCl3): δ 138.0, 136.9, 130.9, 130.7, 129.1, 127.3,
127.0, 124.4, 119.5, 119.4, 53.4. MS: m/z (%) 397.85 ([M + 2]+, 0.53),
395.83 ([M]+, 1.57), 394.82 (8.73), 253.01 (10.88), 240.03 (72.16),
216.89 (79.61), 204.06 (33.73), 178.03 (55.69), 149.85 (100.00),
135.94 (68.63), 89.98 (100.00), 76.99 (91.37), 52.03 (69.41). Anal.
Calcd for C15H11ClIN3: C, 45.54; H, 2.80; N, 10.62. Found: C, 45.68;
H, 2.76; N, 10.73.
1-(4-Fluorophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-
ethanone (Scheme 3, 5ab).14e Yield: 99% (278 mg). Mp: 174−176
°C. IR (KBr): νmax = 3152, 2979, 1695, 1597, 1232, 835, 767 cm−1. 1H
1
2
NMR (400 MHz, CDCl3): δ 8.08 (dd, J = 7.2 Hz, J = 2.0 Hz, 2H),
7.94 (s, 1H), 7.86 (dt, 1J = 7.6 Hz, 2J = 1.6 Hz, 2H), 7.45 (t, J = 7.6 Hz,
2H), 7.36 (tt, 1J = 7.2 Hz, 2J = 1.2 Hz, 1H), 7.24 (td, 1J = 7.2 Hz, 2J =
2.0 Hz, 2H), 5.86 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 188.8,
1-(4-Bromobenzyl)-4-butyl-1H-1,2,3-triazole (Scheme 2,
3da).9i Yield: 97% (285 mg). Mp: 64−65 °C. IR (KBr): νmax
=
1
4
3
167.9 (d, JCF = 257 Hz), 148.3 (d, JCF = 5 Hz), 131.1 (d, JCF = 9
Hz), 130.4, 129.2, 128.9, 128.4, 128.3, 125.8, 121.4, 116.6 (d, 2JCF = 22
Hz), 55.4. Anal. Calcd for C16H12FN3O: C, 68.32; H, 4.30; N, 14.94.
Found: C, 68.15; H, 4.35; N, 14.84.
3109, 2931, 1591, 1489, 1213, 1051, 847, 772, 490 cm−1. H NMR
(400 MHz, CDCl3) δ 7.52 (dt, 1J = 7.6 Hz, 2J = 2.0 Hz, 2H), 7.20 (s,
1H), 7.15 (d, J = 8.4 Hz, 2H), 5.46 (s, 2H), 2.73 (t, J = 8.0 Hz, 2H),
1.68 (quin, J = 7.6 Hz, 2H), 1.42 (sex, J = 7.6 Hz, 2H), 0.95 (t, J = 8.0
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 149.2, 134.1, 132.2, 129.6,
122.7, 120.4, 53.3, 31.5, 29.7, 22.3, 13.8. MS: m/z (%) 295.05 ([M +
1]+, 4.68), 294.07 ([M]+, 2.21), 253.05 (41.57), 171.03 (89.80),
168.94 (100.00), 143.15 (25.10), 115.19 (26.27), 91.17 (44.71), 89.12
(75.29), 69.20 (51.76), 55.20 (41.96), 43.22 (47.84). Anal. Calcd for
C13H16BrN3: C, 53.07; H, 5.48; N, 14.28. Found: C, 52.94; H, 5.53; N,
14.19.
1
1-(4-Nitrophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-
ethanone (Scheme 3, 5ac).14e Yield: 88% (271 mg). Mp: 184−186
°C. IR (KBr): νmax = 3139, 2968, 1693, 1599, 1213, 835, 752 cm−1. 1H
NMR (400 Hz, CDCl3): δ 8.28 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 8.0
Hz, 2H), 7.54 (s, 1H), 7.50−7.53 (m, 2H), 7.42 (d, J = 6.8 Hz, 2H),
6.77 (s, 1H), 5.48 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 189.8,
167.9, 131.9, 130.1, 130.0, 129.0, 128.9, 128.8, 128.7, 127.9, 127.8,
53.4. Anal. Calcd for C16H12N4O3: C, 62.33; H, 3.92; N, 18.17. Found:
C, 62.19; H, 3.96; N, 18.05.
1-(4-Chlorophenyl)-2-(4-(3-methoxyphenyl)-1H-1,2,3-tria-
zol-1-yl)ethanone (Scheme 3, 5bd). Yield: 98% (320 mg). Mp:
131−132 °C. IR (KBr): νmax = 3141, 2924, 1692, 1590, 1470, 1343,
1245, 992, 818, 569 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J =
8.8 Hz, 2H), 7.95 (s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.47 (s, 1H), 7.40
(d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 6.91 (dd, 1J = 8.0 Hz, 2J =
2.0 Hz, 1H), 5.86 (s, 2H), 3.88 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 189.2, 160.0, 141.4, 132.2, 131.6, 129.9, 129.6, 129.59,
121.6, 118.2, 114.5, 110.8, 55.39, 55.37. MS: m/z (%) 329.07 ([M +
2]+, 1.75), 327.01 ([M]+, 5.51), 270.08 (4.78), 183.00 (2.51), 160.10
(76.42), 139.00 (93.40), 111.03 (100.00), 89.04 (97.64), 75.04
(98.11), 50.10 (85.38), 43.17 (30.66). Anal. Calcd for
C17H14ClN3O2: C, 62.30; H, 4.31; N, 12.82. Found: C, 62.15; H,
4.33; N, 12.74.
4-Butyl-1-(4-nitrobenzyl)-1H-1,2,3-triazole (Scheme 2,
3dc).9i Yield: 98% (254 mg). Mp: 60−61 °C. IR (KBr): νmax
=
3115, 3063, 2924, 1606, 1518, 1351, 1217, 1051, 859, 712, 478 cm−1.
1
2
1H NMR (400 MHz, CDCl3): δ 8.26 (dt, J = 8.4 Hz, J = 2.4 Hz,
2H), 7.41 (d, J = 8.8 Hz, 2H), 7.28 (s, 1H), 5.66 (s, 2H), 2.76 (t, J =
8.0 Hz, 2H), 1.70 (quin, J = 7.6 Hz, 2H), 1.44 (sex, J = 8.0 Hz, 2H),
0.96 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 149.5, 148.0,
142.2, 128.4, 124.2, 120.8, 52.9, 31.4, 25.4, 22.3, 13.8. MS: m/z (%)
262.18 ([M + 2]+, 5.10), 260.14 ([M]+, 15.69), 217.06 (75.69), 203.03
(49.02), 188.99 (82.75), 143.08 (40.39), 135.81 (100.00), 121.01
(80.00), 115.05 (25.49), 105.84 (100.00), 91.02 (62.75), 77.60
(100.00), 55.02 (94.51), 41.00 (100.00). Anal. Calcd for
C13H16N4O2: C, 59.99; H, 6.20; N, 21.52. Found: C, 59.85; H, 6.24;
N, 21.41.
1-Butyl-4-phenyl-1H-1,2,3-triazole (Scheme 2, 3ae).9j Yield:
96% (193 mg). Mp: 42−44 °C. IR (KBr): νmax = 3085, 2956, 1609,
1-(3,4-Dimethoxyphenyl)-2-(4-(3-methoxyphenyl)-1H-1,2,3-
triazol-1-yl)ethanone (Scheme 3, 5be). Yield: 98% (346 mg). Mp:
136−138 °C. IR (KBr): νmax = 3135, 2969, 1695, 1590, 1516, 1462,
1
1463, 1217, 1077, 761, 694 cm−1. H NMR (400 MHz, CDCl3): δ
1
2
7.86 (dd, J = 8.4 Hz, J = 2.0 Hz, 2H), 7.80 (s, 1H), 7.46 (t, J = 8.0
1
2
1
1270, 1131, 1015, 854, 691 cm−1. H NMR (400 MHz, CDCl3): δ
Hz, 2H), 7.37 (tt, J = 7.6 Hz, J = 1.2 Hz, 1H), 4.44 (t, J = 7.2 Hz,
2H), 1.99 (quin, J = 7.6 Hz, 2H), 1.46 (sex, J = 7.2 Hz, 2H), 1.01 (t, J
= 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 147.7, 130.8, 128.8,
128.1, 125.7, 119.4, 50.1, 32.3, 19.7, 13.5. MS: m/z (%) 202.09 ([M +
1]+, 3.17), 201.10 ([M]+, 8.93), 145.10 (13.10), 130.08 (20.44),
102.09 (33.53), 90.11 (24.40), 77.14 (24.40), 63.12 (29.56), 41.19
(100.00). Anal. Calcd for C12H15N3: C, 71.61; H, 7.51; N, 20.88.
Found: C, 71.51; H, 7.56; N, 20.77.
1
2
7.94 (s, 1H), 7.66 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.53 (d, J = 1.6
Hz, 1H), 7.48 (s, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.0 Hz,
1H), 6.95 (d, J = 8.4 Hz, 1H), 6.90 (dd, 1J = 8.0 Hz, 2J = 2.0 Hz, 1H),
5.85 (s, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.87 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 188.8, 160.0, 154.5, 149.5, 148.1, 131.8, 129.9, 127.1,
123.0, 121.6, 118.2, 114.4, 110.7, 110.3, 110.1, 56.2, 56.1, 55.4, 55.1.
MS: m/z (%) 353.15 ([M]+, 3.77), 342.12 (0.74), 296.16 (1.33),
266.14 (2.14), 165.10 (100.00), 151.11 (49.71), 135.10 (22.70),
107.07 (35.34), 89.08 (61.78), 51.12 (59.20), 43.17 (29.89). Anal.
Calcd for C19H19N3O4: C, 64.58; H, 5.42; N, 11.89. Found: C, 64.39;
H, 5.49; N, 11.78.
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (Scheme 2,
3af).9g Yield: 94% (263 mg). Mp: 154−155 °C. IR (KBr): νmax
=
1
3127, 3080, 1605, 1518, 1349, 1077, 859, 763, 511 cm−1. H NMR
(400 MHz, CDCl3): δ 8.17 (dt, 1J = 8.4 Hz, 2J = 2.0 Hz, 2H), 7.74 (dt,
2
1J = 8.0 Hz, J = 2.0 Hz, 2H), 7.68 (s, 1H), 7.36−7.32 (m, 4H), 7.28
2-(4-Butyl-1H-1,2,3-triazol-1-yl)-1-(3-methoxyphenyl)-
ethanone (Scheme 3, 5df). Yield: 97% (264 mg). Mp: 72−74 °C.
IR (KBr): νmax = 3059, 2931, 1701, 1596, 1560, 1458, 1343, 1263,
(tt, 1J = 8.0 Hz, 2J = 1.6 Hz, 1H), 5.63 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 141.7, 130.1, 128.9, 128.6, 128.5, 125.8, 124.4, 119.6, 53.2.
E
dx.doi.org/10.1021/jo402170n | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1167, 1024, 868, 790 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.58 (dt,
1J = 8.4 Hz, 2J = 0.8 Hz, 1H), 7.51 (t, J = 2.0 Hz, 1H), 7.46 (t, J = 8.0
116.03 (35.15), 91.10 (25.31), 77.11 (21.76), 57.12 (45.19), 43.19
(100.00). Anal. Calcd for C24H20N6: C, 73.45; H, 5.14; N, 21.41.
Found: C, 73.19; H, 5.18; N, 21.34.
Hz, 2H), 7.21 (dd, 1J = 8.0 Hz, 2J = 2.4 Hz, 1H), 5.80 (s, 2H), 3.87 (s,
3H), 2.79 (t, J = 8.4 Hz, 2H), 1.73 (quin, J = 7.2 Hz, 2H), 1.46 (sex, J
= 7.2 Hz, 2H), 0.97 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 190.5, 160.1, 148.8, 135.3, 130.2, 122.4, 121.0, 120.6, 112.4, 55.5,
55.4, 31.5, 25.4, 22.3, 13.8. MS: m/z (%) 273.16 ([M]+, 1.15), 244.15
(3.80), 174.07 (10.69), 149.04 (61.18), 136.03 (37.65), 120.92
(90.98), 109.98 (100.00), 90.97 (97.25), 76.99 (98.83), 63.98
(90.98), 55.01 (86.27), 43.06 (84.31). Anal. Calcd for C15H19N3O2:
C, 65.91; H, 7.01; N, 15.37. Found: C, 65.78; H, 7.07; N, 15.29.
2-(4-Butyl-1H-1,2,3-triazol-1-yl)-1-(4-cyclohexylphenyl)-
ethanone (Scheme 3, 5dg). Yield: 98% (318 mg). Mp: 144−146
°C. IR (KBr): νmax = 3142, 2927, 1696, 1604, 1567, 1453, 1236, 994,
1,1′,1″-(2,4,6-Trimethylbenzene-1,3,5-triyl)tris(methylene)-
tris(4-phenyl-1H-1,2,3-triazole) (Scheme 4, 7ac). Yield: 90% (531
mg). Mp: 185−187 °C. IR (KBr): νmax = 3133, 2924, 1612, 1562,
1476, 1339, 1150, 763 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.68 (d,
J = 7.6 Hz, 6H), 731 (t, J = 7.2 Hz, 6H), 7.27 (s, 3H), 7.24 (dt, 1J = 8.4
Hz, 2J = 0.8 Hz, 3H), 5.58 (s, 6H), 2.35 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 139.3, 131.7, 128.8, 128.2, 125.7, 118.6, 48.7, 20.2. Anal.
Calcd for C36H33N9: C, 73.07; H, 5.62; N, 21.30. Found: C, 72.88; H,
5.68; N, 21.24.
1,3,5-Tris((4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-
methyl)benzene (Scheme 4, 7bb). Yield: 96% (613 mg). Mp:
211−213 °C. IR (KBr): νmax = 3130, 2937, 1605, 1588, 1557, 1485,
1243, 1042, 847, 783, 691 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.66
(s, 3H), 7.33 (s, 3H), 7.21 (d, J = 7.2 Hz, 6H), 7.12 (s, 3H), 6.80 (d, J
= 6.8 Hz, 3H), 5.42 (s, 6H), 3.75 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 160.0, 137.0, 131.5, 130.0, 127.5, 118.1, 114.5, 110.7, 55.4,
53.4. Anal. Calcd for C36H33N9O3: C, 67.59; H, 5.20; N, 19.71. Found:
C, 67.34; H, 5.26; N, 19.60.
1,3,5-Tris((4-butyl-1H-1,2,3-triazol-1-yl)methyl)benzene
(Scheme 4, 7db). Yield: 92% (450 mg). Mp: 141−143 °C. IR (KBr):
νmax = 3127, 3074, 2929, 1610, 1550, 1460, 1349, 1050, 826, 777 cm−1.
1H NMR (400 MHz, CDCl3): δ 7.21 (s, 3H), 7.08 (s, 3H), 5.41 (s,
6H), 2.70 (t, J = 7.6 Hz, 6H), 1.65 (quin, J = 7.2 Hz, 6H), 1.40 (sex, J
= 7.2 Hz, 6H), 0.93 (t, J = 7.2 Hz, 9H). 13C NMR (100 MHz, CDCl3):
δ 149.2, 137.1, 127.2, 120.8, 53.1, 31.4, 25.3, 22.5, 13.8. MS: m/z (%)
489.16 ([M]+, 0.28), 461.09 (3.22), 366.11 (1.51), 211.10 (4.75),
126.05 (10.69), 117.04 (25.49), 91.03 (17.94), 55.10 (24.02), 41.15
(100.00). Anal. Calcd for C27H39N9: C, 66.23; H, 8.03; N, 25.74.
Found: C, 65.98; H, 8.10; N, 25.62.
1
832 cm−1. H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 7.6 Hz, 2H),
7.45 (s, 1H), 7.38 (d, J = 8.0 Hz, 2H), 5.79 (s, 2H), 2.79 (t, J = 8.4 Hz,
2H), 2.62 (t, J = 7.6 Hz, 1H), 1.89 (d, J = 6.0 Hz, 4H), 1.74 (quin, J =
8.4 Hz, 2H), 1.50−1.37 (m, 6H), 1.32−1.23 (m, 2H), 0.91 (t, J = 8.4
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 190.2, 155.5, 148.8, 131.9,
128.4, 127.6, 122.4, 55.2, 44.8, 34.0, 31.5, 26.6, 26.0, 25.4, 22.3, 13.9.
MS: m/z (%) 325.21 ([M]+, 0.43), 296.22 (1.25), 214.19 (1.42),
187.10 (49.34), 115.1 (17.35), 110.13 (65.46), 91.09 (43.09), 67.11
(28.95), 55.14 (31.91), 41.18 (100.00). Anal. Calcd for C20H27N3O: C,
73.81; H, 8.36; N, 12.91. Found: C, 73.69; H, 8.41; N, 12.82.
1-p-Tolyl-2-(4-p-tolyl-1H-1,2,3-triazol-1-yl)ethanone
(Scheme 3, 5eb).14b Yield: 98% (388 mg). Mp: 164−166 °C. IR
(KBr): νmax = 3109, 2919, 1698, 1604, 1570, 1460, 1343, 1233, 814,
1
731, 567 cm−1. H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz,
2H), 7.92 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H),
7.27 (d, J = 8.0 Hz, 2H), 5.88 (s, 2H), 2.48 (s, 3H), 2.41 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 189.9, 145.8, 138.0, 131.5, 129.9, 129.5,
128.3, 127.8, 125.7, 121.1, 55.4, 21.9, 21.3. MS: m/z (%) 292.07
([M]+, 0.84), 291.08 (4.15), 262.14 (2.21), 234.15 (6.64), 144.11
(70.35), 133.10 (38.94), 119.07 (93.81), 105.10 (73.89), 91.05
(100.00), 77.10 (72.57), 51.11 (71.24), 41.16 (45.13). Anal. Calcd
for C18H17N3O: C, 74.20; H, 5.88; N, 14.42. Found: C, 74.35; H, 5.94;
N, 14.33.
1-(Biphenyl-4-yl)-2-(4-p-tolyl-1H-1,2,3-triazol-1-yl)ethanone
(Scheme 3, 5ei). Yield: 95% (335 mg). Mp: 102−103 °C. IR (KBr):
νmax = 3030, 2922, 1698, 1602, 1403, 1559, 1231, 995, 819, 761 cm−1.
1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.0 Hz, 2H), 7.86 (s, 1H),
ASSOCIATED CONTENT
■
S
* Supporting Information
Crystallographic data in CIF format and copies of H and 13C
1
NMR spectra of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
7.70 (d, J = 8.0 Hz, 4H), 7.58 (dd, 1J = 7.2 Hz, 2J = 1.6 Hz, 3H), 7.44−
7.36 (m, 4H), 5.85 (s, 2H), 2.31 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 189.9, 147.3, 139.3, 138.1, 132.6, 129.5, 129.1, 128.9, 128.8,
128.7, 127.8, 127.3, 126.2, 125.8, 121.1, 55.5, 21.3. MS: m/z (%)
353.18 ([M]+, 0.26), 181.11 (24.02), 152.10 (36.61), 115.11 (35.04),
91.08 (25.89), 77.11 (29.13), 57.14 (60.63), 43.19 (100.00). Anal.
Calcd for C23H19N3O: C, 78.16; H, 5.42; N, 11.89. Found: C, 78.25;
H, 5.45; N, 11.79.
1-(Furan-2-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone
(Scheme 3, 5aj). Yield: 90% (227 mg). Mp: 121−123 °C. IR (KBr):
νmax = 3071, 2925, 1736, 1585, 1461, 1377, 1262, 1094, 821, 518 cm−1.
1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.90 (dd, 1J = 7.6 Hz, 2J
Corresponding Authors
*E-mail: imbaltork@sci.ui.ac.ir.
*E-mail: arkhosropour@sci.ui.ac.ir.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the Research Council of the
University of Isfahan for financial support of this work.
= 1.2 Hz, 2H), 7.72 (d, J = 0.8 Hz, 1H), 7.47−7.43 (m, 2H), 7.42 (d, J
REFERENCES
= 3.6 Hz, 1H), 7.39 (tt, 1J = 7.2 Hz, 2J = 1.2 Hz, 1H), 6.68 (dd, 1J = 3.6
■
2
Hz, J = 1.2 Hz, 1H), 5.77 (s, 2H). 13C NMR (100 MHz, CDCl3): δ
(1) (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057−3064. (b) Sommer, S.; Weikart, N. D.; Brockmeyer,
A.; Janning, P.; Mootz, H. D. Angew. Chem., Int. Ed. 2011, 50, 9888−
9892. (c) Lallana, E.; Riguera, R.; Fernandez-Megia, E. Angew. Chem.,
Int. Ed. 2011, 50, 8794−8804. (d) Meldal, M.; Tornøe, C. W. Chem.
Rev. 2008, 108, 2952−3015.
179.4, 147.7, 130.5, 128.8, 128.2, 126.2, 125.8, 121.3, 119.2, 113.2,
54.9. MS: m/z (%) 253.08 ([M]+, 1.82), 168.10 (4.94), 130.06
(15.38), 102.06 (51.28), 95.03 (100.00), 89.07 (14.23), 77.10 (28.72),
63.10 (19.63), 51.14 (19.36). Anal. Calcd for C14H11N3O2: C, 66.40;
H, 4.38; N, 16.59. Found: C, 66.24; H, 4.40; N, 16.47.
(2) (a) Lutz, J. F. Angew. Chem., Int. Ed. 2008, 47, 2182−2184.
(b) Lutz, J. F.; Borner, H. G. Prog. Polym. Sci. 2008, 33, 1−39.
(c) Brennan, J. L.; Hatzakis, N. S.; Tshikhudo, T. R.; Dirvianskyte, N.;
Razumas, V.; Patkar, S.; Vind, J.; Svendsen, A.; Nolte, R. J. M.; Rowan,
A. E.; Brust, M. Bioconjugate Chem. 2006, 17, 1373−1375. (d) Gupta,
S. S.; Kuzelka, J.; Singh, P.; Lewis, W. G.; Manchester, M.; Finn, M. G.
Bioconjugate Chem. 2005, 16, 1572−1579. (e) Pacini, A.; Caricato, M.;
1,4-Bis((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)benzene
(Scheme 4, 7aa). Yield: 90% (352 mg). Mp: 248−250 °C. IR (KBr):
νmax = 3056, 2956, 2922, 1726, 1606, 1581, 1461, 1263, 1114, 752, 689
1
1
2
cm−1. H NMR (400 MHz, CDCl3): δ 7.70 (dd, J = 7.2 Hz, J = 1.6
Hz, 2H), 7.35−7.29 (m, 4H), 7.24 (d, J = 7.2 Hz, 2H), 7.12 (d, J = 7.2
Hz, 4H), 6.90 (d, J = 7.6 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 5.31 (s,
4H). 13C NMR (100 MHz, CDCl3): δ 129.0, 128.9, 128.8, 128.4,
128.3, 125.8, 125.7, 119.4, 53.5. MS: m/z (%) 393.28 ([M + 1]+, 1.67),
392.27 ([M]+, 1.45), 378.08 (1.70), 252.57 (2.59), 163.10 (16.70),
Ferrari, S.; Capsoni, D.; de Ilarduya, A. M.; Munoz-Guerra, S.; Pasini,
̃
D. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 4790−4799.
F
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The Journal of Organic Chemistry
Note
(3) (a) Whiting, M.; Muldoon, J.; Lin, Y.-C.; Silverman, S. M.;
Lindstrom, W.; Olson, A. J.; Kolb, H. C.; Finn, M. G.; Sharpless, K. B.;
Elder, J. H.; Fokin, V. V. Angew. Chem., Int. Ed. 2006, 45, 1435−1439.
(b) Tron, G. C.; Pirali, T.; Billington, R. A.; Canonico, P. L.; Sorba, G.;
Genazzani, A. A. Med. Res. Rev. 2008, 28, 278−308. (c) Sharpless, K.
B.; Manetsch, R. Expert Opin. Drug Discovery 2006, 1, 525−538.
(4) (a) Liang, L.; Astruc, D. Coord. Chem. Rev. 2011, 255, 2933−
2945. (b) Voit, B. New J. Chem. 2007, 31, 1139−1151.
Aizpurua, M.; Azcune, I.; Miranda, J. I.; Monasterio, Z.; García-Lecina,
E.; Fratila, R. M. Synthesis 2011, 2737−2742.
(18) (a) Schweinfurth, D.; Pattacini, R.; Strobel, S.; Sarkar, B. Dalton
Trans. 2009, 9291−9297. (b) Yan, W.; Ye, X.; Akhmedov, N. G.;
Petersen, J. L.; Shi, X. Org. Lett. 2012, 14, 2358−2361. (c) Zhao, P.; Li,
N.; Salmon, L.; Liu, N.; Ruiz, J.; Astruc, D. Chem. Commun. 2013, 49,
3218−3220.
(19) King, L. C.; Ostrum, G. K. J. Org. Chem. 1964, 29, 3459−3461.
(5) (a) Nandivada, H.; Jiang, X.; Lahann, J. Adv. Mater. 2007, 19,
2197−2208. (b) Caricato, M.; Olmo, A.; Gargiulli, C.; Gattuso, G.;
Pasini, D. Tetrahedron 2012, 68, 7861−7866. (c) Pasini, D. Molecules
2013, 18, 9512−9530. (d) Wong, C.-H.; Zimmerman, S. C. Chem.
Commun. 2013, 49, 1679−1695.
(6) (a) Ouellet, M.; Mercier, S.; Pelletier, I.; Bounou, S.; Roy, J.;
Hirabayashi, J.; Sato, S.; Tremblay, M. J. J. Immunol. 2005, 174, 4120−
4126. (b) Velazquez, S.; Alvarez, R.; Perez, C.; Gago, F.; De Clercq, E.;
Balzarini, J.; Camarasa, M. J. Antiviral Chem. Chemother. 1998, 9, 481−
489.
(7) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.;
Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J.
B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.; Zurenco,
G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J. Med.
Chem. 2000, 43, 953−970.
(8) Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med.
Chem. 1986, 29, 2262−2267.
(9) (a) van Berkel, S. S.; Brauch, S.; Gabriel, L.; Henze, M.; Stark, S.;
Vasilev, D.; Wessjohann, L. A.; Abbas, M.; Westermann, B. Angew.
Chem., Int. Ed. 2012, 51, 5343−5346. (b) Whittaker, M. R.; Urbani, C.
N.; Monteiro, M. J. J. Am. Chem. Soc. 2006, 128, 11360−11361.
(c) Lallana, E.; Riguera, R.; Fernandez-Megia, E. Angew. Chem., Int. Ed.
́
2011, 50, 8794−8804. (d) Clave, G.; Campidelli, S. Chem. Sci. 2011, 2,
1887−1896. (e) Yamada, Y. M. A.; Sarkar, S. M.; Uozumi, Y. J. Am.
Chem. Soc. 2012, 134, 9285−9290. (f) Jin, T.; Yan, M.;
Menggenbateer; Minato, T.; Bao, M.; Yamamoto, Y. Adv. Synth.
Catal. 2011, 353, 3095−3100. (g) Shao, C.; Cheng, G.; Su, D.; Xu, J.;
Wang, X.; Hu, Y. Adv. Synth. Catal. 2010, 352, 1587−1593.
(h) Yamaguchi, K.; Oishi, T.; Katayama, T.; Mizuno, N. Chem.
Eur. J. 2009, 15, 10464−10472. (i) Cook, T. L.; Walker, J. A.; Mack, J.
Green Chem. 2013, 15, 617−619. (j) Zsombor, G.; Zoltan, N. Dalton
Trans. 2010, 39, 726−729.
(10) Rostovtsev, H. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596−2599.
(11) (a) Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6,
3897−3899. (b) Campbell-Verduyn, L. S.; Mirfeizi, L.; Dierckx, R. A.;
Elsinga, P. H.; Feringa, B. L. Chem. Commun. 2009, 2139−2141.
(12) (a) Wang, Q.; Chan, T. R.; Hilgraf, R.; Fokin, V. V.; Sharpless,
K. B.; Finn, M. G. J. Am. Chem. Soc. 2003, 125, 3192−3193. (b) Himo,
F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless,
K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210−216.
(13) (a) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297−
368. (b) Kumaravel, K.; Vasuki, G. Curr. Org. Chem. 2009, 13, 1820−
1841. (c) Jiang, B.; Rajale, T.; Wever, W.; Tu, S.-J.; Li, G. Chem.
Asian J. 2010, 5, 2318−2335. (d) Alonso, F.; Moglie, Y.; Radivoy, G.;
Yus, M. Adv. Synth. Catal. 2010, 352, 3208−3214.
(14) (a) Reddy, P. S.; Sreedhar, B. Synthesis 2009, 4203−4207.
(b) Kumar, D.; Patel, G.; Reddy, V. B. Synlett 2009, 399−402.
(c) Kumar, D.; Reddy, V. B.; Varma, R. S. Tetrahedron Lett. 2009, 50,
2065−2068. (d) Keshavarz, M.; Badri, R. Mol. Diversity 2011, 15,
́
́ ́
ya, K.; Fekete, S.; Abraham, A.; Patonay, T. Mol.
957−962. (e) Kon
Diversity 2012, 16, 91−102.
(15) Nasr-Esfahani, M.; Mohammadpoor-Baltork, I.; Khosropour, A.
R.; Moghadam, M.; Mirkhani, V.; Tangestaninejad, S. J. Mol. Catal. A:
Chem. 2013, 379, 243−254.
(16) Beltran
2010, 12, 1404−1407.
(17) (a) Choi, J. W.; Cho, B.-K. Soft Matter 2011, 7, 4045−4049.
(b) Marcos, M.; Martín-Rapun, R.; Omenat, A.; Barbera, J.; Serrano, J.
L. Chem. Mater. 2006, 18, 1206−1212. (c) Aizpurua, J. M.; Sagartzazu-
́ ́
, E.; Serrano, J. L.; Sierra, T.; Gimenez, R. Org. Lett.
́
́
G
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