Ce(OTf)3-catalyzed [3 + 2] cycloaddition of azides with nitroolefins: Regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles

Article abstract of DOI:10.1021/jo5004339

The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and subsequent elimination reaction is described. In the presence of a catalytic amount of Ce(OTf)₃, both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent yields.

Full text of DOI:10.1021/jo5004339

Article
pubs.acs.org/joc
Ce(OTf)3‑Catalyzed [3 + 2] Cycloaddition of Azides with Nitroolefins:
Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazoles
Ying-Chun Wang,†,‡,§ Yu-Yang Xie,†,§ Hong-En Qu,† Heng-Shan Wang,*,† Ying-Ming Pan,*,†
and Fu-Ping Huang†
†Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of
Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, People’s Republic of China
‡College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, People’s Republic of China
S
* Supporting Information
ABSTRACT: The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and
subsequent elimination reaction is described. In the presence of a catalytic amount of Ce(OTf)3, both benzyl and phenyl azides
react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-
triazoles in good to excellent yields.
cycloaddition reactions of azides with nitroolefins, because, in
the absence of catalysts, these cycloaddition reactions tend to
be extremely sluggish and may take weeks, or even months, at
room temperature or elevated temperatures to get only partial
completion (Scheme 1a; refs 7a and 7b).7 Amantini et al.
reported in 2005 that TBAF could promote addition of azides
to nitroethenes, delivering the corresponding 1H-1,2,3-triazoles
in good yields under solvent-free conditions; nevertheless, the
reaction is limited to particularly activated, electron-deficient
nitroolefins (2-aryl-1-cyano- or 2-aryl-1-carbethoxy-1-nitro-
ethenes) and TMSN3 (Scheme 1a; ref 8).8 For these reasons,
the general, efficient, and highly regioselective protocol for the
synthesis of 1,2,3-triazoles from simple olefins has emerged as
an attractive and challenging goal.
Recently, the use of rare earth metal-catalyzed reactions has
emerged as a versatile tool for developing syntheses due to their
numerous advantages, namely, their relatively high efficiency,
water compatibility, mild reaction conditions, and eco-friendly
catalytic reactions.9 Herein, we report that 1,5-disubstituted
1,2,3-triazoles can be obtained by a Ce(OTf)3-catalyzed [3 + 2]
cycloaddition of azides with nitroolefins (Scheme 1b), thereby
providing a new synthetic method for 1,5-disubstituted 1,2,3-
triazole formation. To the best of our knowledge, this is the first
time that a rare earth metal catalyst has been described for [3 +
2] cycloadditions of azides with electron-deficient olefins.
INTRODUCTION
■
The 1,2,3-triazole nucleus represents a significant class of
biologically active nitrogen compounds that exhibit a number of
important biological properties, such as antibacterial, anti-
cancer, antivirus, and antituberculosis.1 In recent years, more
and more 1,2,3-triazole compounds are frequently employed as
candidates or clinical drugs for the therapy of various types of
diseases. Moreover, 1,2,3-triazoles have found industrial
applications as dyes, agrochemicals, corrosion inhibitors, and
photostabilizers.2 Therefore, the building up of a 1,2,3-triazole
moiety invokes ever growing synthetic efforts. The conven-
tional route to 1,2,3-triazole is the Huisgen dipolar cyclo-
addition of alkynes with organic azides.3 However, because of
the high activation energy, these cycloadditions generally
require elevated temperatures and long reaction times and
usually afford a mixture of the 1,4- and 1,5-regioisomers.
Catalyzed Huisgen cycloaddition of azides and terminal alkynes
by complexes of Cu(I) (CuAAC) represents an extremely
powerful method for the rapid assembly of 1,2,3-triazoles;4
nevertheless, the CuAAC process works only with terminal
alkynes and produces 1,4-disubstituted 1,2,3-triazoles exclu-
sively. Although the ruthenium (RuAAC)-catalyzed process
provides ready access to the complementary 1,5-regioisomers of
1,2,3-triazoles, all the reactions require the use of expensive
ruthenium complexes as catalysts.5 In contrast, there are as yet
few satisfactory catalytic systems for the regioselective
formation of 1,5-disubstituted 1,2,3-triazoles. On the other
hand, although numerous of alternative successful examples
have been reported in the literature for the preparation of 1,2,3-
triazoles,6 less attention has been paid to investigate [3 + 2]
Received: February 22, 2014
© XXXX American Chemical Society
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Scheme 1. Comparison of Previous Study and Our Work
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
solvent
yield of 2a (%)
c
1
none
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
32
2
3
In(OTf)3 (5 mol %)
Cu(OTf)2 (5 mol %)
Bi(OTf)3 (5 mol %)
AgOTf (5 mol %)
18
21
4
16
5
0
6
Zn(OTf)2 (5 mol %)
Y(OTf)3 (5 mol %)
Sc(OTf)3 (5 mol %)
[Rh(COD)Cl]2 (5 mol %)
PdCl2(dppf)2 (5 mol %)
Ce(OTf)3 (5 mol %)
Sm(OTf)3 (5 mol %)
Er(OTf)3 (5 mol %)
Pr(OTf)3 (5 mol %)
Yb(OTf)3 (5 mol %)
Ce(OTf)3 (10 mol %)
Ce(OTf)3 (1 mol %)
Ce(OTf)3 (5 mol %)
Ce(OTf)3 (5 mol %)
Ce(OTf)3 (5 mol %)
Ce(OTf)3 (5 mol %)
24
7
30
8
trace
trace
trace
85
76
9
10
d
11
12
13
14
15
16
17
73
70
74
86
60
e
18
0
19
20
21
DMF
trace
0
DMSO
PhCl
32
a
b
d
Carried out with 0.5 mmol of 1a and 0.6 mmol of benzyl azide in the presence of catalyst in solvent (2 mL) at 100 °C for 8 h (except for entry 1).
c
Isolated yield of pure product based on 1a. Carried out with 0.5 mmol of 1a and 0.6 mmol of benzyl azide in toluene (2 mL) at 100 °C for 3 days.
e
The reaction of 1a was also performed on a 20 mmol scale, and 2a was isolated in 78% yield. Reaction proceeded under reflux.
B
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a b
,
Table 2. Substrate Scope for the Reaction of Nitroolefins 1 and Azides
a
Reaction conditions: 0.5 mmol of 1 and 0.6 mmol of azide in the presence of Ce(OTf)3 (5 mol %) in 2 mL of toluene at 100 °C for 8 or 16 h.
Isolated yield of pure product based on 1.
b
isolated yield upon treatment of a 1:1.2 mixture of 1a and
benzyl azide with 5 mol % Ce(OTf)3 in toluene at 100 °C for 8
h (Table 1, entry 11). Without any catalysts, nitrosytrene 1a
reacted with benzyl azide in toluene at 100 °C to give 2a in a
RESULTS AND DISCUSSION
■
We initiated our research on the model reaction of benzyl azide
with nitrostyrene 1a under different reaction conditions (Table
1). 1,5-Disubstituted 1,2,3-triazole (2a) was obtained in 85%
C
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low yield (32%) after a long reaction time (3 days) (Table 1,
entry 1). Other common Lewis acids were not effective for this
conversion (Table 1, entries 2−7), and only a trace of desired
product was detected with Sc(OTf)3, [Rh(COD)Cl]2, and
PdCl2(dppf)2 as the catalysts (Table 1, entries 8−10). Among
the different rare earth metal catalysts, it was found that
Ce(OTf)3 was the most effective (Table 1, entry 11 vs entries
12−15). Increasing the amount of catalyst to 10 mol % did not
improve the yield (Table 1, entry 16), whereas, when the
amount of catalyst was decreased to 1 mol %, only a 60% yield
of 2a was obtained (Table 1, entry 17). Additionally, toluene
appeared to be the best choice among common solvents, such
as DCE, DMF, DMSO, and PhCl (Table 1, entries 11 and 18−
21).
Using our optimized experimental conditions, the scope of
the Ce(OTf)3-catalyzed formation of 1,5-disubstituted 1,2,3-
triazoles was examined. First, various arylnitroolefins were
investigated in reactions with benzyl azide (Table 2).
Nitroolefins bearing electron-withdrawing substituents on the
aryl ring facilitated the cycloaddition with excellent yields (2b−
2h), and electron-rich aryl nitroolefins also proceeded smoothly
with good yields (2i−2n). Generally, high yields were obtained
with nitroolefins bearing a heterocyclic (2o and 2p) and
naphthyl (2q). Notably, several sensitive functionalities, such as
nitriles (2h), alkoxy (2j, 2k, 2l, 2x), hydroxyl (2n), and nitro
(2f, 2g, 2u), were unaffected under the present reaction
conditions, and the reaction also tolerated ortho substitution in
the aromatic ring (2b, 2d, 2e, 2g). The crystallization of
compound 2n from ethanol gave a single crystal suitable for X-
ray analysis. Figure 1 illustrates the molecular structure of the
1,5-disubstituted 1,2,3-triazole 2n. To our delight, 1,4,5-
trisubstituted 1,2,3-triazole 2r was obtained in 78% yield
upon cycloaddition of 1-phenyl-2-nitropropene with benzyl
azide. In addition, the phenyl azide substrates were further
investigated, and the results indicated that both benzyl and
phenyl azides reacted successfully, whereas, with phenyl azides,
the yields were somewhat lower and a prolonged reaction time
(16 h) was needed (2s−2x). The chemoselectivity of the
reaction was also noteworthy. For all the aryl nitroolefins
tested, 1,5-disubstituted 1,2,3-triazole 2 was observed as the
sole product.
The scope of the reaction with respect to other electron-
deficient olefins, such as chalcone, cinnamonitrile, ethyl
cinnamate, and cinnamic aldehyde, was next investigated, and
satisfyingly, under the present reaction conditions, the [3 + 2]
cycloaddition reactions of chalcones with benzyl azide were
completed in a shorter time (5 h) and 1,4,5-trisubstituted 1,2,3-
triazoles 3a−3c were isolated in excellent yields (85, 92, and
82%, respectively) (Scheme 2). The structure of 3b was
confirmed by X-ray diffraction analysis (Figure 2). Unfortu-
Figure 2. X-ray crystal structure of 1,4,5-trisubstituted 1,2,3-triazole
3b.
nately, when cinnamonitrile, ethyl cinnamate, and cinnamic
aldehyde were used as substrates, respectively, only trace
amounts of the corresponding 1,4,5-trisubstituted 1,2,3-
triazoles were obtained.
A plausible mechanism for this Ce(OTf)3-catalyzed [3 + 2]
cycloaddition reaction is outlined in Scheme 3. As described
previously,7b,8 the first step of the reaction is the regioselective
1,3-dipolar cycloaddition of azide with nitroolefin 1 to form the
triazoline intermediate 4. Probably rare earth metal complexes
Figure 1. X-ray crystal structure of 1,5-disubstituted 1,2,3-triazole 2n.
Scheme 2. Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles 3 from Chalcone
D
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Scheme 3. A Plausible Reaction Mechanism
CDCl3) δ 7.70 (s, 1H), 7.34−7.32 (m, 3H), 7.22−7.14 (m, 3H),
6.97−6.94 (m, 2H), 5.40 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3)
δ 136.5, 134.9, 133.9, 131.7, 128.9, 128.6, 128.3, 128.2, 128.1, 125.9,
52.9 ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd for
C15H12Cl2N3, 304.0408; found 304.0387.
accelerated the reaction by increasing the electrophilicity of the
nitroolefin through coordination. The second step is the
elimination of HNO2 of the intermediate 4 leading to 1,5-
disubstituted 1,2,3-triazoles 2.
1-Benzyl-5-(4-nitrophenyl)-1H-1,2,3-triazole5g (2f). Yellow solid
CONCLUSIONS
1
■
(123 mg, 88%); mp 96−99 °C; H NMR (400 MHz, CDCl3) δ 8.25
We have disclosed the first rare earth metal-catalyzed [3 + 2]
cycloaddition of organic azides with nitroolefins to yield 1,5-
disubstituted 1,2,3-triazoles with good to excellent yields. Easily
available starting materials, experimentally convenient catalytic
process, as well as less expensive catalyst were the advantages of
the present procedure. Furthermore, this catalytic process did
not require dried glassware and an inert atmposphere. Further
study to explore the rare earth metal-catalyzed reactions of
azides with olefins to construct the biologically active molecules
is ongoing in our laboratory.
(d, J = 8.7 Hz, 2H), 7.83 (s, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.31−7.28
(m, 3H), 7.10−7.01 (m, 2H), 5.60 (s, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 148.3, 134.8, 134.1, 131.1, 129.7, 129.1, 128.6, 127.6, 126.9,
124.1, 52.4 ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd for
C15H13N4O2, 281.1039; found 281.1018.
1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazole10 (2g). Yellow solid
1
(126 mg, 90%); mp 149−151 °C; H NMR (400 MHz, CDCl3) δ
8.15−8.07 (m, 1H), 7.68−7.61 (m, 2H), 7.56−7.52 (m, 1H), 7.24−
7.16 (m, 5H), 7.02 (dd, J = 7.6, 1.3 Hz, 1H), 5.41 (s, 2H) ppm; 13C
NMR (100 MHz, CDCl3) δ 148.5, 134.2, 133.9, 133.3, 133.2, 133.1,
131.1, 128.7, 128.4, 127.8, 124.9, 122.1, 52.8 ppm; HRMS (APCI-ion
trap) m/z [M + H]+ calcd for C15H13N4O2, 281.1039; found 281.1019.
4-(1-Benzyl-1H-1,2,3-triazol-5-yl)benzonitrile (2h). Yellow solid
EXPERIMENTAL SECTTION
■
1
(114 mg, 88%); mp 84−86 °C; H NMR (400 MHz, CDCl3) δ 7.80
General Experimental Procedure for Synthesis of 1,5-
Disubstituted 1,2,3-Triazoles 2. A mixture of nitroolefin (1.0
equiv, 0.5 mmol), azide (1.2 equiv, 0.6 mmol), Ce(OTf)3 (0.05 equiv,
0.025 mmol), and 2 mL of toluene was refluxed at 100 °C for 8 or 16
h. The progress of the reaction was monitored by thin-layer
chromatography. The mixture was then cooled and evaporated
under reduced pressure. The target product 2 was purified by column
chromatography on silica gel using a mixture of ethyl acetate and
petroleum ether.
(s, 1H), 7.73−7.65 (m, 2H), 7.39−7.34 (m, 2H), 7.32−7.25 (m, 3H),
7.08−6.98 (m, 2H), 5.57 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3)
δ 136.4, 134.9, 133.909, 132.7, 131.5, 129.4, 129.1, 128.5, 126.9, 117.9,
113.4, 52.3 ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd for
C16H13N4, 261.1140; found 261.1132.
1-Benzyl-5-(4-methylphenyl)-1H-1,2,3-triazole6d (2i). Colorless oil
1
(100 mg, 80%); H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.29−
7.26 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 7.09−
7.07(m, 2H), 5.53 (s, 2H), 2.39 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 139.6, 138.2, 135.7, 133.1, 129.6, 128.8, 128.8, 128.1, 127.1,
123.9, 51.7, 21.3 ppm; HRMS (APCI-ion trap) m/z [M + H]+ calcd
for C16H16N3, 250.1344; found 250.1328.
1-Benzyl-5-phenyl-1H-1,2,3-triazole5g (2a). White solid (100 mg,
1
85%); mp 72−74 °C; H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H),
7.47−7.34 (m, 3H), 7.34−7.27 (m, 5H), 7.11−7.03 (m, 2H), 5.55 (s,
2H) ppm; 13C NMR (100 MHz, CDCl3) δ 138.2, 135.5, 133.3, 129.5,
128.9, 128.9, 128.8, 128.1, 127.1, 126.9, 51.8 ppm; HRMS (ESI-ion
trap) m/z [M + H]+ calcd for C15H14N3, 236.1188; found, 236.1185.
1-Benzyl-5-(2-chlorophenyl)-1H-1,2,3-triazole (2b). White solid
1-Benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazole6d (2j). Pale yel-
1
low oil (99 mg, 75%); H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H),
7.30−7.27 (m, 3H), 7.17−7.14 (m, 2H), 7.09−7.07 (m, 2H), 6.94−
6.90 (m, 2H), 5.53 (s, 2H), 3.84 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 160.5, 137.9, 135.7, 133.1, 130.3, 128.8, 128.1, 127.1, 118.9,
114.4, 55.4, 51.7 ppm; HRMS (APCI-ion trap) m/z [M + H]+ calcd
for C16H16N3O, 266.1293; found 266.1279.
1
(120 mg, 89%); mp 58−60 °C; H NMR (400 MHz, CDCl3) δ 7.71
(s, 1H), 7.49 (dd, J = 8.1, 1.0 Hz, 1H), 7.41−7.38 (m, 1H), 7.28−7.16
(m, 4H), 7.01 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (dd, J = 7.5, 1.7 Hz, 2H),
5.44 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 134.8, 134.8, 134.4,
134.3, 132.0, 131.2, 129.9, 128.6, 128.2, 127.7, 126.9, 126.4, 52.5 ppm;
HRMS (ESI-ion trap) m/z [M + H]+ calcd for C15H13ClN3, 270.0798;
found 270.0781.
5-(1,3-Benzodioxol-5-yl)-1-benzyl-1H-1,2,3-triazole (2k). Yellow
1
oil (106 mg, 76%); H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H),
7.34−7.25 (m, 3H), 7.12−7.05 (m, 2H), 6.83 (d, J = 8.0 Hz, 1H),
6.75−6.66 (m, 2H), 6.01 (s, 2H), 5.53 (s, 2H) ppm; 13C NMR (100
MHz, CDCl3) δ 148.7, 148.1, 137.9, 135.5, 133.2, 128.9, 128.2, 127.1,
123.0, 120.2, 109.1, 108.8, 101.6, 51.7 ppm; HRMS (ESI-ion trap) m/z
[M + H]+ calcd for C16H14N3O2, 280.1086; found 280.1071.
1-Benzyl-5-(3-bromophenyl)-1H-1,2,3-triazole (2c). Yellow solid
1
(140 mg, 90%); mp 68−70 °C; H NMR (400 MHz, CDCl3) δ 7.70
(s, 1H), 7.67 (dd, J = 7.8, 1.4 Hz, 1H), 7.35−7.24 (m, 2H), 7.24−7.15
(m, 3H), 7.02−6.91 (m, 3H), 5.43 (s, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 136.4, 134.7, 134.3, 133.1, 132.1, 131.3, 128.6, 128.4, 128.2,
127.8, 127.4, 124.3, 52.5 ppm; HRMS (ESI-ion trap) m/z [M + H]+
calcd for C15H13N3Br, 314.0293, 316.0272; found 314.0275, 316.0255.
1-Benzyl-5-(2-chloro-6-fluorophenyl)-1H-1,2,3-triazole (2d).
1-Benzyl-5-[3-(benzyloxy)-4-methoxyphenyl]-1H-1,2,3-triazole
1
(2l). Yellow oil (131 mg, 71%); H NMR (400 MHz, CDCl3) δ 7.69
(s, 1H), 7.44−7.26 (m, 8H), 7.11−7.04 (m, 2H), 6.90 (d, J = 8.3 Hz,
1H), 6.76 (dd, J = 8.2, 2.0 Hz, 1H), 6.62 (d, J = 1.9 Hz, 1H), 5.52 (s,
2H), 5.18 (s, 2H), 3.65 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ
149.7, 149.1, 138.1, 136.5, 135.9, 133.1, 128.9, 128.7, 128.1, 128.1,
127.3, 126.9, 121.6, 119.6, 113.8, 112.3, 70.9, 55.8, 51.7 ppm; HRMS
(ESI-ion trap) m/z [M + H]+ calcd for C23H22N3O2, 372.1712; found
372.1688.
1
White solid (126 mg, 88%); mp 62−65 °C; H NMR (400 MHz,
CDCl3) δ 7.72 (s, 1H), 7.37−7.31 (m, 1H), 7.22 (d, J = 8.2 Hz, 1H),
7.20−7.09 (m, 3H), 6.99 (m, 1H), 6.92−6.89 (m, 2H), 5.42 (s, 2H)
1
ppm; 13C NMR (100 MHz, CDCl3) δ 160.4 (d, JCF = 250.1 Hz),
4
3
135.6 (d, JCF = 3 Hz), 135.5, 134.1, 132.2 (d, JCF = 9.4 Hz), 128.6,
128.6, 128.3, 127.6, 125.6 (d, 4JCF = 3.6 Hz), 115.3 (d, 2JCF = 18.6 Hz),
114.3 (d, 2JCF = 21.7 Hz), 52.9 ppm; HRMS (ESI-ion trap) m/z [M +
H]+ calcd for C15H12ClFN3, 288.0704; found 288.0694.
4-(1-Benzyl-1H-1,2,3-triazol-5-yl)-N,N-dimethylamine (2m). Red
solid (97 mg, 70%); mp 132−134 °C (lit.11 132 °C); H NMR (400
1
MHz, CDCl3) δ 7.67 (s, 1H), 7.34−7.25 (m, 3H), 7.13−7.10 (m, 4H),
6.71−6.67 (m, 2H), 5.54 (s, 2H), 3.00 (s, 6H) ppm; 13C NMR (100
MHz, CDCl3) δ 150.9, 138.7, 136.0, 132.6, 129.7, 128.8, 127.9, 127.1,
1-Benzyl-5-(2,6-dichlorophenyl)-1H-1,2,3-triazole (2e). Yellow
solid (144 mg, 95%); mp 118−120 °C; 1H NMR (400 MHz,
E
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113.7, 112.1, 51.5, 40.2 ppm; HRMS (ESI-ion trap) m/z [M + H]+
calcd for C17H19N4, 279.1610; found 279.1592.
ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd for C12H10N3S,
228.0595; found 228.0581.
4-(1-Benzyl-1H-1,2,3-triazol-5-yl)phenol (2n). Yellow solid (85
Methyl 4-(1-Phenyl-1H-1,2,3-triazol-5-yl)phenyl Ether6d (2x).
1
1
mg, 68%); mp 179−181 °C; H NMR (400 MHz, CDCl3) δ 7.70 (s,
Yellow oil (56 mg, 45%); H NMR (400 MHz, CDCl3) δ 7.81 (s,
1H), 7.46−7.35 (m, 5H), 7.17−7.12 (m, 2H), 6.88−6.84 (m, 2H),
3.81 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 160.3, 137.6, 136.7,
133.0, 130.0, 129.4, 129.2, 125.2, 118.9, 114.3, 55.3 ppm; HRMS (ESI-
ion trap) m/z [M + H]+ calcd for C15H14N3O, 252.1137; found
252.1119.
1H), 7.41−7.23 (m, 4H), 7.12−7.09 (m, 3H), 6.97−6.83 (m, 2H),
5.53 (s, 2H), 5.30 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ
157.5, 138.3, 135.5, 132.8, 130.4, 128.8, 128.2, 127.2, 118.4, 116.1, 51.8
ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd for C15H14N3O,
252.1137; found 252.1117.
(1-Benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)(phenyl)methanone
1-Benzyl-5-(2-furyl)-1H-1,2,3-triazole (2o). Yellow solid (95 mg,
84%); mp 79−81 °C; H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H),
7.43 (dd, J = 5.1, 1.2 Hz, 1H), 7.34−7.25 (m, 3H), 7.13−7.05 (m,
3H), 7.01 (dd, J = 3.6, 1.2 Hz, 1H), 5.65 (s, 2H) ppm; 13C NMR (100
MHz, CDCl3) δ 143.6, 141.3, 135.1, 132.4, 129.1, 128.9, 128.2, 127.1,
111.8, 110.4, 52.8 ppm; HRMS (APCI-ion trap) m/z [M + H]+ calcd
for C13H12N3O, 226.0980; found 226.0967.
1
1
(3a). Colorless oil (144 mg, 85%); H NMR (500 MHz, CDCl3) δ
8.34−8.23 (m, 2H), 7.59−7.54 (m, 1H), 7.50−7.41 (m, 5H), 7.30−
7.24 (m, 5H), 7.08−7.04 (m, 2H), 5.47 (s, 2H) ppm; 13C NMR (125
MHz, CDCl3) δ 186.4, 143.8, 141.8, 137.1, 134.7, 133.0, 130.7, 130.1,
129.8, 128.9, 128.7, 128.5, 128.2, 127.7, 126.4, 52.1 ppm; HRMS (ESI-
ion trap) m/z [M + H]+ calcd for C22H18N3O, 340.1450; found
340.1439.
1-Benzyl-5-(2-thienyl)-1H-1,2,3-triazole (2p). Yellow solid (104
1
(1-Benzyl-5-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)(phenyl)-
mg, 86%); mp 77−79 °C; H NMR (400 MHz, CDCl3) δ 7.81 (s,
methanone (3b). White solid (171 mg, 92%); mp 130−132 °C (lit.13
1H), 7.44 (dd, J = 5.1, 1.2 Hz, 1H), 7.34−7.26 (m, 3H), 7.13−7.05
(m, 3H), 7.02 (dd, J = 3.6, 1.2 Hz, 1H), 5.66 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3) δ 135.3, 133.9, 131.8, 128.9, 128.5, 128.2, 128.1,
127.9, 126.9, 126.6, 51.9 ppm; HRMS (APCI-ion trap) m/z [M + H]+
calcd for C13H12N3S, 242.0752; found 242.0739.
1
129−131 °C); H NMR (500 MHz, CDCl3) δ 8.38−8.28 (m, 2H),
7.54−7.49 (m, 2H), 7.47−7.43 (m, 2H), 7.37−7.28 (m, 6H), 7.12−
7.08 (m, 2H), 5.49 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ
186.2, 140.8, 137.0, 136.4, 134.5, 133.2, 131.2, 131.0, 130.7, 129.4,
129.0, 129.0, 128.6, 128.3, 127.6, 52.2 ppm; HRMS (ESI-ion trap) m/z
[M + H]+ calcd for C22H17ClN3O, 374.1060; found 374.1052.
(1-Benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)(phenyl)-
1-Benzyl-5-(2-naphthyl)-1H-1,2,3-triazole11 (2q). Yellow oil (117
mg, 82%); 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.49 (dd, J =
8.1, 1.0 Hz, 1H), 7.42−7.38 (m, 1H), 7.28−7.16 (m, 4H), 7.01 (dd, J
= 7.6, 1.6 Hz, 1H), 6.95−6.93 (m, 2H), 5.44 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3) δ 138.2, 135.6, 133.5, 133.3, 132.9, 128.9, 128.8,
128.6, 128.2, 128.2, 127.8, 127.3, 127.2, 127.0, 125.9, 124.1, 52.0 ppm;
HRMS (APCI-ion trap) m/z [M + H]+ calcd for C19H16N3, 286.1344;
found 286.1331.
1
methanone (3c). Yellow oil (151 mg, 82%); H NMR (500 MHz,
CDCl3) δ 8.30−8.26 (m, 2H), 7.61−7.52 (m, 1H), 7.49−7.45 (m,
2H), 7.31−7.28 (m, 3H), 7.23−7.20 (m, 2H), 7.12−7.09 (m, 2H),
6.99−6.94 (m, 2H), 5.48 (s, 2H), 3.85 (s, 3H) ppm; 13C NMR (125
MHz, CDCl3) δ 186.5, 160.9, 143.6, 141.8, 137.3, 134.9, 133.0, 131.3,
130.7, 128.9, 128.4, 128.2, 127.6, 118.2, 114.2, 55.4, 51.9 ppm; HRMS
(ESI-ion trap) m/z [M + H]+ calcd for C23H20N3O2, 370.1556; found
370.1544.
4-Benzyl-4-methyl-5-phenyl-1H-1,2,3-triazole (2r). Colorless oil
1
(97 mg, 78%); H NMR (400 MHz, CDCl3) δ 7.45−7.39 (m, 3H),
7.25−7.23 (m, 3H), 7.18−7.09 (m, 2H), 7.07−6.96 (m, 2H), 5.43 (s,
2H), 2.30 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 141.6, 135.6,
134.6, 129.5, 129.2, 128.9, 128.7, 128.0, 127.4, 127.3, 52.0, 10.67 ppm;
HRMS (ESI-ion trap) m/z [M + H]+ calcd for C16H16N3, 250.1344;
found 250.1325.
ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental methods; H and 13C NMR spectra of
1
1,5-Diphenyl-1H-1,2,3-triazole (2s). White solid (74 mg, 68%); mp
112−113 °C (lit.6c 113−114 °C); 1H NMR (400 MHz, CDCl3) δ 7.87
(s, 1H), 7.47−7.41 (m, 3H), 7.40−7.32 (m, 5H), 7.24−7.21 (m, 2H)
ppm; 13C NMR (100 MHz, CDCl3) δ 137.7, 136.6, 133.4, 129.4,
129.2, 128.9, 128.6, 126.8, 125.2 ppm; HRMS (ESI-ion trap) m/z [M
+ H]+ calcd for C14H12N3, 222.1031; found 222.1018.
5-(4-Bromophenyl)-1-phenyl-1H-1,2,3-triazole (2t). Yellow solid
(119 mg, 80%); mp 149−151 °C; 1H NMR (400 MHz, CDCl3) δ 7.87
(s, 1H), 7.51−7.41 (m, 5H), 7.38−7.32 (m, 2H), 7.12−7.06 (m, 2H)
ppm; 13C NMR (100 MHz, CDCl3) δ 136.3, 133.4, 132.8, 132.2,
130.0, 129.5, 129.5, 125.7, 125.2, 123.7 ppm; HRMS (ESI-ion trap)
m/z [M + H]+ calcd for C14H11BrN3, 300.0136, 302.0116; found
300.0121, 302.0099.
5-(4-Nitrophenyl)-1-phenyl-1H-1,2,3-triazole (2u). Yellow solid
(100 mg, 75%); mp 143−144 °C (lit.12 144−145 °C); 1H NMR
(400 MHz, CDCl3) δ 8.23−8.18 (m, 2H), 7.99 (s, 1H), 7.53−7.46 (m,
3H), 7.44−7.39 (m, 2H), 7.38−7.32 (m, 2H) ppm; 13C NMR (100
MHz, CDCl3) δ 147.9, 135.9, 134.2, 133.0, 129.9, 129.8, 129.3, 125.3,
124.5, 124.2 ppm; HRMS (APCI-ion trap) m/z [M + H]+ calcd for
C14H11N4O2, 267.0882; found 267.0864.
compounds 2a−2x and 3a−3c; high-resolution mass spectra of
compounds 2a−2x and 3a−3c; and X-ray crystallographic files
(CIF) for 2n and 3b. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: whengshan@163.com. Phone: +86-773-5846279. Fax:
+86-773-5803930 (H.-S.W.).
■
*E-mail: panym2013@hotmail.com (Y.-M.P.).
Author Contributions
§Y.-C.W. and Y.-Y.X. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the project 973 (2011CB512005), Ministry of
Education of China (IRT1225), the National Natural Science
Foundation of China (21362002, 41206077, and 81260472),
the Guangxi Natural Science Foundation of China
(2012GXNSFAA053027 and 2011GXNSFD018010), and the
Bagui Scholar Program of Guangxi for financial support.
5-(2-Naphthyl)-1-phenyl-1H-1,2,3-triazole (2v). Yellow oil (95 mg,
1
70%); H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.84−7.75 (m,
4H), 7.56−7.48 (m, 2H), 7.48−7.35 (m, 5H), 7.22 (dd, J = 8.5, 1.8
Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 137.8, 136.7, 133.7,
133.2, 133.0, 129.4, 129.2, 128.6, 128.3, 128.2, 127.8, 127.2, 126.9,
125.6, 125.2, 124.1 ppm; HRMS (ESI-ion trap) m/z [M + H]+ calcd
for C18H14N3, 272.1188; found 272.1184.
1-Phenyl-5-(2-thienyl)-1H-1,2,3-triazole6d (2w). Brown oil (76 mg,
67%);1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.57−7.49 (m,
3H), 7.48−7.41 (m, 2H), 7.36 (d, J = 5.1 Hz, 1H), 7.01−6.98 (m,
1H), 6.94 (d, J = 3.7 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ
136.3, 133.0, 132.5, 130.0, 129.4, 128.1, 127.7, 127.7, 127.1, 126.1
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