Zn/C-catalyzed cycloaddition of azides and aryl alkynes

Article abstract of DOI:10.1002/ejoc.201000610

Charcoal impregnated with zinc was able to catalyze the cycloaddition of organic azides and alkynes to provide the corresponding 1,4-disubstituted 1,2,3-triazoles and 1,4,5-trisubstituted 1,2,3-triazoles in good to excellent yields. Noteworthy was that th

Full text of DOI:10.1002/ejoc.201000610

FULL PAPER
DOI: 10.1002/ejoc.201000610
Zn/C-Catalyzed Cycloaddition of Azides and Aryl Alkynes
Xu Meng,[a] Xiaoyun Xu,[a] Tingting Gao,[a] and Baohua Chen*[a]
Keywords: Zinc / Cycloaddition / Heterogeneous catalysis / Azides / Click chemistry
Charcoal impregnated with zinc was able to catalyze the cy-
cloaddition of organic azides and alkynes to provide the cor-
responding 1,4-disubstituted 1,2,3-triazoles and 1,4,5-trisub-
stituted 1,2,3-triazoles in good to excellent yields. Note-
worthy was that the novel and heterogeneous catalyst was
successfully applied in this cycloaddition reaction for the first
time and could also be easily recycled.
uct(s) separation and reuse of catalysts.[8] These problems
and the wide applicability of this reaction led us to explore
the possibility of an attractive click-compatible hetero-
geneous version. To the best of our knowledge, there are a
few reports that offer heterogeneous copper catalysts for
such a purpose. The Sommer group showed that CuI–zeo-
lites as a heterogeneous and ligand-free catalyst could be
used efficiently for the Huisgen [3+2] cycloaddition.[9] In
2006, the Lipshutz group developed an efficient cycload-
dition reaction between organic azides with terminal al-
kynes in the presence of a heterogeneous recyclable Cu/C
catalyst.[10] Recently, Mizuno and co-workers group re-
ported that Cu(OH)x/TiO2 could act as an efficient hetero-
geneous catalyst in Huisgen [3+2] cycloadditions.[11] As a
complement to the previous methods, we describe a novel
and heterogeneous Zn/C (zinc-on-charcoal)-catalyzed cy-
cloaddition of aryl/aliphatic azides and aryl alkynes (includ-
ing internal alkynes), and this is the first report of zinc be-
ing used as a catalyst in [3+2] cycloaddition reactions.
Introduction
“Click chemistry”, first defined by Sharpless and co-
workers,[1] offers an almost unlimited array of inert triazole-
containing architectures resulting from Huisgen [3+2] cy-
cloadditions,[2] in particular between organic azides and al-
kynes. In the past years, copper catalysts have played an
important role in cycloadditions between azides and al-
kynes,[3] and the developed methods show various applica-
tions in organic synthesis, chemical biology, and materials
science.[4] Generally, the used copper source comes from di-
rect addition of CuI species[3b,3c,3h] or reduction of CuII
salts to CuI salts,[3a,3i] oxidation of copper metal turnings to
give CuI species,[5] copper nanoclusters,[6] copper combined
with suitable ligands, and copper complexes.[7] Despite the
great advantages of these cases, there remains some draw-
backs, such as that oxidative agents are required and a sig-
nificant amount of catalyst is necessary. As copper(I) salts
are quite prone to redox processes, nitrogen- or phospho-
rus-based ligands must be added to protect and stabilize
the active copper catalyst during the cycloaddition reaction.
Nevertheless, formation of undesired byproducts, primarily
diacetylenes and bistriazoles, was often observed.[3a]
Results and Discussion
Our initial experiments of 4-nitrophenyl azide and phen-
ylacetylene were carried out by using CH2Cl2 as the solvent
at 50 °C for 15 h in air to better the cycloaddition (Table 1).
Firstly, optimization studies revealed that the cycloaddition
reaction could perform with moderate yields when using
various zinc salts (Table 1, Entries 1–5). When simple Zn
powder was used as the catalyst, a reaction was still ob-
served, although the yield of the desired product was poor
(Table 1, Entry 6). To our delight, the reaction performed
smoothly with the use of Zn/C instead of Zn powder as
the catalyst, and it was more effective than other zinc salts
(Table 1, Entry 7). It is encouraging that no bases, ligands,
or other additives were required for Zn/C to efficiently cata-
lyze the cycloaddition and diacetylene and bistriazole by-
products were not observed. Not surprisingly, the reaction
failed when charcoal was used as the catalyst or when no
catalyst was used at all. Secondly, to find the most suitable
View this journal online at
Furthermore, the above approaches are mostly homogen-
eous in nature and minimal progress has been made in the
use of heterogeneous catalysts to perform this kind of cyclo-
addition. It is acknowledged that homogeneous copper-cat-
alyzed systems have serious shortcomings in the difficulty
of catalyst/product separation, reuse of catalysts, and indis-
pensability of additives, such as reducing agents, stabilizing
ligands, and bases. By contrast, heterogeneous systems with
solid catalysts have significant advantages in catalyst/prod-
[a] Key Laboratory of Nonferrous Metal Chemistry and Resources
Utilization of Gansu Province, State Key Laboratory of
Applied Organic Chemistry Lanzhou University, Lanzhou
University,
Lanzhou 730000, P. R. China
Fax: +86-931-8912582
E-mail: chbh@lzu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000610.
wileyonlinelibrary.com
Eur. J. Org. Chem. 2010, 5409–5414
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5409

X. Meng, X. Xu, T. Gao, B. Chen
FULL PAPER
solvent for this catalyst, we used organic solvents, mixed strates, experiments were performed smoothly and the cor-
solvents, and H2O. The results showed that nonpolar and responding triazoles were obtained in good to excellent
protic solvents were poor, and the polar solvent DMF was yields (Table 2, Entries 1, 2, and 4–16). In general, no sig-
the best choice (Table 1, Entries 7 and 10–19). Finally, the nificant difference in reactivity was observed for the exam-
reaction temperature and the loading of the catalyst were ined reactants with varied electronic properties. Both elec-
also examined; the results showed that 50 °C was a suitable tron-rich and electron-poor azides as reactants generated
temperature and that 0.1 equiv. of Zn/C was the optimum good to excellent yields of the products (Table 2, Entries 1,
amount of catalyst (Table 1, Entries 7 and 20).
9, 10, 12, and 14). Moreover, aryl and aliphatic azides could
both react with phenylacetylene efficiently (Table 2, En-
tries 1, 2, and 4–16). Note that low yields were found when
the organic azides were hindered (Table 2, Entries 5–8, 11,
and 13), and sensitive functional groups like 2-nitrophenyl
azide and heterocyclic azide rendered the cycloaddition un-
responsive (Table 2, Entries 3 and 17).
Table 1. Variations in reaction conditions.[a]
Table 2. Zn/C-catalyzed cycloaddition of organic azides with phen-
ylacetylene.[a]
Entry
Catalyst
Solvent
Yield [%][b]
1
2
3
ZnCl2
ZnBr2
ZnO
DMF
DMF
DMF
75
74
58
4
5
6
7
Zn(acac)2
ZnOAc·2H2O
Zn powder
Zn/C
DMF
DMF
DMF
DMF
81
78
27
Entry
Azide (R =)
Time [h]
Triazole
Yield [%][b]
91 (90[c], 68[d]
)
1
2
3
4
5
6
7
8
4-NO2C6H4
3-NO2C6H4
2-NO2C6H4
3-ClC6H4
15
15
15
15
15
15
15
15
15
15
15
15
15
15
20
20
20
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
91
87
0
8
9
none
charcoal
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
Zn/C
CuI
CuSO4/C
DMF
DMF
DMF/H2O (1:1)
EtOH
0
0
47
7
0
0
0
0
56
0
0
10
11
12
13
14
15
16
17
18
19
20
21
22
79
66
70
65
64
93
94
63
94
71
95
85
83
0
2-ClC6H4
H2O
2,5-Cl2C6H4
2-BrC6H4
2-IC6H4
H2O/EtOH (1:1)
acetone
CH3CN
DMSO
THF
9
Ph
10
11
12
13
14
15
16
17
4-CH3C6H4
2-CH3C6H4
4-CH3OC6H4
2-CH3OC6H4
3,4-(CH3)2C6H3
n-C4H9
CH2Cl2
toluene
DMF
DMF
DMF
36
30[e]
trace
0[f]
n-C5H11
2-pyridyl
[a] Reaction conditions:
1 (1.0 equiv.), 2 (1.2 equiv.), catalyst
(0.1 equiv.), solvent (1 mL/mmol of 1), 50 °C, 15 h. [b] Isolated
yield. [c] 20 mol-% of Zn/C was used. [d] 5 mol-% of Zn/C was
used. [e] At room temperature. [f] Trace amount of CuSO4
(0.0005 mol-%) and C (10 mol-%) were used.
[a] Reaction conditions:
(0.1 equiv.), DMF (1 mL/mmol of 1), 50 °C, 15 h. [b] Isolated yield.
1
(1.0 equiv.), 2 (1.2 equiv.), Zn/C
As shown in Table 3, the cycloaddition of aryl alkynes
Zinc dust often has trace CuII impurities (up to 50 mg/ with benzyl azide performed efficiently to provide the de-
kg), whereas charcoal might play a role that could reduce sired products in high yields (Table 3, Entries 1–11). It was
CuII to CuI. Therefore, it is wondered whether a trace concluded that the cycloaddition was slightly influenced by
amount of CuI generated in situ catalyzed the cycloaddition electronic properties. Specifically, electron-rich aryl alkynes
rather than Zn/C. We used CuI (10 mol-%) as the catalyst gave higher yields of the desired products than electron-
instead of Zn/C to carry out the reaction, but the desired poor ones (Table 3, Entries 1–9).
product was not obtained (Table 1, Entry 21). Then, a trace
Surprisingly, this cycloaddition also proceeded success-
quantity of CuII and charcoal as the catalyst was used in- fully in the case of heterocyclic alkynes like 2-pyridylacetyl-
stead of Zn/C to perform control experiments (see the Sup- ene and 3-thienylacetylene, although the yields were lower
porting Information). Finally, we did not observe any cyclo- than other substrates (Table 3, Entries 10 and 11). Disap-
addition products, so it is speculated that Zn/C could cata- pointedly, the use of aliphatic alkynes as reactants gave no
lyze the reaction between azides and alkynes.
reaction (Table 3, Entries 12–14).
After optimizing the process, the Zn/C-catalyzed cyclo-
Interestingly, the one-pot synthesis of triazoles from a
addition of organic azides with alkynes was performed un- halide, NaN3, and an alkyne could be realized
der the standard conditions: Zn/C (10 mol-%) as the cata- (Scheme 1).[12] Triazoles 4a and 4o could be obtained by the
lyst and DMF as the solvent at 50 °C without exclusion of convenient Zn/C-catalyzed three-component reaction,
air. As shown in Table 2, for most of the examined sub- though the yields were slightly low.
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Zn/C-Catalyzed Cycloaddition of Azides and Aryl Alkynes
Table 3. Zn/C-catalyzed cycloaddition of benzyl azide with ter-
minal alkynes.[a]
Entry
Alkyne (R =)
Time [h]
Triazole
Yield [%][b]
1
2
3
4
5
6
7
8
Ph
4-CH3OC6H4
4-n-C5H11OC6H4
3-CH3C6H4
4-NO2C6H4
4-BrC6H4
2-ClC6H4
4-FC6H4
3-NH2C6H4
2-pyridyl
3-thienyl
n-C4H9
2-OH-propyl
BrCH2
15
15
15
15
15
15
15
15
15
15
15
20
20
20
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
90
95
94
92
91
92
89
92
83
81
76
0
Scheme 2. Synthesis of 1,4,5-trisubstituted 1,2,3-triazoles.
9
10
11
12
13
14
0
0
[a] Reaction conditions:
(0.1 equiv.), DMF (1 mL/mmol of 1), 50 °C, 15 h. [b] Isolated yield.
1
(1.0 equiv.), 2 (1.2 equiv.), Zn/C
Scheme 3. Testing of the heterogeneous catalyst.
nitrophenyl azide and phenylacetylene as the reaction part-
ners (Table 4). The catalyst was recovered after 15 h, fil-
tered, washed successively with H2O and CH2Cl2, dried,
and then subjected to the second run of the same reaction
process. After three recycles, the activity of the recovered
catalyst decreased gradually to 73%. However, after the
fifth time, the catalyst efficiency dramatically decreased
(Table 4, run 5 vs. runs 1–4).
Scheme 1. Three-component reaction.
More importantly, some examples of 1,4,5-trisubstituted
1,2,3-triazoles have been obtained in moderate yield by the
Zn/C-catalyzed cycloaddition by using internal alkynes as
the substrates (Scheme 2), which could not be realized by
the Cu-catalyzed system.[13] Because CuI acetylides seem to
be the bona fide intermediates in copper-assisted azide–
alkyne cycloadditions (CuAAC),[3] this transformation is
limited to terminal alkynes. The Zn/C-catalyzed system, in
fortunate contrast, is active with internal alkynes as well. As
shown in Scheme 2, electron-rich and electron-poor azides
could react with 1,2-diphenylethyne to provide the desired
products in moderate yields. However, steric hindrance af-
fected the reaction obviously and limited the scope of the
reaction to some extent.
Table 4. Recovery and reuse of Zn/C.
Run
Product yield [%][a]
Catalyst recovery [%]
1
2
3
4
5
91
88
85
73
45
76
80
82
85
86
To confirm that this procedure catalyzed by Zn/C is un-
ambiguously heterogeneous in nature, an additional experi-
ment was carried out (Scheme 3). After filtering a totally
converted reaction mixture (4-NO2PhN3 as a substrate) to
remove the catalyst, 1.0 equiv. of a different azide (4-
MePhN3) was added as an additional substrate to the fil-
trate, and the filtrate was then treated with the remaining
[a] Isolated yield.
The mechanistic underpinnings for this Zn/C-catalyzed
amount of phenylacetylene. A trace amount of another tri- synthesis of triazoles need much more studies, but we offer
azole, while adding the fresh Zn/C to the filtrate, led to 90% the following tentative hypothesis. As both terminal and in-
yield of the additional desired product.
ternal alkynes participate in the catalyzed reaction, the in-
Finally, we examined the recovery and reuse of Zn/C. volvement of zinc acetylides is unlikely. Therefore, a plaus-
The reuse test of Zn/C was carried out in DMF by using 4- ible mechanism might involve the oxidative coupling of an
Eur. J. Org. Chem. 2010, 5409–5414
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X. Meng, X. Xu, T. Gao, B. Chen
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(400 MHz, CDCl3): δ = 8.19 (s, 1 H), 7.91–7.89 (d, J = 7.2 Hz, 2
H), 7.84 (s, 1 H), 7.72–7.70 (d, J = 8.0 Hz, 1 H), 7.51–7.36 (m, 5
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.6, 137.8, 135.6,
130.8, 129.9, 128.9, 128.8, 128.6, 125.8, 120.7, 118.4, 117.3 ppm.
alkyne and an azide onto zinc, which may give a six-mem-
bered metallacycle. Then, the six-membered metallacycle
would undergo reductive elimination releasing the aromatic
triazole product.[13]
1-(2-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (3e): Colorless oil,
isolated yield 66% (Table 2, Entry 5). 1H NMR (400 MHz, CDCl3):
δ = 8.21 (s, 1 H), 7.93–7.91 (d, J = 7.2 Hz, 2 H), 7.69–7.67 (m, 1
H), 7.61–7.59 (m, 1 H), 7.49–7.46 (m, 4 H), 7.51–7.35 (m, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.9, 134.9, 130.8,
130.7, 130.1, 128.9, 128.5, 128.4, 127.9, 127.7, 125.8, 121.6 ppm.
Conclusions
In summary, we have shown for the first time that 1,4-
disubstituted 1,2,3-triazoles can be constructed from or-
ganic azides and aryl alkynes by using Zn/C as an efficient
and heterogeneous catalyst. The catalytic system could tol-
erate a large variety of functional groups, including elec-
tron-rich and electron poor substrates and heterocyclic al-
kynes. Benzyl halides, NaN3, and alkynes could be con-
verted into 1,4-disubstituted 1,2,3-triazoles by a convenient
one-pot three-component reaction. In addition, the prepa-
ration of 1,4,5-trisubstituted 1,2,3-triazoles was demon-
strated under Zn/C catalysis, but these compounds could
not be synthesized under Cu catalysis. Finally, the hetero-
geneous Zn/C catalyst has significant advantages in cata-
lyst/product separation and reuse.
1-(2,5-Dichlorophenyl)-4-phenyl-1H-1,2,3-triazole (3f): White solid,
1
isolated yield 70% (Table 2, Entry 6), m.p. 111–113 °C. H NMR
(400 MHz, CDCl3): δ = 8.23 (s, 1 H), 7.92–7.90 (m, 2 H), 7.74 (s,
1 H), 7.55–7.36 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
147.8, 135.5, 133.7, 131.6, 130.7, 129.8, 128.9, 128.5, 127.7, 126.6,
125.9, 121.3 ppm.
1-(2-Bromophenyl)-4-phenyl-1H-1,2,3-triazole (3g): Colorless oil,
isolated yield 65% (Table 2, Entry 7). 1H NMR (400 MHz, CDCl3):
δ = 8.17 (s, 1 H), 7.94–7.79 (t, J = 7.6 Hz, 2 H), 7.78–7.76 (t, J =
6.8 Hz, 1 H), 7.62–7.60 (m, 1 H), 7.53–7.35 (m, 5 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 147.5, 136.5, 133.9, 131.1, 130.1,
128.9, 128.5, 128.4, 128.1, 125.8, 121.6, 118.5 ppm.
1-(2-Iodophenyl)-4-phenyl-1H-1,2,3-triazole (3h): White solid, iso-
lated yield 64% (Table 2, Entry 8), m.p. 149–151 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.08 (s, 1 H), 8.03–8.00 (d, J = 8.1 Hz, 1
H), 7.93 (t, J = 7.2 Hz, 2 H), 7.55–7.46 (m, 4 H), 7.44–7.27 (m, 1
H), 7.23 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.6,
140.2, 140.0, 131.1, 130.2, 129.2, 128.9, 128.4, 127.8, 125.8, 121.5,
93.8 ppm.
Experimental Section
General Remarks: All reagents were purchased from commercial
suppliers and were used with further purification. Zn/C (10%, Alfa
Aesar) was commercially available and was used directly. All experi-
ments were carried out in air. Flash chromatography was carried
out with Merck silica gel 60 (63–200 mesh). Analytical TLC was
performed with Merck silica gel 60 F254 plates, and the products
were visualized by UV detection. 1H and 13C NMR (300 or 400
and 75 or 100 MHz, respectively) spectra were recorded in CDCl3.
Chemical shifts (δ) are reported in ppm using TMS as internal stan-
dard.
1,4-Diphenyl-1H-1,2,3-triazole (3i): White solid, isolated yield 93%
1
(Table 2, Entry 9), m.p. 177–179 °C. H NMR (300 MHz, CDCl3):
δ = 8.19 (s, 1 H), 7.93–7.90 (d, J = 7.8 Hz, 2 H) 7.81–7.78 (d, J =
8.4 Hz, 2 H) 7.57–7.36 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 149.4, 137.0, 130.2, 129.7, 128.9, 128.7, 128.4, 123.6, 120.5,
117.5 ppm.
General Procedure for the Zn/C-Catalyzed Cycloaddition Reaction:
Zn/C (100 mg, 1.00 mmol/g, ca. 0.1 mmol), azide (1.0 mmol), al-
kyne (1.2 mmol), and DMF (1 mL) were added to a flask with a
stirring bar. The flask was stirred at 50 °C for the indicated time.
After cooling to room temperature, the mixture was diluted with
ethyl acetate and filtered. The filtrate was concentrated under re-
duced pressure to afford the crude product, which was further puri-
fied by silica gel chromatography (petroleum/ethyl acetate, 5:1) to
yield the corresponding product. The identity and purity of the
products was confirmed by 1H and 13C NMR spectroscopic analy-
sis.
1-(4-Methylphenyl)-4-phenyl-1H-1,2,3-triazole (3j): White solid, iso-
lated yield 94% (Table 2, Entry 10), m.p. 165–167 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.14 (s, 1 H), 7.92–7.69 (d, J = 6.9 Hz, 2
H), 7.67–7.64 (d, J = 8.1 Hz, 2 H), 7.47–7.42 (t, J = 7.2 Hz, 2 H),
7.38–7.31 (m, 3 H), 2.43 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 148.2, 138.8, 134.7, 130.3, 130.2, 128.8, 128.3, 125.8,
120.4, 117.6, 21.1 ppm.
1-(2-Methlyphenyl)-4-phenyl-1H-1,2,3-triazole (3k): Pale-yellow li-
1
quid, isolated yield 63% (Table 2, Entry 11). H NMR (400 MHz,
CDCl3): δ = 7.95–7.90 (m, 3 H), 7.47–7.34 (m, 7 H), 2.27 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.5, 136.4, 133.7,
131.4, 130.3, 129.9, 128.9, 128.2, 126.8, 125.9, 125.7, 121.1,
17.8 ppm.
1-(4-Nitrophenyl)-4-phenyl-1H-1,2,3-triazole (3a): White solid, iso-
lated yield 91% (Table 2, Entry 1), m.p. 152–154 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.31 (s, 2 H), 7.88 (s, 1 H), 7.60–7.57 (m,
2 H), 7.46–7.38 (m, 3 H), 7.26–7.23 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 147.4, 141.2, 137.9, 134.0, 129.8, 129.2,
128.6, 126.0, 125.2, 124.7 ppm.
1-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3l): White solid,
1
isolated yield 94% (Table 2, Entry 12), m.p. 160–162 °C. H NMR
(400 MHz, CDCl3): δ = 8.11 (s, 1 H), 7.91–7.89 (d, J = 8.4 Hz, 2
H) 7.69–7.67 (d, J = 8.8 Hz, 2 H), 7.47–7.34 (m, 3 H), 7.04–7.02
(d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.8, 148.2, 130.5, 130.3, 128.8, 128.3, 125.8, 122.1,
117.8, 114.7, 55.6 ppm.
1-(3-Nitrophenyl)-4-phenyl-1H-1,2,3-triazole (3b): Pale-yellow solid,
1
isolated yield 87% (Table 2, Entry 2), m.p. 192–194 °C. H NMR
(400 MHz, CDCl3): δ = 8.31 (s, 2 H), 7.90 (s, 1 H), 7.70 (s, 1 H),
7.65 (s, 1 H), 7.44–7.39 (m, 3 H), 7.26–7.24 (t, J = 4.0 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.5, 137.4, 130.4,
130.3, 129.9, 129.2, 129.0, 128.6, 125.9, 123.7, 123.1, 120.0 ppm.
1-(2-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3m): Yellow li-
1
quid, isolated yield 71% (Table 2, Entry 13). H NMR (400 MHz,
1-(3-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (3d): White solid,
isolated yield 79% (Table 2, Entry 4), m.p. 167–169 °C. H NMR
CDCl3): δ = 8.32 (s, 1 H), 7.93–7.82 (m, 3 H), 7.46–7.41 (m, 3 H),
7.36–7.32 (m, 1 H), 7.14–7.09 (m, 2 H), 3.90 (s, 3 H) ppm. 13C
1
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Zn/C-Catalyzed Cycloaddition of Azides and Aryl Alkynes
NMR (100 MHz, CDCl3): δ = 147.2, 130.6, 130.0, 128.8, 128.0,
126.3, 125.8, 125.4, 121.8, 121.7, 121.2, 112.2, 55.9 ppm.
1-Benzyl-4-(2-chlorophenyl)-1H-1,2,3-triazole (4g): White solid, iso-
lated yield 89% (Table 3, Entry 7), m.p. 75–77 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.25–8.23 (m, 1 H), 8.11 (s, 1 H), 7.43–
7.28 (m, 8 H), 5.61 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 144.4, 134.6, 131.1, 130.1, 129.8, 129.2, 129.1, 129.0, 128.7, 127.9,
127.1, 123.1, 54.2 ppm.
1-(3,4-Dimethylphenyl)-4-phenyl-1H-1,2,3-triazole (3n): White solid,
1
isolated yield 95% (Table 2, Entry 14), m.p. 138–140 °C. H NMR
(400 MHz, CDCl3): δ = 8.14 (s, 1 H), 7.91–7.89 (d, J = 7.2 Hz, 2
H), 7.56 (s, 1 H), 7.48–7.42 (m, 3 H), 7.37–7.27 (m, 1 H), 7.25 (s,
1 H), 2.35–2.32 (d, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
148.1, 138.3, 137.5, 134.9, 130.6, 130.3, 128.8, 128.2, 125.7, 121.6,
117.7, 117.6, 119.2, 119.8, 119.5, 119.4 ppm.
1-Benzyl-4-(4-fluorophenyl)-1H-1,2,3-triazole (4h): White solid, iso-
lated yield 92% (Table 3, Entry 8), m.p. 106–108 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.78–7.73 (m, 2 H), 7.61 (s, 1 H), 7.40–
7.25 (m, 5 H), 7.07 (t, J = 8.7 Hz, 2 H), 5.56 (s, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 165.0, 160.1, 147.3, 134.5, 129.1,
128.8, 128.0, 127.4, 127.3, 119.2, 115.9, 115.5, 54.2 ppm.
1-Butyl-4-phenyl-1H-1,2,3-triazole (3o): Colorless liquid, isolated
yield 85% (Table 2, Entry 15). 1H NMR (400 MHz, CDCl3): δ =
7.83 (t, J = 7.2 Hz, 2 H), 7.73 (s, 1 H), 7.44–7.32 (m, 3 H), 7.42 (t,
J = 6.9 Hz, 2 H), 1.89–1.83 (m, 2 H), 1.44–1.36 (m, 2 H), 0.97 (t,
J = 6.9 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.1,
130.6, 128.8, 128.0, 125.6, 119.3, 50.1, 32.2, 19.7, 13.4 ppm.
1-Benzyl-4-(3-aminophenyl)-1H-1,2,3-triazole (4i): White solid, iso-
lated yield 83% (Table 3, Entry 9), m.p. 107–109 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.69 (s, 1 H), 7.61 (s, 1 H), 7.48–7.16 (m,
7 H), 6.62 (s, 1 H), 3.65 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 148.2, 146.8, 134.7, 133.0, 129.8, 129.0, 128.7, 127.0, 118.7,
115.9, 114.6, 112.2, 54.1 ppm.
1-Pentyl-4-phenyl-1H-1,2,3-triazole (3p): White solid, isolated yield
83% (Table 2, Entry 16), m.p. 75–77 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.84–7.82 (m, 2 H), 7.74 (s, 1 H), 7.41 (t, J = 7.6 Hz,
2 H), 7.32 (t, J = 7.2 Hz, 1 H), 4.37 (t, J = 7.2 Hz, 2 H), 1.95–1.92 1-Benzyl-4-(2-pyridyl)-1H-1,2,3-triazole (4j): White solid, isolated
(m, 2 H), 1.36–1.32 (m, 4 H), 0.90 (t, J = 6.8 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 147.6, 130.6, 128.7, 128.0, 125.6,
119.3, 50.3, 30.0, 28.5, 22.0, 13.8 ppm.
yield 81% (Table 3, Entry 10), m.p. 111–113 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.53–8.51 (m, 1 H), 8.18–8.15 (d, J =
7.8 Hz, 1 H), 8.04 (s, 1 H), 7.78–7.72 (m, 1 H), 7.37–7.17 (m, 6 H),
5.57 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.2, 149.2,
148.6, 136.8, 134.3, 129.1, 128.8, 128.2, 122.8, 121.9, 120.2,
54.3 ppm.
1-Benzyl-4-phenyl-1H-1,2,3-triazole (4a): White solid, isolated yield
90% (Table 3, Entry 1), m.p. 126–128 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.80–7.88 (m, 2 H), 7.65 (s, 1 H), 7.40–7.36 (m, 5 H),
7.32–7.28 (m, 3 H), 5.55 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 148.2, 134.7, 130.5, 129.1, 128.7, 128.1, 128.0, 125.6, 119.4,
54.1 ppm.
1-Benzyl-4-(3-thienyl)-1H-1,2,3-triazole (4k): White solid, isolated
yield 76% (Table 3, Entry 11), m.p. 92–94 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.50 (s, 2 H), 7.41–7.28 (m, 7 H), 5.55 (s, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 144.4, 134.6, 131.7, 128.9, 127.9,
127.0, 126.2, 125.0, 121.1, 119.2, 54.1 ppm.
1-Benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (4b): White solid,
1
isolated yield 95% (Table 3, Entry 2), m.p. 116–118 °C. H NMR
(300 MHz, CDCl3): δ = 7.73–7.69 (m, 2 H), 7.57 (s, 1 H), 7.38– 1-(2-Chlorobenzyl)-4-phenyl-1H-1,2,3-triazole (4o): White solid, iso-
7.26 (m, 5 H), 6.93–6.91 (d, J = 8.1 Hz, 2 H), 5.55 (s, 2 H), 3.82 lated yield 72% (Scheme 1), m.p. 79–81 °C. 1H NMR (400 MHz,
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.5, 148.0, 134.7,
129.0, 128.6, 128.0, 126.9, 123.2, 118.6, 114.1, 55.2, 54.1 ppm.
CDCl3): δ = 7.82–7.80 (m, 2 H), 7.76 (s, 1 H), 7.45–7.38 (m, 3 H),
7.33–7.20 (4 H), 5.71 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 148.1, 133.4, 132.5, 130.5, 130.3, 130.2, 129.9, 128.7, 128.1,
127.6, 125.7, 119.7, 51.4 ppm.
1-Benzyl-4-(4-penthoxyphenyl)-1H-1,2,3-triazole (4c): White solid,
1
isolated yield 94% (Table 3, Entry 3), m.p. 117–119 °C. H NMR
(300 MHz, CDCl3): δ = 7.71–7.60 (m, 2 H), 7.56 (s, 1 H), 7.37– 1,4,5-Triphenyl-1H-1,2,3-triazole (5a): White solid, isolated yield
7.28 (m, 5 H), 6.92–6.89 (m, 2 H), 5.54 (s, 2 H), 3.99–3.94 (m, 2
H), 1.80–1.76 (t, J = 6 Hz, 2 H), 1.44–1.37 (m, 4 H), 0.95–0.90 (m,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.1, 148.1, 134.7,
130.1, 129.0, 128.0, 127.1, 123.1, 118.6, 114.8, 68.1, 54.1, 28.8, 28.1,
22.4, 13.9 ppm.
61% (Scheme 2), m.p. 223–225 °C. 1H NMR (300 MHz, CDCl3): δ
= 7.61–7.59 (m, 2 H), 7.40–7.28 (m, 11 H), 7.21–7.19 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 144.7, 136.5, 133.6, 130.8, 130.1,
129.3, 129.1, 129.0, 128.9, 128.4, 127.8, 127.7, 127.3, 125.1 ppm.
1-(3,4-Dimethylphenyl)-4,5-diphenyl-1H-1,2,3-triazole (5b): White
solid, isolated yield 69% (Scheme 2), m.p. 157–159 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.60–7.58 (m, 2 H), 7.39–7.32 (m, 6 H),
1-Benzyl-4-(3-methylphenyl)-1H-1,2,3-triazole (4d): White solid,
1
isolated yield 92% (Table 3, Entry 4), m.p. 129–131 °C. H NMR
(300 MHz, CDCl3): δ = 7.65–7.55 (m, 3 H), 7.41–7.10 (m, 7 H), 7.21–7.18 (m, 2 H), 7.07–7.05 (d, J = 8 Hz, 1 H), 6.92–6.90 (m, 1
5.54 (s, 2 H), 2.36 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = H), 2.25 (s, 3 H), 2.22 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
148.3, 138.4, 134.7, 130.4, 129.1, 128.9, 128.7, 128.1, 127.2, 126.3,
122.7, 119.4, 54.2, 21.3 ppm.
δ = 144.6, 137.7, 137.6, 134.3, 133.6, 130.9, 130.2, 129.9, 129.2,
128.9, 128.4, 127.9, 127.7, 127.3, 126.2, 122.3, 19.7, 19.4 ppm.
1-Benzyl-4-(4-nitrophenyl)-1H-1,2,3-triazole (4e): Pale-yellow solid,
isolated yield 91% (Table 3, Entry 5), m.p. 131–133 °C. H NMR
1-(4-Methoxyphenyl)-4,5-diphenyl-1H-1,2,3-triazole (5c): White so-
lid, isolated yield 72% (Scheme 2), m.p. 170–172 °C. 1H NMR
1
(300 MHz, CDCl3): δ = 8.26–8.23 (m, 2 H), 7.99–7.95 (m, 2 H), (400 MHz, CDCl3): δ = 7.60–7.58 (m, 2 H), 7.41–7.18 (m, 10 H),
7.80 (s, 1 H), 7.45–7.28 (m, 5 H), 5.60 (s, 2 H) ppm. 13C NMR 6.88–6.94 (m, 2 H), 3.81 (s, 3 H) ppm. 13C NMR (100 MHz,
(75 MHz, CDCl3): δ = 147.2, 145.9, 136.7, 134.8, 129.2, 129.0, CDCl3): δ = 159.8, 144.5, 133.7, 130.9, 130.2, 129.6, 129.2, 128.9,
128.5, 126.0, 124.2, 120.9, 54.4 ppm.
128.4, 127.9, 127.8, 127.3, 126.6, 114.2, 55.4 ppm.
1-Benzyl-4-(4-bromophenyl)-1H-1,2,3-triazole (4f): White solid, iso-
lated yield 92% (Table 3, Entry 6), m.p. 142–144 °C. 1H NMR
1-(4-Nitrophenyl)-4,5-diphenyl-1H-1,2,3-triazole (5d): White solid,
isolated yield 60% (Scheme 2), m.p. 238–240 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.68–7.64 (m, 3 H), 7.53–7.50 (s, 1 H), (400 MHz, CDCl3): δ = 8.25–8.23 (m, 2 H), 7.60–7.58 (m, 2 H),
7.39–7.30 (m, 5 H), 5.56 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 147.1, 134.4, 131.9, 129.5, 129.1, 128.8, 128.0, 127.2, 122.0,
119.5, 54.2 ppm.
7.54–7.41 (m, 5 H), 7.34–7.31 (m, 3 H), 7.26–7.23 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 147.3, 145.5, 141.3, 133.5, 130.1,
130.0, 129.5, 128.6, 128.3, 127.3, 127.1, 125.1, 124.6 ppm.
Eur. J. Org. Chem. 2010, 5409–5414
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5413

X. Meng, X. Xu, T. Gao, B. Chen
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Received: May 3, 2010
Published Online: August 16, 2010
5414
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Eur. J. Org. Chem. 2010, 5409–5414