Copper(i) acetate-catalyzed azide-alkyne cycloaddition for highly efficient preparation of 1-(pyridin-2-yl)-1,2,3-triazoles

Article abstract of DOI:10.1039/c2ob06942c

A highly efficient copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) of 6-substituted tetrazolo[1,5-a]pyridines was developed for the preparation of 1-(pyridin-2-yl)-1,2,3-triazoles by simply using copper(i) acetate as a catalyst. The in situ formed HOAc played important dual roles and an activation of 2-azidopyridine-copper(i) complex was observed. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2ob06942c

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PAPER
Copper(I) acetate-catalyzed azide–alkyne cycloaddition for highly efficient
preparation of 1-(pyridin-2-yl)-1,2,3-triazoles†
Qun Zhang, Xinyan Wang,* Chuanjie Cheng, Rui Zhu, Nan Liu and Yuefei Hu*
Received 18th November 2011, Accepted 1st February 2012
DOI: 10.1039/c2ob06942c
A highly efficient copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of 6-substituted tetrazolo-
[1,5-a]pyridines was developed for the preparation of 1-(pyridin-2-yl)-1,2,3-triazoles by simply using
copper(I) acetate as a catalyst. The in situ formed HOAc played important dual roles and an activation of
2-azidopyridine–copper(I) complex was observed.
its ring-tautomer tetrazolo[1,5-a]pyridines (3) in the solid state10
and as a chain–ring tautomeric equilibrium between 2 and 3 in
Introduction
Many derivatives of 1-(pyridin-2-yl)-1,2,3-triazole (1) (Fig. 1)
have been used as intermediates1 in organic synthesis or as
ligands2 in coordination compounds and have shown biologi-
cally important properties.3 In the literature, they were usually
prepared by base-promoted substitution between 1,2,3-triazole
and 2-halopyridine4 or by thermal 1,3-dipolar cycloaddition5
and other multi-step procedures.6 Although copper(I)-catalyzed
azide–alkyne cycloaddition (CuAAC) has proven to be the most
efficient method for the preparation of 1,2,3-triazoles7 and many
1,2,3-triazoles substituted by N-containing heterocyclics have
been prepared,8 the low efficiency was observed for CuAAC of
2-azidopyridines (2) even by using the most popular catalytic
system CuSO4·5H2O/NaAsc.9 Only recently, the first article9a
dealing with the CuAAC methodology of 2-azidopyridines (2)
was published. This phenomenon may be caused by three
factors: (a) the substrate 2-azidopyridine (2) naturally occurs as
solution; (b) the pyridine in the key intermediate 5-cupuric
1,2,3-triazole may coordinate with Cu(I) to form the complex 4,
which will lead to difficult protonation of the C–Cu bond; (c) the
product 1 may also coordinate with Cu(I) to form the complex
5,2 by which the catalytic cycle of Cu(I) will be retarded.
Investigation showed that the chain–ring tautomeric equili-
brium between 2 and 3 mostly depended upon the substituent
and its position on the pyridine ring. The early studies proved
that the chain tautomer 2 benefited from 6-substituted electron-
withdrawing groups on tetrazolo[1,5-a]pyridine (3).9a,10
Recently, we developed a novel CuAAC strategy, in which the
protonation of the key intermediate 5-cupuric 1,2,3-triazole was
remarkably promoted by carboxylic acid.11 As shown in
Scheme 1, when the mixture of 6f and 7 was treated with copper(I)
acetate (8, as a polymeric dinuclear complex) for 8 min, 1,2,3-
triazole 9 was obtained in 98% yield, in which HOAc was
produced in situ.11d,e
Therefore, we hypothesized that a highly efficient CuAAC of
tetrazolo[1,5-a]-pyridines (3) bearing 6-substituted electron-
withdrawing groups may be achieved by using copper(I) acetate
(8) as a catalyst because the in situ formed HOAc may play dual
roles to promote the protonation of complex 4 and prevent the
formation of complex 5.
Fig. 1 2-Azidopyridine and its tautomer as well as its CuAAC product
and proposed intermediates.
Department of Chemistry, Tsinghua University, Beijing 100084,
P. R. China. E-mail: wangxinyan@mail.tsinghua.edu.cn, yfh@
mail.tsinghua.edu.cn; Fax: +86 62771149; Tel: +86 6279 5380
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob06942c
Scheme 1
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Table 1 Effects of copper(I) sources on CuAACa
Table 2 Effects of solvents on CuAACa
Entry
Solvent
Time (min)
Yield of 1ab (%)
1
2
3
4
5
EtOH
CHCl3
THF
PhMe
CH2Cl2
60
15
10
6
37
80
84
80
81
Entry
[Cu] (0.025 equiv)
Time (min)
Yield of 1ab (%)
1
2
3
—
CuCl
CuBr
60
60
60
60
20
10
0
37
50
21
71
84
5
a The mixture of 3a (1.1 mmol), 6a (1.0 mmol) and catalyst
[(CuOAc)2]n (8, 0.025 mmol) in solvent (1 mL) was stirred at ambient
temperature. b The isolated yields were obtained.
4
CuI
5c
6
CuSO4·5H2O/NaAsc
[(CuOAc)2]n
a The mixture of 3a (1.1 mmol), 6a (1.0 mmol) and catalyst
(0.025 mmol) in THF (1 mL) was stirred at room temperature. b The
isolated yields were obtained. c The mixture of THF–H2O (1 : 1) was
used as a solvent.
Scheme 2
Results and discussion
Among the well-studied 6-substituted tetrazolo[1,5-a]pyridines
(3), 6-NO2 (3a) and 6-CO2R (3b) derivatives are two desired
candidates due to their relatively high proportions of chain tauto-
mers in aprotic solvents10c,d and their preparations are also rela-
tively easier than others. To quickly scan the reaction conditions,
the CuAAC of 6-nitro-tetrazolo[1,5-a]pyridine (3a) and the high
active dipolarophile ethyl propynoate (6a) was employed as a
model reaction.
Scheme 3
As shown in Table 1, no expected ethyl 1-(5-nitropyridin-2-
yl)-1H-[1,2,3]-triazole-4-carboxylate (1a) was produced in the
absence of Cu(I) species (entry 1). By using different copper(I)
halides as the catalyst (entries 2–4), CuBr showed the highest
catalytic activity to give 1a in 50% yield. As was expected, the
cycloaddition catalyzed by CuSO4·5H2O/NaAsc finished within
20 min to give 1a in 71% yield (entry 5), because the in situ
formed HAsc is, in fact, a vinylogous carboxylic acid with pKa
values of 4.10 and 11.79, respectively (pKa value of acetic acid
is 4.76). To our delight, the same reaction finished within 10 min
to give 1a in 84% yield by using copper(I) acetate (8) as a cata-
lyst (entry 6).
Then, the solvents were screened by using [(CuOAc)2]n (8) as
a catalyst. As shown in Table 2, the protonic solvent EtOH
showed negative effects on the reaction (entry 1), which may be
caused by the fact that the proportion of chain-tautomer was
decreased.10c,d However, all other aprotic solvents gave satisfy-
ing results (entries 2–5). THF gave the highest yield (entry 3)
and CH2Cl2 gave the shortest reaction time (entry 5). Finally,
THF was chosen for our purpose because it was a good solvent
for substrates and product.
Interestingly, we found that the efficiency of the procedure in
Scheme 2 completely depended upon the addition sequence of
the substrates. For example, by addition of 6f to the mixture of
3a and [(CuOAc)2]n (8) in THF, the desired 1f was obtained in
78–83% yield after around 10–18 min. However, the same reac-
tion took for 2 h (72%) by addition of 3a to the mixture of 6f
and [(CuOAc)2]n (8) in THF. As shown in Scheme 3, the
mixture of 3a/8 gave a deep-brown suspension, while the
mixture of 6f/8 gave a light-yellow suspension when they stood
at room temperature for more than 3 min.
The light-yellow suspension was easily assigned to be
[(PhCuCCu)2]n, however the deep-brown suspension could not
be assigned because it could not afford a stable coordination
compound after the solvent was evaporated off. As shown in
Scheme 4, we proposed that this suspension may contain a
coordination compound 11 produced from 3a and [(CuOAc)2]n
(8) based on its IR spectrum and elemental analysis results.
Then, 11 reacted with 6f to form a bis-functional complex 12
including the required copper(I) acetylide and azide, by which an
intramolecular CuAAC occurs easily. This may be the reason
that the deep-brown suspension facilitated to the cycloaddition.
In contrast, once the light-yellow intermediate [(PhCuCCu)2]n
was formed, it will take a regular intermolecular CuAAC. Thus,
this CuAAC actually was activated by 2-azidopyridine–Cu(I)
complex (11).
Unfortunately, when the low activity dipolarophile phenyl-
ethyne (6f) was used as a substrate, its cycloaddition with 3a
could not finish within 24 h when using 0.025 equivalents of
[(CuOAc)2]n (8). But this problem was easily resolved by using
0.1 equivalents of [(CuOAc)2]n (8) and the desired product 5-
nitro-2-(4-phenyl-[1,2,3]triazol-1-yl)-pyridine (1f) was obtained
in 78% yield after 18 min (Scheme 2).
We observed that the most reactive deep-brown suspension
could be prepared by mixing 3a and [(CuOAc)2]n (8) in THF for
10 min. Further tests proved that it could be also prepared easily
2848 | Org. Biomol. Chem., 2012, 10, 2847–2854
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Scheme 4
Scheme 5
by treatment of the solution of 3a and [(CuOAc)2]n (8) with
ultrasonication for 1 min. As shown in Scheme 5, the product 1f
was obtained in 83% yield by using this procedure within
10 min. Unfortunately, no CuAAC occurred when the internal
alkynes diphenylacetylene (13a) and diethyl acetylenedicarboxy-
late (13b) were used as dipolarophiles, even at the boiling temp-
erature of THF for 2 h. This result strongly indicated that the
terminal acetylene is an essential substrate and the hypothesis of
intermediate 12 was supported.
Scheme 6
To generalize this method, the cycloadditions of 3a with
different acetylenes (6a–6n) were tested. As shown in Scheme 6,
the highly active dipolarophiles propynoates 6a–6c gave satisfy-
ing results with low-loading of [(CuOAc)2]n (8, 0.025–0.05
equiv.) even without the help of ultrasonication. However, it was
better to use 0.1 equivalent of [(CuOAc)2]n for all other acety-
lenes (6d–6n) for short reaction time and high quality of pro-
ducts. Under these standard conditions, the cycloadditions
usually finished within minutes to give desired products (1a–1n)
in moderate to excellent yields.
We found that this procedure also worked well for the substrate
ethyl tetrazolo[1,5-a]pyridine-6-carboxylate (3b). Although the
preparation and purification of 3b was less convenient than 3a,
however, its CuAAC usually gave clean products 1o–1v in
moderate to excellent yields (Scheme 7).
Scheme 7
We also tried to extend the method for other tetrazoles, such
as 3c–3i. As shown in Fig. 2, although 6-nitro-7-methyl-tetra-
zolo[1,5-a]pyridine (3c) could afford a good yield of product 1w
with the help of ultrasonication, it also worked well under
heating conditions. Similarly, 6-cyano-tetrazolo[1,5-a]pyridine
(3d), 6,8-dichloro-tetrazolo[1,5-a]pyridine (3e), even tetrazolo
[1,5-a]pyrazine (3f) were smoothly converted into the corre-
sponding products 1x, 1y and 1z in moderate to excellent yields
in boiling THF. Unfortunately, tetrazolo[1,5-a]pyrimidine (3g)
seemed to decompose easily in the presence of [Cu(OAc)2]n (8)
and could not afford the desired product from 0 °C to the boiling
temperature of THF. As was expected, both tetrazolo[1,5-a]
pyridine (3h) and 5-methyl-tetrazolo[1,5-a]pyridine (3i) did not
react, even in boiling THF, because they have very stable ring
structures. Although their cycloadditions could finish within 5 h
in boiling toluene, the desired products were obtained in low
yields as the mixtures included regioisomers, which may be
caused by the fact that the cycloadditions may go through both a
CuAAC pathway and a thermal pathway.
Finally, the transformations of nitropyridine into aminopyri-
dine and ethyl nicotinate into hydroxymethylpyridine were
explored. As shown in Scheme 8, when 1j was hydrogenated
(balloon) in the presence of Pd/C catalyst at room temperature
for 2 h, the desired product 14 was obtained in 92% yield. As
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spectrometer with 70 eV. Elemental analysis data were obtained
on a Perkin-Elmer-241C apparatus. PE is petroleum ether
(60–90 °C).
A typical procedure for the preparation of ethyl 1-(5-nitro-
pyridin-2-yl)-1H-[1,2,3]-triazole-4-carboxylate (1a)
Ethyl propynoate (6a, 108 mg, 1.1 mmol) was added to a sol-
ution of 6-nitro-tetrazolo[1,5-a]-pyridine (3a, 165 mg, 1 mmol)
and [(CuOAc)2]n (8, 3 mg, 0.025 mmol, calculated by CuOAc)
in chemically pure THF (1 mL) under N2. After the resultant
mixture was stirred at ambient temperature for 10 min (moni-
tored by TLC), the solvent was removed under vacuum. The
residue was purified by chromatography (silica gel, EtOAc/PE)
to give 221 mg (84%) of 1a as a white solid.
Fig. 2 The substrates 3c–3i and their products.
A typical procedure for the preparation of 5-nitro-2-(4-phenyl-
[1,2,3]triazol-1-yl)-pyridine (1f)
Scheme 8
A solution of 6-nitro-tetrazolo[1,5-a]-pyridine (3a, 165 mg,
1 mmol) and [(CuOAc)2]n (8, 12 mg, 0.1 mmol, calculated by
CuOAc) in chemically pure THF (1 mL) was ultrasonicated for
1 min to give a deep-red color suspension. Then phenylethyne
(6f, 113 mg, 1.1 mmol) was added and the resultant mixture was
stirred at ambient temperature for 10 min (motored by TLC)
under N2, the solvent was removed under vacuum. The residue
was purified by chromatography (silica gel, EtOAc/PE) to give
222 mg (83%) of 1f as a white solid.
Scheme 9
shown in Scheme 9, by treatment of 1v with LiAlH4 at 0 °C to
25 °C for 1.5 h, its carboxylate group was reduced into hydroxy-
methyl group smoothly.
By the similar procedure of the preparation of 1a or 1f, pro-
ducts 1b–1e and 1g–1z were prepared, respectively.
Ethyl 1-(5-nitropyridin-2-yl)-1H-1,2,3-triazole-4-carboxylate
(1a)
Conclusions
In conclusion, based on the analysis of the structural characters
of tetrazolo[1,5-a]pyridine, highly efficient CuAAC of its 6-sub-
stituted derivatives was achieved by using copper(I) acetate as a
catalyst. The in situ formed HOAc may play dual roles for
efficient protonation of the key intermediate 5-cupuric 1,2,3-tria-
zole (4) and prevention of the formation of coordination com-
pound 5. We observed that the addition sequence of the
substrates could significantly influence on the reaction rate.
Thus, a 2-azidopyridine-copper(I) complex activated intramole-
cular CuAAC pathway was proposed. Since the groups of –NO2
and –CO2Et in the products can be easily converted into the cor-
responding amino and hydroxymethyl groups, it is expected that
this reaction and its products will be found wide uses in organic
synthesis and drug discovery.
It is a white solid, mp 162 °C. IR ν 3137, 3011, 2976, 2954,
1721, 1609, 1578, 1527 cm−1; 1H NMR (DMSO-d6) δ 9.42 (d, J
= 3.5, 2H), 8.91 (dd, J1 = 6.2, J2 = 2.8, 1H), 8.42 (d, J = 8.9,
1H), 4.38 (q, J = 7.2, 2H), 1.36 (t, J = 7.2, 3H); 13C NMR
(DMSO-d6) δ 160.1, 151.2, 145.6, 144.8, 140.6, 136.4, 127.1,
115.3, 61.6, 14.6. MS m/z (%) 263 (M+, 1.4%), 163 (100%);
Anal. Calcd for C10H9N5O4: C, 45.63; H, 3.45; N, 26.61.
Found: C, 45.89; H, 3.49; N, 26.86.
Methyl 1-(5-nitropyridin-2-yl)-1H-1,2,3-triazole-4-carboxylate
(1b)
It is a white solid, mp 216–217 °C. IR ν 3122, 3081, 2955,
1
1719, 1610, 1539 cm−1; H NMR (CDCl3) δ 9.40 (d, J = 2.7,
1H), 9.15 (s, 1H), 8.78 (dd, J1 = 6.5, J2 = 2.4, 1H), 8.49 (d, J =
8.9, 1H), 4.03 (s, 3H); 13C NMR (DMSO-d6) δ 160.4, 151.4,
145.2, 144.0, 140.9, 135.0, 125.5, 114.3, 52.6; MS m/z (%) 249
(M+, 1.08%), 190 (100%). Anal. Calcd for C9H7N5O4: C, 43.38;
H, 2.83; N, 28.11. Found: C, 43.11; H, 2.79; N, 28.30.
Experimental section
General remarks
All melting points were determined on a Yanaco melting point
apparatus and are uncorrected. IR spectra were recorded on a
tert-Butyl 1-(5-nitropyridin-2-yl)-1H-1,2,3-triazole-4-carboxylate
(1c)
1
Nicolet FT-IR 5DX spectrometer with KBr pellets. H NMR and
13C NMR spectra were recorded on a JEOL JNM-ECA 300 spec-
trometer. TMS was used as an internal reference and the J values
are given in Hz. MS were recorded on a VG-ZABMS
It is a white solid, mp 160–162 °C. IR ν 3157, 3104, 2985,
1
2935, 1728, 1614, 1534 cm−1; H NMR (CDCl3) δ 9.35 (d, J =
2850 | Org. Biomol. Chem., 2012, 10, 2847–2854
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2.4, 1H), 9.0 (s, 1H), 8.75 (dd, J1 = 6.2, J2 = 2.7, 1H), 8.45 (d, J
= 8.9, 1H), 1.65 (s, 9H); 13C NMR (CDCl3) δ 159.1, 151.5,
145.1, 143.8, 142.3, 135.0, 125.0, 114.2, 83.0, 28.1 (3C); MS
m/z (%) 291 (M+, 0.6%), 207 (100%). Anal. Calcd for
C12H13N5O4: C, 49.48; H, 4.50; N, 24.04. Found: C, 49.57; H,
4.63; N, 24.18.
1H), 7.91 (t, 9.1, 2H), 7.56 (q, J = 9.0, 1H), 7.25 (m, 1H); 13C
NMR (DMSO-d6) δ 163.1 (J = 241.7), 151.7, 147.1, 145.6,
144.4, 136.3, 132.3 (J = 8.6), 131.7 (J = 8.6), 122.2, 120.2,
115.9 (J = 20.8), 114.7, 112.9 (J = 23.0); MS m/z (%) 258
(15.82%), 176 (100%). Anal. Calcd for C13H8FN5O2: C, 54.74;
H, 2.83; N, 24.55. Found: C, 54.56; H, 2.88; N, 24.70.
2-[4-(2-Fluorophenyl)-1H-1,2,3-triazol-1-yl]-5-nitropyridine (1i)
It is a white solid, mp 206 °C. IR ν 3169, 3099, 1611, 1576,
1-[1-(5-Nitropyridin-2-yl)-1H-1,2,3-triazol-4-yl]ethanone (1d)
It is a white solid, mp 178 °C. IR ν 3130, 3059, 1992, 1893,
1
1526 cm−1; H NMR (DMSO-d6) δ 9.44 (s, 1H), 9.05 (s, 1H),
1
1689, 1615, 1530 cm−1; H NMR (DMSO-d6) δ 9.41 (d, J =
8.90 (d, J = 8.9, 1H), 8.43 (d, J = 8.9, 1H), 8.21 (t, J = 7.6, 1H),
7.52–7.37 (m, 3H); 13C NMR (DMSO-d6) δ 159.5 (J = 122.8),
151.8, 145.6, 144.6, 142.1, 136.2, 131.1 (J = 4.3), 128.6, 125.6,
121.2 (J = 5.0), 117.9 (J = 6.5), 116.7 (J = 10.8), 114.9; MS m/z
(%) 285 (M+, 3.28%), 257 (100%). Anal. Calcd for
C13H8FN5O2: C, 54.74; H, 2.83; N, 24.55. Found: C, 54.63; H,
2.78; N, 24.67.
2.4, 1H), 9.12 (s, 1H), 8.79 (dd, J1 = 6.2, J2 = 2.7, 1H), 8.49 (d,
J = 8.5, 1H), 2.78 (s, 3H); 13C NMR (DMSO-d6) δ 192.0,
151.4, 148.4, 145.3, 144.0, 135.0, 123.4, 114.3, 27.5; MS m/z
(%) 233 (M+, 1.29%), 190 (100%). Anal. Calcd for C9H7N5O3:
C, 46.36; H, 3.03; N, 30.03. Found: C, 46.48; H, 3.08; N, 29.87.
tert-Butyl [1-(5-nitropyridin-2-yl)-1H-1,2,3-triazol-4-yl]-
methylcarbamate (1e)
2-(4-Cyclopropyl-1H-1,2,3-triazol-1-yl)-5-nitropyridine (1j)
It is a white solid, mp 194–195 °C. IR ν 3151, 3093, 3031,
It is a white solid, mp 179–180 °C. IR ν 3143, 3103, 2984,
2940, 2878, 1668, 1610, 1577, 1525 cm−1; H NMR (DMSO-
1
1
1610, 1574, 1530 cm−1; H NMR (DMSO-d6) δ 9.37 (d, J =
d6) δ 9.41 (d, J = 2.8, 1H), 8.87 (dd, J1 = 6.2, J2 = 2.8, 1H),
8.68 (s, 1H), 8.36 (d, J = 9.3, 1H), 7.47 (t, J = 5.5, 1H), 4.31 (d,
J = 5.9, 2H), 1.40 (s, 9H); 13C NMR (DMSO-d6) δ 155.6,
151.2, 147.4, 145.2, 143.7, 135.8, 120.3, 113.9, 78.1, 35.4, 28.2
(3C); MS m/z (%) 320 (M+, 0.19%), 59 (100%). Anal. Calcd for
C13H16N6O4: C, 48.75; H, 5.03; N, 26.24. Found: C, 48.67; H,
5.11; N, 26.27.
2.73, 1H), 8.80 (dd, J1 = 6.2, J2 = 2.7, 1H), 8.72 (s, 1H), 8.32
(d, J = 8.9, 1H), 2.10–2.07 (m, 1H), 1.04–0.83 (m, 4H); 13C
NMR (DMSO-d6) δ 151.8, 151.6, 45.6, 144.0, 136.2, 118.8,
114.3, 8.5 (2C), 7.0; MS m/z (%) 231 (M+, 0.29%), 176 (100%).
Anal. Calcd for C10H9N5O2: C, 51.95; H, 3.92; N, 30.29.
Found: C, 51.71; H, 3.98; N, 30.54.
2-[4-(Cyclohexylmethyl)-1H-1,2,3-triazol-1-yl]-5-nitropyridine
(1k)
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)-5-nitropyridine (1f)
It is a white solid, mp 224–226 °C. IR ν 3157, 3054, 1612,
1580, 1527 cm−1; 1H NMR (DMSO-d6) δ 9.5 (s, 1H), 9.44 (d, J
= 2.8, 1H), 8.90 (dd, J1 = 6.5, J2 = 2.8, 1H), 8.43 (d, J = 8.91,
1H), 8.08 (d, J = 6.0, 2H), 7.54–7.4 (m, 3H); 13C NMR
(DMSO-d6) δ 152.0, 148.4, 145.5, 144.5, 136.1, 130.1, 129.5
(2C), 129.2, 126.4 (2C), 119.3, 114.8; MS m/z (%) 267 (M+,
2.47%), 239 (100%). Anal. Calcd for C13H9N5O2: C, 58.43; H,
3.39; N, 26.21. Found: C, 58.28; H, 3.38; N, 26.64.
It is a white solid, mp 148–149 °C. IR ν 3154, 3116, 3081,
1
2919, 2846, 1612, 1580, 1528 cm−1; H NMR (CDCl3) δ 9.34
(d, J = 2.7, 1H), 8.70 (dd, J1 = 6.6, J2 = 2.7, 1H), 8.38 (dd, J1 =
8.2, J2 = 0.8, 1H), 8.36 (s, 1H), 2.71 (d, J = 6.9, 2H), 1.79–1.65
(m, 6H), 1.31–0.97 (m, 5H); 13C NMR (CDCl3) δ 152.2, 148.3,
145.0, 143.2, 119.1, 134.5, 113.6, 37.8, 33.2, 32.9 (2C), 26.3,
26.1 (2C); MS m/z (%) 258 (16%), 176 (100%). Anal. Calcd for
C14H17N5O2: C, 58.52; H, 5.96; N, 24.37. Found: C, 58.68; H,
6.00; N, 24.55.
2-(4-p-Tolyl-1H-1,2,3-triazol-1-yl)-5-nitropyridine (1g)
2-(4-Butyl-1H-1,2,3-triazol-1-yl)-5-nitropyridine (1l)
It is a slight yellow solid, mp 250 °C. IR ν 3156, 3081, 2918,
1
1615, 1576, 1525 cm−1; H NMR (DMSO-d6) δ 9.42 (s, 1H),
It is a white solid, mp 131–132 °C. IR ν 3155, 3094, 3031,
1
2930, 2866, 1610, 1527 cm−1; H NMR (CDCl3) δ 9.34 (d, J =
9.41 (s, 1H), 8.88 (dd, J1 = 6.5, J2 = 2.4, 1H), 8.40 (d, J = 8.9,
1H), 7.95 (d, J = 7.9, 2H), 7.31 (d, J = 2.9, 2H), 2.36 (s, 3H);
13C NMR (DMSO-d6) δ 152.0, 148.5, 145.5, 144.4, 138.7,
136.1, 130.0 (2C), 127.4, 126.3 (2C), 118.8, 114.8, 21.3; MS
m/z (%) 281 (M+, 3.11%), 253 (100%). Anal. Calcd for
C14H11N5O2: C, 59.78; H, 3.94; N, 24.90. Found: C, 59.67; H,
3.97; N, 24.98.
2.4, 1H), 8.70 (dd, J1 = 6.5, J2 = 2.4, 1H), 8.41 (d, J = 8.9, 1H),
8.37 (s, 1H), 2.84 (t, J = 7.6, 2H), 1.8–1.7 (m, 2H), 1.5–1.39 (m,
2H), 1.0–0.95 (m, 3H); 13C NMR (CDCl3) δ 152.2, 149.8,
145.0, 143.2, 134.6, 118.6, 113.6, 31.1, 25.2, 22.2, 13.8; MS
m/z (%) 247 (M+, 0.33%), 176 (100%). Anal. Calcd for
C11H13N5O2: C, 53.43; H, 5.30; N, 28.32. Found: C, 53.65; H,
5.41; N, 24.55.
2-[4-(3-Fluorophenyl)-1H-1,2,3-triazol-1-yl]-5-nitropyridine (1h)
It is a yellowish solid, mp 143–144 °C. IR ν 3165, 1618, 1572,
2-(4-Hexyl-1H-1,2,3-triazol-1-yl)-5-nitropyridine (1m)
1
1524 cm−1. H NMR (DMSO-d6) δ 9.61 (s, 1H), 9.43 (d, J =
It is a white solid, mp 123–125 °C. IR ν 3157, 3108, 3070,
1
2.43, 1H), 8.90 (dd, J1 = 6.2, J2 = 2.7, 1H), 8.41 (d, J = 8.9,
2925, 2859, 1612, 1530 cm−1; H NMR (CDCl3) δ 9.34 (d, J =
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2847–2854 | 2851

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Ethyl 6-(4-cyclohexyl-1H-1,2,3-triazol-1-yl)nicotinate (1s)
2.1, 1H), 8.70 (dd, J1 = 6.5, J2 = 2.4, 1H), 8.41 (d, J = 8.9, 1H),
8.37 (s, 1H), 2.82 (t, J = 7.6, 2H), 1.81–1.71 (m, 2H), 1.44–1.32
(m, 6H), 0.92–0.87 (m, 3H); 13C NMR (CDCl3) δ 152.2, 150.0,
145.0, 143.2, 134.5, 118.6, 113.6, 31.5, 29.0, 28.8, 25.5, 22.5,
14.0; MS m/z (%) 275 (M+, 0.5%), 176 (100%). Anal. Calcd for
C13H17N5O2: C, 56.71; H, 6.22; N, 25.44. Found: C, 56.68; H,
6.26; N, 25.69.
It is a white solid, mp 126 °C. IR ν 3145, 3070, 2924, 2850,
1
1712, 1598, 1487 cm−1; H NMR (CDCl3) δ 9.09 (d, J = 2.1,
1H), 8.49 (dd, J1 = 6.5, J2 = 2.1, 1H), 8.34 (s, 1H), 8.26 (d, J =
8.6, 1H), 4.45 (q, J = 7.2, 2H), 2.70 (d, J = 6.9, 2H), 1.75–1.64
(m, 6H), 1.44 (q, J = 6.9, 3H), 1.34–0.92 (m, 5H); 13C NMR
(CDCl3) δ 164.3, 151.6, 150.3, 147.7, 140.1, 125.7, 118.9,
112.9, 61.6, 37.9, 33.3, 32.9 (2C), 26.3, 26.1 (2C), 14.2; MS m/z
(%) 314 (M+, 0.45%), 203 (100%). Anal. Calcd for
C17H22N4O2: C, 64.95; H, 7.05; N, 17.82. Found: C, 65.23; H,
7.17; N, 17.64.
2-[4-(3-Chloropropyl)-1H-1,2,3-triazol-1-yl]-5-nitropyridine (1n)
It is a white solid, mp 132–134 °C. IR ν 3155, 3095, 3034,
2957, 2863, 1611, 1583, 1530, 1486, 1350 cm−1 1H NMR
;
(CDCl3) δ 9.35 (d, J = 2.8, 1H), 8.72 (dd, J1 = 6.5, J2 = 2.4,
1H), 8.44 (d, J = 6.2, 1H), 8.40 (s, 1H), 3.64 (t, J = 6.5, 2H),
3.02 (t, J = 7.2, 2H), 2.31–2.22 (m, 2H); 13C NMR (CDCl3) δ
152.1, 147.8, 145.0, 143.3, 134.6, 119.2, 113.6, 43.9, 31.5, 22.6.
MS m/z (%) 267 (M+, 0.32%), 176 (100%). Anal. Calcd for
C10H10ClN5O2: C, 44.87; H, 3.77; N, 26.16. Found: C, 45.03;
H, 3.93; N, 26.08.
Ethyl 6-(4-butyl-1H-1,2,3-triazol-1-yl)nicotinate (1t)
It is a white solid, mp 102 °C. IR ν 3140, 2947, 2864, 1712,
1605, 1489 cm−1; 1H NMR (CDCl3): δ 9.09 (s, 1H), 8.49 (d, J =
7.9, 1H), 8.36 (s, 1H), 8.26 (d, J = 8.2, 1H), 4.45 (q, J = 6.9,
2H), 2.82 (t, J = 6.7, 2H), 1.79–1.69 (m, 2H), 1.50–1.38 (m,
5H), 0.99–0.94 (t, J = 7.6, 3H); 13C NMR (CDCl3) δ 164.3,
151.5, 150.3, 149.2, 140.1, 125.7, 118.3, 112.9, 61.6, 31.2, 25.2,
22.2, 14.2, 13.7; MS m/z (%) 274 (M+, 0.53%), 203 (100%).
Anal. Calcd for C14H18N4O2: C, 61.30; H, 6.61; N, 20.42.
Found: C, 61.43; H, 6.74; N, 20.51.
Ethyl 6-[4-(ethoxycarbonyl)-1H-1,2,3-triazol-1-yl]nicotinate (1o)9a
1
It is a white solid, mp 114 °C. H NMR (CDCl3) δ 9.14 (d, J =
2.1, 1H), 9.13 (s, 1H), 8.56 (dd, J1 = 6.5, J2 = 2.1, 1H), 8.34 (d,
J = 8.6, 1H), 4.52–4.43 (m, 4H), 1.45 (t, J = 6.9, 6H); 13C NMR
(CDCl3) δ 164.0, 160.3, 150.7, 150.6, 140.7, 140.6, 126.8,
125.1, 113.5, 61.9, 61.6, 14.3, 14.2.
Ethyl 6-(4-hexyl-1H-1,2,3-triazol-1-yl)nicotinate (1u)
It is a white solid, mp 100 °C. IR ν 3138, 3082, 2924, 2858,
1
1712, 1602, 1486 cm−1; H NMR (CDCl3) δ 9.09 (d, J = 1.4,
Ethyl 6-(4-phenyl-1H-1,2,3-triazol-1-yl)nicotinate (1p)9a
1H), 8.45 (d, J = 6.5, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.6, 1H),
4.45 (q, J = 7.2, 2H), 2.81 (t, J = 7.2, 2H), 1.80–1.70 (m, 2H),
1.46–1.30 (m, 9H), 0.89 (t, J = 6.9, 3H); 13C NMR (CDCl3) δ
164.3, 151.6, 150.3, 149.2, 140.1, 125.7, 118.3, 112.9, 61.6,
31.5, 29.1, 28.8, 25.6, 22.5, 14.2, 14.0; MS m/z (%) 302
(M+, 0.53%), 217 (100%). Anal. Calcd for C16H22N4O2:
C, 63.55; H, 7.33; N, 18.53. Found: C, 63.36; H, 7.28; N, 18.65.
1
It is a white solid, mp 194–196 °C. H NMR (CDCl3) δ 9.48 (s,
1H), 9.11 (s, 1H), 8.61 (d, J = 8.6, 1H), 8.33 (d, J = 8.6, 1H),
8.07 (d, J = 7.8, 2H), 7.53–7.38 (m, 3H), 4.41 (q, J = 7.2, 2H),
1.38 (t, J = 7.2, 3H); 13C NMR (CDCl3) δ 164.3, 151.4, 150.5,
148.4, 140.3, 129.9, 128.9 (2C), 128.6, 126.1 (2C), 126.0,
117.0, 113.1, 61.8, 14.3.
Ethyl 6-(4-p-tolyl-1H-1,2,3-triazol-1-yl)nicotinate (1q)9a
Ethyl 6-[4-(3-chloropropyl)-1H-1,2,3-triazol-1-yl]nicotinate
(1v)9a
1
It is a white solid, mp 193–194 °C; H NMR (CDCl3): δ 9.12
(d, J = 1.7, 1H), 8.79 (s, 1H), 8.50 (dd, J1 = 6.5, J2 = 2.1, 1H),
8.30 (d, J = 8.3, 1H), 7.82 (d, J = 7.9, 2H), 7.26 (d, J = 7.9,
2H), 4.45 (q, J = 7.2, 2H), 2.40 (s, 3H), 1.44 (t, J = 6.8, 3H);
13C NMR (CDCl3) δ 164.3, 151.4, 150.4, 148.4, 140.2, 138.5,
129.6 (2C), 127.0, 125.9, 125.8 (2C), 116.6, 113.1, 61.7, 21.3,
14.2.
It is a white solid, mp 128–130 °C. 1H NMR (CDCl3) δ 9.10 (d,
J = 0.7, 1H), 8.50 (dd, J1 = 6.5, J2 = 0.7, 1H), 8.43 (s, 1H), 8.26
(dd, J1 = 7.9, J2 = 0.7, 1H), 4.45 (q, J = 6.9, 2H), 3.64 (t, J =
6.5, 2H), 3.01 (t, J = 7.2, 2H), 2.3–2.2 (m, 2H), 1.44 (t, J = 7.2,
3H); 13C NMR (CDCl3) δ 164.2, 151.4, 150.3, 147.2, 140.2,
125.9, 118.9, 112.9, 61.6, 43.9, 31.6, 22.6, 14.2.
Ethyl 6-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)nicotinate (1r)
Ethyl 1-(4-methyl-5-nitropyridin-2-yl)-1H-1,2,3-triazole-4-
carboxylate (1w)
It is a white solid, mp 122 °C. IR ν 3148, 3113, 2983, 1712,
1
1594, 1485 cm−1; H NMR (CDCl3) δ 9.07 (d, J = 6.2, 1H),
8.46 (t, J = 8.6, 1H), 8.29 (d, J = 6.5, 1H), 8.22 (d, J = 8.2, 1H),
4.48–4.38 (m, 2H), 2.1–2.0 (m, 1H), 1.40 (q, J = 6.9, 3H),
1.03–0.86 (m, 4H); 13C NMR (CDCl3) δ 164.4, 151.6, 151.2,
150.4, 140.2, 125.8, 117.3, 113.0, 61.7, 14.3, 8.0 (2C), 6.8; MS
m/z (%): 258 (M+, 0.43%), 201 (100%). Anal. Calcd for
C13H14N4O2: C, 60.45; H, 5.46; N, 21.69. Found: C, 60.63; H,
5.56; N, 21.44.
It is a yellow solid, mp 168–170 °C. IR ν 3146, 2989, 2943,
1727, 1614, 1561, 1480 cm−1; 1H NMR (CDCl3) δ 9.16 (s, 1H),
9.11 (s, 1H), 8.30 (s, 1H), 4.49 (q, J = 7.2, 2H), 2.84 (s, 3H),
1.46 (t, J = 7.2, 3H); 13C NMR (CDCl3) δ 160.0, 149.9, 147.6,
146.0, 145.3, 140.9, 125.3, 116.8, 61.7, 20.7, 14.2. Anal. Calcd
for C11H11N5O4: C, 47.66; H, 4.00; N, 25.26. Found: C, 47.94;
H, 4.13; N, 25.14.
2852 | Org. Biomol. Chem., 2012, 10, 2847–2854
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Ethyl 1-(5-cyanopyridin-2-yl)-1H-1,2,3-triazole-4-carboxylate
(1x)
(80%) of the product 15 as a white solid, mp 62–64 °C. IR ν
1
3410, 2963, 2934, 1602, 1486, 1446 cm−1; H NMR (CDCl3) δ
8.46 (s, 1H), 8.35 (s, 1H), 8.10 (d, J = 8.3, 1H), 7.94 (d, J = 8.3,
1H), 4.82 (d, J = 5.5, 2H), 3.61 (t, J = 6.5, 2H), 3.43 (t, J = 5.5,
1H), 2.97 (t, J = 7.2, 2H), 2.31–2.10 (m, 2H); 13C NMR
(CDCl3) δ 148.2, 146.9, 146.8, 137.9, 136.6, 118.7, 113.3, 61.8,
44.0, 31.6, 22.6. Anal. Calcd for C11H13ClN4O: C, 52.28; H,
5.19; N, 22.17. Found: C, 52.43; H, 5.12; N, 22.01.
It is a white solid, mp 156–159 °C. IR ν 3137, 2991, 2235,
1
1722, 1593, 1486 cm−1; H NMR (CDCl3) δ 9.11 (s, 1H), 8.86
(s, 1H), 8.45 (d, J = 8.6, 1H), 8.29 (d, J = 8.6, 1H), 4.50 (q, J =
7.2, 2H), 1.45 (t, J = 7.2, 3H); 13C NMR (CDCl3) δ 160.0,
152.1, 150.1, 142.7, 140.9, 125.1, 115.4, 114.2, 110.1, 61.7,
14.2. Anal. Calcd for C11H9N5O2: C, 54.32; H, 3.73; N, 28.79.
Found: C, 54.53; H, 3.79; N, 28.85.
Acknowledgements
Ethyl 1-(3,5-dichloropyridin-2-yl)-1H-1,2,3-triazole-4-
carboxylate (1y)
This work was supported by NNSFC (21072112).
It is a white solid, mp 68–69 °C. IR ν 3182, 2993, 2979, 1714,
1557, 1455, 1378 cm−1; 1H NMR (CDCl3) δ 8.7 (s, 1H), 8.5 (d,
J = 1.4, 1H), 8.1 (d, J = 1.4, 1H), 4.5 (q, J = 7.2, 2H), 1.4 (t, J =
7.2, 3H); 13C NMR (CDCl3) δ 160.0, 146.1, 143.6, 140.0 (2C),
133.5, 128.3, 126.3, 61.6, 14.2. Anal. Calcd for C10H8Cl2N4O2:
C, 41.83; H, 2.81; N, 19.51. Found: C, 41.97; H, 2.90; N, 19.39.
Notes and references
1 (a) I. E. Sayed, P. Van der Veken, K. Steert, L. Dhooghe, S. Hostyn,
G. Van Baelen, G. Lemiere, B. U. W. Maes, P. Cos, L. Maes, J. Joossens,
A. Haemers, L. Pieters and K. Augustyns, J. Med. Chem., 2009, 52,
2979–2988; (b) V. Zimmermann and S. Brase, J. Comb. Chem., 2007, 9,
1114–1137; (c) P. Vera-Luque, R. Alajarin, J. Alvarez-Builla and J.
J. Vaquero, Org. Lett., 2006, 8, 415–418; (d) M. H. V. Huynh, M.
A. Hiskey, D. E. Chavez and R. D. Gilardi, Angew. Chem., Int. Ed., 2005,
44, 7089–7094; (e) H. Mastalarz, R. Jasztold-Howorko, F. Rulko,
A. Croisyb and D. Carrezb, Arch. Pharm. Pharm. Med. Chem., 2004,
337, 434–439; (f) Y.-L. Chen, H.-M. Hung, C.-M. Lu, K.-C. Li and C.-
C. Tzeng, Bioorg. Med. Chem., 2004, 12, 6539–6546; (g) W.
K. Janowski, R. H. Prager and J. A. Smith, J. Chem. Soc., Perkin Trans.
1, 2000, 3212–3216; (h) W. Peczynska-Czoch, F. Pognan, E. Kaczmarek
and J. Boratynski, J. Med. Chem., 1994, 37, 3503–3510.
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)-pyrazine (1z)9a
It is a white solid, mp 134–138 °C. 1H NMR (CDCl3) δ 9.59 (d,
J = 1.4, 1H), 8.76 (s, 1H), 8.67 (d, J = 2.8, 1H), 8.51 (d, J = 1.0,
1H), 7.96–7.93 (m, 2H), 7.51–7.39 (m, 3H); 13C NMR (CDCl3)
δ 148.3, 145.3, 144.0, 142.4, 136.4, 129.6, 128.9 (2C), 128.7,
125.9 (2C), 116.7.
2 (a) F. Wang, X.-Y. Wu, R.-M. Yu, Z.-G. Zhao and C.-Z. Lu, J. Coord.
Chem., 2009, 62, 3296–3305; (b) C. Richardson and P. J. Steel, Dalton
Trans., 2003, 992–1000.
3 (a) A. S. Kiselyova, M. Semenova and V. V. Semenov, Bioorg. Med.
Chem. Lett., 2009, 19, 1344–1348; (b) M. Klein, P. Diner, D. Dorin-
Semblat, C. Doerig and M. Grotli, Org. Biomol. Chem., 2009, 7, 3421–
3429; (c) S. Ito, A. Satoh, Y. Nagatomi, Y. Hirata, G. Suzuki, T. Kimura,
A. Satow, S. Maehara, H. Hikichi, M. Hata, H. Kawamoto and H. Ohta,
Bioorg. Med. Chem., 2008, 16, 9817–9829; (d) S. Sviridov, J. Pickens,
S. Tandel, E. Brahmachary, Y. Yang, J. Wang, S. Freel, S. Fisher,
A. Sullivan, J. Zhou, S. Stanfield-Oakley, M. Greenberg, D. Bolognesi,
B. Bray, B. Koszalka, P. Jeffs, A. Khasanov, Y.-A. Ma, C. Jeffries,
C. Liu, T. Proskurina, T. Zhu, A. Chucholowski, R. Li and C. Sexton, J.
Med. Chem., 2007, 50, 6535–6544; (e) C. B. Madsen-Duggan, J.
S. Debenham, T. F. Walsh, R. B. Toupence, S. X. Huang, J. Wang,
X. Tong, J. Lao, T. M. Fong, M.-T. Schaeffer, J. C. Xiao, C. R.-R.
C. Huang, C.-P. Shen, D. S. Stribling, L. P. Shearman, A. M. Strack, D.
E. MacIntyre, L. H. T. Van der Ploegd and M. T. Goulet, Bioorg. Med.
Chem. Lett., 2007, 17, 2031–2035; (f) Y. W. Jo, W. B. Im, J. K. Rhee, M.
J. Shim, W. B. Kimb and E. C. Choi, Bioorg. Med. Chem., 2004, 12,
5909–5915.
Preparation of 2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-5-
aminopyridine (14)
A stirred suspension of compound 1j (231 mg, 1 mmol) and
10% Pd/C (23 mg, 10 wt%) in chemically pure EtOAc (20 mL)
was hydrogenated (balloon) at room temperature overnight. After
the catalyst was filtrated off through a pad of celite, the solvent
was evaporated. The residue was purified by column chromato-
graphy (silica gel, EtOAc/PE = 1 : 1) to give 185 mg (92%) of
the product 14 as a yellowish solid, mp 67–69 °C. IR ν 3428,
3338, 3087, 1589 cm−1 1H NMR (CDCl3) δ 7.99 (s, 1H),
;
7.79–7.72 (m, 2H), 7.07–7.03 (dd, J1 = 2.4, J2 = 10.9, 1H), 4.12
(s, 2H), 1.97–1.88 (m, 1H), 0.91–0.74 (m, 4H); 13C NMR
(CDCl3) δ 150.3, 143.0, 140.8, 134.2, 123.9, 116.4, 114.1, 7.7
(2C), 6.6. Anal. Calcd for C10H11N5: C, 59.69; H, 5.51; N,
34.80. Found: C, 59.97; H, 5.60; N, 34.64.
4 (a) K. Prabakaran, P. Manivel and F. N. Khan, Tetrahedron Lett., 2010,
51, 4340–4343; (b) P. F. Pagoria, J. Heterocycl. Chem., 2000, 37, 1597–
1602.
5 (a) S. V. Chapyshev, Chem. Heterocycl. Compd., 2001, 37, 861–866;
(b) R. A. Abramovitch, S. R. Challand and Y. Yamada, J. Org. Chem.,
1975, 40, 1541–1547; (c) D. Balachari and M. L. Trudell, Tetrahedron
Lett., 1997, 38, 8607–8610.
6 (a) J. M. Keith, J. Org. Chem., 2010, 75, 2722–2725; (b) M.-L. Teyssot,
L. Nauton, J.-L. Canet, F. Cisnetti, A. Chevry and A. Gautier,
Eur. J. Org. Chem., 2010, 3507–3515; (c) N. Kaval, D. Ermolat’ev,
P. Appukkuttan, W. Dehaen, C. O. Kappe and E. Van der Eycken, J.
Comb. Chem., 2005, 7, 490–502; (d) Z.-Y. Chen and M.-J. Wu, Org.
Lett., 2005, 7, 475–477; (e) I. P. Beletskaya, D. V. Davydov and
M. Moreno-Maflas, Tetrahedron Lett., 1998, 39, 5617–5620.
7 For selected reviews, see: (a) L. Liang and D. Astruc, Coord. Chem. Rev.,
2011, 255, 2933–2944; (b) S. Diez-Gonzalez, Catal. Sci. Technol., 2011,
1, 166–178; (c) J. E. Hein and V. V. Fokin, Chem. Soc. Rev., 2010, 39,
1302–1315; (d) M. Meldal and C. W. Tornøe, Chem. Rev., 2008, 108,
2952–3015; (e) V. D. Bock, H. Hiemstra and J. H. van Maarseveen,
Eur. J. Org. Chem., 2006, 51–68.
Preparation of 2-[4-(3-chloropropyl)-1H-1,2,3-triazol-1-yl]-5-
(hydroxylmethyl)pyridine (15)
A THF solution of LiAlH4 (0.6 M, 2 mL, 1.2 mmol) was added
dropwise to a stirred solution of compound 1v (295 mg,
1 mmol) in chemically pure THF (2 mL) at 0 °C under N2. After
the mixture was stirred at 0 °C for 30 min, it was warmed to
room temperature for another 1 h (monitored by TLC). Then, it
was quenched by saturated aqueous solution of NH4Cl (1 mL) at
0 °C. The mixture was filtered through a pad of celite and the
solvent was evaporated. The residue was purified by column
chromatography (silica gel, EtOAc/PE = 1 : 2) to give 202 mg
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8 (a) G. Colombano, C. Travelli, U. Galli, A. Caldarelli, M. G. Chini, P.
L. Canonico, G. Sorba, G. Bifulco, G. C. Tron and A. A. Genazzani, J.
Med. Chem., 2010, 53, 616–623; (b) M. K. Lakshman, M. Singh,
G. Parrish, R. Balachandran and B. W. Day, J. Org. Chem., 2010, 75,
2461–2473; (c) M. Klein, P. Diner, D. Dorin-Semblat, C. Doerig and
M. Grotli, Org. Biomol. Chem., 2009, 7, 3421–3429; (d) B. Saha,
S. Sharma, D. Sawant and B. Kundu, Synlett, 2007, 1591–1599.
9 (a) B. Chattopadhyay, C. I. Rivera Vera, S. Chuprakov and V. Gevorgyan,
Org. Lett., 2010, 12, 2166–2169; (b) S. Gu, H. Xu, N. Zhang and
W. Chen, Chem.–Asian J., 2010, 5, 1677–1686.
Chem., 1999, 12, 470–478; (c) P. Cmocha, J. W. Wiencha, L. Stefaniaka
and G. A. Webbb, J. Mol. Struct., 1999, 510, 165–178; (d) P. Cmoch,
L. Stefaniak and G. A. Webb, Magn. Reson. Chem., 1997, 35, 237–242;
(e) J. H. Boyer and E. J. Miller Jr., J. Am. Chem. Soc., 1959, 81, 4671–
4673.
11 (a) C. Shao, X. Wang, Q. Zhang, S. Luo, J. Zhao and Y. Hu, J. Org.
Chem., 2011, 76, 6832–6836; (b) Y. Liu, X. Wang, J. Xu, Q. Zhang,
Y. Zhao and Y. Hu, Tetrahedron, 2011, 67, 6294–6299; (c) C. Shao,
R. Zhu, S. Luo, Q. Zhang, X. Wang and Y. Hu, Tetrahedron Lett., 2011,
52, 3782–3785; (d) C. Shao, X. Wang, J. Xu, J. Zhao, Q. Zhang and
Y. Hu, J. Org. Chem., 2010, 75, 7002–7005; (e) C. Shao, G. Cheng,
D. Su, J. Xu, X. Wang and Y. Hu, Adv. Synth. Catal., 2010, 352, 1587–
1592.
10 (a) C. Boga, E. Del Vecchio, L. Forlani, A. Mazzanti, C. M. Lario, P.
E. Todesco and S. Tozzi, J. Org. Chem., 2009, 74, 5568–5575;
(b) P. Cmoch, H. Korczak, L. Stefaniak and G. A. Webb, J. Phys. Org.
2854 | Org. Biomol. Chem., 2012, 10, 2847–2854
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