Copper Acetate Catalyzed Regio-selective Synthesis of Substituted 1,2,3-Triazoles: A Versatile Azide–Alk-ene Cycloaddition/Oxidation Approach

Article abstract of DOI:10.1002/ejoc.201501301

A copper acetate catalyzed oxidative cycloaddition reaction of benzyl and aryl azides with terminal and internal olefins that contain electron-withdrawing groups (COOR, CONH₂, CN, CHO, COR) has been developed. The reaction employs air as the oxidant and does not require any base or additives to afford 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles in good to excellent yields with high regioselectivity.

Full text of DOI:10.1002/ejoc.201501301

DOI: 10.1002/ejoc.201501301
Full Paper
Oxidative Cycloaddition
Copper Acetate Catalyzed Regioselective Synthesis of
Substituted 1,2,3-Triazoles: A Versatile Azide–Alkene
Cycloaddition/Oxidation Approach
Sandeep Rohilla,[a] Shyam Sunder Patel,[a] and Nidhi Jain*[a]
Abstract: A copper acetate catalyzed oxidative cycloaddition ploys air as the oxidant and does not require any base or addi-
reaction of benzyl and aryl azides with terminal and internal
olefins that contain electron-withdrawing groups (COOR,
CONH2, CN, CHO, COR) has been developed. The reaction em-
tives to afford 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-
triazoles in good to excellent yields with high regioselectivity.
Introduction
occurs through enamine intermediates formed in situ,[10] (c) an
organocatalytic cycloaddition reaction with alkenes and the loss
of two hydrogen atoms,[11] and (d) a copper-catalyzed reaction
with olefins that have an electron-deficient carbonyl or nitro
group.[12] Although organocatalytic methods [Scheme 1, equa-
tions (b) and (c)] offer the common green features of organo-
catalysis,[13] the approach is restricted in its application because
of substrate scope in some cases and long reaction times in
others.
1,2,3-Triazoles are a privileged class of heterocyclic compounds
with applications in synthetic,[1] medicinal,[2] and materials
chemistry.[3] Among them, 1,4-disubstituted and 1,4,5-trisubsti-
tuted 1,2,3-triazole derivatives are significant, as they are found
in a large number of biologically and pharmaceutically active
molecules that have a broad spectrum of properties and act
as cannabinoid receptor antagonists as well as anti-influenza,
antiepileptic, and anticancer agents (Figure 1).[4]
In one of the previous copper-catalyzed protocols for the
preparation of fully substituted triazoles, Yao[12a] and co-work-
ers used a copper(I) catalyst along with O2 as the oxidant and
N,N-diisopropylethylamine (DIPEA) as the base to synthesize N-
benzylated and N-alkylated 1,2,3-triazoles with aldehyde, keto,
and amide substituents at the 4-position. In the second report,
Chen[12b] used expensive Cu(OTf)2 (OTf = trifluoromethane-
sulfonate) as the catalyst and acetic acid as an additive to syn-
thesize 1,2,3-triazoles with only a nitro substituent at the 4-
position. In our ongoing efforts towards the development of
The copper-catalyzed azide-alkyne cycloaddition (i.e., click
reaction) works remarkably well with terminal alkynes[5] to yield
1,4-disubstituted 1,2,3-triazoles. However, the same reaction
with internal alkynes[6] for the synthesis of fully substituted
1,2,3-triazoles remains a challenge. Recognized solutions in-
clude ruthenium-[7] and iridium-catalyzed[8] cycloaddition reac-
tions of organic azides with internal alkynes. Alternatively, there
are reports of a few other oxidative synthetic methods that use
organic azides and alkenes as substrates (Scheme 1) such as:
(a) a 1,3-dipolar cycloaddition reaction with alkenes that have
a leaving group,[9] (b) an organocatalytic cycloaddition reaction new synthetic strategies by using transition-metal catalysts,[14]
with activated keto esters, enones, aldehydes, and nitriles that we investigated whether a more general and economical route
Figure 1. Biologically relevant substituted 1,2,3-triazole derivatives.
[a] Department of Chemistry, Indian Institute of Technology Delhi,
that has a wide substrate scope with respect to the organic
azide (e.g., benzyl and aryl) and olefin (e.g., ester, amide, nitrile,
aldehyde, and keto functional groups) could be developed.
Herein, we present a highly regioselective synthesis of 1,4-di-
substituted and 1,4,5-trisubstituted 1,2,3-triazoles from olefins
New Delhi 110016, India
E-mail: njain@chemistry.iitd.ac.in
http://web.iitd.ac.in/~njain/#/home
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501301.
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CuSO4, and CuBr2 (Table 1, Entries 15–21). The lowest yields of
5 and 7 %, respectively, were obtained when Cu(NO3)2 and
CuBr2 were employed (Table 1, Entries 19 and 21). With other
copper salts as catalyst, yields were in the range 37–74 % show-
ing Cu(OAc)2 to be the ideal catalyst for this reaction. Further
studies involved the catalyst loading, the reduction of which to
5 mol-% lowered the yield of 3a to 84 % (Table 1, Entry 22).
Increasing the catalyst loading to 20 mol-% did not bring about
any change, and in the absence of the copper catalyst, no con-
version took place (Table 1, Entry 22). Because the reaction was
anticipated to proceed through an oxidative process, the proce-
dure was performed under oxygen, but no variation in the yield
of 3a was observed. As expected, 3a was not formed under
inert conditions (Table 1, Entry 23). Thus, the optimized condi-
tions for the triazole formation included the use of 10 mol-%
of Cu(OAc)2 in DMF in air at 85 °C for 8 h.
Table 1. Optimization of reaction conditions for the synthesis of 1,4-disubsti-
tuted 1,2,3-triazoles.[a]
Scheme 1. Synthesis of substituted 1,2,3-triazoles from azides and alkenes
(TMS = trimethylsilyl, TBAF = tetra-n-butylammonium fluoride, DMF = N,N-
dimethylformamide).
and azides that proceeds through a cycloaddition-oxidation
pathway. This developed method provides significant advanta-
ges over those reported by Yao and Chen. First, it makes use of
inexpensive copper acetate as the catalyst, and second, it is
applicable to olefins that contain ester and nitrile functional
groups that were previously found inert under the conditions
reported by Yao. Finally, this approach does not require any
additional base or additive, and the method is suitable for the
use of aryl azides as well as cyclic enones as substrates.
Entry
Catalyst [mol-%]
Solvent
Temp. [°C]
Yield[b] [%]
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuI
DMF
DMF
DMF
DMF
DMF
DMF
THF
DMSO
DCM
CH3CN
C2H5OH
H2O
100
110
90
85
80
70
85
85
85
85
85
85
85
85
85
85
85
85
85
85
85
85
85
79
76
82
95
92
79
73
82
9
74
Results and Discussion
10
11
12
13
14
15
16
17
18
19
20
21
22
23
86
91[c]
The conditions were examined by using the model reaction be-
tween phenyl azide (1a) and methyl acrylate (2a) with copper
acetate in DMF in air at 100 °C. After 12 h, the isolated product
was found to be 4-substituted 1,2,3-triazole 3a. Pleased with
the preliminary result, we decided to optimize the reaction re-
sults by varying the temperature, solvent, and copper salt. Reac-
tion temperatures in the range 70–110 °C were studied. It was
found that an increase in the temperature from 100 to 110 °C
afforded a slightly decreased product yield (Table 1, Entries 1
and 2), whereas reducing the temperature to 90 and then 85 °C
led to higher conversions (Table 1, Entries 3 and 4). Reducing
the temperature further to 80 and 70 °C, however, afforded a
decreased yield of 3a (Table 1, Entries 5 and 6). Therefore, 85 °C
was identified as the best temperature for this reaction. Next,
the reaction was optimized with regard to the solvent. Tetra-
hydrofuran (THF), dimethyl sulfoxide (DMSO), dichloromethane
(DCM), CH3CN, C2H5OH, H2O, dioxane and 1,2-dichloroethane
(DCE) were tested (Table 1, Entries 7–14) but found to be infe-
30
84
87
74
45
56
74
5
dioxane
DCE
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CuBr
Cu(OTf)2
CuF2
Cu(NO3)2
CuSO4
CuBr2
43
7
Cu(OAc)2
Cu(OAc)2
84[d], 95[e], 0[f]
94[g], 0[h]
[a] Reagents and conditions: 1a (1.0 equiv., 0.17 mmol), 2a (1.5 equiv.,
0.25 mmol), catalyst (10 mol-%, 0.017 mmol), and solvent were heated for
8 h. [b] Yield obtained by HPLC analysis. [c] 3b was obtained as the product.
[d] Cu(OAc)2 (5 mol-%) was employed. [e] Cu(OAc)2 (20 mol-%) was employed.
[f] No copper salt was added. [g] Reaction was performed under O2. [h] Reac-
tion was performed under N2.
As 1,4-disubstituted triazole derivatives are important pre-
rior to DMF, as they gave lower yields of 3a (30–91 %). A trans- cursors to biologically active molecules, the optimized protocol
esterification reaction took place when ethanol was used, and was then applied to their synthesis to explore the scope and
3b was formed in 91 % yield instead of the desired product 3a generality of the reaction (Table 2). In this regard, we first exam-
(Table 1, Entry 11). Next, we screened various copper(I) and ined the reaction of aryl and benzyl azides with a variety of
copper(II) salts including CuI, CuBr, Cu(OTf)2, CuF2, Cu(NO3)2, electron-deficient terminal olefins. The reaction of phenyl azide
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Table 2. Substrate scope of the reaction of azides with electron-deficient terminal olefins.[a]
[a] Reagents and conditions: 1 (1 equiv.), 2 (1.5 equiv.), and Cu(OAc)2 (10 mol-%) in DMF (2.0 mL) was stirred at 85 °C in air. [b] Yield of the isolated product.
[c] Reaction was carried out on a gram scale by using 1a (1.5 g).
with various esters such as methyl, ethyl, n-butyl, pivalyl, and was more complex, and unidentified side products were ob-
benzyl acrylate provided the corresponding ester-substituted tained, thus giving the desired product 3h in only 54 % yield.
triazole derivatives in good yields (Table 2, compounds 3a–3e). When the phenyl azide contained an electron-deficient formyl
When acrylonitrile and acrylamide were employed as sub- group, the yield of the corresponding product 3u was slightly
strates, the reaction afforded the corresponding nitrile- and lower, whereas having a nitro group on the phenyl azide only
amide-substituted triazole derivatives in 81 and 87 % yield, re- afforded trace amounts of the desired product 3v. The reactions
spectively (Table 2, compounds 3f and 3g). A similar copper- of nitro-substituted benzyl azides with methyl and pivalyl acryl-
assisted synthesis of nitrile derivatives 3f and 3m has not been ate went well, and products 3w and 3x were obtained in 82
previously reported.
and 78 % yield, respectively. Yao et al. previously showed that
benzyl azides were unable to react with methyl acrylate under
their reaction conditions.[12a] However, we successfully isolated
the ester derivatives of N-benzyltriazoles 3w and 3x in moder-
ate yields. Finally, this reaction was possible up to a gram scale,
and 3a was formed in 81 % yield by starting from 1.5 g of 1a.
To further evaluate the scope of this method for the synthe-
When the phenyl azide contained an electron-donating
methyl or methoxy group at the ortho or para position of the
aromatic ring, the corresponding ester-, amide-, and nitrile-sub-
stituted N-aryl triazoles were obtained in moderate to high
yields (Table 2, compounds 3h–3t). Although the reaction of 2-
methylphenyl azide smoothly proceeded with acrylamide to
yield 3n in 85 % yield, the similar reaction with methyl acrylate sis of 1,4,5-trisubstituted triazoles, the reaction of azides with
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substituted internal olefins was performed under the optimal However, the reactions required a longer period of time than
reaction conditions. To our delight, the desired products those needed for the terminal olefins, and these times varied
(Table 3, compounds 4a–4f) were obtained in moderate yields. from 12 to 48 h to produce the corresponding triazoles. This
decrease in the rate of the reaction may be attributed to the
Table 3. Substrate scope for the reaction of azides with electron-deficient
steric hindrance from the substituents at the β-position to the
carbonyl group.
internal olefins.[a]
Next, the reaction of azides with cyclic enones was per-
formed as shown in Table 4. We were pleased to find that the
reaction went well under the optimized conditions, and the cor-
responding triazoles (Table 4, compounds 5a–5d, 5f, and 5g)
were formed in moderate to high yields. The presence of an
electron-donating methoxy or methyl group on the phenyl ring
of the azide favored the reaction to yield 5b and 5c in 89 and
85 % yield, respectively.
When the phenyl azide contained a strong electron-with-
drawing nitro group at the para position, the yield of the prod-
uct decreased significantly, and 5d was obtained in 68 % yield.
However, when the nitro substituent occupied the ortho posi-
tion, the effect was more pronounced, and only trace amounts
of 5e were observed. Overall, this protocol has a broad scope
and provides a facile route to access new scaffolds such as 1-
phenyl-6,7-dihydro-1H-benzo[d][1,2,3]triazol-4(5H)-one (5a), the
structure of which was identified by X-ray single-crystal analysis.
A plausible mechanism for the formation of 1,4-disubstituted
and 1,4,5-trisubstituted 1,2,3-triazoles is outlined in Scheme 2.
First, quenching studies with (2,2,6,6-tetramethylpiperidin-1-
yl)oxyl (TEMPO) were carried out to ascertain whether a free
radical was involved in the mechanism. However, the addition
of TEMPO did not have any effect on the reaction or the prod-
uct yield, which suggests that reaction did not follow a radical
pathway. We believe that the reaction between the electron-
deficient alkene and azide is initiated through a copper acetate
assisted stepwise 1,3-dipolar cycloaddition to produce triazoline
intermediate A, which is further oxidized in presence of a cop-
per catalyst and air to yield the final product. A similar copper/
air-assisted oxidative aromatization in heterocyclic molecules
[a] Reagents and conditions: 1 (1.0 equiv.), 2 (1.5 equiv.), and Cu(OAc)2
(10 mol-%) in DMF (2.0 mL) was stirred at 85 °C in air. [b] Yield of isolated
product.
Table 4. Synthesis of 1,4,5-trisubstituted 1,2,3-triazoles from azides and 2-cyclohexen-1-one.[a]
[a] Reagents and conditions: 1 (1.0 equiv.), 2-cyclohexen-1-one (1.5 equiv.), and Cu(OAc)2 (10 mol-%) in DMF (2.0 mL) was stirred at 85 °C in air. [b] Yield of
isolated product.
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Representative Procedure for Synthesis of Benzyl Azides:[17]
A
has been previously reported.[15] Air is also rationalized as the
oxidant that promotes the regeneration of the CuII catalyst.[12]
solution of sodium azide (453.6 mg, 6.98 mmol) in water (5 mL) was
slowly added to solution of p-nitrobenzyl bromide (1 g,
a
4.65 mmol) in acetone (50 mL) at 0 °C. The progress of the reaction
was monitored by TLC analysis, and after 16 h, the reaction reached
completion. The mixture was extracted with ethyl acetate, and the
organic layer was concentrated under reduced pressure. The crude
residue was purified by column chromatography to give p-nitro-
benzyl azide (786.9 mg, 95 % yield).
Scheme 2. Plausible mechanism for substituted 1,2,3-triazoles.
Representative Procedure for the Preparation of the Cinnam-
ates:[18] A mixture of bromobenzene (1 g, 6.37 mmol), methyl
acrylate (764.4 mg, 7.64 mmol), potassium carbonate (1.32 g,
9.56 mmol), palladium acetate (28.5 mg, 0.13 mmol), and triphenyl-
phosphine (66.8 mg, 0.25 mmol) was heated under a reflux con-
denser at 130 °C for 24 h. The progress of the reaction was moni-
tored by TLC analysis. Upon completion of the reaction, the mixture
was extracted with ethyl acetate and concentrated under reduced
pressure. The crude product was purified by column chromatogra-
phy on silica gel (hexane/EtOAc, 90:10) to give methyl cinnamate
(976.9 mg, 94 % yield).
Conclusions
In summary, copper acetate has been employed for the first
time as an inexpensive and efficient catalyst for the regioselect-
ive synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-
triazoles. The oxidative dehydrogenative process uses air as the
oxidant and does not require any base or additive. This protocol
is highly versatile, as it has been applied to both benzyl and aryl
azide derivatives as well as a wide range of electron-deficient
terminal and internal olefins. Herein, the strategy has been em-
ployed as a direct method for the synthesis of 1,2,3-triazoles
that contain ester, amide, nitrile, aldehyde, and keto functionali-
ties, which are otherwise difficult to obtain by the direct deriva-
tization of the C-4 and C-5 positions of 1,2,3-triazoles.
Procedure for the Preparation of Triazoles (3a–3x, 4a–4f, and
5a–5g): An oven-dried round-bottomed flask was charged with the
aryl or phenyl azide (100 mg, 0.84 mmol), Cu(OAc)2 (15 mg,
0.084 mmol), and the acrylate/α,β-unsaturated cyclohexenone
(1.5 equiv.) in N,N-dimethylformamide (2 mL). The flask was sealed
with a septum, and the contents were stirred and heated in a pre-
heated oil bath at 85 °C for 6–39 h. The mixture was cooled to room
temperature and diluted with ethyl acetate. The resulting mixture
was then extracted with ethyl acetate (2 × 10 mL), and the com-
bined organic layers were dried with anhydrous Na2SO4 and con-
centrate under vacuum. The residue was purified over a column of
silica gel (ethyl acetate/hexane eluent) to give the pure triazole.
Experimental Section
General Methods: All reactions were carried out in the air in an
oven-dried round-bottomed flask that was sealed with a septum.
All solvents were purchased from Aldrich and Spectrochem and
used as received. Copper(II) acetate was purchased from Alfa-Aesar
(98 % purity). The aromatic amines and aryl/benzyl bromides were
purchased from Aldrich and Merck. Thin layer chromatography was
performed on aluminium plates precoated with 60 F254 silica gel,
and the compounds were visualized by using either a UV lamp
(λmax = 254 nm) or iodine vapors. The products were purified by
Procedure for Quenching the Reaction with TEMPO: To examine
the mechanistic route of the reaction, TEMPO (131 mg, 0.84 mmol)
was added to a mixture of 1a (100 mg, 0.84 mmol), 2a (108 mg,
1.26 mmol), and Cu(OAc)2 (15 mg, 0.084 mmol) in DMF (2 mL). The
contents were stirred at 85 °C for 8 h. However, the reaction was
not quenched by the addition of the TEMPO, and product 3a was
isolated (155 mg, 91 % yield).
1
column chromatography on silica gel (230–400 mesh). The H and
13C NMR spectroscopic data were recorded with a Bruker DPX-
300 MHz spectrometer (1H NMR: 300 and 400 MHz, 13C NMR: 75
and 100 MHz). CDCl3 was used as the NMR solvent with tetrameth-
ylsilane (TMS) as the internal standard at room temperature. Chemi-
cal shifts (δ) are reported in ppm relative to TMS. The coupling
constants (J) are reported in Hz. ESI-MS was performed with a high
resolution mass spectrometer by using a quadrupole-TOF mass ana-
lyzer. Sodium azide is poisonous and was carefully handled. It
should not be inhaled or have direct contact with skin or eyes.
Methyl 1-Phenyl-1H-1,2,3-triazole-4-carboxylate (3a): White
1
solid (155.2 mg, 91 % yield). H NMR (300 MHz, CDCl3): δ = 8.58 (s,
1 H), 7.77 (d, J = 6.9 Hz, 2 H), 7.55–7.49 (m, 3 H), 3.98 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 160.9, 140.5, 136.3, 129.9, 129.5, 125.6,
120.7, 52.2 ppm. MS (ESI): m/z = 226 [M + Na]+. HRMS: calcd. for
+
C10H9N3NaO2 [M + Na]+ 226.0586; found 226.0581.
Ethyl 1-Phenyl-1H-1,2,3-triazole-4-carboxylate (3b): White solid
Representative Procedure for the Synthesis of Aryl Azides:[16]
Aniline (1 g, 10.75 mmol) was suspended in 17 % hydrochloric acid
(65 mL) at room temperature. The solution was cooled to 0 °C by
using an ice bath. Then NaNO2 (1.11 g, 16.13 mmol) in water (5 mL)
was added in small portions, and the resulting mixture was stirred
at 0 °C for 20–30 min. A solution of NaN3 (1.05 g, 16.13 mmol) in
water (10 mL) was added dropwise over 3 min, and the contents
were stirred for additional 2 h at room temperature. Upon comple-
tion, the reaction mixture was extracted with hexane (3 × 40 mL).
1
(162.3 mg, 89 % yield). H NMR (300 MHz, CDCl3): δ = 8.54 (s, 1 H),
7.77 (d, J = 6 Hz, 2 H), 7.58–7.49 (m, 3 H), 4.46 (q, J = 9 Hz, 2 H),
1.44 (t, J = 15 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.6,
140.8, 136.4, 129.9, 129.5, 125.5, 120.8, 61.4, 14.3 ppm. MS (ESI):
m/z = 218 [M + H]+. HRMS: calcd. for C11H12N3O2 [M + H]+
+
218.0924; found 218.0918.
Butyl 1-Phenyl-1H-1,2,3-triazole-4-carboxylate (3c): White solid
1
(177.1 mg, 86 % yield). H NMR (300 MHz, CDCl3): δ = 8.44 (s, 1 H),
The combined organic phases were washed with a saturated NaH- 7.71–7.67 (m, 2 H), 7.50–7.20 (m, 2 H), 4.33 (t, J = 6.9 Hz, 2 H), 1.77–
CO3 solution (2 × 40 mL) and brine (2 × 40 mL). The organic layer
was dried with Na2SO4 and evaporated under reduced pressure.
The crude residue was purified by column chromatography to give
phenyl azide (1.23 g, 96 % yield).
1.67 (m, 2 H), 1.44–1.37 (m, 2 H), 0.90 (t, J = 7.2 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 160.7, 140.9, 136.4, 129.9, 129.5, 125.5,
120.8, 65.3, 30.7, 19.1, 14.1, 13.7 ppm. MS (ESI): m/z = 246 [M + H]+.
+
HRMS: calcd. for C13H16N3O2 [M + H]+ 246.1237; found 246.1233.
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tert-Butyl 1-Phenyl-1H-1,2,3-triazole-4-carboxylate (3d): White
solid (168.8 mg, 82 % yield). H NMR (300 MHz, CDCl3): δ = 8.44 (s,
1-(p-Tolyl)-1H-1,2,3-triazole-4-carbonitrile (3m): White solid
(116.2 mg, 84 % yield). H NMR (300 MHz, CDCl3): δ = 8.38 (s, 1 H),
1
1
1 H), 7.74 (d, J = 7.5 Hz, 2 H), 7.56–7.48 (m, 3 H), 1.63 (s, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 159.8, 142.1, 136.5, 129.9, 129.4, 125.2,
120.8, 82.5, 28.0 ppm. MS (ESI): m/z = 246 [M + H]+. HRMS: calcd.
7.60 (d, J = 7.2 Hz, 2 H), 7.38 (d, J = 7.8 Hz, 2 H), 2.46 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 140.6, 133.5, 130.5, 127.4, 121.7, 120.8,
111.1, 21.0 ppm. MS (ESI): m/z = 185 [M + H]+. HRMS: calcd. for
for C13H16N3O2 [M + H]+ 246.1237; found 246.1230.
C
10H9N4 [M + H]+ 185.0821; found 185.0814.
+
+
Benzyl 1-Phenyl-1H-1,2,3-triazole-4-carboxylate (3e): White
solid (182.8 mg, 78 % yield). H NMR (300 MHz, CDCl3): δ = 8.50 (s,
1-(o-Tolyl)-1H-1,2,3-triazole-4-carboxamide (3n): White solid
(129.0 mg, 85 % yield). 1H NMR (300 MHz, [D6]DMSO): δ = 8.89 (s,
1 H), 8.00 (s, 1 H), 7.61 (s, 1 H), 7.47–7.40 (m, 4 H), 2.15 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 161.4, 143.6, 133.1, 131.3, 130.1, 128.1,
1
1 H), 7.74 (d, J = 8.1 Hz, 2 H), 7.57–7.47 (m, 5 H), 7.41–7.35 (m, 3 H),
5.44 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.4, 140.5, 136.4,
135.4, 129.9, 129.6, 128.7, 128.6, 128.5, 125.7, 120.9, 67.0 ppm. MS 127.0, 126.1, 17.3 ppm. MS (ESI): m/z = 225 [M + H]+. HRMS: calcd.
(ESI): m/z = 280 [M + H]+. HRMS: calcd. for C16H14N3O2 [M + H]+ for C10H10N4NaO+ [M + H]+ 225.0747; found 225.0736.
+
280.1080; found 280.1071.
1-(p-Tolyl)-1H-1,2,3-triazole-4-carboxamide (3o): White solid
(136.6 mg, 90 % yield). H NMR (300 MHz, CDCl3): δ = 9.18 (s, 1 H),
1
1-Phenyl-1H-1,2,3-triazole-4-carbonitrile (3f): White solid
1
(115.7 mg, 81 % yield). H NMR (300 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.98 (s, 1 H), 7.83 (d, J = 10.1 Hz, 2 H), 7.59 (s, 1 H), 7.41 (d, J =
7.75 (d, J = 6.9 Hz, 2 H), 7.63–7.56 (m, 3 H) ppm. 13C NMR (75 MHz, 8.7 Hz, 2 H), 2.39 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.6,
CDCl3): δ = 135.8, 130.2, 129.5, 127.6, 122.1, 121.0, 111.2 ppm. MS 144.3, 139.3, 134.2, 130.7, 125.1, 120.8 ppm. MS (ESI): m/z = 225 [M
(ESI): m/z = 171 [M + H]+. HRMS: calcd. for C9H7N4 [M + H]+ + H]+. HRMS: calcd. for C10H10N4NaO+ [M + H]+ 225.0747; found
+
171.0665; found 171.0658.
225.0736.
1-Phenyl-1H-1,2,3-triazole-4-carboxamide (3g): White solid
Methyl
1-(4-Methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
1
(137.4 mg, 87 % yield). 1H NMR (300 MHz, [D6]DMSO): δ = 9.25 (s, (3p): White solid (150.1 mg, 96 % yield). H NMR (300 MHz, CDCl3):
1 H), 8.00–7.95 (m, 3 H), 7.62–7.64 (m, 3 H), 7.64–7.54 (m, 3 H), 7.52–
δ = 8.45 (s, 1 H), 7.67 (d, J = 8.7 Hz, 2 H), 7.06 (d, J = 9 Hz, 2 H),
7.54 (m, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 161.8, 144.3,
4.02 (s, 3 H), 3.90 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.2,
136.8, 130.4, 129.6, 125.3, 12.9 ppm. MS (ESI): m/z = 189 [M + H]+. 160.4, 140.4, 129.7, 125.6, 122.5, 115.0, 55.7, 52.3 ppm. MS (ESI):
HRMS: calcd. for C9H9N4O+ [M + H]+ 189.0770; found 189.0762.
m/z = 234 [M + H]+. HRMS: calcd. for C11H12N3O3 [M + H]+
+
234.0873; found 234.0867.
Methyl 1-(o-Tolyl)-1H-1,2,3-triazole-4-carboxylate (3h): Yellow
solid (88.1 mg, 54 % yield). H NMR (300 MHz, CDCl3): δ = 8.28 (s, 1
1
Butyl
1-(4-Methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
H), 7.45–7.35 (m, 4 H), 4.01 (s, 3 H), 2.23 (s, 3 H) ppm. 13C NMR (3q): White solid (166.1 mg, 90 % yield). H NMR (300 MHz, CDCl3):
1
(75 MHz, CDCl3): δ = 160.9, 140.0, 135.9, 133.7, 131.7, 130.5, 128.9,
δ = 8.34 (s, 1 H), 7.54 (d, J = 8.7 Hz, 3 H), 6.96 (d, J = 9 Hz, 2 H),
4.32 (t, J = 6.6 Hz, 2 H), 3.79 (s, 3 H), 1.70 (q, J = 7.2 Hz, 3 H), 1.40
(q, J = 7.5 Hz, 2 H), 0.90 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 160.8, 160.4, 140.6, 129.7, 125.5, 122.5, 114.9, 65.3, 55.7,
30.7, 19.2, 13.7 ppm. MS (ESI): m/z = 276 [M + H]+. HRMS: calcd. for
127.1, 125.9, 52.3, 17.8 ppm. MS (ESI): m/z = 240 [M + Na]+. HRMS:
calcd. for C11H11N3NaO2 [M + Na]+ 240.0743; found 240.0747.
+
Methyl 1-(p-Tolyl)-1H-1,2,3-triazole-4-carboxylate (3i): White
1
solid (151.7 mg, 93 % yield). H NMR (300 MHz, CDCl3): δ = 8.49 (s,
C14H18N3O3 [M + H]+ 276.1342; found 276.1335.
+
1 H), 7.64 (d, J = 6.3 Hz, 2 H), 7.36 (d, J = 6 Hz, 2 H), 4.01 (s, 3 H),
2.46 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.1, 139.4, 138.8,
Benzyl
1-(4-Methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
1
133.0, 129.4, 124.5, 119.7, 51.3, 28.7 ppm. MS (ESI): m/z = 218 [M + (3r): White solid (176.2 mg, 85 % yield). H NMR (300 MHz, CDCl3):
H]+. HRMS: calcd. for C11H12N3O2 [M + H]+ 218.0924; found
218.0917.
δ = 8.48 (s, 1 H), 7.65 (d, J = 8.4 Hz, 3 H), 7.48–7.30 (m, 6 H), 5.42
(s, 2 H), 2.42 (s, 2 H) ppm. 13C NMR (300 MHz, CDCl3): δ = 160.5,
140.3, 139.8, 135.5, 134.0, 130.4, 128.6, 128.6, 128.5, 125.7, 120.7,
66.9, 21.2 ppm. MS (ESI): m/z = 310 [M + H]+. HRMS: calcd. for
+
Butyl 1-(p-Tolyl)-1H-1,2,3-triazole-4-carboxylate (3j): White solid
1
(173.3 mg, 89 % yield). H NMR (300 MHz, CDCl3): δ = 8.38 (s, 1 H),
C17H16N3O3 [M + H]+ 310.1186; found 310.1178.
+
7.55 (d, J = 8.1 Hz, 2 H), 7.26 (d, J = 8.1 Hz, 2 H), 4.32 (t, J = 6.9 Hz,
2 H), 2.36 (s, 3 H), 1.74–1.66 (m, 2 H), 1.43–1.36 (m, 2 H), 0.90 (t, J =
7.5 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.8, 140.7, 139.7,
tert-Butyl 1-(4-Methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
1
(3s): White solid (164.2 mg, 89 % yield). H NMR (300 MHz, CDCl3):
134.1, 130.8, 125.4, 120.7, 65.2, 30.7, 29.7, 21.1, 19.1, 13.7 ppm. MS
δ = 8.33 (s, 1 H), 7.64 (d, J = 8.7 Hz, 2 H), 7.03 (d, J = 8.4 Hz, 2 H),
(ESI): m/z = 260 [M + H]+. HRMS: calcd. for C14H18N3O2 [M + H]+ 3.87 (s, 3 H), 1.63 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.3,
+
260.1393; found 260.1386.
159.9, 141.9, 129.9, 125.2, 122.5, 114.9, 82.4, 55.7, 28.2 ppm. MS
(ESI): m/z = 276 [M + H]+. HRMS: calcd. for C14H18N3O3 [M + H]+
+
tert-Butyl 1-(p-Tolyl)-1H-1,2,3-triazole-4-carboxylate (3k): White
solid (165.5 mg, 85 % yield). H NMR (300 MHz, CDCl3): δ = 8.38 (s,
276.1342; found 276.1337.
1
1 H), 7.62 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H), 2.43 (s, 3 H),
1-(4-Methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide
(3t):
1.63 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.9, 142.0, 139.6,
White solid (137.5 mg, 94 % yield). 1H NMR (300 MHz, [D6]DMSO):
134.2, 130.4, 125.1, 120.7, 82.4, 28.3, 22.0 ppm. MS (ESI): m/z = 260 δ = 9.11 (s, 1 H), 7.95 (s, 1 H), 7.84 (d, J = 9 Hz, 1 H), 7.56 (s, 1 H),
[M + H]+. HRMS: calcd. for C14H18N3O2 [M + H]+ 260.1393; found 7.12 (d, J = 7.12 Hz, 1 H), 3.82 (s, 3 H) ppm. 13C NMR (75 MHz,
+
260.1388.
[D6]DMSO): δ = 161.3, 159.5, 143.6, 129.6, 124.6, 122.1, 114.8,
55.5 ppm. MS (ESI): m/z = 219 [M + H]+. HRMS: calcd. for
Benzyl 1-(p-Tolyl)-1H-1,2,3-triazole-4-carboxylate (3l): White
solid (180.6 mg, 82 % yield). H NMR (300 MHz, CDCl3): δ = 8.48 (s,
C10H11N4O2 [M + H]+ 219.0876; found 219.0869.
+
1
1 H), 7.61 (d, J = 8.4 Hz, 3 H), 7.48–7.28 (m, 6 H), 5.42 (s, 2 H), 2.42
tert-Butyl 1-(3-Formylphenyl)-1H-1,2,3-triazole-4-carboxylate
(3u): White solid (137.4 mg, 74 % yield). H NMR (300 MHz, CDCl3):
1
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.5, 140.3, 139.8,
135.5, 134.0, 130.4, 128.6, 128.6, 128.5, 125.7, 120.7, 66.9, 21.1 ppm. δ = 10.12 (s, 1 H), 8.54 (s, 1 H), 8.27 (d, J = 0.6 Hz, 1 H), 8.13 (d, J =
MS (ESI): m/z = 260 [M + H]+. HRMS: calcd. for C17H16N3O2 [M +
6.6 Hz, 2 H), 8.02 (d, J = 7.5 Hz, 2 H), 7.78 (t, J = 7.5 Hz, 1 H), 1.40
+
H]+ 294.1237; found 294.1229.
(s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 190.5, 159.5, 142.5,
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137.8, 137.7, 130.9, 130.6, 126.2, 125.1, 120.5, 82.9, 28.3 ppm. MS 1-Phenyl-6,7-dihydro-1H-benzo[d][1,2,3]triazol-4(5H)-one (5a):
(ESI): m/z = 276 [M + H]+. HRMS: calcd. for C14H16N3O3 [M + H]+ White solid (148.5 mg, 83 % yield). 1H NMR (300 MHz, CDCl3): δ =
+
276.1186; found 276.1189.
7.81–7.56 (m, 5 H), 3.05 (t, J = 6 Hz, 3 H), 2.83–2.62 (m, 2 H), 2.24
(t, J = 6 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 190.4, 144.6,
142.3, 135.6, 129.8, 129.8, 123.5, 38.2, 23.1, 21.7 ppm. MS (ESI): m/z =
236 [M + Na]+. HRMS: calcd. for C12H11N3NaO+ [M + Na]+ 236.0794;
found 236.0798.
Methyl 1-(4-Nitrobenzyl)-1H-1,2,3-triazole-4-carboxylate (3w):
Yellow solid (120.6 mg, 82 % yield). H NMR (300 MHz, CDCl3): δ =
1
8.27 (d, J = 8.7 Hz, 2 H), 8.11 (s, 1 H), 7.46, (d, J = 8.4 Hz, 2 H), 5.73
(s, 2 H), 3.97 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.8,
148.4, 140.6, 128.8, 127.6, 124.5, 113.5, 53.4, 52.4 ppm. MS (ESI):
1-(4-Methoxyphenyl)-6,7-dihydro-1H-benzo[d][1,2,3]triazol-
4(5H)-one (5b): White solid (145.1 mg, 89 % yield). 1H NMR
(300 MHz, CDCl3): δ = 7.48 (d, J = 9 Hz, 2 H), 7.07 (d, J = 8.7 Hz, 2
H), 3.90 (s, 3 H), 3.00 (t, J = 6.3 Hz, 2 H), 2.67 (t, J = 6.3 Hz, 2 H),
2.30–2.21 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 190.2, 160.5,
144.3, 142.1, 128.5, 114.9, 55.7, 38.2, 29.8, 23.2, 21.6 ppm. MS (ESI):
m/z = 263 [M + H]+. HRMS: calcd. for C11H11N4O4 [M + H]+
+
263.0774; found 263.0768.
tert-Butyl
1-(4-Nitrobenzyl)-1H-1,2,3-triazole-4-carboxylate
(3x): Yellow solid (133.2 mg, 78 % yield). 1H NMR (300 MHz, CDCl3):
δ = 8.20 (d, J = 8.7 Hz, 2 H), 8.03 (s, 1 H), 7.42, (d, J = 8.4 Hz, 2 H),
5.70 (s, 2 H), 1.5 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.7,
148.3, 142.4, 141.2, 128.9, 127.5, 124.5, 82.8, 53.4, 28.3 ppm. MS
+
m/z = 244 [M + H]+. HRMS: calcd. for C13H14N3O2 [M + H]+
244.1080; found 244.1073.
(ESI): m/z = 305 [M + H]+. HRMS: calcd. for C14H17N4O4 [M + H]+
+
1-(p-Tolyl)-6,7-dihydro-1H-benzo[d][1,2,3]triazol-4(5H)-one (5c):
White solid (145 mg, 85 % yield). 1H NMR (300 MHz, CDCl3): δ =
7.46 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 3.03 (t, J = 6 Hz, 2
H), 2.69 (t, J = 6 Hz, 2 H), 2.48 (s, 3 H), 2.31–2.24 (m, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 190.1, 144.2, 142.4, 140.1, 133.2, 130.4,
123.3, 38.3, 23.2, 21.7, 21.2 ppm. MS (ESI): m/z = 228 [M + H]+.
HRMS: calcd. for C13H14N3O+ [M + H]+ 228.1131; found 228.1124.
305.1244; found 305.1238.
Methyl 1,5-Diphenyl-1H-1,2,3-triazole-4-carboxylate (4a): White
solid (185.2 mg, 72 % yield). 1H NMR (300 MHz, CDCl3): δ = 7.43–
7.36 (m, 6 H), 7.31–7.26 (m, 4 H), 3.90 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 161.4, 141.0, 136.6, 135.8, 130.2, 130.0, 129.6,
129.3, 128.4, 125.6, 125.2, 52.1 ppm. MS (ESI): m/z = 280 [M + H]+.
HRMS: calcd. for C16H14N3O2 [M + H]+ 280.1080; found 280.1071.
+
1-(4-Nitrophenyl)-6,7-dihydro-1H-benzo[d][1,2,3]triazol-4(5H)-
one (5d): Pale yellow solid (107 mg, 68 % yield). 1H NMR (300 MHz,
CDCl3): δ = 8.47 (d, J = 9.0 Hz, 2 H), 7.86 (d, J = 8.7 Hz, 2 H), 3.15 (t,
J = 6.0 Hz, 2 H), 2.71 (t, J = 6 Hz, 2 H), 2.36–2.30 (m, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 189.6, 147.9, 144.3, 142.9, 140.4, 125.4,
123.7, 38.1, 23.1, 22.2 ppm. MS (ESI): m/z = 281 [M + Na]+. HRMS:
Methyl
5-Phenyl-1-(p-tolyl)-1H-1,2,3-triazole-4-carboxylate
1
(4b): White solid (167.4 mg, 76 % yield). H NMR (300 MHz, CDCl3):
δ = 7.37–7.34 (m, 3 H), 7.32 (s, 1 H), 7.28–7.18 (m, 5 H), 3.93 (s, 3
H), 1.97 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.6, 142.2,
135.9, 135.1, 134.8, 131.3, 130.5, 129.9, 128.2, 127.8, 126.8, 125.2,
calcd. for C12H10N4NaO3 [M + Na]+ 281.0645; found 281.0648.
+
52.2, 17.5 ppm. MS (ESI): m/z = 294 [M + H]+. HRMS: calcd. for
17H16N3O2 [M + H]+ 294.1237; found 294.1231.
+
1-(Naphthalen-1-yl)-6,7-dihydro-1H-benzo[d][1,2,3]triazol-
4(5H)-one (5f ): Brown solid (121 mg, 78 % yield). 1H NMR
(300 MHz, CDCl3): δ = 8.10 (d, J = 8.4 Hz, 2 H), 8.01 (d, J = 8.4 Hz, 1
H), 7.67–7.53 (m, 2 H), 7.32–7.28 (m, 1 H), 2.78–2.68 (m, 4 H), 2.27–
2.19 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 190.2, 147.0, 141.7,
134.2, 131.4, 131.2, 128.9, 128.6, 128.3, 127.4, 125.1, 124.7, 121.6,
38.4, 23.0, 20.7 ppm. MS (ESI): m/z = 264 [M + H]+. HRMS: calcd. for
C16H14N3O+ [M + H]+ 264.1132; found 264.1131.
C
Methyl 1-(4-Methoxyphenyl)-5-phenyl-1H-1,2,3-triazole-4-carb-
oxylate (4c): White solid (163.8 mg, 79 % yield). 1H NMR (300 MHz,
CDCl3): δ = 7.43–7.40 (m, 4 H), 7.31–7.30 (m, 2 H), 7.22–7.20 (m, 3
H), 3.93 (s, 3 H), 2.39 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
161.5, 140.2, 136.0, 130.2, 130.1, 129.5, 129.3, 129.1, 128.4, 125.3,
122.5, 52.1, 21.4 ppm. MS (ESI): m/z = 294 [M + H]+. HRMS: calcd.
for C17H16N3O2 [M + H]+ 294.1237; found 294.1231.
+
1-(4-Nitrobenzyl)-6,7-dihydro-1H-benzo[d][1,2,3]triazol-4(5H)-
one (5g): Yellow solid (128 mg, 84 % yield). 1H NMR (300 MHz,
CDCl3): δ = 8.27 (d, J = 8.7 Hz, 2 H), 8.11 (s, 1 H), 7.46, (d, J = 8.4 Hz,
2 H), 5.73 (s, 2 H), 3.97 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
190.1, 148.3, 144.9, 142.6, 140.9, 128.6, 124.6, 51.4, 38.2, 29.8, 22.9,
20.3 ppm. MS (ESI): m/z = 273 [M + H]+. HRMS: calcd. for
1-(4-Methoxyphenyl)-5-methyl-1H-1,2,3-triazole-4-carbalde-
hyde (4d): White solid (125.2 mg, 86 % yield). 1H NMR (300 MHz,
CDCl3): δ = 10.28 (s, 1 H), 7.39 (d, J = 9 Hz, 2 H), 7.09 (d, J = 9 Hz,
2 H), 3.91 (s, 3 H), 2.60 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
186.5, 160.9, 143.8, 137.7, 127.7, 126.6, 114.9, 55.7, 9.7 ppm. MS
(ESI): m/z = 218 [M + H]+. HRMS: calcd. for C11H12N3O2 [M + H]+
+
C13H13N4O3 [M + H]+ 273.0982; found 273.0975.
+
218.0924; found 218.0918.
CCDC 1416103 (for 5a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
Methyl 5-(4-Methoxyphenyl)-1-phenyl-1H-1,2,3-triazole-4-carb-
oxylate (4e): White solid (184.3 mg, 71 % yield). 1H NMR (300 MHz,
CDCl3): δ = 7.41–7.38 (m, 4 H), 7.30–7.26 (m, 2 H), 7.24–7.22 (m, 2
H), 7.24–7.22 (m, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 3.92 (s, 3 H), 3.82 (s,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.6, 160.8, 140.9, 131.7,
130.2, 130.0, 129.5, 129.3, 128.4, 125.3, 114.0, 55.3, 52.1 ppm. MS
Supporting Information (see footnote on the first page of this
article): Full experimental details and crystallographic data (Fig-
ure S1 and Table S1).
+
(ESI): m/z = 310 [M + H]+. HRMS: calcd. for C17H16N3O3 [M + H]+
310.1186; found 310.1188.
Acknowledgments
Methyl 5-(4-Cyanophenyl)-1-phenyl-1H-1,2,3-triazole-4-carbox-
ylate (4f): White solid (163.5 mg, 64 % yield). 1H NMR (300 MHz,
CDCl3): δ = 7.69 (d, J = 8.4 Hz, 2 H), 7.47–7.42 (m, 4 H), 7.28 (s, 3 H),
3.39 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.1, 139.1, 137.1,
135.3, 132.1, 131.1, 130.4, 130.1, 129.7, 125.2, 117.8, 114.0, 52.3 ppm.
The authors thank the Council of Scientific and Industrial Re-
search (CSIR), New Delhi (02/0180/14/EMR-II, grant to S. P.) for
financially supporting this work and the Department of Science
and Technology – Fund for Improvement of Science and Tech-
nology (DST-FIST), India for funding the ESI-HRMS facility at the
Indian Institute of Technology (IIT) Delhi. S. R. further thanks
MS (ESI): m/z = 305 [M + H]+. HRMS: calcd. for C17H13N4O2 [M +
+
H]+ 305.1033; found 305.1037.
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[6] For selected examples of the synthesis of 1,4,5-trisubstituted 1,2,3-tri-
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33; Angew. Chem. 2010, 122, 33–36; b) Y. Zhou, T. Lecourt, L. Micouin,
Angew. Chem. Int. Ed. 2010, 49, 2607–2610; Angew. Chem. 2010, 122,
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2013, 52, 13037–13041; Angew. Chem. 2013, 125, 13275–13279.
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Fokin, G. Jia, J. Am. Chem. Soc. 2005, 127, 15998–15999; b) B. C. Boren,
S. Narayan, L. K. Rasmussen, L. Zhang, H. Zhao, Z. Lin, G. Jia, V. V. Fokin,
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the Ministry of Human Resource Development (MHRD), India
for his graduate fellowship.
Keywords: Nitrogen heterocycles · Cycloaddition ·
Regioselectivity · Alkenes · Azides · Copper
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Received: October 9, 2015
Published Online: December 23, 2015
Eur. J. Org. Chem. 2016, 847–854
www.eurjoc.org
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim