A tunable route to oxidative and eliminative [3+2] cycloadditions of organic azides with nitroolefins: CuO nanoparticles catalyzed synthesis of 1,2,3-triazoles under solvent-free condition

Article abstract of DOI:10.1016/j.tetlet.2016.06.004

A regioselective and tunable synthesis of 1,5-disubstituted 1,2,3-triazloles from oxidative and eliminative [3+2] cycloadditions of nitroolefins and organic azides under solvent-free condition in the presence and absence of commercially available CuO nano

Full text of DOI:10.1016/j.tetlet.2016.06.004

Accepted Manuscript
A Tunable Route to Oxidative and Eliminative [3+2] Cycloadditions of Organic
Azides with Nitroolefins: CuO Nanoparticles Catalyzed Synthesis of 1,2,3-Tri-
azoles under Solvent-Free condition
D. Gangaprasad, J. Paul Raj, T. Kiranmye, R. Sasikala, K. Karthikeyan, S. Kutti
Rani, J. Elangovan
PII:
S0040-4039(16)30655-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.004
TETL 47731
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 April 2016
30 May 2016
1 June 2016
Please cite this article as: Gangaprasad, D., Paul Raj, J., Kiranmye, T., Sasikala, R., Karthikeyan, K., Kutti Rani,
S., Elangovan, J., A Tunable Route to Oxidative and Eliminative [3+2] Cycloadditions of Organic Azides with
Nitroolefins: CuO Nanoparticles Catalyzed Synthesis of 1,2,3-Triazoles under Solvent-Free condition, Tetrahedron
Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.06.004
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Tetrahedron Letters
A Tunable Route to Oxidative and Eliminative [3+2] Cycloadditions of Organic
Azides with Nitroolefins: CuO Nanoparticles Catalyzed Synthesis of 1,2,3-Triazoles
under Solvent-Free condition
D. Gangaprasad,a J. Paul Raj,a T. Kiranmye,a R. Sasikala,a K. Karthikeyan,a S. Kutti Rani a and J.
Elangovan* b
a Department of Chemistry, B. S. Abdur Rahman University, Seethakathi
Estate, Vandalur, Chennai - 600048, India. Tel: 91-44-2751450 Ext. 138
b Dr. J. Elangovan, Assistant Professor,
Department of Chemistry, H. H. The Rajah's College, Pudukkottai - 622001,
Tamilnadu, India.
E-mail: elangoorganic@gmail.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A regioselective and tunable synthesis of 1,5-disubstituted 1,2,3-triazloles from oxidative and
eliminative [3+2] cycloadditions of nitroolefins and organic azides under solvent-free condition
in the presence and absence of commercially available CuO nanoparticles catalyst is described.
In the presence of the catalyst under solvent-free condition, nitro group is retained in the product
while it gets eliminated in the absence of the catalyst.
Available online
Keywords:
[3+2] cycloaddition
azide-olefin
CuO nanoparticles
Solvent-free condition
Catalyst recyclability
1,2,3-Triazoles have gained paramount importance for the past
two decades owing to their versatile applications in various fields
such as drug discovery,1 medicinal chemistry,2 supramolecules,3
functional coatings,4 material science and polymers.5 In addition,
they contribute to the chemical synthesis by serving as synthetic
precursors to many valuable compounds.6 Particularly, 1,2,3-
triazoles bearing NO2 group gain additional importance since they
are the starting materials for nitrogen group substituted 1,2,3-
triazoles. Apart from acting as nitrogen source, NO2 group can be
derivatized further to access diverse molecules.7 In spite of the
conventional Huisgen cycloaddition,8 major breakthrough was
achieved in this area only after the discovery of copper catalysed
azide-alkyne cycloaddition (CuAAC)9 which amassed numerous
publications encapsulating a wide spectrum of applications in various
fields. Even though CuAAC epitomises ideal route to access 1,4-
disubstituted 1,2,3-triazoles, it is limited to terminal alkynes only.
Further advancement in this area was achieved by the development
of Ruthenium catalysed azide-alkyne cycloaddition (RuAAC)10
which is stunningly selective to the complementary 1,5-disubstituted
1,2,3-triazoles and it works out for internal alkynes as well. As an
alternative approach to azide-alkyne cycloaddition, olefins were
envisaged in the place of alkynes since olefins are easily accessible
and economically viable than alkynes. This type of azide-olefin
cycloaddition was pioneered by Huisgen and Labbe11 with organic
azides and electron deficient olefins. The product of azide-olefin
cycloaddition is triazoline which is an unstable compound and it
readily decomposes into different products as implicated by the
reaction conditions.12 At this juncture, several methods were sought
out to transform this unstable triazoline into the stable triazole. In
this regard, two ingenious strategies have been reported in the
literature. First strategy is oxidative azide-olefin cycloaddition
(OAOC) where the triazoline formed by the cycloaddition of azide
and olefin will subsequently be oxidized into the triazole [Eq. (1),
Scheme 1].
Scheme 1. Background of [3+2] cycloaddition of nitro alkenes and azides.

2
Tetrahedron
A few research groups have actively contributed in this area
they could achieve decent yields (Table 1, entry 14-18). To our
surprise, even the bulk CuO could not be competent enough to power
the reaction like its nano analogue (Table 1, entry 19). As a
serendipitous outcome, the yield of 3a got exceedingly suppressed
and 4a got amazingly enhanced when the reaction was subjected to
catalyst free and solvent free condition (Table 1, entry 20).
reporting various catalysts such as tetra butyl ammonium hydrogen
sulphate (TBAHS),13 CuI,14 Ce(OTf)3,15 CuO16 etc. to achieve the
oxidative cycloaddition of organic azides with electron deficient
olefins. Recently our research group also has reported the
commercially available CuO nanoparticles catalysed oxidative
cycloaddition of enones and azides.17 The second strategy is
eliminative azide-olefin cycloaddition (EAOC) where the olefin
bearing a leaving group will undergo cycloaddition with the azide
and a concomitant elimination reaction to furnish the triazole [Eq.
(2), scheme 1]. In this area, olefins such as vinyl sulfones,18 vinyl
acetate19 and push-pull olefins have been reported.20 Another
exciting class of reactions in this area is ‘organo click reactions’21
where the enamines generated insitu from carbonyl compounds will
undergo EAOC to achieve 1,2,3-triazoles. Above all, nitroolefin is
yet another potential candidate which has feebly come into limelight.
When nitroalkene is subjected to cycloaddition with azides, HNO2
gets eliminated from the resulting triazoline furnishing the required
triazole [Eq. (3), scheme 1]. A few research groups have made
laudable contributions in the EAOC of nitroolefins in the past
decade. Amantini et al. have reported TBAF promoted EAOC of
nitroethenes to achieve NH-1,2,3-triazoles.22 Guan and co-workers
have reported p-toluene sulfonic acid mediated synthesis of 4-aryl-
NH-1,2,3-triazoles from nitroolefins.23 Wang et al. have achieved
1,5-disubstituted 1,2,3-triazoles by Ce(OTf)3 catalysed EAOC of
nitroolefins with organic azides.24 EAOC on insitu generated
nitroolefins has also been recorded in the literature.25 In addition,
catalyst-free EAOC of nitroolefins is also known even though the
reaction is sluggish and less efficient.26 However 1,2,3-triazoles from
nitroolefins without elimination of nitro group (OAOC) has been
dormant for several years. Recently, Chen et al. have reported
Cu(OTf)2 catalysed regioselective OAOC of nitroalkenes with
organic azides in DMF/AcOH in excellent yields of 78-96%.27 In
continuation to that, we report in this paper a tunable method to
achieve OAOC and EAOC of nitroolefins under solvent-free
condition using commercially available CuO nanoparticles as a
catalyst. Some of the noteworthy features of CuO nanoparticles are:
The catalyst is comparatively cheaper and heterogeneous. CuO
nanoparticles are less cytotoxic than the conventional Cu(I)-
precursors.28 At the outset, we started our preliminary investigations
taking β-nitro styrene and benzyl azide as model substrates for the
synthesis of 4-nitro-1,2,3-triazole (3a). When the reaction was
attempted in water, 50% yield of 3a was obtained. Surprisingly,
small amount of disubstituted triazole (4a) was also obtained (Table
1, entry 1) along with that. Spurred by this intriguing result, we
strived to develop specific conditions to synthesize each 3a and 4a
separately. Next to water system, when methanol/water (1:1) was
examined, yield of 3a dropped down to 24 % though there was no
change in the yield of 4a (Table 1, entry 2). On the other hand, when
methanol alone was employed, the yield of 3a got suppressed
exceedingly to 10 % (Table 1, entry 3). All the other solvents such as
THF, DMF, DMSO, toluene, benzene, acetonitrile, chloroform and
1,4-dioxane were found to be completely ineffective since they could
furnish only small amount of 3a. Besides that, formation of 4a was
also completely ceased in the presence of these solvents (Table 1,
entry 4-11). It was also observed that solvent free condition can cater
with an amicable condition to this reaction since the yield of 3a has
substantially got enhanced (Table 1, entry 12-13). Besides that, it
was observed that the amount of catalyst also plays a pivotal role
which is evident from the variation of yield of 3a while increasing
the amount of catalyst from 5 mol% to 10 mol% (Table 1, entry 12-
13). Other copper catalysts such as CuCl2.2H2O, CuI, CuBr,
CuSO4.5H2O, Cu(OTf)2 could not be on par with CNP even though
Table 1. Optimization of reaction conditionsa
Entry
Catalyst
Solvent
Catalyst
(mol%)
Yield of
Yield
3a (%)b
of 4a
(%)b
1
CNPc
CNP
H2O
10
10
10
10
10
10
10
10
10
10
10
5
50
24
10
12
10
11
8
5
2
MeOH/H2O
5
3
CNP
Methanol
5
4
CNP
THF
-
5
CNP
DMF
-
6
CNP
DMSO
-
7
CNP
Toluene
-
8
CNP
Benzene
8
-
9
CNP
CH3CN
10
11
12
62
79
55
58
61
37
35
47
5
-
10
11
12
13d
14
15
16
17
18
19
CNP
CHCl3
-
CNP
1,4-Dioxane
-
CNP
-
-
-
-
-
-
-
-
-
5
CNP
10
10
10
10
10
10
10
-
7
CuCl2.2H2O
CuI
10
10
10
5
CuBr
CuSO4.5H2O
Cu(OTf)2
CuO
5
10
71
20
-
a
Reaction conditions: nitro-olefin (1.5 mmol), Azide (4.5 mmol) and CuO
nanoparticles (10 mol%) were heated at 90 °C for 12h. b Isolated yields. c CNP
= CuO nanoparticles. d Reaction with 1.5 mmol of azide led to 54 % yield of
triazole and 3.0 mmol of azide furnished 65 % yield of triazole after 12 h.
Having ascertained the optimized condition for the synthesis of 3a
(Table 1, entry 13) and 4a (Table 1, entry 20), we extended those
conditions to other substrates and the results are summarized in table
2 and table 3. As the first part of reactant variation, different
nitroalkenes were screened with benzyl azide and all of them
furnished the nitro triazoles with good to excellent yields (Table 2,
entry 1-10). Particularly electron donating 4-methoxy phenyl
substitution on the nitroolefin accomplished an excellent yield of
nitro triazole (3e) than the other substituents (Table 2, entry 5). In
addition to phenyl substitution, other aromatic substitutions such as
naphthyl, furanyl and thiophenyl have also proved their mettle to
achieve impressive yields (Table 2, entry 8-10). Especially
thiophenyl substitution on the nitroolefin could accomplish the
nitrotriazole (3j) in excellent yield (Table 2, entry 10). In addition,
the scope of azide was also examined by subjecting β-nitrostyrene
(2a) to reaction with various azides (Table 2, entry 1 and entry 11-
18). Considering the overall outcome on the effect of azides, all
benzyl azides could furnish better yields of nitro triazoles with β-

nitrostyrene (Table 2, entry 1 and entry 11-14). In the case of
aliphatic azides, phenethyl azide showed remarkably better
efficiency than octyl azide (Table 2, entry 15-16). Electron deficient
azides such as ethyl-2-azidoacetate and phenyl azide displayed
comparatively low efficiency than the other azides as reflected from
the slump in yields (Table 2, entry 17-18). Most importantly, no
product was detected when the reaction was attempted with aliphatic
nitroolefins with benzyl azide (Table 2, entry 19).
obtained in 4-methoxy phenyl nitroolefin (Table 3, entry 5). When
we move on to the other aromatic rings on the nitroolefin, naphthyl
group tends to reduce the yield while thiophenyl group has
substantially boosted the yield (Table 3, entry 8-10). In the case of
azide variation with β-nitrostyrene (2a), 4-methyl benzyl azide gave
comparatively poor yield than the other benzyl azides (Table 3, entry
13). In the case of aliphatic azides, phenethyl azide gives an
impressive yield than n-octyl azide (Table 3, entry 15-16).
Apparently, electron deficient azides such as ethyl-2-azidoacetate
and phenyl azides led to poor yields (Table 3, entry 17-18). It is also
to be underlined that no product (neither EAOC nor OAOC) was
observed with aliphatic nitroolefin (Table 3, entry 19). This may be
due to the reduction of electrophilicity of the nitroolefin in the
presence of aliphatic group.24
Table 2. OAOC of nitroolefins and azides.a
Entry
1
R
R1
Product Yield (%)b
Table 3. EAOC of nitroolefins and azides.a
Bn
Ph
3a
3b
3c
3d
3e
3f
79
88
84
81
96
84
89
78
88
94
86
84
76
88
92
74
62
68
0
2
Bn
4-ClC6H4
4-BrC6H4
4-CH3C6H4
4-CH3OC6H4
2-BrC6H4
2-NO2C6H4
1-Naphthyl
2-Furanyl
3
Bn
Entry
1
R
R1
Product
4a
4b
4c
Yield (%)b
4
Bn
5
Bn
Bn
Ph
71
84
80
75
94
83
86
65
82
91
82
80
63
78
87
69
40
45
0
6
Bn
2
Bn
4-ClC6H4
4-BrC6H4
4-CH3C6H4
4-CH3OC6H4
2-BrC6H4
2-NO2C6H4
1-Naphthyl
2-Furanyl
2-Thiophenyl
Ph
7
Bn
3g
3h
3i
3
Bn
8
Bn
4
Bn
4d
4e
9
Bn
5
Bn
10
11
12
13
14
15
16
17
18
19
Bn
2-Thiophenyl 3j
6
Bn
4f
4-NO2C6H4CH2
4-Cl C6H4CH2
4-CH3C6H4CH2
Ph
Ph
Ph
3k
3l
7
Bn
4g
4h
4i
8
Bn
3m
3n
3o
3p
3q
3r
3s
9
Bn
4-CH3OC6H4CH2 Ph
10
11
12
13
14
15
16
17
18
19
Bn
4j
Phenethyl
n-Octyl
C2H5OCOCH2
Ph
Ph
4-NO2C6H4CH2
4-Cl C6H4CH2
4-CH3C6H4CH2
4-CH3OC6H4CH2
Phenethyl
n-Octyl
4k
4l
Ph
Ph
Ph
Ph
4m
4n
4o
4p
4q
4r
Ph
Ph
Bn
n-Pr
Ph
a Reaction conditions: nitroolefin (1.5 mmol), Azide (4.5 mmol) and CuO
nanoparticles (10 mol%) were heated at 90 °C for 12 h. b Isolated yields.
Ph
C2H5OCOCH2
Ph
Ph
The structure of compound 3a was unambiguously ascertained by X-
ray single-crystal analysis.
Ph
Bn
n-Pr
4s
a Reaction conditions: nitro-olefin (1.5 mmol) and Azide (4.5 mmol) were
heated at 90 °C for 12h. b Isolated yields.
Table 4. Recycling of CuO nanoparticles.
Entry
Catalyst Recovery (%)
Cycle
Yield (%)
1a
2b
3b
4b
92
88
80
73
1
2
3
4
79
76
74
70
Figure 1. X-ray crystal structure of 4-nitro-1,2,3-triazole (3a).
As the other part of this study, EAOC of nitroolefins also was
attempted as inferred from the optimization study. A series of 1,2,3-
triazoles without nitro group were accomplished under solvent free
and catalyst free conditions and the results are summarized in Table
3. As far as the olefins are concerned, substitution on the olefin
plays a key role in the efficacy of the reaction. For example,
unsubstituted phenyl group caused comparatively poor yield than the
substituted phenyl groups on the nitroalkene (Table 3, entry 1 and
entry 2-7). Among all phenyl substitutions, excellent yield was
a
Reaction conditions: nitro-olefin (6.0 mmol), Azide (18.0 mmol) and
CuO nanoparticles (10 mol%) were heated at 90 °C for 12h. Recovered
catalyst was used under identical reaction conditions to those of the first
run.
Finally recyclability of the catalyst was also carefully studied. The
catalyst was recovered from the reaction mixture after each cycle by
centrifugation. Then it was washed with ethyl acetate and dried at
b

4
Tetrahedron
o
6.
Chemical synthesis: (a) Wacharasindhu, S.; Bardhan, S.; Wan, Z.-
K.; Tabei, K.; Mansour, T. S. J. Am. Chem. Soc. 2009, 131, 4174;
(b) Seo, B.; Jeon, W. H.; Kim, J.; Kim, S.; Lee, P. H. J. Org.
Chem. 2015, 80, 722; (c) Kim, C.-E.; Park, Y.; Park, S.; Lee, P.
H. Adv. Synth. Catal. 2015, 357, 210; (d) Chattopadhyay, B.;
Gevorgyan, V. Angew. Chem., Int. Ed. 2012, 51, 862.
Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH,
Weinheim, Germany, 2001, pp 159.
(a) Huisgen, R. Angew.Chem. Int. Ed. Engl. 1963, 2, 565; (b)
Huisgen, R. Angew. Chem. Int. Ed. Engl. 1963, 2, 633; (c)
Huisgen, R. Angew. Chem. 1963, 75, 604; (d) Huisgen, R. Angew.
Chem. 1963, 75, 742.
110 C for two hours. It was observed that the catalyst remains
active even for four cycles (Table 4).
The reaction is expected to proceed through the following pathway
as described earlier in the literature.29 The triazoline formed as the
cycloadduct of azide and olefin being unstable, spontaneously
aromatizes into the triazole in the absence of catalyst by eliminating
the HNO2. This can be attributed to the aromatic stabilization of the
product and the good leaving ability of NO2 group. At the same
time, in the presence of the catalyst, oxidation predominates by
utilizing the atmospheric oxygen.
7.
8.
9.
(a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057; (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.
10. (a) Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.;
Sharpless, K. B.; Fokin, V. V.; Jia, G. J. Am. Chem. Soc. 2005,
127, 15998; (b) Rasmussen, L. K.; Boren, B. C.; Fokin, V. V. Org.
Lett. 2007, 9, 5337; (c) Boren, B. C.; Narayan, S.; Rasmussen, L.
K.; Zhang, L.; Zhao, H.; Lin, Z.; Jia, G.; Fokin, V. V. J. Am.
Chem. Soc. 2008, 130, 8923.
11. (a) Huisgen, R.; Szeimies, G.; Möbius, L. Chem. Ber. 1966, 99,
475; (b) Broeckx, W.; Overbergh, N.; Samyn, C.; Smets, G.;
L’abbe, G. Tetrahedron 1971, 27, 3527.
Scheme 2. Proposed pathway of OAOC and EAOC of nitro alkenes and
12. (a) Husinec, S.; Porter, A. E. A.; Roberts, J. S.; Strachan, C. H. J.
Chem. Soc., Perkin Trans. 1, 1984, 2517; (b) Anderson, G. T.;
Henry, J. R.; Weinreb, S. M. J. Org. Chem. 1991, 56, 6946; (c)
Prager, R. H.; Razzino, P. Aust. J. Chem. 1994, 47, 1375; (d) Dahl,
R. S.; Finney, N. S. J. Am. Chem. Soc. 2004, 126, 8356; (e)
Mahoney, J. M.; Smith, C. R.; Johnston, J. N. J. Am. Chem. Soc.
2005, 127, 1354; (f) Hong, K. B.; Donahue, M. G.; Johnston, J. N.
J. Am. Chem. Soc. 2008, 130, 2323.
13. (a) Singh, N.; Pandey, S. K.; Tripathi, R. P. Carbohydr. Res. 2010,
345, 1641; (b) Jay, A.; Sharma, S.; Gupt, M. P.; Bajpai, V.;
Hamidullah, Kumar, B.; Kaushik, M. P.; Konwar, R.; Ampapathi,
R. S.; Tripathi, R. P. Org Lett. 2012, 14, 4306.
14. Janreddy, D.; Kavala, V.; Kuo, C.-W.; Chen, W.-C.; Ramesh, C.;
Kotipalli, T.; Kuo, T.-S.; Chen, M.-L.; He, C.-H.; Yao, C.-F. Adv.
Synth. Catal. 2013, 355, 2918.
15. Xie, Y.-Y.; Wang, Y.-C.; Qu, H.-E.; Tan, X.-C.; Wang, H.-S.;
Pan, Y.-M.; Adv. Synth. Catal. 2014, 356, 3347.
16. Zhang, Y.; Li, X.; Li, J.; Chen, J.; Meng, X.; Zhao, M.; Chen, B.
Org. Lett. 2012, 14, 26.
17. Gangaprasad, D.; Paul Raj, J.; Kiranmye, T.; Sagubar Sadik, S.;
Elangovan, J. RSC Adv. 2015, 5, 63473.
18. (a) Kayet, A.; Pathak, T. J. Org. Chem. 2013, 78, 9865; (b) Sahu,
S. Dey, D.; Pathak, T.; Ganguly, B. Org. Lett. 2014, 16, 2100.
19. Hansen, S. G.; Jensen, H. H. Synlett. 2009, 3275.
20. (a) Peng, W.; Zhu, S. Tetrahedron 2003, 59, 4395; (b) Roque, D.
R.; Neill, J. L.; Antoon, J. W.; Stevens, E. P. Synthesis 2005,
2497.
azides.
As concluding note, we have developed an environmentally benign
and economically viable protocol to achieve oxidative cycloaddition
and eliminative cycloaddition of nitroolefins with organic azides
simply by tweaking the reaction condition and a catalyst. This
method can be a potential alternative to the existing copper and
ruthenium catalyzed azide-alkyne cycloadditions due to the
following attributes. Nitroolefins can be easily prepared from readily
available starting materials than the alkynes. The catalyst used here is
comparatively cheaper than Ru catalysts. CuO nanoparticles catalyst
is less cytotoxic than the traditional Cu1 generating agents employed
in the azide-alkyne cycloaddition. As added advantages, this method
offers a very simple avenue to introduce nitro group in 1,5-
disubstituted 1,2,3-triazole moiety which is difficult to achieve. The
nitro substituted 1,5-disubstituted 1,2,3-triazoles prepared by this
method can emerge as precursors of many nitrogen substituted
triazoles and the corresponding analogues which are hitherto
unknown.
Acknowledgments
The authors also thank the DST, New Delhi for financial support
(SR/S1/OC-65/2011).
21. (a) Belkheira, M.; Abed, D. E.; Pons, J.-M.; Bressy, C. Chem. Eur.
J.
2011, 17, 12917; (b) Danence, L. J. T.; Gao, Y.; Li, M.;
Huang, Y.; Wang, J. Chem. Eur. J. 2011, 17, 3584; (c) Wang, L.;
Peng, S.; Danence, L. J. T.; Gao, Y.; Wang, J. Chem. Eur. J. 2012,
18, 6088; (d) Ramachary, D. B.; Shashank, A. B. Chem. Eur. J.
2013, 19, 13175; (e) Yeung, D. K. J.; Gao, T.; Huang, J.; Sun, S.;
Guo, H.; Wang, J. Green Chem. 2013, 15, 2384; (f) Li, W.; Jia, Q.;
Du, Z.; Wang, J. Chem. Commun. 2013, 49, 10187; (g) Li, W.;
Du, Z.; Huang, J.; Jia, Q.; Zhang, K.; Wang, J. Green Chem. 2014,
16, 3003; (h) Zhou, X.; Xu, X.; Liu, K.; Gao, H.; Wang, W.; Li, W.
Eur. J. Org. Chem. 2016, 1886.
References and notes
1.
2.
3.
For reviews on drug discovery see: (a) Kolb, H. C.; Sharpless, K.
B. Drug Discovery Today 2003, 8, 1128; (b) Lutz, J.-F.;
Zarafshani, Z. Adv. Drug Deliv. Rev. 2008, 60, 958; (c) Hou, J.;
Liu, X.; Shen, J.; Zhao, G.; Wang, P. G. Expert Opin. Drug
Discov. 2012, 7, 489; (d) Thirumurugan, P.; Matosiuk, D.;
Jozwiak, K. Chem. Rev. 2013, 113, 4905.
For reviews on medicinal chemistry see: (a) Tron, G. C.; Pirali, T.;
Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani, A. A.
Med. Res. Rev. 2008, 28, 278; (b) Agalave, S. G.; Maujan, S. R.;
Pore, V. S. Chem. Asian J. 2011, 6, 2696; (c) Lauria, A.; Delisi,
R.; Mingoia, F.; Terenzi, A.; Martorana, A.; Barone, G.; Almerico,
A. M. Eur. J. Org. Chem. 2014, 3289.
22. Amantini, D.; Fringuelli, F.; Piermatti, O.; Pizzo, F.; Zunino, E.;
Vaccaro, L. J. Org. Chem. 2005, 70, 6526.
23. Quan, X.-J.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H. Org.
Lett. 2014, 16, 5728.
24. Wang, Y.-C.; Xie, Y.-Y.; Qu, H.-E.; Wang, H.-S.; Pan, Y.-M.;
Huang, F.-P. J. Org. Chem. 2014, 79, 4463.
25. (a) Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X. Org.
Lett. 2008, 10, 1493; (b) Thomas, J.; John, J.; Parekh, N.; Dehaen,
W. Angew. Chem. Int. Ed. 2014, 53, 10155.
26. Zefirov, N. S.; Chapovskaya, N. K.; Kolesnikov, V. V. Chem.
Commun. 1971, 1001.
27. Chen, Y.; Nie, G.; Zhang, Q.; Ma, S.; Li, H.; Hu, Q. Org. Lett.
2015, 17, 1118.
28. Zhang, Z.; Dong, C.; Yang, C.; Hu, D.; Long, J.; Wang, L.; Li, H.;
Chen, Y.; Kong, D. Adv. Synth. Catal. 2010, 352, 1600.
29. A mechanism for similar reaction promoted by bulk CuO has
already been reported in reference 16.
For reviews see: (a) Fahrenbach, A. C.; Stoddart, J. F. Chem.
Asian J. 2011, 6, 2660; (b) Schulze, B.; Schubert, U. S. Chem.
Soc. Rev. 2014, 43, 2522.
4.
5.
Kantheti, S.; Narayan, R.; Raju, K. V. S. N. RSC Adv. 2015, 5,
3687.
For reviews in material science and polymers see: (a) Moses, J. E.;
Moorhouse, A. D. Chem. Soc. Rev. 2007, 36, 1249; (b) Lutz, J.-F.
Angew. Chem. Int. Ed. 2007, 46, 1018; (c) Kempe, K.; Krieg, A.;
Becer, C. R.; Schubert, U. S. Chem. Soc. Rev. 2012, 41, 176; (d)
Beghdadi, S.; Miladi, I. A.; Addis, D.; Romdhane, H. B.; Bernard,
J.; Drockenmuller, E. Polym. Chem. 2012, 3, 1680.

30. CCDC 1035698 (3a) contains the supplementary crystallographic
data for this paper. This data can be obtained free of charge from
the
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.

Graphical Abstract
A tunable approach to the oxidative and eliminative cycloadditions of nitroolefins with organic azides are demonstrated
under solvent free condition. A series of 1,5-Disubstituted-1,2,3-Triazoles with/without nitro group have been synthesized
from moderate to excellent yields.
A Tunable Route to Oxidative and
Leave this area blank for abstract info.
Eliminative [3+2] Cycloadditions of Organic
Azides with Nitroolefins: CuO Nanoparticles
Catalyzed Synthesis of 1,2,3-Triazoles under
Solvent-Free condition
D. Gangaprasad, J. Paul Raj, T. Kiranmye, R. Sasikala, K. Karthikeyan, S. Kutti Rani and J. Elangovan*

A Tunable Route to Oxidative and Eliminative [3+2] Cycloadditions of Organic Azides with
Nitroolefins: CuO Nanoparticles Catalyzed Synthesis of 1,2,3-Triazoles under Solvent-Free
condition
Highlights

Tuning of eliminative cycloaddition and oxidative cycloaddition of nitroolefins with
organic azides is achieved.


Simple method to introduce nitro group into the 1,2,3-triazole is achieved.
A new application of commercially available CuO nanoparticles is demonstrated.