Multicomponent click reaction catalyzed by organic surfactant-free copper sulfide (sf-CuS) nano/micro flowers

Article abstract of DOI:10.1016/j.jorganchem.2019.01.016

The azide-alkyne cycloaddition (Huisgen reaction) is one of the most powerful and widely used copper-mediated reactions. In many such reactions, use of metal or metal oxide nanoparticles as the catalyst is more appealing because of the increased catalytic

Full text of DOI:10.1016/j.jorganchem.2019.01.016

Accepted Manuscript
Multicomponent click reaction catalyzed by organic surfactant-free copper sulfide (sf-
CuS) nano/micro flowers
Venkateswara Rao Velpuri, Krishnamurthi Muralidharan
PII:
S0022-328X(18)31004-0
DOI:
https://doi.org/10.1016/j.jorganchem.2019.01.016
JOM 20694
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 27 November 2018
Revised Date: 17 January 2019
Accepted Date: 23 January 2019
Please cite this article as: V.R. Velpuri, K. Muralidharan, Multicomponent click reaction catalyzed by
organic surfactant-free copper sulfide (sf-CuS) nano/micro flowers, Journal of Organometallic Chemistry
(2019), doi: https://doi.org/10.1016/j.jorganchem.2019.01.016.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Multicomponent click reaction catalyzed by organic surfactant-
free copper sulfide (sf-CuS) nano/micro flowers
Venkateswara Rao Velpuri and Krishnamurthi Muralidharan*†
School of Chemistry, University of Hyderabad, Prof. C. R. Road,
Gachibowli, Hyderabad, Telangana 500 046, India
Abstract
The azide-alkyne cycloaddition (Huisgen reaction) is one of the most
powerful and widely used copper-mediated reactions. In many such
reactions, use of metal or metal oxide nanoparticles as the catalyst is
more appealing because of the increased catalytic activity attributed to
the large surface to volume ratio. However, the nano/micro particles are
synthesized often in the presence of long chain organic molecules as
capping or stabilizing agents. These organic molecules cover the active
centers and restrict or reduce their catalytic activity. Therefore, we have
synthesized the copper sulfide (sf-CuS) nano/micro particles without
having organic surfactant molecules as the capping agent. These particles
with a flower-like architecture (micro flowers, mf) were obtained readily
under the supersaturated condition at room temperature. In these
particles, the surface was freely available for adsorption and desorption
reactions. When utilized as a catalyst in multicomponent cycloaddition
reactions, the sf-CuS mf exhibited excellent catalytic activity compared
with some other nanoparticles with surfactants. This sf-CuS mf catalyzed
the one-pot synthesis of 1,2,3-triazole and β-hydroxy-1,2,3-triazole
effectively from a variety of benzyl bromide derivatives epoxides
respectively. Both these reactions proceeded in the presence of azide and
phenylacetylene in the water at room temperature. The catalyst was
reusable, and there was no catalyst leaching observed during reactions.
Synthesis of β-hydroxy triazoles and 1,2,3-triazoles under exceptionally
mild conditions with high yields proved the sf-CuS mf as the catalyst as
a robust and recyclable catalyst.
Key words: Copper sulfide, Cycloaddition, Multicomponent synthesis,
Triazoles, Micro Flower Architectures
*Corresponding author.
†E-mail: murali@uohyd.ac.in

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1. Introduction
Synthesis of nano/micro particles is fascinating in organic chemistry
since they are used as heterogeneous catalysts in organic reactions. The
capping agents or surfactants that are used commonly in the synthesis of
metal chalcogenides nanoparticles are; amines (hexadecyl amine, alkyl
amine), oleic acid, polymers (PVP, PMMA), thiols (do- decane thiol, 1,
6-hexane dithiol).[1-3] However, the collective properties of nanomaterials
are not utilized fully[4-9] because of the presence of organic surfactant
molecules around the nano/micro particles that are synthesized via
conventional chemical synthetic methods. When the metal nano/micro
particles are used as a catalyst, the chemical reaction occurs on the
surface of the particles. The presence of capping molecules would
hide the active centers and restrict or reduce the catalytic activity so that
capping agents or surfactant molecules around the particles may
contribute negatively to the target applications [10]
.
In recent years metal is decorated on nanomaterials and these
materials are used as heterogeneous catalysts in organic reactions such as
heck reaction (Pd/CuO),[11] Suzuki cross-coupling reaction
(Pd−CuO@Hol S-1),[12] Sonagashira coupling reaction (Cu/CuO),[13]
Heisenberg 1, 3-dipolar reaction (CuNPs/MagSilica),[14] copper(I)-
catalyzed synthesis of azoles by Sharpless,[15] copper(I)-catalyzed azide-
alkyne [3 + 2] cycloaddition by Sharpless and Finn[16] and so on. The
substituted triazoles are exciting materials in organic synthesis,
[17-21]
coordination chemistry, and N-heterocyclic chemistry.
Substituted
triazoles play an essential role in opening calcium channels in cells,
particularly [22] at 1 and 4 positions of triazole. They also show biological
[23-27]
activities as anti-cancer, anti-HIV therapy, anti-bacterial
and anti-
allergy molecules.[28-30] Agricultural and industrial applications of such
compounds include herbicides, fungicides, agrochemicals,[31] optical
brighteners,[32] fluorescence chemosensory[33] corrosion retarding agents,
dyes, and solar cells.[34-37] Further, the heterocyclic compounds that are
rich in nitrogen atoms can be used as high energy materials.[38]
The formation of 1,2,3-triazole derivatives is known to proceed through
heisenbug 1,3-dipolar cycloaddition of organic azides and alkynes using
CuAAC as a catalyst.[38-41] In recent years, multi-component click
synthesis of 1,2,3-triazoles from both in-situ azidolysis of benzyl halide
in the presence of alkynes and β-hydroxy-1,2,3-triazoles via in-situ
azidolysis of epoxides in the presence of alkynes have been developed.[42-
44]
Some heterogeneous catalysts used in the dipolar cycloaddition are
polyuria encapsulated copper(I) chloride[45], CuNP/C,[46] CuFe O
[47]
,
2
4
Cu/Cu2O,[48] [AQ2Cu(II)-APSiO2],[49] copper(I)@phosphorated SiO2
[50]
SiO2-CuI,[51] Clay–Cu(II)/NH2NH2·H2O,[52] GO@PTA-Cu[53] and
copper(I) in ionic liquids.[54] Albeit several catalytic systems have been
used for dipolar cycloaddition, in pursuit of catalyst working under mild
condition and developing simple method of production of nano catalyst,
we have synthesized surfactant-free copper sulfide (sf-CuS) particles

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having micro flower (mf) like architecture formed by the self-assembly
of nanoparticles.
Herein, we report the synthesis of surfactant-free copper sulfide micro
flowers (sf-CuS mf) in an efficient and straightforward synthetic process,
and its practical use in the synthesis of both benzyl halide linked 1,2,3-
triazoles and β-hydroxy- 1,2,3-triazoles via dipolar cycloaddition of azide
and alkyne in the presence of benzyl halide and epoxide. The synthesis
described here was performed in water, and so it was safer, greener, and
used inexpensive, recyclable surfactant free heterogeneous catalyst. The
above synthetic procedure satisfied the most of green chemistry
principles such as (a) one-pot multicomponent synthesis (atom economy)
(b) reactions in a water medium (green solvent) (c) using of readily
separable and recyclable heterogeneous catalyst (d) involving simple
workupprocedure.
2. Results and Discussion
In recent times, the azide-alkyne cycloaddition (Huisgen reaction) has
emerged as one of the most powerful and widely utilized copper-
mediated reactions. However, many reactions catalyzed by metal or
metal oxide nanoparticles are more appealing because of the increased
catalytic activity attributed to the large surface to volume ratio. In
general, the nano/micro particles used as the catalyst are produced in the
presence of long chain organic molecules as capping or stabilizing
agents. These capping agents on the nano/micro particles cover the active
centers and restrict or reduce their catalytic activity. To outwit this
problem, we have developed a method of synthesis of metal
chalcogenides without capping agent so that the catalyst surface is
freely available for adsorption and desorption reactions. [10]
In the present work, we have prepared surfactant-free copper sulfide
(sf-CuS) under the supersaturated condition in a simple chemical
reaction wherein sulfur was dissolved while LiBH4 and
Cu(CH3COO)2·H2O were suspended in dry tetrahydrofuran (THF). The
reaction was conducted for one hour at room temperature and in an inert
atmosphere to avoid any oxidation. The partial solubility of the metal
source and fast reactivity in the presence of LiBH4 provided a
thermodynamically favorable condition [55] which induced the nucleation
of particles. Since the reaction was at room temperature, the digestion
process was avoided,[56-60] which supplemented the formation of black
powder of CuS having nano/micro flower like architecture. These
micron-sized flower-like particles (mf) were formed by the self-assembly

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of nanoflakes [61]. These metal chalcogenide mf were formed under the
supersaturated condition, and no surfactant molecules were used during
synthesis. The particles were stable, and no agglomeration[10] was
observed. The material was characterized by PXRD, SEM, and
spectroscopic techniques (Figure1).[10] Since no organic surfactant
molecules were surrounding the particles, the catalyst surface was freely
available for reactions and that significantly favored high activity in the
reactions of click chemistry and epoxy ring opening.
The catalytic activity of sf-CuS mf having the unhindered surface in
the multicomponent synthesis of 1, 2, 3-triazoles in the dipolar
cycloaddition reactions was investigated. The experiments began with
optimizing the reaction conditions for the multicomponent synthesis of 1,
2, 3-triazoles from benzyl halide, sodium azide and phenylacetylene
(Scheme 1). Later the reaction was extended to the synthesis of β-
hydroxy 1, 2, 3-triazoles from epoxy derivatives, sodium azide and
phenylacetylene (Scheme 2). This reaction proceeded via in-situ ring
opening of epoxides followed by the reaction with phenylacetylene. In
both reactions, water was used as the solvent at room temperature. The
results were very encouraging since the reactions completed in 5-12 h,
and yielded of the desired products quantitatively.
In order to optimize the reaction conditions, the reactions were
performed by varying the quantity of catalyst and using different
solvents. Progress the reaction was monitored by means of TLC. At the
end of the reaction, the catalyst was separated by filtration and worked up
using ethyl acetate and water. There was no difference in yield and
reaction time when catalyst loading was reduced to 15 mg, 10 mg, and 5
mg. However, when 2 mg of the catalyst was used, it required a longer
time for the completion of the reaction (above 12 h). Consequently, it
was decided to use 5 mg of the catalyst for further studies. Similarly, few
more reactions were performed in various solvents to choose the medium
of the reaction (Table 1). In DMF 45%, DMSO 20% yield was obtained.
Among all solvents tried, water was the best solvent to produce the
products in good yields. Other than these solvents no product spot was
observed in TLC. Therefore, water was chosen as the reaction medium
for all reactions.
Different benzyl bromides substituted with halides and methyl were
reacted with sodium azide and terminal alkynes to form 1,2,3- triazoles
using sf-CuS mf as catalyst under optimized condition (Table 2).
Similarly, a series of different aryl epoxy, cyclic epoxy and alkyl-
substituted epoxy derivatives, sodium azide, and terminal alkynes to form

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β-hydroxy 1,2,3- triazole using sf-CuS mf as catalyst and water as solvent
at room temperature (Table 3). The crude products from all reactions
1
were purified by column chromatography and then characterized by H
and 13C NMR spectral data (Figure S1 to S18). Almost all these
reactions (except table 2, entries 3, 4 and 5) yielded the corresponding
product in more 90 % yield in water as the solvent.
Though many catalysts are known, the sf-CuS mf used here was
obtained in a simple reaction condition, and the products were obtained
in excellent yield. The performance of the various catalysts in the model
reaction (styrene oxide, sodium azide, and phenylacetylene) was
compared (Table 4) to understand the effect of sf-CuS micro flowers as
the catalyst. Most of those catalysts were used at above 60ºC except for
Cu/Cu2O while our CuS was working at the room temperature (This
work). Further, most of the literature on scheme 1 type model reaction
was only within benzyl azide and phenylacetylene (two reactants)
whereas we are presenting the catalyst which can work in
multicomponent reactions.
Leaching study was performed to confirm the heterogeneous catalysis
for the reaction shown in scheme 1. For this purpose, a reaction was
stopped after the formation of around 20% product, and the catalyst was
separated from the reaction mixture. The reaction was continued without
the catalyst for 8 h, but no considerable product formation was observed.
This observation explained that the reaction was working under
heterogeneous catalysis.
The lifetime of the catalyst and its reusability play an essential role in
the practical applications of such heterogeneous systems. In order to take
advantage of heterogeneous nature of our catalyst, a set of experiments
were performed in which both 1,2,3-triazole from in-situ azidolysis of
benzyl halide in the presence of alkynes (scheme 2) and epoxy ring
opening followed by cycloaddition of azide (scheme1) and
phenylacetylene using the recycled sf-CuS mf. After the completion of
the first reaction, the product was extracted using ethyl acetate, and the
catalyst was recovered by simple decantation and dried at 50 °C. A new
reaction was performed with new reactants under the same conditions
using the recovered sf-CuS mf. We have also performed a recycling
experiment in Scheme1 using 5 mmol of reagents. After completion of
the reaction, the catalyst was recovered and reused for the next cycle thus
confirming that sf-CuS mf could be reused for five times with little
change in its activity (Figure 2).

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Experimental procedure
Synthesis of catalyst (sf-CuS):
Sulphur (40 mg, 1.3 mmol) was dissolved in 15 mL of dry
tetrahydrofuran (THF) in a 50 mL two neck RB flask, to that LiBH4 (59
mg, 2.5 mmol) and Cu(CH3COO)2·H2O (250 mg, 1.2 mmol) were added.
The reaction mixture was stirred at room temperature under nitrogen
atmosphere for 1 h. Initially, the color of the solution was dark brown,
and after the completion of reaction it turned to dark green along with the
evolution of gaseous side product(s). After one hour, volatile side
products and solvent were removed by applying high vacuum. The
obtained crude product was washed with methanol (40 mL) followed by
THF (40 mL) to remove side products (copper acetate, lithium salt) and
unreacted S, and then centrifuged. The residue was dried under vacuum
for 6 h to get catalyst as a black powder of sf-CuS micro flowers. The
catalyst was characterized by PXRD and SEM techniques.
Synthesis of 1, 2, 3-triazole from benzyl bromide derivatives, sodium
azide and alkyne:
NaN3 (65 mg, 1.0 mmol), the benzyl bromide (1 mmol), and the
alkyne (1 mmol) were added to a suspension of sf-CuS (5 mg) in water.
The reaction mixture was stirred at room temperature and monitored by
TLC until all the starting materials were converted to products. The solid
was obtained by filtration and washed by DCM (3 ×10 mL). The ex-
traction of aqueous phase with DCM was also performed without loss of
product, and collected organic phase were dried with anhydrous Na2SO4,
and concentrated in vacuum. The product was purified through a silica
gel column chromatography as corresponding
β-hydroxy 1, 2, 3-
triazoles. All the products were confirmed by usual spectral methods
1
13
( H-NMR, C NMR) (see Supporting Information S1-S9).
For example: 1-benzyl-4-phenyl-1H-1, 2, 3-triazole: white solid, mp:128-
129 ; 1H NMR (500 MHz, CDCl3) δ = 7.83-7.81 (m, 2H), 7.68 (s, 1H), 7.43
– 7.38 (m, 5H) 7.35 – 7.32 (m, 3H), 5.59 (s, 2H). 13C NMR (400 MHz,
CDCl3) δ =148.2, 134.6, 130.5, 129.1, 128.8, 128.1, 128.0, 125.7, 119.4 and
+
54.2., HRMS calculated for C15H13N3 [M+H] : 236.1182, found:
236.1184. (See Supporting Information S1)
Synthesis of β-hydroxy 1, 2, 3-triazole from benzyl bromide
derivatives, sodium azide and alkyne:

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NaN3 (65 mg, 1.0 mmol), the epoxide (1 mmol), and the alkyne (1
mmol) were added to a suspension of sf-CuS (5 mg). The reaction
mixture was stirred at room temperature and monitored by TLC until all
the starting
materials were converted to products. The solid was obtained by filtration
and washed by DCM (3 ×10 mL). The extraction of aqueous phase with
DCM was also performed without loss of product, and collected organic
phase were dried with anhydrous Na2SO4, and concentrated in vacuum.
The product was isolated through a silica gel column chromatography as
corresponding β-hydroxytriazoles. All the products were confirmed by
1
13
usual spectral methods ( H-NMR,
C NMR) (See Supporting
Information S10-S18).
For example: 3 Phenoxy 2 (4 phenyl 1H 1,2,3
triazol 1
H NMR (500
1
yl)propan-1-
ol: pale yellow solid; mp:126-128
;
MHz, CDCl3) δ = 7.89 (s, 1H), 7.78-7.75 (m, 2H), 7.43- 7.39 (m, 2H),
7.34-7.35 (m, 1H), 7.32-7.30 (m,1H) 7.03-6.99 (m, 1H), 6.95-6.92 (m,
2H), 4.75 (dd, J = 3 Hz, J = 11 Hz, 1H), 4.61-4.54 (m, 2H), 4.09-4.00 (m,
13
2H), 3.57 (s, 1H). C NMR (400 MHz, CDCl3) δ = 158.0, 147.7, 130.2,
129.6, 129.5, 128.8, 128.2, 125.6, 121.6, 121.3, 114.5, 68.9, 68.7 and
+
53.03 HRMS calculated for C17H17N3O2 [M+H] : 296.1398, found:
296.1398. (See Supporting Information S10).
3. Conclusions
Surfactant-free copper sulfide (sf-CuS) catalyst has been utilized
successfully for one-pot synthesis of triazoles by cycloaddition of both
benzyl halide derivatives- alkyne and epoxide derivatives – alkyne in the
presence of sodium azide. The desired products were obtained at ambient
temperature while the reactions were performed in water. Most of the
reactions proceeded faster with the exception of aliphatic epoxide in the
case of epoxide derivatives. While in benzyl halide derivatives, less
electronegative substituted benzyl halide derivative (Bromo and Iodo)
were slower compared with other (flouro and chloro). The catalyst can be
recycled and reused for five times without losing its activity.
Acknowledgement:
The authors thank the Centre for Nanotechnology at the University of
Hyderabad for the TEM facility. V. R. Velpuri acknowledges UGC –BSR
India for doctoral fellowship.

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Funding:
The work is collectively supported by SERB (project No: SB/S1/IC-
47/2013), and UGC-CAS and DST-PURSE grants of the University of
Hyderabad.
Authors’ contributions:
Competing interests:
No competing interest
Consent for publication:
Not applicable
Ethics approval and consent to participate:
Not applicable
References
[1] Q. Lu, F. Gao and D. Zhao, Nano Lett. 2002, 2, 725.
[2] E. C. Greyson, J. E. Barton and T. W. Odom, Small. 2006, 2, 368.
[3] A. Rabkin, N. Belman, J. Israelachvili and Y. Golan, Langmuir. 2012,
28, 15119.
[4] P. Roy, K. Mondal and S. K Srivastava, Cryst. Growth Des. 2008, 8,
1530.
[5] P. Roy and S.K. Srivastava, Mater.Lett. 2007, 61, 1693.
[6] S. Hsu, K. On and A. R. Tao, J. Am. Chem. Soc. 2011, 133, 19072.
[7] W. Bryks, M. Wette, N. Velez, S. Hsu and A. R. Tao, J. Am. Chem.
Soc. 2014, 136, 6175.
[8] S. Hsu, W. Bryks and A. R. Tao, Chem. Mater. 2012, 24, 3765.
[9] S. Hsu, C. Ngo and A. R. Tao, Nano Lett. 2014, 14, 2372
[10] S. Gottepu, V. R. Velpuri and K. Muralidharan, J. Chem. Sci. 2017,
129, 1853.
[11] M. Nasrollahzadeh, S. M. Sajadi, A. Rostami-Vartooni, M.

ACCEPTED MANUSCRIPT
Bagherzadeh, J. Colloid Interface Sci. 2015, 448, 106.
[12] C. Dai, X. Li, A. Zhang, C. Liu, Song, X. Guo, RSC Adv. 2015, 5,
40297.
[13] J. H. Kou, A. Saha, C. Bennett-Stamper, R. S. Varma, Chem.
Commun. 2012, 48, 5862.
[14] F. Nador, M. A. Volpe, F. Alonso, A. Feldhoff, A. Kirschning, G.
Radivoy, Appl. Catal., A. 2013, 455, 39.
[15] F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K.
B. Sharpless, V. V. Fokin, J. Am. Chem. Soc. 2005, 127, 210-216.
[16] Qian Wang, Timothy R. Chan, Robert Hilgraf, Valery V. Fokin, K.
Barry Sharpless and M. G. Finn, J. Am. Chem. Soc.,2003, 125, 3192-
3193
[17] A. S. Felten, N. Petry, B. Henry, N. Pellegrini-Moïse and K.
Selmeczi, New J. Chem. 2016, 40, 1507.
[18] M. Bakthadoss, N. Sivakumar, A. Devaraj and P. V. Kumar, RSC
Adv. 2015, 5, 93447.
[19] M. Rajeswari, S. Kumari and J. M. Khurana, RSC Adv. 2016, 6, 9297.
[20] S. Q. Bai, L. Jiang, A. L. Tan, S. C. Yeo, D. J. Young and T. S. A.
Hor, Inorg. Chem. Front. 2015, 2, 1011.
[21] S. Q. Bai, L. Jiang, D. J. Young and T. S. A. Hor, Aust. J. Chem.
2016, 69, 372.
[22] V. Calderone, I. Giorgi, O. Livi, E. Martinotti, E. Mantuano, A.
Martelli, A. Nardi, Eur. J. Med. Chem. 2005, 40, 521.
[23] C. Menendez, A. Chollet, F. Rodriguez, C. Inard, M. R. Pasca, C.
Lherbet, M. Baltas, Eur. J. Med. Chem. 2012, 52, 275.
[24] F.C. da Silva, M. C. B. de Souza, I. I. Frugulhetti, H. C. Castro, L. O.
Silmara, T. M. L. de Souza, D. Q. Rodrigues, A. M. Souza, P. A.
Abreu, F. Passamani, Eur. J. Med. Chem. 2009, 44, 373.
[25] T. W. Kim, Y. Yong, S. Y. Shin, H. Jung, K. H. Park, Y. H. Lee,
Y. Lim, K.Y. Jung, Bioorg. Chem. 2015, 59, 1.

ACCEPTED MANUSCRIPT
[26] J. N. Sangshetti, R. R. Nagawade, D. B. Shinde, Bioorg. Med. Chem.
Lett. 2009, 19, 3564.
[27] M. F. Mady, G. E. Awad, K. B. Jorgensen, Eur. J. Med. Chem. 2014,
84, 433.
[28] D. R. Buckle, D. J. Outred, C. J. M. Rockell, H. Smith and B. A.
Spicer, J. Med. Chem. 1986, 29, 2267.
[29] D. R. Buckle, D. J. Outred, C. J. M. Rockell, H. Smith and B. A.
Spicer, J. Med. Chem. 1983, 26, 251.
[30] C. J. Buckle and D. R. Rockell, J. Chem. Soc. 1982, 1, 627.
[31] M. Z. Griffiths and P. L. A. Popelier, J. Chem. Inf. Model. 2013, 53,
1714.
[32] N. Gouault, J. F. Cupif, A. Sauleau and M. David, Tetrahedron Lett.
2000, 41, 7293.
[33] E. Hao, T. Meng, M. Zhang, W. Pang, Y. Zhou and L. Jiao, J. Phys.
Chem. A. 2011, 115, 8234. (b) S. A. Ingale and F. Seela, J. Org. Chem.
2012, 77, 9352. (c) C. Y. Wang, J. F. Zou, Z. J. Zheng, W. S. Huang,
L. Li and L.-W. Xu, RSC Adv. 2014, 4, 54256.
[34] H. Wamhoff, A. R. Katritzky and C. W. Rees, Comprehensive
Heterocyclic Chemistry, 1984, 5, 669.
[35] M. Gouault, N. Cupif, J. F. Sauleau and A. David, Tetrahedron Lett.
2000, 41, 7293.
[36] A. C. Lees, B. Evrard, T. E. Keyes, J. G. Vos, C. J. Kleverlaan,
M.Alebbi and C. A. Bignozzi, Eur. J. Org. Chem. 1999, 2309.
[37] D. srinivas, VD. Ghule, SP. Tewari, K. Muralidharan, Chem. Eur. J.
2012, 18, 15031.
[38] A. Domling and I. Ugi, Angew. Chem., Int. Ed. 2000, 39, 3169.
[39] R. Huisgen, Pure Appl. Chem. 1989, 61, 613.
[40] R. Huisgen, G. Szeimies and L. Moebius, Chem. Ber. 1965, 98, 4014.

ACCEPTED MANUSCRIPT
[41] C. S. Radatz, L.do. A. Soares, E. F. Vieira, D. Alves, D. Russowsky
and P. H. Schneider, New J. Chem. 2014, 38, 1410.
[42] G. Kumaraswamy, K. Ankamma and A. Pitchaiah, J. Org. Chem.
2007, 72, 9822.
[43] K. R. Reddy, C. U. Maheswari, M. L. Kantam and P. C. Division,
Synth. Commun. 2008, 38, 2158.
[44] J. S. Yadav, B. V. S. Reddy, G. M. Reddy and D. N. Chary,
Tetrahedron Lett. 2007, 48, 8773.
[45] Y. Chen, W-Q. Zhang, B-X. Yu, Y-M. Zhao, Z-W. Gao, Y-J. Jian, L-
W. Xu, Green Chem. 2016, 18, 6357.
[46] F. Alonso, Y. Moglie, G. Radivoy, and M. Yus, J. Org. Chem. 2011,
76, 8394.
[47] B. S. P. Anil Kumar, K. H. V. Reddy, G. Satish, R. U. Kumar and Y.
V. D. Nageswar, Tetrahedron Letters. 2012, 53, 4595.
[48] H. E. Shahri, H. Eshghi, J. Lari, S. A. Rounagh, Appl Organometal
Chem. 2017; e3947.
[49] H. Sharghi, A. Khoshnood, M. M. Doroodmand , R. Khalifeh, J Iran
Chem. Soc. 2012, 9, 231.
[50] H. Naeimi, V. Nejadshafiee, New J. Chem. 2014, 38, 5429.
[51] T. Shamim and S. Paul Catal Lett. 2010, 136, 260–265
[52] H.N.M Elnagdy, K. Gogoi, A.A. Ali and D.Sarma., Appl
Organometal Chem., 2018, 32, e3931
[53] H. Naeimi and Z. Ansarian, Inorganica Chimica Acta
466, 417–42
. 2017,
[54] N. Singh, C. R. Chimie. 2015, 18, 1257.
[55] B. Li, Y. Xie and Y. Xue, J. Phys. Chem C. 2007, 111, 12181.

ACCEPTED MANUSCRIPT
[56] V. P. P. Weimarn, Chem. Rev. 1925, 2, 217.
[57] A. E. Nielsen, Acta. Chem. Scand. 1960, 14, 1654.
[58] R. A Johnson and J. D. O’ourke, J. Am. Chem. Soc. 1954, 76, 2124.
[59] R. A. Day. Jr. and A. L. Underwood, 6th ed., Quantitative analysis,
Pearson Education India; Sixth edition, (2015).
[60] D. A Skoog, D. M West, F. J Holler and S. R Crouch, Fundamental
analytical chemistry. Cengage Learning (2004).
[61] B. G Kumar and K. Muralidharan, Eur. J. Inorg. Chem. 2013, 32,
2102.

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Tables:
Table 1: Solvent optimization of for the synthesis of scheme 1 in the
model reaction
Entry
Solvent
CH3OH
n-butanol
CH3CN
CHCl2
CHCl3
DMSO
DMF
time
24h
24h
24h
24h
24h
24h
24h
6h
Yield
no
1
2
3
4
5
6
7
8
no
no
no
no
20%
45%
92%
H2O

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Table 4:
Comparison table of numerous catalysts with various Synthesis of 1, 4‐
disubstituted β‐hydroxy‐1, 2, 3‐triazoles:
Catalyst
CPSi
Substrate
Time Temperature Yield Ref.
Styrene Oxide
Styrene Oxide
Styrene Oxide
Styrene Oxide
1h
2h
4h
6h
94%
75%
82%
87%
34
32
33
31
60°C
Cu/Cu2O
RT
AQ2Cu(II)-
APSiO2
CuFe2O4
60°C
60°C
Cu Nano
particles
Cu(I) in Ionic
liquids
Styrene Oxide
Styrene Oxide
Styrene Oxide
8h
10h
5h
83%
95%
30
35
100°C
80°C
RT
91% This
work
Sf-CuS mf

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The major highlights of the present work are listed below.
1. The catalysis by nano/micro particles is dependent on the adsorption of molecules on the
surface of the catalyst. Therefore, it is essential to study the impact of organic surfactant-free
nano/micro particles in heterogeneous catalysis.
2. The azide-alkyne cycloaddition (Huisgen reaction) is one of the most powerful and widely
applied copper-mediated reactions. Organic surfactant-free CuS nano/micro particles have
been found to effectively catalyze the multicomponent, one-pot synthesis of 1, 2, 3-triazole
from a variety of benzyl bromide derivatives and β-hydroxy-1, 2, 3-triazole through the ring
opening of a variety of epoxides.
3. The surfactant-free copper sulfide micro flowers (sf-CuS mf) exhibited excellent catalytic
activity compared with some other nanoparticles with the surfactants. Thus the synthesis of β-
hydroxy triazoles and 1,2,3-triazoles was achieved under exceptionally mild conditions with
high yields.
4. The catalyst described here, i.e., sf-CuS mf is a robust and reusable catalyst system. And there
was no leaching of catalyst observed during reactions, which is a significant finding for the
nanomaterial-based catalysis.
5. The synthesis described here was performed in water at room temperature, and so it was safer,
greener, and uses inexpensive materials.

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The copper sulfide (sf-CuS) micro flowers (mf) without having any organic surfactant
molecules as the capping agent have been synthesized. These sf-CuS mf exhibited excellent
catalytic activity in multicomponent cycloaddition reactions compared with some other
nanoparticles with surfactants. Synthesis of β-hydroxy triazoles and 1,2,3-triazoles under
exceptionally mild conditions with high yields proved sf-CuS mf as a robust and recyclable
catalyst.