An efficient and recyclable thiourea-supported copper(i) chloride catalyst for azide-alkyne cycloaddition reactions

Article abstract of DOI:10.1039/c5gc02545a

A reaction between two equivalents of bulky thiourea, i.e., 1,3-bis(2,6-dimethylphenyl)thiourea (L) [L = (ArNH)₂C = S; Ar = 2,6-Me₂C₆H₃], and CuCl₂ or CuCl in THF solvent afforded a bulky thiourea-sta

Full text of DOI:10.1039/c5gc02545a

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: M. K. Barman, A.
K. Sinha and S. Nembenna, Green Chem., 2015, DOI: 10.1039/C5GC02545A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/greenchem

Page 1 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
An efficient and recyclable thiourea supported copper(I) chloride
catalyst for the azide–alkyne cycloaddition reactions†
Milan Kumar Barman, Ashish Kumar Sinha and Sharanappa Nembenna*
A
reaction between two equivalents of bulky thiourea i.e., 1-3-bis(2,6-
dimethylphenyl)thiourea(L) [L = {(ArNH)2C=S); (Ar = 2,6-Me2C6H3)}] and CuCl2 or CuCl
in THF solvent afforded a bulky thiourea stabilized copper(I) halide complex, LCu(Cl)L(1).
Compound 1 was characterized by NMR spectroscopy, mass spectrometry and X-ray
structural analysis. Further, we tested the catalytic activity of this well defined compound 1
for azide-alkyne cycloaddition (AAC) reactions in solvent free conditions. Compound 1
shows a high catalytic activity for the synthesis of 1,4-di and 1, 4, 5-trisubstituted-1, 2, 3-
triazoles in good to excellent yields from azides (aliphatic or aromatic) and alkynes (both
terminal and di-substituted). Furthermore, three component CuAAC reactions were
successfully carried out to obtain both 1, 4-di and 1, 4, 5- trisubstituted 1, 2, 3-triazoles in
good to excellent yields from an organic halide, sodium azide and alkyne (both terminal and
di-substituted) in greener solvent water. More importantly, the catalyst can be reused
efficiently up to ten consecutive cycles with negligible loss of catalytic activity.
School of Chemical Sciences,
National Institute of Science Education and Research (NISER)
Bhubaneswar, India 751005
Tel.: +91-674-2304126
Fax: +91-674-2302436
Email: snembenna@niser.ac.in
†Electronic supplementary information (ESI) available: Analysis data and NMR spectra (1H
and 13C{1H} ) for compounds 4a – 4y, 6a-6c, 8a-8e. CCDC 1425735; X-ray crystal data,
TGA and Powder XRD for compound 1
1

Green Chemistry
Page 2 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Introduction
In 2001, Sharpless1 was introduced the term “Click chemistry” and signifies a set of reactions
widely utilized, able to join moieties together in a very efficient and reliable manner. These
examples of reactions include cycloadditions,2 nucleophilic ring opening,3 chemistry of non-
aldol type1 and carbon–carbon additions.4 A set of reactions mentioned above, particularly, a
well known copper catalyzed azide alkyne cyaloaddition (CuAAC) reaction is often
considered as “Click chemistry”. In 1963, Huisgen5 reported the uncatalysed reaction of 1, 3-
dipolar cycloaddition of organic azides with alkynes. This reaction is a slow, high
temperature and not regioselective. However, CuAAC reaction is faster, facile and
regioselective. In this context, in 2002, two research groups Sharpless2a and Meldal6 have
shown that the copper catalyzed 1, 3-dipolar cycloaddition of azides with terminal alkynes,
independently. Since then, CuAAC reaction has been gaining huge attention among synthetic
chemists.7 Very recently, Nicasio and Perez et al.8 thoroughly updated the CuAAC reactions
and described that the nature of the catalyst has been classified into copper (I) and copper
salts or complexes, metallic or nano particulate copper and other solid supported copper
systems. Most of the cases in all copper based systems mentioned above, an active catalyst
species is copper(I) metal ion in CuAAC reactions. In more recent times in particular, there is
a huge attention towards design of well defined Cu(I) catalysts in CuAAC reactions,
advantages that include not only avoid excess use of ligand and/or additives, but also better
control of the nature of species present in the reaction medium. In this context, in 2011, Diez-
Gonzalez reviewed on well defined copper(I) complexes for click azide-alkyne
cyclcoaddition reactions.9 Preformed copper (I) complexes bearing nitrogen, phosphrous,
carbon and oxygen based ligands have been employed in CuAAC reactions.
The most employed molecularly defined Cu(I) complexes as catalysts in CuAAC reactions
are those bearing carbon based neutral N-heterocyclic carbene(NHC) ligands. In, 2006,
2

Page 3 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
Nolan10 reported [(SIMes)CuBr] (SIMes = N,N”-bis(2,4,6-tri-metylphenyl)-4,5-dihydro-
imidazol-2-ylidene) as catalyst in CuAAC reactions. Later, [IAd)CuI] (IAd = N,N’-bis
(adamant-1-yl)imidazol-2ylidene) was reported to have better catalytic activity than that of
the SIMes analogue under the same reaction conditions.11
To improve the catalytic activity of [(SIPr)CuCl] in water, Li and co-workers12 synthesized a
series of ammonium salt tagged [(SIPr)CuCl] complexes. Straub and co-workers synthesized
and structurally characterized bis-NHC –dicopper complexes and utilized as catalysts.13 And
also, copper(I) complexes bearing abnormal N-heterocyclic carbene as ligands were also
reported to use as catalysts in CuAAC reactions.14 However, a very few sulphur based ligands
employed in CuAAC reactions.15 Therefore, herein we report a well defined bulky thioureas
supported copper(I) chloride(1) complex as a catalyst for azide-alkyne cycloaddition
reactions to produce 1,4-di and 1,4,5-tri substituted 1,2,3-triazoles at room temperature in
good to excellent yields either in water or under neat conditions. More importantly, catalyst
was reused up to ten consecutive cycles and it retains its catalytic activity without any
decomposition. Furthermore, we have also shown one pot synthesis that uses halides and
sodium azide for direct cycloaddition with alkynes in water as a solvent. To the best our
knowledge there have been no reports on bulky thioureas supported copper(I) chloride
catalyzed azide-alkyne cycloaddition reactions.
3

Green Chemistry
Page 4 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Results and discussion
Synthesis and X-ray crystal structure of complex 1
Ligand (L) [L = {(ArNH)2C=S); (Ar = 2,6-Me2C6H3)}] was prepared using a similar
procedure that described in the literature for its Mes and Dipp analogues
MesN(H)C(S)N(H)Mes (Mes = 2,4,6 trimethyl aniline) or DippN(H)C(S)N(H)Dipp (Dipp =
2,6-iPr2C6H3) by the reaction of drop wise addition of carbon disulphide to a solution of
aromatic amine and triethylamine in water/acetonitrile.16
Scheme 1 Synthesis of bulky thiourea supported copper(I)chloride complex (1)
Two equivalents of 1,3-bis(2,6-dimethylphenyl)thiourea i.e., [L = (ArNH)2C=S); (Ar = 2,6-
Me2C6H3)] in THF was added dropwise to a solution of CuCl2 in THF at room temperature.
The reaction mixture was stirred at room temperature for 12 h and a clear solution was
noticed. After filtration through Celite, the filtrate was concentrated and stored at room
temperature to afford crystalline compound LCu(Cl)L(1) (see Scheme 1), which is confirmed
by X-ray crystal structure (vide infra). Not surprisingly, in this reaction Cu metal ion is
reduced to Cu(I) ion. It is clearly established that the preparation of complexes of CuI with
thiourea derivatives can be easily achieved by the reaction between ligand and CuII salt,
where CuII is reduced to CuI ion.17 Further, synthesis of LCu(I)ClL in good yield was
achieved by reacting two equivalents of L with CuCl in THF.
4

Page 5 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
o
Compound 1 is thermally stable and melts at the range of 210 - 214 C. It is not soluble in
water and sparingly soluble in methanol, ethanol and dichloromethane. However, complex 1
1
is soluble in THF, DMSO and acetonitrile solvents. Compound 1 was characterized by H
and 13C{1H} NMR spectroscopy analyses. The 1H NMR spectrum of 1 exhibits resonances at
δ = 8.78 & 9.95 ppm for N-H protons, 2.14 & 2.32 ppm for Ar-CH3 and remaining expected
peaks for Ar-H (7.03-7.08 ppm) and THF (1.76 & 3.60 ppm). 13C{1H} NMR spectrum of 1
shows a characteristic peak at 177 ppm for C=S moiety. The other chemical shifts are typical
for both bulky thiourea ligands. Compound 1 was further characterized by X-ray structural
and mass spectrometry analyses. Single crystals were obtained from saturated THF solution
Ŭ
at room temperature. Compound 1 crystallizes in triclinic space group P1 with one THF
molecule in the unit cell. The molecular structure of 1 is illustrated in Fig. 1. Selected bond
lengths and bond angles are listed in Fig. 1 caption.
Compound 1 is a mononuclear three coordinated copper(I) chloride complex, in which
copper atom is coordinated by two sulphur atoms of each bulky thiourea ligand and one
chlorine atom (Fig. 1), thus it is exhibiting a trigonal planar molecular configuration with a
butterfly structure. The driving force for this structure might be due to the intamolecular
hydrogen bonds between Cl1 and N1/N4 atoms to form pseudo-six membered rings
(NHClCuSC). Hydrogen bonds D···A distances (Å) and D–H···A angles (o):N4–H4···Cl1
[3.1811 (21), 158] N1–H1···Cl1 [3.2184(22), 152]. Cu–Cl bond distance 2.3058(10) Å is
slightly shorter than that of Cu–Cl bond distance of recently published Roesky’s18 N-(2,6-
disisopropylphenyl)-N’-benzoylthiourea (2.2236 Å). And also, S1–C2 1.706(3) Å and S2–C1
1.709(2) Å bond distances are in good agreement with those in related compounds.19
5

Green Chemistry
Page 6 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Fig. 1 Molecular structure of 1 with thermal ellipsoids drawn at 30% probability. Hydrogen
atoms have been omitted for clarity (except N–H). Selected bond lengths (Å) and bond
angles(o): Cu1–Cl1 2.3059(10), Cu1–S1 2.2250(9), Cu1–S2 2.2401(8), S1–C2 1.706(3), S2–
C1 1.709(2), N2 –C1 1.334(3), N2–C27 1.436(3), N1–C1 1.331(3), N3 –C2 1.340(3), N4 –
C2 1.332(3), N4–C3 1.435(3); S1–Cu1–S(2) 125.30(3), S1–Cu1–Cl1 118.20(4), S2–Cu1–Cl1
116.45(4), C1–S2–Cu1 107.91(8), N1–C1–N2 117.4(2), N1–C1–S2 121.05(17), N3 –C2 –N4
117.8(2), C2 –N4–C3 125.98(19), C2–N3–C11 124.8(2). Hydrogen bonds D···A distances
(Å) and D–H···A angles (o):N4–H4···Cl1 [3.1811 (21), 158] N1–H1···Cl1 [3.2184(22), 152]
6

Page 7 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
Thermo gravimetric analysis (TGA) and Powder XRD
To probe thermal stability of the compound 1 thermo gravimetric analysis (TGA) was
800 oC. Compound 1 exhibits two steps decomposition
performed (see ESI†; Fig. S1) at 30
–
in the range of 166 – 320 oC where the first step is the decomposition of the chlorine atom at
o
temperature range 166 – 184 C which accounts for 6.16 % weight loss (calc. 5.3 %) and in
o
the second step decomposition of the thiourea moiety at temperature range 221 – 305 C
which accounts for the 76.26 % weight loss (calc. 75.57 %). The powder X–ray diffraction
pattern for compound 1 is in good agreement with simulated pattern (see ESI; Fig. S2), this is
generated from the single crystal X-ray data.
Copper complexes have been utilized as catalysts in various organic transformations due to
their low cost, facile reactivity, and broad tolerance of functional groups on substrates.7f, 20 In
this perspective, our interest is to employ compound 1 as a catalyst for azide-alkyne
cycloaddition reaction. We initially carried out LCu(Cl)L (1) catalysed cycloaddition of
benzyl azide with phenyl acetylene as a model reaction either in water or under neat
conditions (Table 1). In both cases the reaction is going very smoothly with quantitative yield
of product formation (4a). From the Table 1, it is very clear that in solvent free condition
shorter reaction time is required when compared to the water media for the product (4a)
formation.
7

Green Chemistry
Page 8 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Table 1 Complex 1 catalyzed cycloaddition of benzyl azide with phenyl acetylene:
Optimization studiesa
Entry Catalyst
Cat.
(mol%)
Solvent
Time
(h)
4
1.5
0.5
3
1.5
2
10
10
8
Yieldb
(%)
94
99
99
96
97
36
65
1
2
1
2
5
2
5
2
2
2
2
2
neat
neat
neat
1
1
3
1
4
water
water
neat
ethanol
methanol
DCM
CH3CN
1
5
1
6
CuCl
7
8
9
10
1
1
1
1
67
87
95
8
aReaction conditions: benzyl azide (0.5 mmol), phenyl acetylene (0.6 mmol), solvent (1 mL).
bIsolated yield
We observed that a less amount of triazole product (4a) formation under these conditions
using ligand free CuCl (Table 1, Entry 6) as a catalyst for the reaction of benzylazide with
21
phenyl acetylene as substrates, such observations also reported in earlier studies.14c,
Further, we explored the same reaction in various organic solvents such as ethanol, methanol,
dichloromethane and acetonitrile. We noticed that less product (4a) formation and longer
reaction time is required for the compound 1 catalyzed cylcloaddition of benzylazide with
phenyl acetylene in solvent media such as ethanol (Table 1, Entry 7), methanol (Table 1,
Entry 8) and dichloromethane(DCM) (Table 1, Entry 9). However, 95% yield conversion of
4a at similar reaction conditions was observed when the reaction performed in acetonitrile
(Table 1, Entry 10).
8

Page 9 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
Further, we explored the scope of the reaction by carrying out reactions of benzyl azide, 4-
nitrobenzylazide and 3-chlorobenzylazide with a variety of terminal alkynes using 2 mol% of
1 as catalyst under solvent free conditions. The results of the catalytic reactions are
summarized in Table 2. We noticed that during the reaction of formation of triazole the initial
substrates were liquid and subsequently the liquid reaction mixture solidified after
consumption of the starting material. Solid reaction mixture dissolved in ethyl acetate and
passed through silica gel column. After removal of solvent in vacuum and washing the
residue with n-hexane afforded pure desired products (4a-4y).
Table 2 Complex 1 catalyzed [3 + 2] cycloaddition of aliphatic azide with alkynea
9

Green Chemistry
Page 10 of 26
View Article Online
DOI: 10.1039/C5GC02545A
a Reaction conditions: azide (1 mmol), alkyne (1.15 mmol), LCu(Cl)L (2 mol%), neat, isolated yield.
Further, we investigated the catalytic efficacy of compound 1 for the reaction of alkynes with
aromatic azides and results are illustrated in Table 3.
Compound 1 catalyzed (2 mol %) reaction of phenyl azide with phenyl acetylene in solvent
free condition at room temperature led to the formation of triazole product 6a in 96% yield in
two hours. Similarly, compound 1 catalyzed reactions of phenyl azide with methyl
carboxylate azide and ethylcarboxylate azide afforded the triazole products 6b (97%) and 6c
(95%), respectively in 1 hour
Table 3 Complex 1 catalyzed [3 + 2] cycloaddition of aromatic azide with alkyne
a Reaction conditions: Phenyl azide (1 mmol), alkyne (1.15 mmol), LCuCl (2 mol%), neat, isolated
yield.
In the literature it is reported that a wide range of copper based catalysts have been utilized
for cycloaddition of azides with terminal alkynes.22 However, a very limited number of
copper based catalysts have been developed for cycloaddition of azides with internal
alkynes.23 In view of this our attention turned towards compound 1 catalysed cycloaddition
reactions of azides with internal alkynes. Our initial attempt was 2 mol% of 1 catalysed
10

Page 11 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
reaction of benzyl azide with dimethyl acetylenedicarboxylate in solvent free conditions. This
reaction leads to the formation 1, 4, 5-trisubstituted 1, 2, 3-triazole (8a) in excellent yield
(91%) in two hours. And also, 2 mol% of 1 catalysed reaction of phenyl azide with dimethyl
acetylenedicarboxylate afforded the desired triazole product (8b) in good yield. Furthermore,
2 mol% of 1 catalysed reactions of chloro and nitro substituted benzyl azides with either
dimethyl acetylenedicarboxylate or diethyl acetylenedicarboxylate have been investigated.
These reactions are also carried out in neat conditions and produced desired products (8c-8e)
in very good yields. However, 2 mol% of 1 catalysed reaction of phenyl azide with diphenyl
acetylene affords the desired product in very low yield (15%) at 70 oC.
Table 4 Results of the CuAAC reaction of azides with disubstituted alkynes using 1 as a catalyst
aReaction conditions: azide (1.0 mmol), di-substituted alkyne (1.15 mmol), isolated yield.
11

Green Chemistry
Page 12 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Organic azides are generally safe and stable towards water and oxygen,24 but low molecular
weight organic azides are explosive and difficult to handle.25 Therefore, the synthetic
protocol that avoids azides isolation is very much desirable. In this context, chemists
developed copper catalysed synthesis of triazoles via a three-component reaction (organic
bromide, sodium azide and an alkyne).12, 26 In view of this, we tested the catalytic activity of
complex 1 in three component reaction and results are summarized in Table 5. All reactions
were performed at room temperature in water by using organic bromide, sodium azide and
alkyne with 2 mol% of catalyst and triazoles products were isolated in good to excellent
yields.
Table 5 Three-component CuAAC from organic halides as azido precursors with complex 1
catalyst
aReaction conditions: azide (1 mmol), alkyne (1.15 mmol), H2O(2mL). bIsolated yield.
Overall, there was no considerable difference of reactivity was noticed for the studied
reactants with different electronic properties, electron-rich and electron-poor azides and
alkynes, and the results prove that the thiourea stabilized copper complex (1) is a highly
12

Page 13 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
efficient catalytic system for the cycloaddition of aliphatic and as well as aromatic azides
with various alkynes.
More importantly, we checked the catalytic longevity by performing the in situ recycling
experiments in the same reaction vial. The catalyst was reused up to ten consecutive cycles
without any appreciable loss of reactivity, using 2 mol% catalyst for benzyl azide and
methylacetylenecarboxylate. For this experiment we noticed 15 minutes was taking to
achieve quantitative yield up to 6 catalytic cycles. After six catalytic cycles to complete the
reaction it took 20 minutes.
Fig. 2 The recyclability test of complex 1
Reaction Conditions: benzyl azide (1 mmol) and methylacetylenecarboxylate (1.15 mmol),
catalyst 0.02 mmol
Procedure for catalyst longevity experiment between benzyl azide and methyl
propiolate
Catalyst 1 (0.02 mmol), benzylazide (1.0 mmol) and methyl propiolate (1.15 mmol) were
taken in screw cap vial and stirred at room temperature. The reaction mixture was monitored
1
by H NMR spectroscopy by taking aliquots of the reaction mixture after 15 min intervals
13

Green Chemistry
Page 14 of 26
View Article Online
DOI: 10.1039/C5GC02545A
and the reaction was stopped when the consumption of substrates was complete. During this
period, a solid product was formed. Second time a fresh batch of substrates benzylazide (1.0
mmol) and methyl propiolate (1.15 mmol) was added for the next cycle without adding any
further catalyst into the reaction vial. This procedure was repeated for a total ten consecutive
catalytic runs.
Many investigations toward elucidation of the mechanism of the CuAAC with terminal
alkynes have been documented. The mechanistic pathway for the complex 1 catalyzed azide-
alkyne cycloadition is depicted in Fig 3.
L = {(ArNH)2C=S); (Ar = 2,6-Me2C6H3)}
Fig 3. Proposed mechanism for the complex 1 catalyzed azide-alkyne cycloaddition reaction
In the first step, LCu(Cl)L complex (1) upon reaction with alkyne would lead to the
formation of acetylide-copper complex. In the second step, acetylide-copper complex interact
14

Page 15 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
with the azide, in which it favours the nucleophilic attack of alkyne carbon atom to the end
nitrogen atom of the azide. Subsequent ring contraction of the generated metallacycle would
allow to a copper-triazolide complex. Finally, copper-triazolide abstracts a proton from HCl
that lead to the formation of the desired triazole product and subsequently regeneration of
LCu(Cl)L complex completes the catalytic cycle. It is worth mentioning that despite the
highly reactive intermediates within catalytic cycle of CuAAC, some research groups isolated
and characterized the copper-actylide and –triazolide intermediates.27 Further, proposed
mechanism for the compound 1 catalysed cyloaddition of azides with internal alkynes is
depicted in Fig S3. (see ESI†).28
Conclusion
In conclusion, we have synthesized and structurally characterized a neutral, air & moisture
stable and monomeric copper (I) chloride complex (1) bearing two bulky thiourea ligands.
And also, we have shown that complex 1 exhibits a highly efficient catalyst for the synthesis
of a wide range of both 1,4 –di and 1,4,5-tri substituted 1,2,3-triazoles from azides (aliphatic
or aromatic) and alkynes (terminal or internal) in solvent free at room temperature conditions.
Further, three component CuAAC reactions were successfully performed to obtain triazoles
from organic bromide, sodium azide and alkynes in greener solvent water. Furthermore, the
catalyst longevity has been checked up to ten consecutive cycles for the reaction of
benzylazide and methylpropiolate substrates and noticed that a marginal loss of catalytic
activity.
15

Green Chemistry
Page 16 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Experimental
General
All manipulations were carried out under air and using technical grade solvents without any
particular precautions to prohibit oxygen or moisture. Chemicals were purchased from
Sigma-Aldrich, Alfa-Aesar and used as received unless otherwise stated. Column
1
chromatography and TLC were performed on silica gel (100-200) and using UV light. H,
13C{1H} NMR spectra were recorded on Bruker AV-400 (1H: 400 MHz, 13C{1H}: 100.6
MHz) and were referenced to the resonances of the solvent used. IR Spectra were recorded in
Perkin-Elmer FT-IR Spectrometer. Mass spectra were recorded on Bruker micrOTOF-Q II
Spectrometer. 1-3-bis(2,6-dimethylphenyl)thiourea(L) [L = {(ArNH)2C=S); (Ar = 2,6-
Me2C6H3)}] was synthesized according to the literature procedure16. Benzyl azide22c, 3-
chlorobenzyl azide29 and 4-nitrobenzylazide30 were prepared according to the literature
procedures. All alkynes were used directly as received.
X-ray crystallographic details
The crystal data for the compound 1 has been collected on a Bruker SMART CCD
diffractometer (MoKα radiation, λ = 0.71073 Å). The structure was solved by direct methods
using the program SHELXS-97 and refined by full-matrix least-squares methods against F2
with SHELXL-97.31 Hydrogen atoms were fixed at calculated positions and their positions
were refined by a riding model. All non-hydrogen atoms were refined with anisotropic
displacement parameters. The crystal data and the cell parameters for compound 1 is
summarized in Table S1 (See ESI†).
16

Page 17 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
TGA and Powder XRD details
Thermogravimetric analysis (TGA) was carried out under nitrogen atmosphere, a ramp rate
of 10 °C/min using a Discovery TGA by TA Instruments-Waters Lab. Powder X-ray
diffraction data for compound 1 has been collected on a Bruker D8 Advance with DIVINCI
design fitted with HTK 16 temperature chamber X-ray powder diffractometer using CuKα
radiation (λ = 1.5418 Å).
Synthesis of complex 1
Method A: Two equivalents of thiourea 1-3-bis(2,6-dimethylphenyl)thiourea [L =
(ArNH)2C=S); (Ar = 2,6-Me2C6H3)] (1 g, 3.52 mmol) in THF(25 mL) was added drop by
drop to a solution of CuCl2 (0.236 g, 1.76 mmol) in THF (10 mL) at room temperature. The
reaction mixture was stirred at room temperature for 12 hours and a clear solution was
noticed. After filtration through Celite, the filtrate was concentrated and stored at room
temperature. Pale yellow colour crystals of compound 1 were isolated after one day. Further
o
product was obtained by crystallization from mother liquor at 0 C. The total yield is 0.99 g
(85 %).
Method B: Complex 1 was synthesised by following similar procedure that employed in
method A and using precursors CuCl (0.088g, 0.88mmol) and L (0.5g , 1.76mmol) yield
(1.05 g, 90 %).
m.p = 210 - 214 oC. 1H NMR (400 MHz, DMSO-D6, 25 oC) δ 9.95 (s, 2H, NH), 8.78 (s, 2H,
NH), 7.25–7.18 (m, 6H, Ar–H), 7.08–7.03 (m, 6H, Ar–H), 3.60 (t, J = 6.6 Hz, 4H,
OCH2CH2), 2.32 (s, 12H, Ar–CH3), 2.14 (s, 12H, Ar–CH3), 1.76 (t, J = 6.6 Hz, 4H,
o
OCH2CH2). 13C NMR (101 MHz, DMSO-D6, 25 C) δ 177.1 (C=S), 136.5 (Ar–C), 136.4
17

Green Chemistry
Page 18 of 26
View Article Online
DOI: 10.1039/C5GC02545A
(Ar–C), 135.9 (Ar–C), 133.7 (Ar–CH3), 128.6 (Ar–C), 128.5 (Ar–C), 127.8 (Ar–C), 127.3
(Ar–CH3), 67.0 (OCH2CH2), 25.1(OCH2CH2), 18.1 (Ar–CH3), 17.8 (Ar–CH3); IR (KBr) ν
(cm-1): 626(m), 697(m), 711 (s), 761(m), 813(m), 902(s), 924(m), 990(m), 1032(m),
1066(m), 1100(m), 1167(m), 1209(m), 1243(w), 1298(m), 1379(m), 1442(w), 1472(w),
1560(w), 1636(w), 1849(s), 1926(s), 2309(w), 2730(m), 2855(m), 2925(w), 3261(w),
3581(w). HRMS (ESI-TOF-Q) m/z: [M –Cl] calcd for C34H40CuN4S2Cl 631.1931; found:
631.1985.
General procedure for the 3 + 2 cycloaddition of azides(aliphatic or aromatic) and
terminal alkynes
Catalyst 1 (0.02 mmol), azide (1 mmol) and an alkyne (1.15 mmol) were placed in a screw
cap vial. The reaction mixture was stirred at room temperature and the progress of the
reaction was monitored by TLC. Solid mass was dissolved in ethyl acetate and passed
through silica gel column. After removal of the solvent in vacuo and washing the residue with
1
13
n-hexane afforded pure desired products. All the products were characterized by H and C
NMR and ESI-MS spectra.
General procedure for the 3 + 2 cycloaddition of azides (aliphatic or aromatic) and
internal alkynes
Catalyst 1 (0.02 mmol), azide (1 mmol) and an alkyne (1.15 mmol) were placed in a screw
cap vial. The reaction mixture was stirred at room temperature and the progress of the
reaction was monitored by TLC. Solid mass was dissolved in ethyl acetate and passed
through silica gel column. After removal of the solvent in vacuo and washing the residue with
1
13
n-hexane afforded pure desired products. All the products were characterized by H and C
NMR and ESI-MS spectra.
18

Page 19 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
General procedure for the three component click reaction catalyzed by complex 1
Catalyst 1 (0.02 mmol), organic bromide (1.0 mmol), NaN3 (1.2 mmol) and an alkyne (1.2
mmol) and water (2 mL) were placed in a screw cap vial. The reaction was carried out at
room temperature and monitored by TLC. After completion of the reaction, 10 mL of water
was added to the reaction mixture and further stirred for 30 min to precipitate the product
completely, which was collected by suction filtration and washed with 10 mL of water
several times affording the desired trizole. All the products were characterized by 1H and 13C
NMR and ESI-MS spectra.
The analysis data for compounds 4a-4l, 4r-4s, 4u, 4x-4y, 6a-6c, 8a-8d were in agreement
with those described in the literature14a, 22a, 22c, 22e, 23, 26c, 32 (see supporting information)
Compound 4m; 1-(3-chlorobenzyl)-4-(m-tolyl)-1H-1,2,3-triazole
1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 9.0 Hz, 2H), 7.52 (d, J = 7.4 Hz, 1H), 7.22 (dd, J
= 12.4, 5.4 Hz, 3H), 7.14 – 7.04 (m, 2H), 5.47 (s, 2H), 2.32 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 148.7, 138.6, 136.7, 135.1, 130.5, 130.3, 129.2, 129.1, 128.8, 128.1, 126.5, 126.1,
122.9, 119.6, 53.6, 21.5. HRMS (ESI-TOF-Q) m/z: [M + H]+ calcd for C16H14ClN3 284.0935;
found 284.0949.
Compound 4n; 1-(3-chlorobenzyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole
1H NMR (400 MHz, CDCl3) δ 7.80 – 7.74 (m, 2H), 7.66 (s, 1H), 7.36 – 7.27 (m, 3H), 7.19-
7.16 (m, 1H), 7.13 – 7.05 (m, 2H), 5.53 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 162.8(d, J =
246Hz), 147.6, 136.6, 135.1, 130.6, 129.1, 128.2, 127.6(d, J = 8Hz), 126.7(d, J = 3Hz),
126.2, 119.4, 115.9(d, J = 22Hz), 53.6 ppm. HRMS (ESI-TOF-Q) m/z: [M + H]+ calcd for
C15H11ClFN3 288.0699; found 288.0698.
19

Green Chemistry
Page 20 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Compound 4o; 4-(4-bromophenyl)-1-(3-chlorobenzyl)-1H-1,2,3-triazole
1H NMR (400 MHz, CDCl3) δ 7.73 – 7.64 (m, 3H), 7.53 (d, J = 8.4 Hz, 2H), 7.36 – 7.28 (m,
3H), 7.18 (d, J = 6.8 Hz, 1H), 5.54 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 136.5, 135.2,
132.1, 130.6, 129.35 (d, J = 18.6 Hz), 128.2, 127.3, 126.2, 122.3, 119.7, 53.7; HRMS (ESI-
TOF-Q) m/z: [M + H]+ calcd for C14H11ClN4 347.9842; found 347.9898.
Compound 4p; 2-(1-(3-chlorobenzyl)-1H-1,2,3-triazol-4-yl)pyridine
1H NMR (400 MHz, CDCl3) δ 8.96 (s, 1H), 8.56 (d, J = 3.9 Hz, 1H), 8.21 (d, J = 7.9 Hz, 1H),
7.80 (s, 1H), 7.39 – 7.28 (m, 4H), 7.19 (d, J = 6.6 Hz, 1H), 5.57 (s, 2H); 13C NMR (101 MHz,
CDCl3) δ 149.2, 146.9, 145.4, 136.4, 135.2, 133.3, 130.6, 129.3, 128.2, 126.7, 126.2, 124.0,
120.0, 53.8; HRMS (ESI-TOF-Q) m/z: [M + H]+ calcd for C14H11ClN4 271.0756; found
271.0745.
Compound 4q; methyl 1-(3-chlorobenzyl)-1H-1,2,3-triazole-4-carboxylate
1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.37 – 7.29 (m, 2H), 7.26 (d, J = 3.4 Hz, 1H),
7.16 (d, J = 7.1 Hz, 1H), 5.55 (s, 2H), 3.92 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 161.1,
135.7, 135.3, 130.7, 129.5, 128.4, 127.6, 126.3, 53.8, 52.3.HRMS (ESI-TOF-Q) m/z: [M +
H]+ calcd for C11H10ClN3O2 252.0539; found 252.0534.
Compound 4t; 1-(4-nitrobenzyl)-4-(m-tolyl)-1H-1,2,3-triazole
1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.2 Hz, 2H), 7.76 (s, 1H), 7.66 (s, 1H), 7.58 (d, J
= 7.6 Hz, 1H), 7.44 (d, J = 8.5 Hz, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H),
5.69 (s, 2H), 2.38 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 148.2, 141.8, 138.8, 129.9, 129.4,
128.9, 128.7, 126.6, 124.4, 123.0, 53.3, 21.5. HRMS (ESI-TOF-Q) m/z: [M + H]+ calcd for
C16H14N4O2 295.1178; found 295.1190.
20

Page 21 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
Compound 4v; 4-(4-bromophenyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole
1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.7 Hz, 2H), 7.77 (s, 1H), 7.69 (d, J = 8.3 Hz, 2H),
7.54 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 5.69 (s, 2H); 13C NMR (101 MHz, CDCl3)
δ 148.3, 141.6, 132.2, 129.2, 128.7, 127.3, 124.5, 122.5, 53.4. HRMS (ESI-TOF-Q) m/z: [M
+ H]+ calcd for C15H11BrN4O2 359.0091; found 359.0138
1
Compound 4w; 2-(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)pyridine H NMR (400 MHz,
CDCl3) δ 8.97 (s, 1H), 8.58 (s, 1H), 8.24 (d, J = 8.6 Hz, 2H), 8.20 (d, J = 7.9 Hz, 1H), 7.86
(s, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.37 (dd, J = 7.4, 4.9 Hz, 1H), 5.72 (s, 2H); 13C NMR (101
MHz, CDCl3) δ 149.6, 148.3, 147.1, 145.8, 141.5, 133.3, 128.8, 124.6, 124.0, 120.2, 53.5.
HRMS (ESI-TOF-Q) m/z: [M + H]+ calcd for C14H11N5O2 282.0988; found 282.0986.
1
Compound 8e; diethyl 1-(4-nitrobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate H NMR
(400 MHz, CDCl3) δ 8.20 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 5.92 (s, 2H), 4.43 (q,
J = 7.1 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 160.1, 158.3, 148.2, 141.2, 141.0, 129.3, 129.0, 124.2, 63.2,
62.2, 53.0, 14.2, 13.9. HRMS (ESI-TOF-Q) m/z: calcd for [M + H]+ C15H16N4O6 349.1186;
found 349.1143.
Acknowledgments
The authors thank the National Institute of Science Education and Research (NISER),
Bhubaneswar for supporting this work. We also thank the anonymous reviewers for their
helpful suggestions.
21

Green Chemistry
Page 22 of 26
View Article Online
DOI: 10.1039/C5GC02545A
References
1
H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed., 2001, 40, 2004.
(a) V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem.
Int. Ed., 2002, 41, 2596; (b) B. Gacal, H. Durmaz, M. A. Tasdelen, G. Hizal, U.
Tunca, Y. Yagci and A. L. Demirel, Macromolecules, 2006, 39, 5330.
T. Siu and A. K. Yudin, J. Am. Chem. Soc., 2002, 124, 530.
2
3
4
5
6
7
I. M. Pastor and M. Yus, Curr. Org. Chem., 2005, 9, 1.
R. Huisgen, Angew. Chem. Int. Ed. Engl., 1963, 2, 565.
C. W. Tornøe, C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057.
(a) K. Ladomenou, V. Nikolaou, G. Charalambidis and A. G. Coutsolelos, Coord.
Chem. Rev., 2016, 306, 1; (b) S. Hassan and T. J. J. Mueller, Adv. Synth. Catal., 2015,
357, 617; (c) F. Alonso, Y. Moglie and G. Radivoy, Acc. Chem. Res., 2015, 48, 2516;
(d) H. Struthers, T. L. Mindt and R. Schibli, Dalton Trans., 2010, 39, 675; (e) J. E.
Hein and V. V. Fokin, Chem. Soc. Rev., 2010, 39, 1302; (f) M. Meldal and C. W.
Tornøe, Chem. Rev., 2008, 108, 2952.
8
E. Haldon, M. C. Nicasio and P. J. Perez, Org. Biomol. Chem., 2015,13, 9578
S. Diez-Gonzalez, Catal. Sci. Technol., 2011, 1, 166.
9
10
S. Díez-González, A. Correa, L. Cavallo and S. P. Nolan, Chem. Eur. J., 2006, 12,
7558.
11
S. Diez-Gonzalez, E. C. Escudero-Adan, J. Benet-Buchholz, E. D. Stevens, A. M. Z.
Slawin and S. P. Nolan, Dalton Trans., 2010, 39, 7595.
12
13
W. Wang, J. Wu, C. Xia and F. Li, Green Chem., 2011, 13, 3440.
R. Berg, J. Straub, E. Schreiner, S. Mader, F. Rominger and B. F. Straub, Adv. Synth.
Catal., 2012, 354, 3445.
22

Page 23 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
14
15
(a) S. C. Sau, S. R. Roy, T. K. Sen, D. Mullangi and S. K. Mandal, Adv. Syn. Catal.,
2013, 355, 2982; (b) S. Hohloch, C.-Y. Su and B. Sarkar, Eur. J. Inorg. Chem., 2011,
3067; (c) T. Nakamura, T. Terashima, K. Ogata and S.-i. Fukuzawa, Org. Lett., 2011,
13, 620.
(a) F. Wang, H. Fu, Y. Jiang and Y. Zhao, Green Chem., 2008, 10, 452; (b) V. O.
Rodionov, V. V. Fokin and M. G. Finn, Angew. Chem. Int. Ed., 2005, 44, 2210; (c) S.
I. Presolski, V. Hong, S.-H. Cho and M. G. Finn, J. Am. Chem. Soc., 2010, 132,
14570; (d) P. Fabbrizzi, S. Cicchi, A. Brandi, E. Sperotto and G. van Koten, Eur. J.
Org. Chem., 2009, 2009, 5423; (e) A. R. McDonald, H. P. Dijkstra, B. M. J. M.
Suijkerbuijk, G. P. M. van Klink and G. van Koten, Organometallics, 2009, 28, 4689;
(f) L. Jiang, Z. Wang, S. Q. Bai and T. S. Hor, Dalton Trans, 2013, 42, 9437-9443;
(g) S.-Q. Bai, L. L. Koh and T. S. A. Hor, Inorg. Chem., 2009, 48, 1207-1213.
(a) M. Findlater, N. J. Hill and A. H. Cowley, Dalton Trans., 2008, 4419; (b) J.
Obenauf, W. P. Kretschmer and R. Kempe, Eur. J. Inorg. Chem., 2014, 1446.
(a) G. A. Bowmaker, J. V. Hanna, C. Pakawatchai, B. W. Skelton, Y. Thanyasirikul
and A. H. White, Inorg. Chem., 2009, 48, 350; (b) G. Li, D.-J. Che, Z.-F. Li, Y. Zhu
and D.-P. Zou, New J. Chem., 2002, 26, 1629.
16
17
18
19
X.-Y. Zhao, C.-B. Zhu, H.-P. Li, Y. Yang and H. W. Roesky, Z. Anorg. Allg. Chem.,
2014, 640, 1614.
(a) J.-T. Wang, Y.-F. Yuan, Y.-M. Xu, Y.-W. Zhang, R.-J. Wang and H.-G. Wang, J.
Organomet. Chem., 1994, 481, 211; (b) Y.-f. Yuan, S.-m. Ye, L.-y. Zhang, B. Wang,
Y.-m. Xu, J.-t. Wang and H.-g. Wang, Inorg. Chim. Acta, 1997, 256, 313.
(a) A. Casitas and X. Ribas, Chem. Sci., 2013, 4, 2301; (b) C. Zhang, C. Tang and N.
Jiao, Chem. Soc. Rev., 2012, 41, 3464; (c) S. R. Harutyunyan, T. den Hartog, K.
Geurts, A. J. Minnaard and B. L. Feringa, Chem. Rev., 2008, 108, 2824.
20
23

Green Chemistry
Page 24 of 26
View Article Online
DOI: 10.1039/C5GC02545A
21
22
K. Yamaguchi, T. Oishi, T. Katayama and N. Mizuno, Chem. Eur. J., 2009, 15,
10464.
(a) S. Saha, M. Kaur and J. K. Bera, Organometallics, 2015, 34, 3047; (b) R. U.
Islam, A. Taher, M. Choudhary, M. J. Witcomb and K. Mallick, Dalton Trans., 2015,
44, 1341; (c) S. J. Bent, M. F. Mahon and R. L. Webster, Dalton Trans., 2015, 44,
10253; (d) B. J. Borah, D. Dutta, P. P. Saikia, N. C. Barua and D. K. Dutta, Green
Chem., 2011, 13, 3453; (e) Z. Gonda and Z. Novak, Dalton Trans., 2010, 39, 726.
C. Vidal and J. Garcia-Alvarez, Green Chem., 2014, 16, 3515.
S. Bräse, C. Gil, K. Knepper and V. Zimmermann, Angew. Chem. Int. Ed., 2005, 44,
5188.
23
24.
25
26
E. F. V. Scriven and K. Turnbull, Chem. Rev., 1988, 88, 297.
(a) F. Alonso, Y. Moglie, G. Radivoy and M. Yus, Adv. Synth. Catal., 2010, 352,
3208; (b) H. Sharghi, R. Khalifeh and M. M. Doroodmand, Adv. Synth. Catal., 2009,
351, 207; (c) L. Wan and C. Cai, Catal. Lett., 2012, 142, 1134; (d) N. Mukherjee, S.
Ahammed, S. Bhadra and B. C. Ranu, Green Chem., 2013, 15, 389; (e) S. Roy, T.
Chatterjee and S. M. Islam, Green Chem., 2013, 15, 2532.
27
28
C. Nolte, P. Mayer and B. F. Straub, Angew. Chem. Int. Ed., 2007, 46, 2101.
B.-H. Lee, C.-C. Wu, X. Fang, C. W. Liu and J.-L. Zhu, Catal. Lett., 2013, 143, 572-
577.
29
30
31
Y.-W. He, C.-Z. Dong, J.-Y. Zhao, L.-L. Ma, Y.-H. Li and H. A. Aisa, Eur. J. Med.
Chem., 2014, 76, 245.
D. R. Banerjee, K. Senapati, R. Biswas, A. K. Das and A. Basak, Bioorg. Med. Chem.
Lett., 2015, 25, 1343.
G. M. Sheldrick Acta Crystallogr. Sect. A 2008, 64, 112.
24

Page 25 of 26
Green Chemistry
View Article Online
DOI: 10.1039/C5GC02545A
32
(a) M. Nasrollahzadeh, B. Jaleh, P. Fakhri, A. Zahraei and E. Ghadery, RSC Adv.,
2015, 5, 2785; (b) W. Zhang, X. He, B. Ren, Y. Jiang and Z. Hu, Tetrahedron Lett.,
2015, 56, 2472; (c) S. T. Abu-Orabi, M. A. Atfah, I. Jibril, F. M. Mari'i and A. A. S.
Ali, J. Heterocycl. Chem., 1989, 26, 1461; (d) S. Lal and S. Díez-González, J. Org.
Chem., 2011, 76, 2367.
25

Green Chemistry
Page 26 of 26
View Article Online
DOI: 10.1039/C5GC02545A
Table of Contents
We have shown that air stable bulky thioureas supported copper (I) chloride complex as an
efficient catalyst for the synthesis of five membered heterocycles from alkynes and azides.