Cu(N-heterocyclic carbene)chloride: An efficient catalyst for multicomponent click reaction for the synthesis of 1,2,3-triazoles in water at room temperature

Article abstract of DOI:10.1039/c4ra08412h

A novel water soluble copper(N-heterocyclic carbene)chloride [Cu(NHC)Cl] complex of vitamin B₁ was synthesized and characterized by EDX, FT-IR and NMR spectroscopy. It was employed for three component click reaction of benzyl chlorides 1a-e, alkynes 2a-c and sodium azide 3 in water at room temperature. All the synthesized compounds 4a-o were characterized by elemental analysis, IR, and ¹HNMR spectroscopy. The catalyst was easy to prepare, very versatile, reusable and was found to be highly active at low catalyst loading for a variety of substrates with a varied nature of substituents. This journal is

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ARTICLE
Cu(N-heterocyclic carbene)chloride: An efficient
catalyst for multicomponent click reaction for
the synthesis of 1,2,3-triazoles in water at room
temperature
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
Vishal B. Purohit*, Sharad C. Karad, Kirit H. Patel, Dipak K. Raval
www.rsc.org/
A novel water soluble copper(N-heterocyclic carbene)chloride [Cu(NHC)Cl] complex of Vitamin B1 was
synthesized and characterized by EDX, FT-IR and NMR spectroscopy. It was employed for three
component click reaction of benzyl chlorides 1a-e, alkynes 2a-c and sodium azide
3 in water at room
temperature. All the synthesized compounds 4a-o were characterized by elemental analysis, IR, and
1HNMR spectroscopy. The catalyst was easy to prepare, very versatile, reusable and was found to be
highly active at low catalyst loading for a variety of substrates with varied nature of substituents.
contains a pyrimidine ring and thiazolium ring linked together
by methylene bridge. In current study, the actual carbine was
formed by deprotonation at positionꢀ2 of thiazole ring which is
most acidicand was mostly applied in organocatalytic
reactions.8
The chemical concept of click chemistry was first introduced
by Sharpless and coworkers in 2001.9 Since then, Cu(I)ꢀ
catalyzed 1,3ꢀdipolar azideꢀalkyne cycloaddition (CuAAC) has
become the most popular click reaction to produce 1,2,3ꢀ
triazoles regioselectively.10 It has found wide applications in
various disciplines including catalysis,11 materials science,12
organic synthesis,13 bioꢀ and medicinal chemistry14 due to its
mild conditions and high efficiency.
1. Introduction
Since the pioneering discovery of first free Nꢀheterocyclic
carbene (NHC) by Arduengo in 1991,1 NHCꢀtransition metal
complexes have attracted considerable attention. They owe
unique properties and have efficient applications in
homogeneous catalysis.2 Being strong
σꢀdonors and very poor
πꢀacceptors, NHCs form strong bonds with the metal centers
and can be employed as alternatives to the widely used
phosphine ligands.3 Various complexes of Cu(I) with NHC
ligands have been prepared for homogeneous catalysis.4 Most
of the complexes of Cu(I) with NHC ligands were derived from
imidazolium ionic liquids and were toxic, poorly
biodegradable5 and complicated to synthesize.2b,
The
4c,
6
However, most of the reported CuAAC reactions dealt with
oneꢀpot two component reactions in which azides were
prepared prior to the cycloaddition.4d, 15 These protocols suffer
from the drawback as organic azides are difficult to handle
because of their toxicity, explosive nature and tedious isolation
and purification.16 To overcome this difficulty, oneꢀpot
methodologies for in situ generation of azides have been
reported.17 Multiꢀcomponent reactions (MCRs) have emerged
as the powerful tool for synthetic chemists. MCRs provide
effective method for manufacture of the diversified structural
scaffolds and combinatorial libraries for drug discovery.18 The
multiꢀcomponent click reactions are enormously convergent
and provide huge number of small molecules by generating
present attempt is to look for new biodegradable and nontoxic
NHC ligand from a natural source to assemble one of the main
principles of green chemistry. The synthesis and
characterization of a water soluble Cu(NHC)Cl complex of
Vitamin B1 and its catalytic application for three component
(CuAAC) click reaction using water at room temperatuer is
attempted for the first time.
We decided to look for a new biodegradable and nontoxic NHC
ligands from natural sources to assemble one of the main
principles of green chemistry.7 It is well known that thiamine
hydrochloride (VB1) is
a nonflammable, cheap, stable,
biodegradable and nonꢀtoxic compound. The structure of VB1
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multiple bonds in a single chemical operation.19 Therefore,
much attention has been paid to the development of novel
MCRs. The use of water the greenest and the most abundant of
all solvents as a reaction medium in chemical reactions is of
greatest interest. It not only fulfills the traditional proponents of
green chemistry principles but also in view of its low cost,
safety and environmentally benign properties.7
As a part of our program dedicated to develop environmentally
benign protocols for synthesis of various heterocyclic
compounds,20 herein we document the first report for the
synthesis and characterization of a water soluble Cu(NHC)Cl
complex of Vitamin B1 and its catalytic application for three
component (CuAAC) click reaction using water as the green
media at room temperature. The protocol was found to be
highly active at low catalyst loadings ranging from 0.01ꢀ0.5
mol % for synthesizing 1,2,3ꢀtriazoles 4a-o in high yield and
purity from benzyl chlorides 1a-e, alkynes 2a-c and sodium
Table 1. Effect of solvent on synthesisa of 1,2,3ꢀtriazole 4a
Entry
Solvent
Nil
Water
Ethanol
Methanol
DMF
Timeb (h)
Yieldc (%)
1
2
3
4
5
6
7
12
1.5
1.5
1.5
1.5
2
n.d.
90
85
81
60
81
80
THF
DMSO
3
aReaction conditions: benzyl chloride (1.0 mmol), phenylacetylene (1.2
mmol), sodium azide (1.2 mmol), Cu(NHC)Cl (0.5 mol %) and solvent (2
mL). bAll the reactions were run till completion as indicated by TLC.
cIsolated yield, n.d., not detected.
DMF, THF and DMSO for the synthesis of 4a. The results are
summarized in Table 1. Water showed advantage over the other
solvents not only in influencing the reaction but also solubility
of Cu(NHC)Cl in it and easy isolation of the targeted
compound 4a (Table 1, entry 2).
azide 3.
The effectiveness of the model reaction was also found to be
affected by various catalysts. No product was observed in
absence of any catalyst (Table 2, entry 1). Cu(OAc)2, Cu2O,
2. Results and discussion
.
2.1 Characterization of catalyst.
CuSO4 5H2O, porous copper and CuCl also promoted the
1
The Cu(NHC)Cl catalyst was characterized by H NMR, EDX
and FTꢀIR spectroscopy. FTꢀIR spectrum of the catalyst
exhibited some characteristic stretching vibration bands due to
the amino group at 3340 and 3310cmꢀ1, while NꢀH bending
absorption appeared at 1665 cmꢀ1. A broad absorption band was
observed at around 3600 cmꢀ1 due to OꢀH stretching. Energy
dispersive spectroscopy analysis of Xꢀrays (EDX) data for the
catalyst showed the existence of copper, chlorine and sulphur
elements (Figure 1) and confirmed the weight % of C, N, O, S,
Cu and Cl respectively as 35.12, 13.18, 3.84, 7.96, 16.88, 8.34
as expected with the calculated values 39.33, 15.11, 4.09, 8.44,
17.14, 9.42.
reaction with low to moderate yields (Table 2, entries 5–9).
Decrease in yield was observed due to the sparingly soluble
nature of CuCl in water. The complexation of CuCl with NHC
made it homogeneous for the reaction. From the results, it was
found that 0.5 mol % of Cu(NHC)Cl was the optimum amount
of catalyst leading to 90 % yield of 4a in water at room
temperature (Table 2, entry 3).
Table 2. Catalyst screening for the synthesisa of 1,2,3ꢀtriazole 4a
Temp.
(ºC)
rt
rt
rt
50
rt
rt
rt
50
rt
Timeb
(h)
12
1.5
1.5
1.5
12
3
12
25
5
Yieldc
(%)
n.d.
90
90
87
Entry
Catalyst
mol %
1
2
3
4
5
6
7
8
9
Nil
ꢀ
1
Cu(NHC)Cl
Cu(NHC)Cl
Cu(NHC)Cl
Cu(OAc)2
Cu2O
0.5
0.5
0.5
0.5
0.5
5
20
75
CuSO4.5H2O
Porous Copper
CuCl
15
9417b
70
0.5
aReaction conditions: benzyl chloride (1.0 mmol), phenylacetylene (1.2
b
mmol), sodium azide (1.2 mmol), and water (2 mL). All the reactions were
run till completion as indicated by TLC. cIsolated yield, n.d., not detected.
2.3 Applications of Cu(NHC)Cl catalyst for the synthesis of
1,2,3-triazoles (4a-o).
With these optimized conditions in hand, the activity of catalyst
Figure 1. EDX analysis of Cu(NHC)Cl
was investigated in the click reaction with benzyl chlorides 1a-
e
(1.0 mmol), alkynes 2a-c (1.2 mmol), sodium azide 3 (1.2
2.2 Optimization of reaction conditions
mmol). The reactions were conducted in water at room
temperature with 0.5 mol % of NHC loading for appropriate
time period to yield triazoles 4a-o in excellent yields and purity
(Table 4). The high yields of triazoles 4a-o led us to examine
the possibility of synthesizing the target compounds at low
catalyst loading. The activity of NHC catalyst was investigated
in the model reaction at various catalyst loadings. The obtained
results are recorded in Table 3. It was observed that at 0.1 mol
To optimize the reaction conditions a series of experiments
were performed with the model reaction of benzyl chloride 1a
(1.0 mmol), phenylacetylene 2a (1.2 mmol), sodium azide
3
(1.2 mmol) in the presence of various catalysts and reaction
media.
In order to search for the best solvent, the model reaction was
performed in various solvents such as water, ethanol, methanol,
2 | J. Name., 2012, 00, 1-3
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Table 4. Cu(NHC)Cl catalyzed three component synthesis of 1,2,3ꢀtriazoles 4a-o at room temperature.
m.p. (ºC)
Entry
Compounds
R
R1
X
Timeb (h)
Yieldc (%)
Found
Reported
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
ꢀH
ꢀH
ꢀH
ꢀNO2
ꢀNO2
ꢀNO2
ꢀCH3
ꢀCH3
ꢀCH3
ꢀCl
ꢀH
ꢀCH3
H
ꢀH
ꢀCH3
ꢀH
ꢀH
ꢀCH3
ꢀH
ꢀH
ꢀCH3
ꢀH
CH
CH
N
CH
CH
N
CH
CH
N
CH
CH
N
1.5
2.5
2.5
3.0
3.5
3.5
2.5
3.0
2.5
2.0
2.5
3.0
2.5
2.0
3.0
90
92
90
85
87
82
92
91
89
90
91
90
90
87
88
122ꢀ124
153ꢀ154
110–112
152ꢀ154
159ꢀ160
172ꢀ174
157ꢀ158
160ꢀ162
102ꢀ104
185ꢀ186
171ꢀ173
110ꢀ112
129ꢀ130
151ꢀ152
98ꢀ100
122–12421
152ꢀ15422
110–11223
154−15524
159ꢀ16025
ꢀ
157ꢀ15922
ꢀ
ꢀ
184ꢀ18622
ꢀCl
ꢀCl
ꢀF
ꢀF
ꢀ
ꢀ
ꢀH
ꢀCH3
ꢀH
CH
CH
N
129ꢀ13116b
150ꢀ15126
ꢀ
ꢀF
Reaction conditions: benzyl chlorides (1.0 mmol), alkynes (1.2 mmol), sodium azide (1.2 mmol), Cu(NHC)Cl (0.5 mol %) and water (2 mL)bAll the reactions
were run till completion as indicated by TLC. cIsolated yield.
change in the yields was not observed after three successive
Table 3. Cu(NHC)Cl catalysed three component synthesisa of 4a at low
runs (Figure 2). The slight decrease in yield may be due to loss
catalyst loadings at room temperature.
of catalyst (˂5%) during handling.
Entry
Catalyst (mol %)
Timeb (h)
Yieldc (%)
1
2
3
4
0.5
0.1
0.02
0.01
1.5
6
9
90
90
82
80
3. Experimental section
3.1 Materials and instrumentation
12
aReaction conditions: benzyl chloride (1.0 mmol), phenylacetylene (1.2 All the chemicals were purchased from Sigma Aldrich and used
mmol), sodium azide (1.2 mmol), Cu(NHC)Cl (0.01ꢀ0.5 mol %) and water (2
as received. All organic solvents were obtained from
mL). bAll the reactions were run till completion as indicated by TLC.
commercial sources and were of analytical grade. Melting
points were measured in ThermoCal10 (Analab Scientific Pvt.
cIsolated yield.
ꢀ
Ltd.) melting point apparatus and are uncorrected. All the
reactions were monitored by thinꢀlayer chromatography carried
out on fluorescent coated plates (aluminium plates coated with
silica gel 60 F254, 0.25 mm thickness, Merck) and detection of
the components was made by exposure to UV light. IR spectra
% level, the catalyst showed comparable activity to give high
yield with four fold increase in reaction time. With further
decrease in the amount of catalyst, prolonged duration is
required to complete the reaction with deplement in % yield. At
0.01 mol % loading, reaction took 12 h to yield the product
only up to 80 %.
were recorded on
a FTꢀIR PerkinElmer Spectrum 100
1
spectrometer in KBr pellets with absorption in cm−1. H NMR
2.4 Recyclability of the catalyst
spectra were recorded in DMSOꢀd6 on Bruker Avance 400 MHz
spectrometer. The chemical shifts are reported in
ꢁ parts per
To make the synthetic protocol more economical, the catalytic
efficiency of the recycled catalyst was investigated in three
successive cycle of the model reaction using recovered catalyst
from the previous run. It was observed that the catalyst showed
higher activity under the reaction conditions and any significant
million. The EDX was performed using JOEL JSMꢀ5610
scanning electron microscope (SEM). Elemental analyses were
performed on PerkinElmer 2400 seriesꢀII elemental analyzer
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(PerkinElmer, USA) and all results are found within
the theoretical compositions.
ꢂ
0.4 % of 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.32 (s, 3H),5.63 (s,
2H),7.21ꢀ7.26 (m, 2H),7.32ꢀ7.42 (m, 5H), 7.73 (d, = 8.0 Hz,
J
2H),8.57 (s, 1H), FTꢀIR (KBr): 3146, 3023, 2920, 2857, 1742,
1640, 1456, 1344, 1219, 1055, 975, 822, 765, 731 cmꢀ1, Anal.
Calcd. for C16H15N3: C, 77.08; H, 6.06; N, 16.85. Found: C,
76.78; H, 5.83; N, 16.41.
3.4.3 2ꢀ(1ꢀbenzylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)pyridine (4c)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.68 (s, 2H), 7.32ꢀ
7.39 (m, 6H), 7.87ꢀ7.91 (m, 1H), 8.03(d,
J = 8.0 Hz, 1H), 8.59
(d, = 4.4 Hz, 1H), 8.67 (s, 1H), FTꢀIR (KBr): 3106, 3083,
J
2947, 2852, 1641, 1597, 1571, 1545, 1455, 1419, 1345, 1223,
1044, 994, 786, 727 cmꢀ1, Anal. Calcd. for C14H12N4: C, 71.17;
H, 5.12; N, 23.71, Found: C, 71.03; H, 5.19; N, 23.52.
Figure 2. Catalyst recyclability study. Reaction conditions: benzyl chloride (1.0
mmol), phenylacetylene (1.2 mmol), sodium azide (1.2 mmol), Cu(NHC)Cl (0.5
mol %), water (2 mL), room temperature, 1.5 h.
3.4.4 1ꢀ(4ꢀnitrobenzyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (4d)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.85 (s, 2H),7.35 (d, J =
7.2 Hz,1H), 7.45 (t, 2H), 7.58 (d, J = 8.4Hz,2H), 7.86 (d, J = 7.6
Hz,2H), 8.26 (d, J = 8.4 Hz, 2H), 8.70 (s, 1H), FTꢀIR (KBr): 3126,
3080, 2930, 1605, 1518, 1465,1348, 1078, 860, 763, 696 cmꢀ1, Anal.
Calcd. for C15H12N4O2: C, 64.28; H, 4.32; N, 19.99. Found: C,
64.36; H, 4.15; N, 19.59.
3.2 Synthesis of N-Heterocyclic Carbene Copper Chloride
Complex.
50 mL Round bottom flask was charged with Thiamine
hydrochloride (Vitamin B1) (1 mmol). Fresh CuCl (1 mmol),
NaOtꢀBu (1 mmol), and THF (5 mL) were added to this flask.
The mixture was stirred at room temperature for 4 h. The
resulting solid was filtered, washed with cold methanol then
with methanol/acetone (1:1) and finally with acetone. The title
compound was obtained as a light green powder (0.307 g, 85%
yield). Melting point: >300ºC
3.4.5 1ꢀ(4ꢀnitrobenzyl)ꢀ4ꢀ(pꢀtolyl)ꢀ1Hꢀ1,2,3ꢀtriazole (4e)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.33 (s, 3H), 5.83 (s,
2H), 7.26 (d,
J
= 8.0 Hz, 2H), 7.57 (d,
J = 8.4 Hz, 2H), 7.74 (d,
3.2.1 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.53 (s, 3H),
2.57 (s, 3H), 3.07 (t, 2H), 3.66 (t, 2H), 5.59 (s, 2H), 8.35 (s,
1H), 9.11 (s, 2H), 9.94 (s, 1H). FTꢀIR (KBr): 3600, 3340, 3310,
3110, 1665, 1610, 1555, 1454, 1066, 1234, 780, 608 cmꢀ1
J
= 8.0 Hz, 2H), 8.26 (d,
J
= 8.8 Hz, 2H), 8.63 (s, 1H), FTꢀIR
(KBr): 3085, 2921, 2860, 1607, 1522, 1460, 1348, 1220, 1186,
1076, 1044, 974, 809, 727 cmꢀ1, Anal. Calcd. for C16H14N4O2:
C, 65.30; H, 4.79; N, 19.04. Found: C, 65.02; H, 4.33; N, 18.88.
3.3 General procedure for the synthesis of 1,2,3-triazoles (4a-o).
3.4.6 2ꢀ(1ꢀ(4ꢀnitrobenzyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)pyridine (4f)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.87 (s, 2H), 7.36 (dd,
A mixture of variously substituted benzyl chlorides 1a-e (1.0
J
= 5.6 Hz,
(m, 1H), 8.05 (d,
(d,
= 4.4 Hz, 1H), 8.77 (s, 1H), 13C NMR (400 MHz, DMSOꢀ
J
= 7.2 Hz, 1H), 7.60 (d,
J
= 8.4 Hz, 2H), 7.88ꢀ7.92
mmol), alkynes 2a-c (1.2 mmol), sodium azide
3 (1.2 mmol) in
J
= 7.6 Hz, 1H), 8.26 (d,
J
= 8.8 Hz, 2H), 8.60
2 mL of water was magnetically stirred at room temperature in
the presence of Cu(NHC)Cl complex (0.5 mol %). The
progress of reaction was monitored by TLC. After completion
of the reaction, 10 mL of water was added to the resulting
mixture followed by extraction with ethyl acetate. The collected
organic phase was dried with anhydrous Na2SO4 and the
solvent was removed under vacuum to afford the desired
triazoles. All the products were obtained with NMR purity. The
collected residual aqueous catalyst phase was washed by ethyl
J
d6): δ 52.60, 119.93, 123.58, 124.38, 124.42, 129.52, 137.70,
143.82, 147.74, 148.10, 150.12, 150.23; FTꢀIR (KBr): 3110,
3084, 2932, 2859, 1639, 1595, 1571, 1545, 1453, 1420, 1340,
1246, 1042, 994, 850, 785, 721 cmꢀ1, Anal. Calcd. For
C14H11N5O2: C, 59.78; H, 3.94; N, 24.90. Found: C, 59.41; H,
3.63; N, 24.98.
3.4.7 1ꢀ(4ꢀmethylbenzyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (4g)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.29 (s, 3H), 5.59 (s,
acetate (2
ꢃ5 mL), concentrated up to 2 mL using IKA RV10
control rotary evaporator and reused for recyclability study.
2H), 7.19ꢀ7.27 (m, 4H), 7.33 (d,
J = 7.2 Hz,1H), 7.43 (t, 2H),
7.84 (t, 2H), 8.60 (s, 1H), 13C NMR (400 MHz, DMSOꢀd6): δ
21.17, 53.30, 121.87, 125.61, 128.38, 129.50, 131.16, 133.48,
134.35, 137.97, 139.29, 147.08; FTꢀIR (KBr): 3087, 2920,
2857, 1615, 1453, 1350, 1220, 1109, 1075, 1045, 976, 915,
763, 699 cmꢀ1, Anal. Calcd. for C16H15N3: C, 77.08; H, 6.06; N,
16.85. Found: C, 77.20; H, 5.78; N, 16.56.
3.4 Spectral data of 1,2,3-triazoles (4a-o).
3.4.1 1ꢀbenzylꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (4a)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.65 (s, 2H), 7.31ꢀ
7.46 (m, 8H), 7.85 (d,
J = 7.2 Hz2H), 8.64 (s, 1H), FTꢀIR
(KBr): 3142, 3028, 2926, 2856, 1636, 1451, 1436, 1346, 1223,
1073, 1045, 768, 731, 696 cmꢀ1, Anal. Calcd. for C15H13N3: C,
76.57; H, 5.57; N, 17.86, Found: C, 76.25; H, 5.34; N, 17.69.
3.4.8 1ꢀ(4ꢀmethylbenzyl)ꢀ4ꢀ(pꢀtolyl)ꢀ1Hꢀ1,2,3ꢀtriazole (4h)
3.4.2 1ꢀbenzylꢀ4ꢀ(pꢀtolyl)ꢀ1Hꢀ1,2,3ꢀtriazole (4b)
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1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.29 (s, 3H),2.32 (s, 2H), 8.56 (s, 1H), FTꢀIR (KBr): 3123, 3055, 2930, 2851, 1603,
3H),5.57 (s, 2H), 7.18ꢀ7.27 (m, 6 H),7.72 (d,
= 8.0 Hz, 1433, 1360, 1225, 1162, 1041, 970, 923, 850, 762, 701 cmꢀ1,
J
2H),8.53 (s, 1H), FTꢀIR (KBr): 3132, 3015, 2914, 1643, 1507, Anal. Calcd. for C16H14FN3: C, 71.89; H, 5.28; N, 15.72.
1453, 1348, 1219, 1190, 1111, 1055, 975, 911, 753 cmꢀ1, Anal. Found: C, 71.43; H, 4.89; N, 15.37.
Calcd. for C17H17N3: C, 77.54; H, 6.51; N, 15.96. Found: C,
77.12; H, 6.04; N, 15.55.
3.4.15 2ꢀ(1ꢀ(4ꢀfluorobenzyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)pyridine (4o)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.67 (s, 2H), 7.20ꢀ
7.25 (m, 2H), 7.26ꢀ7.36 (m, 1H), 7.45ꢀ7.48 (m, 2H), 7.87ꢀ7.91
3.4.9 2ꢀ(1ꢀ(4ꢀmethylbenzyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)pyridine (4i)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.29 (s, 3H), 5.61 (s, (m, 1H), 8.02 (d,
J
= 8.0 Hz, 1H) 8.59 (d,
(s, 1H), 13C NMR (400 MHz, DMSOꢀd6): δ 52.70, 116.10,
J = 4.0 Hz, 1H), 119.80, 123.49, 123.81, 130.84, 132.69, 137.67, 147.99,
J = 4.8 Hz, 1H), 8.68
2H), 7.20 (d,
7.6 Hz, 1H), 8.02 (d,
J
= 7.6 Hz, 2H), 7.30ꢀ7.35 (m, 3H), 7.87 (d,
= 7.6 Hz, 1H), 8.58 (d,
J =
J
8.63 (s, 1H), 13C NMR (400 MHz, DMSOꢀd6): δ 21.20, 53.26, 150.20, 161.18, 163.61; FTꢀIR (KBr):3110, 3090, 2951, 2921,
119.84, 123.36, 123.81, 128.58, 129.84, 133.46, 137.68, 1642, 1590, 1572, 1540, 1449, 1421, 1342, 1222, 1042, 994,
138.08, 150.14, 150.30; FTꢀIR (KBr): 3103, 3081, 2943, 781, 723, 699 cmꢀ1, Anal. Calcd. for C14H11FN4: C, 66.13; H,
1640,1595, 1545, 1455, 1420, 1350, 1221, 1045, 991, 783, 727, 4.36; N, 22.04. Found: C, 66.25; H, 4.01; N, 21.88.
711 cmꢀ1, Anal. Calcd. for C15H14N4: C, 71.98; H, 5.64; N,
22.38. Found: C, 71.55; H, 5.39; N, 22.45.
Conclusion
A novel water soluble Cu(NHC)Cl catalyst has been developed
for oneꢀpot three component click reaction of benzyl chlorides,
alkynes and sodium azide at room temperature using water as
the greener media. The catalyst could be easily recovered and
recycled up to three times without much loss in its activity. The
protocol was also found to be simple, environmentally benign
and highly efficient at low catalyst loadings.
3.4.10 1ꢀ(4ꢀchlorobenzyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (4j)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.66 (s, 2H), 7.31ꢀ
7.48 (m, 7H), 7.84 (d,
J = 7.6 Hz, 2H), 8.64 (s, 1H), FTꢀIR
(KBr): 3121, 3059, 2923, 2854, 1609, 1430, 1341, 1221, 1160,
1042, 970, 922, 850, 761 cmꢀ1, Anal. Calcd. for C15H12ClN3: C,
66.79; H, 4.48; N, 15.58. Found: C, 66.88; H, 4.12; N, 15.18.
3.4.11 1ꢀ(4ꢀchlorobenzyl)ꢀ4ꢀ(pꢀtolyl)ꢀ1Hꢀ1,2,3ꢀtriazole (4k)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.32 (s, 3H), 5.64 (s,
Acknowledgements
2H), 7.25 (d,
J
= 8.0 Hz, 2H), 7.38 (d,
J = 8.4 Hz, 2H), 7.46 (d,
The authors thank Head, Department of Chemistry, Sardar Patel
University for providing necessary research facilities. VBP and
SCK acknowledge University Grants Commission–New Delhi,
India for UGC Basic Scientific Research Fellowship to
Meritorious Students awarded to them during 2013ꢀ2015. The
authors also acknowledge Dr. V. S. Patel, Director, SICART,
Vallabh Vidyanagar for elemental analysis at concessional
rates.
J
= 8.4 Hz, 2H), 7.73 (d,
J
= 8.0 Hz, 2H), 8.57 (s, 1H), 13C
NMR (400 MHz, DMSOꢀd6): δ 21.30, 52.65, 121.64, 125.57,
128.31, 129.27, 129.91, 130.35, 133.33, 135.49, 137.69,
147.22; FTꢀIR (KBr): 3120, 3061, 2925, 2850, 1609, 1433,
1358, 1343, 1221, 1162, 1043, 970, 922, 850, 762, 696 cmꢀ1,
Anal. Calcd. for C16H14ClN3: C, 67.72; H, 4.97; N, 14.81.
Found: C, 67.30; H, 4.49; N, 14.97.
3.4.12 2ꢀ(1ꢀ(4ꢀchlorobenzyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)pyridine (4l)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.68 (s, 2H), 7.33ꢀ
Notes
Department of Chemistry, Sardar Patel University, Vallabh
Vidyanagarꢀ 388 120, Gujarat, India
*Corresponding author. Tel.: +91ꢀ02692ꢀ226856 ꢀ Ext. ꢀ 208;
Fax: +91ꢀ02692 236475.
7.47 (m, 5H),7.89 (t, 1H),8.03 (d,
J = 7.6 Hz, 1H),8.59 (s, 1H),
8.70 (s, 1H), 13C NMR (400 MHz, DMSOꢀd6): δ 52.69, 119.89,
123.51, 123.96, 129.27, 130.42, 133.38, 135.43, 137.68,
148.01, 150.09, 150.31; FTꢀIR (KBr): 3106, 3082, 2947, 2925,
1641, 1595, 1571, 1540, 1452, 1420, 1342, 1223, 1045, 994,
781, 723, 704cmꢀ1, Anal. Calcd. for C14H11ClN4: C, 62.11; H,
4.10; N, 20.70. Found: C, 61.86; H, 3.87; N, 20.33.
Eꢀmail: vishalpurohit113@gmail.com , dipanalka@yahoo.com
The spectral data of synthesized compounds are shown in
supplementary data.
3.4.13 1ꢀ(4ꢀfluorobenzyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (4m)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 5.64 (s, 2H), 7.23 (t,
2H), 7.33 (t, 1H), 7.42ꢀ7.46 (m, 4H),7.84 (d,
J = 8.0 Hz,
References
2H),8.63 (s, 1H), FTꢀIR (KBr):3123, 3057, 2920, 2855, 1609,
1505, 1430, 1343, 1224, 1159, 1075, 1046, 973, 922, 849, 761,
696 cmꢀ1, Anal. Calcd. for C15H12FN3: C, 71.13; H, 4.78; N,
16.59. Found: C, 70.78; H, 4.68; N, 16.21.
1. A. J. Arduengo III, R. L. Harlow and M. Kline, J. Am. Chem. Soc.
1991, 113, 361.
,
2. (a) S. DíezꢀGonzález, N. Marion and S. P. Nolan, Chem. Rev., 2009,
109, 3612; (b) S. Roy and H. Plenio, Adv. Synth. Catal., 2010,
352, 1014; (c) L.ꢀA. Schaper, S. J. Hock, W. A. Herrmann and
F. E. Kühn, Angew. Chem. Int. Ed., 2013, 52, 270.
3.4.14 1ꢀ(4ꢀfluorobenzyl)ꢀ4ꢀ(pꢀtolyl)ꢀ1Hꢀ1,2,3ꢀtriazole (4n)
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.32 (s, 3H), 5.62 (s,
2H), 7.20ꢀ7.25 (m, 4H), 7.41ꢀ7.44 (m, 2H),7.72 (d,
J = 8.0 Hz,
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

Page 7 of 7
ARTICLE
RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4RA08412H
3. (a) A. J. Arduengo, Acc. Chem. Res., 1999, 32, 913; (b) W. A.
Herrmann, Angew. Chem. Int. Ed., 2002, 41, 1290; (c) H. D.
Velazquez and F. Verpoort, Chem. Soc. Rev., 2012, 41, 7032.
Saha, S. Sharma, D. Sawant and B. Kundu, Synlett, 2007,
2007, 1591; (c) I. Bae, H. Han and S. Chang, J. Am. Chem.
Soc., 2005, 127, 2038; (d) J. Zhang, J. Wu, L. Shen, G. Jin and
S. Cao, Adv. Synth. Catal., 2011, 353, 580.
4. (a) S. Díez‐González, A. Correa, L. Cavallo and S. P. Nolan, Chem.
Eur. J., 2006, 12, 7558; (b) S. DíezꢀGonzález and S. P. Nolan, 20. (a) J. R. Avalani, D. S. Patel and D. K. Raval, J. Mol. Catal. B:
Angew. Chem. Int. Ed., 2008, 47, 8881; (c) C. Gaulier, A.
Hospital, B. Legeret, A. F. Delmas, V. Aucagne, F. Cisnetti
and A. Gautier, Chem. Commun., 2012, 48, 4005; (d) F.
Enzym., 2013, 90, 70; (b) S. P. Satasia, P. N. Kalaria and D. K.
Raval, RSC Adv, 2013, , 3184; (c) P. N. Kalaria, J. A.
3
Makawana, S. P. Satasia, D. K. Raval and H.ꢀL. Zhu,
MedChemComm, 2014, 10.1039/C4MD00238E; (d) P. N.
Kalaria, S. P. Satasia, J. R. Avalani and D. K. Raval, Eur. J.
Med. Chem., 2014, 83, 655; (e) P. N. Kalaria, S. P. Satasia and
D. K. Raval, Eur. J. Med. Chem., 2014, 78, 207; (f) P. N.
Kalaria, S. P. Satasia and D. K. Raval, New J. Chem., 2014,
38, 1512; (g) P. N. Kalaria, S. P. Satasia and D. K. Raval, RSC
Lazreg, A. M. Z. Slawin and C. S. J. Cazin, Organometallics
2012, 31, 7969.
,
5. (a) R. P. Swatloski, J. D. Holbrey and R. D. Rogers, Green Chem.
,
2003,
5, 361; (b) M. T. Garcia, N. Gathergood and P. J.
Scammells, Green Chem., 2005,
7, 9; (c) D. Zhao, Y. Liao and
Z. Zhang, CLEAN – Soil, Air, Water, 2007, 35, 42; (d) M. A.
P. Martins, C. P. Frizzo, D. N. Moreira, N. Zanatta and H. G.
Bonacorso, Chem. Rev., 2008, 108, 2015.
Adv, 2014,
Raval, Eur. J. Med. Chem., 2014, 84, 51; (i) S. P. Satasia, P. N.
Kalaria, J. R. Avalani and D. K. Raval, Tetrahedron, 2014, 70,
4, 32353; (h) S. C. Karad, V. B. Purohit and D. K.
6. (a) C. Fleckenstein, S. Roy, Leuthau and H. Plenio, Chem. Commun.
,
2007, 10.1039/B703658B, 2870; (b) H. Ohta, T. Fujihara and
Y. Tsuji, Dalton Trans., 2008, 10.1039/B715412G, 379.
5763; (j) S. P. Satasia, P. N. Kalaria and D. K. Raval, Org.
Biomol. Chem., 2014, 12, 1751; (k) S. P. Satasia, P. N. Kalaria
and D. K. Raval, J. Mol. Catal. A: Chem., 2014, 391, 41; (l) P.
N. Kalaria, S. P. Satasia and D. K. Raval, New J. Chem., 2014,
38, 2902.
7. P. Anastas and N. Eghbali, Chem. Soc. Rev., 2010, 39, 301.
8. (a) M. S. Kerr, J. Read de Alaniz and T. Rovis, J. Am. Chem. Soc.
,
2002, 124, 10298; (b) A. E. Mattson, A. R. Bharadwaj, A. M.
Zuhl and K. A. Scheidt, J. Org. Chem., 2006, 71, 5715; (c) O. 21. M. Chtchigrovsky, A. Primo, P. Gonzalez, K. Molvinger, M.
Bortolini, G. Fantin, M. Fogagnolo, P. P. Giovannini, V.
Venturi, S. Pacifico and A. Massi, Tetrahedron, 2011, 67
Robitzer, F. Quignard and F. Taran, Angew. Chem., 2009, 121,
,
6030.
8110; (d) S. Singh, P. Mishra, M. Srivastava, S. B. Singh, J. 22. M. N. Tahir, R.ꢀu. Qamar, A. Adnan, E. Cho and S. Jung,
Singh and K. P. Tiwari, Green Chem. Lett. Rev., 2012,
5, 587.
Tetrahedron Lett., 2013, 54, 3268.
9. H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed.
,
23. O. Fleischel, N. Wu and A. Petitjean, Chem. Commun., 2010, 46,
2001, 40, 2004.
8454.
10. (a) V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, 24. C. Shao, G. Cheng, D. Su, J. Xu, X. Wang and Y. Hu, Adv. Synth.
Angew. Chem. Int. Ed., 2002, 41, 2596; (b) C. W. Tornøe, C.
Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057.
Catal., 2010, 352, 1587.
25. Y. M. Yamada, S. M. Sarkar and Y. Uozumi, J. Am. Chem. Soc.
2012, 134, 9285.
,
11. (a) T. Nakamura, T. Terashima, K. Ogata and S.ꢀi. Fukuzawa, Org.
Lett., 2011, 13, 620; (b) S. Hohloch, B. Sarkar, L. Nauton, F. 26. B. R. Buckley, S. E. Dann, D. P. Harris, H. Heaney and E. C. Stubbs,
Cisnetti and A. Gautier, Tetrahedron Lett., 2013, 54, 1808.
12. (a) J. F. Lutz, Angew. Chem. Int. Ed., 2007, 46, 1018; (b) J. E. Moses
and A. D. Moorhouse, Chem. Soc. Rev., 2007, 36, 1249.
13. M. Meldal and C. W. Tornøe, Chem. Rev., 2008, 108, 2952.
14. P. Thirumurugan, D. Matosiuk and K. Jozwiak, Chem. Rev., 2013,
113, 4905.
Chem. Commun., 2010, 46, 2274.
15. (a) C. Le Droumaguet, C. Wang and Q. Wang, Chem. Soc. Rev.
,
2010, 39, 1233; (b) R. B. N. Baig and R. S. Varma, Green
Chem., 2013, 15, 1839.
16. (a) S. Bräse, C. Gil, K. Knepper and V. Zimmermann, Angew. Chem.
Int. Ed., 2005, 44, 5188; (b) L. S. CampbellꢀVerduyn, L.
Mirfeizi, R. A. Dierckx, P. H. Elsinga and B. L. Feringa,
Chem. Commun., 2009, 10.1039/B822994E, 2139.
17. (a) W. Wang, J. Wu, C. Xia and F. Li, Green Chem., 2011, 13, 3440;
(b) C. Zhang, B. Huang, Y. Chen and D.ꢀM. Cui, New J.
Chem.
,
2013, 37
,
2606; (c) M. NasrꢀEsfahani, I.
MohammadpoorꢀBaltork, A. R. Khosropour, M. Moghadam,
V. Mirkhani, S. Tangestaninejad and H. Amiri Rudbari, J. Org.
Chem., 2014, 79, 1437.
18. J. Zhu and H. Bienaymé, Multicomponent reactions, John Wiley &
Sons, 2006.
19. (a) I. Kozawa, Y. Akashi, K. Takiguchi, D. Sasaki, D. Sawamoto, K.ꢀ
i. Takao and K.ꢀi. Tadano, Synlett, 2007, 2007, 0399; (b) B.
6 | J. Name., 2012, 00, 1-3
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