Zwitterionic liquid (ZIL) coated CuO as an efficient catalyst for the green synthesis of bis-coumarin derivatives: via one-pot multi-component reactions using mechanochemistry

Article abstract of DOI:10.1039/c6nj03763a

A convenient, solvent free strategy for the synthesis of bis-coumarins has been developed using zwitterionic liquid (ZIL) coated copper oxide (CuO) and mechanical ball milling. The ZIL were fabricated from imidazolium/benzimidazolium and sulfonate/carboxy

Full text of DOI:10.1039/c6nj03763a

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

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Zwitterionic Liquid (ZIL) Coated CuO as an Efficient Catalyst for the
Green Syntheses of Bis-Coumarins derivatives via One-Pot Multi-
component Reactions Using Mechanochemistry
Received 00th January 20xx,
Accepted 00th January 20xx
Mayank,a Amanpreet Singh,a Pushap Raj,a Randeep Kaur,b Ajnesh
Singh,c Navneet Kaurd and Narinder Singh*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
A convenient solvent free strategy for the synthesis of bis-coumarins has been developed using zwitterionic liquids (ZILs)
coated copper oxide (CuO) using mechanical ball milling. The zwitterionic liquids are fabricated of
imidazolium/benzimidazolium and sulfonate/carboxylate based moieties. The ZIL has offered an interesting
multifunctional opportunity to immobilize them over CuO through anionic part and the cationic part is freely available for
catalytic applications. The hybrid catalysts are fully characterized with scanning electron microscopy (SEM), transmission
electron microscopy (TEM), energy-dispersive X-ray (EDX), powder X-ray diffraction (PXRD), cyclic voltammetry (CV), solid
state UV-Vis absorption and emission spectroscopic methods. The three zwitterionic liquid based and CuO coupled hybrid
catalysts (ZIL@CuO1-3) have been generated with diversity in size, shape, photophysical signature and electrochemical
properties. The supramolecular assembly of ZIL and CuO in ZIL@CuO1 has extensively enhanced the catalytic activity as
compared to their parent components individually as well as other two tested hybrid materials ZIL@CuO2-3. Furthermore,
the reaction conditions are optimized through varying thenumber of balls, milling time and milling speed. The reaction
1
mechanism has been elucidated using H NMR spectroscopy and all the final products have been fully characterized with
spectroscopic methods. Finally, the performance of reaction at multi-gram scale is also detailed; high eco-scale score and
low E-factor are the most pleasing features of the methodology; thus authenticate its use for eco-friendly synthesis of bis-
coumarins and offers the advancements over the existing literature.
demand because this category of compounds have pronounced
Introduction
pharmacological
activities
including
anti-inflammatory,10
13
antimicrobial,11 antiviral,12anti-coagulant,13 and anti-cancer
;
Heterocyclic compounds are the backbone of the medicinal
chemistry possessing therapeutic efficacy varying from simpler COX
inhibitors to complex signaling cascades.1-4 On the other hand, the
heterocyclic compounds are the integral part of biological system
such as genetic material, energy sources, structural as well as
enzymatic proteins.5 Thus, to understand the bio-chemical
processes and development of new chemical entities (NCEs)
synthetic strategies are reported and nevertheless, there is room
for the improvement to cater the need of sustainable
which warrant these as attractive moiety in drug designing.13 Within
the context of improved methods for coumarin derivatives; the
green synthetic approach is the significant progression toward the
sustainable development of pharmaceutical industry and hence
some serious efforts have been made in this direction.14 The ball
milling is smart green synthetic methodology, which involves
solvent free synthesis of organic molecules and even prominent for
one pot multicomponent reactions including oxidations, reductions,
condensations, Wittig reactions, asymmetric Michael addition
reactions, Baylis–Hillman reactions, 1-3,dipolar cycloaddition,
enamine formation, transition metal-catalyzed coupling reactions
and synthesis of pyrimidines and variety of heterocycles.15-
20Furthermore, many metal catalysts have been fabricated and
successfully used for the synthesis of multiple compounds such as
pyrimidine derivatives,21 C-C bond formation,22 amino andhydroxyl
substituted dehydrophenylalanine derivatives,23benzothiazole,
benzimidazole andbenxoxazole derivatives.16The synthesis of bis-
coumarins using ball milling with efficient catalyst having high eco-
scale score (Table ST1, supplementary information)16 and low E-
factor (Table ST2)16 is relatively unexplored research arena. Under
present investigation, we have made attempts to improve the
shortcomings of existing methodologies in terms of green solvent;
energy source and catalyst reuse ability(Table ST3). To achieve the
desired objective, we have engineered supramolecular catalysts,
7
development.6, In general, the new synthetic strategy must
sculpture the complex molecular structure from the easily
accessible commercial building blocks.7 However, majority of
reported methods involves the extensive use of organic solvents
and tedious post reaction workup which restrict its industrial scale
9
up-gradation.8, Moreover the drawbacks including low yield,
catalyst reuse inability and thus improved method for the synthesis
of heterocyclic compounds such as coumarin derivatives is of high
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which are fabricated of zwitterionic liquids (ZILs)(Figure 1) coated Singe crystal X-ray structure determination revealed that compound
copper oxide (CuO).
ZIL1 crystallizes in triclinic crystal system and consists of two
molecules of compound ZIL1. Two oxygen atoms O4 and O5 of
carboxylic groups are disordered over two positions each. One of
the carboxylic group present on ZIL1 is unionized while other is
ionized which is counter balancing the positive charge of
imidazolium nitrogen atom. The ORTEP diagram along with atom
numbering scheme of complex is shown in Figure 2. The selected
bond lengths and bond angles are given in Table ST4. In the crystal
lattice, different moieties are interacting with each other through
O-H…O hydrogen bonding which result in formation of chains of
ZIL1 moieties. These chains are held together in crystal lattice
through number of C-H…O hydrogen bonds and π−π stacking
interactions whereas distance between centroids of two phenyl
rings is 3.666Å, while the closest C…C distance is C6…C18= 3.355 Å.
The packing diagram of compound ZIL1 is shown in Figure SF1
(Supplimentary information). The hydrogen bonding parameters are
given in Table ST5.
O
O
O
O
S
O
O
O
N
N
N
N
N
N
OH
O
(ZiL2)
(ZiL1)
(ZiL3)
Figure 1. Chemical structures of zwitterionic liquids ZIL 1-3.
The motivation for the use of hybrid assembly of ZIL@CuO is due to
the distinctive implementation of such type of ILs in heterocyclic
synthesis, Biginelli reaction,24 alkylation reaction,25 Diels-Alder
reaction26 and Michael addition reaction27 and multicomponent
reactions. Furthermore, excellent organic transformations were
introduced using ILs/ZILs-metal hybrid system showing its
importance in organic synthesis. 16, 28-30In this context, CuO was also
investigated as versatile catalyst for multiple organic
32
transformations.31,
We envisioned the hybrid assembly of
ZIL@CuO as efficient and reusable catalyst fulfilling special
requirements in solvent free synthesis. The cationic part of ZIL is
Our mandate is to perform the solvent free synthesis using
ball mill; and metal oxides have been used to comply the catalysis in
ball mill.38 Hence, to realize the synergistic catalytic effect of ZIL and
metal oxide; we have used the ZILs as structure directing agents as
well as catalytic module with CuO. In general, structure directing
agents immobilize themselves on the surface of the metal oxide and
determine the size, shape and morphology of the final catalyst. The
hybrid catalysts ZIL@CuO were prepared using sol-gel method.38, 39
Copper nitrate was dissolved in 100 ml of double distilled water to
form 0.1 M solution. The ZILs were than incorporated to the
aforementioned solution. The resulting solution was stirred
vigorously for fifteen minutes. Finally, 0.1 M solution of NaOH was
added dropwise to the vigorously stirred solution. Refluxing for 2 h
was performed to get ZIL@CuO1-3. Similarly, bare CuO
nanoparticles without ZIL were also produced and precisely
controlled identical conditions were applied in all cases. The as-
prepared ZIL@CuO1-3 were characterized with SEM, TEM, powder
XRD and their size distribution was realized with DLS based particle
size analyzer (Figure 3). The SEM analysis of ZIL@CuO1 (Figure 3,
A)has shown the formation of flakes, which is expected due to the
bidentate nature of ZIL1. Thus, it is expected that two carboxylate
group of each ZIL1 are not coordinating with same CuO particle
rather they are diverging to coordinate with different CuO and
hence endorsing the formation of sheet. Moreover, the flakes are
arranged in a particular pattern, presumably due to the π- π
stacking prevailed in the benzimidazolium moieties as clearly
noticed in the crystal structure of ZIL1. Unlike ZIL1, the ZIL2-3 are
the unidentate ligands; thus, they are not anticipated to yield any
supramolecular assembly and as per expectation, TEM images of
ZIL@CuO1-3 further clarified the fact. In case of ZIL@CuO1 (B)
supramolecular assembly production was anticipated by the TEM
images. TEM images of ZIL@CuO2-3 (C and D respectively) showed
the formation of spherical particles. Furthermore, PXRD studies
were performed for CuO as well as ZIL@CuO1-3. The PXRD pattern
of CuO (E) clarified the single phase CuO nanoparticles formation.
composed
of
imidazolium/benzimidazolium;
while
the
sulfonate/carboxylate are the anionic moieties. The ZILs are
designed in such a way that they must present multifunctional
prospects such as anionic part immobilize them over CuO and the
cationic part obligate the synergistic catalysis in augmentation to
CuO. Herein, solvent free synthesis tends to reduce wastage of
organic solvents as in solvent mediated synthesis (ST 3) resulted to
penalty pointsin green chemistry metrics of the reaction.
Results and Discussion
ZIL coating and structurally diverse ZIL@CuO formation:ZILs are
the special class of ionic liquids (ILs), which are composed of
cationic part prevailed in ionic liquids.33 The choice of such types of
ZILs is based upon the splendid activities of ILs as catalysts in
organic synthesis mostly due to precise control over
Bronstead/Lewis acidity that is mandatory for widespread catalytic
activities.25 Moreover, the ILs are the foremost choice of synthetic
chemists due to their least vapor pressure, ability to solubilize wide
range of compounds, reusability and recyclability associated with
them. 34, 35 In order to customize the catalytic activities required for
the eco-friendly synthesis of bis-coumarins; the ZIL1-3 were
planned with diversity in the cationic and anionic part and were
37
synthesized using reported methods.36,
The ZIL1-3 were
characterized with NMR Spectroscopy, elemental analysis and the
zwitterionic structure of ZIL1 was illustrated with the single crystal
structure (Figure 2).
Figure 2.ORTEP diagram along with atom numbering scheme of
complex ZIL1 with 40% probability thermal ellipsoids
2 | J. Name., 2012, 00, 1-3
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The diffraction data was found to be in good agreement with the ZIL@CuO1(F), ZIL@CuO2 (G) and ZIL@CuO3 (H) were found to be
JCPDS card of CuO (JCPDS 80- 1268). Average crystallite size (L) was 447 nm, 100 nm and 85 nm respectively. Thus, size distribution for
ZIL@CuO1 was significantly higher compared to ZIL@CuO2&3. The
EDX data was recorded to confirm the presence of organic part
along with CuO. In case of ZIL@CuO1 along with base element
copper and oxygen, carbon as well as nitrogen was also observed
(I). Similarly carbon and nitrogen for ZIL@CuO2 (J) and carbon,
nitrogen and sulfur for ZIL@CuO3 (K)along with copper and oxygen
were confirmed through EDX data. The abovementioned results are
in well agreement with elements profile of ZIL1-3 and provided
evidences for the presence of proper ZIL coating on the surface of
calculated using Scherrer’s equation “L = 0.9λ/βCosθ” where λ is
the X-ray wavelength (1.5405 Å), and β is full width at half
maximum in radian. The Crystallite size calculated for bare CuO and
ZIL@CuO1-3 was found to be 25, 8, 17 and 21 nm respectively. The,
significant change in PXRD pattern compared to CuO, was observed
for ZIL@CuO1-3 and crystallinity was thus extensively changed
upon ZIL coating. Major variation was observed for ZIL@CuO1;
while for ZIL@CuO2-3 are expected to produce similar size. DLS
histograms were also recorded to quantify the average size and size
distributions of catalysts produced. The average size of
CuO
nanoparticles
for
ZIL@CuO1-3.
A
B
C
D
E
F
G
H
I
K
J
Figure 3. (A), SEM images of ZIL@CuO1; (B-D), TEM images of ZIL@CuO1-3;(E), PXRD of ZIL@CuO1-3; (F-H),DLS of ZIL@CuO1-3 and (I-K),
EDX of ZIL@CuO1-3respectively.
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Photophysical properties of ZIL@CuO: The Lewis acid directed ZIL coating tends to change theelectrochemical behaviour in case
catalyst may govern through the photophysical signature of the of ZIL@CuO1-3: The electrochemical behaviour of ZIL@CuO1-3
catalyst and thus possibly these properties may decide the fate of were studies through cyclicvoltammetry in aqueous medium
reactivity. In this intension, the photophysical properties are containing 0.1 M tetrabutyl ammonium perchlorate as a supporting
evaluated by recording the UV-Vis absorption and emission spectra electrolyte using Ag/AgCl and Pt based electrodes. The parameters
of ZIL@CuO1-3 (Figure 4, A&B respectively);further the results are used include 1500 mV as initial as well as final potential and -1500
compared with the pure CuO.When ZILs were used as surface mV as switching potential. The redox behavior of ZIL@CuO1
directing agent in the synthesis of ZIL@CuO1-3 through sol-gel showed cathodic peak at - 0.549 mV corresponding to Cu2+ /Cu and
method, the absorption spectrum should depicted changes anodic peak occur at - 0.344 mV attributed to Cu/Cu2+ 44
. The redox
compared to CuO, happening in the system during nucleation and process of ZIL@CuO1 are quassi-revesible in nature which was
crystal growth of ZIL@CuO1-3. The solid state absorption confirmed through scan rate experiment. It was observed from the
spectrums of precipitated ZIL@CuO1-3 were recorded and results
were compared with solid state absorption spectrum of bare CuO.
The spectrum of bare CuO revealed clearer and broad band which
became diminished with ZIL@CuO1-3. Further, blue shift in case of
ZIL@CuO1-3 with respect to bare CuO was also observed. Based on
the absorption profile, by implementing tauh plot, band gap for
CuO and ZIL@CuO1-3 was established. Band gap for CuO was found
to be 1.3 eV, which was exactly as documented in literature.40 For
ZIL@CuO1-3 the band gap was comparatively higher and found to
be 1.7, 2.1 and 1.9 eV respectively. With the availability of capping
agents as in case of ZIL@CuO1-3, size of produced nanoparticles
tends to reduce compared to bare CuO. Here, size dependency of
band gap in case of nanoparticles was found to be inversely allied
and is correlating with already documented results.41 To understand
the emission profile of materials at room temperature the
fluorescence spectra of ZIL@CuO1-3 have been surveyed with
excitation at 330 nm. The CuO has exhibited the emission at 402 nm
and this is described as band edge emission of CuO.42 However, the
ZIL@CuO1-3 have pronounced broad band and it is plausible to
deconvulate this band into different emission states on account of
defect-related emission or surface impurities including intrinsic
defects, interstitial metal ions, and oxygen vacancies survived
during crystal growth of CuO.43
scan rate experiment that the δE value is greater than 59/n mV and
increase with increase in the scan rate. The ratio of cathodic peak
current to anodic peak current is also morethanone (Ic/Ia>1). These
result confirmed the quassi-revesible redox behaviour of
ZIL@CuO1. Furthermore,
a linear correlation was observed
between cathodic peak current versus square root of scan as shown
in figure SF2. The slope of the linear curve is used to calculate the
diffusion control of Cu2+/ Cu by applying Randles–Sevcik equation 45
Icp = 0.4463nFAc(αnFDv/RT)1/2
Here, Icp, A, D, C, R, T, α, n, and, F represents cathodic peak current,
electrode area, diffusion coefficient, concentration of ZIL@CuO1,
gas constant, absolute temperature, transfer coefficient, electron
transfer number and faraday coefficient respectively. Further, to
calculate the value of αn the following equation can be used.45
|Ecp - Ecp/2| = 1.857RT/αnF
Similarly, The cathodic peak potential of ZIL@CuO2 and ZIL@CuO3
shown at -0.507 mV and –0.637 mV corresponding to Cu2+/ Cu and
the anodic peak potential shown at
– 0.476, 0.457 mV.
Furthermore, in the similar manner quassi-reversible nature in case
of ZIL@CuO2&3 was also observed using scan rate experiment.46
Finally, the diffusion coefficient was calculated and in case of
ZIL@CuO1 it was found to be 1.38 x 10-7. The diffusion coefficient
for ZIL@CuO2 and ZIL@CuO3 was found to be 3.32 x10-7 and 9 x 10-
B
A
7
respectively. Further, the redox behaviour of ZIL@CuO1-3 were
compared with the bare CuO as well free ionic liquid (Figure 5) and
the redox data were summarized in table ST6. The experimental
data clearly confirmed that the peak current density was high in
case of ZIL@CuO1-3 compared to bare copper oxide as well as ionic
liquid which is due to the high porosity associated with these
materials.47 The porous nature enhances the surface reactivity
andcatalytic efficiency of the catalyst which was later confirmed
from their application part.
Figure 4. (A) Solid state UV-Vis absorption spectra of CuO and
ZIL@CuO1-3 (B) Solid state emission profile of ZIL@CuO1-3.
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A
B
supramolecular assembly with significantly higher size and surface
area was produced (A). In case of CuO@ZIL2-3 simpler assemblies
were constructed (B and C respectively). Further, ZIL@CuO1-3 was
calcined at 500 oC for 5h and PXRD were taken again (Figure SF3).
The PXRD pattern obtained showed typical peaks of CuO in all the
cases. Thus, difference created in PXRD of ZIL@CuO1-3 was due to
surface coating which was burned away upon calcination.
D
C
E
(C)
(B)
(A)
F
Figure 7.Structural feature of ZIL@CuO1 (A), ZIL@CuO2 (B) and
ZIL@CuO3 (C) catalysts produced in our study
Surface properties and acidic strength of CuO and ZIL@CuO1-3:
Furthermore, to analyze the surface behaviour of CuO and
ZIL@CuO1-3, BET studies were performed. The surface area (SA),
pore volume (PV) and average pore diameter (APD) is represented
in Table 1. Compared to CuO, SA, PV and APD were found to be
increased in case of ZIL@CuO1-3. Herein, ZIL@CuO1 have shown
extensive increase in SA, PV and APD based parameters. N2
adsorption isotherm of CuO and ZIL@CuO1-3 is also represented in
Figure 8. In case of ZIL@CuO1, the isotherm was also distinctively
changed compared to CuO and ZIL@CuO2-3.
Figure 5. (A-C), comparative CV profile of ZILs, CuO, ZIL-Cu complex
and ZIL@CuO for ZIL1, 2 and 3 respectively;(D-F), scan rate data for
ZIL@CuO1, 2 and 3 receptively with increasing scan rate.
Surface coated ZIL quantification: The thermal stability and
composition of the ZIL@CuO1-3 were further investigated
using TGA analysis (Figure. 6).
Table1.N2 adsorbed BET measurements of CuO and ZIL@CuO
Sr
No.
Catalyst
Surface Area Pore
Average Pore
Diameter (nm)
m2/g
Volume
cc/g
1
2
3
CuO
8.5
0.035
0.086
0.038
3.3
4.291
4.243
ZIL@CuO1 28.4
ZIL@CuO2 18
4
ZIL@CuO3 12
0.047
3.7
Figure 6. TGA graph of CuO and ZIL@CuO1-3 engineered during
study
Initial weight loss in case of CuO and ZIL@CuO1-3, it was
showing from 50 to 150 °C, was due to the loss of water or some
organic solvent. Thereafter, no considerable weight loss was
observed for bare CuO; however, weight loss in case of ZIL@CuO1-3
was observed and indicating the decomposition of coated ZILs.
Here,ZIL@CuO1, showed about 26%, ZIL@CuO2 showed 13% and
ZIL@CuO3 showed 12% weight loss, which represents the fraction
of ZILs coated on CuO nanoparticles. 48 Thus, higher fraction of ZIL1
coating was established for CuO@ZIL1 compared to CuO@ZIL2-3.
Finally, on the basis of structure aspect of ZILs as well as
experimental evidences, models of ZIL@CuO1-3 were proposed
(Figure 7). Accordingly, in case of ZIL@CuO1 meshwork like
Figure8. N2 adsorption isotherm of CuO and ZIL@CuO1-3
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Finally, the acidic strength of CuO and ZIL@CuO1-3 were calculated, diameterwere significantly higher compared toCuO. The result
using titrametric analysis.49 Herein 10 mg of CuO and ZIL@CuO1-3, signifies the role of structural parameters of engineered catalysts in
were dissolved separatelyin 10 ml of 0.5N, HCl solution and stirred determining the yield of the reaction. Thus, it is not only the ZIL
for half an hour. CuO NPs tends to neutralize the HCl, whereas based coator core CuO material; however the structural feature of
remaining portion of HCl was estimated via back titrated using 0.5N catalysts as a whole is also critical in determining the rate of the
sodium hydroxide solution. The results obtained are as represented reaction. The, highest yield obtained for ZIL@CuO1 is attributed to
in Table 2.Herein maximum basic strength per unit area was the exceedingly efficient morphological aspect (Figure 3; A) as well
observed in case of ZIL@CuO1 followed by ZiL@CuO2-3. Whereas as maximum surface area, porosity and pore diameter of ZIL1in
bare CuO have shown least basic strength per unit area.
case of ZIL@CuO1 (Table 1).
Table 3. Yield at the end of 180 min of milling using different forms
Table 2.Acidic strength calculation for CuO and ZIL@CuO
Sr.
No
Catalyst
0.5N HCl Basic unit (RBA)
Relative Basic
units
(RBA/1.95)**
Volume#
count
(BU)
mmol*
Sr.
No
Catalyst Specification
Catalyst Code
Yiel
d %a
__
No Catalyst
CuO
50
69
72
1
2
3
(mmol)##
1.95
Copper Oxide
1
2
CuO
0.65
1.95
4.67
1
1,3-bis(carboxymethyl)-1H-
benzo[d]imidazol-3-ium bromide
3-(carboxymethyl)-1-methyl-1H-
imidazol-3-ium
(1-methyl-1H-imidazol-3-ium-3-
yl)methanesulfonate
1,3-bis(carboxymethyl)-1H-
benzo[d]imidazol-3-ium bromide
Coated on CuO-NPs
3-(carboxymethyl)-1-methyl-1H-
imidazol-3-ium coated on CuO-NPs
(1-methyl-1H-imidazol-3-ium-3-
yl)methanesulfonate coated CuO-
NPs
ZIL1
ZIL@CuO1 0.45
1.4
2.4
3
4
ZIL@CuO2 0.54
ZIL@CuO3 0.57
1.62
1.71
3.43
2.41
1.75
1.23
ZIL2
68
64
92
4
5
6
ZIL3
# Volume of 0.5N HCl require to neutralize 1 mg catalysts
(ml)Calculated via Back Titration, ## Number of units equivalent to
“OH” present in 1 mg of sample, *Relative surface area based
exposure of basic units to reactants, calculated using formula BU X
Surface area of catalyst/Surface area of CuO (Surface areas from
table), ** Calculated using formula RBU X RBU/RBU for CuO
ZIL@CuO1
ZIL@CuO2
ZIL@CuO3
81
80
7
8
Investigation/optimization of catalytic behaviour of ZIL@CuO1-
3: The
reaction
between
4-hydroxycoumarin
and
4-
a. Yield calculation was based on integration of 1H NMR signals
.
hydroxybenzaldehyde was selected as a model reaction (Figure 9).
Further time dependent 1H NMR spectrum for the reaction
between 4-hydroxycoumarin and 4-hydroxybenzaldehyde was
taken at different interval of time (Figure 10).At 0 min of time,
typical reactant specific signals were observed; then gradual
elimination of reactant specific signals at 5.5 and 9.6 clearly
indicated that reactants were steadily consumed during the
reaction process.
OH
O
O
HO
OH
O
OH
O
Catalyst, Ball mill rt
balls, (45, 5mm); 600 rpm
Continuous
O
OH
OO
4-Hydroxycoumerin
4-Hydroxy benzaldehyde
Compound (1)
Figure 9. Reaction scheme utilized to validatethe reaction condition
In this typical reaction, 2 equivalent of 4-hydroxycoumarin, 1
equivalent of 4-hydroxybenzaldehyde and 0.5 mole% of catalyst
were taken in tungsten carbide ball mill without any solvent and
allowed to grind upto 240 minutes at the speed of 600 rpm. In
order to optimize the reaction at different intervals of time; 1H NMR
of crude reaction mixture was obtained to analyze the efficacy of all
combination of catalysts. The results obtained with variation in
catalyst for the reaction at the end of 180 minutes is summarized in
Table 3. The results clearly indicated that ZIL@CuO1-3 significantly
increased the rate of the reaction compared to parent ZIL or CuO
with highest yield of 92% as observed for ZIL@CuO1. In case of
ZIL@CuO1-3 surface area, pore volume and average pore
Figure 10. Time dependent 1H NMR spectrum for the reaction
between 4-hydroxycoumarin and 4-hydroxybenzaldehyde at
different interval of time
6 | J. Name., 2012, 00, 1-3
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Similarly, the appearance of product specific signals at 6.1 indicated well as1HNMR based evidences, potential impact of temperature on
the product formation during the milling condition. At the end of yield of the reaction was justified and the catalytic cycle of
180 minutes the reactant specific peaks were almost eliminated and ZIL@CuO1-3 was further purposed (Figure 11)
further milling produced least effects on the NMR spectrum profile
of the same.
Other reaction conditions including milling speed, ball to
powder ratio and reactant load were also validated to optimize the
reaction scheme. To optimize the parameters, we have used 1H
NMR studies of reaction mixture at different time interval and
monitored the progress of the reaction (Table ST7). The results
obtained clearly indicated that with the increase in milling time
there was continuous increase in yield up to certain edge. The,
milling time of 180 min and speed of 600 rpm was found to be
optimum. Furthermore, at a constant milling time of 180 min,
change in milling speed also tends to influence the rate of the
Figure 11. Plausible catalytic mechanism of ZIL@CuO1-3for the
reaction. Increase or decrease in milling speed from 600
reaction
rpmdecreased the yield of reaction. The aforementioned
The catalytic cycle of ZIL@CuO initially include adsorption of
observations were obvious because catalytic activity depends upon
reactant molecules on the surface of ZIL@CuO. When reactants get
adsorption phenomenon. Thus, increase in milling speed in one
adsorbed on the surface of the catalyst, favorable orientation was
hand tends to intensify the heat productions required to fulfill the
provided and catalytic cycle was initiated (Figure 11). Initial,
activation energy need of the reaction resulted in increased yield.
nucleophilic attack of 4-hydroxycoumarin occurred on the
On the other hand continuous increase in milling speed produced
aldehydes. Here, in this step ZIL@CuO1 activates aldehydes
resulted in enhanced rate of the reaction.52 Finally second attack of
excessive vibrations as well as heat thus, facilitating surface
desorption of reactants from catalyst and resulted in decrease
4-hydroxycoumarin resulted in formation of bis-coumarin with
catalytic efficacy. Further, to evaluate the actual link between
regeneration of catalyst. Here coated ZILs as well as associated CuO
reaction time and heat produced, a reaction was carried out in a
both have the ability to catalyze the reaction, thus synergistic effect
typical jar having special lid and a transmitter. Temperature was
is observed. Finally, using aforementioned optimized conditions
monitored using EASY-GTM software (Table ST8). Experiment was
various other bis-coumarin analogs have also been synthesized
carried out for about one hour and results specified that
(Figure 12). To purify the product the reaction mixture was washed
temperature produced during milling condition is proportional to
with water several times. Finally, it was suspended in 10 ml of
the milling time of the reaction.50According to the literature based
methanol to separate the products. The yield obtained was found
evidences,the temperature produced inside the jar during milling is
to be more than 90% in all the cases (Figure 12). The involvement of
unevenly distributedwhereas, because of the mixing process,
green solvents is also a distinguishable factor, creating its real utility
material inside the milling jar get exposed to different temperature
range. 50Herein, average temperature range exposed by reactant
towards industrial scale up-gradation.
OH
molecules at milling time of 180 min and milling speed of 600 rpm
was found to be optimum whereas adsorption as well as activation
energy needs are sufficiently satisfied and thus, producing
maximum yield.The number of balls used is also an important
parameter as with the increase in its number, collision frequency
increases and resulted inheat production. Experiment was carried
out with increasing number of balls and taking other parameters
constant and 45 balls (5mm size)produced maximum yield (Table
ST9).Furthermore, to investigate the ball to powder ratio, the
reaction was performed using varied amount of reactant molecules
and yield was found to be almost unaffected up to 1 mmol-20mmol
of reactant range.Finally,proportion of 4-hydroxycoumerin and 4-
hydroxy benzaldehyde was also adjusted to 2.5:1, whereas the
efficacy of the catalyst was found to be unaffected but atom
economy gets compromised.
OH
OH
HO
N
OH
HO
OH
OH
HO
OH
O
OH
O
O
O
O
O
O
O
OO
(1) 90%
N
O
O
O
O
O
O
(2) 91%
(3)93%
(4)90%
N
NO2
HO
OH
HO
OH
OH
HO
O
O
O
O
O
O
O
O
O
O
O
O
(7)
(6)94%
94%
(5)
93%
OH
OH
OH
HO
OH
HO
OH
OH
OH
HO
O
O
O
O
O
O
O
O
O
(8)
O
(9)
95%
O O
92%
(10)90%
O
Cl
NO2
O
O
OH
O
OH
HO
OH
OH
HO
OH
O
OH
O
O
O
O
O
O
O
O
O
OO
O
O
O
O
91%
(13)
95%
(14)
(12) 92%
(11)93%
Thus, considering the influence oftemperature inside the jar,
and its correlation with milling time, ball number, milling speed51 as
Figure 12. Structure along with yields of compounds synthesized
using ball milling based strategy
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ARTICLE
Journal Name
The maximum catalytic efficiency was observed for ZIL@CuO1 recovered catalyst after fifth (A and B) and tenth run (C and D) of
followed by ZIL@CuO2-3 and least for CuO. Herein, Both ZIL and the reaction is shown in Figure 14.
CuO have the tendency to catalyze the reaction in some extend and
B
A
thus hybrid of both the components, resulted in synergistic effect
causing increased reaction rate in case of ZIL@CuO1-3 compared to
bare CuO. Furthermore, as observed in case of BET analysis, SA, PV
and APD is increased in case of ZIL@CuO1-3 as compared to CuO.
Moreover, relative basic units (Units equivalent of “OH” of base)
were also increased for ZIL@CuO1-3. Thus also along with high
surface area provided by ZIL@CuO1-3 compared to CuO other
parameters were also favourably modified in case of ZIL@CuO1-3
resulting in increased yield. Herein, ZIL@CuO1 provided maximum
SA, PV, AVD and relative basic units and thus yield obtained was
also maximum.
C
D
Single crystal XRD pattern of one of the synthesized compound
i.e.
3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-2H-chromen-2-
Figure 14. (A-B), SEM and DLS images of ZIL@CuO1 after fifth cycle
and (C-D),SEM and DLS images of ZIL@CuO1 after fifth cycle
one), (12) was solved for the purpose of characterization. It
crystallizes in triclinic crystal system with space group P-1 and
consists of two molecules. The ORTEP diagram along with atom
numbering scheme of complex is shown in Figure 13.
The obtained SEM images clearly revealed that the surface texture
of ZIL@CuO1 was significantly changed after fifth (A) and tenth (C)
cycle of the reaction. Furthermore, in case of DLS study, average
size of catalyst was found to be 380 nm after fifth cycle (B) and at
the end of tenth cycle average size was reduced andbecame 290
nm. Herein, notable reduced size and thus significantly increased
surface area as well as formation of entirely new surface
morphology was observed, that was also found to be equally
efficient and thus producing significant yield as observed up to
tenth cycle of the reaction.
Conclusion
We have validated simple and efficient solvent free protocol for the
synthesis of bis-coumarin derivatives using ZIL coated CuO NPs as a
catalyst using ball milling technique. The advantages provided
include high yield, recyclable catalyst as well as easy workup
method. Furthermore, industrial scale upgradability is the major
advantage provided by it over conventional methods. Green
chemistry aspect is also covered with the used of least solvent
during purification of product. Water and methanol which are the
only solvents used belongs to the preferable category of green
solvent. Thus, we have developed method which is environment
friendly, and is applicable for laboratory as well as industrial scale
application.
Figure 13. ORTEP diagram along with atom numbering scheme of
3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one),
(12)with 40% probability thermal ellipsoids
The selected bond lengths and bond angles are given in Table ST10.
In the crystal lattice, different moieties are interacting with each
other through O-H…O and C-H...O hydrogen bonding interactions
(Figure SF4). The hydrogen bonding parameters are given in Table
ST11. Finally, characterization of all the compounds was done using
1H and 13C as well as elemental analysis.
The recovery and reusability of catalyst is one of the major
factors to determine the cost effectiveness of the developed
method. After the completion of the reaction, the reaction mixture
was washed with water and finally suspended in 10 ml of methanol
to precipitate the product. Finally, remaining water and methanol
fraction was centrifuged at 8000 RPM for 5 min. The solid fraction
so obtained was washed using 10 ml of methanol and finally with
10 ml of methanol-acetone mixture (1:1, v/v) to recover the
catalyst. Recovered catalyst was further used for the reaction. The
catalytic efficiency of ZIL@CuO1 was checked up to tenth cycle of
reactionwhich remained unaffected. SEM and DLS investigation of
Experimental section
Materials: The starting materials were procured from various
suppliers. Benzimidazole, bromoacetic acid, 1-methyl imidazole and
bromo-sulfonic acid used for the synthesis of ZILs were obtained
from Sigma Aldrich. Cuppric nitrate and sodium hydroxide used for
the development of NPs were obtained from LobaChem and SDFCL
respectively. Major reactants including 4-Hydroxycoumarin and
benzaldehyde derivatives were again procured from Sigma Aldrich.
8 | J. Name., 2012, 00, 1-3
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ARTICLE
Synthesis and characterization of Ionic liquids: ZILs were added dropwise to the vigorously stirred solution and refluxed for 2
synthesized using chemical reaction. For the synthesis of ZIL1, h. The nanoparticles formed were characterized by SEM, TEM, EDX,
benzimidazole (1 eq) andbromoacetic acid (2 eq) were dissolved in CV and DLS based methods. The precipitates obtained were filtered
acetonitrile. The pH was adjusted to 8 using sodium hydroxide and washed and dried at 80 oC under vacuum condition. The dried
refluxed for 6 h. After the completion of reaction pH was adjusted precipitates were further characterized using PXRD, solid state UV
to about 2-3 to separate product. Synthesis of ZIL2was done by and fluorescence spectroscopic methods.
refluxing 1-methyl imidazole (1 eq) and bromo acetic acid (1 eq) at
80 oC using acetonitrile as a solvent. ZIL3 was done using method
Synthesis and characterization of bis-coumarin derivatives:
Grinding beaker of 80ml with 45 balls(5 mm) were used to perform
the synthesis of bis-coumarin. The grinding beakers as well as balls
were made up of tungsten carbide. A concoction of 2 equivalents of
4-hydroxycoumerin, 1 equivalent of benzaldehyde derivatives and
similar to ZIL2 by using bromo-sulfonic acid instead of bromoacetic
acid. The synthesized ZILs were characterized using 1H, 13C NMR
spectroscopy (Figure SF5-7) and elemental analysis method.
Catalyst development and characterization: CuO nanoparticles 0.5 mol% catalyst were taken in grinding beaker and milling was
were prepared using method reported in literature 53. Initially, performed continuously for 180 min at the speed of 600 rpm.
copper nitrate was dissolved in 100 ml of double distilled water to Finally, crude reaction mixture was washed with water and
form 0.1 M solution. The ZILs were than incorporated to the suspended 10 ml of methanol to get pure product. NMR technique
aforementioned solution. The resulting solution was stirred (Table ST 12 &Figure SF 8-21) and elemental analysis was used to
vigorously for fifteen minutes. Finally, 0.1 M solution of NaOH was characterize the product.
17.
18.
19.
M. Vashishtha, M. Mishra and D. O. Shah, Green Chem.,
2016, 18, 1339-1354.
A. Stolle, T. Szuppa, S. E. Leonhardt and B. Ondruschka,
Chem. Soc. Rev, 2011, 40, 2317-2329.
A. Stolle, Ball milling towards green synthesis:
applications, projects, challenges,Royal Society of
Chemistry, 2014.
R. Thorwirth and A. Stolle, Synlett, 2011, 2011, 2200-
2202.
T. Raj, H. Sharma, Mayank, A. Singh, T. Aree, N. Kaur, N.
Singh and D. O. Jang, ACS Sus. Chem. Eng., 2017, DOI:
10.1021/acssuschemeng.6b02030.
F. Schneider, A. Stolle, B. Ondruschka and H. Hopf, Org.
Process Res. Dev., 2008, 13, 44-48.
S. L. James, C. J. Adams, C. Bolm, D. Braga, P. Collier, T.
Friščić, F. Grepioni, K. D. Harris, G. Hyett and W. Jones,
Chem. Soc. Rev., 2012, 41, 413-447.
J. Peng and Y. Deng, Tetrahedron Lett., 2001, 42, 5917-
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Q. Zhang, S. Zhang and Y. Deng, Green Chem., 2011, 13,
2619-2637.
C. E. Song, W. H. Shim, E. J. Roh, S.-g. Lee and J. H. Choi,
Chem. Commun., 2001, 1122-1123.
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B. Zhang and N. Yan, Catalysts, 2013, 3, 543-562.
J. Isaad, RSC Adv., 2014, 4, 49333-49341.
H. Singh, J. Sindhu, J. M. Khurana, C. Sharma and K. Aneja,
Eur. J. Med. Chem., 2014, 77, 145-154.
K. Tokarek, J. L. Hueso, P. Kuśtrowski, G. Stochel and A.
Kyzioł, Eur. J. Inorg. Chem., 2013, 2013, 4940-4947.
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Acknowledgement:
Mayank is thankful to IIT Ropar for fellowship
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DOI: 10.1039/C6NJ03763A
Zwitterionic Liquid (ZIL) Coated CuO as an Efficient Catalyst for the Green
Syntheses of Bis-Coumarins derivatives via One-Pot Multi-component
Reactions Using Mechanochemistry
ꢀ
ꢀ
ZIL@CuO1-3 were developed as a catalyst for the synthesis of bis-coumarins under environmentally
benign conditions.
Mechanochemistry induced synthesis of bis-coumarin derivatives with more than 90% yield was
accomplished.