Gold modified zeolite: An efficient heterogeneous catalyst for n-arylation of indazole

Article abstract of DOI:10.1166/jnn.2016.12905

We herein report N-arylation of indazole with aryl halides using gold modified zeolites (Au-zeolites) as an efficient catalytic system. Au-zeolites with three different gold loading were prepared by ion-exchange method and characterized by UV-visible diffuse reflectance spectroscopy (UV-DRS), transmission electron microscopy and energy-dispersive X-ray spectroscopy (TEM-EDX) and X-ray photoelectron spectroscopy (XPS). The Brunauer-Emmett-Teller (BET) and Langmuir surface areas of the prepared Au(5)-zeolite catalyst were found to be 644 and 929 m²g^-1 respectively. Goldmodified zeolites performed as an efficient catalytic system for N-arylation of indazole using diverse aryl halides afforded N1 arylated products in appreciable yield under mild reaction conditions. The catalyst was reusable for at least five times with only a marginal loss of activity. This simple, effective and environmentally benign heterogeneous protocol provides a safer alternative to hazardous, corrosive and more polluting conventional catalysts.

Full text of DOI:10.1166/jnn.2016.12905

Article
Journal of
Nanoscience and Nanotechnology
Vol. 16, 9093–9103, 2016
Copyright © 2016 American Scientific Publishers
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Printed in the United States of America
Gold Modified Zeolite: An Efficient Heterogeneous
Catalyst for N-Arylation of Indazole
P. Emayavaramban1, K. Kadirvelu2, and N. Dharmaraj1ꢀ∗
1Inorganic and Nanomaterials Research Laboratory, Department of Chemistry, Bharathiar University, Coimbatore 641046, India
2Defence Research Development Organization—Bharathiar University, Center for Life Sciences,
Bharathiar University Campus, Coimbatore 641046, India
We herein report N-arylation of indazole with aryl halides using gold modified zeolites (Au-zeolites)
as an efficient catalytic system. Au-zeolites with three different gold loading were prepared by
ion-exchange method and characterized by UV-visible diffuse reflectance spectroscopy (UV-DRS),
transmission electron microscopy and energy-dispersive X-ray spectroscopy (TEM-EDX) and X-ray
photoelectron spectroscopy (XPS). The Brunauer-Emmett-Teller (BET) and Langmuir surface areas
of the prepared Au(5)-zeolite catalyst were found to be 644 and 929 m2g−1 respectively. Gold-
modified zeolites performed as an efficient catalytic system for N-arylation of indazole using diverse
aryl halides afforded N1 arylated products in appreciable yield under mild reaction conditions. The
catalyst was reusable for at least five times with only a marginal loss of activity. This simple, effec-
tive and environmentally benign heterogeneous protocol provides a safer alternative to hazardous,
IP: 79.133.106.103 On: Sun, 30 Sep 2018 14:45:53
corrosive and more polluting conventional catalysts.
Copyright: American Scientific Publishers
Keywords: Zeolites, Gold Modification, Aryl Indazole, N-Arylation, Heterogeneous Catalyst.
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1. INTRODUCTION
steps. Moreover, excess quantity of copper reagents is
needed.
Recently, researchers have found that metal nanopar-
Nitrogen heterocycles such as quinazoline, quinoline,
indole, indazole etc., isolated from natural products
showed prominent medicinal properties.1 Among them,
N -aryl-indazoles exhibited various therapeutic properties
as listed in the following Table I.
ticle catalysts can be used to achieve facile synthesis
of N -aryl-indazoles. For instance, Ganesh Babu et al.
reported a simple, effective, ligand free and reusable het-
erogeneous catalyst for N -arylation of benzimidazole with
copper oxide nanoparticles.15 In addition, Yong et al.
studied N -arylation of a series of nitrogen-containing
heterocycles using Cu2O and tetrabutylammonium bro-
mide (TBAB) catalyst in water.16 The Cu-catalyzed
N -arylation of pyrazole or indazole with aryl halides
using flash vacuum photolysis and microwave-based heat-
ing yielded N -alkylated and N -bromoalkenylated pyra-
zole or indazole.17ꢀ18 Further, Corma and co-workers have
reported Suzuki and Sonogashira cross-coupling reac-
tions using Au(I) and Au(III) complexes as catalysts.19
Many researchers have reported cross-coupling reactions
between aryl halides and phenylboronic acids with gold
nanoparticles supported on MgO as catalysts.20ꢀ21Hence,
synthesis of N -aryl-indazoles by simple methodology is
still a challenging task for organic chemists.
From the synthetic viewpoint, direct arylation and
alkenylation of the nitrogen atom present in nitrogen het-
erocycles are a difficult task. For example, synthesis of
N -aryl-indazoles include cyclization of arylhydrazones of
2-bromoaldehydes and 2-bromoacetophenones and diazo-
tization of 2-alkylaniline.7ꢀ8 Dell’Erba et al. investigated
a base promoted cyclization of (O-alkylaryl)azosulfides
derived from 2-alkylaniline and [3 + 2] cycloadditions
of arynes with diazo compounds or hydrazones using
copper or palladium catalysts.9ꢀ10 Ullmann coupling is
a well known reaction for cross-coupling of N–H het-
erocycles with aryl lead, aryl bismuth, aryl borane and
aryl silane reagents using copper salts as a catalyst.11–14
However, Ullmann coupling reactions has serious lim-
itations such as elevated temperatures, extended reac-
tion time, low tolerance functional groups and multiple
Zeolites have unique adsorption and ion-exchange prop-
erties and proved its importance in the petroleum refining
∗Author to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2016, Vol. 16, No. 9
1533-4880/2016/16/9093/011
doi:10.1166/jnn.2016.12905
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Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Table I. Some of the biologically important N-aryl-indazoles.
Emayavaramban et al.
2.2. Preparation of Gold Modified Zeolite (Au-Zeolite)
In a 250 mL round bottom flask, 1 g of sodium Y zeo-
lite and 100 mL of an aqueous solution containing dif-
ferent molar concentration of [HAuCl4]·3H2O were taken
(1 mM, 3 mM and 5 mM) and the resulting slurry was
stirred for 24 h in nitrogen atmosphere at room tem-
perature. The Au3+-exchanged Y zeolite (Au3+-zeolite)
was filtered using Whatman-1 filter paper and the residue
(Au3+-Y zeolite) was rinsed with deionised water to
remove chloride ions. The resulting Au3+-Y zeolite was
dried under vacuum overnight. The prepared samples
Biological
properties
Compound name
Structure
Reference
analgesic,
antipyretic and
anti-
N
2,3
Benzydamine
O
N
N
inflammatory
O
N-[[1-(2-
Methoxyphenyl)-
1H-indazol-5-
N
H
N
smoothened
antagonists and
antitumor agent
N
4
e
OM
yl]methyl]-2-
propylpentanamide
3-(5’-hydroxymethyl
-2’-furyl)-1-
benzylindazole
ꢀ
5
6
were calcined in muffle furnace at 400 C for 5 h. The
anti-cancer agent
O
N
N
HO
obtained gold modified Y zeolite catalysts were named
as Au(1)-zeolite, Au(3)-zeolite and Au(5)-zeolite respec-
tively, according to different gold content.
R
O
4-aryl-1-(indazol-
5-yl)pyridin-
2(1H)ones
N
anti-obesity
agent
N
N
N
2.3. Characterization
UV-visible spectra of the Au-zeolites were recorded with a
double beam UV/vis. and UV-DRS-JASCO (model V550)
spectrophotometer. Powder X-ray diffraction (XRD) pat-
terns were recorded with a PAN analytical X’PERT-
PRO diffractometer using Cu Kꢁ radiation (wavelength
1.54056 Å, 40 kV, 55 mA). Fourier transform infrared
spectra (FT-IR) were recorded using KBr pellets on a
JASCO FT-IR-460 spectrophotometer in the range of
4000–400 cm−1. Raman spectra of the samples were
recorded from a laser Raman spectrometer (Horiba Jobin-
and organic synthesis.22 In addition, zeolites have large
surface area, thermal stability and well-defined microp-
orous structures.23ꢀ24 Among the zeolites, Y zeolite is used
as cracking catalyst because of higher activity and stability
even at high temperatures due to the higher Si/Al ratio.22
Y zeolite is a faujasite (FAU) type, crystalline, microp-
orous aluminosilicate with typically 0.4–1.2 nm size and
built from infinitely extending three-dimensional network
of SiO4 and AlO4 tetrahedra that are linked together
3+
through oxygen bridges.25 The presence of Al instead
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LabRam-HR-UV) using a 20 mW argon laser operating
Copyright: American Scientific Publishers
at 514 nm. Field emission scanning electron microscopic
of Si4+ creates a negative charge, which is compensated
Delivered by Ingenta
(FE-SEM) images were taken using a FEI Quanta 250
by exchangeable transition-metal cations, after dehydra-
tion it may occupy different sites in zeolite.26 Modification
of zeolites by different metal ions is one of the meth-
ods to improve electronic and catalytic characteristics of
supported metal nanoparticles.27 Lakshmi Kantam et al.
synthesised N -aryl hetrocycles with aryl halides by cop-
per exchanged NaY zeolite catalyst with excellent yields
under mild reaction conditions.28
Hence, in this paper, we describe the preparation of
gold modified zeolite (Au-zeolite) by simple ion-exchange
method to utilize as a heterogeneous and reusable cata-
lyst for synthesis of N -arylated indazoles. To the best of
our knowledge, this is the first report on the application
of gold modified zeolite as a catalyst for N -arylation of
indazoles.
at 30 kV and 33 Pa in a low-vacuum mode without
metal coating on aluminium support. Transmission elec-
tron microscopy (TEM) was performed on a JEM-2100 F
microscope (JEOL) operating at 200 kV. Elemental anal-
ysis was performed by an energy dispersive X-ray (EDX)
analyzer attached with TEM instrument. XPS analysis
was performed on a Physical Electronics 5800 spectrom-
eter equipped with a hemispherical analyzer and using
monochromatic Al Kꢁ radiation (1486.6 eV, the X-ray
tube working at 15 kV and 350 W) and pass energy of
23.5 eV. The nitrogen adsorption/desorption experiments
were carried out at 77 K using an ASAP 2020 system
of micromeritics the autosorp-iQ (Quantachrome instru-
ments). Gold content of the modified zeolite catalysts were
determined by inductively coupled plasma atomic emis-
sion spectroscopy (ICP-AES) using a PerkinElmer, optima
3000 model. ICP-AES samples prepared by dissolving Au-
zeolites in a mixture of HCl/HNO3 (3:1), to make clear
solution adequate amount of HF solution added and then
solutions were kept in microwave digester for 20 min.
Thermogravimetric and differential thermal analyses (TG-
DTA) were recorded in a PerkinElmer Pyris Diamond
TG/DTA under nitrogen atmosphere with a heating rate of
2. EXPERIMENTAL DETAILS
2.1. Materials
Sodium Y zeolite (ion exchangeable zeolite) and hydrogen
tetrachloroaurate [HAuCl4] · 3H2O were purchased from
Aldrich chemicals. All other chemicals used were of ana-
lytical grade and used without further purification. Deion-
ized water was prepared by water purification system.
All glasswares and Teflon coated magnetic stir bars were
washed with aqua regia, followed by copious rinsing with
ꢀ
10 C per min. The sample was de-gassed under vacuum
at 423 K for 24 h before the adsorption of nitrogen. The
product conversion was quantified by PerkinElmer Clarus
ꢀ
deionised water before drying in an oven at 150 C.
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Emayavaramban et al.
Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
(ii) reduction of Au3+ ions to gold modified Y zeolite sup-
port was achieved by the thermal process.
The optical properties of Au-zeolite(1), Au-zeolite(3) and
Au-zeolite(5) were studied and are shown in Figure 1,
where the ability of Au3+ ions to exchange with sodium
Scheme 1. Au-zeolite catalyzed N-arylation of indazole with aryl
Y zeolite was found to increase with increasing concentra-
tion of gold solution from 1 mM, 3 mM and 5 mM. The
characteristic surface plasmon resonance band (SPR) for
gold nanoparticles was observed at 526 nm.29 In absence
of gold no characteristic SPR band was identified for
(a) sodium Y zeolite. The band (b) showed a weak
absorption due to the presence of low content of gold
and it is well supported by ICP-AES analysis (Table II).
On the other hand, the sharp SPR bands were observed
in (c) and (d) curves. However, an increase in the intensity
of absorption bands was observed without any shift in the
position of SPR bands upon increasing the concentration
of gold solution.
halides.
600 gas chromatography and mass spectroscopy (GC-MS).
Nuclear magnetic resonance (NMR) spectra were recorded
in CDCl3with BRUKER AMX 500 at 500 MHz with tetra
methyl silane as an internal standard.
2.4. GC-MS Analysis
GC-MS analysis was carried out by PerkinElmer Clarus
600 gas chromatograph/mass spectrometer instrument
equipped with a 5% diphenyl and 95% dimethyl polysilox-
ane, Restek-5 capillary column (60 m length, 0.32 mm
dia). GC was coupled with MSD and triple axis mass
selective ion detector. The initial temperature was kept at
50 ꢀC and reached a maximum of 280 ꢀC. One ꢂL of sam-
ple was injected with split mode (10:1). Helium used as
a carrier gas at flow rate of 0.8 mL/min and the total run
time was 23 mins. Electron impact mass spectrometry was
performed, with electron energy of 70 eV and ion source
Figure 2 displays a comparison of XRD patterns of
sodium Y zeolite, Au3+-exchanged Y zeolite and gold
modified Y zeolite (Au(5)-zeolite). However, the XRD
patterns did not show any noticeable change in both the
intensities and positions of the Bragg peaks, indicating
that neither the crystallinity nor the lattice of Y zeolite
was altered by ion exchange with Au3+ ions followed by
thermal process.30 The XRD patterns did not show any
diffraction due to AuNPs because of its very low content
ꢀ
and interface temperature of 250 C. The acquisition was
performed in scanning mode (mass range m/z 50–500).
MS library (NIST-MS library) was conducted for identifi-
cation of products using the database of National Institute
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in Au-zeolites.
Copyright: American Scientific Publishers
FT-IR spectra of the Au-zeolites were recorded to iden-
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tify structural stability of the material after modification
from sodium form of Y zeolite to gold form of Y zeo-
lite and are shown in Figure 3. The spectra of Y zeolite
before and after gold loading were recorded to understand
the stability of the samples. The strong bands observed at
3469 and 1642 cm−1 were assigned to hydroxyl groups
present in framework of the Y zeolite and other bands at
581 and 473 cm−1 were related to six membered rings
which is a key structural feature of FAU type (sodium
Standard and Technology.
2.5. Procedure for N-Arylation of Indazole
In a typical N -arylation reaction, Au(5)-zeolite catalyst
(100 mg) was added to a mixture of indazole (118 mg,
1 mM), 4-chlorobenzonitrile (206 mg, 1.5 mM) and
K2CO3 (276 mg, 2.0 mM) in N ,N -dimethylacetamide
(DMAc, 4 mL) and stirred at 110 ꢀC (Scheme 1).
Completion of the reaction was monitored by thin-layer
chromatography (TLC) and then the reaction mixture was
centrifuged to separate the catalyst followed by several
time washings with ethyl acetate. Then, the organic layer
was quenched with ice and the product was extracted twice
with ethyl acetate. The combined organic extracts were
dried over anhydrous sodium sulphate, filtered and concen-
trated to a very small volume. The residue obtained was
used for GC-MS analysis and purified by column chro-
matography on silica gel (petroleum ether/ethyl acetate,
70/30) to afford pure N 1 and N 2 arylated products.
3. RESULTS AND DISCUSSION
Three different samples of gold modified Y zeolites were
prepared by two step processes as described below.
(i) Au3+ ions was exchanged with sodium Y zeolite by
ion exchange method and
Figure 1. UV-DRS spectra of (a) sodium Y zeolite, (b) Au(1)-zeolite,
(c) Au(3)-zeolite and (d) Au(5)-zeolite.
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016
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Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Table II. Amount of gold loaded on sodium Y zeolite.a
Emayavaramban et al.
Concentration of Au3+
solution (mM)
Au loading on sodium Y
zeolite (ppm)
S. no.
1
2
3
1
3
5
0ꢃ0237
0ꢃ5863
0ꢃ7520
Note: aAu content measured by ICP-AES.
Y zeolite) framework.31ꢀ32 However, there was no predom-
inate changes in FT-IR spectra during the modification as
well as gold ion exchange processes.
Raman spectroscopy was recorded to characterize
sodium Y zeolite and Au(5)-zeolite. The spectrum of
sodium Y zeolite and Au(5)-zeolite are given in Figure 4.
From Raman spectra of the samples, interaction between
gold and zeolite was identified. The sodium Y zeolite dis-
played sharp bands at 505 cm−1 and 300 cm−1 which
were assigned to the T–O–T (T = Si/Al) bending vibration
of zeolite framework.33–35 In contrast, the Au(5)-zeolite
showed only weak absorption band at these wavelengths
probably due to the fluorescence quenching from gold on
the surface of zeolite.36
Figure 3. FT-IR spectra of (a) sodium Y zeolite, (b) Au3+ ion-
exchanged Y zeolite and (c) Au(5)-zeolite.
spectrum are given in Figures 6(a and b). The presences of
gold nanoparticles are not seen in TEM images. But, it was
as identified through TEM-EDX and further it was sup-
ported by ICP-AES results. In addition, the zeolite frame-
work elements Si, Al, O, Na and Cu from the grid were
also observed in the EDX.
X-ray photoelectron spectroscopy (XPS) provides fur-
ther insight into the oxidation state of gold in Au(5)-zeolite
and the elemental composition. Figure 7 shows the XPS
The morphology and composition of gold modified
Y zeolite were investigated by FE-SEM, TEM-EDX and
ICP-AES analysis. FE-SEM images of gold modified
Y zeolite shown in Figures 5(a–d) revealed that
(i) there exist only crystals of Y zeolite,
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Copyright: American Scientific Publishers
(ii) there was no bulk metal outside the zeolite crystals
Delivered bysIpnegcetrnutma of Au(5)-zeolite and the peaks for possible ele-
and
ments such as Al 2p, Si 2p and O 1s were observed at
binding energies of 74, 102.8 and 532 eV respectively.37
In addition, very small peaks were found at 84 and 88 eV
due to the presence of gold nanoparticles.38 However, the
above peaks for metallic gold are not clear due to less
content of gold on the surface of zeolite.
(iii) the method used for the preparation of gold modified
does not cause any observable defects in the structure of
Y zeolite.
These results were also supported by XRD results. The
TEM image of gold modified Y zeolite and its TEM-EDX
N2-adsorption/desorption isotherms of Au(5)-zeolite
presented in Figure 8 showed type I nature, a characteris-
tic of microporous materials. The micropore volume and
Figure 2. XRD patterns of (a) sodium Y zeolite, (b) Au3+ ion-
exchanged Y zeolite and (c) gold modified Y zeolite (Au(5)zeolite) after
thermal treatment.
Figure 4. Raman spectra of (a) sodium Y zeolite and (b) Au(5)-zeolite.
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016
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Emayavaramban et al.
Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
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Copyright: American Scientific Publishers
Figure 5.
FE-SEM images of Au(5)-zeolite (a–d) (from lowDeremliavgenrifiecdatibonytIonhgigehnertamagnification).
ꢀ
surface area of Au(5)-zeolite determined by DFT method
were found to be 0.323 cm3g−1 and 1108.2 m2g−1. The
BET and Langmuir surface area of the prepared Au(5)-
zeolite catalyst were found to be 644.5 and 929.4 m2g−1
respectively (Fig. 9). Then, the pore size derived from the
N2-adsorption isotherms using DFT method suggested the
average pore size of the Au(5)-zeolite was ∼0.614 nm
(Fig. 10).
to 200 C, attributed to the surface water molecules in
ꢀ
zeolite matrix. But, above 200 C there was no predomi-
nant weight loss occurred even up to 800 ꢀC indicating the
stability of Au(5)-zeolite. The obtained DTA curve showed
an exothermic peak at 200 C due to the removal of sur-
face bound water molecules present in Au(5)-zeolite.
ꢀ
3.1. Catalytic Test
A thermogravimetric (TG) (Fig. 11) analysis was carried
out to study the weight loss and stability of Au(5)-zeolite.
Initially, the TG curve showed 22% of weight loss up
3.1.1. Optimization of Reaction Conditions
To identify suitable conditions for catalytic studies, the
parameters such as substrate-catalyst ratio, solvent, nature
Figure 6. (a) TEM image of an individual matrix of Au(5)-zeolite and (b) corresponding EDX spectrum.
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016
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Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Emayavaramban et al.
Figure 7. XPS spectrum of Au(5)-zeolite.
Figure 9. Multipoint BET surface area of Au(5)-zeolite.
reaction from 0.5 to 2.0 mM produced higher yields of the
N -arylated compounds. But, addition of 2.5 mM quantity
of the base caused a negative effect and decreased the
product yield (Table III, entries 5–8). Finally, N -arylation
of indazoles was successfully carried out under the opti-
mized reaction conditions involving aryl halide (1.5 mM),
indazole (1 mM), K2CO3 (2 mM) and 100 mg of Au(5)-
and quantity of base and mole percent of gold in the
catalyst were optimized. Hence, the reaction between
indazole and 4-chlorobenzonitrile was carried out at differ-
ent reaction conditions. From the data given in Table III,
it was concluded that among the five solvents (acetoni-
trile, toluene, tetrahydrofuran (THF), water and N ,N -
dimethylacetamide (DMAc)), only DMAc produced higher
yield of the product (100%) and hence, it was cho-
sen for all the reactions (Table III, entries 8–12). Sim-
ilarly, four different bases such as potassium carbonate
(K2CO3ꢄ, potassium hydroxide (KOH), potassium phos-
ꢀ
zeolite as catalyst in DMAc as solvent at 110 C.
3.1.2. Extension of Scope
Scope of the present catalytic system (Au(5)-zeolite) to
a series of reaction between indazole and various aryl
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phate (K3PO4ꢄ and potassium tert-butoxide ((CH ꢄ COK)
were tested for their performance in the above cataly-
Copyright:3A3merican Scientific Publishers
halides was tested. In majority of the cases, arylated prod-
ucts were obtained in appreciable yields (Table IV) and
compared with earlier reported catalytic systems for the
same reaction to obtain N -arylated indazole.16ꢀ39 Among
the halogens, the bromo group was one of the best leav-
ing groups as compared to the chlorine and fluorine
(leaving group ability of halogens was in the order of
Br > Cl > F) and hence, the aryl bromides reacted faster
than the respective aryl chlorides and fluorides.40 Usu-
ally C–F bond activation is not so easy because of poor
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sis reactions. Among them, potassium carbonate (2 mM)
was found to be an effective base (Table III, entries 8,
13–16). Moreover, Au(5)-zeolite showed better catalytic
activity than the other two catalysts (Au(3)-zeolite and
Au(1)-zeolite) (Table III, entries 2, 3 and 8). However, the
same reaction conducted with sodium Y zeolite as catalyst
yielded only 10% of product (Table III, entry 1), which
indicated that the presence of Au in the chosen catalytic
system is mainly responsible for its activity in N -arylation.
Further, upon increasing the quantity of base added in this
Figure 10. Pore size distributions of Au(5)-zeolite evaluated by the
Figure 8. N2-adsorption/desorption isotherms of Au(5)-zeolite.
DFT method.
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Emayavaramban et al.
Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
than 2,4,7-trichloroquinoline (Table IV, entries 10 and 11).
1-Bromonaphthalene gave lower yield due to an absence of
activating groups (donating or withdrawing groups) in the
ring (Table IV, entry 12).40 Interestingly, higher yield of
N -aryl indazole was obtained when 4-bromobenzophenone
and 4-chlorobenzophenone were used as aryl halides as
presented in Table IV, entries 13 and 14.
Sheldon test was performed to identify any possible
leaching of gold nanoparticles from Au(5)-zeolite during
catalysis.41 The obtained results clearly indicated that there
was no appreciable leaching of gold nanoparticles under
the present reaction conditions. The absence of leaching
is further confirmed from ICP-AES analysis of the fil-
trate from the reaction mixture and also of the filtrate
from a ꢀstirred solution of Au(5)-zeolite in DMAc for 24 h
Figure 11. (a) TG and (b) DTA curves of Au(5)-zeolite.
at 110 C.
Simultaneously, the recovery and reusability of Au(5)-
zeolite were also investigated (Table V). After comple-
tion of the reaction, products were extracted with ethyl
acetate, dried over anhydrous sodium sulphate and con-
centrated. Au(5)-zeolite was washed three times with ethyl
acetate, filtered and air dried prior to reuse. After each
cycle, the recovered Au(5)-zeolite retained its activity and
afforded 92% yield after the fifth cycle. ICP-AES analy-
sis of the reused Au(5)-zeolite confirmed the presence of
0.752 ppm of gold and supported the heterogeneous nature
of Au(5)-zeolite.
leaving group ability of the fluoride. As the electron with-
drawing effect of the substituent at the phenyl ring of
aryl halides increases, the reactivity towards N -arylation
also increases (Table IV, entries 1–3). On the other hand,
ortho-substituted aryl halides gave poor yield for Br >
Cl > F compared to the para-substituted aryl halides due
to the steric effect of cyano group at the ortho posi-
tion (Table IV, entries 4–6). Since nitro group is one
of the strongest electron withdrawing group, the aryl
halide possessing such substituent gave better yield com-
pared to trifluoromethyl substituted compounds (–CF ꢄ
(Table IV, entries 7–9). When N -arylation of indazole
and aryl halides with electron donating groups were car-
ried out, lower yield of arylated products were obtained
compared to electron withdrawing substituent. The ratio
of N 1:N 2 products was higher for 4,7-dichloroquinoline
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Copyright: Ameri3can Scientific Publishers
3.2. Mechanism
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The mechanism proposed for Au(5)-zeolite catalyzed
N -arylation of indazole with aryl halide is given in
Figure 12. In the first step, aryl halide was adsorbed on the
surface of the gold modified Y zeolite. The excess charge
generated due to this adsorption could be shared among
the gold atoms. Then it undergoes a reaction with indazole
that has two tautomeric forms N 1 and N 2 in basic medium
and the catalytic cycle was completed by the elimination
of N -arylated indazoles.
Table III. Optimization of reaction conditions for N-arylation of
indazole.a
Total yield
Entry
Catalyst
Solvent
Base (mM)
N1+N2 (%)b
1
2
3
4
5
6
7
8
Y zeolite
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.5)
K2CO3 (0.5)
K2CO3 (1.0)
K2CO3 (1.5)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
Na2CO3 (2.0)
K3PO4 (2.0)
KOH (2.0)
10
20
90
96
72
88
96
100
80
76
–
57
92
32
56
87
1
3.3. FT-IR, GC-MS, H and 13C NMR Spectral Data
Au(1)-zeolite
Au(3)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
(In the interpretation of NMR data, following abbre-
viations are used: s-singlet, t-triplet, m-multiplet and
J-coupling constant).
3.3.1. 1-(Benzophenone-4-yl)-1H-Indazole (Table IV,
Entry 14, N1-Arylated Product)
1H NMR (500 MHz, CDCl3ꢄ: ꢅ 7.29 (t, 1H, J = 7.5
Hz, Ar-H), 7.48–8.02 (m, 10H, Ar-H), 8.26 (s, 1H,
CH N) ppm.
9
Au(5)-zeolite Acetonitrile
10
11
12
13
14
15
16
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Au(5)-zeolite
Toluene
Water
THF
DMAc
DMAc
DMAc
DMAc
13C NMR (125 MHz, CDCl3ꢄ: ꢅ 110.7 (–CH), 121.5
(–CH), 121.7 (–CH), 122.3 (–CH), 126.0 (–C), 127.9
(–CH), 128.5 (–CH), 130.1 (–CH), 131.8 (–CH), 132.6
(–CH), 135.1 (C), 136.8 (–C), 137.7 (–C), 138.8 (–C),
143.7 (–CH), 195.7 (C O) ppm.
(CH3ꢄ3COK (2.0)
Note: aReaction condition: Indazole (1 mM, 118 mg), ArX (1.5 mM),
K2CO3, 100 mg of Au(5)-zeolite) in 4 mL of DMAc at 110 ꢀC for 24 h; bGC-MS
yield.
FTIR (KBr): ꢆmax 1643 cm−1; GC-MS m/z: 291 (M+ꢄ.
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016
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Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Table IV. Au(5)-zeolite-catalyzed N-arylation of indazole with various aryl halides.a
Emayavaramban et al.
Product
Yield
(%)b
Entry
1
Aryl halide
N1 Arylated Product
N2 Arylated Product
N1
N2
100
100
100
100
58
42
F
Cl
N
C
N
N
N
C
N
N
N
CN
CN
CN
N
N
N
2
3
4
64
60
68
36
40
32
CN
N
N
CN
Br
N
N
N
C
N
C
F
N
N
N
C
N
N
N
C
C
N
NC
70
40
26
30
23
Cl
5
6
N
N
N
C
N
N
N
C
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Copyright: American Scientific Publishers
49c
Br
N
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N
NC
N
NC
N
NC
7
8
7
4
3
Br
F
C
F
C
3
N
3
N
N
N
F
C
3
N
N
82
62
20
Br
Cl
N
O2
NO2
N
N
N
O2
N
N
9
100c
100
60
51
40
49
N
O2
NO2
N
N
N
O2
N
10
Cl
N
N
N
N
N
N
Cl
Cl
Cl
9100
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Emayavaramban et al.
Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Table IV. Continued.
Product
Yield
Entry
11
Aryl halide
N1 Arylated product
N2 Arylated product
(%)b
N1
N2
Cl
N
Cl
N
92
56
36
Cl
N
N
Cl
N
N
N
Cl
Cl
Cl
12
12
10
2
Br
N
N
N
N
O
O
O
O
13
14
98
54
52
44
48
N
N
Cl
Br
N
N
O
O
N
100c
N
N
IP: 79.1N33.106.103 On: Sun, 30 Sep 2018 14:45:53
Notes: Reaction condition: Indazole (1 mM, 118 mg), ArX (1.5 mM), K2CO3 (2 mM, 276 mg), Au(5)-zeolite (100 mg) in 4 mL of DMAc at 110 ꢀC for 24 h; bGC-MS
a
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yield; cIsolated yield after column chromatography.
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3.3.2. 2-(Benzophenone-4-yl)-2H-Indazole (Table IV,
Entry 14, N2-Arylated Product)
1H NMR (500 MHz, CDCl3ꢄ: ꢅ 7.12–8.08 (m, 13H, Ar-H),
8.52 (s, 1H, CH N) ppm.
13C NMR (75 MHz, CDCl3ꢄ: ꢅ 110.6 (–CH), 119.4
(–C), 121.5 (–CH), 122.0 (–CH), 122.8 (–CH), 125.5
(–CH), 128.4 (–CH), 137.7 (–CH), 138.7 (–C), 145.2 (–C),
145.5 (–C) ppm.
13C NMR (125 MHz, CDCl3ꢄ: ꢅ 118.1 (–CH), 120.4
(–CH), 120.6 (–CH), 120.7 (–C), 123.1 (–CH), 123.2
(–CH), 127.7 (–CH), 128.6 (–CH), 130.1 (–CH), 131.8
(–C), 132.8 (–CH), 136.8 (–C), 137.5 (–C), 143.3 (–C),
150.3 (–C), 195.6 (–C O) ppm.
FTIR (KBr): ꢆmax1643 cm−1; GC-MS m/z: 291 (M+ꢄ.
3.3.3. 1-(4-Nitrophenyl)-1H-Indazole (Table IV, Entry 9,
N1-Arylated Product)
1H NMR (500 MHz, CDCl3ꢄ: ꢅ 7.32 (t, 1H, J = 7.0 Hz,
Ar-H), 7.51–7.98 (m, 5H, Ar-H), 8.27 (s, 1H, CH N)
8.38 (d, 2H, J = 4.0 Hz, Ar-H) ppm.
Table V. Reusability of Au(5)-zeolite for N-arylation of indazole with
4,7-dichloroquinoline.a
Cycle
First
98
Second
97
Third
97
Forth
96
Fifth
92
Yield (%)b
Note: aReaction condition: Indazole (1 mM, 118 mg), ArX (1.5 mM), K2CO3
(2 mM, 276 mg), Au(5)-zeolite catalyst (100 mg) in 4 mL of DMAc at 110 ꢀC for
24 h; bGC-MS yield.
Figure 12. Proposed mechanisms for Au(5)-zeolite catalyzed
N-arylation of indazole with aryl halides.
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016
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Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
Emayavaramban et al.
FTIR (KBr): ꢆmax 1511 cm−1 (asym, –NO2ꢄ, ꢆmax
1336 cm−1 (sym, –NO2ꢄ; GC-MS m/z: 239 (M+ꢄ.
5. Q. Zhao, J. Du, H. Gu, X. Teng, Q. Zhang, H. Qin, and N. Liu,
Pancreas 34, 242 (2007).
6. M. Hadden, D. M. Deering, A. J. Henderson, M. D. Surman,
M. Luche, Y. Khmelnitsky, S. Vickers, J. Viggers, S. Cheetham,
and P. R. Guzzo, Bioorg. Med. Chem. Lett. 20, 7020
(2010).
7. A. Y. Lebedev, A. S. Khartulyari, and A. Z. Voskoboynikov, J. Org.
Chem. 70, 596 (2005).
8. V. Collot, J. C. Ros, C. Alayrac, B. Witulski, and S. Rault, Tetrahe-
dron Lett. 43, 2695 (2002).
9. C. Dell’Erba, M. Novi, G. Petrillo, and C. Tavani, Tetrahedron 50,
3529 (1994).
10. P. Li, J. Zhao, C. Wu, R. C. Larock, and F. Shi, Org. Lett. 13, 3340
(2011).
11. P. López-Alvarado, C. Avendaño, and J. C. Menéndez, Tetrahedron
Lett. 33, 6875 (1992).
12. P. López-Alvarado, C. Avendaño, and J. C. Menéndez, J. Org. Chem.
61, 5865 (1996).
3.3.4. 1-(2-Cyanophenyl)-1H-Indazole (Table IV, Entry
6, N1-Arylated Product)
1H NMR (500 MHz, CDCl3ꢄ: ꢅ 7.30 (t, 1H, J =
8 Hz, Ar-H), 7.49–7.94 (m, 7H, Ar-H), 8.25 (s, 1H,
CH N) ppm.
13C NMR (75 MHz, CDCl3ꢄ: ꢅ 109.5 (–C), 110.5
(–CH), 118.0 (–CH), 118.6 (–C), 121.9 (–C), 122.0 (–CH),
122.6 (–CH), 126.3 (–C), 128.2 (–CH), 133.7 (–CH), 137.4
(–CH), 138.7 (–C) ppm.
FTIR (KBr): ꢆmax 2222 cm−1 (-CN); GC-MS m/z:
219 (M+ꢄ.
13. G. I. Elliott and J. P. Konopelski, Org. Lett. 2, 3055 (2000).
14. P. Y. S. Lam, S. Deudon, K. M. Averill, R. Li, M. Y. He, P. DeShong,
and C. G. Clark, J. Am. Chem. Soc. 122, 7600 (2000).
15. S. Ganesh Babu and R. Karvembu, Ind. Eng. Chem. Res. 50, 9594
(2011).
16. F.-F. Yong, Y.-C. Teo, S.-H. Tay, B. Y.-H. Tan, and K.-H. Lim, Tetra-
hedron Lett. 52, 1161 (2011).
17. R. F. C. Brown, F. W. Eastwood, G. B. Fallon, S. C. Lee, and
R. P. McGeary, Aust. J. Chem. 47, 991 (1994).
18. G. A. Burley, D. L. Davies, G. A. Griffith, M. Lee, and K. Singh,
J. Org. Chem. 75, 980 (2010).
4. CONCLUSION
In summary, Au-zeolites with different content of gold
were prepared by an ion-exchange method and charac-
terized by various analytical techniques. UV-DRS spec-
trum of the prepared Au-zeolites exhibited the surface
plasmon resonance at 526 nm, which is characteristic
feature of gold nanoparticles. TEM image clearly indi-
cated the well crystalline nature of gold modified zeo-
lite and absence of any defects in the crystals. Though
we could not detect gold nanoparticles on the surface of
zeolite crystals, EDX measurement confirmed the pres-
19. C. G. Arellano, A. Corma, and M. Iglesias, J. Catal. 238, 497
(2006).
20. V. K. Kanuru, G. Kyriakou, S. K. Beaumont, A. C. Papageorgiou,
ence of gold in them. Nitrogen adsorption/desorption and
IP: 79.133.106.103 On: Sun, 30 Sep 2018 14:45:53
D. J. Watson, and R. M. Lambert, J. Am. Chem. Soc. 132, 8081
BET surface area analysis revealed thCaotptyhreigmhti:crAompoerroiucsan Scientific Publishers
(2010).
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nature of the catalyst with an average surface area of
21. D. K. Dumbre, P. N. Yadav, S. K. Bhargava, and V. R. Choudhary,
J. Catal. 301, 134 (2013).
644 m2g−1. From the application point of view of the
newly prepared catalyst, Au-zeolite was used as an effi-
cient heterogeneous catalyst for N -arylation of indazoles
with various substituted aryl halides in presence of K2CO3
and DMAc at 110 ꢀC. Reusability of gold modified zeolite
was tested for five cycles and it’s stability against leach-
ing of gold was confirmed by ICP-AES. The N -arylated
heterocyclic products obtained in this study were char-
acterized by 1H, 13C NMR spectroscopy and GC-MS
analysis.
22. J. D. Sherman, Proc. Natl. Acad. Sci. USA 96, 3471 (1999).
23. H. S. Nalwa (ed.), Encyclopedia of Nanoscience and Nanotechnol-
ogy, American Scientific Publishers, Los Angeles, CA (2004/2011),
Vol. 1–25.
24. A. A. Elzatahry, T. A. Salah El-Din, E. A. Elsayed, D. M. Aldhayan,
M. A. M. Wadaan, A. M. Al.-Enizi, and S. S. Al.-Deyab, Sci. Adv.
Mater. 6, 1531 (2014).
25. K. Honda, M. Itakura, Y. Matsuura, A. Onda, Y. Ide, M. Sadakane,
and T. Sano, J. Nanosci. Nanotechnol. 13, 3020 (2013).
26. V. Rama, K. Kanagaraj, and K. Pitchumani, J. Org. Chem. 76, 9090
(2011).
27. E. Smolentseva, N. Bogdanchikova, A. Simakov, A. Pestryakov,
M. Avalos, M. H. Farias, A. Tompos, and V. Gurin, J. Nanosci.
Nanotechnol. 7, 1882 (2007).
28. M. Lakshmi Kantam, B. Purna Chandra Rao, B. M. Choudary, and
R. Sudarshan Reddy, Synlett 14, 2195 (2006).
Acknowledgment: We
acknowledge
University
Grants Commission (UGC), New Delhi (UGC) F.
No. 37–98/2009(SR) dated 19th December 2009 for
the financial support in the form of a major research
project.
29. P. Emayavaramban, K. Selvam, and N. Dharmaraj, Adv. Sci. Eng.
Med. 6, 649 (2014).
30. J. A. Rabo, Zeolite Chemistry and Catalysis, ACS, Washington,
(1976).
31. S. Markovic, V. Dondur, and R. Dimitrijevic, J. Mol. Struct. 654, 223
(2003).
References and Notes
1. Z. Ali, D. Ferreira, P. Carvalho, M. A. Avery, and I. A. J. Khan, Nat.
Prod. 71, 1111 (2008).
32. N. Ninan, M. Muthiah, I-K. Park, A. Elain, T. W. Wong,
S. Thomas, and Y. Grohens, J. Biomed. Nanotechnol. 11, 1550
(2015).
33. F. Fan, Z. Feng, and C. Li, Chem. Soc. Rev. 39, 4794 (2010).
34. P. K. Dutta, D. C. Shieh, and M. Prui, J. Phys. Chem. 91, 2332
(1987).
2. L. Mosti, G. Menozzi, P. Schenone, D. Cervo, G. Esposito, and
E. Marmo, Farmaco 45, 415 (1990).
3. A. Thangadurai, M. Minu, S. Wakode, S. Agrawal, and
B. Narasimhan, Med. Chem. Res. 21, 1509 (2012).
4. G. Dessole, D. Branca, F. Ferrigno, O. Kinzel, E. Muraglia,
M. C. Palumbi, M. Rowley, S. Serafini, C. Steinkühler, and P. Jones,
Bioorg. Med. Chem. Lett. 19, 4191 (2009).
35. X. Zhang, X. Ke, and H. Zhu, Chem. Eur. J. 18, 8048 (2012).
9102
J. Nanosci. Nanotechnol. 16, 9093–9103, 2016

Emayavaramban et al.
Gold Modified Zeolite: An Efficient Heterogeneous Catalyst for N-Arylation of Indazole
36. E. O. Ganbold, J. H. Park, U. Dembereldorj, K. S. Ock, and
S. W. Joo, J. Raman Spectrosc. 42, 1614 (2011).
39. J. C. Antilla, J. M. Baskin, T. E. Barder, and S. L. Buchwald, J. Org.
Chem. 69, 5578 (2004).
37. S. J. Kulkarni, S. Badrinarayan, and S. B. Kulkarni, J. Catal. 75, 423
(1982).
38. A. Afzal, C. D. Franco, E. Mesto, N. Ditaranto, N. Cioffi, F. Scordari,
G. Scamarcio, and L. Torsi, Mater. Express 5, 171 (2015).
40. P. Emayavaramban, S. Ganesh Babu, R. Karvembu, and
N. Dharmaraj, J. Nanosci. Nanotechnol. 15, 9358 (2015).
41. H. E. B. Lempers and R. A. Sheldon, J. Catal. 175, 62
(1998).
Received: 1 October 2015. Accepted: 4 November 2015.
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9103