Synthesis of 2,4,5-trisubstituted imidazoles, quinoxalines and 1,5-benzodiazepines over an eco-friendly and highly efficient ZrO2-Al2O3 catalyst

Article abstract of DOI:10.1039/c6ra13956f

ZrO₂-Al₂O₃ containing 80 mol% of ZrO₂ was prepared by solution combustion, impregnation and precipitation methods. All the prepared catalytic materials were characterized by PXRD, NH₃-TPD, N₂ adsorption isotherms, FTIR, TEM, SEM, EDAX and ICP-OES techniques. These catalytic materials were used in a rapid, simple, versatile and efficient synthesis of 2,4,5-trisubstituted imidazoles under solvent-free conditions at moderate temperature in shorter reaction time (20 min). This is achieved by three-component cyclo-condensation of benzil, aldehydes and ammonium acetate in excellent yields. The derivatives of quinoxalines and 1,5-benzodiazepines were synthesized effectively by cyclo-condensation of 1,2-diamine with α-diketones and carbonyl compound with O-phenylenediamines respectively over ZrO₂-Al₂O₃ at moderate temperature (80 °C) for the reaction time of 20-40 min in presence of ethanol as a solvent. The present method is experimentally simple, non-toxic and involves inexpensive reagents, clean reaction pathways and an eco-friendly catalyst. The catalytic materials used can be easily separated from the reaction mixture and reused for several reaction cycles without much loss of catalytic activity.

Full text of DOI:10.1039/c6ra13956f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: T. N and M. S. S Z,
RSC Adv., 2016, DOI: 10.1039/C6RA13956F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
Synthesis of 2,4,5-trisubstituted imidazoles, quinoxalines and 1,5-
benzodiazepines over eco-friendly and highly efficient ZrO2-Al2O3 catalyst
N. Thimmaraju1,2 and S. Z. Mohamed Shamshuddin*1,2
1Chemistry Research Laboratory, HMS Institute of Technology, Tumkurꢀ572104, Karnataka,
India.
2Research and Development Center, Bharathiar University, Coimbatore, India.
∗Corresponding author: Eꢀmail address: mohamed.shamshuddin@gmail.com
Phone no: +91ꢀ9844718742
Abstract
ZrO2ꢀAl2O3 containing 80 mole% of ZrO2 was prepared by solution combustion,
impregnation and precipitation methods. All the prepared catalytic materials were
characterized by PXRD, NH3ꢀTPD, N2 adsorption isotherms, FTIR, TEM, SEM, EDAX and
ICPꢀOES techniques. These prepared catalytic materials were used in a rapid, simple,
versatile and efficient synthesis of 2,4,5ꢀtrisubstituted imidazoles under solventꢀfree
conditions at moderate temperature in shorter reaction time (20 min). This is achieved by
threeꢀcomponent cycloꢀcondensation of benzil, aldehydes and ammonium acetate with
excellent yields. The derivatives of quinoxalines and 1,5ꢀbenzodiazepines were synthesized
effectively by cycloꢀcondensation of 1,2ꢀdiamine with αꢀdiketones and carbonyl compound
with Oꢀphenylenediamines respectively over ZrO2ꢀAl2O3 at moderate temperature (80 °C) for
the reaction time of 20ꢀ40 min in presence of ethanol as a solvent. The present method is
experimentally simple, nonꢀtoxic and involves inexpensive reagents, clean reaction pathways
and ecoꢀfriendly catalyst. The catalytic materials used can be easily separated from the
reaction mixture and reused for several reaction cycles without much loss of catalytic
activity.
1

RSC Advances
Page 2 of 33
View Article Online
DOI: 10.1039/C6RA13956F
1. Introduction
Metal oxide and mixed metal oxide based solid acid catalysts are most important and
widely employed in the largest family of heterogeneous catalysts because they utilize both
acid–base and redox properties.1ꢀ4 Among various metal oxides, ZrO2 and Al2O3 have been
widely used in both acid and base catalyzed reactions in the field of heterogeneous catalysis
as catalysts as well as catalytic supports.5ꢀ7 The Al2O3ꢀZrO2 based catalysts were found to
exhibit better catalytic properties than either Al2O3 or ZrO2 and are attracting considerable
interest because of their potential use as catalysts.8ꢀ10 Therefore, ZrO2ꢀAl2O3 has been used in
many catalytic processes involving liquid, vapour and gas phase reactions.
Multiꢀcomponent reactions (MCRs) are powerful and outstanding tool in generating
products in medicinal chemistry and modern organic synthesis because MCRs are oneꢀpot
process is wherein three or more components are assemble and produce product with high
selectivity and high atom efficiency.11ꢀ12 MCRs have great contribution and considerable
attention since they are performed without the need to isolate any intermediate and save both
raw materials and energy and also reduce time.13ꢀ14 MCRs find great interest to synthesize of
important and complex organic molecules from simple and readily available starting
materials in a single synthetic operation.12, 15
Nꢀheterocyclic compounds represent one of the most valuable building blocks for
biologically active molecules, drugs and functional materials.16 Naturally occurring
substituted imidazoles as well as synthetic derivatives are most important class of
heterocyclic compounds and play an important role in chemical and biological system.17ꢀ18
The imidazoles ring system and its derivatives are used as antibacterial agent, fungicides and
herbicides, antitumor and antiꢀinflammatory agents, plant growth regulators and therapeutic
agents.19ꢀ24 Various substituted imidazoles act as inhibitor of BꢀRaf kinase, p38 MAP kinase
and glucagon receptors.25ꢀ27 They are also useful building blocks for the synthesis of other
2

Page 3 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
classes of compounds. Therefore, the organic synthesis of these imidazole derivatives has a
significant impact on synthetic organic and medicinal chemistry.
A number of methods have been developed for the synthesis of 2,4,5ꢀtrisubstistuted
imidazoles. The best reported route for the synthesis of 2,4,5ꢀtrisubstistuted imidazoles is
three components cycloꢀcondensation of benzil, aldehyde and ammonium acetate in the
presence of an acid catalyst. There are several methods available to synthesize imidazole
derivatives over microwaves, Lꢀproline, acetic acid, ionic liquids, tetrabutylammonium
bromide, molecular iodine, montmorillonite K 10, zeolite, nano sulfated zirconia,
heteropolyacids, CAN (ceric ammonium nitrate), silica gel/NaHSO4, K5CoW12O40ꢀ3H2O,
FeCl3.6H2O, silica sulphuric acid, NiCl2.6H2O/Al2O3, ZrCl4, etc.28ꢀ34
Quinoxaline derivatives are an important class of benzo heterocyclic compounds,
since they have a wide area of biological activities such as antiꢀHIV, antiꢀviral, antiꢀdiabetic,
antiꢀfungal, antiꢀbacterial, antiꢀcancer, antiꢀdepression, etc.35ꢀ36 Numerous methods are
available for the synthesis of quinoxaline derivatives which involve cycloꢀcondensation of
1,2ꢀdiamine with αꢀdiketones using MnO2, POCl3, Zeolites, iodine, CAN, etc.37ꢀ38
Benzodiazepine and its derivatives are another interesting class of heterocyclic
compounds, because they are used as drugs, antiꢀanxiety, antiꢀconvulsant, sedative, analgesic,
antiꢀdepressive, hypnotic agents, etc.39ꢀ40 The common procedure for the synthesis of 1,5ꢀ
benzodiazepines is the condensation between carbonyl compound and Oꢀphenylenediamines.
Few methods have been reported with reagents such as BF3.OEt2, InBr3, polyphosphoric
acidꢀSiO2, sulfated zirconia, Yb(OTf)3, Sc(OTf)3, molecular iodine, acetic acid, ionic liquids,
etc.41ꢀ42
Some of these synthetic methods suffer from one or more serious drawbacks such as
harsh reaction conditions, moistureꢀsensitive metallic reagents, laborious and complex workꢀ
up and purification, poor yields, significant amount of waste materials, prolonged time
3

RSC Advances
Page 4 of 33
View Article Online
DOI: 10.1039/C6RA13956F
periods, high temperatures, occurring side reactions and use of hazardous and often expensive
acid catalysts. Moreover, the synthesis of these heterocyclic compounds has been usually
carried out in polar solvents like N, Nꢀ dimethylformamide, acetic acid and dimethylsulfoxide
leading to complex isolation and recovery procedure.
In the present work, an attempt has been made for the synthesis of 2,4,5ꢀtrisubstituted
imidazoles, quinoxalines and 1,5ꢀbenzodiazepines at moderate temperature in a shorter
reaction time over ZrO2ꢀAl2O3 as a simple, low cost, ecoꢀfriendly reusable and highly
efficient catalyst.
2. Experimental
2.1. Chemicals
Zirconyl nitrate hydrate, aluminium nitrate nonahydrate and urea were supplied by M/S
LOBA Chemie, India. Substituted benzil, aromatic aldehydes, ketones, αꢀdiketones and Oꢀ
phenylenediamines were supplied by Sigma Aldrich or AlfaꢀAesar and the solvents were
supplied by ChemLabs, India.
2.2. Preparation of ZrO2-Al2O3
i. Solution combustion method (SCM)
ZrO2ꢀAl2O3 mixed oxide consists of 80 mole% of ZrO2 by using urea as a fuel was
prepared by solution combustion method by taking aqueous solutions containing known
amounts of aluminium nitrate nonahydrate, zirconyl nitrate hydrate and a fuel.43 The
combustion was carried out by using an aqueous mixture (20 mL) containing 10.0 g of
aluminium nitrate nonahydrate, 12.32 g of zirconyl nitrate hydrate and 9.33 g of urea in a
pyrex dish. Combustion was carried out in a preheated muffle furnace (400 ± 10 oC) resulting
in a flaming type reaction wherein foamy solid was formed.
4

Page 5 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
ii.
Impregnation method
10.0 g of aluminium nitrate nonahydrate was dissolved in 5 mL of deionized water,
resulting solution was made into a paste with 12.32 g of zirconyl nitrate hydrate. The
resulting paste was dried in a hot air oven at 120 °C for 12 h.
iii.
Precipitation method
The aqueous solution of 10.0 g of aluminium nitrate nonahydrate and 12.32 g of zirconyl
nitrate hydrate in 200 mL of deionized water was stirred at 60 °C for 1 h. To this hot solution
1:1 aqueous ammonia solution was added drop wise with constant stirring until precipitation
is complete. Thus obtained precipitate was filtered and dried in hot air oven at 120 °C for 12
h.
Thus all the prepared samples were powdered finely and calcined in a muffle furnace
at 550° C for 5 h before their use as catalytic material. ZrO2ꢀAl2O3 prepared by solution
combustion method was abbreviated as ZAꢀSCM, impregnation method as ZAꢀIMG and
precipitation as ZAꢀPPT.
2.3. Characterization of catalytic materials
PXRD patterns of these solid acids were obtained from X’pert Pro Philips diffractometer
equipped with a Ni filtered CuꢀKα radiation with λ=1.5418 Å using a graphite crystal
monochromator with a scanning range 20oꢀ70°. Specific surface area of solid acid catalytic
materials was determined by N2 adsorption isotherms. NOVA 1000 Quanta chrome highꢀ
speed gas sorption analyzer instrument was used to measure the specific surface area of all
the prepared catalytic materials. The TSA of the catalytic materials were obtained from NH3ꢀ
TPD method using Mayura TPD unit. The FTꢀIR spectrums were recorded with 4 cmꢀ1
resolution using a Nicolet IR200 FTꢀIR Spectrophotometer in the range 400ꢀ4000 cmꢀ1 using
KBr as standard reference. TEM images of all prepared catalytic materials were performed on
PHILIPS CM200 electron microscope at an acceleration voltage of 20ꢀ200kV. SEM images
5

RSC Advances
Page 6 of 33
View Article Online
DOI: 10.1039/C6RA13956F
and EDAX of all the prepared catalytic materials were obtained using a JEOL JXAꢀ8530F
microscope. The amount of zirconia present in all the solid acid catalysts was estimated by
Inductively Coupled PlasmaꢀOptical Emission Spectrometer (ICPꢀOES) analysis technique
using ThermoꢀiCAP 6000 Series instrument.
2.4. Catalytic activity studies of ZrO2-Al2O3 catalytic material in the synthesis of
imidazole
To the stirred suspension of benzil (1.43 mmol), aldehydes (1.43 mmol), ammonium
acetate (4.29 mmol) in a 5 mL round bottomed flask fitted with water cooled condenser,
catalytic material (0.03 g of ZrO2ꢀAl2O3) was added and the resulting mixture was heated at a
120 °C. The progress of the reaction was monitored by thin layer chromatography. After the
completion of the reaction, the reaction mixture was cooled, the residue was dissolved in
acetone and the resulting solution was filtered, residue was washed with acetone to recover
the catalyst. Filtrate was poured to 100 mL of ice cold water, obtained precipitate was
filtered, washed with hexane and dried to get the desired product. Thus obtained product was
then characterized by melting point (Melting points were measured on a Büchi Bꢀ540
1
capillary melting point apparatus and are uncorrected), H NMR spectroscopy (Bruker, 400
MHz) and LCꢀMS (Varian).
Quinoxalines and 1,5ꢀbenzodiazepines were synthesized by stirring the mixture of 1, 2
dicarbonyl (1.43 mmol), Oꢀphenylenediamines (1.43 mmol), 0.03 g of ZAꢀIMG and ethanol
(10 mL) at 80 °C and the mixture of Oꢀphenylenediamines (1.43 mmol), ketones (2.86mmol),
0.03 g of ZAꢀIMG and ethanol (10 mL) at 80 °C respectively and the progress of the
reactions were monitored by thin layer chromatography (TLC).
6

Page 7 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
2.5. Reusability study of ZrO2-Al2O3 catalytic materials
After each reaction cycle of cycloꢀcondensation reaction, ZrO2ꢀAl2O3 catalytic
material was filtered from the reaction mixture, washed with acetone, dried at 120 oC for 1 h
o
and calcined at 550 C for 0.5 h. Thus reactivated ZrO2ꢀAl2O3 catalytic material was used in
the next cycle of the synthesis of imidazole under similar reaction conditions.
The reactivation and reusability of the used ZrO2ꢀAl2O3 catalytic material was
repeated for 5 reaction cycles by following the procedure as described above (section 2.4).
3. Results and discussion
3.1. Characterization of catalytic materials
All the prepared ZrO2ꢀAl2O3 catalytic materials were characterized for their physicoꢀ
chemical properties such as PXRD, NH3ꢀTPD, N2 adsorption isotherms, FTIR, TEM, SEM,
EDAX and ICPꢀOES technique.
3.1.1. Crystalinity by powder XRD (PXRD) studies
The crystalline phase of ZrO2ꢀAl2O3 catalytic material was characterized by PXRD
technique and the PXRD patterns of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT are shown in Fig. 1.
Interestingly no peaks corresponding to the monoclinic ZrO2 are observed in the PXRD
patterns of all ZrO2ꢀAl2O3 samples. However, pure tetragonal phase of ZrO2 is formed in case
of ZAꢀSCM and ZAꢀIMG due to phase transition of stable monoclinic to tetragonal phase.
Very low intense diffraction peaks corresponding to rhombohedral Al2O3 are also observed
only in ZAꢀSCM. In case of ZrO2ꢀAl2O3 catalytic material prepared by precipitation method a
small lump was observed at around 30° which corresponds to moderate plateau of tetrahedral
ZrO2, which indicates that the presence of an incipient crystalline structure in the synthesized
ZrO2ꢀAl2O3 mixed oxides.44ꢀ46 Major peaks corresponding to Al2O3 were not observed in all
the three ZrO2ꢀAl2O3 catalytic materials which confirm a clear coꢀordination between
zirconia and alumina metal oxides. More interestingly, it was observed from the PXRD
7

RSC Advances
Page 8 of 33
View Article Online
DOI: 10.1039/C6RA13956F
patterns that full crystallization of ZrO2ꢀAl2O3 could be achieved by SCM and impregnation
method and in case of ZAꢀPPT amorphous nature was observed.
ZA-PPT
ZA-IMG
T
ZA-SCM
T
T
T
T
R
20
30
40
50
60
70
2θ (degree)
Figure 1. PXRD patterns of ZrsO2ꢀAl2O3 catalytic material prepared by SCM, impregnation
and precipitation method. [R- rhombohedral Al2O3, T- tetragonal ZrO2].
3.1.2. Total surface acidity (TSA) by NH3-TPD method
The TSA values of all prepared ZrO2ꢀAl2O3 catalytic materials obtained by NH3ꢀTPD
are listed in Table 1a and the NH3‐TPD profiles of all the ZrO2ꢀAl2O3 catalytic material are
shown in Fig. 2. The TSA values of all catalytic materials are in the following order ZAꢀIMG
> ZAꢀSCM > ZAꢀPPT. In general the surface acidity of ZrO2ꢀAl2O3 mixed oxide is because
of the coordination number of the inserted cation maintained in the host oxide lattice. i.e.,
when Zr4+ is inserted into the Al3+ lattice, positive charge imbalance is occurred. As a result,
Lewis acid sites are generated. Surface acidity can also result due to the charge imbalance
8

Page 9 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
formed on the surface of metal oxide and while Lewis acid sites will be formed when the
charge imbalance is positive.47
The ZAꢀIMG catalytic material was comparatively found possess higher total surface
acidity than ZAꢀSCM and ZAꢀPPT. This may be due to tetragonal crystalinity. It is very
interesting to observe that the total surface acidity is not dependent on the surface area.
Desorption peaks of weak, medium, strong and very strong acid sites of ZrO2ꢀAl2O3 catalytic
materials are observed from Fig. 2.
Table 1a. Surface properties of ZrO2ꢀAl2O3 catalytic materials.
Pore
Sl.
Catalytic
materials
Surface area
(m2/g)
TSA
Pore volume
(cm3/g)
diameter
(Å)
No.
(mmolg-1)
1
2
3
ZAꢀSCM
ZAꢀIMG
ZAꢀPPT
10.607
119.68
168.98
1.33
1.52
1.27
57.84
0.016
0.119
0.291
39.95
68.97
9

RSC Advances
Page 10 of 33
View Article Online
DOI: 10.1039/C6RA13956F
100
200
300
400
500
600
-2200
-2400
ZA-PPT
-2600
-2200
ZA-IMG
ZA-SCM
-2400
-2600
-2400
-2600
100
200
300
400
500
600
Temperature (°C)
Figure 2. NH3ꢀTPD profiles of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT catalytic materials.
3.1.3. Surface area by N2 adsorption isotherms methods
The surface area, pore volume and pore diameter of the all the prepared ZrO2ꢀAl2O3
catalytic materials are given in Table 1. N2 adsorptionꢀdesorption isotherms and poreꢀsize
distribution of the ZrO2ꢀAl2O3 catalysts are given in Fig 3. The surface area of ZrO2ꢀAl2O3
catalytic materials were found to be in the following order: ZAꢀSCM < ZAꢀIMG < ZAꢀPPT.
A 12 and 17 fold higher surface area of ZAꢀIMG and ZAꢀPPT respectively was observed
than ZAꢀSCM. This higher surface area may be due amorphous nature of ZrO2ꢀAl2O3
catalytic materials. The N2 adsorptionꢀdesorption isotherms of these catalysts showed type IV
isotherms with well defined H1 hysteresis loop with relative pressure of 0.4 to 1, which is the
characteristic of mesoporous structure. This is confirmed by PXRD pattern, TEM and SEM
images. The pore diameters of these catalysts were not uniform as indicted from BJH pore
size distribution curve shown in Fig. 3. The pore diameters of ZAꢀSCM, ZAꢀIMG and ZAꢀ
10

Page 11 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
PPT catalysts were found maximum at 36.9 nm, 35.7 nm and 47.8 nm respectively as
indicated from pore size distribution curve.
14
200
12
10
8
150
6
4
ZA-PPT
2
100
0
-2
0
50
100
150
200
250
Pore diameter (Å)
50
0
80
8
6
4
2
0
60
40
20
ZA-IMG
0
50
100
150
200
250
Pore diameter (Å)
1.0
0.8
0.6
0.4
0.2
0.0
15
10
5
ZA-SCM
0
50
100
150
200
250
Pore diameter (Å)
0
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Relative pressure (P/P0)
Figure 3. N2 adsorptionꢀdesorption isotherm and corresponding pore size distributions of ZAꢀ
SCM, ZAꢀIMG and ZAꢀPPT catalysts.
11

RSC Advances
Page 12 of 33
View Article Online
DOI: 10.1039/C6RA13956F
3.1.4. FT-IR studies
The FTꢀIR spectra of all the prepared ZrO2ꢀAl2O3 catalytic materials are presented in
Fig. 4. The bands at 690 cmꢀ1, 770 cmꢀ1 and 1050 cmꢀ1 correspond to the OꢀAl vibrations.48
The broad band at ~1600 cmꢀ1 is attributed to the vibrations of acidic –OH bending mode and
broad band at ~3450 cmꢀ1 due to stretching mode with hydrogen bonding are present in all the
catalytic materials.49
ZA-PPT
ZA-IMG
ZA-SCM
500 1000 1500 2000 2500 3000 3500 4000
-1
Wavenumber (cm )
Figure 4. The FTꢀIR spectrum of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT catalytic materials.
3.1.5. TEM, SEM and EDAX studies
The TEM images of all the prepared ZrO2ꢀAl2O3 catalytic materials are given in Fig.
5a. As seen from the figure, ZAꢀSCM shows a uniform and compact distribution of particles
and spherical geometry with particle size of 34ꢀ43 nm. In case of ZAꢀIMG particle size lesser
than that of ZAꢀSCM and in case ZAꢀPPT the boundary between the particles was not
detectable from TEM images which may be due to interactions between the neighboring
12

Page 13 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
particles and due to its amorphous nature. This amorphous nature of ZAꢀPPT and ZAꢀIMG
are in good agreement with the PXRD patterns because, smaller sized particles bring strong
adsorption force, because of which most of the particles are aggregated with each other.50
SEM images and EDAX spectrums of all the prepared ZrO2ꢀAl2O3 catalytic materials are
presented in Fig. 5b and Fig 5c respectively. The SEM images confirm that the catalytic
materials are nonꢀuniformly sized and are porous in nature. The EDAX spectrum of all the
four solid acid catalysts showed that the atomic composition of aluminium, oxygen and
zirconia are same. This confirms that all the prepared samples have similar atomic
composition.
Figure 5a. TEM images of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT catalytic materials.
13

RSC Advances
Page 14 of 33
View Article Online
DOI: 10.1039/C6RA13956F
Figure 5b. SEM images of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT catalytic materials.
Figure 5c. EDAX spectrums of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT catalytic materials.
3.1.6. Elemental analysis by ICP-OES
The ICPꢀOES results indicate that ZAꢀSCM, ZAꢀIMG and ZAꢀPPT consisted of 87.23
weight%, 87.30 weight% and 87.19 weight% of zirconia respectively. Theoretically, ZrO2ꢀ
Al2O3 containing 80 mole% of ZrO2 must contain 87.25 weight% of zirconia because the
atomic weight of zirconia is higher than that of alumina.
3.2. Catalytic activity studies
Test reaction was conducted, the threeꢀcomponent cycloꢀcondensation of benzil,
aldehydes and ammonium acetate with ZrO2ꢀAl2O3 catalytic materials under solventꢀfree
conditions was carried out at optimized reaction conditions at 120 °C (Scheme 1).51 All the
14

Page 15 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
three ZrO2ꢀAl2O3 catalytic materials were used in the present work were active in this
reaction.
Scheme 1a. Cycloꢀcondensation of benzil, aldehydes and ammonium acetate with ZrO2ꢀ
Al2O3 catalytic materials.
O
O
O
ZrO2ꢀAl2O3
+
+
3NH4OAc
N
H
Solvent free,
120 °C
N
R
H
R
Scheme 1b. Cycloꢀcondensation between
O
ꢀphenylenediamines and αꢀdiketone over ZrO2ꢀ
Al2O3 catalytic materials.
R
R
NH2
NH2
O
O
N
N
ZrO2ꢀAl2O3
+
Ethanol
80 °C
R
R
Scheme 1c. Cycloꢀcondensation between
O
ꢀphenylenediamines and ketones over ZrO2ꢀAl2O3
catalytic materials.
R
H
NH2
O
R
ZrO2ꢀAl2O3
N
+
Ethanol,
80 °C
R
R
NH2
N
R
Where, R is alkyl, aryl, alkoxy, N,Nꢀdiethyl and halo group.
When the reaction was carried out in the absence of ZrO2ꢀAl2O3 catalytic material, there
was a negligible amount of formation of reaction product. This indicates that the cycloꢀ
condensation catalyzed reactions.
15

RSC Advances
Page 16 of 33
View Article Online
DOI: 10.1039/C6RA13956F
3.3. Effect of nature of ZrO2, Al2O3 and ZrO2-Al2O3 on the yield 2,4,5 triphenyl-1
H-
imidazole
In an initial study the reactions were carried out 0.03 g of ZAꢀSCM, ZAꢀIMG and ZAꢀ
PPT in cycloꢀcondensation reaction of benzil (1.43 mmol), benzaldehyde (1.43 mmol) and
ammonium acetate (4.29 mmol). It is interesting to note that a maximum yield (99.2%) of
2,4,5 triphenylꢀ1
Hꢀimidazole (Table 2, entry 1) was observed for ZAꢀIMG under solvent free
condition at 120 °C for 20 min. 95.1 % and 89.9 % of 2,4,5 triphenylꢀ1
H
ꢀimidazole was
obtained with ZAꢀSCM and ZAꢀPPT catalytic materials respectively. There is no particular
correlation observed between the activity and surface area. This indicates that the distribution
of catalytic active species on the surface plays significant role than the surface area of the
catalysts.
In order to compare the catalytic activity of ZAꢀSCM, ZAꢀIMG and ZAꢀPPT with similar
catalytic materials in cycloꢀcondensation reaction of benzil (1.43 mmol), benzaldehyde (1.43
mmol) and ammonium acetate (4.29 mmol), the reactions were carried out in presence of
0.03 g of Al2O3, ZrO2, 10 mole% ZrO2ꢀ Al2O3 (10ZA), 20 mole% ZrO2ꢀ Al2O3 (20ZA), 40
mole% ZrO2ꢀ Al2O3 (40ZA) and 80 mole% ZrO2ꢀ Al2O3 (80ZA) or ZAꢀSCM prepared by
SCM using urea as a fuel and the results are shown in Table 1b. When the catalytic activity of
these catalytic materials was compared under solvent free condition at 120 °C for 20 min,
ZAꢀIMG showed better yield of 2,4,5 triphenylꢀ1Hꢀimidazole derivatives than other catalytic
materials used for the present study. The better catalytic activity of ZAꢀIMG can be due to its
higher surface acidity when compared to other similar metal oxides.52
16

Page 17 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
Table 1b. Surface properties and the yield of triphenylꢀ1Hꢀimidazole over ZrO2, Al2O3 and
ZrO2ꢀAl2O3.
Sl. No. Catalytic materials TSA (mmolg-1) Yield of 2,4,5 triphenyl-1
H
-imidazole (%)
1
2
3
4
5
6
7
8
Al2O3
ZrO2
0.49
0.43
0.65
0.76
1.05
1.33
1.52
1.27
60.0
53.6
65.2
73.5
80.7
95.1
99.2
89.9
10ZA
20ZA
40ZA
ZAꢀSCM (80ZA)
ZAꢀIMG
ZAꢀPPT
It was observed that the yield of 2,4,5ꢀtriphenylꢀ1Hꢀimidazole is directly proportional to
tetragonal phase and total surface acidity of the catalytic material. Therefore, ZAꢀIMG
catalyst was chosen for further studies for the synthesis of different 2,4,5ꢀtri substituted
imidazoles.
3.4. Synthesis of different 2,4,5 tri substituted imidazoles over ZA-IMG
The cycloꢀcondensation reaction of benzil (1.43 mmol) with various aldehydes (1.43
mmol) bearing electronꢀdonating groups (methyl or diethyl amine) or electronꢀwithdrawing
groups (halides) at para or meta position and ammonium acetate (4.29 mmol) was carried out
in presence of 0.03 g of ZAꢀIMG catalytic material at 120 °C and the progress of the
reactions were monitored by thin layer chromatography (TLC). Workup procedure for the
reaction and characterization of reaction products has been discussed in Section 2.4. These
reaction time and isolated yield (%) of desired reaction products are listed in Table 2a and the
spectral data of isolated products are presented in Appendixꢀ1.
17

RSC Advances
Page 18 of 33
View Article Online
DOI: 10.1039/C6RA13956F
3.5. Synthesis of different quinoxalines over ZA-IMG
A mixture of 1, 2 dicarbonyl (1.43 mmol),
Oꢀphenylenediamines (1.43 mmol), 0.03 g of
ZAꢀIMG and ethanol (10 mL) was stirred at 80 °C and the progress of the reactions were
monitored by thin layer chromatography (TLC).37c After completion of reaction, the reaction
mixture was filtered to recover the catalytic material, filtrate was evaporated in vacuum to
afford crude, which was purified by silica gel column chromatography using suitable solvent
(ethyl acetate in hexane) afford to desired product of quinoxaline. The reaction time and
isolated yield (%) of desired reaction products are listed in Table 2b and the spectral data of
isolated products are presented in Appendixꢀ1.
3.6. Synthesis of different 1,5-benzodiazepines over ZA-IMG
A mixture of Oꢀphenylenediamines (1.43 mmol), ketones (2.86mmol), 0.03 g of ZAꢀIMG
and ethanol (10 mL) was stirred at 80 °C and the progress of the reactions were monitored by
thin layer chromatography (TLC).41c After completion of reaction, the reaction mixture was
filtered to recover the catalytic material, filtrate was evaporated in vacuum to afford crude,
which was purified by silica gel column chromatography using suitable solvent (ethyl acetate
in hexane) to afford desired product 1,5ꢀbenzodiazepines. The reaction time and isolated
yield (%) of desired reaction products are listed in Table 2c and the spectral data of isolated
products are presented in Appendixꢀ1.
18

Page 19 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
Table 2a. List of aldehydes, products, reaction time and yield of imidazole products.
Reaction
Yield
(%)
Entry
Aldehyde
Reaction product
time (min)
O
H
1
20
99.2
97.6
98.0
97.3
N
N
H
O
H
2
3
4
20
20
20
N
N
H
O
H
N
N
H
O
H
N
N
H
19

RSC Advances
Page 20 of 33
View Article Online
DOI: 10.1039/C6RA13956F
O
H
5
6
7
8
9
20
20
20
20
20
96.5
N
F
N
H
F
O
H
96.2
95.9
97.5
97.7
N
Cl
Cl
N
H
O
H
N
Br
Br
N
H
O
H
N
N
H
Cl
Cl
O
H
N
N
H
Br
Br
20

Page 21 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
O
H
N
10
20
97.1
N
H
N
N
Reaction conditions: 0.03 g of ZAꢀIMG at 120 °C, benzil (1.43 mmol), aldehyde (1.43
mmol) and ammonium acetate (4.29).
Table 2b. List of benzil, products, reaction time and yield of quinoxaline products.
Reaction
Yield
(%)
Entry
1,2 diketone
Reaction product
time (min)
N
N
O
O
1
20
90.3
O
N
N
2
20
91.6
O
21

RSC Advances
Page 22 of 33
View Article Online
DOI: 10.1039/C6RA13956F
O
O
O
O
O
N
N
3
20
91.0
O
Reaction conditions: 0.03 g of ZAꢀIMG at 80 °C, 1,2 diketone (1.43 mmol),
Oꢀ
phenylenediamines (1.43 mmol) and ethanol (10.0 mL).
Table 2c. List of benzil, products, reaction time and yield of 1,5ꢀ benzodiazepine products.
Reaction
Yield
Entry
Ketone
Reaction product
time (min)
(%)
N
N
O
1
30
30
95.7
H
N
O
2
96.1
N
H
N
O
3
40
92.3
N
22

Page 23 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
Reaction conditions: 0.03 g of ZAꢀIMG at 80 °C,
Oꢀphenylenediamines (1.43 mmol),
ketones (2.86 mmol) and ethanol (10.0 mL).
Appendix – 1
Spectral data of synthesized esters (Refer to table 2a, 2b and 2c)
-imidazole (Table 2a, Entry 1): 1H NMR (DMSOꢀ
2,4,5-triphenyl-1
H
d
6, 400 MHz): δ (ppm)
= 7.2 Hz), 7.408ꢀ7.497 (m,
J = 7.6 Hz), 12.641 (br s, 1H, D2O
7.184 (t, 1H,
J
= 7.2 Hz), 7.286 (t, 2H,
J = 7.2 Hz), 7.358 (t, 2H, J
6H), 7.532 (d, 2H,
J
= 7.6 Hz), 8.063 (d, 2H,
exchangeable). Calculated for C21H16N2 [M+H+]: 297.13, found [M+H+]: 297.1, physical
state: offꢀwhite solid; melting point: 271ꢀ273 °C.
4,5-diphenyl-2-(
δ (ppm) 2.621 (s, 3H), 7.192 (t, 1H,
Hz), 7.489 (d, 2H, = 7.6 Hz), 7.537 (d, 2H,
o
-tolyl)-1
H
-imidazole (Table 2a, Entry 2): 1H NMR (DMSOꢀ
= 7.6 Hz), 7.262ꢀ7.357 (m, 6H), 7.411 (t, 2H,
= 7.2 Hz), 7.692 (t, 1H, = 7.6 Hz), 12.426
d
6, 400 MHz):
= 7.6
J
J
J
J
J
(br s, 1H, D2O exchangeable). Calculated for C22H18N2 [M+H+]: 311.15, found [M+H+]:
311.1, physical state: offꢀwhite solid; melting point: 204ꢀ206 °C.
1
4,5-diphenyl-2-(
m
-tolyl)-1
H
-imidazole (Table 2a, Entry 3): H NMR (DMSOꢀ
d
6, 400
MHz): δ (ppm) 2.368 (s, 3H), 7.165ꢀ7.220 (m, 2H), 7.265ꢀ7.370 (m, 4H), 7.422 (t, 2H,
7.2 Hz), 4.483 (d, 2H, = 6.8 Hz), 7.530 (d, 2H, = 7.6 Hz), 7.852 (d, 1H, = 7.6 Hz), 7.911
J =
J
J
J
(s, 1H), 12.595 (br s, 1H, D2O exchangeable). Calculated for C22H18N2 [M+H+]: 311.15,
found [M+H+]: 311.1, physical state: offꢀwhite solid; melting point: 229ꢀ231 °C.
4,5-diphenyl-2-(
p
-tolyl)-1
H
-imidazole (Table 2a, Entry 4): 1H NMR (DMSOꢀ
d
6, 400 MHz):
= 7.6
δ (ppm) 2.340 (s, 3H), 7.261ꢀ7.351 (m, 8H), 7.508 (d, 4H,
J
= 7.2 Hz), 7.959 (d, 2H,
J
Hz), 12.573 (br s, 1H, D2O exchangeable). Calculated for C22H18N2 [M+H+]: 311.15, found
[M+H+]: 311.1, physical state: offꢀwhite solid; melting point: 228ꢀ230 °C.
1
2-(3-fluorophenyl)-4,5-diphenyl-1
H
-imidazole (Table 2a, Entry 5): H NMR (DMSOꢀd6
,
400 MHz): δ (ppm) 7.164ꢀ7.232 (m, 2H), 7.293 (t, 2H, J = 6.8 Hz), 7.372 (t, 1H, J = 6.8 Hz),
23

RSC Advances
Page 24 of 33
View Article Online
DOI: 10.1039/C6RA13956F
7.418 (t, 2H,
J
= 7.2 Hz), 7.455ꢀ7.535 (m, 5H), 7.853 (d, 1H, J = 10.4 Hz), 7.916 (d, 1H, J =
8.0 Hz), 12.755 (br s, 1H, D2O exchangeable). Calculated for C21H15FN2 [M+H+]: 315.12,
found [M+H+]: 315.1, physical state: offꢀwhite solid; melting point: 284ꢀ286 °C.
1
2-(3-chlorophenyl)-4,5-diphenyl-1
400 MHz): δ (ppm) 7.216 (t, 1H, = 7.2 Hz), 7.294 (t, 2H,
8.029 (d, 1H, = 8.0 Hz), 8.131 (s, 1H), 12.783 (br s, 1H, D2O exchangeable). Calculated for
H
-imidazole (Table 2a, Entry 6): H NMR (DMSOꢀd6
,
J
J = 7.6 Hz), 7.369ꢀ7.541 (m, 9H),
J
C21H15ClN2 [M+H+]: 331.09, found [M+H+]: 331.1, physical state: offꢀwhite solid; melting
point: 281ꢀ283 °C.
1
2-(3-bromophenyl)-4,5-diphenyl-1
400 MHz): δ (ppm) 7.216 (t, 1H, = 7.2 Hz), 7.293 (t, 2H,
8.068 (d, 1H, = 8.0 Hz), 8.277 (s, 1H), 12.780 (br s, 1H, D2O exchangeable). Calculated for
H
-imidazole (Table 2a, Entry 7): H NMR (DMSOꢀd6
,
J
J = 7.2 Hz), 7.350ꢀ7.554 (m, 9H),
J
C21H15BrN2 [M+H+]: 375.04, found [M+H+]: 375.0, physical state: offꢀwhite solid; melting
point: 299ꢀ301 °C.
1
2-(4-chlorophenyl)-4,5-diphenyl-1
400 MHz): δ (ppm) 7.209 (t, 1H, 7.6 Hz), 7.286 (t, 2H,
7.429 (t, 2H, = 7.6 Hz), 7.485 (d, 2H, = 7.6 Hz), 7.527 (d, 4H,
H
-imidazole (Table 2a, Entry 8): H NMR (DMSOꢀd6
,
J
= 7.6 Hz), 7.363 (t, 1H,
J
= 7.2 Hz),
J
J
J
= 8.0 Hz), 8.078 (d, 2H, J
= 8.4 Hz), 12.735 (br s, 1H, D2O exchangeable). Calculated for C21H15ClN2 [M+H+]: 331.09,
found [M+H+]: 331.1, physical state: offꢀwhite solid; melting point: 262ꢀ264 °C.
1
2-(4-bromophenyl)-4,5-diphenyl-1
400 MHz): δ (ppm) 7.208 (t, 1H, = 7.2 Hz), 7.286 (t, 2H,
Hz), 7.428 (t, 2H, = 7.2 Hz), 7.483 (d, 2H,
2H, = 7.2 Hz), 8.013 (d, 2H,
H
-imidazole (Table 2a, Entry 9): H NMR (DMSOꢀd6
,
J
J
= 7.2 Hz), 7.362 (t, 1H,
J
= 7.2
J
J
= 7.2 Hz), 7.527 (d, 2H,
J
= 7.2 Hz), 7.663 (d,
J
J
= 8.4 Hz), 12.744 (br s, 1H, D2O exchangeable). Calculated
for C21H15BrN2 [M+H+]: 375.04, found [M+H+]: 375.0, physical state: offꢀwhite solid;
melting point: 260ꢀ262 °C.
24

Page 25 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
1
4-(4,5-diphenyl-1
(DMSOꢀ
= 8.8 Hz), 7.177ꢀ7.331 (m, 4H), 7.395 (t, 2H,
2H, = 6.8 Hz), 7.843 (d, 2H, = 8.4 Hz), 12.214 (br s, 1H, D2O exchangeable). Calculated
H
-imidazol-2-yl)-N,N-diethylaniline (Table 2a, Entry 10): H NMR
d
6, 400 MHz): δ (ppm) 1.107 (t, 6H, 7.2 Hz), 3.369 (q, 4H, 6.8 Hz), 6.709 (d, 2H,
= 6.8 Hz), 7.459 (d, 2H, = 7.6 Hz), 7.515 (d,
J
J
J
J
J
for C25H25N3 [M+H+]: 368.20, found [M+H+]: 368.2, physical state: offꢀwhite solid; melting
point: 220ꢀ222 °C.
2,3-diphenylquinoxaline (Table 2b, Entry 1): 1H NMR (CDCl3, 400 MHz): δ (ppm) 7.332ꢀ
7.371 (m, 6H), 7.565 (dd, 4H, J1 = 7.8 Hz, J2 = 1.2 Hz), 7.759 (dd, 2H, J1 = 6.3 Hz, J2 = 3.4
Hz), 8.223 (dd, 2H, J1 = 6.3 Hz, J2 = 3.4 Hz). Calculated for C20H14N2 [M+H+]: 283.35,
found [M+H+]: 283.3, physical state: offꢀwhite solid; melting point: 127ꢀ129 °C.
2,3-di-
p
-tolylquinoxaline (Table 2b, Entry 2): 1H NMR (CDCl3, 400 MHz): δ (ppm) 2.401
(s, 6H), 7.180 (d, 4H,
J
= 7.9 Hz), 7.478 (d, 4H,
J = 7.9 Hz), 7.763 (dd, 2H, J1 = 6.3 Hz, J2 =
3.4 Hz), 8.189 (dd, 2H, J1 = 6.3 Hz,
J
2 = 3.4 Hz). Calculated for C22H18N2 [M+H+]: 311.40,
found [M+H+]: 311.4, physical state: yellow solid; melting point: 146ꢀ148 °C.
2,3-bis-(4-methoxyphenyl)-quinoxaline (Table 2b, Entry 3): 1H NMR (CDCl3, 400 MHz): δ
(ppm) 3.831 (s, 6H), 6.889 (d, 4H,
J
= 8.3 Hz), 7.522 (d, 4H,
J = 8.3 Hz), 7.720 (dd, 2H, J1 =
6.1 Hz, 2 = 3.2 Hz), 8.136 (dd, 2H, J1 = 6.05 Hz,
J
J2 = 3.2 Hz). Calculated for C22H18N2O2
[M+H+]: 343.40, found [M+H+]: 343.4, physical state: offꢀwhite solid; melting point: 152ꢀ
153 °C.
1
2,2,4-trimethyl-2,3-dihydro-1
H
-benzo-1,5-benzodiazepine (Table 2c, Entry 1): H NMR
(CDCl3, 400 MHz): δ (ppm) 1.349 (s, 6H), 2.201 (s, 2H), 2.352 (s, 3H), 2.94 (br s, 1H, D2O
exchangeable), 6.652ꢀ7.302 (m, 4H). Calculated for C12H16N2 [M+H+]: 189.27, found
[M+H+]: 189.3, physical state: yellow solid; melting point: 135ꢀ136 °C.
2,2,4-triethyl-3-methyl-2,3-dihydro-1H
-1,5-benzodiazepine (Table 2c, Entry 2): 1H NMR
(CDCl3, 400 MHz): δ (ppm) 0.751ꢀ1.049 (m, 10H), 1.191ꢀ1.380 (m, 4H), 1.501ꢀ1.646 (m,
25

RSC Advances
Page 26 of 33
View Article Online
DOI: 10.1039/C6RA13956F
2H), 2.398ꢀ2.601 (m, 2H), 2.867 (q, 1H,
6.573 (d, 1H, = 8.0 Hz), 6.647 (t, 1H,
J
= 6.9 Hz), 3.750 (br s, 1H, D2O exchangeable),
J
J
= 8.0 Hz), 6.904 (t, 1H, J = 8.0 Hz), 7.376 (d, 1H, J
= 8.0 Hz). Calculated for C16H24N2 [M+H+]: 245.38, found [M+H+]: 245.4, physical state:
offꢀwhite solid; melting point: 141ꢀ143 °C.
1
2-methyl-2,4-diphenyl-2,3-dihydro-1
H
-1,5-benzodiazepine (Table 2c, Entry 3): H NMR
(CDCl3, 400 MHz): δ (ppm) 1.801 (s, 3H), 2.946 (d, 1H,
J
= 12.8 Hz), 3.152 (d, 1H, J = 12.8
Hz), 3.451 (br s, 1H, D2O exchangeable), 6.555ꢀ7.001 (m, 3H), 7.153ꢀ7.348 (m, 7H), 7.555ꢀ
7.649 (m, 4H). Calculated for C22H20N2 [M+H+]: 313.42, found [M+H+]: 313.4, physical
state: yello solid; melting point: 152ꢀ153 °C.
3.7. Effect of re-usability of ZA-IMG catalytic materials on the yield of 2,4,5-triphenyl-
1H-imidazole
In order to study the reusability of ZAꢀIMG catalyst, the reaction was carried out between
◦
benzil, benzaldehyde and ammonium acetate in presence of 0.03 g of ZAꢀIMG at 120 C for
20 min. The catalyst (ZAꢀIMG) was recovered after the each cycle of the reaction, followed
o
by washing with acetone, drying in an oven at 120 C for 1 h. Thus thermally regenerated
ZAꢀIMG was reꢀused in the next reaction cycle. Such studies were carried out for 6
consecutive reaction cycles and the results are presented in Fig. 6. It can be seen from the
figure that, not much change in yield of 2,4,5ꢀtriphenylꢀ1Hꢀimidazole could be observed.
Hence, ZAꢀIMG catalyst could be reused at least for six or more reaction cycles without
much loss of its catalytic activity. PXRD and FTIR patterns of the ZAꢀIMG after 6th reaction
cycles are showed in Fig. S1 and S2 respectively and not much change in the total surface
acidity (1.52 mmolgꢀ1) of the ZAꢀIMG after 6th reaction cycles was observed.
26

Page 27 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
100
80
60
40
20
0
1
2
3
4
5
6
No. of reaction cycles
Figure 6. Effect of reusability of ZAꢀIMG catalyst on the yield of 2,4,5ꢀtriphenylꢀ1Hꢀ
imidazole. [Reaction conditions: 0.03 g of ZAꢀIMG catalyst at 120 °C for 20 min, benzil =
1.43 mmol, benzaldehyde = 1.43 mmol, ammonium acetate = 4.29 mmol].
4. Conclusion
In conclusion, the authors of this article have developed an efficient and green ZrO2ꢀ
Al2O3 catalytic material by following different methods. ZrO2ꢀAl2O3 prepared by
impregnation method possesses comparatively high surface acidity than ZrO2ꢀAl2O3 prepared
by either solution combustion or precipitation method. ZrO2ꢀAl2O3 prepared by impregnation
method could effectively catalyze the cycloꢀcondensation of benzil, different aldehydes with
ammonium acetate, carbonyl compound with
Oꢀphenylenediamines and 1,2ꢀdiamine with αꢀ
diketones with excellent yield of desired products such as 2,4,5ꢀtrisubstituted imidazoles,
quinoxalines and 1,5ꢀbenzodiazepines respectively at moderate temperature in shorter
reaction time under solvent free conditions. ZrO2ꢀAl2O3 catalytic materials could be
recovered and reused for at least six reaction cycles without much loss of its activity.
27

RSC Advances
Page 28 of 33
View Article Online
DOI: 10.1039/C6RA13956F
Acknowledgement
The authors thank to VGST, GoK (GRDꢀ375/2014ꢀ15) for the part financial support.
1
Authors also thank the authorities of IISc, Bangalore for SEM, TEM, H NMR, LCMS and
ICPꢀOES analysis. The authors are thankful to the department of chemistry, St. Joseph’s
college, Bangalore for PXRD and FTꢀIR analysis.
References
1. T. M. Miller and V. H. Grassian, J. Am. Chem. Soc., 1995, 117 (44), 10969.
2. N. Pernicone, F. Lazzerin, G. Liberti and G. Lanzavecchia, J. Catal., 1969, 14 (4), 391;
(b) N. Thimmaraju, S. Z. M. Shamshuddin, S. R. Pratap and Venkatesh, J. Mol. Catal A:
Chem., 2014, 391, 55.
3. (a) A. V. Biradar, S. B. Umbarkar and M.K. Dongare, Appl. Catal. A., 2005, 285, 190; (b)
A. P. Amrute, A. Bordoloi, N. Lucas, K. Palraj and S. B. Halligudi, Catal. Lett., 2008,
126, 286.
4. (a) E. L. S. Ngee, Y. Gao, X. Chen, T. M. Lee, Z. Hu, D. Zhao and N. Yan, Ind. Eng.
Chem. Res., 2014, 53, 14225; (b) N. Thimmaraju, S. Z. M. Shamshuddin, S. R. Pratap
and K. Raja, RSC Adv., 2015, 5, 99517.
5. L. E. Davies, N. A. Bonini, S. Locatelli and E. E. Gonzo, Latin Am. Appl. Res., 2005, 35,
23.
6. B. M. Reddy, K. V. R. Chary, B. Rama Rao, V. S. Subrahmanyam and C. S. Sunandanat,
Polyhedron, 1986, 5 (112), 191.
7. H. Pines and W.O. Haag, J. Am. Chem. Soc., 1960, 82, 2471.
8. (a) Y. X. Hao, J. S. Li, X. J. Yang, X. Wang and L. D. Lu, Materials Science and
Engineering A, 2004, 367, 243; (b) G. V. Sagar, P. V. R. Rao, C. S. Srikanth and K. V.
R. Chary, J. Phys. Chem. B., 2006, 110, 13881.
9. J. D'Souza and N. Nagaraju, Ind. J. Chem.Technol., 2004, 11, 401.
28

Page 29 of 33
RSC Advances
View Article Online
DOI: 10.1039/C6RA13956F
10. L. Har, J. Am. Ceram. Soc., 1990, 6, 329.
11. (a) A. Domling, Chem. Rev., 2006, 106, 17. (b) C. C. A Cariou, G. J. Clarkson and M.
Shipman, J. Org. Chem., 2008, 73, 9762.
12. S. Samai, G. H. Nandi, P. Singh, and M. S. Singh, Tetrahedron, 2009, 65, 10155.
13. R. R. Nagawade and D. B. Shinde, Acta Chim. Slov., 2007, 54, 642.
14. K. Sivakumar, A. Kathirvel and A. Lalitha, Tetrahedron Lett., 2010, 51, 3018.
15. (a) L. Weber, Drug Discov. Today., 2002. 7, 143. (b) S. H. Reza, R. Mohammed and A.
Kobra, Chin. J. Chem., 2011, 29, 1635
16. (a) X. Gao, X. Chen, J. Zhang, W. Guo, F. Jin and N. Yan, ACS Sustainable Chem. Eng.,
2016, DOI: 10.1021/acssuschemeng.6b00767; (b) X. Chen, S. L. Chew, F. M. Kerton and
N. Yan, Green Chem., 2014, 16, 2204
17. T. N. Doman, S. L. McGovern, B. J. Witherbee, T. P. Kasten, R. Kurumbail, W. C.
Stallings, D. T. Connolly and B. K. Shoichet, J. Med. Chem., 2002, 47, 2213.
18. J. G. Lambardino and E. H. Wiseman, J. Med. Chem., 1979, 17, 1182.
19. M. Antolini, A. Bozzoli, C. Ghiron, G. Kennedy, T. Rossi and A. Ursini, Bioorg. Med.
Chem. Lett., 1999, 9, 1023.
20. V. H. V Bossche, G. Willemsens, W. Cools, P. Marichal and W. Lauwers, Biochem. Soc.
Trans., 1983, 11, 665.
21. L. Wang, K. W. Woods, Q. Li, K. J. Barr, R. W. McCroskey, S. M. Hannick, L. Gherke,
R. B. Credo, Y. H. Hui, K. Marsh, R. warner, J. Y. Lee, N. Zielinskyꢀmozng, D. Frost, S.
H. Rosenberg and H. L Sham, J. Med. Chem., 2002, 45, 1697.
22. A. Puratchikody and M. Doble, Bioorg. Med. Chem., 2007, 15, 1083.
23. R. Schmierer, H. Mildenbergr and H. Buerstell, German Pat., 361464, 1987, Chem.
Abstr. 108, 37838 (1988).
29