preparation and characterization of alumina, zirconia...
TRANSCRIPT
Chapter II
Page 25
Preparation and characterization of alumina, zirconia, manganese oxide
modified alumina and zirconia catalyst and there catalytic activity in
the synthesis of Benzimidazoles and Benzodiazepines
Chapter II
Page 26
Introduction
Benzimidazole (I) and benzodiazepine (II) are organic heterocyclic structural units found
in many pharmaceutical agents which exhibit a wide range of biological applications [1].
N
NH
R
Substituted benzimidazole
NH
N
R1
R
R
Substituted benzodiazepine
I II
Benzimidazoles
Various pharmacophores of N-1 substituted and 2-substituted benzimidazole
derivatives are employed as subunits of biologically important molecules[2, 3]. These
derivatives are structural isosteres of naturally occurring nucleotides, which allow them
to interact easily with the biophores [4]. Biological activities of benzimidazole
derivatives includes antimicrobial [5], anticancer [6], anti-inflammatory [7], antiviral [8],
antiparasitic [9], antiprotozoal [10], antihelminitics [11], protein kinase inhibitors [12]
and H+/K
+ ATPase inhibitors [13].
Polyfunctionality of 2-aminobenzimidazole molecule synthesized from the cyclic
guanidine moiety has made it a building block for the further synthesis of a large number
of derivatives of pharmacological interest [14], for instance in vivo and in vitro growth
inhibition activity against various strains of bacteria, fungi and yeast. Benzimidazoles
also exhibit significant activity against several viruses including HIV [15], herpes (HSV-
1) [16], influenza [17] and human cytomegalovirus (HCMV) [18].
Benzimidazoles and their derivatives are generally prepared starting from o-
phenylenediamine (OPDA) with a carboxylic acid and its derivative [19-21], orthoesters
[22, 23] in the presence of a strong acid such as p-TsOH and silica supported fluoroboric
acid at elevated temperature. Several other protocols have also been introduced in which
aldehydes [24], acid chloride [25], o-dinitrobenzene [26], (CH3)2NCH=NCH=N(CH3)2Cl,
Chapter II
Page 27
Gold’s reagent[27] and 2-nitroanilines [28] are used as one of the starting materials for
the synthesis of benzimidazoles. Brain and Steer have developed a new procedure for the
preparation of benzimidazole derivatives by palladium-catalyzed aryl-amination
chemistry [29].A solvent free synthesis of benzimidazoles under microwave irradiation
using Yb(OTf)3 [30] has been reported by Wang. et al. KSFclay [31], PPA [32], metal
halide supported alumina [33] and solid support [34, 35] have been used as catalysts in
the preparation of a number of substituted benzimidazoles. It is also evident from the
literature that not only different catalysts were investigated to activate the reactants in the
synthesis of benzimidazole derivatives but also the effect of variation of experimental
conditions has been studied.
Benzodiazepines
Benzodiazepines are another important class of organic heterocyclic compounds which
findapplications in medicinal chemistry. They are used astranquilizers [36], anti-anxiety
agents [37], anti-inflammatory agents [38], anticonvulsants and hypnotics [39, 40].
Benzodiazepines are valuable synthons used for the preparation of other fused ring
compounds such as triazolo- [41], oxadiazolo- [42], oxazino- [43] or furano-
benzodiazepines [44]. Benzodiazepine derivatives find commercial applications as dyes
for acrylic fibers and photography [45, 46].
Due to wide range of pharmacological activities, industrial and synthetic applications of
benzodiazepines and its derivatives, their synthesis has received good attention of
synthetic organic chemists;as a result several methods for their preparation have been
reported in the literature. These include condensation of o-phenylenediamines with
unsaturated carbonyl compounds [47]. These reactions have been carried out in the
presence of different kind of homogeneous and heterogeneous Lewis acid catalysts which
are either supported or unsupported.
The following are a few reports in which unsupported homogeneous catalysts were used
in the synthesis of benzodiazepines: Herbert and Suschitzky have synthesized
benzodiazepines using ketones in presence of BF3-OEt2 [48]. The applications of ionic
Chapter II
Page 28
liquid [49], Yb-(OTf)3 [50], Silver complex in CH3OH [51], ionicliquid (1-butyl-3-
methylimidazolium bromide) ([bmim]Br) [52] as homogeneous catalysts have also been
reported.
Unsupported heterogeneous catalysts such as MCM-41 [53], Amberlyst-15 [54],
heteropoly acids [55] and supported heterogeneous catalysts such as polyphosphoric acid
supported on SiO2 [56], POCl3 supported on MgO [57] and CeCl3·7H2O/NaI supported
on silica gel [58] are found to be good catalysts in the synthesis of
benzodiazepines.Microwave induced synthesis of benzodiazepines in the presence of
acetic acid [59], and Al2O3/P2O5 [60] have also been reported.
The homogeneous catalysts in general have been found to be selective, however the main
disadvantages of using these catalysts seems to be the separation and reusability of the
catalyst. Many times these methodologies are suitable only under certain synthetic
conditions. There also exist drawbacks such as long reaction time, use of environmentally
unfriendly reagents and high boiling solvents like dimethyl formamide (DMF) and
dimethyl sulfoxide (DMSO). However when heterogeneous catalysts were used, not only
the selectivity and yield of the product were good but also the catalysts could be easily
separated from the reaction mixture and reused, thus making the process environmentally
benign and economical. There is a scope for further development of a mild, efficient,
greener solid acid catalysts which can be easily recovered and reused from the reaction
mixture and thus overcome some of the above mentioned disadvantages. It is further
evident from the literature that no attempt has been made to correlate the catalytic activity
of the heterogeneous solid acid catalysts and their textural properties. In light of the
above, herein we have made an attempt to:
Prepare alumina, zirconia, manganese oxide supported alumina and manganese
oxide supported zirconia materials by simple precipitation-impregnation
technique. The selected materials are inexpensive, non-toxic and environmentally
benign.
Chapter II
Page 29
Characterize the materials for their textural properties such as crystallinity,
surface area, pore size, pore volume, surface acidty and surface morphology by
suitable techniques, inorder to correlate the catalytic activity with their textural
properties.
Determine the catalytic activity of the material under different reaction conditions
in the synthesis of pharmacologically important derivatives of benzimidazoles and
benzodiazepines.
Author’s work
The experimental work carried out involves the following three sections. These are
1. Preparation of catalysts
2. Characterization of the catalyst
3. Catalytic activity determination.
Each of the above sections follows a presentation of the results and discussions.
2.1 Preparation of the catalyst
In the present work alumina and zirconia were prepared from commercial aluminum
hydroxide and zirconium hydroxide. Manganese oxide supported on alumina and
manganese oxide supported on zirconia was prepared by simple precipitation-
impregnation method.The procedure followed and conditions are described below.
2.1.1 Preparation of alumina support
Commercial aluminium hydroxide Al(OH)3 (Across, Belgium. 99%pure) was used to
obtain alumina support. A required amount of aluminium hydroxide was transferred into
a silica crucible and dried at 120oC. A part of it taken in a silica crucible was placed in an
electric muffle furnace at 450oC for 5 h. These samples were stored in air tight containers
separately and used for further studies. Thus obtained alumina samples were abbreviated
as Al2O3-120 and Al2O3-450, where the numbers indicate the heat treatment
temperatures.
Chapter II
Page 30
2.1.2 Preparation of manganese oxide supported on alumina.
Manganese (5%) in the form of its oxide supported on alumina was prepared by simple
precipitation-impregnation method using manganese sulphate as a precursor. In a typical
procedure for the preparation of manganese oxide supported on alumina containing 5%of
manganese, 30.87 g of aluminum hydroxide (Al(OH)3) powder (Across chemicals,
Belgium, 99%pure) was suspended in 2 L of distilled water and mixed with 3.84 g of
manganese sulfate (MnSO4. H2O, Merck). The suspension thus obtained was heated to 70
oC on a heating Remi make Rota Mantle. The hot solution was stirred for 1 h and liquor
ammonia (28%aqueous NH3) was added slowly using a burette with stirring to precipitate
manganese as its hydroxide (pH 9).
The thick brown precipitate thus obtained was stirred for 2 h at 70oC to get a
homogeneous mixture which was left overnight undisturbed at room temperature. The
supernatant liquid was decanted and the solid was separated by filtration using Buchner
funnel fitted with Whatmann-1filter paper. The solid was washed with deionized water
until the washings were free from sulfate ions as confirmed by barium chloride test. The
solid wasdried in an air oven at 120oC for 12 h followed by calcination at 450
oC for 5 h
in a muffle furnace.The material dried at 120oC was abbreviated as Mn/Al2O3-120,
whereas the one calcined at 450oC was abbreviated as Mn/Al2O3-450.
2.1.3 Preparation of zirconia support.
Commercial zirconium hydroxide, Zr(OH)4 (Sigma Aldrich, 99.99% pure, India)
was used to obtain zirconia support. A certain amount of zirconium hydroxide was
transferred into silica crucible and dried at 120oC and a part of it taken in a silica crucible
was placed in an electric muffle furnace at 450oC for 5 h. these samples were stored in
airtight containers separately and used for further studies. These zirconia materials were
abbreviated as ZrO2-120 and ZrO2-450, where the numbers indicate the heat treatment
temperatures.
Chapter II
Page 31
2.1.4. Preparation of manganese oxide supported on zirconia
Manganese (5%) in the form of its oxide supported on zirconia was prepared by
simple precipitation-impregnation method using manganese sulphate as a precursor. In a
typical procedure for the preparation of manganese oxide supported on zirconia
containing 5% of manganese, 29.65 g of zirconium hydroxide [Zr(OH)4] powder (Sigma
Aldrich, 99.99% pure, India) was suspended in 2 L of distilled water and mixed with 3.84
g of manganese sulfate (MnSO4. H2O, Merck). The suspension thus obtained was heated
to 70oC on a heating Remi make Rota Mantle. The hot solution was stirred for 1 h and
liquor ammonia (28%aqueous NH3) was added slowly using a burette with stirring to
precipitate manganese as its hydroxide (pH 9).
Thus obtained thick brown precipitate was stirred for 2 h at 70oC to get a homogeneous
mixture which was left overnight undisturbed at room temperature. The supernatant
liquid was decanted and the solid was separated by filtration using Buchner funnel fitted
with Whatmann-1 filter paper. The solid was washed with deionized water until the
washings were free from sulfate ions as confirmed by barium chloride test. The solid was
dried in an air oven at 120oC overnight followed by calcination at 450
oC for 5 h in a
muffle furnace. The material dried at 120oC was abbreviated as Mn/ZrO2-120, whereas
the one calcined at 450oC was abbreviated as Mn/ZrO2-450.
2.2 Characterization of the catalysts
All the catalytic materials as prepared in the previous sections were thoroughly
characterized for their surface and bulk properties by appropriate techniques as indicated
below:
The exact percentage composition of manganese by Inductively Coupled Plasma-
Optical Emission Spectrometer (ICP-OES),
Crystallinity by Powder X-ray diffraction (PXRD).
Functional group analysis by Fourier Transform Infrared spectrophotometry (FT-
IR).
Specific surface area, pore size and pore volume by N2 adsorption method.
Brunauer-Emmett-Teller (BET) method.
Chapter II
Page 32
Quality and quantity of surface acid sites by Temperature programmed desorption
of ammonia (TPD-NH3) and n-butyl amine back titration method.
Thermal stability by Thermo gravimetric analysis (TGA)
Surface morphology by scanning electron microscopy (SEM) and transmission
electron microscopy (TEM).
The experimental procedures used in the above characterization techniques have been
briefly described in the following sections.
2.2.1 Inductively Coupled Plasma-Optical Emission Spectrometer (ICP-OES)
Quantity of manganese present in alumina and zirconia based catalysts was
estimated by ICP OES analysis technique using Thermo-iCAP 6000 Series instrument.
The operation conditions are mentioned as shown in Table 2.1. The standards ranging
from 20-140 ppm were prepared by digesting the catalyst material at pH 1-2 using nitric
acid (HNO3) and this solution was filtered through 0.45µ (micron) membrane filter and
used for further analysis by the instrument.
Table 2.1.Operating conditions of ICP-OES instrumental analysis
Auxiliary Flow (l/min) 0.5
RF power (W) 1200
Nebulization Pressure (psi) on
Speed peristaltic pump - Flush pump rate and Analysis pumprate
(rpm)
50
Speed peristaltic pump - Analysis pump rate (rpm) 50
Pump stabilization time (sec) 5
Integration Time in the UV and visible 15 - 10
Chapter II
Page 33
2.2.2. Powder X-ray diffraction (PXRD)
In order to ascertain crystalline/amorphous nature of the materials, their Powder
X-ray diffraction patterns were recorded on a Panalytical Xpert pro X-ray diffractometer
using Cu Kα radiation (λ=0.154 nm) a graphite crystal monochromator. Diffractograms
were obtained in the 2θ range from 5o to 70
o at 40 KV with a scanning rate of 2
o min
-1.
2.2.3 Fourier Transform Infrared spectrophotometry (FT-IR)
The characteristic bond vibrational frequencies of supports and supported
catalysts, as well as any anions of the precursor salts occluded into the catalysts during
their preparations, were identified by recording their FT-IR spectra as KBr pellets, with 4
cm-1
resolution using a Nicolet IR200 FT-IR Spectrophotometer in the range 400-4000
cm-1
.
2.2.4 Specific surface area, pore size and pore volume by N2 adsorption method.
Brunauer-Emmett-Teller (BET) method
The specific surface area, pore diameter and pore volume were evaluated by a
Micromeritics TriStar 3000 instrument. In this analysis the samples were degassed at 523
K for 5 h before the measurement. A calculated amount of sample was taken in a U
shaped tube. The sample was cooled to room temperature and then bought to 77 K using
liquid nitrogen as coolant. The sample was saturated with nitrogen when it is physically
adsorbed on the sample at the temperature of 77 k. The amount of nitrogen adsorbed was
recorded using a detector from which surface area is calculated. The pore volume and
pore size distributions were estimated at a relative pressure p/po and N2 adsorption
desorption isotherm using BJH model respectively.
2.2.5 Temperature programmed desorption of ammonia (TPD-NH3)
The TPD-NH3is a powerful technique used to determine total number of acidic
sites (total acidity) and the strength of acidic sites present on catalyst surfaces. The later
is temperature dependent. In a typical Temperature Programmed Desorption of ammonia
(TPD-NH3) experiment, 0.1 g of the catalyst was pretreated in He gas at 300 oC for 2 h
and cooled to room temperature. The adsorption studies were conducted at 100 oC by
Chapter II
Page 34
passing He gas containing 5% of NH3 over the catalyst. The catalyst surface was then
flushed with He gas for 2 h to flush of the physisorbed NH3. The catalyst with adsorbed
ammonia is then heated in the temperature range 50-700 oC. The amount of NH3desorbed
was calculated from the peak area of the already calibrated TCD signal.
2.2.6 n-butyl amine back titration method.
The total surface acidity of the material can be estimated by this method. About 0.5 g of
the catalyst was suspended in 25 ml of dry benzene solution of 0.05 M n-butyl amine.
The mixture was left for 24 h. during this period all the acid sites on the surface of the
solid get neutralized. The unreacted n-butyl amine was estimated by titrating against 0.05
M HCl using bromothymol blue as an indicator. The surface acidity of the solid catalyst
was calculated from the decrease in concentration of n-butyl amine. The calculation of
total acidity is as follows:
Molarity of n-butyl amine before the catalyst = x mole/L
Molarity of n-butyl amine after treating with the catalyst = y mole/L
Weight of the catalyst = W g.
The surface acidity of the catalyst = ( )
= m mol/g of the catalyst.
2.2.7 Thermo gravimetric analysis (TGA)
The percentage of weight loss at particular temperature and also the phase transitions
taking place during thermal treatment of the materials is given by TGA technique.
Thermo gravimetric analysis was carried out using a Mettle-teledo 851e TGA/SDTA
India private limited system driven by star e7.1 software. About 300 mg of the catalyst
sample was taken in an alumina crucible and heated in the TG balance at the rate of
5oC/min till 700
oCin the presence of 50 ml/min O2 gas. The temperature was plotted on
Chapter II
Page 35
abscissa and weight was plotted as ordinate and from the plot at different temperatures
the weight loss of the sample was measured.
2.2.8 Scanning electron microscopy (SEM)
The catalyst particle morphology was investigated by field-emission scanning electron
microscopy. SEM (Jeol JSM-7500F microscope operating at 20 kV at a working distance
of 8 mm).The sample for SEM analysis was prepared by physically adsorbing a thin layer
of the sample on an aluminum stud and subsequent coating of the sample with an electro
active material. SEM gives a 3D image of the catalyst at lower resolution and give
information on the surface topography on the average atomic number in the scattered
area.
2.2.9 Transmission electron microscopy (TEM)
TEM is a powerful method for investigating the morphology of supported metal catalysts.
TEM provides direct images of the catalyst's microstructure, enabling accurate particle
size distributions to be determined. In addition to the above it also provides information
about the deposition of the supported particles.
Samples for TEM were prepared by dispersion in ethanol for 10 min in an ultrasonic
bath. A drop of the sample was deposited on a holey carbon-coated copper grid and
allowed to dry before imaging. The sample was observed using a Philips Tecnai 10
electron microscope operated at 80 kV.
2.3 Catalytic activity studies
The catalytic activity of alumina, zirconia, manganese oxide supported alumina and
manganese oxide supported zirconia was investigated in a condensation reaction between
OPDA and an aldehyde or a ketone (Scheme 2.1).
Chapter II
Page 36
+
aetophenone
Ethanol, 80 oC
NH2
NH2
+O
H C6H5Ethanol, 80
oC
N
NH
C6H5
benzaldehyde
O
H5C6CH3
NH2
NH2
o-phenylenediamine
o-phenylenediamine
0.2 g catalyst
NH
N
CH3
C6H5
C6H5
0.2 g catalyst
1,5 substituted benzodiazepine
2-substituted benzodiazepine
Scheme 2.1 Synthesis of benzodiazepines and benzimidazoles from OPDA and an
aldehyde/ketone.
The catalytic activity studies were carried out in a 100 ml RB flask fitted with a water
cooled condenser on a heating rota mantle. In a typical procedure a mixture of OPDA (1
mmol), benzaldehyde (1 mmol) or acetophenone (2.2 mmol), ethanol (5 ml) and the
catalyst (0.2 g) taken in a 100 ml RB flask was heated to 80oC. The progress of the
reaction was monitored periodically by analyzing the reaction mixture by thin layer
chromatography technique (TLC) using a mixture of petroleum ether and ethyl acetate in
8:2 ratio as an eleuent. After completion of the reaction as indicated by the absence of
any reactant peak in TLC plate, the reaction mixture was diluted with 10 ml of ethanol
and filtered to recover the solid catalyst. The recovered catalyst was further washed with
acetone to remove any adsorbed organic molecule on the surface of the catalyst. The
filtrate was poured into a beaker containing crushed ice and stirred well for 10 min using
a glass rod. The precipitate obtained was separated by filtration from ice cold water, dried
and further purified by column chromatography using silica gel [100-200 mesh] with
petroleum ether and ethyl acetate as solvent. The solvent from the collected fractions
containing the pure product was removed using rota evaporator.
Chapter II
Page 37
2.4 Characterization of products
The melting points of the products were recorded in open capillary tube and were
uncorrected. The pure products were further analyzed by IR, GC-MS and1H NMR
techniques. Infrared spectra were recorded as KBr pellets of the samples using Nicolet
Model Impact 400D FT-IR Spectrometer with 4 cm-1
resolution from 4000 to 400 cm-1
.
The mass spectra were recorded on GC-MS Shimadzu QP 5000, GC-17A instrument. 1H
NMR spectrum was obtained in DMSO at 300 MHz using Bruker Avance NMR
spectrometer. 1H NMR Spectra was referenced to tetramethylsilane (TMS). Multiplicity
is indicated using the following abbreviations: s (singlet), d (doublet), dd (double
doublet), t (triplet), m (multiplet).
2.5 Results and discussion
The results obtained from various characterization techniques and catalytic activity
studies and a detailed discussions on these results are presented in the following sections.
2.5.1 Inductively Coupled Plasma-Optical Emission Spectrometer (ICP-OES)
The amount of manganese present in Mn/Al2O3-450 and Mn/ZrO2-450 was estimated by
ICP OES analysis technique. The exact percentages of manganese present were found to
be 4.32 and 4.77 respectively in Mn/Al2O3-450 and Mn/ZrO2-450. The results indicate
near quantitative precipitation of the manganese ions and also indicate that there is no
significant loss of manganese species upon calcinations of the catalyst at 450oC. The ICP
OES analysis of the catalysts recycled from catalytic activity studies was also performed.
It was observed that the leaching of manganese in alumina catalyst was very significant
after each cycle as the percentage of manganese dropped after each cycle, whereas in
Mn/ZrO2-450 catalyst leaching of manganese was very less compared to alumina
catalyst. The results obtained are as shown in the Table 2.2. The results indicate the
difference in the tenacity with which manganese species are associated with alumina and
zirconia supports.
Chapter II
Page 38
Table 2.2 The % of manganese present in alumina and zirconia catalyst before and after
first and second run.
Catalyst Mn % actual Mn % after first cycle Mn % after second cycle
Mn/Al2O3-450 4.32 4.03 3.72
Mn/ZrO2-450 4.77 4.65 4.43
2.5.2 Fourier Transform infrared spectroscopy (FT-IR)
Initially the FT-IR spectra of the precursors of alumina and zirconia supports i.e
aluminum hydroxide and zirconium hydroxide dried at 120oC were recorded for
reference and these spectra are provided Figure 2.1.
In the IR spectra of Al2O3-120 and ZrO2-120 are given in Figure 2.1. The -OH stretching
vibrational band of Al2O3-120 in the frequency range around 3500 cm-1
are sharp in
nature. This indicates the OH groups in this sample are relatively free and not formed
extensive hydrogen bonding. The Al-O bond stretching vibrations at 1050 and 751 cm-1
and bending vibrations at 596 cm-1 are also evident from the spectrum. These bands are
attributed to six-coordinated Al3+
ions [61]. The -OH stretching vibrational band of ZrO2-
120 around 3400 cm-1
is very broad, which indicates the presence of extensive hydrogen
bonded hydroxyl group and bending vibrational bands were observed in the region 1600
cm-1
and the absorption bands at 514-523 cm-1
correspond to Zr-O vibrations.
The IR spectra of Al2O3-450 and ZrO2-450 are shown in Figure 2.2. The -OH stretching
vibrational band around 3500 cm-1
in the IR spectra Al2O3-450 is very broad indicating
hydrogen bonded OH bonds. Further the bands corresponding to Al-O stretching and
bending vibrations are significantly altered indicating a possible change in the
arrangement of constituent atoms of the support. In case of ZrO2-450 no significant
change was observed upon calcinations. The broad hydroxyl stretching band in zirconia
also indicates the existence of surface water and interstitial water at 3650 cm-1
-3000 cm-1
[62].
Chapter II
Page 39
Manganese oxide is associated with alumina and zirconia support calcined at 450oC is
given in Figure 2.2. Mn/Al2O3-450 sample exhibited in its IR spectra a broad band with
decreased intensity of -OH bond stretching. Mn/Al2O3-450 and Mn/ZrO2-450 exhibited
bands in the region 1385-1377 cm-1
due to stretching vibrations of S=O bonds which are
ascribed to the presence of highly covalent sulfates [63]. These bands are not exhibited
by Al2O3-450 and ZrO2-450 samples. It may be inferred that the SO42-
ions were
incorporated into Mn/Al2O3-450 and Mn/ZrO2-450 catalysts during their synthesis.
4000 3500 3000 2500 2000 1500 1000 500
30
40
50
6040
50
60
Aluminum hydroxide
Tra
nsm
itta
nce
(%
)
Wave length (cm
-1)
Zirconium hydroxide
Figure2.1 FTIR spectra of pure aluminum hydroxide, Al(OH)3 and Zirconium hydroxide,
Zr(OH)4 heated at 120oC overnight.
Chapter II
Page 40
4000 3500 3000 2500 2000 1500 1000 500
(Al2O
2- 450)
Wavelength (Cm-1)
Tra
nsm
itta
nce
(%
)
(Mn/Al2O
2- 450)
(Mn/ZrO2- 450)
(ZrO2- 450)
Figure 2.2 FT-IR spectra of Al2O3-450, Mn/Al2O3-450, ZrO2-450 and Mn/ZrO2-450.
2.5.3 Powder X-ray diffraction pattern (PXRD)
PXRD patterns of Al2O3-120 and ZrO2-120 are given in Figure 2.3. The sharp diffraction
pattern of Al2O3-120 indicates its high crystalline nature. The diffraction patterns Al2O3-
120 reveal that it is present in Gibbsite phase [64]. This is known to be the most
crystalline phase of alumina. ZrO2-120 exhibited a broad X-ray diffraction patterns which
show its amorphous nature.
Calcination of Al2O3-120 and ZrO2-120 at 450oC induce phase transition in both the
samples. The PXRD patterns of Al2O3-450 and ZrO2-450 are given in Figure 2.4. The
Gibbsite alumina has changed to Boehmite phase. The diffraction peaks of Al2O3-450 at
2θ=14.54o, 28.31
o, 38.34
o, 49.03
o, 49.37
o, 55.35
o corresponding to the (020), (120),
(140), (031), (051) and (200) crystal planes respectively, corroborate the Boehmite phase
of alumina [65, 66]. Amorphous zirconia (ZrO2-120) turned crystalline upon calcinations
at 450oC and ZrO2-450 exhibited diffraction peaks at 2θ=28.14
o, 30.34
o, 31.52
o, 35.24
o,
Chapter II
Page 41
50.46o and 60.22
o corresponding to (111), (002), (022), (113) [67, 68] representing
tetragonal and monoclinic phases.
Upon manganese oxide deposition on both alumina and zirconia, phase changes are
observed. Mn/Al2O3-450 exhibited diffraction patterns at 2θ=32.67o and 36.14
o
corresponding to the Hausmannite Mn3O4 phase [69] in addition to the Boehmite phase
of alumina. The intensity of the peaks corresponding to Mn3O4 phase was very weak.
This is probably due low concentration of manganese present. W. Wang et.al have
reported that the appearance of crystalline Mn3O4 becomes predominant on Al2O3 support
only when the manganese loading reaches higher than 20% [70]. It is to be noted that in
the present investigation the percentage of manganese in Mn/Al2O3-450 is less than 5%.
In Mn/ZrO2-450 the diffraction peaks due to monoclinic phase (2θ=28.14o and 31.52
o)
have disappeared and peaks corresponding to tetragonal phase (2θ=30.34o, 35.24
o, 50.46
o
and 60.22o) were retained.
The tetragonal phase is known to be metastable and catalytically active. Several attempts
have been made to stabilize the tetragonal phase by pre and post synthesis modifications
[71]. It is reported that incorporation of SO42-
ions, WO3, MoO3, CeO2 [72-75] not only
stabilizes the tetragonal phase but also increases the acidity of zirconia and hence its
catalytic activity. We have noticed in the present studies that in the case of Mn/ZrO2-450
the intensity of the diffraction peaks corresponding to the tetragonal phase have increased
where as those of monoclinic phase have disappeared. The stabilization of catalytically
active tetragonal phase is attributed to the decrease in the particle size of zirconia [76].
Chapter II
Page 42
10 20 30 40 50 60 70
0
20
40
60
80
100
120
140
0
500
1000
1500
2000
2500
3000
3500
Zirconium hydroxide
2 (Degree)
Rel
ati
ve
inte
nsi
ty (
a.u
)
Aluminum hydroxide
Figure 2.3 PXRD patterns of aluminum hydroxide and Zirconium hydroxide heated at
120 oC overnight.
10 20 30 40 50 60 70
ZrO2-450
Inte
nsi
ty (
a.u
)
Mn/ZrO2-450
Al2O
3-450
2 (Degree)
Mn/Al2O
3-450
Figure 2.4 PXRD patterns of Al2O3-450, Mn/Al2O3-450, ZrO2-450 and Mn/ZrO2-450 .
Chapter II
Page 43
2.5.4 BET specific surface area, pore size and pore volume
The BET surface area, pore size and pore volumes of all the catalysts are given in the
Table.2.3. Al2O3-120 sample had very low BET surface area (1.38 m2/g) [64].
Whereas ZrO2-120 was relatively very high (174.26 m2/g), this is in agreement with
the crystalline nature of the former and amorphous nature of the later sample. Upon
calcination, the surface area of Al2O3-120 has increased where as that of ZrO2-120
has decreased significantly. This is in concurrence with the change in their PXRD
patterns.
The surface area of Mn/Al2O3-450 (209.67m2/g) was higher than Al2O3-120 but less
than Al2O3-450 (262.81m2/g). Whereas, the surface area of Mn/ZrO2-450 (92.37
m2/g) was lower than ZrO2-120 but more than ZrO2-450 (61.39 m
2/g). Thus the effect
of addition of manganese oxide on the surface area of alumina was different from that
of zirconia. Similar observations were made by Einaga, H etal, [77] and Qiang Zhao
[78]. It is reported that the presence of manganese oxide on zirconia strongly interacts
with zirconia which reduces surface diffusion and sintering. This results in
stabilization of tetragonal phase of zirconia and an increase in its surface area. Parida
et al., have made similar observation when molybdovanadophosphoric acid was
deposited on zirconia [79].
Table 2.3 BET surface area,Pore size and Pore volume of all the catalysts.
Catalyst BET surface area (m2/g) Pore size (Ǻ) Pore volume (cm
3/g)
Al2O3-120 1.38 147.7 0.0051
Al2O3-450 262.81 36.5 0.240
Mn/Al2O3-450 209.67 44.9 0.235
ZrO2-120 174.26 24.9 0.108
ZrO2-450 61.39 36.7 0.052
Mn/ZrO2-450 92.37 34.9 0.061
Chapter II
Page 44
2.5.5 Temperature programmed desorption of ammonia (TPD-NH3) analysis
Graphical representation of the amount of ammonia (mmolg-1
) desorbed from the surface
of Al2O3-450, Mn/Al2O3-450, ZrO2-450 and Mn/ZrO2-450 when subjected to heat
treatment in the temperature range 50oC to 700
oC are given in the Figure 2.5. Desorption
peak in the range 50-250oC accounts for weak acid sites, 250-350
oC for moderate strong
acid sites and above 350oC to strong acid sites present on the surface of the catalysts [80,
81].
The NH3 desorption on Al2O3-450 catalyst showed a strong peak around 400-600oC
indicating the presence of strong acid sites. The width of the peak indicates that the
distribution of acid site strength is very narrow. Similar observations were made in the
case of Mn/Al2O3-450. It is to be noted from the area under the peak that Al2O3-450
possessed higher concentration of weak acid sites compared to Mn/Al2O3-450.ZrO2-450
and Mn/ZrO2-450 exhibited the TPD-NH3 profiles characteristic of the presence of the
acid sites with a wide range of distribution of their strength. The area under the
desorption curves indicated that Mn/ZrO2-450 had higher concentration of acid sites than
ZrO2-450. Thus, incorporation of manganese oxide increased the strength and
concentration of acid sites in Mn/ZrO2-450. Further zirconia catalysts exhibited higher
concentrations of acid sites especially in the moderate to intermediate strong region than
the alumina catalysts.
Chapter II
Page 45
Figure 2.5 TPD-NH3 profile of various catalysts Al2O3-450 (a), Mn/Al2O3-450 (b), ZrO2-
450 (c) and Mn/ZrO2-450 (d).
2.5.6 Scanning electron microscopy (SEM)
SEM images of Al2O3-450, ZrO2-450, Mn/Al2O3-450 and Mn/ZrO2-450 samples are
shown in the Figure 2.6. Morphologies of Mn/Al2O3-450 and Mn/ZrO2-450 samples were
distinctly different from those of Al2O3-450 and ZrO2-450. In the case of Al2O3-450 the
large particles converted into a powder like texture whereas powder like ZrO2-450
developed into tubular like particles upon incorporation of manganese oxide. Thus the
influence of manganese oxide on the textural properties of zirconia in particular is
noteworthy, if one is interested in the preparation of nano rods of zirconium oxide under
uncomplicated conditions.
Chapter II
Page 46
Figure 2.6 SEM images of Al2O3-450 (a), ZrO2-450 (b), Mn/Al2O3-450 (c) and Mn/ZrO2-
450 (d) catalysts.
2.5.7 Transmission electron microscopy (TEM)
TEM images of Al2O3-450, ZrO2-450, Mn/Al2O3-450 and Mn/ZrO2-450 samples are
shown in Figure 2.7. It was interesting to observe that the big crystalline like particles of
alumina changed to powder like material on deposition of manganese oxide. It is also
noteworthy that powder like material of zirconia developed into rod like structures. TEM
images shows that the rods of Mn/ZrO2-450 have a diameter of 30 nm. These
morphological changes observed due to the incorporation of manganese into alumina and
zirconia has been found to have a significant effect on their catalytic properties as
described in the subsequent sections. This change in morphology is related to the higher
surface area of Mn/ZrO2 compared to ZrO2.
Chapter II
Page 47
Figure 2.7 TEM images of Al2O3-450 (a), ZrO2-450 (b), Mn/Al2O3-450 (c) and Mn/ZrO2-
450 (d) catalysts.
2.6 Catalytic activity studies
The results and discussions pertaining to the catalytic activity studies of all the catalysts
in the synthesis of substituted benzimidazoles and benzodiazepines, described in the
previous sections have been discussed in the following sections.
2.6.1 Catalytic activity and surface acidity of the catalysts
Catalytic activity of all the catalysts prepared and characterized as described in the
previous section was investigated in the synthesis of benzimidazoles and benzodiazepines
starting from OPDA and an aldehyde/ketone. This synthetic reaction is activated by an
acid catalyst. It is also mentioned in section (2.6.5) that all the catalysts investigated in
the present studies possessed acid sites with different strength and concentrations. The
following trends were observed in catalytic activity of the materials with respect to
isolated yield of the product in the synthesis of benzimidazoles and benzodiazepines.
Chapter II
Page 48
Alumina catalysts:Mn/Al2O3-450 > Al2O3-450 > Mn/Al2O3-120 > Al2O3-120
Zirconia catalysts:Mn/ZrO2-450 > Mn/ZrO2-120 > ZrO2-450 > ZrO2-120
The percentage yields of the isolated products in the condensation reaction between
OPDA and benzaldehyde/acetophenone conducted in the presence of solid acid
catalysts are given in the Table 2.4.The%yield of the isolated product was in the
range 30 to 95. When the reaction was carried out in the absence of the catalyst the
product yield was significantly very low (< 10%).
It is interesting to note that the catalytic activity order is same as that of total surface
acidity order. This signifies the importance of surface acidity in activating a
condensation reaction between OPDA and an aldehyde or a ketone.
Zirconia based catalysts exhibited higher surface acidity and hence catalytic activity
than the alumina based catalysts. The materials calcined at 450oC showed higher
catalytic activity than those dried at 120oC. Further the catalysts containing
manganese oxide performed better as catalysts than the pure supports. These
observations imply an increase in the surface acidity upon calcinations and
incorporation of manganese oxide. The increase in acidity may be attributed not only
to the increase but also to the generation of new Lewis acid sites on the surface of
supports. Transition metals are known to increase the Lewis acidity of the solid acids
such as metal oxides, zeolites, clays etc. [82]
Further, taking into account, the variation of other textural properties of the catalyst
on calcinations and incorporation of manganese oxide, it is worthwhile to mention
here that synergistic effects of the following parameters contribute to the overall
increase in the catalytic activity of the solid catalysts.
Enhancement of the intrinsic surface acid sites concentration of the supports on
calcination.
Contribution to the additional acidity by the presence of manganese oxide on the
solid supports
Stabilization of catalytically active tetragonal phase of zirconia on calcination in
the presence of manganese oxide.
Chapter II
Page 49
Table 2.4 Effect of catalyst, their acidity on the% yield of the product.
Catalyst Surface acidity (m.mol/g) Yield (%)*
benzimidazole benzodiazepine
Al2O3-120 0.75 30 30
Mn/Al2O3-120 1.00 67 60
Al2O3-450 1.01 52 35
Mn/Al2O3-450 1.25 90 85
ZrO2-120 0.50 34 47
Mn/ZrO2-120 1.50 70 74
ZrO2-450 1.25 65 70
Mn/ZrO2-450 1.70 95 93
*Isolated yield.
It is evident from the above discussions that Mn/ZrO2-450 exhibited highest catalytic
activity in terms of isolated yield and selectivity of the product. Hence further
optimization reactions were carried out to check the effect of the nature of the
solvent, reaction temperature, amount of the catalyst, generality of the catalyst in the
presence of Mn/ZrO2-450 as the catalyst.
2.6.2 Effect of Solvent and temperature
The percentage of isolated yields of benzimidazoles and benzodiazepines from the
reactions conducted in the presence of different solvents using Mn/ZrO2-450 as the
catalyst is shown in Figure 2.8(a). The high boiling solvents such as
dimethylsulphoxide (DMSO) and dimethylformamide (DMF) resulted in low yield of
the product and also presented handling problems. Acetonitrile and chloroform also
Chapter II
Page 50
resulted in lower yields. When water was used as a solvent, isolation of the products
from reaction mixture was found to be tedious. Though methanol when used as a
solvent did not pose any problem, it is not a preferred solvent because of its toxic
nature. Ethanol was found to be the best solvent for this reaction due to the following
advantages: low cost, easy work-up of the reaction mixture and good isolated yield of
the products. Hence for further studies in synthesis of substituted benzimidazoles and
benzodiazepines ethanol was used as a solvent.
The results of the experiments conducted at different temperatures are shown in
Figure 2.8 (b). When the reaction was conducted at room temperature the yield was
only 25%to 30%. However the percentage conversion of OPDA was found to
increase with good selectivity with an increase in the temperature up to 80oC, above
which the conversion of OPDA remained constant while the selectivity towards the
expected product decreased.
50
55
60
65
70
75
80
85
90
95
100
Ethan
ol
Meth
anol
Wat
er
Chloro
form
Aceto
nitrile
DM
F
DMSO
Solvents
% y
ield
Benzimidazole
Benzodiazepine
(a)
Chapter II
Page 51
Figure 2.8.Effect of (a) Solvents and (b) Temperature on the % of isolated yield of
benzimidazoles and benzodiazepines in the presence of Mn/ZrO2-450catalyst.
2.6.3 Effect of the amount and reusability of the catalyst
The condensation reactions were conducted using ethanol as the solvent at 80oC
using different amounts of Mn/ZrO2-450 catalyst in the range 0.05 to 1 g. The best
yield of the reaction product was obtained with 0.2 g of the catalyst. Higher amounts
of the catalyst did not improve the yield. The catalyst could be easily recovered by
simple filtration of the reaction mixture, followed by washing with acetone and
drying in oven at 120oC for 2 h. Recovery of the catalytic activity of the zirconia
based catalysts was better than alumina based catalysts. Zirconia catalysts could be
reused upto 5 cycles without any significant loss in catalyst efficiency (Table 2.5).
0
20
40
60
80
100
120
25 30 40 50 60 70 80 90 100
Temperature (oC)
% y
ield
Benzimidazole
Benzodiazepine
(b)
Chapter II
Page 52
Table 2.5 Recyclability of Mn/ZrO2-450 catalyst on the % yield of the products.
Entry No of cycles Yield (%)*
benzimidazolea benzodiazepine
b
a 1 95 93
b 2 90 85
c 3 88 83
d 4 87 75
*Isolated yield.
aReaction conditions: OPDA (1 mmol), aldehyde (1 mmol), 0.2 g Mn/ZrO2-450
catalyst, 5 ml ethanol.
bReaction condition: OPDA (1 mmol), ketone (2.2 mmol), 0.2 g Mn/ZrO2-450
catalyst, 5 ml ethanol.
2.6.4 Generality of the catalytic activity of Mn/ZrO2-450 catalyst
The activity of Mn/ZrO2-450 catalyst was investigated for its general application in
the condensation reaction of OPDA with other substituted aldehydes and ketones. All
the reactions were conducted using ethanol as the solvent at 80oC. The results in
terms of the isolated yield of the expected product with various substituted aldehydes
and ketones are presented in the Table 2.6 and Table 2.7 respectively. It is
noteworthy that an excellent yield of the expected product could be obtained within
1-2 h of the reaction time. Isolated products were analyzed by MP, IR, GC-MS and
1HNMR techniques. The condensation of OPDA with aldehydes was more efficient
than the ketones in terms of the duration of the reaction. Thus Mn/ZrO2-450 is a good
general catalyst to activate the condensation reaction between OPDA and
aldehyde/ketone for the synthesis of derivatives of benzimidazoles and
benzodiazepines in excellent yield and selectivity.
Chapter II
Page 53
Table 2.6 Condensation of OPDA with various substituted aldehydes in presence of
Mn/ZrO2-450 catalyst.
Entry Diamine Aldehyde Product Time
(min)
Yield
(%)
1
Benzaldehyde
60
95
2
2-Methyl
butyraldehyde
90
87
3
2-Ethylbutyraldehyde
90
90
4
4-Fluorobenzaldehyde
45
91
5
4-Chlorobenzaldehyde
45
85
6
Cinnamicaldehyde
35
92
7
Anisaldehyde
45
93
8
4-Cyanobenzaldehyde
45
90
NH2
NH2
N
NH
NH2
NH2
N
NH
CH3
CH3
NH2
NH2
N
NH
CH3
CH3
NH2
NH2
N
NH
F
NH2
NH2
N
NH
Cl
NH2
NH2
N
NH
Ph
NH2
NH2
N
NH
Ph O CH3
NH2
NH2
N
NH
CN
Chapter II
Page 54
Table 2.7 Condensation of OPDA with various substituted ketones in presence of
Mn/ZrO2-450 catalyst.
Entry Diamine Ketone Product Time (min) Yield (%)
1
Acetone
45
93
2
2-butanone
60
87
3
3-pentanone
90
92
4
Cyclopentanone
90
85
5
Cyclohexanone
90
85
6
Cycloheptanone
90
92
7
Acetophenone
60
90
8
4-nitro-
acetophenone
60
87
NH2
NH2
CH3NH
NCH3
CH3
NH2
NH2
CH3NH
N
CH3
CH3
NH2
NH2
EtNH
NEt
Et
CH3
NH2
NH2
NH
N
NH2
NH2
NH
N
NH2
NH2
NH
N
NH2
NH2
PhNH
N
CH3
Ph
NH2
NH2
4-NO2 Ph
NH
N
CH3
4-NO2 Ph
Chapter II
Page 55
The spectral data of some representative products
Entry 1 in Table 2.6
2-phenyl–1H–benzimidazole: Pale yellow solid. M.P 293-296 ºC; IR (KBr) 3042,
1440, 1403, 1271, 971 cm-1
. Ms: m/z=193(M+).
1HNMR (300 Hz, DMSO),
δH:7.22(m,2H), 7.48(m, 5H), 7.58(s, IH), 8.04(d, 2H,Ј=1.6Hz).
Entry 5 in table 2.6
2-(4-chlorophenyl)-1H-benzimidazole: pale yellow solid. M.P 291-293 ºC; IR (KBr)
3039, 1449, 1400, 1275, 961 cm-1
. Ms: m/z=228(M+).
1HNMR (300 Hz, DMSO), δH:
7.10(m, 2H), 7.6(d,2H,Ј=8.4Hz), 7.3(m, 2H), 8.2(d,2H,Ј=8.7Hz), 8.04(d,
2H,Ј=1.6Hz).
Entry 7 in Table 2.6
2-(4-methoxyphenyl)-1H-benzimidazole: yellow solid. M.P 225–226 ºC; IR (KBr)
3478, 2985, 1625, 1537, 1341, 1127, 1038, 835cm-1
. Ms: m/z=224(M+).
1HNMR
(300 Hz, DMSO), δH:8.00 – 8.08 (m, 2H), 7.20–7.60 (m, 6H), 3.52 (m, 3H).
Entry 1 in Table 2.7
2-methyl-2, 4-diphenyl-2,3–dihydro–1H-1,5-benzodiazepine: yellow solid. M.P 150-
152 ºC. IR (KBr) 3351, 1647, 1593 cm-1
. Ms: m/z=188 (M+).
1HNMR (300 Hz,
DMSO), δH: 1.73(s, 3H), 2.95(d, 2H, Ј =0.17Hz), 3.12 (d, 2H, Ј=0.17Hz), 3.38(br,
1H), 6.80-7.72(m, 14 H).
Entry 3 in Table 2.7
2,2,4,-triethyl-3-methyl-2,3-dihydro–1H-1,5-benzodiazepine: Yellow solid; M.P 143–
145 ºC; IR (KBr) 3324, 1637, 1582 cm-1
. Ms: m/z=245 (M+).
1HNMR (300 Hz,
DMSO), δH: 0.78-1.75(m, 14H), 2.63 (m, 2H), 3.13 (q, 1H, Ј=7.0Hz), 3.69 (br, 1H),
6.71-7.48 (m, 4H).
Chapter II
Page 56
Entry 7 in table 2.7
2-methyl-2,4-diphenyl-2-3-dihydro–1H-1,5-benzodiazepine: Yellow solid; M.P 149-
151 ºC; IR (KBr) 3349, 1643, 1593 cm-1
. Ms: m/z=313 (M+).
1HNMR (300 Hz,
DMSO), δH: 1.72 (s, 3H), 2.95 (d, 2H, J=0.17Hz), 3.68 (br, 1H), 6.93-7.79 (m, 14H).
2.6.5 Comparison of catalytic activity of Mn/ZrO2-450 catalyst with other reported
catalysts:
The superiority of the present method over reported methods was noticed by comparing
our results with those reported in the literature (Table 2.8). The reaction of OPDA with
an aldehyde or a ketone in presence of Mn/ZrO2-450catalyst was selected as the model
reaction and the comparison was made in terms of reaction temperature, and isolated
yield of the product. Some of the other reported methods require longer duration of the
reaction and the isolated yield is less compared to Mn/ZrO2-450 catalyst. The present
methodology progresses in the presence of an ecofriendly solvent ethanol at 80oC for 1 h.
The reaction distinctly requires shorter reaction time and the catalyst can be recycled
without significant loss in its activity for 4 cycles.
Table 2.8 Comparison of catalytic activity of MnZrO2-450 catalyst with other reported
catalysts.
Catalyst Solvent RT B1 B2 Reference
5% MnZrO2 Ethanol 1 85-95 - this work
Lewis acid catalysts Ethanol 1-14 5-93 - 83
Heteropoly acids Acetic acid 3 50-97 - 84
Amberlite IR-120 Ethanol/water 1.45-6.5 70-95 - 85
Chapter II
Page 57
PAS CH2Cl2 2 90 - 86
5% MnZrO2 Ethanol 1 - 85-93 this work
MCM-41 Ethanol 8 - 50-60 87
Ag3PW12O40 Solvent free 3-7 - 72-90 88
NbCl5 n-hexane 3-6 - 85-95 89
SbCl3-Al2O3 Solvent free 3-4 - 83-90 90
NOTE: RT. Reaction time (h), B1. Benzimidazoles yield (%),B2. Benzodiazepines yield
(%). PAS: Polyanilinesulphate.
Conclusion:
The catalytic activity of alumina, zirconia, and manganese oxide supported on alumina
and zirconia was determined in the condensation reaction between OPDA and
benzaldehyde/acetophenone for the synthesis of Benzimidazoles and Benzodiazepines.
The catalytic activity is dependent on the amount of surface acid sites of the catalyst. The
surface acid sites concentration on the supports increases on calcinations. Presence of
manganese oxide on the solid supports contributes to the additional acidity of the acidity.
Mild reaction conditions, easy work up and high yields along with reusability of the
catalyst make MnZrO2-450 a valuable alternative to the existing catalysts in the literature.
Chapter II
Page 58
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