Formation of benzoxanthenones and benzochromenones via cerium-impregnated- MCM-41 catalyzed, solvent-free, three-component reaction and their biological evaluation as anti-microbial agents

Article abstract of DOI:10.1016/j.molcata.2014.02.012

We report here, three-component condensation reaction of naphthols, aldehydes and 1,3-dicarbonyl compounds catalyzed by Ce-MCM-41 under solvent-free conditions. Several advantages can be perceived using this eco-friendly protocol such as, a green and cost

Full text of DOI:10.1016/j.molcata.2014.02.012

Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Formation of benzoxanthenones and benzochromenones via
cerium-impregnated-MCM-41 catalyzed, solvent-free,
three-component reaction and their biological evaluation as
anti-microbial agents
Adinarayana Murthy Akondia, Mannepalli Lakshmi Kantama,c,∗, Rajiv Trivedia,∗∗
Bojja Sreedhara, Sudheer Kumar Buddanab, Reddy Shetty Prakashamb,
Suresh Bhargavac,d
,
a Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
b Bioengineering and Environmental Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
c RMIT-IICT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
d Advanced Materials & Industrial Chemistry Group, School of Applied Sciences, RMIT University, Melbourne, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here, three-component condensation reaction of naphthols, aldehydes and 1,3-dicarbonyl
compounds catalyzed by Ce-MCM-41 under solvent-free conditions. Several advantages can be perceived
using this eco-friendly protocol such as, a green and cost-effective procedure with excellent yield, shorter
reaction time, simpler work-up, recovery and reusability of solid acid heterogeneous catalyst and toler-
ance towards a wide range of functional groups. We also report here the anti-microbial activities of the
new compounds. Particularly, it was found that the new compounds have shown promising effect on
Pseudomonal infections.
Received 20 December 2013
Received in revised form 5 February 2014
Accepted 7 February 2014
Available online 17 February 2014
Keywords:
Benzoxanthenones
Benzochromenones
Heterogeneous catalysis
Ce-MCM-41
© 2014 Elsevier B.V. All rights reserved.
Solvent-free conditions
Anti-microbial activity.
1. Introduction
of multicomponent procedures in organic synthesis has opened
up new avenues and vistas for augmenting these aspects [2].
The central theme in the present day organic synthesis
predominantly encompasses the carbon carbon (C C) and
carbon heteroatom (C X) bond forming and bond breaking reac-
tions. These reactions are often mediated by an efficient catalyst
system. The development of simple, practical and eco-friendly
processes usually involves the assistance of a new reagent or a
new catalyst for improving the rate as well as yield of a reaction.
Structural diversity and complexity can possibly be achieved by
formulating reaction sequences that allow minimum number
of steps for synthesizing compounds [1]. Enormous potential
Hence, the need of the hour is to develop inorganic solid mate-
rials for facilitating simple product isolation, catalyst recovery,
reuse and reduction of waste by-products [3]. Multicomponent
reactions, over a period of time, have been utilized extensively
for the preparation of diverse range of chemical libraries of het-
erocyclic compounds [4]. These methodologies have effectively
demonstrated their versatility in synthesizing various important
biologically active compounds. These include Hantzsch reaction
[5], Biginelli reactions [6], Schopf’s tropinone synthesis [7], Tietze’s
reaction [8], Ugi [9] and Mannich type reactions [10].
Xanthenes represent the most common structural motifs found
in several natural products and synthetic bioactive compounds.
Xanthenes, benzoxanthenes and benzochromenes form a distinct
class of compounds having diverse applications in dyes [11], as fluo-
rescent agents [12] and in laser technologies [13]. They also display
a wide range of biological and therapeutic properties such as anal-
gesic [14], anti-inflammatory [15], antibacterial [16], antiviral [17]
∗
Corresponding author at: Inorganic and Physical Chemistry Division, CSIR-Indian
Institute of Chemical Technology, Hyderabad 500007, India.
∗∗
Corresponding author. Tel.: +91 40 27191667; mobile: +91 9959602620.
E-mail addresses: mlakshmi@iict.res.in (M.L. Kantam), rtrajiv401@gmail.com,
trivedi@iict.res.in (R. Trivedi).
http://dx.doi.org/10.1016/j.molcata.2014.02.012
1381-1169/© 2014 Elsevier B.V. All rights reserved.

50
A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
and non-peptidic inhibitor properties etc. [18]. The predominant
route adopted in this process involves an ortho-quinone methide
[o-QM] intermediate and its interaction with carbon nucleophiles
[19]. It has been reported that these intermediates mainly interact
with various dienophiles via [4 + 2] cycloaddition reactions [20].
Xanthenes and benzoxanthenes are usually formed by an in situ
trapping of the o-QM with carbon nucleophiles like phenols and
napththols.
During the past decade, the scope of three-component conden-
sation of 2-naphthol, aldehyde and 1,3-dicarbonyl compounds has
been explored by the use of a wide range of solid catalysts and
inorganic salts. These predominantly include the inorganic com-
pounds; namely, BF3. Et2O [21], I2 [22], HClO4–SiO2 [23], HClSO3
[24] and inorganic salts such as InCl3 [25], Zr(HSO4)4 [26], Sr(OTf)2
[27], Caro’s acid-silica [28], tungstophosphoric acid [29], CAN [30]
and Ce (IV) salts [31]. Some of the organic acids like PTSA [32], TBAF
[33], sulfamic acid [34], cyanuric acid [35] and N,Nꢀ-dibromo-N,Nꢀ-
1,2-ethanediyl-bis(p-toluenesulfonamide) [36] have also been
reported. Most of such solid acid catalyzed reactions often involve
elongated reaction time, drastic reaction conditions and formation
of non-desirous side products. The intrinsic reaction conditions
preferably utilize strong acidic media, high reaction tempera-
tures and stoichiometric ratios resulting in tedious work-up and
purification processes. Thus, there is tremendous scope for the
development of new greener synthetic protocols to assemble such
frameworks.
The inherent properties of mesoporous materials such as, their
tuneable pore size and acid-base sites have been utilized for
widespread applications in catalysis [37]. MCM-41 [38] and SBA-15
[39] have demonstrated exceptional properties by virtue of their
hexagonal pore array arrangement and narrow pore size distri-
bution [40]. It was observed from the literature that the Ce(IV)
derivatives have shown better catalytic activity among other cata-
lysts such as FeCl3, SnCl4, ZnCl2 and AlCl3 are normally employed
as single-electron oxidants [30]. The commercial availability, ease
of handling and inexpensive ceric ammonium nitrate (CAN) in
carbon carbon and carbon heteroatom bond forming reactions
has recently attracted much attention [41]. The catalyst, Ce-MCM-
41, has received considerable attention due to its low toxicity,
cost effectiveness, air and water compatibility, ease of handling,
good reactivity, experimental simplicity and remarkable ability to
suppress side reactions in acid sensitive substrates [42]. Recently,
we have explored the activity of Ce-MCM-41 catalyst towards the
regioselective dual C H bond activation under heterogeneous con-
ditions [42b]. In furtherance of our studies, we report the use
of cerium containing MCM-41 as a heterogeneous and reusable
catalyst for the multicomponent one pot synthesis of benzoxan-
thenones.
spectra were acquired on a Q STAR XL Hybrid LC/MS/MS system,
Applied Biosystems, USA. FT-IR data were acquired on a Thermo
Nicolet Nexus 670 FT-IR spectrometer with DTGS KBr detector. XPS
spectra were recorded on a Kratos AXIS 165 with a dual anode
apparatus using the Mg K␣ anode. X-ray powder diffraction data
was collected on a Siemens/D-5000 diffractometer using Cu K␣
radiation. Pore size distribution measurements were performed
on Auto sorb-1 instrument (Quanta chrome, USA) using by nitro-
gen physisorption. The particle size and external morphology of
the samples were observed on a Philips TECNAI F12 FEI transmis-
sion electron microscopy (TEM). SEM-EDX was performed on a
Hitachi SEM S-520, EDX-Oxford Link ISIS-300 instrument. Diffuse
reflectance UV/vis spectra for samples as KBr pellets were recorded
on a GBC Cintra 10e UV–vis spectrometer in the range 200–800 nm
with a scan speed 400 nm/min.
2.2. Synthesis of catalyst (Ce-MCM-41)
The pure MCM-41 was prepared by direct hydrothermal method
described in the previously reported procedures [43] and was
activated by heating in oven prior to use. The cerium-loaded meso-
porous material MCM-41, designated by Ce-MCM-41, was prepared
by a wet impregnation method using aqueous solution of ceric
ammonium nitrate [44]. To 10 mL of an aqueous solution of ceric
ammonium nitrate (0.12 g, 0.02 M), the MCM-41 (calcined) support
(0.21 g) was added and stirred vigorously for 24 h at room tem-
perature. The pale yellow solid, obtained after evaporation of the
solvent, was dried overnight at 100 ◦C and then again calcined at
500 ◦C in air for 5 h to obtain Ce-MCM-41 with (0.247 g) 75% yield.
The EDX analysis result showed the presence of cerium, oxygen and
silicon at 14.97 wt%, 55.18 wt% and 29.85 wt%, respectively, which
indicates the formation of ceric ion functionalized MCM-41. All the
characterization studies were carried out with 15 wt% Ce-MCM-41.
2.3. General procedure for the synthesis of benzoxanthenone
In a 25 mL round-bottom flask, aldehyde (1 mmol), naphthol
(1 mmol), 1,3 diketone (1 mmol) and Ce-MCM-41 (1.7 mol %) were
taken. The reaction mixture was stirred at 80 ◦C under solvent-free
conditions for 30–50 min. The reaction was monitored by TLC and
on completion of the reaction, the reaction mixture was cooled
to room temperature and ethyl acetate was added to dissolve all
organic components and filtered to remove catalyst. The filtrate
was concentrated and purified by silica gel column chromatogra-
phy.
3. Results and discussion
In the present work, we demonstrate Ce-MCM-41 as an inexpen-
sive, highly efficient, heterogeneous and reusable solid acid catalyst
for the preparation of aryl benzoxanthenone derivatives under
mild reaction conditions. In recent years, solvent-free reactions
have been explored extensively [45]. This convention offers sev-
eral advantages such as higher yield, shorter reaction time, simpler
work-up, recovery, reusability of catalyst and tolerance towards a
wide range of functional groups with no side products. In contin-
uation of our work on the applications of heterogeneous catalysts
for organic reactions [42b], we intend to utilize Ce-MCM-41 as a
promising candidate to perform the condensation of naphthols,
aldehydes with 1,3-dicarbonyls (Scheme 1).
The improved ability of Ce-MCM-41 in the catalytic one pot mul-
ticomponent reaction is attributed to the inherent high surface area
of the mesoporous catalyst that offers enough space for organic
substrates to interact with active acidic sites present on the solid
surface inside the ordered mesopore [37]. In addition, compared
with pure MCM-41, a decrease in BET surface area, pore volume and
2. Experimental
2.1. Instrumentation
The thin layer chromatography (TLC) was performed on Merck
silica gel 60 F254 plates using ethyl acetate and hexane as eluting
agents. Thin layer chromatography plates were visualized by expo-
sure to UV-light/iodine and/or by immersion in an acidic staining
solution of phosphomolybdic acid followed by heating on a hot
plate. Purification of products was carried out by column chro-
matography using silica gel and a mixture of ethyl acetate and
hexane as eluting agent. All the products were characterized by
mass, 1H and 13C NMR spectroscopy. The NMR spectra of samples
were acquired on a Varian Unity Inova 500 MHz, Inova 400 MHz
and Bruker Avance 300 MHz spectrometer using TMS as an inter-
nal standard in CDCl3 and DMSO. Mass spectra were acquired on a
Thermo LCQ fleet ion trap mass spectrometer. High resolution mass

A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
51
Scheme 1.
pore diameter confirm the incorporation of the cerium in the chan-
3.1.2. XRD analysis
nels of MCM-41 [46]. Such immobilized silica might show improved
catalytic behaviour as compared to the parent silica. The catalytic
cerium species was anchored on the inner surface of the mesopore
of MCM-41 to exhibit high activity and good reusability. The sur-
face acidity of the catalyst, calculated by using NH3-TPD analysis,
was found to be 0.633 mmol/g (Fig. 1).
The powder X-ray diffractograms of synthesized pure MCM-41
and Ce-MCM-41 samples are shown in Fig. 3. The most intense
diffraction peak of MCM-41 appeared at 2ꢁ = 2–3◦. Other low inten-
sity shoulder diffraction peaks appeared at 2ꢁ = 3–5◦. The relative
decrease in the intensity of diffraction patterns of Ce-MCM-41
samples compared to parent silica indicates the incorporation of
cerium. This diffraction pattern was observed in Ce-MCM-41 (fresh)
and Ce-MCM-41 (after 2nd recycle) samples suggesting that these
mesoporous frameworks were similar. In addition, the high angle
XRD patterns observed at 2ꢁ = 28.5◦, 47.4◦ and 56.3◦ in both fresh
and used Ce-MCM-41 matched well with ceria [48].
3.1. Characterization of the Ce-MCM-41 catalyst
3.1.1. FT-IR analysis
From the IR spectra (Fig. 2), it was observed that the wavenum-
ber, ꢀas, due to (Si
O
Si) decreased from 1090 to 1080 cm−1
3.1.3. N2 adsorption
and the band around 960 cm−1 (in MCM-41; Fig. 2a), assigned
N2 adsorption–desorption isotherm and the corresponding pore
size distribution curve of MCM-41 and Ce loaded MCM-41 are
shown in Fig. 4. Both the isotherms display the typical type IV
isotherm of mesoporous materials with a sharp inflection in the
relative pressure range of 0.3–0.4, which is due to capillary con-
densation of nitrogen in the pores. Brunauer–Emmett–Teller (BET)
surface area, average pore diameter and pore volume for pure
MCM-41 and cerium impregnated MCM-41 materials assessed
from their respective adsorption isotherms are given in Table 1.
The results show that, compared with MCM-41 the decrease in
BET surface area, pore volume and average pore diameter in
Ce-MCM-41 can be attributed to the existence of Ce species in
the channels. The Barrett–Joyner–Halenda (BJH) pore distribution
curve of both MCM-41 and Ce-MCM-41 show sharp peaks in the
to Si
O Ce bond was shifted towards the higher wave number,
970 cm−1 (as shown by dotted lines in Fig. 2) in the case of Ce
impregnated MCM-41samples (Fig. 2b and c) [47]. It can be stated
that the absorption around 970 cm−1 was essentially due to the
increased degeneracy of the elongation vibration in the tetrahedral
structure of SiO4 induced by the change in the polarity of the Ce
O
bond when Si is linked to cerium. This is generally taken as evidence
for the incorporation of metal into the framework [47]. Notably, IR
spectra of both the fresh Ce-MCM-41 and used Ce-MCM-41 (after
2nd recycle) were identical to that of MCM-41, signifying that the
MCM-41 framework was retained after incorporation of cerium.
˚
range of 22–29 A and suggest that both possess narrow pore size
Fig. 2. FT-IR spectra of (a) MCM-41 (uncalcined); (b) fresh Ce-MCM-41 and (c) Used
Fig. 1. NH3-TPD profile of fresh Ce-MCM-41 catalyst.
Ce-MCM-41 (after 2nd recycle).

52
A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
Fig. 3. Low and high angle X-ray diffraction patterns of (a) MCM-41; (b) fresh Ce-MCM-41 and (c) used Ce-MCM-41.
Fig. 4. N2 adsorption–desorption isotherm and pore size distribution for (a) MCM-41; (b) Ce-MCM-41.
Table 1
3.1.4. XPS analysis
BET surface areas of MCM-41 and Ce-MCM-41 samples.
The XPS analysis of the fresh and used (after 3rd recycle) Ce-
MCM-41 catalyst is displayed in Fig. 5. The XPS signal appeared at
binding energies 883.14 eV and 898.33 eV can be assigned to the
Ce 3d5/2, while the peaks located at 901.39 and 916.39 eV can be
assigned to the Ce 3d3/2. These values are consistent with CeO2 sig-
nals. It was also observed that the peak located at about 530.4 eV,
Sample
Surface area
(m2/g)
Pore volume
(cm3/g)
Pore
diameter (Å)
MCM-41
15% Ce-MCM-41
942
689
0.68
0.39
29.0
22.6
corresponding to the O 1s, can be attributed to the oxygen in Ce
O
distribution (Fig. 4). Although the average pore diameter and pore
volume decreases a little, the Ce loaded MCM-41 shows a relatively
large surface area, indicating that the mesoporous structure was
retained [42a,47a].
linkages. The intense peak at 532.4 eV (see Fig. 10 in Supplemen-
tary information) can be assigned to the Si O bond [43,49]. Similar
results were also obtained for the used catalyst. Therefore, it can be
Fig. 5. XPS spectra of (a) fresh Ce-MCM-41; (b) used Ce-MCM-41 (after 3rd recycle).

A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
53
and further increasing the amount of catalyst did not increase
the yields. However, the best results were obtained under sol-
vent free conditions as compared to dichloromethane, methanol,
acetonitrile and tetrahydrofuran (Table 2). Moreover, no side prod-
uct formation was observed under solvent free conditions. The
desired product was not obtained in the absence of the catalyst,
under similar reaction conditions, even after a long time (120 min).
Cerium impregnated MCM-41 catalyzed this condensation reaction
smoothly and afforded the corresponding benzoxanthenones and
benzochromenones in excellent yield at 80 ◦C under solvent-free
conditions. The electronic nature of the substituents in the aromatic
ring did not show any noticeable effect on this conversion (Table 3).
Trace amount of the product was obtained with cinnamaldehyde
(Table 3, entry 12) and phenyl acetaldehyde (Table 3, entry 13). No
significant change in the yield was observed when more than one
substituent was present in the phenyl ring (Table 3, entries 14–16,
20 and 22). These results clearly suggested that electronic factors
play a limited role and steric factors play a key role in the product
formation. Moreover, it was observed that, long reaction times and
slightly higher temperatures were required for the aliphatic alde-
hydes to obtain comparative yields vis-a-vis aromatic aldehydes
(Table 3, entries 26, 27 and 28).
Fig. 6. The diffuse reflectance UV–vis spectra of (a) MCM-41; (b) Ce-MCM-41.
Encouraged by the successful condensation of aldehydes,
2-naphthol and dimedone under solvent-free condition
to give benzoxanthenone derivatives, we next attempted
the reaction with 1-naphthol, substituted aldehydes and
various 1,3-diketones (5,5-dimethyl-1,3-cyclohexanedione/1,3-
cyclohexanedione/indane-1,3-dione/acetyl acetone) under the
optimized reaction conditions, which led to the exclusive forma-
tion of benzo[c]xanthenone in good yields (Table 3). This greener
approach provides a mild and general route to synthesize various
classes of 7-aryl substituted benzo[c]xanthenones and 12-aryl
substituted benzo[a]xanthenones. On comparison with the pre-
vious literature reports [21–36], it was observed that the present
method offers reduced amount of catalyst loading, eco friendliness
of the process, higher yield, reduced reaction time and reusability
of the catalyst. The reusability of the catalyst was tested up to 5
successive runs, with only marginal decrease in catalytic activity
(Table 3, entry 1).
concluded that the cerium cations in both the fresh and used cat-
alysts were retained in the pore wall of the mesoporous molecular
sieves through Ce
O Si bond. On quantification it was observed
that the ratio of SiO2:CeO2 was 2:1 in both the fresh and used cat-
alyst, which also confirmed that the homogeneity of the catalyst
remains unaltered.
3.1.5. UV-DRS
The overlay of the diffuse reflectance UV–vis spectra of the
MCM-41 and Ce-MCM-41 is shown in Fig. 6. The UV–vis spec-
trum of Ce-MCM-41 displayed a high intensity band with a maxima
around 245, 266 and 296 nm which can be attributed to the pres-
ence of Ceria and two different types of well dispersed Ce4+ species
(higher energy tetra-coordinated, lower energy hexa-coordinated)
[42a]. This was also evident by the high reactivity of the catalyst.
Hence, we predict that the synthesized Ce-MCM-41 sample is a
combination of ceria along with some Ce4+ species [47a].
3.2. Plausible mechanism
3.1.6. SEM and TEM
Fig. 7 shows the SEM micrographs of MCM-41, fresh Ce-MCM-41
and used Ce-MCM-41. Fig. 8 displays the TEM images of fresh and
used catalyst. Both the SEM and TEM micrographs for the fresh and
used Ce-MCM-41 (after 3rd recycle) showed similar particle mor-
phology. The Si/Ce ratios of these samples do not differ significantly,
as demonstrated by EDX analysis, indicating the incorporation of
well-dispersed cerium into the framework of the MCM-41 [47a].
However, there was a gradual change in the catalyst morphologies
with the increasing number of recycles.
A tentative mechanism has been proposed to explain the for-
mation of benzoxanthenones and benzochromenones (Scheme 2).
As shown in Scheme 2, we propose that the catalyst Ce-MCM-41
(
Ce (IV)) activates the reactants and the intermediates in this reac-
tion. It was assumed that the reaction occurs via the ortho-quinone
methide intermediate 8, formed by the nucleophilic addition of 2-
naphthol with aldehydes. Subsequent Michael addition of the o-QM
intermediate to the enolic form of dimedone gives 9. Then com-
pound 9 eliminated one molecule of H2O and afforded compound
7 [21–36,50].
3.1.7. Screening of reaction conditions
We started our study by examining the reaction of benz-
aldehyde, 2-naphthol and 5,5-dimethyl-1,3-cyclohexanedione in
1 mmol scale using 5, 10, 15 and 20 wt% CeO2 loading on MCM-
41. After initial screening of various Ce-MCM-41 catalysts, 15 wt%
of cerium loaded MCM-41 showed better catalytic activity under
solvent-free conditions (Table 2, entry 4). An increase in the reac-
tion temperature from room temperature to 60 ◦C and 80 ◦C hastens
the reaction to give the desired product in optimum yield and
further increase in the yield was not observed on increasing the
temperature to 90 ◦C and 100 ◦C (Table 2, entries 7 and 8). When
0.9 mol%, 1.3 mol% and 1.7 mol% of Ce-MCM-41 were used, the
yields were 68%, 81% and 96%, respectively (Table 2, entry 5).
Therefore, 1.7 mol% of catalyst was ideal for the forward reaction
3.3. Reusability
The recovery and reuse of a catalyst is highly desirable for
a greener procedure. Thus, the recyclability of Ce-MCM-41 was
examined by using benzaldehyde, 2-naphthol and dimedone as
exemplary substrates. Upon completion of the reaction, the cat-
alyst was easily separated by filtration and washed with ethyl
acetate, dried under vacuum and reused in the succeeding reaction.
Almost quantitative catalyst could be recovered from each run. In
an assessment of five cycles, the catalyst could be reused without
any substantial loss of catalytic activity (Fig. 9). This was evident
from the SEM (Fig. 7) as well as from TEM analysis (Fig. 8) of the
used catalyst, wherein these analyses reveal a gradual change in

54
A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
Fig. 7. SEM images of (a) MCM-41; (b) fresh Ce-MCM-41 and (c) used Ce-MCM-41.
Fig. 8. TEM images of (a) fresh catalyst; (b) used catalyst (after 3rd recycle).
the catalyst morphologies with increasing number of recycles. In
addition, no quantifiable amount of leached cerium was detected
in the filtrate by ICP-AES analysis, hence it can be concluded that
the catalytic process is truly heterogeneous.
set of benzoxanthenone and benzochromenone derivatives, we
decided to further explore the efficacy as anti-bacterial agents.
Hence, all the newly synthesized compounds were evaluated for
in vitro antibacterial activity against five gram-positive bacteria
(Bacillus subtilis, Micrococcus luteus, Bacillus circulans, Streptococ-
cus mutans and Lysinibacillus sp.) and four gram-negative bacteria
(Escherichia coli, Klebsiella pneumoniae, Salmonella paratyphi and
Pseudomonas putida) (Table 4) by agar well diffusion method.
Streptomycin sulphate (Hi Media) was used as standard drug
3.4. Biological evaluation studies
It is well known that xanthenes and benzoxanthenes display
significant anti-bacterial properties [51]. Having a library of new
Table 2
Optimization of reaction conditions in synthesis of benzoxanthenones.a
R
H
R
O
O
O
O
Ce-MCM-41
neat, 80 oC
OH
O
.
Entry
Catalyst
Solvent
Temperature (◦C)
Time (min)
Yield (%)d
1b
2
3
CeO2
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
CH3OH
120
120
120
60
80
100
90
100
100
100
100
100
120
120
120
90
30
60
60
60
120
120
120
120
78
30
59
61
68, 81, 96
94
96
95
41
5% Ce-MCM-41
10% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
20% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
15% Ce-MCM-41
4
5c
6
7
8
9
10
11
12
CH3CN
THF
DCM
52
10
23
a
Reaction conditions: 2-naphthol (1 mmol), benzaldehyde (1 mmol) and 5,5-dimethyl-1,3-cyclohexanedione (1 mmol) and catalyst (1.7 mol%).
Reaction carried out with 5 mol% of catalyst.
Yields obtained with 0.9, 1.3 and 1.7 mol% of catalyst, respectively.
b
c
d
Isolated yields after column chromatography.

A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
55
Table 3
Synthesis of benzoxanthenone and benzochromenone derivatives using Ce-MCM-41 catalyst.a
Entry
Aldehyde
Diketone
Productb
Time (min)
Yield (%)c
O
O
1
[4a]
30
96, 94, 94, 92, 91d
O
O
O
O
O
O
O
O
O
O
2
[4b]
30
92
O
O
F
F
3
[4c]
[4d]
[4e]
30
95
93
90
O
O
O
O
O
Cl
O
O
Cl
Br
4
40
O
O
Br
5
40
O
O
O
O
O
6
[4f]
30
95
O
O
O
O
N
N
7
[4g]
40
94
O
O
O

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A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
Table 3 (Continued)
Entry
Aldehyde
Diketone
Productb
Time (min)
Yield (%)c
Cl
O
O
8
[4h]
40
86
O
Cl
O
O
O
O
OH
HO
O
9
[4i]
30
85
O
O
O
N
N
O
O
O
O
10
[4j]
30
96
O
N
O
O
Br
N
11
[4k]
45
93
O
Br
O
O
O
O
12
[4l]
90
Traces
O
O
O
O
O
13
[4m]
90
Traces
O
O
O
O
O
O
HO
14
[4n]
45
86
O
HO
O
O

A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
57
Table 3 (Continued)
Entry Aldehyde
Diketone
Productb
Time (min)
Yield (%)c
O
O
O
O
O
O
15
[4o]
50
87
O
O
O
O
O
O
O
O
O
O
O
O
16
[4p]
50
83
O
O
O
O
O
O
O2N
17
[7a]
45
85
O
NO
O
2
O
O
O
O
18
19
20
[7b]
[7c]
[7d]
40
45
35
89
90
92
O
O
O
O
N
N
O
F
O
O
Br
Br
F
O
HO
Br
O
O
Br
OH

58
A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
Table 3 (Continued)
Entry
Aldehyde
Diketone
Productb
Time (min)
Yield (%)c
O
O
O
21
[7e]
50
89
O
O
O
O
O
O
O
22
[7f]
50
86
O
O
O
O
N
O
O
O
23
[3a]
30
96
O
N
O
N
O
N
O
O
Br
24
25
[6a]
[5a]
45
40
88
86
O
O
Br
N
O
O
N
O
O
O
O
O
O
O
26e
[10a]
[10b]
90
90
85
82
O
O
O
O
O
27e
O
O
O
O
28e
[10c]
90
87
O
O
a
Reaction conditions: aldehyde (1 mmol), 2-naphthol (1 mmol) and 1,3-diketone (1 mmol), Ce-MCM-41(1.7 mol%), 80 ◦C, 30–50 min.
All products are characterized by NMR and mass spectroscopy.
Isolated yields after column chromatography.
b
c
d
e
Yields from first to fifth cycle.
reactions carried out at 90 ◦C.

A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
59
Scheme 2. Proposed reaction pathway for the multicomponent condensation reaction with Ce-MCM-41.
Table 4
Antibacterial activities of benzoxanthenones determined by agar well diffusion method (zone of inhibition in mm) in Muller–Hinton Agar.
Compound
E. coli
M. luteus
K. pneumoniae
B. subtilis
S. mutans
S. paratyphi
P. putida
B. circulans
Lysini-bacillus
3a
4f
4k
4n
4o
4p
5a
6a
7a
7b
7c
7d
7e
7f
(Std)
(Control)
00
16
12
15
18
17
00
10
00
11
12
14
00
00
30
00
15
12
15
15
12
13
00
13
00
16
14
16
11
15
28
00
00
00
11
12
11
13
00
00
00
12
11
15
00
12
27
00
00
00
14
00
00
00
00
00
00
00
11
00
14
00
28
00
00
16
17
13
14
15
00
00
12
00
12
12
13
11
27
00
12
13
13
14
12
13
00
00
11
00
00
12
00
00
12
00
00
12
15
15
00
13
17
13
00
18
12
17
11
15
00
00
00
11
12
00
12
13
00
00
11
12
11
13
13
12
25
00
00
11
11
12
13
14
00
12
11
00
11
13
13
12
25
00
for comparative evaluation of antibacterial activity of the com-
pounds. 100 ␮l of 1 mg/ml concentration of each compound was
loaded along with the standard and control (DMSO). It was
noticed that tested compounds (Table 4, entries 4f, 4k, 4n–4p
and 7d) showed promising antibacterial activity with either of
the tested both gram positive and negative bacterial strains. How-
ever, the antibacterial activity profile differed with type of bacterial
strain and nature of compounds. For example, compounds 4o and
7b displayed superior inhibitory activity on gram-negative bac-
terium E. coli and gram positive bacterium Pseudomonas putida,
respectively. In case of gram-positive bacteria the synthesized
compounds, showed significant activity except for Bacillus sub-
tilis. While in the case of gram-negative bacteria the synthesized
compounds showed good anti-bacterial activity ranging from 11
to 18 mm zone (Table 4). Compounds 3a, 5a, 6a and 7a did not
show significant zone of inhibition (Table 4). Interestingly, for
Pseudomonas putida, the synthesized compounds exhibited good
antibacterial activity when compared to standard streptomycin
sulphate (Table 4). From these studies we infer that the synthe-
sized compounds may be effectively used against Pseudomonal
Fig. 9. Recycling experiment of Ce-MCM-41.

60
A.M. Akondi et al. / Journal of Molecular Catalysis A: Chemical 386 (2014) 49–60
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Acknowledgments
R.T. acknowledges the XIIth five year plan project CSC-0125 of
CSIR-IICT for financial support. A.A.M. thanks the Council of Sci-
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