A multicomponent, solvent-free, one-pot synthesis of benzoxanthenones catalyzed by HY zeolite: Their anti-microbial and cell imaging studies

Article abstract of DOI:10.1016/j.tetlet.2011.10.143

An atom-economical, multicomponent condensation of naphthols, aldehydes, and cyclic 1,3-dicarbonyl compounds catalyzed by HY zeolites under solvent-free conditions is reported. This ecofriendly protocol offers several advantages such as a green and cost-e

Full text of DOI:10.1016/j.tetlet.2011.10.143

Tetrahedron Letters 53 (2012) 1018–1024
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A multicomponent, solvent-free, one-pot synthesis of benzoxanthenones
catalyzed by HY zeolite: their anti-microbial and cell imaging studies
⇑
Velladurai Rama, Kuppusamy Kanagaraj, Kasi Pitchumani
School of Chemistry, Madurai Kamaraj University, Madurai 625021, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An atom-economical, multicomponent condensation of naphthols, aldehydes, and cyclic 1,3-dicarbonyl
compounds catalyzed by HY zeolites under solvent-free conditions is reported. This ecofriendly protocol
offers several advantages such as a green and cost-effective procedure with excellent yield, shorter reac-
tion time, simpler work-up, recovery, and reusability of metal-free solid acid heterogeneous catalyst and
tolerance of a wide range of functional groups. The biological studies such as in vitro anti-microbial activ-
ities of the prepared new compounds and cell imaging studies on K562 leukemia cell lines by selected
benzoxanthenones are evaluated.
Received 19 September 2011
Revised 22 October 2011
Accepted 26 October 2011
Available online 31 October 2011
Keywords:
HY zeolite
Heterogeneous catalysts
Benzoxanthenones
Multicomponent reaction
Solvent-free conditions
Ó 2011 Elsevier Ltd. All rights reserved.
Multicomponent reactions are valuable tools for the preparation
of structurally diverse chemical libraries of drug-like heterocyclic
compounds.1 Xanthenes are one of the most widely distributed clas-
ses of natural compounds. Multicomponent one-pot strategies to ac-
cess xanthenes and benzoxanthenones, have attracted considerable
attention over the years due to their diverse biological properties,
such as antiviral,2 anti-inflammatory,3 antibacterial activities, as
well as their use as dyes and fluorescent materials.4 Some of them
have been used as antagonists for paralyzing the action of zoxazola-
mine,5 in photodynamic therapy (PDT)6 and as antagonists for drug-
resistant leukemia lines.7 Thus a broad utility range has made xanth-
enes prime synthetic candidates thereby accentuating the need to
develop newer routes for scaffold manipulation of xanthenes deriv-
atives. Recent strategies to synthesize xanthenones scaffolds in-
clude palladium-catalyzed cyclization of polycyclic aryl triflate
esters,8 resorcinol, and various analytes, such as phthalic anhydride,
acid chloride, ester or aldehyde,9 intramolecular trapping of benzy-
nes by phenols,10 reaction of aryloxy magnesium halides with tri-
ethyl orthoformate11 and reaction of 2-tetralones with substituted
2-hydroxyarylaldehydes.12
HClO4–SiO2,13n CAN,13o N,N0-dibromo-N,N0-1,2-ethanediylbis(p-tol-
uenesulfonamide),13p and HClSO3.13q Many of these synthetic
methods, however, have limitations such as longer reaction time,
harsher reaction conditions, expensive catalysts, and generation
of noticeable amount of side products. These catalysts also suffer
from other drawbacks, such as strongly acidic media, high temper-
ature, inert atmosphere, stoichiometric amounts of reaction pro-
moters, moisture sensitiveness of the catalysts, and difficulty in
the separation of the products such as tedious work-up or purifica-
tion. Thus there is ample scope for the development of new greener
synthetic protocols to assemble such scaffolds.
Heterogeneous catalysis by zeolites by the virtue of their tunable
larger pore sizes and inherent acid/base catalytic properties finds
extensive applications as novel catalysts, as they provide greener
alternatives to homogeneous catalysis. The success of multicompo-
nent one-pot transformation is centered on the design of highly
selective catalysts with well optimized isolated active sites. HY zeo-
lite is an important heterogeneous catalyst used in various chemical
transformations such as one-pot synthesis of 2,3-dihydro-2,2-dim-
ethylbenzofurans,14a 1,4-dihydropyridines,14b methyl N-phenyl
carbamate,14c tetrahydrocarbazole,14d bis(indolyl)methanes,14e 2-
substituted benzimidazoles,14f polyhydroquinolines,14g substituted
quinazolin-4(3H)ones,14h and tetrasubstituted imidazoles.14i
In continuation of our work15 on the applications of heteroge-
neous catalysts on organic transformations, we proposed to utilize
HY zeolite in the present work as a promising candidate to perform
the condensation of naphthols, aldehydes with cyclic 1,3-dicabo-
nyls (Scheme 1). In the search toward eco-compatibility, the sol-
vent-based chemistry has stimulated us to study the reactions
Recently enormous progress has been made in expanding the
scope of condensation of b-naphthol, aldehyde with 1,3-dicarbonyl
compounds by employing a wide array of acid catalysts, such as
BF3ꢀEt2O,13a InCl3,
PTSA,13c Zr(HSO4)4,13d Sr(OTf)2,13e TBAF,13f
13b
I2,13g sulfamic acid,13h NaHSO4–SiO2,13i Caro’s acid-SiO2,13j 12-
tungstophosphoric acid,13k cyanuric acid,13l proline triflates,13m
⇑
Corresponding author. Tel.: +91 452 2456614; fax: +91 452 2459181.
E-mail addresses: pit12399@yahoo.com, profpitlab@yahoo.co.in (K. Pitchumani).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.143

V. Rama et al. / Tetrahedron Letters 53 (2012) 1018–1024
1019
O
R
H
O
+
R'
R'
2
O
3
OH
OH
5
1
R
O
O
R
O
O
HY zeolite
neat, 80oC, 1 h
R'
R'
R'
R'
R' = CH3, H
R' = CH3, H
Benzo[a]xanthenones 4
Benzo[c]xanthenones 6
Scheme 1. HY zeolite catalyzed synthesis of benzoxanthenones by reaction of naphthols, aldehydes and cyclic 1,3-dicarbonyl compounds.
Table 1
Optimization of reaction conditions in synthesis of benzoxanthenones using b-naphthol, benzaldehyde and 5,5-dimethyl-1,3-cyclohexanedionea
R
O
O
3
H
O
Conditions
2a
+
R'
R'
R'
O
OH
O
R'
4a
1
Entry
Catalyst
Solvent
Neat
Toluene
DMF
EtOH
THF
ACN
Bmim
Ethyl acetate
n-Hexane
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
None
HY
HY
HY
HY
HY
HY
HY
HY
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
0
72
60
Trace
Trace
36
25
58
65
93
40
55
58
43
55
52
9
10
11
12
13
14
15
16
17
18
19c
20
21d
HY
NaY
CaY
FeY
CoY
NiY
CuY
ZnY
AlY
HY
54
65
0, 80, 93, 93, 94
93, 93, 93, 93, 93, 82
93, 93, 93,93, 80
HY
HY
5, 4, 3, 2, 1, 0.5
1
Neat
a
b
c
Reaction conditions: b-naphthol (1.0 mmol), benzaldehyde (1.0 mmol), and 5,5-dimethyl-1,3-cyclohexanedione (1.0 mmol), catalyst (20 mg), 100 °C for 5 h.
Isolated yield based on 1.
Reaction carried out at room temperature, 60, 80, 90 and 100 °C, respectively.
Reaction carried out with 30, 25, 20, 15, 10 mg of catalyst, respectively.
d
under solvent-free conditions.16 This protocol offers several advan-
tages such as higher yield, shorter reaction time, simpler work-up,
recovery, and reusability of catalyst and tolerates a wide range of
functional groups with no side products.
At the outset, the reaction parameters such as temperature,
time, identification of the best catalyst, quantity, and solvent for
the synthesis of benzoxanthenones are examined by choosing
b-naphthol 1, benzaldehyde 2a, and 5,5-dimethyl-1,3-cyclohex-
anedione 3 as model substrates (Table 1). Control experiments
have shown that no desired product is detected in the absence of
catalyst (Table 1, entry 1). The use of organic solvents results in
lower conversion (Table 1, entries 2–9), and the reaction proceeds
smoothly under solvent-free conditions (Table 1, entry 10). The
acidity of zeolites can be finetuned using exchangeable metal

1020
V. Rama et al. / Tetrahedron Letters 53 (2012) 1018–1024
Table 2
Synthesis of substituted benzo[a]xanthenones25 using b-naphthol, substituted aldehydes and cyclic 1,3-dicarbonyl compoundsa
R
R
O
O
H
O
HY zeolite
2
neat, 80oC, 1 h
R'
R'
4a-z, A, B
R'
R'
O
OH
+
O
3
1
Entry
R
R0
Time (h)
Product
Yieldb (%)
m.p. (°C)
1
2
3
4
5
6
7
8
C6H5–
p-NO2C6H4–
p-FC6H4–
p-ClC6H4–
m-ClC6H4–
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
1
1
1
1
1
1
1
1
1
1
1
1
1
1
4
24
4
4
24
1
1
1
4
4
4
4
4
4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
93
92
95
90
85
84
90
85
80
85
82
89
88
80
78
Trace
78
70
Trace
80
95
85
80
80
78
82
78
79
152–15413i
175–17713i
190–19313c
180-18213i
172–173
180–18213b
207–20913i
223–224
218–220
203–20513i
204–20613c
203–20513i
219–220
185–187
Oil
o-ClC6H4–
p-HOC6H4–
o-HOC6H4–
p-N(CH3)2–C6H4–
p-CH3OC6H4–
m-CH3OC6H4–
p-CH3C6H4–
p-Cl,m-NO2C6H3–
p-HO,m-OCH3C6H3–
Cyclohexyl–
C6H5CH2–
(CH3)2CHCH2–
CH3CH@CH–
C6H5CH@CH–
20-Pyridinyl–
20-Thiophenyl–
50-Methylfurfuryl-
H–
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23c
24
25
26
27
28
n.d.
190–192
Oil
4s
4t
n.d.
204–206
180–18213i
208–210
173–175
202–20313i
204–20613i
244–24613k
231–23413i
270–27113l
4u
4v
4w
4x
4y
4z
4A
4B
C6H5–
p-ClC6H4-
o-ClC6H4–
p-NO2C6H4–
p-HOC6H4–
H
H
H
H
a
b
c
Reaction conditions: b-naphthol (1.0 mmol), aldehyde (1.0 mmol) and cyclic 1,3-dicarbonyl compound (1.0 mmol), catalyst (20 mg), at 80 °C, neat.
Isolated yield based on 1.
Formaldehyde (3.0 mmol).
cations.14,24 HY, NaY, CaY, FeY, CuY, NiY, ZnY, and AlY zeolites are
examined for their catalytic activity for the synthesis of benzoxan-
thenones. However, when compared to HY zeolite, they exhibit re-
duced activity (Table 1, entries 11–18),17 which is attributed to the
significant reduction in their Bronsted acidity (though they possess
considerable Lewis acidic sites).
Various functional groups such as NO2, Cl, OH, OCH3, and CH3 are tol-
erated. When substituents are present in the para-position (Table 2,
entries 2–4, 7, 9, 10 and 12) higher yield is obtained compared to
substituents present in the meta- and ortho- positions (Table 2, en-
tries 5, 6, 8 and 11). When more than one substituent is present in
the phenyl ring, the yield does not change significantly (Table 2, en-
tries 13 and 14). Interestingly, aliphatic aldehydes such as formalde-
hyde (Table 2, entry 23), 3-methylbutyraldehyde (Table 2, entry 17)
crotonaldehyde (Table 2, entry 18), and cyclohexanecarboxalde-
hyde (Table 2, entry 15) gave the expected products in moderate
to good yield. Trace amount of the product is obtained with phenyl-
acetaldehyde (Table 2, entry 16) and cinnamaldehyde (Table 2, entry
19). These results clearly suggested that electronic factors play a
limited role and steric factors play a major role in the product
formation.
It is thus found that HY zeolite is the best choice of strong solid
metal-free catalyst under solvent-free conditions.25 An increase in
the reaction temperature from room temperature to 60 and 80 °C
accelerates the reaction to give the desired product in optimum
yield, but further increase in the temperature to 90 and 100 °C does
not cause any improvement in yield (Table 1, entry 19). When
20 mg of HY zeolite is used, the reaction proceeds smoothly to give
the product (Table 1, entry 21) in a 93% yield. Consequently opti-
mum reaction conditions for HY zeolite catalyzed synthesis of ben-
zoxanthenones under solvent-free conditions are at 80 °C for 1 h.
This easy and clean protocol for the synthesis of functionalized
benzo[a]xanthenones and benzo[c]xanthenones is extended to var-
ious substituted aldehydes and cyclic 1,3-dicarbonyl compounds
and the observed results are depicted in Tables 2 and 3. This reaction
works very well for a variety of electronically divergent aldehydes,
with 5,5-dimethyl-1,3-cyclohexanedione and b-naphthol in very
good to excellent isolated yield. The reaction proceeds smoothly
with electron-rich, as well as electron-deficient aromatic, aliphatic,
cyclic, and heterocyclic aldehydes with moderate to excellent yield.
Encouraged by successful condensation of aldehydes, b-naph-
thol with 5,5-dimethylcyclohexane-1,3-dione, we decided to ex-
plore the condensation reaction of cyclohexane-1,3-dione with
substituted aldehydes and b-naphthol and products are obtained
with very good to excellent isolated yield.
To extend the scope of the reaction with the above optimized
conditions, the reactions are also extended to
a-naphthol, substi-
tuted aldehydes, and cyclic 1,3-dicarbonyl compounds. HY zeolite
catalyzes this condensation reaction smoothly and affords the corre-
sponding benzo[c]xanthenones in excellent yield under solvent-free

V. Rama et al. / Tetrahedron Letters 53 (2012) 1018–1024
1021
Table 3
Synthesis substituted benzo[c]xanthenones25 using
a
-naphthol, substituted aldehydes and cyclic 1,3-dicarbonyl compoundsa
R
O
O
R
O
H
HY zeolite
2
R'
R'
R'
neat, 80oC, 1 h
OH
+
O
O
R'
6a-l
3
5
Entry
R
R0
Time (h)
Product
Yieldb (%)
m.p. (°C)
1
2
3
4
5
6
7
8
C6H5–
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
1
1
1
1
1
1
1
1
1
1
1
1
6a
6b
6c
6d
6e
6f
6g
6h
6i
87
62
93
87
77
92
84
82
82
82
90
92
155–15713m
157–15813m
176–177
m-NO2C6H4–
p-FC6H4–
p-ClC6H4–
p-HOC6H4–
p-CH3OC6H4–
m-CH3OC6H4–
C6H5CH@CH–
20-Thiophenyl–
C6H5–
178–17913m
185–187
148–150
176–17813m
61–6213n
9
163–16413m
173–17513m
177–179
10
11
12
6j
6k
6l
p-NO2C6H4–
p-ClC6H4–
H
H
175–177
a
Reaction conditions: a-naphthol (1.0 mmol), aldehyde (1.0 mmol) and cyclic 1,3-dicarbonyl compound (1.0 mmol), catalyst (20 mg), at 80 °C, neat.
Isolated yield based on 5.
b
1,3-dicarbonyl compounds catalyzed by HY zeolite, prompted us
to evaluate the antibacterial activity of these synthesized
benzoxanthenones.21
Table 4
Reusability of HY zeolite in synthesis of benzo[a]xanthenones from b-naphthol,
benzaldehyde and 5,5-dimethyl-1,3-cyclohexanedionea
We tested the strains of Escherichia coli, Klebsiella pneumoniae,
Enterobacter sps, Proteus mirabilis, Proteus vulgaris, Pseudomonas
aeruginosa, Bacillus subtilis, Bacillus coagulase, Staphylococcus aureus,
and Staphylococcus saprophyticus against the 10 new benzoxanthe-
nones given in Figure 1 (not reported in literature) (Table 5). The re-
sults suggest that, products 4e, 4h, 4i, 4m, 4o, 4q, 4r, 4v, 4t, and 4w
exhibited mild to good inhibitory effect against most of the tested
microbes. Compounds 4h and 4i are found to have good inhibitory
effect on the K. pneumonia and S. aureus, respectively. Compound
4q is effective against S. aureus and B. coagulase and 4v is shown to
be effective against B. subtilis and E. coli. The studies, thus confirm,
the potential biological activity and consequent utility of these
derivatives as potent drug sources.
Runb
First
93
Second
90
Third
85
Fourth
82
Fifth
82
Yield (%)
a
Reactions are performed on a 1 mmol scale of all reactants in solvent-free
conditions for 1 h at 80 °C.
b
After completion of the reaction, catalyst is filtered and washed thrice with
ethyl acetate, air dried, activated and reused for successive runs.
conditions, and also tolerates various functional groups such as
OCH3, F, Cl, NO2, and OH with excellent yield (Table 3). This greener
approach provides a mild and general route to synthesize various
classes of 7-aryl substituted benzo[c]xanthenones and 12-alkyl/aryl
substituted benzo[a]xanthenones. These results clearly prove that
this method is more advantageous than the previously reported
methods13a–n in terms of ecofriendliness in catalyst, much higher
yield, reduced reaction time, and above all reusability. Reusability
of the catalyst was also tested upto 5 successive runs, with only mar-
ginal decrease in catalytic activity (Table 4).
Cell imaging studies26
Organic fluorophores have found extensive applications in cell
imaging.22 However, their drawbacks, such as narrow excitation,
single, wide emission with a long tail, poor photostability, etc., lim-
ited their applications in areas such as multiplexing and real-time
measurements. Generally benzoxanthenones have wide, long
wavelength emission and also exhibit unique properties such as
multiple emissions, wide excitation window, low cytotoxicity,
and excellent photostability (vide infra) to make them ideal candi-
dates for cellular imaging. Benzo[c]xanthenones were marketed by
Molecular Probes (formerly Invitrogen, and now Life Technologies)
in the early 1990s. These dyes are long wavelength fluorescent pHi
indicators and have one benzene and a naphthalene component in
the fluorophore.23
To account for the facile catalysis by HY zeolite in the synthesis
of benzoxanthenones,
a plausible mechanism is proposed
(Scheme 2). The reaction proceeds via the ortho-quinone methides
intermediate, formed by the nucleophilic addition of 2-naphthol to
protonated aldehydes catalyzed by the Bronsted acidic sites of HY
zeolite.18–20 Subsequent Michael addition of this in situ formed
ortho-quinone methides to 1,3-dicarbonyl compound followed by
addition of the phenolic hydroxyl moiety to the carbonyl groups
of ketone provides cyclic hemiketal which on dehydration affords
the product.
In the present preliminary study, selected benzoxanthenones
are tested for cell imaging studies of K562, a human erythromyel-
oblastoidleukemia cell line. Cellular imaging studies using confocal
microscope reveal that benzoxanthenone dye 4h readily enters
K562 cells whereas the other dyes 4m and 4t are not taken by
the cells (Fig. 2). Compound 4h is localized on K562 cells, and
Antimicrobial activity of benzoxanthenones
The synthesis of several new derivatives of benzoxanthenones
(Fig. 1) by condensation of b-naphthol, various substituted aro-
matic, aliphatic, cyclic, and heterocyclic aldehydes with cyclic

1022
V. Rama et al. / Tetrahedron Letters 53 (2012) 1018–1024
R'
R'
O
OH
H
O
H
O
O H
OH
R'
R'
R
H
O
R
O
O
O
CHR
O
Si Al Si
Al
O
OH
R
H
O
OH
H
R'
R'
R'
H
O
O
O
R
O
O
O
R'
O
-H2O
Si Al Si
Al
+
R
O
O
Scheme 2. Proposed mechanistic pathway for the condensation reaction of aldehyde, b-naphthol, and cyclic 1,3-dicarbonyl compound.
N
Cl
Cl
O
NO2
O
OH
O
O
O
O
O
4h
O
O
4i
O
4q
4e
4m
CH3
O
O
O
N
O
O
O
O
O
4o
O
4r
O
4t
O
4v
4w
Figure 1. 12-Substituted 8H-benzo[a]xanthen-11(12H)-one reported for the first time.
Table 5
Antimicrobial activities of 12-substituted benzoxanthenones determined by disk-diffusion method (zone of inhibition in mm) at10 lg/mL in Muller-Hinton Agar
Organisms
Control (ampicillin)
4e
4h
4i
4m
4o
4q
4r
8.3
4v
4t
4w
S. aureus
S. saphyrophiticus
B. subtilis
B. coagulase
E. coli
P. aeruginosa
K. pneumoniae
Enterobacter
P. mirabilis
P. vulgatis
17.5
15.5
15.0
18.5
17.5
15.0
17.2
15.5
15.2
17.0
—
—
11.0
—
13.0
9.0
8.0
10.0
10.0
9.2
—
—
9.8
10.5
10.5
—
17.5
10.5
9. 6
10.2
18.0
—
11.0
—
—
—
—
—
—
10.0
10.2
10.0
12.4
10.5
—
—
—
10.5
9. 6
10.2
—
17.5
10.5
13.5
18.5
12.0
—
12.5
12.3
10.5
11.5
—
—
11.0
—
9.4
10.0
—
10.1
—
—
—
14.5
—
13.8
—
—
—
9.8
10.5
8.5
—
—
10.5
9. 8
10.0
15.0
10.5
17.5
11.5
10.0
9.8
—
—
10.2
12.2
10.0
11.0
—
11.0
10.0
9. 0
10.2
9.8
10.5
10.5
9. 0
10.
13.4
has emitted red and green fluorescence. The intensity profiles are
shown in Figure 2 (g).
heterogeneous solid acid catalyst with good to high yield, shorter
reaction times, tolerancy toward wide range of functional groups,
operational simplicity, and easy separation. Some of the new com-
pounds exhibit significant biological activity against various mi-
crobes. Observations using confocal microscopy in living cells,
(K562, a human erythromyeloblastoidleukemia cell lines) by se-
lected substrates, highlight the importance of benzoxanthenone
In conclusion, a mild and efficient method for the synthesis of
benzoxanthenones via three-component reaction catalyzed by HY
zeolite under solvent-free aerobic conditions is reported. The sali-
ent features of this atom economical procedure are its reusability,
inexpensiveness environmentally benign nature, use of metal-free

V. Rama et al. / Tetrahedron Letters 53 (2012) 1018–1024
1023
Figure 2. (a) Unstained cells used as control showing no fluorescence; (b) staining of cells by 4h shows fluorescence emission confirming the uptake of the dye by cells,
monitored at 40ꢁ magnification; (c) intensity of green and red fluorescence of 4h, monitored at 40ꢁ magnification; (d) and (f) staining of cells with 4m and 4t did not show
any fluorescence emission.
13. (a) Mirjalili, B. F.; Bamoniri, A.; Akbari, A. Tetrahedron Lett. 2008, 49, 6454; (b)
dyes in cell imaging studies. Further works are in progress for cell
imaging and live cell measurement with a wide range of substi-
tuted benzoxanthenones.
Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S. Tetrahedron 2009, 65, 7129; (c)
Khurana, J. M.; Magoo, D. Tetrahedron Lett. 2009, 50, 4777; (d) Foroughifar, N.;
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Acknowledgment
Financial support from UGC Hyderabad, for an award under FDP
to V.R. is gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.10.143.
References and notes
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(1.0 mmol), cyclic 1,3-dicarbonyl compound (1.0 mmol) and HY zeolite
(20 mg) is heated at 80 °C for 1 h in oil bath under solvent-free condition.
The progress of the reaction is monitored by TLC. After completion of the
reaction, the product is extracted by ethanol and filtered using Whatmann No.
4 filter paper. The filtered catalyst is washed thrice with ethyl acetate, air dried,
activated and reused for successive runs. The filtrate is concentrated and the
crude product is recrystalized from ethanol. All the products are well
characterized by 1H & 13C NMR spectra and melting points which are all
found to be comparable with the reported ones.13a–n
23. Han, J.; Burgees, K. Chem. Rev. 2010, 110, 2709.
24. General method for the preparation of cation-exchanged zeolites: NaY zeolite
powder is purchased from Sigma–Aldrich and used as such. The
physicochemical parameters of NaY zeolite are Si/Al ratio 2.43, unit cell size
24.65 Å and surface area, m2/g: 900 with supercages of a diameter of ca.
26. General procedure for the cell imaging studies of benzoxanthenones22: The ability
of the dye to enter the cells is studied by staining K562 cell lines with the dyes.
K562 is a human erythromyeloblastoidleukemia cell line, non-adherent and
characterized by round cells, are grown in RPMI 1640 media supplemented
with 10% Foetal Bovine Serum in a humidified atmosphere containing 5% CO2
at 37 °C. Stock solutions containing 10 mM of the dyes 4h, 4m and 4t are
prepared in DMSO. The cells are treated with the dyes at a final concentration
1.3 nm. Cation-exchanged zeolites (Ca2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+ and Al3+
)
are prepared by ion-exchange method.14j The cations of interest are exchanged
into the NaY zeolite powder (10 g) by stirring with the corresponding nitrate
solution (100 ml, 10%) at 90 °C for about 12 h. The exchange is repeated at least
four times. Each time, after exchange, the zeolite powder is washed repeatedly
with distilled water and then dried. All these cation-exchanged zeolites are
activated at 450 °C for about 6 h prior to use.
of 10 lM and are incubated for 1 h. The cells are centrifuged at 2000 rpm for
25. General procedure for the synthesis of benzoxanthenones over HY zeolite catalyst:
NH4Y zeolite powder is purchased from Sigma–Aldrich and used as such. The
physicochemical parameters of NH4Y zeolite are Si/Al ratio 2.9, unit cell size
24.68 Å and surface area, m2/g: 925 with supercages of a diameter of ca.
1.38 nm. Zeolite HY is obtained by the thermal deammonification of NH4Y
zeolite at 450 °C. A heterogeneous mixture of naphthol (1.0 mmol), aldehyde
5 min. The supernatant portion is removed and the pellet is suspended in
Phosphate Buffered Saline (PBS). The cells are spotted on the slide and
observed for fluorescences using confocal microscope (Zeiss LSM 510 META) by
exciting at 514 and 633 nm and the emissions are obtained using emission
filters BP 505-550 and LP 585, respectively. Cells without treatment with the
dye are used as control.