Microwave-assisted green synthesis of dibenzo[a,j]xanthenes using p-dodecylbenzenesulfonic acid as an efficient Bronsted acid catalyst under solvent-free conditions

Article abstract of DOI:10.1016/j.crci.2012.05.018

The p-dodecylbenzenesulfonic acid (DBSA) has been successfully applied as an efficient acidic catalyst for the microwave-assisted synthesis of a series of 14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes (3a-m) via a one-pot condensation-cyclization reaction o

Full text of DOI:10.1016/j.crci.2012.05.018

C. R. Chimie 15 (2012) 675–678
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Full paper/Memoire
Microwave-assisted green synthesis of dibenzo[a,j]xanthenes using
p-dodecylbenzenesulfonic acid as an efficient Bronsted acid catalyst
under solvent-free conditions
*
Davinder Prasad, Amreeta Preetam, Mahendra Nath
Department of Chemistry, University of Delhi, 110007 Delhi, India
A R T I C L E I N F O
Article history:
A B S T R A C T
Received 1 March 2012
Accepted after revision 22 May 2012
The p-dodecylbenzenesulfonic acid (DBSA) has been successfully applied as an efficient
acidic catalyst for the microwave-assisted synthesis of a series of 14-aryl- or alkyl-14H-
Available online 29 June 2012
dibenzo[a,j]xanthenes (3a-m) via a one-pot condensation-cyclization reaction of
b-
Keywords:
naphthol with various aliphatic or aromatic aldehydes under solvent-free conditions.
Operational simplicity, short reaction times, excellent yields and environmentally-benign
conditions are other advantages of this protocol.
DBSA
Microwave irradiation
Solvent-free conditions
Green synthesis
Dibenzo[a,j]xanthenes
´
ß 2012 Published by Elsevier Masson SAS on behalf of Academie des sciences.
1. Introduction
trapping of benzynes by phenols [11], reaction of
aryloxymagnesium halides with triethylorthoformate
Xanthenes are pharmaceutically useful oxygen hetero-
cycles that occupy an important place in the realm of
medicinal and material chemistry. They are known to
exhibit a wide range of biological properties such as
antibacterial [1], anti-proliferative [2], anticancer [3],
anti-inflammatory [4], antiviral agents [5] and photo-
sensitizers in photodynamic therapy for the treatment of
localized tumours [6]. In addition, various xanthene
derivatives have also been utilized as fluorescent dyes
[7], pH-sensitive fluorescent materials for the visualiza-
tion of bio-molecular scaffolds [8], substrates for the
construction of heteroatoms containing positively
charged polycyclic aromatic hydrocarbons [9] and in
laser technology [10]. Consequently, the synthesis of
various xanthene derivatives has drawn notable atten-
tion. A number of diverse approaches are available for the
synthesis of these molecules such as intramolecular
[12], condensation of primary alcohols with resorcinol
[13], heating of sodium or potassium 2-naphthyloxide
under CO and CO2 pressure [14] or condensation cycliza-
tion reaction of salicylaldehydes with 2-tetralone [15].
However, the synthesis of dibenzoxanthenes via one-pot
condensation of
b-naphthol with aldehydes has been
widely studied. This reaction has been catalyzed by a wide
range of catalysts including pTSA [16], P2O5/Al2O3 [17],
ruthenium chloride hydrate [18], ionic liquids [19],
methanesulfonic acid [20], LiBr [21], silica sulphuric acid
[22], K5CoW12O40.3H2O [23], HClO4 [24], sulfamic acid
[25], alum [26], In(OTf)3 [27], or Sc[N(SO2C8F17)2]3 [28]
etc. Though each of above mentioned methods has
demonstrated its own merits, several of these protocols
suffer from one or more drawbacks such as prolonged
reaction times, use of hazardous solvents, necessity of
excess reagents or catalysts, harsh reaction conditions or
low yields of the desired products. Hence, there is a scope
for the development of an efficient, economical and eco-
friendly synthetic strategy for the preparation of these
important heterocyclic molecules.
* Corresponding author.
E-mail address: mnath@chemistry.du.ac.in (M. Nath).
1631-0748/$ – see front matter ß 2012 Published by Elsevier Masson SAS on behalf of Acade´mie des sciences.
http://dx.doi.org/10.1016/j.crci.2012.05.018

676
D. Prasad et al. / C. R. Chimie 15 (2012) 675–678
R
OH
MW, 2 mol% DBSA
RCHO
2
+
125 oC, 4-15 minutes
O
2a-m
3a-m
1
Scheme 1.
Table 1
In recent years, p-dodecylbenzenesulfonic acid (DBSA)
Optimization of the reaction conditions for microwave-assisted synthesis
of 14-phenyl-14H-dibenzo[a,j]xanthene (3a) under solvent-free condi-
tions.
has gained considerable popularity as an efficient
Bronsted-acid surfactant combined catalyst for carrying
out various organic transformations in water as well as
under solvent-free conditions [29]. Additionally, the
microwave-accelerated synthesis has been recognized in
constituting eco-friendly protocols as it offers several
advantages such as high efficiency, short reaction times,
minimum energy consumption, high yields and better
purity of the products [30]. Hence, the combination of a
catalytic system with microwave irradiation under sol-
vent-free conditions could afford an entirely greener
approach to assemble diverse biologically relevant com-
pounds in short reaction times [31]. Keeping this in mind,
we envision the possibility to synthesize dibenzox-
anthenes in the presence of a catalytic amount of DBSA
using microwave irradiation under solvent-free condi-
tions. To the best of our knowledge, DBSA has not been
employed yet to synthesize 14-aryl- or alkyl-14H-diben-
zo[a,j]xanthenes under solvent-free microwave condi-
tions.
Entry
Catalyst
Catalyst load
(mol%)
Temperature
Time
Yield
(%)a
(8C)
(min)
1
2
3
4
5
DBSA
DBSA
–
2
2
–
2
2
125
125
125
100
80
180
4
90b
99
30
4
NR
82
DBSA
DBSA
4
37
NR: no reaction; DBSA: p-dodecylbenzenesulfonic acid.
a
Isolated yields.
b
Conventional heating.
yield within 4 min (Table 1, entry 2). Indeed, no product
formation was observed even after 30 min in the absence
of the catalyst under microwave irradiation (Table 1 entry
3), indicating the crucial role of DBSA in the synthesis of
dibenzoxanthenes. Furthermore, the effect of temperature
on the rate of reaction was examined. We found that 125 8C
is the optimal temperature and the reaction was incom-
plete at lower temperatures (Table 1, entries 4 and 5).
Hence, 2 mol% DBSA at 125 8C temperature was chosen as
optimal catalyst load to carry out the solvent-free
synthesis of target dibenzoxanthene derivatives under
microwave irradiation.
In continuation of our ongoing work to develop eco-
friendly methods [32] for the synthesis of various bioactive
heterocycles, we wish to report herein a microwave-
assisted green protocol for the synthesis of 14-aryl- or
alkyl-14H-dibenzo[a,j]xanthenes through one-pot con-
densation of
b-naphthol with alkyl or aryl aldehydes in
the presence of DBSA as an efficient Bronsted acid catalyst
at 125 8C under solvent-free conditions (Scheme 1).
After optimization, the scope and generality of this
condensation reaction was investigated by synthesizing a
series of 14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes (3a–
2. Results and discussion
m) via microwave-assisted one-pot condensation of b-
naphthol with various alkyl or aryl aldehydes at 125 8C
temperature under solvent-free conditions. All the desired
products were obtained in good to excellent yields (78-
99%) with high purity within 4–15 min (Table 2). In
general, the reaction proceeded well with high rate of
conversion in the case of benzaldehyde or aryl aldehydes
having electron withdrawing substituents such as F, Br and
NO2 on the meta-position of aromatic ring (Table 2, entries
1–4) while the aromatic aldehyde bearing electron
donating substituent such as CH3 afforded comparatively
lower yield of the desired product 3e (Table 2, entry 5). On
the other hand, the sterically hindered ortho-substituted
aryl aldehydes reacted with slow rate in comparison to
meta-substituted aromatic aldehydes to afford the corre-
sponding products (3f–h) in 90–95% yields (Table 2, entries
6, 7 and 8). In addition, p-formylbenzaldehyde and less
reactive aliphatic aldehydes provided the desired diben-
zoxanthenes (3i–m) in slightly lower yields (Table 2,
entries 9–13).
Previously, Jin et al. [33] have synthesized 14-aryl- or
alkyl-14H-dibenzo[a,j]xanthenes in aqueous medium by
using DBSA as an acidic catalyst under conventional
heating conditions but the reported procedure is restricted
to using the higher load of catalyst (20 mol% DBSA) to
generate the desired products after prolonged heating (16–
24 h) at reflux temperature. In contrast, the present
methodology requires only 2 mol% DBSA to afford various
14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes in good to
excellent yields (78–99%) within 4–15 min under solvent-
free microwave conditions.
To obtain the optimum conditions for the synthesis of
these molecules, we initiated our investigation by heating
b-naphthol and benzaldehyde as model substrates at
125 8C in the presence of 2 mol% DBSA under solvent-free
conditions. Interestingly, the reaction afforded the corre-
sponding 14-phenyl-14H-dibenzo[a,j]xanthene (3a) in
90% isolated yield after 180 min (Table 1, entry 1). In
contrast, the reaction performed under microwave irradi-
ation provided the desired product (3a) in quantitative
Furthermore, the catalytic potential of DBSA was
compared with other reported catalysts for the synthesis

D. Prasad et al. / C. R. Chimie 15 (2012) 675–678
677
Table 2
p-dodecylbenzenesulfonic acid (DBSA) catalyzed, microwave-assisted
one-pot condensation of -naphthol with aryl or alkyl aldehydes at 125 8C
under solvent-free conditions.
4. Experimental
b
All the chemicals were purchased from Sigma-Aldrich
and used without further purification. The progress of the
reactions was monitored by thin layer chromatography
(TLC) using silica gel 60 F254 (pre-coated aluminium
sheets) from Merck. TLC spots were visualized by UV-light
followed by iodine. NMR spectra were obtained in CDCl3 or
DMSO-d6 on Jeol ECX 400 MHz NMR spectrometer and
chemical shifts are expressed in parts per million (ppm).
Infrared spectra were recorded on Perkin Elmer IR
Entry
R
Products
Time
Yields
(%)a
(min)
1
2
C6H5
3a
3b
3c
3d
3e
3f
4
4
99
99
99
99
93
90
90
95
84
80
89
78
86
3-FC6H4
3
3-BrC6H4
3-NO2C6H4
3-CH3C6H4
2-CH3C6H4
2-BrC6H4
2-CF3C6H4
4-CHOC6H4
CH3CH2CH2
(CH3)2CH
CH3CH2
4
4
4
5
4
6
4
7
3g
3h
3i
4
spectrometer and absorption maxima (vmax) are given in
8
4
cmÀ1. The melting points were determined in open
capillary tubes on Buchi M-560 melting point apparatus
and are uncorrected. Microwave reactions were carried out
in a CEM Discover Microwave by using standard 10 mL
Pyrex microwave tube at medium stirring mode.
9
4
10
11
12
13
3j
15
15
15
15
3k
3l
3mb
CH3(CH2)7
a
Isolated yields after chromatographic purification.
Oil.
b
4.1. General procedure for the synthesis of 14-aryl- or alkyl-
14H-dibenzo[a,j]xanthenes (3a–m)
of 14-phenyl-14H-dibenzo[a,j]xanthene (3a) under micro-
wave irradiation. It is evident from Table 3 that DBSA has
demonstrated relatively comparable catalytic efficiency
with K5CoW12O40.3H2O (Table 3, entries 4 and 7) while it
can be considered as a better catalyst than n-Bu4NBr,
methanesulfonic acid, LiBr and sulfamic acid for the
synthesis of 3a under solvent-free microwave conditions.
A mixture of b-naphthol (2 mmol), alkyl or aryl
aldehydes (1 mmol) and DBSA (0.02 mmol) was irradiated
in a sealed 10 mL Pyrex microwave tube at preset 300 W
power, 100 psi pressure and 125 8C temperature for 4–
15 min. During the reaction, the power was varied between
117 and 135 W and no pressure was developed. After
compressed air cooling to room temperature, a saturated
aqueous solution of NaHCO3 (5 mL) and brine (5 mL) were
added to the reaction mixture. The aqueous solution was
extracted with ethyl acetate (10 mL Â 3) and the combined
organic layers were dried over anhydrous Na2SO4 and
evaporated under vacuum to dryness. The crude products
were purified on silica gel (60–120 mesh size) column by
using 1% ethyl acetate in heptane as eluent to afford the
pure products (3a–m).
3. Conclusion
In summary, we have demonstrated an efficient,
economical and eco-friendly protocol for the synthesis
of various 14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes
under solvent-free conditions. A variety of aromatic and
aliphatic aldehydes reacted successfully with
b-naphthol
All the synthesized compounds are known and their
physical and spectral data are found in agreement with the
reported data [16,18,21,25,28,34]. The characterization
data of two representative compounds (3g and 3h) are
given below.
to afford the desired products in good to excellent yields.
The notable features of the present methodology include
operational simplicity, short reaction times, high yields of
the products and the release of water as the only byproduct
during the reaction.
4.1.1. 14-(2-Bromophenyl)-14H-dibenzo[a,j]xanthenes (3g)
White solid; mp 215 8C. IR (CHCl3):
1517, 1459, 1431, 1402, 1250, 1242, 1020, 962, 828, 808,
759, 748 cmÀ1 1H NMR (400 MHz, CDCl3):
= 8.88 (d,
J = 8.79 Hz, 2H, ArH), 7.80 (t, J = 8.79 Hz, 4H, ArH), 7.64–
7.60 (m, 2H, ArH), 7.48 (d, J = 8.79 Hz, 2H, ArH), 7.44-7.40
(m, 4H, ArH), 6.98–6.94 (m, 1H, ArH), 6.83–6.79 (m, 1H,
ArH), 6.73 (s, 1H, CH) ppm; 13C NMR (100 MHz, CDCl3):
y = 3058, 1593,
Table 3
Comparative study of catalytic potential of p-dodecylbenzenesulfonic
acid (DBSA) with other reported catalysts for the synthesis of 14-phenyl-
14H-dibenzo[a,j]xanthene (3a) under microwave irradiation.
;
d
Entry Catalysts
Catalyst load Temperature Time Yields
(mol%)
(8C)
130
125
(min) (%)a
1
2
n-Bu4NBr
10
4
2
94[19]
d
= 148.85, 145.39, 133.03, 132.00, 131.70, 130.84, 129.01,
Methanesulfonic 10
acid
86[20]
128.56, 128.42, 128.05, 126.71, 124.35, 124.01, 120.86,
118.25, 118.06, 37.10 ppm; Anal. calcd for C27H17BrO: C,
74.15; H, 3.92. Found: C, 74.45; H, 4.02.
3
4
5
6
7
LiBr
15
1
130
125
125
125
125
4
83[21]
89[23]
95[25]
99b
K5CoW12O40.3H2O
Sulfamic acid
DBSA
2
4.1.2. 14-(2-(Trifluoromethyl)phenyl)-14H-
4
2.5
4
dibenzo[a,j]xanthenes (3h)
2
White solid; mp 247 8C. IR (CHCl3):
1519, 1442, 1379, 1245, 1024, 882, 844, 814, 695 cmÀ1; 1H
NMR (400 MHz, CDCl3): = 8.43 (d, J = 8.05 Hz, 2H, ArH),
7.82–7.78 (m, 4H, ArH), 7.61–7.55 (m, 3H, ArH), 7.49
y = 3059, 1584,
DBSA
2
2
95b
a
d
References.
b
Present work.

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