An efficient KHSO4 catalyzed synthesis of xanthenes

Article abstract of DOI:10.1515/hc-2011-0057

KHSO₄ is an efficient catalyst for the condensation of β-naphthol, aromatic aldehydes, and 5,5-dimethyl-1,3-cyclohexanedione at 100°C to afford 9,9-dimethyl-12-phenyl-8, 10,11,12-tetrahydro-9H-benzo[a] xanthen-11-one derivatives in 80-95% yield

Full text of DOI:10.1515/hc-2011-0057

Heterocycl. Commun., Vol. 18(1), pp. 53–56, 2012 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/hc-2011-0057
An efficient KHSO4 catalyzed synthesis of xanthenes
Nemallapudi Bakthavatchala Reddy1, Kunda Uma
Several synthetic methods for the preparation of xan-
thenes derivatives under solvent-free conditions in the pres-
ence of I2 (Wang et al., 2009), NH2SO3H (Heravi et al.,
Maheswara Rao1, Chereddy Syama Sundar1,
Sandip Kumar Nayak2 and Cirandur Suresh Reddy1,*
2010), HBF4-SiO2 (Zhang et al., 2009) have been reported.
1 Department of Chemistry, Sri Venkateswara University,
Xanthenes derivatives have also been synthesized using
Tirupati 517 502, India
solvents and Sr(OTf)2 (Li et al., 2008), NaHSO4-SiO2 (Das
2 Bio-Organic Division, Bhabha Atomic Research Center,
et al., 2007), BF3-OEt2 (Sethukumar et al., 2011), prolin-
Mumbai 400 085, India
etriflate (Li et al., 2010), and TBAF (Gao et al., 2009) as
*Corresponding author
e-mail: csrsvu@gmail.com
catalysts. Xanthenes have also been obtained in the presence
of ionic liquid (Khurana and Magoo, 2009) and surfactant-
combined catalyst (Shinde et al., 2011), However, in spite
of their potential utility, many of these methods suffer draw-
backs such as unsatisfactory product yields, expensive cata-
Abstract
lysts, and prolonged reaction times.
In continuation of our interest to develop efficient synthetic
routes for biologically active compounds using green chemi-
cal techniques (Chandra Sekhar Reddy et al., 2010), we suc-
cessfully used KHSO4 as a catalyst instead of Lewis acids
for the synthesis of xanthenes derivatives under a neat condi-
KHSO4 is an efficient catalyst for the condensation of
β-naphthol, aromatic aldehydes, and 5,5-dimethyl-1,3-cyclo-
hexanedione at 100°C to afford 9,9-dimethyl-12-phenyl-8,
10,11,12-tetrahydro-9H-benzo[a]xanthen-11-one derivatives
in 80–95% yields.
tion. This catalyst is inexpensive, mild, and does not require
the maintenance of anhydrous conditions. There have been
no reports on the synthesis of xanthenes derivatives using
Keywords: aromatic aldehydes; 5,5-dimethyl-1,3-cyclo-
hexanedione; KHSO4; β-naphthol; xanthenes.
KHSO4 as catalyst.
Introduction
Results and discussion
Multicomponent reactions (MCRs) have attracted much
attention due to their synthetic and practical efficiency, reduc-
tion of isolation and purification steps, minimization of costs,
energy, time, and waste production (Anary-Abbasinejad and
Saidipoor, 2008; Ghosh et al., 2008; Habibi et al., 2008). As
a result, considerable efforts have been paid to the develop-
ment of new and improved one-pot MCRs in recent years
(Cui et al., 2006; Ghosh et al., 2007; Huang and Xue, 2007).
In addition to this, the utility of MCRs is well represented
in the synthesis of privileged medicinal scaffolds such as
1,4-dihydropyridines, dihydropyrimidines, decahydroqui-
nolin-4-ones, and substituted indoles (Yadav et al., 2010).
MCRs involve three or more substrates together reacting in a
single vessel to form the desired product.
Xanthenes and benzoxanthenes are important intermedi-
ates in organic synthesis due to their wide range of biologi-
cal properties such as antibacterial (El-Brashy et al., 2004),
antiviral (Jamison et al., 1990), and anti-inflammatory activi-
ties (Chibale et al., 2003). Furthermore, these heterocycles
display useful spectroscopic properties and are used as dyes
in laser technologies and as fluorescent materials for the
visualization of biomolecules (Wu et al., 2010). Several xan-
thene dyes are extracted naturally from soil and plants such
as Indogofera longeracemosa (Licudine et al., 1997). Thus,
the synthesis of benzoxanthene derivatives is currently of
great interest.
A simple and an efficient procedure for the synthesis of
9,9-dimethyl-12-phenyl-8,10,11,12-tetrahydro-9H-benzo[a]
xanthen-11-one derivatives 4 (Scheme 1) by condensation of
aromatic aldehydes with β-naphthol and 5,5-dimethyl-1,3-cy-
clohexanedione in the presence of KHSO4 under solvent-free
conditions at 100°C is reported.
The reaction proceeds smoothly under these solvent-free
conditions and gives the title compounds 4a–l in 80–95%
yields. The effect of various catalytic amounts of KHSO4 on
the synthesis of 4a–l was examined and it was found that 10
mol% catalyst gave the maximum product yield.
The reusability of the catalyst is an important factor from an
economical and environmental point of view and has been the
focus of much attention in recent years. Thus, the reusability
of KHSO4 was studied in this system. The catalyst can easily
be separated by dispersing the reaction mixture in ice water.
In particular, it was found that the yield of 4b decreased only
slightly after the reuse of KHSO4 for five times (Table 1). The
yield of 4b was 95%, 92%, 89%, 86%, and 85% for the first
to fifth use of the same catalyst, respectively. To assess the
efficiency and generality of this methodology, the synthesis
of 4b was compared with the previously reported methods
(Das et al., 2007; Li et al., 2008; Khurana and Magoo, 2009;
Nandi et al., 2009; Zhang et al., 2010; Shinde et al., 2011). It
was found that the present method is superior to the reported

54 N. Bakthavatchala Reddy et al.
OH
O
O
R
O
KHSO4 (10 mol%)
100ºC, solvent-free
R
H
O
O
1
2a-l
3
4a-l
Product
R
Product
R
Ph
4-OH-C6H4
4a
4g
4-Cl-C6H4
4-Br-C6H4
4-F-C6H4
4-Me-C6H4
4-MeO-C6H4
4-NO2-C6H4
3-NO2-C6H4
2-NO2-C6H4
5-Cl-2-OHC6H3
2-C5H4N
4b
4c
4d
4e
4f
4h
4i
4j
4k
4l
Scheme 1 Synthesis of xanthenes catalysed by KHSO4.
cyclohexanedione 3 (1 mmol) in a 50-mL flask. The mixture was
heated and maintained at 100°C for 30 min. After completion of
the reaction as indicated by thin layer chromatography (TLC),
ice-water was added. The resultant solid was collected by filtra-
tion, washed with water, dried, and crystallized from ethanol. The
physical and spectral data of the known compounds 4a–j were in
agreement with those reported in the literature (Das et al., 2007;
Li et al., 2008; Foroughifar et al., 2009; Wang et al., 2009).
methods with respect to reaction time, yield of the product,
and amount of the catalyst.
Conclusion
A novel and highly efficient methodology for the synthesis of
9,9-dimethyl-12-phenyl-8,10,11,12-tetrahydro-9H-benzo[a]
xanthen-11-one derivatives 4 by condensation reaction of
aldehydes, β-naphthol and 5,5-dimethyl-1,3-cyclohexane-
dione in the presence of catalytic amounts of KHSO4
(10 mol%) under solvent-free conditions is reported. The
advantages of this method over other existing methods are
reduced reaction times, higher yields, mild reaction condi-
tion, and easy work-up procedure.
9,9-Dimethyl-12-phenyl-9,10-dihydro-8H-benzo[a]xanthen-11-
(12H)-one (4a) mp 148–150°C, lit. mp 149–150°C.
12-(4-Chlorophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4b) mp 188–189°C, lit. mp 188–189°C.
12-(4-Bromophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4c) mp 186–187°C, lit. mp 187–189°C.
Experimental
General
12-(4-Fluorophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4d) mp 185–186°C, lit. mp 184–186°C.
Infra red (IR) spectra were recorded on a Perkin-Elmer 683 spectro-
photometer using KBr pellets. The nuclear magnetic resonance (NMR)
spectra were recorded in CDCl3 with tetra methyl silane (TMS) as ref-
erence on Bruker Avance 500 MHz spectrometer operating at 500 MHz
for 1H NMR and 125 MHz for 13C NMR. Mass spectra were recorded
on a JEOL GCMATE II GC-MS spectrometer. Elemental analyses were
performed on Perkin-Elmer 2400 instrument. All chemicals were pur-
chased from Sigma Aldrich and were used without further purification.
9,9-Dimethyl-12-p-tolyl-9,10-dihydro-8H-benzo[a]xanthen-11-
(12H)-one (4e) mp 174–176°C, lit. mp 175–176°C.
12-(4-Methoxyphenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4f) mp 205–207°C, lit. mp 207–208°C.
12-(4-Hydroxyphenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4g) mp 151–153°C, lit. mp 151–152°C.
Typical experimental procedure
12-(4-Nitrophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4h) mp 174–176°C, lit. mp 175–176°C.
KHSO4 (10 mol%) was added to a mixture of β-naphthol
1 (1 mmol), aldehyde 2 (1 mmol), and 5,5-dimethyl-1,3-
12-(3-Nitrophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4i) mp 167–169°C, lit. mp 169–170°C.
Table 1 Synthesis of 4b using various amounts of KHSO4.
Entry
KHSO4 (mol%)
Time (min)
Yield (%)
12-(2-Nitrophenyl)-9,9-dimethyl-9,10-dihydro-8H-benzo[a]
xanthen-11(12H)-one (4j) mp 221–223°C, lit. mp 222–224°C.
1
2
3
4
No catalyst
60
30
15
15
45
65
95
95
5
10
15
12-(5-Chloro-2-hydroxyphenyl)-9,9-dimethyl-9,10-dihydro-8H-
benzo[a]xanthen-11(12H)-one (4k) Yield 86%; mp 263–265°C;

Synthesis of xanthenes 55
1H NMR: δ 1.00 (s, 3H), 1.13 (s, 3H), 2.39 (s, 2H), 2.62 (s, 2H), 5.71
(s, 1H), 6.94–9.34 (m, 10H); 13C NMR: δ 200.8, 167.4, 151.8, 147.9,
134.5, 131.7, 129.6, 128.5, 128.2, 127.7, 126.3, 125.5, 123.3, 120.5,
118.2, 116.8, 116.7, 113.5, 50.3, 41.6, 32.5 29.1, 28.9, 28.2, 27.4; IR:
ν 3300, 2950, 1630, 1575, 1370, 1210, 1175, 1030 cm-1; GC-MS:
m/z (%) 404 (M+, 100). Anal. Calcd for C25H21ClO3: C, 74.16; H,
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then-11(12H)-one (4l) Yield 84%, mp 203–205°C; H NMR: δ
0.99 (s, 3H), 1.10 (s, 3H), 2.26 (s, 2H), 2.55 (s, 2H), 5.62 (s, 1H),
6.55–8.05 (m, 10H); 13C NMR: δ 197.6, 164.1, 149.4, 148.2, 133.8,
132.1, 132.0, 129.5, 128.9, 128.8, 127.4, 125.2, 124.3, 118.8, 117.5,
115.2, 112.9, 51.5, 41.9, 41.1, 34.1, 32.8, 29.7, 27.9; IR: ν 2950,
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Received September 15, 2011; accepted December 22, 2011

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