Microwave-assisted and scandium triflate catalyzed synthesis of tetrahydrobenzo[a]xanthen-11-ones

Article abstract of DOI:10.1007/s00706-011-0577-4

Synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[fl]xanthen-11-ones was achieved by one-pot condensation of β-naphthol, substituted benzaldehydes, and 1,3-dicarbonyl compounds catalyzed by Sc(OTf)₃ under microwave irradiation in excellent isolat

Full text of DOI:10.1007/s00706-011-0577-4

Monatsh Chem (2012) 143:263–268
DOI 10.1007/s00706-011-0577-4
ORIGINAL PAPER
Microwave-assisted and scandium triflate catalyzed synthesis
of tetrahydrobenzo[a]xanthen-11-ones
•
Madharam Sudershan Rao Bhupender S. Chhikara
•
•
•
•
Rakesh Tiwari Amir N. Shirazi Keykavous Parang
Anil Kumar
Received: 16 February 2011 / Accepted: 12 July 2011 / Published online: 12 August 2011
Ó Springer-Verlag 2011
Abstract Synthesis of 12-aryl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-ones was achieved by one-pot con-
densation of b-naphthol, substituted benzaldehydes, and
1,3-dicarbonyl compounds catalyzed by Sc(OTf)3 under
microwave irradiation in excellent isolated yields. The
catalyst was recycled up to four cycles with no appreciable
loss in catalytic activity. The compounds were evaluated
for Src kinase activity and anticancer activity.
spectrum of applications, development of novel synthetic
methods for these heterocyclic compounds has received
considerable interest in organic chemistry. Several methods
have been reported for the synthesis of xanthenes [7–9];
however, there are only few methods available for the
synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-
11-ones using tetrabutylammonium fluoride (TBAF) and
tetradecyltrimethylammonium bromide (TTAB) [10, 11],
NaHSO4ꢀSiO2 [12], strontium triflate [13], H3PW12O40
[14], p-toluenesulfonic acid (p-TSA) under solvent-free
conditions and in [bmim][BF4] [15, 16], I2 [17], NH2SO3H
[18], cyanuric chloride [19], HBF4/SiO2 [20], and proline
triflate [21] as catalysts. Many of the reported methods for
the synthesis of these heterocyclic compounds involve the
use of toxic chemicals, require stoichiometric amounts of
catalysts or longer reaction times, and afford products in
low yields. Thus, it is still desirable to develop an efficient
and convenient method in terms of operational simplicity
and economical viability for the synthesis of tetra-
hydrobenzo[a]xanthen-11-one derivatives.
Keywords Lewis acids ꢀ Multi-component reaction ꢀ
Microwave-assisted synthesis ꢀ Solvent-free ꢀ Anticancer ꢀ
Src kinase activity
Introduction
Xanthenes are important oxygen-containing heterocyclic
molecules. Xanthenes and their derivatives exhibit a
diverse array of biological and pharmacological properties,
such as antiviral, antifungal, antibacterial, anti-inflamma-
tory, and anticancer activities [1–3]. They have also been
used as dyes, fluorescent materials to monitor changes in
intracellular pH and visibility of bimolecular assemblies
[4, 5], and in laser technology [6]. As a result of their wide
Microwave-assisted organic synthesis offers many
advantages including faster and cleaner reactions, high
product yields, and operational simplicity [22–29]. Several
methods have been developed for performing reactions
with microwave irradiation in solution and under solvent-
free conditions [30–33]. The use of multi-component
reactions (MCRs) has been shown to be remarkably suc-
cessful in generating molecular complexity in a single pot
with high selectivity and atom economy. Recently rare
earth metal triflates have emerged as Lewis acid catalysts,
and have been used in various organic transformations
because of their low toxicity, high stability, and resistance
to water [34–36].
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-011-0577-4) contains supplementary
material, which is available to authorized users.
M. S. Rao ꢀ A. Kumar (&)
Department of Chemistry, Birla Institute of Technology and
Science, Pilani 333031, India
e-mail: anilkumar@bits-pilani.ac.in
B. S. Chhikara ꢀ R. Tiwari ꢀ A. N. Shirazi ꢀ K. Parang
Department of Biomedical and Pharmaceutical Sciences,
University of Rhode Island, Kingston, RI 02881, USA
MCRs consist of two or more synthetic steps, which
are performed without isolation of intermediates. MCR
123

264
M. S. Rao et al.
Scheme 1
R'
O
CHO
R
O
R'
OH
Sc(OTf)3
R''
R''
MW, 300 W
O
R''
R
O
2
1
3
R''
4
Table 1 Synthesis of 12-(4-chlorophenyl)-8,9,10,12-tetrahydro-9,9-
dimethyl-11H-benzo[a]xanthen-11-one (4a) under different conditions
strategies offer significant advantages over conventional
linear-type syntheses such as reduction in overall reaction
time and cost by saving energy and raw materials [37–41].
Thus, the development of new MCRs is very important in
organic synthesis. In this regard the ortho-quinone meth-
ides (o-QMs) are useful intermediates in many tandem
processes [42]; o-QMs can be generated by reaction of
naphthols or phenols with different aldehydes under basic
or acidic conditions [43, 44].
Entry
Catalyst
Catalyst/
mol%
Solvent/
method
Time/
min
Yield/
a
%
1
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Zn(OTf)3
Yb(OTf)3
Y(OTf)3
Ce(OTf)3
La(OTf)3
Nd(OTf)3
Eu(OTf)3
20
20
20
20
20
20
20
30
10
20
20
20
20
20
20
20
CH3CN
600
600
600
600
600
600
5
43b
35b
30b
55b
60b
2
Toluene
DMF
3
4
CHCl3
5
PEG-400
H2O
In continuation of our work on metal triflate catalyzed
generation of o-QMs and their application in organic
transformations [45] and our interest in the MCR synthesis
of xanthenes, we herein report the synthesis of 12-aryl-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives
by condensation of 2-naphthol, aldehydes, and 1,3-dicar-
bonyl compounds catalyzed by Sc(OTf)3 under microwave
irradiation (Scheme 1).
b,c
6
–
7
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
Neat/MW
83
85
60
56
50
40
60
10
10
8
5
9
5
10
11
12
13
14
15
16
5
5
10
8
10
12
12
Results and discussion
c
–
Initially we examined the model reaction of 4-chloro-
benzaldehyde (1a), 2-naphthol (2), and dimedone (3) using
Sc(OTf)3 as catalyst under different reaction conditions
(Table 1). The reaction was very slow and gave only
30–60% yield of the desired 12-(4-chlorophenyl)-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-one (4a) in dif-
ferent solvents such as acetonitrile, toluene, chloroform,
dimethylformamide (DMF), or polyethylene glycol (PEG)
under reflux conditions, whereas in water the formation of
product was not observed. Encouraged by reported efficient
rate enhancements by microwave irradiation [27–29], we
next investigated this reaction under microwave irradiation
(MW). After several attempts, it was observed that
microwave irradiation for 5 min at 300 W with internal
temperature of 120 °C is optimal in terms of efficient
condensation to afford the desired product 4a in a higher
yield. Subsequently, the condensation was attempted with
different metal triflate catalysts but Sc(OTf)3 (20 mol%)
was found to give the highest yield of the product thereby
making it the most suitable catalyst for the reaction. After
establishing Sc(OTf)3 as an optimal catalyst in the one-pot
reaction, we next studied the effect of catalyst loading.
Thus the model reaction was carried out with varying
amounts of catalysts. As shown in Table 1, decreasing the
Conditions: 1, 2, 3 (1 mmol each)
a
Isolated yield
b
Reaction carried out under reflux
c
No reaction
amount of Sc(OTf)3 from 20 to 10 mol% decreased the
yield of 4a to 60%, whereas increasing the catalyst to
30 mol% did not significantly increase yield of 4a. Thus,
20 mol% of Sc(OTf)3 was selected as the optimum amount
for further studies.
To generalize the suitability of this protocol, the reaction
was extended to different substituted naphthols, aromatic
aldehydes, and 1,3-diones (Table 2). Three substrates (1–3)
as solids were first dissolved in 1 cm3 ethyl acetate and
mixed well before microwave irradiation. The reactions
proceeded smoothly with excellent yields (65–97%) for
substituted aldehydes with both electron-withdrawing and
electron-donating groups. All products were characterized
1
by H, 13C NMR, and high-resolution time-of-flight elec-
trospray mass spectrometry (ESI-TOF) (see Electronic
supplementary information). In the case of aldehydes with
electron-donating groups a minor amount (5–15%) of
123

Microwave-assisted and scandium triflate catalyzed synthesis
265
Table 2 Synthesis of 12-aryl-8,9,10,12-tetrahydro-11H-benzo[a]-
xanthen-11-ones catalyzed by Sc(OTf)3 under microwave irradiation
Table 3 Recycling and reuse of Sc(OTf)3for synthesis of 4a
Run
1
2
3
4
Comp.
R
R0
R00 Yield/%a M.p. (Lit. m.p.)/°C
Yield/%a
83
82
80
81
4a
4b
4c
4d
4e
4f
4-Cl
H
H
H
H
H
H
H
H
CH3 83
CH3 76
CH3 79
CH3 71
CH3 90
CH3 65
CH3 96
CH3 97
180–182 (182–183 [6])
154–155 (152–153 [6])
177–179 (175–176 [9])
207–209 (211–212 [6])
181–182 (180–181 [15])
199–201 (177–178 [21])
179–180 (183–185 [6])
170–171 (169–170 [14])
218–220
a
Isolated yield
H
4-CH3
4-OCH3
3-Cl
tetrahydrobenzo[a]xanthen-11-one by elimination of a
water molecule. Formation of dihydroxy compounds as a
minor product in the case of 4-methoxybenzaldehyde fur-
ther supports the mechanism.
3-OCH3
4-NO2
3-NO2
4-Cl
4g
4h
4i
We studied the recyclability of catalysts for the syn-
thesis of 4a. After completion of the reaction and
extraction of product with ethyl acetate; the aqueous layer
was concentrated and the recovered catalyst was directly
used for the next cycle. It is noteworthy that Sc(OTf)3 was
recovered and recycled conveniently up to four times
without much loss in its catalytic activity (Table 3).
Although the main objective was to synthesize novel
xanthene derivatives using one-pot microwave-assisted
synthesis, we investigated the biological activities of the
compounds. Xanthenes have been reported to demonstrate
anticancer activity. The effect of compounds 4a–4s (at a
concentration of 50 lM) on the cell proliferation of cancer
cells was evaluated against the colon adenocarcinoma
(HT-29) cell line. Compounds 4c, 4h, 4j, and 4s inhibited
the proliferation HT-29 cells only by 23–26%. Other
compounds showed minimal inhibitory activities. Further-
more, among all the compounds 4s minimally inhibited the
Src kinase activity by 11%. It is postulated that these
compounds could not fit into ATP binding site of Src
kinase appropriately, because of their bulky nature and/or
suboptimal bonding interactions. The data suggest that
further optimization of these compounds is required to
generate compounds with higher anticancer and Src kinase
inhibitory activities, and/or these compounds should be
screened for other previously reported biological activities
for xanthenes [2, 3].
OCH3 CH3 95
OCH3 CH3 90
4j
H
152–153
4k
4l
4–CH3 OCH3 CH3 87
4-OCH3 OCH3 CH3 72
181–182
166–167
4m
4n
4o
4p
4q
4r
4s
3-Cl
OCH3 CH3 73
137–139
3-OCH3 OCH3 CH3 88
213–214
4-Cl
H
H
93
207–209 (205–206 [9])
229–231
4-NO2
3-NO2
4-NO2
3-OCH3
OCH3 CH3 83
OCH3 CH3 85
195–196
H
H
H
H
88
78
241–243 (246–247 [6])
221–223 (205–206 [21])
Conditions: 1, 2, 3 (1 mmol each), Sc(OTf)3 (10 mol%), MW irra-
diation at 300 W
a
Isolated yield
uncyclized dihydroxy compound was obtained. The yields
of tetrahydrobenzo[a]xanthen-11-ones 4 were higher from
aldehydes with electron-withdrawing groups as compared
to the corresponding aldehydes with electron-donating
groups.
A probable mechanistic rationalization of the Sc(OTf)3
catalyzed reaction is shown in Scheme 2. It is expected that
the reaction proceeds via an o-QM intermediate which is
generated by the nucleophilic attack of 2-naphthol on the
aldehyde followed by dehydration. In the next step,
the enolic form of dimedone attacks undergoes conju-
gate addition to the o-QM to generate a dihydroxy
intermediate. Finally, the dihydroxy compound gives the
In conclusion, we have developed an efficient and
greener method for the synthesis of 12-aryl-8,9,10,12-tet-
rahydrobenzo[a]xanthen-11-ones catalyzed by Sc(OTf)3
under microwave irradiation and evaluated their Src kinase
Sc(OTf)3
Scheme 2
O
H
O
Ph
Sc(OTf)3
O
Ph
H
H
Ph
R''
O
-H2O
H
O
O
H
O
R''
-Sc(OTf)3
Sc(OTf)3
O
Ph
O
Ph
O
O
Ph
O
Ph
H
H
R''
R''
-H2O
R''
R''
R''
R''
R''
R''
OH
HO
O
O
H
O
O
Sc(OTf)3
Sc(OTf)3
H
123

266
M. S. Rao et al.
26.65 ppm; MS (ESI): calcd for C26H23ClO3 418.1336,
found m/z = 419.0346 [M ? H]?.
inhibition and anticancer activities. A simple reaction
procedure, shorter reaction time, high isolated yields of the
pure products, tolerance of a wide range of functional
groups, use of an environmentally safer catalyst, and
recycling of the catalyst are the advantages of this protocol.
8,9,10,12-Tetrahydro-2-methoxy-9,9-dimethyl-12-phenyl-
11H-benzo[a]xanthen-11-one (4j, C26H24O3)
Rf = 0.51 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 7.69–7.61 (m, 2H), 7.36 (d,
J = 7.5 Hz, 2H), 7.26–7.21 (m, 1H), 7.17 (t, J = 8.2 Hz,
3H), 7.05 (t, J = 7.3 Hz, 1H), 7.00 (dd, J = 8.9, 2.2 Hz,
1H), 5.57 (s, 1H), 3.80 (s, 3H), 2.56 (s, 2H), 2.28 (d,
J = 16.3 Hz, 1H), 2.24 (d, J = 16.3 Hz, 1H), 1.11 (s, 3H),
0.96 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 196.55, 163.37, 157.93, 147.67, 144.23, 129.33,
128.09, 127.99, 127.72, 125.78, 116.91, 116.26, 113.94,
113.65, 102.11, 54.73, 50.40, 40.92, 34.73, 31.78, 28.81,
26.70 ppm; MS (ESI): calcd for C26H24O3 384.1725, found
m/z = 385.1720 [M ? H]?.
Experimental
Melting points were determined in open capillary tubes on
an MPA120 automated melting point apparatus. IR spectra
1
were recorded with a JASCO IR-Report-100. The H and
13C NMR spectra were recorded on a Bruker Heaven
11400 (400 MHz) spectrometer using TMS as internal
standard and CDCl3 as solvent and the chemical shifts are
expressed in ppm. All reactions were carried out in a CEM
microwave digester MARS 5TM as a multi-mode micro-
wave oven at 120 °C and 300 W using microwave reaction
vessel HP 500. All metal triflates, aldehydes, and 1,3-
dicarbonyl compounds were purchased from Sigma–
Aldrich. The products were purified by column chroma-
tography using silica gel (60–120 mesh, S.D. Fine, India).
8,9,10,12-Tetrahydro-2-methoxy-12-(4-methylphenyl)-9,9-
dimethyl-11H-benzo[a]xanthen-11-one (4k, C27H26O3)
Rf = 0.52 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(500 MHz, CDCl3): d 7.57–7.54 (m, 2H), 7.17–7.10 (m,
3H), 7.08–7.06 (m, 1H), 6.91–6.81 (m, 3H), 5.45 (s, 1H),
3.74 (s, 3H), 2.47 (s, 2H), 2.21 (d, J = 16.3 Hz, 1H), 2.14
(d, J = 16.3 Hz, 1H), 2.11 (s, 3H), 1.03 (s, 3H), 0.89 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3): d = 196.98,
163.70, 158.38, 148.08, 141.79, 135.67, 132.83, 128.88,
128.32, 126.69, 117.33, 116.92, 114.40, 114.25, 102.62,
55.20, 50.91, 41.41, 34.80, 32.26, 29.26, 27.27, 20.97 ppm;
MS (ESI): calcd for C26H24O3 398.1882, found
m/z = 399.0477 [M ? H]?, 797.0876 [2M ? H]?.
General procedure for the synthesis of 12-aryl-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones 4a–4s
2-Naphthol (144 mg, 1.0 mmol), aldehyde (1.0 mmol),
140 mg dimedone (1.0 mmol), and Sc(OTf)3 (10 mol%)
were taken in a Teflon reaction vessel, mixed well, and
irradiated in the microwave at 300-W power, programmed
at 120 °C for 5 min; the irradiation continued at this tem-
perature for 5–10 min and the mixture cooled for 20 min.
Afterwards the reaction mixture was cooled to room tem-
perature, 5 cm3 of water was added, and extracted with
ethyl acetate (2 9 20 cm3). The organic layer was washed
with brine, dried over anhydrous sodium sulfate, and
concentrated under reduced pressure. The crude product
was recrystallized with hot ethanol or purified by column
chromatography on silica gel (100–200 mesh) using ethyl
acetate and hexane as eluent. All compounds were char-
8,9,10,12-Tetrahydro-2-methoxy-12-(4-methoxyphenyl)-
9,9-dimethyl-11H-benzo[a]xanthen-11-one
(4l, C27H26O4)
Rf = 0.52 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 7.66 (d, J = 3.2 Hz, 1H), 7.64 (d,
J = 3.3 Hz, 1H), 7.30–7.24 (m, 2H), 7.23 (d, J = 2.0 Hz,
1H), 7.15 (d, J = 8.8 Hz, 1H), 7.00 (dd, J = 8.9, 2.3 Hz,
1H), 6.71 (d, J = 8.6 Hz, 2H), 5.52 (s, 1H), 3.82 (s, 3H),
3.69 (s, 3H), 2.56 (s, 2H), 2.29 (d, J = 16.3 Hz, 1H), 2.25
(d, J = 16.3 Hz, 1H), 1.12 (s, 3H), 0.98 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): d = 196.67, 163.18, 157.89,
147.62, 136.62, 129.32, 128.99, 127.87, 126.21, 116.84,
113.94, 113.06, 102.15, 54.73, 54.60, 50.43, 40.91, 33.81,
31.79, 28.80, 26.74 ppm; MS (ESI): calcd for C27H26O4
414.1831, found m/z = 415.1843 [M ? H]?.
1
acterized by H NMR, 13C NMR, and ESI-TOF.
12-(4-Chlorophenyl)-8,9,10,12-tetrahydro-2-methoxy-9,9-
dimethyl-11H-benzo[a]xanthen-11-one (4i, C26H23ClO3)
Rf = 0.52 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 7.70 (d, J = 6.3 Hz, 2H), 7.31 (d,
J = 6.8 Hz, 2H), 7.16 (d, J = 5.6 Hz, 3H), 7.04 (d,
J = 6.4 Hz, 1H), 5.57 (s, 1H), 3.83 (s, 3H), 2.59 (s, 2H),
2.42–2.18 (m, 2H), 1.14 (s, 3H), 0.99 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): d = 196.15, 163.58, 142.76,
131.02, 129.31, 128.61, 128.00, 127.91, 126.64, 124.54,
122.97, 116.56, 50.37, 40.90, 33.69, 31.78, 28.82,
12-(3-Chlorophenyl)-8,9,10,12-tetrahydro-2-methoxy-9,9-
dimethyl-11H-benzo[a]xanthen-11-one
(4m, C26H23ClO3)
Rf = 0.53 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 7.67 (t, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.2 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.11 (t,
123

Microwave-assisted and scandium triflate catalyzed synthesis
267
J = 7.7 Hz, 1H), 7.07–6.95 (m, 2H), 5.55 (s, 1H), 3.82 (s,
3H), 2.57 (s, 2H), 2.30 (d, J = 16.3 Hz, 1H), 2.26 (d,
J = 16.3 Hz, 1H), 1.12 (s, 3H), 0.98 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): d = 196.70, 163.95, 158.33,
147.95, 146.47, 129.73, 129.19, 128.47, 126.67, 126.39,
117.30, 115.67, 114.26, 113.31, 102.17, 55.01, 50.62,
41.17, 34.83, 32.08, 29.03, 27.03 ppm; MS (ESI): calcd for
C26H23ClO3 418.1336, found m/z = 419.0320 [M ? H]?.
MS (ESI): calcd for C26H23NO5 429.1576, found
m/z = 430.1542 [M ? H]?.
Acknowledgements We thank UGC New Delhi for financial sup-
port. MSR thanks BITS, Pilani for the institutional fellowships and
US National Science Foundation, Grant Number CHE 0748555 and
the American Cancer Society Grant # RSG-07-290-01-CDD for the
financial support.
8,9,10,12-Tetrahydro-2-methoxy-12-(3-methoxyphenyl)-
9,9-dimethyl-11H-benzo[a]xanthen-11-one
References
(4n, C27H26O4)
1. Giri R, Goodell JR, Xing C, Benoit A, Kaur H, Hiasa H, Ferguson
DM (2010) Bioorg Med Chem 18:1456
2. Poupelin JP, Saint-Ruf G, Lacroix R (1978) Eur J Med Chem
13:381
3. El-Brashy AM, El-Sayed Metwally M, El-Sepai FA (2004)
Farmaco 59:809
4. Knight CG, Stephens T (1989) Biochem J 258:683
5. Gonc¸alves MST (2008) Chem Rev 109:190
6. Ahmad M, King TA, Ko DK, Cha BH, Lee J (2002) J Phys D
Appl Phys 35:1473
7. Wawzonek S (1951) Xanthenes, xanthydrols and xanthylium
salts. In: Elderfield RC (ed) Heterocyclic compounds, vol 2.
Wiley, New York, p 419
8. Brimble MA, Gibson JS, Sperry J (2008) In: Katritzky AR,
Ramsden CA, Scriven EFV, Taylor RJK (eds) Comprehensive
heterocyclic chemistry III. Elsevier, Oxford, p 419
9. Bo E, Hillringhaus T, Nitsch J, Klussmann M (2011) Org Biomol
Chem 9:1744
Rf = 0.51 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 7.67 (d, J = 4.3 Hz, 1H), 7.64 (d,
J = 4.4 Hz, 1H), 7.26 (s, 1H), 7.16 (d, J = 8.8 Hz, 1H),
7.10 (t, J = 7.9 Hz, 1H), 7.00 (dd, J = 14.0, 5.0 Hz, 2H),
6.89 (s, 1H), 5.56 (s, 1H), 3.82 (s, 3H), 3.69 (s, 3H), 2.57 (s,
2H), 2.35–2.19 (m, 2H), 1.12 (s, 3H), 0.99 (s, 3H) ppm; 13
C
NMR (100 MHz, CDCl3): d = 196.83, 163.73, 159.28,
158.20, 147.94, 146.09, 132.65, 129.59, 128.27, 126.48,
121.00, 117.17, 114.54, 114.24, 111.04, 102.39, 55.02, 54.85,
50.69,41.21,34.93,32.06,29.04,27.07 ppm;MS(ESI):calcd
for C27H26O4 414.1831, found m/z = 415.1843 [M ? H]?.
8,9,10,12-Tetrahydro-2-methoxy-9,9-dimethyl-12-(4-nitro-
phenyl)-11H-benzo[a]xanthen-11-one
(4p, C26H23NO5)
10. Shinde PV, Kategaonkar AH, Shingate BB, Shingare MS (2011)
Beilstein J Org Chem 7:53
11. Gao S, Tsai CH, Yao CF (2009) Synlett 949
12. Das B, Laxminarayana K, Krishnaiah M, Srinivas Y (2007)
Synlett 3107
13. Li J, Tang W, Lu L, Su W (2008) Tetrahedron Lett 49:7117
14. Wang H-J, Ren X-Q, Zhang Y-Y, Zhang Z-H (2009) J Braz
Chem Soc 20:1939
15. Li J, Li J, Fang J, Su W (2010) Synth Commun 40:1029
16. Khurana JM, Magoo D (2009) Tetrahedron Lett 50:4777
17. Wang R-Z, Zhang L-F, Cui Z-S (2009) Synth Commun 39:2101
18. Heravi M, Alinejhad H, Bakhtiari K, Oskooie H (2011) Mol
Diver 15:239
Rf = 0.52 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 8.05 (d, J = 8.7 Hz, 2H), 7.72 (d,
J = 8.9 Hz, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.53 (d,
J = 8.6 Hz, 2H), 7.20 (d, J = 8.8 Hz, 1H), 7.08–7.01
(m, 2H), 5.69 (s, 1H), 3.80 (s, 3H), 2.60 (s, 2H), 2.29 (d,
J = 16.4 Hz, 1H), 2.25 (d, J = 16.4 Hz, 1H), 1.14 (s, 3H),
0.95 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 196.39, 164.17, 158.24, 151.41, 147.78, 131.98,
129.65, 128.92, 128.78, 126.28, 123.12, 117.00, 114.56,
113.98, 112.41, 101.74, 54.74, 50.28, 40.92, 34.75, 31.79,
28.81, 26.61 ppm; MS (ESI): calcd for C26H23NO5
429.1576, found m/z = 430.1463 [M ? H]?.
19. Zhang ZH, Zhang P, Yang SH, Wang HJ, Deng J (2010) J Chem
Sci 122:427
20. Zhang ZH, Wang HJ, Ren XQ, Zhang YY (2009) Monatsh Chem
140:1481
8,9,10,12-Tetrahydro-2-methoxy-9,9-dimethyl-12-
(3-nitrophenyl)-11H-benzo[a]xanthen-11-one
21. Li J, Lu L, Su W (2010) Tetrahedron Lett 51:2434
22. Larhed M, Moberg C, Hallberg A (2002) Acc Chem Res 35:717
23. Kappe CO (2004) Angew Chem Int Ed 43:6250
24. Roberts BA, Strauss CR (2005) Acc Chem Res 38:653
25. Polshettiwar V, Varma RS (2008) Chem Soc Rev 37:1546
26. Polshettiwar V, Varma RS (2008) Acc Chem Res 41:629
27. Chauhan SMS, Sahoo BB, Srinivas KA (2001) Synth Commun
31:33
28. Strauss CR, Rooney DW (2010) Green Chem 12:1340
29. Caddick S, Fitzmaurice R (2009) Tetrahedron 65:3325
30. Ju Y, Kumar D, Varma RS (2006) J Org Chem 71:6697
31. Ju Y, Varma RS (2006) J Org Chem 71:135
32. Paolini L, Petricci E, Corelli F, Botta M (2003) Synthesis 1039
33. Sabitha G, Rao VRS, Sudhakar K, Kumar MR, Reddy EV, Yadav
JS (2008) J Mol Catal A Chem 280:16
(4q, C26H23NO5)
Rf = 0.51 (TLC, ethyl acetate/hexane 2:8); 1H NMR
(400 MHz, CDCl3): d 8.19 (s, 1H), 7.94 (d, J = 8.1 Hz,
1H), 7.77 (d, J = 7.6 Hz, 1H), 7.70 (dd, J = 13.9, 8.9 Hz,
2H), 7.36 (t, J = 7.9 Hz, 1H), 7.20 (d, J = 8.8 Hz, 1H),
7.11 (s, 1H), 7.03 (d, J = 8.8 Hz, 1H), 5.69 (s, 1H), 3.81 (s,
3H), 2.61 (s, 2H), 2.31 (d, J = 16.3 Hz, 1H), 2.27 (d,
J = 16.3 Hz, 1H), 1.14 (s, 3H), 0.97 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): d = 196.45, 164.13, 158.22,
147.84, 147.74, 146.30, 134.27, 129.68, 128.78, 128.57,
126.28, 122.86, 121.13, 117.08, 114.10, 112.55, 101.59,
54.76, 50.25, 40.88, 34.69, 31.84, 28.78, 26.69 ppm;
34. Kobayashi S (1999) Eur J Org Chem 15
35. Kobayashi S, Hachiya I (1994) J Org Chem 59:3590
123

268
M. S. Rao et al.
36. Kobayashi S, Sugiura M, Kitagawa H, Lam WWL (2002) Chem
Rev 102:2227
37. Chetia A, Saikia CJ, Lekhok KC, Boruah RC (2004) Tetrahedron
Lett 45:2649
38. Devi I, Bhuyan PJ (2004) Tetrahedron Lett 45:8625
39. Trost BM (1995) Angew Chem Int Ed 34:259
40. Wang L, Xia J, Qin F, Qian C, Sun J (2003) Synthesis 1241
41. Weber L (2002) Curr Med Chem 9:2085
42. Van de Water RW, Pettus TRR (2002) Tetrahedron 58:5367
43. Wolff A, Boehmer V, Vogt W, Ugozzoli F, Andreetti GD (1990)
J Org Chem 55:5665
44. Mashraqui SH, Paul MB, Mistry HD, Ghadigaonkar S, Meetsma
A (2004) Chem Lett 33:1058
45. Kumar A, Rao MS, Ahmad I, Khungar B (2009) Can J Chem
87:714
123