Cu/SiO2-catalyzed one-pot synthesis of 12-aryl-8,9,10,12- tetrahydrobenzo[α]xanthen-11-ones under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2010.515353

An efficient and straightforward procedure for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthen-11-ones has been achieved by three-component cyclocondensation of aldehyde, β-naphthol, and dimedone under solvent-free conditions. Taylor & Franci

Full text of DOI:10.1080/00397911.2010.515353

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Cu/SiO2-Catalyzed One-Pot
Synthesis of 12-Aryl-8,9,10,12-
tetrahydrobenzo[α]xanthen-11-ones
Under Solvent-Free Conditions
Hossein A. Oskooie a , Majid M. Heravi a , Narges Karimi a & Golnaz
Kohansal a
a Department of Chemistry, School of Sciences, Alzahra University,
Vanak, Tehran, Iran
Published online: 29 Jun 2011.
To cite this article: Hossein A. Oskooie , Majid M. Heravi , Narges Karimi & Golnaz Kohansal (2011):
Cu/SiO2-Catalyzed One-Pot Synthesis of 12-Aryl-8,9,10,12-tetrahydrobenzo[α]xanthen-11-ones
Under Solvent-Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 41:18, 2763-2768
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Synthetic Communications1, 41: 2763–2768, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515353
Cu/SiO2-CATALYZED ONE-POT SYNTHESIS OF
12-ARYL-8,9,10,12-TETRAHYDROBENZO[a]XANTHEN-
11-ONES UNDER SOLVENT-FREE CONDITIONS
Hossein A. Oskooie, Majid M. Heravi, Narges Karimi, and
Golnaz Kohansal
Department of Chemistry, School of Sciences, Alzahra University,
Vanak, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract An efficient and straightforward procedure for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-ones has been achieved by three-component cyclocondensa-
tion of aldehyde, b-naphthol, and dimedone under solvent-free conditions.
Keywords Aldehyde; dimedone; b-naphthol; one-pot reaction; solvent-free
INTRODUCTION
The development of multicomponent reactions (MCRs) designed to produce
elaborate biologically active compounds has become an important area of research
in organic, combinatorial, and medicinal chemistry.[1] The MCR strategy offers a
significant advantage over conventional linear synthesis because of its flexible, con-
vergent, and atom-efficient nature. In recent years, the synthesis of combinatorial
small-molecule heterocyclic libraries has emerged as a valuable tool in the search
for novel lead structures.[2] Thus, the success of combinatorial chemistry in the drug
discovery process is considerably dependent on further advances in heterocyclic
MCR methodology and, according to current synthetic requirements, environmen-
tally benign multicomponent procedures are particularly welcome.[3] Furthermore,
the MCRs, by virtue of their convergence, productivity, facile execution, and gener-
ally good yields of products, have attracted much attention from the vantage point
of combinatorial chemistry.[4]
Received April 22, 2010.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Science,
Alzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
2763

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H. A. OSKOOIE ET AL.
Xanthenes and their derivatives have been received special attention because of
their diverse array of biological activities such as anti-inflammatory, antibacterial,
and antiviral activities.[5–7]
In addition to this, they can be employed as dyes, intracellular pH indicators,[8]
molecular probes in chemical biology, and fluorescent materials for visualization of
biomolecules.[9] In particular, the xanthone moiety is a core structure of series of
natural products with interesting biological and pharmacological activities.[10–14]
The synthesis of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones has been reported in
the presence of strontium triflate,[15] NaH-SO2 ꢀ SiO2,[16] InCl3,[17] and heteropoly
acid.[18]
Transition metals that have a catalytically active site can be anchored to a che-
mically stable framework to secure recovery without loss of catalytic properties. In
recent years, Cu=SiO2 has emerged as a powerful Lewis acid catalyst.[19]
Here, we report our results obtained with Cu=SiO2 composites as catalyst in
the synthesis of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones.
RESULTS AND DISCUSSION
The catalyst plays an important role in the formation of 8,9,10,12-
tetrahydrobenzo[a]xanthen-11-ones. Benzaldehyde, b-naphthol, and dimedone were
selected as representative substrates to investigate the reaction conditions (Scheme 1).
In the absence of the catalyst, the reaction of benzaldehyde and b-naphthol
with dimedone could be carried out but the product was obtained in very poor yield
after a prolonged time. Therefore, our efforts focused on the search for a suitable
catalyst. Initially glycin was chosen as the catalyst to carry out this reaction. As a
result, long reaction times were needed, and low transformation rate were observed.
Attempts with Lewis acid KAl(SO4)2 ꢀ 12H2O as a catalyst were successful. The reac-
tion furnished 70% yield within 2 h. Encouraged by this result, we turned our atten-
tion to various Lewis acids. They were screened in our model reaction (Table 1).
Finally, we found that Cu=SiO2 showed high catalytic activity in terms of reaction
time as well as yields of the products.
The effects of amount of catalyst on the conversion and rate of the reaction
were studied by varying the amount of Cu=SiO2 under solvent-free conditions
(Table 2).
It was found that 0.05 g Cu=SiO2 was sufficient to carry out this reaction
smoothly. An increase in the amount of Cu=SiO2 to more than 0.05 g showed no sub-
stantial improvement in the yield, whereas the yield was reduced by decreasing the
amount of Cu=SiO2 to 0.02 g.
Scheme 1. Synthesis of tetrahydrobenzo[a]xanthen-11-one.

12-ARYL-8,9,10,12-TETRAHYDROBENZO[a]XANTHEN-11-ONES
2765
Table 1. One-pot reaction of benzaldehyde, b-naphthol, and dime-
done using different catalysts
Catalysta
Time (min)
Yield (%)b
H2NCH2COOH
KAl(SO4)2 ꢀ 12H2O
Fe=SiO2
180
120
30
50
70
87
90
Cu=SiO2
20
aThe amount of 0.05 g of catalyst was used.
bYields were based on GC analysis.
Table 2. Optimization of amount of catalyst
Catalyst amount (g)
Time (min)
Yield (%)
0.02
0.04
0.05
0.07
50
35
20
20
81
85
90
91
Recently, organic synthesis involving MCRs under solvent-free conditions has
attracted much attention. Therefore, we explored the possibility of obtaining the
target compounds under solvent-free conditions.
We found that the reaction proceeded smoothly in much shorter time at
elevated temperature and resulted in the formation of products in greater yields.
We extended our study using Cu=SiO2 (0.05 g) as catalyst under solvent-
free conditions with different aromatic aldehydes to prepare a series of
benzo[a]xanthene-11-one derivatives (Table 3).
We suggest that the reaction may proceed via the ortho-quinone methide inter-
mediate, which was formed by the nucleophilic addition of 2-naphthol to aldehyde
catalyzed by Cu=SiO2, subsequent Michael addition of O-QM with dimedone, and
addition of the phenolic hydroxyl moiety to the carbonyl of ketone to provide cyclic
hemiketal, which on dehydration afforded the product (Scheme 2).
Table 3. Synthesis of various tetrahydrobenzo[a]xanthen-11-one derivatives catalyzed by Cu=SiO2
Entry
R
Producta
Time (min)
Mp (ꢁC)
Yield (%)b
1
2
3
4
5
6
7
8
C6H5
4OH-C6H5
2Cl-C6H5
3a
3b
3c
3d
3e
3f
20
30
35
35
30
23
30
25
148–150[18]
223–226[18]
180–183[18]
175–177[18]
170–172[18]
178–179[18]
170–174[18]
203–205[18]
90
80
87
88
85
89
92
87
4NO2-C6H5
3NO2-C6H5
4Cl-C6H5
4Me-C6H5
4OMe-C6H5
3g
3h
aAll the products were characterized by GC, mass, IR, and melting points with those reported in the
literature.
bYield refers to the pure isolated products.

2766
H. A. OSKOOIE ET AL.
Scheme 2. Proposed mechanism for synthesis of tetrahydrobenzo[a]xanthen-11-one derivatives.
All reaction products were known and characterized by infrared (IR), gas
chromatography (GC), mass, and melting point in comparison with those obtained
from authentic samples.
The isolated Cu=SiO2 composite catalyst from the crude mixture was reutilized
two times, and yields were comparable with the first run (with the yields of the
product 3a being 90%, 88%, and 87%, respectively).
CONCLUSION
In summary, we have demonstrated the efficiency of Cu=SiO2 composite as a
new catalyst for the synthesis of tetrahydrobenzo[a]xanthen-11-ones. The recovered
solid catalyst can be reused at least two times without a significant loss of activity.
EXPERIMENTAL
Chemicals and Apparatus
All the chemicals were purchased from Merck Company. Melting points were
measured using a Barnstead Electrothermal instrument. GC mass analysis was per-
formed using an Agilent 6890 GC system Hp-5 capillary (30 m ꢂ 530 mm ꢂ 1.5 mm
nominal). IR spectra were recorded as KBr discs on a Brucker Tensor 27 FT-IR
spectrometer.
General Procedure for the Synthesis of
12-Aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones
A mixture of aldehyde (1 mmol), dimedone (1.2 mmol), b-naphthol (1 mmol),
and Cu=SiO2 (0.05 g) were mixed in an oil bath at 60 ꢁC for the appropriate time

12-ARYL-8,9,10,12-TETRAHYDROBENZO[a]XANTHEN-11-ONES
2767
(Table 3). After completion of the reaction, the mixture was washed and filtered
under vacuum with hot EtOH (2 ꢂ 5 mL). The recovered catalyst was first dried in
a vacuum at room temperature and dried then for 3 h in an oven at 100 ꢁC, after
which it was reutilized in a subsequent reaction. The organic layers were combined,
and the solvent was removed in vacuum. The crude product was recrystallized from
EtOH.
ACKNOWLEDGMENT
We are grateful to Alzahra University Research Council for partial support of
this work.
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