Rapid and Efficient One-Pot Green Synthesis of 12-Aryl-8,9,10,12-tetrahydrobenzo[ a ]xanthene-11-ones Using Zr-MCM-41 Catalyst

Article abstract of DOI:10.1080/00397911.2014.958784

A new green protocol has been developed for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones via a three-component, one-pot condensation reaction of dimedone, naphthols, and aromatic aldehydes using Zr-MCM-41 nanoreactors as a reusable

Full text of DOI:10.1080/00397911.2014.958784

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Rapid and Efficient One-Pot Green Synthesis of 12-
Aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones
Using Zr-MCM-41 Catalyst
Abolfazl Olyaeia & Mona Ghodrat Alidousta
a Department of Chemistry, Payame Noor University (PNU), Tehran, Iran
Accepted author version posted online: 25 Sep 2014.
To cite this article: Abolfazl Olyaei & Mona Ghodrat Alidoust (2014): Rapid and Efficient One-Pot Green Synthesis of 12-
Aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones Using Zr-MCM-41 Catalyst, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.958784
To link to this article: http://dx.doi.org/10.1080/00397911.2014.958784
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Rapid and efficient one-pot green synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-ones using Zr-MCM-41 catalyst
Abolfazl Olyaei1, Mona Ghodrat Alidoust1
1Department of Chemistry, Payame Noor University (PNU), Tehran, Iran
Corresponding Address: Department of Chemistry, Payame Noor University (PNU), PO
BOX 19395-3697, Tehran, Iran, Email: olyaei_a@pnu.ac.ir
Abstract
A new green protocol has been developed for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-ones via a three component, one-pot condensation reaction
of dimedone, naphthols and aromatic aldehydes using Zr-MCM-41 nanoreactors as a
reusable and novel catalyst at 80 oC under solvent-free conditions. Various aromatic
aldehydes containing electron-withdrawing and electron-donating substituent at ortho,
meta or para-positions show equalease towards the product formation in high to excellent
yields. Operational simplicity, mild reaction conditions, enhanced rates, environmentally
benign, high isolated yields of the pure products and purification of products by non-
chromatographic methods are significant advantages of the protocol presented here. The
catalyst could be recycled and reused without a noticeably decrease in its activity.
1

KEYWORDS: Naphthol, xanthene, aldehyde, dimedone, Zr-MCM-41.
INTRODUCTION
Xanthenes and benzoxanthenes are important heterocycles that are known to possess
multiple biological activities. Although not widely found in nature, xanthenes and
compounds based on these core templates exhibit a broad spectrum of pharmaceutical
activities such as anti-bacterial and anti-viral. These structural motifs have also found a
niche as antagonists for paralyzing the action of zoxazolamine and demonstrate efficacy
in photodynamic therapy[1]. In addition, these compounds have been employed as dyes[2],
and pH-sensitive fluorescent materials for visualization of biomolecular assemblies[3] and
utilized in laser technologies[4]. Thus a broad utility range has made xanthenes prime
synthetic candidates thereby accentuating the need to develop newer synthetic routes for
scaffold manipulation of xanthene derivatives. Previously tetrahydrobenzo[a]xanthenes
have been synthesized under reflux for long hours in dichloromethane or 1,2-
[6]
dichloroethane in the presence of acid catalysts such as Sr(OTf)2[5], InCl3 or P2O5
,
pTSA in ionic liquid[7], 2,4,6-Trichloro-1,3,5-triazine (TCT)[8], BF3·Et2O[9], TBAF[10] and
_
[11]
NaHSO4 SiO2
.
These synthetic methods afforded good yields however, have limitations of long reaction
time, harsh reaction conditions and often expensive catalysts. Consequently, the
development of new and simple synthetic methods such as further improvement towards
lower reaction time and improved yields for the preparation of heterocyclic compounds
containing xanthene fragment remains an interesting challenge.
2

Considerable attention has been given to mesoporous materials such as MCM-41 family
because of their unique properties[12-14]. They have high specific surface areas, high pore
volumes, and tunable pore sizes with a narrow distribution. However, Si-based MCM-41
exhibits only mild acidity, which is much weaker than that of the microporous zeolites.
The incorporation of zirconium into the MCM-41 framework increases both the Lewis
and Brönsted acidity[15]
.
Due to our interest in developing solvent-free multi-component reactions[16], we report
here, a simple and facile protocol for the synthesis of a series of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one derivatives from aldehydes, naphthols and dimedone
in the presence of Zr-MCM-41[17] as an efficient and reusable catalyst under solvent-free
conditions. To the best of our knowledge in the open literature, one-pot synthesis of
xanthenone derivatives catalyzed by Zr-MCM-41 has not previously been reported.
RESULTS AND DISCUSSION
Based on the green chemistry approach, we report an efficient and environmentally
benign protocol for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
derivatives by multi-component condensation of naphthols, aromatic aldehydes, and
dimedone catalyzed by Zr-MCM-41 under solvent-free conditions. The products were
obtained in high to excellent yields by a simple work-up. Moreover, to optimize the
temperature in the mentioned reaction, we have carried out a model study with
salicylaldehyde (1.0 mmol), 2-naphthol (1.0 mmol) and dimedone (1.0 mmol) using 10
3

mol% of catalyst at various temperatures under solvent-free conditions. Our investigation
demonstrated that 80 °C is an effective temperature in terms of reaction time and
obtained yield. Then, we screened the catalyst concentration on model reaction at this
temperature. We have varied the concentration of catalyst to 2, 5, 7, 10 and 15 mol %.
The results indicated that when the reaction was carried out in the presence of 10 mol %
of catalyst it gave excellent yield of product. Even after increasing the catalyst
concentration at 15 mol % the yield of the product was found to be constant. So, the use
of 10 mol % of catalyst appears to be optimal (Table 1).
After optimising the conditions, several syntheses of 12-aryl-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives from the condensation of 2-
naphthol (2) and 2,7-dihydroxynaphthalene (3) with a wide range of aromatic aldehydes
o
(1) and dimedone utilizing Zr-MCM-41 under solvent-free conditions at 80 C were
examined (Scheme 1). All reactions were complete with in 10-20 minutes, as indicated in
Table 2; in all cases the reactions afforded the desired products in high to excellent
yields.
The surface acidity of the mesoporous solids is significantly influenced by the
incorporation of zirconium ions into the framework. The addition of zirconium creates
Brönsted acid sites and also enhances the acid strength of both the Lewis and Brönsted
acid sites. The diameter of Zr4+ is much larger than that of Si4+ and when smaller Si4+
ions are replaced by larger Zr4+ ions in the framework of the solid the bond length of Zr–
O–Si clearly differs from that of Si–O–Si. This must lead to the deformation of some
4

structures and the generation of microstrain in the lattice cell. This feature can be useful
for reactions that require both types of acid sites. Therefore, a plausible mechanism for
the formation of xanthenones is shown in Scheme 2.
The reaction is thought to proceed in a stepwise manner. Firstly, we assumed that the
reaction may proceed via the 2-(2-hydroxybenzylidene)-5,5-dimethylcyclohexane-1,3-
dione (7a) intermediate, which was formed by the nucleophilic addition of dimedone to
aldehyde catalyzed by Zr-MCM-41. The reaction proceeds via intermediate 8a, which is
formed by the activation of carbonyl group of 7a by Zr-MCM-41. Subsequent Michael
addition of the intermediate 8a with 2-naphthol and followed nucleophilic addition of
hydroxy of naphthol to carbonyl of dimedone and dehydration is occurred in the presence
of Zr-MCM-41 to give the final product. Various aromatic aldehydes containing electron-
withdrawing and electron-donating substituent at ortho, meta or para-positions show
equalease towards the product formation in high to excellent yields.
Finally we investigated the reusability of the catalyst. At the end of the reaction, the
catalyst was removed by centrifugation and washed with ethyl acetate and re-used in
reaction. It was found that the recycled catalyst was used for four consecutive reactions
without significant decrease of the yields (Table 3).
All products were well characterized by 1H NMR, 13C NMR, FTIR, mass spectra,
elemental analyses and melting point. For example, the 1H NMR spectrum of synthesized
compounds contained two singlet signals at about δ 0.90 and 1.06 ppm corresponding to
5

two chemically different methyl protons. Moreover, methylene protons appeared as two
AB quartet patterns at about δ 2.10 and 2.30 ppm (J = 16.0 Hz) and at δ 2.50 and 2.70
ppm (J = 17.2 Hz) corresponding to two chemically different moieties. Methine and
aromatic protons showed as a sharp singlet at about δ 5.50 and multiplet at about δ 6.50-
7.70 ppm, respectively. Hydroxy protons appeared as a sharp singlet at δ 9.90 ppm. To
the best of our knowledge, synthesis of compounds 5d-g has not previously been reported
in literature.
In summary, a novel and highly efficient method for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-ones by condensation reaction of naphthols with aromatic
aldehydes and dimedone catalyzed by Zr-MCM-41 nanoreactors has been described. The
attractive features of this protocol are simple experimental procedure, solvent-free
reaction conditions, utilization of an inexpensive, non toxic, short reaction times, reusable
catalyst in high yields and its adaptability for synthesis of a diverse set of xanthenone
derivatives. To the best of our knowledge this is the first report on synthesis of 12-aryl-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones with Zr-MCM-41.
EXPERIMENTAL
General Procedure For The Synthesis Of Xanthenones (4,5)
To a mixture of aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (1 mmol) and
naphthol (1 mmol), Zr-MCM-41 (10 mol %) was added and heated at 80 oC for the
appropriate amount of time as indicated in Table 2. The progress of the reaction was
monitored by thin-layer chromatography (TLC). After completion, ethyl acetate (10 mL)
6

was added and centrifugated until catalyst was separated. Then, Ethyl acetate was
evaporated under vacuum to give the crude product. The crude product was recrystallized
from EtOH to yield pure xanthenes-11-one derivatives.
SUPPORTING INFORMATION
Spectral data for the synthesized compounds can can be accessed on the publisher’s
website.
ACKNOWLEDGMENT
The authors thank the Research Council of Payame Noor University for financial support.
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10

Table 1. Choice of amount of Zr-MCM-41 for xanthenones formation
Entry
Catalyst loading (mol %) Yield (%)
1
2
3
4
5
2
72
80
85
92
92
5
7
10
15
11

Table 2. Zr-MCM-41 catalyzed one-pot synthesis of xanthenones
Entry Aldehyde Naphthol Product
Time Yield
(min) %
1
20
92
CHO
OH
OH
OH
O
CH3
CH3
O
4a
4b
4c
4d
2
15
88
CHO
Br
Br
OH
O
CH3
CH3
O
3
15
92
CHO
Cl
OH
Cl
O
CH3
CH3
O
4
OCH3
20
87
CHO
OH
OCH3
O
CH3
CH3
O
12

5
20
91
CHO
CH3
OH
CH3
O
CH3
CH3
O
4e
6
7
CHO
12
10
90
88
OH
OCH3
OH
OH
O
OCH3
CH3
CH3
O
4f
CHO
Cl
HO
HO
HO
OH
OH
OH
OH
OH
OH
Cl
O
CH3
CH3
O
5a
5b
5c
8
16
88
CH3
CHO
CH3
O
CH3
CH3
O
9
OCH3
12
90
CHO
OCH3
O
CH3
CH3
O
13

10
11
12
13
10
10
12
14
91
89
90
87
CHO
Cl
HO
HO
HO
HO
OH
OH
OH
OH
OH
OH
Cl
O
CH3
CH3
O
O
O
O
5d
5e
5f
CHO
OCH3
OH
OH
O
OCH3
CH3
CH3
CHO
OH
Br
OH
OH
O
Br
CH3
CH3
CHO
OH
OH
OH
O
CH3
CH3
5g
14

Table 3. Recyclability of the nanocatalyst for the synthesis of xanthenones
No of Cycles
Yield (%)
Fresh
92
Run 1
92
Run 2
90
Run 3
89
15

Scheme 1. Zr-MCM-41 promoted one-pot synthesis of xanthenones (4, 5)
16

Scheme 2. Plausible mechanism for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-ones
17