Silica sulfuric acid as an efficient and reusable catalyst for the pechmann synthesis of coumarins under solvent-free conditions

Article abstract of DOI:10.3987/COM-06-10956

Silica sulfuric acid is used as an efficient catalyst in the Pechmann condensation of phenols with β-keto-esters leading to the formation of coumarin derivatives in excellent yields under solvent-free conditions. It was found that the catalyst could be recycled and reused for several runs.

Full text of DOI:10.3987/COM-06-10956

HETEROCYCLES, Vol. 71, No. 3, 2007
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HETEROCYCLES, Vol. 71, No. 3, 2007, pp. 677 - 682. © The Japan Institute of Heterocyclic Chemistry
Received, 22nd November, 2006, Accepted, 29th January, 2007, Published online, 30th January, 2007. COM-06-10956
SILICA SULFURIC ACID AS AN EFFICIENT AND REUSABLE
CATALYST FOR THE PECHMANN SYNTHESIS OF
COUMARINS UNDER SOLVENT-FREE CONDITIONS
Minoo Dabiri,a,* Peyman Salehi,b,* Mohammad Ali Zolfigol,c and Mostafa
Baghbanzadeha
aDepartment of Chemistry, Faculty of Science, Shahid Beheshti University, Postal
Code 1983963113, Evin, Tehran, Iran, E-mail: m-dabiri@sbu.ac.ir
bDepartment of Phytochemistry, Medicinal Plants and Drugs Research Institute,
Shahid Beheshti University, P.O. Box 19835-389, Evin, Tehran, Iran, E-mail:
p-salehi@sbu.ac.ir
cDepartment of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan,
Iran
Abstract – Silica sulfuric acid is used as an efficient catalyst in the Pechmann
condensation of phenols with β-keto-esters leading to the formation of coumarin
derivatives in excellent yields under solvent-free conditions. It was found that the
catalyst could be recycled and reused for several runs.
INTRODUCTION
Coumarin and its derivatives are widely used as additives in food, perfumes, cosmetics, pharmaceuticals,
and agrochemicals.1,2 A wide range of biologically active coumarins is also reported in literature which for
example posses antiprotozoal, cytotoxic,3 and antiplasmodial activity4 and inhibitory of
acetylcholinesterase and monoamine oxidase,5 and HIV integrase.6
Due to importance of coumarin, synthesis of its nucleus is a topic of current interest.7 There have been
many synthetic routes to coumarins, including Pechmann,8 Perkin,9 Knoevenagel,10 Reformatsky,11 and
Wittig reactions.12 However, the Pechmann reaction has been the most widely applied for the synthesis of
coumarins as it proceeds from very simple starting materials and gives good yields. Several acidic reagents
have been used in the Pechmann reaction such as sulfuric acid,8 aluminum chloride,13 phosphorus
pentoxide,14 trifluoroacetic acid,15 and etc. However, these reagents have to be used in excess amounts and
in all cases mixtures of the reagents were allowed to stand for a long time, depending on their reactivity, or

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were heated above 150 °C, that caused the formation of unwanted side products. As a result, the disposal of
excess acid waste leads to increasing environmental pollution. Therefore it is important to investigate a new
method using less hazardous reagents and catalysts or without harmful organic solvents. To overcome these
problems some environmentally benign procedures have been reported such as using solid supports,16 ionic
liquids,17 and solid Lewis acids.18
It is an established fact in the literature that Pechmann reaction proceeds through transesterification and
intramolecular hydroxyalkylation, followed by dehydration.19 These three steps are all typical
acid-catalyzed reactions. Therefore, the outcome of the Pechmann reaction depends very much on the
acidity of the catalysts.20
RESULTS AND DISCUSSION
In continuation of our interest in using solid supports in organic reactions,21 and specially silica sulfuric
acid (SSA),22 here we wish to report an efficient and environmentally benign procedure for the synthesis of
coumarins via Pechmann condensation in the presence of SSA as a solid and reusable catalyst.
For optimizing the reaction conditions, the reaction of resorcinol with ethyl acetoacetate in the presence of
SSA at different temperatures was investigated. The best results obtained with 15 mol% of SSA at 80 ˚C.
Encouraged by the above results, other coumarin derivatives were synthesised under the same conditions
(Scheme 1).
R
OH
O
O
SSA (15 mol%)
solvent-free, 80 oC
+
R
OEt
O
O
X
X
Scheme 1
Several types of phenolic substrates and β-keto-esters with different functionalities were used in the
reaction. As could be seen in Table 1, the reaction was found to be adaptable to a variety of substrates and
the yields, in general, were very high. It is worth noting that with simple phenol as a substrate also good
result was obtained (Table 1, entry 13), but ortho- and para-dihydroxybenzene afforded mixture of
products. The experimental procedure is very simple and work up includes the addition of ethanol followed
by filtration for separation of the catalyst. Hence there will not be any unnecessary acidic waste stream to
create environmentally hazardous pollution.
In order to find the possibility of recycling the catalyst, an investigation was made on the reaction of
resorcinol and ethyl acetoacetate in the presence of 15 mol% of SSA. After completion of the reaction,

HETEROCYCLES, Vol. 71, No. 3, 2007
679
ethanol was added and the mixture was filtered to separate the catalyst. The recycled catalyst was used for
further runs. No decrease in catalytic activity of SSA was observed even after five runs (Table 1, entry 1).
Table 1. Synthesis of coumarins by the reaction of phenols with β-keto-esters in the presence of 15 mol%
of SSA
Mp (˚C)
Entry
1
Phenol
ß-Keto-ester
Producta
Time (h)
0.5
Yield (%)
Found
Reported
HO
HO
HO
O
O
O
O
HO
HO
HO
OH
OH
OH
93, 92,
91, 94,
89b
O
O
187-188 186-18918a
255-257 256-25718c
Me
Ph
OEt
OEt
Me
O
O
O
2
3
4
0.5
1
95
90
90
Ph
O
O
O
192-193
246-248
190-19118a
244-24617a
ClH2C
O
OEt
CH2Cl
O
HO
HO
O
O
HO
HO
OH
OH
O
O
1
OEt
O
O
5
6
0.5
92
92
285-287 289-29018a
Me
Ph
OEt
OH
OH
OH Me
HO
OH
HO
HO
O
O
O
O
0.75
241-242
245-246
243-24618c
OEt
OH
Ph
O
HO
OH
O
O
O
7
8
1
90
94
246-24818a
ClH2C
OEt
OH
Me
OH
Me
CH2Cl
HO
O
O
HO
OH
O
O
0.5
264-266 263-26518c
Me
OEt
Me

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HETEROCYCLES, Vol. 71, No. 3, 2007
Table 1. Synthesis of coumarins by the reaction of phenols with β-keto-esters in the presence of 15 mol%
of SSA (Continued)
Mp (˚C)
Entry
9
Phenol
ß-Keto-ester
Producta
Time (h) Yield (%)
Found
Reported
Me
O
Me
HO
O
HO
OH
O
O
0.5
97
93
282-284 284-28518c
Ph
OEt
Ph
O
OH
O
O
O
10
11
1
152-153 153-15518c
Me
OEt
Me
O
OH
OH
O
O
O
1
96
166-169 165-16718c
ClH2C
OEt
CH2Cl
O
O
O
O
O
12
13
1
2
85
70
213-214 215-21717a
OEt
OH
O
O
O
80-81
78-8018d
Me
OEt
Me
a The products were characterised by comparison of their spectroscopic and physical data with authentic samples synthesised by
reported procedures.
bThe catalyst was used for five runs.
In conclusion, we have demonstrated an efficient and simple alternative for the preparation of substituted
coumarins via the SSA catalyzed Pechmann reaction under solvent-free conditions. Prominent among the
advantages of this new method are operational simplicity, good yields, short reaction times and an easy
work-up procedure. The catalyst is also reusable and can be recycled for several runs.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9200 apparatus. IR spectra were recorded on FT-IR
102MB BOMEM apparatus. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer
1
operating at an ionization potential of 70 eV. H and 13C NMR spectra were recorded on a BRUKER
DRX-300 AVANCE spectrometer at 300.13 and 75.47 MHz. All the products are known compounds,

HETEROCYCLES, Vol. 71, No. 3, 2007
681
1
which were characterized by melting point, IR, H NMR and 13C NMR spectral data and mass
spectroscopy.
General Procedure
Phenolic substrate (1mmol), β-keto ester (1mmol) and SSA (0.06 g equal to 0.15 mmol H+) were mixed
together in a round bottom flask. The mixture was stirred at 80 ̊C for the appropriate time (see Table 1).
After completion of the reaction indicated by TLC (eluent: n-hexane/EtOAc: 3/1), hot EtOH was added and
filtered. EtOH was evaporated under reduced pressure and crude product was recrystallized from EtOH.
ACKNOWLEDGEMENTS
Financial support by the Research Council of Shahid Beheshti University is gratefully acknowledged.
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