Microwave-assisted synthesis of coumarins via pechmann condensation in wet phosphoric acid imidazolium dihydrogenphosphate

Article abstract of DOI:10.1080/10426500802667125

Phosphoric acid imidazolium dihydrogenphosphate was found to work well as a catalyst and excellent reaction medium in the Pechmann condensation of substituted phenols or α-naphthol with ethyl acetoacetate to give 4-methyl coumarins under microwave irradiation. This method is simple, cost effective, requires short reaction times, and gives very good to excellent yields.

Full text of DOI:10.1080/10426500802667125

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Microwave-Assisted Synthesis
of Coumarins via Pechmann
Condensation in Wet
Phosphoric Acid Imidazolium
Dihydrogenphosphate
Hassan Valizadeh a , F. Mahmoodi Kordi b , Hamid
Gholipur a & Mohammad Amiri a
a Department of Chemistry, Faculty of Sciences ,
Azarbaijan University of Tarbiat Moallem , Tabriz,
Iran
b Department of Biology, Faculty of Sciences ,
Azarbaijan University of Tarbiat Moallem , Tabriz,
Iran
Published online: 03 Nov 2009.
To cite this article: Hassan Valizadeh , F. Mahmoodi Kordi , Hamid Gholipur
& Mohammad Amiri (2009) Microwave-Assisted Synthesis of Coumarins via
Pechmann Condensation in Wet Phosphoric Acid Imidazolium Dihydrogenphosphate,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:11, 3075-3081, DOI:
10.1080/10426500802667125
To link to this article: http://dx.doi.org/10.1080/10426500802667125
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Phosphorus, Sulfur, and Silicon, 184:3075–3081, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802667125
Microwave-Assisted Synthesis of Coumarins via
Pechmann Condensation in Wet Phosphoric Acid
Imidazolium Dihydrogenphosphate
Hassan Valizadeh,1 F. Mahmoodi Kordi,2
Hamid Gholipur,1 and Mohammad Amiri1
1Department of Chemistry, Faculty of Sciences, Azarbaijan University of
Tarbiat Moallem, Tabriz, Iran
2Department of Biology, Faculty of Sciences, Azarbaijan University of
Tarbiat Moallem, Tabriz, Iran
Phosphoric acid imidazolium dihydrogenphosphate was found to work well as a
catalyst and excellent reaction medium in the Pechmann condensation of substi-
tuted phenols or α-naphthol with ethyl acetoacetate to give 4-methyl coumarins
under microwave irradiation. This method is simple, cost effective, requires short
reaction times, and gives very good to excellent yields.
Keywords Coumarin; microwave-assisted; Pechmann reaction; phosphoric acid imida-
zolium dihydrogenphosphate
INTRODUCTION
The coumarins are heterocyclic organic compounds, also known as
benzo-2-pyrone derivatives, and constitute an important group of nat-
ural products having varied activities. Among the various coumarin
derivatives, 7-substituted coumarins are an important group of deriva-
tives showing various biological applications such as anthelmintic and
hypnotic properties.1 They are widely used as additives in food, per-
fumes, agrochemicals, cosmetics, and pharmaceuticals,2 and in the
preparation of insecticides, optical brightening agents, dispersed flu-
orescent, and tunable dye lasers.3 They have varied bioactivities, such
as the inhibition of platelet aggregation,4,5 antibacterial,6 anticancer,7
Received 12 September 2008; accepted 3 December 2008.
The office of the Research Vice Chancellor of Azerbaijan University of Tarbiat-
Moallem is gratefully acknowledged.
Address correspondence to Hassan Valizadeh, Department of Chemistry, Faculty of
Science, Azerbaijan University of Tarbiat-Moallem, P. O. Box 53714-161, Tabriz, Iran.
E-mail: h-valizadeh@azaruniv.edu
3075

3076
H. Valizadeh et al.
and inhibition of steroid 5α-reductase8 and HIV-1 protease9 activi-
ties. Coumarins also act as intermediates for the synthesis of fluo-
rocoumarins, chromenes, coumarones, and 2-acylresorcinols.10,11
Coumarins can be synthesized by various methods such as
Pechmann,12 Perkin,13,14 Knoevenagel,15,16 Reformatsky,17 and Wit-
ting18 reactions. Pechmann condensation is one of the most common
procedures for the preparation of coumarin and its derivatives.
Conventionally, the Pechmann reaction is carried out in the pres-
ence of a concentrated sulfuric acid catalyst,19 phosphorous pentaox-
ide,20 trifluoroacetic acid,21 or aluminum chloride.22 These acids are
corrosive and required in excess. For example, nearly one liter of
concentrated H2SO4 is required to synthesize 1 mol of 7-hydroxy-4-
methylcoumarin23; the reaction also requires 12–24 h of reaction time24
and may also result in the formation of undesired side products.25
With the increasing public concern over environmental degradation
and future resources, it is of great importance for chemists to come
up with new approaches that are less hazardous to human health and
environment. Being employed in large amounts and usually volatile
in nature, the solvents used in organic synthesis are high on the list
of environmental pollutants. For overcoming these problems, one ap-
proach is to use water as a green medium;26 another approach is to de-
velop new processes involving solvent-free conditions. In recent years,
ionic liquids have been emerged as a powerful alternative to conven-
tional molecular organic solvents due to their particular properties,
such as undetectable vapor pressure and wide liquid range, as well
as ease of recovery and reuse, and making them a greener alternative
to volatile organic solvents. Ionic liquids (IL), as new generation sol-
vents, have proven their utility in various reactions of synthetic impor-
tance.27–29 Apart from the tunable physical and chemical properties of
ionic liquids, their immiscibility with various organic solvents enables
the biphasic separation of the desired products.
Potdar et al. have reported coumarin synthesis via the Pechmann
condensation in Lewis acidic chloroaluminate ionic liquid.30 However,
there are some disadvantages associated with the use of chloroalu-
minate ionic liquids: they are moisture sensitive and cannot be re-
cycled after the reaction. In the present study, we have studied the
possibility of Pechmann condensation employing neutral ionic liquids.
We have carried out Pechmann condensation of phenols and ethy-
lacetoacetate catalyzed by using phosphorus oxychloride in 1-butyl-3-
methylimidazolium chloride ([bmim]Cl), 1-butyl-3-methylimidazolium
bromide ([bmim]Br), and 1-butyl-3-methylimidazolium tetrafluorobo-
rate ([bmim]BF4) ionic liquids (Scheme 1). The reaction of phenols
bearing electron-donating groups afforded high yields of coumarins

Synthesis of Coumarins via Pechmann Condensation
3077
SCHEME 1
under microwave irradiation. The results are recorded in I. Evidently,
[bmim]BF4 was found to be superior in terms of yield (up to 88%) and
reaction time (15 min) as compared with other ILs.
To study the extent of present conversion, we thought of us-
ing phosphoric acid imidazolium dihydrogenphosphate as a catalyst
and reaction medium for Pechmann condensation. Potdar et al. have
used 1-methylimidazolium p-toluenesulfonic acid ([Hmim]Tsa) and 1-
methylimidazolium trifluoroacetic acid ([Hmim]Tfa) ionic liquids for
this reaction, and they have observed that neither of the ionic liquids
mentioned above gave the required conversion at room temperature
as well as at high temperature.34 We extended the microwave synthe-
sis of coumarins via the Pechmann condensation employing phosphoric
acid imidazolium dihydrogenphosphate to establish cleaner synthetic
methodologies (Scheme 2).
SCHEME 2
Herein, we report that the substituted phenols and ethyl acetoac-
etate undergo condensation in the presence of phosphoric acid imida-
zolium dihydrogenphosphate catalyst under microwave irradiation to
produce the coumarins in excellent yields (Table II). We have carried
out these reactions with a series of monohydric and polyhydric phenols
with ethyl acetoacetate to obtain the corresponding coumarins. Sub-
strates having electron-donating groups in the para position to the site
of electrophilic substitution gave maximum yields under reaction con-
ditions in short periods of time. The present catalyst can be prepared
according to the procedure reported in the literature.35 From Table II,

3078

Synthesis of Coumarins via Pechmann Condensation
3079
TABLE II Coumarin Synthesis via Pechmann Condensation in Phos-
phoric Acid Imidazolium Dihydrogenphosphate
Phenolic
substrate 1
Time
(min)
(Mp)
(◦C)
Yielda
(%)
Product 2
Phenol
Resorcinol
A-naphthol
2-Methylresorcinol
Phloroglucinol
Pyrogallol
Salicylic acid
Meta-cresol
4-Methyl-
35
25
30
35
25
25
–
30
–
–
181–183
183–187
152–155
260–264
280–282
240–243
–
83
85
87
81
78
79
–
–
78
–
4-Methyl-7-hydroxy-
4-Methyl-[h]-benzo-
7-Hydroxy-4,8-dimethyl-
5,7-Dihydroxy-4-methyl-
7,8-Dihydroxy-4-methyl-
Not obtained
4,5-Dimethyl-
Not obtained
Not obtained
128–131
–
Para-nitrophenol
Ortho-nitrophenol
–
aIsolated yield after recrystallization.
it is observed that the reactions proceeded faster than the conventional
methods, and the yields are comparable. All the products were fully
1
characterized by mp, IR, and H NMR, and the values were in agree-
ment with those reported in literature.
In conclusion, we have demonstrated the use of phosphoric acid imi-
dazolium dihydrogenphosphate for Pechmann condensation to synthe-
sis of coumarins. We believe our procedure is environmentally benign
and will find important applications in the synthesis of coumarins.
EXPERIMENTAL
All of the melting points are uncorrected and were determined with a
Stuart scientific apparatus. Infrared spectra were recorded in KBr and
were determined on a Perkin-Elmer FT-IR spectrometer. 1H NMR spec-
tra were recorded on a Bruker Avance 300 MHz spectrometer in DMSO-
d6 as solvent and TMS as internal standard. All solvents and chemicals
were of research grade and were used as obtained from Merck. Mi-
crowave experiments were conducted in an unmodified oven. Melting
points and spectra were compared to those reported in the literature.
GENERAL PROCEDURE
The phenol derivative or naphthol (2.00 mmol) and ethyl acetoac-
etate (2.20 mmol) were taken in a mortar, and to it phosphoric acid
imidazolium dihydrogenphosphate (0.45 mmol) was added and the

3080
H. Valizadeh et al.
components were mixed thoroughly. Then the reaction mixture was
transferred to a 30 mL beaker and was covered with a watch glass
and subjected to microwave irradiation (140 W) for various time in-
tervals. The progress of the reaction was monitored by TLC using
(EtOAc:petroleum, 1:8) as an eluent. After completion of the reaction,
it was allowed to cool and crushed ice was added into it. The beaker was
scratched to obtain a solid, which was filtered, dried, and recrystallized
from ethanol to obtain coumarins in good yield and high purity.
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