Mesoporous zirconium phosphate: An efficient catalyst for the synthesis of coumarin derivatives through Pechmann condensation reaction

Article abstract of DOI:10.1016/j.apcata.2010.12.027

Mesoporous zirconium phosphate (m-ZrP) is used as a solid acid catalyst for the synthesis of coumarins via Pechmann condensation reaction and gave high catalytic activity for the condensation of phenols and ethyl acetoacetate in both conventional heating as well as microwave assisted method. The condensation reaction is studied in detail by varying the reaction parameters like effect of solvent, molar ratio of the reactants, temperature, and catalyst loading. Among the substituted phenols, m-amino phenol is more reactive and 100% yield is obtained in very short time at low temperature due to the presence of ring activating amine group in meta position. The m-ZrP is also active even for simple phenol and 57% yield of 4-methyl coumarin is obtained in conventional heating method. Microwave assisted synthetic method is found to be advantageous over conventional heating for the synthesis of coumarins, as it provides improved yield in very less time.

Full text of DOI:10.1016/j.apcata.2010.12.027

Applied Catalysis A: General 394 (2011) 93–100
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Mesoporous zirconium phosphate: An efficient catalyst for the synthesis of
coumarin derivatives through Pechmann condensation reaction
Apurba Sinhamahapatra, Narottam Sutradhar, Sandip Pahari, Hari C. Bajaj, Asit Baran Panda∗
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (Council of Scientific and Industrial Research), G.B. Marg, Bhavnagar 364021,
Gujarat, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Mesoporous zirconium phosphate (m-ZrP) is used as a solid acid catalyst for the synthesis of coumarins
via Pechmann condensation reaction and gave high catalytic activity for the condensation of phenols and
ethyl acetoacetate in both conventional heating as well as microwave assisted method. The condensation
reaction is studied in detail by varying the reaction parameters like effect of solvent, molar ratio of the
reactants, temperature, and catalyst loading. Among the substituted phenols, m-amino phenol is more
reactive and 100% yield is obtained in very short time at low temperature due to the presence of ring
activating amine group in meta position. The m-ZrP is also active even for simple phenol and 57% yield of
4-methyl coumarin is obtained in conventional heating method. Microwave assisted synthetic method
is found to be advantageous over conventional heating for the synthesis of coumarins, as it provides
improved yield in very less time.
Received 27 August 2010
Received in revised form
11 December 2010
Accepted 21 December 2010
Available online 4 January 2011
Keywords:
Mesoporous zirconium phosphate
Pechmann condensation reaction
Coumarin
© 2010 Elsevier B.V. All rights reserved.
Microwave-assisted synthesis
1. Introduction
for the synthesis of coumarin and their derivatives. Beside these,
uses of different other homogeneous catalyst like metal chlorides
Coumarins, the benzo-2-pyrone derivatives, are one of the
most important compounds of natural product and in synthetic
organic chemistry. They have been used largely in pharmaceutical,
perfumery, agrochemical industries as starting material or inter-
mediate. It is also used as fluorescent brightener, efficient laser dye
and as additives in food and cosmetics [1–3]. Several bioactivities of
coumarins, such as antibacterial, anticancer, inhibitory of platelet
aggregation, inhibitory of steroid 5␣-reductase and inhibitory of
HIV-1 protease, have also been reported [1,4–6].
Plants are the most important source of coumarins, but
extraction from plant is tedious, time consuming and needs sophis-
ticated instrumentation. Many synthetic methods, like Pechmann
condensation, Perkin, Reformatsky Wittig reaction, Knoevenagel
condensation and Claisen rearrangement have been investigated
for the synthesis of coumarins [7–10]. The Pechmann condensa-
tion reaction is the most simple and widely used method, involving
reactions between activated phenols and beta-ketonic esters or an
unsaturated carboxylic acid through an acid catalysed transester-
ification, keto-enol tautomerisation, Michael addition and lastly
an acid catalysed dehydration [7]. Generally concentrated sulfuric
acid, trifluroacetic acid, or phosphorous pentoxide [7,11,12] is used
and sulfonic acid are reported as acid catalyst for the Pechmann
condensation reaction [13–15]. However, most of these acid cata-
lysts are required in stoichiometric amount or more for high yield.
They are corrosive, difficult to separate and create severe environ-
mental problems due to disposal of post reaction wastes. On the
other hand heterogeneous solid systems are the appropriate as they
are easily recoverable, reusable and minimized the wastes. During
recent past, various solid acid catalysts such as zeolite [16], nafion-
H [17], amberlyst [18], montmorillonite K 10 [19], poly aniline
sulfate salt [20], heteropoly acids [21], functionalized mesoporous
silica (e.g. Zr-TMS, Al-MCM-41) [22,23], metal oxide or modified
metal oxides (e.g. sulfated zirconia) [24,25], inorganic ion exchang-
ers and other supported catalyst [26] have been employed for the
synthesis of coumarins. These established solid acid catalysts have
disadvantages like poor thermal stability, lack of reproducibility,
complex separation, low surface area, less water tolerance ability
and small pores for large-size reactants for which large amount of
catalyst is required to produce high yield [16–18,27–29]. For exam-
ple due to small pore size, zeolite [16] is required in stoichiometric
amount for better yield, nafion based catalysts are not thermally
stable [28], sulfated zirconia is moisture sensitive [27]. In this
regard, layered zirconium phosphate (L-ZrP) may be an important
alternative solid acid catalyst [30–33] with high thermal stabil-
ity, high water tolerance ability and easy sedimentation [28,33].
However, the use of layered zirconium phosphate limits its appli-
cation to bulkier molecules only at its external surface because of its
∗
Corresponding author. Tel.: +91 278 2567760x704; fax: +91 278 2567562.
E-mail addresses: abpanda@csmcri.org, asit012@gmail.com (A.B. Panda).
0926-860X/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2010.12.027

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A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
Scheme 1. Schematic representation of liquid phase Pechmann condensation of phenol and EAA.
˚
small inter-layered distance [34]. Chudasama et al. have reported
only 61% yield of 7-hydroxy-4-methyl coumarin using layered ZrP
[35]. The use of mesoporous zirconium phosphate, with high sur-
face area and uniform pore size, as heterogeneous acid catalyst may
be the appropriate for the synthesis of coumarins with better yield.
Recently we have reported the synthesis of mesoporous zir-
conium phosphate (m-ZrP) having high specific surface area and
narrow pore size distributions with excellent catalytic activity
towards various organic reactions involving bulkier molecules [36].
Herein we report the detailed study of the Pechmann condensation
reaction of different substituted phenols with ethyl acetoacetate
(EAA) to produce respective coumarins using the mesoporous zir-
conium phosphate as solid acid catalyst. The effect of solvent, molar
ratio of reactants, amount of catalyst, reaction temperature and
time were investigated. Besides the conventional heating method,
microwave assisted synthesis of coumarins was also studied. Here,
it should be mentioned that recently microwave irradiation has
been found a more useful tool for the synthesis of coumarins in
order to minimize the reaction time [37,38].
filtered Cu K␣ radiation, ꢁ = 1.5404 A). The BET surface area, total
pore volume, and the average pore diameter were measured by N2
adsorption–desorption method by ASAP 2010 Micromeritics (USA),
at −196 ◦C, after degassing of sample under vacuum (10−2 Torr) at
250 ◦C for 3 h. A scanning electron microscope (SEM) (Leo series
1430 VP) was used to determine the morphology of samples. The
sample powder was supported on aluminum stubs and then coated
with gold by plasma prior to measurement. Transmission elec-
tronic microscope (TEM) images were collected using a JEOL JEM
microscope and samples were prepared by mounting an ethanol
dispersed samples on lacy carbon coated Cu grid. 31P solid-state
NMR was performed using a Bruker Advance II-500 spectrometer.
2.4. Acidity measurement
The FT-IR and DRIFT spectra in a range of 400–4000 cm−1 and
1200–1800 cm−1, respectively were recorded on a Perkin-Elmer
GX spectrophotometer using a Diffuse Reflectance Scanning disc
technique. DRIFT experiment was carried out using pyridine as a
probe to investigate the types of acid sites present in the cata-
lyst. Temperature-programmed desorption (TPD) measurements
were carried out to measure the acid strength of m-ZrP using
ammonia as an adsorbate. TPD measurements were conducted on
a Micromeritics Autochem-II Chemisorption analyzer by placing
200 mg of sample in a U-shaped sample tube. Sample was pre-
treated in helium (35 cm3 min−1) at 250 ◦C for 30 min and then, 1 h
at 350 ◦C and cooled to100 ◦C. Ammonia (100 Torr) was adsorbed
on the samples for 1 h. The physisorbed ammonia was removed by
flushing the sample with helium for 1 h. TPD measurements were
carried out in the temperature range of 100–900 ◦C.
2. Experimental
2.1. Materials
Zirconium oxychlorideoctahydrate (ZrOCl2·8H2O, 96.0%), di-
ammonium hydrogen ortho-phosphate [(NH4)2HPO4, 98.5%] and
cetyltrimethylammonium bromide (CTAB, 98%) were purchased
from s. d. Fine Chemicals, India. Ammonium carbonate (ammo-
nia 31% equivalent to 95.3%) was purchased from Rankem, India
and used as such. Water with a resistivity of 18 Mꢀ cm was used
for all the reactions. High purity phenols (98–99.5%) and EAA (99%)
were purchased from Spectrochem and SRL, India and used without
further purification.
2.5. Pechmann condensation of phenolic compounds
High purity resorcinol, 3-amino phenol, 2-methyl resorcinol,
phloroglucinol, pyrogallol, 2-hydroxy acetophenone, phenol, were
used and reacted with EAA in the presence of m-ZrP for the synthe-
sis of coumarin derivatives (Scheme 1) without and with solvent
(polar solvent nitrobenzene and non polar solvent toluene). The
reactions were performed by conventional heating using an oil bath
as well as microwave irradiation (MWI) method using a microwave
reactor (MAS-II, SSMCT Co. Ltd., China).
2.2. Synthesis of catalyst
The m-ZrP was synthesized using in situ zirconium carbonate
complex as zirconium source, adopting the reported synthetic pro-
cedure [36]. In a typical procedure, zirconium carbonate complex
solution (prepared from zirconium oxychloride and ammonium
carbonate), (NH4)2HPO4, CTAB and H2O was added in a beaker
with a molar ratio of 0.1 Zr4+:2 PO43−:0.25 CTAB:1000 H2O. After
stirring the reaction mixture for 12 h, the solution was kept in pre-
heated oven at 60 ◦C for two days followed by one day at 80 ◦C
in a glass bottle. Then the mixture was transferred into autoclave
and autoclaved for another one day at 120 ◦C. The resultant white
solid was filtered off and washed with water at least 4–5 times.
The solid was dried at 100 ◦C overnight and calcined at 550 ◦C for
6 h. The resultant white calcined powder was used for the catalytic
reaction.
2.5.1. Synthesis of coumarins by conventional heating
The solvent free liquid phase catalytic condensation was per-
formed in a 25 ml round bottom flask. The temperature of the
reaction vessel was maintained using a pre-heated oil bath. In a
typical Pechmann condensation of phenols and EAA, 5 mmol phe-
nols, 10 mmol of EAA and 15 wt% (weight percent) catalysts with
respect to phenols were magnetically stirred (500 rpm) and heated
at 160 ◦C for 5 h. During the progress of reaction, reaction mixture
was periodically withdrawn and analyzed by a GC (Shimadzu GC
2010) to monitor the extent of reaction. The product was also iden-
tified by GC–MS (Shimadzu, GCMS-QP 2010). The conversion of
phenols and selectivity of coumarins were calculated on the basis
2.3. Catalyst characterization
The powder X-ray diffraction pattern of synthesized m-ZrP was
recorded on a Philips X’pert X-ray powder diffractometre (Ni-

A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
95
of its weight percent using GC data as follows:
ꢀ
ꢁ
[100 × (initial wt% − final wt%)]
% conversion =
initial wt%
[GC peak area % of coumarin]
ꢂ
% selectivity = 100 ×
total GC peak area % for all the products.
After completion of the reaction, the reaction mixture was
cooled to room temperature and dissolved in ethanol. The cata-
lyst was separated by filtration and concentrated on rotavapour.
The concentrated reaction mixture was subjected 10 g of crashed
ice and solid product was obtained. The product was collected by
filtration and re-crystallized using ethanol. Finally the product was
characterized by 1H NMR analysis and melting point measurement.
To attain the maximum conversion and selectivity, the reaction
of resorcinol and EAA was optimized by varying the reaction time,
temperature, molar ratio of resorcinol to EAA, amount of catalyst
with respect to resorcinol. Here it should be mentioned that the
reaction of 3-amino phenol and EAA was very fast. So this reaction
was performed at 110 ◦C for 1 h only.
Fig. 1. DRIFT spectra of pyridine absorbed m-ZrP at room temperature.
3.2. Acidity measurement
2.5.2. Synthesis of coumarins by microwave irradiation
To understand the acidity of the catalyst, DRIFT spectrum was
recorded by using pyridine as probe. The spectrum (Fig. 1) showed
bands at 1541, 1489, 1440 cm−1 indicating the presence of the
Brönsted acid site as well as the Lewis acid site with a ratio 3:2.
With increasing temperature (from room temperature to 450 ◦C)
during DRIFT analysis, the intensity of the adsorption band due to
the pyridine adsorbed on Lewis acid sites decreased gradually, how-
ever, the adsorption band due to pyridine adsorption on Brönsted
acid sites remained almost constant, indicating that the weak Lewis
acid sites compared to the Brönsted acid sites. The NH3-TPD profile
showed one distinct peak, centre at 433 ◦C with a hump at ∼326 ◦C
(Supporting Information) and desorption of NH3 continued even
at 900 ◦C. The result indicates the presence of significant amount
of strong acidic sites, probably due to the presence of a reasonable
amount of Brönsted acid sites. The extent of desorption is found
to be ca. 1.89 mmol NH3/g of catalyst. The detail discussion can be
found in our previous report [36].
Synthesis of coumarins by microwave irradiation was carried
out in solvent free condition. In a typical reaction protocol, phe-
nols, EAA (1:2 molar ratio) and m-ZrP (15 wt% with respect to
phenols) were taken into a specially designed round bottom flask
for microwave reactor, and placed under the MWI at required tem-
perature, time and power. After completion of the reaction, the
resultant mass was analyzed by GC–MS and GC. The conversion
of phenols and selectivity of coumarins were calculated as outlined
above. The product was isolated following above stated procedure.
The m-ZrP, which was used for the reaction between resorcinol
and EAA in both conventional heating and microwave method, was
regenerated by a simple method and reused for 5 times. In a typical
regeneration method, 1 g of used catalyst was refluxed with 40 ml
30% (w/v) H2O2 for 3 h at 80 ◦C under continuous stirring. Then
the catalyst was filtered off, washed with distilled water, and dried
overnight at 100 ◦C. After every cycle the regenerated catalyst was
analyzed by XRD, FT-IR and 31P NMR.
3.3. Pechmann condensation of phenolic compounds
3. Results and discussions
3.1. Catalyst characterization
3.3.1. Synthesis of coumarins by conventional heating
In the first set of reaction, intermolecular Pechmann condensa-
tion performed in nitrobenzene as solvent (polar), taking resorcinol
and EAA (1:1 molar ratio) in the presence of m-ZrP (10 wt% with
respect to resorcinol) as catalyst yielded 25% conversion of resor-
cinol at 120 ◦C after 4 h. On increasing of temperature to 150 ◦C
conversion was increased to 38% in 4 h and 53% after 8 h. Further
increase in conversion was not observed by changing the reaction
time or the amount of catalyst (Table 1). The same reaction when
performed in non polar solvent (toluene) resulted in only 34% con-
version after 15 h at 120 ◦C. When same reaction was performed
The textural properties of catalyst m-ZrP, calcined at 550 ◦C,
used in the present study are given in brief. The surface area,
total pore volume and average pore diameter of the m-ZrP were
found to be 497 m2 g−1, 0.37 cm3 g−1 and 3.0 nm, respectively. The
observed N2 adsorption–desorption isotherms were similar to type
IV isotherm (Supporting Information) and reveals the mesoporous
nature of m-ZrP catalyst. In the low angle X-ray diffraction pattern,
presence of single broad peak suggests the existence of worm-
hole like porous in short range order (Supporting Information). The
presence of two broad peaks in the ranges of 10–40◦ and 40–70◦
confirms the amorphous nature of the synthesized m-ZrP cata-
lyst. The TEM image of the synthesized m-ZrP catalyst showed the
presence of worm like pores (Supporting Information). The pores
are nearly mono-dispersed with an average pore size of ∼3 nm,
almost equivalent to the pore size obtained from the surface area
measurement data. The phosphate/zirconium ratio was 1.89 (from
ICP experiment). 31P MAS NMR spectroscopy showed one dis-
tinguishable resonance positions centre at ∼ı −21 ppm, assigned
to tetrahedral phosphorus connected with three [(OH) P–(OZr)3]
zirconium atom (Supporting Information). The corresponding res-
onance peak in 31PNMR is broad due to the amorphous nature of
m-ZrP and lacks the atomic resolution.
Table 1
Effect of solvent on Pechmann condensation reaction of resorcinol and EAA over
m-ZrP.
Solvent
Time (h)
Temp (◦C)
Conversion (%)
Nitrobenzene
4
4
8
16
15
4
120
150
150
150
120
120
150
25
38
53
54
34
51
76
Toluene
Solvent free
Solvent free
4
Reaction condition: resorcinol:EAA, 1:1; catalyst, 10 wt% with respect to resorcinol.

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A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
Fig. 3. Effect of catalyst weight with respect to resorcinol on conversion of resorci-
nol and selectivity of 7-hydroxy 4-methyl coumarin under solvent free Pechmann
condition (reaction condition: resorcinol/EAA, 1:2; reaction time, 4 h; temperature,
140 ◦C).
Fig. 2. Effect of substrate (resorcinol/EAA) ratio on conversion of resorcinol in sol-
vent free synthesis of 7-hydroxy 4-methyl coumarin with m-ZrP (reaction condition:
catalyst amount, 10 wt%; temperature, 120 ◦C; reaction time, 4 h).
100% selectivity, which remained almost constant up to 20 wt% of
catalyst. With further increase in the amount of catalyst, no signif-
icant change in the conversion was observed, however selectivity
decreased with the formation of side product 3-(2,4-dihydroxy-
phenyl)-but-2-enoic acid ethyl ester.
With increase in the amount of catalyst, dispersion of catalyst
increased in the reaction system and also the availability of active
acid sites of catalyst to substrate increased. Hence the conversion
was increased and reached to maximum. Again in the presence of
excess amount of acid catalyst (beyond 20 wt%), a side reaction, the
ring opening of product coumarin followed by acetylation, resulted
in the additional product 3-(2,4-dihydroxy-phenyl)-bute-2-enoic
acid ethyl ester.
Effect of temperature: The effects of reaction temperature on
catalytic activity (conversion of resorcinol) and selectivity of 7-
hydroxy 4-methyl coumarin were examined in the temperature
range of 100–180 ◦C in solvent free condition for 4 h using 15 wt%
of m-ZrP as catalyst (Fig. 4). It was found that the conversion of
resorcinol increased gradually with the increase in temperature
and reached maximum (94%) at 160 ◦C with 100% selectivity for
7-hydroxy 4-methyl coumarin. Further increase in temperature,
resulted in a slight decrease in selectivity of coumarin with the
in solvent free condition, maximum conversion (76%) of resorci-
nol was obtained in 4 h at 150 ◦C (Table 1). The conversion in the
presence of solvent is low may be due to the competitive adsorp-
tion of reactants and solvent on the catalyst active sites. Polarity
of solvent is also an important factor for the Pechmann condensa-
tion reaction, non-polar solvents favour the Pechmann reaction and
polar solvents cause the cleavage [18]. Toluene is the mostly used
solvent in Pechmann reaction [16,18]. Moreover, different obser-
vations have been reported in the literature on solvent study. For
instance, Sabou et al. [18] reported that toluene is a better solvent
than dichloromethane and THF when amberlyst ion-exchange resin
was used as catalyst. Romanelli et al. [21] also reported similar
result using heteropolyacid as catalyst. Wang et al. [39] reported
that when Yb(OTf)3 used as catalyst, THF was found to be the best
solvent rather than toluene and dichloromethane, however toluene
was better than that of THF. Tyagi et al. [24] reported that the
nitrobenzene is the good solvent than that of toluene when sul-
fated zirconia is used as catalyst. These indicate that the variation
in the yield depends on the combination of solvent and the catalyst
used. Further study for the synthesis of coumarins was performed
under solvent free condition.
3.3.1.1. Synthesis of 7-hydroxy 4-methyl coumarin. Initially, the
liquid phase Pechmann condensation of resorcinol and EAA to 7-
hydroxy-4-methylcoumarin was performed at 120 ◦C for 4 h using
10 wt% m-ZrP catalyst with varying ratio of substrate (resorci-
nol:EAA::1:1 to 1:3). The yield of 7-hydroxy 4-methyl coumarin
was found to be maximum (63%), when the resorcinol:EAA ratio
was 1:2 as compared to that of 1:1 (51%) (Fig. 2). Further increase
in the ratio of substrate, the yield was almost same. The ratio of
resorcinol:EAA, 1:2, was found to be optimum for the solvent free
synthesis of coumarin. Similar result was also reported in previ-
ous work [24]. Further experiments for optimization of amount
of catalyst, reaction temperature, and reaction time, to attain the
maximum conversion and selectivity were performed using the
substrate ratio of 1:2.
Effect of catalyst loading: To study the effect of amount of cat-
alyst for the synthesis of 7-hydroxy 4-methyl coumarin on the
yield, the reaction was carried out at 140 ◦C for 4 h by changing
the amount of catalyst in the range of 5–30 wt% with respect to
resorcinol. The amount of catalyst in the reaction mixture has sig-
nificant effect on the yield of 7-hydroxy 4-methyl coumarin (Fig. 3).
When the amount of catalyst was 15 wt%, conversion was 84% with
Fig. 4. Effect of reaction temperature on conversion of resorcinol, selectivity and
yield of 7-hydroxy 4-methyl coumarin under solvent free Pechmann condensation
over m-ZrP (reaction condition: resorcinol/EAA, 1:2; amount of catalyst, 15 wt%;
reaction time, 4 h).

A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
97
Fig. 5. Reaction profile (conversion) obtained for the Pechmann condensation of
resorcinol and EAA at 160 ◦C over m-ZrP (reaction condition: resorcinol/EAA, 1:2;
amount of catalyst, 15 wt%; temperature, 160 ◦C).
Fig. 6. Effect of reaction temperature on the yield of 7-amino 4-methyl coumarin
under solvent free Pechmann condensation of 3-amino phenol and EAA over m-ZrP
(reaction condition: 3-amino phenol/EAA, 1:2; amount of catalyst, 15 wt%; reaction
time, 30 min).
formation of side product 3-(2,4-dihydroxy-phenyl)-bute-2-enoic
acid ethyl ester, without significant change in the conversion.
Effect of time: Fig. 5 represents the kinetic study of the conden-
sation reaction of resorcinol and EAA. The conversion increased
rapidly with increase in reaction time and resulted 94% conver-
sion with 100% selectivity in 4 h (Fig. 5). No effect on conversion
and selectivity was observed on further increase in reaction time,
may be due to the deactivation of active sites or decrease in
effective concentration of reactants. Hence the Peachmann con-
densation reaction of resorcinol and EAA in solvent free condition
with substrate ratio of 1:2 and 15 wt% catalyst at 160 ◦C for 4 h in
conventional heating is the optimize condition to get maximum
yield (94%) using m-ZrP as solid acid catalyst. This result is better
than that obtained using other solid acid catalyst [18,21,29,39].
Mainly two mechanistic pathways have been proposed in the lit-
erature for the Pechmann condensation reaction for the synthesis of
7-hydroxy-4-methyl coumarin [22,23]. One reported by Sudha et al.
[22], is based on proton transfer to a keto group of EAA from acid
sites of catalyst by interaction of EAA with catalyst followed by the
nucleophilic attack of the hydroxyl group of resorcinol, resulting in
an intermediate and ethanol. The intermediate rapidly undergoes
cyclization through acid catalysed intra-molecular condensation
yielding 7-hydroxy-4-methyl coumarin. Another possible mech-
anism as reported by Selvakumar et al. [23] is based on reaction
catalysed by acid sites of the catalysts i.e., electrophilic reaction of
chemisorbed ethyl acetoacetate on resorcinol wherein chromones
is produced as side product. In the present reaction, we have not
observed the formation of chromones during reaction, so the mech-
anism proposed by Selvakumar et al. [23] was ruled out. Based on
the above discussion, a probable mechanism for the formation of
7-hydroxy-4-methylcoumarin using synthesized mesoporous ZrP
was proposed and presented in Scheme 2.
coumarins. Pyrrogallol was less active than that of phloroglucinol,
nevertheless both substrate have two electron donating hydroxyl
groups. This may be due to the presence of two hydroxyl group of
phloroglucinol at meta-positions activates the aromatic ring more
than that of one hydroxyl group at ortho-positions positions in
pyrrogallol. Activity decreased gradually with the decrease in the
strength of the ring activating group. Phenol was least reactive than
other substituted phenols studied here. Still, 57% yield of 4-methyl
coumarin was obtained in only 4 h when phenol was used as sub-
strate. Reports on Peachmann condensation involving phenol are
rare. Tyagi et al. [38] reported that the reactivity of phenol over sul-
fated zirconia was nil even using microwave irradiation, whereas,
the solid acid K-10 [19], was resulted 4-methyl coumarin with 65%
yield in 10 h. Again over heteropoly acid [21], pyrogallol gave 86%
yield in 5 h. From the above results, it is evident that the catalytic
activity is not only dependent on phenolic substrates activity, but
also highly dependent on the composition and textural features of
catalyst.
3.3.1.3. Condensation of 3-amino phenol and EAA. The condensa-
tion reaction of 3-amino phenol with EAA was completed within
30 min with 100% yield of 7-amino-4-methyl coumarin. We also
investigated the temperature effect for 3-amino phenol (Fig. 6),
keeping the other parameters constant (catalyst amount = 15 wt%;
reactants ratio = 1:2; time = 30 min). The condensation reaction was
performed in the temperature range of 60–160 ◦C. It was found that
the yield remained unchanged (100%) from 100 to 160 ◦C and after
that the conversion decreased gradually. At 60 ◦C the yield was 73%.
The condensation reaction between 3-amino phenol and EAA was
found to be very fast and highly selective. This may be due to the
presence of –NH2 group at meta position with phenolic OH group,
which accelerates the reaction through the donation of electrons.
Electron donating ability of –NH2 group also increased the electron
density at the para position in the ring and felicitates cyclization of
the intermediate to give 7-amino-4-methyl coumarin.
3.3.1.2. Synthesis of other substituted coumarines using different
phenol. Due to its better catalytic activity for the Pechmann con-
densation of resorcinol and EAA to 7-hydroxy-4-methylcoumarin,
m-ZrP was used as acid catalyst for the condensation of a series
of activated as well as less activated phenols with EAA under
optimized reaction conditions, except reaction with m-amino phe-
nol. Reaction of m-amino phenol was very fast, so we optimized
the reaction condition separately. Table 2 represents the results
obtained using different phenols. From Table 2, it is evident that
the presence of activated group and position of the activated group
in phenol ring has great influence on the yield of corresponding
3.3.2. Synthesis of coumarins by microwave irradiation
Microwave irradiation (MWI) process is fast, energy efficient,
economical and advantageous for selective dielectric heating due to
the variation in dielectric constant of solvent and reactant, and pro-
vides significant enhancement in reaction rates [37,38]. We have
studied Pechmann condensation reaction under solvent free condi-
tion using a laboratory microwave reactor. Initially, the microwave

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A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
Scheme 2. Proposed reaction mechanism for the Pechmann condensation of resorcinol with EAA using m-ZrP as catalyst under liquid phase reaction condition.
power and reaction temperature was optimized in synthesis of
7-hydroxy-4-methyl coumarin and 7-amino-4-methyl coumarin
keeping other reaction parameters same (phenol:EAA = 1:2, cat-
alyst amount = 15 wt%). The results are shown in Fig. 7. The
microwave assisted Pechmann condensation reaction was highly
dependent on the reaction temperature and microwave power. For
the condensation of resorcinol and EAA maximum 97% yield of
7-hydroxy-4-methyl coumarin was obtained in 15 min at 160 ◦C
under microwave power of 600 W. With the increase of temper-
ature at a constant power (600 W), the yield was decreased due
to the formation of side products. One of the main side product 3-
(2,4-dihydroxy-phenyl)-but-2-enoic acid ethyl ester was produced
due to the ring opening, followed by acytylation which appear to
be temperature sensitive. Again, at constant temperature the yield
was also decreased with the increase of power. At lower temper-
ature and power, reduction of yield was observed. On lengthening
the reaction time at lower temperature and lower power the for-
mation of side product was also observed. Table 3 represents the
yields of corresponding coumarins obtained using different pheno-
lic compounds in optimized conditions.
For the condensation of 3-amino phenol and EAA, 100% yield
was observed in 10 min at 100 ◦C under microwave power 400 W
(Table 3). Up to 140 ◦C (400 W) there was no effect of temperature
on yield of 7-amino-4-coumarin. But at 500 W, 93% product yield
was obtained and it started decreasing with the increase of temper-
ature. At 120 ◦C (500 W) the yield was 87%. In both, on increasing
or decreasing the temperature at constant power the lower yield of
the 7-amino-4-methyl coumarin was observed. At 100 ◦C (400 W)
the observed yield was 93% and at 80 ◦C (300 W) the yield was 80%.
From the reported literature and results as discussed above, it
is evident that synthesis of coumarins using conventional heating
takes longer time ranging from 3 to 10 h to achieve the maximum
yield using solid acid catalyst, whereas synthesis of coumarins by
microwave irradiation not only reduces the reaction time from
several hours to few minutes, but also increases the yield of the
coumarin. As for example, in present case 94% yield was obtained
in conventional heating at 160 ◦C in 4 h whereas, 97% yield was
obtained in microwave irradiation method at 160 ◦C in 15 min with
600 W power.
Here it should be mentioned that the use of m-ZrP as solid
acid catalyst is advantageous not only for its thermal stability,
high water tolerance ability, and easy sedimentation property, and
better catalytic activity, but also it is an effective catalyst for non-
activated phenols. As for example, sulfated zirconia is not active
Fig. 7. Effect of temperature and microwave power (W) on the yield of (a) 7-
hydroxy 4-methyl coumarin (reaction condition: resorcinol/EAA, 1:2; amount of
catalyst, 15 wt%; reaction time, 15 min) and (b) 7-amino 4-methyl coumarin in
microwave assisted synthesis over m-ZrP (reaction condition: 3-amino phenol/EAA,
1:2; amount of catalyst, 15 wt%; reaction time, 10 min).

A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
99
Table 2
Pechmann condensation of different phenols and EAA over m-ZrP by conventional heating.
Entry
Substrate
Product
Time (h) and temperature (◦C)
Yield (%)
HO
O
O
O
O
HO
OH
OH
1
4 and 160
94
HO
H2N
HO
HO
2
3
4 and 160
91
O
O
HO
HO
NH2
OH
0.5 and 110
100
O
O
O
O
OH
OH
OH
OH
4
4 and 160
95
HO
HO
OH
5
6
4 and 160
4 and 160
90
56
O
O
OH
Me
O
OH
O
O
O
7
4 and 160
85
Phenolic compound:EAA, 1:2; catalyst, 15 wt% with respect to phenolic compound.
for phenol, even in microwave irradiation [38], whereas m-ZrP
resulted 57% and 68% yield of 4 methyl coumarin in conventional
heating and microwave irradiation respectively in the Pechmann
condensation of phenol and EAA.
on subsequent runs. After five cycles, the activity was reduced by
∼2–3% (Fig. 8). The selectivity of the product was almost unaffected
with the reuse of regenerated catalyst. Here it should be noted that
the acetone washed catalyst gave only 73% conversion of resor-
cinol, may be due to the blockage of active site of the catalyst by
reactant or product which may not be fully removed during acetone
wash. The regenerated catalyst was characterized for its chemical
composition by elemental analysis, FT-IR and 31P NMR after each
reaction. No significant changes in composition or in environment
of phosphate group in zirconium phosphate were observed after
regeneration (Supporting Information). Fig. 9 represents the FT-IR
spectrum of as-synthesized, acetone washed and H2O2 treated cat-
3.4. Reuse of catalyst
In order to check the recyclability of the catalyst, after each
cycle, the catalyst was filtered, washed with acetone successively,
then refluxed with 30% (w/v) H2O2 for 3 h, followed by washing
with water and drying. The dried catalyst was reused for succes-
sive cycles. The activity of regenerated m-ZrP was almost identical

100
A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100
Table 3
free synthesis was found to be better than that of both polar and non
polar solvent. Among the substituted phenols, m-amino phenol was
found to be more reactive than other phenols. 100% conversion of m-
amino phenol with 100% selectivity of 7-amino 4-methyl coumarin
was obtained at 110 ◦C in 30 min by conventional heating method.
The catalyst m-ZrP was also active for phenol with 57% yield in 4 h
at 160 ◦C using conventional heating. Microwave assisted synthe-
sis method was found to be the most appropriate for the synthesis
of coumarin derivatives with improved yield as compared to con-
ventional heating method. The m-ZrP is easily recoverable from
reaction system and can be reused without reasonable change in
catalytic activity.
Pechmann condensation of different phenols under microwave irradiation over m-
ZrP.
Entry
Substrate
Yield (%)
1
2
3
4
5
6
7
Resorcinol
97
3-Amino phenola
2-Methyl resorcinol
Pohloroglucinol
Pyrogallol
∼100
92
97
94
91
67
o-Hydroxy acetophenone
Phenol
Reaction condition: phenols 5 mmol, EAA 10 mmol; temperature: 160 ◦C; time
15 min; power 600 W; catalyst 15 wt%.
a
In case of 3-amino phenol; temperature: 110 ◦C; time 10 min; power 400 W.
Acknowledgements
The authors are thankful to DST, India (SR/S1/IC-11/2008) and
CSIR (India), Network project (NWP010) for funding.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.apcata.2010.12.027.
References
[1] O. Kennedy, R. Zhorenes, Coumarins: Biology, Applications and Mode of Action,
John Wiley and Sons, Chichester, 1997.
[2] A. Takadate, T. Tahara, H. Fujino, S. Goya, Chem. Pharm. Bull. 30 (1982)
4120–4125.
[3] M. Jimeˇınez, J.J. Mateo, R.J. Mateo, Chromatogr. A 870 (2000) 473–481.
[4] G. Cravotto, G.M. Nano, G. Palmisano, S. Tagliapietra, Tetrahedron: Asymmetry
12 (2001) 707–709.
[5] G.J. Fan, W. Mar, M.K. Park, E. Wook Choi, K. Kim, S. Kim, Bio-org. Med. Chem.
Lett. 11 (2001) 2361–2363.
Fig. 8. Re-use of catalyst m-ZrP for the synthesis of 7-hydroxy 4-methyl coumarin
(reaction condition: resorcinol/EAA, 1:2; amount of catalyst, 15 wt%; temperature,
160 ◦C; reaction time, 4 h).
[6] C.J. Wang, Y.J. Hsieh, C.Y. Chu, Y.L. Lin, T.H. Tseng, Cancer Lett. 183 (2002)
163–168.
[7] A. Russell, J.R. Frye, Org. Synth. 21 (1941) 22–27.
[8] I. Yavari, R. Hekmat-shoar, A. Zonuzi, Tetrahedron Lett. 39 (1998) 2391–2392.
[9] F. Bigi, L. Chesini, R. Maggi, G. Sartori, J. Org. Chem. 64 (1999) 1033–1035.
[10] N. Cairns, L.M. Harwood, D.P. Astles, J. Chem. Soc. Perkin Trans. 1 (1994)
3101–3107.
[11] F.W. Canter, F.H. Curd, A. Robertson, J. Chem. Soc. (1931) 1255–1265.
[12] L.L. Woods, J. Sapp, J. Org. Chem. 27 (1962) 3703–3705.
[13] H. Valizadeha, A. Shockravi, Tetrahedron Lett. 46 (2005) 3501–3503.
[14] P. Sun, Z. Hu, Synth. Commun. 35 (2005) 1875–1880.
[15] T. Sugino, K. Tanaka, Chem. Lett. (2000) 110–111.
[16] E.A. Gunnewegh, A.J. Hoefnagel, H. van Bekkum, J. Mol. Catal. A: Chem. 100
(1995) 87–92.
[17] D.D. Chaudhari, Chem. Ind. (1983) 568–569.
[18] R. Sabou, W.F. Hoelderich, D. Ramprasad, R. Weinand, J. Catal. 232 (2005) 34–37.
[19] T.S. Li, Z.H. Zhang, F. Yang, C.G. Fu, J. Chem. Res. (S) (1998) 38–39.
[20] S. Palaniappan, A. John, J. Mol. Catal. A: Chem. 233 (2005) 9–15.
[21] G.P. Romanelli, D. Bennardi, D.M. Ruiz, G. Baronetti, H.J. Thomasb, J.C. Autino,
Tetrahedron Lett. 45 (2004) 8935–8939.
[22] S. Sudha, K. Venkatachalam, S. Vishnu Priya, J. Herbert Mabel, M. Palanichamy,
V. Murugesan, J. Mol. Catal. A: Chem. 291 (2008) 22–29.
[23] S. Selvakumar, M. Chidambaram, A.P. Singh, Catal. Commun. 8 (2007) 777–783.
[24] B. Tyagi, M.K. Mishra, R.V. Jasra, J. Mol. Catal. A: Chem. 276 (2007) 47–56.
[25] B.M. Reddy, P.M. Sreekanth, P. Lakshmanan, J. Mol. Catal. A: Chem. 237 (2005)
93–100.
Fig. 9. FT-IR spectra of m-ZrP catalyst (a), used m-ZrP catalyst after acetone wash
(b) and regenerated catalyst after H2O2 treatment (c) for the synthesis of 7-hydroxy
4-methyl coumarin.
[26] M. Maheswara, V. Siddaiah, G. Lakishmi, V. Damu, Y.K. Rao, C.V. Rao, J. Mol.
Catal. A: Chem. 255 (2006) 49–52.
[27] Y. Kamiya, S. Sakata, Y. Yashinaga, R. Ohnishi, T. Okuhara, Catal. Lett. 94 (2004)
45–47.
alyst. The IR of the acetone washed used catalyst gave additional
peaks along with the peaks due to pristine m-ZrP catalyst, indicated
the presence of organic substance in the acetone washed catalyst.
However, IR of H2O2 treated regenerated m-ZrP catalyst is identical
to that of pristine m-ZrP.
[28] S.X. Song, R.A. Kydd, J. Chem. Soc. Faraday Trans. 94 (1998) 1333–1338.
[29] S. Palaniappan, R.C. Shekhar, J. Mol. Catal. A: Chem. 209 (2004) 117–124.
[30] K. Segawa, Y. Kurusu, Y. Nakaiima, M. Kinoshita, J. Catal. 94 (1985) 491–500.
[31] A. Clearfield, D.S. Thakur, Appl. Catal. 26 (1986) 1–26.
[32] T. Hattori, H. Hanai, Y. Murakami, J. Catal. 56 (1979) 294–295.
[33] G. Alberti, M. Casciola, F. Marmottni, R. Vivani, J. Porous Mater. 6 (1999)
299–305.
[34] K. Segawa, S. Nakata, S. Asaoka, Mater. Chem. Phys. 17 (1987) 181–200.
[35] R. Joshi, U. Chudasama, J. Sci. Ind. Res. 67 (2008) 1092–1097.
[36] A. Sinhamahapatra, N. Sutradhar, B. Roy, A. Tarafdar, H.C. Bajaj, A.B. Panda, Appl.
Catal. A: Gen. 385 (2010) 22–30.
4. Conclusion
Mesoporous zirconium phosphate with high surface area and
narrow pore size distribution showed excellent catalytic activity for
the synthesis of substituted coumarins through Pechmann conden-
sation even in very low catalyst to substrate ratio (15 wt%). Solvent
[37] A. de la Hoz, A. Moreno, E. Vazquez, Synlett (1999) 608–610.
[38] B. Tyagi, M.K. Mishra, R.V. Jasra, J. Mol. Catal. A: Chem. 286 (2008) 41–46.
[39] L. Wang, J. Xia, H. Tian, C. Qian, Y. Ma, Int. J. Chem. 42B (2003) 2097–2099.