Mesoporous zirconium phosphate: An efficient catalyst for the synthesis of coumarin derivatives...

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Applied Catalysis A: General 394 (2011) 93–100

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Applied Catalysis A: General

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Mesoporous zirconium phosphate: An efficient catalyst for the synthesis ofcoumarin 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

Article history:Received 27 August 2010Received in revised form11 December 2010Accepted 21 December 2010Available online 4 January 2011

Keywords:Mesoporous zirconium phosphatePechmann condensation reactionCoumarinMicrowave-assisted synthesis

a b s t r a c t

Mesoporous zirconium phosphate (m-ZrP) is used as a solid acid catalyst for the synthesis of coumarinsvia Pechmann condensation reaction and gave high catalytic activity for the condensation of phenols andethyl acetoacetate in both conventional heating as well as microwave assisted method. The condensationreaction is studied in detail by varying the reaction parameters like effect of solvent, molar ratio of thereactants, temperature, and catalyst loading. Among the substituted phenols, m-amino phenol is morereactive and 100% yield is obtained in very short time at low temperature due to the presence of ringactivating amine group in meta position. The m-ZrP is also active even for simple phenol and 57% yield of4-methyl coumarin is obtained in conventional heating method. Microwave assisted synthetic methodis found to be advantageous over conventional heating for the synthesis of coumarins, as it providesimproved yield in very less time.

© 2010 Elsevier B.V. All rights reserved.

1. Introduction

Coumarins, the benzo-2-pyrone derivatives, are one of themost important compounds of natural product and in syntheticorganic 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 dyeand as additives in food and cosmetics [1–3]. Several bioactivities ofcoumarins, such as antibacterial, anticancer, inhibitory of plateletaggregation, inhibitory of steroid 5�-reductase and inhibitory ofHIV-1 protease, have also been reported [1,4–6].

Plants are the most important source of coumarins, butextraction from plant is tedious, time consuming and needs sophis-ticated instrumentation. Many synthetic methods, like Pechmanncondensation, Perkin, Reformatsky Wittig reaction, Knoevenagelcondensation and Claisen rearrangement have been investigatedfor the synthesis of coumarins [7–10]. The Pechmann condensa-tion reaction is the most simple and widely used method, involvingreactions between activated phenols and beta-ketonic esters or anunsaturated carboxylic acid through an acid catalysed transester-ification, keto-enol tautomerisation, Michael addition and lastlyan acid catalysed dehydration [7]. Generally concentrated sulfuricacid, trifluroacetic acid, or phosphorous pentoxide [7,11,12] is used

∗ Corresponding author. Tel.: +91 278 2567760x704; fax: +91 278 2567562.E-mail addresses: [email protected], [email protected] (A.B. Panda).

for the synthesis of coumarin and their derivatives. Beside these,uses of different other homogeneous catalyst like metal chloridesand sulfonic acid are reported as acid catalyst for the Pechmanncondensation 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 theother hand heterogeneous solid systems are the appropriate as theyare easily recoverable, reusable and minimized the wastes. Duringrecent past, various solid acid catalysts such as zeolite [16], nafion-H [17], amberlyst [18], montmorillonite K 10 [19], poly anilinesulfate salt [20], heteropoly acids [21], functionalized mesoporoussilica (e.g. Zr-TMS, Al-MCM-41) [22,23], metal oxide or modifiedmetal oxides (e.g. sulfated zirconia) [24,25], inorganic ion exchang-ers and other supported catalyst [26] have been employed for thesynthesis of coumarins. These established solid acid catalysts havedisadvantages like poor thermal stability, lack of reproducibility,complex separation, low surface area, less water tolerance abilityand small pores for large-size reactants for which large amount ofcatalyst is required to produce high yield [16–18,27–29]. For exam-ple due to small pore size, zeolite [16] is required in stoichiometricamount for better yield, nafion based catalysts are not thermallystable [28], sulfated zirconia is moisture sensitive [27]. In thisregard, layered zirconium phosphate (L-ZrP) may be an importantalternative 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

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94 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 reportedonly 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 maybe 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 andnarrow pore size distributions with excellent catalytic activitytowards various organic reactions involving bulkier molecules [36].Herein we report the detailed study of the Pechmann condensationreaction 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, molarratio of reactants, amount of catalyst, reaction temperature andtime were investigated. Besides the conventional heating method,microwave assisted synthesis of coumarins was also studied. Here,it should be mentioned that recently microwave irradiation hasbeen found a more useful tool for the synthesis of coumarins inorder to minimize the reaction time [37,38].

2. Experimental

2.1. Materials

Zirconium oxychlorideoctahydrate (ZrOCl2·8H2O, 96.0%), di-ammonium hydrogen ortho-phosphate [(NH4)2HPO4, 98.5%] andcetyltrimethylammonium bromide (CTAB, 98%) were purchasedfrom s. d. Fine Chemicals, India. Ammonium carbonate (ammo-nia 31% equivalent to 95.3%) was purchased from Rankem, Indiaand used as such. Water with a resistivity of 18 M� cm was usedfor all the reactions. High purity phenols (98–99.5%) and EAA (99%)were purchased from Spectrochem and SRL, India and used withoutfurther purification.

2.2. Synthesis of catalyst

The m-ZrP was synthesized using in situ zirconium carbonatecomplex as zirconium source, adopting the reported synthetic pro-cedure [36]. In a typical procedure, zirconium carbonate complexsolution (prepared from zirconium oxychloride and ammoniumcarbonate), (NH4)2HPO4, CTAB and H2O was added in a beakerwith a molar ratio of 0.1 Zr4+:2 PO4

3−:0.25 CTAB:1000 H2O. Afterstirring 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 ◦Cin a glass bottle. Then the mixture was transferred into autoclaveand autoclaved for another one day at 120 ◦C. The resultant whitesolid 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 for6 h. The resultant white calcined powder was used for the catalyticreaction.

2.3. Catalyst characterization

The powder X-ray diffraction pattern of synthesized m-ZrP wasrecorded on a Philips X’pert X-ray powder diffractometre (Ni-

filtered Cu K� radiation, � = 1.5404 A). The BET surface area, totalpore volume, and the average pore diameter were measured by N2adsorption–desorption method by ASAP 2010 Micromeritics (USA),at −196 ◦C, after degassing of sample under vacuum (10−2 Torr) at250 ◦C for 3 h. A scanning electron microscope (SEM) (Leo series1430 VP) was used to determine the morphology of samples. Thesample powder was supported on aluminum stubs and then coatedwith gold by plasma prior to measurement. Transmission elec-tronic microscope (TEM) images were collected using a JEOL JEMmicroscope and samples were prepared by mounting an ethanoldispersed samples on lacy carbon coated Cu grid. 31P solid-stateNMR 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 and1200–1800 cm−1, respectively were recorded on a Perkin-ElmerGX spectrophotometer using a Diffuse Reflectance Scanning disctechnique. DRIFT experiment was carried out using pyridine as aprobe to investigate the types of acid sites present in the cata-lyst. Temperature-programmed desorption (TPD) measurementswere carried out to measure the acid strength of m-ZrP usingammonia as an adsorbate. TPD measurements were conducted ona Micromeritics Autochem-II Chemisorption analyzer by placing200 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 hat 350 ◦C and cooled to100 ◦C. Ammonia (100 Torr) was adsorbedon the samples for 1 h. The physisorbed ammonia was removed byflushing the sample with helium for 1 h. TPD measurements werecarried out in the temperature range of 100–900 ◦C.

2.5. Pechmann condensation of phenolic compounds

High purity resorcinol, 3-amino phenol, 2-methyl resorcinol,phloroglucinol, pyrogallol, 2-hydroxy acetophenone, phenol, wereused 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). Thereactions were performed by conventional heating using an oil bathas well as microwave irradiation (MWI) method using a microwavereactor (MAS-II, SSMCT Co. Ltd., China).

2.5.1. Synthesis of coumarins by conventional heatingThe solvent free liquid phase catalytic condensation was per-

formed in a 25 ml round bottom flask. The temperature of thereaction vessel was maintained using a pre-heated oil bath. In atypical Pechmann condensation of phenols and EAA, 5 mmol phe-nols, 10 mmol of EAA and 15 wt% (weight percent) catalysts withrespect to phenols were magnetically stirred (500 rpm) and heatedat 160 ◦C for 5 h. During the progress of reaction, reaction mixturewas periodically withdrawn and analyzed by a GC (Shimadzu GC2010) to monitor the extent of reaction. The product was also iden-tified by GC–MS (Shimadzu, GCMS-QP 2010). The conversion ofphenols and selectivity of coumarins were calculated on the basis


A. Sinhamahapatra et al. / Applied Catalysis A: General 394 (2011) 93–100 95

of its weight percent using GC data as follows:

% conversion =[

[100 × (initial wt% − final wt%)]initial wt%

]% selectivity = 100 × [GC peak area % of coumarin]∑

total GC peak area % for all the products.

After completion of the reaction, the reaction mixture wascooled 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 crashedice and solid product was obtained. The product was collected byfiltration and re-crystallized using ethanol. Finally the product wascharacterized by 1H NMR analysis and melting point measurement.

To attain the maximum conversion and selectivity, the reactionof resorcinol and EAA was optimized by varying the reaction time,temperature, molar ratio of resorcinol to EAA, amount of catalystwith respect to resorcinol. Here it should be mentioned that thereaction of 3-amino phenol and EAA was very fast. So this reactionwas performed at 110 ◦C for 1 h only.

2.5.2. Synthesis of coumarins by microwave irradiationSynthesis 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 tophenols) were taken into a specially designed round bottom flaskfor microwave reactor, and placed under the MWI at required tem-perature, time and power. After completion of the reaction, theresultant mass was analyzed by GC–MS and GC. The conversionof phenols and selectivity of coumarins were calculated as outlinedabove. The product was isolated following above stated procedure.

The m-ZrP, which was used for the reaction between resorcinoland EAA in both conventional heating and microwave method, wasregenerated by a simple method and reused for 5 times. In a typicalregeneration method, 1 g of used catalyst was refluxed with 40 ml30% (w/v) H2O2 for 3 h at 80 ◦C under continuous stirring. Thenthe catalyst was filtered off, washed with distilled water, and driedovernight at 100 ◦C. After every cycle the regenerated catalyst wasanalyzed by XRD, FT-IR and 31P NMR.

3. Results and discussions

3.1. Catalyst characterization

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 werefound to be 497 m2 g−1, 0.37 cm3 g−1 and 3.0 nm, respectively. Theobserved N2 adsorption–desorption isotherms were similar to typeIV isotherm (Supporting Information) and reveals the mesoporousnature 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). Thepresence 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 thepresence of worm like pores (Supporting Information). The poresare nearly mono-dispersed with an average pore size of ∼3 nm,almost equivalent to the pore size obtained from the surface areameasurement data. The phosphate/zirconium ratio was 1.89 (fromICP experiment). 31P MAS NMR spectroscopy showed one dis-tinguishable resonance positions centre at ∼ı −21 ppm, assignedto 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 ofm-ZrP and lacks the atomic resolution.

Fig. 1. DRIFT spectra of pyridine absorbed m-ZrP at room temperature.

3.2. Acidity measurement

To understand the acidity of the catalyst, DRIFT spectrum wasrecorded by using pyridine as probe. The spectrum (Fig. 1) showedbands at 1541, 1489, 1440 cm−1 indicating the presence of theBrönsted 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 tothe pyridine adsorbed on Lewis acid sites decreased gradually, how-ever, the adsorption band due to pyridine adsorption on Brönstedacid sites remained almost constant, indicating that the weak Lewisacid sites compared to the Brönsted acid sites. The NH3-TPD profileshowed one distinct peak, centre at 433 ◦C with a hump at ∼326 ◦C(Supporting Information) and desorption of NH3 continued evenat 900 ◦C. The result indicates the presence of significant amountof strong acidic sites, probably due to the presence of a reasonableamount of Brönsted acid sites. The extent of desorption is foundto be ca. 1.89 mmol NH3/g of catalyst. The detail discussion can befound in our previous report [36].

3.3. Pechmann condensation of phenolic compounds

3.3.1. Synthesis of coumarins by conventional heatingIn the first set of reaction, intermolecular Pechmann condensa-

tion performed in nitrobenzene as solvent (polar), taking resorcinoland EAA (1:1 molar ratio) in the presence of m-ZrP (10 wt% withrespect to resorcinol) as catalyst yielded 25% conversion of resor-cinol at 120 ◦C after 4 h. On increasing of temperature to 150 ◦Cconversion was increased to 38% in 4 h and 53% after 8 h. Furtherincrease in conversion was not observed by changing the reactiontime or the amount of catalyst (Table 1). The same reaction whenperformed in non polar solvent (toluene) resulted in only 34% con-version after 15 h at 120 ◦C. When same reaction was performed

Table 1Effect of solvent on Pechmann condensation reaction of resorcinol and EAA overm-ZrP.

Solvent Time (h) Temp (◦C) Conversion (%)

Nitrobenzene 4 120 254 150 388 150 53

16 150 54Toluene 15 120 34Solvent free 4 120 51Solvent free 4 150 76

Reaction condition: resorcinol:EAA, 1:1; catalyst, 10 wt% with respect to resorcinol.



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).

in solvent free condition, maximum conversion (76%) of resorci-nol was obtained in 4 h at 150 ◦C (Table 1). The conversion in thepresence of solvent is low may be due to the competitive adsorp-tion of reactants and solvent on the catalyst active sites. Polarityof solvent is also an important factor for the Pechmann condensa-tion reaction, non-polar solvents favour the Pechmann reaction andpolar solvents cause the cleavage [18]. Toluene is the mostly usedsolvent in Pechmann reaction [16,18]. Moreover, different obser-vations have been reported in the literature on solvent study. Forinstance, Sabou et al. [18] reported that toluene is a better solventthan dichloromethane and THF when amberlyst ion-exchange resinwas used as catalyst. Romanelli et al. [21] also reported similarresult using heteropolyacid as catalyst. Wang et al. [39] reportedthat when Yb(OTf)3 used as catalyst, THF was found to be the bestsolvent rather than toluene and dichloromethane, however toluenewas better than that of THF. Tyagi et al. [24] reported that thenitrobenzene is the good solvent than that of toluene when sul-fated zirconia is used as catalyst. These indicate that the variationin the yield depends on the combination of solvent and the catalystused. Further study for the synthesis of coumarins was performedunder solvent free condition.

3.3.1.1. Synthesis of 7-hydroxy 4-methyl coumarin. Initially, theliquid phase Pechmann condensation of resorcinol and EAA to 7-hydroxy-4-methylcoumarin was performed at 120 ◦C for 4 h using10 wt% m-ZrP catalyst with varying ratio of substrate (resorci-nol:EAA::1:1 to 1:3). The yield of 7-hydroxy 4-methyl coumarinwas found to be maximum (63%), when the resorcinol:EAA ratiowas 1:2 as compared to that of 1:1 (51%) (Fig. 2). Further increasein the ratio of substrate, the yield was almost same. The ratio ofresorcinol:EAA, 1:2, was found to be optimum for the solvent freesynthesis of coumarin. Similar result was also reported in previ-ous work [24]. Further experiments for optimization of amountof catalyst, reaction temperature, and reaction time, to attain themaximum conversion and selectivity were performed using thesubstrate 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 theyield, the reaction was carried out at 140 ◦C for 4 h by changingthe amount of catalyst in the range of 5–30 wt% with respect toresorcinol. 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. 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 Pechmanncondition (reaction condition: resorcinol/EAA, 1:2; reaction time, 4 h; temperature,140 ◦C).

100% selectivity, which remained almost constant up to 20 wt% ofcatalyst. With further increase in the amount of catalyst, no signif-icant change in the conversion was observed, however selectivitydecreased 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 catalystincreased in the reaction system and also the availability of activeacid sites of catalyst to substrate increased. Hence the conversionwas increased and reached to maximum. Again in the presence ofexcess amount of acid catalyst (beyond 20 wt%), a side reaction, thering opening of product coumarin followed by acetylation, resultedin the additional product 3-(2,4-dihydroxy-phenyl)-bute-2-enoicacid ethyl ester.

Effect of temperature: The effects of reaction temperature oncatalytic activity (conversion of resorcinol) and selectivity of 7-hydroxy 4-methyl coumarin were examined in the temperaturerange 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 ofresorcinol increased gradually with the increase in temperatureand reached maximum (94%) at 160 ◦C with 100% selectivity for7-hydroxy 4-methyl coumarin. Further increase in temperature,resulted in a slight decrease in selectivity of coumarin with the

Fig. 4. Effect of reaction temperature on conversion of resorcinol, selectivity andyield of 7-hydroxy 4-methyl coumarin under solvent free Pechmann condensationover m-ZrP (reaction condition: resorcinol/EAA, 1:2; amount of catalyst, 15 wt%;reaction time, 4 h).



Fig. 5. Reaction profile (conversion) obtained for the Pechmann condensation ofresorcinol and EAA at 160 ◦C over m-ZrP (reaction condition: resorcinol/EAA, 1:2;amount of catalyst, 15 wt%; temperature, 160 ◦C).

formation of side product 3-(2,4-dihydroxy-phenyl)-bute-2-enoicacid 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 increasedrapidly with increase in reaction time and resulted 94% conver-sion with 100% selectivity in 4 h (Fig. 5). No effect on conversionand selectivity was observed on further increase in reaction time,may be due to the deactivation of active sites or decrease ineffective concentration of reactants. Hence the Peachmann con-densation reaction of resorcinol and EAA in solvent free conditionwith substrate ratio of 1:2 and 15 wt% catalyst at 160 ◦C for 4 h inconventional heating is the optimize condition to get maximumyield (94%) using m-ZrP as solid acid catalyst. This result is betterthan 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 of7-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 acidsites of catalyst by interaction of EAA with catalyst followed by thenucleophilic attack of the hydroxyl group of resorcinol, resulting inan intermediate and ethanol. The intermediate rapidly undergoescyclization through acid catalysed intra-molecular condensationyielding 7-hydroxy-4-methyl coumarin. Another possible mech-anism as reported by Selvakumar et al. [23] is based on reactioncatalysed by acid sites of the catalysts i.e., electrophilic reaction ofchemisorbed ethyl acetoacetate on resorcinol wherein chromonesis produced as side product. In the present reaction, we have notobserved the formation of chromones during reaction, so the mech-anism proposed by Selvakumar et al. [23] was ruled out. Based onthe above discussion, a probable mechanism for the formation of7-hydroxy-4-methylcoumarin using synthesized mesoporous ZrPwas proposed and presented in Scheme 2.

3.3.1.2. Synthesis of other substituted coumarines using differentphenol. 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 seriesof activated as well as less activated phenols with EAA underoptimized reaction conditions, except reaction with m-amino phe-nol. Reaction of m-amino phenol was very fast, so we optimizedthe reaction condition separately. Table 2 represents the resultsobtained using different phenols. From Table 2, it is evident thatthe presence of activated group and position of the activated groupin phenol ring has great influence on the yield of corresponding

Fig. 6. Effect of reaction temperature on the yield of 7-amino 4-methyl coumarinunder 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%; reactiontime, 30 min).

coumarins. Pyrrogallol was less active than that of phloroglucinol,nevertheless both substrate have two electron donating hydroxylgroups. This may be due to the presence of two hydroxyl group ofphloroglucinol at meta-positions activates the aromatic ring morethan that of one hydroxyl group at ortho-positions positions inpyrrogallol. Activity decreased gradually with the decrease in thestrength of the ring activating group. Phenol was least reactive thanother substituted phenols studied here. Still, 57% yield of 4-methylcoumarin was obtained in only 4 h when phenol was used as sub-strate. Reports on Peachmann condensation involving phenol arerare. 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 catalyticactivity is not only dependent on phenolic substrates activity, butalso highly dependent on the composition and textural features ofcatalyst.

3.3.1.3. Condensation of 3-amino phenol and EAA. The condensa-tion reaction of 3-amino phenol with EAA was completed within30 min with 100% yield of 7-amino-4-methyl coumarin. We alsoinvestigated 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 wasperformed in the temperature range of 60–160 ◦C. It was found thatthe yield remained unchanged (100%) from 100 to 160 ◦C and afterthat the conversion decreased gradually. At 60 ◦C the yield was 73%.The condensation reaction between 3-amino phenol and EAA wasfound to be very fast and highly selective. This may be due to thepresence 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 electrondensity at the para position in the ring and felicitates cyclization ofthe intermediate to give 7-amino-4-methyl coumarin.

3.3.2. Synthesis of coumarins by microwave irradiationMicrowave irradiation (MWI) process is fast, energy efficient,

economical and advantageous for selective dielectric heating due tothe variation in dielectric constant of solvent and reactant, and pro-vides significant enhancement in reaction rates [37,38]. We havestudied Pechmann condensation reaction under solvent free condi-tion using a laboratory microwave reactor. Initially, the microwave



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 of7-hydroxy-4-methyl coumarin and 7-amino-4-methyl coumarinkeeping other reaction parameters same (phenol:EAA = 1:2, cat-alyst amount = 15 wt%). The results are shown in Fig. 7. Themicrowave assisted Pechmann condensation reaction was highlydependent on the reaction temperature and microwave power. Forthe condensation of resorcinol and EAA maximum 97% yield of7-hydroxy-4-methyl coumarin was obtained in 15 min at 160 ◦Cunder microwave power of 600 W. With the increase of temper-ature at a constant power (600 W), the yield was decreased due

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 ofcatalyst, 15 wt%; reaction time, 15 min) and (b) 7-amino 4-methyl coumarin inmicrowave assisted synthesis over m-ZrP (reaction condition: 3-amino phenol/EAA,1:2; amount of catalyst, 15 wt%; reaction time, 10 min).

to the formation of side products. One of the main side product 3-(2,4-dihydroxy-phenyl)-but-2-enoic acid ethyl ester was produceddue to the ring opening, followed by acytylation which appear tobe temperature sensitive. Again, at constant temperature the yieldwas also decreased with the increase of power. At lower temper-ature and power, reduction of yield was observed. On lengtheningthe reaction time at lower temperature and lower power the for-mation of side product was also observed. Table 3 represents theyields of corresponding coumarins obtained using different pheno-lic compounds in optimized conditions.

For the condensation of 3-amino phenol and EAA, 100% yieldwas 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 temperatureon yield of 7-amino-4-coumarin. But at 500 W, 93% product yieldwas obtained and it started decreasing with the increase of temper-ature. At 120 ◦C (500 W) the yield was 87%. In both, on increasingor decreasing the temperature at constant power the lower yield ofthe 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, itis evident that synthesis of coumarins using conventional heatingtakes longer time ranging from 3 to 10 h to achieve the maximumyield using solid acid catalyst, whereas synthesis of coumarins bymicrowave irradiation not only reduces the reaction time fromseveral hours to few minutes, but also increases the yield of thecoumarin. As for example, in present case 94% yield was obtainedin conventional heating at 160 ◦C in 4 h whereas, 97% yield wasobtained in microwave irradiation method at 160 ◦C in 15 min with600 W power.

Here it should be mentioned that the use of m-ZrP as solidacid catalyst is advantageous not only for its thermal stability,high water tolerance ability, and easy sedimentation property, andbetter catalytic activity, but also it is an effective catalyst for non-activated phenols. As for example, sulfated zirconia is not active



Table 2Pechmann condensation of different phenols and EAA over m-ZrP by conventional heating.

Entry Substrate Product Time (h) and temperature (◦C) Yield (%)

1

HO OH

O OHO

4 and 160 94

2

HO OH

O OHO

4 and 160 91

3

HO NH2

O OH2N

0.5 and 110 100

4 OH

HO OH O OHO

OH 4 and 160 95

5

HO

OH

OH

O O

OH

HO

4 and 160 90

6

OH O O

4 and 160 56

7

OH O O

O Me

O

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-ZrPresulted 57% and 68% yield of 4 methyl coumarin in conventionalheating and microwave irradiation respectively in the Pechmanncondensation of phenol and EAA.

3.4. Reuse of catalyst

In order to check the recyclability of the catalyst, after eachcycle, the catalyst was filtered, washed with acetone successively,then refluxed with 30% (w/v) H2O2 for 3 h, followed by washingwith water and drying. The dried catalyst was reused for succes-sive cycles. The activity of regenerated m-ZrP was almost identical

on subsequent runs. After five cycles, the activity was reduced by∼2–3% (Fig. 8). The selectivity of the product was almost unaffectedwith the reuse of regenerated catalyst. Here it should be noted thatthe acetone washed catalyst gave only 73% conversion of resor-cinol, may be due to the blockage of active site of the catalyst byreactant or product which may not be fully removed during acetonewash. The regenerated catalyst was characterized for its chemicalcomposition by elemental analysis, FT-IR and 31P NMR after eachreaction. No significant changes in composition or in environmentof phosphate group in zirconium phosphate were observed afterregeneration (Supporting Information). Fig. 9 represents the FT-IRspectrum of as-synthesized, acetone washed and H2O2 treated cat-



Table 3Pechmann condensation of different phenols under microwave irradiation over m-ZrP.

Entry Substrate Yield (%)

1 Resorcinol 972 3-Amino phenola ∼1003 2-Methyl resorcinol 924 Pohloroglucinol 975 Pyrogallol 946 o-Hydroxy acetophenone 917 Phenol 67

Reaction condition: phenols 5 mmol, EAA 10 mmol; temperature: 160 ◦C; time15 min; power 600 W; catalyst 15 wt%.

a In case of 3-amino phenol; temperature: 110 ◦C; time 10 min; power 400 W.

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).

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-hydroxy4-methyl coumarin.

alyst. The IR of the acetone washed used catalyst gave additionalpeaks along with the peaks due to pristine m-ZrP catalyst, indicatedthe presence of organic substance in the acetone washed catalyst.However, IR of H2O2 treated regenerated m-ZrP catalyst is identicalto that of pristine m-ZrP.

4. Conclusion

Mesoporous zirconium phosphate with high surface area andnarrow pore size distribution showed excellent catalytic activity forthe synthesis of substituted coumarins through Pechmann conden-sation even in very low catalyst to substrate ratio (15 wt%). Solvent

free synthesis was found to be better than that of both polar and nonpolar solvent. Among the substituted phenols, m-amino phenol wasfound to be more reactive than other phenols. 100% conversion of m-amino phenol with 100% selectivity of 7-amino 4-methyl coumarinwas 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 hat 160 ◦C using conventional heating. Microwave assisted synthe-sis method was found to be the most appropriate for the synthesisof coumarin derivatives with improved yield as compared to con-ventional heating method. The m-ZrP is easily recoverable fromreaction system and can be reused without reasonable change incatalytic activity.

Acknowledgements

The authors are thankful to DST, India (SR/S1/IC-11/2008) andCSIR (India), Network project (NWP010) for funding.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, inthe online version, at doi:10.1016/j.apcata.2010.12.027.

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Mesoporous zirconium phosphate: An efficient catalyst for the synthesis of coumarin derivatives...

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