Solvent-free syntheses of some quinazolin-4(3H)-ones derivatives

S. Mohana Roopan, T. Maiyalagan, and F. Nawaz Khan

Abstract: Solvent-free syntheses of quinazolin-4(3H)-ones were performed by reaction of anthranillic acid with differ-ent amides, such as nicotinamide, benzamide, formamide, etc., on montmorillonite K-10. Products were confirmed byFTIR, 1HNMR, and 13CNMR spectroscopic techniques. All synthesized compounds exhibited antioxidant properties andhave been compared with standard antioxidant BHT.

Key words: quinazolinone, montmorillonite K-10, solvent-free conditions, antioxidant properties.

Résumé : On a réalisé des synthèses sans solvant de quinazolin-4(3H)-ones par réaction de l’acide anthranillique avecdivers amides, tel le nicotinamide, le benzamide et le formamide sur de la montmorillonite K-10. Les produits ont étécaractérisés par la spectroscopie infrarouge avec transformée de Fourier (IR-TF), et par les méthodes spectroscopiquesde RMN du 1H et du 13C. Tous les produits synthétisés présentent une propriété antioxydante et ils ont été comparésavec l’antioxydant standard, BHT.

Mots-clés : quinazolinone, montmorrillonite K-10, conditions sans solvant, propriétés antioxydante

[Traduit par la Rédaction] Roopan et al. 1025

Introduction

The quinazoline ring skeleton is widely found in alkaloidsand many biologically active compounds. In general, quina-zolones were considered important compounds in the fieldsof pharmacology and biology (1) because of their wide rangeof strong biological activities (2–6). Some of these com-pounds are identified as drugs (7) and as diuretics. Amongthis class of molecules, quinazolin-4-ones and their deriva-tives are well-known to possess an array of physiologicalactivities, e.g., antitubercular (8), antifungal (9), antibacterial(10), anti-inflammatory, anticancer (11), and anti-proliferative(5) activities.

Quinazolin-4(3H)-one was prepared by many methods (5,8, 10–13). However, quinazoline derivatives were synthe-sized mainly by a common approach involving amidation,starting from anthranilic acid, 2-aminobenzonitrile, and 2-aminobenzamide. Other methods included the condensationof anthranilic acid, ammonium acetate, and the orthoesters(14), reaction of imidates and anthranilic acid (15), reactionof polymer-bound isothioureas with isatoic anhydride deriv-atives (16), and were associated with drawbacks such asmultistep procedures (17), costly reagents, harse reactionconditions, complex experimental procedures, and lowyields (18). Previous methods have been excluded frompractical applications because of environmental and eco-nomic considerations. Finding an efficient method for thesynthesis of quinazolin-4(3H)-one is still a challenge. Nowa-days, solvent-free organic reactions have led to experimen-

tally and industrially important organic syntheses that aremore effective and eco-friendly than conventional reactions(19, 20).

In continuation of our interest in C–C bond-forming reac-tions (21–25), we have explored a one-pot synthesis ofquinazolin-4(3H)-ones (Schemes 1 and 2, Tables 1 and 2)from anthranillic acid and amides, such as formamide,acetamide, benzamide, nicotinamide, etc., in the presence ofmontmorillonite K-10 catalyst and other inorganic catalystssuch as acidic alumina, bentonite, etc., (Table 3), undersolvent-free conditions. The above reactions, carried outover montmorillonite K-10 clay, give good yields because ofthe ditopic nature (26, 27) of montmorillonite K-10 clay.However, the reaction takes less time to complete. The opti-mization of catalyst amount was also done (Table 4). Thus,we have developed a simple, economical, and environmen-tally benign synthesis of classical procedures, by avoidingvolatile and toxic organic solvents. The reusability of thecatalyst in synthesis has also been explored (Table 5). Scopeof the reaction (Tables 1 and 2) and antioxidant properties ofthe reaction products have also been discussed.

Experimental

Anthranillic acid and amides used for the reaction werefrom Sigma-Aldrich Co., and montmorillonite K-10 was ob-tained from Fluka. The substances were used as providedwith no other purification. Melting points were taken inopen capillary tubes and are corrected with reference to ben-

Can. J. Chem. 86: 1019–1025 (2008) doi:10.1139/V08-149 © 2008 NRC Canada

1019

Received 17 March 2008. Accepted 29 August 2008. Published on the NRC Research Press Web site at canjchem.nrc.ca on8 October 2008.

S.M. Roopan, T. Maiyalagan,1 and F.N. Khan.1 School of Science and Humanities, Organic Chemistry Division, VIT University,Vellore 632 014, Tamil Nadu, India.

1Corresponding authors (e-mail: maiyalagan@gmail.com, nawaz_f@yahoo.co.in).

zoic acid. IR spectra in KBr pellets were recorded on Nuconinfrared spectrophotometer. Nuclear Magnetic Resonance(1H and 13C) spectra were recorded on a Bruker SpectrospinAvance DPX400 Ultrashield (400 MHz) spectrometer.Chemical shifts are reported in parts per million (δ)downfield from an internal tetramethylsilane reference.

General procedure for the synthesis of 2-substituted-3H-quinazolin-4-ones and 1H,3H-quinazolin-2,4-diones

A mixture of anthranillic acid, 1 amide, 2 or 4a or 4b, andmontmorillonite K-10 clay when heated under refluxconditions gave 2-substituted-3H-quinazolin-4-one 3 or1H,3H-quinazolin-2,4-dione 5 (Scheme 1). After completion

© 2008 NRC Canada

1020 Can. J. Chem. Vol. 86, 2008

Scheme 1. Montmorillonite K-10 catalysed reaction ofanthranillic acid and different amides.

Scheme 2. Montmorillonite K-10 catalysed reaction ofanthranillic acid with urea and thiourea.

Table 1. Synthesis of 2-substituted quinazolinone by solvent-free montmorillonite K-10 catalysis.

of the reaction, ethyl acetate was added to the reaction mix-ture, and the catalyst was recovered by filtration. Filtratewas washed with a 10% NaHCO3 solution to remove anyunreacted acid and further washed with water to remove anyinorganic materials. The organic layer was dried, solventevaporated to obtain the products. FT-IR and NMR spectraltechniques were used for product analysis.

Synthesis of 2-pyridin-3-yl-3H-quinazolin-4-one (3a)Anthranillic acid 1 (10 mmol), nicotinamide 2a

(10 mmol), and montmorillonite K-10 (0.1 g) were placed ina mortar and mixed well, transferred to a 50 mL round-bottomed flask, and refluxed at 150 °C for 30 min. The reac-tion was monitored by TLC, and after completion of the re-action, work-up was performed as above to give crude

© 2008 NRC Canada

Roopan et al. 1021

Table 1 (concluded).

Note: 1 = 10 mmol, 2 = 10 mmol, catalyst = 0.1 g.a3 in isolated yields after column chromatography.bAll products were characterized by 1H NMR and IR spectroscopic data and their melting points were compared with

literature values (31–32).

© 2008 NRC Canada

1022 Can. J. Chem. Vol. 86, 2008

Refluxing at 150 °C solvent-free conditions

Sl. No. Catalyst used Catalyst amount (mg) Time (h) Product 3a

1 Silica gel 10 4 Nil2 Bentonite 10 4 Nil3 Montmorillonite KSF 10 4 Nil4 Acidic alumina 10 4 Low yield5 Montmorillonite K10 10 0.5 High yield

Note: Anthranilic acid 1 (1 mmol) and nicotinamide 2a (1 mmol).

Table 3. Selection of catalyst.

Table 2. Synthesis of quinazolidione by solvent-free montmorillonite K-10 catalysis.

Note: 1 = 10 mmol, 4 = 10 mmol, catalyst = 0.1g.a5 in isolated yields.

Refluxing at 150 °C solvent-free conditions

Sl. No.Amide, RRCONH2

MontmorilloniteK-10 (g)

Time(h)

Product 3a(R)

Yielda

(%)

1 -C5H4N None 2 -C5H4N 40

2 -C5H4N 0.02 1 -C5H4N 59

3 -C5H4N 0.04 1 -C5H4N 67

4 -C5H4N 0.06 1 -C5H4N 65

5 -C5H4N 0.08 0.5 -C5H4N 71

6 -C5H4N 0.1 0.5 -C5H4N 85

7 -C5H4N 0.12 0.5 -C5H4N 86

8 -C5H4N 0.14 0.5 -C5H4N 86

Note: 1 = 10 mmol, 2a = 10mmol, refluxed at 150 °C.a3a in isolated yields.

Table 4. Optimization of catalyst concentration.

product. Pure 2-pyridin-3-yl-3H-quinazolin-4-one 3a wasobtained by performing column chromatography using silicagel and petroleum ether/ethyl acetate as eluent. Yield wasdetermined (Table 1, compound 3a). The quinazolinone 3awas recrystallized from petroleum ether and ethyl acetate.The melting point was found to be 114 °C.

A similar procedure was followed to obtain otherquinazolinone derivatives 3 from different amides 2(Scheme 1 and Table 1). Products were characterized byFTIR, 1HNMR, 13CNMR, and GCMS spectral techniques,and known compounds were compared with literature re-ports. The recrystallization of products was effected usingpetroleum ether and ethyl acetate.

Synthesis of 1H,3H-quinazolin-2,4-dione (5a)A mixture of anthranillic acid 1 (10 mmol), urea 4a

(10 mmol), and 0.1 g of montmorillonite K-10 was heatedunder reflux conditions (150 °C) for 2 h. After completionof the reaction, the catalyst was removed by filtration; themixture was poured into ice-cooled water and extracted withethyl acetate. The product 5a, obtained after solvent re-moval, was purified by performing column chromatographyusing silica gel and petroleum ether/ethyl acetate as eluent(Scheme 2, Table 2). The quinazolindione 5a wasrecrystallized from petroleum ether and ethyl acetate. Themelting point was found to be >300 °C.

Synthesis of 2-thioxo-2,3-dihydro-1H-quinazolin-4-one(5b)

A mixture of anthranillic acid 1 (10 mmol), thiourea 4b(10 mmol), and 0.1 g of montmorillonite K-10 was heatedunder reflux conditions (150 °C) for 2 h. After completionof the reaction, the catalyst was removed; the mixture waspoured into ice-cooled water and extracted with ethyl ace-tate. The product 5b, obtained after solvent removal, was pu-rified by column chromatography (Scheme 2, Table 2). Thedihydroquinazolinone 5b was recrystallized from ethyl ace-tate. The melting point was found to be >300 °C.

Life cycle of the catalystThe reusability of catalyst was explored by checking the

successive runs of the reactions on recycled catalyst; i.e., af-ter first run of the reaction, the catalyst was recovered by asimple filtration from reaction mixture, washed with ethylacetate, and dried. Then it was utilized in the second run ofthe reaction. It was noticed that use of recycled catalyst insubsequent experiments gave similar yields (Table 5). Thus,the catalyst is not leached.

Free-radical scavenging activity of quinazolinonederivatives

Radical scavenging activities are very important due to thedeleterious role of free radicals in foods and biological sys-

tems. In this study, the free-radical scavenging activity ofquinazolin-4(3H)-ones derivative was measured by a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method. This activitywas measured by the following Blos methodology as as-sessed by Ansari et al. (28). The absorbance of DPPH ismonitored at a characteristic wavelength in the presence of asynthesized sample. In its radical form, DPPH absorbs at517 nm, but upon reduction by an antioxidant or a radicalspecies its absorption decreases. Briefly, a 1.5 × 10–4

mmol/L solution of DPPH in ethanol was prepared and 1mL of this solution was added to 3 mL of 1.5 × 10–4 mmol/Lof quinazolinone in ethanol. At each 5 min interval,absorbance was measured at 517 nm until 30 min. The stan-dard used was butylated hydroxyl toluene (BHT), (1.5 × 10–

4 mmol/L) in ethanol solution. Lower absorbance of reactionmixture indicates higher free-radical scavenging activity.Absorbance of the DPPH (control) is 1.544. The capabilityto scavenge DPPH radical (28, 29) was calculated using thefollowing equation,

DPPH Scavenging effect (%)

= [(Acontrol – Asample / Acontrol) * 100]

where Acontrol is the absorbance of the DPPH solution andAsample is the absorbance in the presence of quinazolinone.Two different graphs (Figs. 1 and 2) are plotted with timevs. absorbance and time vs. % inhibition.

Results and discussion

Solvent-free syntheses of quinazolinone 3a fromanthranillic acid 1 and nicotinamide 2a have been exploredby using inorganic catalysts such as montmorillonite K-10,silica gel, acidic alumina, etc. (Table 3). Preliminary resultsindicated the formation of quinazolinone in high yield onlyin the case of montmorillonite K-10. The optimization ofcatalyst amount was done to improve the yield (Table 4).Montmorillonite K-10 has had a great impact in organic syn-thesis and has offered major breakthroughs for the manufac-ture of fine chemicals. This reagent has advantages over the

© 2008 NRC Canada

Roopan et al. 1023

Entry Cycle No.Catalystamount (g)

Yield(%)

1 Cycle I 0.1 852 Cycle II 0.096 823 Cycle III 0.091 81

Table 5. Life cycle of catalyst. Fig. 1. Time vs. absorbance graph for antioxidant property ofquinazolinone derivatives.

conventional homogeneous solution techniques: easy set-upand work-up, mild experimental conditions, and high yield.As part of our research, quinazolin-4(3H)-ones were synthe-sized using K-10 as catalyst (Schemes 1 and 2). The resultsof the quinazolinones synthesis are summarized (Tables 1–5). The essence of the catalyst can be understood from thefollowing facts: when anthranillic acid 1 was treated withmontmorillonite K-10 under conventional heating in thepresence of nicotinamide 2a, the product 3a was obtained inquantitative yield (Table 3, entry 5). When the same reactionwas performed without montmorillonite catalyst, 3a wasobtained in much lower yield in 2 h (Table 4, entry 1). Thereaction optimization with different amounts of montmoril-lonite K-10 was carried out, and at 0.1 g, the yield was good(Table 4).

In the IR spectra of all 4-quinazolinones 3, absorptionbands are observed in the region of 1690–1730 (Ar C=O),1600–1635, 1510–1570, 1460–1500 cm –1 (the quinazolonering). Assignments of 1H NMR signals of quinazolinones 3were derived from splitting patterns and characteristic chem-ical shift values. The data consistently show that thehomocyclic proton signal with the lowest field shift in seriesof compounds is a doublet with additional fine structure dueto further meta and para couplings. This signal is assignedto H-5 on the basis of the proximity to the carbonyl group.The assignment of H-5 led to the assignment of H-8 by de-fault. In the same spectral region, the signal for H-2 is foundas a singlet. The signals for protons H-6 and H-7 show twoortho couplings. We have assigned the H-7 signal to thelower field.

In the present study, quinazolinone derivatives were evalu-ated for their free-radical scavenging activity using theDPPH radical assay. Reduction of DPPH radicals can be ob-served by a decrease in absorbance at 517 nm. Different de-rivatives of quinazolinones reduced DPPH radicalssignificantly. The activity of quinazolinone derivatives was

compared with commercial antioxidant butylated hydroxyltoluene (BHT). 2-Thioxo-2,3-dihydro-1H-quinazolin-4-onehad relatively high DPPH radical-scavenging activity. Asshown in Figs. 1 and 2, all quinazolinone derivatives werefound to have the ability to scavenge hydroxyl radical at aconcentration of 1.5 × 10–4 mmol/L.

Analytical dataData of the new compound 3a and that of a few known

compounds, 3b–3d, 5a–5b, which have not been reportedearlier are given below. The data of a few compounds thathave been found to be identical to those reported (30–32) aregiven as Supplementary Data available with this paper.2

2-Pyridin-3-yl-3H-quinazolin-4-one (3a)Colourless solid, mp 114 °C. IR (KBr pellets, cm–1) ν:

3351.67, 1655.03, 1601.16, 1585.32, 1535.27, 1491.45. 1HNMR (300MHz, CDCl3) δ : 9.1 (s, 1H), 8.76–8.75 (d, J =4.56Hz, 1H), 8.23–8.20 (d, J = 7.77Hz, 1H), 8.13 (s, 1H),7.66–7.64 (d, 1H), 7.46–7.41 (m, 1H), 7.39–7.36 (d, J =7.56, 2H), 7.21–7.16 (m, 1H). 13C NMR (100 MHz, CDCl3)δ : 163.92 (C=O), 152.37, 147.82, 137.49, 135.49, 130.86,129.17, 125.08, 123.73, 120.51. EI-Mass: 223. GC-MS m/z223 (M+) C13H9N3O (mol. wt. 223.23) calcd.: C 69.95, H4.06, N 18.82, O 7.17; found: C 69.83, H 4.14, N 18.75, O7.01.

2-Phenyl-3H-quinazolin-4-one (3b)Mp 242–246 °C (lit. value (32), 242–246 °C). IR (KBr

pellets, cm–1) ν: 3342.55, 1654.76, 1437.47. 13C NMR(100MHz, CDCl3) δ : 165.70 (C=O), 137.85, 134.93, 131.78,129.03, 128.72, 126.95, 124.51, 120.14. C14H10N2O (mol.wt. 222.24) calcd.: C 75.66, H 4.54, N 12.60, O 7.20; found:C 75.54, H 4.46, N 12.52, O 7.11.

2-Methyl-3H-quinazolin-4-one (3c)Mp 240–248 °C (lit. value (32), 238–240 °C). IR (KBr

pellets, cm–1) ν: 3295.81, 1666.07, 1434.67. C9H8N2O (mol.wt. 160.17) calcd.: C 67.49, H 5.03, N 17.49, O 9.99; found:C 67.31, H 5.13, N 17.51.

3H-Quinazolin-4-one (3d)White solid, mp 216 °C (lit. value (32), 215–216 °C). IR

(KBr pellets, cm–1) ν: 3428.88, 1704.98, 1665.87. 13C NMR(75MHz, CDCl3) δ : 143.34, 134.89, 127.76, 127.42, 126.35.C8H6N2O (mol. wt. 146.15) calcd.: C 65.75, H 4.14, N19.17, O 10.95; found: C 65.80, H 4.03, N 19.04, O 10.86.

(4-Oxo-quinazolin-2yl)-acetonitrile (3e)Colourless solid, mp 240 °C (lit. value (32), 242 °C.

C10H7N3O (mol. wt. 185.18) calcd.: C 64.86, H 3.81, N22.69, O 8.64; found: C 64.74, H 3.91, N 22.57, O, 8.58.

2-(4-Methylphenyl)quinazolin-4(3H)-one (3g)Colourless solid, mp 240 °C (lit. value (31), 239 °C). 13C

NMR (75MHz, CDCl3) δ : 159.9, 147.34, 146.20, 134.31,133.20, 131.58, 128.15, 127.12, 126.35, 125.14, 124.81,124.13, 122.11, 19.30. GC-MS m/z 236 (M+).

© 2008 NRC Canada

1024 Can. J. Chem. Vol. 86, 2008

Fig. 2. Time vs. % inhibition graph for antioxidant property ofquinazolinone derivatives.

2 Supplementary data for this article are available on the journal Web site (canjchem.nrc.ca) or may be purchased from the Depository ofUnpublished Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 3833. For moreinformation on obtaining material refer to cisti-icist.nrc-cnrc.gc.ca/cms/unpub_e.shtml.

2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3h)Pale yellow, mp 245–247 °C (lit. value (31), 244 °C). 13C

NMR (75MHz, CDCl3) δ : 161.22, 148.33, 146.20, 134.32,133.20, 131.56, 128.11, 127.10, 126.22, 125.14, 124.81,124.21, 122.13, 19.31. GC-MS m/z 252 (M+).

2-(4-Chlorophenyl)quinazolin-4(3H)-one (3j)Colourless solid, mp 306–308 °C (lit. value (31), 312 °C).

13C NMR (75MHz, CDCl3) δ : 160.12, 147.73, 146.64,136.45, 135.26, 134.66, 132.62, 130.55, 128.33, 127.91,126.84, 124.14, 122.43, 19.31. GC-MS m/z 240 (M+).

1H,3H-Quinazolin-2,4-dione (5a)Pale yellow solid, mp >300 °C (lit. value (32) >280 °C).

IR (KBr pellets, cm–1) ν: 3367.88 (br), 1673.92, 1609.99.C8H6N2O2 (mol. wt. 162.15) calcd.: C 59.26, H 3.73, N17.28, O 19.73; found: C 59.14, H 3.67, N 17.16, O 19.82.

2-Thioxo-2,3-dihydro-1H-quinazolin-4-one (5b)Colourless solid, mp >300 °C. IR (KBr pellets, cm–1) ν:

3406.32, 3203.67, 3008.42, 1696.52, 1263.87. 1H NMR(400MHz, CDCl3) δ : 7.89 (s, 1H, NH), 7.45–7.44 (d, 1H),7.43–7.42 (d, 1H), 7.41–7.37(m, 2H) 7.34 (s, 1H, NH). 13CNMR (100MHz, CDCl3) δ : 179.94 (C=S), 137.05, 129.62,127.15, 125.30. C8H6N2OS (mol. wt. 178.21) calcd.: C53.92, H 3.39, N 15.72, O 8.98, S 17.99; found: C 53.84, H3.48, N 15.81, O 8.87, S 17.87.

Conclusion

In conclusion, we have reported a facile synthesis ofquinazolin-4(3H)-ones under solvent-free conditions andconventional heating, demonstrating the use of montmorillo-nite K-10 as an efficient, rapid, mild, and inexpensive cata-lyst. The procedure has the advantages of simplicity andeasy product isolation, coupled with high purity and yields.

Acknowledgement

The authors wish to express their gratitude to SyngeneInternational Limited for their support of their NMR andGCMS facilities to carry this research work.

References

1. D.J. Brown. In Comprehensive heterocyclic chemistry. Vol. 3.Edited by A.R. Katritzky and C.W Rees. Pergamon Press, Ox-ford, UK. 1984. p. 57.

2. H. Wamhoff and J. Dzenis. Adv. Heterocyclic. Chem. 55, 129(1992).

3. S. Sinha and M. Srivastava. Prog. Drug Res. 43, 143 (1994).4. X. Gao, X. Cai, K. Yan, B. Song, L. Gao, and Z. Chen. Mole-

cules, 12, 2621 (2007).

5. S. Yang, Z. Li, L. Jin, B. Song, G. Liu, J. Chen, Z. Chen, D.Hu, W. Xue, and R. Xu. Bioorg. Med. Chem. Lett. 17, 2193(2007).

6. J. Bartroli, E. Turmo, M. Alguero, E. Boncompte, M.L.Vericat, L.Conte, J. Ramis, M. Merlos, J.G. Rafanell, and J.Forn. J.Med.Chem. 41, 1869 (1998).

7. B.A. Keay and P.W. Dibble. In Comprehensive HeterocyclicChemistry. Vol. II. Edited by A.R. Katritzky, C.W. Rees, andE.F.V. Scriven. Pergamon Press, Oxford, UK. 1996. pp. 395–436.

8. J. Kunes, J. Bazant, M. Pour, K. Waisser, M. Slosarek, and J.Janota. Il Farmaco, 55, 725 (2000).

9. G. Grover and S.G. Kini. Eur. J. Med. Chem. 41, 256 (2006).10. A.K. Tiwari, V.K. Singh, A. Bajpai, G. Shukla, S. Singh, and

A.K. Mishra. Eur. J. Med. Chem. 42, 1234 (2007).11. P.M. Chandrika, T. Yakaiah, A.R.R. Rao, B. Narsaiah, N.C.

Reddy, V. Sridhar, and J.V. Rao. Eur. J. Med. Chem. 43, 846(2008).

12. D.J. Connolly, D.Cusack, T.P.O. Sullivan, and P.J. Guiry. Tet-rahedron, 61, 10153 (2005).

13. G.M. Buckley, N. Davies, H.J. Dyke, P.J. Gilbert, D.R.Hannah, A.F. Haughan, C.A. Hunt, W.R. Pitt, R.H. Profit, N.C.Ray, M.D. Richard, A. Sharpe, A.J. Taylor, J.M. Whitworth,and S.C. Williams. Bioorg. Med. Chem. Lett. 15, 751 (2005).

14. K. Rad-Moghadam and M. Mohseni. J. Chem. Res.Synop. 487 (2003).

15. W. Ried and W. Stephan. Chem. Ber. 96, 1218 (1963).16. R.Y. Yang and A. Kaplan. Tetrahedron Lett. 41, 7005 (2000).17. V. Alagarsamy, S. Murugesan, K. Dhanabal, M. Murugan, and

E. De Clercq. Indian J. Pharm. Sci. 69, 304 (2007).18. P. Pannerselvam, R.V. Pradeepchandran, and S.K. Sridhar. In-

dian J. Pharm. Sci. 65, 268 (2003).19. R.S. Varma. Green Chem. 1, 43 (1999).20. R.S. Varma. Clean Prod. Pros. 1, 132 (1999).21. F. Nawaz Khan, R. Jayakumar, and C. N. Pillai. J. Mol. Catal.

A: Chem. 195, 139 (2003).22. F. Nawaz Khan, R. Jayakumar, and C.N. Pillai. Tetrahedron

Lett. 43, 6807 (2002).23. V.R. Hathwar, P. Manivel, F. Nawaz Khan, and T.N. Guru

Row. Acta Crystallogr. Sect. E, 63, o3707 (2007).24. V.R. Hathwar, P. Manivel, F. Nawaz Khan, and T.N. Guru

Row. Acta Crystallogr. Sect. E, 63, o3708 (2007).25. S. Syed Tajudeen and F. Nawaz Khan. Synth. Commun. 37,

3649 (2007).26. M.D. Bhor, N.S. Nandurkar, M.J. Bhanushali, and B.M.

Bhanage. Ulrasonics Sonochemistry, 15, 195 (2008).27. M. Kidwai and R. Mohan. J. Chin. Chem. Soc. 47, 1205 (2006).28. N.M. Ansari, L. Houlihan, B. Hussain, and A. Pieroni.

Phytother. Res. 19, 907 (2005).29. H. Chen, M. Zhang, and B. Xie. J. Agric. Food Chem. 52, 11

(2004).30. C.A. Jaleel, P. Manivannan, B. Sankar, A. Kishorekumar, R.

Gopi, R. Somasundaram, and R. Panneerselvam. ColloidsSurf. B Biointerfaces, 60, 201 (2007).

31. T.Mc.C. Paterson, R.K. Smalley, and H. Suschitzky. Synthesis,187 (1975).

32. F. Li, Y. Feng, Q. Meng, W. Li, Z. Li, Q. Wang, and F. Tao.ARKIVOC, i, 40 (2007).

© 2008 NRC Canada

Roopan et al. 1025