Research ArticleSynthesis and Biological Evaluation of4-(3-Hydroxy-benzofuran-2-yl)coumarins

Puttaraju Boregowda1 Shivashankar Kalegowda1 Vijaykumar Pandurang Rasal2

Jagadeeshreddy Eluru2 and Ebenezer Koyye2

1 PG Department of Chemistry Central College Campus Bangalore University Bangalore Karnataka 560 001 India2Department of Pharmacology KLE Universityrsquos College of Pharmacy Belgaum Karnataka 590 010 India

Correspondence should be addressed to Shivashankar Kalegowda shivashankarkgmailcom

Received 27 November 2013 Accepted 27 January 2014 Published 27 March 2014

Academic Editor Vito Ferro

Copyright copy 2014 Puttaraju Boregowda et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Various 4-bromomethylcoumarins (1a-k) were reacted with methyl salicylate to yield 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid methyl esters (2a-k) Formations of (3a-k) were achieved by using DBU under microwave irradiation Structures of allthe compounds were established on the basis of their spectral data All the compounds were tested in vitro for their antimicrobialactivity and cell cytotoxicity All the tested compounds (2b-k) and (3a-k) were shown to be better activity against Staphylococcusaureus than the standard Ciprofloxacin The compound (3k) (R = 6-OMe) was found to be more potent cytotoxic than the standard5-fluorouracil

1 Introduction

Benzofuran and its derivatives [1] have attracted consid-erable interest in recent years for their versatile proper-ties in chemistry and pharmacology 3-Benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin [2] was found tobe the most potent antitubercular agent against Mycobac-terium tuberculosis even better than standard drug isoniazidBenzofuran derivatives [3] were found to exhibit favorableantibacterial activity against Staphylococcus aureus and Bacil-lus subtilis which were better than the control drugs Cefo-taxime and Ketoconazole 2-Phenylbenzofurans [4] exhibitedenhanced antiprotozoal activity against Trypanosoma bruceirhodesiense and Plasmodium falciparum 2-Arylbenzofurans[5] were isolated from the roots ofGlycyrrhiza uralensisTheyshowed significant in vitro protein tyrosine phosphate-1Binhibitory activity Technetium-99m labeled pyridyl benzofu-ran derivatives [6] was tested as potential probes for imaging120573-amyloid plaques in Alzheimerrsquos brains using single photonemission computed tomography

Coumarin moieties are widely featured in a broad rangeof pharmacological and biologically active compounds [78] Phosphorohydrazine derivatives of coumarin displayed

high in vivo antitumour activity against P388 leukemia [9]Coumarin pyrazoline hybridswere found to possess the high-est cytotoxicity against colorectal cell line HCT-116 with IC

50

value of 001120583M [10]Thiazolyl coumarin derivatives showedsignificant inhibition against Haemophilus influenzae with aMIC value of 15 120583M which is less than that of tetracycline[11] Benzo[d]thiazolyl coumarins [12] demonstrated anti-HIV activity against HIV-1 cell with EC

50lt 7 120583gmL

Based on the survey of recent literature studies oncoumarins and benzofurans and in our effort to discovernovel antimicrobial [13ndash16] and anticancer agents [17 18] theaim of our work is synthesis of 4-(3-hydroxy-benzofuran-2-yl)coumarins and the evaluation of them for their therapeuticimportance

2 Chemistry

The synthetic scheme for the target molecules wasinitiated by the Pechmann cyclisation of phenols with4-bromoethylacetoacetate [19] leading to the required4-bromomethylcoumarins [20ndash22] (1a-k) The compound 4-(6-methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid

Hindawi Publishing CorporationOrganic Chemistry InternationalVolume 2014 Article ID 297586 7 pageshttpdxdoiorg1011552014297586

2 Organic Chemistry International

methyl ester [23] (2a) (R = 6-CH3) was synthesized by

reacting 4-bromomethyl-6-methylcoumarin and methylsalicylate in the presence of anhydrous K

2CO3 Using this

method the compounds (2b-k) were synthesized Theseintermediates (2a-k) did not yield the products (3a-k) inthe presence of DBU in DMF under thermal conditionsHowever when subjected to microwave irradiation affordedthe compounds (3a-k) (Scheme 1) The completion of thereaction is monitored by TLC A plausible mechanisticpathway proposed for the title compounds involves thegeneration of a carbanion at the active methylene group(C4ndashCH2) which is stabilized by coumarin ring [24] The

intramolecular ring closure occurred when carbanionattacked the carbonyl carbon of methyl ester and eliminatedmethanol to form 4-(3-oxo-23-dihydro-benzofuran-2-yl)-coumarins that underwent in situ aromatization under thereaction conditions to yield 4-(3-hydroxy-benzofuran-2-yl)-coumarins (Figure 1) The high melting solids separated inthe reaction mixture were filtered off to obtain compounds(3a-k) as crystalline solids

3 Results and Discussion

The structures of novel (2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid methyl esters and 4-(3-hydroxy-benzofuran-2-yl)-coumarins were established from IR 1HNMR 13CNMRand LC-MS data as illustrated for a representative exampleIn the IR spectrum of 2-(7-methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid methyl ester (2b) (R = 7-CH

3)

the lactone carbonyl stretching frequency was appeared at1720 cmminus1 whereas the methyl ester carbonyl stretchingfrequency was observed at 1742 cmminus1The 1HNMR spectrumof the compound (2b) displayed a singlet at 120575 240 385552 and 685 due to CH

3 OCH

3 OCH

2and C

3ndashH protons

respectively The aromatic protons resonated as a multiplet at120575 710ndash783

The IR spectrum of the compound 4-(3-hydroxy-benzofuran-2-yl)-6-methylcoumarin (3a) (R = 6-CH

3)

displayed a lactone carbonyl stretching frequency at1729 cmminus1 whereas the ndashOH stretching frequency appearedat 3450 cmminus1 The 1H NMR spectrum of the compound (3a)showed a singlet at 120575 242 and 693 due to CH

3and C

3ndashH

protons respectively The aromatic protons were resonatedas a multiplet at 120575 723ndash848 The ndashOH proton observed as asinglet at 120575 1142 that was confirmed by D

2O exchange The

mass spectrum (LC-MS) of the compound (3g) displayed a[M+H] peak at 307The 13CNMR spectral data of compound(3h) are given in the experimental section

4 Antimicrobial Activity

All the newly synthesized compounds (2b-k) and (3a-k)were screened for their antibacterial and antifungal activityat different concentrations of 100 50 25 125 625 312516 08 and 02 120583gmL via broth microdilution method Theminimum inhibitory concentrations (MIC) were determinedby serial dilution method [25]

Antibacterial activity was carried out against three Gram-positive bacteria namely Staphylococcus aureus Enterococcusfaecalis and Streptococcus mutans and three Gram-negativebacteria namely Escherichia coli Klebsiella pneumonia andPseudomonas aeruginosa Ciprofloxacin was used as a stan-dard Antifungal activity was carried out against two funginamelyCandida albicans andAspergillus fumigatus Flucona-zole was used as a standard

The investigation of antimicrobial screening data(Table 1) showed thatmost of the tested compounds exhibitedgood bacterial and fungal inhibition The compounds (2b)(R = 7-CH

3) (2c) (R = 6-Cl) (2e) (R = 6-F) and (2f) (R =

56-benzo) were found to be very active against S mutanswith MIC of 02 120583gmL The compounds (2c) (R = 6-Cl)and (2i) (R = 6-tert-butyl) were found to be highly activeagainst E coli with MIC of 02 120583gmLThe compound (2i) (R= 6-tert-butyl) displayed high activity against A fumigatuswith MIC of 02 120583gmL The compounds (3a) (R = 6-CH

3)

and (3b) (R = 7-CH3) were found to be highly active against

S aureus E faecalis and S mutans with MIC of 02 120583gmLThe compounds (3e) (R = 6-F) and (3f) (R = 56-benzo)were found to be highly active against S aureus and Calbicans with MIC of 02 120583gmL The compounds (3g) (R =68-dimethyl) (3h) (R = 6-isopropyl) (3i) (R = 6-tert-butyl)and (3j) (R = 6-benzyl) exhibited high activity against Saureus S mutans and C albicans with MIC of 02 120583gmLThe compound (3k) (R = OMe) showed high activityagainst S aureus and C albicans with MIC of 02 120583gmLIt is to be noted that most of these compounds exhibitedmoderate activity against P aeruginosa and inactive againstK pneumonia

In general uncyclized compounds (2b-k) aremore potentthan the cyclized compounds (3a-k) against S mutans andE coli The cyclized compounds (3a-k) are more potentthan the uncyclized compounds (2b-k) against E faecalisand C albicans It is interesting to found that both cyclizedand uncyclized compounds showed better activity against Saureus than the standard Ciprofloxacin

5 In Vitro Cell Cytotoxicity

All the newly synthesized compounds (2b-k) and (3a-k)were evaluated for their cytotoxicity against DAL cell usingtrypan blue dye exclusion assay The detail procedure hasbeen described in our earlier publications [26 27]

The investigation of in vitro cell cytotoxicity (Table 2)revealed that most of the tested compounds exhibited goodactivity The compounds (2d) (R = 6-Br) (2h) (R = 6-isopropyl) (2i) (R = 6-tert-butyl) (2j) (R = 6-benzyl) (2k)(R = 6-OMe) (3a) (R = 6-CH

3) (3c) (R = 6-Cl) (3f)

(R = 56-benzo) (3g) (R = 68-dimethyl) (3h) (R = 6-isopropyl) (3i) (R = 6-tert-butyl) and (3k) (R = 6-OMe)were found to be highly active (gt70) against DAL cell atthe concentration of 100 120583gmLThe compound (2f) (R = 56-benzo) was found to be poor active (25) against DAL cell atthe concentration of 100 120583gmL The rest of the compoundswere found to be moderately active (gt40) In general thecyclized compounds (3a-k) were found to be more potentthan the uncyclized compounds (2b-k)

Organic Chemistry International 3

O

Br

OR

Anhydrous

OH

O

O

O

OR

O

O

O

DBUDMF

OR

O

O OH

11 examples

Dry acetone

R = a 6-CH3 b 7- c 6-Cl d 6-Br e 6-F f 56-benzo g 68-dimethyl h 6-isopropyl k 6-OCH3

K2CO3

140∘C 4min

84ndash96

RT 24h stirrMWI 370W

CH3

(1andashk) (2andashk) (3andashk)

i 6-tert-butyl j 6-benzyl

Scheme 1 Synthesis of compounds (2a-k) and (3a-k)

O

O

O

O

O

O O

O OH

R

O

O

O

O

O

R

R

O O

O OH

R

NN

O

O

O

O

O

H

DBU =

R

4-(3-oxo-23-dihydro-benzofuran-2-yl)-coumarins

MeOminus

DBU H+

DBU MW

minus

minus

Figure 1 Plausible mechanism for the synthesis of (3a-k)

6 Experimental Section

The melting points were measured with an electric meltingpoint apparatus and are uncorrected The IR spectra wereobtained using a Shimadzu-8400S FT-IR spectrophotometer1H NMR and 13C NMR spectra in DMSO-119889

6solution were

recorded at 25∘Con a Bruker 300 and 400MHz spectrometerrespectively The 1H chemical shifts were reported in 120575 ppmand referenced toTMSThemass spectrawere recorded on anAgilent-Single Quartz LC-MS The purity of the compoundswas checked by TLC Microwave reactions were carried outon Milestone Laboratoryrsquos microwave reactor The elemental

analyses were carried out using Elemental Vario Micro CubeCHNS Rapid Analyzer All the compounds gave satisfactoryelemental analysis

General Procedure for the Synthesis of Compounds (2a-k)Methyl salicylate (0304 g 20mmol) and anhydrous K

2CO3

(138 g 10mmol) were stirred in 25mL of dry acetonefor 30min 4-Bromomethylcoumarin (1a-k) (20mmol) wasadded and stirring was continued for 24 h The reactionmixture was concentrated to one-fourth volume and pouredonto crushed iceThe solid separated was filtered and washedwith 10mL of 5HClThen it was washedwith 50mL of cold

4 Organic Chemistry International

Table 1 Results of antimicrobial activities of the synthesized compounds (2bndashk) and (3andashk) MICs (120583gmL)

Compounds Gram-positive Gram-negative FungiNumber R S aureus E faecalis S mutans E coli K pneumonia P aeruginosa C albicans A fumigatus2b 7-CH3 04 50 02 625 100 625 125 042c 6-Cl 04 16 02 02 50 312 125 042d 6-Br 08 25 04 16 100 312 125 042e 6-F 04 312 02 16 100 625 gt100 082f 56-benzo 04 50 02 625 100 625 125 042g 68-dimethyl 16 08 08 312 100 50 100 162h 6-isopropyl 08 625 04 04 100 25 125 042i 6-tert-butyl 08 625 08 02 100 25 125 022j 6-benzyl 08 125 04 16 100 625 100 082k 6-OMe 08 312 08 312 100 100 100 083a 6-CH3 02 02 02 50 100 50 125 mdash3b 7-CH3 02 02 02 100 50 gt100 02 mdash3c 6-Cl 02 04 02 100 100 25 312 mdash3d 6-Br mdash mdash mdash mdash mdash mdash mdash mdash3e 6-F 02 04 04 100 100 gt100 02 mdash3f 56-benzo 02 04 312 50 100 02 02 mdash3g 68-dimethyl 02 04 02 100 100 50 02 mdash3h 6-isopropyl 02 04 02 50 100 312 02 mdash3i 6-tert-butyl 02 08 02 50 gt100 625 02 mdash3j 6-benzyl 02 08 02 100 100 50 02 mdash3k 6-OMe 02 04 312 50 100 625 02 mdash

Ciprofloxacin 2 2 2 1 1 4 mdash mdashFluconazole mdash mdash mdash mdash mdash mdash 16 8

water The crude product was dried and recrystallised fromethanol

2-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2b) Yield 90 colorless solid mp 168ndash170∘CIR (KBr cmminus1) 1720 (lactone C=O) 1742 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 240 (s 3H CH

3)

385 (s 3H OCH3) 552 (s 2H OCH

2) 685 (s 1H C

3ndashH)

710ndash783 (m 7H ArndashH) ppm Anal Cald for C19H16O5 C

7036 H 497 Found C 7027 H 489

2-(6-Chloro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2c) Yield 92 colorless solid mp 188ndash191∘C IR(KBr cmminus1) 1730 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 381 (s 3H OCH

3)

546 (s 2H OCH2) 690 (s 1H C

3ndashH) 707ndash804 (m 7H

ArndashH) ppm Anal Cald for C18H13ClO5 C 6271 H 380

Found C 6265 H 373

2-(6-Bromo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2d) Yield 89 yellow solid mp 147ndash149∘C IR(KBr cmminus1) 1714 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (s 3H OCH

3)

549 (s 2H OCH2) 679 (s 1H C

3ndashH) 712ndash782 (m 7H

ArndashH) ppm Anal Cald for C18H13BrO5 C 5555 H 337

Found C 5548 H 332

2-(6-Fluoro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2e) Yield 90 colorless solid mp 186ndash149∘CIR (KBr cmminus1) 1724 (lactone C=O) 1739 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 386 (s 3H

OCH3) 550 (s 2H OCH

2) 692 (s 1H C

3ndashH) 710ndash812

(m 7H ArndashH) ppm Anal Cald for C19H15FO4 C 6993 H

463 Found C 6986 H 458

2-(56-Benzo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2f ) Yield 90 light yellow solid mp 183ndash186∘C IR (KBr cmminus1) 1728 (lactone C=O) 1746 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 383 (s 3H

OCH3) 595 (s 2H OCH

2) 712ndash842 (m 11H ArndashH) ppm

Anal Cald for C22H16O5 C 7333 H 448 Found C 7326

H 440

2-(68-Dimethyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2g) Yield 91 colorless solid mp 193ndash195∘C IR (KBr cmminus1) 1727 (lactone C=O) 1739 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 236 (d 6H

68-dimethyl) 385 (s 3H OCH3) 547 (s 2H OCH

2) 684

Organic Chemistry International 5

Table 2 Results of in vitro cytotoxicity of the synthesized compounds (2bndashk) and (3andashk) against Daltonrsquos Ascitic Lymphoma cell (1 times 105)at the concentration of 100 120583gmL

Number of compounds R Number of cells of dead cellsLive Dead

2b 7-CH3 49 51 512c 6-Cl 41 59 592d 6-Br 19 81 812e 6-F 42 58 582f 56-benzo 75 25 252g 68-dimethyl 55 45 452h 6-isopropyl 12 88 882i 6-tert-butyl 16 84 842j 6-benzyl 13 87 872k 6-OMe 18 82 823a 6-CH3 21 79 793b 7-CH3 56 44 443c 6-Cl 15 85 853d 6-Br mdash mdash mdash3e 6-F 34 66 663f 56-benzo 13 87 873g 68-dimethyl 21 79 793h 6-isopropyl 26 74 743i 6-tert-butyl 15 85 853j 6-benzyl 53 47 473k 6-OMe 11 89 895-Fluorouracil mdash 12 88 88

(s 1H C3ndashH) 708ndash782 (m 6H ArndashH) ppm Anal Cald for

C22H22O5 C 7110 H 536 Found C 7103 H 529

2-(6-Isopropyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2h) Yield 97 colorless solid mp 179ndash182∘CIR (KBr cmminus1) 1718 (lactone C=O) 1746 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 127 (d 6H 2-CH

3of

isopropyl) 302 (m 1H CHof isopropyl) 388 (s 3H OCH3)

555 (s 2H OCH2) 688 (s 1H C

3ndashH) 710ndash787 (m 7H Arndash

H) ppm Anal Cald for C21H20O5 C 7158 H 572 Found

C 7150 H 566

2-(6-Tert-butyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2i) Yield 89 colorless solid mp 172ndash173∘CIR (KBr cmminus1) 1716 (lactone C=O) 1728 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 137 (s 9H 6-tert-butyl)

381 (s 3H OCH3) 553 (s 2H OCH

2) 693 (s 1H C

3ndashH)

723ndash791 (m 7H ArndashH) ppm Anal Cald for C21H20O5 C

7200 H 605 Found C 7183 H 597

2-(6-Benzyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2j) Yield 89 colorless solid mp 172ndash175∘CIR (KBr cmminus1) 1712 (lactone C=O) 1738 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 384 (s 3H OCH

3) 403

(s 2H C6ndashCH2) 551 (s 2H OCH

2) 686 (s 1H C

3ndashH)

710ndash789 (m 12H ArndashH) ppm Anal Cald for C25H20O5 C

7499 H 503 Found C 7491 H 495

2-(6-Methoxy-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2k) Yield 95 colorless solid mp 174ndash176∘CIR (KBr cmminus1) 1720 (lactone C=O) 1739 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (d 6H 6-OCH

3

OCH3) 552 (s 2H OCH

2) 684 (s 1H C

3ndashH) 713ndash782 (m

7H ArndashH) ppm Anal Cald for C19H16O6 C 6705 H 474

Found C 6697 H 467

General Procedure for the Synthesis of Compounds (3a-k)A mixture of 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2a-k) (20mmol) DBU (03 g 20mmol)and DMF (25mL) were added to a microwave tube equippedwith a magnetic stir bar The microwave tube was fitted witha reflux condenser and irradiated in a microwave reactor ata temperature of 140∘C for 4min at a maximum power of370WThen completion of the reaction mixture was pouredonto ice cold water and neutralizedwith dil HCl solutionThesolid separated was filtered and washed with 100mL of coldwater The crude product was dried and recrystallised fromethanol

4-(3-Hydroxy-benzofuran-2-yl)-6-methyl-chromen-2-one (3a)Yield 90 yellow solid mp 221ndash224∘C IR (KBr cmminus1) 1729(lactone C=O) 3450 (OH) 1HNMR (300MHz DMSO-119889

6)

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

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Carbohydrate Chemistry

International Journal of

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Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

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Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Analytical ChemistryInternational Journal of

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Quantum Chemistry

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Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

2 Organic Chemistry International

methyl ester [23] (2a) (R = 6-CH3) was synthesized by

reacting 4-bromomethyl-6-methylcoumarin and methylsalicylate in the presence of anhydrous K

2CO3 Using this

method the compounds (2b-k) were synthesized Theseintermediates (2a-k) did not yield the products (3a-k) inthe presence of DBU in DMF under thermal conditionsHowever when subjected to microwave irradiation affordedthe compounds (3a-k) (Scheme 1) The completion of thereaction is monitored by TLC A plausible mechanisticpathway proposed for the title compounds involves thegeneration of a carbanion at the active methylene group(C4ndashCH2) which is stabilized by coumarin ring [24] The

intramolecular ring closure occurred when carbanionattacked the carbonyl carbon of methyl ester and eliminatedmethanol to form 4-(3-oxo-23-dihydro-benzofuran-2-yl)-coumarins that underwent in situ aromatization under thereaction conditions to yield 4-(3-hydroxy-benzofuran-2-yl)-coumarins (Figure 1) The high melting solids separated inthe reaction mixture were filtered off to obtain compounds(3a-k) as crystalline solids

3 Results and Discussion

The structures of novel (2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid methyl esters and 4-(3-hydroxy-benzofuran-2-yl)-coumarins were established from IR 1HNMR 13CNMRand LC-MS data as illustrated for a representative exampleIn the IR spectrum of 2-(7-methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acid methyl ester (2b) (R = 7-CH

3)

the lactone carbonyl stretching frequency was appeared at1720 cmminus1 whereas the methyl ester carbonyl stretchingfrequency was observed at 1742 cmminus1The 1HNMR spectrumof the compound (2b) displayed a singlet at 120575 240 385552 and 685 due to CH

3 OCH

3 OCH

2and C

3ndashH protons

respectively The aromatic protons resonated as a multiplet at120575 710ndash783

The IR spectrum of the compound 4-(3-hydroxy-benzofuran-2-yl)-6-methylcoumarin (3a) (R = 6-CH

3)

displayed a lactone carbonyl stretching frequency at1729 cmminus1 whereas the ndashOH stretching frequency appearedat 3450 cmminus1 The 1H NMR spectrum of the compound (3a)showed a singlet at 120575 242 and 693 due to CH

3and C

3ndashH

protons respectively The aromatic protons were resonatedas a multiplet at 120575 723ndash848 The ndashOH proton observed as asinglet at 120575 1142 that was confirmed by D

2O exchange The

mass spectrum (LC-MS) of the compound (3g) displayed a[M+H] peak at 307The 13CNMR spectral data of compound(3h) are given in the experimental section

4 Antimicrobial Activity

All the newly synthesized compounds (2b-k) and (3a-k)were screened for their antibacterial and antifungal activityat different concentrations of 100 50 25 125 625 312516 08 and 02 120583gmL via broth microdilution method Theminimum inhibitory concentrations (MIC) were determinedby serial dilution method [25]

Antibacterial activity was carried out against three Gram-positive bacteria namely Staphylococcus aureus Enterococcusfaecalis and Streptococcus mutans and three Gram-negativebacteria namely Escherichia coli Klebsiella pneumonia andPseudomonas aeruginosa Ciprofloxacin was used as a stan-dard Antifungal activity was carried out against two funginamelyCandida albicans andAspergillus fumigatus Flucona-zole was used as a standard

The investigation of antimicrobial screening data(Table 1) showed thatmost of the tested compounds exhibitedgood bacterial and fungal inhibition The compounds (2b)(R = 7-CH

3) (2c) (R = 6-Cl) (2e) (R = 6-F) and (2f) (R =

56-benzo) were found to be very active against S mutanswith MIC of 02 120583gmL The compounds (2c) (R = 6-Cl)and (2i) (R = 6-tert-butyl) were found to be highly activeagainst E coli with MIC of 02 120583gmLThe compound (2i) (R= 6-tert-butyl) displayed high activity against A fumigatuswith MIC of 02 120583gmL The compounds (3a) (R = 6-CH

3)

and (3b) (R = 7-CH3) were found to be highly active against

S aureus E faecalis and S mutans with MIC of 02 120583gmLThe compounds (3e) (R = 6-F) and (3f) (R = 56-benzo)were found to be highly active against S aureus and Calbicans with MIC of 02 120583gmL The compounds (3g) (R =68-dimethyl) (3h) (R = 6-isopropyl) (3i) (R = 6-tert-butyl)and (3j) (R = 6-benzyl) exhibited high activity against Saureus S mutans and C albicans with MIC of 02 120583gmLThe compound (3k) (R = OMe) showed high activityagainst S aureus and C albicans with MIC of 02 120583gmLIt is to be noted that most of these compounds exhibitedmoderate activity against P aeruginosa and inactive againstK pneumonia

In general uncyclized compounds (2b-k) aremore potentthan the cyclized compounds (3a-k) against S mutans andE coli The cyclized compounds (3a-k) are more potentthan the uncyclized compounds (2b-k) against E faecalisand C albicans It is interesting to found that both cyclizedand uncyclized compounds showed better activity against Saureus than the standard Ciprofloxacin

5 In Vitro Cell Cytotoxicity

All the newly synthesized compounds (2b-k) and (3a-k)were evaluated for their cytotoxicity against DAL cell usingtrypan blue dye exclusion assay The detail procedure hasbeen described in our earlier publications [26 27]

The investigation of in vitro cell cytotoxicity (Table 2)revealed that most of the tested compounds exhibited goodactivity The compounds (2d) (R = 6-Br) (2h) (R = 6-isopropyl) (2i) (R = 6-tert-butyl) (2j) (R = 6-benzyl) (2k)(R = 6-OMe) (3a) (R = 6-CH

3) (3c) (R = 6-Cl) (3f)

(R = 56-benzo) (3g) (R = 68-dimethyl) (3h) (R = 6-isopropyl) (3i) (R = 6-tert-butyl) and (3k) (R = 6-OMe)were found to be highly active (gt70) against DAL cell atthe concentration of 100 120583gmLThe compound (2f) (R = 56-benzo) was found to be poor active (25) against DAL cell atthe concentration of 100 120583gmL The rest of the compoundswere found to be moderately active (gt40) In general thecyclized compounds (3a-k) were found to be more potentthan the uncyclized compounds (2b-k)

Organic Chemistry International 3

O

Br

OR

Anhydrous

OH

O

O

O

OR

O

O

O

DBUDMF

OR

O

O OH

11 examples

Dry acetone

R = a 6-CH3 b 7- c 6-Cl d 6-Br e 6-F f 56-benzo g 68-dimethyl h 6-isopropyl k 6-OCH3

K2CO3

140∘C 4min

84ndash96

RT 24h stirrMWI 370W

CH3

(1andashk) (2andashk) (3andashk)

i 6-tert-butyl j 6-benzyl

Scheme 1 Synthesis of compounds (2a-k) and (3a-k)

O

O

O

O

O

O O

O OH

R

O

O

O

O

O

R

R

O O

O OH

R

NN

O

O

O

O

O

H

DBU =

R

4-(3-oxo-23-dihydro-benzofuran-2-yl)-coumarins

MeOminus

DBU H+

DBU MW

minus

minus

Figure 1 Plausible mechanism for the synthesis of (3a-k)

6 Experimental Section

The melting points were measured with an electric meltingpoint apparatus and are uncorrected The IR spectra wereobtained using a Shimadzu-8400S FT-IR spectrophotometer1H NMR and 13C NMR spectra in DMSO-119889

6solution were

recorded at 25∘Con a Bruker 300 and 400MHz spectrometerrespectively The 1H chemical shifts were reported in 120575 ppmand referenced toTMSThemass spectrawere recorded on anAgilent-Single Quartz LC-MS The purity of the compoundswas checked by TLC Microwave reactions were carried outon Milestone Laboratoryrsquos microwave reactor The elemental

analyses were carried out using Elemental Vario Micro CubeCHNS Rapid Analyzer All the compounds gave satisfactoryelemental analysis

General Procedure for the Synthesis of Compounds (2a-k)Methyl salicylate (0304 g 20mmol) and anhydrous K

2CO3

(138 g 10mmol) were stirred in 25mL of dry acetonefor 30min 4-Bromomethylcoumarin (1a-k) (20mmol) wasadded and stirring was continued for 24 h The reactionmixture was concentrated to one-fourth volume and pouredonto crushed iceThe solid separated was filtered and washedwith 10mL of 5HClThen it was washedwith 50mL of cold

4 Organic Chemistry International

Table 1 Results of antimicrobial activities of the synthesized compounds (2bndashk) and (3andashk) MICs (120583gmL)

Compounds Gram-positive Gram-negative FungiNumber R S aureus E faecalis S mutans E coli K pneumonia P aeruginosa C albicans A fumigatus2b 7-CH3 04 50 02 625 100 625 125 042c 6-Cl 04 16 02 02 50 312 125 042d 6-Br 08 25 04 16 100 312 125 042e 6-F 04 312 02 16 100 625 gt100 082f 56-benzo 04 50 02 625 100 625 125 042g 68-dimethyl 16 08 08 312 100 50 100 162h 6-isopropyl 08 625 04 04 100 25 125 042i 6-tert-butyl 08 625 08 02 100 25 125 022j 6-benzyl 08 125 04 16 100 625 100 082k 6-OMe 08 312 08 312 100 100 100 083a 6-CH3 02 02 02 50 100 50 125 mdash3b 7-CH3 02 02 02 100 50 gt100 02 mdash3c 6-Cl 02 04 02 100 100 25 312 mdash3d 6-Br mdash mdash mdash mdash mdash mdash mdash mdash3e 6-F 02 04 04 100 100 gt100 02 mdash3f 56-benzo 02 04 312 50 100 02 02 mdash3g 68-dimethyl 02 04 02 100 100 50 02 mdash3h 6-isopropyl 02 04 02 50 100 312 02 mdash3i 6-tert-butyl 02 08 02 50 gt100 625 02 mdash3j 6-benzyl 02 08 02 100 100 50 02 mdash3k 6-OMe 02 04 312 50 100 625 02 mdash

Ciprofloxacin 2 2 2 1 1 4 mdash mdashFluconazole mdash mdash mdash mdash mdash mdash 16 8

water The crude product was dried and recrystallised fromethanol

2-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2b) Yield 90 colorless solid mp 168ndash170∘CIR (KBr cmminus1) 1720 (lactone C=O) 1742 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 240 (s 3H CH

3)

385 (s 3H OCH3) 552 (s 2H OCH

2) 685 (s 1H C

3ndashH)

710ndash783 (m 7H ArndashH) ppm Anal Cald for C19H16O5 C

7036 H 497 Found C 7027 H 489

2-(6-Chloro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2c) Yield 92 colorless solid mp 188ndash191∘C IR(KBr cmminus1) 1730 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 381 (s 3H OCH

3)

546 (s 2H OCH2) 690 (s 1H C

3ndashH) 707ndash804 (m 7H

ArndashH) ppm Anal Cald for C18H13ClO5 C 6271 H 380

Found C 6265 H 373

2-(6-Bromo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2d) Yield 89 yellow solid mp 147ndash149∘C IR(KBr cmminus1) 1714 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (s 3H OCH

3)

549 (s 2H OCH2) 679 (s 1H C

3ndashH) 712ndash782 (m 7H

ArndashH) ppm Anal Cald for C18H13BrO5 C 5555 H 337

Found C 5548 H 332

2-(6-Fluoro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2e) Yield 90 colorless solid mp 186ndash149∘CIR (KBr cmminus1) 1724 (lactone C=O) 1739 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 386 (s 3H

OCH3) 550 (s 2H OCH

2) 692 (s 1H C

3ndashH) 710ndash812

(m 7H ArndashH) ppm Anal Cald for C19H15FO4 C 6993 H

463 Found C 6986 H 458

2-(56-Benzo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2f ) Yield 90 light yellow solid mp 183ndash186∘C IR (KBr cmminus1) 1728 (lactone C=O) 1746 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 383 (s 3H

OCH3) 595 (s 2H OCH

2) 712ndash842 (m 11H ArndashH) ppm

Anal Cald for C22H16O5 C 7333 H 448 Found C 7326

H 440

2-(68-Dimethyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2g) Yield 91 colorless solid mp 193ndash195∘C IR (KBr cmminus1) 1727 (lactone C=O) 1739 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 236 (d 6H

68-dimethyl) 385 (s 3H OCH3) 547 (s 2H OCH

2) 684

Organic Chemistry International 5

Table 2 Results of in vitro cytotoxicity of the synthesized compounds (2bndashk) and (3andashk) against Daltonrsquos Ascitic Lymphoma cell (1 times 105)at the concentration of 100 120583gmL

Number of compounds R Number of cells of dead cellsLive Dead

2b 7-CH3 49 51 512c 6-Cl 41 59 592d 6-Br 19 81 812e 6-F 42 58 582f 56-benzo 75 25 252g 68-dimethyl 55 45 452h 6-isopropyl 12 88 882i 6-tert-butyl 16 84 842j 6-benzyl 13 87 872k 6-OMe 18 82 823a 6-CH3 21 79 793b 7-CH3 56 44 443c 6-Cl 15 85 853d 6-Br mdash mdash mdash3e 6-F 34 66 663f 56-benzo 13 87 873g 68-dimethyl 21 79 793h 6-isopropyl 26 74 743i 6-tert-butyl 15 85 853j 6-benzyl 53 47 473k 6-OMe 11 89 895-Fluorouracil mdash 12 88 88

(s 1H C3ndashH) 708ndash782 (m 6H ArndashH) ppm Anal Cald for

C22H22O5 C 7110 H 536 Found C 7103 H 529

2-(6-Isopropyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2h) Yield 97 colorless solid mp 179ndash182∘CIR (KBr cmminus1) 1718 (lactone C=O) 1746 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 127 (d 6H 2-CH

3of

isopropyl) 302 (m 1H CHof isopropyl) 388 (s 3H OCH3)

555 (s 2H OCH2) 688 (s 1H C

3ndashH) 710ndash787 (m 7H Arndash

H) ppm Anal Cald for C21H20O5 C 7158 H 572 Found

C 7150 H 566

2-(6-Tert-butyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2i) Yield 89 colorless solid mp 172ndash173∘CIR (KBr cmminus1) 1716 (lactone C=O) 1728 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 137 (s 9H 6-tert-butyl)

381 (s 3H OCH3) 553 (s 2H OCH

2) 693 (s 1H C

3ndashH)

723ndash791 (m 7H ArndashH) ppm Anal Cald for C21H20O5 C

7200 H 605 Found C 7183 H 597

2-(6-Benzyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2j) Yield 89 colorless solid mp 172ndash175∘CIR (KBr cmminus1) 1712 (lactone C=O) 1738 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 384 (s 3H OCH

3) 403

(s 2H C6ndashCH2) 551 (s 2H OCH

2) 686 (s 1H C

3ndashH)

710ndash789 (m 12H ArndashH) ppm Anal Cald for C25H20O5 C

7499 H 503 Found C 7491 H 495

2-(6-Methoxy-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2k) Yield 95 colorless solid mp 174ndash176∘CIR (KBr cmminus1) 1720 (lactone C=O) 1739 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (d 6H 6-OCH

3

OCH3) 552 (s 2H OCH

2) 684 (s 1H C

3ndashH) 713ndash782 (m

7H ArndashH) ppm Anal Cald for C19H16O6 C 6705 H 474

Found C 6697 H 467

General Procedure for the Synthesis of Compounds (3a-k)A mixture of 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2a-k) (20mmol) DBU (03 g 20mmol)and DMF (25mL) were added to a microwave tube equippedwith a magnetic stir bar The microwave tube was fitted witha reflux condenser and irradiated in a microwave reactor ata temperature of 140∘C for 4min at a maximum power of370WThen completion of the reaction mixture was pouredonto ice cold water and neutralizedwith dil HCl solutionThesolid separated was filtered and washed with 100mL of coldwater The crude product was dried and recrystallised fromethanol

4-(3-Hydroxy-benzofuran-2-yl)-6-methyl-chromen-2-one (3a)Yield 90 yellow solid mp 221ndash224∘C IR (KBr cmminus1) 1729(lactone C=O) 3450 (OH) 1HNMR (300MHz DMSO-119889

6)

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Organic Chemistry International 3

O

Br

OR

Anhydrous

OH

O

O

O

OR

O

O

O

DBUDMF

OR

O

O OH

11 examples

Dry acetone

R = a 6-CH3 b 7- c 6-Cl d 6-Br e 6-F f 56-benzo g 68-dimethyl h 6-isopropyl k 6-OCH3

K2CO3

140∘C 4min

84ndash96

RT 24h stirrMWI 370W

CH3

(1andashk) (2andashk) (3andashk)

i 6-tert-butyl j 6-benzyl

Scheme 1 Synthesis of compounds (2a-k) and (3a-k)

O

O

O

O

O

O O

O OH

R

O

O

O

O

O

R

R

O O

O OH

R

NN

O

O

O

O

O

H

DBU =

R

4-(3-oxo-23-dihydro-benzofuran-2-yl)-coumarins

MeOminus

DBU H+

DBU MW

minus

minus

Figure 1 Plausible mechanism for the synthesis of (3a-k)

6 Experimental Section

The melting points were measured with an electric meltingpoint apparatus and are uncorrected The IR spectra wereobtained using a Shimadzu-8400S FT-IR spectrophotometer1H NMR and 13C NMR spectra in DMSO-119889

6solution were

recorded at 25∘Con a Bruker 300 and 400MHz spectrometerrespectively The 1H chemical shifts were reported in 120575 ppmand referenced toTMSThemass spectrawere recorded on anAgilent-Single Quartz LC-MS The purity of the compoundswas checked by TLC Microwave reactions were carried outon Milestone Laboratoryrsquos microwave reactor The elemental

analyses were carried out using Elemental Vario Micro CubeCHNS Rapid Analyzer All the compounds gave satisfactoryelemental analysis

General Procedure for the Synthesis of Compounds (2a-k)Methyl salicylate (0304 g 20mmol) and anhydrous K

2CO3

(138 g 10mmol) were stirred in 25mL of dry acetonefor 30min 4-Bromomethylcoumarin (1a-k) (20mmol) wasadded and stirring was continued for 24 h The reactionmixture was concentrated to one-fourth volume and pouredonto crushed iceThe solid separated was filtered and washedwith 10mL of 5HClThen it was washedwith 50mL of cold

4 Organic Chemistry International

Table 1 Results of antimicrobial activities of the synthesized compounds (2bndashk) and (3andashk) MICs (120583gmL)

Compounds Gram-positive Gram-negative FungiNumber R S aureus E faecalis S mutans E coli K pneumonia P aeruginosa C albicans A fumigatus2b 7-CH3 04 50 02 625 100 625 125 042c 6-Cl 04 16 02 02 50 312 125 042d 6-Br 08 25 04 16 100 312 125 042e 6-F 04 312 02 16 100 625 gt100 082f 56-benzo 04 50 02 625 100 625 125 042g 68-dimethyl 16 08 08 312 100 50 100 162h 6-isopropyl 08 625 04 04 100 25 125 042i 6-tert-butyl 08 625 08 02 100 25 125 022j 6-benzyl 08 125 04 16 100 625 100 082k 6-OMe 08 312 08 312 100 100 100 083a 6-CH3 02 02 02 50 100 50 125 mdash3b 7-CH3 02 02 02 100 50 gt100 02 mdash3c 6-Cl 02 04 02 100 100 25 312 mdash3d 6-Br mdash mdash mdash mdash mdash mdash mdash mdash3e 6-F 02 04 04 100 100 gt100 02 mdash3f 56-benzo 02 04 312 50 100 02 02 mdash3g 68-dimethyl 02 04 02 100 100 50 02 mdash3h 6-isopropyl 02 04 02 50 100 312 02 mdash3i 6-tert-butyl 02 08 02 50 gt100 625 02 mdash3j 6-benzyl 02 08 02 100 100 50 02 mdash3k 6-OMe 02 04 312 50 100 625 02 mdash

Ciprofloxacin 2 2 2 1 1 4 mdash mdashFluconazole mdash mdash mdash mdash mdash mdash 16 8

water The crude product was dried and recrystallised fromethanol

2-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2b) Yield 90 colorless solid mp 168ndash170∘CIR (KBr cmminus1) 1720 (lactone C=O) 1742 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 240 (s 3H CH

3)

385 (s 3H OCH3) 552 (s 2H OCH

2) 685 (s 1H C

3ndashH)

710ndash783 (m 7H ArndashH) ppm Anal Cald for C19H16O5 C

7036 H 497 Found C 7027 H 489

2-(6-Chloro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2c) Yield 92 colorless solid mp 188ndash191∘C IR(KBr cmminus1) 1730 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 381 (s 3H OCH

3)

546 (s 2H OCH2) 690 (s 1H C

3ndashH) 707ndash804 (m 7H

ArndashH) ppm Anal Cald for C18H13ClO5 C 6271 H 380

Found C 6265 H 373

2-(6-Bromo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2d) Yield 89 yellow solid mp 147ndash149∘C IR(KBr cmminus1) 1714 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (s 3H OCH

3)

549 (s 2H OCH2) 679 (s 1H C

3ndashH) 712ndash782 (m 7H

ArndashH) ppm Anal Cald for C18H13BrO5 C 5555 H 337

Found C 5548 H 332

2-(6-Fluoro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2e) Yield 90 colorless solid mp 186ndash149∘CIR (KBr cmminus1) 1724 (lactone C=O) 1739 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 386 (s 3H

OCH3) 550 (s 2H OCH

2) 692 (s 1H C

3ndashH) 710ndash812

(m 7H ArndashH) ppm Anal Cald for C19H15FO4 C 6993 H

463 Found C 6986 H 458

2-(56-Benzo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2f ) Yield 90 light yellow solid mp 183ndash186∘C IR (KBr cmminus1) 1728 (lactone C=O) 1746 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 383 (s 3H

OCH3) 595 (s 2H OCH

2) 712ndash842 (m 11H ArndashH) ppm

Anal Cald for C22H16O5 C 7333 H 448 Found C 7326

H 440

2-(68-Dimethyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2g) Yield 91 colorless solid mp 193ndash195∘C IR (KBr cmminus1) 1727 (lactone C=O) 1739 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 236 (d 6H

68-dimethyl) 385 (s 3H OCH3) 547 (s 2H OCH

2) 684

Organic Chemistry International 5

Table 2 Results of in vitro cytotoxicity of the synthesized compounds (2bndashk) and (3andashk) against Daltonrsquos Ascitic Lymphoma cell (1 times 105)at the concentration of 100 120583gmL

Number of compounds R Number of cells of dead cellsLive Dead

2b 7-CH3 49 51 512c 6-Cl 41 59 592d 6-Br 19 81 812e 6-F 42 58 582f 56-benzo 75 25 252g 68-dimethyl 55 45 452h 6-isopropyl 12 88 882i 6-tert-butyl 16 84 842j 6-benzyl 13 87 872k 6-OMe 18 82 823a 6-CH3 21 79 793b 7-CH3 56 44 443c 6-Cl 15 85 853d 6-Br mdash mdash mdash3e 6-F 34 66 663f 56-benzo 13 87 873g 68-dimethyl 21 79 793h 6-isopropyl 26 74 743i 6-tert-butyl 15 85 853j 6-benzyl 53 47 473k 6-OMe 11 89 895-Fluorouracil mdash 12 88 88

(s 1H C3ndashH) 708ndash782 (m 6H ArndashH) ppm Anal Cald for

C22H22O5 C 7110 H 536 Found C 7103 H 529

2-(6-Isopropyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2h) Yield 97 colorless solid mp 179ndash182∘CIR (KBr cmminus1) 1718 (lactone C=O) 1746 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 127 (d 6H 2-CH

3of

isopropyl) 302 (m 1H CHof isopropyl) 388 (s 3H OCH3)

555 (s 2H OCH2) 688 (s 1H C

3ndashH) 710ndash787 (m 7H Arndash

H) ppm Anal Cald for C21H20O5 C 7158 H 572 Found

C 7150 H 566

2-(6-Tert-butyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2i) Yield 89 colorless solid mp 172ndash173∘CIR (KBr cmminus1) 1716 (lactone C=O) 1728 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 137 (s 9H 6-tert-butyl)

381 (s 3H OCH3) 553 (s 2H OCH

2) 693 (s 1H C

3ndashH)

723ndash791 (m 7H ArndashH) ppm Anal Cald for C21H20O5 C

7200 H 605 Found C 7183 H 597

2-(6-Benzyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2j) Yield 89 colorless solid mp 172ndash175∘CIR (KBr cmminus1) 1712 (lactone C=O) 1738 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 384 (s 3H OCH

3) 403

(s 2H C6ndashCH2) 551 (s 2H OCH

2) 686 (s 1H C

3ndashH)

710ndash789 (m 12H ArndashH) ppm Anal Cald for C25H20O5 C

7499 H 503 Found C 7491 H 495

2-(6-Methoxy-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2k) Yield 95 colorless solid mp 174ndash176∘CIR (KBr cmminus1) 1720 (lactone C=O) 1739 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (d 6H 6-OCH

3

OCH3) 552 (s 2H OCH

2) 684 (s 1H C

3ndashH) 713ndash782 (m

7H ArndashH) ppm Anal Cald for C19H16O6 C 6705 H 474

Found C 6697 H 467

General Procedure for the Synthesis of Compounds (3a-k)A mixture of 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2a-k) (20mmol) DBU (03 g 20mmol)and DMF (25mL) were added to a microwave tube equippedwith a magnetic stir bar The microwave tube was fitted witha reflux condenser and irradiated in a microwave reactor ata temperature of 140∘C for 4min at a maximum power of370WThen completion of the reaction mixture was pouredonto ice cold water and neutralizedwith dil HCl solutionThesolid separated was filtered and washed with 100mL of coldwater The crude product was dried and recrystallised fromethanol

4-(3-Hydroxy-benzofuran-2-yl)-6-methyl-chromen-2-one (3a)Yield 90 yellow solid mp 221ndash224∘C IR (KBr cmminus1) 1729(lactone C=O) 3450 (OH) 1HNMR (300MHz DMSO-119889

6)

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

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Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

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Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

4 Organic Chemistry International

Table 1 Results of antimicrobial activities of the synthesized compounds (2bndashk) and (3andashk) MICs (120583gmL)

Compounds Gram-positive Gram-negative FungiNumber R S aureus E faecalis S mutans E coli K pneumonia P aeruginosa C albicans A fumigatus2b 7-CH3 04 50 02 625 100 625 125 042c 6-Cl 04 16 02 02 50 312 125 042d 6-Br 08 25 04 16 100 312 125 042e 6-F 04 312 02 16 100 625 gt100 082f 56-benzo 04 50 02 625 100 625 125 042g 68-dimethyl 16 08 08 312 100 50 100 162h 6-isopropyl 08 625 04 04 100 25 125 042i 6-tert-butyl 08 625 08 02 100 25 125 022j 6-benzyl 08 125 04 16 100 625 100 082k 6-OMe 08 312 08 312 100 100 100 083a 6-CH3 02 02 02 50 100 50 125 mdash3b 7-CH3 02 02 02 100 50 gt100 02 mdash3c 6-Cl 02 04 02 100 100 25 312 mdash3d 6-Br mdash mdash mdash mdash mdash mdash mdash mdash3e 6-F 02 04 04 100 100 gt100 02 mdash3f 56-benzo 02 04 312 50 100 02 02 mdash3g 68-dimethyl 02 04 02 100 100 50 02 mdash3h 6-isopropyl 02 04 02 50 100 312 02 mdash3i 6-tert-butyl 02 08 02 50 gt100 625 02 mdash3j 6-benzyl 02 08 02 100 100 50 02 mdash3k 6-OMe 02 04 312 50 100 625 02 mdash

Ciprofloxacin 2 2 2 1 1 4 mdash mdashFluconazole mdash mdash mdash mdash mdash mdash 16 8

water The crude product was dried and recrystallised fromethanol

2-(7-Methyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2b) Yield 90 colorless solid mp 168ndash170∘CIR (KBr cmminus1) 1720 (lactone C=O) 1742 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 240 (s 3H CH

3)

385 (s 3H OCH3) 552 (s 2H OCH

2) 685 (s 1H C

3ndashH)

710ndash783 (m 7H ArndashH) ppm Anal Cald for C19H16O5 C

7036 H 497 Found C 7027 H 489

2-(6-Chloro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2c) Yield 92 colorless solid mp 188ndash191∘C IR(KBr cmminus1) 1730 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 381 (s 3H OCH

3)

546 (s 2H OCH2) 690 (s 1H C

3ndashH) 707ndash804 (m 7H

ArndashH) ppm Anal Cald for C18H13ClO5 C 6271 H 380

Found C 6265 H 373

2-(6-Bromo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2d) Yield 89 yellow solid mp 147ndash149∘C IR(KBr cmminus1) 1714 (lactone C=O) 1750 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (s 3H OCH

3)

549 (s 2H OCH2) 679 (s 1H C

3ndashH) 712ndash782 (m 7H

ArndashH) ppm Anal Cald for C18H13BrO5 C 5555 H 337

Found C 5548 H 332

2-(6-Fluoro-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2e) Yield 90 colorless solid mp 186ndash149∘CIR (KBr cmminus1) 1724 (lactone C=O) 1739 (methyl esterC=O) 1H NMR (300MHz DMSO-119889

6) 120575 386 (s 3H

OCH3) 550 (s 2H OCH

2) 692 (s 1H C

3ndashH) 710ndash812

(m 7H ArndashH) ppm Anal Cald for C19H15FO4 C 6993 H

463 Found C 6986 H 458

2-(56-Benzo-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2f ) Yield 90 light yellow solid mp 183ndash186∘C IR (KBr cmminus1) 1728 (lactone C=O) 1746 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 383 (s 3H

OCH3) 595 (s 2H OCH

2) 712ndash842 (m 11H ArndashH) ppm

Anal Cald for C22H16O5 C 7333 H 448 Found C 7326

H 440

2-(68-Dimethyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2g) Yield 91 colorless solid mp 193ndash195∘C IR (KBr cmminus1) 1727 (lactone C=O) 1739 (methylester C=O) 1H NMR (300MHz DMSO-119889

6) 120575 236 (d 6H

68-dimethyl) 385 (s 3H OCH3) 547 (s 2H OCH

2) 684

Organic Chemistry International 5

Table 2 Results of in vitro cytotoxicity of the synthesized compounds (2bndashk) and (3andashk) against Daltonrsquos Ascitic Lymphoma cell (1 times 105)at the concentration of 100 120583gmL

Number of compounds R Number of cells of dead cellsLive Dead

2b 7-CH3 49 51 512c 6-Cl 41 59 592d 6-Br 19 81 812e 6-F 42 58 582f 56-benzo 75 25 252g 68-dimethyl 55 45 452h 6-isopropyl 12 88 882i 6-tert-butyl 16 84 842j 6-benzyl 13 87 872k 6-OMe 18 82 823a 6-CH3 21 79 793b 7-CH3 56 44 443c 6-Cl 15 85 853d 6-Br mdash mdash mdash3e 6-F 34 66 663f 56-benzo 13 87 873g 68-dimethyl 21 79 793h 6-isopropyl 26 74 743i 6-tert-butyl 15 85 853j 6-benzyl 53 47 473k 6-OMe 11 89 895-Fluorouracil mdash 12 88 88

(s 1H C3ndashH) 708ndash782 (m 6H ArndashH) ppm Anal Cald for

C22H22O5 C 7110 H 536 Found C 7103 H 529

2-(6-Isopropyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2h) Yield 97 colorless solid mp 179ndash182∘CIR (KBr cmminus1) 1718 (lactone C=O) 1746 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 127 (d 6H 2-CH

3of

isopropyl) 302 (m 1H CHof isopropyl) 388 (s 3H OCH3)

555 (s 2H OCH2) 688 (s 1H C

3ndashH) 710ndash787 (m 7H Arndash

H) ppm Anal Cald for C21H20O5 C 7158 H 572 Found

C 7150 H 566

2-(6-Tert-butyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2i) Yield 89 colorless solid mp 172ndash173∘CIR (KBr cmminus1) 1716 (lactone C=O) 1728 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 137 (s 9H 6-tert-butyl)

381 (s 3H OCH3) 553 (s 2H OCH

2) 693 (s 1H C

3ndashH)

723ndash791 (m 7H ArndashH) ppm Anal Cald for C21H20O5 C

7200 H 605 Found C 7183 H 597

2-(6-Benzyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2j) Yield 89 colorless solid mp 172ndash175∘CIR (KBr cmminus1) 1712 (lactone C=O) 1738 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 384 (s 3H OCH

3) 403

(s 2H C6ndashCH2) 551 (s 2H OCH

2) 686 (s 1H C

3ndashH)

710ndash789 (m 12H ArndashH) ppm Anal Cald for C25H20O5 C

7499 H 503 Found C 7491 H 495

2-(6-Methoxy-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2k) Yield 95 colorless solid mp 174ndash176∘CIR (KBr cmminus1) 1720 (lactone C=O) 1739 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (d 6H 6-OCH

3

OCH3) 552 (s 2H OCH

2) 684 (s 1H C

3ndashH) 713ndash782 (m

7H ArndashH) ppm Anal Cald for C19H16O6 C 6705 H 474

Found C 6697 H 467

General Procedure for the Synthesis of Compounds (3a-k)A mixture of 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2a-k) (20mmol) DBU (03 g 20mmol)and DMF (25mL) were added to a microwave tube equippedwith a magnetic stir bar The microwave tube was fitted witha reflux condenser and irradiated in a microwave reactor ata temperature of 140∘C for 4min at a maximum power of370WThen completion of the reaction mixture was pouredonto ice cold water and neutralizedwith dil HCl solutionThesolid separated was filtered and washed with 100mL of coldwater The crude product was dried and recrystallised fromethanol

4-(3-Hydroxy-benzofuran-2-yl)-6-methyl-chromen-2-one (3a)Yield 90 yellow solid mp 221ndash224∘C IR (KBr cmminus1) 1729(lactone C=O) 3450 (OH) 1HNMR (300MHz DMSO-119889

6)

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Organic Chemistry International 5

Table 2 Results of in vitro cytotoxicity of the synthesized compounds (2bndashk) and (3andashk) against Daltonrsquos Ascitic Lymphoma cell (1 times 105)at the concentration of 100 120583gmL

Number of compounds R Number of cells of dead cellsLive Dead

2b 7-CH3 49 51 512c 6-Cl 41 59 592d 6-Br 19 81 812e 6-F 42 58 582f 56-benzo 75 25 252g 68-dimethyl 55 45 452h 6-isopropyl 12 88 882i 6-tert-butyl 16 84 842j 6-benzyl 13 87 872k 6-OMe 18 82 823a 6-CH3 21 79 793b 7-CH3 56 44 443c 6-Cl 15 85 853d 6-Br mdash mdash mdash3e 6-F 34 66 663f 56-benzo 13 87 873g 68-dimethyl 21 79 793h 6-isopropyl 26 74 743i 6-tert-butyl 15 85 853j 6-benzyl 53 47 473k 6-OMe 11 89 895-Fluorouracil mdash 12 88 88

(s 1H C3ndashH) 708ndash782 (m 6H ArndashH) ppm Anal Cald for

C22H22O5 C 7110 H 536 Found C 7103 H 529

2-(6-Isopropyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2h) Yield 97 colorless solid mp 179ndash182∘CIR (KBr cmminus1) 1718 (lactone C=O) 1746 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 127 (d 6H 2-CH

3of

isopropyl) 302 (m 1H CHof isopropyl) 388 (s 3H OCH3)

555 (s 2H OCH2) 688 (s 1H C

3ndashH) 710ndash787 (m 7H Arndash

H) ppm Anal Cald for C21H20O5 C 7158 H 572 Found

C 7150 H 566

2-(6-Tert-butyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2i) Yield 89 colorless solid mp 172ndash173∘CIR (KBr cmminus1) 1716 (lactone C=O) 1728 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 137 (s 9H 6-tert-butyl)

381 (s 3H OCH3) 553 (s 2H OCH

2) 693 (s 1H C

3ndashH)

723ndash791 (m 7H ArndashH) ppm Anal Cald for C21H20O5 C

7200 H 605 Found C 7183 H 597

2-(6-Benzyl-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2j) Yield 89 colorless solid mp 172ndash175∘CIR (KBr cmminus1) 1712 (lactone C=O) 1738 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 384 (s 3H OCH

3) 403

(s 2H C6ndashCH2) 551 (s 2H OCH

2) 686 (s 1H C

3ndashH)

710ndash789 (m 12H ArndashH) ppm Anal Cald for C25H20O5 C

7499 H 503 Found C 7491 H 495

2-(6-Methoxy-2-oxo-2H-chromen-4-ylmethoxy)-benzoic acidmethyl ester (2k) Yield 95 colorless solid mp 174ndash176∘CIR (KBr cmminus1) 1720 (lactone C=O) 1739 (methyl ester C=O)1H NMR (300MHz DMSO-119889

6) 120575 385 (d 6H 6-OCH

3

OCH3) 552 (s 2H OCH

2) 684 (s 1H C

3ndashH) 713ndash782 (m

7H ArndashH) ppm Anal Cald for C19H16O6 C 6705 H 474

Found C 6697 H 467

General Procedure for the Synthesis of Compounds (3a-k)A mixture of 2-(2-oxo-2H-chromen-4-ylmethoxy)-benzoicacid methyl ester (2a-k) (20mmol) DBU (03 g 20mmol)and DMF (25mL) were added to a microwave tube equippedwith a magnetic stir bar The microwave tube was fitted witha reflux condenser and irradiated in a microwave reactor ata temperature of 140∘C for 4min at a maximum power of370WThen completion of the reaction mixture was pouredonto ice cold water and neutralizedwith dil HCl solutionThesolid separated was filtered and washed with 100mL of coldwater The crude product was dried and recrystallised fromethanol

4-(3-Hydroxy-benzofuran-2-yl)-6-methyl-chromen-2-one (3a)Yield 90 yellow solid mp 221ndash224∘C IR (KBr cmminus1) 1729(lactone C=O) 3450 (OH) 1HNMR (300MHz DMSO-119889

6)

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

6 Organic Chemistry International

120575 242 (s 3H 6-CH3) 693 (s 1H C

3ndashH) 723ndash848 (m 7H

ArndashH) 1142 (s 1HOHD2Oexchangeable) ppmAnal Cald

for C18H12O4 C 7397 H 414 Found C 7389 H 407

4-(3-Hydroxy-benzofuran-2-yl)-7-methyl-chromen-2-one (3b)Yield 93 yellow solid mp 229ndash232∘C IR (KBr cmminus1) 1730(lactone C=O) 3440 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 243 (s 3H 7-CH3) 691 (s 1H C

3ndashH) 721ndash842 (m 7H

ArndashH) 1122 (s 1H OH) ppm Anal Cald for C18H12O4 C

7397 H 414 Found C 7389 H 408

4-(3-Hydroxy-benzofuran-2-yl)-6-chloro-chromen-2-one (3c)Yield 86 yellow solid mp 260ndash263∘C IR (KBr cmminus1) 1743(lactone C=O) 3460 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 704 (s 1H C3ndashH) 734ndash861 (m 7H ArndashH) 1166 (s 1H

OH) ppm Anal Cald for C17H9ClO4 C 6530 H 290

Found C 6519 H 281

4-(3-Hydroxy-benzofuran-2-yl)-6-bromo-chromen-2-one (3d)Yield 90 yellow solid mp 247ndash250∘C IR (KBr cmminus1)1736 (lactone C=O) 3435 (OH) 1HNMR (300MHz DMSO-1198896) 120575 700 (s 1H C

3ndashH) 735ndash870 (m 7H ArndashH) 1165 (s

1H OH) ppm Anal Cald for C17H9BrO4 C 5714 H 254

Found C 5702 H 241

4-(3-Hydroxy-benzofuran-2-yl)-6-flouro-chromen-2-one (3e)Yield 84 yellow solid mp 242ndash244∘C IR (KBr cmminus1)1723 (lactone C=O) 3456 (OH) 1HNMR (300MHz DMSO-1198896) 120575 706 (s 1H C

3ndashH) 735ndash863 (m 7H ArndashH) 1170 (s

1H OH) ppm Anal Cald for C17H9FO4 C 6892 H 306

Found C 6880 H 293

4-(3-Hydroxy-benzofuran-2-yl)-56-benzo-chromen-2-one (3f )Yield 89 yellow solid mp 222ndash225∘C IR (KBr cmminus1) 1725(lactone C=O) 3409 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 699 (s 1H C3ndashH) 725ndash930 (m 10H ArndashH) 115 (s 1H

OH) ppmAnal Cald forC21H12O4 C 7682H 368 Found

C 7670 H 354

4-(3-Hydroxy-benzofuran-2-yl)-68-dimethyl-chromen-2-one(3g) Yield 91 colorless solid mp 228ndash231∘C IR (KBrcmminus1) 1719 (lactone C=O) 3416 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 235 (d 6H 68-dimethyl) 692 (s 1H C

3ndashH)

730ndash815 (m 6H ArndashH) 1045 (s 1H OH) ppm LC-MS 307[M + H] Anal Cald for C

20H18O5 C 7141 H 536 Found

C 7128 H 524

4-(3-Hydroxy-benzofuran-2-yl)-6-isopropyl-chromen-2-one(3h) Yield 93 yellow solid mp 209ndash211∘C IR (KBr cmminus1)1714 (lactone C=O) 3428 (OH) 1HNMR (300MHz DMSO-1198896) 120575 126 (d 6H 2-CH

3of isopropyl) 300 (m 1H CH of

isopropyl) 693 (s 1H C3ndashH) 733ndash842 (m 7H ArndashH) 1141

(s 1H OH) ppm 13C NMR (400MHz DMSO-1198896) 120575 245

323 1102 1119 1128 1175 1218 1256 1261 1274 12811293 1317 1452 1483 1576 1588 1586 1601 ppm AnalCald for C

20H16O4 C 7499 H 503 Found C 7488 H

492

4-(3-Hydroxy-benzofuran-2-yl)-6-tert-butyl-chromen-2-one(3i) Yield 93 yellow solid mp 214ndash216∘C IR (KBrcmminus1) 1710 (lactone C=O) 3432 (OH) 1H NMR (300MHzDMSO-119889

6) 120575 137 (s 9H tert-butyl) 686 (s 1H C

3ndashH)

692ndash858 (m 7H ArndashH) 1142 (s 1H OH) ppm Anal Caldfor C21H18O4 C 7543 H 503 Found C 7532 H 490

4-(3-Hydroxy-benzofuran-2-yl)-6-benzyl-chromen-2-one (3j)Yield 96 yellow solid mp 224ndash227∘C IR (KBr cmminus1) 1717(lactone C=O) 3422 (OH) 1H NMR (300MHz DMSO-119889

6)

120575 407 (s 2H C6ndashCH2) 696 (s 1H C

3ndashH) 707ndash839 (m 12H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C24H16O4 C

7825 H 438 Found C 7812 H 426

4-(3-Hydroxy-benzofuran-2-yl)-6-methoxy-chromen-2-one (3k)Yield 95 yellow solid mp 220ndash222∘C IR (KBr cmminus1) 1718(lactone C=O) 3424 (OH) 1HNMR (300MHz DMSO-119889

6)

120575 381 (s 3H 6-OCH3) 699 (s 1H C

3ndashH) 728ndash810 (m 7H

ArndashH) 1149 (s 1H OH) ppm Anal Cald for C18H12O5 C

7013 H 392 Found C 7001 H 381

7 Conclusion

All the tested compounds (2b-k) and (3a-k) were shown toexhibit better activity against Staphylococcus aureus than thestandard Ciprofloxacin The compound (3k) (R = 6-OMe)was found to be more potent cytotoxic than the standard 5-fluorouracil

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to the Council of Scientific andIndustrial Research NewDelhi India for financial assistance[no 02(0172)13EMR-II]They are also thankful to ProfessorY S Bhat Bangalore Institute of Technology Bangalore forproviding Microwave Reactor facility and for his encourage-ment They are also thankful to Indian Institute of ScienceBangalore for the spectral analysis

References

[1] J-Y Yeh M S Coumar J-T Horng et al ldquoAnti-influenzadrug discovery structure-activity relationship and mechanisticinsight into novel angelicin derivativesrdquo Journal of MedicinalChemistry vol 53 no 4 pp 1519ndash1533 2010

[2] K Manna and Y K Agrawal ldquoDesign synthesis and antitu-bercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyra-zolylcarbonyl-4-oxo-naphthyridin analogsrdquo European Journalof Medicinal Chemistry vol 45 no 9 pp 3831ndash3839 2010

[3] X Jiang W Liu W Zhang et al ldquoSynthesis and antimicrobialevaluation of new benzofuran derivativesrdquo European Journal ofMedicinal Chemistry vol 46 no 8 pp 3526ndash3530 2011

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Organic Chemistry International 7

[4] S A Bakunov S M Bakunova TWenzler et al ldquoSynthesis andantiprotozoal activity of cationic 2-phenylbenzofuransrdquo Journalof Medicinal Chemistry vol 51 no 21 pp 6927ndash6944 2008

[5] S Li W Li Y Wang Y Asada and K Koike ldquoPrenylflavonoidsfrom Glycyrrhiza uralensis and their protein tyrosinephosphatase-1B inhibitory activitiesrdquo Bioorganic and MedicinalChemistry Letters vol 20 no 18 pp 5398ndash5401 2010

[6] Y Cheng M Ono H Kimura M Ueda and H SajildquoTechnetium-99m labeled pyridyl benzofuran derivatives assingle photon emission computed tomography imaging probesfor 120573-amyloid plaques in Alzheimerrsquos brainsrdquo Journal of Medic-inal Chemistry vol 55 no 5 pp 2279ndash2286 2012

[7] H A Stefani K Gueogjan F Manarin et al ldquoSynthesisbiological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives effect on inducible nitric oxidesynthaserdquo European Journal of Medicinal Chemistry vol 58 pp117ndash127 2012

[8] M Basanagouda M V Kulkarni D Sharma et al ldquoSynthesisof some new 4-aryloxmethylcoumarins and examination oftheir antibacterial and antifungal activitiesrdquo Journal of ChemicalSciences vol 121 no 4 pp 485ndash495 2009

[9] J N Modranka E Nawrot and J Graczyk ldquoIn vitro antitumorin vitro antibacterial activity and alkylating properties of phos-phorohydrazine derivatives of coumarinrdquo European Journal ofMedicinal Chemistry vol 41 pp 1301ndash1309 2006

[10] K M Amin A A M Eissa S M A Seri F M Awadallahand G S Hassan ldquoSynthesis and biological evaluation of novelcoumarin-pyrazoline hybrids endowed with phenylsulfonylmoiety as antitumorrdquo European Journal of Medicinal Chemistryvol 60 pp 187ndash198 2013

[11] A Arshad H Osman M C Bagley C K Lam S Mohamadand A S M Zahariluddin ldquoSynthesis and antimicrobial prop-erties of some new thiazolyl coumarin derivativesrdquo EuropeanJournal of Medicinal Chemistry vol 46 no 9 pp 3788ndash37942011

[12] D Bhavsar J Trivedi S Parekh et al ldquoSynthesis and invitro anti-HIV activity ofN-13-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT methodrdquoBioorganic and Medicinal Chemistry Letters vol 21 no 11 pp3443ndash3446 2011

[13] K Shivashankar M V Kulkarni L A Shastri V P Rasaland S V Rajendra ldquoThe synthesis and biological evaluationof regioisomeric benzothiazolyl coumarinsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 181 no 9 pp 2187ndash2200 2006

[14] K Shivashankar L A Shastri M V Kulkarni V P Rasaland S V Rajendra ldquoSynthetic and biological studies on 4-aryloxymethyl coumarinyl thiazolidinonesrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 183 no 1 pp 56ndash682008

[15] K Shivashankar L A Shastri M V Kulkarni V P Rasaland D M Saindane ldquoMulti-component reactions of formyl-4-aryloxymethylcoumarins under microwave irradiationrdquo Jour-nal of the Indian Chemical Society vol 86 no 3 pp 265ndash2712009

[16] K Shivashankar L A Shastri M V Kulkarni V P Rasal andD M Saindane ldquoHalogenated 4-aryloxymethylcoumarins aspotent antimicrobial agentsrdquo Journal of the Indian ChemicalSociety vol 85 no 11 pp 1163ndash1168 2008

[17] D Shamala K Shivashankara V P Rasal and V PandildquoSynthesis of new series of quinolinoxymethylcoumarins as

potent anticancer agentsrdquo Mapana Journal of Sciences vol 12pp 49ndash56 2013

[18] K B Puttaraju K Shivashankar V P Rasal P N V VivekR R Korivi and B S G Chand ldquoInCl

3-assisted synthesis

and cytotoxic studies of some novel heteroaryl thiazolesrdquoInternational Journal of Chemical and Pharmaceutical Sciencesvol 4 pp 44ndash47 2013

[19] A Burger and G E Ullyot ldquoAnalgesic studies 120573-Ethyl and 120573-isopropylamine derivatives of pyridine and thiazolerdquo Journal ofOrganic Chemistry vol 12 no 2 pp 342ndash355 1947

[20] K B Puttaraju K Shivashankar Chandra et al ldquoMicrowaveassisted synthesis of dihydrobenzo[4 5]imidazo[1 2-a]pyri-midin-4-ones synthesis in vitro antimicrobial and anticanceractivities of novel coumarin substituted dihydrobenzo[4 5]imi-dazo[1 2-a]pyrimidin-4-onesrdquo European Journal of MedicinalChemistry vol 69 pp 316ndash322 2013

[21] L A Shastri K Shivashankar and M V Kulkarni ldquoFacile syn-thesis of some novel 4-3-aryl-3 4-dihydro-2H-benzo[b][14]thiazin-2-yl-2H-chromen-2-one derivativesrdquo Journal of SulfurChemistry vol 28 no 6 pp 625ndash630 2007

[22] H Nagarajaiah K B Puttaraju K Shivashankar and NS Begum ldquo4-Bromomethyl-6-tert-butyl-2H-chromen-2-onerdquoActa Crystallographica E vol 69 part 7 article o1056 2013

[23] S S Hanamanthgad M V Kulkarni and V D Patil ldquoSynthesisof some biomimetic 4-substituted coumarinsrdquo Revue Roumainede Chimie vol 30 pp 735ndash741 1985

[24] L A Shastri M V Kulkarni V Gupta and N Sharma ldquoFirstthermal chemoselective synthesis of novel 2101584031015840-dihydro-31015840-hydroxy-benzofuranylcoumarinsrdquo Synthetic Communicationsvol 38 no 9 pp 1407ndash1415 2008

[25] M Basanagouda K Shivashankar M V Kulkarni et al ldquoSyn-thesis and antimicrobial studies on novel sulfonamides contain-ing 4-azidomethyl coumarinrdquo European Journal of MedicinalChemistry vol 45 no 3 pp 1151ndash1157 2010

[26] N Jagadish Babu K Shivashankar V P Rasal J R Eluru andE Koyye ldquoSynthesis and cytotoxic studies of a new series ofpyridinoxymethylcoumarinsrdquo International Journal of Chemicaland Pharmaceutical Sciences vol 4 pp 74ndash77 2013

[27] D Shamala K Shivashankar V P Rasal P N V Vivek andV Pandi ldquoSynthesis and cytotoxic studies of a new series ofquinolinoxymethylcoumarinsrdquo International Journal of Phar-maceutical Sciences Review and Research vol 21 pp 109ndash1142013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of