Research ArticleSynthesis Structural Elucidation and AntibacterialEvaluation of Some New Molecules Derived from Coumarin134-Oxadiazole and Acetamide

Shahid Rasool1 Aziz-ur-Rehman1 Muhammad Athar Abbasi1 Sabahat Zahra Siddiqui1

Syed Adnan Ali Shah23 Sidra Hassan4 and Irshad Ahmad4

1Department of Chemistry Government College University Lahore 54000 Pakistan2Faculty of Pharmacy University Technology MARA Puncak Alam Campus 42300 Bandar Puncak AlamSelangor Darul Ehsan Malaysia3Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns) Level 9 FF3 University Technology MARAPuncak Alam Campus 42300 Bandar Puncak Alam Selangor Darul Ehsan Malaysia4Department of Pharmacy The Islamia University of Bahawalpur Bahawalpur 63100 Pakistan

Correspondence should be addressed to Aziz-ur-Rehman azizrykyahoocom

Received 30 April 2016 Accepted 25 July 2016

Academic Editor Jonathan White

Copyright copy 2016 Shahid Rasool et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Because of the reported biological activities of coumarin 134-oxadiazole and acetamides some new compounds incorporatingthese moieties were synthesized and evaluated for their biological potential against Gram-positive and Gram-negative bacteriaIn the present work 4-chlororesorcinol (1) and ethyl acetoacetate (2) were mixed in a strong acidic medium to synthesize 6-chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) which was subjected to the intermolecular cyclization after consecutive threesteps to synthesize 5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-thiol (6) A series of acetamoylelectrophiles 8andasho were synthesized from aralkylalkylaryl amines 7andasho in an aqueous basic medium The final compounds9andasho were synthesized by the reaction of compounds 6 and 8andasho in DMFNaH The synthesized compounds were structurallyelucidated by spectral data analysis of IR 1H-NMR and EIMS The most of the synthesized compounds remained moderate toexcellent antibacterial agents The molecules 9e 9j and 9k were the most efficient ones against all the five bacterial strains takeninto account

1 Introduction

Coumarin is a naturally occurring heterocyclic class of com-pounds [1ndash3] The compounds of this class were used byancient Egyptians as drug [4]The field of agriculture has alsofound the applications of these molecules [4 5]The differentderivatives of various coumarins have been introduced syn-thetically and also by plant extraction to possess a number ofbiological activities including antibacterial antioxidant andanti-inflammatory activities [6ndash9] The heterocyclic moiety134-oxadiazole and its various 25-disubstituted productsare also known to be biologically active compounds [10ndash12]

The presence of amide functionality is also known to boost upthe potential of bioactive compounds including antifungalanti-inflammatory anticancer antibacterial and antioxidantactivities [13ndash16]

The increased resistance by microbes against the existingdrugs is the key point for search of new drug molecules [1718] In continuation of our previous work on O-substitutedderivatives [19] and notable bioactivity of ether derivatives ofcoumarin [6 9 20] this prompted us to incorporate coum-arin with 134-oxadiazole and acetamides to evaluate theirantibacterial activity

Hindawi Publishing CorporationOrganic Chemistry InternationalVolume 2016 Article ID 8696817 10 pageshttpdxdoiorg10115520168696817

2 Organic Chemistry International

2 Experimental

21 Material and Methods 4-Chlororesorcinol ethyl ace-toacetate ethyl 2-bromoacetate hydrated hydrazine carbondisulfide aralkylalkylaryl amines and 2-bromoacetyl bro-mide were purchased from Merck Riedel-de Haen Aldrichand Alfa Aesar through local suppliers along with analyticalgrade solventsThe Jasco-320-A spectrophotometer was usedto record IR spectra by KBr pellet method The Brukerspectrometers at 125 and 400MHz were used to recordthe 13C and 1H NMR spectra in CDCl

3 respectively The

JMS-HX-110 spectrometer was used to record EIMS spectraSilica plates coated on alumina were used for thin layerchromatography (TLC) run in mobile phase of n-hexaneand ethyl acetate and observed under UV

254 Griffin-George

apparatus was used to record the melting points in opencapillary tubes which were uncorrected

22 Synthesis of 6-Chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) 4-Chlororesorcinol (005mol 1) was dissolvedin ethyl acetoacetate (005mol 2) on heating in an iodineflask (500mL)Then concentratedH

2SO4(25mL) was added

on continuous shaking at low temperature The mixture wasaged for 12ndash16 hours Excess cold distilled water was added toprecipitate the title compound which was separated throughfiltration washed by distilled water and dried

23 Synthesis of Ethyl 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetate (4) Compound 3 (0045mol) wasdissolved in DMF (25mL) in a round bottom (RB) flask(250mL) and then NaH (0045mol) was added The mixturewas stirred for 05 hours and then ethyl 2-bromoacetate(0045mol) was added The stirring was continued for 3-4hours along with monitoring through TLC Excess colddistilled water was added and the formed precipitates werefiltered out washed and dried

24 Synthesis of 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetohydrazide (5) The ethyl ester 4 (004mol) wasmixed with methanol (35mL) in a RB flask (250mL) Thehydrated hydrazine (004mol) was added and the mixturewas set to stir for 2-3 hours TLC was frequently developedto monitor the reaction Solvent was evaporated to one-thirdand then excess of distilled water was added to precipitatethe productThe precipitates were acquired through filtrationand subjected to washing and drying

25 Synthesis of 5-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-thiol (6) Compound 5(0035mol) was added to absolute ethanol (50mL) in aRB flask (250mL) followed by solid KOH (0035mol) Themixture was homogenized on reflux and then cooled toroom temperature and liquid CS

2(007mol) was added The

mixture was again set to reflux for 4-5 hours along withsupervision by TLC Solvent was evaporated to one-third andthen excess cold distilled water was added The pH of thishomogeneous solution was adjusted to 6-7 by dilute HCland aged for 05 hours to allow maximum precipitation The

precipitates were filtered washed with distilled water anddried

26 General Synthesis of N-Aralkylalkylaryl-2-bromoacet-amide (8andasho) Aralkylalkylaryl amines (0005mol 7andasho) were dispersed in distilled water (15mL) in an iodineflask (125mL) The pH was adjusted to 8-9 by aqueousNa2CO3solution (15 4mL) Then 2-bromoacetyl bromide

(0005mol) was added on vigorous stirring and further setto stir for 1 hour on maintained pH The precipitates of titleproductswere filtered offwashed by distilledwater anddried

27 General Synthesis of N-Aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9andasho) Compound 6(0002mol) was dissolved in DMF (12mL) in a round bottomflask (50mL) followed by NaH (0002mol) The mixturewas stirred for 05 hours and then N-aralkylalkylaryl-2-bromoacetamide (0002mol 8andasho) were added Thestirring was continued for 4ndash6 hours along with monitoringthrough TLC Excess cold distilled water was added and theprecipitates were filtered out washed and dried

28 Antibacterial Activity Assay The sterilized 96-wellmicroplates under aseptic conditions were used to evaluatethe antibacterial activity by the reported method of Kaspadyet al 2009 andYang et al 2006with slightmodifications [2122]The change in absorbance before and after the addition ofsample compound was noted The absorbance is varied withnumber of microbial cells which are varied with log phasemicrobial growth

The clinically isolated three Gram-negative and twoGram-positive bacteria were stored on stock culture agarmedium A mixture of 200 120583L was prepared by 180 120583L freshnutrient broth with suitable dilutions and 20120583g test sampleswith suitable dilutions All the dilutions were performedusing specific suited solvents Before and after incubation at37∘C for 16ndash24 hrs with lid on the microplate the absorbance(012ndash019 at beginning) was measured at 540 nm The varia-tion in absorbance was the criteria for bacterial growth Thepercent inhibition was calculated by the following formula

Inhibition () = X minus YXtimes 100 (1)

where119883 is absorbance in control with bacterial culture and119884is absorbance in test sample Ciprofloxacin was taken as ref-erence standard Minimum inhibitory concentration (MIC)was measured with suitable dilutions (5ndash30120583gwell) andresults were calculated using EZ-Fit Perrella Scientific IncAmherst USA software

29 Statistical Analysis Theantibacterial activity results werereported as percentage of age inhibition and minimuminhibitory concentration (MIC) values after performing eachexperiment three times The results were reported as mean plusmnSEM after statistical analysis by Microsoft Excel 2010

Organic Chemistry International 3

210 Characterization of the Synthesized Compounds(3ndash6 9andasho)

2101 6-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3)Light brown amorphous solid Yield 78 MP 262ndash264∘CMF C

10H7ClO3 MM 210 gmolminus1 IR (KBr 120592max cm

minus1)3310 (O-H) 3055 (Ar C-H) 1732 (ester C=O) 1586 (Ar C=C)1146 (C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575

ppm) 754 (s 1H H-51015840) 698 (s 1H H-81015840) 617 (s 1H H-31015840) 237 (s 3H CH

3-111015840) 13C-NMR (125MHz CHCl

3-1198891

120575 ppm) 1605 (C-21015840) 1577 (C-71015840) 1534 (C-41015840) 1515 (C-91015840)1254 (C-51015840) 1187 (C-61015840) 1136 (C-101015840) 1127 (C-31015840) 1003 (C-81015840) 185 (C-111015840) EIMS (mz) 212 (6) 210 [M]∙+ (17) 193(7) 182 (5) 175 (BP 100) 165 (3) 149 (2) 134 (5)

2102 Ethyl 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetate (4) Cream white amorphous solid Yield73 MP 184ndash186∘C MF C

14H13ClO5 MM 296 gmolminus1

IR (KBr 120592max cmminus1) 3316 (O-H) 3062 (Ar C-H) 1735 (ester

C=O) 1594 (Ar C=C) 1159 (C-O) 702 (C-Cl) 1H-NMR(400MHz CHCl

3-1198891 120575 ppm) 759 (s 1H H-51015840) 671 (s

1H H-81015840) 618 (s 1H H-31015840) 474 (s 2H H-121015840) 427 (q J =72Hz 2H H-1101584010158401015840) 237 (s 3H CH

3-111015840) 130 (t J = 72Hz

3H CH3-2101584010158401015840) EIMS (mz) 298 (6) 296 [M]∙+ (17) 261

(19) 251 (4) 210 (91) 193 (18) 182 (BP 100) 165(8) 149 (7) 134 (16)

2103 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]ace-tohydrazide (5) Light yellow amorphous solid Yield 67MP 190ndash192∘C MF C

12H11ClN2O4 MM 282 gmolminus1 IR

(KBr 120592max cmminus1) 3421 (N-H) 3061 (Ar C-H) 1735 (ester

C=O) 1671 (amide C=O) 1594 (Ar C=C) 1159 (C-O) 703(C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 884 (s 1H

CON-H) 757 (s 1H H-51015840) 672 (s 1H H-81015840) 619 (s 1H H-31015840) 472 (s 2H H-121015840) 238 (s 3H CH

3-111015840) EIMS (mz)

284 (7) 282 [M]∙+ (16) 249 (7) 247 (18) 230 (4)214 (14) 210 (89) 193 (15) 182 (BP 100) 165 (4) 149(7) 134 (17)

2104 5-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]meth-yl-134-oxadiazol-2-thiol (6) Light brown amorphoussolid Yield 73 MP 188ndash190∘C MF C

13H9ClN2O4S

MM 324 gmolminus1 IR (KBr 120592max cmminus1) 3078 (Ar C-H)

1736 (ester C=O) 1689 (C=N) 1595 (Ar C=C) 1158 (C-O)697 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 759

(s 1H H-51015840) 675 (s 1H H-81015840) 621 (s 1H H-31015840) 474 (s2H H-121015840) 239 (s 3H CH

3-111015840) EIMS (mz) 326 (7) 324

[M]∙+ (16) 289 (14) 251 (3) 249 (7) 230 (2) 214(13) 210 (86) 193 (13) 182 (BP 100) 165 (7) 149(4) 134 (16)

2105 N-Cyclohexyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9a) White amorphous solid Yield 78 MP 100ndash102∘C MF C

21H22ClN3O5S MM 463 gmolminus1 IR (KBr

120592max cmminus1) 3445 (N-H) 3073 (Ar C-H) 1739 (ester C=O)

1676 (amide C=O) 1684 (C=N) 1596 (Ar C=C) 1159 (C-O)

697 (C-Cl) 1H-NMR (400MHz CHCl3-1198891 120575 ppm) 871 (s

1H CON-H) 757 (s 1H H-51015840) 704 (s 1H H-81015840) 623 (s1H H-31015840) 533 (s 2H H-121015840) 405 (s 2H H-2101584010158401015840) 376ndash373(m 1H H-110158401015840) 238 (s 3H CH

3-111015840) 185ndash182 (m 2H Heq-

210158401015840 ampHeq-6

10158401015840) 167ndash156 (m 4H H-310158401015840 ampH-510158401015840) 135ndash132 (m2H Hax-2

10158401015840 ampHax-610158401015840) 122ndash116 (m 2H H-410158401015840) EIMS (mz)

465 (9) 463 [M]∙+ (20) 428 (16) 251 (4) 249 (8)230 (4) 214 (13) 210 (90) 193 (17) 182 (BP 100) 165(4) 149 (8) 134 (17) 126 (28) 98 (34)

2106 N-Benzyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9b) Light yellow amorphous solid Yield 84 MP 126ndash128∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR (KBr

120592max cmminus1) 3464 (N-H) 3053 (Ar C-H) 1736 (ester C=O)

1672 (amide C=O) 1689 (C=N) 1609 (Ar C=C) 1156 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 864

(s 1H CON-H) 761 (s 1H H-51015840) 725ndash719 (m 5H H-210158401015840to H-610158401015840) 706 (s 1H H-81015840) 623 (s 1H H-31015840) 537 (s 2HH-121015840) 437 (s 2H H-710158401015840) 406 (s 2H H-2101584010158401015840) 234 (s 3HCH3-111015840) EIMS (mz) 473 (8) 471 [M]∙+ (24) 436 (13)

251 (5) 249 (9) 230 (3) 214 (8) 210 (84) 193 (11)182 (BP 100) 165 (7) 149 (5) 134 (47) 106 (35)

2107 N-(2-Phenylethyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9c) Light grey amorphous solid Yield 87 MP126ndash128∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3441 (N-H) 3065 (Ar C-H) 1743 (ester

C=O) 1659 (amide C=O) 1684 (C=N) 1602 (Ar C=C) 1174(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

862 (s 1H CON-H) 761 (s 1H H-51015840) 715ndash710 (m 5H H-210158401015840 to H-610158401015840) 705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2HH-121015840) 407 (s 2H H-2101584010158401015840) 343 (t J = 76Hz 2H H-810158401015840) 273(t J = 76Hz 2H H-710158401015840) 238 (s 3H CH

3-111015840) EIMS (mz)

487 (6) 485 [M]∙+ (17) 450 (13) 251 (4) 249 (8) 230(1) 214 (9) 210 (88) 193 (15) 182 (BP 100) 165 (7)149 (8) 148 (31) 134 (9) 120 (34)

2108 N-Phenyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9d) Light grey amorphous solid Yield 77 MP 94ndash96∘C MF C

21H16ClN3O5S MM 457 gmolminus1 IR (KBr

120592max cmminus1) 3436 (N-H) 3046 (Ar C-H) 1735 (ester C=O)

1667 (amide C=O) 1681 (C=N) 1588 (Ar C=C) 1121 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 859

(s 1H CON-H) 763 (s 1H H-51015840) 757 (d J = 76Hz 2HH-210158401015840 ampH-610158401015840) 734 (t J = 76Hz 2H H-310158401015840 ampH-510158401015840) 717(t J = 76Hz 1H H-410158401015840) 705 (s 1H H-81015840) 620 (s 1HH-31015840) 536 (s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 239 (s 3HCH3-111015840) EIMS (mz) 459 (6) 457 [M]∙+ (21) 422 (18)

251 (6) 249 (10) 230 (4) 214 (12) 210 (87) 193(15) 182 (BP 100) 165 (7) 149 (4) 134 (17) 120(37) 92 (29)

4 Organic Chemistry International

2109 N-(2-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9e) White amorphous solid Yield 69MP 100ndash102∘CMF C

22H18ClN3O5SMM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3442 (N-H) 3069 (Ar C-H) 1733 (ester

C=O) 1678 (amide C=O) 1691 (C=N) 1603 (Ar C=C) 1150(C-O) 701 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

873 (s 1H CON-H) 772 (d J = 80Hz 1H H-610158401015840) 763 (s1H H-51015840) 721 (d J = 80Hz 1H H-310158401015840) 715 (t J = 80Hz 1HH-510158401015840) 707 (t J = 80Hz 1H H-410158401015840) 702 (s 1H H-81015840) 622(s 1H H-31015840) 534 (s 2H H-121015840) 406 (s 2H H-2101584010158401015840) 238 (s3H CH

3-111015840) 228 (s 3H CH

3-710158401015840) EIMS (mz) 473 (7)

471 [M]∙+ (24) 436 (12) 251 (4) 249 (7) 230 (5)214 (16) 210 (81) 193 (13) 182 (BP 100) 165 (8) 149(3) 134 (47) 106 (32)

21010 N-(3-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulf-anyl]acetamide (9f) Yellowish grey amorphous solidYield 83 MP 88ndash90∘C MF C

22H18ClN3O5S MM

471 gmolminus1 IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar

C-H) 1736 (ester C=O) 1668 (amide C=O) 1689 (C=N)1591 (Ar C=C) 1153 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 882 (s 1H CON-H) 761 (s 1H H-51015840)

733 (s 1H H-210158401015840) 730 (d J = 76Hz 1H H-610158401015840) 717 (t J =80Hz 1H H-510158401015840) 704 (s 1H H-81015840) 691 (d J = 76Hz 1HH-410158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s 2HH-2101584010158401015840) 237 (s 3H CH

3-111015840) 230 (s 3H CH

3-710158401015840) EIMS

(mz) 473 (5) 471 [M]∙+ (19) 436 (13) 251 (7) 249(8) 230 (2) 214 (15) 210 (83) 193 (14) 182 (BP100) 165 (9) 149 (5) 134 (42) 106 (28)

21011 N-(4-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9g) White amorphous solid Yield 79MP 98ndash100∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3435 (N-H) 3061 (Ar C-H) 1734 (ester

C=O) 1668 (amide C=O) 1689 (C=N) 1584 (Ar C=C) 1141(C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 736 (d J = 84Hz2H H-210158401015840 ampH-610158401015840) 717 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) 226 (s 3H CH

3-710158401015840)

EIMS (mz) 473 (8) 471 [M]∙+ (23) 436 (15) 251 (7)249 (9) 230 (3) 214 (15) 210 (87) 193 (14) 182 (BP100) 165 (9) 149 (4) 134 (49) 106 (31)

21012 N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9h) Light brown amorphous solid Yield 84MP 92ndash94∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3447 (N-H) 3069 (Ar C-H) 1738 (ester

C=O) 1677 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1149(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

861 (s 1H CON-H) 758 (s 1H H-51015840) 716 (d J = 80Hz 1HH-610158401015840) 711 (t J = 80Hz 1H H-510158401015840) 707 (t J = 80Hz 1HH-410158401015840) 704 (s 1H H-81015840) 698 (d J = 80Hz 1H H-310158401015840) 621(s 1H H-31015840) 535 (s 2H H-121015840) 409 (s 2H H-2101584010158401015840) 246 (q

J = 72Hz 2H H-710158401015840) 236 (s 3H CH3-111015840) 103 (t J = 72Hz

3H CH3-810158401015840) EIMS (mz) 487 (6) 485 [M]∙+ (17) 450

(13) 251 (4) 249 (5) 230 (2) 214 (13) 210 (88)193 (14) 182 (BP 100) 165 (6) 149 (7) 148 (33) 134(16) 120 (32)

21013 N-(4-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9i) Cream white amorphous solid Yield 84MP 104ndash106∘C MF C

23H20ClN3O5S MM 485 gmolminus1

IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar C-H) 1736 (ester

C=O) 1671 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1147(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

872 (s 1H CON-H) 761 (s 1H H-51015840) 709 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 704 (s 1H H-81015840) 696 (d J = 80Hz2H H-310158401015840 ampH-510158401015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 254 (q J = 72Hz 2H H-710158401015840) 236 (s3H CH

3-111015840) 113 (t J = 72Hz 3H CH

3-810158401015840) EIMS (mz)

487 (8) 485 [M]∙+ (17) 450 (15) 251 (4) 249 (7)230 (5) 214 (9) 210 (92) 193 (17) 182 (BP 100) 165(7) 149 (5) 148 (35) 134 (11) 120 (38)

21014 N-(2-Methoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9j) Cream yellow amorphous solid Yield78 MP 106ndash108∘C MF C

22H18ClN3O6S MM

487 gmolminus1 IR (KBr 120592max cmminus1) 3437 (N-H) 3069 (Ar

C-H) 1733 (ester C=O) 1683 (amide C=O) 1689 (C=N)1603 (Ar C=C) 1158 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 859 (s 1H CON-H) 822 (d J = 80Hz

1H H-610158401015840) 762 (s 1H H-51015840) 705 (s 1H H-81015840) 701 (t J =76Hz 1H H-510158401015840) 692 (t J = 76Hz 1H H-410158401015840) 681 (d J =80Hz 1H H-310158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 382 (s 3H CH

3-710158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 489 (5) 487 [M]∙+ (17) 452 (16) 251 (4)249 (6) 230 (2) 214 (13) 210 (86) 193 (12) 182 (BP100) 165 (4) 150 (31) 149 (8) 134 (18) 122 (39)

21015 N-(2-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9k) Light grey amorphous solid Yield 86MP 96ndash98∘C MF C

23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3453 (N-H) 3056 (Ar C-H) 1736 (ester

C=O) 1667 (amide C=O) 1681 (C=N) 1606 (Ar C=C) 1155(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 743 (d J = 84Hz 1HH-610158401015840) 717 (t J = 84Hz 1H H-410158401015840) 703 (s 1H H-81015840) 684 (tJ = 84Hz 1H H-510158401015840) 675 (d J = 80Hz 1H H-310158401015840) 620 (s1H H-31015840) 535 (s 2H H-121015840) 404 (s 2H H-2101584010158401015840) 374 (q J =72Hz 2H H-710158401015840) 237 (s 3H CH

3-111015840) 111 (t J = 72Hz 3H

CH3-810158401015840) EIMS (mz) 503 (8) 501 [M]∙+ (22) 466 (11)

251 (4) 249 (7) 230 (2) 214 (14) 210 (85) 193 (18)182 (BP 100) 165 (8) 164 (30) 149 (9) 136 (28) 134(17)

21016 N-(4-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9l) Reddish purple amorphous solid Yield 74

Organic Chemistry International 5

MP 108ndash110∘CMF C23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3443 (N-H) 3078 (Ar C-H) 1734 (ester

C=O) 1679 (amide C=O) 1688 (C=N) 1597 (Ar C=C) 1155(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

882 (s 1H CON-H) 759 (s 1H H-51015840) 739 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 703 (s 1H H-81015840) 681 (d J = 84Hz 2HH-310158401015840 ampH-510158401015840) 620 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s2H H-2101584010158401015840) 397 (q J = 68Hz 2H H-710158401015840) 237 (s 3H CH

3-

111015840) 086 (t J = 68Hz 3H CH3-810158401015840) EIMS (mz) 503 (9)

501 [M]∙+ (21) 466 (13) 251 (6) 249 (8) 230 (3)214 (15) 210 (81) 193 (19) 182 (BP 100) 165 (9) 164(32) 149 (6) 136 (25) 134 (19)

21017 N-(2-Methoxycarbonylphenyl)-2-[(5-[(6-chloro-4-meth-yl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9m) Yellow amorphous solidYield 75 MP 122ndash124∘C MF C

23H18ClN3O7S MM

515 gmolminus1 IR (KBr 120592max cmminus1) 3429 (N-H) 3050 (Ar

C-H) 1731 (ester C=O) 1671 (amide C=O) 1683 (C=N)1601 (Ar C=C) 1159 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 881 (s 1H CON-H) 868 (d J = 84Hz

1H H-610158401015840) 810 (d J = 76Hz 1H H-310158401015840) 762 (s 1H H-51015840)751 (t J = 76Hz 1H H-510158401015840) 718 (t J = 76Hz 1H H-410158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840) 407(s 2H H-2101584010158401015840) 381 (s 3H CH

3-810158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 517 (9) 515 [M]∙+ (19) 480 (13) 251 (6)249 (9) 230 (2) 214 (14) 210 (92) 193 (17) 182 (BP100) 178 (37) 165 (6) 150 (33) 149 (7) 134 (15)

21018 N-(4-Bromophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9n) Light grey amorphous solid Yield 73MP 102ndash104∘CMF C

21H15BrClN

3O5S MM 535 gmolminus1

IR (KBr 120592max cmminus1) 3422 (N-H) 3056 (Ar C-H) 1734 (ester

C=O) 1662 (amide C=O) 1684 (C=N) 1593 (Ar C=C) 1143(C-O) 702 (C-Cl) 639 (C-Br) 1H-NMR (400MHz CHCl

3-

1198891 120575 ppm) 828 (s 1H CON-H) 762 (s 1HH-51015840) 747 (d J =

84Hz 2H H-210158401015840 ampH-610158401015840) 741 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) EIMS (mz) 539

(7) 537 (18) 535 [M]∙+ (20) 500 (14) 251 (6) 249(8) 230 (4) 214 (13) 210 (92) 198 (33) 193 (13)182 (BP 100) 170 (31) 165 (6) 149 (8) 134 (11)

21019 N-(4-Nitrophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9o) Light yellow amorphous solid Yield81 MP 108ndash110∘C MF C

21H15ClN4O7S MM

502 gmolminus1 IR (KBr 120592max cmminus1) 3438 (N-H) 3053 (Ar

C-H) 1735 (ester C=O) 1678 (amide C=O) 1688 (C=N)1606 (Ar C=C) 1163 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 934 (s 1H CON-H) 841 (d J = 80Hz

2H H-310158401015840 ampH-510158401015840) 806 (d J = 80Hz 2H H-210158401015840 ampH-610158401015840)762 (s 1H H-51015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534(s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840)

EIMS (mz) 504 (5) 502 [M]∙+ (17) 467 (18) 251 (8)249 (7) 230 (5) 214 (11) 210 (91) 193 (18) 182 (BP100) 165 (42) 149 (8) 137 (32) 134 (17)

3 Results and Discussion

The different N-aralkylalkylaryl acetamides incorporatingcoumarin and 134-oxadiazole rings 9andasho were synthesizedby the multistep protocol given in Scheme 1 The synthesiswas aimed at combining multiple functionalities in a singlemolecule so these may be able to demonstrate more effi-cient biological activity The antibacterial behavior of thesemolecules was tested against Gram-bacteria including posi-tive and negative strains The three negative and two positivebacterial strains have been reported to be the cause of variousdiseases [23ndash27]

31 Chemistry First 4-chlororesorcinol (1) was treated withethyl acetoacetate (2) in a strong acidic medium to yield6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) whichwas separated through filtration Compound 3 was furtherO-substituted by ethyl 2-bromoacetate in a polar aproticsolvent with the aid of a weak base This substituted ester4 was converted to corresponding carbohydrazide 5 aftera simple nucleophilic substitution reaction by hydrazine inmethanol The carbohydrazide was cyclized to 5-substituted-134-oxadiazol-2-thiol by CS

2in an alcoholic KOH medium

on reflux A list of electrophiles 8andasho was synthesized fromdifferent aralkylalkylaryl amines 7andasho on simple stirringwith 2-bromoacetyl bromide in aqueous Na

2CO3medium

The final compounds were geared up by stirring 6 with 8andashoagain in DMF in the presence of NaH and separated throughfiltration after addition of excess distilled water

All the compounds were structurally corroboratedthrough IR 1H-NMR and EIMS spectral data Compound3 is also aided by 13C-NMR data One molecule descriptionis given for 9h Its molecular formula was nominated asC23H20ClN3O5S elucidated with the aid of molecular ion

peak in EIMS spectrum and integration of protons in 1H-NMR spectrum The suggested fragmentation pattern of thismolecule is also sketched in Figure 1 The specific absorptionbands for different functionalities in the molecule appearedin IR spectrum at 120592max (cm

minus1) 3447 (N-H) 3069 (Ar C-H)1738 (ester C=O) 1677 (amide C=O) 1689 (C=N) 1606 (ArC=C) 1149 (C-O) and 705 (C-Cl) In aromatic region of1H-NMR spectrum the three singlets with single protonintegration resonating at 120575 758 (H-51015840) 704 (H-81015840) and 621(H-31015840) were allocated for the chlorinated coumarin partof the molecule The other four signals in the same regionwith single proton integration resonated at 120575 716 (d J =80Hz H-610158401015840) 711 (t J = 80Hz H-510158401015840) 707 (t J = 80HzH-410158401015840) and 698 (d J = 80Hz H-310158401015840) for 2-ethylphenyl partof the molecule The ethyl group was confirmed through aquartet and a triplet both with coupling constant of 72Hzappearing at 120575 246 (2H H-710158401015840) and 103 (3H CH

3-810158401015840)

respectively in the aliphatic region The protons of twomethylene groups linked to oxygen and sulfur appeared astwo singlets at 120575 535 (H-121015840) and 409 (H-2101584010158401015840) respectivelyThe three protons of methyl group attached to coumarinnucleus resonated as singlet at 120575 236 (CH

3-111015840) The whole

discussion confirmed 9h as N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide

6 Organic Chemistry International

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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2 Organic Chemistry International

2 Experimental

21 Material and Methods 4-Chlororesorcinol ethyl ace-toacetate ethyl 2-bromoacetate hydrated hydrazine carbondisulfide aralkylalkylaryl amines and 2-bromoacetyl bro-mide were purchased from Merck Riedel-de Haen Aldrichand Alfa Aesar through local suppliers along with analyticalgrade solventsThe Jasco-320-A spectrophotometer was usedto record IR spectra by KBr pellet method The Brukerspectrometers at 125 and 400MHz were used to recordthe 13C and 1H NMR spectra in CDCl

3 respectively The

JMS-HX-110 spectrometer was used to record EIMS spectraSilica plates coated on alumina were used for thin layerchromatography (TLC) run in mobile phase of n-hexaneand ethyl acetate and observed under UV

254 Griffin-George

apparatus was used to record the melting points in opencapillary tubes which were uncorrected

22 Synthesis of 6-Chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) 4-Chlororesorcinol (005mol 1) was dissolvedin ethyl acetoacetate (005mol 2) on heating in an iodineflask (500mL)Then concentratedH

2SO4(25mL) was added

on continuous shaking at low temperature The mixture wasaged for 12ndash16 hours Excess cold distilled water was added toprecipitate the title compound which was separated throughfiltration washed by distilled water and dried

23 Synthesis of Ethyl 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetate (4) Compound 3 (0045mol) wasdissolved in DMF (25mL) in a round bottom (RB) flask(250mL) and then NaH (0045mol) was added The mixturewas stirred for 05 hours and then ethyl 2-bromoacetate(0045mol) was added The stirring was continued for 3-4hours along with monitoring through TLC Excess colddistilled water was added and the formed precipitates werefiltered out washed and dried

24 Synthesis of 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetohydrazide (5) The ethyl ester 4 (004mol) wasmixed with methanol (35mL) in a RB flask (250mL) Thehydrated hydrazine (004mol) was added and the mixturewas set to stir for 2-3 hours TLC was frequently developedto monitor the reaction Solvent was evaporated to one-thirdand then excess of distilled water was added to precipitatethe productThe precipitates were acquired through filtrationand subjected to washing and drying

25 Synthesis of 5-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-thiol (6) Compound 5(0035mol) was added to absolute ethanol (50mL) in aRB flask (250mL) followed by solid KOH (0035mol) Themixture was homogenized on reflux and then cooled toroom temperature and liquid CS

2(007mol) was added The

mixture was again set to reflux for 4-5 hours along withsupervision by TLC Solvent was evaporated to one-third andthen excess cold distilled water was added The pH of thishomogeneous solution was adjusted to 6-7 by dilute HCland aged for 05 hours to allow maximum precipitation The

precipitates were filtered washed with distilled water anddried

26 General Synthesis of N-Aralkylalkylaryl-2-bromoacet-amide (8andasho) Aralkylalkylaryl amines (0005mol 7andasho) were dispersed in distilled water (15mL) in an iodineflask (125mL) The pH was adjusted to 8-9 by aqueousNa2CO3solution (15 4mL) Then 2-bromoacetyl bromide

(0005mol) was added on vigorous stirring and further setto stir for 1 hour on maintained pH The precipitates of titleproductswere filtered offwashed by distilledwater anddried

27 General Synthesis of N-Aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9andasho) Compound 6(0002mol) was dissolved in DMF (12mL) in a round bottomflask (50mL) followed by NaH (0002mol) The mixturewas stirred for 05 hours and then N-aralkylalkylaryl-2-bromoacetamide (0002mol 8andasho) were added Thestirring was continued for 4ndash6 hours along with monitoringthrough TLC Excess cold distilled water was added and theprecipitates were filtered out washed and dried

28 Antibacterial Activity Assay The sterilized 96-wellmicroplates under aseptic conditions were used to evaluatethe antibacterial activity by the reported method of Kaspadyet al 2009 andYang et al 2006with slightmodifications [2122]The change in absorbance before and after the addition ofsample compound was noted The absorbance is varied withnumber of microbial cells which are varied with log phasemicrobial growth

The clinically isolated three Gram-negative and twoGram-positive bacteria were stored on stock culture agarmedium A mixture of 200 120583L was prepared by 180 120583L freshnutrient broth with suitable dilutions and 20120583g test sampleswith suitable dilutions All the dilutions were performedusing specific suited solvents Before and after incubation at37∘C for 16ndash24 hrs with lid on the microplate the absorbance(012ndash019 at beginning) was measured at 540 nm The varia-tion in absorbance was the criteria for bacterial growth Thepercent inhibition was calculated by the following formula

Inhibition () = X minus YXtimes 100 (1)

where119883 is absorbance in control with bacterial culture and119884is absorbance in test sample Ciprofloxacin was taken as ref-erence standard Minimum inhibitory concentration (MIC)was measured with suitable dilutions (5ndash30120583gwell) andresults were calculated using EZ-Fit Perrella Scientific IncAmherst USA software

29 Statistical Analysis Theantibacterial activity results werereported as percentage of age inhibition and minimuminhibitory concentration (MIC) values after performing eachexperiment three times The results were reported as mean plusmnSEM after statistical analysis by Microsoft Excel 2010

Organic Chemistry International 3

210 Characterization of the Synthesized Compounds(3ndash6 9andasho)

2101 6-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3)Light brown amorphous solid Yield 78 MP 262ndash264∘CMF C

10H7ClO3 MM 210 gmolminus1 IR (KBr 120592max cm

minus1)3310 (O-H) 3055 (Ar C-H) 1732 (ester C=O) 1586 (Ar C=C)1146 (C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575

ppm) 754 (s 1H H-51015840) 698 (s 1H H-81015840) 617 (s 1H H-31015840) 237 (s 3H CH

3-111015840) 13C-NMR (125MHz CHCl

3-1198891

120575 ppm) 1605 (C-21015840) 1577 (C-71015840) 1534 (C-41015840) 1515 (C-91015840)1254 (C-51015840) 1187 (C-61015840) 1136 (C-101015840) 1127 (C-31015840) 1003 (C-81015840) 185 (C-111015840) EIMS (mz) 212 (6) 210 [M]∙+ (17) 193(7) 182 (5) 175 (BP 100) 165 (3) 149 (2) 134 (5)

2102 Ethyl 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetate (4) Cream white amorphous solid Yield73 MP 184ndash186∘C MF C

14H13ClO5 MM 296 gmolminus1

IR (KBr 120592max cmminus1) 3316 (O-H) 3062 (Ar C-H) 1735 (ester

C=O) 1594 (Ar C=C) 1159 (C-O) 702 (C-Cl) 1H-NMR(400MHz CHCl

3-1198891 120575 ppm) 759 (s 1H H-51015840) 671 (s

1H H-81015840) 618 (s 1H H-31015840) 474 (s 2H H-121015840) 427 (q J =72Hz 2H H-1101584010158401015840) 237 (s 3H CH

3-111015840) 130 (t J = 72Hz

3H CH3-2101584010158401015840) EIMS (mz) 298 (6) 296 [M]∙+ (17) 261

(19) 251 (4) 210 (91) 193 (18) 182 (BP 100) 165(8) 149 (7) 134 (16)

2103 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]ace-tohydrazide (5) Light yellow amorphous solid Yield 67MP 190ndash192∘C MF C

12H11ClN2O4 MM 282 gmolminus1 IR

(KBr 120592max cmminus1) 3421 (N-H) 3061 (Ar C-H) 1735 (ester

C=O) 1671 (amide C=O) 1594 (Ar C=C) 1159 (C-O) 703(C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 884 (s 1H

CON-H) 757 (s 1H H-51015840) 672 (s 1H H-81015840) 619 (s 1H H-31015840) 472 (s 2H H-121015840) 238 (s 3H CH

3-111015840) EIMS (mz)

284 (7) 282 [M]∙+ (16) 249 (7) 247 (18) 230 (4)214 (14) 210 (89) 193 (15) 182 (BP 100) 165 (4) 149(7) 134 (17)

2104 5-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]meth-yl-134-oxadiazol-2-thiol (6) Light brown amorphoussolid Yield 73 MP 188ndash190∘C MF C

13H9ClN2O4S

MM 324 gmolminus1 IR (KBr 120592max cmminus1) 3078 (Ar C-H)

1736 (ester C=O) 1689 (C=N) 1595 (Ar C=C) 1158 (C-O)697 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 759

(s 1H H-51015840) 675 (s 1H H-81015840) 621 (s 1H H-31015840) 474 (s2H H-121015840) 239 (s 3H CH

3-111015840) EIMS (mz) 326 (7) 324

[M]∙+ (16) 289 (14) 251 (3) 249 (7) 230 (2) 214(13) 210 (86) 193 (13) 182 (BP 100) 165 (7) 149(4) 134 (16)

2105 N-Cyclohexyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9a) White amorphous solid Yield 78 MP 100ndash102∘C MF C

21H22ClN3O5S MM 463 gmolminus1 IR (KBr

120592max cmminus1) 3445 (N-H) 3073 (Ar C-H) 1739 (ester C=O)

1676 (amide C=O) 1684 (C=N) 1596 (Ar C=C) 1159 (C-O)

697 (C-Cl) 1H-NMR (400MHz CHCl3-1198891 120575 ppm) 871 (s

1H CON-H) 757 (s 1H H-51015840) 704 (s 1H H-81015840) 623 (s1H H-31015840) 533 (s 2H H-121015840) 405 (s 2H H-2101584010158401015840) 376ndash373(m 1H H-110158401015840) 238 (s 3H CH

3-111015840) 185ndash182 (m 2H Heq-

210158401015840 ampHeq-6

10158401015840) 167ndash156 (m 4H H-310158401015840 ampH-510158401015840) 135ndash132 (m2H Hax-2

10158401015840 ampHax-610158401015840) 122ndash116 (m 2H H-410158401015840) EIMS (mz)

465 (9) 463 [M]∙+ (20) 428 (16) 251 (4) 249 (8)230 (4) 214 (13) 210 (90) 193 (17) 182 (BP 100) 165(4) 149 (8) 134 (17) 126 (28) 98 (34)

2106 N-Benzyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9b) Light yellow amorphous solid Yield 84 MP 126ndash128∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR (KBr

120592max cmminus1) 3464 (N-H) 3053 (Ar C-H) 1736 (ester C=O)

1672 (amide C=O) 1689 (C=N) 1609 (Ar C=C) 1156 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 864

(s 1H CON-H) 761 (s 1H H-51015840) 725ndash719 (m 5H H-210158401015840to H-610158401015840) 706 (s 1H H-81015840) 623 (s 1H H-31015840) 537 (s 2HH-121015840) 437 (s 2H H-710158401015840) 406 (s 2H H-2101584010158401015840) 234 (s 3HCH3-111015840) EIMS (mz) 473 (8) 471 [M]∙+ (24) 436 (13)

251 (5) 249 (9) 230 (3) 214 (8) 210 (84) 193 (11)182 (BP 100) 165 (7) 149 (5) 134 (47) 106 (35)

2107 N-(2-Phenylethyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9c) Light grey amorphous solid Yield 87 MP126ndash128∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3441 (N-H) 3065 (Ar C-H) 1743 (ester

C=O) 1659 (amide C=O) 1684 (C=N) 1602 (Ar C=C) 1174(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

862 (s 1H CON-H) 761 (s 1H H-51015840) 715ndash710 (m 5H H-210158401015840 to H-610158401015840) 705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2HH-121015840) 407 (s 2H H-2101584010158401015840) 343 (t J = 76Hz 2H H-810158401015840) 273(t J = 76Hz 2H H-710158401015840) 238 (s 3H CH

3-111015840) EIMS (mz)

487 (6) 485 [M]∙+ (17) 450 (13) 251 (4) 249 (8) 230(1) 214 (9) 210 (88) 193 (15) 182 (BP 100) 165 (7)149 (8) 148 (31) 134 (9) 120 (34)

2108 N-Phenyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9d) Light grey amorphous solid Yield 77 MP 94ndash96∘C MF C

21H16ClN3O5S MM 457 gmolminus1 IR (KBr

120592max cmminus1) 3436 (N-H) 3046 (Ar C-H) 1735 (ester C=O)

1667 (amide C=O) 1681 (C=N) 1588 (Ar C=C) 1121 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 859

(s 1H CON-H) 763 (s 1H H-51015840) 757 (d J = 76Hz 2HH-210158401015840 ampH-610158401015840) 734 (t J = 76Hz 2H H-310158401015840 ampH-510158401015840) 717(t J = 76Hz 1H H-410158401015840) 705 (s 1H H-81015840) 620 (s 1HH-31015840) 536 (s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 239 (s 3HCH3-111015840) EIMS (mz) 459 (6) 457 [M]∙+ (21) 422 (18)

251 (6) 249 (10) 230 (4) 214 (12) 210 (87) 193(15) 182 (BP 100) 165 (7) 149 (4) 134 (17) 120(37) 92 (29)

4 Organic Chemistry International

2109 N-(2-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9e) White amorphous solid Yield 69MP 100ndash102∘CMF C

22H18ClN3O5SMM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3442 (N-H) 3069 (Ar C-H) 1733 (ester

C=O) 1678 (amide C=O) 1691 (C=N) 1603 (Ar C=C) 1150(C-O) 701 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

873 (s 1H CON-H) 772 (d J = 80Hz 1H H-610158401015840) 763 (s1H H-51015840) 721 (d J = 80Hz 1H H-310158401015840) 715 (t J = 80Hz 1HH-510158401015840) 707 (t J = 80Hz 1H H-410158401015840) 702 (s 1H H-81015840) 622(s 1H H-31015840) 534 (s 2H H-121015840) 406 (s 2H H-2101584010158401015840) 238 (s3H CH

3-111015840) 228 (s 3H CH

3-710158401015840) EIMS (mz) 473 (7)

471 [M]∙+ (24) 436 (12) 251 (4) 249 (7) 230 (5)214 (16) 210 (81) 193 (13) 182 (BP 100) 165 (8) 149(3) 134 (47) 106 (32)

21010 N-(3-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulf-anyl]acetamide (9f) Yellowish grey amorphous solidYield 83 MP 88ndash90∘C MF C

22H18ClN3O5S MM

471 gmolminus1 IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar

C-H) 1736 (ester C=O) 1668 (amide C=O) 1689 (C=N)1591 (Ar C=C) 1153 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 882 (s 1H CON-H) 761 (s 1H H-51015840)

733 (s 1H H-210158401015840) 730 (d J = 76Hz 1H H-610158401015840) 717 (t J =80Hz 1H H-510158401015840) 704 (s 1H H-81015840) 691 (d J = 76Hz 1HH-410158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s 2HH-2101584010158401015840) 237 (s 3H CH

3-111015840) 230 (s 3H CH

3-710158401015840) EIMS

(mz) 473 (5) 471 [M]∙+ (19) 436 (13) 251 (7) 249(8) 230 (2) 214 (15) 210 (83) 193 (14) 182 (BP100) 165 (9) 149 (5) 134 (42) 106 (28)

21011 N-(4-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9g) White amorphous solid Yield 79MP 98ndash100∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3435 (N-H) 3061 (Ar C-H) 1734 (ester

C=O) 1668 (amide C=O) 1689 (C=N) 1584 (Ar C=C) 1141(C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 736 (d J = 84Hz2H H-210158401015840 ampH-610158401015840) 717 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) 226 (s 3H CH

3-710158401015840)

EIMS (mz) 473 (8) 471 [M]∙+ (23) 436 (15) 251 (7)249 (9) 230 (3) 214 (15) 210 (87) 193 (14) 182 (BP100) 165 (9) 149 (4) 134 (49) 106 (31)

21012 N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9h) Light brown amorphous solid Yield 84MP 92ndash94∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3447 (N-H) 3069 (Ar C-H) 1738 (ester

C=O) 1677 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1149(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

861 (s 1H CON-H) 758 (s 1H H-51015840) 716 (d J = 80Hz 1HH-610158401015840) 711 (t J = 80Hz 1H H-510158401015840) 707 (t J = 80Hz 1HH-410158401015840) 704 (s 1H H-81015840) 698 (d J = 80Hz 1H H-310158401015840) 621(s 1H H-31015840) 535 (s 2H H-121015840) 409 (s 2H H-2101584010158401015840) 246 (q

J = 72Hz 2H H-710158401015840) 236 (s 3H CH3-111015840) 103 (t J = 72Hz

3H CH3-810158401015840) EIMS (mz) 487 (6) 485 [M]∙+ (17) 450

(13) 251 (4) 249 (5) 230 (2) 214 (13) 210 (88)193 (14) 182 (BP 100) 165 (6) 149 (7) 148 (33) 134(16) 120 (32)

21013 N-(4-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9i) Cream white amorphous solid Yield 84MP 104ndash106∘C MF C

23H20ClN3O5S MM 485 gmolminus1

IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar C-H) 1736 (ester

C=O) 1671 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1147(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

872 (s 1H CON-H) 761 (s 1H H-51015840) 709 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 704 (s 1H H-81015840) 696 (d J = 80Hz2H H-310158401015840 ampH-510158401015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 254 (q J = 72Hz 2H H-710158401015840) 236 (s3H CH

3-111015840) 113 (t J = 72Hz 3H CH

3-810158401015840) EIMS (mz)

487 (8) 485 [M]∙+ (17) 450 (15) 251 (4) 249 (7)230 (5) 214 (9) 210 (92) 193 (17) 182 (BP 100) 165(7) 149 (5) 148 (35) 134 (11) 120 (38)

21014 N-(2-Methoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9j) Cream yellow amorphous solid Yield78 MP 106ndash108∘C MF C

22H18ClN3O6S MM

487 gmolminus1 IR (KBr 120592max cmminus1) 3437 (N-H) 3069 (Ar

C-H) 1733 (ester C=O) 1683 (amide C=O) 1689 (C=N)1603 (Ar C=C) 1158 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 859 (s 1H CON-H) 822 (d J = 80Hz

1H H-610158401015840) 762 (s 1H H-51015840) 705 (s 1H H-81015840) 701 (t J =76Hz 1H H-510158401015840) 692 (t J = 76Hz 1H H-410158401015840) 681 (d J =80Hz 1H H-310158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 382 (s 3H CH

3-710158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 489 (5) 487 [M]∙+ (17) 452 (16) 251 (4)249 (6) 230 (2) 214 (13) 210 (86) 193 (12) 182 (BP100) 165 (4) 150 (31) 149 (8) 134 (18) 122 (39)

21015 N-(2-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9k) Light grey amorphous solid Yield 86MP 96ndash98∘C MF C

23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3453 (N-H) 3056 (Ar C-H) 1736 (ester

C=O) 1667 (amide C=O) 1681 (C=N) 1606 (Ar C=C) 1155(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 743 (d J = 84Hz 1HH-610158401015840) 717 (t J = 84Hz 1H H-410158401015840) 703 (s 1H H-81015840) 684 (tJ = 84Hz 1H H-510158401015840) 675 (d J = 80Hz 1H H-310158401015840) 620 (s1H H-31015840) 535 (s 2H H-121015840) 404 (s 2H H-2101584010158401015840) 374 (q J =72Hz 2H H-710158401015840) 237 (s 3H CH

3-111015840) 111 (t J = 72Hz 3H

CH3-810158401015840) EIMS (mz) 503 (8) 501 [M]∙+ (22) 466 (11)

251 (4) 249 (7) 230 (2) 214 (14) 210 (85) 193 (18)182 (BP 100) 165 (8) 164 (30) 149 (9) 136 (28) 134(17)

21016 N-(4-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9l) Reddish purple amorphous solid Yield 74

Organic Chemistry International 5

MP 108ndash110∘CMF C23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3443 (N-H) 3078 (Ar C-H) 1734 (ester

C=O) 1679 (amide C=O) 1688 (C=N) 1597 (Ar C=C) 1155(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

882 (s 1H CON-H) 759 (s 1H H-51015840) 739 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 703 (s 1H H-81015840) 681 (d J = 84Hz 2HH-310158401015840 ampH-510158401015840) 620 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s2H H-2101584010158401015840) 397 (q J = 68Hz 2H H-710158401015840) 237 (s 3H CH

3-

111015840) 086 (t J = 68Hz 3H CH3-810158401015840) EIMS (mz) 503 (9)

501 [M]∙+ (21) 466 (13) 251 (6) 249 (8) 230 (3)214 (15) 210 (81) 193 (19) 182 (BP 100) 165 (9) 164(32) 149 (6) 136 (25) 134 (19)

21017 N-(2-Methoxycarbonylphenyl)-2-[(5-[(6-chloro-4-meth-yl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9m) Yellow amorphous solidYield 75 MP 122ndash124∘C MF C

23H18ClN3O7S MM

515 gmolminus1 IR (KBr 120592max cmminus1) 3429 (N-H) 3050 (Ar

C-H) 1731 (ester C=O) 1671 (amide C=O) 1683 (C=N)1601 (Ar C=C) 1159 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 881 (s 1H CON-H) 868 (d J = 84Hz

1H H-610158401015840) 810 (d J = 76Hz 1H H-310158401015840) 762 (s 1H H-51015840)751 (t J = 76Hz 1H H-510158401015840) 718 (t J = 76Hz 1H H-410158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840) 407(s 2H H-2101584010158401015840) 381 (s 3H CH

3-810158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 517 (9) 515 [M]∙+ (19) 480 (13) 251 (6)249 (9) 230 (2) 214 (14) 210 (92) 193 (17) 182 (BP100) 178 (37) 165 (6) 150 (33) 149 (7) 134 (15)

21018 N-(4-Bromophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9n) Light grey amorphous solid Yield 73MP 102ndash104∘CMF C

21H15BrClN

3O5S MM 535 gmolminus1

IR (KBr 120592max cmminus1) 3422 (N-H) 3056 (Ar C-H) 1734 (ester

C=O) 1662 (amide C=O) 1684 (C=N) 1593 (Ar C=C) 1143(C-O) 702 (C-Cl) 639 (C-Br) 1H-NMR (400MHz CHCl

3-

1198891 120575 ppm) 828 (s 1H CON-H) 762 (s 1HH-51015840) 747 (d J =

84Hz 2H H-210158401015840 ampH-610158401015840) 741 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) EIMS (mz) 539

(7) 537 (18) 535 [M]∙+ (20) 500 (14) 251 (6) 249(8) 230 (4) 214 (13) 210 (92) 198 (33) 193 (13)182 (BP 100) 170 (31) 165 (6) 149 (8) 134 (11)

21019 N-(4-Nitrophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9o) Light yellow amorphous solid Yield81 MP 108ndash110∘C MF C

21H15ClN4O7S MM

502 gmolminus1 IR (KBr 120592max cmminus1) 3438 (N-H) 3053 (Ar

C-H) 1735 (ester C=O) 1678 (amide C=O) 1688 (C=N)1606 (Ar C=C) 1163 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 934 (s 1H CON-H) 841 (d J = 80Hz

2H H-310158401015840 ampH-510158401015840) 806 (d J = 80Hz 2H H-210158401015840 ampH-610158401015840)762 (s 1H H-51015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534(s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840)

EIMS (mz) 504 (5) 502 [M]∙+ (17) 467 (18) 251 (8)249 (7) 230 (5) 214 (11) 210 (91) 193 (18) 182 (BP100) 165 (42) 149 (8) 137 (32) 134 (17)

3 Results and Discussion

The different N-aralkylalkylaryl acetamides incorporatingcoumarin and 134-oxadiazole rings 9andasho were synthesizedby the multistep protocol given in Scheme 1 The synthesiswas aimed at combining multiple functionalities in a singlemolecule so these may be able to demonstrate more effi-cient biological activity The antibacterial behavior of thesemolecules was tested against Gram-bacteria including posi-tive and negative strains The three negative and two positivebacterial strains have been reported to be the cause of variousdiseases [23ndash27]

31 Chemistry First 4-chlororesorcinol (1) was treated withethyl acetoacetate (2) in a strong acidic medium to yield6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) whichwas separated through filtration Compound 3 was furtherO-substituted by ethyl 2-bromoacetate in a polar aproticsolvent with the aid of a weak base This substituted ester4 was converted to corresponding carbohydrazide 5 aftera simple nucleophilic substitution reaction by hydrazine inmethanol The carbohydrazide was cyclized to 5-substituted-134-oxadiazol-2-thiol by CS

2in an alcoholic KOH medium

on reflux A list of electrophiles 8andasho was synthesized fromdifferent aralkylalkylaryl amines 7andasho on simple stirringwith 2-bromoacetyl bromide in aqueous Na

2CO3medium

The final compounds were geared up by stirring 6 with 8andashoagain in DMF in the presence of NaH and separated throughfiltration after addition of excess distilled water

All the compounds were structurally corroboratedthrough IR 1H-NMR and EIMS spectral data Compound3 is also aided by 13C-NMR data One molecule descriptionis given for 9h Its molecular formula was nominated asC23H20ClN3O5S elucidated with the aid of molecular ion

peak in EIMS spectrum and integration of protons in 1H-NMR spectrum The suggested fragmentation pattern of thismolecule is also sketched in Figure 1 The specific absorptionbands for different functionalities in the molecule appearedin IR spectrum at 120592max (cm

minus1) 3447 (N-H) 3069 (Ar C-H)1738 (ester C=O) 1677 (amide C=O) 1689 (C=N) 1606 (ArC=C) 1149 (C-O) and 705 (C-Cl) In aromatic region of1H-NMR spectrum the three singlets with single protonintegration resonating at 120575 758 (H-51015840) 704 (H-81015840) and 621(H-31015840) were allocated for the chlorinated coumarin partof the molecule The other four signals in the same regionwith single proton integration resonated at 120575 716 (d J =80Hz H-610158401015840) 711 (t J = 80Hz H-510158401015840) 707 (t J = 80HzH-410158401015840) and 698 (d J = 80Hz H-310158401015840) for 2-ethylphenyl partof the molecule The ethyl group was confirmed through aquartet and a triplet both with coupling constant of 72Hzappearing at 120575 246 (2H H-710158401015840) and 103 (3H CH

3-810158401015840)

respectively in the aliphatic region The protons of twomethylene groups linked to oxygen and sulfur appeared astwo singlets at 120575 535 (H-121015840) and 409 (H-2101584010158401015840) respectivelyThe three protons of methyl group attached to coumarinnucleus resonated as singlet at 120575 236 (CH

3-111015840) The whole

discussion confirmed 9h as N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide

6 Organic Chemistry International

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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CatalystsJournal of

Organic Chemistry International 3

210 Characterization of the Synthesized Compounds(3ndash6 9andasho)

2101 6-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3)Light brown amorphous solid Yield 78 MP 262ndash264∘CMF C

10H7ClO3 MM 210 gmolminus1 IR (KBr 120592max cm

minus1)3310 (O-H) 3055 (Ar C-H) 1732 (ester C=O) 1586 (Ar C=C)1146 (C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575

ppm) 754 (s 1H H-51015840) 698 (s 1H H-81015840) 617 (s 1H H-31015840) 237 (s 3H CH

3-111015840) 13C-NMR (125MHz CHCl

3-1198891

120575 ppm) 1605 (C-21015840) 1577 (C-71015840) 1534 (C-41015840) 1515 (C-91015840)1254 (C-51015840) 1187 (C-61015840) 1136 (C-101015840) 1127 (C-31015840) 1003 (C-81015840) 185 (C-111015840) EIMS (mz) 212 (6) 210 [M]∙+ (17) 193(7) 182 (5) 175 (BP 100) 165 (3) 149 (2) 134 (5)

2102 Ethyl 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetate (4) Cream white amorphous solid Yield73 MP 184ndash186∘C MF C

14H13ClO5 MM 296 gmolminus1

IR (KBr 120592max cmminus1) 3316 (O-H) 3062 (Ar C-H) 1735 (ester

C=O) 1594 (Ar C=C) 1159 (C-O) 702 (C-Cl) 1H-NMR(400MHz CHCl

3-1198891 120575 ppm) 759 (s 1H H-51015840) 671 (s

1H H-81015840) 618 (s 1H H-31015840) 474 (s 2H H-121015840) 427 (q J =72Hz 2H H-1101584010158401015840) 237 (s 3H CH

3-111015840) 130 (t J = 72Hz

3H CH3-2101584010158401015840) EIMS (mz) 298 (6) 296 [M]∙+ (17) 261

(19) 251 (4) 210 (91) 193 (18) 182 (BP 100) 165(8) 149 (7) 134 (16)

2103 2-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]ace-tohydrazide (5) Light yellow amorphous solid Yield 67MP 190ndash192∘C MF C

12H11ClN2O4 MM 282 gmolminus1 IR

(KBr 120592max cmminus1) 3421 (N-H) 3061 (Ar C-H) 1735 (ester

C=O) 1671 (amide C=O) 1594 (Ar C=C) 1159 (C-O) 703(C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 884 (s 1H

CON-H) 757 (s 1H H-51015840) 672 (s 1H H-81015840) 619 (s 1H H-31015840) 472 (s 2H H-121015840) 238 (s 3H CH

3-111015840) EIMS (mz)

284 (7) 282 [M]∙+ (16) 249 (7) 247 (18) 230 (4)214 (14) 210 (89) 193 (15) 182 (BP 100) 165 (4) 149(7) 134 (17)

2104 5-[(6-Chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]meth-yl-134-oxadiazol-2-thiol (6) Light brown amorphoussolid Yield 73 MP 188ndash190∘C MF C

13H9ClN2O4S

MM 324 gmolminus1 IR (KBr 120592max cmminus1) 3078 (Ar C-H)

1736 (ester C=O) 1689 (C=N) 1595 (Ar C=C) 1158 (C-O)697 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 759

(s 1H H-51015840) 675 (s 1H H-81015840) 621 (s 1H H-31015840) 474 (s2H H-121015840) 239 (s 3H CH

3-111015840) EIMS (mz) 326 (7) 324

[M]∙+ (16) 289 (14) 251 (3) 249 (7) 230 (2) 214(13) 210 (86) 193 (13) 182 (BP 100) 165 (7) 149(4) 134 (16)

2105 N-Cyclohexyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9a) White amorphous solid Yield 78 MP 100ndash102∘C MF C

21H22ClN3O5S MM 463 gmolminus1 IR (KBr

120592max cmminus1) 3445 (N-H) 3073 (Ar C-H) 1739 (ester C=O)

1676 (amide C=O) 1684 (C=N) 1596 (Ar C=C) 1159 (C-O)

697 (C-Cl) 1H-NMR (400MHz CHCl3-1198891 120575 ppm) 871 (s

1H CON-H) 757 (s 1H H-51015840) 704 (s 1H H-81015840) 623 (s1H H-31015840) 533 (s 2H H-121015840) 405 (s 2H H-2101584010158401015840) 376ndash373(m 1H H-110158401015840) 238 (s 3H CH

3-111015840) 185ndash182 (m 2H Heq-

210158401015840 ampHeq-6

10158401015840) 167ndash156 (m 4H H-310158401015840 ampH-510158401015840) 135ndash132 (m2H Hax-2

10158401015840 ampHax-610158401015840) 122ndash116 (m 2H H-410158401015840) EIMS (mz)

465 (9) 463 [M]∙+ (20) 428 (16) 251 (4) 249 (8)230 (4) 214 (13) 210 (90) 193 (17) 182 (BP 100) 165(4) 149 (8) 134 (17) 126 (28) 98 (34)

2106 N-Benzyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9b) Light yellow amorphous solid Yield 84 MP 126ndash128∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR (KBr

120592max cmminus1) 3464 (N-H) 3053 (Ar C-H) 1736 (ester C=O)

1672 (amide C=O) 1689 (C=N) 1609 (Ar C=C) 1156 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 864

(s 1H CON-H) 761 (s 1H H-51015840) 725ndash719 (m 5H H-210158401015840to H-610158401015840) 706 (s 1H H-81015840) 623 (s 1H H-31015840) 537 (s 2HH-121015840) 437 (s 2H H-710158401015840) 406 (s 2H H-2101584010158401015840) 234 (s 3HCH3-111015840) EIMS (mz) 473 (8) 471 [M]∙+ (24) 436 (13)

251 (5) 249 (9) 230 (3) 214 (8) 210 (84) 193 (11)182 (BP 100) 165 (7) 149 (5) 134 (47) 106 (35)

2107 N-(2-Phenylethyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acet-amide (9c) Light grey amorphous solid Yield 87 MP126ndash128∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3441 (N-H) 3065 (Ar C-H) 1743 (ester

C=O) 1659 (amide C=O) 1684 (C=N) 1602 (Ar C=C) 1174(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

862 (s 1H CON-H) 761 (s 1H H-51015840) 715ndash710 (m 5H H-210158401015840 to H-610158401015840) 705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2HH-121015840) 407 (s 2H H-2101584010158401015840) 343 (t J = 76Hz 2H H-810158401015840) 273(t J = 76Hz 2H H-710158401015840) 238 (s 3H CH

3-111015840) EIMS (mz)

487 (6) 485 [M]∙+ (17) 450 (13) 251 (4) 249 (8) 230(1) 214 (9) 210 (88) 193 (15) 182 (BP 100) 165 (7)149 (8) 148 (31) 134 (9) 120 (34)

2108 N-Phenyl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chrom-en-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide(9d) Light grey amorphous solid Yield 77 MP 94ndash96∘C MF C

21H16ClN3O5S MM 457 gmolminus1 IR (KBr

120592max cmminus1) 3436 (N-H) 3046 (Ar C-H) 1735 (ester C=O)

1667 (amide C=O) 1681 (C=N) 1588 (Ar C=C) 1121 (C-O)704 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm) 859

(s 1H CON-H) 763 (s 1H H-51015840) 757 (d J = 76Hz 2HH-210158401015840 ampH-610158401015840) 734 (t J = 76Hz 2H H-310158401015840 ampH-510158401015840) 717(t J = 76Hz 1H H-410158401015840) 705 (s 1H H-81015840) 620 (s 1HH-31015840) 536 (s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 239 (s 3HCH3-111015840) EIMS (mz) 459 (6) 457 [M]∙+ (21) 422 (18)

251 (6) 249 (10) 230 (4) 214 (12) 210 (87) 193(15) 182 (BP 100) 165 (7) 149 (4) 134 (17) 120(37) 92 (29)

4 Organic Chemistry International

2109 N-(2-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9e) White amorphous solid Yield 69MP 100ndash102∘CMF C

22H18ClN3O5SMM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3442 (N-H) 3069 (Ar C-H) 1733 (ester

C=O) 1678 (amide C=O) 1691 (C=N) 1603 (Ar C=C) 1150(C-O) 701 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

873 (s 1H CON-H) 772 (d J = 80Hz 1H H-610158401015840) 763 (s1H H-51015840) 721 (d J = 80Hz 1H H-310158401015840) 715 (t J = 80Hz 1HH-510158401015840) 707 (t J = 80Hz 1H H-410158401015840) 702 (s 1H H-81015840) 622(s 1H H-31015840) 534 (s 2H H-121015840) 406 (s 2H H-2101584010158401015840) 238 (s3H CH

3-111015840) 228 (s 3H CH

3-710158401015840) EIMS (mz) 473 (7)

471 [M]∙+ (24) 436 (12) 251 (4) 249 (7) 230 (5)214 (16) 210 (81) 193 (13) 182 (BP 100) 165 (8) 149(3) 134 (47) 106 (32)

21010 N-(3-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulf-anyl]acetamide (9f) Yellowish grey amorphous solidYield 83 MP 88ndash90∘C MF C

22H18ClN3O5S MM

471 gmolminus1 IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar

C-H) 1736 (ester C=O) 1668 (amide C=O) 1689 (C=N)1591 (Ar C=C) 1153 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 882 (s 1H CON-H) 761 (s 1H H-51015840)

733 (s 1H H-210158401015840) 730 (d J = 76Hz 1H H-610158401015840) 717 (t J =80Hz 1H H-510158401015840) 704 (s 1H H-81015840) 691 (d J = 76Hz 1HH-410158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s 2HH-2101584010158401015840) 237 (s 3H CH

3-111015840) 230 (s 3H CH

3-710158401015840) EIMS

(mz) 473 (5) 471 [M]∙+ (19) 436 (13) 251 (7) 249(8) 230 (2) 214 (15) 210 (83) 193 (14) 182 (BP100) 165 (9) 149 (5) 134 (42) 106 (28)

21011 N-(4-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9g) White amorphous solid Yield 79MP 98ndash100∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3435 (N-H) 3061 (Ar C-H) 1734 (ester

C=O) 1668 (amide C=O) 1689 (C=N) 1584 (Ar C=C) 1141(C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 736 (d J = 84Hz2H H-210158401015840 ampH-610158401015840) 717 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) 226 (s 3H CH

3-710158401015840)

EIMS (mz) 473 (8) 471 [M]∙+ (23) 436 (15) 251 (7)249 (9) 230 (3) 214 (15) 210 (87) 193 (14) 182 (BP100) 165 (9) 149 (4) 134 (49) 106 (31)

21012 N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9h) Light brown amorphous solid Yield 84MP 92ndash94∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3447 (N-H) 3069 (Ar C-H) 1738 (ester

C=O) 1677 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1149(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

861 (s 1H CON-H) 758 (s 1H H-51015840) 716 (d J = 80Hz 1HH-610158401015840) 711 (t J = 80Hz 1H H-510158401015840) 707 (t J = 80Hz 1HH-410158401015840) 704 (s 1H H-81015840) 698 (d J = 80Hz 1H H-310158401015840) 621(s 1H H-31015840) 535 (s 2H H-121015840) 409 (s 2H H-2101584010158401015840) 246 (q

J = 72Hz 2H H-710158401015840) 236 (s 3H CH3-111015840) 103 (t J = 72Hz

3H CH3-810158401015840) EIMS (mz) 487 (6) 485 [M]∙+ (17) 450

(13) 251 (4) 249 (5) 230 (2) 214 (13) 210 (88)193 (14) 182 (BP 100) 165 (6) 149 (7) 148 (33) 134(16) 120 (32)

21013 N-(4-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9i) Cream white amorphous solid Yield 84MP 104ndash106∘C MF C

23H20ClN3O5S MM 485 gmolminus1

IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar C-H) 1736 (ester

C=O) 1671 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1147(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

872 (s 1H CON-H) 761 (s 1H H-51015840) 709 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 704 (s 1H H-81015840) 696 (d J = 80Hz2H H-310158401015840 ampH-510158401015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 254 (q J = 72Hz 2H H-710158401015840) 236 (s3H CH

3-111015840) 113 (t J = 72Hz 3H CH

3-810158401015840) EIMS (mz)

487 (8) 485 [M]∙+ (17) 450 (15) 251 (4) 249 (7)230 (5) 214 (9) 210 (92) 193 (17) 182 (BP 100) 165(7) 149 (5) 148 (35) 134 (11) 120 (38)

21014 N-(2-Methoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9j) Cream yellow amorphous solid Yield78 MP 106ndash108∘C MF C

22H18ClN3O6S MM

487 gmolminus1 IR (KBr 120592max cmminus1) 3437 (N-H) 3069 (Ar

C-H) 1733 (ester C=O) 1683 (amide C=O) 1689 (C=N)1603 (Ar C=C) 1158 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 859 (s 1H CON-H) 822 (d J = 80Hz

1H H-610158401015840) 762 (s 1H H-51015840) 705 (s 1H H-81015840) 701 (t J =76Hz 1H H-510158401015840) 692 (t J = 76Hz 1H H-410158401015840) 681 (d J =80Hz 1H H-310158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 382 (s 3H CH

3-710158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 489 (5) 487 [M]∙+ (17) 452 (16) 251 (4)249 (6) 230 (2) 214 (13) 210 (86) 193 (12) 182 (BP100) 165 (4) 150 (31) 149 (8) 134 (18) 122 (39)

21015 N-(2-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9k) Light grey amorphous solid Yield 86MP 96ndash98∘C MF C

23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3453 (N-H) 3056 (Ar C-H) 1736 (ester

C=O) 1667 (amide C=O) 1681 (C=N) 1606 (Ar C=C) 1155(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 743 (d J = 84Hz 1HH-610158401015840) 717 (t J = 84Hz 1H H-410158401015840) 703 (s 1H H-81015840) 684 (tJ = 84Hz 1H H-510158401015840) 675 (d J = 80Hz 1H H-310158401015840) 620 (s1H H-31015840) 535 (s 2H H-121015840) 404 (s 2H H-2101584010158401015840) 374 (q J =72Hz 2H H-710158401015840) 237 (s 3H CH

3-111015840) 111 (t J = 72Hz 3H

CH3-810158401015840) EIMS (mz) 503 (8) 501 [M]∙+ (22) 466 (11)

251 (4) 249 (7) 230 (2) 214 (14) 210 (85) 193 (18)182 (BP 100) 165 (8) 164 (30) 149 (9) 136 (28) 134(17)

21016 N-(4-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9l) Reddish purple amorphous solid Yield 74

Organic Chemistry International 5

MP 108ndash110∘CMF C23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3443 (N-H) 3078 (Ar C-H) 1734 (ester

C=O) 1679 (amide C=O) 1688 (C=N) 1597 (Ar C=C) 1155(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

882 (s 1H CON-H) 759 (s 1H H-51015840) 739 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 703 (s 1H H-81015840) 681 (d J = 84Hz 2HH-310158401015840 ampH-510158401015840) 620 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s2H H-2101584010158401015840) 397 (q J = 68Hz 2H H-710158401015840) 237 (s 3H CH

3-

111015840) 086 (t J = 68Hz 3H CH3-810158401015840) EIMS (mz) 503 (9)

501 [M]∙+ (21) 466 (13) 251 (6) 249 (8) 230 (3)214 (15) 210 (81) 193 (19) 182 (BP 100) 165 (9) 164(32) 149 (6) 136 (25) 134 (19)

21017 N-(2-Methoxycarbonylphenyl)-2-[(5-[(6-chloro-4-meth-yl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9m) Yellow amorphous solidYield 75 MP 122ndash124∘C MF C

23H18ClN3O7S MM

515 gmolminus1 IR (KBr 120592max cmminus1) 3429 (N-H) 3050 (Ar

C-H) 1731 (ester C=O) 1671 (amide C=O) 1683 (C=N)1601 (Ar C=C) 1159 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 881 (s 1H CON-H) 868 (d J = 84Hz

1H H-610158401015840) 810 (d J = 76Hz 1H H-310158401015840) 762 (s 1H H-51015840)751 (t J = 76Hz 1H H-510158401015840) 718 (t J = 76Hz 1H H-410158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840) 407(s 2H H-2101584010158401015840) 381 (s 3H CH

3-810158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 517 (9) 515 [M]∙+ (19) 480 (13) 251 (6)249 (9) 230 (2) 214 (14) 210 (92) 193 (17) 182 (BP100) 178 (37) 165 (6) 150 (33) 149 (7) 134 (15)

21018 N-(4-Bromophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9n) Light grey amorphous solid Yield 73MP 102ndash104∘CMF C

21H15BrClN

3O5S MM 535 gmolminus1

IR (KBr 120592max cmminus1) 3422 (N-H) 3056 (Ar C-H) 1734 (ester

C=O) 1662 (amide C=O) 1684 (C=N) 1593 (Ar C=C) 1143(C-O) 702 (C-Cl) 639 (C-Br) 1H-NMR (400MHz CHCl

3-

1198891 120575 ppm) 828 (s 1H CON-H) 762 (s 1HH-51015840) 747 (d J =

84Hz 2H H-210158401015840 ampH-610158401015840) 741 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) EIMS (mz) 539

(7) 537 (18) 535 [M]∙+ (20) 500 (14) 251 (6) 249(8) 230 (4) 214 (13) 210 (92) 198 (33) 193 (13)182 (BP 100) 170 (31) 165 (6) 149 (8) 134 (11)

21019 N-(4-Nitrophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9o) Light yellow amorphous solid Yield81 MP 108ndash110∘C MF C

21H15ClN4O7S MM

502 gmolminus1 IR (KBr 120592max cmminus1) 3438 (N-H) 3053 (Ar

C-H) 1735 (ester C=O) 1678 (amide C=O) 1688 (C=N)1606 (Ar C=C) 1163 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 934 (s 1H CON-H) 841 (d J = 80Hz

2H H-310158401015840 ampH-510158401015840) 806 (d J = 80Hz 2H H-210158401015840 ampH-610158401015840)762 (s 1H H-51015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534(s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840)

EIMS (mz) 504 (5) 502 [M]∙+ (17) 467 (18) 251 (8)249 (7) 230 (5) 214 (11) 210 (91) 193 (18) 182 (BP100) 165 (42) 149 (8) 137 (32) 134 (17)

3 Results and Discussion

The different N-aralkylalkylaryl acetamides incorporatingcoumarin and 134-oxadiazole rings 9andasho were synthesizedby the multistep protocol given in Scheme 1 The synthesiswas aimed at combining multiple functionalities in a singlemolecule so these may be able to demonstrate more effi-cient biological activity The antibacterial behavior of thesemolecules was tested against Gram-bacteria including posi-tive and negative strains The three negative and two positivebacterial strains have been reported to be the cause of variousdiseases [23ndash27]

31 Chemistry First 4-chlororesorcinol (1) was treated withethyl acetoacetate (2) in a strong acidic medium to yield6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) whichwas separated through filtration Compound 3 was furtherO-substituted by ethyl 2-bromoacetate in a polar aproticsolvent with the aid of a weak base This substituted ester4 was converted to corresponding carbohydrazide 5 aftera simple nucleophilic substitution reaction by hydrazine inmethanol The carbohydrazide was cyclized to 5-substituted-134-oxadiazol-2-thiol by CS

2in an alcoholic KOH medium

on reflux A list of electrophiles 8andasho was synthesized fromdifferent aralkylalkylaryl amines 7andasho on simple stirringwith 2-bromoacetyl bromide in aqueous Na

2CO3medium

The final compounds were geared up by stirring 6 with 8andashoagain in DMF in the presence of NaH and separated throughfiltration after addition of excess distilled water

All the compounds were structurally corroboratedthrough IR 1H-NMR and EIMS spectral data Compound3 is also aided by 13C-NMR data One molecule descriptionis given for 9h Its molecular formula was nominated asC23H20ClN3O5S elucidated with the aid of molecular ion

peak in EIMS spectrum and integration of protons in 1H-NMR spectrum The suggested fragmentation pattern of thismolecule is also sketched in Figure 1 The specific absorptionbands for different functionalities in the molecule appearedin IR spectrum at 120592max (cm

minus1) 3447 (N-H) 3069 (Ar C-H)1738 (ester C=O) 1677 (amide C=O) 1689 (C=N) 1606 (ArC=C) 1149 (C-O) and 705 (C-Cl) In aromatic region of1H-NMR spectrum the three singlets with single protonintegration resonating at 120575 758 (H-51015840) 704 (H-81015840) and 621(H-31015840) were allocated for the chlorinated coumarin partof the molecule The other four signals in the same regionwith single proton integration resonated at 120575 716 (d J =80Hz H-610158401015840) 711 (t J = 80Hz H-510158401015840) 707 (t J = 80HzH-410158401015840) and 698 (d J = 80Hz H-310158401015840) for 2-ethylphenyl partof the molecule The ethyl group was confirmed through aquartet and a triplet both with coupling constant of 72Hzappearing at 120575 246 (2H H-710158401015840) and 103 (3H CH

3-810158401015840)

respectively in the aliphatic region The protons of twomethylene groups linked to oxygen and sulfur appeared astwo singlets at 120575 535 (H-121015840) and 409 (H-2101584010158401015840) respectivelyThe three protons of methyl group attached to coumarinnucleus resonated as singlet at 120575 236 (CH

3-111015840) The whole

discussion confirmed 9h as N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide

6 Organic Chemistry International

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Quantum Chemistry

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Organic Chemistry International

ElectrochemistryInternational Journal of

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CatalystsJournal of

4 Organic Chemistry International

2109 N-(2-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9e) White amorphous solid Yield 69MP 100ndash102∘CMF C

22H18ClN3O5SMM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3442 (N-H) 3069 (Ar C-H) 1733 (ester

C=O) 1678 (amide C=O) 1691 (C=N) 1603 (Ar C=C) 1150(C-O) 701 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

873 (s 1H CON-H) 772 (d J = 80Hz 1H H-610158401015840) 763 (s1H H-51015840) 721 (d J = 80Hz 1H H-310158401015840) 715 (t J = 80Hz 1HH-510158401015840) 707 (t J = 80Hz 1H H-410158401015840) 702 (s 1H H-81015840) 622(s 1H H-31015840) 534 (s 2H H-121015840) 406 (s 2H H-2101584010158401015840) 238 (s3H CH

3-111015840) 228 (s 3H CH

3-710158401015840) EIMS (mz) 473 (7)

471 [M]∙+ (24) 436 (12) 251 (4) 249 (7) 230 (5)214 (16) 210 (81) 193 (13) 182 (BP 100) 165 (8) 149(3) 134 (47) 106 (32)

21010 N-(3-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulf-anyl]acetamide (9f) Yellowish grey amorphous solidYield 83 MP 88ndash90∘C MF C

22H18ClN3O5S MM

471 gmolminus1 IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar

C-H) 1736 (ester C=O) 1668 (amide C=O) 1689 (C=N)1591 (Ar C=C) 1153 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 882 (s 1H CON-H) 761 (s 1H H-51015840)

733 (s 1H H-210158401015840) 730 (d J = 76Hz 1H H-610158401015840) 717 (t J =80Hz 1H H-510158401015840) 704 (s 1H H-81015840) 691 (d J = 76Hz 1HH-410158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s 2HH-2101584010158401015840) 237 (s 3H CH

3-111015840) 230 (s 3H CH

3-710158401015840) EIMS

(mz) 473 (5) 471 [M]∙+ (19) 436 (13) 251 (7) 249(8) 230 (2) 214 (15) 210 (83) 193 (14) 182 (BP100) 165 (9) 149 (5) 134 (42) 106 (28)

21011 N-(4-Methylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9g) White amorphous solid Yield 79MP 98ndash100∘C MF C

22H18ClN3O5S MM 471 gmolminus1 IR

(KBr 120592max cmminus1) 3435 (N-H) 3061 (Ar C-H) 1734 (ester

C=O) 1668 (amide C=O) 1689 (C=N) 1584 (Ar C=C) 1141(C-O) 703 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 736 (d J = 84Hz2H H-210158401015840 ampH-610158401015840) 717 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) 226 (s 3H CH

3-710158401015840)

EIMS (mz) 473 (8) 471 [M]∙+ (23) 436 (15) 251 (7)249 (9) 230 (3) 214 (15) 210 (87) 193 (14) 182 (BP100) 165 (9) 149 (4) 134 (49) 106 (31)

21012 N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9h) Light brown amorphous solid Yield 84MP 92ndash94∘C MF C

23H20ClN3O5S MM 485 gmolminus1 IR

(KBr 120592max cmminus1) 3447 (N-H) 3069 (Ar C-H) 1738 (ester

C=O) 1677 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1149(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

861 (s 1H CON-H) 758 (s 1H H-51015840) 716 (d J = 80Hz 1HH-610158401015840) 711 (t J = 80Hz 1H H-510158401015840) 707 (t J = 80Hz 1HH-410158401015840) 704 (s 1H H-81015840) 698 (d J = 80Hz 1H H-310158401015840) 621(s 1H H-31015840) 535 (s 2H H-121015840) 409 (s 2H H-2101584010158401015840) 246 (q

J = 72Hz 2H H-710158401015840) 236 (s 3H CH3-111015840) 103 (t J = 72Hz

3H CH3-810158401015840) EIMS (mz) 487 (6) 485 [M]∙+ (17) 450

(13) 251 (4) 249 (5) 230 (2) 214 (13) 210 (88)193 (14) 182 (BP 100) 165 (6) 149 (7) 148 (33) 134(16) 120 (32)

21013 N-(4-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9i) Cream white amorphous solid Yield 84MP 104ndash106∘C MF C

23H20ClN3O5S MM 485 gmolminus1

IR (KBr 120592max cmminus1) 3432 (N-H) 3067 (Ar C-H) 1736 (ester

C=O) 1671 (amide C=O) 1689 (C=N) 1606 (Ar C=C) 1147(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

872 (s 1H CON-H) 761 (s 1H H-51015840) 709 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 704 (s 1H H-81015840) 696 (d J = 80Hz2H H-310158401015840 ampH-510158401015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 254 (q J = 72Hz 2H H-710158401015840) 236 (s3H CH

3-111015840) 113 (t J = 72Hz 3H CH

3-810158401015840) EIMS (mz)

487 (8) 485 [M]∙+ (17) 450 (15) 251 (4) 249 (7)230 (5) 214 (9) 210 (92) 193 (17) 182 (BP 100) 165(7) 149 (5) 148 (35) 134 (11) 120 (38)

21014 N-(2-Methoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9j) Cream yellow amorphous solid Yield78 MP 106ndash108∘C MF C

22H18ClN3O6S MM

487 gmolminus1 IR (KBr 120592max cmminus1) 3437 (N-H) 3069 (Ar

C-H) 1733 (ester C=O) 1683 (amide C=O) 1689 (C=N)1603 (Ar C=C) 1158 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 859 (s 1H CON-H) 822 (d J = 80Hz

1H H-610158401015840) 762 (s 1H H-51015840) 705 (s 1H H-81015840) 701 (t J =76Hz 1H H-510158401015840) 692 (t J = 76Hz 1H H-410158401015840) 681 (d J =80Hz 1H H-310158401015840) 621 (s 1H H-31015840) 534 (s 2H H-121015840) 406(s 2H H-2101584010158401015840) 382 (s 3H CH

3-710158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 489 (5) 487 [M]∙+ (17) 452 (16) 251 (4)249 (6) 230 (2) 214 (13) 210 (86) 193 (12) 182 (BP100) 165 (4) 150 (31) 149 (8) 134 (18) 122 (39)

21015 N-(2-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9k) Light grey amorphous solid Yield 86MP 96ndash98∘C MF C

23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3453 (N-H) 3056 (Ar C-H) 1736 (ester

C=O) 1667 (amide C=O) 1681 (C=N) 1606 (Ar C=C) 1155(C-O) 702 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

866 (s 1H CON-H) 759 (s 1H H-51015840) 743 (d J = 84Hz 1HH-610158401015840) 717 (t J = 84Hz 1H H-410158401015840) 703 (s 1H H-81015840) 684 (tJ = 84Hz 1H H-510158401015840) 675 (d J = 80Hz 1H H-310158401015840) 620 (s1H H-31015840) 535 (s 2H H-121015840) 404 (s 2H H-2101584010158401015840) 374 (q J =72Hz 2H H-710158401015840) 237 (s 3H CH

3-111015840) 111 (t J = 72Hz 3H

CH3-810158401015840) EIMS (mz) 503 (8) 501 [M]∙+ (22) 466 (11)

251 (4) 249 (7) 230 (2) 214 (14) 210 (85) 193 (18)182 (BP 100) 165 (8) 164 (30) 149 (9) 136 (28) 134(17)

21016 N-(4-Ethoxyphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]ac-etamide (9l) Reddish purple amorphous solid Yield 74

Organic Chemistry International 5

MP 108ndash110∘CMF C23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3443 (N-H) 3078 (Ar C-H) 1734 (ester

C=O) 1679 (amide C=O) 1688 (C=N) 1597 (Ar C=C) 1155(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

882 (s 1H CON-H) 759 (s 1H H-51015840) 739 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 703 (s 1H H-81015840) 681 (d J = 84Hz 2HH-310158401015840 ampH-510158401015840) 620 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s2H H-2101584010158401015840) 397 (q J = 68Hz 2H H-710158401015840) 237 (s 3H CH

3-

111015840) 086 (t J = 68Hz 3H CH3-810158401015840) EIMS (mz) 503 (9)

501 [M]∙+ (21) 466 (13) 251 (6) 249 (8) 230 (3)214 (15) 210 (81) 193 (19) 182 (BP 100) 165 (9) 164(32) 149 (6) 136 (25) 134 (19)

21017 N-(2-Methoxycarbonylphenyl)-2-[(5-[(6-chloro-4-meth-yl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9m) Yellow amorphous solidYield 75 MP 122ndash124∘C MF C

23H18ClN3O7S MM

515 gmolminus1 IR (KBr 120592max cmminus1) 3429 (N-H) 3050 (Ar

C-H) 1731 (ester C=O) 1671 (amide C=O) 1683 (C=N)1601 (Ar C=C) 1159 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 881 (s 1H CON-H) 868 (d J = 84Hz

1H H-610158401015840) 810 (d J = 76Hz 1H H-310158401015840) 762 (s 1H H-51015840)751 (t J = 76Hz 1H H-510158401015840) 718 (t J = 76Hz 1H H-410158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840) 407(s 2H H-2101584010158401015840) 381 (s 3H CH

3-810158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 517 (9) 515 [M]∙+ (19) 480 (13) 251 (6)249 (9) 230 (2) 214 (14) 210 (92) 193 (17) 182 (BP100) 178 (37) 165 (6) 150 (33) 149 (7) 134 (15)

21018 N-(4-Bromophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9n) Light grey amorphous solid Yield 73MP 102ndash104∘CMF C

21H15BrClN

3O5S MM 535 gmolminus1

IR (KBr 120592max cmminus1) 3422 (N-H) 3056 (Ar C-H) 1734 (ester

C=O) 1662 (amide C=O) 1684 (C=N) 1593 (Ar C=C) 1143(C-O) 702 (C-Cl) 639 (C-Br) 1H-NMR (400MHz CHCl

3-

1198891 120575 ppm) 828 (s 1H CON-H) 762 (s 1HH-51015840) 747 (d J =

84Hz 2H H-210158401015840 ampH-610158401015840) 741 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) EIMS (mz) 539

(7) 537 (18) 535 [M]∙+ (20) 500 (14) 251 (6) 249(8) 230 (4) 214 (13) 210 (92) 198 (33) 193 (13)182 (BP 100) 170 (31) 165 (6) 149 (8) 134 (11)

21019 N-(4-Nitrophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9o) Light yellow amorphous solid Yield81 MP 108ndash110∘C MF C

21H15ClN4O7S MM

502 gmolminus1 IR (KBr 120592max cmminus1) 3438 (N-H) 3053 (Ar

C-H) 1735 (ester C=O) 1678 (amide C=O) 1688 (C=N)1606 (Ar C=C) 1163 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 934 (s 1H CON-H) 841 (d J = 80Hz

2H H-310158401015840 ampH-510158401015840) 806 (d J = 80Hz 2H H-210158401015840 ampH-610158401015840)762 (s 1H H-51015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534(s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840)

EIMS (mz) 504 (5) 502 [M]∙+ (17) 467 (18) 251 (8)249 (7) 230 (5) 214 (11) 210 (91) 193 (18) 182 (BP100) 165 (42) 149 (8) 137 (32) 134 (17)

3 Results and Discussion

The different N-aralkylalkylaryl acetamides incorporatingcoumarin and 134-oxadiazole rings 9andasho were synthesizedby the multistep protocol given in Scheme 1 The synthesiswas aimed at combining multiple functionalities in a singlemolecule so these may be able to demonstrate more effi-cient biological activity The antibacterial behavior of thesemolecules was tested against Gram-bacteria including posi-tive and negative strains The three negative and two positivebacterial strains have been reported to be the cause of variousdiseases [23ndash27]

31 Chemistry First 4-chlororesorcinol (1) was treated withethyl acetoacetate (2) in a strong acidic medium to yield6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) whichwas separated through filtration Compound 3 was furtherO-substituted by ethyl 2-bromoacetate in a polar aproticsolvent with the aid of a weak base This substituted ester4 was converted to corresponding carbohydrazide 5 aftera simple nucleophilic substitution reaction by hydrazine inmethanol The carbohydrazide was cyclized to 5-substituted-134-oxadiazol-2-thiol by CS

2in an alcoholic KOH medium

on reflux A list of electrophiles 8andasho was synthesized fromdifferent aralkylalkylaryl amines 7andasho on simple stirringwith 2-bromoacetyl bromide in aqueous Na

2CO3medium

The final compounds were geared up by stirring 6 with 8andashoagain in DMF in the presence of NaH and separated throughfiltration after addition of excess distilled water

All the compounds were structurally corroboratedthrough IR 1H-NMR and EIMS spectral data Compound3 is also aided by 13C-NMR data One molecule descriptionis given for 9h Its molecular formula was nominated asC23H20ClN3O5S elucidated with the aid of molecular ion

peak in EIMS spectrum and integration of protons in 1H-NMR spectrum The suggested fragmentation pattern of thismolecule is also sketched in Figure 1 The specific absorptionbands for different functionalities in the molecule appearedin IR spectrum at 120592max (cm

minus1) 3447 (N-H) 3069 (Ar C-H)1738 (ester C=O) 1677 (amide C=O) 1689 (C=N) 1606 (ArC=C) 1149 (C-O) and 705 (C-Cl) In aromatic region of1H-NMR spectrum the three singlets with single protonintegration resonating at 120575 758 (H-51015840) 704 (H-81015840) and 621(H-31015840) were allocated for the chlorinated coumarin partof the molecule The other four signals in the same regionwith single proton integration resonated at 120575 716 (d J =80Hz H-610158401015840) 711 (t J = 80Hz H-510158401015840) 707 (t J = 80HzH-410158401015840) and 698 (d J = 80Hz H-310158401015840) for 2-ethylphenyl partof the molecule The ethyl group was confirmed through aquartet and a triplet both with coupling constant of 72Hzappearing at 120575 246 (2H H-710158401015840) and 103 (3H CH

3-810158401015840)

respectively in the aliphatic region The protons of twomethylene groups linked to oxygen and sulfur appeared astwo singlets at 120575 535 (H-121015840) and 409 (H-2101584010158401015840) respectivelyThe three protons of methyl group attached to coumarinnucleus resonated as singlet at 120575 236 (CH

3-111015840) The whole

discussion confirmed 9h as N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide

6 Organic Chemistry International

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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

MP 108ndash110∘CMF C23H20ClN3O6S MM 501 gmolminus1 IR

(KBr 120592max cmminus1) 3443 (N-H) 3078 (Ar C-H) 1734 (ester

C=O) 1679 (amide C=O) 1688 (C=N) 1597 (Ar C=C) 1155(C-O) 705 (C-Cl) 1H-NMR (400MHz CHCl

3-1198891 120575 ppm)

882 (s 1H CON-H) 759 (s 1H H-51015840) 739 (d J = 80Hz2H H-210158401015840 ampH-610158401015840) 703 (s 1H H-81015840) 681 (d J = 84Hz 2HH-310158401015840 ampH-510158401015840) 620 (s 1H H-31015840) 534 (s 2H H-121015840) 398 (s2H H-2101584010158401015840) 397 (q J = 68Hz 2H H-710158401015840) 237 (s 3H CH

3-

111015840) 086 (t J = 68Hz 3H CH3-810158401015840) EIMS (mz) 503 (9)

501 [M]∙+ (21) 466 (13) 251 (6) 249 (8) 230 (3)214 (15) 210 (81) 193 (19) 182 (BP 100) 165 (9) 164(32) 149 (6) 136 (25) 134 (19)

21017 N-(2-Methoxycarbonylphenyl)-2-[(5-[(6-chloro-4-meth-yl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide (9m) Yellow amorphous solidYield 75 MP 122ndash124∘C MF C

23H18ClN3O7S MM

515 gmolminus1 IR (KBr 120592max cmminus1) 3429 (N-H) 3050 (Ar

C-H) 1731 (ester C=O) 1671 (amide C=O) 1683 (C=N)1601 (Ar C=C) 1159 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 881 (s 1H CON-H) 868 (d J = 84Hz

1H H-610158401015840) 810 (d J = 76Hz 1H H-310158401015840) 762 (s 1H H-51015840)751 (t J = 76Hz 1H H-510158401015840) 718 (t J = 76Hz 1H H-410158401015840)705 (s 1H H-81015840) 621 (s 1H H-31015840) 536 (s 2H H-121015840) 407(s 2H H-2101584010158401015840) 381 (s 3H CH

3-810158401015840) 237 (s 3H CH

3-111015840)

EIMS (mz) 517 (9) 515 [M]∙+ (19) 480 (13) 251 (6)249 (9) 230 (2) 214 (14) 210 (92) 193 (17) 182 (BP100) 178 (37) 165 (6) 150 (33) 149 (7) 134 (15)

21018 N-(4-Bromophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9n) Light grey amorphous solid Yield 73MP 102ndash104∘CMF C

21H15BrClN

3O5S MM 535 gmolminus1

IR (KBr 120592max cmminus1) 3422 (N-H) 3056 (Ar C-H) 1734 (ester

C=O) 1662 (amide C=O) 1684 (C=N) 1593 (Ar C=C) 1143(C-O) 702 (C-Cl) 639 (C-Br) 1H-NMR (400MHz CHCl

3-

1198891 120575 ppm) 828 (s 1H CON-H) 762 (s 1HH-51015840) 747 (d J =

84Hz 2H H-210158401015840 ampH-610158401015840) 741 (d J = 84Hz 2H H-310158401015840 ampH-510158401015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534 (s 2H H-121015840)408 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840) EIMS (mz) 539

(7) 537 (18) 535 [M]∙+ (20) 500 (14) 251 (6) 249(8) 230 (4) 214 (13) 210 (92) 198 (33) 193 (13)182 (BP 100) 170 (31) 165 (6) 149 (8) 134 (11)

21019 N-(4-Nitrophenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9o) Light yellow amorphous solid Yield81 MP 108ndash110∘C MF C

21H15ClN4O7S MM

502 gmolminus1 IR (KBr 120592max cmminus1) 3438 (N-H) 3053 (Ar

C-H) 1735 (ester C=O) 1678 (amide C=O) 1688 (C=N)1606 (Ar C=C) 1163 (C-O) 703 (C-Cl) 1H-NMR (400MHzCHCl

3-1198891 120575 ppm) 934 (s 1H CON-H) 841 (d J = 80Hz

2H H-310158401015840 ampH-510158401015840) 806 (d J = 80Hz 2H H-210158401015840 ampH-610158401015840)762 (s 1H H-51015840) 705 (s 1H H-81015840) 622 (s 1H H-31015840) 534(s 2H H-121015840) 407 (s 2H H-2101584010158401015840) 236 (s 3H CH

3-111015840)

EIMS (mz) 504 (5) 502 [M]∙+ (17) 467 (18) 251 (8)249 (7) 230 (5) 214 (11) 210 (91) 193 (18) 182 (BP100) 165 (42) 149 (8) 137 (32) 134 (17)

3 Results and Discussion

The different N-aralkylalkylaryl acetamides incorporatingcoumarin and 134-oxadiazole rings 9andasho were synthesizedby the multistep protocol given in Scheme 1 The synthesiswas aimed at combining multiple functionalities in a singlemolecule so these may be able to demonstrate more effi-cient biological activity The antibacterial behavior of thesemolecules was tested against Gram-bacteria including posi-tive and negative strains The three negative and two positivebacterial strains have been reported to be the cause of variousdiseases [23ndash27]

31 Chemistry First 4-chlororesorcinol (1) was treated withethyl acetoacetate (2) in a strong acidic medium to yield6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) whichwas separated through filtration Compound 3 was furtherO-substituted by ethyl 2-bromoacetate in a polar aproticsolvent with the aid of a weak base This substituted ester4 was converted to corresponding carbohydrazide 5 aftera simple nucleophilic substitution reaction by hydrazine inmethanol The carbohydrazide was cyclized to 5-substituted-134-oxadiazol-2-thiol by CS

2in an alcoholic KOH medium

on reflux A list of electrophiles 8andasho was synthesized fromdifferent aralkylalkylaryl amines 7andasho on simple stirringwith 2-bromoacetyl bromide in aqueous Na

2CO3medium

The final compounds were geared up by stirring 6 with 8andashoagain in DMF in the presence of NaH and separated throughfiltration after addition of excess distilled water

All the compounds were structurally corroboratedthrough IR 1H-NMR and EIMS spectral data Compound3 is also aided by 13C-NMR data One molecule descriptionis given for 9h Its molecular formula was nominated asC23H20ClN3O5S elucidated with the aid of molecular ion

peak in EIMS spectrum and integration of protons in 1H-NMR spectrum The suggested fragmentation pattern of thismolecule is also sketched in Figure 1 The specific absorptionbands for different functionalities in the molecule appearedin IR spectrum at 120592max (cm

minus1) 3447 (N-H) 3069 (Ar C-H)1738 (ester C=O) 1677 (amide C=O) 1689 (C=N) 1606 (ArC=C) 1149 (C-O) and 705 (C-Cl) In aromatic region of1H-NMR spectrum the three singlets with single protonintegration resonating at 120575 758 (H-51015840) 704 (H-81015840) and 621(H-31015840) were allocated for the chlorinated coumarin partof the molecule The other four signals in the same regionwith single proton integration resonated at 120575 716 (d J =80Hz H-610158401015840) 711 (t J = 80Hz H-510158401015840) 707 (t J = 80HzH-410158401015840) and 698 (d J = 80Hz H-310158401015840) for 2-ethylphenyl partof the molecule The ethyl group was confirmed through aquartet and a triplet both with coupling constant of 72Hzappearing at 120575 246 (2H H-710158401015840) and 103 (3H CH

3-810158401015840)

respectively in the aliphatic region The protons of twomethylene groups linked to oxygen and sulfur appeared astwo singlets at 120575 535 (H-121015840) and 409 (H-2101584010158401015840) respectivelyThe three protons of methyl group attached to coumarinnucleus resonated as singlet at 120575 236 (CH

3-111015840) The whole

discussion confirmed 9h as N-(2-Ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfanyl]acetamide

6 Organic Chemistry International

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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

HO OH O O O OHO

Cl Cl

C

O

Br RR

NaH DMF

O

O OO

ClMeOH

O

O OO

Cl

EtOH

N

O

N

O OO

Cl

HS

N

O

N

O OO

Cl

SHN

O

R

NH

1 2 3

4 5

69andasho

8andasho 7andasho

NaH DMF

143

Comp Comp Comp minusRminusRminusR

9a 9f 9k

9b 9g 9l

9c 9h 9m

9d 9i 9n

Br

9e 9j 9o

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2

+C2H5O

C2H5O

Conc H2SO4 BrCH2COOC2H5

COOCH3

OCH3

BrCH2COBr

CS2 KOH

1998400

3998400

5998400

7998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400 1

998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

1998400998400

3998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

7998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

8998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

3998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400 5

998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

5998400998400

2998400998400

11998400

12998400

Na2CO3H2O

N2H4middotH2O H2NHN

H3C

O2N

OCH2CH3

H3CH2CO

H3CH2C

CH2CH3

Scheme 1 Synthesis of N-aralkylalkylaryl-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadiazol-2-yl)sulfa-nyl]acetamide (9andasho)

Organic Chemistry International 7

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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

O OO

Cl

mz = 450 (13)

O OHO

Cl

OHO

Cl

mz = 210 (88)

mz = 182 (100)

mz = 148 (33)

O O

mz = 134 (16)

O O

Cl

mz = 193 (14)

O

Cl

mz = 165 (6)

mz = 149 (7)

Cl

HN

O

NN

OS

HN

O

O OOHN

O

NN

OS

O OOO

mz = 251 (4) mz = 249 (5)

O OON

mz = 120 (32)

HNO OO

N

mz = 214 (13)

Cl Cl

mz = 230 (2)

O OON

O

+

+

+ +

+

++

++

minusCO

CH2CH3

CH3

CH3

CH3

CH3

CH3CH3 CH3

CH3 CH3 CH3 CH3

CH3

minusC11H12N2OS minusC11H12N2O2S

minusC11H12N2O2S minusCOminusCO

minusC13H13N3O2S

minusC2HClO

H3CH2CH2C

H2C

CH2CH3

CH2CH3minus∙C14H10ClN2O4S

13H14N3O3Sminus∙C

11H12N3OSminus∙C

minus∙Cl

minusCO2

+∙

+∙

+∙

+∙

+∙

mz = 485 [M]+∙ (17)

mz = 487 [M + 2]+∙ (6)

Figure 1 Mass fragmentation pattern of N-(2-ethylphenyl)-2-[(5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-134-oxadia-zol-2-yl)sulfanyl]acetamide (9h)

32 Antibacterial Activity (In Vitro) The results of antibacte-rial activity evaluation against Gram-bacteria were presentedas percentage of age inhibition and MIC values in Tables 1and 2 The ciprofloxacin was used as reference standard Allthe compounds demonstrated moderate to excellent activityexcept a few The Gram-negative strain S typhi was notinhibited by 9b and 9d It was the most efficiently inhibitedby 9e 9f 9h 9j 9k and 9m The best activity against it wasobserved for 9j with MIC value of 887 plusmn 120 120583gmL and9k as 884 plusmn 200 120583gmL with respect to that of referenceas 800 plusmn 254 120583gmL Only 9o was inactive against E coliand remaining moderate to good with the efficient ones as9e 9f 9j 9k and 9m The most active one was 9f withMIC of 1015 plusmn 412 relative to 796 plusmn 114 120583gmL Against

P aeruginosa 9b and 9o were inactive and remaining weaklymoderate The efficient ones against this strain were 9a9c 9e 9f 9h 9j and 9m It was most actively inhibitedby 9e presenting MIC of 1022 plusmn 333 120583gmL as comparedto 805 plusmn 160 120583gmL B subtilis was moderately inhibitedby all the molecules and efficiently by 9n with MIC of1195 plusmn 471 120583gmL in comparison with 832 plusmn 100 120583gmLThe compounds against S aureus were moderate to excellentinhibitors including 9c 9e 9j 9k and 9l The molecule 9ewas the most efficient with MIC of 890 plusmn 208 120583gmL relativeto 743 plusmn 045 120583gmL The three compounds 9d 9i and 9nwere inactive at all against this strain Overall the Gram-negative strains were efficiently inhibited by the synthesizedmolecules relative to Gram-positive ones The best activity

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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

8 Organic Chemistry International

Table 1 The age inhibition for antibacterial activity

CompoundPercentage inhibition ()

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 5972 plusmn 017 5871 plusmn 089 6330 plusmn 165 5135 plusmn 105 5168 plusmn 095

9b 4706 plusmn 350 6965 plusmn 114 4052 plusmn 500 7560 plusmn 310 5732 plusmn 079

9c 5161 plusmn 028 6663 plusmn 020 5603 plusmn 067 6655 plusmn 225 6111 plusmn 447

9d 4689 plusmn 333 5005 plusmn 450 5191 plusmn 119 5435 plusmn 305 4332 plusmn 005

9e 7422 plusmn 044 7426 plusmn 040 7180 plusmn 026 7200 plusmn 250 6789 plusmn 032

9f 7300 plusmn 044 7515 plusmn 228 7191 plusmn 139 6995 plusmn 295 6432 plusmn 021

9g 5800 plusmn 144 5554 plusmn 485 5057 plusmn 490 5635 plusmn 285 5068 plusmn 163

9h 6756 plusmn 222 7025 plusmn 203 6845 plusmn 082 6400 plusmn 060 6221 plusmn 305

9i 5128 plusmn 250 5084 plusmn 460 5005 plusmn 366 5655 plusmn 085 4732 plusmn 058

9j 7311 plusmn 089 7322 plusmn 015 6742 plusmn 041 6495 plusmn 165 6258 plusmn 089

9k 7189 plusmn 044 7391 plusmn 025 6789 plusmn 263 6455 plusmn 075 5732 plusmn 195

9l 6756 plusmn 494 5950 plusmn 287 5351 plusmn 412 5300 plusmn 080 6921 plusmn 089

9m 6989 plusmn 089 7129 plusmn 005 6629 plusmn 134 6635 plusmn 225 5032 plusmn 295

9n 6050 plusmn 028 6084 plusmn 054 5680 plusmn 237 5875 plusmn 005 4363 plusmn 226

9o 5017 plusmn 183 4431 plusmn 371 4485 plusmn 113 4535 plusmn 355 5300 plusmn 289

Ciprofloxacin 9243 plusmn 107 9067 plusmn 065 9033 plusmn 022 9199 plusmn 200 9100 plusmn 165

Table 2 The MIC values for antibacterial activity

CompoundMIC (120583gmL)

Gram-negative bacteria Gram-positive bacteriaS typhi E coli P aeruginosa B subtilis S aureus

9a 1259 plusmn 460 1298 plusmn 156 1130 plusmn 225 1958 plusmn 108 1786 plusmn 065

9b mdash 1341 plusmn 500 mdash 1447 plusmn 500 1335 plusmn 225

9c 1446 plusmn 110 1107 plusmn 194 1142 plusmn 317 1319 plusmn 183 1091 plusmn 287

9d mdash 1993 plusmn 181 1540 plusmn 500 1651 plusmn 198 mdash9e 1061 plusmn 500 1039 plusmn 162 1022 plusmn 333 1286 plusmn 385 890 plusmn 208

9f 950 plusmn 130 1015 plusmn 412 1043 plusmn 465 1594 plusmn 306 1318 plusmn 217

9g 1719 plusmn 370 1486 plusmn 500 1950 plusmn 267 1212 plusmn 400 1953 plusmn 165

9h 916 plusmn 220 1128 plusmn 106 1152 plusmn 342 1532 plusmn 500 1295 plusmn 315

9i 1907 plusmn 040 1424 plusmn 125 1997 plusmn 350 1487 plusmn 271 mdash9j 887 plusmn 120 1041 plusmn 144 1054 plusmn 080 1458 plusmn 187 1114 plusmn 222

9k 884 plusmn 200 1094 plusmn 125 1200 plusmn 133 1296 plusmn 182 1214 plusmn 148

9l 1275 plusmn 450 1207 plusmn 500 1561 plusmn 500 1575 plusmn 335 1135 plusmn 200

9m 901 plusmn 140 1086 plusmn 119 1104 plusmn 417 1418 plusmn 435 1862 plusmn 100

9n 1764 plusmn 500 1597 plusmn 500 1756 plusmn 200 1195 plusmn 471 mdash9o 1992 plusmn 321 mdash mdash mdash 1832 plusmn 111

Ciprofloxacin 800 plusmn 254 796 plusmn 114 805 plusmn 160 832 plusmn 100 743 plusmn 045

Noteminimum inhibitory concentration (MIC)wasmeasuredwith suitable dilutions (5ndash30120583gwell) and results were calculated using EZ-Fit Perrella ScientificInc Amherst USA software

was presented by the threemolecules 9e 9j and 9k and theiractivity might be owed to the presence of ortho-substitutedphenyl rings attached to nitrogen of acetamoyl linkage

The alkyl substitution resulted in moderate to goodactivity against all the strains Among aralkyl groups the longaliphatic chain containing was moderate to good against allthe strains The molecules bearing ortho-substituted phenylrings remained active against all the strains also goodto excellent and more efficient against the Gram-negative

strains The meta-substituted ones were also good againstnegative strain The para-substituted phenyl rings presentedvarying activities but moderate ones

4 Conclusion

The multistep synthesis was carried out to incorporate dif-ferent functionalities with an aim to obtain more potentmolecules The most of the synthesized molecules remained

Organic Chemistry International 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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 9

efficient against all the strains specially Gram-negative bac-teria The most of the compounds were pharmacologicallyimportant including 9e 9j and 9k These molecules may befurther modified to get more comparable or even better MICresults by more variation to the group linked to nitrogen ofacetamoyl functionality So the above listed compounds alongwith some others might be considered for drug designingprogram in search of new drug candidates

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

Authors are much grateful to Higher Education Commission(HEC) of Pakistan regarding financial support for chemicalssolvents and spectral analysis

References

[1] A Behrami and I Krasniqi ldquoAntibacterial activity of coumarinederivatives synthesized from 4-chloro-chromen-2-one Thecomparison with standard drugrdquo Research Journal of Pharma-ceutical Biological and Chemical Sciences vol 3 no 3 pp 369ndash375 2012

[2] T Smyth V N Ramachandran and W F Smyth ldquoA study ofthe antimicrobial activity of selected naturally occurring andsynthetic coumarinsrdquo International Journal of AntimicrobialAgents vol 33 no 5 pp 421ndash426 2009

[3] A KinzaMK KhosaN Jahan and SNosheen ldquoSynthesis andapplications of coumarinrdquo Pakistan Journal of PharmaceuticalSciences vol 23 no 4 pp 449ndash454 2010

[4] B R Dekic N S Radulovic V S Dekic R D Vukicevic andR M Palic ldquoSynthesis and antimicrobial activity of new 4-heteroarylamino coumarin derivatives containing nitrogen andsulfur as heteroatomsrdquoMolecules vol 15 no 4 pp 2246ndash22562010

[5] A Sinhamahapatra N Sutradhar S Pahari H C Bajaj and AB Panda ldquoMesoporous zirconium phosphate an efficient cat-alyst for the synthesis of coumarin derivatives through Pech-mann condensation reactionrdquoApplied Catalysis A General vol394 no 1-2 pp 93ndash100 2011

[6] Y Shi and C-H Zhou ldquoSynthesis and evaluation of a class ofnew coumarin triazole derivatives as potential antimicrobialagentsrdquo Bioorganic amp Medicinal Chemistry Letters vol 21 no3 pp 956ndash960 2011

[7] N N Farshori M R Banday A Ahmad A U Khan andA Rauf ldquo7-Hydroxy-coumarin derivatives synthesis charac-terization and preliminary antimicrobial activitiesrdquo MedicinalChemistry Research vol 20 no 5 pp 535ndash541 2011

[8] M Roussaki C A Kontogiorgis D Hadjipavlou-Litina SHamilakis and A Detsi ldquoA novel synthesis of 3-aryl coumarinsand evaluation of their antioxidant and lipoxygenase inhibitoryactivityrdquo Bioorganic amp Medicinal Chemistry Letters vol 20 no13 pp 3889ndash3892 2010

[9] Y Zhang B Zou Z Chen et al ldquoSynthesis and antioxidantactivities of novel 4-Schiff base-7-benzyloxy- coumarin deriva-tivesrdquo Bioorganic and Medicinal Chemistry Letters vol 21 no22 pp 6811ndash6815 2011

[10] A Hasan N F Thomas and S Gapil ldquoSynthesis characteriza-tion and antifungal evaluation of 5-substituted-4-amino-124-triazole-3-thioestersrdquo Molecules vol 16 no 2 pp 1297ndash13092011

[11] P J Shirote and M S Bhatia ldquoSynthesis and goat pulmonaryvasodilatory activity of some novel 134-oxadiazolesrdquo ArabianJournal of Chemistry vol 4 no 4 pp 413ndash418 2011

[12] H Gadegoni S Manda and S Rangu ldquoSynthesis and screeningof some novel 2-[5-(Substituted phenyl)-[134]oxadiazol-2-yl]-benzoxazoles as potential antimicrobial agentsrdquo Journal of theKorean Chemical Society vol 57 no 2 pp 221ndash226 2013

[13] R Sawant and D Kawade ldquoSynthesis and biological evaluationof some novel 2-phenyl benzimidazole-1-acetamide derivativesas potential anthelmintic agentsrdquo Acta Pharmaceutica vol 61no 3 pp 353ndash361 2011

[14] G Autore A Caruso S Marzocco et al ldquoAcetamide derivativeswith antioxidant activity and potential anti-inflammatory activ-ityrdquoMolecules vol 15 no 3 pp 2028ndash2038 2010

[15] G Ayhan-Kılcıgil S Gurkan T Coban E D Ozdamar and BCan-Eke ldquoSynthesis and Evaluation of Antioxidant Propertiesof Novel 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-N-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl) acet-amides-Irdquo Chemical Biology and Drug Design vol 79 no 5 pp869ndash877 2012

[16] V Kanagarajan JThanusu andM Gopalakrishnan ldquoSynthesisand in vitro microbiological evaluation of an array of biolabile2-morpholino-N-(46-diarylpyrimidin-2-yl)acetamidesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 4 pp 1583ndash1589 2010

[17] P C Sharma and S Jain ldquoSynthesis and antibacterial activity ofcertain novel 1-cyclopropyl-6-flouro-14-dihydro-7-4-substitut-ed-piperazin- 1-yl-4-oxoquinolin-3-carboxylatesrdquo Acta Phar-maceutica Sciencia vol 50 pp 35ndash40 2008

[18] P C Sharma and S Jain ldquoSynthesis and in-vitro antibacte-rial activity of some novel N-nicotinoyl-1-ethyl-6-fluoro-14-dihydro-7-piperazin-1-yl-4-oxoquinoline-3-carboxylatesrdquo ActaPoloniae PharmaceuticamdashDrug Research vol 65 no 5 pp 551ndash556 2008

[19] Aziz-ur-Rehman S Rasool M A Abbasi et al ldquoSynthe-sis characterization and biological screening of some 4-O-substituted derivatives of N-(4-hydroxyphenyl)-N-methyl-4-methylbenzenesulfonamiderdquo Asian Journal of Pharmaceuticaland Biological Research vol 2 no 2 pp 100ndash105 2012

[20] S Ghosh P Tiwari S Pandey et al ldquoSynthesis and evaluation ofantitubercular activity of glycosyl thio- and sulfonyl acetamidederivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 18no 14 pp 4002ndash4005 2008

[21] M Kaspady V K Narayanaswamy M Raju and G K RaoldquoSynthesis antibacterial activity of 24-disubstituted oxazolesand thiazoles as bioisosteresrdquo Letters in Drug Design andDiscovery vol 6 no 1 pp 21ndash28 2009

[22] C-R Yang Y Zhang M R Jacob S I Khan Y-J Zhangand X-C Li ldquoAntifungal activity of C-27 steroidal saponinsrdquoAntimicrobial Agents and Chemotherapy vol 50 no 5 pp 1710ndash1714 2006

[23] S S Bhattacharya U Das and B K Choudhury ldquoOccurrenceampantibiogram of Salmonella typhi amp S paratyphi A isolated fromRourkela Orissardquo Indian Journal ofMedicinal Research vol 133no 4 pp 431ndash433 2011

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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

10 Organic Chemistry International

[24] R L Vogt and L Dippold ldquoEscherichia coli O157H7 outbreakassociated with consumption of ground beef June-July 2002rdquoPublic Health Reports vol 120 no 2 pp 174ndash178 2005

[25] T Pressler C Bohmova S Conway et al ldquoChronic Pseu-domonas aeruginosa infection definition EuroCareCF Work-ing Group reportrdquo Journal of Cystic Fibrosis vol 10 supplement2 pp S75ndashS78 2011

[26] V Barbe S Cruveiller F Kunst et al ldquoFrom a consortiumsequence to a unified sequence the Bacillus subtilis 168 refer-ence genome a decade laterrdquo Microbiology vol 155 no 6 pp1758ndash1775 2009

[27] L G Harris S J Foster R G Richards P Lambert D Sticklerand A Eley ldquoAn introduction to Staphylococcus aureus andtechniques for identifyingand quantifying S aureus adhesins inrelation to adhesion to biomaterials reviewrdquo European Cells andMaterials vol 4 pp 39ndash60 2002

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