Research Article Synthesis, Characterization, and...

Research ArticleSynthesis Characterization and Antibacterial Activities ofNovel Sulfonamides Derived through Condensation of AminoGroup Containing Drugs Amino Acids and Their Analogs

Muhammad Abdul Qadir1 Mahmood Ahmed1 and Muhammad Iqbal2

1 Institute of Chemistry University of Punjab Lahore 54590 Pakistan2Department of Chemistry Minhaj University Lahore Pakistan

Correspondence should be addressed to Mahmood Ahmed mahmoodresearchscholargmailcom

Received 16 December 2014 Accepted 9 February 2015

Academic Editor Ajit S Narang

Copyright copy 2015 Muhammad Abdul Qadir et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Novel sulfonamides were developed and structures of the new products were confirmed by elemental and spectral analysis (FT-IRESI-MS 1HNMR and 13CNMR) In vitro developed compounds were screened for their antibacterial activities against medicallyimportant gram (+) and gram (minus) bacterial strains namely S aureus B subtilis E coli and K pneumoniae The antibacterialactivities have been determined by measuring MIC values (120583gmL) and zone of inhibitions (mm) Among the tested compoundsit was found that compounds 5a and 9a have most potent activity against E coli with zone of inhibition 31 plusmn 012mm (MIC781 120583gmL) and 30 plusmn 012mm (MIC 781 120583gmL) respectively nearly as active as ciprofloxacin (zone of inhibition 32 plusmn 012mm)In contrast all the compounds were totally inactive against the gram (+) B subtilis

1 Introduction

Sulfa drugs containing sulfonamide functional group whichhave extensive biological activities revolutionised the field ofmedical sciences [1] Folic acid an important chemical forsynthesis of bacterial DNA and RNA is inhibited by sulfon-amides production of new DNA and RNA is decreased bythe deficiency of tetrahydrofolate which ultimately decayedthe bacteria Microorganismrsquos normal growth is inhibiteddue to mistaken attempt by bacteria to convert sulfonamideinstead of p-amino benzoic acid for synthesis of folic acidDue to such activities sulfonamides are also efficiently usedin agriculture field for antibacterial activities [2 3] Inhi-bition of carbonic anhydrases has been done by the drugscontaining sulfonamide functional group and these carbonicanhydrase inhibitors are also reported as potential anticancerantiglaucoma (as substituted heterocyclic and aromatic sul-fonamides) diuretics and antiobesity agents [4] Therapeu-tically sulfonamides are being widely used in human (espe-cially where other antibiotics are nontolerable to patients)

and veterinary practice [5] For agricultural purposes manyderivatives of sulfonamide have been reported due to theirantifungal [6ndash8] and herbicidal [9] properties The newerantibacterial drugs with different mode of action andmecha-nismhave become an emerging demand to overcome existingdrugs resistant pathogens As the pathogenic organisms (bac-teria fungi and mold) are exposed or treated medically withroutine antibiotic drug molecules they become considerablyresistant with emergence of new species as per mutationconjugation transduction or transformation The synthesisof new sulfonamides has got more attention of researchersfor their previous success in the field of pharmaceuticalsciences and medicinal chemistry In recent studies ten newsulfonamides have been synthesized and characterized by thereaction of p-toluene sulphonyl chloride with essential aminoacids (histidine and tryptophan) and amino group containingdrugs such as levetiracetam (anticonvulsant) famotidine(antiulcer) celecoxib (NSAID) ribavirin (antiviral) tranex-amic acid (antifibrinolytic) furosemide (diuretic) aspartame(nonsaccharide sweetener) and nicotinamide (vitamin B)

Hindawi Publishing CorporationBioMed Research InternationalVolume 2015 Article ID 938486 7 pageshttpdxdoiorg1011552015938486

2 BioMed Research International

respectively Antibacterial activities of synthesized com-pounds were also evaluated against both gram (+) and gram(minus) bacteria

2 Experimental

21 Chemistry Chemicals used in present work were ofanalytical grade obtained from E-Merck (Germany) andBDH (UK) without further purification to synthesize desiredcompounds grade 1 quality water (001120583Scm) [10] wasprepared in our own laboratory Alpha IR spectrometer(FTIR-ATR) and Bruker and NMR spectrometer Brukerwere used to record the IR and 1HNMR (500MHz) and13CNMR (125MHz) spectra respectively PG-T80+ UV-visspectrophotometer and Flash HT Plus elemental analyzerThermo Scientific were used for 120582max and concentration ofhydrogen (H) carbon (C) nitrogen (N) and sulfur (S) ofrespective synthesized compounds respectively while themelting point was measured by Gallenkamp apparatus JMS-HX-110 spectrometer with electron ionization interface wasused for mass spectra The 1HNMR and 13CNMR spectra ofall the synthesized compounds were measured using MeODand concentration of all the compoundswas 10ndash20mg in 08ndash10mL of solvent Purification and progress of the synthesizedcompounds were confirmed on precoated TLC silica plate(Merck Germany)

22 Antibacterial Activity Assay Escherichia coli ATCC25922 Staphylococcus aureus ATCC 25923 Bacillus subtilisATCC 6633 and Klebsiella pneumoniae ATCC 13887 werecollected from Mycology Department University of Pun-jab Lahore Pakistan and were maintained in tryptic soyagar (TSA) medium slants at 5∘C until use A series often 2-fold dilutions were made by dissolving 10ndash30mg ofeach sulfonamide separately in 1mL dimethyl sulphoxide(DMSO) All the dilutions were made sterile in an autoclaveat 121∘C for 30minwith 15 psi pressure after filtration through022120583m membrane filter The minimal inhibitory concen-tration (MIC) was reported as absence of no observablegrowth by the lowest concentration of tested compoundsafter twofold serial dilution Ten individually numbered testtubes with screw capped are sterilized Tube 1 was filled with2mL of tryptic soy broth culture media including the stocksolution of synthesized compounds 10mL of this solutionwas introduced into Tube 2 and diluted with 10mL culturemedia and the procedure was repeated up to Tube 10 Theconcentration of all the compounds used for MIC valuewas 2ndash00039mgmL obtained by twofold serial dilutiontechnique The tubes were incubated at 25∘C for 72 hrsCiprofloxacinwas used as reference (positive control to checkthe sensitivity of tested bacterial strains) 1ndash3 times 108 cfumLof each of gram negative E coli and K pneumoniae andgram positive S aureus and B subtilis were obtained afteradjusting the optical density of inoculum at 02-03 and 03-04 (620 nm) respectively All the compounds and referencesolutions were applied (50120583L) onto a 6mm sterile filter paperdisc separately and the inoculated plates were incubated at37∘C for 24 hrsThe zones of inhibition (mm) were measured

and the antibacterial activities were evaluated Studies wereperformed in triplicate and zone of inhibition was calculatedwith the mean plusmn SD values

23 General Procedure for Synthesis of Sulfonamides A sim-ple method in aqueous media under dynamic pH controlis adopted for synthesis of sulfonamides Filtration afteracidification is involved for isolation of products [11] Allthe drugs were weighed accurately and dissolved completelyby addition of distilled water by constant stirring usingmagnetic stirrer The pH of the reaction contents was strictlymonitored andmaintained at 8ndash10 at regular intervals duringthe experimental reaction usingNa

2CO3solution (1M)Then

p-toluene sulphonyl chloride was accurately weighed andadded carefully into the above solution The reaction wascarried in round bottomflask equippedwithmagnetic stirrerAlkaline environment made the removal of hydrogen easierDuring stirring p-toluene sulphonyl chloride initially floatson the surface and the completion of reaction was examinedby the change in pH value due to formation of HCl bythe consumption of p-toluene sulphonyl chloride during thereaction On completion of the reaction pH was adjusted at2-3 using HCl solution (2M) The precipitates formed werefiltered throughWhatmanFilter PaperNo 42 washed severaltimes with distilled water and recrystallized using methanoland finally washed with water and acetone (9 1) and driedover anhydrous MgSO

4 Products formation was confirmed

through TLC (methanol water acetone in 60 20 20 ratio)

24 Spectral Characterization of Sulfonamides

241 119873-[(4-Methylphenyl) sulfonyl] Nicotinamide (3a)6110mg (50mmol) nicotinamide reacts with 9540mg 119901-toluenesulfonyl chloride (50mmol) and 3a compoundwas obtained as white solid IR 120592max (cmminus1) 3062(C-Haromatic stretching) 2978 (C-Hmethyl stretching) 1705(C=Ocarbonyl) 1620 (N-Hbending) 1018 (S=Ostretching) 1126(-N- S=Ostretching) 1458 (C=C-Caromatic stretching) 706 (Oslash-Sstretching)

1HNMR (MeOD 120575ppm) 911 (s 1H CH) 898 (d119869 = 508Hz 1H CH) 838 (s 1H NH) 806 (d 119869 = 829Hz1H CH) 781 (q 119869 = 726Hz 1H CH) 742 (d 119869 = 821Hz1H CH) 245 (s 3H CH

3) 13CNMR (MeOD 120575ppm) 164

(C-7) 151 (C-2) 1468 (C-6) 137 (C-4) 129 (C-17) 126 (C-18)22 (C-19) ESI-MS119898119911 27848 [M+2]+ 27634 [M]+

242 (2119878)-119873-[(4-Methylphenyl) sulfonyl]-2-(2-oxopyrrolidin-1-yl) Butanamide (3b) 5670mg (334mmol) levetiracetamreacts with 6350mg 119901-toluenesulfonyl chloride (334mmol)and 3b compound was obtained as white solid IR 120592max(cmminus1) 3363 (N-Hamine stretching) 3063 (C-Haromatic stretching)2960 (C-Hmethyl stretching) 1720 (C=Ocarbonyl) 1658 (N-Hbending) 1010 (S=Ostretching) 1144 (-N- S=Ostretching) 1504(C=C-Caromatic stretching) 675 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 968 (br s 1H NH) 761 (d 119869 = 824Hz 1H CH)735 (d 119869 = 827Hz 1H CH) 443 (t 119869 = 886Hz H CH)352 (dt 119869 = 721 152Hz 2H CH

2) 245 (s 3H CH

3) 241

(dd 119869 = 1541 742Hz 2H CH2) 208ndash213 (m 2H CH

2)

091 (t 119869 = 736Hz 3H CH3) 13CNMR (MeOD 120575ppm)

BioMed Research International 3

1721 (C-5) 1683 (C-7) 1453 (C-19) 1354 (C-16) 1259(C-21) 635 (C-6) 441 (C-2) 308 (C-4) 253 (C-10) 174(C-3) 119 (C-11) ESI-MS119898119911 32625 [M+2]+ 32427 [M]+

243 1-[34-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-119873-[(4-methylphenyl) sulfonyl]-1119867-12 4-triazole-3-carboxamide (3c) 6110mg (25mmol) ribavirin reactswith 4770mg 119901-toluenesulfonyl chloride (25mmol) and3c compound was obtained as white solid IR 120592max (cmminus1)3371 (N-Hamine stretching) 3155 (C-Haromatic stretching) 2962(C-Hmethyl stretching) 1711 (C=Ocarbonyl) 1597 (N-Hbending)1010 (S=Ostretching) 1174 (-N- S=Ostretching) 1496 (C=C-Caromatic stretching) 1357 (O-Hbending) 678 (Oslash-Sstretching)1HNMR (MeOD 120575ppm) 888 (s 1H CH) 781 (d119869 = 824Hz 1H CH) 745 (d 119869 = 827Hz 1H CH)703 (br s H NH) 592 (t 119869 = 531 1H CH) 445 (t 119869 = 5411H CH) 421 (t 119869 = 531 1H CH) 412 (t 119869 = 548 1HCH) 381 (dd 119869 = 88 516Hz 2H CH

2) 243 (s 3H CH

3)

13CNMR (MeOD 120575ppm) 1571 (C-8) 1541 (C-15) 1457(C-24) 1404 (C-10) 1354 (C-21) 1292 (C-23) 911 (C-2)868 (C-5) 751 (C-3) 694 (C-4) 619 (C-3) 21 (C-27)ESI-MS119898119911 40035 [M+2]+ 39827 [M]+

244 119873-[(4-Methylphenyl) sulfonyl] Histidine (5a)Compound 5a as white solid was obtained by thereaction of 5180mg (334mmol) histidine with 6360mg(334mmol) of 119901-toluenesulfonyl chloride IR 120592max (cmminus1)3125 (O-Hcarboxylic stretching) 2962 (C-Hmethyl stretching) 1591(N-Hbending) 1010 (S=Ostretching) 1170 (-N- S=Ostretching)1496 (C=C-Caromatic stretching) 1650 (C=Nstretching) 678 (Oslash-Sstretching)

1HNMR (MeOD 120575ppm) 831 (s 1H CH) 791(s 1H CH) 761 (d 119869 = 807Hz 1H CH) 733 (br s HNH) 723 (d 119869 = 801 1H CH) 475 (q 119869 = 821 1HCH) 301 (qd 119869 = 1458 831 2H CH

2) 239 (s 3H CH

3)

13CNMR (MeOD 120575ppm) 1751 (C-11) 1432 (C-17) 1357(C-2) 1301 (C-16) 1254 (C-15) 539 (C-7) 312 (C-6) 215(C-21) ESI-MS119898119911 31128 [M+2]+ 30929 [M]+

245 119873-[(4-Methylphenyl) sulfonyl] Tryptophan (5b) Com-pound 5b as white solid was obtained by the reac-tion of 5110mg (25mmol) tryptophan with 4770mg(25mmol) of 119901-toluenesulfonyl chloride IR 120592max (cmminus1)3300 (N-Hamine stretching) 3025 (O-Hcarboxylic stretching) 1581 (N-Hbending) 1040 (S=Ostretching) 1165 (-N- S=Ostretching) 1496(C=C-Caromatic stretching) 708 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 801 (br s 1H NH) 782 (d 119869 = 776Hz 1H CH) 771(s H CH) 765 (d 119869 = 807Hz 1H CH) 723 (d 119869 = 817Hz1H CH) 713 (t 119869 = 811 1H CH) 675 (d 119869 = 771 1HCH) 461 (t 119869 = 831 1H CH) 350 (dt 119869 = 1433 823 2HCH2) 239 (s 3H CH

3) 13CNMR (MeOD 120575ppm) 1759 (C-

15) 1435 (C-21) 1347 (C-2) 1301 (C-22) 1229 (C-9) 1186(C-4) 1118 (C-3) 635 (C-11) 297 (C-10) 214 (C-25) ESI-MS119898119911 36045 [M+2]+ 35837 [M]+

246 Methyl 119873-[(4-Methylphenyl) sulfonyl]-120572-aspartyl-L-phenylalaninate (7a) White crystals of compound 7a wereobtained by charging 5890mg aspartame (20mmol) with

3810mg of 119901-toluenesulfonyl chloride (20mmol) IR 120592max(cmminus1) 3340 (N-Hamine stretching) 2950 (O-Hcarboxylic stretching)1219 (C-Namine stretching) 1735 (C=Oester stretching) 1581 (N-Hbending) 1040 (S=Ostretching) 1170 (-N- S=Ostretching) 1496(C=C-Caromatic stretching) 700 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 761 (br s 1H NH) 742 (d 119869 = 806Hz 1H CH) 725(d 119869 = 737Hz 1H CH) 693 (d 119869 = 814Hz 1H CH) 533(d 119869 = 911 1H CH) 465 (d 119869 = 767 1H CH) 361 (s 3HCH3) 293 (dt 119869 = 1373 683 2H CH

2) 239 (s 3H CH

3)

13CNMR (MeOD 120575ppm) 1743 (C-21) 1707 (C-12) 1435(C-27) 1368 (C-1) 1297 (C-6) 1261 (C-4) 556 (C-8) 523(C-19) 378 (C-7) 215 (C-31) ESI-MS 119898119911 45043 [M+2]+44847 [M]+

247 trans-4-([(4-Methylphenyl)sulfonyl]aminomethyl)cy-clohexanecarboxylic Acid (9a) White crystals of compound9a were obtained by charging 3930mg tranexamic acid(25mmol) with 4770mg of p-toluenesulfonyl chloride(25mmol) IR 120592max (cmminus1) 3263 (N-Hamine stretching) 2962(O-Hcarboxylic stretching) 1219 (C-Namine stretching) 1597 (N-Hbending) 1067 (S=Ostretching) 1157 (-N- S=Ostretching) 1496(C=C-Caromatic stretching) 680 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 771 (d 119869 = 806Hz 1H CH) 756 (br s H NH)722 (d 119869 = 806Hz 1H CH) 285 (d 119869 = 1517Hz 1HCH) 233 (s 3H CH

3) 229 (d 119869 = 1071 1H CH) 165 (dt

119869 = 1167 971 2H CH2) 141 (qd 119869 = 1293 1083 2H

CH2) 13CNMR (MeOD 120575ppm) 1825 (C-11) 1403 (C-17)

1365 (C-14) 1295 (C-16) 468 (C-7) 385 (C-1) 296 (C-6)223 (C-21) ESI-MS119898119911 31335 [M+2]+ 31137 [M]+

248 4-Chloro-2-[(2-furylmethyl)amino]-5-([(4-methylphen-yl)sulfonyl]aminosulfonyl)benzoic Acid (11a) Compound11a as white solid was obtained by the reaction of 6610mg(20mmol) furosemide with 3810mg (20mmol) of119901-toluenesulfonyl chloride IR 120592max (cmminus1) 3348 (N-Hamine stretching) 3250 (O-Hcarboxylic stretching) 1607 (N-Hbending) 1072 (S=Ostretching) 1160 (-N- S=Ostretching) 1496(C=C-Caromatic stretching) 702 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 1181 (br s H NH) 842 (s 1H CH) 789 (d119869 = 817Hz 1H CH) 758 (d 119869 = 811Hz 1H CH) 739 (sH CH) 665 (s H CH) 621 (s H CH) 616 (d 119869 = 327H CH) 441 (s H CH) 242 (s H CH) 13CNMR (MeOD120575ppm) 1725 (C-14) 1539 (C-8) 1435 (C-28) 1308 (C-27)1238 (C-13) 1205 (C-9) 1104 (C-4) 423 (C-6) 215 (C-31)ESI-MS119898119911 48695 [M+2]+ 48487 [M]+

249 4-Methyl-119873-(4-[5-(4-methylphenyl)-3-(trifluorometh-yl)-1119867-pyrazol-1-yl]phenylsulfonyl)Benzenesulfonamide(11b)Compound 11b as white solid was obtained by the reactionof 4240mg (111mmol) celecoxib with 2120mg (111mmol)of p-toluenesulfonyl chloride IR 120592max (cmminus1) 3327 (N-Hamine stretching) 1607 (N-Hbending) 1065 (S=Ostretching)1142 (-N- S=Ostretching) 1502 (C=C-Caromatic stretching) 1650(C=Nstretching) 703 (Oslash-Sstretching) 1095ndash1125 (C-Fstretching)1HNMR (MeOD 120575ppm) 1611 (br s H NH) 862 (d119869 = 819Hz 1H CH) 837 (d 119869 = 801Hz 1H CH) 808(d 119869 = 991Hz 1H CH) 791 (d 119869 = 817Hz 1H CH) 765


S OOCl

R O

+

R

OHNS OO

R O

OH

S OOHN

O

OH

R

R

R

SR O

O

S OOHN

SO

O R

SNN N

S OO

R S

(2)

(4)

(6)

(8)

(10)

(12) SO

O

HN

S OO N

N NS

R

S

HNR

S OOHN

R

S OO

(3)(5)

(7)

(9)

(11)

(13)

R R

3aN

7a HO

ONH

NH

OO

O3b

NO

9a

O

OH

3cNN N

O

OHHO

HO

11a OO

Cl

OH

5a N

NH

11bNN

FF

F

5b

NH

13aS OO S OO S OO

NH2

NH2

NH2

NH2

R1

NH2

NH2

R1

R1

R2

R2

CH3

CH3

R1

CH3

CH3

CH3 CH3

R1 R2

CH3

NH2NH2

CH3 CH3

NH2

CH3

CH3

CH3

1

Scheme 1 Synthesis of sulfonamides


Table1Ph

ysiochem

icalandanalyticaldataof

sulfo

namides

Com

poun

dsMP

(∘ C)

Time(h)

Yield(

)119877

119891

avalue120582

max

b(nm)

Molecular

form

ula(

MolW

t)Elem

entalanalysis

(foun

dcal)

C

HN

S3a

178ndash180

3848

072

219

C 13H

12N

2O3S

(27631

)5653

5651

435438

1012

1016

11631160

3b270ndash

272

3765

061

221

C 15H

20N

2O4S

(32440)

55505554

619621

868864

98298

83c

174ndash

176

3473

057

229

C 15H

18N

4O7S

(39840)

4513

4522

458455

1410

1406

801805

5a184ndash

186

3331

053

223

C 13H

15N

3O4S

(30934)

50435047

485489

1352

1358

1033

1037

5b136ndash

138

3415

067

277

C 18H

18N

2O4S

(35841)

60286032

515

06

78878

2892895

7a207ndash209

3698

061

257

C 21H

24N

2O7S

(44849)

5613

5624

528539

626625

711715

9a145ndash147

3819

072

229

C 15H

21NO

4S(31140)

57835786

675680

442450

10231030

11a

186ndash

188

3775

068

233

C 19H

17N

2O7S

2Cl(48493)

4710

470

6346

353

581578

1315

1322

11b

148ndash150

3769

072

235

C 24H

20F 3N

3O4S 2

(53556)

53735382

372376

77678

511861197

13a

95ndash9

73

767

076

274

C 36H

39N

7O10S 7

(95420)

4533

4531

405412

1019

1028

23462352

a 119877119891valuem

easuredin

methano

lwateracetone

in60

20

20ratio

b 120582

maxmeasuredin

methano

l


Table 2 Zonea of inhibition and MICb of sulfonamides against pathogenic bacterial strains

Compounds

Name of bacteriaGram (+) bacterial strains Gram (minus) bacterial strains

S aureus (ATCC 25923) B subtilis (ATCC 6633) E coli (ATCC 25922) K pneumoniae (ATCC 13887)Zone of inhibition MIC Zone of inhibition MIC Zone of inhibition MIC Zone of inhibition MIC

3a mdash gt500 mdash gt500 mdash gt500 26 plusmn 133 6253b 19 plusmn 122 125 mdash gt500 28 plusmn 091 1563 28 plusmn 033 6253c mdash gt500 mdash gt500 18 plusmn 132 125 mdash gt5005a mdash gt500 mdash gt500 31 plusmn 012 781 18 plusmn 038 1255b 19 plusmn 081 125 mdash gt500 18 plusmn 048 125 mdash gt5007a mdash gt500 mdash gt500 mdash gt500 mdash gt5009a mdash gt500 mdash gt500 30 plusmn 012 781 mdash gt50011a 12 plusmn 092 250 mdash gt500 18 plusmn 151 250 16 plusmn 055 25011b 18 plusmn 104 625 mdash gt500 20 plusmn 190 250 18 plusmn 087 25013a mdash gt500 mdash gt500 28 plusmn 053 125 18 plusmn 091 125Ciprofloxacinc 32 plusmn 022 125 32 plusmn 013 125 32 plusmn 012 0625 30 plusmn 012 0625aZone of inhibition was measured in mmbMIC (minimum inhibitory concentrations) were measured in 120583gmLcControl drug

(d 119869 = 797Hz 1H CH) 681 (s H CH) 246 (s H CH)235 (s H CH) 13CNMR (MeOD 120575ppm) 1472 (C-5) 1418(C-33) 1385 (C-13) 1318 (C-9) 1283 (C-31) 1175 (C-12)1107 (C-4) 215 (C-24) ESI-MS 119898119911 53755 [M+2]+ 53557[M]+

2410 (1119864)-3-[(2-[(Bis [(4-methylphenyl) sulfonyl] aminomethylene) amino]-13-thiazol-4-ylmethyl) thio]-119873-[(4-methylphenyl) sulfonyl]-1198731015840-([(4-methylphenyl) sulfonyl]am-ino sulfonyl) Propanimidamide (13a) Compound 13aas white solid was obtained by the reaction of 2820mgfamotidine (0833mmol) with 6350mg of 119901-toluenesulfonylchloride (334mmol) IR 120592max (cmminus1) 3327 (N-Hamine stretching) 1674 (N-Hbending) 1072 (S=Ostretching)1172 (-N- S=Ostretching) 1496 (C=C-Caromatic stretching) 1650(C=Nstretching) 702 (Oslash-Sstretching) 652 (C-Sstretching)

1HNMR(MeOD 120575ppm) 951 (br s H NH) 812 (d 119869 = 819Hz1H CH) 787 (d 119869 = 811Hz 1H CH) 768 (d 119869 = 891Hz1H CH) 731 (d 119869 = 810Hz 1H CH) 385 (s H CH)293 (d 119869 = 1597Hz 1H CH) 281 (s 2H CH

2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR

(MeOD 120575ppm) 1748 (C-15) 1641 (C-2) 1535 (C-4) 1444(C-7) 1321 (C-54) 1265 (C-38) 1045 (C-5) 352 (C-11)323 (C-13) 212 (C-59) ESI-MS 119898119911 95621 [M+2]+ 95417[M]+

3 Results and Discussion

A series of ten sulfonamides were synthesized in aqueousbasic media by simple reaction of six amino group contain-ing drugs two amino acids and two amino acid analogs(nicotinamide is used as source of vitamin B and aspartameis sweetener used in various pharmaceutical liquid formula-tions) with paratoluene sulphonyl chloride with continuousstirring and details of reaction conditions are explained in

experimental section and synthetic pathway of sulfonamidesis explained in Scheme 1 The compounds 3a and 9a wereobtained in excellent yield (above 80) while the 3c 5aand 5b gave the poor yield (below 50) The remainingcompounds were obtained in good yield (69ndash77) Ele-mental analysis was performed for the conformation of allthe compounds and measurement of absorption maximum(120582max) provided the justification The physiochemical andanalytical data of synthesized sulfonamides are presented inTable 1 The synthesized compounds were characterized byFT-IR the characteristics band at 3263ndash3371 cmminus1 of N-Hamide stretching and 1174ndash1127 cmminus1 for (-N- S=O) and 1072ndash1010 cmminus1 (S=O) for all compounds reveals the formation ofsulfonamides [M+2]+ peaks obtained by ESI-MS representedthe isolation of sulfonyl group in all synthesized compoundsThe structures of all the compounds were also confirmedby 1HNMR and 13CNMR by dissolving in MeOD 1HNMRspectra of compounds 3c 5a 7a and 9a showed a signal at 120575703ndash761 while a signal at 120575 1611 and 1181 ppm for 11b and 11acorresponds to NH group of sulfonamide

A broad singlet due to ndashNH group was also obtainedfor compounds 3a 3b 5b and 13a at 120575 838 968 801and 951 ppm respectively The characteristics C- SO-NHsignals at 120575 131ndash139 ppm of all the compounds were shownby 13CNMRwhich identified the structures correctly Synthe-sized compounds were also screened for their antibacterialactivities against gram negative bacterial E coli and Kpneumoniae and gram positive S aureus and B subtilis byfollowing the guidelines of CLSI [12 13] using ciprofloxacin asreference antibacterial agent Among the bacterial strains thecompounds 3a and 3b have excellent antibacterial activitiesagainst K pneumoniae with zone of inhibition comparablewith control drug (MIC 625) Compounds 3c 5b 7a and9a showed moderate activities while remaining compoundshave no activity against the prescribed bacterial strainCompounds 5a and 9a exhibited excellent activities against


E coli almost the same zone of inhibition as by referenceciprofloxacin (MIC 781) while 3a and 7a showed no activity(MIC gt 500) The remaining compounds were moderateactive against the mentioned strain All the compounds weretotally inactive against the B subtilis Compounds 3b (MIC125) 5b (MIC 125) and 11b (MIC 625) showed moderateactivity while 11a exhibited poor activity against the S aureusand remaining compounds are totally inactive The MICvalues and zone of inhibitions are presented in Table 2

4 Conclusion

In conclusion ten novel sulfonamides were synthesizedthe reactions conditions are easy and excellent yields ofcompoundswere obtained and progress of reactionwasmon-itored byTLC and their structureswere confirmed by spectraland elemental analysis All the synthesized compounds wereevaluated for their antibacterial activities and the results oftheir bioassay indicated that the sulfonamides attached toamino acid (histidine) and antifibrinolytic (tranexamic acid)showed antibacterial activities comparable to ciprofloxacinalthough these two agents alone have no antibacterial activityThe results confirmed that the compounds which are inactiveagainst bacterial strains showed antibacterial activities afterformation of sulfonamides

Conflict of Interests

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

References

[1] A Ali G S K K Reddy H Cao et al ldquoDiscovery of HIV-1 protease inhibitors with picomolar affinities incorporatingN-aryl oxazolidinone-5-carboxamides as novel p2 ligandsrdquoJournal of Medicinal Chemistry vol 49 no 25 pp 7342ndash73562006

[2] R Li G L Kenyon F E Cohen et al ldquoIn vitro antimalarialactivity of chalcones and their derivativesrdquo Journal of MedicinalChemistry vol 38 no 26 pp 5031ndash5037 1995

[3] B F Abdel-Wahab H A Abdel-Aziz and E M AhmedldquoSynthesis and antimicrobial evaluation of some 13-thiazole134-thiadiazole 124-triazole and 124-triazolo[34-b][134]-thiadiazine derivatives including a 5-(benzofuran-2-yl)-1-phenylpyrazole moietyrdquo Monatshefte fur Chemie vol 140 no6 pp 601ndash605 2009

[4] B Siesky A Harris E Brizendine et al ldquoLiterature reviewand meta-analysis of topical carbonic anhydrase inhibitors andocular blood flowrdquo Survey of Ophthalmology vol 54 no 1 pp33ndash46 2009

[5] F A N El-Dien G G Mohamed E Khaled and E YZ Frag ldquoExtractive spectrophotometric determination ofsulphonamide drugs in pure and pharmaceutical preparationsthrough ion-pair formation with molybdenum(V) thiocyanatein acidic mediumrdquo Journal of Advanced Research vol 1 no 3pp 215ndash220 2010

[6] L Saız-Urra M P Gonzalez I G Collado and RHernandez-Galan ldquoQuantitative structure-activity relationship

studies for the prediction of antifungal activity of N-arylbenzenesulfonamides against Botrytis cinereardquo Journalof Molecular Graphics and Modelling vol 25 no 5 pp680ndash690 2007

[7] W-J Zhu P Wu X-M Liang et al ldquoDesign synthesis andfungicidal activity of macrolactones and macrolactams witha sulfonamide side chainrdquo Journal of Agricultural and FoodChemistry vol 56 no 15 pp 6547ndash6553 2008

[8] I R Ezabadi C Camoutsis P Zoumpoulakis et alldquoSulfonamide-124-triazole derivatives as antifungal and anti-bacterial agents synthesis biological evaluation lipophilicityand conformational studiesrdquoBioorganicampMedicinal Chemistryvol 16 no 3 pp 1150ndash1161 2008

[9] M A Gonzalez D B Gorman C T Hamilton and G ARoth ldquoProcess development for the sulfonamide herbicidepyroxsulamrdquo Organic Process Research amp Development vol 12no 2 pp 301ndash303 2008

[10] G H Jeffery J Bassett J Mendham and R C Denney VogelrsquosTextbook of Quantitative Chemical Analysis JohnWiley amp SonsNew York NY USA 1989

[11] X Deng and N S Mani ldquoA facile environmentally benignsulfonamide synthesis in waterrdquo Green Chemistry vol 8 no 9pp 835ndash838 2006

[12] Clinical and Laboratory Standard Institute Performance Stan-dard for Anti-Microbial Disk Susceptibility Tests ApprovedStandard M2-A-9 Clinical and Laboratory Standard InstituteWayne Pa USA 2006

[13] Clinical and Laboratory Standard InstituteMethod for DilutionAnti-Microbial Susceptibility Tests for Bacteria That Grow Aer-obically Approved Standard M7-a-9 Clinical and LaboratoryStandard Institute Wayne Pa USA 2006

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of


StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of



Advances in Pharmacological Sciences

Tropical MedicineJournal of


Medicinal ChemistryInternational Journal of


AddictionJournal of



BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


respectively Antibacterial activities of synthesized com-pounds were also evaluated against both gram (+) and gram(minus) bacteria

2 Experimental

21 Chemistry Chemicals used in present work were ofanalytical grade obtained from E-Merck (Germany) andBDH (UK) without further purification to synthesize desiredcompounds grade 1 quality water (001120583Scm) [10] wasprepared in our own laboratory Alpha IR spectrometer(FTIR-ATR) and Bruker and NMR spectrometer Brukerwere used to record the IR and 1HNMR (500MHz) and13CNMR (125MHz) spectra respectively PG-T80+ UV-visspectrophotometer and Flash HT Plus elemental analyzerThermo Scientific were used for 120582max and concentration ofhydrogen (H) carbon (C) nitrogen (N) and sulfur (S) ofrespective synthesized compounds respectively while themelting point was measured by Gallenkamp apparatus JMS-HX-110 spectrometer with electron ionization interface wasused for mass spectra The 1HNMR and 13CNMR spectra ofall the synthesized compounds were measured using MeODand concentration of all the compoundswas 10ndash20mg in 08ndash10mL of solvent Purification and progress of the synthesizedcompounds were confirmed on precoated TLC silica plate(Merck Germany)

22 Antibacterial Activity Assay Escherichia coli ATCC25922 Staphylococcus aureus ATCC 25923 Bacillus subtilisATCC 6633 and Klebsiella pneumoniae ATCC 13887 werecollected from Mycology Department University of Pun-jab Lahore Pakistan and were maintained in tryptic soyagar (TSA) medium slants at 5∘C until use A series often 2-fold dilutions were made by dissolving 10ndash30mg ofeach sulfonamide separately in 1mL dimethyl sulphoxide(DMSO) All the dilutions were made sterile in an autoclaveat 121∘C for 30minwith 15 psi pressure after filtration through022120583m membrane filter The minimal inhibitory concen-tration (MIC) was reported as absence of no observablegrowth by the lowest concentration of tested compoundsafter twofold serial dilution Ten individually numbered testtubes with screw capped are sterilized Tube 1 was filled with2mL of tryptic soy broth culture media including the stocksolution of synthesized compounds 10mL of this solutionwas introduced into Tube 2 and diluted with 10mL culturemedia and the procedure was repeated up to Tube 10 Theconcentration of all the compounds used for MIC valuewas 2ndash00039mgmL obtained by twofold serial dilutiontechnique The tubes were incubated at 25∘C for 72 hrsCiprofloxacinwas used as reference (positive control to checkthe sensitivity of tested bacterial strains) 1ndash3 times 108 cfumLof each of gram negative E coli and K pneumoniae andgram positive S aureus and B subtilis were obtained afteradjusting the optical density of inoculum at 02-03 and 03-04 (620 nm) respectively All the compounds and referencesolutions were applied (50120583L) onto a 6mm sterile filter paperdisc separately and the inoculated plates were incubated at37∘C for 24 hrsThe zones of inhibition (mm) were measured

and the antibacterial activities were evaluated Studies wereperformed in triplicate and zone of inhibition was calculatedwith the mean plusmn SD values

23 General Procedure for Synthesis of Sulfonamides A sim-ple method in aqueous media under dynamic pH controlis adopted for synthesis of sulfonamides Filtration afteracidification is involved for isolation of products [11] Allthe drugs were weighed accurately and dissolved completelyby addition of distilled water by constant stirring usingmagnetic stirrer The pH of the reaction contents was strictlymonitored andmaintained at 8ndash10 at regular intervals duringthe experimental reaction usingNa

2CO3solution (1M)Then

p-toluene sulphonyl chloride was accurately weighed andadded carefully into the above solution The reaction wascarried in round bottomflask equippedwithmagnetic stirrerAlkaline environment made the removal of hydrogen easierDuring stirring p-toluene sulphonyl chloride initially floatson the surface and the completion of reaction was examinedby the change in pH value due to formation of HCl bythe consumption of p-toluene sulphonyl chloride during thereaction On completion of the reaction pH was adjusted at2-3 using HCl solution (2M) The precipitates formed werefiltered throughWhatmanFilter PaperNo 42 washed severaltimes with distilled water and recrystallized using methanoland finally washed with water and acetone (9 1) and driedover anhydrous MgSO

4 Products formation was confirmed

through TLC (methanol water acetone in 60 20 20 ratio)

24 Spectral Characterization of Sulfonamides

241 119873-[(4-Methylphenyl) sulfonyl] Nicotinamide (3a)6110mg (50mmol) nicotinamide reacts with 9540mg 119901-toluenesulfonyl chloride (50mmol) and 3a compoundwas obtained as white solid IR 120592max (cmminus1) 3062(C-Haromatic stretching) 2978 (C-Hmethyl stretching) 1705(C=Ocarbonyl) 1620 (N-Hbending) 1018 (S=Ostretching) 1126(-N- S=Ostretching) 1458 (C=C-Caromatic stretching) 706 (Oslash-Sstretching)

1HNMR (MeOD 120575ppm) 911 (s 1H CH) 898 (d119869 = 508Hz 1H CH) 838 (s 1H NH) 806 (d 119869 = 829Hz1H CH) 781 (q 119869 = 726Hz 1H CH) 742 (d 119869 = 821Hz1H CH) 245 (s 3H CH

3) 13CNMR (MeOD 120575ppm) 164

(C-7) 151 (C-2) 1468 (C-6) 137 (C-4) 129 (C-17) 126 (C-18)22 (C-19) ESI-MS119898119911 27848 [M+2]+ 27634 [M]+

242 (2119878)-119873-[(4-Methylphenyl) sulfonyl]-2-(2-oxopyrrolidin-1-yl) Butanamide (3b) 5670mg (334mmol) levetiracetamreacts with 6350mg 119901-toluenesulfonyl chloride (334mmol)and 3b compound was obtained as white solid IR 120592max(cmminus1) 3363 (N-Hamine stretching) 3063 (C-Haromatic stretching)2960 (C-Hmethyl stretching) 1720 (C=Ocarbonyl) 1658 (N-Hbending) 1010 (S=Ostretching) 1144 (-N- S=Ostretching) 1504(C=C-Caromatic stretching) 675 (Oslash-Sstretching)

1HNMR (MeOD120575ppm) 968 (br s 1H NH) 761 (d 119869 = 824Hz 1H CH)735 (d 119869 = 827Hz 1H CH) 443 (t 119869 = 886Hz H CH)352 (dt 119869 = 721 152Hz 2H CH

2) 245 (s 3H CH

3) 241

(dd 119869 = 1541 742Hz 2H CH2) 208ndash213 (m 2H CH

2)

091 (t 119869 = 736Hz 3H CH3) 13CNMR (MeOD 120575ppm)




2) 243 (s 3H CH

3)




2) 239 (s 3H CH

3)




3) 13CNMR (MeOD 120575ppm) 1759 (C-





2) 239 (s 3H CH

3)




3) 229 (d 119869 = 1071 1H CH) 165 (dt

119869 = 1167 971 2H CH2) 141 (qd 119869 = 1293 1083 2H


1365 (C-14) 1295 (C-16) 468 (C-7) 385 (C-1) 296 (C-6)223 (C-21) ESI-MS119898119911 31335 [M+2]+ 31137 [M]+





S OOCl

R O

+

R

OHNS OO

R O

OH

S OOHN

O

OH

R

R

R

SR O

O

S OOHN

SO

O R

SNN N

S OO

R S

(2)

(4)

(6)

(8)

(10)

(12) SO

O

HN

S OO N

N NS

R

S

HNR

S OOHN

R

S OO

(3)(5)

(7)

(9)

(11)

(13)

R R

3aN

7a HO

ONH

NH

OO

O3b

NO

9a

O

OH

3cNN N

O

OHHO

HO

11a OO

Cl

OH

5a N

NH

11bNN

FF

F

5b

NH

13aS OO S OO S OO

NH2

NH2

NH2

NH2

R1

NH2

NH2

R1

R1

R2

R2

CH3

CH3

R1

CH3

CH3

CH3 CH3

R1 R2

CH3

NH2NH2

CH3 CH3

NH2

CH3

CH3

CH3

1



Table1Ph

ysiochem


sulfo

namides

Com

poun

dsMP

(∘ C)

Time(h)

Yield(

)119877

119891

avalue120582

max

b(nm)

Molecular

form

ula(

MolW

t)Elem

entalanalysis

(foun

dcal)

C

HN

S3a

178ndash180

3848

072

219

C 13H

12N

2O3S

(27631

)5653

5651

435438

1012

1016

11631160

3b270ndash

272

3765

061

221

C 15H

20N

2O4S

(32440)

55505554

619621

868864

98298

83c

174ndash

176

3473

057

229

C 15H

18N

4O7S

(39840)

4513

4522

458455

1410

1406

801805

5a184ndash

186

3331

053

223

C 13H

15N

3O4S

(30934)

50435047

485489

1352

1358

1033

1037

5b136ndash

138

3415

067

277

C 18H

18N

2O4S

(35841)

60286032

515

06

78878

2892895

7a207ndash209

3698

061

257

C 21H

24N

2O7S

(44849)

5613

5624

528539

626625

711715

9a145ndash147

3819

072

229

C 15H

21NO

4S(31140)

57835786

675680

442450

10231030

11a

186ndash

188

3775

068

233

C 19H

17N

2O7S

2Cl(48493)

4710

470

6346

353

581578

1315

1322

11b

148ndash150

3769

072

235

C 24H

20F 3N

3O4S 2

(53556)

53735382

372376

77678

511861197

13a

95ndash9

73

767

076

274

C 36H

39N

7O10S 7

(95420)

4533

4531

405412

1019

1028

23462352

a 119877119891valuem

easuredin

methano

lwateracetone

in60

20

20ratio

b 120582

maxmeasuredin

methano

l



Compounds







2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR








4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




2) 243 (s 3H CH

3)




2) 239 (s 3H CH

3)




3) 13CNMR (MeOD 120575ppm) 1759 (C-





2) 239 (s 3H CH

3)




3) 229 (d 119869 = 1071 1H CH) 165 (dt

119869 = 1167 971 2H CH2) 141 (qd 119869 = 1293 1083 2H


1365 (C-14) 1295 (C-16) 468 (C-7) 385 (C-1) 296 (C-6)223 (C-21) ESI-MS119898119911 31335 [M+2]+ 31137 [M]+





S OOCl

R O

+

R

OHNS OO

R O

OH

S OOHN

O

OH

R

R

R

SR O

O

S OOHN

SO

O R

SNN N

S OO

R S

(2)

(4)

(6)

(8)

(10)

(12) SO

O

HN

S OO N

N NS

R

S

HNR

S OOHN

R

S OO

(3)(5)

(7)

(9)

(11)

(13)

R R

3aN

7a HO

ONH

NH

OO

O3b

NO

9a

O

OH

3cNN N

O

OHHO

HO

11a OO

Cl

OH

5a N

NH

11bNN

FF

F

5b

NH

13aS OO S OO S OO

NH2

NH2

NH2

NH2

R1

NH2

NH2

R1

R1

R2

R2

CH3

CH3

R1

CH3

CH3

CH3 CH3

R1 R2

CH3

NH2NH2

CH3 CH3

NH2

CH3

CH3

CH3

1



Table1Ph

ysiochem


sulfo

namides

Com

poun

dsMP

(∘ C)

Time(h)

Yield(

)119877

119891

avalue120582

max

b(nm)

Molecular

form

ula(

MolW

t)Elem

entalanalysis

(foun

dcal)

C

HN

S3a

178ndash180

3848

072

219

C 13H

12N

2O3S

(27631

)5653

5651

435438

1012

1016

11631160

3b270ndash

272

3765

061

221

C 15H

20N

2O4S

(32440)

55505554

619621

868864

98298

83c

174ndash

176

3473

057

229

C 15H

18N

4O7S

(39840)

4513

4522

458455

1410

1406

801805

5a184ndash

186

3331

053

223

C 13H

15N

3O4S

(30934)

50435047

485489

1352

1358

1033

1037

5b136ndash

138

3415

067

277

C 18H

18N

2O4S

(35841)

60286032

515

06

78878

2892895

7a207ndash209

3698

061

257

C 21H

24N

2O7S

(44849)

5613

5624

528539

626625

711715

9a145ndash147

3819

072

229

C 15H

21NO

4S(31140)

57835786

675680

442450

10231030

11a

186ndash

188

3775

068

233

C 19H

17N

2O7S

2Cl(48493)

4710

470

6346

353

581578

1315

1322

11b

148ndash150

3769

072

235

C 24H

20F 3N

3O4S 2

(53556)

53735382

372376

77678

511861197

13a

95ndash9

73

767

076

274

C 36H

39N

7O10S 7

(95420)

4533

4531

405412

1019

1028

23462352

a 119877119891valuem

easuredin

methano

lwateracetone

in60

20

20ratio

b 120582

maxmeasuredin

methano

l



Compounds







2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR








4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


S OOCl

R O

+

R

OHNS OO

R O

OH

S OOHN

O

OH

R

R

R

SR O

O

S OOHN

SO

O R

SNN N

S OO

R S

(2)

(4)

(6)

(8)

(10)

(12) SO

O

HN

S OO N

N NS

R

S

HNR

S OOHN

R

S OO

(3)(5)

(7)

(9)

(11)

(13)

R R

3aN

7a HO

ONH

NH

OO

O3b

NO

9a

O

OH

3cNN N

O

OHHO

HO

11a OO

Cl

OH

5a N

NH

11bNN

FF

F

5b

NH

13aS OO S OO S OO

NH2

NH2

NH2

NH2

R1

NH2

NH2

R1

R1

R2

R2

CH3

CH3

R1

CH3

CH3

CH3 CH3

R1 R2

CH3

NH2NH2

CH3 CH3

NH2

CH3

CH3

CH3

1



Table1Ph

ysiochem


sulfo

namides

Com

poun

dsMP

(∘ C)

Time(h)

Yield(

)119877

119891

avalue120582

max

b(nm)

Molecular

form

ula(

MolW

t)Elem

entalanalysis

(foun

dcal)

C

HN

S3a

178ndash180

3848

072

219

C 13H

12N

2O3S

(27631

)5653

5651

435438

1012

1016

11631160

3b270ndash

272

3765

061

221

C 15H

20N

2O4S

(32440)

55505554

619621

868864

98298

83c

174ndash

176

3473

057

229

C 15H

18N

4O7S

(39840)

4513

4522

458455

1410

1406

801805

5a184ndash

186

3331

053

223

C 13H

15N

3O4S

(30934)

50435047

485489

1352

1358

1033

1037

5b136ndash

138

3415

067

277

C 18H

18N

2O4S

(35841)

60286032

515

06

78878

2892895

7a207ndash209

3698

061

257

C 21H

24N

2O7S

(44849)

5613

5624

528539

626625

711715

9a145ndash147

3819

072

229

C 15H

21NO

4S(31140)

57835786

675680

442450

10231030

11a

186ndash

188

3775

068

233

C 19H

17N

2O7S

2Cl(48493)

4710

470

6346

353

581578

1315

1322

11b

148ndash150

3769

072

235

C 24H

20F 3N

3O4S 2

(53556)

53735382

372376

77678

511861197

13a

95ndash9

73

767

076

274

C 36H

39N

7O10S 7

(95420)

4533

4531

405412

1019

1028

23462352

a 119877119891valuem

easuredin

methano

lwateracetone

in60

20

20ratio

b 120582

maxmeasuredin

methano

l



Compounds







2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR








4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Table1Ph

ysiochem


sulfo

namides

Com

poun

dsMP

(∘ C)

Time(h)

Yield(

)119877

119891

avalue120582

max

b(nm)

Molecular

form

ula(

MolW

t)Elem

entalanalysis

(foun

dcal)

C

HN

S3a

178ndash180

3848

072

219

C 13H

12N

2O3S

(27631

)5653

5651

435438

1012

1016

11631160

3b270ndash

272

3765

061

221

C 15H

20N

2O4S

(32440)

55505554

619621

868864

98298

83c

174ndash

176

3473

057

229

C 15H

18N

4O7S

(39840)

4513

4522

458455

1410

1406

801805

5a184ndash

186

3331

053

223

C 13H

15N

3O4S

(30934)

50435047

485489

1352

1358

1033

1037

5b136ndash

138

3415

067

277

C 18H

18N

2O4S

(35841)

60286032

515

06

78878

2892895

7a207ndash209

3698

061

257

C 21H

24N

2O7S

(44849)

5613

5624

528539

626625

711715

9a145ndash147

3819

072

229

C 15H

21NO

4S(31140)

57835786

675680

442450

10231030

11a

186ndash

188

3775

068

233

C 19H

17N

2O7S

2Cl(48493)

4710

470

6346

353

581578

1315

1322

11b

148ndash150

3769

072

235

C 24H

20F 3N

3O4S 2

(53556)

53735382

372376

77678

511861197

13a

95ndash9

73

767

076

274

C 36H

39N

7O10S 7

(95420)

4533

4531

405412

1019

1028

23462352

a 119877119891valuem

easuredin

methano

lwateracetone

in60

20

20ratio

b 120582

maxmeasuredin

methano

l



Compounds







2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR








4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of



Compounds







2) 266 (s

3H CH3) 236 (s 3H CH

3) 230 (s 3H CH

3) 13CNMR








4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of



4 Conclusion




References



















Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

Research Article Synthesis, Characterization, and...

Documents

Transcript of Research Article Synthesis, Characterization, and...