research article facile synthesis and antimicrobial...

Research ArticleFacile Synthesis and Antimicrobial Evaluation of SomeNew Heterocyclic Compounds Incorporating a BiologicallyActive Sulfamoyl Moiety

Elham S Darwish

Department of Chemistry Faculty of Science Cairo University Giza 12613 Egypt

Correspondence should be addressed to Elham S Darwish elham darwishyahoocom

Received 7 March 2014 Accepted 4 April 2014 Published 17 August 2014

Academic Editor Valdir Cechinel Filho

Copyright copy 2014 Elham S Darwish 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

A facile and convenient synthesis of new heterocyclic compounds containing a sulfamoyl moiety suitable for use as antimicrobialagents was reported The precursor 3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide was coupled smoothly with arenedia-zonium salt producing hydrazones which reacted with malononitrile or triethylorthoformate affording pyridazine and triazinederivatives respectively Also the reactivity of the same precursor with DMF-DMA was followed by aminotriazole aromaticaldehydes was followed by hydrazine hydrate triethylorthoformate or thiourea affording triazolo[15-a]pyrimidine pyrazoleacrylamide and dihydropyrimidine derivatives respectively On the other hand treatment of the precursor propionamide withphenyl isothiocyanate and KOH in DMF afforded the intermediate salt which was treated with dilute HCl followed by 2-bromo-1-phenylethanone affording carboxamide derivative While the same intermediate salt reacted in situ with chloroacetone ethyl2-chloroacetate 3-(2-bromoacetyl)-2H-chromen-2-one methyl iodide or 2-oxo-N-phenylpropane hydrazonoyl chloride affordedthe thiophene keteneNS-acetal and thiadiazole derivatives respectively The structure of the new products was established basedon elemental and spectral analysis Antimicrobial evaluation of some selected examples from the synthesized products was carriedout whereby four compounds were found to have moderate activities and one compound showed the highest activity

1 Introduction

Sulfonamides have been reported to exhibit antimicrobial [1ndash3] antifungal [4] insulin releasing [5] carbonic anhydraseinhibitory [6] anti-inflammatory [7] and antitumor [8]properties Some active sulfonamides as antibacterial are alsoknown for their immunemodifying effects [9] Also pyrazolederivatives are known to exhibit diverse bioactivities suchas antidepressant [10] anticonvulsant [11] antimicrobial [12]analgesic [13] and antitumor [14] activity and also serve ashuman acyl-CoA cholesterol acyltransferase inhibitors [15]In addition thiophene compounds are well known to exhibitvarious biological and medicinal activities such as BACEIinhibitors [16] antitubercular [17] antidepressant [18] anti-inflammatory [19] and anti-HIV PR inhibitors [20] andantibreast cancer activities [21] These facts coupled withour desire to develop efficacious antimicrobial agents andin continuation of our work in heterocycles of biological

interest [22ndash25] prompted us to devise an efficient and con-venient method of synthesis of hitherto unknown and novelhydrazone pyridazine acrylamide pyrazole triazolo[15-a]pyrimidine thiadiazole dihydropyrimidine and thiophenederivatives with a sulfonamide nucleus Results from assess-ment of the antimicrobial activity of these newly synthesizedcompounds are reported in this study

2 Experimental Part

All melting points were determined on an electrothermalGallenkamp apparatus and are uncorrected The IR spectrawere measured on a Pye-Unicam SP300 instrument in potas-sium bromide discs The 1H-NMR spectra were recordedon a Varian Mercury VXR-300 spectrometer (300MHz)The mass spectra were recorded on a GCMS-Q1000-EXShimadzu andGCMS 5988-AHP spectrometers the ionizing

Hindawi Publishing Corporatione Scientific World JournalVolume 2014 Article ID 165495 10 pageshttpdxdoiorg1011552014165495

2 The Scientific World Journal

voltage was 70 eV Elemental analyses were carried out by theMicroanalytical Center of Cairo University Giza Egypt Thebiological evaluation of the products 3a 3c 6 7 8b 10 15 16and 17 was carried out at the Medical Mycology Laboratoryof the Regional Center for Mycology and Biotechnology ofAl-Azhar University Cairo Egypt

3-Oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide(1) and 3-(2-bromoacetyl)-2H-chromen-2-one [26ndash29] wereprepared as previously described

21 Coupling of 3-Oxo-3-phenyl-N-(4-sulfamoylphenyl)pro-pionamide (1) with the Appropriate Diazonium Salt of Aro-matic Amines

General Procedure To a cold solution of 3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide (1) (0318 g 1mmol) inpyridine (20mL) the appropriate diazonium salt of aromaticamine (aniline or 4-methylaniline or 4-chloroaniline or 4-methoxy-aniline or 4-nitroaniline) (1mmol) was added (pre-pared according to literature procedures) [30] The additionwas carried out portionwise with stirring at 0ndash5∘C overa period of 30min After complete addition the reactionmixture was stirred for further 4 hrs then kept in an ice chestfor 12 hrs and finally diluted with water The precipitatedsolid was collected by filtration washed with water driedand finally recrystallized from the proper solvent to afford thecorresponding coupling products 3andashe

22 2-[(4-Methoxyphenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide (3a) Yield (80) mp 270∘C(dioxane) IR (KBr) ]max 3351 3264 (NH NH

2) 3073

(aromatic CH) 1657 (C=O) cmminus1 1H NMR (DMSO-d6) 120575

375 (s 3H OCH3) 696 (d 2H 119869 = 9Hz) 728 (d 2H 119869 =

9Hz) 730 (s 2H D2O-exchangeable NH

2) 761 (d 2H 119869 =

8Hz) 777 (d 2H 119869 = 8Hz) 779ndash793 (m 5H Ar-H) 1147 (s1H D

2O-exchangeable NH) 1382 (s 1H D

2O-exchangeable

NH) MS mz () 452 (M++2 333) 452 (M+ 1837) 347(407) 252 (1566) 196 (351) 172 (549) 105 (1000) AnalCalcd for C

22H20N4O5S (45249) C 5840 H 446 N 1238

S 709 Found C 5836 H 436 N 1232 S 701

23 2-(p-Tolylhydrazono)-3-oxo-3-phenyl-N-(4-sulfamoyl-phenyl)propionamide (3b) Yield (75) mp 280∘C(dioxane) IR (KBr) ]max 3352 3265 (NH NH

2) 2924

2858 (aliphatic CH) 1660 (C=O) cmminus1 1H NMR (DMSO-d6) 120575 226 (s 3H CH

3) 714 (s 2H D

2O-exchangeable NH

2)

717ndash730 (m 5H Ar-H) 756 (d 2H 119869 = 9Hz) 762 (d 2H 119869= 9Hz) 781 (d 2H 119869 = 8Hz) 793 (d 2H 119869 = 8Hz) 1137 (s1H D


2O-exchangeable

NH) MS mz () 437 (M++1 2512) 436 (M+ 3575) 332(2657) 329 (3285) 279 (5121) 263 (3382) 171 (4203) 157(3140) 104 (2802) 57 (1000) Anal Calcd for C

22H20N4O4S

(43649) C 6054 H 462 N 1284 S 735 Found C 6050H 455 N 1272 S 727

24 2-(Phenylhydrazono)-3-oxo-3-phenyl-N-(4-sulfamoylphen-yl)propionamide (3c) Yield (70) mp 282∘C (dioxane) IR(KBr) ]max 3349 3256 (NH NH

2) 3059 (aromatic CH)

1650 (C=O) cmminus1 1H NMR (DMSO-d6) 120575 718 (s 2H D

2O-

exchangeable NH2) 720ndash766 (m 5H Ar-H) 770 (d 2H 119869 =



2O-exchangeable

NH) MS mz () 422 (M+ 76) 223 (19) 199 (04) 171(18) 121 (203) 119 (30) 105 (1000) 77 (577) Anal Calcdfor C21H18N4O4S (42247) C 5971 H 429 N 1326 S 759

Found C 5966 H 426 N 1330 S 753

25 2-[(4-Chlorophenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sul-famoylphenyl)propionamide (3d) Yield (60) mp 304∘C(dioxane) IR (KBr) ]max 3364 3262 and 3152 (NH NH

2)

1660 (C=O) cmminus1 1HNMR (DMSO-d6) 120575 724 (s 2H D

2O-

exchangeable NH2) 752 (d 2H 119869 = 8Hz) 762 (d 2H 119869 =

8Hz) 764 (d 2H 119869 = 9Hz) 783 (d 2H 119869 = 9Hz) 785ndash793(m 5H Ar-H) 1121 (s 1H D

2O-exchangeable NH) 1305

(s 1H D2O-exchangeable NH) MS mz () 457 (M++1

1325) 456 (M+ 1664) 329 (810) 285 (1119) 199 (1090) 128(1149) 105 (1000) Anal Calcd for C

21H17ClN4O4S (45691)

C 5520 H 375 Cl 776 N 1226 S 702 Found C 5515 H366 Cl 766 N 1221 S 700

26 2-[(4-Nitrophenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sul-famoylphenyl)propionamide (3e) Yield (55) mp 302∘C(dioxane) IR (KBr) ]max 3368 3265 and 3161 (NH NH

2)


2O-


9Hz) 778ndash789 (m 5H Ar-H) 791 (d 2H 119869 = 8Hz) 820 (d2H 119869 = 8Hz) 1108 (s 1H D

2O-exchangeable NH) 1245 (s

1H D2O-exchangeable NH) MS mz ()468 (M++1 389)

467 (M+ 725) 362 (471) 296 (426) 199 (433) 172 (1988)105 (1000) Anal Calcd for C

21H17N5O6S (46746) C 5396

H 367 N 1498 S 686 Found C 5387 H 359 N 1488 S678

27 N-[4-(Aminosulfonyl)phenyl]-5-cyano-6-imino-4-phenyl-p-tolyl-16-dihydropyridazine-3-carboxamide (4) To a solu-tion of (3b) (0436 g 1mmol) and malononitrile (1mmol) indioxane (20mL) few drops of piperidine were added and thereaction mixture was refluxed for 6 hrs The solid productthat formed was filtered off washed with ethanol and thenrecrystallized from the proper solvent to give 4

Yield (55) mp gt 300∘C (DMF) IR (KBr) ]max 34623305 and 3181 (NH NH

2) 2203 (CequivN) 1637 (C=O) cmminus1

1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 732 (d 2H

D2O-exchangeable NH

2) 740 (d 2H 119869 = 8Hz) 759 (d

2H 119869 = 9Hz) 767ndash790 (m 9H Ar-H) 1120 (s 1H D2O-

exchangeable NH) 1460 (s 1H D2O-exchangeable NH) MS

mz () 484 (M+ 232) 409 (742) 393 (909) 313 (694) 285(658) 199 (789) 91 (1651) 77 (2656) 69 (1000) Anal Calcdfor C25H20N6O3S (48454) C 6197 H 416 N 1734 S 662

Found C 6192 H 411 N 1730 S 659

28 4-(6-Benzoyl-3-ethoxy-5-oxo-2-p-tolyl-23-dihydro-124-triazin-4-(5H)-yl)benzenesulfonamide (5) To a solution ofthe compound 3b (0436 g 1mmol) in acetic acid (20mL)triethyl orthoformate (02mL 1mmol) was added and thereactionmixturewas refluxed for 8 hrs then it was left to cool

The Scientific World Journal 3

So the solid product formed was filtered off washed withEtOH and dried Recrystallization from dioxane afforded4-(6-benzoyl-3-ethoxy-5-oxo-2-p-tolyl-23-dihydro-124-triazin-4-(5H)-yl)benzenesulfonamide (5)

Yield (50) mp 296∘C (DMF) IR (KBr) ]max 3370 3311and 3236 (NH NH

2) 3056 (aromatic CH) 2982 (aliphatic-

H) 1678 (C=O) cmminus1 1HNMR (DMSO-d6) 120575 132 (t 3H 119869 =

72Hz CH3) 224 (s 3H CH

3) 427 (q 2H 119869= 72 CH

2) 594

(S 1H) 736 (s 2H D2O-exchangeable NH

2) 737ndash757 (m

9H Ar-H) 760 (d 2H 119869 = 9Hz) 771 (d 2H 119869 = 9Hz) MSmz () 494 (M++2 01) 492 (M+ 05) 352 (042) 335 (16)156 (06) 105 (1000) 91 (15) Anal Calcd for C

25H24N4O5S

(49256) C 6096 H 491 N 1137 S 651 Found C 6088H 485 N 1131 S 650

29 2-Benzoyl-3-dimethylamino-N-(4-sulfamoylphenyl)acryl-amide (6) A mixture of the compound 1 (318 g 10mmol)and NN-dimethylformamide dimethyl acetal (DMF-DMA)(10mmol) in dry dioxane (30mL) was refluxed for 6 hrsthen it was left to cool at room temperature The yel-low precipitated product was filtered off washed withpetroleum ether and dried Crystallization from MeOHwas carried out to give 2-benzoyl-3-dimethylamino-N-(4-sulfamoylphenyl)acryl-amide (6) in 44 yield

Yield (44) mp 190∘C (MeOH) IR (KBr) ]max 32503112 (NH NH

2) 3056 (aromatic CH) 1683 (C=O) cmminus1

1H NMR (DMSO-d6) 120575 342 (s 6H 2CH

3) 662 (d 2H 119869

= 9Hz) 703 (s 2H D2O-exchangeable NH

2) 728ndash731 (m

5H Ar-H) 758 (d 2H 119869 = 9Hz) 810 (s 1H olefinic-H)998 (s 1H D

2O-exchangeable NH) MS mz () 373 (M+

04) 291 (11) 190 (05) 155 (163) 105 (1000) Anal Calcdfor C18H19N3O4S (37343) C 5790 H 513 N 1125 S 859

Found C 5789 H 503 N 1115 S 861

210 5-Phenyl-[124]triazolo[15-va]pyrimidine-6-carboxylicAcid (4-sulfamoylphenyl)amide (7) To a solution of thecompound 6 (037 g 1mmol) in acetic acid (20mL)amino triazolo (01 g 1mmol) was added and the reactionmixture was refluxed for 8 hrs then it was left to coolThe solid product formed was filtered off washed withEtOH and dried Recrystallization from dioxane afforded5-phenyl-[124]triazolo[15-a]-pyrimidine-6-carboxylicacid(4-sul-famoylphenyl)amide (7)

Yield (48) mp 290∘C (dioxane) IR (KBr) ]max 32613110 (NH NH

2) 1685 (C=O) cmminus1 1HNMR (DMSO-d

6) 120575

661 (s 1H D2O-exchangeable NH

2) 705 (d 2H 119869 = 9Hz)

734ndash744 (m 5H Ar-H) 750 (d 2H 119869 = 9Hz) 768 (s 1Htriazole-H) 809 (s 1H pyrimidine-H) 848 (s 1H D

2O-

exchangeable NH) MSmz () 397 (M++3 200) 394 (M+02) 157 (160) 121 (520) 76 (840) 63 (1000) Anal Calcdfor C18H14N6O3S (39441) C 5482 H 358 N 2131 S 813

Found C 5480 H 353 N 2125 S 801

211 2-Benzoyl-3-aryl-2-yl-N-(4-sulfamoylphenyl)acrylamide(8a b)

General Procedure To a solution of (1) (0318 g 1mmol)and the appropriate aromatic aldehydes (1mmol) in dioxane

(20mL) few drops of piperidine were added and the reactionmixture was refluxed for 6 hrs So the solid product formedwas filtered off washed with EtOH dried and finally recrys-tallized from the proper solvent to give 8a b

212 2-Benzoyl-3-furan-2-yl-N-(4-sulfamoylphenyl)acrylam-ide (8a) Yield (45) mp 220∘C (EtOH) IR (KBr) ]max3349 3255 (NH NH

2) 1687 (C=O) cmminus1 1HNMR (DMSO-

d6) 120575 743 (s 2H D

2O-exchangeable NH

2) 746ndash761 (m 8H

Ar-H) 764 (d 2H 119869 = 9Hz) 794 (d 2H 119869 = 9Hz) 848 (s1H olefinic-H) 914 (s 1H D

2O-exchangeable NH) MSmz

() 396 (M+ 01) 225 (03) 197 (04) 171 (224) 157 (28) 105(1000) Anal Calcd for C

20H16N2O5S (39642) C 6060 H

407 N 707 S 809 Found C 6053 H 401 N 711 S 800

213 2-Benzoyl-3-(13-diphenyl-1H-pyrazol-4-yl)-N-(4-sulfa-moylphenyl)acrylamide (8b) Yield (50) mp 180∘C(EtOH) IR (KBr) ]max 3341 3261 (NH NH

2) 3060

(aromatic CH) 1675 (C=O) cmminus1 1H NMR (DMSO-d6)

120575 725 (s 2H D2O-exchangeable NH

2) 749ndash700 (m 15H

Ar-H) 764 (s 1H pyrazole-H) 777 (d 2H 119869 = 9Hz)781 (d 2H 119869 = 9Hz) 786 (s 1H olefinic-H) 1085 (s 1HD2O-exchangeable NH) MS mz () 548 (M+ 01) 217

(167) 199 (200) 172 (167) 105 (967) 92 (200) 77 (1000)Anal Calcd for C

31H24N4O4S (54863) C 6787 H 441 N

1021 S 584 Found C 6782 H 435 N 1016 S 578

214 5-Furan-2-yl-3-phenyl-23-dihydro-1-H-pyrazole-4-car-boxylic Acid (4-sulfamoylphenyl)amide (9a) To a solutionof the compound 8a (04 g 1mmol) in dioxane (20mL)hydrazine hydrate (80 02mL 1mmol) was added and thereaction mixture was refluxed for 6 hrs then it was left tocool So the solid product formedwas filtered offwashedwithEtOH and dried Recrystallization from dioxane afforded 9a

Yield (40) mp 244∘C (EtOH) IR (KBr) ]max 3281 3111(NH NH


6) 120575 633ndash

637 (m 2H) 721 (s 2H D2O-exchangeable NH

2) 744 (d

2H 119869 = 9Hz) 750 (d 2H 119869 = 9Hz) 756ndash775 (m 6H Ar-H) 999 (s 1H D


2O-

exchangeable NH) MS mz () 408 (M+ 35) 171 (204)142 (35) 77 (100) Anal Calcd for C

20H16N4O4S (40844)

C 5881 H 395 N 1372 S 785 Found C 5879 H 393 N1365 S 780

215 2-Benzoyl-3-ethoxy-N-(4-sulfamoylphenyl)acrylamide(10) To a solution of the compound 1 (318 g 10mmol)in acetic anhydride (20mL) triethyl orthoformate (2mL10mmol) was added and the reaction mixture was refluxedfor 8 hrs then it was left to cool So the solid productformed was filtered off washed with EtOH and driedRecrystallization from dioxane afforded 2-benzoyl-3-ethoxy-N-(4-sulfamoylphenyl)acrylamide (10)

Yield (60)mp 280∘C (DMF) IR (KBr) ]max 3359 3239and 3107 (NH NH

2) 1655 (C=O) cmminus1 1H NMR (DMSO-

d6) 120575 126 (t 3H 119869 = 72Hz CH

3) 432 (q 2H 119869 = 72 CH

2)


2) 740 (d 2H 119869 = 9Hz)

769 (d 2H 119869 = 9Hz) 787ndash800 (m 5H Ar-H) 863 (s 1HCH) 1125 (s 1H D

2O-exchangeable NH) MS mz () 374


(M+ 05) 370 (06) 301 (727) 198 (180) 172 (336) 156 (596)105 (708) 77 (850) 65 (1000) Anal Calcd for C

18H18N2O5S

(37442) C 5774 H 485 N 748 S 856 Found C 5770 H476 N 741 S 850

216 4-(6-Phenyl-2-thioxo-23-dihydropyrimidin-4-ylamino)benzenesulfonamide (11) To a mixture of 1 (0318 g 1mmol)and thiourea (0076 g 1mmol) in dimethylformamide(20mL) triethylamine (05mL) was added and the reactionmixture was refluxed for 6 hrs then it was left to coolThe precipitated product was filtered off and purified byrecrystallization from the suitable solvent to afford thecorresponding 11

Yield (45) mp gt 300∘C (dioxane) IR (KBr) ]max3500ndash3368 (NH NH

2) 3057 (aromatic CH) 1675 (C=O)

cmminus1 1HNMR (DMSO-d6) 120575 727 (s 2H D

2O-exchangeable

NH2) 754 (d 2H 119869 = 9Hz) 766 (d 2H 119869 = 9Hz) 768ndash797

(m 6H Ar-H) 1185 (s 1H D2O-exchangeable NH) 1223 (s

1H D2O-exchangeable NH) Anal Calcd for C

16H14N4O2S2

(35844) C 5361 H 394 N 1563 S 1789 Found C 53 60H 390 N 1559 S 1784

217 2-Benzoyl-3-mercapto-3-phenylamino-N-(4-sulfamoyl-phenyl)acrylamide (13) To a stirred solution of potassiumhydroxide (011 g 1mmol) in dimethylformamide (20mL)the 1 (0318 g 1mmol) was added After stirring for 30minphenylisothiocyanate (027 g 024mL 1mmol) was added tothe resulting mixture and stirring was continued for 6 h thenit was poured over crushed ice containing hydrochloric acidThe solid product formed was filtered off washed with waterdried and finally recrystallized from dioxane to afford 13


2) 1689 (C=O) 1661 (C=O) cmminus1 1H NMR

(DMSO-d6) 120575 719 (s 2H D

2O-exchangeable NH

2) 739 (d

2H 119869 = 9Hz) 769 (d 2H 119869 = 9Hz) 771ndash790 (m 10HAr-H) 1039 (s 1H D

2O-exchangeable NH) 1113 (s 1H

D2O-exchang-eable NH) 1276 (s 1H SH) MSmz () 455

(M++2 263) 453 (M+ 15) 121 (263) 105 (1000) 91 (474)89 (368) 77 (895) Anal Calcd for C

22H19N3O4S2(45354)

C 5826 H 422 N 926 S 1414 Found C 5822 H 420N 920 S 1411

218 N-[4-(Aminosulfonyl)phenyl]-2-anilino-4-phenyl-thio-phene-5-benzoyl-3-carboxamide (14) To a mixture ofacrylamide 13 (1mmol) and 2-bromo-1-phenylethanone(02 g 1mmol) in dimethylformamide (20mL) triethylamine(05mL) was added and the reaction mixture was refluxedfor 6 hrs then it was left to cool The precipitated productwas filtered off and purified by recrystallization from dioxaneto afford the corresponding N-[4-(aminosulfonyl)phenyl]-2-anilino-4-phenyl-thiophene-5-benzoyl-3-carboxamide(14)

Yield (40) mp 280∘C (dioxane) IR (KBr) ]max 34253276 3111 (NH NH

2) 3059 (aromatic CH) 1698 (C=O) 1658

(C=O) cmminus1 1H NMR (DMSO-d6) 120575 719 (s 2H D

2O-


9Hz) 822 (d 2H 119869 = 9Hz) 955 (s 1H D2O-exchangeable

NH) 998 (s 1H D2O-exchangeable NH) MS mz () 555

(M++2 160) 553 (M+ 15) 450 (200) 395 (200) 198 (24) 171(360) 156 (240) 105 (920) 91 (160) 76 (200) Anal Calcdfor C30H23N3O4S2(55366) C 6508 H 419 N 759 S 1158

Found C 6502 H 415 N 755 S 1154

219 Synthesis of 15 16 17 18 and 20 To a stirredsolution of potassium hydroxide (011 g 1mmol) in DMF(20mL) compound 1 (0318 g 1mmol) was added Afterstirring for 30min phenyl isothiocyanate (027 g 1mmol)was added to the resulting mixture Stirring was continuedfor 6 hrs and then chloroacetone ethyl chloroacetate 3-(2-bromoacetyl)-2H-chromen-2-one methyl iodide or 2-oxo-N-phenylpropane hydrazonoyl chloride (1mmol) was addedportionwise over a period of 30min After the addition wascomplete the reactionmixture was stirred for additional 12 hduring which the reactant dissolved and a yellow productprecipitated The solid product was filtered off washedwith EtOH and dried recrystallization from proper solventafforded 15 16 17 18 and 20

220 N-[4-(Aminosulfonyl)phenyl]-2-anilino-4-phenyl-thio-phene-5-acetyl-3-carboxamide (15) Yield (65) mp 268∘C(dioxane) IR (KBr) ]max 3371 3289 and 3220 (NH NH

2)

3059 (aromatic CH) 1636 (C=O) cmminus1 1H NMR (DMSO-d6) 120575 172 (s 3H CH

3) 711 (s 2H D

2O-exchangeable NH

2)

713 (d 2H 119869 = 9Hz) 738ndash746 (m 10H Ar-H) 763 (d2H 119869 = 9Hz) 946 (s 1H D


(s 1H D2O-exchangeable NH) 13C NMR (DMSO-d

6) 120575

2815 11868 11993 12388 12636 12785 12842 1287112920 12945 13489 13497 13846 14091 14132 1453315702 16259 18930 MS mz () 492 (M++1 132) 491(M+ 151) 320 (283) 292 (113) 187 (208) 105 (1000) 77(943) Anal Calcd for C

25H21N3O4S2(49159) C 6108 H

431 N 855 S 1304 Found C 6100 H 424 N 85 S1311

221 3-Phenyl-5-phenylamino-4-(4-sulfamoylphenyl-carbam-oyl)thiophene-2-carboxylic Acid Ethyl Ester (16) Yield (55)mp 280∘C(dioxane) IR (KBr) ]max 3367 3310 and 3235 (NHNH2) 3060 (aromatic CH) 1713 (C=O) 1635 (C=O) cmminus1

1HNMR (DMSO-d6) 120575 101 (s 3H 119869 = 72Hz CH

3) 404 (q

2H 119869 = 72Hz CH2) 708ndash713 (m 5H Ar-H) 721 (d 2H 119869

= 9Hz) 739ndash744 (m 7H Ar-H and NH2) 763 (d 2H 119869 =

9Hz) 954 (s 1H D2O-exchangeable NH) 973 (s 1H D

2O-

exchangeableNH)MSmz () 521 (M+ 263) 322 (158) 218(1000) 199 (158) 77 (860) Anal Calcd for C

26H23N3O5S2

(52162) C 5987 H 444 N 806 S 1229 Found C 5977H 441 N 802 S 1221

222 N-[4-(Aminosulfonyl)phenyl]-2-anilino-4-phenyl-5-[(2-oxo-2H-chromen-3-yl)carbonyl]-thiophene-3-carboxamide(17) Yield (55) mp 200∘C (EtOH) IR (KBr) ]max 33753261 (NH NH

2) 1713 (C=O) cmminus1 1H NMR (DMSO-d

6)

120575 671ndash727 (m 7H Ar-H and NH2) 729 (d 2H 119869 = 9Hz)

742ndash759 (m 10H Ar-H) 763 (d 2H 119869 = 9Hz) 988 (s 1HD2O-exchangeable NH) 1002 (s 1H D

2O-exchangeable

NH) MS mz () 621 (M+ 68) 423 (1000) 250 (151) 221(82) 199 (82) 145 (247) 105 (658) 77 (877) Anal Calcd


SO

O

PhCOCHSO

O

NH

O O

Ph

SO

O

NH

O

NNAr

Me

O

SO

ONH

O

NNHAr

O

Ph

b c d ea

Ar

Pyridine

H2

2

N

H2N H2N

H2NNH2

ArN2+Clminus

2andashc 3andashc

4-OMe 4-Me Ph 4-Cl

1

3

COOEt

4-NO2

Scheme 1 Synthesis of hydrazones derivatives

for C33H23N3O6S2(62170) C 6376 H 373 N 676 S

1032 Found C 6370 H 361 N 667 S 1025

223 2-Benzoyl-3-methylsulfanyl-3-phenylamino-N-(4-sulfa-moylphenyl)acrylamide (18) Yield (30) mp 260∘C (diox-ane) IR (KBr) ]max 3343 3242 (NHNH

2) 1696 (C=O) cmminus1

1H NMR (DMSO-d6) 120575 356 (s 3H SCH

3) 724 (d 2H 119869


9Hz) 1050 (s 2H D2O-exchangeable 2NH) MS mz ()

467 (M+ 229) 296 (457) 197 (257) 139 (229) 105 (143) 92(543) 63 (100) Anal Calcd for C

23H21N3O4S2(46756) C

5908 H 453 N 899 S 1372 Found C 5912 H 450 N896 S 1366

224 2-(5-Acetyl-3-phenyl-3H-[134]thiadiazol-2-ylidene)-3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide (20)Yield (35) mp 220∘C (dioxane) IR (KBr) ]max 33403244 (NH NH


1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 715 (s 2H

D2O-exchangeable NH

2) 730 (d 2H 119869 = 9Hz) 762 (d


exchangeable NH) MS mz () 522 (M++2 146) 520 (M+416) 320 (270) 306 (139) 247 (102) 214 (73) 189 (88) 114(73) 105 (204) 77 (1000) Anal Calcd for C

25H20N4O5S2

(52059) C 5768 H 387 N 1076 S 1232 Found C 5763H 382 N 1071 S 1229

225 Agar DiffusionWell Method to Determine the Antimicro-bial Activity Themicroorganism inoculums were uniformlyspread using sterile cotton swab on a sterile Petri dish maltextract agar (for fungi) and nutrient agar (for bacteria) Onehundred 120583L of each sample was added to each well (10mmdiameter holes cut in the agar gel 20mm apart from oneanother) The systems were incubated for 24ndash48 hours at37∘C (for bacteria) and at 28∘C (for fungi) After incubationthe microorganismrsquos growth was observed Inhibition of

the bacterial and fungal growth was measured in mm Testswere performed in triplicate [31]

3 Results and Discussion

Heterocyclic azo compounds are well known for their useas antineoplastics [32] antidiabetics [33] antiseptics [34]and antibacterial activity [35] and are known to be involvedin a number of biological reactions such as inhibition ofDNA RNA protein synthesis carcinogenesis and nitrogenfixation [34ndash36]Thus propionamide 1was coupled smoothlywith diazonium salts derived from the appropriate aro-matic amines [4-methoxyaniline 4-methylaniline aniline 4-chloroaniline and 4-nitroaniline) in pyridine to afford therespective hydrazones 3andashe (Scheme 1) The structures of theproducts were established on the basis of their elementalanalyses and spectral data (IR 1H NMR and MS) [seeExperimental Part] In the 1H NMR spectra of compounds3andashe absence of signal assignable to azomethine group (CHndashN=Nndash) [37] at 120575 300ndash400 ppm ruled out azo form andsupported the hydrazone structure of the products

Further elucidation of the structure of 3b came fromthe reaction with malononitrile and triethyl orthformateto furnish the final isolable products corresponding to the5-cyano-6-imino-4-phenyl-1-p-tolyl-16-dihydropyridazine-3-carboxylic acid (4-sulfamoylphenyl)amide (4) and4-(6-benzoyl-3-ethoxy-5-oxo-2-p-tolyl-23-dihydro-124-triazin-4-(5H)-yl)benzenesulfonamide (5) respectivelyThe structures of compounds 4 and 5 were confirmedbased on elemental analysis and spectral data studied(Scheme 2 and Experimental Part) Treatment of compound1 with NN-dimethylformamide-dimethylacetal (DMF-DMA) in refluxing dry dioxane afforded 2-benzoyl-3-dimethylamino-N-(4-sulfamoylphenyl)acrylamide (6) The1H NMR spectrum of compound 6 showed signals at 120575342 810 and 998 due to NN-dimethylamino C=CHndashN


SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip

Scheme 2 Synthesis of 16-dihydropyridazine and 23-dihydro-124-triazine derivatives

SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3

and amide-NH protons respectively When compound6 was treated with 3-amino-124-triazole in acetic acidunder reflux this led to formation of 124-triazolo [15-a]pyrimidine derivative 7 (Scheme 3) The IR spectrum ofthe isolated product showed absorption bands at 3261

and 3110 cmminus1 characteristic for NH and NH2function

Its 1H NMR spectrum showed signals at 120575 768 809and 848 corresponding to triazole-H pyrimidine-H andD2O-exchangeable signal corresponding to NH protons

respectively The pathway of formation of product 7 involves


Michael addition of the exocyclic amino group of theheteroamines to the enaminone double bond of 6 followedby in situ tandem elimination of dimethylamine anddehydrative cyclization

Also 1 reacts with aromatic aldehydes to afford thecorresponding 2-benzoyl-3-aryl-2-yl-N-(4-sulfamoylphen-yl)acrylamide derivatives 8ab (Scheme 3) The IR spectrumof compound 8a taken as a typical example revealedabsorption bands at 3349 3255 and 1687 cmminus1 correspondingto NH NH

2and CO functions respectively Its 1H NMR

spectrum showed signals at 120575 848 and 914 correspondingto CH and NH protons in addition to aromatic protonsat 120575 746ndash794 Its mass spectrum showed a molecular ionpeak at mz 396 When the acrylamide derivative 8a wastreated with hydrazine hydrate it afforded the correspondingpyrazole derivative 9a (Scheme 3) Spectroscopic dataas well as elemental analyses of the obtained productswere in complete agreement with the assigned structures9a

On the other hand the reactivity of propionamide 1towards triethylorthoformate and thiourea was investigatedThus condensation of 1 with triethylorthoformate in reflux-ing acetic anhydride afforded the ethoxymethylene derivative10 Establishing of structure 10 was based on the elementalanalysis and spectral data Treatment of 1 with thioureaafforded the pyrimidine derivative 11 Establishing of com-pound 11 is based on its elemental analysis and spectral data(IR and 1H NMR) (Scheme 3)

Next the nucleophilic addition of 1 to phenyl isothiocy-anate in dimethylformamide in the presence of potassiumhydroxide afforded the corresponding potassium salt 12When the intermediate potassium salt was treated withdilute HCl it gave the corresponding 2-benzoyl-3-mercapto-3-phenylamino-N-(4-sulfamoylphenyl)acrylamide (13)(Scheme 4)

The IR spectrum of compound 13 revealed the absorptionbands at 3350ndash3256 and 1689ndash1661 cmminus1 corresponding toNH NH

2and CO groups respectively Its 1H NMR

spectrum showed two D2O-exchangeable signals at 1039

1113 and 1276 corresponding to 2NH and SH protonrespectively Moreover the mass spectrum of the product13 exhibited a molecular ion peak at mz 453 Treatmentof compound 13 with 2-bromo-1-phenylethanone in dim-ethylformamide in the presence of a catalytic amount oftriethylamine afforded the carboxamide 14 (Scheme 4)The structure of compound 14 was elucidated from itsspectroscopic and elemental analytical data Thus it showedabsorption bands at 3425ndash3111 and 1698ndash1658 cmminus1 due toNH NH

2 and CO functions whereas its 1H NMR spectra

revealed two D2O-exchangeable signals at 955 and 998

corresponding to 2NH protons Heterocyclisation of theintermediate with chloroacetone or ethyl 2-chloroacetate and3-(2-bromoacetyl)-2H-chromen-2-one furnished in eachcase one isolable product (as tested by TLC) The reactionproducts were identified as N-[4-(aminosulfonyl)phenyl]-2-anilino-4-phenylthiophene-5-acetyl-3-carboxami-de (15)3-phenyl-5-phenylamino-4-(4-sulfa-moylphenyl-carbam-oyl)thiophene-2-carboxylic acid ethyl ester (16) and

N-[4-(aminosulfonyl)phenyl]-2-anilino-4-phenyl-5-[(2-oxo-2H-chromen-3-yl)carbonyl]thiophene-3-carboxamide(17) The reaction proceeds via nucleophilic displacementof bromide to give S-alkylated intermediate followed byloss of water of the latter intermediate to give thiophenederivatives 15 or 16 or 17 as the final products The structuresof the products 15ndash17 were determined from spectroscopicand elemental analytical data Thus compound 15 taken asa typical example showed absorption bands at 3371 32893220 and 1636 cmminus1 corresponding to NH NH

2and C=O

groups respectively Its 1H NMR spectrum revealed theabsence of CH

2protons of chloroacetone and showed signals

at 120575 946 and 988 due to 2NH protons in addition to anaromatic multiplet in the region 120575 713ndash763 The 13C NMR ofcompound 15 revealed signals at 2815 16259 and 18930 forthe carbons of the CH

3of (COCH

3) CO of (CONH) and

CO of (COCH3) groups

Furthermore the nonisolated potassium salt was methy-lated by treatment with methyl iodide to afford the novelketene N S-acetal 18 The structure of the synthesized prod-uct was established on the basis of their elemental analysisand spectral data [see the Experimental Part]

Heterocyclisation of the intermediate 12 with 2-oxo-N-phenylpropane hydrazonoyl chloride [38] furnished oneisolable product (as tested by TLC)The reaction product wasidentified as 2-(5-acetyl-3-phenyl-3H-[134]-thiadiazol-2-ylidene)-3-oxo-3-phenyl-N -(4-sulfamoylphenyl)propiona-mide (20) (Scheme 4) The structure of the product 20 wasdetermined from spectroscopic and elemental analytical dataThus the IR spectrum of compound 20 revealed absorptionbands at 3340 3244 and 1614 cmminus1 corresponding to NHNH2and CO groups respectively Its 1H NMR spectrum

revealed signals at 120575 249 and 1195 due to CH3and NH

protons in addition to an aromatic multiplet in the region120575 730ndash839 The aforementioned results indicate that thereaction proceeds via S-alkylation [39] to give S-alkylatedintermediate 19 which cyclized in situ under the employedreaction conditions and elimination of aniline molecule gavethe desired product 20 (Scheme 4)

Screening for Antimicrobial Activity The newly synthesizedcompounds 3a 3c 6 7 8b 10 15 16 and 17 wereevaluated for their in vitro antibacterial activity againstStaphylococcus aureus (RCMB-000106) (SA) and Bacillussubtilis (RCMB-000108) (BS) as examples of Gram-positivebacteria and Pseudomonas aeruginosa (RCMB-000102) (PA)and Escherichia coli (RCMB-000103) (EC) as examples ofGram-negative bacteria They were also evaluated for theirin vitro antifungal activity against Aspergillus fumigatus(RCMB-002003) (AF) Saccharomyces cerevisiae (RCMB-006002) (SC) and Candida albicans (RCMB-005002) (CA)fungal strains Inhibition zone diameter (IZD) in mm wasused as criterion for the antimicrobial activity using theagar diffusion well method The fungicide clotrimazole andthe bactericide streptomycin were used as references toevaluate the potency of the tested compounds under thesame conditions The results are depicted in Table 1 Fromthe data given by Table 1 we concluded that most of the


SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt

CH3COC(Cl)=NndashNHPh

PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4

tested compounds displayed variable degrees of antibacterialactivity against Gram-positive bacteria Gram-negative bac-teria strains and also against fungal strains in comparisonto the standard in each case which revealed that thesecompounds are biologically active Compound 7 exhibitedhigh degree of antibacterial activity against Gram-positivebacteria (SA) Compounds 3c and 7 have moderate degreeof antibacterial activity against Gram-negative bacteria (EC)and (PA) All the compounds exhibited moderate antifungalactivity against (AF) and high activity against (SC CA)The structure antimicrobial activity relationship of the syn-thesized compounds revealed that the maximum activity

was attained with compound 15 having acetyl thiophenemoiety

4 Conclusions

Several new hydrazones pyridazines triazines acrylamidespyrazoles triazolo[15-a]pyrimidines thiadiazoles dihydro-pyrimidines and thiophenes containing sulfamoyl moi-ety were prepared using simple methods via a versa-tile readily accessible 3-oxo-3-phenyl-N-(4-sulfamoylphen-yl)propionamide (1) is demonstrated The structures of the


Table 1 Antimicrobial and Antifungal Activities of the Synthesized Compounds

Sample noInhibition zone diameter (mm)

Gram (minus) Gram (+) Fungi(PA) (EC) (SA) (BS) (AF) (SC) (CA)

3a 107 plusmn 03 101 plusmn 04 122 plusmn 03 111 plusmn 04 119 plusmn 04 125 plusmn 04 134 plusmn 04

3c 129 plusmn 04 117 plusmn 04 121 plusmn 04 123 plusmn 04 187 plusmn 04 208 plusmn 06 147 plusmn 05

6 106 plusmn 03 108 plusmn 04 122 plusmn 04 113 plusmn 04 171 plusmn 05 179 plusmn 06 148 plusmn 04


8b 111 plusmn 03 127 plusmn 04 118 plusmn 03 115 plusmn 04 153 plusmn 05 191 plusmn 04 152 plusmn 05





Clotrimazole mdash mdash mdash mdash 261 plusmn 05 231 plusmn 04 183 plusmn 06

Streptomycin mdash mdash 251 plusmn 05 301 plusmn 06 mdash mdash mdashStreptomycin 243 plusmn 04 256 plusmn 05 mdash mdash mdash mdash mdashData are expressed in the form of mean plusmn SD Mean zone of inhibition in mm plusmn Standard deviation beyond well diameter (6mm) produced on a range ofenvironmental and clinically pathogenic microorganism using (5mgmL) concentration of tested sample (100 120583L was tested)

newly synthesized compoundswere proven by spectralmeth-ods and they were tested for their antimicrobial activi-ties Most of these compounds showed promising activitiesagainst both Gram-positive Gram-negative bacteria andfungi

Conflict of Interests

The author declares that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The support fromChemistry Department Faculty of ScienceCairo University is gratefully acknowledged

References

[1] M S A El-Gaby A A Atalla A M Gaber and K A AbdAl-Wahab ldquoStudies on aminopyrazoles antibacterial activityof some novel pyrazolo[15-a]pyrimidines containing sulfon-amido moietiesrdquo Farmaco vol 55 no 9-10 pp 596ndash602 2000

[2] M S A El-Gaby N M Taha J A Micky and M A M SEl-Sharief ldquoPreparation of some novel 35-diaminopyrazolepyrazolo[15-a][1 3 5]triazine and pyrazolo[15-a]-pyrimidinederivatives containing sulfonamido moieties as antimicrobialagentsrdquo Acta Chimica Slovenica vol 49 no 1 pp 159ndash171 2002

[3] M E Azab M M Youssef and E A El-Bordany ldquosynthesisand antibacterial evaluation of novel heterocyclic compoundscontaining a sulfonamido moietyrdquo Molecules vol 18 pp 832ndash844 2013

[4] M S A El-Gaby A M Gaber A A Atalla and K A Abd Al-Wahab ldquoNovel synthesis and antifungal activity of pyrrole andpyrrolo[23-d]pyrimidine derivatives containing sulfonamidomoietiesrdquo Farmaco vol 57 no 8 pp 613ndash617 2002

[5] THMaren ldquoRelatons between structure and biological activityof sulfonamidesrdquo Annual Review of Pharmacology and Toxicol-ogy vol 16 pp 309ndash327 1976

[6] C T Supuran A Scozzafava B C Jurca and M A Ilies ldquoCar-bonic anhydrase inhibitorsmdashpart 49 synthesis of substitutedureido and thioureido derivatives of aromaticheterocyclicsulfonamides with increased affinities for isozyme Irdquo EuropeanJournal of Medicinal Chemistry vol 33 no 2 pp 83ndash93 1998

[7] J J Li G D Anderson E G Burton et al ldquo12-Diarylcyclopentenes as selective cyclooxygenase-2 inhibitorsand orally active anti-inflammatory agentsrdquo Journal ofMedicinal Chemistry vol 38 no 22 pp 4570ndash4578 1995

[8] H Yoshino N Ueda J Niijima et al ldquoNovel sulfonamidesas potential systemically active antitumor agentsrdquo Journal ofMedicinal Chemistry vol 35 no 13 pp 2496ndash2497 1992

[9] M T Labro ldquoImmunomodulation by antibacterial agents is itclinically relevantrdquo Drugs vol 45 no 3 pp 319ndash328 1993

[10] Y Rajendra Prasad A Lakshmana Rao L Prasoona KMurali and P Ravi Kumar ldquoSynthesis and antidepressant activ-ity of some 135-triphenyl-2-pyrazolines and 3-(210158401015840-hydroxynaphthalen-110158401015840-yl)-15-diphenyl-2-pyrazolinesrdquo Bioorganic andMedicinal Chemistry Letters vol 15 no 22 pp 5030ndash5034 2005

[11] Z Ozdemir H B Kandilci B Gumusel U Calis and A ABilgin ldquoSynthesis and studies on antidepressant and anticon-vulsant activities of some 3-(2-furyl)-pyrazoline derivativesrdquoEuropean Journal ofMedicinal Chemistry vol 42 no 3 pp 373ndash379 2007

[12] A Ozdemir G Turan-Zitouni Z Asim Kaplancikli G Revialand K Guven ldquoSynthesis and antimicrobial activity of 1-(4-aryl-2-thiazolyl)-3-(2-thienyl)-5-aryl-2-pyrazoline derivativesrdquoEuropean Journal ofMedicinal Chemistry vol 42 no 3 pp 403ndash409 2007

[13] A Gursoy S Demirayak G Capan K Erol and K VuralldquoSynthesis and preliminary evaluation of new 5-pyrazolinonederivatives as analgesic agentsrdquo European Journal of MedicinalChemistry vol 35 no 3 pp 359ndash364 2000

[14] Z Brzozowski F Sczewski and M Gdaniec ldquoSynthesis struc-tural characterization and antitumor activity of novel 24-diamino-135-triazine derivativesrdquo European Journal of Medic-inal Chemistry vol 35 no 12 pp 1053ndash1064 2000

[15] C S Konkoy D B Fick S X Cai N C Lan and J F W KeanaldquoSubstituted 5-oxo-5678-tetrahydro-4H-1-benzopyrans and


benzothiopyrans and the use thereof as potentiators of AMPArdquoChemical Abstracts vol 134 Article ID 29313a 2001 Interna-tional Application WO 0075123 A1 2000

[16] F Giordanetto O Karlsson J Lindberg et al ldquoDiscovery ofcyclopentane- and cyclohexane-trans-13-diamines as potentmelanin-concentrating hormone receptor 1 antagonistsrdquo Bioor-ganic and Medicinal Chemistry Letters vol 17 no 15 pp 5222ndash5231 2007

[17] M K Parai G Panda V Chaturvedi Y K Manju and SSinha ldquoThiophene containing triarylmethanes as antitubercu-lar agentsrdquo Bioorganic and Medicinal Chemistry Letters vol 18no 1 pp 289ndash292 2008

[18] W W Wardakhan O M E Abdel-Salam and G A ElmegeedldquoScreening for antidepressant sedative and analgesic activitiesof novel fused thiophene derivativesrdquo Acta Pharmaceutica vol58 no 1 pp 1ndash14 2008

[19] P R Kumar S Raju P Satish Goud et al ldquoSynthesis andbiological evaluation of thiophene [32-b] pyrrole derivatives aspotential anti-inflammatory agentsrdquo Bioorganic and MedicinalChemistry vol 12 no 5 pp 1221ndash1230 2004

[20] C Bonini L Chiummiento M de Bonis et al ldquoSynthesisbiological activity and modelling studies of two novel anti HIVPR inhibitors with a thiophene containing hydroxyethylaminocorerdquo Tetrahedron vol 61 no 27 pp 6580ndash6589 2005

[21] L Brault E Migianu A Neguesque E Battaglia D Bagrel andG Kirsch ldquoNew thiophene analogues of kenpaullone synthesisand biological evaluation in breast cancer cellsrdquo EuropeanJournal ofMedicinal Chemistry vol 40 no 8 pp 757ndash763 2005

[22] E S Darwish ldquoFacile synthesis of heterocycles via 2-picolinium bromide and antimicrobial activities of theproductsrdquoMolecules vol 13 no 5 pp 1066ndash1078 2008

[23] E S Darwish N A Kheder and A M Farag ldquoSynthesisand antimicrobial evaluation of some new pyridine basedheterocyclesrdquo Heterocycles vol 81 no 10 pp 2247ndash2256 2010

[24] E S Darwish A M Abdel Fattah F A Attaby and O N Al-Shayea ldquoSynthesis and antimicrobial evaluation of some novelthiazole pyridone pyrazole chromene hydrazone derivativesbearing a biologically active sulfonamide moietyrdquo InternationalJournal of Molecular Sciences vol 15 pp 1237ndash1254 2014

[25] E S Darwish K A Atia and A M Farag ldquoSynthesis andantimicrobial evaluation of some isoxazole based heterocyclesrdquoHeterocycle vol 89 no 6 pp 1393ndash1411 2014

[26] J Tang L M Shewchuk H Sato M Hasegawa Y Washio andN Nishigaki ldquoAnilinopyrazole as selective CDK2 inhibitorsdesign synthesis biological evaluation and X-ray crystallo-graphic analysisrdquo Bioorganic and Medicinal Chemistry Lettersvol 13 no 18 pp 2985ndash2988 2003

[27] M S T Makki R M Abdel-Rahman and M El-ShahawildquoSynthesis of polyfunctional organic systems containing 1-acylaroyl-anilido-butadienes and their uses as photochemicalprobes and chelating agents for removal of bismuth (III) fromindustrial wastewaterrdquo Journal of Bioanalysis and Biomedicinevol 2 no 4 pp 85ndash90 2010

[28] C F Koelsch ldquoBromination of 3-acetocoumarinrdquo Journal of theAmerican Chemical Society vol 72 no 7 pp 2993ndash2995 1950

[29] P Czerney and H Hartman ldquo3-120572-bromacetyl-coumarines assynthones for heterocyclic substituted coumarinesrdquo Journal furPraktische Chemie vol 325 pp 551ndash560 1983

[30] RN Butler ldquoThediazotization of heterocyclic primary aminesrdquoChemical Reviews vol 75 no 2 pp 241ndash257 1975

[31] E F A Smania F D Monache A Smania Jr R A Yunes andR S Cuneo ldquoTriterpenes and sterols from ganoderma australe(Fr) Pat (Aphyllophoromycetideae)rdquo International Journal ofMedicinal Mushrooms vol 1 pp 325ndash334 1999

[32] R G Child R G Wilkinson and A Tomcu-Fucik ldquoeffectof substrate orientation of the adhesion of polymer jointsrdquoChemical Abstracts vol 87 p 6031 1977

[33] H G Garg and C Prakash ldquoPotential antidiabetics 11 Prepa-ration of 4-arylazo-35-disubstituted-(2H)-126-thiadiazine 11-dioxidesrdquo Journal ofMedicinal Chemistry vol 15 no 4 pp 435ndash436 1972

[34] C H Browing J B Cohen S Ellingworth and R GulbransenldquoThe antiseptic properties of the aminoderivatives of styryl andanil quinolinerdquo Journal Storage vol 100 pp 293ndash325 1926

[35] G Swati K Romila I K Sharma and P S Verma ldquoSyn-thesis characterisation and antimicrobial screening of someazo compoundsrdquo International Journal of Applied Biology andPharmaceutical Technology vol 2 pp 332ndash338 2011

[36] R N Goyal M S Verma and N K Singhal ldquoVoltammetricinvestigations of the reduction of direct orange-31 a bisazo dyerdquoCroatica Chemica Acta vol 71 no 3 pp 715ndash726 1998

[37] M C Hamzacebi S Rollas S G Kucukguzel and BK Kaymakcıoglu ldquoSynthesis and structure elucidationof hydrazones derived from N-(24-dimethylphenyl)-3-oxobutanamiderdquo Arkivoc vol 12 pp 188ndash194 2008

[38] N F Eweiss and A Osman ldquoSynthesis of heterocyclesmdashpartII New routes to acetylthiadiazolines and alkylazothiazolesrdquoJournal of Heterocyclic Chemistry vol 17 pp 1713ndash1717 1980

[39] A A Geies A M Kamal-Eldeen A A Abdelhafez and AM Gaber ldquoSynthesis of some thiazolo(32-a) pyrimidinesrdquoPhosphorus Sulfur and Silicon and the Related Elements vol 56pp 87ndash93 1991

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

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Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


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Applied ChemistryJournal of



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voltage was 70 eV Elemental analyses were carried out by theMicroanalytical Center of Cairo University Giza Egypt Thebiological evaluation of the products 3a 3c 6 7 8b 10 15 16and 17 was carried out at the Medical Mycology Laboratoryof the Regional Center for Mycology and Biotechnology ofAl-Azhar University Cairo Egypt

3-Oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide(1) and 3-(2-bromoacetyl)-2H-chromen-2-one [26ndash29] wereprepared as previously described

21 Coupling of 3-Oxo-3-phenyl-N-(4-sulfamoylphenyl)pro-pionamide (1) with the Appropriate Diazonium Salt of Aro-matic Amines

General Procedure To a cold solution of 3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide (1) (0318 g 1mmol) inpyridine (20mL) the appropriate diazonium salt of aromaticamine (aniline or 4-methylaniline or 4-chloroaniline or 4-methoxy-aniline or 4-nitroaniline) (1mmol) was added (pre-pared according to literature procedures) [30] The additionwas carried out portionwise with stirring at 0ndash5∘C overa period of 30min After complete addition the reactionmixture was stirred for further 4 hrs then kept in an ice chestfor 12 hrs and finally diluted with water The precipitatedsolid was collected by filtration washed with water driedand finally recrystallized from the proper solvent to afford thecorresponding coupling products 3andashe

22 2-[(4-Methoxyphenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide (3a) Yield (80) mp 270∘C(dioxane) IR (KBr) ]max 3351 3264 (NH NH

2) 3073

(aromatic CH) 1657 (C=O) cmminus1 1H NMR (DMSO-d6) 120575

375 (s 3H OCH3) 696 (d 2H 119869 = 9Hz) 728 (d 2H 119869 =

9Hz) 730 (s 2H D2O-exchangeable NH

2) 761 (d 2H 119869 =



2O-exchangeable

NH) MS mz () 452 (M++2 333) 452 (M+ 1837) 347(407) 252 (1566) 196 (351) 172 (549) 105 (1000) AnalCalcd for C

22H20N4O5S (45249) C 5840 H 446 N 1238

S 709 Found C 5836 H 436 N 1232 S 701

23 2-(p-Tolylhydrazono)-3-oxo-3-phenyl-N-(4-sulfamoyl-phenyl)propionamide (3b) Yield (75) mp 280∘C(dioxane) IR (KBr) ]max 3352 3265 (NH NH

2) 2924

2858 (aliphatic CH) 1660 (C=O) cmminus1 1H NMR (DMSO-d6) 120575 226 (s 3H CH

3) 714 (s 2H D

2O-exchangeable NH

2)

717ndash730 (m 5H Ar-H) 756 (d 2H 119869 = 9Hz) 762 (d 2H 119869= 9Hz) 781 (d 2H 119869 = 8Hz) 793 (d 2H 119869 = 8Hz) 1137 (s1H D


2O-exchangeable

NH) MS mz () 437 (M++1 2512) 436 (M+ 3575) 332(2657) 329 (3285) 279 (5121) 263 (3382) 171 (4203) 157(3140) 104 (2802) 57 (1000) Anal Calcd for C

22H20N4O4S

(43649) C 6054 H 462 N 1284 S 735 Found C 6050H 455 N 1272 S 727

24 2-(Phenylhydrazono)-3-oxo-3-phenyl-N-(4-sulfamoylphen-yl)propionamide (3c) Yield (70) mp 282∘C (dioxane) IR(KBr) ]max 3349 3256 (NH NH

2) 3059 (aromatic CH)

1650 (C=O) cmminus1 1H NMR (DMSO-d6) 120575 718 (s 2H D

2O-




2O-exchangeable

NH) MS mz () 422 (M+ 76) 223 (19) 199 (04) 171(18) 121 (203) 119 (30) 105 (1000) 77 (577) Anal Calcdfor C21H18N4O4S (42247) C 5971 H 429 N 1326 S 759

Found C 5966 H 426 N 1330 S 753

25 2-[(4-Chlorophenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sul-famoylphenyl)propionamide (3d) Yield (60) mp 304∘C(dioxane) IR (KBr) ]max 3364 3262 and 3152 (NH NH

2)


2O-


8Hz) 764 (d 2H 119869 = 9Hz) 783 (d 2H 119869 = 9Hz) 785ndash793(m 5H Ar-H) 1121 (s 1H D


(s 1H D2O-exchangeable NH) MS mz () 457 (M++1

1325) 456 (M+ 1664) 329 (810) 285 (1119) 199 (1090) 128(1149) 105 (1000) Anal Calcd for C

21H17ClN4O4S (45691)

C 5520 H 375 Cl 776 N 1226 S 702 Found C 5515 H366 Cl 766 N 1221 S 700

26 2-[(4-Nitrophenyl)hydrazono]-3-oxo-3-phenyl-N-(4-sul-famoylphenyl)propionamide (3e) Yield (55) mp 302∘C(dioxane) IR (KBr) ]max 3368 3265 and 3161 (NH NH

2)


2O-


9Hz) 778ndash789 (m 5H Ar-H) 791 (d 2H 119869 = 8Hz) 820 (d2H 119869 = 8Hz) 1108 (s 1H D

2O-exchangeable NH) 1245 (s

1H D2O-exchangeable NH) MS mz ()468 (M++1 389)

467 (M+ 725) 362 (471) 296 (426) 199 (433) 172 (1988)105 (1000) Anal Calcd for C

21H17N5O6S (46746) C 5396

H 367 N 1498 S 686 Found C 5387 H 359 N 1488 S678

27 N-[4-(Aminosulfonyl)phenyl]-5-cyano-6-imino-4-phenyl-p-tolyl-16-dihydropyridazine-3-carboxamide (4) To a solu-tion of (3b) (0436 g 1mmol) and malononitrile (1mmol) indioxane (20mL) few drops of piperidine were added and thereaction mixture was refluxed for 6 hrs The solid productthat formed was filtered off washed with ethanol and thenrecrystallized from the proper solvent to give 4

Yield (55) mp gt 300∘C (DMF) IR (KBr) ]max 34623305 and 3181 (NH NH

2) 2203 (CequivN) 1637 (C=O) cmminus1

1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 732 (d 2H

D2O-exchangeable NH

2) 740 (d 2H 119869 = 8Hz) 759 (d


exchangeable NH) 1460 (s 1H D2O-exchangeable NH) MS

mz () 484 (M+ 232) 409 (742) 393 (909) 313 (694) 285(658) 199 (789) 91 (1651) 77 (2656) 69 (1000) Anal Calcdfor C25H20N6O3S (48454) C 6197 H 416 N 1734 S 662

Found C 6192 H 411 N 1730 S 659

28 4-(6-Benzoyl-3-ethoxy-5-oxo-2-p-tolyl-23-dihydro-124-triazin-4-(5H)-yl)benzenesulfonamide (5) To a solution ofthe compound 3b (0436 g 1mmol) in acetic acid (20mL)triethyl orthoformate (02mL 1mmol) was added and thereactionmixturewas refluxed for 8 hrs then it was left to cool






72Hz CH3) 224 (s 3H CH

3) 427 (q 2H 119869= 72 CH

2) 594


2) 737ndash757 (m


25H24N4O5S

(49256) C 6096 H 491 N 1137 S 651 Found C 6088H 485 N 1131 S 650




1H NMR (DMSO-d6) 120575 342 (s 6H 2CH

3) 662 (d 2H 119869


2) 728ndash731 (m




Found C 5789 H 503 N 1115 S 861




6) 120575


2) 705 (d 2H 119869 = 9Hz)


2O-


Found C 5480 H 353 N 2125 S 801






d6) 120575 743 (s 2H D

2O-exchangeable NH

2) 746ndash761 (m 8H



() 396 (M+ 01) 225 (03) 197 (04) 171 (224) 157 (28) 105(1000) Anal Calcd for C

20H16N2O5S (39642) C 6060 H

407 N 707 S 809 Found C 6053 H 401 N 711 S 800


2) 3060



2) 749ndash700 (m 15H


(167) 199 (200) 172 (167) 105 (967) 92 (200) 77 (1000)Anal Calcd for C

31H24N4O4S (54863) C 6787 H 441 N

1021 S 584 Found C 6782 H 435 N 1016 S 578




6) 120575 633ndash


2) 744 (d



2O-


20H16N4O4S (40844)

C 5881 H 395 N 1372 S 785 Found C 5879 H 393 N1365 S 780




d6) 120575 126 (t 3H 119869 = 72Hz CH

3) 432 (q 2H 119869 = 72 CH

2)


2) 740 (d 2H 119869 = 9Hz)




(M+ 05) 370 (06) 301 (727) 198 (180) 172 (336) 156 (596)105 (708) 77 (850) 65 (1000) Anal Calcd for C

18H18N2O5S

(37442) C 5774 H 485 N 748 S 856 Found C 5770 H476 N 741 S 850



2) 3057 (aromatic CH) 1675 (C=O)


2O-exchangeable




16H14N4O2S2

(35844) C 5361 H 394 N 1563 S 1789 Found C 53 60H 390 N 1559 S 1784




(DMSO-d6) 120575 719 (s 2H D

2O-exchangeable NH

2) 739 (d





22H19N3O4S2(45354)

C 5826 H 422 N 926 S 1414 Found C 5822 H 420N 920 S 1411



2) 3059 (aromatic CH) 1698 (C=O) 1658


2O-





Found C 6502 H 415 N 755 S 1154



2)


3) 711 (s 2H D

2O-exchangeable NH

2)




6) 120575


25H21N3O4S2(49159) C 6108 H

431 N 855 S 1304 Found C 6100 H 424 N 85 S1311



3) 404 (q




2O-


26H23N3O5S2

(52162) C 5987 H 444 N 806 S 1229 Found C 5977H 441 N 802 S 1221



6)



2O-exchangeable



SO

O

PhCOCHSO

O

NH

O O

Ph

SO

O

NH

O

NNAr

Me

O

SO

ONH

O

NNHAr

O

Ph

b c d ea

Ar

Pyridine

H2

2

N

H2N H2N

H2NNH2

ArN2+Clminus

2andashc 3andashc

4-OMe 4-Me Ph 4-Cl

1

3

COOEt

4-NO2


for C33H23N3O6S2(62170) C 6376 H 373 N 676 S

1032 Found C 6370 H 361 N 667 S 1025



1H NMR (DMSO-d6) 120575 356 (s 3H SCH

3) 724 (d 2H 119869



467 (M+ 229) 296 (457) 197 (257) 139 (229) 105 (143) 92(543) 63 (100) Anal Calcd for C

23H21N3O4S2(46756) C

5908 H 453 N 899 S 1372 Found C 5912 H 450 N896 S 1366



1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 715 (s 2H

D2O-exchangeable NH

2) 730 (d 2H 119869 = 9Hz) 762 (d



25H20N4O5S2

(52059) C 5768 H 387 N 1076 S 1232 Found C 5763H 382 N 1071 S 1229







SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip


SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3




















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of






72Hz CH3) 224 (s 3H CH

3) 427 (q 2H 119869= 72 CH

2) 594


2) 737ndash757 (m


25H24N4O5S

(49256) C 6096 H 491 N 1137 S 651 Found C 6088H 485 N 1131 S 650




1H NMR (DMSO-d6) 120575 342 (s 6H 2CH

3) 662 (d 2H 119869


2) 728ndash731 (m




Found C 5789 H 503 N 1115 S 861




6) 120575


2) 705 (d 2H 119869 = 9Hz)


2O-


Found C 5480 H 353 N 2125 S 801






d6) 120575 743 (s 2H D

2O-exchangeable NH

2) 746ndash761 (m 8H



() 396 (M+ 01) 225 (03) 197 (04) 171 (224) 157 (28) 105(1000) Anal Calcd for C

20H16N2O5S (39642) C 6060 H

407 N 707 S 809 Found C 6053 H 401 N 711 S 800


2) 3060



2) 749ndash700 (m 15H


(167) 199 (200) 172 (167) 105 (967) 92 (200) 77 (1000)Anal Calcd for C

31H24N4O4S (54863) C 6787 H 441 N

1021 S 584 Found C 6782 H 435 N 1016 S 578




6) 120575 633ndash


2) 744 (d



2O-


20H16N4O4S (40844)

C 5881 H 395 N 1372 S 785 Found C 5879 H 393 N1365 S 780




d6) 120575 126 (t 3H 119869 = 72Hz CH

3) 432 (q 2H 119869 = 72 CH

2)


2) 740 (d 2H 119869 = 9Hz)




(M+ 05) 370 (06) 301 (727) 198 (180) 172 (336) 156 (596)105 (708) 77 (850) 65 (1000) Anal Calcd for C

18H18N2O5S

(37442) C 5774 H 485 N 748 S 856 Found C 5770 H476 N 741 S 850



2) 3057 (aromatic CH) 1675 (C=O)


2O-exchangeable




16H14N4O2S2

(35844) C 5361 H 394 N 1563 S 1789 Found C 53 60H 390 N 1559 S 1784




(DMSO-d6) 120575 719 (s 2H D

2O-exchangeable NH

2) 739 (d





22H19N3O4S2(45354)

C 5826 H 422 N 926 S 1414 Found C 5822 H 420N 920 S 1411



2) 3059 (aromatic CH) 1698 (C=O) 1658


2O-





Found C 6502 H 415 N 755 S 1154



2)


3) 711 (s 2H D

2O-exchangeable NH

2)




6) 120575


25H21N3O4S2(49159) C 6108 H

431 N 855 S 1304 Found C 6100 H 424 N 85 S1311



3) 404 (q




2O-


26H23N3O5S2

(52162) C 5987 H 444 N 806 S 1229 Found C 5977H 441 N 802 S 1221



6)



2O-exchangeable



SO

O

PhCOCHSO

O

NH

O O

Ph

SO

O

NH

O

NNAr

Me

O

SO

ONH

O

NNHAr

O

Ph

b c d ea

Ar

Pyridine

H2

2

N

H2N H2N

H2NNH2

ArN2+Clminus

2andashc 3andashc

4-OMe 4-Me Ph 4-Cl

1

3

COOEt

4-NO2


for C33H23N3O6S2(62170) C 6376 H 373 N 676 S

1032 Found C 6370 H 361 N 667 S 1025



1H NMR (DMSO-d6) 120575 356 (s 3H SCH

3) 724 (d 2H 119869



467 (M+ 229) 296 (457) 197 (257) 139 (229) 105 (143) 92(543) 63 (100) Anal Calcd for C

23H21N3O4S2(46756) C

5908 H 453 N 899 S 1372 Found C 5912 H 450 N896 S 1366



1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 715 (s 2H

D2O-exchangeable NH

2) 730 (d 2H 119869 = 9Hz) 762 (d



25H20N4O5S2

(52059) C 5768 H 387 N 1076 S 1232 Found C 5763H 382 N 1071 S 1229







SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip


SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3




















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


(M+ 05) 370 (06) 301 (727) 198 (180) 172 (336) 156 (596)105 (708) 77 (850) 65 (1000) Anal Calcd for C

18H18N2O5S

(37442) C 5774 H 485 N 748 S 856 Found C 5770 H476 N 741 S 850



2) 3057 (aromatic CH) 1675 (C=O)


2O-exchangeable




16H14N4O2S2

(35844) C 5361 H 394 N 1563 S 1789 Found C 53 60H 390 N 1559 S 1784




(DMSO-d6) 120575 719 (s 2H D

2O-exchangeable NH

2) 739 (d





22H19N3O4S2(45354)

C 5826 H 422 N 926 S 1414 Found C 5822 H 420N 920 S 1411



2) 3059 (aromatic CH) 1698 (C=O) 1658


2O-





Found C 6502 H 415 N 755 S 1154



2)


3) 711 (s 2H D

2O-exchangeable NH

2)




6) 120575


25H21N3O4S2(49159) C 6108 H

431 N 855 S 1304 Found C 6100 H 424 N 85 S1311



3) 404 (q




2O-


26H23N3O5S2

(52162) C 5987 H 444 N 806 S 1229 Found C 5977H 441 N 802 S 1221



6)



2O-exchangeable



SO

O

PhCOCHSO

O

NH

O O

Ph

SO

O

NH

O

NNAr

Me

O

SO

ONH

O

NNHAr

O

Ph

b c d ea

Ar

Pyridine

H2

2

N

H2N H2N

H2NNH2

ArN2+Clminus

2andashc 3andashc

4-OMe 4-Me Ph 4-Cl

1

3

COOEt

4-NO2


for C33H23N3O6S2(62170) C 6376 H 373 N 676 S

1032 Found C 6370 H 361 N 667 S 1025



1H NMR (DMSO-d6) 120575 356 (s 3H SCH

3) 724 (d 2H 119869



467 (M+ 229) 296 (457) 197 (257) 139 (229) 105 (143) 92(543) 63 (100) Anal Calcd for C

23H21N3O4S2(46756) C

5908 H 453 N 899 S 1372 Found C 5912 H 450 N896 S 1366



1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 715 (s 2H

D2O-exchangeable NH

2) 730 (d 2H 119869 = 9Hz) 762 (d



25H20N4O5S2

(52059) C 5768 H 387 N 1076 S 1232 Found C 5763H 382 N 1071 S 1229







SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip


SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3




















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


SO

O

PhCOCHSO

O

NH

O O

Ph

SO

O

NH

O

NNAr

Me

O

SO

ONH

O

NNHAr

O

Ph

b c d ea

Ar

Pyridine

H2

2

N

H2N H2N

H2NNH2

ArN2+Clminus

2andashc 3andashc

4-OMe 4-Me Ph 4-Cl

1

3

COOEt

4-NO2


for C33H23N3O6S2(62170) C 6376 H 373 N 676 S

1032 Found C 6370 H 361 N 667 S 1025



1H NMR (DMSO-d6) 120575 356 (s 3H SCH

3) 724 (d 2H 119869



467 (M+ 229) 296 (457) 197 (257) 139 (229) 105 (143) 92(543) 63 (100) Anal Calcd for C

23H21N3O4S2(46756) C

5908 H 453 N 899 S 1372 Found C 5912 H 450 N896 S 1366



1H NMR (DMSO-d6) 120575 249 (s 3H CH

3) 715 (s 2H

D2O-exchangeable NH

2) 730 (d 2H 119869 = 9Hz) 762 (d



25H20N4O5S2

(52059) C 5768 H 387 N 1076 S 1232 Found C 5763H 382 N 1071 S 1229







SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip


SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3




















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


SO

ONH

O

NNH

O

Me

Ph

SO

ONH

O

NN

Me

NH

PhCN

SO

O NN

Me

O O

N Ph

EtO

3

4

5

H2N

H2N

H2N

CH(OEt)3ACOH

CH2(CN)2dioxanepip


SO O

NHO

OPh

O NN

Ph

Ph

SO

ONH

O O

NMe Me

Ph NHN

N

NH2

SO

ONH

N

N N

N

O

Ph

SO

ONH

O O

Ph

H Ar

SO

ONH NH

N

O

Ar

Ph

SO

ONH

O O

Ph

H OEt

NH N

SO

ONH

S

Ph

Ar

a b8 9

ACOH7

ArCHODioxane

Dry dioxane

9a

10

DMF-DMA H2N

H2N

H2N

H2N

H2N

H2N

NH2

Dioxanepip

Ac2O

(EtO)3CH

NH2CSNH2

DMFEt3N

8a b

6

11

1

NH2NH2

Scheme 3




















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of
















2and C=O




3of (COCH

3) CO of (CONH) and








SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


SO

ONH

O O

Ph

SO

ONH

O O

PhHN SK

Ph

PhNCS

S

SO

ONH

O

PhNH

Ph

COMe

SPhNH

PhNH

PhHN

PhHN

COOEt

SO

ONH

OPh

O

OBr

O OO

S

SO

ONH

O Ph

O

SO

ONH

O O

S

Ph

SO

ONH

O O

S

Ph

NNH

Ph

NN

SPh

SO

ONH

O O

Ph

SO

ONH

O O

SH

Ph

S

SO

ONH

O

PhNH

Ph

COPh

1

12

15

16

18

MeI

20

13

14

17

19

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

H2N

KOHDMF

minus +

Dil HCl

DMFEt3N PhCOCH2Br

ClCH2COCH3

ClCH2COOEt


PhNH

CH3

COCH3

COCH3

minusPhNH2

Scheme 4



4 Conclusions




















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



















Acknowledgment


References



















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

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