Acta Chim. Slov. 2002, 49, 159-171. 159 PREPARATION OF SOME NOVEL 3,5-DIAMINOPYRAZOLE, PYRAZOLO-[l,5-a][ 1, 3, 5 ]TRIAZINE AND PYRAZOLO[ l,5-a]-PYRIMIDINE DERIVATIVES CONTAINING SULFONAMIDO MOIETIES AS ANTIMICROBIAL AGENTS Mohamed S. A. El-Gaby,a* Nadia M. Taha,b Jehane A. Micky,b Marwa A. M. Sh. El-Sharief "Department of Chemistry, Faculty of Science, Al-Azhar University at Assiut, Assiut 71524, Egypt bDepartment of Chemistry, Faculty of Science (Girl's), Al-Azhar University, Nasr City, Cairo, Egypt. Received 10-09-2001 Abstract Various sulfa drugs were coupled with active methylene compounds to give various hydrazones 2a-e. The reactivity of hydrazones 2a-e towards hydrazines was investigated. Thus , a novel series of 3, 5- diaminopyrazoles 3, 5, 6, 7a, and b and 9a, b were obtained by treatment of 2 with hydrazines. Pyrazolo[l,5-a][l,3,5] triazine derivatives 10, 11 and 12 were synthesized by interaction of aminopyra-zole 9a with triethyl orthoformate, acetic anhydride and benzoyl chloride , respectively. When aminopyrazole 6 and 8 were allowed to react with ketene dithioacetal 13, the novel pyrazolo[l,5-a] pyrimidine 15a,b were obtained. Structures of the new compounds were established by their elemental analysis and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Introduction A considerable number of sulfonamides were found to have antibacterial, insulin releasing, carbonic anhydrase inhibitory, antiinflammatory, anticancer, activities. Aminopyrazoles possess a wide variety of biological activities. " Also, 3- amino or 5-aminopyrazoles are used as a starting materials for the preparation of purine analogues as pyrazolo[l,5-a]pyrimidines. Substituted pyrazolo[l,5-a]pyrimidine was synthesized as anticancer, antipyretic, hypotensive and anxiety agents. In addition, pyrazolotriazines are applied as herbicides. Having the above facts in mind and in continuation of our II I ^ efforts to synthesize heterocyclic compounds containing sulfonamido moiety, " we were interested to prepare 3,5-diaminopyrazole, pyrazolo [l,5-a][l,3,5]triazine and pyrazolo[l,5-a]pyrimidine derivatives containing sulfona-mido moieties to investigate their antimicrobial activity of them. M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 160 Acta Chim. Slov. 2002, 49, 159-171. Results and Discussion Hydrazones 2a-e were synthesized by diazotization of sulfonamides 1 at 5-10 °C in hydrochloric acid followed by coupling with active methylene compounds in the presence of sodium acetate at room temperature, Scheme (1) . On the basis of spectral data, compounds 2 exist in hydrazone form 2a-e. The H-NMR spectrum of 2b recorded in deuterated dimethylsulfoxide showed a signal at 8 11.46 ppm which could be assigned to NH group, in addition to a multiple at 8 7.61-7.92 ppm which was assigned to aromatic protons and SO2NH group. Scheme (1) RHN-S- II O // w -NH. NaN02/HCI ?\ // \ II O (1) -N2CI H2< X Y RHN-S- II O // w -nhn=c; .X VY (2a-e) X X ^ RHN-S^^ V— N=N-C / H.Y O (2) R 2a CN CN COCH3 bCN CN 5-(3-methyl) isoxazolyl cCN CN 5-(3,4- dimethyl) isoxazolyl dCN COOEt 5-(3-methyl) isoxazolyl eCN COOEt 5-(3,4- dimethyl) isoxazolyl It was reported that, P-enaminonitriles reacted with hydrazine to afford pyrazole derivatives. The reactivity of the enaminonitriles 2a-e with hydrazines (namely, benzoyl hydrazine, hydrazine, phenyl hydrazine and thiosemicarbazide) was investigated.Thus, condensation of hydrazone 2a with benzoyl hydrazine in dioxane under reflux furnished the 3,5-diaminopyrazole derivative 3. The structure of 3 was M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... Acta Chim. Slov. 2002, 49, 159-171. 161 inferred from its elemental analysis and spectral data. The IR spectrum revealed characteristic bands for NH2, C=0, N=N and SO2 functional groups. H-NMR spectrum of 3 in DMSO-^6 showed a signal at 8 1.96 ppm assignable to COCH3 group, a multiplet at 8 7.51- 8.01 ppm assigned for aromatic protons and amino group and a broad singlet at. 8 8.60 ppm assignable to amino group. On the other hand, when hydrazone 2a was allowed to react with hydrazine hydrate in ethanol under reflux, the novel sulfonylhydrazide 5 was obtained. Structure of 5 was readily established on the basis of analytical and spectral data. HNMR spectrum of 5 in DMSO-Jg showed the absence of COCH3 fragment and the presence of two broad singlet at 8 6.00-6.50 (2 NH2) and 7.31 ppm (NH2). The formation of 5 was proceeded via initial formation of pyrazole 4 followed by nucleophilic attack of hydrazine molecule on sulfonyl group and elimination of acetamide molecule. 3,5-Diaminopyrazole 6 was obtained by re fluxing of compound 2b with hydrazine for 5 min. Also, hydrazones 2a and b were subjected to react with phenyl hydrazine to yield the novel substituted pyrazoles 7a and b in good yields. 3-Amino-5- pyrazolinone derivatives 8a and b were synthesized by reacting 2d and e with hydrazine hydrate in ethanol. Thiosemicarbazide was reacted smoothly with hydrazones 2b and d in dioxane containing a catalytic amount of triethylamine to give thiocarbamoyl derivatives 9a and b Scheme (2). The mass spectrum of 9a revealed a molecular ion peak M+ at m/z = 421 ( 22% ) corresponding to molecular formula C14H15N9O3S2. The starting material 9a was proved to be a versatile starting material for the synthesis of some novel pyrazolo[l,5-a] [l,3,5]triazines. Thus, cyclocondensation of 9a with triethyl orthoformate as carbon donor moiety under boiling condition yielded the novel pyrazolo[l,5-a][l,3,5]triazine derivative 10. The structure 10 was proved by the presence of a signal at 8 8.21 ppm characteristic for the triazine proton in the HNMR spectrum. Also, upon treatment of 9a with acetic anhydride afforded the pyrazolotriazine 11. In the same manner, 9a reacted with benzoyl chloride in pyridine under reflux, furnishing the corresponding pyrazolotriazine derivative 12, Scheme (3). M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 162 Acta Chim. Slov. 2002, 49, 159-171. Scheme (2) PhCONHNH (2a) O O II II HX-C-N-S- v 3 H II \—/ O r\ -N=N H2N -NH, NH2NH2 (2a) O O II II HX-C-N-S 3 H II O ^V -N=N O H2NHN-S- O _ ^.xN-C-Ph N ii O (3) -NH, H2N NH2NH2 (4) -CH3CONH2 r\ -N=N H2N -NH, H3C- NH2NH2 X X (2b) PhNHNH, O N-S- x H II \—/ O V \ N (5) N=N ,NH -NH„ (2a and b) O RHN-S O H2N V X -N=N ^- xNH N (6) —-NH, H2N N (7a and b) -N-Ph H3C R 7a; R = COCH3 7b; R = 5-(3-methyl isoxazolyl) H2NNH2 (2d and e) N> X' O -N-S- H II O V \ -N=N -NH, ,NH (8a and b) O N U H 8a; R = H 8b;R = CH, H3C. NH2NHCSNH2 (2b and d) ^O-^N-S N-S—f ^—m= H II \= O N=N X -NH, ,N-C-NH, N 11 2 9a;X = NH O H (9a and b) 9b; X = O M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... Acta Chim. Slov. 2002, 49, 159-171. 163 Scheme (3) CH(OC2H5)3 H3C- (9a)- ¦^0 N-S^f V"N=Nk -N O (10) s H3C- (CH3CQ)f N.JLN4 // Vn=N. ___.N^CH H II O H2N^N'VNH 3 NH (11) S PhCOCI H3C- u H II \—/ ^--------^ ^^ O rr H2N N Y S (12) Ketene dithioacetals and related compounds are well known as useful starting materials for the synthesis of heterocycles. The reactivity of aminopyrazoles 6 and 8a towards ketene dithioacetals was also investigated. Thus, [bis(methylsulfanyl) methylidene]malononitrile 13 was reacted with aminopyrazoles 6 and 8a under reflux in dimethylformamide in the presence of catalytic amount of triethylamine to afford the corresponding pyrazolo[l,5-a]pyrimidines 15a and b. Assignment of compound 15 was proved by analytical and spectral data . H NMR spectrum of compound 15a in DMSO-d.6 exhibited a signal at 8 2.41 ppm assignable to methylthio group. The formation of 15 was proceeded via initial alkylation at N-l to give 14 and subsequent ring closure to yield final products 15a and b, Scheme (4). On the other hand, when aminopyrazoles 6 and 8a were allowed to react with ethyl [bis(methylsulfanyl)methylidene]cyanoacetate 16 in dioxane containing triethyl-amine, for three products 17 and 18 a and b can be formulated, Scheme (5) . on the basis of analytical and spectral data structure 17 was readily eliminated. HNMR spectrum of M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 164 Acta Chim. Slov. 2002, 49, 159-171. 18a in DMSO-fl^ exhibited the presence of SCH3 group and the absence of OC2H5 moiety. Scheme (4) C II H,CS SChL (6 and 8a )^J?________I (13) H3C- X, N-q-^^N-S—K V— N=N. O NH H3C- N. 15a;X = NH 15b; X = O X N A H ,N C=N CN SChL (14) -X-J/ w -N-S H II O N=ISL ,N A H ,N a NH, CN SChL (15a,b) Scheme (5) EtOOCv.CN H,CS SCH, (6 and 8a) - (16) H3C- 1h DLJL// w o N=N ^N^NH2 X' sN'Nvr^COOC,H 2' '5 SCH, (17) H3C- ,/-----M —«5- N^0^N-S^f Vn=N O ,N CT O (18a and b) SCH, 18a;X=NH b;X = 0 M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... Acta Chim. Slov. 2002, 49, 159-171. 165 Biological Activity Fourteen compounds were screened in vitro for their antimicrobial activities against four strains of bacteria Staphylococcus aureus (NCTC-7447), Bacillus cereus (ATCC-14579), Serratia marcesens (IMRU-70), Proteus mirabilis (NCTC-289) and two strains of fungi Aspergillus ochraceus Wilhelm (AUCC-230) and penicillium chrysogenum 1 7 Thorn (AUCC-530) by the agar diffusion technique. A 1 mg/mL solution in dimethylformamide was used. The bacteria and fungi were maintained on nutrient agar and Czapek's-Dox agar media, respectively. DMF showed no inhibition zones. The agar media were inoculated with different microorganisms culture tested. After 24h. of incubation at 30°C for bacteria and 48 h of incubation at 28°C for fungi, the diameter of inhibition zone (mm) was measured (Table 1). Ampicillin in a concentration 25 |ug m" and Mycostatine (30 |ug m" ) used as a references for antibacterial and antifungal activities, respectively. The minimal inhibitory concentration (MIC) of some of the tested compounds was measured by a twofold serial dilution method. The most of the synthesized compounds exhibited various antimicrobial activity towards all the microorganisms used. Table(l): Antimicrobial activity of some synthesized compounds and inhibition zones Compd. No. Gram positive bacteria Staphyloccus aureus (NCTC 7447) Bacillus cereus (ATCC-14579) Gram negative bacteria Serratia marcesens (IMRU-70) Proteus mirabilis (NCTC-289) Fungi Aspergillus ochraceus Wilhelm (AUCC-230) Penicillium chrysogenum Thorn (AUCC-530) 2a 2c 3 5 6 7b 8a 8b 9a 10 11 12 15a 18a Standar d ++ ++ ++ + ++ + ++ +++ ++ ++ +++ +++ +++ +++ ++++ ++ ++ + ++ ++ ++ ++ + ++ ++ + + +++ +++ ++++ ++ +++ + ++ + ++ ++ ++ ++ ++ ++ ++ ++ ++ ++++ ++ ++ ++ + ++ + + ++ ++ ++ ++ ++ ++ ++ f+++ + ++ + + + + + + + + + ++ + + ++++ + + + + + ++ ++ ++ ++ ++ ++ ++ + + f++^ + : Less active (0.2-0.5 cm);++ : Moderately active (0.6-1.4 cm);+++ (1.5-3.0 cm); ++++ : Very highly active (over 3.0 cm) Highly active M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 166 Acta Chim. Slov. 2002, 49, 159-171. Experimental All melting points are uncorrected. IR spectra were recorded on a Shimadzu - 440 infrared spectrophotometer (v; cm" ) using the KBr technique (Shimadzu, Japan). H-NMR spectra were measured on a Varian EM 360-90 MHz spectrophotometer (Varian, UK), (8, ppm) using TMS as an internal standard. The mass spectra were performed by a Shimadzu GC-MS-QP 100 Ex (Shimadzu, Japan). Elemental analyses were carried out by the Microanalytical Research Center, Faculty of Science, Cairo university. The characteristics data for the prepared compounds are given in Table (2). Formation of hydrazones (2a-e). Sulfonamide (0.01 mole) was dissolved in a mixture of concentrated HCI (7 mL) and water (5 mL) and cooled to 5- 10°C in ice bath. To a stirred mixture a cold aqueous solution of sodium nitrite (0.01 mole 5mL) was then added. The diazonium salt so obtained was filtered into a cold mixture of sodium acetate (3 gm) and active methylene compound ( 0.01 mole ) in ethanol (30 mL). The resulting solid was washed with water (100 mL) and recrystallized from proper solvent to give 2a-e, Table (2). IR (2a): 3250, 3100 (NH), 2950 (CH-aliph.), 2200 (CN), 1710 (CO). IR (2b): 3450, 3250 (NH), 2900 (CH-aliph.), 2200 (CN^H-NMR (2b; DMSO-J6): 2.31 (s, 3H, CH3), 6.15 (s,lH, isoxazole-H), 7.61-7.92 (m,5H, Ar-H+S02NH) 11.46 (s, 1H. NH; exchangeable). IR ( 2d): 3450, 3250 (NH), 2200 (CN), 1700 (CO). !HNMR (2d; DMSO-J6); 1.29 ( t, 3H, CH3 ), 2.30 ( s, 3H. CH3), 4.32 (q,2H,OCH2), 6.14 (s, 1H, isoxazole-H), 7.90 ( m, 4H, Ar-H), 8.51 ( broad, 1H, NH; exchangeable ), 12.40 (s, 1H, NH; exchangeable). l-Benzoyl-3,5-diamino-4-[4-(N-acetylsulfamoyl)]phenylazopyrazole](3). A solution of hydrazone 2a (0.01 mole) and benzoyl hydrazine (0.01 mole) in dioxane (20 mL) was refluxed for 24 h, then allowed to cool and poured into cold water (50 mL). The solid product was collected and recrystallized from proper solvent to give 3, Table (2). IR: 3420, 3380 (NH2), 1705, 1640 (CO), 1600 (N= N). JH-NMR (DMSO-d6): 1.96 (s,3H, COCH3),7.51- 8.01( m, 11H, Ar-H + NH2), 8.60 (s, 2H, NH2; exchangeable), 12.20 (s, 1H, NH; exchangeable). M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... Acta Chim. Slov. 2002, 49, 159-171. 167 3,5-Diamino-4-(4-sulfonylhydrazide)phenylazo-pyrazole(5). A mixture of hydrazone 2a (0.01 mole) and hydrazine hydrate (0.012 mole) in ethanol (40 mL) was heated under reflux for 2 hr. The solid product which produce on heating was collected and recrystallized from proper solvent to give 5, Table (2). IR 3480, 3200 (NH2), 1600 (N=N). !H-NMR (DMSO-d6): 6.00 - 6.50 ( broad, 4H , 2NH2; exchangeable), 7.31 (s, 2H, NH2; exchangeable), 7.81(m, 5H, Ar-H+NH), 10.90 (s,lH, NH; exchangeable). 3,5- diamino-4-[ 4 -N-(3-methylisoxazolyl)sulfamoyl]phenylazo-pyrazole (6). A mixture of hydrazone 2b (0.01 mole) and hydrazine hydrate (0.012 mole) in ethanol (40 mL) was heated under reflux for 5 min, the solid product which formed on heating was collected and recrystallized from proper solvent to give 6, Table (2). IR 3400, 3230 (NH2), 1610 (N=N). 3,5-diamino-l-phenyl-4-[4-(N-substituted)sulfamoyl]phenylazo-pyrazoles (7a,b). A mixture of hydrazone 2a or 2b (0.01 mole) and phenyl hydrazine (0.01 mole) in ethanol (30 mL) was refiuxed for 24 hr. and then allowed to cool. The solid product was collected and recrystallized from proper solvent to give 7, Table (2). IR (7b): 3475, 3369, 3272 (NH,NH2), 2940 (CH-aliph), 1600 (N=N). JHNMR (7b; DMSO-J6): 2.31 (s, 3H, CH3), 6.19 (s, 1H, isoxazole-H), 7.34, 7.37 (2s, 4H, 2NH2; exchangeable), 7.52-7.95 (m, 9H, Ar-H), 11.40 (s, 1H,NH; exchangeable). 3-Amino-4-[4-(N-substituted)sulfamoyl]phenylazo-pyrazol-5-ones(8a,b). A mixture of hydrazone 2d or 2e (0.01 mole) and hydrazine hydrate (0.012 mole) in ethanol (40 mL) was refiuxed for 24 hr, then allowed to cool and poured into cold water (50 mL) and acidified with HC1. The solid product was collected and recrystallized from proper solvent to give 8, Table (2). IR (8a): 3450, 3400 (NH2), 1680 (CO), 1600 (N=N). !HNMR (8a;DMSO-J6): 2.30 (s, 3H, CH3), 5.99 (s, 2H, NH2; exchangeable), 6.17(s,lH, isoxazole-H), 7.70-7.87 ( m, 5H, Ar-H + NH), 10.80 (s, 2H, 2NH, exchangeable ). M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 168 Acta Chim. Slov. 2002, 49, 159-171. 5-Amino-l-thiocarbamoyl-3-[imino(oxo)]-4-[4-N-(3-methylisoxazolyl)sulfamoyl-phenylazo-pyrazoles (9a, b). A mixture of hydrazone 2b or 2d (0.01 mole), thiosemicarbazide (0.01 mole) and triethylamine (0.5 mL) in dioxane (30 mL) was heated under reflux for 12 hr. The solid product which produced on heating was collected and recrystallized from proper solvent to give 9, Table (2). IR (9a): 3400, 3220 (NH2), 1600 (N=N). 1HNMR (9a; DMSO-d6): 2.31 (s, 3H, CH3), 6.19 (s, 1H, isoxazole-H), 7.87- 8.00 ( m, 6H, Ar-H + NH2), 8.20 (s, 1H, S02NH; exchangeable), 9.80, 11.60 (2s, 4H, 2NH2; exchangeable). MS (9a): 421 (M+; 22%), 397 (47%), 339 (31%), 312 (36%), 257 (base peak; 100%), 227 (60%), 209 (39%) and 164 (39.6%). 2-Amino-3-[4-(N-3-methylisoxazolyl)sulfamoyl]phenylazo-6,7-dihydro-7-thioxo-pyrazolo[l,5-a][l,3,5]triazine (10). A mixture of pyrazole 9a (0.01 mole) and triethyl orthoformate (10 mL) was refiuxed for 10 hr at 100°C. The excess of reagent was removed and to the cold mixture was added ether. The obtained solid was filtered, dried and recrystallized from proper solvent to give 10, Table (2).IR :3430, 3370,3320,(NH,NH2) and 1610 (N=N).1HNMR (DMSO-d6): 2.29 (s, 3H, CH3), 6.20 (s, 1H, isoxazole-H ), 7.91-7.95 ( m, 6H , Ar - H+ NH), 8.40, 11.60 ( 2s, 2H , 2NH; exchangeable ), 8.21 (s, 1H, triazine- H). 2-Amino-5-methyl-3-[4-(N-3-methylisoxazolyl)sulfamoyl]phenylazo-6,7-dihydro-7- thioxo-pyrazolo[l,5-a][l,3,5]triazine (11). Compound 9a (0.01 mole) was refiuxed in acetic anhydride (10 mL) for 3 hr, then allowed to cool. The solid product was collected and recrystallized from proper solvent to give 11, Table (2). IR: 3432, 3309, 3141 (NH, NH2), 2985 (CH - aliph), 1604 (N= N). 1HNMR (DMSO-J6): 2.19, 2.26 (2s, 6H, 2CH3), 6.14 (s, 1H, isoxazole-H), 7.40-7.91 (m, 6H, Ar-H + NH), 9.80, 11.20 ( 2s, 2H, 2NH; exchangeable) . 2- Amino-5-phenyl-3-[4-N-(3-methylisoxazolyl)sulfamoyl]phenylazo- 6,7 dihydro-7-thioxo-pyrazolo[l,5-a][l,3,5]triazine(12). A mixture of 9a (0.01 mole) and benzoyl chloride (0.01 mole) in pyridine (15 mL) was refiuxed for 12 hr and then allowed to M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... Acta Chim. Slov. 2002, 49, 159-171. 169 cool. The solid product was collected and recrystallized from proper solvent to give 12, Table (2). IR: 3410, 3320 (NH2), 1600 (N=N). 5-Amino-7-methylsulfanyl-3-[4-N-(3-methylisoxazolyl)sulfamoyl]phenylazo-2-imino(or oxo)- 1,2- dihydro-pyrazolo[l,5-a]pyrimidin-6- carbonitriles (15a ,b). To a suspension of 6 or 8 a (0.01 mole) and [bis(methylsulfanyl) methylidene]-malononitrile 13 (0.01 mole) in dimethylformamide (20 mL), (0.5mL) of triethylamine was added. The mixture was refluxed for 3 h. and then allowed to cool. The precipitated material was isolated by suction and recrystallized from proper solvent to give 15, Table (2): IR (15a): 3400, 3200 (NH2), 2200 (CN), 1600 (N=N). 1HNMR (15a) (DMSO-dè): 2.31 (s, 3H, CH3), 2.41 (s, 3H, SCH3), 3.71 (broad, 2H ,NH2), 6.19 (s, 1H, isoaxzole-H), 7.81-8.00 (m, 6H, Ar-H+NH2), 11.80 (broad, 1H. NH; exchangeable). MS (15a): 487 (M+, 26%), 484 (36%), 464 (base peak ; 100%), 411 (29%), 386 (50.7%), 377 (52%), 364 (40%) and, 350 (55%). IR (15b): 3450, 3300 (NH2), 2200 (CN), 1670 (CO), 1600 (N=N). 7-Methylsulfanyl-3-[4-N-(3-methylisoxazolyl)sulfamoyl]phenylazo-2-imino(or oxo) -l,2,4,5-tetrahydro-5-oxo-pyrazolo[l,5-a]pyrimidin-6-carbonitriles(18a,b). To a mixture of the compound 6 or 8a (0.01 mole) and ethyl [bis (methylsulfanyl) methylidene] cyanoacetate 16 (0.01 mole) in dioxane (20 mL), three drops of triethylamine were added. The resulting mixture was refluxed for 4 hr and then allowed to cool at room temperature and diluted with water (30 mL). The solid product so formed was collected by filtration and recrystallized from proper solvent to give 18, Table (2). IR (18a): 3320, 3150 (NH2), 2950 (CH-aliph), 2210 (CN), 1660 (CO). !HNMR (18a; DMSO -d6 ): 2.31 ( s.3 H , CH3 ), 2.61 ( s, 3H , SCH3), 4.01 (broad, 2H, NH2), 6.91 (s, 1H, isoxazole-H), 7.90-7.98 (m, 5H, Ar-H+NH), 11.51 (s, 1H, NH; exchangeable). MS (18a): 485 (M+ ; 30%). IR (18b): 3400, 3200 (NH2), 2200 (CN), 1650 (broad CO). Table (2): Characteristics data for the prepared compounds M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel... 170 Acta Chim. Slov. 2002, 49, 159-171. Com M. p [C0] Yield % Solv. Cryst. Mol. Formula (Mole. Wt) Elemental analysis pd. Calcd./Found No. C H N 2a 2b 2c 2d 2e 3 5 6 7a 7b 8a 8b 9a 9b 10 11 12 15a 15b 18a 18b 183-4 225-6 170-1 220-2 150-2 185-6 250-2 220-1 255-6 100-2 240-1 243-4 180-2 150-2 110-3 198-9 >300 210-1 190-1 180-2 210-2 82 85 75 90 87 80 74 84 80 76 75 77 92 87 60 65 67 64 76 74 73 Ethanol Ethanol Ethanol Ethanol Ethanol Ethanol Dioxane Dioxane Ethanol Ethanol Ethanol Ethanol Dioxane Benzene Ethanol DMF Ethanol Ethanol Ethanol Ethanol Ethanol CnH9N503S (291) C13H10N6O3S (330) C14H12N603S (344) C15H15N505S (377) C16H17N505S (391) C18H17N704S (427) C9H12N802 S (296) C« H14N803 S (362) C17 H17N7 03 S (399) Ci9 H18N8 03 S (438) C13 H13 N7 04 S (363) C14 H15 N7 04 S (377) C14 H15 N9 03 S2 (421) Ci4 H14 N8 04 S2 (422) C15H13N903S2 (431) C16 H15 N9 03 S2 (445) C21 H17 N9 03 S2 (507) C18H16N10O3S2 (484) Ci8 H15 N9 04 S2 (485) Ci8 H15 N9 04 S2 (485) Ci8 H14 N8 05 S2 (486) 45.36 45.30 47.27 47.20 48.84 48.70 47.75 47.60 49.11 49.10 50.59 50.50 36.49 36.50 43.09 43.10 51.13 51.20 52.06 52.10 42.98 42.90 44.56 44.60 39.91 39.80 39.81 39.80 41.76 41.70 43.15 43.20 49.71 49.60 44.63 44.60 44.54 44.50 44.54 44.60 44.45 44.30 3.11 3.10 3.05 3.00 3.51 3.50 4.00 3.90 4.38 4.20 4.00 3.90 4.08 4.10 3.89 3.80 4.29 4.10 4.14 4.20 3.61 3.40 4.01 3.90 3.59 3.50 3.34 3.30 3.04 3.10 3.39 3.40 3.38 3.30 3.33 3.30 3.11 3.10 3.11 3.10 2.90 2.70 24.05 24.00 25.45 25.30 24.42 24.50 18.57 18.50 17.90 17.80 22.94 22.90 37.81 37.80 30.92 30.90 24.56 24.50 25.57 25.60 26.99 26.80 25.99 25.90 29.91 29.90 26.52 26.50 29.22 29.20 28.30 28.30 24.84 24.70 28.91 28.80 25.96 25.90 25.96 25.90 23.03 23.10 References A. 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Grady, Antibiotic and Chemotherapy, 3rd ed., Churchill livingestoner Edinburgh, 1972,477. 18. Pcourvalin, interpretive reading antimicrobial susceptibility tests, Am. Soc, Microbial. News 1992, 85, 368-375. Povzetek Vrsto sulfa zdravil smo pustili reagirati s spojinami z aktivirano metilensko skupino in pripravili hidrazone 2a-e in preverili njihovo reaktivnost s hidrazini. Opisali smo tudi druge pretvorbe. Nekatere pripravljene spojine so bile testirane in vitro za morebitno antimikrobno delovanje. M. S. A. El-Gaby, N. M. Taha, J. A. Micky, M. A. M. Sh. El-Sharief: Preparation of some novel...