Synthesis and antimicrobial activity of some new pyrazoline derivatives bearing sulfanilamido moiety European Journal of Chemistry 10 (1) (2019) 30-36 European Journal of Chemistry View Journal Online View Article Online Synthesis and antimicrobial activity of some new pyrazoline derivatives bearing sulfanilamido moiety Maysoon Mohammed Almahdi 1,*, Ahmed Elsadig Mohammed Saeed 2 and Nadia Hanafy Metwally 3 1 Department of Chemistry, College of Education, Alzaiem Alazhari University, 1432, Khartoum, Sudan maysoon256@hotmail.com (M.M.A.) 2 Department of Chemistry, College of Science, Sudan University of Science and Technology, 407, Khartoum, Sudan asmsaeed@gmail.com (A.E.M.S.) 3 Department of Chemistry, Faculty of Science, Cairo University, 12613, Giza, Egypt nhmmohamed@yahoo.com (N.H.M.) * Corresponding author at: Department of Chemistry, College of Education, Alzaiem Alazhari University, 1432, Khartoum, Sudan. Tel: +249.9245.65006 Fax: +249.185.344511 e-mail: maysoon256@hotmail.com (M.M. Almahdi). 10.5155/eurjchem.10.1.30-36.1791 Received: 27 September 2018 Received in revised form: 04 November 2018 Accepted: 08 November 2018 Published online: 31 March 2019 Printed: 31 March 2019 In the present study, a series of new pyrazoline derivatives bearing sulfanilamido moiety were synthesized and obtained in good yields. The chemical structures of the compounds were elucidated by spectral data (FT-IR, MS, UV-VIS and NMR). The synthesized compounds 41-70 were screened for their antimicrobial activity and compared with controls. The in vitro antibacterial activity of compounds 41-45 and 48-57 was checked against two Gram positive microorganisms (S. aureus and S. mutans) and three Gram negative microorganisms (E. coli, K. pneumonia and P. aureginosa), their antifungal activity was checked against C. albicans. The preliminary results showed that these compounds had moderate activity against the tested organisms. Compounds 41, 48, 51 and 56 exhibited promising antimicrobial activity against S. aureus compared to standard drug Ampicilin. Final synthesized compounds 58-70 were tested against two Gram positive (S. aureus and B. subtilis) and two Gram negative (E. coli and P. aureginosa) microorganisms, their activity against C. albicans was also checked and they did not exhibit any antimicrobial activity. Synthesis Cyclization Sulfadoxine 2-Pyrazoline Sulfanilamide Antimicrobial activity Cite this: Eur. J. Chem. 2019, 10(1), 30-36 Journal website: www.eurjchem.com 1. Introduction 2-Pyrazolines (4,5-dihydro-1H-pyrazole) are an important class of five-membered heterocyclic compounds and were found to be vital building blocks in medicinal chemistry and led to the discovery of a number of bioactive derivatives [1,2]. 2-Pyrazolines were considered as a cyclic hydrazine moiety [3]. It exhibits the monoamino character and hence is more stable than the rest of the reduced forms. 2-pyrazolines were the most frequently studied form of pyrazolines because they have a considerably easy route of synthesis and rich biological activities [4]. As follows from the X-ray diffraction analysis, it has the structure of the five-membered dihydropyrazole ring, has an envelope conformation [5]. Carbon atom No. 5 in heterocyclic ring is deviated from the almost planar system of the other four atoms of the ring [6]. Derivatives of pyrazolines have played a crucial role in the history of heterocyclic chemistry and been used as important pharmacores and synthons in field of organic chemistry in drug designing [7,8]. Pyrazoline derivatives were found to have potential antipyretic-analgesic, muscle relaxant, psycho analeptic, tranquillizing, antiepileptic, antidepressant, anti- inflammatory, insecticidal and antimicrobial and antihypo- tensive activities. Their derivatives were also found to exhibit cytotoxic activity, inhibitory activity of platelet aggregation, herbicidal activity and cannabinoid type 1 receptor (CB1) modulators [9-11]. Biological activity potency associated with pyrazolines has made them popular synthetic target. Keeping these obser- vations in mind, we decided to synthesis some new pyrazo- lines derivatives bearing sulfanilamido moiety and evaluating their biological activities as antimicrobial agents. 2. Experimental 2.1. Materials and methods All reagents were used as purchased from commercial suppliers without further purification. Melting points were determined by using Fisher-Johns 6200 melting point ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2019 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.10.1.30-36.1791 http://dx.doi.org/10.5155/eurjchem.10.1.30-36.1791 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.1.30-36.1791&domain=pdf&date_stamp=2019-03-31 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.1.30-36.1791 mailto:maysoon256@hotmail.com mailto:asmsaeed@gmail.com mailto:nhmmohamed@yahoo.com mailto:maysoon256@hotmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.1.30-36.1791&domain=pdf&date_stamp=2019-03-31� Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 31 O HR + O R1 R R1 O HN N R R1 N N R R1 Cl O Ha Hx Hb (a) (b) (c) N N R R1 NH O Ha Hx Hb S O O NH2 N N R R1 NH O Ha Hx Hb S O O NH N N OCH3 OCH3 (d) (d) Sulfanilamide Sulfadoxine 1 - 20 21 - 40 41 - 57 58 - 67 68 - 70 1, 21, 41, 58: R = C6H5, R1 = H 2, 22, 42, 59: R = p-ClC6H4, R1 = H 3, 23, 43, 60, 68: R = p-Me2NC6H4, R1= H 4, 24, 44, 61: R = Cinnamyl phenyl, R1= H 5, 25, 45, 62: R = Furyl, R1 = H 6, 26, 46: R = C6H5, R1 = p-Br 7, 27: R = p-ClC6H4, R1 = p-Br 8, 28: R = p-Me2NC6H4, R1 = p-Br 9, 29: R = Cinnamyl phenyl, R1 = p-Br 10, 30, 47: R = Furyl, R1 = p-Br 11, 31, 48: R = C6H5, R1 = p-NO2 12, 32, 49: R = p-ClC6H4, R1 = p-NO2 13, 33, 50: R = p-Me2NC6H4, R1 = p-NO2 14, 34, 51: R = Cinnamyl phenyl, R1 = p-NO2 15, 35, 52, 63: R = Furyl, R1 = p-NO2 16, 36, 53, 64, 69: R = C6H5, R1 = p-CH3 17, 37, 54, 65: R = p-ClC6H4, R1 = p-CH3 18, 38, 55, 66, 70: R = p-Me2NC6H4, R1 = p-CH3 19, 39, 56: R = Cinnamyl phenyl, R1 = p-CH3 20, 40, 57, 67: R = Furyl, R1 = p-CH3 Reagents and conditions: (a) 10% aqueous sodium hydroxide solution, ethanol, str. rt, 4 h. (b) hydrazine hydrate, ethanol, reflux, 8 h; (c) chloroacetyl chloride, dry toluene, Et3N, str. 6 h; (d) anhydrous K2CO3, DMF, stirring under reflux. Scheme 1. The synthetic route for the preparation of compounds 1-70. apparatus and were uncorrected (Fisher Scientific Company, USA). The purity of final compounds was checked on pre- coated TLC silica gel 60F254, with different solvent system and visualizing the spots in ultraviolet light (model UVGL-58 multiband UV.254-365 NM, Upland, CA91786, USA). FT-IR spectra were recorded on a Shimadzu FT-IR-4100 spectrophotometer. UV-Vis spectroscopic data were recorded on Shimadzu UV-3101PC spectrophotometer, and mass spectra were recorded on GC/MS Shimadzu QP-2010 Plus mass spectrometer. Nuclear magnetic resonance (1H NMR) spectra were recorded using Bruker 400 MHz NMR instrument. Chemical shift values are reported in ppm relative to tetramethyl silane (TMS) as internal reference in DMSO-d6 and peak multiplicities are designed as follows: s, singlet; d, doublet; t, triplet; m, multiplet. 2.2. Synthesis 2.2.1. Synthesis of α,β-unsaturated carbonyl derivatives (1- 20) A mixture of various substituted aromatic aldehydes (0.05 mol), substituted aromatic acetophenone (0.05 mol) and sodium hydroxide 10% in ethanol (30 mL) was stirred at room temperature until the mixture is so thick that stirring is no longer effective (3-5 h), the reaction mixture was removed and kept in refrigerator overnight. The resulting solid was filtered, washed with cold water until the washings are neutral to litmus. The crude α,β-unsaturated carbonyl derivative, was air dried, recrystallized from ethanol and was taken for the next step (Scheme 1). 2.2.2. Synthesis of 3,5-diaryl-2-pyrazoline derivatives (21- 40) A mixture of appropriate α,β-unsaturated carbonyl derivative (0.03 mol) and hydrazine hydrate (0.06 mol) in ethanol (30 mL) were refluxed for 8 h. The reaction mixture was cooled and kept in refrigerator overnight. The resulting solid was filtered and crude pyrazoline after drying and recrystallized from ethanol was taken for the next step (Scheme 1). 2.2.3. General method for the synthesis of 1-(chloroacetyl)- 3,5-diaryl-2-pyrazolines derivatives (41-57) 3,5-Diaryl-2-pyrazoline (0.025 mol) and triethylamine (0.025 mol) were dissolved in dry toluene (30 mL) with constant stirring. Later, the mixture was cooled in an ice bath, and chloroacetyl chloride (0.025 mol) was added drop wise with stirring. The reaction mixture thus obtained was further agitated for 3 h at room temperature. The precipitate was 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 32 Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 filtrated, the solvent was evaporated to dryness under reduced pressure, and the solid obtained was recrystallized from ethanol (Scheme 1). 2-Chloro-1-(3, 5-diphenyl-4, 5-dihydro-1H-pyrazol-1-yl) ethan-1-one (41): Color: Pale yellow powder. Yield: 46 %. M.p.: 130-132 °C. Rf value: 0.75. FT-IR (KBr, ν, cm−1): 1757 (C=O), 1665 (C=N), 1443 (aromatic C=C). 1H NMR (400 MHz, DMSO- d6, δ, ppm): 3.17 (dd, 1H, JHa,Hb= 18.2 Hz, JHa,Hx= 4.72 Hz, Ha), 3.87 (dd, 1H, JHb,Ha= 18.2 Hz, JHb,Hx= 11.72 Hz, Hb), 4.68 (d, 1H, J = 13.8 Hz, CO-CH), 4.77 (d, 1H, J = 13.8 Hz, CO-CH) 5.57 (dd, 1H, JHb,Hx= 11.72 Hz, JHa,Hx= 4.64 Hz, Hx), 7.22-7.84 (m, 10H, Ar- H). MS (EI, m/z (%)): 298 (M+, 100). UV/VIS (DMSO, λmax, nm): 300, 293. 2-Chloro-1-[5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H- pyrazol-1-yl]ethan-1-one (42): Color: Light yellow powder. Yield: 48%. M.p.: 128-130 °C. Rf value: 0.72. FT-IR (KBr, ν, cm−1): 1668 (C=O), 1599 (C=N), 1573 (aromatic C=C). 1H1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.19 (dd, 1H, JHa,Hb= 18.24 Hz, JHa,Hx = 4.88 Hz, Ha), 3.87 (dd, 1H, JHb,Ha = 18.28 Hz, JHb,Hx = 11.76 Hz, Hb), 4.67 (d, 1H, J = 13.84 Hz, CO-CH), 4.77 (d, 1H, J = 13.84 Hz, CO-CH), 5.58 (dd, 1H, JHb,Hx = 11.76 Hz, JHa,Hx = 4.84 Hz, Hx), 7.26-7.83 (m, 9H, Ar-H). MS (EI, m/z (%)): 332 (M+, 86.9). UV/VIS (DMSO, λmax, nm): 349. 2-Chloro-1-{5-[4-(dimethylamino) phenyl]-3-phenyl-4,5- dihydro-1H-pyrazol-1-yl} ethan-1-one (43): Color: Yellow powder. Yield: 64%. M.p.: 130-132 °C. Rf value: 0.53. FT-IR (KBr, ν, cm−1): 1664 (C=O), 1612 (C=N), 1565 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.85 (s, 6H, CH3-N), 3.14 (dd, 1H, JHa,Hb = 18.16 Hz, JHa,Hx = 4.44 Hz, Ha), 3.80 (dd, 1H, JHb,Ha = 18.16 Hz, JHb,Hx = 11.59 Hz, Hb), 4.64 (d, 1H, J = 13.72 Hz, CO-CH), 4.72 (d, 1H, J = 13.72 Hz, CO-CH), 5.45 (dd, 1H, JHb,Hx = 11.56 Hz, JHa,Hx = 4.4 Hz, Hx), 6.66 (d, 2H, J = 8.72 Hz, Ar-H), 7.03 (d, 2H, J = 8.72 Hz, Ar-H) 7.48-7.83 (m, 5H, Ar-H). MS (EI, m/z (%)): 341 (M+, 61.1). UV/VIS (DMSO, λmax, nm): 350, 265. 2-Chloro-1-{3-phenyl-5-[(E)-2-phenylethenyl]-4, 5-dihyd ro-1H-pyrazol-1-yl}ethan-1-one (44): Color: Pale yellow powder. Yield: 49%. M.p.: 136-138 °C. Rf value: 0.70. FT-IR (KBr, ν, cm−1): 1748 (C=O), 1666 (C=N), 1599 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.25 (dd, 1H, JHa,Hb = 18 Hz, JHa,Hx = 4.68 Hz, Ha), 3.65 (dd, 1H, JHb,Ha = 17.96Hz, JHb,Hx = 11.32 Hz, Hb), 4.67 (d, 1H, J = 13.84 Hz, CO-CH), 4.73 (d, 1H, J = 13.72 Hz, CO-CH), 5.19-5.25 (m, 1H, Hx), 6.30 (dd, 1H, Jα-H,β-H = 15.88 Hz, Jα-H,Hx = 7.08 Hz, α-H), 6.57 (d, 1H , J = 15.88 Hz, β-H), 7.32-7.83 (m, 10H, Ar-H). MS (EI, m/z (%)): 324 (M+, 54.6). UV/VIS (DMSO, λmax, nm): 351. 2-Chloro-1-[5-(furan-2-yl)-3-phenyl-4,5-dihydro-1H-pyra zol-1-yl]ethan-1-one (45): Color: Light brown powder. Yield: 51%. M.p.: 136-138 °C. Rf value: 0.69. FT-IR (KBr, ν, cm−1): 1669 (C=O) , 1599 (C=N), 1501 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.40 (dd, 1H, JHa,Hb = 18.04 Hz, JHa,Hx = 4.72 Hz, Ha), 3.74 (dd, 1H, JHb,Ha = 18.04 Hz, JHb,Hx = 11.8 Hz, Hb), 4.65 (d, 1H, J = 14 Hz, CO-CH), 4.70 (d, 1H, J = 14.04 Hz, CO-CH), 5.67 (dd, 1H, JHb,Hx = 11.76 Hz, JHa,Hx = 4.72 Hz, Hx), 6.38-6.42 (m, 2H, furan-H), 7.47-7.52 (m, 3H, Ar-H), 7.58 (d, 1H, J = 1.60 Hz, furan-H), 7.82-7.85 (m, 2H, Ar-H). MS (EI, m/z (%)): 288 (M+, 93.4). UV/VIS (DMSO, λmax, nm): 347. 1-[3-(4-Bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol- 1-yl]-2-chloroethan-1-one (46): Color: Pale yellow powder. Yield: 54%. M.p.: 122-124 °C. Rf value: 0.29. FT-IR (KBr, ν, cm−1): 1683 (C=O), 1589 (C=N), 1490 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.17 (dd, 1H, JHa,Hb = 18.24 Hz, JHa,Hx = 4.8 Hz, Ha), 3.86 (dd, 1H, JHb,Ha = 18.24 Hz, JHb,Hx = 11.8 Hz, Hb), 4.67 (d, 1H, J= 13.84 Hz, CO-CH), 4.77 (d, 1H, J = 13.84 Hz, CO-CH), 5.57 (dd, 1H, JHb,Hx = 11.72 Hz, JHa,Hx = 4.76 Hz, Hx), 7.22-7.37 (m, 5H, Ar-H), 7.67 (d, 2H, J = 8.56 Hz, Ar-H), 7.75 (d, 2H, J = 8.56 Hz, Ar-H). MS (EI, m/z (%)): 376 (M+, 75.1). UV/VIS (DMSO, λmax, nm): 299, 293. 1-[3-(4-Bromophenyl)-5-(furan-2-yl)-4,5-dihydro-1H-py razol-1-yl]-2-chloroethan-1-one (47): Color: White powder. Yield: 50%. M.p.: 128-130 °C. Rf value: 0.31. FT-IR (KBr, ν, cm−1): 1678 (C=O), 1589 (C=N), 1500 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.39 (dd, 1H, JHa,Hb = 18.12 Hz, JHa,Hx = 4.84 Hz, Ha), 3.73 (dd, 1H, JHb,Ha = 18.08 Hz, JHb,Hx = 11.8 Hz, Hb), 4.65 (d, 1H, J = 14.08 Hz, CO-CH), 4.70 (d, 1H, J = 14.04 Hz, CO-CH), 5.68 (dd, 1H, JHb,Hx = 11.8 Hz, JHa,Hx = 4.84Hz, Hx), 6.39-6.42 (m, 2H, furan-H), 7.58 (d, 1H, J = 0.72 Hz, furan-H), 7.69 (d, 2H, J = 8.56 Hz, Ar-H), 7.76 (d, 2H, J = 8.52 Hz, Ar-H). MS (EI, m/z (%)): 367 (M+, 16.4). UV/VIS (DMSO, λmax, nm): 300, 255. 2-Chloro-1-[3-(4-nitrophenyl)-5-phenyl-4,5-dihydro-1H- pyrazol-1-yl] ethan-1-one (48): Color: Yellow powder. Yield: 65%. M.p.: 136-138 °C. Rf value: 0.43. FT-IR (KBr, ν, cm−1): 1672 (C=O), 1577 (C=N), 1515 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.25 (dd, 1H, JHa,Hb = 18.36 Hz, JHa,Hx = 4.96 Hz, Ha), 3.93 (dd, 1H, JHb,Ha = 18.32 Hz, JHb,Hx = 11.92 Hz, Hb), 4.72 (d, 1H, J = 13.96 Hz, CO-CH), 4.82 (d, 1H, J = 14 Hz, CO-CH), 5.63 (dd, 1H, JHb,Hx = 11.88 Hz, JHa,Hx = 4.96 Hz, H5a), 7.24-7.38 (m, 4H, Ar-H), 8.05 (d, 2H, J = 8.88 Hz, Ar-H), 8.30 (d, 2H, J = 8.88 Hz, Ar-H). MS (EI, m/z (%)): 343 (M+, 56.9). UV/VIS (DMSO, λmax, nm): 350. 2-Chloro-1-[5-(4-chlorophenyl)-3-(4-nitrophenyl)-4,5-di hydro-1H-pyrazol-1-yl]ethan-1-one (49): Color: Pale yellow powder. Yield: 61%. M.p.: 160-162 °C. Rf value: 0.30. FT-IR (KBr, ν, cm−1): 1667 (C=O), 1598 (C=N), 1513 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.27 (dd, 1H, JHa,Hb = 18.36 Hz, JHa,Hx = 5.16 Hz, Ha), 3.92 (dd, 1H, JHb,Ha = 18.36Hz, JHb,Hx = 11.99 Hz, Hb), 4.71 (d, 1H, J = 14 Hz, CO-CH), 4.81 (d, 1H, J = 14 Hz, CO-CH), 5.63 (dd, 1H, JHb,Hx = 11.92 Hz, JHa,Hx = 5.2 Hz, Hx), 7.28 (d, 2H, Ar-H), 7.40 (d, 2H, Ar-H), 8.04 (d, 2H, Ar- H), 8.30 (d, 2H, Ar-H). MS (EI, m/z (%)): 378 (M+, 17). UV/VIS (DMSO, λmax, nm): 300. 2-Chloro-1-{5-[4-(dimethylamino)phenyl]-3-(4-nitrophen yl)-4,5-dihydro-1H-pyrazol-1-yl}ethan-1-one (50): Color: Red powder. Yield: 52%. M.p.: 196-198 °C. Rf value: 0.50. FT-IR (KBr, ν, cm−1): 1673 (C=O), 1608 (C=N), 1566 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.87 (s, 6H, CH3-N), 3.22 (dd, 1H, JHa,Hb = 18.28 Hz, JHa,Hx = 4.76 Hz, Ha), 3.86 (dd, 1H, JHb,Ha = 18.24 Hz, JHb,Hx = 11.8, Hz, Hb), 4.68 (d, 1H, J = 13.88 Hz, CO-CH), 4.77 (d, 1H, J = 13.88 Hz, CO-CH), 5.51 (dd, 1H, JHb,Hx = 11.68 Hz, JHa,Hx = 4.68 Hz, Hx), 6.71-8.34 (m, 8H, Ar-H). MS (EI, m/z (%)): 386 (M+, 55.1). UV/VIS (DMSO, λmax, nm): 301, 265. 2-Chloro-1-{3-(4-nitrophenyl)-5-[(E)-2-phenylethenyl]-4, 5-dihydro-1H-pyrazol-1-yl}ethan-1-one (51): Color: Yellow powder. Yield: 71%. M.p.: 142-144 °C. Rf value: 0.42. FT-IR (KBr, ν, cm−1): 1684 (C=O), 1573 (C=N), 1510 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.32 (dd, 1H, JHa,Hb = 18.04 Hz, JHa,Hx = 4.96 Hz, Ha), 3.70 (dd, 1H, JHb,Ha = 18.08 Hz, JHb,Hx = 11.44 Hz, Hb), 4.71 (d, 1H, J = 14 Hz, CO-CH), 4.77 (d, 1H, J = 14.04 Hz, CO-CH), 5.25-5.31 (m, 1H, Hx), 6.32 (dd, 1H, Jα-H,β-H = 15.88 Hz, Jα-H,Hx = 7.28 Hz, α-H), 6.60 (d, 1H, J = 15.88 Hz, β-H), 7.23-7.45 (m, 5H, Ar-H), 8.05-8.34 (m, 4H, Ar-H). MS (EI, m/z (%)): 369 (M+, 32.4). UV/VIS (DMSO, λmax, nm): 295, 255. 2-Chloro-1-[5-(furan-2-yl)-3-(4-nitrophenyl)-4,5-dihyd ro-1H-pyrazol-1-yl]ethan-1-one (52): Color: Yellow powder. Yield: 72%. M.p.: 162-164 °C. Rf value: 0.18. FT-IR (KBr, ν, cm−1): 1667 (C=O), 1597 (C=N), 1573 (aromatic C=C).1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.48 (dd, 1H, JHa,Hb = 18.16 Hz, JHa,Hx = 5.00 Hz, Ha), 3.80 (dd, 1H, JHb,Ha = 18.16 Hz, JHb,Hx = 11.88 Hz, Hb), 4.69 (d, 1H, J = 14.16 Hz, CO-CH), 4.75 (d, 1H, J = 14.16 Hz, CO-CH), 5.74 (dd, 1H, JHb,Hx = 11.92 Hz, JHa,Hx = 4.96 Hz, Hx), 6.42-6.43 (m, 2H, J = 1.24 Hz, furan-H), 7.59 (d, 1H, J = 0.72 Hz, furan-H), 8.07-8.33 (m, 4H, Ar-H). MS (EI, m/z (%)): 333 (M+, 79). UV/VIS (DMSO, λmax, nm): 294, 254. 2-Chloro-1-[3-(4-methylphenyl)-5-phenyl-4, 5-dihydro- 1H-pyrazol-1-yl] ethan-1-one (53): Color: Pale yellow powder. Yield: 64%. M.p.: 118-120 °C. Rf value: 0.60. FT-IR (KBr, ν, cm−1): 1750 (C=O), 1664 (C=N), 1442 (aromatic C=C). 1H NMR 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 33 (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 3.14 (dd, 1H, JHa,Hb = 18.16 Hz, JHa,Hx = 4.64 Hz, Ha), 3.84 (dd, 1H, JHb,Ha = 18.2 Hz, JHb,Hx = 11.76 Hz, Hb), 4.66 (d, 1H, J = 13.76 Hz, CO-CH), 4.76 (d, 1H, J = 13.8 Hz, CO-CH), 5.55 (dd, 1H, JHb,Hx = 11.68 Hz, JHa,Hx = 4.6 Hz, Hx), 7.21-7.36 (m, 7H, Ar-H), 7.70 (d, 2H, J = 8.16 Hz, Ar-H). MS (EI, m/z (%)): 312 (M+, 100). UV/VIS (DMSO, λmax, nm): 300. 2-Chloro-1-[5-(4-chlorophenyl)-3-(4-methylphenyl)-4, 5- dihydro-1H-pyrazol-1-yl]ethan-1-one (54): Color: Light yellow powder. Yield: 62%. M.p.: 138-140 °C. Rf value: 0.56. FT-IR (KBr, ν, cm−1): 1684 (C=O), 1667 (C=N), 1603 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 3.14 (dd, 1H, JHa,Hb = 18.24 Hz, JHa,Hx = 4.8 Hz, Ha), 3.83 (dd, 1H, JHb,Ha = 18.2Hz, JHb,Hx = 11.76 Hz, Hb), 4.65 (d, 1H, J = 13.8 Hz, CO- CH), 4.75 (d, 1H, J = 13.8 Hz, CO-CH), 5.55 (dd, 1H, JHb,Hx = 11.72 Hz, JHa,Hx = 4.76 Hz, Hx), 7.24-7.30 (m, 4H, Ar-H), 7.39 (d, 2H, J = 8.44 Hz, Ar-H), 7.69 (d, 2H, J = 8.12 Hz, Ar-H). MS (EI, m/z (%)): 346 (M+, 100). UV/VIS (DMSO, λmax, nm): 298, 266. 2-Chloro-1-{5-[4-(dimethylamino)phenyl]-3-(4-methyl phenyl)-4,5-dihydro-1H-pyrazol-1-yl}ethan-1-one (55): Color: Light brown powder. Yield: 46%. M.p.: 134-136 °C. Rf value: 0.47. FT-IR (KBr, ν, cm−1): 1673 (C=O), 1613 (C=N), 1524 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.36 (s, 3H, CH3), 2.85 (s, 6H, CH3-N), 3.11 (dd, 1H, JHa,Hb = 18.12 Hz, JHa,Hx = 4.36 Hz, Ha), 3.76 (dd, 1H, JHb,Ha = 18.08 Hz, JHb,Hx = 11.56 Hz, Hb), 4.62 (d, 1H, J = 13.72 Hz, CO-CH), 4.70 (d, 1H, J = 13.68 Hz, CO-CH), 5.43 (dd, 1H, JHb,Hx = 11.48 Hz, JHa,Hx = 4.32 Hz, Hx), 6.65 (d, 2H, J = 8.72 Hz, Ar-H), 7.01 (d, 2H, J = 8.72 Hz, Ar-H), 7.28 (d, 2H, J = 8.00 Hz, Ar-H), 7.70 (d, 2H, J = 8.12 Hz, Ar-H). MS (EI, m/z (%)): 355 (M+, 74.6). UV/VIS (DMSO, λmax, nm): 295, 255. 2-Chloro-1-{3-(4-methylphenyl)-5-[2-phenylethenyl]-4, 5- dihydro-1H-pyrazol-1-yl}ethan-1-one (56): Color: Pale yellow powder. Yield: 65%. M.p.: 108-110 °C. Rf value: 0.62. FT-IR (KBr, ν, cm−1): 1751 (C=O), 1671 (C=N), 1608 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 3.20 (dd, 1H, JHa,Hb = 18.00 Hz, JHa,Hx = 4.72 Hz, Ha), 3.59 (dd, 1H, JHb,Ha = 17.96Hz, JHb,Hx = 11.28 Hz, Hb), 4.65 (d, 1H, J = 13.80 Hz, CO-CH), 4.71 (d, 1H, J = 13.84 Hz, CO-CH), 5.16-5.22 (m, 1H, Hx), 6.28 (dd, 1H, Jα-H,β-H = 15.88 Hz, Jα-H,Hx = 7.08 Hz, α-H), 6.57 (d, 1H, J = 15.88 Hz, β-H), 7.22-7.34 (m, 5H, Ar-H), 7.42 (d, 2H, J = 7.40 Hz, Ar-H), 7.69 (d, 2H, J = 8.08 Hz, Ar-H). MS (EI, m/z (%)): 338 (M+, 75.8). UV/VIS (DMSO, λmax, nm): 296. 2-Chloro-1-[5-(furan-2-yl)-3-(4-methylphenyl)-4,5-dihyd ro-1H-pyrazol-1-yl]ethan-1-one (57): Color: Pale yellow powder. Yield: 56%. M.p.: 124-126 °C. Rf value: 0.64. FT-IR (KBr, ν, cm−1): 1683 (C=O), 1604 (C=N), 1563 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.36 (s, 3H, CH3), 3.36 (dd, 1H, JHa,Hb = 18.04Hz, JHa,Hx = 4.72 Hz, Ha), 3.71 (dd, 1H, JHb,Ha = 18.00 Hz, JHb,Hx = 11.76 Hz, Hb), 4.63 (d, 1H, J = 14.00 Hz, CO- CH), 4.68 (d, 1H, J = 13.96 Hz, CO-CH), 5.65 (dd, 1H, JHb,Hx = 11.68 Hz, JHa,Hx = 4.72 Hz, Hx), 6.37-6.42 (m, 2H, furan-H), 7.29 (d, 2H, J = 8.00 Hz, Ar-H), 7.57 (d, 1H, J = 0.84 Hz, furan-H), 7.71 (d, 2H, J = 8.12 Hz, Ar-H). MS (EI, (m/z (%)): 302 (M+, 100). UV/VIS (DMSO, λmax, nm): 300. 2.2.4. General method for the synthesis of 1-(subistituted aminoacetyl) -3,5-diaryl-2-pyrazolines derivatives (58-70) A mixture of 10 mmol sulfanilamide or sulfadoxine, 10 mmol of 1-(chloroacetyl)-3,5-diaryl-2-pyrazolines, and appro- priate amount of potassium carbonate anhydrous was stirred under reflux in 10 mL of dry DMF. Reaction was followed by thin layer chromatography (TLC), the mixture obtained after time complete was poured in crushed ice. The products were separated by filtration, washed with water, ethanol, and dried. Recrystallization from ethanol/dioxane rendered desired products in pure form (Scheme 1). 4-((2-(3, 5-Diphenyl-4, 5-dihydro-1H-pyrazol-1-yl)-2-oxoeth yl)amino)benzene sulfonamide (58): Color: White powder. Yield: 70%. M.p.: 200-202 °C. Rf value: 0.62. FT-IR (KBr, ν, cm−1): 3482-3392 (NH2), 3232 (NH), 1660 (C=O), 1625 (C=N), 1395-1155 (SO2), 1594 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.10 (dd, 1H, JHa,Hb = 18.12 Hz, JHa,Hx = 4.72 Hz, Ha), 3.80 (dd, 1H, JHb,Ha = 18.16 Hz, JHb,Hx = 11.80 Hz, Hb), 4.02 (d, 2H, J = 6.00 Hz, CO-CH2), 5.44 (dd, 1H, JHb,Hx = 11.76 Hz, JHa,Hx = 4.64 Hz, Hx), 5.95 (s, 2H, NH2), 6.58 (d, 2H, J = 8.68 Hz, Ar-H), 7.13 (d, 2H, J = 7.16 Hz, Ar-H), 7.24 (t, 1H, NH), 7.32- 7.78 (m, 10H, Ar-H). MS (EI, m/z (%)): 434 (M+, 15.4). UV/VIS (DMSO, λmax, nm): 291, 276. 4-((2-(5-(4-Chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol- 1-yl)-2-oxoethyl)amino) benzene sulfonamide (59): Color: White powder. Yield: 75%. M.p.: 198-200 °C. Rf value: 0.55. FT- IR (KBr, ν, cm−1): 3479-3375 (NH2) , 3224 (NH), 1651 (C=O), 1593 (C=N), 1396-1153 (SO2), 1500 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.11 (dd, 1H, JHa,Hb = 18.24 Hz, JHa,Hx = 4.72 Hz, Ha), 3.80 (dd, 1H, JHb,Ha = 18.20 Hz, JHb,Hx = 11.80 Hz, Hb), 4.01 (d, 2H, J= 5.72 Hz, CO-CH2), 5.44 (dd, 1H, JHb,Hx =11.72 Hz, JHa,Hx = 4.54 Hz, Hx), 5.95 (s, 2H, NH2), 6.58 (d, 2H, J= 8.48 Hz, Ar-H), 7.16 (d, 2H, J= 8.24 Hz, Ar-H), 7.31 (t, 1H, NH), 7.36-7.77 (m, 9H, Ar-H). MS (EI, m/z (%)): 468 (M+, 16.8). UV/VIS (DMSO, λmax, nm): 286, 271. 4-((2-(5-(4-(Dimethylamino)phenyl)-3-phenyl-4, 5-dihydro- 1H-pyrazol-1-yl)-2-oxoethyl)amino)benzene sulfonamide (60): Color: Pale yellow powder. Yield: 57%. M.p.: 110-112 °C. Rf value: 0.71. FT-IR (KBr, ν, cm−1): 3441-3363 (NH2), 3228 (NH), 1651 (C=O), 1600 (C=N), 1392-1153 (SO2), 1523 (aromatic C=C). 1H1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.84 (s, 6H, CH3- N), 3.07 (dd, 1H, JHa,Hb = 18.12 Hz, JHa,Hx = 4.36 Hz, Ha), 3.73 (dd, 1H, JHb,Ha = 18.08 Hz, JHb,Hx = 11.60 Hz, Hb), 3.92-4.04 (m, 2H, CO-CH2), 5.33 (dd, 1H, JHb,Hx = 11.52 Hz, JHa,Hx = 4.32 Hz, Hx), 5.95 (s, 2H, NH2), 6.59 (dd, 2H, J = 8.60 Hz, Ar-H), 6.94 (d, 2H, J = 8.60 Hz, Ar-H), 7.25 (t, 1H, NH), 7.45-7.77 (m, 9H, Ar-H). MS (EI, m/z (%)): 477 (M+, 100). UV/VIS (DMSO, λmax, nm): 292, 267. 4-((2-Oxo-2-(3-phenyl-5-styryl-4, 5-dihydro-1H-pyrazol- 1-yl)ethyl)amino)benzene sulfonamide (61): Color: Yellow powder. Yield: 42%. M.p.: 140-142 °C. Rf value: 0.68. FT-IR (KBr, ν, cm−1): 3464-3360 (NH2), 3236 (NH), 1654 (C=O), 1597 (C=N), 1388-1149 (SO2), 1504 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.17 (dd, 1H, JHa,Hb = 17.84 Hz, JHa,Hx = 4.56 Hz, Ha), 3.98-3.99 (m, 1H, Hb), 4.62 (m, 2H, CO-CH2), 5.11- 5.15 (m, 1H, Hx), 5.94 (s, 2H, NH2), 6.29 (m, 2H, α-H & β-H), 6.44-7.76 (m, 14H, Ar-H), 7.25 (s, 1H, NH). MS (EI, m/z (%)): 460 (M+, 6.8). UV/VIS (DMSO, λmax, nm): 293. 4-({2-[5-(Furan-2-yl)-3-phenyl-4, 5-dihydro-1H-pyrazol- 1-yl]-2-oxoethyl}amino)benzene-1-sulfonamide (62): Color: Yellow powder. Yield: 40%. M.p.: 184-186 °C. Rf value: 0.55. FT-IR (KBr, ν, cm−1): 3471-3371 (NH2), 3224 (NH), 1658 (C=O), 1597 (C=N), 1311-1153 (SO2), 1507 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.67-3.71 (m, 1H, Ha), 3.93- 3.98 (m, 1H, Hb), 4.54 (m, 2H, CO-CH2), 5.54-5.56 (m, 1H, Hx), 5.94 (s, 2H, NH2), 6.28-7.79 (m, 12H, Ar-H), 7.35 (s, 1H, NH). MS (EI, m/z (%)): 424 (M+, 15.1). UV/VIS (DMSO, λmax, nm): 349, 287. 4-((2-(5-(Furan-2-yl)-3-(4-nitrophenyl)-4, 5-dihydro-1H- pyrazol-1-yl)-2-oxoeth yl)amino)benzene sulfonamide (63): Color: Yellow powder. Yield: 45%. M.p.: 190-192 °C. Rf value: 0.58. FT-IR (KBr, ν, cm−1): 3448-3383 (NH2), 3240 (NH), 1670 (C=O), 1631 (C=N), 1342-1153 (SO2), 1597 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 3.10-3.17 (m, 1H, Ha), 3.72 (dd, 1H, JHb,Ha = 18.12 Hz, JHb,Hx = 11.84 Hz, Hb), 3.97-4.01 (m, 2H, CO-CH2), 5.59 (dd, 1H, JHb,Hx = 11.8 Hz, JHa,Hx = 4.72 Hz, Hx), 5.94 (s, 2H, NH2), 6.32-8.33 (m, 11H, Ar-H), 7.21 (s, 1H, NH). MS (EI, m/z (%)): 469 (M+, 4.7). UV/VIS (DMSO, λmax, nm): 288, 279. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 34 Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 Table 1. Antimicrobial activities of synthesized chloroacetyl pyrazolines. Compound Diameter of zone of inhibition (mm) * Gram negative bacteria Gram positive bacteria Fungi E. coli. K. pneumonia P. aeruginosa S. aureus S. mutans C. albicans 41 19 10.3 - 34 - 14.6 42 13 16 - 10 8.6 15.3 43 23 24.3 - 21 18 14.3 44 - 11.3 11 19 - 12.6 45 - 12.3 - - - 13.6 48 11.3 11.3 - 32 19.6 18.6 49 - 11.6 - 27 29 15.3 50 15 12.6 - - 23.6 10.3 51 - - - 33 - 16.3 52 - - - - - 12.3 53 - 19.3 - 14 22 16.3 54 - 12.3 - 28 - 15.3 55 19 22.3 13 24 22 11.6 56 - - - 34 - 16.6 57 - - - - - 13.6 Gentamicin 35 35 30 - - - Ampicilin - - - 30 35 - Nystatin - - - - - 20 * “-”: no activity. 4-((2-Oxo-2-(5-phenyl-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol- 1-yl)ethyl)amino)benzene sulfonamide (64): Color: White powder. Yield: 59%. M.p.: 210-212 °C. Rf value: 0.59. FT-IR (KBr, ν, cm−1): 3448-3356 (NH2), 3217 (NH), 1670 (C=O), 1635 (C=N), 1311-1153 (SO2), 1597 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 3.06 (dd, 1H, JHa,Hb = 18.16 Hz, JHa,Hx = 4.64 Hz, Ha), 3.77 (dd, 1H, JHb,Ha = 18.12 Hz, JHb,Hx = 11.76 Hz, Hb), 4.00 (d, 2H, J = 6.00 Hz, CO-CH2), 5.42 (dd, 1H, JHb,Hx = 11.68 Hz, JHa,Hx = 4.64 Hz, Hx), 5.94 (s, 2H, NH2), 6.57 (d, 2H, J = 8.68 Hz, Ar-H), 7.12 (d, 2H, J = 7.12H z, Ar-H), 7.28 (t, 1H, NH), 7.30-7.67 (m, 9H, Ar-H). MS (EI, m/z (%)): 448 (M+, 19.4). UV/VIS (DMSO, λmax, nm): 294 4-((2-(5-(4-Chlorophenyl)-3-(p-tolyl)-4, 5-dihydro-1H-pyra zol-1-yl)-2-oxo ethyl) amino)benzene sulfonamide (65): Color: Yellow powder. Yield: 48%. M.p.: 216-218 °C. Rf value: 0.45. IR (KBr, ν, cm−1): 3448-3367 (NH2), 3213 (NH), 1651(C=O), 1597 (C=N), 1319-1149 (SO2), 1492 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.34 (s, 3H, CH3), 3.10-3.13 (m, 1H, Ha), 3.76-3.87 (m, 1H, Hb), 4.00 (d, 2H, CO-CH2), 5.42-5.58 (m, 1H, Hx), 5.95 (s, 2H, NH2) 6.59-7.95 (m, 12H, Ar-H), 7.35 (t, 1H, NH). MS (EI, m/z (%)): 482 (M+, 16.3). UV/VIS (DMSO, λmax, nm): 293, 291, 276. 4-((2-(5-(4-(Dimethylamino)phenyl)-3-(p-tolyl)-4, 5-dihyd ro-1H-pyrazol-1-yl)-2-oxoethyl)amino)benzene sulfonamide (66): Color: Yellow powder. Yield: 39%. M.p.: 118-120 °C. Rf value: 0.72. FT-IR (KBr, ν, cm−1): 3452-3363 (NH2), 3213 (NH), 1651 (C=O), 1597 (C=N), 1311-1153 (SO2), 1519 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 2.84 (s, 6H, CH3-N), 3.04-3.08 (m, 1H, Ha), 3.69 (dd, 1H, JHb,Ha = 18.00 Hz, JHb,Hx = 11.52 Hz, Hb), 3.95 (m, 2H, CO-CH2), 5.31 (dd, 1H, JHb,Hx = 11.44 Hz, JHa,Hx = 4.20 Hz, Hx), 5.94 (s, 2H, NH2), 6.59 (dd, 4H, J = 8.64, 15.96 Hz, Ar-H), 6.93 (d, 2H, J = 8.640 Hz, Ar- H), 7.23 (t, 1H, NH), 7.26-7.29 (m, 2H, Ar-H), 7.44 (d, 2H, J = 8.60 Hz, Ar-H), 7.64 (d, 2H, J = 8.00 Hz, Ar-H). MS (EI, 70 ev) (m/z): 491 (M+, 100). UV/VIS (DMSO, λmax, nm): 294, 267. 4-((2-(5-(Furan-2-yl)-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol-1- yl)-2-oxoethyl)amino)benzene sulfonamide (67): Color: Yellow powder. Yield: 51%. M.p.: 202-204 °C. Rf value: 0.62. FT-IR (KBr, ν, cm−1): 3444-3356 (NH2), 3213 (NH), 1654 (C=O), 1597 (C=N), 1315-1153 (SO2), 1504 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.36 (s, 3H, CH3), 3.40 (m, 1H, Ha), 3.89 (m, 1H, Hb), 4.62 (s, 2H, CO-CH2), 5.19 (m, 1H, Hx), 5.95 (s, 2H, NH2), 6.27-7.68 (m, 11H, Ar-H), 7.29 (t, 1H, NH). MS (EI, m/z (%)): 438 (M+, 11.4). UV/VIS (DMSO, λmax, nm): 280, 276. N-(5,6-Dimethoxypyrimidin-4-yl)-4-((2-(5-(4-(dimethyl amino)phenyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)-2-oxo ethyl)amino) benzene sulphonamide (68): Color: Yellow powder. Yield: 50%. M.p.: 168-170 °C. Rf value: 0.67. FT-IR (KBr, ν, cm−1): 3398 (NH), 1662 (C=O), 1597 (C=N), 1338-1157 (SO2), 1523 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.85 (s, 6H, CH3-N), 3.66 (s, 3H, OCH3), 3.13 (dd, 1H, JHa,Hb = 17.88 Hz, JHa,Hx = 4.36 Hz, Ha), 3.82-3.87 (m, 1H, Hb), 4.00 (s, 3H, OCH3), 4.33-4.44 (m, 2H, CO-CH2), 4.76-4.78 (t, 1H, NH-CH2), 5.44-5.47 (m, 1H, Hx), 6.63-7.87 (m, 14H, Ar-H). MS (EI, m/z (%)): 615 (M+, 4.7). UV/VIS (DMSO, λmax, nm): 294, 265. N-(5,6-Dimethoxypyrimidin-4-yl)-4-( (2-oxo-2-(5-phenyl- 3-(p-tolyl)-4, 5-dihydro-1H-pyrazol-1-yl)ethyl)amino)benze ne sulfonamide (69): Color: Yellow powder. Yield: 47%. M.p.: 192-194 °C. Rf value: 0.32. FT-IR (KBr, ν, cm−1): 3425 (NH), 1658 (C=O), 1600 (C=N), 1330-1118 (SO2), 1519 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.34 (s, 3H, CH3), 3.62 (s, 3H, OCH3), 3.13-3.15 (m, 1H, Ha), 3.78-3.80 (m, 1H, Hb), 3.85 (s, 3H, OCH3), 4.42-4.49 (m, 2H, CO-CH2), 4.83 (t, 1H, NH-CH2), 5.52-5.59 (m, 1H, Hx), 6.27-7.95 (m, 14H, Ar-H). MS (EI, m/z (%)): 583 (M+, 4.40). UV/VIS (DMSO, λmax, nm): 294. N-(5,6-Dimethoxypyrimidin-4-yl)-4-( (2-(5-(4-(dimethylami no)phenyl)-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl) amino )benzene sulfonamide (70): Color: Yellow powder. Yield: 40%. M.p.: 184-186 °C. Rf value: 0.61. FT-IR (KBr, ν, cm−1): 3394 (NH), 1658 (C=O), 1312 (C=N), 1130-1157 (SO2), 1597 (aromatic C=C). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 2.35 (s, 3H, CH3), 2.84 (s, 6H, CH3-N), 3.01-3.05 (m, 1H, Ha), 3.65-3.66 (m, 1H, Hb), 3.83 (s, 3H, OCH3), 4.00 (s, 3H, OCH3), 4.39-4.42 (m, 2H, CO-CH2), 4.73 (t, 1H, NH-CH2), 5.41-5.45 (m, 1H, Hx), 6.64-7.68 (m, 13H, Ar-H). MS (EI, m/z (%)):629 (M+, 5.3). UV/VIS (DMSO, λmax, nm): 295, 265. 2.3 Antimicrobial activity The synthesized 2-pyrazoline derivatives 41-70 were screened for their in vitro antimicrobial activity against some bacteria employing the disk-diffusion technique. Chloroacetyl pyrazoline derivatives (41-45 and 48-57) was tested against different strains of bacteria, Escherichia coli (ATCC 3008), Klebsiella pneumonia (ATCC 4415), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 6538), Streptococcus mutans (ATCC 25175) and anti fungal activity against Candida albicans (ATCC 10231), compared with standard drug gentamicin, ampicilin and nystatin (Table 1). Micro dilution technique was used to obtain the minimum inhibitory concentrations (MICs) for compound derivatives (41-45 and 48-57), it was determined using 6-well microtiter plates (Table 2). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 35 Table 2. Determination of minimum inhibition concentration (MIC) *. Compound Minimum inhibition concentration, µg/mL Gram negative bacteria Gram positive bacteria Fungi E. coli K. pneumonia P. aeruginosa S. aureus S. mutans C. albicans 41 62.5 - - 31.2 - 250 42 - 62.5 - - - 250 43 31.2 31.2 - 31.5 125 125 44 - - - 125 - - 45 - - - - - 125 48 - - - 31.2 250 125 49 - - - 31.2 - 500 50 250 - - - 31.2 - 51 - - - 15.6 - 62.5 52 - - - - - - 53 - 62.5 - - 125 125 54 - - - 31.2 - 250 55 62.5 - - 31.2 31.2 - 56 - - - - 15.6 125 57 - - - - - 250 * “-”: no activity. 1-(Subistituted-aminoacetyl)-3,5-diaryl-2-pyrazolines de- rivatives (58-70) was tested against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Bacillus subtilis (NCTC 8236), Staphylococcus aureus (ATCC5923) to obtain their anti-bacterial activity and Candida albicans (ATCC 7596) for their anti-fungal activity. 3. Results and discussion All the synthesized compounds were isolated in satisfactory yields, α,β-unsaturated carbonyl derivatives (1- 20) 52-97%, 2-pyrazoline derivatives (21-40) 60-87%, 1- (chloroacetyl)-3,5-diaryl-2-pyrazolines derivatives (41-57) 46-72% and 1-(substituted aminoacetyl)-3,5-diaryl-2-pyrazo- lines derivatives (58-70) 39-75%. The structures of the synthesized α,β-unsaturated carbonyl derivatives (1-20) were confirmed by using FT-IR spectroscopy. It showed several characteristic sharp bands in the IR region, where the bands in the range between 1644- 1665 cm-1 indicated the appearance of the carbonyl C=O group of the formed ketone, which was conjugated to the alkene systems. -C=C- olefein which conjugated to C=O appeared at 1562-1608 cm-1. The absorption band at 1407-1594 cm-1 confirms the aromatic -C=C- group. Resulted α,β-unsaturated carbonyl derivatives undergoes selective cyclization in presence of hydrazine hydrate, in alcohol medium yields 2-pyrazoline derivatives (21-40). The IR spectra of these compounds show the disappearance of C=C (olefinic) and C=O stretching bands at α,β-unsaturated carbonyl derivatives due to the ring closure and appeared of pyrazoline -NH (3249-3421 cm-1) and C=N stretching (1588- 1681 cm-1). IR spectra of chloroacetyl pyrazoline derivatives (41-57), which obtained by the reaction of 2-pyrazoline derivatives with chloroacetyl chloride in presence of triethyl amine, showed disappearance of -NH of pyrazoline derivatives and absorption bands in the regions 1664-1757cm-1 due to the C=O and 1573-1671 cm-1 corresponding to C=N stretching . Compounds 58-67 showed two stretching vibration absorption bands at range 3482-3441 (asym) and 3392-3356 (sym) associated with NH2, and stretching vibration absorption bands at 3240-3213 cm-1 for NH group. All this type of compounds showed two bands at 1396-1311 (asym) and 1155-1149 cm-1 due to appearance of SO2 group. Compounds 68-70 showed absorption band at 3425-3394 cm-1 confirms the NH group. Two bands at 1338-1330 (asym) and 1157-1118 cm-1 (sym) confirm SO2 group. 1H NMR spectra of compounds 58-67 showed ABX system due to germinal-vicinal multiple coupling between two protons Ha, Hb and Hx proton of pyrazoline ring. Ha trans proton showed doublet of doublets at about δ 3.11-3.48 ppm. Hb cis proton appeared at δ 3.65-3.93 ppm as doublet of doublets. Hx proton also showed doublet of doublets at δ 5.19- 5.74 ppm due to vicinal coupling with two magnetically non- equivalent protons Ha, Hb. COCH2 methylene protons, present in all compounds, appeared at δ 4.62-4.82 ppm as two doublets. All the other aromatic and aliphatic protons were observed at the expected regions. Ha proton of compounds 68-70 appeared at δ 3.01-3.40, δ 3.57-4.54 Hb proton and δ 5.11-5.59 ppm Hx. The signal for protons attached with carbonyl group appeared at δ 4.01-4.33 ppm. Protons of primary amine showed singlet peak at δ 5.94- 5.95 ppm. Proton of secondary amine appeared as triplet or distorted triplet at δ 4.73-7.44 ppm. Synthesized compounds 41-70 were tested for in vitro antimicrobial activity by the disk diffusion technique. The antimicrobial screening suggests that the synthesized compounds 41-57 showed moderate activity against the tested organisms (Table 1). The compounds 41, 48, 51 and 56 tested against S.aureus, showed significant antimicrobial activity when compared to standard drug ampicillin. The preliminary in vitro test results of new synthesized compounds 58-70 which bearing sulfanilamido moiety was negatives against the five studied microorganisms such as E. coli, P. aeruginosa, B. subtilis, S. aureus and C. albicans. On the bases of these results, we summarized that introduce of sulfonilamide or sulfadoxine moiety in chloroacetylpyrazline derivatives led to complete loss of their antimicrobial activity. 4. Conclusion In summary, a series of 2-pyrazoline derivatives bearing sulfanilamido moiety have been prepared. Initially, α,β- unsaturated carbonyl derivatives (1-20) were synthesized via the base-catalyzed Claisene Schmidt condensation of equilmolar quantities of aromatic aldehydes and aromatic ketones in presence of 10% NaOH in ethanol (Scheme 1). Secondly, 3,5-diaryl-2-pyrazoline derivatives (21-40) were obtained by the cyclization of α,β-unsaturated compounds with hydrazine monohydrate 98% in absolute ethanol. The ring closure reaction of 3,5-diaryl-2-pyrazolines (21-40) with chloroacetyl chloride afforded 1-(chloroacetyl)-3,5-diaryl-2- pyrazolines derivatives (41-57). The reaction of chloroacetyl pyrazoline derivatives with aryl amine (sulfanilamide/ sulfadoxine) in dimethylformmaide yielded the final compounds 1-(substituted aminoacetyl)-3,5-diaryl-2-pyrazo- lines derivatives (58-70). The purity of the prepared compounds was checked by TLC and the structures are identified by spectral data. Also, the antibacterial and antifungal evaluations of synthesized compounds 41-45 and 48-70 against different microorganism were reported. Most of 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 36 Almahdi et al. / European Journal of Chemistry 10 (1) (2019) 30-36 the synthesized compounds 41-57 showed moderate antimicrobial activity and no activity observed in synthesized compounds 58-70. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID Maysoon Mohammed Almahdi http://orcid.org/0000-0002-9970-5662 Ahmed Elsadig Mohamed Saeed http://orcid.org/0000-0002-7317-8040 Nadia Hanafy Metwally http://orcid.org/0000-0002-3591-7148 References [1]. Yusuf, M.; Jain, P. Arab. J. Chem. 2014, 7, 553-596. [2]. Rani, M.; Yusuf, M. Eur. J. Chem. 2012, 3(4), 406-410. [3]. Gokhan-Kelekci, N.; Koyunoglu, S.; Yabanoglu, S.; Yelekci, K.; Ozgen, O.; Ucar, G.; Erol, K.; Kendi, E.; Yesilada, A. Bioorg. Med. Chem. 2009, 17, 675-689. [4]. Shinkar, S. A.; Shetty, V. J.; Jagdale, D. M. World J. Pharm. Pharm. Sci. 2015, 4, 505-514. [5]. Shah, S.; Ziauddin, H. M.; Zameer, M.; Khan, T.; Baseer, M. A. Int. J. Curr. Pharm. Res. 2011, 2, 34-36. [6]. Karabacak, M.; Altıntop, M. D.; Ciftci, H. I.; Koga, R.; Otsuka, M.; Fujita, M.; Ozdemir, A. Molecules 2015, 20, 19066-19084. [7]. Kumar, K. A.; Govindaraju, M. Int. J. Chem. Tech. Res. 2015, 8, 313- 322. [8]. Ziani, N.; Lamara, K.; Sid, A.; Willem, Q.; Dassonneville, B.; Demonceau, A. Eur. J. Chem. 2013, 4(2), 176-179. [9]. Rahman, Md. A.; Siddiqui, A. A.; Int. J. Pharm. Sci. Drug Res. 2010, 2, 165-175. [10]. Khan, S. A.; Asiri, A. M.; Kumar, S.; Sharma, K. Eur. J. Chem. 2014, 5(1), 85-90. [11]. Mahdi, M. F.; Raauf, A. M. R.; Mohammed, N. M. Eur. J. Chem. 2015, 6(4), 461-467. Copyright © 2019 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.1.30-36.1791 http://orcid.org/0000-0002-9970-5662 http://orcid.org/0000-0002-7317-8040 http://orcid.org/0000-0002-3591-7148 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Materials and methods 2.2. Synthesis 2.2.1. Synthesis of α,β-unsaturated carbonyl derivatives (1-20) 2.2.2. Synthesis of 3,5-diaryl-2-pyrazoline derivatives (21-40) 2.2.3. General method for the synthesis of 1-(chloroacetyl)-3,5-diaryl-2-pyrazolines derivatives (41-57) 2.2.4. General method for the synthesis of 1-(subistituted aminoacetyl) -3,5-diaryl-2-pyrazolines derivatives (58-70) 2.3 Antimicrobial activity 3. Results and discussion 4. Conclusion ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: