Evaluating the Synthesis of Bis-pyrazolines

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  • 336 Evaluating the Synthesis of Bis-pyrazolines Vol 51

    Nosrat O. Mahmoodi,* Bahman Sharifzadeh, Manouchehr Mamaghani, and Khalil Tabatabaeian

    Department of Organic Chemistry, Universitoodnd iem02/iley

    azids. Bl aund

    and biosynth s heterocy-clic compouChalcone

    thiazines, pforms: pyra

    Following our interest in synthesis of bis-intelligent

    Synthetic efforts toward bis-chalcones 5ah commencedwith exploration of the critical base-catalyzed aldol reac-

    etophenonedroxide asis processon reaction 2013 HeteroCorporation1-thiocarboxamides (bis-pyrazolines) 6ah (Tabheterocyclic compounds and various procedures have beendeveloped for their syntheses [21]. Developing the realmof heterocyclic chemistry for the past several years becauseof its ready accessibility and the broad spectrum of bio-logical activity of the products as antibacterial [19], anti-fungal [21], and anti-inammatory [20] substances wasconsidered extensively. A survey of literature in the recentpast reveals that some pyrazoline derivatives possessantibacterial [19], anti-inammatory [20], and antifungaleffects [21].

    was completed within 30min in a variety of solvents. Incontrast, formation of the second chalcone was far moresluggish. This procedure gave high yields of the desiredbis-a, b-unsaturated ketone with no undesirable side reac-tions. The products precipitated from the reaction mixturein a relatively pure state and were easily recrystallized.Reaction of 1 equiv bis-2-propen-1-ones 5ah with

    2 equiv thiosemicarbazide in reuxing ethanolic KOH solu-tion directly afforded bis-3-aryl-4,5-dihydro-1H-pyrazole-

    le 1).nds [1620].cyclization leads to the preparation ofyrimidines, pyrazoles, and their reducedzolines are well-known nitrogen-containing

    tion of bis-aldehydes 3ae with appropriate acderivatives 4a-d in ice bath using sodium hycatalyst (Scheme 1). Detailed studies of thconrmed that the rst aldol-type condensatiesis of other avonoids and variou[15]. The importance of these compounds is due not onlyto these properties but also to their biological activitiesand the fact that they are intermediates in the synthesisRESULTS AND DISCUSSION*E-mail: mahmSupporting Information may be fou

    Received NovDOI 10.10

    Published online 6 November 2013 in W

    The bis-cyclization of chalcone with thiosemicarbcompounds, thiocarbamoyl bis-pyrazoline derivativecondensation between 1mol bis-aldehyde and 2mohydroxide as a catalyst. The structures of all compospectral data and by elemental analyses.

    J. Heterocyclic Chem., 51, 336 (2014).

    INTRODUCTION

    a,b-Unsaturated ketones are biogenetic precursors ofavonoids in higher plants. Also known chemically aschalcones, they consist of open-chain avonoids in whichthe two aromatic rings are joined by a three-carbon chain[1]. They display a wide range of pharmacological proper-ties, including cytotoxity toward cancer cell lines [2,3],antimitotic [4], antimutagenic [5] and antitumor-promotingactivities, antibacterial [6], antiviral [7], anti-inammatory[8], antiulcerative [9], and hepatoprotective activities[10]. They are also useful in materials science elds suchas nonlinear optics [11], optical limiting [12], electrochem-ical sensing [13], Langmuir lms, and photoinitiatedpolymerization [14]. Various chalcone derivatives arenotable materials for their second harmonic generationcompounds [2229], here we report synthesis of bis-pyrazolines capable of serving as bis-drugs. The reportsdescribing some bis-heterocyclic compounds beingcompared with their mono-heterocyclic analogues, whichpresent superior medicinal and pharmacological activities[30], prompted us to design and synthesize bis-pyrazolines6ah. The structural evaluations, properties, and syntheticroutes toward bis-pyrazolines have been reported in limitedsources [31,32].These observations led us to synthesize new bis-chalcones

    and their corresponding bis-pyrazoline. All new compoundshave been characterized by IR, 1H-NMR, 13C-NMR, andelemental analyses.y of Guilan, P.O. Box 1914, Rasht, Irani@guilan.ac.irn the online version of this article.ber 28, 2011jhet.1683Online Library (wileyonlinelibrary.com).

    e under basic condition led to the formation of newis-chalcones were prepared by a ClaisenSchmidt

    cetophenone derivatives in the presence of sodiums were elucidated by IR, 1H NMR, and 13C NMR

  • Scheme 1

    337Evaluating the Synthesis of Bis-pyrazolinesMarch 2014The cyclization of the bis-chalcones into thecorresponding bis-pyrazolines 6ah was accomplished bythe reaction of the chalcones with thiosemicarbazide over24 h. The rst pyrazoline reaction was completed within~5 h in a variety of solvents and was attended by the lossof water followed by endo-fashion intramolecular cycliza-tion. The second pyrazoline formation was much slower;probably, this is attributed to the result of increased sterichindrance around the second chalcone moiety relative tothe rst one or the decreased electrophilicity and/or itslipophilicity of this intermediate.The mechanism of this reaction involves formation of

    hydrazones followed by subsequent addition of NH to theolenic bond leading to the formation of target bis-pyrazolines.

    Journal of Heterocyclic ChemiThe chemical structures of the synthesized compoundswere established by spectroscopic data (FTIR, 1H NMR,and 13C NMR) and elemental analyses. The IR spectrumof bis-chalcones 5ah exhibited the characteristic band at16451690 cm1, which indicates the presence of a,b-unsaturated CO group. The IR spectra of bis-pyrazolines6ah reveal the presence of thiocarboxamide amino-stretching vibration bands at = 34823123 cm1, absorp-tion bands in the regions 15091610 cm1 correspondingto CN stretching bands because of ring closure, andpeaks in the regions 13551365 and 10551096 cm1,which indicate the presence of CS and CN groups.The structure of the compounds was further conrmed

    by 1H NMR and 13C NMR in CDCl3 as solvent. The1H

    stry DOI 10.1002/jhet

  • Table 1

    Structures of synthesized bis-pyrazolines (6ah) with alkyl linkages.

    mp (C) Yield (%) Product Entry

    220225 79 6a

    215220 78 6b

    184189 70 6c

    179185 70 6d

    171179 71 6e

    174180 74 6f

    227235 72 6g

    (Continued)

    338 N. O. Mahmoodi, B. Sharifzadeh, M. Mamaghani, and K. Tabatabaeian Vol 51

    Journal of Heterocyclic Chemistry DOI 10.1002/jhet

  • NMR spectrum bis-chalcones 5ah showed two signals atd 7.787.80 (CCH) and 7.527.56 ppm (COCH) asdoublet with J = 15.6Hz that demonstrate trans HCCHformation of bis-chalcones. The 1H NMR spectrum of bis-pyrazolines 6ah showed a sharp singlet at d 9.6 10.4 dueto the NH2 protons that disappear when adding a drop ofD2O to the CDCl3 solution. The geminal methylene protonsof the pyrazoline CH2 protons (HA and HB) appear in theregion of 3.113.2 ppm (JAB=17.44Hz, JAX=3.08Hz, HA)and 3.833.9 ppm (JAB = 17.45Hz, JBX = 11.13Hz, HB)as doublet of doublets in all of the compounds. The CH(HX) proton appeared as doublet of doublets in the region

    5.996.11 ppm (JAX = 3.08Hz, JBX = 11.12Hz, HX) due tovicinal coupling with two nonequivalent geminal protonsof the adjacent carbon atom. Protons belonging to the aro-matic ring were observed within the expected chemicalshift region along with their integral values (Scheme 2).The 13C NMR spectra of bis-pyrazolines 6ah showed

    signals at 153.2-159.2 ppm assigned to azomethine carbonof the pyrazoline ring. Thiocarboxamide carbons (CS)displayed a signal at 174.0179.1 ppm for all of the com-pounds. The signals due to the aromatic and aliphaticcarbon groups resonate at their usual positions (see theSection on Experimental).

    Table 1

    (Continued)

    mp (C) Yield (%) Product Entry

    199206 77 6h

    eme

    March 2014 339Evaluating the Synthesis of Bis-pyrazolinesSchJournal of Heterocyclic Chemi2stry DOI 10.1002/jhet

  • as white crystals from EtOHwater as 3 : 1 v/v, mp 128130C,

    340 N. O. Mahmoodi, B. Sharifzadeh, M. Mamaghani, and K. Tabatabaeian Vol 51EXPERIMENTAL

    The IR absorption bandmaxima weremeasuredwith a ShimadzuUV-2100 spectrophotometer (Japan). Chemicals were purchasedfrom Fluka (Buchs, Switzerland), Merck (Darmstadt, Germany),and Aldrich (Munich, Germany). Melting points are uncorrectedand determined by Mettler Fp5 melting point apparatus. AllNMR data were recorded in CDCl3 using a Bruker Avance400-MHz spectrometer. Chemical shifts are reported in partsper million (d) using deuterated solvents as internal references.Elemental analyses were made by a Carlo Erba EA1110CNNO-S analyzer and agreed with the calculated values.

    General procedure for the synthesis of bis-chalcones (5ah). Asolution of acetophenone derivatives (2 equiv) and appropriatecarboxaldehydes 3ae (1 equiv) in ethanolic solution of NaOH(10%) was stirred for 5 h at room temperature. The separated solidwas collected and recrystallized from EtOH.

    Synthesis of bis(3-aryl-4, 5-dihydro-1H-pyrazole-1-thiocarbo-xamides) 6ah (general procedure). A solution of bis-chalcones5ah (2.5mmol) and thiosemicarbazide (5mmol) in absoluteEtOH (25mL) containing KOH (6mmol) was boiled under reuxfor 24 h. The separated solid after reuxing was cooled by addinga few pieces of cracked ice. The pale yellow crystals werecollected, washed with water, and recrystallized from a suitablesolvent affording 6ah.

    (E)-1-(2,3-Dimethoxyphenyl)-3-(3-((4-((3-((E)-3-(3,4-dimetho-xyphenyl)-3-oxoprop-1-en-1-yl)phenoxy)methyl)benzyl)oxy)phenyl)prop-2-en-1-one (5a). This compound was obtained as whitecrystals from EtOHwater as 3 : 1 v/v, mp 115117C, yield 85%.IR (KBr): n=3040 (ArH), 2921 (C-H), 1647 (CO), 1584 (CC).1H NMR (400-MHz, CDCl3): 7.78 (d, 2H, J=15.6Hz, CCH),7.62 (d, 2H, J=15.6Hz, COCH), 6.97.7 (m, 18H, ArH), 5.2 (s,4H, benzyl-CH2), 3.964.00 (s, 12H, substituted-OCH3),

    13C NMR(400MHz, CDCl3) (d/ppm): 190.07 (CO), 112159 (Ar-C andCC), 69.89 (CH2-benzyl), 56.21 (substituted-OCH3). Molecularweight: 670.75. Anal. Calcd. for C42H38O8: C, 75.21; H, 5.71;found C, 75.23; H, 5.70.

    (E)-3-(3-((4-((3-((E)-3-Oxo-3-(m-tolyl)prop-1-en-1-yl)phenoxy)methyl)benzyl)oxy)phenyl)-1-(p-tolyl)prop-2-en-1-one (5b). Thiscompound was obtained as white crystals from EtOHwater as3 : 1 v/v, mp 109111C, yield 85%. IR (KBr): n=3060 (ArH),2924 (CH), 1653 (CO), 1610 (CHCH), 1541 (CC); 1HNMR (400MHz, CDCl3): 7.96 (d, 2H, J=15.6Hz, CCH), 7.78(d, 2H, J=15.6Hz, COCH), 6.97.7 (m, 18H, ArH), 5.17(s, 4H, benzyl-CH2), 2.46 (s, 6H, substituted-CH3),

    13C NMR(400MHz, CDCl3) (d/ppm): 190.08 (CO), 112159 (Ar-C andCC), 69.89 (CH2-benzyl), 21.72 (substituted-CH3). Molecularweight: 578.70. Anal. Calcd. for C40H34O4: C, 83.02; H, 5.92;found C, 83.33; H, 5.90.

    (2E,20E)-3,30-((Butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(1-phenylprop-2-en-1-one) (5c). This compound was obtainedas white crystals from EtOHwater as 3 : 1 v/v, mp 101104C,yield 81%. IR (KBr): n=3060 (ArH), 2924 (CH), 1653 (CO),1610 (CHCH), 1541 (CC); 1H NMR (400MHz, CDCl3): 7.82(d, 2H, J=15.6Hz, CCH), 7.45 (d, 2H, J=15.6Hz, COCH),6.97.9 (m, 18H, ArH), 4.174.16 (t, 4H, OCH2, J=5.2Hz),2.682.55 (t, 4H, CH2, J= 5.2Hz),

    13C NMR (400MHz,CDCl3) (d/ppm):190.70 (CO), 112161 (Ar-C and CC), 67.60(OCH2), 26.00 (CH2). Molecular weight: 502.60. Anal. Calcd.for C34H30O4: C, 81.25; H, 6.02; found C, 81.24; H, 6.06.

    (2E,20E)-3,30-((Butane-1,4-diylbis(oxy))bis(3,1-phenylene))bis(1-(p-tolyl)prop-2-en-1-one) (5d). This compound was obtainedJournal of Heterocyclic Chemiyield 80%. IR (KBr): n=3040 (ArH), 2917 (CH), 1650 (CO),1602 (CHCH), 1537 (CC); 1H NMR (400MHz, CDCl3):7.79 (d, 2H, J=16Hz, CCH), 7.54 (d, 2H, J=16Hz, COCH),6.97.9 (m, 16H, ArH), 4.154.13 (t, 4H, OCH2), 2.41 (s, 6H,substituted-CH3), 2.082.06 (t, 4H, CH2),

    13C NMR(400MHz, CDCl3) (d/ppm): 190.02 (CO), 112159 (Ar-C andCC), 67.6 (OCH2), 26.00 (CH2), 21.72 (substituted-CH3).Molecular weight: 530.25. Anal. Calcd. for C36H34O4: C, 81.48;H, 6.46; found C, 81.44; H, 6.46.

    (2E,20E)-3,30-(3,30-(Butane-1,4-diylbis(oxy))bis(3,1-phenylene))bis(1-(4-methoxyphenyl)prop-2-en-1-one) (5e). This compoundwas obtained as white crystals from EtOHwater as 3 : 1 v/v, mp107110C, yield 80%. IR (KBr): n=3061 (ArH), 2936 (CH),1649 (CO), 1612 (CHCH), 1538 (CC); 1H NMR (400MHz,CDCl3): 7.78 (d, 2H, J=15.6Hz, CCH), 7.55 (d, 2H,J = 15.6 Hz, COCH), 6.97.9 (m, 16H, ArH), 4.154.14(t, 4H, OCH2), 3.90 (s, 6H, substituted-OCH3), 2.072.06(t, 4H, CH2),

    13C NMR (400MHz, CDCl3) (d/ppm): 192.20(CO), 112163 (Ar-C and CC), 67.5 (OCH2), 55.53(substituted-OCH3), 25.99 (CH2). Molecular weight: 562.65. Anal.Calcd. for C36H34O6: C, 76.85; H, 6.09; found C, 76.84; H, 6.08.

    (2E,20E)-3,30-(3,30-(Pentane-1,5-diylbis(oxy))bis(3,1-phenylene))bis(1-p-tolylprop-2-en-1-one) (5f). This compoundwas obtainedas white crystals from EtOHwater as 3 : 1 v/v, mp 140142C,yield 83%. IR (KBr): n=3055 (ArH), 2914 (CH), 1653 (CO),1611 (CHCH), 1539 (CC); 1H NMR (400MHz, CDCl3): 7.79(d, 2H, J=15.6Hz, CCH), 7.54 (d, 2H, J=15.6Hz, COCH),6.97.9 (m, 16H, ArH), 4.104.06 (m, 4H, OCH2), 2.46(s, 6H, substituted-CH3), 1.981.92 (m, 4H, CH2), 1.781.71(m, 2H, CH2),

    13C NMR (400MHz, CDCl3) (d/ppm): 190.25(CO), 112160 (Ar-C and CC), 67.90 (OCH2), 28.91(CH2), 22.81 (CH2), 21.70 (substituted-CH3). Molecular weight:544.68. Anal. Calcd. for C37H36O4: C, 81.59; H, 6.66;found C,81.58; H, 6.67.

    (2E,20E)-3,30-(3,30-(Hexane-1,6-diylbis(oxy))bis(3,1-phenylene))bis(1-(4-methoxyphenyl)prop-2-en-1-one) (5g). This compoundwas obtained as white crystals from EtOHwater as 3 : 1 v/v, mp109110C, yield 81%. IR (KBr): n=3055 (ArH), 2924 (CH),1648 (CO), 1600 (CHCH), 1546 (CC); 1H NMR (400MHz,CDCl3): 7.79 (d, 2H, J=15.6Hz, CCH), 7.53 (d, 2H,J= 15.6Hz, COCH), 6.98.1 (m, 16H, ArH), 4.07 (s, 6H,substituted -OCH3), 3.923.89 (t, 4H, OCH2), 1.891.87 (m,4H, CH2), 1.611.59 (m, 4H, CH2)

    13C NMR (400MHz,CDCl3) (d/ppm): 192.24 (CO), 112164 (Ar-C and CC),68.12 (OCH2), 55.53 (substituted-OCH3), 29.2 (CH2), 25.9(CH2). Molecular weight: 590.70. Anal. Calcd. for C38H38O6: C,77.26; H, 6.48; found C, 77.25; H, 6.49.

    (2E,20E)-3,30-(3,30-(Hexane-1,6-diylbis(oxy))bis(3,1-phenylene))bis(1-(3,4-dimethoxyphenyl)prop-2-en-1-one) (5h). Thiscompound was obtained as white crystals from EtOHwater as3 : 1 v/v, mp 111114C, yield 84%. IR (KBr): n=3059 (ArH),2912 (CH), 1651 (CO), 1609 (CHCH), 1541 (CC); 1HNMR (400MHz, CDCl3): 7.79 (d, 2H, J= 15.6Hz, CCH),7.56 (d, 2H, J=15.6Hz, COCH), 6.97.8 (m, 16H, ArH),4.084.04 (m, 4H, OCH2), 4.003.97 (s, 12H, substituted-OCH3), 1.901.88 (m, 4H, CH2), 1.631.61 (m, 4H, CH2),

    13CNMR (400MHz, CDCl3) (d/ppm): 192.24 (CO), 112164(Ar-C and CC), 68.02 (OCH2), 56.11 (substituted-OCH3), 29.23 (CH2), 25.9 (CH2). Molecular weight: 650.76.Anal. Calcd. for C40H42O8: C, 73.83; H, 6.51; found C,73.85; H, 6.49.stry DOI 10.1002/jhet

  • 5-(3-(4-((3-(1-Carbamothioyl-3-(2,3-dimethoxyphenyl)-4, (CH-pyrazoline), 63.3 (OCH ), 43.18 (CH -pyrazoline), 25.96

    March 2014 341Evaluating the Synthesis of Bis-pyrazolines5-dihydro-1H-pyrazol-5-yl)phenoxy)methyl)benzyloxy)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide)(6a). This compound was obtained as pale yellow crystals fromEtOHwater as 3 : 1 v/v, mp 220225C, yield 79%. IR (KBr):n=3441, 3221, 3112 (NH2), 1571, 1509, 1359, 1258 (CN,CC, CS, CO). 1H NMR (400MHz, CDCl3): 9.58 (s, 4H,NH2, D2O exch.), 6.97.7 (m, 18H, ArH), 6.016.04 (dd, 2H,Hx, JAX=3.2Hz, JBX= 11.2Hz), 5.15.14 (d, 2H, J=16Hzbenzyl-CH), 5.035.07 (d, 2H, J=16Hz benzyl-CH), 3.944.00(s, 12H, substituted-OCH3), 3.793.86 (dd, 2H, HB,JBX= 11.2Hz, JAB= 17.3Hz), 3.163.22 (dd, 2H, HA,JAX=3.2Hz, JAB= 17.3Hz),

    13C NMR (400MHz, CDCl3)(d/ppm): 176.28 (CS), 152.35 (CN), 112159 (Ar-C), 69.98(CH-pyrazoline), 63.33 (CH2-benzyl), 56.06 (substituted-OCH3),43.13 (CH2-pyrazoline). Molecular weight: 816.99. Anal. Calcd.for C44H44N6O6S2: C, 64.69; H, 5.43; N, 10.29; found C, 64.67;H, 5.41; N, 10.27.

    5-(3-(4-((3-(1-Carbamothioyl-3-m-tolyl-4,5-dihydro-1H-pyrazol-5-yl)phenoxy)methyl)benzyloxy)phenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b). This compoundwas obtained as pale yellow crystals from EtOHwater as 3 : 1 v/v,mp 215220C, yield 78%. IR (KBr): n=3439, 3223, 3115(NH2), 1573, 1508, 1359, 1259 (CN, CC, CS, CO).

    1HNMR (400MHz, CDCl3): 9.48 (s, 4H, NH2, D2O exch.), 6.97.8(m, 20H, ArH), 6.016.04 (dd, 2H, Hx, JAX=3.4Hz,JBX= 11.4Hz), 5.15.14 (d, 2H, J=17Hz benzyl-CH), 5.025.07(d, 2H,, J=17Hz benzyl-CH), 3.793.86 (dd, 2H, HB,JBX= 11.4Hz, JAB= 17.6Hz), 3.163.22 (dd, 2H, HA,JAX=3.4Hz, JAB= 17.6Hz), 2.42 (s, 6H, substituted-CH3),

    13CNMR (400MHz, CDCl3) (d/ppm): 176.44 (CS), 155.54 (CN),112159 (Ar-C), 69.59 (CH-pyrazoline), 63.13 (CH2-benzyl),42.83 (CH2-pyrazoline), 21.55 (substituted-CH3). Molecularweight: 724.94. Anal. Calcd. for C42H40N6O2S2: C, 69.59; H,5.56; N, 11.59; found C, 69.58; H, 5.53; N, 11.56.

    5,5 0-((Butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(3-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide) (6c).This compound was obtained as pale yellow crystals from N,N-dimethylformamidewater as 3 : 1 v/v, mp 184189C, yield70%. IR(KBr): n=3423, 3240, 3132 (NH2), 1597, 1501, 1349,1253(CN, CC, CS, CO); 1H NMR (400MHz, CDCl3): 9.56(s, 4H, NH2, D2O exch.), 6.97.8 (m, 18H, ArH), 6.045.99(dd, 2H, Hx, JAX=3.2Hz, JBX= 11.2Hz), 4.083.99 (t, 4H,OCH2), 3.853.78 (dd, 2H, HB, JBX= 11.2Hz, JAB= 18Hz),3.223.17 (dd, 2H, HA, JAX=3.2Hz, JAB= 17.6Hz), 1.991.94(t, 4H, CH2),

    13C NMR (400MHz, CDCl3) (d/ppm): 176.60(CS), 156.11 (CN), 112159 (Ar-C), 67.50 (CH-pyrazoline),62.99 (OCH2), 43.15 (CH2-pyrazoline), 25.93 (CH2),Molecular weight: 648.84. Anal. Calcd. for C36H36N6O2S2: C,66.64; H, 5.59; N, 12.95; found C, 66.61; H, 5.56; N, 12.93.

    5,50-(3,30-(Butane-1,4-diylbis(oxy))bis(3,1-phenylene))bis(3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide) (6d).This compound was obtained as pale yellow crystals fromEtOHwater as 3 : 1 v/v, mp 179185C, yield 70%. IR (KBr):n=3441, 3221, 3112 (NH2), 1585, 1489, 1339, 1252 (CN,CC, CS, CO). 1H NMR (CDCl3): 10.25 (s, 4H, NH2, D2Oexch.), 6.97.8 (m, 16H, ArH), 6.046.01 (dd, 2H, Hx,JAX = 3.2 Hz, JBX = 11.2 Hz), 4.063.98 (t, 4H, OCH2),3.853.78 (dd, 2H, HB, JBX= 11.2Hz, JAB= 17.6Hz), 3.223.17(dd, 2H, HA, JAX=3.2Hz, JAB= 17.6Hz), 2.41 (s, 6H,substituted-CH3), 2.031.93 (t, 4H, CH2),

    13C NMR (CDCl3)(d/ppm): 176.42 (CS), 156.27 (CN), 112159 (Ar-C), 67.64Journal of Heterocyclic Chemi2 2

    (CH2), 21.62 (substituted-CH3). Molecular weight: 676.89.Anal. Calcd. for C38H40N6O2S2: C, 67.43; H, 5.96; N, 12.42;found C, 67.41; H, 5.93; N, 12.40.

    5,50-(3,30-(Butane-1,4-diylbis(oxy))bis(3,1-phenylene))bis(3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide)(6e). This compound was obtained as pale yellow crystals fromEtOHwater as 3 : 1 v/v, mp171179C, yield 71%. IR (KBr):n=3432, 3211, 3122 (NH2), 1585, 1507, 1354, 1265 (CN,CC, CS, CO). 1H NMR (400MHz, CDCl3) : 10.25 (s, 4H,NH2, D2O exch.), 6.97.8 (m, 16H, ArH), 6.035.99 (dd, 2H,Hx, JAX = 3.2Hz, JBX = 12Hz), 4.063.98 (t, 4H, OCH2), 3.87(s, 6H, substituted-OCH3), 3.843.77 (dd, 2H, HB, JBX = 12Hz,JAB = 18Hz), 3.23.15 (dd, 2H, HA, JAX = 3.2Hz, JAB = 18Hz),1.961.92 (t, 4H, CH2),

    13C NMR (400MHz, CDCl3) (d/ppm):176.05 (CS), 156.04 (CN), 112159 (Ar-C), 67.65(CH-pyrazoline), 63.25 (OCH2), 55.51 (substituted-OCH3)43.17 (CH2-pyrazoline), 25.9 (CH2). Molecular weight: 708.89.Anal. Calcd. for C38H40N6O4S2: C, 64.38; H, 5.69; N, 11.86;found: C, 64.36; H, 5.65; N, 11.84.

    5,50-(3,30-(Pentane-1,5-diylbis(oxy))bis(3,1-phenylene))bis(3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide) (6f). Thiscompound was obtained as pale yellow crystals from EtOHwateras 3 : 1 v/v, mp174180C, yield 74%. IR (KBr): n=3421, 3251,3109 (NH2), 1579, 1510, 1349, 1260 (CN, CC, CS, CO).1H NMR (400MHz, CDCl3): 10.3 (s, 4H, NH2, D2O exch.),6.97.8 (m, 16H, ArH), 6.016.04 (dd, 2H, Hx, JAX=3.2Hz,JBX= 11.2Hz), 3.944.03 (m, 4H, OCH2), 3.793.86 (dd, 2H,HB, JBX= 11.2Hz, JAB= 17.6Hz), 3.163.22 (dd, 2H, HA,JAX=3.2Hz, JAB= 17.6Hz), 2.41 (s, 6H, substituted-CH3),1.881.80 (m, 4H, CH2), 1.681.66 (m, 2H, CH2)

    13C NMR(400MHz, CDCl3) (d/ppm): 176.47 (CS), 156.24 (CN),112159 (Ar-C), 68 (CH-pyrazoline), 63.30 (OCH2), 43.18(CH2-pyrazoline), 29 (CH2), 22.7 (CH2), 21.6 (substituted-CH3) .Molecular weight: 690.92. Anal. Calcd. for C39H42N6O2S2: C,67.80; H, 6.13; N, 12.16; found C, 67.77; H, 6.10; N, 12.12.

    5,50-(3,30-(Hexane-1,6-diylbis(oxy))bis(3,1-phenylene))bis(3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide)(6g). This compound was obtained as pale yellow crystals fromMeOHwater as 3 : 1 v/v, mp 227235C, yield 72%. IR (KBr):n=3439, 3241, 3132 (NH2), 1591, 1503, 1361, 1248 (CN,CC, CS, CO). 1H NMR (400MHz, CDCl3) : 10.15 (s, 4H,NH2, D2O exch.), 6.97.8 (m, 16H, ArH), 6.035.99 (dd, 2H,Hx, JAX = 3.2Hz, JBX = 11.6Hz), 3.944.03 (m, 4H, OCH2),3.87 (s, 6H, substituted-OCH3), 3.853.78 (dd, 2H, HB,JBX = 11.6Hz, JAB = 17.6Hz), 3.223.16 (dd, 2H, HA,JAX = 3.2Hz, JAB = 17.6Hz), 1.841.80 (m, 4H, CH2),1.381.34 (m, 4H, CH2).

    13C NMR (400MHz, CDCl3)(d/ppm): 176.02 (CS), 156.01 (CN), 112159 (Ar-C), 68.01(CH-pyrazoline), 63.28 (OCH2), 55.49 (substituted-OCH3)43.19 (CH2-pyrazoline), 29.1 (CH2), 25.9 (CH2). Molecularweight: 736.95. Anal. Calcd. for C40H44N6O4S2: C, 65.19; H,6.02; N, 11.40; found C, 65.16; H, 6.00; N,11.37.

    5,50-(3,30-(Hexane-1,6-diylbis(oxy))bis(3,1-phenylene))bis(3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide)(6h). This compound was obtained as pale yellow crystals fromDMFwater as 3 : 1 v/v, mp 199206C, yield 77%. IR (KBr):n=3433, 3225, 3116 (NH2), 1589, 1492, 1352, 1254 (CN, CC,CS, CO). 1H NMR (400MHz, CDCl3) : 10.1 (s, 4H, NH2, D2Oexch.), 6.97.8 (m, 14H, ArH), 6.036.00 (dd, 2H, Hx,JAX=3.2Hz, JBX=11.2Hz), 3.994.03 (m, 4H, OCH2), 3.943.96(s, 12H, substituted-OCH3), 3.853.78 (dd, 2H, HB, JBX=11.6Hz,stry DOI 10.1002/jhet

  • JAB=17.2Hz), 3.223.16 (dd, 2H, HA, JAX=3.2Hz, JAB=17.2Hz),1.81.79 (m, 4H, CH2), 1.561.52 (m, 4H, CH2).

    13C NMR(400MHz, CDCl3) (d/ppm): 176.24 (CS), 156.10 (CN), 112159(Ar-C), 67.98 (CH-pyrazoline), 63.36 (OCH2), 56.06 (substituted-OCH3), 43.18 (CH2-pyrazoline), 29.2 (CH2), 25.9 (CH2). Molecularweight: 797.00. Anal. Calcd. for C42H48N6O6S2: C, 63.29; H, 6.07;N, 10.54; found C, 63.26; H, 6.05; N, 10.51.

    Acknowledgment. Financial support from the Research Committeeof University of Guilan is gratefully appreciated.

    REFERENCES AND NOTES

    [1] Rane, R. A.; Telekar, V. N. Bioorg Med Chem Lett 2010,20, 5681.

    [2] Konieczny,M. T.; Konieczny,W.; Sabisz, M.; Skladanowski, A.;Wakiec, R.; Augustynowicz-Kopec, E.; Zwolska, Z. Eur J Med Chem2007, 42, 729.

    [3] Kumar, D.; Kumar, N.M.; Akamatsu, K.; Kusaka, E.; Harada, H.;Ito, T. Bioorg Med Chem Lett 2010, 20, 3916.

    [4] Ducki, S.; Forrest, R.; Hadeld, J. A.; Kendall, A.; Lawrence,N. J.; McGown, A. T.; Rennison, D. Bioorg Med Chem Lett 1998,8, 1051.

    [5] Edenharder, R.; Petersdorff, I. V.; Rauscher, R. Mutat Res1993, 287, 261.

    [12] Shettigar, S.; Umesh, G.; Chandrasekharan, K.; Sarojini, B. K.;Narayana, B. Opt Mater 2008, 30, 1297.

    [13] Delavaux-Nicot, B.; Maynadie, J.; Lavabre, D.; Fery-Forgues,S. J Organomet Chem 2007, 692, 874.

    [14] Lu, Z.; Zhang, F.; Lei, X.; Yang, L.; Xu, S.; Duan, X. ChemEng Sci 2008, 63, 4055.

    [15] Patil, P. S.; Dharmaprakash, S.M.; Ramakrishna, K.; Fun, H. K.;Sai, R.; Kumar, S.; Rao, D. N. J Cryst Growth 2007, 303, 520.

    [16] Chun, H. S.; Hung, C.; Lee, K. T.; Wataru, S.; Masahiko, M.;Ivan, K. C.; Mingfu, W.; Clive, L. Planta 2007, 228, 1043.

    [17] Winkel, B. S. J. The Science of Flavonoids, Springer Science &BusinessMedia, Inc., NY, USA 2006, DOI: 10.1007/9780387288222_3

    [18] Gadow, A.; Joubert, E.; Hansmann, C. F. J Agric Food Chem1997, 45, 632.

    [19] Kumar, Y.; Green, R.; Wise, D. S.; Wotring, L. L.; Townsend,L. B. J Med Chem 1993, 36, 3849.

    [20] Shoman, M. E.; Abdel-Aziz, M.; Aly, O. M.; Farag, H. H.;Morsy, M. A. Eur J Med Chem 2009, 44, 3068.

    [21] Shaharyar, M.; Siddiqui, A. A.; Ali, M. A. Bioorg Med ChemLett 2006, 16, 4571.

    [22] Mahmoodi, N. O.; Zanjanchi, M. A.; Kiyani, H. J Chem Res1997, 6, 438.

    [23] Mahmoodi, N. O.; Kiyani, H.; Tabatabaeian, K.; Zanjanchi, M.A.; Arvand, M.; Sharifzadeh, B. Russ J Org Chem 2010, 46, 884.

    [24] Mahmoodi, N. O.; Kiyani, H. Bull Korean Chem Soc 2004,25, 1417.

    [25] Mahmoodi, N. O.; Yazdanbakhsh, M. R.; Kiyani, H. J ChinChem Soc 2007, 54, 635.

    [26] Arvand, M.; Moghimi, M.; Afshari, A.; Mahmoodi, N. O.Anal Chin Acta 2006, 579, 102.

    342 N. O. Mahmoodi, B. Sharifzadeh, M. Mamaghani, and K. Tabatabaeian Vol 51[6] Pandeya, S. N.; Sriram, D.; Nath, G.; DeClercq, E. Eur J MedChem 1999, 9, 25.

    [7] Biradar, J. S.; Sasidhar, B. S.; Parveen, R. Eur J Med Chem2010, 45, 4074.

    [8] Nowakowska, Z. Eur J Med Chem 2007, 42, 125.[9] Devi, J.M.; Ali, K. S.; Venkatraman, V. R.; Ramakrishnan, S. K.;

    Ramachandran, K. Therochim Acta 2005, 438, 29.[10] Sabzevari, O.; Mahmoudian, S.; Minaei, B.; Paydar, H. Toxicol

    Lett 2010, 196, S213.[11] Sarojini, B. K.; Narayana, B.; Ashalatha, B. V.; Indira, J.;

    Lobo, K. G. J Cryst Growth 2006, 295, 54.Journal of Heterocyclic Chemi[27] Zanjanchi, M. A.; Arvand, M.; Islamnezhad, A.; Mahmoodi,N. O. Talanta 2007, 74, 125.

    [28] Kiyani, H.; Mahmoodi, N. O.; Tabatabaeian, K.; Zanjanchi, M.A.; J Phys Org Chem 2009, 22, 559.

    [29] Kiyani, H.; Mahmoodi, N. O.; Tabatabaeian, K.; Zanjanchi, M.A.; Mendeleev Commun 2009, 19, 203.

    [30] Mahmoodi, N. O.; Rineh, A.; Abdollahi, M.; Foroumadi, A.;Sorkhi, M.; Shaee, A. Arch Pharm Chem Life Sci 2007, 340, 409.

    [31] Ahmed, M. S. H.; El-Sharief Ziad, M. Eur J Med Chem 2009,44, 4315.

    [32] Khan-Kelekc, N. G. Bioorg Med Chem 2007, 15, 5775.stry DOI 10.1002/jhet

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