‘Jour. Chem. Soe. Pak, Vol, 11 No. 2, 1989 1 (Chemistry of Pyrazolines. Part VI. Synthesis of Some New Pyrazolines A.AISMAIL, MEL-MOBAYED, G.H.SAYED AND E.AMOHAMED ‘Chemistry Department, Faculty of Science, Ain Shams Universi, Abbassia, Cairo, Epi. (Receive 100 Octobe, 1967) Previous reports [1-3] dealing with the synthesis and Screening of pyrazolines revealed that some of these compounds exhibited a local anesthetic activity. This paper deals with the Preparation of a new series of pyrazolines. The syn- thesis of 2-pyrazoline derivatives II-XU are outlined in Scheme 1, Reaction of lag with hydrazine hydrate, phenyl ‘hydrazine and benzenesulfonyl hydrazide in ethanol Save the corresponding pyrazolines Tat, Marc and TVars, respectively, ‘The 1-acety, -4ormyi, 1-propionyl and Lbutyryl derivatives V, Vla-c, Vila and VIllab respectively were prepared from the erude pyrazoline IT through the action of acetic, formic, propionic and butyric Acids respectively. Alternatively, the 1- acyl com- Pounds V-VIMI were obtained directly from the chal- ‘one I and hydrazine hydrate in appropriate acid, as solvent, ‘The 'H-NMR (DMSO-d6) spectrum of V showed signals at 7.56.5 (7H, m ArH), 5.74 (2H, $OCH20), 5.17 (1H, q, Cs-Pyrazoline), 3.62 (3H, s, OCHs), 292 (1H, d, Ce-pyrazoline), 262 (1H, d, Cs. yrazoline), 2.10 (3H, s, COCHs). ‘The reaction of the crude parent 2-pyrazotines IL ‘with benzenesulfony! chloride in pyridine afforded an alternative preparation of the 1-benzenesulfonyl Pyrazolines IV, above, whereas with benzoyl chloride the I-benzoyl derivatives IXa-g were obtained. The latter compounds were reduced with lithium ‘Aluminium hydride to the I-benzyl derivatives Xa-b; this is in accordance with our previous results [4], ‘The I-benzyl derivatives were also obtained by N- allylation of crude Hab with benzyl bromide in ‘acetone in the presence of potassium carbonate. Sig- nificantly, chalcones Ia-c react with benzoylhydrazine in refluxing butanol to give pyrazolines IXa-c which ‘were identified by direet comparison with authentic ‘samples (mp, mixed mp and IR). Similarly, the reac- tion of chaleones ta-g with nicotinoylhydrazine af- forded the pyrazolines XIab. The reaction analogous 10 that involving acetylenic ketones and acylhydrazines giving pyrazoles [5]. ‘Treatment of methanolic solution of pyrazolines ih with secondary amine, namely piperidine and aqueous formaldehyde yielded N-Mannich bases Xllab, Attempted a-brominat Presumably via dibromination followed by elimina- tion of hydrogen bromide through the nucleophi action of the N-1 lone pair of electrons. This ‘cordance with the results obtained by Dyakonov 6} ‘When the chalcone Ia was condensed with hhydroxylamine hydrochloride in pyridine, the ‘soxmzoline derivative XIV was obtained.92 Jour. Cherm, Soc. Pak. Vol. 11.No. 2, 1989 MEL-MOBAYED ET.AL Gene >NEW PYROZOLINES Jour. Chem. Soc. Pak. Vol. 11 No, 2, 1989 ‘Table 1: Characterisation of the new Compounds Compousd MPC Viele 5 M Forma Anais % (Found Cale) me Mowe cH N ma 10 8s Cato) nm 530 70 am m9 538 133 me 1s e cameo 90 540 790 sas me 54 1m Me 20 " CaHtycns0: On 40 ™ 365 m2 5 mm Me 90 Py Coranos eo 450 630 36 an 49 ear rm 10 o CoHWaNsos a 40 6=0 5; 6190 44s 637 We ms x0 catanos 2m 40 630 ans 3 386 ow v 0 6 Cuttans0, m0 50 850 ES os 50 528 Ve 1a » Curae04 1% s20 380 m4 oT 494 ast vo 188 % Cottsci m0» 10480 a0 3M ous 477 850 Vie 105, » Cokincisos en 410 880 a8 e039 ase vim ns 6 Cabani0. 70s an a2 eas a8 795 vue 1 n CsthyaNs02 630580 750 aes 657535 a8 via 105 « caltano, 10 sm 70 vu 10 6 Cakinano: 130 610 750 3865 2 se 15 a 105 o Cato m0 510 620 382 m0 sm 00 De 1s o Calwcror mm 4m 730 soos, me 487 aa 9394 Jour. Chem. Soc. Pak. Vol.11 No.2, 1989 M.EL-MOBAYED ET.AL. Continued Table 1: Compound merc iets MFormula ‘Anas % (Found Cale) MMe cH x xe 10 » CatiycI20s an 40 20 404s ap 1m 6 x us ® CoinN0s mm sm “0 0 ras 570 ws x % a cutcNo nwo 560 1 3765 nal 558 78 Xia 10 s Catl0e am 4m 1050 ‘aS an 4m 1007 xD ry 2 Catlucvos as ato 1030 85 10 395 1036 xia s “8 Cattens0s mo 710 1070 3 mn 6sT 1068 x ” * caiwcnsO am 69 110 305 amu 67 sass ala 10 *” Cups sum 380 70 3 sp 30 751 xm = s cuttuBroN0 am 01M Mas 2m 300 1m xiv us » CcaHsnou am 4m 480 sr ae 55 an xv 158 a CctaNOu a 450 490 Ea is 4at 45 ‘As a point of interest, the chalcone dibromide XV was condensed with hydroxylamine hydrochloride in boiling acetic acid, where the isoxazole derivative XVI was obtained. Experimental Mekking points are uncorrected, LR, spectra ‘were measured on a Beckmann IR-20 infrared Spectrophotometer in KBr. The H-NMR spectrum ‘of compound V on a Varian S-60 T instrument using ‘TMS. as an internal standard. All the compounds ‘were crystallized from ethano: except for Ic, TVa, IVb, Xb(benzene), IXa (Pet.ther) and Xa (acetic: acid). Preparation of pyrazolines Hae Utars Ware, Kars and Xlab ‘To a solution of chalcone I (0.01 mol) in ethanol and/or butanol (20 mal), hydrazine hydrate, phenyl- hydrazine, benzenesulfonyl hydrazide, benzoylNEW PYROZOLINES. hydrazine or nicotinoyl hydrazine (0.01 mol) was Added. The reaction misture was relaxed for 5 brs. and then cooled to give solid Hla, Mae, IVa, [Xa £ or Xlach respectively. The IR spectra of Ula-c, Tare IXa-c and Xlach showed bands at 1625-1580 em’ @CHN), those of IXa-c, and Xlach showed ‘bands at 1660-1635 cm’? (vC =O) and those of TVa-¢ ‘showed bands at 1355-1335 em"! (»S02), Preparation of pyrazolines V; Via-s, Viach and VIM @- a To. solution of chalcone I (0.01 mol) in acetic, formic, propionic or butytic acid (20 mi, hydrazine hydrate (0.01 mol) was added and the reaction mix: ture refluxed for 5 hrs. Cooling and evaporation of the solvent afforded sold V, Via-g, Vlac or Villa b THe IR spectra of V, Vig, Vil and Villa b showed bands at 1605-1585 em"(¥C=N) and 1650. 1635 em" (C=O), Preparation of hacl-2_pyrazotines V, Viars, Vilach and VitTach A Solution of II in acetic, formic, propionic or butyric acid (20 ml) was refluxed for 5 hrs. Cooling and evaporation of the solvent gave V, VIa-c, VII oF Villa:b as solids. The IR spectra of V, Vla-c, ‘Vilach and Vifla-h showed bands at 1640-1650 cm! (C=O) and at 1580-1605 em" (vC=N), Preparation of TV1-c and IX AA solution of (0.01 mol) in pyridine (10 ml) was treated with benzenesulfonsl or benzoyl chloride (0.01 mol) and the reaction mixture heated on a ‘water-bath for 2 hrs, cooled and poured into diL HCI to give solid IVacor IXa-g. Preparation of Karls A misture of IXa or IXb (0.01 mol) and lithium ‘aluminum hydride (0.1 mol) in dry ether (20 ml) was refluxed for S hrs, and filtered while hot. Evaporation ‘of the solvent gave Xa or Xb as solids. The IR spectra showed bands between 1605-1600 em’! duc (0(C=n), Jour. Chem. Soe. Pak. Vol. 1 No.2, 198995 Preparation of Xaand Xb ‘To a solution of Hla or I (0.01 mol) in acetone (20 mi) containing anbyd, potassium carbonate (11g), benzyl bromide (0.01 mol) was added and the reac. ‘tion mixture refluxed for 10 hrs. Filtration of the hot reaction mixture followed by evaporation of the sol- vent yielded Xa or Xb. Preparation of the Mannich bases XII. or XM, To a suspension of the pyrazolines Ta or Ub (0.01 mol) and piperidine (0.02 ml) in methanol (20 rm), aqueous formaldehyde (35%, 2.5 ml) was added. ‘The reaction misture was heated on a water-bath for ‘hrs, kept overnight at room temperature and then diluted with water. The resulting solid product was ‘cyptallized to afford the N-Mannich bases XIla or Xllb-The IR spectra showed bands at 1610-1600 emt dueto (”C=N). Preparation of Xa, A solution of pyrazoline Ha or Hb (0.01 mol) in Chloroform (20 ml) was treated with a solution of bromine (0.03 mol) in chloroform (20 ml), The Product obtained was crystallized to give Xilla or XIllb, The IR spectra showed bands at 1610-1600 em" ( C=) and 3420-3380 em" (» NH). Preparation of XIV ‘A mixture of each of Ta (2 g), hydroxylamine hydrochloride (1 g) and pyridine (20 ml) was heated on a water-bath for 5 hrs, cooled and poured into dil, HCl to give XTV. The TR spectra showed bands at 1610 cm due to(v C=N), Preparation of XVI A. minure of XV (2g), hydroxyla hydrochloride (1 g) and acetic acid (20 ml) was refluxed for 5 hrs. The product that separated on cooling was crytalized to give XVI. The IR spectra showed bands at 1600 em" due to (v C=).96 Jour. Chem, Soc. Pak. Vol. 11 No. 2, 1989 References 1. GHosni, and S.F. Saad, Acta Chim. Acad. Sci. Hung. 86, 263 (1975). 2. H.K-Sinha,J.Pharmacol,, 66,54 (1939). 3, R. Andresano, L. Chierici and F. Grivere, 4 5. 6 Arzncio-Forsch., 8, 706 (1958). GH. Sayed, IndJ.Chem., 19, 364 (1980). F.S, AlHajar and S. S. Sabre, J. Heterocyclic Chem. 23, 727 (1986). 1A. Dyakonov, J.Gen. Chem. 17, 67 (1986).