Synthesis and Spectroscopic Investigation of Some New Chalcones and their transformation to pyrazoline derivatives

A series of a new chalcone derivatives (2a-i) containing benzyloxy moiety have been synthesized on the basis of base catalyzed claisen –Schmidt condensation in high yields from the reaction of the prepared starting material 3-(4-cholrobenzyloxy) paraldehyde (1)with different substituted acetophenones. The prepared chalcones were treated with hydrazine hydrate according to the Michael addition reaction to obtain new pyrazoline deivatives (3a-i). Finally the structures of the synthesized compounds were elucidated by using spectral methods such as; FT-IR, 1 H-nm, 13 C-nmr and 13 CDept 135 spectra. Introduction Chalcones (1,3-diaryl-2-propen-1-ones) are α,β-unsaturated aromatic ketones, constitute a class of naturally occurring and synthetic compounds belonging to the flavonoid family(Buckingham,1994) which synthesized by the base catalyzed Claisen-Schmidt condensation reaction(Mirjalal et al., 20008), and considered as a very useful precursor for the preparation of different important heterocyclic compounds like ; pyridines(Kolosov et al., 2007), pyrimidines (Munawar et al., 2008 and Prasad et al.,2008), thiazepines(Cherkupally et al., 2008), isoxazoles(Al-Issa et al.,2008) (Mustafa et al., 2003), and pyrazolines(Spivey et al., 2000; Guo et al., 2002; Azarifar et al., 2002; Goda et al.,2003 and Patel et al., 2004) . pyrazolines are the five membered heterocyclic compounds with two adjacent nitrogen atoms (Buchmeiser, 2003) would prepared by the Michael addition reaction(Otera, 2000) . Chalcone and pyrazoline derivatives are found to possess a broad spectrum of biological activity, such as anti-malarial (Kenyon et al.,1995), antibacterial (Asiri et al.,2009), anti-oxidative (Arty et al.,2000), anti-fungal (Prasad et al.,2008), anti-inflammatory (Al-Hajjar, 2007), anti-hipatotoxic (Khan et al.,2006), anti-plasmodial(Liu et al., 2004), anti-tumor (Abunada et al.,2008), anti-mitotic (Fdward et al.,1990), anti-aldos reductase (Babin Journal of Kirkuk University –Scientific Studies, vol.7, No.1, 2012 51 et al.,1982), anti-trichomonal (Oyedapo et al., 2004), anti-prostate, anticolon cance (Zhou et al., 2006), anti-histamic (Sridevi et al., 2009), antimicrobial(Srinivasa et al., 2007) anti-hypertensive, anti-depressant (Zhang et al.,2007), anti-viral activities (Hajos, 2002) (Alam et al., 2005), Also chalcones can be used as eco-friendly bio-pesticides (Nalwar et al., 2009). The present investigation describes the synthesis and spectroscopic studies of some new chalcones and their transformations to pyrazoline derivatives. Experimental Melting points were determined using an Electrothermal melting point apparatus, IR spectra were recorded on a Bio-rad Merlin FT-IR spectroscopy Mod FTS 3000, using KBr disc. 1 H-NMR and C 13 -NMR and 13 C-DEPT 135 spectra were recorded on a Bruker(300MHz) with TMS as internal reference in( Jordon) . 1-Synthesis of 3-(4-chlorobenzyloxy)benzaldehyde(1) (Ching et al.,2008) A mixture of 3-hydroxy-benzaldehyde (12.2gm, 0.1mol), 4chlorobenzylchloride (18.3 gm, 0.12 mol) and anhydrous K2CO3 (27.6 gm, 0.2 mol), in ethanol (100 ml 96%) was refluxed with stirring for 6 hours. When the reaction is completed, the cooled solution poured into water, solid materials immediately was obtained. The product filtered off, washed several times with water and cold ethanol, dried and recrystallized from ethanol to obtain white crystals of 3-(4-chlorobenzyloxy)benzaldehyde (1) (C14H11ClO2), m.p. (47-48 0 C), and in the yield of (23 gm , 93%). IR (cm -1 ); 1679 (C=O), 1594 (C=C), 1275 and 1182 (C-O-C). 1 H-NMR: 5.1(s, 2H, H5); 7.26(d, 1H, H11); 7.38(s, 4H, H2,2`3,3`); 7.48(m, 3H, H7,9,10); 9.98 (s, 1H, H12). 13 C-NMR: 69.42: C5; 113.12:C7; 122.15: C11; 123.95:C9; 128.83:C2,2`,3,3`; 130.2:C10; 134.02:C1; 134.85:C8; 137.87:C4; 159.08:C6; 191.94:C12. 13 C-DEPT: -69.42: C5; 113.12:C7; 122.15: C11; 123.95:C9; 128.83:C2,2`,3,3`; 130.2:C10; 191.94:C12. 2Synthesis of chalcones: 3[3(4-chlorobenzyloxy) phenyl]-1(substitutedphenyl) -2-propene-1-one (2 a-i)(Patil et al.,2007) Chalcones (2a-i) were synthesized by dissolving 3-(4-chlorobenzyloxy)benzaldehyde (1) (1.48 gm, 0.006 mol) in ethanol (15ml 96%), and added to the solution of an appropriate substituted acetophenones (0.006 mol) in ethanol (15 ml 96%) and (12 ml) of 4% ethanolic sodiumhydroxide. The mixture was stirred at room temperature for (1-5 min.) until the formation of pale yellow crystals of chalcone, then kept the solution at room temperature for (1-2 hrs.). Chalcone crystals were separated by suction Journal of Kirkuk University –Scientific Studies, vol.7, No.1, 2012 52 filteration, washed with ethanol and water to neutralize, dried and purified by recrystalization from ethanol or xylene as a suitable Solvents, table(1). 3-Synthesis of pyrazolines 5[3(4-chlorobenzyloxy)phenyl]1-phenyl -3(substituted phenyl) pyrazolines (3 a-i)(Yar et al.,2009) A mixture of phenyl hydrazine (0.16 gm, 0.0015 mol), chalcones ( 2ai) (0.001 mol) and sodium hydroxide (0.001 mol) in (25 ml 96%) ethanol was refluxed with stirring about (1-2 hrs.) until complete the reaction which was monitored by the formation of ppt.of the pyrazoline products (3 a-i). The ppt. was isolated by suction filtration, washed with ethanol and water to neutralize, dried and purified by recrystalization from xyleneethanol as suitable double solvent. The physical properties of the prepared pyrazolines (3a-i) were summarized in table (2). Results and Discussion The present investigation involves the synthesis of some new pyrazolines from the preparation of starting material 3-(4-chlorobenzyloxy) benzaldehyde (1), on the basis of Williamson synthesis of ethers. Compound (1) subjected to react with a series of substituted acetophenones to give new chalcones (2a-i), the later compounds were treated with phenylhydrazine to form a new derivatves of pyrazolines (3a-i) scheme (1).