Conseguences of soil crude oil pollution on some wood properties of olive trees Chemistry |68 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Synthesis, Characterization and Antibacterial Activity of New Chalcones Derived from New Aldehyde; 4-[5-(4`- tolyl)-1,3,4-thiadiazole-2-yl] benzaldehyde Jumbad H. Tomma . Dept. of Chemistry/College of Education for Pure Science (Ibn Al- Haitham)/ University of Baghdad, Baghdad Mustafa S. Khazaal Standrads Department/ Central Organisation of Standardisation and Quality Control Rajaa K. Baker Dept. of Chemistry/College of Education for Pure Science (Ibn Al- Haitham)/ University of Baghdad Received in:10/October/2016,Accepted in:28/December/2016 Abstract New chalcones of -{ - - - y - - hi di z e- -y he y - - e e- - e- - - substituted phenyl have been prepared from condensation of a new of 4-[5-(4`-tolyl)- 1,3,4-thiadiazole-2-yl] benzaldehyde (which is synthesized by the reaction of 2- amino-5- (4`-tolyl) -1,3,4-thiadiazole and benzaldehyde) with 3- or 4- substituted acetophenones in alkaline medium. The physical, CHNS analysis and spectral data of the synthesized compounds were determined. The biological activity evaluated of new compounds showed that many of these compounds possess antibacterial activity. Key words: 1,3,4-thiadiazole; chalcones; aldehyde; antibacterial activity Chemistry |69 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Introduction In drugs and biological field, 1,3,4-thiadiazoles have occupied an important place [1-4]. Furthermore, some of these 1,3,4-thiadiazoles are interested in photography and as potential anticancer agents [5,6]. Claisen-Schmidt condensation includes synthesis chalcones from proper aldehydes and ketones in base catalyzed or acid catalyzed followed by dehydration. Which have been possessed anti-oxidant [7], anti-fungal [8,9], anti-cancer [10], anti- inflamatory [11], antibacterial activity[12-15] and anthelmintic activity [16]. The reactive and unsaturated keto function in chalcones is found to be responsible for their antimicrobial activity [17]. Additionally, some of chalcone derivatives have been found to inhibit several enzymes in cellular[18]. Many workers synthesized new chalcones containing heterocyclic moiety which have a good biological activities [19,20]. From our knowledge that, the synthesis of chalcones containing 1,3,4-thiadiazole unit have not been reported in literature. Thus, we decided to synthesize, identify and have antibacterial activity of new chalcones containing 1,3,4-thiadiazole ring. Experimental Chemicals: All chemicals were supplied by fluka, GCC, merek and Aldrich chemicals Co. Techniques: : FTIR spectra were recorded (by KBr discs) on a Shimadzo (Ir prestige -21) ¹HNMR spectra were examined by: Bruker , model: ultra shield 300 MHz , origin : Swi ze d d e e ed i DMSO s s ve m δ uses TMS s i e standard were made in Al-al Bayt University, Jordan . Hot-Stage, Gallen Kamp melting point apparatus was used for determined (uncorrected) melting points. UV spectra of solutions were performed on CECL 7200 England Spectrophotometer using CHCl3 as a solvent. Elemental analysis (C.H.N.S) were carried out by a Perkin-Elmer model 2400 instrument. The purity of the synthesized compounds was determined using thin layer chromatography (the spots were observed using employing iodine chamber). General procedures The compounds [I] , [II] and [III]a-f were synthesized via Scheme 1. preparation of 2- amino-5- (4`-tolyl) -1,3,4-thiadiazole[I] Thiosemicarbazide (0.01mol) was a mixed with tuloic acid (0.01mol) in POCl3 (5mL) , the mixture was refluxed for 6 hrs. After cooling, the reaction mixture was poured onto ice water (50mL) with stirring. The yellow precipitate was separated by filtered, washed (with water), dried and re-crystallized from ethanol [21]. Thin layer Chromatography was used toconfirmed the purity of this compound. Yield 77%, mp 219-222 o C. IR(KBr, υ, cm− 1 ): 3160,3257(NH2) , 2965-2945 (CH aliph.) ,1627(C=N). 4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl]benzaldehyde[II]: Was synthesized following the procedure described by D. Bhoot et al. [22]. pale brown , yield (70%) , m.p 226-228°C; IR (KBr, υ, cm− 1 ): 2700,2790 (C-H ,aldehdic), 1692 (C=O) , 1627 (C=N);Anal. Calcd. (%) for C16H12N2OS: C= 68.57 ; H=4.28 ; N=10 ; S=11.42. found (%): C=68.25 ; H=4.40 ; N= 10.05; S=11.44 ; 1 H-NMR (DMSO-d6 , δ ppm): 2.50 (3H, s, CH3), 6.95-7.71 (8H, d-d, arH), 9.01 (1H, s, CHO). Chemistry |70 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Synthesis of chalcones [III]a-f Equi-molar quantities of different 4-substituted acetophenone (0.01mol) and aldehyde[II] (0.01 mol) were dissolved in 20mL of alcohol. Sodium hydroxide solution (0.02mol) was added slowly (and the mixture becomes cold), then the mixture was poured onto 400mL of ice water with stirring. The precipitate obtained was filtered after kept in refrigerator for 24 hrs. washed and re-crystallized from chloroform . 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl] phenyl}-2-propene-1-one-phenyl[III]a .Dark orange , re-crystallized from chloroform. Yield 80%, mp 198- 00 ˚C. UV ch form , nm, λm x : 97. . IR KB υ, cm− 1 ): 1650(C=N), 1636 (C=O), 1625(CH=CH) ; Anal. Calcd. (%) for C24H18N2OS: C= 75.39 ; H=4.71 ; N=7.32; S=8.37. found (%): C=75.45 ; H=4.98 ; N= 7.22; S=8.54 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl] phenyl}-2-propene-1-one-3``-nitrophenyl[III]b .Pale brown, re-crystallized from chloroform. Yield 85%, mp 182- 8 ˚C. UV ch f m m λm x : 97. IR KB υ, cm− 1 ): 1669(C=N) ,1636 (C=O), 1616(CH=CH), 1516 and 1346 (3-NO2) ; Anal. Calcd. (%) for C24H17N3O3S: C= 67.44 ; H=3.98 ; N=9.83; S=7.49. found (%): C=67.49 ; H=3.92 ; N= 9.85; S=7.55; 1 H-NMR (DMSO-d6 , δ ppm): 2.69 (3H, s, CH3 ), 7.25-7.86(12H,d,t,s,C-H arm.), 7.81-7.86(H,t,C-H arm.), 8.37-8.49(2H,d,CH=CH). 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl] phenyl}-2-propene-1-one-4``-nitrophenyl[III]c .Pale yellow, re-c ys ized f m ch f m. Yie d 8 % m 0 ˚C. UV ch f m m λm x : 99. . IR KB υ, cm− 1 ): 1670(C=N), 1635(C=O), 1610(CH=CH) , 1510 and 1339 (4-NO2) ; Anal. Calcd. (%) for C24H17N3O3S: C= 67.44 ; H=3.98 ; N=9.83; S=7.49. found (%): C=67.04 ; H=4.06 ; N= 9.89; S=7.92. 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl] phenyl}-2-propene-1-one-4``-bromophenyl[III]d .Pale orange, re-crystallized from chloroform. Yield 78%, mp 214- ˚C. UV ch f m m λm x : 98. IR KB υ, cm− 1 ): 1665(C=N), 1635(C=O), 1613(CH=CH) , 692 (4-Br) . 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl]phenyl}-2-propene-1-one-4``-hydroxyphenyl[III]e .Pale yellow, re-crystallized from ethanol. Yield 80%, mp 208- 09 ˚C. UV ch f m m λ max) :296. IR (KBr, υ, cm− 1 ): 1670(C=N), 1636(C=O), 1612(CH=CH) , 3269 (4-OH) 3-{4-[5-(4`-tolyl)-1,3,4-thiadiazole-2-yl] phenyl}-2-propene-1-one-4``-aminophenyl[III]f .Pale yellow, re-crystallized from acetone. Yie d 7 % m 8 ˚C. UV ch f m m λ m x :295.5. IR (KBr, υ, cm− 1 ): 1648(C=N), 1638(C=O), 1628(CH=CH) , 3287 and 3100 (4-NH2); Anal. Calcd. (%) for C24H19N3OS: C= 72.54; H=4.78; N=10.57; S=8.06. found (%): C=72.82 ; H=4.69 ; N=10.65 ; S=8.12. ; 1 H-NMR (DMSO-d6, δ,ppm):2.37(3H,s,CH3),7.5-7.94(12H,d- d,C-Harm.),8.12-8.26(2H,d,CH=CH), 6.24(2H,s,NH2). Results and Discussion 2-Amino-1,3,4-thiadiazole derivatives was synthesized from condensation of tuloic acid with thiosemicarbazide in POCl3. The FTIR absorption spectrum gives two bands at 3258cm -1 , 3180 cm -1 related to NH2 group, 3020cm -1 for CH aromatic, peak at 1628cm -1 due to C=N of thiadiazole ring , para substituted in benzene ring indicated by a good bending band at 813cm -1 . The UV-VIS s ec sc y exhibi ed λmax at 296.5 nm. The new aldehyde[II] was synthesized from reaction of 2-amino-1,3,4-thiadiazole with bezaldehyde in a preoperative conditions . FTIR spectrum of this compound showed a good Chemistry |71 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 stretching band at 1692 cm ˉ dueto aldehydic carbonyl and two vibration bands at 2750 cm ˉ and 2820 cm ˉ for C-H aldehydic stretching. The UV-VIS s ec sc y exhibi ed λmax at 294.5 nm. 1 HNMR spectrum (in DMSO) of synthesized [II](Figure 2), showed a signal sh δ 9.0 m f e c u d be ibu ed he dehydic e h ee d ub e s be wee δ 6.9 -7.71)ppm due to the eight aromatic protons and a singlet signals at δ . 0 m due h ee s f CH3 group. By claisen-schmidt condensation of aldehyde[I] and 3- or 4-substituted acetophenone using base catalyzed followed by dehydration led to produce new chalcones [III]. The structural assignments of the chalcones [III]a-f based on C.H.N.S analysis and their spectral data (FTIR, UV and ¹HNMR spectroscopy). The FTIR specta indicated the disappearance of two bands which could be attributed to asymmetric and symmetric stretching vibration of CH of aldehydic group, besides, two peaks appearance around (1638-1635)cm ˉ and around (1628- 1610)cm ˉ due to of C=O, C=C (CH=CH) stretching vibrations, respectively. The 1 HNMR of chalcone [III]b (Figure 3) showed the following features: two pairs of doublet in the region δ8. 7-8.49 ppm which could be attributed to two protons of CH=CH group. doublet of d ub e s si g e d i e e ed i he egi δ7. -7.86 ppm due to twelve protons of benzene rings having different substituents at positions 3- or 4-, a sharp signal appearance in he s ec um δ .69 m due h ee s f CH3 group. The 1 HNMR of chalcone [III]f sh wed he f wi g fe u es: w i s f d ub e i he egi δ8. -8.26 ppm which can be attributed to two protons of CH=CH group, three d ub e s e ed i he egi δ7. 0- 7.94ppm due to twelve protons of benzene rings having different substituents at positions I,4. A s he s ec um sh w w e ks s sh sig s δ . 7 m d b d sig δ 6.24ppm for three protons of CH3 group and one proton of NH2 group, respectively. Chemistry |72 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Antibacterial activity The agar diffusion method [23] was used well to evaluate the antibacterial activity for synthesized compounds, with [10 -3 M] concentration for each compound. The microorganisms were spread on Muller -Hinton agar by cottons wab. .The plates were incubated for 24 hrs at 37 0 c the inhibition zone was measuring to evaluate the antibacterial activity for the synthetic compounds. The result of activities of the synthesis compounds[II] and [III]d possess moderate to high specific activity (inhibition) against Burkholderia, E.coli, Shigella , Serratia and Acinetobacter . The compound [II] which is contains CHO group showed a higher activity than chalcones. The antibacterial activity data, as in Table 1and Figure 3, may be explained depending on the molecular structure and nature of the substituted group. Also, We can observe differences in the biological activity of the synthesized compounds against different types of bacteria, that could be related to cell membrane permeability or other genetic factor [24]. References 1- Yar, M. and Akhter, M. (2009) Synthesis and Anticonvulsant Activity of Substituted Oxadiazole and Thiadiazole Derivatives. Polish Pharmaceutical Society, 66(4), 393-397. 2- Salimon, J.; Salih , N.; Hameed , A.; Ibraheem , H. and Yousif, E. 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Key of symbols : 1. active (slightly) = + 5 – 10mm, 2. active (Moderately) = ++ 11 – 15mm 3. active ( Highly) = +++ more than 15mm . Con: DMSO Acinetob acter sp. Gram( -) Serratia marcescens Gram( -) Shigellad ysentria Gram( -) Staphyou s aureas Gram( +) Esherich ia coli Gram( -) Burkhold eriacepacia Gram( -) Comp. No. 17 _ 13 10 22 12 [II] 2 _ _ _ _ _ _ [III]a _ 12 _ _ _ _ [III]b _ 12 _ _ _ _ [III]c 13 _ 12 _ 19 11 [III]d _ _ _ _ _ _ [III]e _ _ 14 _ 16 _ [III]f _ _ _ _ _ _ Control DMSO Chemistry |75 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Figure( 1): Antibacterial activity of compounds[I]-[III] against Burkholderia, E.coli , Stap . aureus ,Shigella , Serratia and Acinetobater Symbol: c= control (DMSO); 2=compound [II]; 101=compound [III]a; 5=compound [III]b; 4=compound[III]c; 6=compound [III]d; 7=compound [III]e; 8=compound [III]f. Figure (2): 1 HNMR spectrum of compound[II]. Chemistry |76 https://doi.org/10.30526/30.3.1603 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Figure (3): 1 HNMR spectrum of compound[III]b. CCH3 CH CCH O O C H O H3C NN S H3C NN S NH 2 X= H, 3-NO 2 , 4-NO 2 , 4-Br, 4-OH and 4-NH 2 H3C NH 2 NHCSNH 2 POCl 3 Benzaldehyde NaNO2/HCl CuCl2 H3C NN S [I] [II] [III]a-f Base Scheme 1. Synthetic route to the prepartion compounds [III]a-f . X X COOH