Microsoft Word - 9 421 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Synthesis ,Characterization and Study Biological Activity of Some New 1, 3, 4-Thiadiazole and Pyrazolone Derivatives Containing Indole Ring Khalid F. Ali Kadhim M. Lazim Jumbad H. Tomma Dept.of Chemistry/College of Education For Pure Science (Ibn Al- Haitham)/ University of Baghdad Received in: 12 june 2014,Accepted in: 29 September 2014 Abstract This work involves synthesis and characterization of some new 1, 3, 4-thiadiazole or pyrazoline derivatives heterocyclic containing indole ring. The new 2-amino-1, 3, 4- thiadiazole derivatives[IV] and [V]a, b were synthesized by cyclization reaction of 2-methyl- 1H-indole-carbothiosemicarbazide[III] in H2SO4 acid or by reaction of indole-3-acetic acid or indole-3-butanoic acid with thiosemicarbazide in the presence of phosphorous oxychloride, respectively. Amide derivatives [VI]-[VIII] were synthesized by the reaction equimolar of 2- amino-1, 3, 4-thiadiazoles and (acetyl chloride, benzoyl chloride, anisoyl chloride and heptanoyl chloride) in DMF and pyridine as accepter. The new pyrazolone derivatives [XI]a, b were synthesized from heating under reflux equimolar from a mixture of acid hydrazides [X]a or [X]b and ethylacetoacetate in absolute ethanol. Acetyl pyrazolone compounds[XII]a, b were synthesized by the reaction of pyrazolone derivatives [X]a or [X]b with acetyl chloride in 1,4-Dioxane in present of calcium hydroxide to give 4-acetyl pyrazolone derivatives[XI]a, b. The new aryl hydrazone derivatives of pyrazoline [XIII] and [XIV] were synthesized by the reaction of one mole of compounds [XII]a or [XII]b with one mole of phenyl hydrazine or substituted phenyl hydrazine in ethanol. All the synthesized compounds have been characterized by melting points , FTIR, 1HNMR and Mass spectroscopy (of some of theme). Key Words : 1,3,4-thiadiazole, pyrazole, pyrazolone, Indole, hydrazone. 422 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Introduction The indole ring system has become an important structural requirement in many pharmaceutical agents[1]. Indole and its derivatives occupied a unique place in the chemistry of nitrogen heterocyclic compounds because of their varied biodynamic properties [2]. Most of the Indole derivatives are biologically active chemicals present in microorganisms, plants and animals representing an important class of therapeutic agent in medicinal chemistry [3]. The five-member heterocyclic compounds particularly nitrogen and sulphur heterocyclic: thiadiazole, contains the five membered unsaturated ring structure composed of two nitrogen atoms and one sulfur atom. There are four isomeric types: 1,2,3-thiadiazole; 1,3,4-thiadiazole; 1,2,4-thiadiazole and 1,2,5-thiadiazole[4]. In view of the standard reference work shows that more work has been carried out on the 1,3,4-thiadiazole than all other isomers combined[5]. 1,3,4-Thiadiazole moiety in which sulfur present at position-1, and two nitrogen atom at position-3 and position-4. Thiadiazoles are an important class of heterocyclic compounds that exhibit diverse applications in organic synthesis, pharmaceutical and biological applications, among them 2,5-disubstituted-1,3,4-thiadiazoles are associated with divers biological activities probably by the virtue (-N=C-S-) grouping[6]. 1,3,4-Thiadiazole derivatives possessed a wide range of therapeutic activities [7-14]. Pyrazoles represent one of the most active classes of compounds possessing wide spectrum of biological activities[15]. Hydrazones possessing an azomethines -NH-N=CH- proton constituent an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities[16]. In view of these facts, we decided to synthesize new 1,3,4-thiadiazole, pyrazoline and their hydrazone derivatives containing indole ring. Experimental Materials All chemicals were supplied from Merck, GCC and Aldrich Chemicals Co. and used as received. Techniques FTIR spectra were recorded using potassium bromide discs on a Shimadzo (Ir prestige- 21) FTIR spectrophotometer. 1HNMR spectra were carried out by company: Bruker, model: ultra-shield 300 MHz origin: Switzerland, and Bruker model: ER-av-400 MHz, origin: Switzerland are reported in ppm(δ), DMSO was used as solvents with TMS as an internal standard . Measurements were made at Chemistry Department, Al-albyat University and University of Science and Technology, respectively in Jordan. Uncorrected melting points were determined by using Hot-Stage, Gallen Kamp melting point apparatus. The mass spectrum was recorded on Shimadzo model: 6CMS QD 1000 EX, made in Japan. New compounds are synthesized according to scheme1 and scheme 2: 423 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 N H C O O CH3 C2H5Ph NHNH2 CH3COCH2COEt N H C O NHNH2 CH3GAA NH4SCN HClEtOH [I] [III] NH2NH2.H2O EtOH [II] [IV] [VI]a-d [V]a, b [VII] [VIII]and Scheme(1) N H (CH2)n C O OH N H C O H N CH3 H N C NH2 S N H S NN NH2 CH3 N H (CH2)n POCl3 S NN NH2 H2SO4 DMF Pyridine N H S NN H N CH3 C O RN H (CH2)n S NN H N C O R R = Me, Ph, 4-MeO-C6H4 and heptyln = 1, 3 ; RCOCl RCOCl: DMF Pyridine: NH2NHCSNH2 : RCOCl CH3COCH2COEt N H (CH2)n C O OH Et OH NH2NH2.H2O EtOH H2SO4 N H (CH2)n C O OMe N H (CH2)n C O NHNH2 MeOH N H (CH2)n C O N N O Me N H (CH2)n C O N N O Me C O Me N H (CH2)n C O N N O Me C NMe H N R EtOH R NHNH2 EtOH R = Ph, 4-O2N-C6H4, 4-Br-C6H4, 2,4-diO2N-C6H4 Schems (2) n = 1, 3 ; [IX] [X]a, b [XI]a, b [XII]a, b [XIII]a-d [XIV]a-dand Method Procedure Ethyl-2-methyl-1H-indole-3-carboxylate [I] This compound was prepared according to the let. [17]. 2-methyl-1H-indole-3-carbohydrazide [II] This compound was prepared according to the procedure method in let. [18]. Yield 84%, m.p = (144-146) 0C. 2-(2-methyl-1H-indole-3-carbonyl)hydrazine carbothioamide[III] This compound was prepared according to the procedure method in let. [19], Yield 90 %; m.p.: (200-202) 0C. 2-Amino-5-(2-methyl-1H-indol-3-yl)-1,3,4-thiadiazole [IV] This compound was prepared according to the procedure method in let. [10 ], Yield 65 %; m.p.: (190-192) 0C. 424 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 2-Amino-5-(substituted-(1H-indol-3-yl)alkyl)-1,3,4-thiadiazole [V]a, b A mixture of 1H-indole-3-acetic acid or 1H-indole-3-butanoic acid (0.01 mol), thiosemicarbazide (0.91g, 0.01mol) , phosphorus oxy chloride (5 mL) was refluxed gently for 6 hrs. After cooling, ice water (50 mL) was added in portions with stirring at (0-4) 0C . The precipitate was filtered, washed with water , dried and recrstalization from ethanol. Synthesis of Amide Derivatives [VI]a-d, [VII]a-d and [VIII]a-d 2-Amino-1,3,4-thiadiazoles, (0.001 mol) was dissolved in mixture of pyridine and DMF (1:2 mL) on ice bath then different acid chloride (0.001 mol) was added, the mixture was stirred for 3 hrs at room temperature , afterward 10% HCl was added, the precipitate was filtered and washed with water, dried and recrystalized from ethanol. Methyl Substituted-(1H-indol-3-yl) alkyloate [IX] a, b This compound was prepared according to the procedure method in let. [20], compound [II]a ; yield 94%, m.p. oily. compound [IV]a; yield 94%, m.p. (82-84) 0C. Substituted-(1H-indol-3-yl)alkylhydrazide[X]a, b These compounds was prepared according to the procedure method in let. [19], compound[IV]a, Yield 97%; m.p.= (142-144) 0C. compound[IV]b Yield 92%; m.p. = (151- 153) 0C. Synthesis of 1-(substituted-(1H-indol-3-yl)alkanoyl)-3-methyl-pyrazol-5(4H) -one[XI]a, b The acid hydrazides (0.0028 mol) and ethyl acetoacetate (0.364g, 0.0028 mol) in absolute ethanol(20mL) was refluxed for 3 hrs. The reaction mixture was allowed to cool and the formed precipitate was filtered off and recrystallized from methanol to give new compounds. Synthesis of 1-[substituted-(1H-indol-3-yl)alkanoyl]-4-acetyl-3-methyl- pyrazol-5(4H)-one [XII]a, b 1,4-Dioxane solution (25 mL) of compounds[XI]a or [XI]b (0.013 mol) and acetyl chloride (1.027g, 0.013 mol) was refluxed for 4 hrs on oil bath with calcium hydroxide (1.397g) and cooled to room temperature. The resulting reaction mass is added to the dilute hydrochloric acid (4.5mL Conc. in 20 mL water), the cured product was collected by filtrations and washed several times with water and recrystallized from acetone. Synthesis of 1-[substituted-(1H-indol-3-yl)alkanoyl]-3-methyl-4-[1-(2- arylhydrazono) ethyl]-4-hydro-pyrazol-5-one[XIII]a-d and [XIV]a-d A mixture of compounds [XII]a, b (0.001 mol) and phenyl hydrazine or substituted phenyl hydrazine (0.001mol) in ethanol (5mL) was refluxed for 3 hrs. Cool, pour onto water. The formed solid, was collected by filtrations and crystallized from chloroform. The physical properties of the synthesized compounds[V]-[XIV] are given in Table(1). 425 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Results and Discussion Ethyl-2-methyl-1H-indole-3-carboxylate [I] was obtained by Fischer indole synthesis from the reaction of phenyl hydrazine with ethyl acetoacetate in glacial acetic acid, following the procedure described by P. Kumar et al[20]. This structure was identified by melting point and FTIR spectroscopy. The characteristic FTIR spectrum of compound[I], showed the disappearance of absorption stretching bands of NH2 group of phenyl hydrazine and C=O of ketone group of ethyl acetoacetate together with the appearance of a new stretching band at 1714cm-1 which is assigned to υ C═O of ester moiety in addition, two stretching bands at 1620cm-1and 3392 cm-1 due to the υ C=N(endocyclic) and N-H of indole ring, respectively. On the other hand methyl substituted-(1H-indol-3-yl) alkyloate [II]a, b were obtained by esterification of indole-3-acetic acid or indole-3-butanoic acid in absolute methanol using conc. H2SO4 as a catalyst, following the procedure described by Vogel[21]. These compounds were identified by melting points and FTIR spectroscopy. The FTIR absorption spectra showed the disappearance of absorption stretching bands of O─H and C═O groups of (carboxylic moiety) in indole-3-acetic acid and indole-3-butanoic acid together with the appearance of a stretching bands at 1732cm-1 which is assigned to C═O of ester moiety of compound[IX]a and at 1722cm-1 of compound[IX]b, respectively. The condensation ester compounds with hydrazine hydrate produce the acid hydrazide [II], [X]a and [X]b which are characterized by higher melting points and the FTIR spectra revealed stretching vibration of (N-H, NH2) groups as well as stretching absorption at of C═O (amid) group between (3323-3200)cm-1 and (1681-1649)cm-1, respectively and disappearance of absorption stretching band due to C═O of ester moiety. Neucleophilic addition reaction of acid hydrazide [II] to ammonium thiocyanate in ethanol using hydrochloric acid as a catalyst to give 2-(2-methyl-1H-indole-3-carbonyl) hydrazine carbothioamide[III]. The structure of this compound was identified by melting point , FTIR spectroscopy. FTIR spectrumindicated absorption stretching band at 1288cm-1 that could be assigned to C=S group in addition to new bands which could be attributed to asymmetric and symmetric stretching vibration of NH2 and N-H groups appear between (3356-3169)cm-1, also showed shifting of C═O (amid) group to 1637cm-1. Cyclization 2-(2-methyl-1H-indole-3-carbonyl)hydrazine carbothioamide [III] is carried out in conc. H2SO4 followed by neutralized with liquid ammonia yielded 2-amino-5- (2-methyl-1H-indol-3-yl)-1,3,4-thiadiazole[IV], this compound is identified by melting point and FTIR spectroscopy. The FTIR absorption spectrum of this compound showed two peaks at 3296 and 3155 for stretching bands of NH2, also show the disappearance of the characteristic bands of starting material[III], in addition of new peak at 690 for C-S-C bond. 1HNMR spectrum (in DMSO as a solvent) for compound [IV], showed that the singlet signal at δ2.2 ppm could be attributed to three protons of CH3 group. Also, the spectrum show many signals in the region δ(6.93-7.69)ppm due to four aromatic protons and two protons of NH2 group which is in toutomerism forms (NH2↔NH) therefore NH2 protons appeared as very weak a broad peak in the region δ(3.06-5.0)ppm, while the protons NH forms appeared as a singlet signal at δ7.69 ppm. Finally signal at δ11.21 ppm for one proton of N-H indole ring. The new 2-amino-1, 3, 4-thiadiazole derivatives[V]a, b, were synthesized by the reaction of indole-3-acetic acid or indole-3-butric acid with thiosemicarbazide in the presence of phosphorous oxychloride under reflux for 6 hrs. These compounds were identified by melting points , FTIR, 1HNMR and Mass spectroscopy. The FTIR absorption spectra of compounds[V]a, b showed two peaks in the region (3400-3178) cm-1 that attributed to the NH2 group, peak at 1635 cm-1 or at 1630cm-1 of compounds[VII]a, b, respectively due to C=N of thiadiazole ring, also show new peak around 710cm-1 for C-S-C group. The FTIR spectral data for these compounds are listed in Table (2). 426 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 The 1HNMR spectrum (in DMSO as a solvent) for compound [V]a, showed the following signals: a singlet signal at δ9.82 ppm for one proton of N-H indole ring, signals in region δ(6.7-8.1) ppm that could be attributed to the five aromatic protons, Also, the spectrum shows signals between δ(4.04-4.95) ppm for two protons of the NH2 group. Finally, a singlet signal at δ(3.44)ppm for two protons of CH2 group. The mass spectrum, Figure(1) of compound[V]b, given molecular ion at m/z = 258, which is correspond to the molecular weight of structures suggested for this compound. The results obtained from the mass spectrum suggested that fission was more easily accomplished at the carbon- nitrogen bond rather than at the carbon-carbon bond such as fragments at m/z = 112, 72 and 71. This peak at m/z = 85 is characteristic for 1, 3, 4-thiadiazole ring in addition to peak at m/z= 71. This spectrum showed interesting peak at m/z = 130 due to the indole ring. The other important fragments given in scheme (3). Scheme(3) N H (CH2)3 S NN NH2 N H CH2CH2CH3 S NN CH2CHCH3H2N N H CH2 NH S N N S CH H m/z: 258 m/z: 159 m/z: 130 m/z: 92 m/z: 65 m/z: 142 m/z: 72 S NN CHCH3H2N m/z: 128 S NN CHCH3 m/z: 112 S NN CH2 m/z: 98 S NN m/z: 85 CH2 -14 -CH2 -16 -NH2 -14 -CH2 -14 -CH2 m/z: 71 N H2 CH2CH2CH3 m/z: 160 +H m/z: 77 Amide derivatives [VI]-[VIII] were synthesized by the reaction equimolar of 2- amino-1,3,4-thiadiazoles[IV], [V]a and [V]b and different acid chlorides in DMF and pyridine as accepter. These compounds were identified by melting points , FTIR and 1HNMR spectroscopy. The FTIR spectra of amide derivatives[VI]-[VIII], as in Figure(2) showed the disappearance of bands of NH2 groups of starting material with the appearance of a new stretching band of NH group in the range (3408-3200)cm-1, also the appearance of carbonyl amide (C=O) in the range (1690-1674) cm-1, the characteristics FTIR absorption bands of these compounds are given in Table(2). The 1HNMR spectrum (in DMSO as a solvent) for compound [VIII]d, Figure(3) showed the following signals: a weak singlet signal at δ (11.57) ppm for proton of NH indole ring, a broad signal at δ(3.49)ppm due to one proton of (NH-CO) group, signals in the region δ(7.08-7.68) ppm that could be attributed to the five aromatic protons, many signals in the region δ(0.84-2.95) ppm that could be attributed to the aliphatic protons. The new pyrazolone derivatives [XI]a, b were synthesized from heating under reflux equimolar from a mixture of acid hydrazides [X]a or [X]b and ethylacetoacetate in absolute ethanol. These compounds were identified by melting points and FTIR spectroscopy. FTIR spectra of pyrazoline compounds[XI]a, b showed new stretching band due to C=O of 427 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 pyrazoline ring appear near 1700 cm-1, in addition of the band of the (C=O amide) group. The appearance of new absorption band between1625 cm-1 is due to C=N group (endocyclic) of pyrazoline ring . The FTIR spectral data of pyrazolines [XI]a, b are listed in Table (3). New 4-acetyl pyrazolone compounds[XII]a, b were synthesized by the reaction of pyrazolone derivatives[XI]a or [XI]b and acetyl chloride in 1,4-Dioxane in present of calcium hydroxide. The synthesized compounds were characterized by melting points, and FTIR spectroscopy. The FTIR spectra of acetyl pyrazolines as in Figure(4) showed new stretching band due to C=O (acetyl) group at 1735cm-1. The FTIR spectral data of 4-acetyl pyrazolones[XII]a, b are listed in Table (3). Aryl hydrazone derivatives [XIII]a-d and [XIV]a-d were synthesized by the reaction of one mole of acetyl compounds[XI]a, b with one mole of phenyl hydrazine or substituted phenyl hydrazine in ethanol. The structure of these compounds were studied by melting points , FTIR and 1HNMR spectroscopy. The FTIR spectra, as in Figure(5) showed the disappearance of absorption band of the C=O(acetyl) group and appearance of new absorption stretching bands of NH and C=N groups in the regions(3408-3200) cm-1 and (1645-1618) cm-1, respectively. The FTIR spectral data of aryl hydrazone derivatives [XIII]a-d and [XIV]a-d are listed in Table (3). The 1HNMR spectrum (in DMSO as a solvent ), Figure(6)for compound [XIII]c showed: a singlet signal at δ10.90 ppm for one proton of NH indole ring, a singlet signal at δ9.90 ppm for one proton of (C=N-NH) group(264), another singlet signal at δ8.97 ppm for one proton of NH pyrazoline ring (the proton at C-4 is toutomerism with NH pyrazoline ring) as in scheme (3-20) (302) , signals in region δ(6.73-8.32) ppm that could be attributed to the nine aromatic protons, two signals at δ1.20 ppm and at δ1.80ppm for six protons of (CH3-C=N) and CH3 at C-3 of pyrazoline ring of pyrazoline ring. Finally a signal at δ(3.60) ppm for two protons of CH2 group. 1HNMR spectrum (in DMSO as a solvent ), for compound[XIV]b showed: a singlet signal at δ10.18 ppm for one proton of NH indole ring, singlet signal at δ8.40 ppm for one proton of (C=N-NH) group, two doublets and mulitiple signals in region δ(6.90-7.48)ppm that could be attributed to the nine aromatic protons, singlet signal at δ(1.14-1.35)ppm for eight protons of CH3 group at C-3 of pyrazolone ring, CH3C=N and C-CH2-C groups. Finally signals in the region δ(3.2-4.2) ppm for four aliphatic protons of two -CH2- groups and the proton at C-4 of pyrazolone ring which is toutomerism with NH, the later proton appeared at δ7.83ppm for proton of NH form. 1HNMR spectrum (in DMSO as a solvent ), Figure(7)for compound [XIV]c showed: a singlet signal at δ(9.94)ppm for one proton of NH indole ring, singlet signal at δ(8.98)ppm for one proton of (C=N-NH) group, two doublets and mulitiple signals in region δ(6.58-7.95) ppm that could be attributed to the nine aromatic protons, singlet signal at δ(1.3-2.00) ppm for eight protons of CH3 group at C-3 of pyrazolone ring, CH3C=N and C-CH2-C. Signals in the region δ(3.4-4.1) ppm for four aliphatic protons of two -CH2- groups and a proton of C-4 of pyrazolone ring which is toutomerism with NH, the later proton appeared at δ8.07 ppm. Biological Activity The antibacterial activity of the synthesized compounds was performed according to the agar diffusion method[21]. The synthesized compounds were tested against E.coli and Staph. aureus. Each compound was dissolved in DMSO to give concentration 1ppm. The plates were then incubated at 370C and examined after 24 hrs. The zones of inhibition formed were measured in millimeter and are represented by (-), (+), (+ +) and (+ + +) depending upon the diameter and clarity as in Table (4). The synthesized compounds exhibit the highest, moderately or low biological activity or no active of some of them against one of the organisms. Compounds showed good inhibition against of the two types of the bacteria, this 428 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 could be related to the presence of the indole, 1,3,4-thiadiazole, amide or pyrazolone and hydrazone units. References 1. Partha, P. and Chandrajit. D. (2013) "Synthetic approaches for bis (indole) methanes", IJPSR, 4(4): 1312-1322. 2. Doddappa, P. and Biradar, J. (2013) "Synthesis, characterization and antimicrobial activities of 2-(5-substituted-3-phenyl-1H-indol-2-yl)-5-substituted-7H-[1,3,4]oxadiazolo/ thiadiazolo [3,2-a][1,3,5]triazine-7-thiones", J. Chem. Pharm. Res., 5(1): 75-85. 3. Srivastava, K. and Singh, V., (2010) "Quantum Chemical Studies on Conformations of Indoles", Der. Pharma. Chemica, 2(6): 385-393. 4.Kushwaha, N.; Swatantra, K.; Kushwaha, S. and Rai, A. (2012) "Biological Activities of Thiadiazole Derivatives", IJCRGG, 4(2): 517-531. 5.Nayak, A. (2014) "synthesis and evaluation of some new thiadiazole as antimicrobial agents", Int J Pharm Bio Sci., 5(2): 344-347. 6.Hussan, F. (2012) "synthesis and biological evaluation of 1, 3, 4-thiadiazole derivative on some parameters of immunity and liver enzymes", IJRPC, 2(1): 58-65. 7. Salih, N.; Salimon, J. and Yousif, E. (2012) "Synthesis, characterization and antimicrobial activity of some carbamothioyl-1,3,4-thiadiazole derivatives", 4(2): 655-660. 8. Hasmin, M.; Gajjar, A.; Savjani, J. and Masi, I. (2011) "Synthesis And Anticonvulsant Activity Of Novel 2,5-Disubstituted -1,3,4-Thiadiazole Derivatives", Int. J. Pharm. Tech Res., 3(4): 2017-2024. 9. Arvind, K.; Parthsarthy, R.; Kshitiz, j. and Geeta, M. (2011) "Synthesis, characterization and antibacterial activity of 1, 3, 4-thiadiazole derivatives", IJSID, 1(3):353-361. 10. Seelam, N.; Satya, P. and Prasanthi, S. (2013) "Synthesis and antimicrobial activity of some novel fused heterocyclic moieties", Org. Commun., 6(2): 78-85. 11. Raj, M.; Patel, H.; Raj, L. and Patel, N. (2013) "Synthesis, Characterization and Antimicrobial Evaluation of some 5-(substituted)-2-amino-Thiadiazoles", Int. J. Res. Chem. Environ., 3(3): 9-15. 12. Noolvi, M.; Patel, H.; Singh, N.; Gadad, A. ; Cameotra, S. and Badiger, A. (2011) "Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives", European Journal of Medicinal Chemistry, 46: 4411-4418. 13. Dugdu, E.; Unver, Y.; Unluer, D. and Sancak, K. (2014) "Synthesis and Biological Properties of Novel Triazole-Thiol and Thiadiazole Derivatives of the 1,2,4-Triazole-3(5)-one Class", Molecules, 19: 2199-2212. 14. Abdel Rahman, D. and Mohamed, K. "(2014) Synthesis of novel 1,3,4-thiadiazole analogues with expected anticancer activity", Der. Pharma Chemica, 6(1): 323-335. 15. Bule, S.; Kumbhare, M. and Dighe, P. ( 2013) "Synthesis and in-vitro Biological Evaluation of a Novel Series of 4-(Substituted)-5-Methyl-2-Phenyl-1,2-Dihydro-3H-Pyrazol- 3-One as Antioxidant", J. Chem. Bio. Phy. Sci. Sec. , 3(3): 1996-2005. 16. Gadhawala, Z.; Modasiya, M.; DOI, R.; HarsolIiya, M. and Panchbhayya, M. (2012) "Synthesis and Biological evaluation of some new oxime, phenyl hydrazone and 2, 4 dinitro phenyl hydrazone derivatives of ketones", Ultra Chemistry, 8(2): 269-272. 17. Kumar, P.; Subramaniyan, S.; Yamini, K. and Suthakaran, R. (2011) "Synthesis of some novel 1-H pyrazole derivatives and their antibacterial activity studies", Rasayan J. Chem., 4(2): 400-404. 18- Kumar, P.; Subramaniyan, S.; Yamini, K. and Suthakaran, R. (2011) "Synthesis of some novel 1-H pyrazole derivatives and their antibacterial activity studies", Rasayan J. Chem., 4(2): 400-404. 429 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 19. Patila, B.; Machakanura, S.; Hunoora, R.; Badigera, D.; Gudasia, K. and Blighb, S. (2011) "Synthesis and anti-cancer evaluation of cyclotriphosphazene hydrazone derivatives", Der. Pharma Chemica, 3(4):377-388. 20. Vogel I. (1974) "A textbook of practical organic chemistry", 3rd Ed Longman Group Ltd., London. 21. Al-Rawi, M.; Tomma, J. and Abdullah, R. (2013) "Synthesis and Study Biological Activity of Some New Isoxazoline and Pyrazoline derivatives", Ibn Al-Haitham Jour. for Pure & Appl. Sci., 26(1): 208-217. Table No.(1) : Physical properties of synthesized compounds [V]-[XIV] Comp. No. Nomenclature Structural formula Molecular formula M.P ◦C Yiel d% Color [V]a 2-amino-5-[(1H-indol-3-yl)methyl ]- 1,3,4-thiadiazole N H S NN NH2 C11H10N4S 210-212 93 Brown [V]b 5-(3-(1H-indol-3-yl)propyl)-1,3,4- thiadiazol-2-amine N H (CH2)3 S NN NH2 C13H14N4S 168-170 88 Red [VI]a N-(5-(2-methyl-1H-indol-3-yl)-1,3,4- thiadiazol-2-yl) acetamide N H S NN CH3 N H C O CH3 C13H12N4OS 170-172 81 Yellow [VI]b N-(5-(2-methyl-1H-indol-3-yl)-1,3,4- thiadiazol-2-yl) benzamide N H S NN CH3 N H C O Ph C18H14N4OS 124-126 87 Pale yellow [VI]c 4-methoxy-N-(5-(2-methyl-1H-indol-3- yl)-1,3,4-thiadiazol-2-yl)benzamide N H S NN CH3 N H C O OCH3 C19H16N4O2S 154-156 90 Pale brown [VI]d N-(5-(2-methyl-1H-indol-3-yl)-1,3,4- thiadiazol-2-yl)octanamide N H S NN CH3 N H C O C7H15 C19H24N4OS Gummy 63 brown [VII]a N-(5-((1H-indol-3-yl)methyl )-1,3,4- thiadiazol-2-yl) acetamide N H S NN N H C O CH3 C13H12N4OS 164-166 93 brown [VII]b N-(5-((1H-indol-3-yl)methyl)-1,3,4- thiadiazol-2-yl)benzamide N H S NN N H C O Ph C18H14N4OS 175-177 87 pale brown [VII]c N-(5-((1H-indol-3-yl)methyl)-1,3,4- thiadiazol-2-yl)-4-methoxybenzamide N H S NN N H C O OCH3 C19H16N4O2S 158-160 89 brown [VII]d N-(5-((1H-indol-3-yl)methyl)-1,3,4- thiadiazol-2-yl)octanamide N H S NN N H C O C7H15 C19H24N4OS 188-190 75 Orange [VIII]a N-(5-(3-(1H-indol-3-yl)propyl) -1,3,4- thiadiazol-2-yl)acetamide N H (CH2)3 S NN N H C O CH3 C15H16N4OS 196-198 86 gray [VIII]b N-(5-(3-(1H-indol-3-yl)propyl)-1,3,4- thiadiazol-2-yl)benzamide N H (CH2)3 S NN N H C O Ph C20H18N4OS 122-124 71 yellow [VIII]c N-(5-(3-(1H-indol-3-yl)propyl)-1,3,4- thiadiazol-2-yl)-4-methoxy benzamide NH (CH2)3 S NN N H C O OCH3 C21H20N4O2S 144-146 76 brown [VIII]d N-(5-(3-(1H-indol-3-yl)propyl)-1,3,4- thiadiazol-2-yl)octanamide N H (CH2)3 S NN N H C O C7H15 C21H28N4OS 128-130 81 Black [XI]a 1-(2-1H-indol-3-yl-acetyl)-3-methyl-4- hydro-pyrazol-5(4H)-one N H C O N N O Me C14H13N3O2 112-114 90 Brown [XI]b 1-(4-1H-indol-3-yl-butanoyl)-3-methyl- 4-hydro-pyrazol-5-one N H (CH2)3 C O N N O Me C16H17N3O2 154 -1 56 69 Red [XII]a 1-(2-1H-indol-3-yl-acetyl)-4-acetyl-3- methyl-4-hydro-pyrazol-5-one N H C O N N O Me C OH3C C16H15N3O3 212-214 77 Brown [XII]b 1-(4-1H-indol-3-yl-butanoyl)-4-acetyl- 3-methyl-4-hydro-pyrazol -5-one N H (CH2)3 C O N N O Me C OH3C C18H19N3O3 268-270 87 Brown 430 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Table No.(2): Characteristic FTIR absorption bands data of new amide compounds[V]a- [VIII]d Table No.(3): Characteristic FTIR absorption bands data of new pyrazolone compounds[XI]-[XIX] [XIII]a 1-(2-(1H-indol-3-yl-acetyl)-3-methyl-4- [1-(2-phenylhydrazono)ethyl]-4-hydro- pyrazol-5-one NH C O N N CH3 O C NH3C H N Ph C22H21N5O2 162-164 83 Yellow [XIII]b 1-(2-(1H-indol-3-yl-acetyl)-3-methyl -4- {1-[(4-bromophenyl) hydrazono]ethyl}- 4-hydro-pyrazol-5-one NH C O N N CH3 O C NH3C H N Br C22H20BrN5O2 128-130 82 Brown [XIII]c 1-(2-1H-indol-3-yl-acetyl)-3-methyl-4- {1-[(4-nitrophenyl) hydrazono]ethyl}-4- hydro-pyrazol-5-one N H C O N N CH3 O C NH3C H N NO2 C22H20N6O4 98-100 87 Dark red [XIII]d 1-(2-1H-indol-3-yl-acetyl) -3-methyl-4- {1-[(2,4-dinitrophenyl) hydrazono] ethyl}-4-hydro- pyrazol-5-one N H C O N N CH3 O C NH3C H N NO2 NO2 C22H19N7O6 140-142 79 Red [XIV]a 1-(4-1H-indol-3-yl-butanoyl)-3-methyl- 4-[1-(phenylhydrazono) ethyl]-4-hydro- pyrazol-5-one N H (CH2)3 C O N N CH3 O C NH3C H N Ph C24H25N5O2 113-115 81 Pale orange [XIV]b 1-(4-1H-indol-3-yl-butanoyl)-3-methyl- -4-{1-[(4-bromophenyl) hydrazono] ethyl}-4-hydro-pyrazol-5-one NH (CH2)3 C O N N CH3 O C NH3C H N Br C24H24BrN5O2 120-122 80 Brown [XIV]c 1-(4-1H-indol-3-yl-butanoyl)-3-methyl- 4-{1-[(4-nitrophenyl) hydrazono] ethyl}-4-hydro-pyrazol-5-one NH (CH2)3 C O N N CH3 O C NH3C H N NO2 C24H24N6O4 108-110 76 Brown [XIV]d 1-(4-1H-indol-3-yl-butanoyl)-3-methyl- 4-{1-[(2,4-dinitrophenyl) hydrazono]ethyl}-4-hydro-pyrazol -5- one N H (CH2)3 C O N N CH3 O C NH3C H N NO2 NO2 C24H23N7O6 192 -194 70 Orange Comp. No. VN-H VC-H arom. VC-H alipha. VC=O Amide VC=C arom. VC-S-C [VI]a 3446, 3151 3012 2920-2850 1684 1595 698 [VI]b 3412, 3190 3072 2950-2837 1689 1602 684 [VI]c 3400, 3200 3070 2981-2843 1685 1604 684 [VI]d 3400, 3170 3050 2956-2872 1690 1593 696 [VII]a 3392, 3167 3057 2924-2858 1683 1590 680 [VII]b 3407, 3159 3062 2926-2845 1666 1600 694 [VII]c 3398-2178 3053 2953-2843 1685 1602 698 [VII]d 3400-3180 3050 2953-2854 1683 1600 685 [VIII]a 3400-2209 3055 2929-2850 1681 1600 680 [VIII]b 3388-3201 3057 2927-2862 1674 1602 681 [VIII]c 3398-3172 3050 2981-2843 1685 1602 698 [VIII]d 3400-3184 3055 2953-2854 1689 1590 690 Com. No. VN-H VC-H arom. VC-H alipha. VC=O VC=O amide VC=N pyrazolone VC=C arom. Other [XI]a 3404,3287 3057 2970-2858 1795 1670 1625 1600 ____ [XI]b 3400,3273 3014 2983-2864 1701 1669 1625 1600 ____ [XII]a 342, 3280 3057 2933-2850 1735,1995 1662 1620 1591 ____ [XII]b 3400,3271 3055 2981-2866 1735,1705 1684 1638 1600 ____ [XIII]a 3400-3200 3055 2981-2850 1700 1670 1625 1602 mono-sub.: 694,746 [XIII]b 3400-3205 3053 2956-2856 1693 1662 1622 1589 p-Br: 611 [XIII]c 3400-3220 3055 2954-2854 1695 1670 1625 1597 p-NO2 :1520,1323 [XIII] d 3400-3250 3090 2929-2850 1699 1675 1645 1593 p-NO2 :1517,1319 [XIV]a 3406-3200 3080 2929-2856 1690 1670 1635 1602 mono-sub.:694, 752 [XIV]b 3408-3263 3055 2950-2850 1699 1680 1640 1595 p-Br: 615 [XIV]c 3400-3200 3055 2927-2872 1696 1665 1625 1597 p-NO2 :1519,1325 [XIV]d 3383-3267 3072 2929-2856 1701 1647 1618 1593 p-NO2 :1519,1309 431 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Table No. (4) : antibacterial activity of the synthesized compounds [V]a -[XIX]d Staphlococcus aurus (G+) E.Coli(G-) Comp. No. Staphlococcus aurus (G+) E.Coli(G-) Comp. No. +++ - [VII]d - - DMSO +++ -[VIII]a +++- [V]a ++ - [VIII]b +++ - [V]b +++ +++ [VIII]c ++ ++ [VI]a ++ - [VIII]d +++ +++ [VI]b ++ - [XI]a + ++ [VI]c + +++ [XI]b ++ +++ [VI]d - +++[XII]b++++ [VII]a ++ +++ [XIII]b +++ ++ [VII]b +++ +++ [XIV]d +++ ++ [VII]c Key to symbols: Highly active = + + +(more than)15 mm. Moderately active = + +(11-15) mm. Slightly active = + (5-10) mm . (-)Zone of inhibition. Figure No. (1) :Mass-spectrum of compound[V]b Figure No. (2): FTIR –spectrum of compound [VI]a 50.0 75.0 100.0 125.0 150.0 175.0 200.0 225.0 250.0 275.0 300.0 0 25 50 75 100 % 64 256 128 96 160 192 98 14957 71 185164111 248224 231213 285268 295 432 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No. (3) 1 HNMR - spectrum of compound[VIII]d Figure No. (4): FTIR –spectrum of compound [XII]b Figure No. (5): FTIR –spectrum of compound [XIV]d 433 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No. (6) 1 HNMR - spectrum of compound[XIII]c Figure No. (7) 1 HNMR - spectrum of compound[XIV]c 434 | Chemistry 2014) عام 3العدد ( 27مجلة إبن الھيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 تشخيص ودراسة وتحضير -4, 3, 1مشتقات لبعض البايولوجي السلوك البايرازولون الجديدة التي تحتوي على حلقة االندول و ثاياديازول خالد فھد علي العلياوي الزم كاظم ماذي جمبد ھرمز توما بغداد جامعة )/ مھيثال ابن( الصرفة للعلوم -التربية كلية/ الكيمياء قسم 2014ايلول29,قبل البحث في: 2014حزيران12استلم البحث: الخالصة البايرازولون تحتوي على حلقة االندول إذ أو ثاياديازول- 4, 3,1ل من ھذا البحث تحضير مشتقات جديدةيتض ھايدرازين - كاربونيل)-3- اندول-H1-(مثيل-2من تحلق V[I[و ]a, bII]V ثاياديازول- 4, 3,1 - امينو- 2حضرت مركبات اندول البيوتانويك مع - 3اندول االيثانويك أو حامض - 3في حامض الكبريتيك أو من تفاعل حامض [III] كاربوثايوامايد ) بوصفه عامل مساعد. بينما حضرت مشتقات االميد الجديدة 3POClيميكاربازايد بوجود كلوريد اوكسي الفسفور (الثاياس ]VIII[- [VI] من تفاعل األمينات االروماتية المحضرةb,a[V]- [IV] مع كلوريدات الحامض الكاربوكسيلي المختلفة مع ]X[bأو ]X[a من تفاعل مشتقي الھادرازايد X]a, b]I لبوجود البردين. كما تضمن البحث تحضير مشتقي البايرازو 4-في الموقع لاثيل اسيتواستيت باستعمال االيثانول المطلق مذيبا. ومن ثم تم إدخال مجموعة االسيتايل على حلقة البايرازو V[XI[d-aو XI]h-aI]I نعن طريق التفاعل مع كلوريد االسيتايل في وسط قاعدي. أخيرا حضرت مشتقات والھايدرازو مع ھايدرازينات اروماتية مختلفة باستعمال االيثانول المطلق مذيبا. a, bI]I[Xمن تفاعل مركبات البايرازولون الطيفية الطرائق عن فضال أنصھارھا درجات قياس خالل من البحث ا ھذ في المحضرة المركبات جميع شخصت كما )امنھ للبعض (, وطيف الماس البروتوني المغناطيسي النووي الرنين وطيف, الحمراء تحت األشعة بطيف المتمثلة (-). وكرام (+) كرام ھي .البكتريا من أنواع ضد المحضرة المركبات لمعظم البايولوجية الفعالية درست .ھايدرازوناندول و ،بايرازولون بايرازول, ،ثاياديازول- 4, 3,1 : الكلمات المفتاحية