Microsoft Word - 8 407 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Synthesis and Characterization of Novel Schiff Bases of Imide Moiety *Sulaiman M. Hasan Ali H. Samir Ismaeel Y. majeed Dept.of Chemistry/College of Education for Pure Science/(Ibn Al- Haitham)/University of Baghdad. Received in: 22 April 2014,Accepted in:29 September 2014 Abstract In our research novel schiff bases of imides moiety have been synthesized . Novel Schiff base derivatives of imides moiety have been synthesized by multistep reaction . First step involves prepare 2-amino -5-mercapto-1,3,4-thiadiazole (I) by the cyclization of thiosemicarbazide with carbon disulphide and anhydrous sodium carbonate in ethanol as a solvent . Then , compound (I) was reacted with phthalic anhydride in the presence of glacial acetic acid to give 2-(5-mercapto-1,3,4-thiadiazol-2-yl) isoindoline-1,3-dion (II).Compound (II)was heated with ethyl chloracetate in the presence of potassium carbonatproduced ethyl 2- (5-(1,3-dioxoisoindoline -2-yl)-1,3,4-thiadiazole-2-yl thio) acetate (III).The reaction of compound (III) with hydrazine hydrate yielded 2-(5-(1,3-dioxoisoindoline -2-yl)-1,3,4- thiadiazol-jm2-ylthio)acetohydrazide (IV).The fifth step involves reaction of compound (IV) with N,N-dimethyl aminobenzaldehyde to yield N´-(4-(dimethyl amino)benzylidene )-2-(5- (1,3-dioxoisoindoline-2-yl)-1,3,4-thiadiazole-2-yl-thio)acetohydrazide (V).The structures of the newly synthesized compounds were confirmed by physical properties and spectral (FT- IR,1H-NMR)analysis . KeyWords:2-(5-(1,3-dioxoisondolin-2-yl)-1,3,4-thiadizole-2-yl thio)acetohydrazide , phthalic anhydride , Schiff bases. * This paper is extracted from master thesis of the first author . 408 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Introduction Imides are the biologically active compounds having different pharmacological activities such as analgesic ,anti-inflammatory ,anti-microbial ,anti-depressant and anti-cancer etc. These compounds play an important role in medicinal chemistry in drug development and drug discovery . Cyclic imide moiety and their derivatives play an integral part in various important molecules such as thalidomide ,isogranulatimide and rebeccamycinetc . These are the compounds which possess various pharmacological activities such as analgesic ,anti- inflammatory , anti-depressant and anti-viral etc[1-7] . The discovery and development of schiff basesof imide moiety are the most powerful technology . A heterocyclic compounds plays an important role in regulating the biological activities . Schiff bases contain carbon –nitrogen double bonds in which nitrogen atom get linked to aryl and alkyl atoms . Schiff bases can possess different pharmacological activities and also have industrial applications .Schiff bases of imides possess different pharmacological activities such as antimicrobial ,anti-inflammatory, antidepressant ,antipyretic etc[8-9] Natural and synthetic macrocycles continue to attract extensive scientific interest, with research developments proceeding in many directions including anion receptors , molecular recognition , drug discovery , therapeutics and nanoscience [10] . Macrocyclic systems have evolved from the original crown ethers spherands , cryptands and prophyrins , through calixarenes , resorcinarenes , rotaxanes , catenanes and beyond, as wellas into interdisciplinary fields and biological applications [11] . Experimental A-Materials All the chemical used in the synthesis were of analytical grandes . B – Instrumentation Melting points were recorded using electro thermal melting point apparatus and are uncorrected . Infrared spectra were recorded as KBr disc on SHIMADZU-FT-IR-8400 spectrometer.1H-NMR spectra was recorded on Bruker 300 MHz instrument using DMSO-d6 as a solvent and TMS as internal reference,measurement were made at Al-Albayt University. Jordan . . the progress of the reaction was monitored by TLC using aluminum silica gel plates . Synthesis of 2- amino - 5- mercapto-1,3,4- thiadiazole (I) [12] . A mixture of (2 gm , 0.02 mol.) of thiosemicarbazide and (2.33gm,o.o2 mol.) of anhydrous sodium carbonate were dissolved in 25 ml. abs .ethanol .To this solution (3.2 gm,0.04 mol.) of carbon disulphide was added . The resulting mixture was heated under reflux for 10 h . The reaction mixture was then allowed to cool down at room temperature . Most of solvent was removed under reduced pressure and the residue was dissolved in 20 ml .distilled water , carfefully acidified with cold conc . hydrochloric acid to give pale yellow precipitate . The crude product was filtered and washed with cold water , recrystallized from hot water to give the desired product as yellow needles , yield (75%), m.p (230-232)co. Synthesis of 2-(5-mercapto- 1,3,4-thiadiazole -2-yl) isoindoline -1,3-dione (II) [13] . To a solution of 2- amino -5- mercapto 1,3,4-thiadiazole (0.01mol.) in ethanol (20 ml.) .phthalic anhydride (0.01mol.) and acetic acid were added drop by drop, the solution was stirred magnetically for 2h at room temperature and then reaction mixture was refluxed for 6 h, then the mixture was allowed to stirring for one hour at room temperature . The mixture was poured on distilled water .The product was filtered , washed by hot water and recrystallized from acetone . yield (93%), m.p (266-268)co. 409 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Synthesis of Ethyl 2-(5-(1,3-dioxoisoindoline-2-yl)1,3,4-thiadiazole-2 -yl-thio) acetate (III) [14] . Ethyl chloroacetate (0.01 mol.) was added drop wise to a hot solution of compound (II) and potassium carbonate in acetone as a solvent .The mixture was refluxed for 4h .and allowed to stand .Evaporating the solvent under reduced pressure , water was added and the crude product was extracted with ethyl acetate and dried over anhydrous magnesium sulphate .Evaporating of the organic layer gave solid products , recrystallized from ethanol . yield (60%) , m.p (119-120) co. Synthesis of 2-(5-(1,3-dioxoisoindoline-2-yl)-1,3,4-thiadiazole-2-yl-thio) acetohydrazide (IV) [14] . To a hot solution of hydrazine hydrate (0.01 mol) in ethanol (10 ml) a solution of compound (III) in ethanol (10 ml) was added and the mixture was reflux for 6 h . The mixture was allowed to cool and the precipitate was filtered ,dried and recrystallized from ethanol . yield (88 %) , m.p (209-212)co . SynthesisofN´-(4-(dimethylamino) benzylidene)-2-(5-(1,3-dioxoisoindolin-2- yl)-1,3,4-thiadiazol-2-yl-thio)acetohydrazide (V) [14]. A mixture of compound (IV) (0.01 mol) and N,N-dimethyl aminobenzaldehyde (0.01 mol) in absolute ethanol was refluxed for 6 h .then the mixture was cooled . The solid product was filtered , dried and recrystallized from ethanol . yield (31 %) , m.p (215-217)co. 410 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 H2N H N C S NH2 Na2CO3 CS2 S NN SHH2N O O O CH3COOH glacial N O S NN SH ClCH2COOC2H5K2CO3 N O O S NN S C H2 C O H2 C O ( I ) O ( II ) ( III ) N2H4.H2OEthanol N O O S NN S C H2 C N H NH2 CH3 O ( IV ) Ar-CHOH N O O S NN S C H2 N H N O C H Ar Ar = CHO N H3C CH3 Scheme (1) Ethanol abs. Acetone (V) 411 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Results and Discussion Compound (I) 2-amino-5-mercapto-1,3,4-thiadiazole was prepared through the reaction of thiosemicarbazide with carbon disulphide in the presence of anhydrous sodium carbonate in absolute ethanol .The structure of compound (I) was identified by its melting point and FT-IRspectroscopy.The FT-IR spectrum of compound (I)[15], figure (I) shows the following characteristic bands , two bands at 3396 cm-1 and 3277 cm-1 were due to asymmetric and symmetric stretching vibration of (-NH2) group respectively , an absorption band at 3093 cm-1 was due to the (N-H) stretching (tautomeric form ).The (-SH ) stretching band found as very weak shoulder at 2331 cm-1 , a band at 1604cm-1 was due to ( C=N ) stretching of the thiadiazole ring moiety . The sharp band at 1533 cm-1 and 1330 cm-1 are due to the (N-H) bending and (C-N) stretching vibration respectively . Also , the absorption band at 1055 cm-1 for the (C=S) group which gives an evidence that compound (I)can exist in two tautomericfroms , thiol (A) and thione form (B) as shown in scheme (2). S NN SH2N H S NN SH2N H (A) (B) Scheme (2) The second strategy used in the present work involved treatment of phthalic anhydride with 2-amino-5-mercapto-1,3,4-thiadiazole in glacial acetic acid under reflux condition for many hours . Structure of this compound (II)was confirmed by FT-IR and1H-NMR. FT-IR spectra of compound (II),figure(2) showed disappearance of absorption bands belong to (- NH2) amine at (3396-3277)cm-1 . Also , FT-IR spectra showed many clear absorption bands including band at (1735-1786)cm-1 , (1602)cm-1 , (1544)cm-1 , (1354-1363)cm-1 due to (C=O)imide , (C=N) ,(C=C) , (C-N) imide and (C-S) respectively .1H-NMR spectrum of compound (II),figure(3) showed signals at ᵟ(3.33 ,2.33,7.96 -8.04 ,14.66) ppm due to amine proton ,SH, aromatic protons and NH tautomer [16] . Compound (III) was synthesized by the reaction of compound (II) with ethyl chloroacetate in the presence ofanhydrus potassium carbonate in acetone . FT-IR spectrum of compound (III),figure(4) showed appearance of absorption band at 1749 cm-1 due to carbonyl group of ester [17] . 1H-NMR spectrum of compound (III) ,figure (5) , shows the following characteristic chemical shifts ( DMSO-d6,ppm ):the aromatic ring protons appeared as multiplies atᵟ(7.60 , 8.05) ppm. Single signal (4.30) ppm due to the (-CH2-S-) group [18].Triplet signal atᵟ (1.21) ppm for the methyl group and the guartet signal at (4.13) ppm for the methylene group . Compound (IV) was synthesized by the reaction of compound (III) with hydrazine hydrate in ethanol absolute , the compound was identified by FT-IR and 1H-NMR spectra .The FT-IR spectra of compound (IV), figure (6)showed disappearance of carbonyl group at 1749 cm-1 and appearance band at 3415-3267 cm-1 due to (-NH2) group and at 1660 cm-1 for carbonyl group of amide.The1 H-NMR data of compound (IV) ,figure (7)shows the following characteristic chemical shifts ( DMSO-d6 ,ppm): the aromatic ring proton appeared as multiplies at ᵟ(7.53-8.07)ppm and at 3.96 (s,2H,of SCH2), 11.5 (br. s,H of NH amide ), 3.34 (br. s,2H of NH2 ) [19]. The condensation reaction of equimolar quantity of compound [IV] with aromatic aldehyde was the major method to prepare schiffsbases .FT-IR spectrum of compound (V) , figure (8) , 412 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 showed the disappearance of two absorption bands at 3415- 3267 cm-1 due to the (-NH2) stretching of amino group , and appearance of band at 1654 cm-1 due to (C=N) group of imine .1H-NMR was more informative , characteristic peaks were observed atᵟ( 6.69-8.17) (mult ,H of two benzene ring ) , 4.05 (s,2H,of SCH2), 2.67 (s,6H, of N(CH3)2), 11.38 (s,1H,of NH of amide ), 4.43(s,1H,CH=N). 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(2012)((synthesis of Heterocyclic compounds Derived from 2-mercapto quinoline ,Ibn Al-Haitham .J.for pure and Applied science ,25(3):242-252 . 15-SeedR.S; Samir,A.H and Ali,K.F. (2013)((synthesis and characterization of some new thiazine-4-ones containing 1,3,4-thiadiazole moiety)), Inter.J.for sciences and technology,8(2):55-61 . 413 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 16-Al-Azzawi,A.M and A.S.Hamd (2011)((synthesis ,characterization and Evaluation of Biological activity of Novel cyclic imides containing Heterocycles based on 2,5-disubstituted- 1,3,4-thiadiazoles)),Al-Anbar.J.vet.Sci.,4(2):152-164. 17-Said,S.A.(2006)((synthesis of some New 2-(2-Isopropyl-5-methyl phenoxymethyl)-5- aryl-1,3,4-Oxadiazoles)) ,Raf.Jour.Sci.,17(4):52-58 . 18-Bayrak,H;Demirbas,A;Karaoglu,S.Aand Demirbas,N. (2009) ((synthesis of some new 1,2,4-triazole, their Mannich and Schiff base and evaluation of their antimicrobial activities)).Eur.J.of Medicinal chemistry ,44:1057-1066 . 19-Faghihi,K.;Nourbakhsh,M.and Hajibeygi,M. (2011)((New optically active poly (amide- imide)s from N-trimellityimido-L-amino acid and 1,2-bis[4-aminophenoxy] ethane in the main chain :synthesis and characterization))J.of Saudi chemical society,10:1016 . Table No. (1):physical properties of prepared compounds Yield % color Recrystallize d solvent M.p .Co Structural formula Molecular formula Com. No. 75 yellow Water 230-232 S NN SH H2N C2H3N3S2 1 93 Dark Yellow Acetone 266-268 N O O S NN SH C10H5O2S2 2 60 Brown Ethanol 119-120 N O O S O OS NN C14H11N3O4S2 3 88 white Ethanol 209-212 N O O S O NHNHS NN C12H9N5O3S2 4 31 Pale yellow Ethanol 215-217 N O O S O NHN S NN C21H18N6S2 5 414 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Table No.(2):FT-IR Spectral data of the prepared compounds FT-IR spectral data cm-1 Comp. No. (N- H)amine, amide (C=C) arom. (C=O)amid e, ester (C=N)endo. , exo. (C=O) imide C-H aliphatic C-H aromatic 3396 3277 3174 1604 I 3199 1544 1602 1735 1786 II 1550 1749 ester 1608 1724 1793 2985 2953 2900 3099 3068 III 3415 3267 3167 1558 1660 amide 1600 1724 2980 2899 3018 IV 3167 3120 1558 1662 amide 1600 endo. 1654 exo. 2968 2918 2899 3016 V 415 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No.(1):FT-IR spectrum of compound (I) Figure No.(2):FT-IR spectrum of compound (II) 416 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No.(3):1H-NMR spectrum of compound (II) Figure No.(4):FT-IR spectrum of compound (III) 417 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No.(5):1H-NMR spectrum of compound (III) Figure No.(6):FT-IR spectrum of compound (IV) 418 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No.(7):1H-NMR spectrum of compound (IV) Figure No.(8):FT-IR spectrum of compound (V) 419 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 Figure No.(9):1H-NMR spectrum of compound (V) 420 | Chemistry 2014) عام 3(العدد 27المجلد مجلة إبن الھيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (3) 2014 تحضيروتشخيص قواعد شف جديدة لوحدة االمايد سليمان محمود حسن علي حمادي سمير أسماعيل ياسين مجيد ابن الھيثم)/جامعة بغداد (قسم الكيمياء/كلية التربية للعلوم الصرفه 2014ايلول 29, قبل البحث في: 2014نيسان 22استلم البحث في: الخالصة على والحاويه الجديدة شف قواعد مشتقات .االيمايد على جديدةتحتوي تحضيرقواعدشف بحثنا ھذا تم في ثياديازول -,1,3,4- مركبتو - 5 امينو -2 تحضيرالمركب الخطوةاالولى تضمنت. متعددالخطوات بتفاعل حضرت االيمايد )I (كحولي مذيب وفي الالمائيه الصوديوم كاربونات بوجود كبريتيدالكاربون ثنائي مع الثايوسيمكاربازايد بتحولق , - 2-ثياديازول-1,3,4 -مركبتو -5(- 2 ليعطي الثلجي الخليك حامض بوجود انھيدريدالفثاليك مع المركب ھذا تفاعل بعدذلك ليعطي البوتاسيوم كاربونات بوجود كلوريداالثيل خالت مع تفاعل) II( المركب) . II( ون – ثنائي - 1,3-ايزواندولين) يل مع) III(المركب تفاعل) . III( استيت) ثايو يل -2- ثياديازول - 1,3,4-) يل - 2- اوكسوايزواندولين ثنائي -1,3(-5(-2 اسيتوھايدرازايد) يلثايو -2-ثياديازول - , 1,34)يل -2- اوكسوايزواندولين ثنائي - 1,3(- 5(-2 ليعطي ھايدريت الھيدرازين )IV . (الخطوةالخامسھتضمنتتفاعاللمركب )IV (معN,N -ليعطي فثالمينوبنزلديھايد ثنائيN´-(4-مثيل ثنائي ) .V( اسيتوھايدرازايد)يل ثايو-2- ثياديازول 4-3-1- )يل-2- ثنائي اوكسوايزواندولين – 3,1(-5(-2-)مينوبنزلدينا ) .NMR-H1IR , -FT( تراكيب المركبات المحضرةالجديدة شخصت من خالل الخواص الفيزيائية وتحاليل اطياف ) ثايو يل - 2- ثياديازول -1,3,4-) يل - 2- ثنائياوكسوايزواندولين -1,3(- 5(- 2الكلمات المفتاحية: قواعد شف,انھدريدالفثالك,استيت