293 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Synthesis And Characterization Of New Oxazepines Derived From D-Erythroascorbic Acid A. A. Mukhlus , M. S. Al-Rawi, J. H. Tomma, A. H. Al-Dujaili Department of Chemistry , College of Education Ibn Al- Haitham University of Baghdad Abstract The new schiff bases derived from D-erythroascorbic acid contaning heterocyclic unit were synthesized by condensation of D-erythroascorbic acid with aromatic amine (containing 1,3,4- oxadiazole or 1,3,4-thiadiazole unit) in dry benzene using glacial acetic acid as a catalyst. D- erythroascorbic acid [IV] was synthesized by four steps (Scheme 1), while the primary aromatic amine which is containing 1,3,4-oxadiazole [VII] or 1,3,4-thiadiazole [VIII] synthesized by the reaction of 4- methoxy benzoyle hydrazine [VI] with 4-amino benzoic acid or by the reaction tuloic acid with thiosemicarbazide, respectively in the presence of POCl3. The new 1,3-oxazepine derivatives were obtained by addition reaction of Schiff bases with different anhydrides in dry benzene, The new 1,3- oxazepine derivatives [XII]a-d- [XIV]a-d were synthesized by refluxing compound [IX] , [X] or [XI] with different anhydride (maleic, phthalic, naphthalic anhydride or pyromellitic dianhydride) in presence of dry benzene. The structure of synthesized compounds have been characterized by their melting points , elemental analysis and by their spectral data; FTIR , UV-Vis, Mass and (1HNMR , 13CNMR of some of them) spectroscopy . All the synthesized compounds have been screened for their antibacterial activities. They exhibited good antibacterial activity against Escherichia coli (G-) and Staphylococus aureus (G+) . Key word : 1,3-oxazepine, Schiff bases , L-Ascorbic acid . Introduction L-Ascorbic acid is one of the most important biomolecules . It acts as an antioxidant and radical scavenger widely distributed in aerobic organisms [1]. L-Ascorbic acid derivatives have been found to possess antitumor and antiviral activities [2-4]. Schiff bases are used as substrates in the preparation of a large of bioactive and industrial compounds via ring closure , cyclo addiation and replacement reactions. In addition , Schiff bases are well known to have biological activities [5-7]. 1,3-Oxazepines is non-homologous seven member ring, that contains two heteroatoms (Oxygen and Nitrogen). Oxazepines is used as antibiotics , enzyme inhibitors pharmacological interst , it has much chemical and biological studied[8-12]. Hussein [13] et. al. ,synthesized 1,3- oxazepine -4,7-dione (2) and (3) from the reaction of Shciff bases (1) with maleic or phthalic anhydride, respectively. 294 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 O N O O O N O O R R O2N R O2N O2N- (1) m al ei c a nh yd rid e phthalic anhydride (2) (3) N=CH Recently, Tomma et al. [14] synthesized a new 1,3-oxazepines (5), (6) derivatives by the cycloaddition reaction of Schiff bases [4] with phthalic anhydride and naphthalic anhydride, respectively. X CH=N NN S S NN N=CH X N aphthalic anhydridep hth ali c a nh yd rid e X CH - N NN S O O O 2 X CH - N NN S O O O 2 (5) (6) (4) X= 4-NO2 , 3-NO2 , 4-Cl The literatures servey revales that no evidience to synthesis oxazepines derived from D-erythroascorbic acid therefor we decided synthesis , characterization and study anti-bacterial activity of new derivatives of D-erythroascorbic acid containing imidazole unit. Experimental Mate rials : All chemicals were supplied from Merck , GCC and Aldrich Chemicals Co. and used as received . Te chnique s : FTIR spectra were recorded using potassium bromide discs on a 8400s Shimadzu spectrophotometer and FTIR spectrophotometer , Shimadzo (Ir prestige-21) . 1HNMR spectra were carried out by : Bruker , model: ultra shield 300 MHz , origin : Switzerland and are reported in ppm(δ), DMSO or CDCl3 were used as a solvent with TMS as an internal standard . Measurements were made at chemistry department, Al-albyat university, Jordan. Uncorrected melting points were determined by using Hot-Stage, Gallen Kamp melting point apparatus. UV-Vis spectra were performed on CECL 7200 England Spectrophotometer using CHCl3 as a solvent . Mass spectra were recorded on IEOL JMS-7 high resolution instrument. 13C-NMR spectra of the compounds were recorded on a varian Mercury plus 100 MHZ spectrometer, Jordan. 295 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Scheme(1) H3CO NN O NH2 O OOHC O O HO HO HO OH [I] [II] [III] [IV] O O O O HO OH Me Me O O O O HO Me Me O2CAr O O HO NaIO4 ArCO2 ArCO2 ArCO2 O2CAr O2CAr O OOHC [VI] ArCO2 O2CAr [V] O O ArCO2 O2CAr H3C NN S NH2 [VIII] O OOHC [IV] ArCO2 O2CAr CO2H COOMe CO2H CH3O CH3O NH2NH2.H2O CONHNH2CH3O [VII] H3C [IV] acetone dry HCl 65% GAA ansoyl chloride py + + + MeOH H2SO4 4-H2NC6H4CO2H POCl3 H2NCONH2NH2 POCl3 Benzene GAA Ar-N=CH [IX] - [XI] NN O O Me NN S When Ar' = Me[XIII]a-d [XIV]a-d When Ar = 4 - MeOC6H4 [XII]a-d When Ar'= COMeO -NH O O H CN O CC O O Ar ' O CC OO O OCHN O CC O O Ar ' O CC OO O O CHN O CC O O Ar ' O CC OO OCOArArOCO O Ar ' Ar' = O CC OO dry benzene O O O ON C O C C N C O CC H H O CC OO Ar ' O O O OAr C O OAr C O OAr C O OAr C O ArO C O ArO C O ArO C O ArO C O 296 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Synthesis pre paration of 5,6-O-is opropylide ne -L-as corbic acid[I]: This compound was prepared from the reaction of L-ascorbic acid with Acetone in acidic media , following Salomon methode [15]. Synthe s is of 2,3-O-dianis oyl-5,6-O-is opropylide ne -L-as corbic acid [II]: To a cold solution of [I](10gm , 0.046mol) in pyridine (50 mL) , Anisoyl chloride was added (17.5mL , 0.129mol) with stirring for 2 hrs, then kept in dark place at room temperature for 24 hrs. The mixture was poured into ice-water the organic layer was extracted with (150mL) chloroform , washed with water and driyed over anhydrous magnesium sulfate [16] . Filtered and the solvent evaporated , purified from chloroform:petroleum ether(1:5) to give [II] (76.5%) as a pale yellow solid ,m.p (102-104 0C) , Rf(0.80) (benzene:methanol) (5:5). Synthe s is of 2,3-O-dianis oyl-L-as corbic acid[III]: Compound[II](10g, 0.0236 mol) was dissolved in a mixture of (65%) acetic acid (30mL) add absolute methanol(10mL) and stirred for 48 hrs at room temperature. To the resulting solution a benzene(40mL) was added and evaporated to yield[III] [16], (78%) as a white crystals, m.p(130-132 0C), Rf (0.42) (benzene:methanol) (4:6). Synthe s is of pe ntulos ono-Lacton-2,3- e ne - dianis oate [IV]: To a stirred solution of sodium periodate (5.6gm) in distilled water ( 60mL) at (0 0C) , a solution of [III](10gm,0.026mol) in absolute ethanol (60mL) was added dropwise . After stirring15 min, ethylene glycol(0.5mL) was added and stirred for one hour. The mixture was extracted with ethyl acetate (3x50mL) [16]. The extracts dried over anhydrouse MgSO4 , filtered and the solvent evaporated , the residue recrystallized from benzene to yield [IV] (45%) as a white crystals , m.p (156- 158 0C), Rf(0.7) (benzene: methanol) (6:4). pre paration of Me thyl 4-me thoxy be nzoate [V] It was prepared following the procedure described by Vogel [17]. m.p.(49-51°C). pre paration of Me thoxy be nzoyl hydrazine [VI] It was prepared following the procedure described by Smith [18]. m.p.(135-137°C). pre paration of 2-(4′-aminophe nyl) -5-(4′′-me thoxyphe nyl) -1,3,4-oxadiazole [VII] A mixture of 4-methoxybenzoyl hydrazine (0.01 mol), 4-aminobenzoic acid (0.01 mol) and phosphorus oxy chloride (5 mL) was refluxed for 7 hrs. The cold reaction mixture was poured into ice- water and made alkaline using sodium bicarbonate solution . The solid product was filtered , dried and purified by refluxing with ethanol ,yield (89%), m.p.(196 °C)[19]. pre paration of 2- amino-5- (4`-tolyl) -1,3,4-thiadiazole [VIII ] A mixture of tuloic acid (0.01mol), thiosemicarbazide(0.01mol) , phosphorus oxy chloride (5mL) was refluxed gently for 6 hrs. After cooling, ice water (50mL) was added in portions with stirring . The yellow precipitate was filterd, washed with water , dried and crystallized from ethanol yield(68%), m.p.(246-248°C)[20]. Synthe s is of Schiff bas e s [IX] - [XI] A mixture of new primary amine compounds [VI], [VII] or [VIII] (0.01 mol) , aldehyde [IV] (0.01 mol) , dry benzene (15 mL) and 2 drops of glacial acetic acid were refluxed for 6hrs. The solvent was evaporated under vaccum and the residue crystallized from chloroform. The physical properties of all Schiff bases are listed in Table(1). 297 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Synthe s is of 1,3-oxaze pine [XII]a-d-[XIV]a-d A mixture of equimolar amounts (0.01mol) of Schiff bases [IX], [X] or [XI] and different acid anhydriedes in dry benzene was refluxed for 6 hrs [14] , the solvent was removed and the resulting colored crystalline solid recrystallized from petroleum ether to obtained 1,3-oxazipenes [XII]a-c , [XIII]a-c and [XIV]a-c. To synthesis compounds [XII]d , [XIII]d and [XIV]d , a mixture of (0.02mol) of Schiff bases [IX] , [X] or [XI] and pyromellitic dianhydride (0.01mol) in dry benzene was refluxed for 6 hrs , the solvent was removed and the resulting colored crystalline solid recrystallized from petroleum ether . The physical properties of all synthesized 1,3-oxazepines are listed in Table (2) . Elemental analysis of compound [XII]b: Calcd. : C% = 62.71 , H% = 3.95 , N% = 3.95 Found : C% = 62.82 , H% = 3.86 , N% = 3.49 Results and Discussion 5,6-O-isopropylidene-L-ascorbic acid[I] was prepared by the reaction of L-ascorbic acid with acetone in dry HCl [15] . The FTIR spectrum showed a broad stretching band at(3240-3074) cm-1 for O-H vinylic, stretching bands at (2993-2908) cm-1 for C-H aliphatic, a stretching band at 1751 cm-1 due to C=O of Lactone ring, a stretching band at 1663 cm-1 for C=C and stretching bands at (1141- 900) cm-1 for C-O stretching . Compound [I] reacts with excess of anisoyl chloride in dry pyridine to give the corresponding ester[II]. The FTIR spectrum exhibited appearance of a stretching band at 1712 cm-1 for C=O of the ester, and disappearance of the stretching bands for O-H of compound[I] ,a stretching bands at( 2961-2834)cm-1 for C-H aliphatic group ,finally a stretching band at 1604 cm-1 could be attributed to C=C aromatic. The hydrolysis of compound [II] in acid media result hydrolyzed of isopropylidene ring to yield 2,3-O-dianisoyl-L-ascorbic acid [III] which characterized by melting point and FTIR . The FTIR spectrum showed band at 3444 cm-1 for O-H , a stretching at 3009 cm-1 for C-H aromatic. Compound [III] oxidized by periodate, which cleaves the C5-C6 bond (bearing OH groups) and formation the aldehyde derivative of D-erythroascorbic acid [IV].This compound is characterized by melting point , FTIR, UV-Vis, Mass and 1HNMR spectroscopy. The FTIR spectrm showed two bands at (2873-2661)cm-1 for C-H aldehyde stretching, a stretching band at 1715 cm-1 for C=0 of aldehydic group[21] ,UV-Vis showed λmax at 300 nm and Mass spectrum showed M+1=413. 1HNMR spectrum( δ, DMSO) showed the following signals: a singlet signal at δ( 12.5)ppm that could be attributed to the aldehydic proton. Two doublet of doublets in the region δ (7.00-7.97) ppm due to eight aromatic protons, a singlet at δ( 3.86)ppm for proton of lactone ring at C4 . A sharp singlet at δ(3.82)ppm for the (OCH3) group. 13CNMR spectrum (δ , Acetic) two signal in the region δ(167.5- 163.32) ppm for carbon C=O of the lactone ring and carbonyl ester, respectively. signals at δ(131.86, 131.83, 131.81) ppm for C4, C3, C2, signals at δ(114.31, 114.26, 123.44) ppm for aromatic carbons [22], signal at δ(55.90)ppm for OCH3 group. The signal of aldehydic carbonyl was disappeared due to it showed out of the scale . Methyl-4-methoxy benzoate [V] was obtained by esterification of 4-methoxy benzoic acid (anisic acid) with methanol [18]. The reaction of 4-methoxy benzoate with hydrazine hydrate in ethanol under reflux give 4-methoxy benzoyl hydrazide[VI] in good yield. Condensation of acid 298 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 hydrazid with 4-aminobenzoic acid in the presence of dehydrating agent phosphorus oxychloride yielded the oxadiazole derivative[VII]. The FTIR absorption spectrum showed the disappearance of absorption bands due to C=O group (amid) of the hydrazide together with appearance of a stretching band at 1610 cm-1which is assigned to C=N stretching of oxadiazole ring. It also shows two peaks at 3200cm-1, 3350 cm-1, which are assigned to the symmetric and asymmetric stretching bands of NH2 group and two peaks at1070 cm-1 , 1245 cm-1 due to symmetrical and asymmetrical C-O-C stretching vibration. Stretching bands at (2841-2935) cm-1 due to aliphatic CH2 group. The 1HNMR spectrum(δ, CDCl3) showed a broad signal at δ (1.6-1.75)ppm for two protons singlet NH2 group , two pair doublet of doublets at δ (6.7-8.01)ppm doublets that could be attributed to the eight aromatic protons and a singlet signal at δ 3.90 which could be to three protons of the OCH3 group. The 13C NMR spectrum showed signals at δ( 162.22)pmm (C-NH2), δ(114.54-128.63) (C6H4) , δ(76.64-77.49) (O- C=N) and δ(55.53) (OCH3). Elemental analysis: Found : C%=67.89 , H%=5.44 , N%=15.49 : Calcd. :C%=67.41 , H%=4.86 , N%=15.73. The reaction of tuloic acid with thiosemicarbazide in the presence of phosphorous oxychloride under reflux for 8 hrs gave 2- amino-5- (4′-tolyl) -1,3,4-thiodiazole [VIII]. The FTIR absorption spectrum showed two peaks at 3179cm-1 ,3280 cm-1 attributed to the NH2 group, 3020cm -1 for CH aromatic, peak at 1635cm-1 due to C=N of thiadiazole ring and peak at 813cm-1 of bending para substituted benzene ring . The novel Schiff bases[IX] and [X] were synthesized by refluxing equemolare amount of D-erythroascorbic acid [VI] with amino compounds [VII] or [VIII] in dry benzene with some drops of glacial acetic acid (GAA). These Schiff bases[IX] and [X] were identified by their melting points, FTIR, UV-Vis and 1HNMR spectroscopy. FTIR absorption spectra showed the disappearance of absorption bands due to NH2 and C=O groups of the starting meterials together with appearance of new absorption band at 1635 cm-1 in the region (1627-1637) cm-1 which is assigned to azomethine group( C=N stretching), peak at 1685 cm-1 due to C=C of lactone ring and stretching band at 1770 cm- 1 for C=O of lactone ring[16]. UV-Vis spectra showed λ max at 262 and 267.5 data which are characteristic of compounds [IX] and [X] , respectively. 1HNMR spectrum (in DMSO) of Schiff bases [IX], showed a sharp signals at δ 10.3ppm for one proton could be attributed to the CH=N, two doublet pairs at δ (7.10-8.20)ppm that could be attributed to the sixteen aromatic protons and a sharp signals at δ 3.85ppm due to nine protons of three OCH3 groups, and a singlet signal at δ 3.99 ppm that could be attributed to the proton at C4 of lactone ring. The 1HNMR spectrum (in DMSO) of Schiff bases [X] showed two sharp signals at δ 8.9 ppm and δ 3.81 ppm for one proton and six protons which could be to the (CH=N) and two (OCH3) groups , respectively. Two doublet pairs of at δ (6.99-7.90)ppm that could be attributed to the tweleve aromatic protons , a singlet signal at δ 3.81 ppm which could be to the six protons of two OCH3 groups. Also a sharp peak at δ 2.35 ppm could be assigned to three proyons of CH3 group. The 1,3-oxazepine derivatives were obtained by addition reaction of Schiff bases with different anhydrides in dry benzene. The mechanism for this reaction [14] may be outlined in scheme(2): C=N + C O C OO O C C N C C O C N O OO C O C C O C N O O [c] [b][a] Scheme(2) 299 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 The mechanism involves the addition of one σ- carbonyl to π-bond ( N=C) to give 4- membered cyclic and 5-membered cyclic ring of anhydride in the same transition state [T.S]a , which opens into maleic anhydride , phthalic maleic, naphthalic anhydride or pyromellitic dianhydride to give 7-membered cyclic ring 1,3-oxazepine [C]. The characteristic FTIR absorption bands of these compounds, Figure (1), was confirmed from the disappearance of band due to C=N of schiff base and other peaks characterized of cyclic anhydride of the starting materials together, Besides this, the appearance of two bands at 1770 cm-1and 1710 cm-1for two carbonyl groups in lactone ring and oxazepine ring, respectively. A peak around 1730 cm-1 due to C=O of lactone ring, C-H aliphatic band in the region ( 2983 -2845)cm-1 and bands around (1280 and 1103 cm-1) belong to asymmetric and symmetric (C-O-C) band. All the spectral data of FTIR and UV-Vis for other compounds are listed in Table (3). The UV-Vis spectra, have electron transition (n → π*) and (π →π*). The 1HNMR spectrum (in DMSO), Figure (2) of compounds [XII]a showed a sharp signal at δ 3.8 ppm for nine protons of OCH3 groups and doublet signal at δ 6.1ppm for two protons of CH=CH, twelve aromatic protons appear at the range (δ 7.00-7.89) ppm. Furthermore, a sharp signal of N-H proton absorbed at δ 10.3 ppm . The 1HNMR spectrum of compound [ XIII]b , showed twenty aromatic ring protons appear as multiplet at the range (δ 7.02-8.19) ppm, a singlet signal of N-CH proton of oxazepine absorbed at δ 6.75 ppm . Furthermore, a singlet signals at δ 3.39ppm for OCH3 protons absorbed. The 1HNMR spectrum of compound [XII]c (in DMSO), showed a singlet signal of N-CH proton absorbed at δ 7.00 ppm, the aromatic ring protons appears at the range (δ 7.87- 8.57) ppm, two singlet signals at δ3.82 ppm and 3.83 for OCH3 protons absorbed, finally, a singlet signal at δ 10.3 ppm that could be attributed to the proton of NH group. Finally, the 1HNMR spectrum of compound [XIV]d (in DMSO), also showed a singlet signal that could be attributed to the proton of N-CH absorbed at δ 7.15 ppm, a singlet signals for aromatic benzene ring[22] center appears at δ 8.05ppm and the other aromatic ring protons appear at the range (δ 7.0-7.90) ppm. . Furthermore a singlet signals at δ3.81ppm that could be attributed to eighteen protons of six OCH3 groups [22]. Biological Activity The antibacterial activity of the synthesized compounds was performed according to the agar diffusion method [18]. The prepared compounds were tested against E.coli and Staph. aureus .Each compounds was dissolved in DMSO to give concentration 1ppm. The plates were then incubated at 37 0C 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). All the compounds exhibit the high or low biological activity while the compound [XIII]C showed no activity against both the organisms. The compounds showed good inhibition against of the two types of the bacteria, this could be related to the presence of the D-erythroascorbic acid , 1,3-oxazepine and imine linkage. References 1.Du ,c.; Liu , j.; Su, w.; Ren, y.and Wei, d(2003)"The protective effect of ascorbic acid derivative on PC12 cells,Involvement of Its ROS scavenging ability" , Life Sci. , 74 , 771-780. 300 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 2. Tanuma, S.; Shiokawa, D.; Tanimoto,Y.; Ikekita, M. and Takeda, M.(1993)"Benzylidene ascorbate induces apoptosis in L929 Tumor cell", Biochem, Biophys, Rrs, Commun., 194:29-35. 3. Velri, R.; Fodor, G.; Liu, C. and Woolverton , C.,1986, "A new class of synthetic biological response modifiers,the methylfuryl butyrolactones" , J. Biol, Res. Mod. 5:444-461. 4. Woolverton,C.; Veltri, R.; Snyder , I. (1986) "Stimulation of human pmn in vitroi by asuccinimide molecular complex of methylfuryl butyrolactones", J.Biol,Res.Mod., 5:527-538 . 5. 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J. (1998) "Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat", Toxycological, 42:1-12. 11. Arias, M. J.; Moyano, J. R. and Gines, J. M.(1998)"Study by DSC and HSM of the oxazepam– PEG 6000 and oxazepam–D-mannitol systems", Therochimica Acta ., 321:33-41. 12. Yeap,G. Y.; Mohammad, T. and Osman, H.(2011)"1,3-Oxazepane-4,7-Diones Compounds : 1H and 13C NMR High-Resolution Spectroscopy (1D and 2D), J. of Molecular structure, 982(1):33-44. 13. Hussein, F. A. and Najim, S. T.(2002)Irq. J. Chem., 28:13-25. 14. Tomma, J. H.; Ali,E. T. ;Tomi,I. H.; Al-Witry, Z. A.; Hassan,H. A.(2011)"Synthesis and Characterzation of New Heterocyclic Compounds", Al- Mustansiriyah Journal of Science, 22(2): 15. Salomon, L. (1963)Experientia ,19(12): 619. 16. Mukhlus, A. A.; Al-Rawi, M. S.; Tomma, J. H.; Al-Dujaili, A. H.(2011)"Synthesis and characterization of New Schiffs Bases derived from D-Erythroascorbic acid and Pyrimidines", Ibn Al- Haitham J. for pure & appl. sci., 24 (2): 70-85. 17. 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Sharma, Y. R.(2009)"Elementary Organic Spectroscopy", 4t h Ed., Ramnagar , New Delhi, Ind. 122:233. Table(1)The physical properties of compounds[IX],[X] and[XI] Color Yield % M. P.° C Molecular Formula Structural Formula Nomenclature Comp .No. Yellow 65 138 - 140 C29H24O10N2 O O ArCOO OOCAr N CHH3CO CONH- 5-C-(4-metho xyphenyl) semicarbazone - pentulose-γ-lactone-2,3- enedianisoate [IX] Yellow 75 170 - 172 C36H27O10N3 O O ArCOO OOCAr N CHH3CO NN O 4-{4′[-5-(4′′- methoxyphenyl)-1,3,4- oxadiazole-2-yl]phenyl- imine}-pentulose-γ- lactone-2,3-enedianisoate [X] 302 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Table(2)The physical properties of compounds[XII]a-d, [XIII]a-d and [XIV]a-d Yellow 60 166 - 168 C30H23O6N3S O O ArCOO OOCAr N CH NN S H3C 5-(4′-tolyl)-2[ (pentulose-γ- lactone – 2 ,3 –ene dianisoate)-imine]- 1,3,4-thiadiazole [XI] Color M.P . °C Yiel d% Molecular Formula St ruct ural Formula Nomenclat ure Comp. No. 303 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Brown 178-180 60 C33H26O13N2 O O CHN OCC6H4OCH3 O H3COC6H4CO O O CC O O CONHH3CO 2-( pent ulose-γ- lact one-2,3- enedianisoate) -3- (4'-methoxy benzamide)-2,3-dihydro-[1,3]- oxazepine-4,7-diones [XII]a Yellow 164- 166 65 C37H28O13N2 O O CHN OCC6H4OCH3 O H3COC6H4CO O O C C O O CONHH3CO 2-( pent ulose-γ- lact one-2,3- enedianisoate)-3- (4′-methoxy benzamide)-2,3-dihydro benz [1,2e][1,3]- oxazepine-4,7- diones [XII]b Brown 198-200 75 C40H30O13N2 O O H CN OCC6H4OCH3 O H3COC6H4CO O O C C O O CONHH3CO 2-( pent ulose-γ- lact one-2,3- enedianisoate)-3- (4-met hoxy benzamide)-2,3-dihydro napht ha[2,3e][1,3]-oxazepine- 4,7-diones [XII]c Brown 172-174 60 C68H50O26N4 CONHH3CO O O OCC6H4OCH3 O H3COC6H4CO O CONHH3CO O O OCC6H4OCH3 O H3COC6H4CO O N O C N C O H H C O C O CO CO Benzene1,2,4,5-bis{2-( pent ulose -γ- lact one-2,3- enedianisoate)-3- (4′-methoxy benzamide) -2,3-dihydro-[1,3] oxazepine-4,7-diones} [XII]d P ale Yellow 220d ec. 55 C40H29O13N3 O O H CN OCC6H4OCH3 O H3COC6H4CO O O CC O O H3CO NN O 2-( pent ulose-γ- lact one-2,3- enedianisoat e)-3-{4′-[5-(4′′- met hoxyphenyl)-1,3,4-oxadi- azole -2-yl]-phenyl}-2,3- dihydro-[1,3]-oxazepine-4,7- diones [XIII]a Yellow 160-162 70 C44H31O13N3 O O CHN OCC6H4OCH3 O H3COC6H4CO O O CCO O H3CO NN O 2- pent ulose-γ- lact one-2,3- enedianisoat e-3-4′-[5-(4′′- met hoxy phenyl) -1,3,4- oxadiazole -2-yl]phenyl} -2,3- dihydrobenz-[1,2e] [1,3]- oxazepine-4,7-diones [XIII]b 304 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Brown 180-182 70 C48H33O13N3 O O H CN OCC6H4OCH3 O H3COC6H4CO O O CC O O H3CO NN O 2- pent ulose-γ- lact one-2,3- enedianisoat e-3-{4′-5-( 4′′- met hoxyphenyl) -1,3,4- oxadiazole-2-yl]phenyl} -2,3- dihydro naphthal [2,3e] [1,3] oxazepine-4,7-diones [XIII]c Yellow 162-164 58 C82H64O26N6 O O OCC6H4OCH3 O H3COC6H4CO O O O OCC6H4OCH3 O H3COC6H4CO O N O C N C O H H C O C O CO CO H3CO NN O H3CO NN O Benzene1,2,4,5-bis{2-( pent ulose -γ- lact one-2,3- enedianisoat e)-3-{4′-[5-(4′′- met hoxyphenyl)-1,3,4- oxadiazole-2-yl] phenyl}-2,3- dihydro-[1,3]oxazepine-4,7- diones} [XIII]d Brown 228-230 50 C34H25O11N3S O O H CN OO O CC O O H3C NN S H3COC6H4CO OCC6H4OCH3 2- (pent ulose-γ- lact one-2,3- enedianisoat e)[ 5-(4′-t olyl) - 1,3,4-thiadiazole-2-yl] )-2,3- dihydro-[1,3]-oxazepine-4,7- diones [XIV]a Brown 195-197 58 C38H27O11N3S O O CHN OCC6H4OCH3 O H3COC6H4CO O O CC O O H3C NN S 2- (pent ulose-γ- lact one-2,3- enedianisoate)-3- [5-(4′-t olyl) 1,3,4-thiadiazole-2-yl] )-2,3- dihydro benz[1,2e][1,3]- oxazepine-4,7-diones [XIV]b Brown 182-184 50 C42H29O11N3S O O CHN OCC6H4OCH3 O H3COC6H4CO O O CC O O H3C NN S 2- (pent ulose-γ- lact one-2,3- enedianisoate)-3- [5-(4′-t olyl) 1,3,4-thiadiazole-2-yl] )-2,3- dihydro napht h[2,3e][1,3]- oxazepine-4,7-diones [XIV]c Brown 150-152 50 C66H48O22N6S 2 O O OCC6H4OCH3 O H3COC6H4CO O O O OCC6H4OCH3 O H3COC6H4CO O N O C N C O H H C O C O CO CO H3C NN S H3C NN S Benzene1,2,4,5-bis{2-( pent ulose -γ- lact one-2,3- enedianisoate)-3′-[5-(4′-tolyl) - 1,3,4- t hiadiazole-2-yl] phenyl}-2,3- dihydro- [1,3]oxazepine-4,7-diones} [XIV]d 305 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Table(3) Charcterrisitic FTIR absorption band and UV-VIS ( λ max) of compounds [XII]a-d [XIV]a-d Table(4)Anti bac terial activity of the synthesized compounds [IV]-[XIV]a-d. Comp.No. E.Coli(G-) Staph. aurus(G+) Comp.No. E.Coli(G-) Staph. aurus(G+) [IV] + + + + [XII]c + + [VI] + + + + + + [XII]d + + [VII] + + [XIII] a + + [VIII] + + + + + + [XIII] b + + [IX] + + [XIII] d + + + + + + [X] + + [XIII]a + + + + + [XI] + + [XIV]b ++ + + + [XII]a + + [XIVc + + + + + [XII]b + + + + [XIV]d + + Comp. No. UV-VIS λmax (nm) Characteristic bands FTIR spectra(cm-1) Ѵ(C-H) aromatic Ѵ(C-H) Aliphatic Ѵ (C=O) Lactone Ѵ (C=O) lactam Ѵ (C=C) aromatic [XII]a 234 3010 2982-2843 1770,1685 1740 1604 [XII]b 259 3093 2974-2846 1765,1642 1755 1604 [XII]c 317.5 3088 2956-2848 1772,1685 1735 1604 [XII]d 262 3024 2943-2843 1760,1676 1728 1606 [XIII]a 322 3066 2924-2851 1778,1685 1713 1600 [XIII]b 325 3028 2927-2856 1770,1681 1730 1600 [XIII]c 330 3072 2927-2846 1770,1689 1739 1604 [XIII]d 261 3030 2941-2843 1760,1685 1730 1604 [XIV]a 292 3020 2904-2850 1770,1685 1740 1600 [XIV]b 289 3020 2924-2727 1770,1687 1740 1627 [XIV]c 246 3066 2920-2850 1770,1674 1739 1630 [XIV]d 270 3059 2940-2842 1770,1685 1740 1600 306 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 Key to symbols: Highly active = + + +(mor than)15 mm. Moderately active = + +(11-15) mm. and Slightly active = + (5-10) . Fig. (1): FTIR- spectrum of compound [XII]b Fig. (2):1HNMR spectrum of compound [XII]c 307 مجلة إبن الهيثم للعلوم الصرفة و التطبيقية 2012 السنة 25 المجلد 2 العدد Ibn Al-Haitham Journal for Pure and Applied S cience No. 2 Vol. 25 Year 2012 ارثروحامض - Dمن االوكسازبين المشتقة تحضير و تشخيص مركبات االسكوربيك عبد الجبار عبد القادر مخلص ، منى سمير الراوي ، جمبد هرمز توما ، عمار هاني الدجيلي ابن الهيثم ،جامعة بغداد –قسم الكيمياء،كلية التربية الخالصة ارثرو حامض اسكوربيك التي تحتوي على - Dالمشتقة من [IX]و [X] دة لقواعد شف حضرت المركبات الجدي -اوكسادايازول او 4,3,1-ارثرو حامض اسكوربيك مع االمينات االروماتية (المحتوية على وحدة- Dحلقة غير متجانسة من تكاثف ارثرو حامض - Dالثلجي محفزا . حضر المركب ثايادايازول) في البنزين الجاف وباستعمال قطرات من حامض الخليك 4,3,1 4,3,1-اوكسادايازول او 4,3,1-) بينما حضر االمين االروماتي المحتوي 1اسكوربيك باربع خطوات متتالية كما في المخطط رقم ( تلويك مع امينو حامض البنزويك او من تفاعل حامض ال-4ميثوكسي بنزوايل هايدرازين مع -4ثايادايازول من تفاعل وعلى التوالي . POCl3ثايوسميكاربازايد بوجود تناول البحث تحضير وتشخيص مشتقات االوكسازبين الجديدة والمشتقة اساسا من قواعد شف [XIV]- [XII] الى االنهايدرايدات المختلفة من تفاعل االضافة في البنزين الجاف . حضرت مشتقات االوكسازبين- الجديدة بالتصعيد العكسي لقواعد شف مع مختلف االنهايدرايدات ( ماليك ، فثاليك، نفثالك، بايرومالتيك داي انهايدرايد) في البنزين الجاف. ، UV-Vis ، طيف FTIRشخصت جميع المركبات المحضرة بقياس درجات انصهارها وبوساطة طيف ) للبعض منها .درست الفعالية البايولوجية للمركبات المحضرة (C.H.N، طيف الكتلة والتحليل الدقيق للعناصر 1HNMRطيف Staphylococcus (G+) .Echerichia coliد نوعين من البكتريا واظهرت النتائج فعالية بايولوجية جيدة ضد البكتريا بنوعيها ض (G-), . اوكسازبين ، قواعد شف، حامض االسكوربيك. – 3,1: المفتاحية الكلمات Introduction Results and Discussion Table(3) Charcterrisitic FTIR absorption band and UV-VIS ( λ max) of compounds [XII]a-d [XIV]a-d