Microsoft Word - 6 381 | 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 1,3-Oxazepines Derived from Diamic Acid : N,N‾-Bis-(4-methyl phenyl ) pyromellitamic Diacid Shaimaa A. Saued Jumbad H. Tomma Emad T. Ali Dept. of Chemistry / College Education for Pure Science /(Ibn AL-Haitham) / University of Baghdad Received in: 3 March 2014 ,Accepted in:22 June 2014 Abstract The symmetrical N,N‾-Bis-(4-methyl phenyl) pyromellitamic diacid (I) was synthesized from the reaction of toludine with pyromellitic dianhydride in dry acetone. Esterification of amic acid (I) with dimethyl sulphate in basic medium using acetone as a solvent give symmetrical N,N‾-bis-( 4- methyl phenyl ) pyromellitam diacetate (II). The condensation of new ester with hydrazine hydrate in ethanol leads to the formation symmetrical N,N‾-bis- (4-methyl phenyl) pyromellitamic hydrazide (III). New symmetrical 1,3-oxazepine derivatives (V)a-e can be synthesized from the reaction of the new synthesized Schiff bases (III)a-e (which are synthesized from the reaction new hydrazide (II) with different aromatic aldehyde) with naphthalic anhydride in dry benzene . The synthesized compounds have been characterized by their melting points and by their spectral data, FTIR and 1HNMR spectroscopy of compound (V)c. Key words: 1,3-Oxazepines, Schiff bases, hydrazides, Easters 382 | 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 1,3 –oxazepine (1) is a seven member ring compound with two hetero atoms, oxygen atom at position (1) and nitrogen atom at position (3). O N (1) Oxazepine derivatives showed various biological activities [1,2] Also, oxazepine derivatives are used in another applied fields [3] . 1,3 oxazepines (3) synthesized from the reaction of compound (2) with maleic anhydride in EtOH as a solvent [4] . NO H3C NH S NO H3C NH S O N R H O O O O EtOH O N RH O O C O O C reflux 3h (3) (2) R=HCOH , -CH=CH-CH3 , Ph , -Ph-Br ,4-(CH3)2-Ph or -H In addition , 2-disubstituted -3 - (pyrimidine -2-yl)-1,3-dihydro-1,3-oxazepine - 4,7diones (5) were synthesized from condensation of compound (4) with malice anhydride in dry dioxane as a solvent [5] . N N N R O C C OO R' N N OCH 3 R'= CH 3 CH 3 H N N N R R' O O O , or , R= dry dioxane or (4) (5) Recently, Al-Jamali et. al [6] synthesized 2-(p- methoxy phenyl) -2,3-(quinolone) - [1,3]-oxazpine -4,7 dione (7) from reflux of Schiff base (6) with malice anhydride in dry benzene . N NHC N H3CO N H C C O C O O H3CO O O O dry benzene (6) (7) More recently S. Al- Zobaydi et .al [7] synthesized a new oxazepines (9) from reaction of Schiff bases (8) with phthalic anhydride in dry benzene. 383 | 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 N N N C C R R' R R' N N NC C C R R R' R' O CO O O O CCO 5 hrs dry benzen phthalic anhydride (9) (8) According to above facts , we decided to synthesize a new symmetrical Schiff bases and thier novel 1,3-oxazepine derivatives. Experimental Materials All the 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 FTIR spectrophotometer , Shimadzo (Ir prestige-21) . 1HNMR spectrum was carried out by company : Bruker , model: ultra shield 300 MHz , origin : Switzerland and are reported in ppm(δ), DMSO was used as a solvent with TMS as an internal standard . Measurements were made at Chemistry Department, Al-albyat University , Uncorrected melting points were determined by using Hot-Stage, Gallen Kamp melting point apparatus. General procedure Compounds (IV)a-e and (V)a-ewere synthesized according to Scheme 1. Synthesis of symmetrical diamic acid N,N‾-Bis-( 4-methyl phenyl ) pyromellitamic diacid (I) . To a solution of pyromellitic dianhydride (0.218g, 0.001mole) in (15mL) acetone , a solution of 4-toludine ( 0.214g, 0.002 mole) in (15mL) acetone was added dropwise during one hour, the mixture was then left at room temperature with continuous stirring for 24 hrs [8], the pale yellow product was then filtered off and recrystallized from acetone to give the a corresponding pyromellitamic diacid (I) . yield 76% , mp > 300o C. Synthesis of symmetrical N,N‾-bis-(4-methyl phenyl ) pyromellitam diacetate (II). A mixture of compound (I)a-c (4.3 g, 0.01mole) and anhydrous sodium carbonate (1.8g, 0.02 mole) was dissolved in 20mL of acetone , to this solution (0.02 mole) of dimethyl sulphate was added . After 20 min , the resulting mixture was heated under reflux for 4 hrs. The reaction mixture was allowed to cool down to room temperature, extraction with chloroform[9]. The yellow oily product was collected by evaporating the chloroform to give compound (II) . yield 65% , mp = 180-181o C. Synthesis of symmetrical N,N‾-bis-(4-methyl phenyl) pyromellitamic hydrazide (III) A solution of ester compounds (II) (4.6g, 0.01 mole ) and hydrazine hydrate (15mL) in 25 mL of ethanol was heated under reflex for 2 hrs , the mixture was then cooled to room 384 | 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 temperature, and the obtained solid was filtered and recrystallized from ethanol[10] .The physical properties data of new yellow hydrazide compound (III) , yield 80% , mp =228-230 o C. Ar Ar C C C C OO OO OCH3 H3CO HN NH Ar NH2NH2 EtOH C C C C OO OO NH HN HN NH ArH2N NH2 Ar C C C C OO OO OH HO HN NH Ar (II) (III) (IV)a-e (V)a-e Na2CO3 (CH3)2SO4 NH C O NH C O C O C O HNN N CH CH HN Ar Ar NH C O NH C O C O C O HNN N CH CH HN Ar Ar O O O O O O 3- or 4-XC6H4CHO X X X X Ar= 4-MeC6H4- X= 3-NO2, 4-Cl , 4-Br, 4-OH or 4-OCH3 2 (I) O O O O O O 4-toludine acetone EtOH dry benzene ; Scheme 1 naphthalic anhydride Synthesis of symmetrical new Schiff bases. (IV )a-e . 385 | 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 A mixture of new acid hydrazide (III) (0.46g, 0.001 mole) , different aromatic aldehyde (0.002 mole) , ethanol absolute (3 mL) was heated to reflux for 4hrs[6] . Then the mixture was cooled to room temperature , and the solid obtained was filtered and recrystallized from ethanol .The physical data of new Schiff bases are listed in Table (1). Synthesis of symmetrical novel 1,3-oxazepine derivatives (V)a-e . A mixture of synthesized Schiff bases (0.001mole) and naphthalic anhydride (0.296g ,0.002 mole) in dry benzene 5mL was refluxed for 6 hrs. The solvent was removed and the resulting colored crystalline solid was recrystallized from 1,4-dioxane to obtain new 1,3-oxazipenes . The physical data for all synthesized 1,3-oxazepines are given in Table (2) . Results and Discussion N,N‾-Bis-(4-methyl phenyl) pyromellitamic diacid (I) was synthesized by the reaction of one mole of pyromellitic dianhydride with two moles of toluedine in acetone as a solvent. The structure of amic acid was studied by it′s melting point and FTIR spectroscopy . FTIR spectrum showed the disappearance of absorption bands of NH2 group and other peaks characterized of cyclic anhydride of the starting materials together with the appearance of new absorption stretching bands due to O-H of carboxylic moiety in the region ( 3292-2546) cm-1, a stretching band of carboxylic acid (C=O) appeared 1701 cm-1 , a stretching band of N-H group appeared at 3257 cm-1 . While a stretching band which is appeared at 1653cm-1 could be attributed to amid group( C=O) . Also the FTIR spectrum exhibited new absorption bands in the region 2922-2868 cm-1 due to C-H aliphatic group[11] . The esterification of N,N‾-Bis-(4-methylphenyl) pyromellitamic diacid using dimethyl sulphate in presence of anhydrous sodium carbonate in dry acetone to get the corresponding esters. The ester compound (II) was charecteized by their melting point and FTIR sprcetroscopy . The FTIR spectrum showed a new absorption band at 1728 cm-1 due to stretching vibration of the (C=O) for ester , also the appearance of a new band at 1199 cm-1 due to (C-O) of ester , besides to the disappearance of two bands of O-H and C=O of carboxylic moiety [12]. The acid hydrazide (III) was synthesized by the reaction of compounds [II]with hydrazine hydrate in ethanol . This compound was characterized by its melting point and FTIR spectrum which was showed new absorption bands in the region (3327- 3217) cm-1 due to the (NH and NH2) groups and new stretching vibration band due to (C=O) of amide group at 1631 cm-1 for hydrazide moiety . The new Schiff bases (IV)a-e were synthesized by condensation of one mole of acid hydrazide (III) with two moles of different aromatic aldehyde in ethanol . These compounds were identified by their melting points , FTIR and ¹HNMR spectrum of compound (IV) c. FTIR absorption-spectra which showed the disappearance of absorption bands due to NH2 group together with appearance of new absorption band in the region (1645-1608) cm¯¹ which is assigned to imine group (C=N) stretching. The other FTIR data of functional groups which are characteristic of these compounds are given in Table 3. The new 1,3-oxazepine derivatives (V)a-e were synthesized by refluxing one mole of compounds (IV) with two moles of naphthalic anhydride in dry benzene. The mechanism involves the addition of one σ bond of C-O group to -bond (N=C) to give 4-membered cyclic ring and 5-membered cyclic ring of naphthalic anhydride in the same transition state [T.S]a , which opens into phthalic anhydride to give 7-membered cyclic ring (C). The mechanism of this reaction [13] may be outlined as follows in Scheme (2). 386 | 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 The characteristic FTIR absorption bands of these compounds were confirmed from the disappearance of stretching band due to C=N of Schiff bases and other peaks characterized of cyclic anhydride of the starting materials with appearance of two bands characteristic of two carbonyl groups of oxazepine ring. The FTIR spectral data of new oxazepine compounds are listed in Table 4. The 1HNMR spectrum of compound (V)c , Figure 1 showed aromatic protons , C-H protons of oxazepine rings[14] and protons of N-H group of CONHAr moiety appear as triplet ,doublet and singlet signals in the region δ(7.13 – 8.99) ppm and the NH protons of CONH-Hetrocyclic moiety appear at δ 3.09ppm [15]. A good sharp singlet signal at δ 1.05ppm due to protons of two CH3 groups . References 1- Serrano-Wu, M. H.; Laurent D. R.; and Chen , Y. (2002) "Sordarin Oxazepine Derivatives as Potent Antifungal Agents" , Bioorganic and Medicinal Chemistry Letters , 12(19), 2757-2760. 2- Smith, L. Wong, W. C. and Kiselyov, A. S. (2006) " Arylphthalazines. Part 2: 1- (Isoquinolin5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II" , Bioorganic and Medicinal Chemistry Letters, 16(6)1579-1581. 3- Blain, P. G. , (2003). " Toxicological Review" , www.biomedexperts.com, 22( 2) , 103- 110. 4- Yass , A. (2010) "Synthesis of substitutead 1,3-Oxazepine and 1,3-Diazepine Via Schiff Bases for Selfamethoxazole drug" , Kerbala Journal Of Pharmaceutical Sciences,1,49-58. 5- Ahmad, Sh. M. (2011) "Synthesis and Characterization of 1,2-disubstituted -3- (pyrimidine-2-yl)-2,3-dihydro-1H-1,3-diazepine-4,7-dione" , Journal of Al-Nahrain University ,14:3, 24-34. 6- Aljamali, N.M. and Salman , H. E. (2012). "Synthesis and Chemico-Biological Studying of Various Organic Compounds" , Kerbala Journal of Pharmaceutical Sciences ,4,73-84. 7- Al- Zobaydi, S. F. and Hassan, E. M. (2013) "Synthesis Some Heterocyclic Compound based on 2,5–disubsituted Pyridine" , Journal of Al-Nahrain University, 16:1, 60-70 . 8- Lazim, K. M. (2011) "Synthesis and Characterization of Symmetrical and Asymmetrical Pyromellitimides and Thier Amic Acids Containing Heterocyclic Unit", MSc. Thesis , College of Education for ure Science Ibn Al- Haitham University of Baghdad . 9- Al-Rwbaiy, Z. (1998) "Synthesis and Characterization of Some New Derivatives 1,2,4- Triazole and 1,3,4-Thiadiazole", M.Sc thesis ,college of Education for pure Science –Ibn –Al Haitham ,University of Baghdad . 10- Abbas, S.; Ali, E. and Tomma, J. (2013) "Synthesis and Characterization of New Heterocyclic Derived from Pyromellic Dianhydride", Ibn AL- Haitham J. for pure & Appl. SCI ., 26(3) , 268-280. 11- Ali , E. ; AL-Aliawy, K. and Tomma, J. (2011) "Synthesis and Characterization of New Symmetrical Pyromellitdiimide Derivatives and Their Amic Acids", Ibn AL- Haitham J. for pure & Appl. SCI ., 24 (3) , 110-121. 387 | 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 12- Silverstein, R., Bassler, G. and Morrill, T. (1981) "Spectrometric Identification of organic compounds", 4thed,Johin Wiley and sons ,New York. 13- Al-Jamali, N. M., (2008), “Synthesis, Characterization of New 1,3-Oxazepine, Diazepine, Thiazepine derivatives and Open Ring of Thio Compounds”, Ph.D. Thesis, College of Education for pure Science Ibn –Al Haitham , University of Baghdad. 14- Muhsin, T. R . (2012) "Synthesis and Biological Activity of New Compounds Derived from 3-[4-(4-Methoxybenoyloxy)benzylideneamino]-2-thioxo-imidazolidin-4-one", M.Sc. Thesis , College of Education for pure Science Ibn Al- Haitham University of Baghdad. 15- Al-Mamory, S. T. H. (2012) "Synthesis and Characterization of Some New Asymmetrical imid/ isoimide Derived from Pyromellic Dianhydride", MSc. Thesis , College of Education ure Science for Ibn Al-Haitham University of Baghdad. 388 | 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.(1): The physical properties of new Schiff bases[IV] Comp . No. Nomenclature Structural formula Molecuar formula M. P 0C Yiel d % Color [IV]a Bis[N,N′-( 4- methyl phenyl)- 2,2′-(3′′- nitrophenyl) benz ylidene amino ]pyromellit diamid C O NH C O C O HN C O N N CH CH NH NH CH3 H3C NO2 NO2 C38 H30 N8O8 192- 194 86 Glow yellow [IV] b Bis[N,N′-( 4- chlorol phenyl)- 2,2′-(4′′- nitrophenyl) benz ylidene amino ]pyromellit diamid C O NH C O C O HN C O N N CH CH NH NH CH3 H3C Cl Cl C38H30 N6O4Cl2 >29 0 83 Pale yellow [IV]c Bis[N,N′-( 4- bromo phenyl)- 2,2′-(4′′- nitrophenyl) benz ylidene amino ]pyromellit diamid C O NH C O C O HN C O N N CH CH NH NH CH3 H3C Br Br C38H30N6 O4 Br2 218- 220 87 Yellow [IV] d Bis[N,N′-( 4- hydr- oxy phenyl)-2,2′-(4′′- nitrophenyl) benz ylidene amino ]pyromellit diamid C O NH C O C O HN C O N N CH CH NH NH CH3 H3C HO OH C38H32 N6 O6 250- 252 78 Orange yellow [IV]e Bis[N,N′-( 4- meth- oxy phenyl)-2,2′-(4′′- nitrophenyl) benz ylidene amino ]pyromellit diamid C O NH C O C O HN C O N OCH3 H3CO N CH CH NH NH CH3 H3C C40 H36 N6 O6 160- 162 81 yellow 389 | 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): The physical properties of new 1,3-oxazepines [V]. Comp. No. Nomenclature Structural formula Molecuar formula M. P 0C Yield % Color [V]a Bis [N,N′- [(4- methylphenyl)-2,2′- (3′′-methoxy phenyl)(2,3-dihydro- naphth[1,2e]1,3- oxazepin -4,7- diones-3-yl)] pyromellit diamide NH C O NH C O C O HN C O NH NHC N CH O C O C O O CCO O CH3 H3C NO2 O2N C62 H 42 N8 O14 184- 185 79 Dark yellow [V]b Bis [N,N′- [(4- methyl phenyl)-2,2′- (4′′-chloro phenyl )- (2,3-dihydro- naphth[1,2e]1,3- oxazepin -4,7- diones-3-yl)] pyromellit diamide NH C O NH C O C O HN C O NH N Cl HC N CH O C O C O O CCO O CH3 H3C Cl C 62 H42 N6 O10 Cl2 207- 208 78 Dark yellow [V]c Bis [N,N′- [(4- methyl phenyl)-2,2′- (4′′-bromo phenyl )- (2,3-dihydro- naphth[1,2e]1,3- oxazepin -4,7- diones-3-yl)] pyromellit diamide NH C O NH C O C O HN C O NH N Br HC N CH O C O C O O CCO O CH3 H3C Br C62 H42 N6 O10 Br2 207- 208 81 Dark yellow [V]d Bis [N,N′- [(4- methyl phenyl)-2,2′- (4′′-hydroxy phenyl )-(2,3- dihydro- naphth[1,2e]1,3- oxazepin -4,7- diones-3-yl)] pyromellit diamide NH C O NH C O C O HN C O NH N OH HC N CH O C O C O O CCO O CH 3 H 3C HO C62H44 N6 O12 234- 235 80 Pale orange [V]e Bis [N,N′- [(4- methyl phenyl)-2,2′- (4′′-methoxy phenyl )-(2,3- dihydro- naphth[1,2e]1,3- oxazepin -4,7- diones-3-yl)] pyromellit diamide NH C O NH C O C O HN C O NH N OCH 3 HC N CH O C O C O O CCO O CH 3 H 3C CH 3O C64H48 N6 O12 165- 166 83 Dark yellow 390 | 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.(3):Characteristic FTIR absorption bands of new schiff bases compounds[IV]ae. Table No.( 4): Characteristic FTIR absorption bands of 1,3 oxazepine[V]. Comp . No. Characteristic bands FTIR spectra(cm-1) υ (NH) υ (C-H)aliph. υ (C=O) Lacton, lactam υ (C=O) amide υ (C=C) [V]a 3464 2924-2852 1770,1735 1660,1625 1589 [V]b 3203 2910-2860 1770,1741 1654,1640 1586 [V]c 3421 2939-2852 1770,1734 1668,1625 1583 [V]d 3468 2899-2829 1772,1736 1654,1645 1600 [V]e 3446 2944-2850 1772,1735 1645,1622 1602 Comp . No. Characteristic bands FTIR spectra(cm-1) υ (NH) υ (C- H) arom. υ (C=O) amide υ (C=N) υ (C=C) other [IV]a 3450-3423 3005 1660,1625 1645 1585 NO2:1527,1307 [IV]b 3286-3215 3014 1654,1635 1609 1600 C-Cl: 940 [IV]c 3442-3430 3059 1668,1653 1640 1583 C-Br: 619 [IV]d 3485-3470 3030 1654,1630 1608 1597 O-H: 3305 [IV]e 3462-3420 3020 1645,1628 1620 1602 C-O: 1251 391 | 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): 1H-NMR spectra of compound [V]c 392 | 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 اوكسازبين جديدة مشتقة من حامض ثنائي -3,1تحضير وتشخيص مركبات ثنائي الحامضمثيل فنيل )بايرومالتاميك -4(-االميك : بس حميدشيماء عبد سعود جمبد ھرمز توما موسى عماد تقي علي جامعة بغداد) /ابن الھيثم (كلية التربية للعلوم الصرفة /قسم الكيمياء 2014حزيران 22,قبل البحث في: 2014اذار 3استلم البحث في: الخالصة -′N,N ثنائي الحامض مثيل فنيل )بايرومالتاميك -4(-بس[I] توليدين مع بايرومالتيك ثنائي -4من تفاعل حضر تمت استرة حامض االميك مع داي مثيل سلفيت و كاربونات الصوديوم الالمائية في .االنھيدرايد في االسيتون الجاف . ومن تكاثف ھذا [II] مثيل فنيل )بايرومالتام ثنائي اسيتيت- 4( -بسN,N′-للحصول على المركب بوصفه مذيبا االسيتون مثيل فنيل )بايرومالتاميك -4( -بس-N,N′-ستر مع الھيدرازين المائي في االيثانول ينتج المركب الجديد اال e-a [VIII]من تفاعل مركبات الشف الجديدة e -a[V] اوكسازبين-3,1.حضرت مركبات جديدة من [III]ھيدرازايد وماتية المتنوعة) مع فثاللك انھيدرايد في البنزين الجاف . مع االلديھايدات االر [III](التي حضرت من تفاعل الھيدرازايد من خالل قياس درجة االنصھار لھا واطياف االشعة تحت الحمراء ودرست جميع المركبات المحضرة اعاله شخصت وطيف الرنين النووي المغناطيسي للبعض منھا . اوكسازبين , قواعد شف , ھيدرازيد , استرات.- 1,3الكلمات المفتاحية: