Microsoft Word - 144-154 Chemistry | 144 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Synthesis of New 10-Amido phenoxazine Derivatives Israa T. Ibraheem Suad M. Al-Araji Dept. of Chemistry/ College of Science/ University of Baghdad Received in:22/October/2015,Accpted in:15/December/2015 Abstract This work includes synthesis of new phenoxazine derivatives containing N-substituted phenoxazine starting from phenoxazine (1).10-nitrosyl phenoxazine was prepared through the reaction of phenoxazine with sodium nitrite to give compound (2), which reacted with zinc in acetic acid to give 10-amino phenoxazine (3). Condensation of compound (3) with benzoyl chloride, isovaleryl chloride and 4-bromophenacyl chloride gave 10-amido phenoxazine derivatives (4-6). Keyword: phenoxazine, ethyl acetate phenoxazine, 10-aceto hydrazide phenoxazine. Chemistry | 145 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Introduction Heterocyclic compounds are cyclic compound in which the ring atoms consist of carbon and some other elements like nitrogen, oxygen or sulfur are by the most common other atom such as boron, phosphorus or silicon compounds also be members of heterocyclic ring[1-4]. In 1887 the phenoxazine was made by Bernth [5] and though known for many years it doesn,t have a systematic study made of its chemistry. And till the last decade, a little was known about the metabolism of phenoxazine in biological systems [6]. The nomenclature and numbering of phenoxazine nucleus. At present only two systems (a) and (b) are widely used The numbering system (a) has been adopted as being the most frequent and also approved in the “Revised Ring Index” (no.3290), used in chemical abstract and recommended by the IUPAC rules of organic nomenclature[7]. The heterocyclic oxygen atom of the phenoxazine nucleus places certain restriction on the aromaticity of this ring system, which appears to be somewhat less aromatic than the phenothiazine system for instance. The aromatic model shows that the phenoxazine nucleus is slightly folded along its short axis i.e., the axis passing through the two central hetero atoms. The dipole moment of phenoxazine which was found to be 1.93 D (benzene) [8] is also consistent with the non planarity of molecule. Phenoxazine nucleus is highly non-planer, i.e., folded along the axis passing through the two heteroatoms [9,10]. Now the proton or the substituent at the nitrogen atom may be placed either between or out of the planes of the two latral ring. Thus two geometrical configurations can be predicted for the phenoxazine ring, which on analogy to phenothiazine may be called H-extra (I) and H-antra (II) configuration. Oxazine derivative have been reported to possess [11] antifungal, antibacterial, anticonvulsant, antiviral, analgesic, anticancer, anti inflammatory [12], antimalarial [13], antimicrobial [14]. Oxazine derivatives have played a crucial role in the theoretical development of heterocyclic chemistry and are used extensively in organic Chemistry | 146 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 synthesis due to the rapid development of bacterial agent to help in the battle against pathogenic. Aim of the work N-substituted phenoxazine have been reported to be biologically and industrially versatile compounds. Biologically, they are used in many drugs as antiviral, antibacterial, anticancer and fungicidal agents. In industry, most of phenoxazine dyes are derived from benzo phenoxazine e.g., Meldola blue or from more complex ring system containing the phenoxazine residue. The present work was directed toward the synthesis of new N-substituted phenoxazine derivatives expected to possess possible biological activity. Material and Methods FT-IR spectra were recorded on (SHIMADZU) FT-IR 8400 S spectrophotometer; solid samples were run in KBr disc, liquid were run as smears. UV spectra were recorded on UV-visible spectrophotometer (SHIMADZU) UV-160 A. 1H-NMR spectra were recorded on Ultra Sheild 300 MHz with tetramethyl silane as internal standard. Melting points were determined in a (Gallen kamp) melting point apparatus with sample contained in open capillary glass tube in an electrically heated metal block apparatus. Thin Layer chromatography (TLC) were performed on pre-coated plastic sheet with 0.25 mm Layer of silica-gel F 254. Spots were detected with iodine vapour. General procedure for synthesis of phenoxazine and its derivatives: Phenoxazine (1) [15] A mixture of (109g, 1mol) of o-aminophenol, (2g, 0.018 mol) ZnCl2 and 5 ml conc. H3PO4 was heated in a sand bath maintained at 270-275 0C for 4 hrs. The reaction mixture was cooled and extracted with cyclohexane in soxhlet extraction apparatus. The solvent was removed and the formed colorless needles crystallized from ethanol m.p. 152-154 oC, yield (54g,50%) IR: 3405 cm-1 (N-H) str. 10-nitroso-10H-phenoxazine (2) [16] A mixture of phenoxazine (10g, 0.05 mole) and sodium nitrite (4.2 g ) in (150 mL) of ethanol was refluxed for 2 hrs., after cooling (12mL) of concentrated HCl drop-wise was added. The brown precipitate obtained was filtered, dried and recrystallized from ethyl acetate. m.p. (172 oC), yield (3.5g,56 %). 10-amino phenoxazine (3) [16] A mixture of 10-nitrosylphenoxazine (9.0 g, 0.05mole) and zinc powder (5.0 g) in (25mL) acetic acid was stirred for 2 hrs., at 00C. The filtered was poured on to about (500mL) of water. The brown precipitate obtained was filtrated, dried, recrystallized from ethanol. m.p. (190 oC ), yield(2g, 62 %). 10-Benzamido phenoxazine (4) A mixture of 10-aminophenoxazine (0.5g,0.0027 mole) and (0.1mL) of benzoyl chloride with (0.2mL) of triethylamine in (10mL) of THF was stirred for (2hrs.) at room temperature. The reaction mixture was left overnight and the precipitate formed Chemistry | 147 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 was filtered and the filtrate dried and recrystallized from ethanol. m.p. (196 oC), yield(0.15g,50%). Similarly, the following compounds were prepared similar to this procedure in this manner. The physical data are recorded in Table (1). Result and Discussion Phenoxazine was prepared by the reaction of o-aminophenol with zinc chloride in presence of phosphoric acid as shown in scheme (1). Phenoxazine (1), showed strong stretching band at 3342 cm-1 (N-H), strong stretching bands at 1570 cm-1 and 1596 cm-1 for (C=C) assigned to phenoxazine ring.The 1H-NMR spectrum showed signal at δ (6.39-6.81) ppm, due to aromatic protons and signal at δ (8.2) ppm a signed to (N-H) as shown in figure (1). The phenoxazine (1) was then converted to 10-nitrosyl phenoxazine (2) using sodium nitrite. IR spectrum of compound (2) showed the disappearance of (N-H) band at 3342 cm-1 and showed a stretching band at 1271 cm-1 due to (NO). The IR spectrum also, showed a band at 3062 cm-1 (C-H) aromatic and 1587 cm-1 for (C=C). Compound (2) reacted with zinc powder in acetic acid to give compound (3) as shown in scheme (2). The IR spectrum of compound (3) showed astrong stretching band at 3386 cm-1 and 3370 cm-1 due to (NH2) and 1593 cm-1 for (C=C) as shown in Table (2). Compound (3) reacted with benzoyl chloride, isovaleryl chloride and 4-bromophenacyl chloride to give 10-benzamide phenoxazine, 10-(3- methyl propenyl)amide phenoxazine and 10-(4-bromophenyl)amide phenoxazine compounds (4-6). IR spectra of compounds (4-6) showed astrong absorption bands at (3342-3300) cm-1 for (N-H), at (1650-1697) cm-1 for (C=O), at (1583-1593) cm-1 for (C=C) str., 1HNMR spectrum (Fig. 2) for compound (4) which showed a signal at ( 8.7) ppm belong to (N-H) proton and signals at  (6.5-8) ppm belong to aromatic protons. References 1- Bahl, A. and Bahl, B.S., (2000), Organic Chemistry, 21st Edition, S.chand, India. 2- Raj ,K.B., (2007), Organic Chemistry., 5 edition, New AGE, India. 3- Bahl, A. and Bahl, B.S., (2008), Advanced Organic Chemistry., 2 edition, S.chand, India. 4- Jone, A.J. and Mills, K. , (2006), Heterocyclic Chemistry at a Glance., 1st edition, Wiley, Blackwell. 5- Bernthsen, A., (1887), Synthesis of phenoxazine, J. org. chem., (20), 939-942. 6- Crossley, M. L.; Hofmann ,C. M. and Dreisbach P. F., (1952), Chemo therapentic Dyes.lll.5-Heterocyclic amino-9-dialkyl amino benzo [a] phenoxazins. J. Am. Chem. Soc., 74(3), 584-586. 7- Patterson, A.M.; Capell, L.T. and Walker, D.F., (1960), Synthesis of oxazolo- phenoxazines, J. Amer.Chem. Soc., 82(7), 1607-1609. 8- Freedlander A., (1944), System of phenoxazine, J. Proc. Soc. Exp. Biol., (57), 106- 109. 9- Yang, L.;Feng, J. K.; Ren Am. and Sun Cc, (2006), Theoretical investigations on the modulation of the polymer electronic and optical properties by introduction of phenoxazine, J. Polymer, 47(9), 3229-3239. Chemistry | 148 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 10- Keleş ,H. and Dehri I., (2005), Electrochemical synthesis of poly-6-amino-m- cresol(poly-AmC), J. Appl. Surf. Sci., 252(20), 7545-7552. 11- Beena ,K.P. and Akelesh, T., (2013), Design, synthesis, characterization and evaluation of some 1,3-oxazine derivatives as potent antimicrobial agents, Der pharmacia Lettre, 5(4), 257-260 12- Tilak, S.; Tyagi, R.; Goel, B. and Saxena, K., (1998), Synthesis and anti inflammatory activity of some potential cyclic phenoxazines, J.Indian drugs, (35), 221-225. 13- Dominguez, J.; Lopez, S.; Charris ,J.; Iarruso ,L.; Lobo, G.; Semenow, A.; Olson, J. and Rosenthal, P., (1997), Synthesis and antimalarial effects of phenoxazine inhibitors of a plasmodium falciparum cysteine protease, J. Med. Chem., 40(17), 2726-2732. 14- Raval, J. and Desai, K., (2005), Synthesis and antimicrobial activity of new triazolopyridinyl phenoxazines, Arkat Usa, (3), 21-28. 15- Dotsha, J. A., (2006), Synthesis of new 10-substituted phenoxazine derivatives, Thesis, College of Science, University of Baghdad, 16- Jiao, C.; Cheng, N.; Shuang, H. and Shen, Q., (2004), Areversible chemosenor for nitrite based on the fluorescence quenching of a carbazole derivative, Talanta., 64(3), 637-643. Chemistry | 149 2016) عام 2العدد ( 29مجلة إبن الهيثم للعلوم الصرفة و التطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Table (1) Physical properties of compounds (2-6) Comp. No. Scientific name Structure M.P. oC %Yield Color of crystal Solvent 2 10-nitroso-10H- phenoxazine 172 57 Brown Ethanol 3 10-amino phenoxazine 190 62 Brown Ethanol 4 10-Benzamido phenoxazine 196 50 Green Ethanol 5 10-(3-methyl propenyl) amido phenoxazine 222 48 Black Ethanol 6 10-(4- Bromophenyl) amidophenoxazine 130 90 Green Ethanol Chemistry | 150 2016) عام 2(العدد 29المجلد مجلة إبن الهيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Table (2) Infrared spectra data of compounds (2-6) Other bands cm-1 υ C=O cm-1 υ C=C cm-1 υ C-H Aromatic υ N-H cm-1 Structure Com. No. NO 1271s C-O-C 1029 m - 1587 s 3062 w - 2 C-O-C 1112 m - 1593 s 3062 m 3386 m 3370 m 3 C-O-C 1110 m 1683 s 1593 s 3055 m 3300 s 4 C-O-C 1119 m 1650 s 1589 s 3068 m 3342 m 5 C-O-C 1110 m 1697 s 1583 s 3083 w 3300 m 6 Chemistry | 151 2016) عام 2(العدد 29المجلد مجلة إبن الهيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Figure (1): 1H-NMR spectrum of compound (1) Figure (2): 1H-NMR spectrum for compound [4] Chemistry | 152 2016) عام 2(العدد 29المجلد مجلة إبن الهيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 N O NO (2) N O N O NH2 (3) N O H (1) Zn/CH3COOH HCl/C2H5OH G-C=O N-H G = - , ,- Br- -CH2CH(CH3)2 (4-6) Triethyl amine / THF OH NH2 ZnCl2 H3PO4 NaNO2 Scheme (1): Preparation of new Hetrocyclic compounds Chemistry | 153 2016) عام 2(العدد 29المجلد مجلة إبن الهيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 Scheme (2): Reaction mechanism for the reduction of 10- nitrosylphenoxazin Chemistry | 154 2016) عام 2(العدد 29المجلد مجلة إبن الهيثم للعلوم الصرفة و التطبيقية Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 29 (2) 2016 أمينو فينوكسازين -10جديدة من تحضير مشتقات إسراء طه إبراهيم سعاد مصطفى األعرجي جامعة بغداد /كلية العلوم /قسم الكيمياء 2015/األول/كانون 15قبل في: ،2015/األول/تشرين 22ستلم في:ا الخالصة يتضمن البحث تحضير مشتقات جديدة من الفينوكسازين وهي مشتقات معوضة على ذرة النتروجين مبتدأ من ), 2نتروسل فينوكسازين من مفاعلة الفينوكسازين مع نتريت الصوديوم ليعطي المركب ( -10). حضر 1الفينوكسازين ( ) مع كلوريد 3). فوعل المركب (3كسازين (أمينو فينو - 10الذي بدوره يتفاعل مع الزنك في حامض الخليك ليعطي ). 6-4أمينو فينوكسازين ( - 10برومو فينيسيل فأعطى مشتقات -4بنزويل, كلوريد آيزوفاليريل و كلوريد أسيتو هيدرازايد فينوكسازين-1أستيت فينوكسازين, , أثيل فينوكسازين: الكلمات المفتاحية