Synthesis of some New Schiff Bases and Hydrazones Containing Benzonaphthyridine/ Benzonaphthyridone Moiety

The N-(4-methyl-2-pyridyl)anthranilic acid (I) was synthesized by Ullmann condensation. The compound (I) was cyclized by polyphosphoric acid (PPA) to give 4-methyl-10Hbenzo[b][1,8]naphthyridin-5-one (II). The compound (II) was treated with selenium dioxide (SeO2) and thionyl chloride (SOCl2) to give the 4-formyl-10H-benzo[b][1,8]naphthyridin-5-one (III) and 4methyl-5-chloro-benzo[b][1,8]naphthyridine (IV) respectively.The compound (III) was reacted with various substituted anilines and aliphatic amines to give the Schiff bases (Va-j). The compound (IV) was reacted with hydrazine hydrate to yield the 5-hydrazino derivative (VI), which was reacted with various aromatic aldehydes to yield the hydrazones (VIIa-j) and the Rf values reported.The reaction progress was followed by thin layer chromatography (TLC). The synthesized compounds were confirmed by spectral data (I.R, H-NMR, C-MNR). The possible fragmentation pattern of GC/MS for the compounds (III), (Vc) and (VIIg) were reported. ـــــــــــــــــــــــــ ــــــــــ ـــــــــــــــــــــــــــــ ب ريضحت ةديدج تانوزارديهو فش دعاوق ضع ىلع ةيوتحم ةعومجم نيدراثفنوزنبلا / نوديراثفنوزنبلا صخلملا ضماح رضح N ) 4 ليثم 2 ليديريب ( ارثنلاا ن ل ي ك ) I ( لعافت ةطساوب أ ناملو . ث لوح م ةق بكرملا ) I ( ماح ةطساوب ض ددعتملا كيروفسفلا PPA) ( يطعيل 4 ليثم 10 -H وزنب [8,1][b] نيدراثفن 5 أ نو ) II .( بكرملا لموع ) II ( يئانث عم موينيليسلا ديسكوا ) SeO2 ( لينوياثلا ديرولكو ) SOCl2 ( يطعيل 4 ليمروف 10 -H وزنب [8,1][b] نيدراثفن 5 نوا ) III ( و 4 ليثم 5 وزنب ورولك [8,1][b] نيدراثفن IV) ( يلاوتلا ىلع . دنع بكرملا ةلعافم ) III ( ةدع عم أ ضوعم تانيلين ة و أ تانيم يتافيلا ة ىطعا ش دعاوق ف (V) . لعافت ىطعا امنيب بكرملا ) IV ( ملا نيزارديهلا عم يئا لا قتشم ـ 5 ونيزارديه ) VI ( ، يذلا تلاعافت لخدا ةدع عم أ هيدل ا تادي أ تانوزارديهلا يطعيل هيتامور ) VIIa-j .( نقت تمدختسا ةي ايفاركوتامورك ةقبطلا ةقيقرلا ) TLC ( لعافتلا ريس ةعباتمل . امك ةيوايزيفلا تباوثلا تلجس ميقو ) R f .( تصخش ةطساوب ةرضحملا تابكرملا بيكارت ءارمحلا تحت ةعشلاا فيط لثم ةيفيطلا قرطلا ) I.R ( يسيطانغملا يوونلا نينرلا فيطو ) H-NMR,C-NMR ( حضوو ل لمتحملا ؤزجتلا ططخم فيط ةلتكلا ) GC/MS ( ل تابكرمل ) III, Vc, VIIg ( . ـــــــــــــــــــــــــــــــــــــــــــ ـــــــــ ــــــــــــــ INTRODUCTION Many Benzonaphthyridine derivatives have current interest due to their planner linear structure (Ivanove et al., 2005). Ullmann synthesis involves the condensation of o-halobenzoic acid with substituted 2-aminopyridine in presence of cupric oxide and anhydrous potassium carbonate to give N-pyridylanthranilic acids (Jameel and Al-Hadedi, 2010). Cyclization of N-pyridylanthranilic acid can be achived by concentrated H2SO4 (Acheson, 1973), polyphosphoric acid (PPA) (Meftah et al., 1994) and POCl3 (Al-Hadedi, 2008) to give different types of tricyclic hetero compounds. The literatures showed that the benzonaphthyridine/ benzonaphthyridone derivatives have versatile biological activities such as antitumor (Chen et al., 1994), trypanocidal (Mefetah et Rafid K. Jameel and Attallah M. Sheat

In  (Al-Obaydee, 2010). The aim of the present study is preparation of new Schiff bases and hydrazones derivatives cotaining benzonaphthyridine/ benzonaphthyridone which were expected to be biologically active compounds.
EXPERIMENTAL Melting points were determined on an electrothermal IA 9300 Digital-series (1998) apparatus, and they were uncorrected. Infrared spectra were recorded on a Bruker FT-IR spectrophotometer Tensor 27, Germany (College of Education, University of Mosul). 1 H, 13 C-NMR spectra were recorded on a Bruker 300 MHz, in (Al-Al-Bayt University, Jordan) using TMS as an internal reference, and DMSO-d 6 as a solvent, and coupling constant J(Hz) with the use of the following abbreviations: s, singlet; d, doublet; t, triplet; m, multiplet and br, broad. Mass spectra (MS) were obtained from perkin Elmer Clarus 500 Gas chromatography-Mass spectrometer in (I.I.T Roorkee. Chemistry Dept., India), and from a trace 2000 series GC-MS in CH 2 Cl 2 University of Southampton, Chemistry Dept., UK).
In a 100 ml three-necked flask with sealed stirrer, a reflux condenser and a thermometer, 15 ml of dioxane was placed,then (1.32 g, 0.0119 mol) of selenium dioxide SeO 2 and (1 ml) water was added to the flask. The mixture was heated to 50-55˚C until the solid was dissolved. The thermometer was removed and (2.5 g, 0.0119 mol) of compound (II) was added in one partion. The mixture was refluxed with stirring for 4 hrs. The progress of the reaction was monitored by TLC. The hot solution was decanted from the precipitated (black) selenium through fluted filter paper. The dioxane and water were removed by distillation to give a solid product. The product was recrystallized from ethanol to yield a brown powder, m.p = 170-172 ˚C, R f = 0.62, yield 2.2 g (83%).
In a 25 ml dry methanol, (0.1 g, 0.00044 mol) of III was dissolved by stirring and mixed with (0.00044 mol) of appropriate amine. The solution was refluxed with stirring for at least 6 hrs. The progress of the reaction was monitored by TLC. The mixture was cooled and left overnight to complete the precipitation. The product was filtered off and dried in air. Table (1) summarizes the physical data for compounds Va-j. • Elution solvent = CHCl 3 :MeOH (9.5:0.5).

Preparation of 5-chloro-4-methylbenzo[b][1,8]naphthyridine (IV). (Atwell et al., 1984).
A mixture of (2.5 g, 0.012 mol) of compound II with excess (30 ml) of SOCl 2 containing (2 drops) DMF was refluxed for 3 hrs. The excess SOCl 2 was distilled off under reduced pressure, then the deep scarlet thick residue was diluted with cold chloroform, 150 ml (needs 2 hrs). The solution was slowly added with vigorous stirring to cold ammonia solution. The chloroform layer was separated and the aqueous alkaline solution was further extracted with (30ml×2) of chloroform. The combined chloroform extracts were dried by magnesium sulfate for over night. The Chloroform filtrate was evaporated until dryness. The solid residue was recrystalyzed from ethanol to yield a brown powder, m.p = 116 -118 °C. R f = 0.95, (CHCl 3 :MeOH, 9.5:0.5), yield 85%. Compound IV(3g) was added with stirring to the refluxing solution of hydrazine hydrate (30 ml, 80%) in (150 ml) ethanol during 10 min, and the refluxing continued for 40 min. The completion of the reaction was monitored by TLC. The solvent was distilled under reduced pressure, then extracted by chloroform (100ml×3), and dried by magnesium sulfate overnight.  (Kannappan, et al., 2009). General procedure A mixture of (0.1 g, 0.00044 mol) of VI in 25 ml of methanol was mixed with (0.00044 mol) of appropriate aldehydes. The solution was refluxed with stirring for at least 6 hrs. The progress of the reaction was monitored by TLC. The mixture was cooled and left overnight to complete the fine precipitation. The product was filtered off and dried in air. Table (2) summarizes the physical data for compounds VIIa-j. Elution solvent = CHCl 3 :MeOH (9.5:0.5). dec. = decomposition; sub.=sublimation

RESULTS AND DISCUSSION
The methyl group in compound (II) was easily oxidized to the corresponding formyl group to form the compound III as shown in Scheme 1. (Chen and Deady.,1993;Deady et al., 2003) PPA 120 -130 o C I structure of compound III was confirmed via IR spectrum which showed characteristic absorption peaks in the region (3479 cm -1 ) due to the stretching of (N-H) bond, (1705 cm -1 ) due to the stretching of (C=O) bond of the aldehyde group, (1687 cm -1 ) due to stretching of (C=O) bond of the ketone group, and (1637 cm -1 ) due to stretching of (C=N) bond. The 1 H-NMR and 13 C-NMR spectral data of compound III confirmed the above results, and showed the following significant peaks: multiplet at 7.13-7.25 for 1H (H-9), multiplet at 7.43-7.65 for 2H (H-7, H-8 . The mass spectral data Fig. (1) confirmed the above structure. The possible fragments (m/z) with their relative abundance (%) was reported as shown in Scheme (2). Similar data were found in Lit (Tian et al., 2012)

Scheme 3: Fragmentation pattern of compound (Vc)
Compound VI has been prepared through the reaction of compound IV with hydrazine hydrate (Chandra et al., 2010;Al-Hadedi, 2009) as shown in Scheme (1). The structure of the synthesized compound VI was confirmed by means of physical data (m.p, R f ) and spectral data. The IR spectrum showed a characteristic broad absorption peaks in the region (3422-3314 cm -1 ) which is due to the bond stretching of (NH, NH 2 ) bonds, 1649 cm -1 for stretching of (C=N) bond, and (1590 cm -1 ) for stretching of (C=C) bond. The 1 H-NMR and 13 C-NMR spectral data for compound VI (Fig. 6)  The compounds VIIa-j have been prepared through the condensation of compound VI with various aromatic aldehydes (Chilin et al., 2002;Manoj and prasad ., 2011) as illustrated in Scheme (1). The structure of the prepared compounds was elucidated by means of physical data (Table 2) (m.p, R f ) and spectral data ( Table 4). The IR spectra of compounds VIIa-j showed a characteristic absorption bands at (3340-3300 cm -1 ) for stretching of (N-H) band, (1625-1635 cm -1 ) for stretching of (C=N) bond. The 1 H-NMR spectrum for compound VIIb confirmed the structure of these compounds. The mass spectrum for compound VIIg showed the possible following fragmentation (m/z) with relative abundance (%) as shown in Scheme (4).