الفهرس 
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Abstract
Derivation of Some Substituted Quinolinones As Biological Active Ingredients
The research work in this thesis focused on synthesis of 3-amino-4-hydroxy-1-methylquinolin-2(1H)-one (2) and 4-hydroxy-3-nitro-6-phenyl-6H-pyrano[3,2-c]quinoline-2,5-dione (18) as the key compounds. The chemical reactivity of these new precursors towards different reagents was studied. The new products were screened for their antitumor and antioxidant activities.
Part I. Synthesis of oxazolo and oxazinoquinolinone derivatives
Herein, we report the synthesis of 3-amino-4-hydroxy-1-methylquinolin-2(1H)-one (2) and study of its chemical reactivity towards different electrophiles to obtain tricyclic system namely; oxazoloquinolinones and oxazinoquinolinones. In addition, N-alkylated quinoline and some azodyes were synthesized.
4-Hydroxy-3-nitroquinoline 1 was reduced with tin and hydrochloric acid at 100 °C to produce 3-amino-4-hydroxy-1-methylquinolin-2(1H)-one (2) in 80% yield. Then, reactions of amine 2 with some electrophiles were investigated. Treatment of compound 2 with acetic anhydride and propionyl chloride under solvent-free conditions for 5h, gave amide derivatives 3 and 4, respectively.
Under different conditions, desired oxazolo[4,5-c]quinolones 5 and 6a-d were obtained via intramolecular cyclocondensation reaction of 3-aminoquinoline 2 with triethylorthoformate, some anhydrides and decanoyl chloride under fusion conditions for 13h.
Treatment of amine 2 with diethyloxalate under solvent-free conditions afforded 6-methyl-4H-[1,4]oxazino[3,2-c]quinoline-2,3,5(6H)-trione (8).
Otherwise, refluxing compound 2 with excess ethyl chloroacetate in absence of organic solvents produced 6-methyl-4,6-dihydro-2H-[1,4]oxazino[3,2-c]quinoline-2,5(3H)-dione (10). The reaction proceeded via nucleophilic addition of amine to ethyl chloroacetate followed by cyclization to afford oxazine 10.
N-alkylation of 3-amino-4-hydroxyquinoline 2 with benzyl chloride at a molar ratio (1:1) in pyridine produced N-alkylated quinoline 11. The same reaction was carried out at a molar ratio (1:2) to afford N,N-dialkylated quinoline 12.
Diazotization of amine 2 with sodium nitrite and hydrochloric acid gave 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-diazonium chloride (13).
Diazotization of amine 2 and coupling with 4-hydroxy-1-methylquinolin-2(1H)-one afforded azodye derivative 14. Similar reaction and coupling with β-naphthol gave azodye 15.
Part II. Ring Transformation Reactions of 4-Hydroxy-3-nitro-6-phenyl-6H-pyrano[3,2-c]quinoline-2,5-dione
Herein, we expose the synthesis of worthy 4-hydroxy-3-nitro-6-phenyl-6H-pyrano[3,2-c]quinoline-2,5-dione (18) as pioneer in order to get a novel series of quinolinones bearing pyrazole, isoxazole, diazepine, oxazepine or thiadiazepine at position 3 with anticipated biological activities.
Heating diphenylamine 16 with two equivalents of diethyl malonate produced 4-hydroxypyrano[3,2-c]quinoline-2,5(6H)-dione 17. Nitration of the latter compound using HNO3/H2SO4 afforded 4-hydroxy-3-nitro-6-phenyl-6H-pyrano[3,2-c]quinoline-2,5-dione (18) in good yield.
Nitropyranoquinolinone 18 was subjected to react with some 1,2-binucleophilic reagents such as hydrazine, phenylhydrazine and hydroxylamine under reflux in DMF for 4h, producing the novel pyrazolyl and isoxazolylquinoline derivatives 19, 20 and 21, respectively.
Treatment of nitropyranoquinolinone 18 with ethylenediamine, in refluxing DMF for 4h gave the desired 3-(2,3,4,7-tetrahydro-6-nitro-7-oxo-1H-1,4-diazepin-5-yl)-4-hydroxy-1-phenylquinolin-2(1H)-one (22). Reaction of nitropyranoquinolinone 18 with o-phenylenediamine in refluxing DMF produced 4-(1,2-dihydro-4-hydroxy-2-oxo-1-phenylquinolin-3-yl)-3-nitro-1H-benzo[b][1,4]diazepin-2(5H)-one (23).
Similarly, oxazepine derivative 24 was synthesized via refluxing pyranoquinolinone 18 with o-aminophenol in DMF for 4h. A similar reaction of nitropyranoquinolinone 18 and 4-amino-5-(trifluoromethyl)-4H-1,2,4-triazole-3-thiol (25) in DMF afforded the desired thiadiazepine 26.