الفهرس 
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Abstract
Part I : Synthesis, reactions and antioxidant activity of 4,6-dimethyl-2-substituted-pyridine-3-carbonitrile derivatives :- the starting compound 2-chloro-4,6-dimethylnicotinonitrile (2) was prepared by treating the corresponding 3-cyano-4,6-dimethyl-2-pyridone (1) with phosphorous oxychloride according the previously reported method. Refluxing 2 with 4-amino-acetophenone in ethanol containing few drops of concentrated HCl gave the corresponding 2-(4-acetylphenyl)aminonicotinonitrile derivative (3). The reaction of 2-[(4-acetylphenyl)amino]-4,6-dimethyl-nicotino-nitrile (3) with thiosemicarbazide in refluxing ethanol led to the formation of the corresponding thiosemicarbazone derivative (4). 4-Thiazolidinones and their derivatives are an important class of compounds in organic and medicinal chemistry. Thus, the thiosemicarbazone 4 was cyclized with compounds 5a-d (namely, chloroacetic acid 5a, chloroacetone 5b, phenacyl chloride 5c and hydrazonoyl chloride 5d) to form the non-isolable S-alkyalted intermediates via nucleophilic substitution followed by intramolecular cyclocondesation to give the corresponding polyfunctionally substituted thiazole derivatives 6-9. Cyclization of the thiosemicarbazone 4 with chloroacetic acid was achieved by reflux in acetic acid containing fused sodium acetate to furnish the corresponding thiazolidin-4-one derivative (6). In addition, heating the thiosemicarbazone 4 with α-chloroketones (namely, chloroacetone and phenacyl chloride) in ethanol containing drops of triethylamine afforded the corresponding 4-substituted thiazole derivatives 7 and 8, respectively. Treatment of the thiosemicarbazone 4 with 2-oxo-2-phenyl-N-(p-tolyl)-acetohydrazonoyl chloride (5d) afforded the corresponding p-tolylazothiazole derivative (9).PART II: SYNTHESIS OF SOME NEW HETEROCYCLIC COMPOUNDS CONTAINING THIENO[2,3-B]PYRIDINE MOIETY 2-Mercapto-4,6-dimethylnicotinonitrile (10) was synthesized by treatment of 2-chloro-4,6-dimethylnicotinonitrile (2) with thiourea under reflux in ethanol. When compound 10 was allowed to react with chloroacetone in ethanol / sodium ethoxide solution, 2-acetyl-3-amino-4,6-dimethylthieno[2,3-b]pyridine (11) was obtained exclusively. The synthesis of 4,7,9-trimethyl-3-phenylpyrido[3’,2’:4,5]thieno[3,2-d]pyrimidine-2(3H)-thione (12) was performed in good yield by the reaction of 2-acetyl-3-amino-4,6-dimethylthieno[2,3-b]pyridine (11) with phenyl isothiocyanate in the presence of pyridine. The reactivity of 2-acetyl-3-amino-4,6-dimethylthieno[2,3-b]-pyridine (11) towards Vilsmeier reaction was investigated. Thus, 11 reacted with a mixture of phosphorus oxychloride and dimethylformamide to afford the corresponding 2-acetyl-3-formamido-4,6-dimethylthieno[2,3-b]-pyridine (13) via the formylation of the NH2 group. Treatment of compound 11 with aromatic aldehydes e.g., benzaldehyde under reflux in absolute ethanol afforded 2-acetyl-3-(benzylideneamino)-4,6-dimethylthieno[2,3-b]pyridine (14). Acetylation of compound 11 with acetic anhydride in pyridine afforded the corresponding 2-acetyl-3-acetamido-4,6-dimethylthieno[2,3-b]pyridine (15). dimethylamino)benzaldehyde]. The reaction was performed in refluxing ethanol containing a catalytic amount of piperidine to afford 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-yl)-3-phenylacrylamide derivatives 22.Treatment of compound 23 with hydrochloric acid in water afforded the corresponding 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-mercapto-3-(phenylamino)acrylamide (24). In addition, 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(3,4-diphenylthiazol-2(3H)-ylidene)acetamide (25) was prepared by in situ reaction of 23 with chloroacetone. In situ treatment of the non-isolable intermediate potassium sulphide salt 23 with phenacyl chloride afforded 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(4-methyl-3-phenylthiazol-2(3H)-ylidene)-acetamide(26).2-Cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(4-oxo-3-phenyl-thiazolidin-2-ylidene)acetamide (27) was obtained by the reaction of 23 with ethyl bromoacetate in dimethyl formamide. Moreover, 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (28) was obtained from the reaction of 23 with chloroacetyl chloride in dimethyl formamide. In addition, 2-(4-(2-(4-chlorophenyl)hydrazono)-5-oxo-3-phenyl-thiazolidin-2-ylidene)-2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]-pyridine-3-yl)acetamide (29) was obtained by diazocoupling of 28 with 4-chlorophenyl diazonium chloride. We aimed to investigate further the behavior of the 28 towards aromatic aldehyde namely (4-methylbenzaldehyde). The reaction was performed in refluxing ethanol containing a catalytic amount of piperidine to furnish 2-cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(4-(-4-methyl-benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-acetamide (30). Antioxidant Activity. The newly synthesized pyrazole derivatives were tested for their antioxidant activities by using ABTS Radical Cation Decolorization Assay. The results (Table 1) indicated that most of the examined compounds exhibited moderate to good antioxidant activity. Among the tested compounds, 2 and 9 displayed excellent antioxidant property (90.4%) and (89.4%) respectively. They were even more active than the standard inhibitor (L-Ascorbic acid 88.20%).