الفهرس 
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Abstract
Synthesis and Antioxidant Activity of Some New 2-pyrazolin-5-one-1-carbothioamide Derivatives :- The key compound 3-methyl-2-pyrazolin-5-one-1-carbothioamide (2) was prepared using a known method exploiting the reaction of thiosemicarbazide with ethyl acetoacetate followed by treatment of the resulting ethyl 3-thiosemicarbazidobutanoate (1) with ammonia in methanol. In order to explore the potential of compound 2 in heterocyclic synthesis, the diazocoupling reaction of 3-methyl-2-pyrazolin-5-one-1-carbothioamide (2) with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-diazonum chloride (4) to afford 4-(2-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-yl)hydrazono)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothioamide (5). The base catalyzed reaction of 3-methyl-2-pyrazolin-5-one-1-carbothioamide (2) with phenyl isothiocyanate in DMF and in the presence of KOH followed by addition of dimethyl sulfate afforded the corresponding 3-methyl-4-(methylthio)-(phenylamino)methylene)-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothio-amide (7). When 3-methyl-2-pyrazolin-5-one-1-carbothioamide (2) was treated with carbon disulfide in presence of KOH and DMSO followed by addition of dimethyl sulfate, it afforded the corresponding 4-(bis(methylthio)-methylene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothioamide (9). When compound (9) was condensed independently with o-phenylenediamine or o-aminophenol afforded the expected, 4- (benzo[d]oxazol-2(3H)-ylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothioamide (10a) or 4-(1,3-dihydro-2H-benzo[d]imidazol-2-ylidene))-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothioamide (10b) respectively. While treatment of 9 with ethyl 4-aminobenzoate, gave only the open ethyl 4-[((1-carbamothioyl-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)-(methylthio)-methyl)amino]-benzoate (11). Under similar conditions compound 9 was also treated with ethyl mercaptoacetate to yield the corresponding 3-methyl-4-(1,3-oxathiolan-2-ylidene)-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothioamide (12).PART II: Utilization of 3-aminopyrazolopyridine derivative in organic synthesis : 4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridin-3-amine (3) was prepared by the reaction of 2-chloro-4,6-dimethylnicotinonitrile (13) with hydrazine hydrate in ethanol according to the reported method.Diazotization of 3 by the action of nitrous acid (NaNO2/HCl) at 0-5ºC afforded the corresponding 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-diazonium chloride (4), which underwent diazocoupling reaction with 8-hydroxyquinoline furnished 8-hydroxy-5-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-azo)-quinoline(14). In addition, 5-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-azo)-2,6-dihydroxy-4-methylnicotinonitrile (15) was synthesized by diazocoupling of 2,6-dihydroxy-4-methylnicotinonitrile with the 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-diazonium chloride (4). Coupling of 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-diazonium chloride (4) with N-aryl cyanoacetamide derivatives 16 in pyridine at 0-5°C afforded the corresponding hydrazono derivatives 17 . Heterocyclization of 17 in hot acetic acid resulted in the 4-amino-8,10-dimethyl-N-aryl-pyrido[2’,3’:3,4]pyrazolo[5,1-c][1,2,4]triazine-3-carboxamide derivatives 18. 2-Cyano-N-(4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)acetamide (20) was obtained from the reaction of 3 with 1-cyanoacetyl-3,5-dimethylpyrazole (19) by refluxing in dioxane. The chemical reactivity of methylene group in cyanoacetamide derivative 20 was investigated towards electrophilic coupling reaction. Thus, cyanoacetamide compound 20 was coupled with different aryl diazonium chloride to afford the corresponding 2-((4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine-3-yl)amino)-2-oxo-N-phenyl-acetohydrazonoyl-cyanide derivatives 21 We aimed to investigate further the behavior of 20 towards Aldol type condensation with aromatic aldehydes namely [benzaldehyde, 4-nitrobenzaldehyde and 4-(N,N-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).