الفهرس 
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Abstract
We are informing here the synthesis of some more analogues of various heterocyclic systems (namely; imidazo-thiazole, imidazo-tetrazole, imidazo-triazole, imidazo-pyridine, imidazo-imidazole, thiazole and/or thiophene) incorporating 2-thienyl moiety and evaluating their in vitro anti-oxidant activity.The highly versatile α-bromocarbonyl reagent, 5-bromo-2-(bromoacetyl)-thiophene (1), has been prepared by the reported conditions through the free radical bromination of 2-acetylthiophene substrate. The chemical behavior of (1) was verified towards the reaction with several bi-nucleophilic reagents in order to prepare several bridge nitrogen compounds. Thus, (1) was heated with 2-aminobenzothiazole derivatives 2, 2-aminothiazole (4), 2-aminotetrazole (6), 2-aminotriazole (8), 2-aminopyridine derivatives 10, 2-aminobenzimidazole (12) and/or o-phenylenediamine (14) in absolute ethanol in a non-catalyzed reaction. The reaction afforded a series of the corresponding nitrogen containing heterocycles bearing thiophene moiety, 3 5, 7, 9, 11, 13 and 15, respectively (Scheme 1). The treatment of activated nitriles 16 (namely; malononitrile, ethyl cyanoacetate and cyanoacetamide) with phenyl isothiocyanate was carried out by stirring in dimethylformamide in the presence of potassium hydroxide to afford the 17. In situ treatment of 17 with (1) promoted heterocyclization to obtain a series of 18a, 18b and 18c in good yields (Scheme 2). On the other hand, acidification of 17 with dilute HCl furnished their corresponding 19. The reaction of 19 with (1) was achieved in boiling ethanol and triethylamine to present different cyclization behavior and afforded the 20a, 20b and 20c in good yields (Scheme 2). The reaction mechanism strating the establishment of compounds 18a, 18b and 18c hypothesized by the authors is depicted in (Scheme 3). In a first step, the sulfide nucleophile can be readily attacking the α-carbon carrying the bromide atom in a bimolecular nucleophilic substitution reaction to give the intermediate 21, which is not stable and undergo intramolecular heterocyclization through compound 22. Dehydration of 22 results in the formation of the scaffolds 18a, 18b and 18c. The open-chain precursor 21 is also the intermediate for treatment of (1) with the thiocarbamoyl nucleophiles 19 under reflux in absolute ethanol and triethylamine. The authors described the synthesis of the 20a, 20b and 20c depending on the tendency of the open-chain precursors 21 to undergo in situ heterocyclization through nucleophilic addition of methylene group to the carbonyl group and elimination of water molecule (Scheme 4). In line with our research plan, the highly functionalized 25a, 25b and 25c were obtained as the main products, on treating 24 with (1) in the presence of ethanol and triethylamine as a catalyst (Scheme 5).