S. M. Basavarajaiah, B. H. M. Miuthyunjayaswamy,
2009
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0
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10
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Journal
Heterocyclic Communications
Abstract
Indole and its derivatives occupied a unique place in the chemistry of nitrogen heterocyclic compounds, because of their varied biodynamic properties. New substituted indole Schiff bases 5-substituted -N'-[(lE)-(2-carboxo-l//quinolin-3-yI)methylene]-3-phenyl-lH-indole-2-carbohydrzide 3a-d are synthesized by condensation of 5-Substituted3-phenyl-2-carboxahydrazide (0.01 mol) and substituted 3-formyl-2-carboxo-l//-quinolines (0.01 mol) in presence of catalytic amount of the glacial acetic acid. These Schiff bases on further reacting with acetic anhydride/ thioglycolic acid in DMF / FeCl3-AcOH and con Sulphuric acid gives respective pyrrazole 4a-d, thioazolidine 5a-d, 1, 3, 4oxadiazole 6a-d and oxadiazino 7a-d indole derivatives. All the above synthesized compounds are conformed by spectral data and elemental analysis. The newly synthesized compounds were screened for their antimicrobial activity. Introduction Literature survey reveals that indole and its derivatives possess wide spectrum of biological activities. In continuation of our research work on the synthesis of indole derivatives viz, antimicrobial, analgesic (1), anticatatonic (2), and anti-inflammatory (3) activities. Several indole derivatives are reported to possess antiviral (4), antihepatitis-B virus(HBV) (5) and COX-2 inhibitors (6). Qunolines analogues have attracted great attention of medicinal and synthetic chemists because of their presence in natural products and physiological activities. There are many methods available for synthesis qunolines, the Vilsmeier approach has been recently, explored by Katritzky etal (7) and Srivastav etal (8). In recent years, the chemistry of qunolines and their derivatives as gained increasing attention, particularly because substituted qunolines are associated with immense biological activities (8-9). Fused indolo[2,3c]isoquinolines possesses various biological activities such as bactericidal, fungicidal, anticancer and autihistaminic activity(10-14). Among the wide variety of heterocycles that have been explored for developing pharmaceutically important molecules, oxadiazoles (15-16). thioazolidines (17-18) and oxadiazino (19-20) derivator have played vital role in the medicinal chemistry. In this paper we report here the synthesis of some pyrrazole, ihioazolidine, 1, 3. 4oxadiazole and oxadiazino ring moieties containing indole and quinoline moieties by making use of 3.5-disubstituted indole-2-carboxyhydrazide and substituted 3-formyl-2-carboxo-l//-quinolines as starting materials. 217 Vol. 15, No. 3, 2009 Synthesis and Anti-microbial Activity of Some New 5-subslituted Experimental: Melting points were determined in open capillary tubes and are unconnected. IR spectra were recorded in KBr on Perkin-Elmer FT-1R (spectrum 1000); NMR spectra on a Bruker AMX (500 MHz) spectrophotometer using DMSO or CHC13 as solvent and TMS as an internal standard (chemical shifts in D) and mass spectra on a FAB-MS instrument. Synthesis of 5-substituted-N-[(l£)-(2-carboxo-//^-quinolin-3-yl)methylene]-3-phenyl-l//-indole-2carbohydrzide 3a-d: 5-substituted-3-phenyl-2-carboxyhydrazide la-b (O.Olmol) and substituted-3-formyl-2-hydroxy-quinoline 2a-b (0.01 mol) and a catalytic amount of glacial acetic acid were taken in ethanol (20 ml) and refluxed for 7-8hr on water bath. The resulting solid were filtered, washed with little alcohol dried and recrystallised to get 5-chloro-N'-[(l£)-(2carboxo-7A/-quinolin-3-yl)methylene]-3-phenyl-l//-indole-2-carbohydrzide3a-d. Synthesis of 3-l(25)-3-acetyl-5-(-5-susbtituted-3-phenyI-l//-indol-2-yI) 2,3-dihydro-l,3,4-oxadiazol-2-yl]quinolin2-yl acetate 4a-d: A mixture of the 3a-d (O.Olmol) and acetic anhydride (10 ml) was refluxed for 3hr on refluxed for 3 hr on oil bath. The reaction mixture was cooled to room temperature, poured into ice-cold water and the solid separated was recrystallised from suitable solvent to yield 3-[(2S)-3-acetyl-5-(5-susbtituted -3-phenyl-l//-indol-2-yl) 2,3-dihydrol,3,4-oxadiazol-2-yl]quinolin-2-yl acetate 4a-d. Synthesis of 5substituted -A'-|(2A)-2-(2-carboxo-/// quinolin-3-yl)-4-oxo-l,3-thiazolidin-3-yl]-3-phenyll-l//indole-2-carboxamide 5a-d: 3a-d (0.01 mol) was refluxed in DMF (30 ml) containing a pinch of anhydrous zinc chloride and thioglycolic acid (0.01 mol) for 8hr. The reaction mixture was cooled and poured into ice cold water. The separated solid was filtered washed and recrystallised from suitable solvent to get 5substituted -/V-[(2Ä)-2-(2-carboxo-7W quinolin-3-yl)4-oxo-l ,3-thiazolidin-3-yl]-3-phenyll-l A/-indole-2-carboxamide 5a-d.. Synthesis of 2-carboxo-l//3-|5-(5substituted -3-phenyl-l//-indol-2-yl)-l,3,4-oxadiazol-2-yl]quinolin 6a-d: To a well stirred solution of 3a-d (0.01 mol) in acetic acid (15 ml), a solution of ferric chloride (1.5 g) in water (5 ml) was added. The mixture was stirred for Ihr and diluted with water (100) and kept at room temperature for two days. The solid separated was filtered, washed with water and crystallized to get 6a-d Synthesis of 2-(5-chloro-3-phenyl-lf/-inol-2yl)[l,3,4]oxadiazepino|7,6-b]quinoIine7a-d. 3a-d (O.Olmol) was added slowly to concentrated Sulphuric acid (AR grade, O.OlSmol) in the cold, with stirring. The resulting mass was allowed to attain room temperature and poured into cold water. After neutralization with liquid ammonia, the product 2-(5-chloro-3-phenyl-l//-inol-2yl)[l,3,4]oxadiazepino[7,6-b]quinoline 7a-d were obtained, filtered washed dried and crystallized from suitable solvents.