Synthesis, Characterization and Biological Screening of Some New N and O Containing Heterocyclic Compounds

Abstract

The derivatives of isocoumarins, coumarins and 1,2,4-triazoles are prominent biological agents used as a cure against a number of human ailments. The present work deals with their synthesis. 3-(Halobenzyl)isocoumarins (5a-i) were synthesized by condensation of 2-(halophenyl)acetyl chlorides (3a-i) with homophthalic acid (4) at elevated temperature. 3-(Halobenzyl)isocoumarins (5a-i) were converted into 3-(halobenzyl)-3,4- dihydroisocoumarins (8a-i) via ketoacids (6a-i) and hydroxyacids (7a-i). 3- (Halobenzyl)isocoumarins (5a-i) converted to their thio analogues (10a-i) by treating with Lawesson’s reagent (11) while their nitrogen analogues (12a-i) were obtained by passing ammonia into the solution of 3-(halobenzyl)isocoumarins (5a-i) in 2-ethoxy ethanol. These synthesized compounds were evaluated for urease inhibition and anti- inflammatory activity. 3-(Halobenzyl)isocoumarins (5a-i) and ketoacids (6a-i) exhibited moderate urease inhibition activity. While others showed non significant activity. The isoquinolinone (12c) showed anti-inflammatory activity higher than standard compound i-e indomethacin while all other compounds showed non significant anti-inflammation. Reaction of hitherto unknown 4-chloro-3-(2,2,2-trifluoroacetyl)-2H-chromen-2-one (16a) with different commercially availble anilines (19a-l) gave respective 3-(trifluoroacetyl) - 4-(arylamino)-2H-chromen-2-one (20a-l) which were then successfully cyclized to 7- (trifluoromethyl)-6H-chromeno[4,3-b]quinolin-6-ones (21a-l) using conc. H2SO4. The synthesis of 4-aryl-3-(trifluoroacetyl)-2H-chromen-2-ones (18a-n) was accomplished by Suzuki coupling reaction of 4-chloro-3-(2,2,2-trifluoroacetyl)-2H-chromen-2-one (16a) and aryl boronic acids (17a-n). Synthesis of 1,2,4-triazoles (31a-o) was carried out by dehydrative cyclization of thiosemicarbazides (20a-o) which in turn were synthesized by addition of hydrazides (29a-i) on isothiocyanate (27m-n). These triazoles showed moderate antibacterial activity. Finally the synthesized 1,2,4-triazoles (31a-o) were evaluated for their toxicity and these showed low toxicity.