Synthesis and Characterization of 2(3 H )-Furanones, 2(3 H )-Pyrrolones,Quinolinones, Thienochromenones, Thienopyridinones and Biological Activity of Some Selective Compounds

Abstract

Reaction of 3-(4-substitutedbenzoyl)propionic acid with appropriate aromatic aldehydes in the presence of triethylamine in acetic anhydride gave 3-arylidene-5-(4- substititutedphenyl)furan-2(3H)-ones. Reaction of furanones with benzylamine gave γ-ketobenzylamides which were then cyclized to 1-benzyl-3-arylidene-5-(4- substituted phenyl)-1H-pyrrol-2-(3H)-ones by refluxing with 6N-HCl. Two series of furanones and pyrrolones were synthesized. The synthesized compounds were evaluated for antioxidant, cytotoxicity and urease inhibition activities. These compounds showed non significant antioxidant activity, nil brine shrimp lethality and low to moderate urease inhibition activity. Reaction of hitherto unknown 4-chloro-3-(2,2,2-trifluoroacetyl)-2H-chromen- 2-one with different commercially available anilines gave 3-(trifluoroacetyl)-4- (arylamino)-2H-chromen-2-ones which were then successfully cyclized to 7-(trifluoromethyl)-6H-chromeno[4,3-b]quinolin-6-ones with conc. H 2 SO 4 . Suzuki cross-coupling reaction of methyl-3-bromothiophene-2-carboxylate and ethyl-2-bromo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate methoxy phenylboronic acids gave the successfully cyclized to with o- arylated products which were then thieno[2,3-c]chromen-4-ones and 7,8,9,10- tetrahydrobenzothieno[3,2-c]chromen-6-ones via BBr 3 mediated lactonization. The Sonogashira cross-coupling reaction of methyl-3-bromothiophene-2- carboxylate and 2-bromo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile with terminal alkynes gave respective alkynyl products. The ester and nitrile groups of these substituted thiophenes were then converted into amides which were then cyclized to 5-substituted-thieno[2,3-c]pyridin-7(6H)-ones and 3-substituted-5,6,7,8- tetrahydrobenzothieno[3,2-c]pyridin-1(2H)-ones via base-promoted-cyclization. 4,5-Disubstituted thieno[3,2-b]pyridin-7(4H)-ones were synthesized by Pd- catalyzed tandem amination reaction of α,β-ynone with commercailly available anilines/amines. The method provides an efficient thienopyridinones.