An efficient cyclocondensation reactions, antimicrobial activity and molecular orbital calculations of α-benzopyrone derivatives

Abstract

An efficient synthesis of 4,6,8-trimethyl-2-oxo-2H-chromene-3-carbonitrile (2) via Claisen condensation of 3,5-dimethyl-2-hydroxyacetophenone with ethyl cyanoacetate in the presence of sodium metal is reported. Cyclocondensation reactions of compound (2) with ethyl acetate or with ethyl cyanoacetate in the presence of ethoxide gave sodium salt of 7-amino-9-hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one derivatives (3) and (4) respectively, which upon neutralization with 10 % hydrochloric acid gave 7-amino-9hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one (5). Hydrolysis of compound (2) with ethanolic sodium hydroxide solution gave 4,6,8-trimethyl-2-oxo-2H-chromene-3-carboxylic acid (6). Treatment of compound (2) with Vilsmier reagent using excess POCl3 gave 4-(chloro(formyl)methyl-6,8-dimethyl-2-oxo-2H-chromene-3-carbonitrile (7). Also, condensation of compound (2) with DMF-DMA in xylene or with POCl3/DMF in pyridine gave the same product 4-((E)-2-(dimethylamino)vinyl)-6,8-dimethyl-2-oxo-2H-chromene-3-carbonitrile (8). The cyclocondensation reactions of compound (8) with hydroxylamine hydrochloride, urea, and with hydrazinecarbodithioic acid gave 3,4-dihydro-3-hydroxy-4imino-7,9-dimethylchromeno[3,4-c]pyridin-5-one (9), 4-imino-7,9-dimethyl-5-oxo-4H-chromeno[3,4-c]pyridine-3(5H)-carboxamide (10) and 3-amino-3,4-dihydro-4-imino-7,9-dimethyl chromeno[3,4-c]pyridin-5-one (11), respectively. Also, acid hydrolysis of compound (8) gave 7,9-dimethyl-3H-chromeno[3,4-c]pyridine-4,5-dione (12). Structures of the products were established on the basis of elemental analysis, IR, 1 H and 13 C NMR, mass spectra and semiempirical AM1-MO calculations. The antimicrobial activities of the synthesized products were also studied. Synthesis α-Benzopyrone Cyclocondensation Antimicrobial Activity Chromeno[3,4-c]pyridinones Molecular orbital calculations

An efficient synthesis of some new isolated and fused 2-oxo-2H-chromene derivatives as antimicrobial and antitumor agents

“…In our recent work, we described the condensation of 3,5-dichloro-2-hydroxyacetophenone [2], 3,5-dimethyl-2-hydroxy acetophenone [18] and unsubstituted 2-hydroxyacetophenone [2] with ethyl cyanoacetate in the presence of sodium metal gave 7-amino-2,4-dichloro(or 2,4-dimethyl)-9-hydroxy-6-oxo-6H-benzo[c]chromene-8-carbonitrile, and a mixture of 4-methyl-2-oxo-2H-chromene-3-carbonitrile and 7-amino-9-hydroxy-6-oxo-6H-benzo[c]chromene-8-carbonitrile, respectively.…”

“…With the expectations to find biological activity, we decided to investigate the synthesis of some novel systems of 2-oxo-2H-chromene derivatives bearing fused and isolated moieties. Recently, the synthesis [14], photochemical [15], and theoretical [2,[16][17][18] properties of chromene derivatives were investigated.…”