CYCLIZATION REACTIONS LEADING TO BETA-HYDROXYKETO ESTERS

The purpose of the research was to synthesize beta-diketo esters and t o evaluate them for anticonvulsant activity. The reaction of methyl vi nyl ketone with dimethyl malonate in the presence of potassium carbona te gave an uncyclized product that underwent a Claisen condensation to yield methyl 2-hydroxy-4-oxocyclohex-2-en-1-oate (5a). Similariy, oth er cyclized beta-hydroxyketo esters were prepared, and their spectrome tric data confirmed that the enol tautomers were preferred to the beta -diketo tautomers. The synthetic work clarified the reaction pathway f or the Michael addition of malonate esters to enones. Of the intermedi ates and products tested for anticonvulsant activity, dimethyl2,2-bis- (3-oxobutyl)malonate (9a) was found to possess anticonvulsant property . However, it is emphasized that the beta-hydroxyketo esters could be useful intermediates in the synthesis of enaminone anticonvulsants.