Cyclization of substituted 2′-hydroxychalcones to flavanones. Solvent and isotope effects

Abstract

The kinetic isotope effects on the cyclization of substituted 2′-hydroxychalcones (R = 3-hydroxy, 4′-hydroxy, 4,4′-dihydroxy, 4′-hydroxy-4-nitro, 4-nitro, or 5′-methyl) into the corresponding substituted flavanones have been measured in water and/or methanol. The pronounced isotope effects observed are consistent with the slow rupture of a bond to hydrogen. The effect of the medium permittivity on the rate of cyclization of 2′-hydroxy, 2′,4-dihydroxy, and 2′,4-dihydroxychalcones have been also studied in several mixed solvents and the observed dependence is consistent with a reaction between one ion and one dipole. These results confirm a mechanism that involves general acid attack of the ionized form of the 2′-hydroxychalcones, concerted rotation through the CO–C_α bond, and annellation to the flavanone.