Preparation of 3-hydroxy-2,3-dialkoxy-2-phenylchroman-4-ones and 3,3-dihydroxy-2-alkoxy-2-phenylchroman-4-ones by oxidation of 3-hydroxyflavone with copper(II) bromide: Structure, reactivity and characterization

The reaction of 3-hydroxyflavone with copper(II) bromide in various alcohols (ethanol, isopropanol, and methanol) yielded a mixture of their respective 3-hydroxy-2,3-dialkoxy-2-phenylchroman-4-ones (hemiacetals) and 3,3-dihydroxy-2-alkoxy-2-phenylchroman-4-ones (hydrates). Herein, we report the synthesis, reactivity and characterization of three hemiacetals (1, 3, and 5) and three hydrates (2, 4, and 6) as well as the single crystal X-ray structures of 1–4 & 6. While the hemiacetals were shown to be kinetically accessible, the hydrates were thermodynamically preferred. The single X-ray structures of compounds 1–4 & 6 reveals the alkoxy groups occupying the axial position of the coumarin ring, which is surmised to be the source of the instability of the hemiacetals. As a result of the axial strain, the hemiacetals (1, 3, and 5) readily convert in to their respective hydrates (2, 4, and 6) when heated in non-alcoholic solvents. The qualitative rate of these conversion was largely a function of the size of the alkoxy group (i-Pr > Et > Me). We propose a mechanism for the conversion of hemiacetals to hydrates that involves a chromane-3,4-dione intermediate, which was evidenced by trapping it as a diimine, quinoxaline heterocycle.