Oxa-Chromanols

The oxidation behavior of 3-oxa-chromanols was mainly studied by means of the 2,4-dimethyl-substituted compound 2,4,5,7,8-pentamethylM /-benzo[ 1,3]dioxin-6-ol (59) applied as mixture of isomers 27a it showed an extreme dependence on the amount of coreacting water present. In aqueous media, 59 was oxidized by one oxidation equivalent to 2,5-dihydroxy-3,4,6-trimethyl-acetophenone (61) via 2-(l-hydroxyethyl)-3,5,6-trimethylbenzo-l,4-quinone (60) that could be isolated at low temperatures (Fig. 6.41). This detour explained why the seemingly quite inert benzyl ether position was oxidized while the labile hydroquinone structure remained intact. Two oxidation equivalents gave directly the corresponding para-quinone 62. Upon oxidation, C-2 of the 3-oxa-chroman system carrying the methyl substituent was always lost in the form of acetaldehyde. 

FIGURE 6.40 Synthesis of 3-oxa-chromanols (58) as mixture of cis/trans-isomers. 

FIGURE 6.41 Oxidation of 3-oxa-chromanol 59 in aqueous media (excess water present), leading to acetophenone 61 with an equimolar amount of oxidant, and further to para-quinone 62 in the presence of excess oxidant. 

FIGURE 6.42 Oxidation of 3-oxa-chromanol 58 in the presence of 1 equivalent of water mechanistic study hy means of selectively deuterated starting material. The initially formed ortho-quinone dimethide 63 rearranges into styrene derivative 64, which then reacts with water to provide acetophenone 61. 

If the formation of an exocyclic methylene group at C-4, and thus the formation of a styrene intermediate such as 64, is impossible due to structural prerequisites, oxidation of the corresponding 3-oxa-chromanols will involve the o-QM formed 

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FIGURE 6.43 Oxidation of 3-oxa-chromanol 59 in the absence of water, providing chromenone 66 as the final product mechanism and reaction intermediates. 

FIGURE 6.44 Oxidation of 3-oxa-chromanol 67, having no protons at position C-4a able to undergo rearrangements by analogy to 3-oxa-chromanol 59 with its oxidation intermediates 63 and 64. Due to this blocking at C-4/C-4a, the oxidation behavior of 67 resembles that of a-tocopherol (1). 

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