Oxidation Reactions of 5-Hydroxy-2,3-dihydrobenzofurans and 5-Hydroxy-2,3-dihydronaphtho[1,2-b]furans

Abstract

The oxidation of 5-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (1) and 5-hydroxy-2,2,4-trimethyl-2,3-dihydronaphtho[1,2-b]furan (2) in various systems was examined. For 1 the reaction mainly took place at the 6-position. On oxidation with silver nitrate we obtained 2,2,4,7-tetramethyl-2,3-dihydrobenzofuran-5,6-dione (4) and with silver oxide via 2,2,4,7-tetramethyl-6-methylene-2,3-dihydrobenzofuran-5(6H)-one (5), which can be trapped with ethyl vinyl ether, trimeric and dimeric products. Dimers are also the main products in the oxidation of 2.5-Hydroxy-2,3-dihydrobenzofurans and 5-hydroxy-2,3-dihydronaphtho[1,2-b]furans have been shown to be extremely effective antioxidants in various systems. 1-3 They became more interesting when they were found to be even more efficient than a-tocopherol, which was shown to be the major lipid-soluble chain-breaking antioxidant in human blood. 4 In addition, 5-hydroxy-2,3-dihydrobenzofurans have proved to be good free radical scavengers in biological systems, i.e. to work as lipoperoxidatio 5 inhibitors 2 or as inhibitors of leukotriene biosynthesis. Moreover, 5-hydroxy-2,3-dihydrobenzofuran is a widely occurring structural moiety in natural products. 6,7 Despite their promising biological and antioxidant activity, comparatively little work has been done on the synthesis and reactions of these compounds. At present the main research area of 5-hydroxy-2,3-dihydrobenzofurans is their antioxidation capability. Therefore, we considered it most interesting to investigate the oxidation reactions of these compounds in various chemical environments. For our work we chose 5-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (1) and 5-hydroxy-2,2,4-trimethyl-2,3-dihydronaphtho[1,2-b]furan (2) as model compounds. This choice was made to maintain the comparability of our results with those obtained for a-tocopherol and the corresponding 6-hydroxychromans. Analogous to 2,2,4,7,8-pentamethyl-2,3-dihydrochroman-6-ol, the model compound most frequently used instead of a-tocopherol, we chose the pentamethyl derivative of the 5-hydroxy-2,3-dihydrobenzofurans.The oxidation of 1 with iron(III) chloride in aqueous methanol yielded the p-quinoid product 3 (Scheme 1), as described earlier by Karrer and Jensen. 8 This product was also formed by treating 2 in this way (Scheme 5). Yellow needles of 9 were obtained which were unstable in air and decomposed into a black oil. By treating products 3 and 9 with zinc and acetic acid the substrates were recovered.The oxidation of 1 with silver nitrate in ethanol gave purple needles as described by Smith et al. 9 However, these needles do not have the structure 7 which was proposed by Smith but could be shown to have the o-quinoid structure 4. The latter is supported by data gained from 2D-NOESY spectra. While the 1 H NMR spectra shows only a very weak coupling of the H-4a protons with the H-3 protons the 2D-NOESY spectra shows a clear cross peak of the H-3 and the H-4a signals which should be possible for 4, but would not be expected for 7. Further s...

Chiroptical Properties of Organic Radical Cations. The Electronic and Vibrational Circular Dichroism Spectra of α-Tocopherol Derivatives and Sterically Hindered Chiral Hydroquinone Ethers

“…We first chose tocopherol and the related chromanols as substrate donors for the SET oxidation, not only because this class of compounds is known to be biologically active and behave as a natural antioxidant, but also because the first and only chiral organic radical cation for which the CD spectrum was claimed to have been measured was prepared from vitamin E acetate . Tocopherols have attracted much attention, especially in the fields of peroxyl radical chemistry and of oxidations in vitro and in organic solvents . More recently, the EPR and ENDOR spectra of radical cations of vitamin E-related compounds measured in various solvents revealed that these radical cations are very short-lived and are spontaneously converted to the corresponding neutral radicals through the release of a proton .…”