title: Synthesis and oxidation behavior of 2,4,5,7,8-pentamethyl-4H-1,3-benzodioxin-6-ol, a multifunctional oxatocopherol-type antioxidant.
abstract: 2,4,5,7,8-Pentamethyl-4H-1,3-benzodioxin-6-ol (PBD, 1) is a novel 3-oxa-tocopherol-type stabilizer, which is obtained as a mixture of two diastereomers by condensation of trimethylhydroquinone with acetaldehyde in an acid-catalyzed reaction. The oxidation behavior of 1 is governed by the amount of water available. In aqueous media, 1 is oxidized by one oxidation equivalent to 2,5-dihydroxy-3,4,6-trimethylacetophenone (3) via 2-(1-hydroxyethyl)-3,5,6-trimethylbenzo-1,4-quinone (2). The acid-catalyzed conversion of 2 into 3 proceeds in solution with first-order kinetics with regard to 2 but works also in solid phase. Oxidation in the presence of just 1 equiv of water produces acetophenone 3 as well, but according to a different mechanism involving o-quinone methide 5 and styrene derivative 6, from which finally acetaldehyde is released. A [1,5]-sigmatropic proton shift from the C-4a methyl group to the exocyclic methylene group in 5 causes formation of 6, as demonstrated by labeling experiments. In addition, the presence of both intermediates was proven by hetero-Diels-Alder trapping reactions. In the absence of water, oxidation of 1 produces chromenone 10 via the intermediates 5 and 6 and chromanone 9, and oxidation of 9 to 10 is preferred to oxidation of starting material 1. When the formation of an exocyclic methylene group at C-4 is impossible as a result of structural prerequisites, as in the diphenyl derivative 12, the initially generated o-quinone methide 5 cannot form 6 but undergoes dimerization to spiro-compounds. The transformation of p-quinone 2 into acetophenone 3 might contribute to the chemistry of tocopherols oxidized at C-4, i.e., 4-hydroxy-alpha-tocopherol and 4-oxo-alpha-tocopherol, which have been proposed as precursors of natural vitamin E metabolites.
authors.affiliation: Institute of Chemistry, Christian-Doppler Laboratory, University of Agricultural Sciences, Muthgasse 18, A-1190 Vienna, Austria. trosenau@edv2.boku.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenau
authors.forename: Antje
authors.initials: A
authors.lastname: Potthast
authors.forename: Thomas
authors.initials: T
authors.lastname: Elder
authors.forename: Thomas
authors.initials: T
authors.lastname: Lange
authors.forename: Herbert
authors.initials: H
authors.lastname: Sixta
authors.forename: Paul
authors.initials: P
authors.lastname: Kosma
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry; D004147:Dioxins / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D014867:Water / Q000737:chemistry; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
chemical_list: C467956:2,4,5,7,8-pentamethyl-4H-1,3-benzodioxin-6-ol; D000975:Antioxidants; D004147:Dioxins; D014867:Water; D024502:alpha-Tocopherol