56 Effect of Alcohols on the Oxidation of the Vitamin E Model Compound, 2,2,5,7,8-Pentamethyl-6-chromanol C. Suarna and P.T. Southwell-Keely* Department of Organic Chemistry, University of New South Wales, P.O. Box I, Kensington, NSW 2033, Australia The vitamin E model compound, 2,2,5,7,8-pentamethyl-6- chromanol, has been oxidized with t-butyl hydroperox- ide in chloroform in order to simulate in vivo oxidations due to lipid hydroperoxides. In the presence of a variety of alcohols, ranging from methanol to cholesterol the cor- responding 5-alkoxymethyl-2,2,7,8-tetramethylJ'~-chroma- nols were formed in fair to good yield and were the major products in each reaction. Lipids 24, 56-60 (1989). Recent work has shown that, when a-tocopherol (la) (Scheme 1) and its model compound, 2,2,5,7,8-penta- methyl-6-chromanol (lb) are oxidized by t-butyl hydroper- oxide in chloroform to which a small amount of ethanol has been added, the major products are 5-ethoxymethyl- 7,8-dimethyltocol (7a; R' = CH3-CH2-) and 5-ethoxy- methyt-2,2,7,8-tetramethyl-6-chromanol (7b; R' = CHa-CH2-), respectively (1). It appears that these prod- ucts are formed by the oxidation of la and lb to a quinone methide intermediate which then adds ethanol. The aim of the present work was to determine whether this reac- tion was general for all alcohols. MATERIALS AND METHODS IR spectra were determined on a Perkin Elmer 580B spec- trometer, UV spectra on a Perkin Elmer 124 double beam spectrophotometer, 1H NMR spectra on a Bruker AM 500 spectrometer and electron impact mass spectra on an A.E.I MS 12 mass spectrometer. NMR spectra were taken in CDC13 and are reported in parts per million downfield from tetramethylsilane as internal standard. Chloroform was purified by washing with 18 M sulfuric acid, distilled water until the washings were neutral, dry- ing (Na2SO4) and distilling immediately before use. Phytol (Sigma Chemical Co., St. Louis, MO) was used without purification. t-Butyl hydroperoxide (70%, EGA CHEMIE, Stein- helm, West Germany) was purified by the sodium salt method (2). Purity (iodometrically) was 95%. Cholesterol (E. Merck, Darmstadt, West Germany) was purified by a bromination-debromination procedure (3). Compound lb together with its spirodimer (5b) and spirotrimer (6b) and 2-(3-hydroxy-3-methylbutyl)-3,5,6- trimethyl-l,4-benzoquinone (9b) were prepared as refer- ence compounds by known methods (4-7). Oxidation of lb by t-butyl hydroperoxide. To lb (220 mg, 1.0 mmol) in chloroform (24 ml, containing the respective alcohol (6.0 g) (Table 1) was added t-butyl hydroperoxide (91 mg, 1.0 mmol) and the solution refluxed for 3 hr. The solution was then washed with 5% ferrous sulfate solution (2 • 30 ml), distilled water (3 • 30 ml), dried (Na2SO4) and the solvent removed in vacuo. The residue was chromatographed on thin layers of Silica Gel GF254 (solvent: light petroleum (bp 60-80~ 0 R -H. > R HO .0 lo 20 b b c HOH 80 b / 3a b > O~ R 90 b R R'OH > R o H 0 J /,a b 7" R O~R 0 R O 0 O0 o. A R R 5a b a.c R = C16H33 b.d R = CH 3 SCHEME 1 *To whom correspondence should be addressed. LIPIDS, Vol. 24, No. 1 (1989)