Reaction of trimethyl‐hydroquinone with methyl vinyl ketone in acidic methanol gave rac.‐2‐methoxy‐2,5,7,8‐tetramethyl‐chroman‐6‐ol (8). This acetal was converted in four steps to rac.‐(6‐hydroxy‐2,5,7,8‐tetramethyl‐chroman‐2‐yl)acetic acid (13). Acid 13 was readily resolved with α‐methyl‐benzylamine to give the (S)‐enantiomer 14. Treatment of the unwanted (2 R)‐isomer with acid regenerated 13, thus leading to an efficient use of this compound. Employing a side chain derived from phytol, 14 was converted to (2R, 4′R, 8′R)‐α‐tocopherol (1d, ‘natural’ vitamin E). A reaction sequence from 14 involving two highly stereoselective Claisen rearrangements has provided the first total synthesis of (2R,'E,7′E)‐α‐tocotrienol (2d).

6‐Hydroxychroman‐2‐carboxylic acids (I) have been found to be effective antioxidants in animal fats, vegetable oils, and emulsion systems. Two new syntheses of these compounds have been developed. Structure‐activity correlations for I with various substitutents at C2, C5, C7, and C8 in various test systems have been obtained. In addition, the homologous chroman acetic acids, which are also antioxidants, and a number of other derived compounds have been synthesized. The most effective antioxidant in this series is the tetramethyl compound I (R2=R5=R7=R8=CH3). This compound has activity which compares well with the better commercial antioxidants.

Abstract6‐Hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid in thin layer tests in vegetable oils and animal fats has two‐four times the antioxidant activity of butylated hydroxytoluene and butylated hydroxyanisole and is more active than propyl gallate, nordihydroquaiaretic acid, ascorbyl palmitate, and α‐ and γ‐tocopherols. It is also more active than tertiary butylhydroquinone in chicken and pork fats and corn, peanut, sunflower, and safflower oils in thin layer tests. Tertiary butylhydroquinone is slightly more active in corn, soybean, cottonseed, and peanut oils in the active oxygen method, probably due to decomposition of the chroman at 98 C. This decomposition is inhibited by ascorbic acid. The chroman is synergized by ascorbyl palmitate‐thiodipropionate and ascorbic acids. Active oxygen method values of 190 hr are obtained in combination with the latter. A spectrofluorometric assay for 6‐hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid has been developed. The compound is 95–100% stable for 2 months at room temperature and 45 C, and a low level of toxicity is found. The copper and iron breakdown products of the chroman have been determined. A possible relationship between these products, protection of the chroman by ascorbic acid and ethylene diaminetetraacetic acid, and a mechanism of action is presented.

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