1. Field of the Invention
The present invention relates to a novel method for preparing di-.alpha.-tocopherol comprising condensing trimethylhydroquinone with phytyl halide in a chlorinated lower aliphatic hydrocarbon solvent in the presence of metallic tin and a Friedel-Crafts catalyst.
2. Description of Prior Art
Typically, dl-.alpha.-tocopherol is prepared by condensing trimethyl hydroquinone [hereunder referred to as "TMHQ"] with isophytol, phytol or phytyl halide in the presence of a Friedel-Crafts catalyst. Such condensation, however, entails concurrent side reactions, such as oxidation, which tends to give rise to formation of colored impurities, and generally results in production of colored dl-.alpha.-tocopherol. It is therefore necessary to separate and remove such colored impurities in order to utilize the dl-.alpha.-tocopherol practically, e.g., in the pharmaceutical field. However, such colored impurities formed have physical properties similar to those of dl-.alpha.-tocopherol, wherefore complete separation and removal thereof by high vacuum distillation or molecular distillation is rendered difficult. Furthermore, such purifications require highly sophisticated refining means. It is, therefore, of the utmost importance in the manufacture of dl-.alpha.-tocopherol on an industrial scale to establish reaction conditions which minimize the formation of such colored impurities during the condensation reaction.
With a view towards the immediately aforesaid, various preparations and syntheses have been studied to provide dl-.alpha.-tocopherol with less coloring. For example, proposed have been:
[i] Condensation of TMHQ and phytyl halide in a petroleum hydrocarbon system, such as ligroin, petroleum benzine, hexane, etc., in the presence of metallic zinc [cf. Japanese Patent Publication No. 31662/70; the Comparative Example 1 which follows]; PA1 [ii] Condensation of TMHQ and phytol, isophytol or phytyl halide in an organic solvent such as ethyl acetate, isopropyl ether, etc., in the presence of an acidic catalyst such as zinc chloride, aluminum chloride, boron trifluoride etherate, sulfuric acid, formic acid, stannous chloride, with addition of metal powder selected from among aluminum, iron or tin [cf. Japanese Patent Publication No. 27187/74; the comparative Example 2 which follows]; PA1 [iii] Condensation of TMHQ and phytyl halide in a non-polar organic solvent such as petroleum ether, hexane, petroleum benzine, ligroin, benzene, toluene, ether, etc., in the presence of a Friedel-Crafts catalyst and metallic tin [cf. Japanese published Patent Application No. 91075/73; the Comparative Example 3 which follows].
Above noted methods [i], [ii] and [iii] and modifications of the method [iii] [cf. Comparative Examples 4 and 5 which follow], however, are not appropriate or suitable for manufacturing dl-.alpha.-tocopherol on an industrial scale, either because the product obtained thereby is still highly colored for practical use in the pharmaceutical field, or because the yield is unsatisfactorily low.
USPTO Backgrounds
USPTO Backgrounds