2,3,6-Trimethylhydroquinone TMHQ

Figure 6.18 Schematical Synthesis of (AII-rac)-a-Tocopherol (Vitamin E) via Two-Step Friedel-Crafts Alkylation-Cyclization of 2,3,6-Trimethylhydroquinone (TMHQ) with Isophytol (IP).

The industrial synthesis of this valuable compound is based on the condensation of 2,3,6-trimethylhydroquinone (TMHQ) with isophytol (IP), which proceeds through consecutive Friedel-Crafts alkylation-cyclization (Figure 6.18) steps [91] in the presence of ZnClj/HCl as catalyst [92],... 

The synthesis of Vitamin E, that is, a-tocopherol (5,7,8-trimethyltocol) in the past has been accomplished primarily by reacting trimethylhydroquinone (TMHQ) with isophytol (3,7,ll,15-tetramethylhexadec-l-en-3-ol) or phytol (3,7,ll,15-tetramethylhexadec-2-en-l-ol) in a condensation reaction. The reaction is well known and has been practiced for many years (Stalla-Bourdillon, Ind. Chim. Belg., 35, 13 (1970) "The Vitamins" Vol. 5, pages 168-223, Academic Press, New York, 1967). 

Vitamin E is the most important lipid-soluble antioxidant in biological systems. (all-rac)-a-Tocopherol (synthetic vitamin E, 1) is the economically most important product industrially prepared on a multi-10 OOOt/year scale and mainly used in animal nutrition [50]. In the large-scale syntheses of 1, 2,3>5-trimethylhydroquinone (6) is used as the aromatic key building block, which is condensed with isophytol (2) to yield 1 by all producers worldwide (Scheme 7.1). Trimethylhydroquinone (TMHQ, 6), in turn, is obtained from trimethylquinone (TMQ, 5) by reduction procedures, in particular catalytic hydrogenation. Besides other possibilities to access TMHQ (6), this route is generally preferred, and efficient oxidation processes for the production of quinone 5 from alkylated phenols are, therefore, of high interest [51]. 

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