PEP Review 99-13
α-Tocopherol (Vitamin E) Acetate Production From Citral Via Isophytol
Published: December 2002
Vitamin E activity is shown by a family of compounds that includes tocopherols and tocotrienols. Vitamin E can be extracted from natural oils (e.g. soybean oil), or can be synthesized. Humans and mammals are unable to synthesize Vitamin E. Clinical symptoms of Vitamin E deficiency include neuropathy, fetal death, and myopathy (muscle disease). Major uses include animal feeds (approx 75% of use), as a food supplement, as an antioxidant, and in pharmaceutical formulations. Major producers of Vitamin E include Roche, BASF and Rhone-Poulenc.
The compound exhibiting the highest Vitamin E activity is α-tocopherol, particularly the RRRoptical isomer. Vitamin E activity is measured in international units (IU); one IU is equivalent to 1 mg of racemic α-tocopherol. Synthetic Vitamin E is usually racemic α-tocopherol or its derivatives (such as α-tocopherol acetate). α-Tocopherol is produced by the condensation of isophytol, a C20 alcohol, with trimethylhydroquinone (TMHQ).
In this review, we describe the synthesis of isophytol from a citral starting material, and the subsequent condensation of isophytol with TMHQ to form α-tocopherol, which is then acetylated to form the more oxidation-stable α-tocopherol acetate. Costs are estimated for a 20,000 tonne/year plant. In SRI Consulting's analysis, despite the process having several complex reaction steps, raw material costs are approx. 70% of the production costs. Access to inexpensive raw material confers significant competitive advantage, therefore we would expect that Vitamin E plants back-integrated into feedstocks, or processes that can use less expensive feedstocks, would dominate in the market.
Patents used for design bases in this analysis are primarily drawn from BASF. BASF has recently commissioned a 20,000 tonne/year plant in Ludwigschafen, which reportedly will use a nearby 40,000 tonne/year citral plant for feedstock.