SYNTHESIS OF THE TOCOPHEROLS 809 



(4) d-Tocopherol 



5-TocopheroI or 8-methyltocol, has been found t(j have an empirical 

 formula of C27H4602.^* The structural formula (XVII) has been proved by 

 synthesis. 



HOC C CHj ^^ ^^ ^^ 



1 il I I r I 



HC. C C— CHjCHjCHjCHCHjCH^CHjCHCHjCH^CH^CHCH, 



C \h^ 



CHj 



SZtt 



Because of its composition, it was suspected that 5-tocopherol was a non- 

 methylated or monomethyl chroman. The fact that its elimination 

 maximum (170°C.), when it is subjected to molecular distillation with a con- 

 stant yield oil, is 10° lower than that of 7-tocopherol also supports this con- 

 clusion. 



When 5-tocopherol was subjected to pyrolysis by the method of Fern- 

 holz,^" it was found that the end product was 2,6-dimethylhydroquinone.^^ 

 This was proved on the basis of melting point (found 144-147. 5°C., theoiy 

 147-149°C.) and of conversion to a diacetate which had a melting point 

 of 89-91°C. (theory 91-92°C.). Mixed melting points of the two hydro- 

 quinones and diacetates (prepared from 5-tocopherol and synthetically) 

 showed no depression. The infrared spectrum was also identical for the 

 two hydroquinones. On the other hand, the pyrolysis product was shown 

 not to be toluhydroquinone (m.p., 124-125°C.), which is monomethyl- 

 hydroquinone. This was proved on the basis of melting point and mixed 

 melting point. The latter hydroquinone would be expected if 5-tocopherol 

 were non-methylated on the aromatic ring. The melting points of the 

 hj^droquinones which would be formed from 5-methyl-, 7-methyl-, or 5,7- 

 dimethyltocol were so much higher than that found that they could be ex- 

 cluded from consideration. Stern et al.^^ completed their proof of the 

 structure of the natural 5-tocopherol by demonstrating its identity with a 

 product synthesized from toluhydroquinone monobenzoate and natural 

 phytol by the method of Jacob et al.^^ and of Karrer and Fritzsche.^^ 



4. Synthesis of the Tocopherols 



The most practical synthesis, which serves equally well for a-, jS-, 7-, and 

 6-tocopherol, has been discovered by Karrer. and his associates. ^^~^^ This 

 invoh'es the condensation of the appropriate alkylated hydroquinone with 

 phytyl halide in the presence of a catalyst. In one reaction, the desired 

 tocopherol is formed, usually in excellent yield. Thus, when trimethylhy- 



«^ A. Jacob, F. K. Sutcliffe, and A. R. Todd, J. Chem. Soc, 1940, 327-332. 



