STRUCTURE OF THE TOCOPHEROLS 805 



Karrer and Fritzsche^- proposed the designation "tocol" for the hypo- 

 thetical nucleus with the structure shown here (II). 



H Hz 



HOC- C CH^ 



^C^ A C-(CH2)3CH(CH2)3CH(CH,)3CHCH. 



X,/ \ / \ I I I 



C CH3 CH3 CH3 CH, 



n 



Since the tocopherols readily form esters^* as well as ethers, ^^ it is certain 

 that one of the oxygens is present as an hydroxyl. On the basis of change 

 of the spectral absorption on esterification, John and co-workers*^ "^^postu- 

 lated that the hydroxyl group possesses a phenolic character. 



One of the most important reactions which have indicated the nature of 

 the a-tocopherol molecule is that produced by pyrolysis. Under these con- 

 ditions durohydroquinone (III) is formed,^* whereas, when the heating is 

 combined with an hydriodic acid reduction, isopseudocumenol (IV) re- 

 sults.*^-** The aromatic nature of tocopherol is further indicated by the 



H H 



C C 



/ \ y- \ 



HOC GCH, HOC CCHj 



I 



H3CC. COH "' HjCC, CH 



c ^C 



H CHj 



m 31 



fact that it absorbs 4 molecules of hydrogen upon hydrogenation.*^ Three 

 of these are used to saturate the benzene ring, and the fourth to break the 

 oxygen bond in the chroman ring between positions 1 and 2. 



Femholz^'' was able to obtain the additional evidence necessary for com- 

 pleting the knowledge of the structure of a-tocopherol by separating and 

 identifying the oxidation products resulting from treatment with chromic 

 acid. The degradation products include acetone (V), dimethylmaleic an- 

 hydride (VI), diacetyl (VII), a C21 lactone (VIII), a Cis ketone (IX), and a 

 Ci6 acid (X). The probable source of these oxidation products, based upon 

 our known formula for tocopherol, is given in Figure 1. 



The structure of VIII was deduced from the fact that it lactonizes read- 

 ily, which characterizes it as a 7- or 5-lactone; moreover, since the hy- 

 droxyl group on the methyl ester of the acid could not be oxidized to a ke- 



»2 p. Karrer and H. Fritzsche, Helv. Chim. Acta, 21, 1234-1240 (1938). 

 " W. John, Z. physiol. Chem., 250, 11-24 (1937). 



8* W. John, E. Dietzel, and P. Gunther, Z. physiol. Chem., 252, 208-221 (1938). 

 ^ W. John, E. Dietzel, P. Gunther, and W. Emte, Naturwissenschaflen, 26, 366-367 

 (1938). 



8« F. Bergel, A. R. Todd, and T. S. Work, J. Chem. Soc., 1938, 253-258. 



