SYNTHESIS OF THE TOCOPHEROI S 811 



of the tocopherols are obtained when esters such as monobenzoate are used 

 for the condensation instead of the free quinols.^^ 



A second synthesis which can be employed for the tocopherols but which 

 is more satisfactoiy for certain of their homologues invoh'es the Grignard 

 reaction on the dimethyoxyketone (XIX) derivative. For example, the 

 eth3i group can be inserted on the side chain and the open ring changed to 

 the chroman ring (XX) by the accompanying reaction.^^-^-^ 



CHj CH3 



CH,OC C CH, HOC C CHj 



I i| I C,H,MgBr ^ I ;| I 



H3CC. .C C=0 H^Ca C C-CH,CH, 



V ^0 ^CHj \^ V CHj 



CH, CH, CH, 



Synthesis of the Chroman Ring 



The side chain can be varied by employing the appropriate alkyl magne- 

 sium bromide for the Grignard reagent. 



A third partial synthesis suggested by John and SchmeiP'' involves the use 

 of 2-methyl-6-hydroxylchroman (XXI) as the starting material. The 

 open-chain hydroxyquinone (XXII) is produced; this is converted to the 

 corresponding ketone (XXIII) bj^ means of chromic acid. Treatment with 

 alkyl magnesium bromide causes a closing of the chroman ring with the in- 

 troduction of the appropriate alkyl group on position 2 (XXIV). 



CHj . CH3 



/\ /\! /\ /\' 



HOC C CHz 0=C C CHj 



I ;| I CHXOGAg I I I CrO, 



HjCC, C CH HXC,. C, HOCH 



VV\h. V\ \h. 



CH, CH, 



CHj CH3 



0=C C CH, ., Q hoc' C CHz 



I I I ALKYL MgBr I ji I ^ 



H3CC C C=G H3CC. C^ C-.LKVL 



C ^0 CH, C CH, 



CH, CH, 



Sjnthesis of Tocopherol Homologues by the Introduction of a Second Alkyl Group 

 into the Chroman Ring at Position 2 



9' .\. Jacob, M. Steiger, and A. R. Todd, ./. Soc. Chem. Ind., 57, 1188 (1938). 

 »' W. Jolui and P. Giinther, Ber., 72, 1649-1653 (1939). 



^ L. I. Smith, H. E. Ungnade, J. W. Opie, W. W. Prichard, R. B. Carlin, and E. W. 

 Kaiser, J. Org. Chem., 4, 323-333 (1939). 



9« W. John and M. Schmeil, Ber., 72, 1653-1656 (1939). 



