716 



VII. VITAMINS A 



ionone and no aldehyde when this distillation was carried out, while Karrer 

 and Ruegger"'*' reported only ;S-ionone. The synthesis of this key intermedi- 

 ate by the modifications in method introduced by Krauze and Slobodin,^"^ 

 who obtained a 64% yield, could not be repeated by Milas and Edgerton,^"^ 

 who also obtained only jS-ionone. It is evident that until reproducible 

 methods have been developed for the synthesis of /3-ionylideneacetaldehyde 

 in the pure state, the Kuhn-Morris method will not offer a practical solution 

 for the synthesis of vitamin A. 



(S) Milas Syntheses 



Several different syntheses have recently been described by Milas"*^'"^'"^ 

 which involve the preparation of vitamin A ethers or vitamin A esters. Al- 

 though the products prepared by these reactions have the correct chemical 

 composition, a satisfactory absorption spectrum, and the typical reaction 

 with antimony trichloride, the order of potency obtained by bioassay was 

 only 50,000 to 100,000 U.S.P. units per gram. However, the reactions do 

 offer practicable methods for such syntheses, in spite of the low potency of 

 the product. The key substance Avhich is used as a starting material in 

 both tjTpes of sjiithesis is the aldehyde obtained on decarboxylation of 

 glycidic acid.^°* The ester of glycidic acid is formed when (8-ionone is con- 

 densed with ethyl chloroacetate at —30 to — 60°C. in anhydrous ether or 

 toluene, using alcohol-free sodium ethoxide or methoxide as a condensing 

 agent. After hydrolysis, the free acid so produced can be decarboxylated 

 by several methods, but the best results were obtained when it was dis- 

 tilled at reduced pressure in the presence of pyridine. Heilbron et a/.^"^ 

 proposed an alternate structure (IV) for the aldehyde formed on decar- 

 boxylation of glycidic acid, but Milas, Lee, et al}^^ believe that formula V is 

 the correct one, since geronic acid, rather than 3,3-dimethyloctan-2,7- 

 dione, originates on ozonolysis. 



""' S. Ishikawa and T. Matsuura, Sci. Repts. Tokyo Bunrika Daigaku, A3, No. 60' 

 173-179 (1937); Chem. Zentr., 1937, II, 3452-3453; Chem. Abst., 31, 7851 (1937). 

 Cited by I. M. Heilbron, et al, J. Chem. Soc, 1942, 727-733. 



204 1. M. Heilbron, A. W, Johnson, E. R. H. Jones, and A. Spinks, /. Chem. Soc, 1942, 

 727—733. 



205 N. A. Milas, S. W. Lee, E. Sakal, H. C. Wohlers, N. S. McDonald, F. X. Grossi, 

 and H. F. Wright, /. Am. Chem. Soc, 70, 1584-1591 (1948). 



