SYNTHESIS OF VITAMIN A AN"D lliaVTED COMPOUNDS 713 



ing to the Hickman ""•i'-'^ procedure. The fraction distiUing at 190-260°C. 

 was rich in kitol. This was stripped at 160°C., after a constant-yield oil 

 and residue oil had been added. The distilland was rich in kitol, and was 

 practically free from vitamin A. The unsaponifiable extract of the distil- 

 land was treated with succinic anhydride to form the acid succinate, which 

 was neutralized in 83% ethanol. The non-hydroxylic materials could be 

 separated by extraction with petroleum ether. On saponification, the kitol 

 was sufficiently pure to form a crystalline di-p-phenylazobenzoate ester. 

 Crystalline kitol was subsequently prepared by crystallization of the non- 

 saponifiable matter from the phenylazobenzoate with methyl alcohol. 

 The yield amounted to only 10% of the original amount present in the 

 whale-liver oil. 



A number of synthetic esters of kitol have been prepared. These in- 

 clude the di-p-phenylazobenzoate ester, which exists in two forms; the 

 lower one melts at 125-126°C., while the higher one melts at 149-150°C.i»^ 

 It is considered that these may be geometric isomers of the carbon-carbon 

 type, although the possibility that a nitrogen-nitrogen stereoisomerism 

 may be responsible is not excluded. A crystalline anthraquinone carboxyl- 

 ate ester melting at 195-197 °C. has also been prepared. It apparently 

 exists in a lower melting form as well, but this ester cannot be purified. 

 The dinitrophthalate ester was also prepared by Clough and associates, ^^'^ 

 but it could not be obtained in crystalline form. 



5. Synthesis of Vitamin A and Related Conapounds 



(1) Introduction 



Extensive investigations to develop practical methods for the synthesis of 

 vitamin A were pursued at an increased pace during World War II ; they 

 have now reached the point where vitamin A is being produced in con- 

 siderable amounts synthetically for commercial use ; facilities are at present 

 being developed which will render possible the further replacement of the 

 diminishing natural supply of vitamin A by the synthetic product. The 

 earlier methods of synthesis are reviewed by Bogert,^^^ Sobotka and 

 Bloch,^"^ and Heilbron, Jones, and Bacharach,^'^ while current procedures 

 are admirably treated in a more recent comprehensive article by Milas.^^ 

 The subject will be briefly reviewed here, but the reader is referred to 

 Milas^^ and to the original sources for a more complete treatise on the sub- 

 ject. 



After the elucidation of the structure of vitamin A by Karrer, Morf, and 

 Schopp^'''^^ in 1931, and its confirmation and extension by other workers 



192 ]\,i "p Hogcit, "Curoteiiuids. The Polyene Pigments of Plants and Animals," in 

 II. Gilmaii, Organic Chemistry, Vol. II, Wiley, New York, 1938, pp. 1138-1219. 

 1" H. Sobotka and E. Bloch, Chein. Revs., 34, 435-460 (1944). 



