SYNTHESIS OF VITAMTN A AND RELATED COMPOUNDS 



721 



(8) Synthesis of Vitamin A Acid by the Milas Method 



In addition to the methods for the synthesis of vitamin A ah'eady men- 

 tioned which involve the preparation of the acid,^®^-^^^""' Milas ^^^ and 

 Milas, Edgerton et al."^^^ reported the synthesis of vitamin A acid from (3- 

 ionyhdene acid chloride (XXVITT) as the starting material. 



R- ch:ch-c :CH-C-CI 



CHj(CO0C2H5)j 



MglOCjH^lj or 

 LifOCjH.) 



COOH 

 CH, I CH, 

 R- CH:CH-C: CH -C- C-C: CH -COOH — 



XXXI I 



CjH50H 



xxx: 



COOC.H. 



CHj CH, Silver soil 



R-CH:CH-C:CH-C-CH2-C: CH-COOH — °^y ^'" • 



CH, CH, 



R- CH: CH> C:CH-C- CHj-C: CH-C-OC2H5 



xxxnr 



(CHjjjCHOH 

 Al ( iso-ptopoiil)«) J 



CH, 



HjC CHj 



\/ 



/\ hhIhhhIh /,0 

 HjC c • C : c • c: c • c : C • c : c • C-OC^H, 



I li 



HjC C 



\ / \ 



C CH, 



H? 



(COOHij 

 ■ Antly lOUS 



R- CH:CH- C: CH- CH-CH.-C:CH-C- OC,H, 



Synthesis of Vitamin A Acid 



(9) Synthesis of Vitamin A Acid Ethyl Ester by the Method of Schwarzkopf 



and Collaborators 



Another approach to the synthesis of vitamin A has been suggested by 

 Schwarzkopf et al.,^^^ which employs the Cis ketone (XVII) as the starting 

 material. This ketone is condensed with ethyl bromoacetate to give a C20 

 hydroxy ester (XXXVI) . When the hydroxy ester (XXXVI) is dehydrated 

 under rigorous conditions, it is isomerized to vitamin A acid ethyl ester 

 (XXXVII). 



"2 N. A. Milas, R. O. Edgerton, E. Sakal, and J. K. Gladding, Unpublished results, 

 1947. Cited by N. A. Milas, Vitamins and Hormones, 5, 30 (1947). 



"« O. Schwarzkopf, H. J. Cahnmnn, A. D. Lewis, J. Swiduisky, and H. M. Wuest. 

 Presented before the 115th Meeting of the American Chemical Society in San Francisco, 

 March 27- Apr. 1, 1949, No. 20, pp. lie, 12c. 



