SYNTHESIS OF VITAMIN A AND RELATED COMPOUNDS 



723 



several procedures. The ethyl, isopropyl, or ter^-butyl ethers can be pro- 

 duced by using the corresponding glycol ethers. 



HjC CH3 



p C H 3 C H 3 



/ \ H H I H H H I 

 _ HjC C-C:C-C-C-C:C-C- CH,'CH2 0CH3_ 



H 



HjC C 



\ / \ 

 C OH. 



Hz 



(1) Pyridine HBr -i- Pyridine 



(2) Alcoholic KOH 



OH 



I 

 OH 



(1) PBr^ or SOCIp< Pyridine 



(2) Alcoholic KOH or 

 NoNHj (in liquid NH3) 



CH, 



CH. 



HjC CH, 



\ / 

 C 



/\ hhIhhhIh 



HjC C • C : C- C: C- C: C- C: C • CHjOCHj 



HjC C 



\ / \ 

 C CHj 



Hj 



Milas Synthesis of Vitamin A Methyl Ether 



b. Milas Synthesis from 5-Dehydrovitamin A Methyl Ether. Another 



synthesis of the vitamin A methyl etlier, by Milas el al.,*^'""^ is by the selec- 

 tive hydrogenation of 5-dehydrovitamin A methyl ether (XLI). The 

 latter compound was prepared by the dehydration of the glycol with 

 catalytic quantities of p-toluenesiilfonic acid. 



HsC CHi 



\/ CH 



/ \ H H I H H H I 

 HzC C • C : C • C • C • C : C • C • CH^- CHsOCHj _t 



I II H 1.. L. sulfonic ocid 



HzC C 



\ / \ 

 C CHj 



Hj 



OH 

 XL 



CHj 



OH 



HjC CHj 



C CHj CHj 



/ \ H H I H I H 



'— H2C C-C:C-C:C'C:C-C:C' CHjOCHj 



HzC C 



\ / \ 

 C CH3 



Hi 



xn 



CoCO, 

 HjC CHj 



C C H 3 C H 3 



/\ hhIhhhIh 

 HjC c • c :c- c; c • c: c- c : c • CH 0CH3 



I II 



H?C C 



\ / \ 

 C CHs 



Second Milas Synthesis of Vitamin A Methyl Ether 



The corresponding 5-dehydro\'itamin A ethyl ether was also readily 

 prepared by dehydration of the glycol ethyl ether or of the carbinol in the 

 presence of p-toluenesulfonic acid. However, the preparation of the vita- 

 min A eth}'! ether could not be brought about by selective dehydrogenation. 



