42 VITAMINS A AND CAROTENES 



of lemon grass oil, acetone, and formaldehyde. Citral is first condensed by 

 an old and well-known process with acetone to form pseudoionone which 

 is cyclized, in the presence of mineral acids, to /3-ionone which has been an 

 article of commerce for many decades. /3-Ionone is then converted via the 

 Darzens reaction (p. 35) to give an over 80 % yield of Cu-aldehyde. To 

 prepare the other key intermediate, LXVI, acetone is first condensed with 

 formaldehyde in weak basic solution, and the product formed is dehy- 

 drated to give methyl vinyl ketone. This ketone has also been produced 

 industrially by the alcoholysis of vinyl acetylene. Methyl vinyl ketone is 

 then allowed to react with lithium acetylide in liquid ammonia under a 

 slightly increased pressure of acetylene to give the acetylenic carbinol LXIX 

 in good yields. The hazardous nature of acetylene under pressure requires 

 concave construction of the equipment to resist blasts in the event of an 

 explosion. The acetylenic carbinol is then allowed to undergo an anionic 

 rearrangement, in the presence of dilute mineral acids, to give the acetyl- 

 enic carbinol LXVI. When this carbinol is allowed to react via the Grignard 

 reaction with Ci4-aldehyde, the solid C2o-acetylenic glycol LXVII (m.p, 

 59°) is produced in yields of 90 % or over. This glycol is selectively hydro- 

 genated using the poisoned palladium catalyst mentioned elsewhere to give 

 almost quantitative yields of the olefinic glycol which is acetylated at 0° 

 with one equivalent of acetic anhydride in the presence of pyridine to give 

 the C2c-glycol monoacetate LXVIII (m.p. 74°). Several methods have been 

 employed to carry out the final dehydration step. In the original announce- 

 ment^*"* iodine was used to carry out the dehydration of the C2o-glycol mono- 

 acetate to give vitamin A acetate, but later^*^ phosphorus oxychloride in 

 pyridine was found to give better results. Yields up to 45 % were reported 

 in this step. The yields were increased by recovering the unconverted 

 C2o-glycol acetate and retreating it in the same manner. To protect the 

 vitamin A acetate during its formation it is necessary to use small amounts 

 of a-tocopherol together with the C2o-glycol monoacetate. With pyridine 

 hydrobromide or pyridine p-toluenesulfonate in pyridine or in glacial acetic 

 acid, yields as high as 70 % of the vitamin A acetate have been reported. ^*^ 

 The over-all yields of vitamin A from ^S-ionone are about 25 to 45 %. 



The synthetic vitamin A is marketed either as the acetate or the palmi- 

 tate. Pfizer has developed a crystalline preparation of either the acetate or 

 the palmitate coated with gelpiin. This preparation is tasteless and odorless 

 and maintains its potency in air at 45° for over 1000 hours. '^^ It is also 

 claimed that this preparation is more easily utilized b}' human beings than 

 other preparations, and when fed to chickens or hogs in conjunction with 

 terramycin and penicillin it is absorbed more eflBciently than when fed 

 alone. '^^ The industrial preparations of synthetic vitamin A usually range 



'60 II. G. Luther, Ind. Eng. News 30, 539 (1952). 



