Roche synthesis of vitamin

Carotenoid synthons from the Roche synthesis of vitamin A 

Cyclization of 2 in concentrated sulphuric acid [14-16] predominantly leads to p-ionone (17). The reaction proceeds rapidly even below room temperature and, to avoid secondary reactions, is carried out continuously. The precooled streams of sulphuric acid and the solution of 2 in petroleum ether or liquid CO2 are mixed in a reactor and then quenched with cold water. Small amounts of a-ionone (18) can be separated off by distillation during isolation of the product. In the cyclization step large amounts of approximately 40% aqueous sulphuric acid are produced. Treatment to deal with this is expensive but is essential for environmental reasons. Organic impurities are broken down to carbon dioxide in a cracking furnace with heavy oil burners. In the course of this process, sulphuric acid is thermally converted into sulphur dioxide, which is reoxidized in the contact plant. 

Allylic rearrangement of 22 with aqueous sulphuric acid gives the primary alcohol 19 2l mixture of ( /Zj-isomers which can be separated by distillation [10,18]. The (Zj-isomer, which is the major product, is used in the synthesis of vitamin A. The ( j-isomer has proved to be particularly useful as a synthon for carotenoids. 

Under the action of hydrochloric acid, two molecules of water are eliminated from 34 to form 15,15 -didehydro-p,p-carotene (35) this also provides a purification step because of the stability and excellent crystallization properties of 35. Partial hydrogenation of 35 yields (15Z)-p,P Carotene (15Z)-3 virtually quantitatively. The reaction is carried out at approximately 20°C under a slight superatmospheric pressure of hydrogen in a petroleum ether suspension. 

The commercial apo-(i-carotenoids 1 and 482 may also be prepared from the C 19-aldehyde 27. A particularly important intermediate in this synthesis is 15,15 -didehydro-12 -apo- 3-caroten-12 -al (36)[2 ]. As 1,6-branched polyene chains cannot be synthesized by the enol ether condensation, the Ce-acetal 37 is prepared for the chain lengthening from 27 to 36. 

---