Retinol preparation from retinal

The C2o + C2o = Qo route was also applied for the preparation of the (13Z)-isomer of P,P-carotene (3) (Scheme 2), which was first obtained in small amounts in 1966 [17]. As the carbonyl component, (13Z)-retinal (4) was employed this is readily available from (13Z)-retinol [6]. (13Z)-Retinal (4) was identified by m.p. [7], UVA is [7], H-NMR [8,9] and C-NMR [9]. Wittig reaction with the (all- )-retinyl phosphonium salt (3) [10] gave a mixture of (13Z)-3 and (13Z,15Z)-3 which were separated into the pure isomers by chromatography and crystallization. In this case also, the olefination reaction proved to be unselective. 

Dissolve methyl 4-oxoretinoate in methanol. Reduce with sodium borohy-dride as previously described for preparation of retinol from retinal. The... 

Chabardes developed a process for the preparation of vitamin A and its intermediates, from cyclogeranylsulfone and Cio aldehyde-acetals [30]. For example, chlorocitral reacted with ethylene glycol, HC(OMe)3 and pyridinium tosylate to provide the chloroacetal (40%), as a mixture of two isomers. Reaction of this allylchloride with A-methylmorpholine oxide (NMO) and Nal furnished the aldehyde, as a mixture of four isomers. These compounds underwent condensation with P-cyclogeranylsulfone. Further chlorination of the sulfone-alkoxide salts, led to a mixture of sulfone-chloride acetals and their products of hydrolysis in 45-50% yield. Double elimination of the chloride and the sulfone, followed by hydrolysis with pyridinium tosylate (PPTS) gave retinal, as a mixture of all E and 13Z isomers (78/22). The overall yield from the chloroacetal was 18%. In another one-pot example, retinal was obtained in 52% yield from the aldehyde, and was then isomerised and reduced to retinol (all E 95.5, 13Z 4, 9Z 0.5) Fig. (8). 

Several papers have described the synthesis of epoxyretinoids. The 5,6-epoxides of fmns-retinal (88) and its (9Z)-, (IIZ)-, and (13Z)-isomers were prepared by direct epoxidation of retinal with w-chloroperbenzoic acid. The 7,8-epoxides (89) of retinal, retinol, and retinoic acid and its methyl esters were synthesized from the jS-ionone epoxide (90). The exceedingly labile methyl 13,14-epoxy-13,14-dihydroretinoate (91) was made by addition of the epoxyaldehyde (92) to the phosphorane (93). Chromogen 574 , a product of the epoxidation of retinol first described in 1945, has now been identified as the... 

Retinol or its solutions do not keep well even when kept under an inert gas at low temperature. Commercial retinol often contains substantial amounts of impurities because of its instability. Retinal and retinyl acetate are commercially readily available and are quite stable when kept under an inert gas and at low temperatures If a pure standard of retinol is not available, it can be prepared easily from either retinal or retinyl acetate as follows. 

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