Ionones, isomerisation

It has been proved that whilst concentrated sulphuric acid at a low temperature caused isomerisation of pseudo-ionone, so that the resulting product consists chiefly of j8-ionone, the use of phosphoric, hydrochloric, and hydrobromic acids at low temperatures yields chiefly -ionone. 

Mestres et al. [40] published a regioselective addition of a lithium trienediolate (generated from hexa-2,4-dienoic acid or dihydropyran-2-one) to p-ionone. Dehydration of the hydroxyacid, afforded a mixture of 9E/Z, 13E/Z retinoic acids which, isomerised in the presence of I2, led to all E retinoic acid in 35% and 30% yield, starting from dienic acid and pyranone, respectively, Fig. (16). 

A short synthesis of retinal was described by Taylor et al. [42] based on the addition of a C]3 vinylalane to a methylpyrylium salt. The 13Z-retinal (48%) was isomerised to all E retinal by a previous procedure [43]. P-Ionone was first converted into the alkyne and then into the vinylalane, using the Negishi methodology [44], Addition of an excess of this alane to 4-methylpyrilium tetrafluoroborate [45] gave 13Z-retinal, being isomerized to the all E isomer (L in benzene/ether), Fig. (18). 

By the Darzens reaction. -ionone afforded a C14 aldehyde which as the diethyl acetal underwent addition to ethyl vinyl ether in the presence of boron trifluoride etherate to yield a Cl6 acetal. After hydrolysis, loss of ethanol and formation of the diethyl acetal as before, reaction under acidic condiions with ethyl propenyl ether gave the unsaturated Cl9 aldehyde after hydrolysis and removal of ethanol. Reaction of two moles with ethyne dimagnesiuro bromide produced the C40 chain and dehydration of the diol, selective catalytic hydrogenation followed by isomerisation completed a remarkable technical synthesis of i-carotene. Further variations have involved the use of two moles of the C14 aldehyde and a Cl2 divinyl ether. An independent approach (ref.29) has utilised vitamin A (32) converted to a phosphonium salt, thence to the corresponding phosphoran, autoxidation of which afforded s-carotene ( scheme 16). 

The lipidic vitamins (ref.84) include vitamin A (32), a substance intrinsic to the physiology of vision, vitamin E (83), a natural protective antioxidant, and vitamins K, (84) with Kj (85), antihemorrhagic compounds, each of which is derivable from an initial natural product intermediate. Although traditionally a -ionone obtained from citral (a major constituent of lemon grass oil) was used for the synthesis of vitamin A, a synthetic source has now replaced this in a process which also gives /g-carotene. In one method the Cl4 aldehyde in that process is reacted with a C6 eneyne component and selective hydrogenation followed by dehydration and isomerisation affords the final product (ref.85). 

The isomerisation of 15,15 -cis-/5-carotene to the all-trans isomer is catalysed by singlet oxygen. Under more vigorous conditions 5,6-oxides, 5,8-oxides, hydroxy-ketones, allenes, and acetylenes were claimed. Further oxidation broke up the carbon skeleton to give /5-ionone, dihydroactinidiolide (99), and... 

Starting from their experience in manufacturing /3-ionone, Hoffmann-La Roche initially favoured acetylene as the universal building block for further syntheses. The reaction of methyl vinyl ketone with lithium acetylide in ammonia gives a tertiary alcohol, which is isomerised with sulfuric acid into a mixture of the (Eland (Z)-isomers of 3-methylpent-2-en-4-ynol. The isomers can be separated by distillation. Whereas the main component, the (Z)-isomer, is used for the production of Vitamin A, the (E)-isomer finds application in carotenoid synthesis. 

Retinol and its derivatives isomerise to a mixture of products in which 13-ds- (5-17) and 9-ds-stereoisomers (5-18) dominate. These isomers of retinol generally have a less intense colour than ah-trans isomers. At the same time, and especially in acidic media, there is a shift of the double bonds towards the P-ionone ring with the formation of a positional isomer, retrovitamin A, also known as a-retinol (5-19). Retrovitamin A partially dehydrates to all-trans anhydroretinol (anhydrovitamin A, 5-20). 

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