Vitamin BASF route

Two key intermediates in the production of vitamin A are citral and the so-called C5 aldehyde. In the modem routes to these intermediates, developed by BASF and Hoffmann-La Roche, catalytic technologies are used (see Fig. 2.29 and 2.30). Thus, in the synthesis of citral, the key intermediate is 2-methyl-l-butene-4-ol, formed by acid-catalyzed condensation of isobutene with formaldehyde. Air oxidation of this alcohol over a silver catalyst at 500°C (the same catalyst as is used for the oxidation of methanol to formaldehyde) affords the corresponding aldehyde. Isomerization of 2-methyl-l-butene-4-ol over a palladium-on-charcoal catalyst affords 2-methyl-2-butene-4-ol. The latter is then reacted with the aldehyde from the oxidation step to form an enol ether. Thermal Claisen rearrangement of the enol ether gives citral (see Fig. 2.29). 

The most significant application of the C5-unit 73 (Scheme 7) is in the BASF process for the production of vitamin A [22]. Industrial syntheses of 73 [23] proceed via but-l-ene-3,4-diol diacetate (74) by acetylation and copper-catalysed rearrangement of 75. A new route is emerging via the vinyloxirane 76, which has recently become accessible via silver-catalysed gas-phase oxidation [24]. The diacetate 74 is formed as a byproduct in the oxidative acetoxylation of butadiene (14), which is performed on an industrial scale to produce butane-1,4-diol (77) [25]. 

Vitamin A acetate is an important nutrient additive and its synthesis is now carried out on a technical scale. The three major routes of preparation used today were developed by HofFmann-La Roche, Rhone Poulenc, and BASF [43]. For the work presented here, we were particularly concerned with the Wittig-Horner reaction between a C15 and a C5 precursor as it occurs in the BASF process [44,45]. This study describes the investigation of important process parameters for a synthesis that involves a thermally unstable ylide intermediate. In the current experiments, this intermediate is generated in situ and immediately converted in order to simulate the conditions in the technical process. However, while in a conventional process the reaction hardly can be performed under isothermal conditions due to the exothermic heat of reaction of about 250kJ/mol, the microreactor setup offers the opportunity to study relevant process parameters such as temperature, concentrations of starting materials, and mixing protocol of the components. 

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