Citral BASF synthesis

Constraints on commercial-scale chemistry can lead to excellence and elegance, as demonstrated by the BASF synthesis of citral. 

Citral, B, is a component of lemon grass and as such used in perfumery (lemon and verbena scents). It is also an important intermediate in the BASF synthesis of vitamin A (Section 14-7, Real Life 18-2). The last step in the synthesis of citral requires simply heating the enol ether A. How do you get from A to B ... 

Citral is a key intermediate in the synthesis of vitamin A, and in Chapter 31 you had a go at designing a synthesis of it. BASF manufacture citral by a remarkable process that involves two successive [3,3] -sigmatropic rearrangements, Claisen followed by a Cope. 

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). 

Another conspicuous innovation is the ultrafast oxidation reactor developed by BASF for the oxidation of isoprenol (2 methyl-butl-ene-4 ol.) to isoprenal for the synthesis of citral ... 

Another process patented by BASF is shown in Figure 4.10. This process uses only isobutylene, formaldehyde and air as reagents the only by-product is two molar equivalents of water per mole of product and it gives citral in just four steps, two of which run in parallel. Such elegance not only has intellectual appeal but also is an excellent example of how industrial chemical synthesis should be carried out, producing valuable products efficiently, at low cost and with minimal environmental impact. 

For both, the perfumery market and also as a building block in carotenoid synthesis, BASF currently prepares citral, starting from isobutene and formaldehyde. The only side-product is water (cf. Section 3.2). 

BASF carries out a synthesis of citral which requires, apart from isobutene and formaldehyde, only air for the oxidation. The only by-product is water. With the domino Claisen-Cope rearrangement one can obtain a value-added product in only a single step. 

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