MRT One Step Retinol Synthesis

By: Matthias Junkers, Aldrich ChemFiles 2009, 9.4, 10.

Aldrich ChemFiles 2009, 9.4, 10.

Benefit from MRT & Flow Chemistry: 70% improvement in yield by protecting the extremely sensitive product.

Retinol (Sigma 95144 ) was the first product that was produced on industrial scale with Microreactor Technology at the Swiss Sigma- Aldrich facility in Buchs. The batch synthesis procedure that was used before the transfer into a flow chemistry process was unreliable and low yielding. The underlying chemical conversion - a simple basic ester hydrolysis - is not the cause of problems in this case (Scheme 2). The ester is cleaved quantitatively, but this process takes some time until it is completely finished. Portions of cleaved product that are formed right at the beginning of the process need to stay in the batch reactor under reaction conditions until all the remaining ester is cleaved. During this time the majority of the highly sensitive product degrades. Another observation was a serious unreliability of the batch process. Due to small and uncontrollable contributing factors, the yield of the reaction varied tremendously. By transferring the batch synthesis routine into a flow chemistry process in a microreactor the yield of the reaction was improved by 70%, now giving a constant output of 70% product each time the synthesis is performed. This improvement is a direct result of the flow process. In the continuous flow, every portion of product is streamed out of the reaction zone instantly after it has formed. The product outlet can lead directly into a protected storage vessel where the sensitive product is protected from degradation. The flow process facilitates quantitative conversion where as any yield lost is during work-up. It should be highlighted that the savings achieved with this single new synthesis procedure have already justified all investments into microreactor technology at Sigma-Aldrich.

Scheme 2: Retinol synthesis (95144)

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