(341d) Horizontal Reactive Distillation Concepts and Their Application for Continuous Multicomponent Chiral Resolution

Frank, T. C., The Dow Chemical Company
Au-Yeung, P. H., The Dow Chemical Company
Resnick, S. M., The Dow Chemical Company
Witt, P. M., The Dow Chemical Company
Donate, F. A., The Dow Chemical Company
Robbins, L. A., The Dow Chemical Company

This presentation will describe a new reactive distillation technology involving a novel horizontal reactive distillation apparatus and a new overall process scheme.*  The new technology enables simultaneous production and isolation of up to four enantiomers via reversible enzymatic enantioselective acylation.  Reactive distillation is used to drive the reaction forward and auxiliary distillation columns are used to isolate the enantiomers.  In the (R)-enantioselective acylation reaction scheme, both the organic substrate and the acyl donor are chiral compounds (supplied as racemates), so the process can produce two (R)-enantiomer reaction products plus two unreacted (S)-enantiomers.  The effective overall reaction is:

 (R,S)-A + (R,S)-B    <---->   (R)-C + (R)-D + (S)-A + (S)-B

The results of kinetic studies, miniplant experiments, and process simulations will be presented for a model reaction system: lipase-catalyzed (R)-enantioselective transesterification of (R,S)-1-n-butoxy-2-propanol with (R,S)-1-methoxy-2-acetoxypropane to yield (R)-1-n-butoxy-2-acetoxypropane and (R)-1-methoxy-2-propanol plus unreacted (S)-1-n-butoxy-2-propanol and (S)-1-methoxy-2-acetoxypropane.  A horizontal compartmentalized reactive distillation vessel is specified instead of a conventional reactive distillation column to provide long liquid-phase residence time needed for good conversion (on the order of hours).  Low vapor-traffic pressure drop within the headspace of the vessel allows operation under vacuum at reduced temperatures (about 5 mm Hg and 25 °C) for good enzyme stability and enantioselectivity.  The technology has potential to enable a number of enzymatic equilibrium-limited enantioselective reactions including acylation, transamidation, and transamination – as a means to producing a variety of small molecule chiral compounds including hydroxy compounds, esters, amines, and amides.  In principle, these compounds may be used as chiral synthons (synthetic building blocks) in the asymmetric synthesis of biologically-active products such as pharmaceuticals, agricultural chemicals, and flavor and aroma chemicals.  More broadly, this new approach to conducting reactive distillation may be useful for any system requiring long liquid-phase residence time or low vapor-traffic pressure drop.

* Additional background is available in an article accepted for publication in AIChE Journal (2013). DOI: 10.1002/aic.14138.  Sol Resnick is now with Calysta Energy, Menlo Park, California, U.S.A.


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