Scalable Reactor Design for Pharmaceuticals and Fine Chemicals Production. 2: Evaluation of Potential Scale-up Obstacles for Asymmetric Transfer Hydrogenation

This paper is a continuation of our previous work, which reviewed the main factors that inhibit fine chemical and pharmaceutical reactor scalability. For scalable reactor design, it is suggested to first identify potential scale-up obstacles and then use shortcut calculations for their evaluation. This approach is demonstrated in this paper for the asymmetric transfer hydrogenation of acetophenone to its chiral alcohols, in the presence of the homogeneous catalyst, (1 R,2 S-amino-indanol/pentamethylcyclopentadienylrhodium) with isopropanol as hydrogen donor. The investigation reveals that removal of the by-product acetone from the reaction system shortens the required reaction time to achieve high conversion and reduces enantioselectivity erosion. A simple search algorithm is presented which can be used in principle for liquid reactions systems, where stripping of a reaction product or by-product is beneficial. The algorithm identified that the most influential factors that accelerate acetone removal are ...