Continuous Nanofiltration and Recycle of an Asymmetric Ketone Hydrogenation Catalyst

The continuous nanofiltration and recycle of a ruthenium diphosphine/diamine catalyst for the asymmetric hydrogenation of α-tetralone is demonstrated in a small scale flow system. Batch experiments show that the catalyst can be recycled under hydrogen pressure. Subsequent transient packed bed experiments serve to characterize the reaction and inform the design of the recycle experiments. The total internal volume of the resulting system is ∼50 mL, making this pilot useful for testing catalyst recyclability via nanofiltration during the early stages of process development. The high-pressure catalyst recycle system is run with an automatic control system to respond to membrane flux decline during the course of operation and enable long duration runs. In 24 h, we achieved a turnover number approaching 5000 for ruthenium diphosphine/diamine catalyst used in the asymmetric hydrogenation of α-tetralone, demonstrating significant reuse of the catalyst since the substrate-to-catalyst ratio in the reactor approaches 250. During the 24 h period, the equivalent of 60 batch separation/recycle experiments is automatically performed. Ruthenium concentration in the product stream remains below 200 ppb. A slow decline in enantiomeric selectivity from 96% to 93% is observed during the run.