Low-Loading Pd/C-Catalyzed Continuous-Flow Chemoselective Hydrogenation of Cinnamaldehyde Derivatives for Scalable Production

A continuous-flow protocol for the chemoselective partial hydrogenation of α,β-unsaturated carbonyl compounds has been developed using a commercially available 1% Pd/C catalyst diluted with Celite. Cinnamaldehyde was selectively converted to hydrocinnamaldehyde in toluene at 100 °C with a liquid flow rate of 1 mL min–1 and a hydrogen flow rate of 10 mL min–1, affording yields exceeding 90% while effectively suppressing the formation of cinnamyl and hydrocinnamyl alcohols. The Pd/C packed-bed cartridge operated continuously for 168 h without any detectable loss of catalytic activity, corresponding to a turnover number of 50,300, a turnover frequency of 299 h–1, and a space-time yield of 1.64 mol Lcat–1 h–1. Substrate scope investigations revealed that methoxy-substituted cinnamaldehydes, ferulic acid, 4-phenyl-3-buten-2-one, and chalcone underwent analogous transformations, delivering the corresponding partially hydrogenated products in isolated yields ranging from 83% to quantitative. This methodology employs low catalyst loading, moderate reaction temperatures, and atmospheric hydrogen pressure, offering a cost-effective, scalable, and inherently safer alternative to conventional high-pressure batch processes for the production of fragrance and pharmaceutical intermediates. Notably, no detectable Pd leaching was observed in the product stream.