Direct synthesis of p-methyl benzaldehyde from acetaldehyde via an organic amine-catalyzed dehydrogenation mechanism

Summary p -Methyl benzaldehyde ( p -MBA) is a class of key chemical intermediates of pharmaceuticals. Conventional industrial processes for p -MBA production involve the consecutive photochlorination, amination, and acid hydrolysis of petroleum-derived p -xylene, while producing vast pollutants and waste water. Herein, we report a direct, green route for selective synthesis of p -MBA from acetaldehyde using a diphenyl prolinol trimethylsilyl ether catalyst. The optimized p -MBA selectivity is up to 90% at an acetaldehyde conversion as high as 99.8%. Intermediate structure and 18 O-isotope data revealed that the conversion of acetaldehyde to p -methylcyclohexadienal intermediates proceeds in an enamine-iminium intermediate mechanism. Then, controlled experiments and D-isotope results indicated that the dehydrogenation of p -methylcyclohexadienal to p -MBA and H 2 is catalyzed by the same amines through an iminium intermediate. This is an example that metal-free amines catalyze the dehydrogenation (releasing H 2 ), rather than using metals or stoichiometric oxidants.