Abstract
A ligand-free, palladium-based heterogeneous nanocatalyst supported on TiO₂ was synthesised with the aid of
wet impregnation method and incorporated into an automated continuous flow system for the synthesis of
pharmaceutically relevant biaryls and stilbenes via Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions.
With the use of 21.2 mg of palladium acetate on 1 g of TiO₂, the catalyst was prepared and characterised, using
BET, FTIR, XRD, SEM, TEM, and EDX, which showed a high distribution and revealed the stability of the
palladium nanoparticles. Reactions were conducted using 1.0 mmol of substrate, 1.2 mmol of coupling partner,
2.0 mmol of base, and 200 mg of catalyst under a 35-min residence time. In the Mizoroki-Heck reaction, DMF
was used as the solvent, and an optimised temperature of 130 ◦C yielded up to 90 % conversion. In contrast,
studies on base and solvent effects indicated that triethylamine and potassium carbonate provided superior reaction
performance. Catalyst loading experiments demonstrated that the loading of 3.0 mol% of Pd/TiO₂ is
optimal, as lower amounts resulted in reduced conversion and higher loadings. Notably, the reaction selectively
produced Z-stilbene, contrary to the common formation of the trans isomer in similar processes. This methodology
offers a greener, faster, and more reproducible approach for on-demand synthesis in pharmaceutical
manufacturing.