The C-H activation and C-C coupling of 4-methyl pyridine to 4,4 -dimethyl-2,2 -bipyridine was studied over palladium catalysts supported on nanoparticle alumina [nano-Al 2 O 3 (+)]. Even though Pd/Al 2 O 3 catalysts are traditionally poor catalysts in this reaction, the Pd/nano-Al 2 O 3 (+) catalysts prepared via the precipitation method give the highest yield observed to date for this reaction system. The catalytic activity is very dependent on the catalyst preparation as Pd/nano-Al 2 O 3 (+) catalysts prepared via the wet impregnation method exhibit poor activities in the reaction. Additionally, a catalyst prepared using another nanoparticle alumina with larger particle sizes [nano-Al 2 O 3 (-)] does not have a significant activity. It was shown that using a commercial bimodal ␥-Al 2 O 3 support can result in an active catalyst if prepared via the precipitation method, but compared to the best performing catalyst, Pd/nano-Al 2 O 3 (+), the yields obtained from Pd/bimodal-␥-Al 2 O 3 are lower and less reproducible. Pd surface area measurements indicate that the reaction is structure sensitive as there is no correlation between the Pd surface area and the catalytic activity. The reaction is also very sensitive to reactant quality and the 4-methyl pyridine must be distilled over KOH to ensure reproducible yields. Additional experiments indicate that this reaction requires a solid phase for catalysis.