The formation of polypyridine-derivatives by reaction of propargylamine with bis-alpha-H-methylketones in a two step micro continuous flow system was investigated. The use of continuous flow micro reaction system enables fast process optimization, production upscaling and the application of enhanced process windows. Polypyridines such as 2,2'-bipyridine (1), phenanthroline (2) or terpyridine (3) are important ligands in the filed of complex chemistry. The synthesis was optimized using two subsequent packed bed capillary reactors (PBCRs) filled with different catalyst materials. The best results were obtained with Montmorillonite K-10 clay and alumina supported gold nanoparticles as subsequent catalyst combination. Metal nanoparticles posses a great catalytic potential for different organic reactions used in fine chemical synthesis. Hence, alumina supported gold nanoparticles were prepared by an easy coating process without calcination. Desired polypyridine-derivatives were received by an aerobic oxidation at reaction temperatures of about 120-140 degrees C and residence times of about 10 min. The overall process yields the desired polypyridine-derivatives in excellent purity and good yield after evaporation of all volatile compounds. (C) 2010 Elsevier B.V. All rights reserved.