In the present work, the highly efficient Erlenmeyer synthesis of azlactones catalyzed by 2- aminopyridine, supported on nano-sphere SiO2 is reported. First, the silica nanoparticles were modified with triethoxysilylpropyl chloride and then 2-aminopyridine was attached to the support via covalent linkages. This new heterogenized catalyst was used for efficient microwave-assisted synthesis of azlactone derivatives with Ac2O as a condensing agent under solvent-free conditions. The present method offers advantages including high yields, short reaction times and simple work-up. Also, the catalyst can be easily recycled and reused several times, which makes this method attractive, economic and environmentally-benign.