In this work, for the first time, laccase (metalloenzyme 3,5-di-tert-butylcatechol (DTBC) as a new class of bioinspired quinone-based cooperative catalytic oxidation system and laccase/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) catalyst system were used for the aerobic oxidative synthesis of 2- substituted quinazolines through cascade reaction of structur- ally divers aldehydes with 2-aminobenzylamine. The products were obtained in good to high yields in phosphate buffer (0.1 M, 12.5 mL, pH = 4.5) and acetonitrile (4 vol.-%) mixture as solvent at 45 °C. Other N-heterocycles are also successfully oxidized to their aromatic counterparts.