An efficient and novel method was developed for the synthesis of 4-substituted-1,5-benzodiazepine derivatives via a one-pot three-component catalytic reaction. The o-phenylenediamine and dimedone were reacted with aldehyde derivatives in the presence of ZnS nanoparticles as a heterogeneous catalyst under thermal conditions. The reaction was completed with high to excellent product yields and short reaction times. Simplicity of operation, high yields, easy work-up, easily accessible catalyst and purification of products through a crystallization method (non-chromatographic) are the key advantages of this work.