Isatin is a special heterocyclic compound because of its various biological activities. This research aims to synthesize isatin derivatives catalyzed by iron (III) trifluoromethanesulfonate, Fe(OTf)3. In this study, Fe(OTf)3 catalysts were synthesized using Fe3+ ions and Lewis acid and characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray Diffraction (XRD), and Transmission ElectronMicroscope (TEM). The characterization results showed that the catalyst Fe(OTf)3 was successfully formed. Furthermore, Fe(OTf)3 catalysts were applied in the synthesis of isatin derivatives. Schiff base of isatin is a group of organic compounds with azomethine groups that play an essential role in biological systems and act as ligands in developing new chemical entities. The Schiff base of isatin is the product of condensation between the carbonyl compounds of isatin with different aromatic primary amines. In this paper, the synthesis of several Schiff bases of isatin derivatives applies conventional heating methods. The results were described by physicochemical analysis and characterized using UV-Vis spectrophotometry, FT-IR, and LC-MS. The characterization results support the successful synthesis of the isatin compound derivative.