A revolution method of microwave assisted organic synthesis is one of the major roles for synthesis of new drug molecules. Considering the benefits of microwave organic synthesis we have synthesized 12 novel Schiff base compounds (10 E-10 P) of 2-amino-N-[3-fluoro-4-(morpholin-4-yl) phenyl] benzene-1-sulfonamide derivatives from commercially available 3,4-Difluoronitrobenzene. The existing conventional heating method consumes 16-24 hours, but utilizing microwave irradiation method the reaction occurs faster and the time reduced to 4–6 minutes. The structure confirmation of all the synthesized molecules was confirmed by means of 1HNMR and MS study. The synthesized NCE’s were further tested for their antibacterial and antifungal studies. Some of the molecules were showed better antibacterial and antifungal activity.