Background: A useful and simple strategy for the synthesis of sulfonyl-spiro-pyrimidines derivatives via a five-component reaction between sodium arylsulfinates, trichloroacetonitrile, primary amines, isatin and malononitrile in the DMF at room temperature is described in this study.Methods: Initially, we performed the five-component reaction of trichloroacetonitrile, benzylamine, sodium arylsulfinate, isatin and malononitrile as a simple model, and then we optimized the reaction conditions by changing the solvent. DMF proved to be the most optimal solvent with highest yield for this reaction compared to MeOH, EtOH, MeCN, CH2Cl2, acetone, and tetrahydrofuran (THF). Therefore, the reaction was carried out in DMF at room temperature for 7 h, by using 1 mmol of benzylamine, 1 mmol of sodium arylsulfinate, 1 mmol of trichloroacetonitrile, 1.5 mmol of isatin, and 1.5 mmol of malononitrile. Under these conditions, functionalized sulfonyl-spiro-pyrimidines was indeed obtained with 89% yield. Results: Using the optimized conditions described above, various sulfonyl-spiro-pyrimidines derivatives were synthesized from sodium arylsulfinates, malononitrile, isatin, trichloroacetonitrile, and various benzylamines with various electron-withdrawing or electron-donating substituents on the aromatic rings in DMF at room temperature. Conclusion: In summary, the one-pot tandem reaction of benzylamine, sodium arylsulfinate, trichloroacetonitrile, isatin and malononitrile in DMF at room temperature led to the formation of functionalized sulfonyl-spiro-pyrimidines in good yields. The procedure described here has the advantage that the reaction is mild and fairly general, thus providing a useful path for the synthesis of functionalized spiro systems containing various sulfonyl groups.