Synthesis of 4‐(5‐Amino‐1,3,4‐thiadiazol‐2‐yl)pyrrolidin‐2‐ones and Their Antifungal Activity

Abstract A novel series of 1‐aryl‐ and 1‐alkyl‐4‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)pyrrolidin‐2‐ones was synthesized by the condensation of 1‐aryl‐ or 1‐alkyl‐5‐oxopyrrolidine‐3‐carboxylic acids and thiosemicarbazide upon heating with concentrated sulfuric acid and characterized using IR, 1H NMR, 13C NMR, and HRMS spectral data. The proposed approach was suitable for the synthesis of some 4‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐1‐heteroarylpyrrolidin‐2‐ones. The protocol ensures the stability of the pyrrolidinone cycle under reaction conditions. The synthesized compounds showed significant antifungal activity against phytopathogens R. solani and V. inaequalis. Two the most active compounds, 4‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐1‐(4‐chlorobenzyl)pyrrolidin‐2‐one and 4‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐1‐(6‐nitrobenzothiazol‐2‐yl)pyrrolidin‐2‐one, also showed moderate activity against B. sorokiniana. They inhibited the mycelial growth of R.solani, V. inaequalis and B. sorokiniana by 100, 60‐78, and 53‐55%, respectively, which is higher than that of the reference compound triadimefon (43%, 41%, and 44%, respectively).