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

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, 1 H NMR, 13 C 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).