Iodine‐Promoted Synthesis of 3,5‐Disubstituted 1,2,4‐Thiadiazoles From Thiooxamates and Their Acetylcholinesterase Inhibitory Activity

ABSTRACT A practical and transition‐metal‐free protocol has been developed for the synthesis of 3,5‐disubstituted 1,2,4‐thiadiazoles via iodine‐promoted oxidative dimerization of alkyl/arylmethyl thiooxamates. This transformation proceeds rapidly under mild conditions through sequential oxidative S─N and N─C bond formation. The method exhibits broad substrate scope and excellent functional group tolerance, affording the desired thiadiazoles in good yields. The structure of one of the products was confirmed by single‐crystal x‐ray diffraction. Furthermore, the synthesized compounds were evaluated for in vitro acetylcholinesterase inhibitory (AChEI) activity, with compound 3d exhibiting promising activity compared to the standard drug rivastigmine.