A one-pot chemoselective S-alkylation and acetylation of thiohydantoins using the alkyl orthoformate-ZnCl2-Ac2O reagent system

The chemoselective S-alkylation of 2-thiohydantoins is reported. The methodology involves the use of alkyl orthoformates (trimethyl and triethyl) as alkylating agents, which in the presence of Ac2O and ZnCl2 chemoselectively alkylate the thio group whilst other nucleophilic groups present in the thiohydantoins are acetylated simultaneously in moderate to high yields. A plausible mechanism for this reaction is delineated.