Cyclododecanone as a recyclable protecting group for the synthesis of highly functionalized 3-amino-2-thiohydantoins from conventional starting materials

Abstract

A simple and efficient approach has been developed for the synthesis of highly substituted 3-amino-2-thiohydantoins using cyclododecanone as a protecting group and thiosemicarbazide, chloroacetic acid and substituted benzaldehyde as reactants. This high yielding (79–96%) protocol is a milder alternative to the traditional method that uses unprotected thiosemicarbazide. It was identified that the preferred pathway is the deprotection of 3-amino-2-thiohydantoins followed by the attack of chloroacetic acid on a secondary nitrogen with subsequent formation of the Knoevenagel product and its reaction with imine leading to the final product.