Reformation of Thalidomide from Its Hydrolysis Compound via Intramolecular Dehydration

Thalidomide, a famous chiral drug, can be hydrolyzed into three different compounds depending on the reaction site of hydrolysis. This work presents the reformation of thalidomide from one of the hydrolysis compounds through an intramolecular dehydration reaction in acetonitrile. The difference of dehydration behavior between hydrolysis compounds was rationalized based on molecular structures: the reformable molecule has the preferable geometric environment for intramolecular dehydration. Thalidomide, a famous chiral drug, can be hydrolyzed into three different compounds depending on the reaction site of hydrolysis. This work presents the reformation of thalidomide from one of the hydrolysis products through an intramolecular dehydration reaction in acetonitrile. The difference of dehydration behavior was rationalized based on molecular structures: the reformable molecule has the preferable geometric environment for intramolecular dehydration.