Synthesis of N(3),N‘(3)-Polymethylene-bis-hydantoins and Their Macrocyclic Derivatives

N. Dieltiens, D.D. Claeys, C.V. Stevens
Journal of Organic Chemistry
71(10), 3863–3868


An efficient and straightforward two-step approach toward N(3),N‘(3)-polymethylene-bis-hydantoins was developed. As a first step, a pyroglutamate is reacted with a diisocyanate to produce a bis-carbamoyllactam. The second step is a double-ring transformation by treatment of this bis-carbamoyllactam with KOtBu in ethanol. In this fashion N(3),N‘(3)-polymethylene-bis-hydantoins are produced in two quantitative steps and under very mild conditions. When properly derivatized, these compounds can be converted to their macrocyclic derivatives upon treatment with 5 mol % of second-generation Grubbs' catalyst. These macrocyclic derivatives are so far not described in the literature. It was proven that exclusively (E)-isomers are formed.