Dibromohydantoins as halogen bond (XB) donors: a route toward the introduction of chirality in halogen bonded systems

Abstract

N,N′-Dibromohydantoins, known as electrophilic bromination reagents, are successfully used here as halogen bond (XB) donors, as demonstrated in their crystalline adducts with para-substituted pyridines acting as halogen bond acceptors. 1 : 1 adducts of the achiral 5,5-dimethyl-N,N′-dibromohydantoin (DBH) are crystallized with methylisonicotinate, 4-trifluoromethylpyridine and 4-cyanopyridine, while both nitrogen atoms of pyrazine are engaged in halogen bonding in the 2 : 1 adduct (DBH)2·(pyrazine). A strengthening of the XB interaction between the imidic N–Br group of DBH and the pyridinic nitrogen atom is observed with the more electron rich pyridines in the order Py–CO2Me > Py–CF3 > Py–CN > pyrazine. Chiral hydantoins and their N,N′-dibromo derivatives are obtained in good yields from different amino acids (phenylglycine, phenylalanine, valine and leucine). The ability of such enantiopure N-iodoimide derivatives to act as halogen-bond donors is demonstrated in the 1 : 1 methylisonicotinate adduct with (S)-5-isobutyl-N,N′-dibromohydantoin.