title: Mechanochemical preparation of hydantoins from amino esters: application to the synthesis of the antiepileptic drug phenytoin.
abstract: The eco-friendly preparation of 5- and 5,5-disubstituted hydantoins from various amino ester hydrochlorides and potassium cyanate in a planetary ball-mill is described. The one-pot/two-step protocol consisted in the formation of ureido ester intermediates, followed by a base-catalyzed cyclization to hydantoins. This easy-handling mechanochemical methodology was applied to a large variety of α- and β-amino esters, in smooth conditions, leading to hydantoins in good yields and with no need of purification steps. As an example, the methodology was applied to the "green" synthesis of the antiepileptic drug Phenytoin, with no use of any harmful organic solvent.
authors.affiliation: Université Montpellier II, Institut des Biomolécules Max Mousseron UMR 5247 CNRS - Universités Montpellier I & II - ENSCM , Place E. Bataillon, cc 1703, 34095 Montpellier, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Konnert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Reneaud
authors.forename: Renata Marcia
authors.initials: RM
authors.lastname: de Figueiredo
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Campagne
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamaty
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Evelina
authors.initials: E
authors.lastname: Colacino
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003500:Cyclization; D004952:Esters; D006827:Hydantoins / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010672:Phenytoin / Q000138:chemical synthesis* / Q000737:chemistry*; D012997:Solvents
chemical_list: D000927:Anticonvulsants; D004952:Esters; D006827:Hydantoins; D012997:Solvents; D010672:Phenytoin