posted on 2014-11-07, 00:00authored byLaure Konnert, Benjamin Reneaud, Renata
Marcia de Figueiredo, Jean-Marc Campagne, Frédéric Lamaty, Jean Martinez, Evelina Colacino
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.