Mechanochemical Preparation of Hydantoins from Amino Esters: Application to the Synthesis of the Antiepileptic Drug Phenytoin

作者：Konnert Laure; Reneaud Benjamin; de Figueiredo Renata Marcia; Campagne Jean Marc; Lamaty Frederic; Martinez Jean; Colacino Evelina^*

来源：Journal of Organic Chemistry, 2014, 79(21): 10132-10142.

DOI：10.1021/jo5017629

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 alpha- and beta-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.

• 出版日期2014-11-7