Russian Journal of Organic Chemistry, Vol. 40, No. 3, 2004, pp. 377–382. From Zhurnal Organicheskoi Khimii, Vol. 40, No. 3, 2004, pp. 406–411. Original English Text Copyright © 2004 by Mahmoodi, Emadi. 1070-4280/04/4003-0377 © 2004 MAIK “Nauka/Interperiodica” One-Pot Synthesis of Phenytoin Analogs* N. O. Mahmoodi and S. Emadi Organic Research Laboratory, Department of Chemistry, University of Guilan, Rasht, 1914, Iran e-mail: mahmoodi@guilan.ac.ir Received December 25, 2002 Abstract—A series of phenytoin analogs (5,5-diphenylimidazolidine-2,4-dione or 5,5-diphenyl- hydantoin) were synthesized in 65–75% yield from the corresponding substituted benzils. The same products were also obtained directly from α-hydroxy ketones via one-pot procedure. 5,5-Diphenylimidazolidine-2,4-dione or 5,5-di- phenylhydantoin (PHT) is an antiepileptic drug [1]. In the recent publication [2], the design and synthesis of new antiepileptic targets for neuronal voltage-sensitive sodium channel (NVSC) have been extensively con- sidered. Study of these model hydantoin derivatives could provide an important knowledge and predict how to enhance binding site to NVSC [3]. Structural information about phenytoin binding site is scanty [3]. The exact location of these sites and structure require- I–III, R = R' = H (a), R = R' = Me (b), R = Me 2 N, R' = H (c), R = R' = MeO (d), R = MeO, R' = H (e). Scheme 1. ments for optimal binding have not yet been deter- mined. According to the results of recent studies, 5,5-diphenylhydantoin inhibits binding of human immunodeficiency virus (HIV) to lymphocytes [4], affects hepatic thyroxine [5], selectively enhances vincristine cytotoxicity [6], affects myocardial contrac- tivity and hemodynamics [7], and reduces pesticide residue in human adipose tissue [8]. In the present article specific attention is given to the novel synthesis of phenytoin analogs. The * The original article was submitted in English. R O O R' R O OH R' IIa–IIe IIIa–IIIe NH 2 CONH 2, EtOH H 2 O, NaOH, 2–3 h HN NH R R' O O Ia–Ie HN NH O O R R' XIV