African Journal of
Pure and Applied Chemistry

  • Abbreviation: Afr. J. Pure Appl. Chem.
  • Language: English
  • ISSN: 1996-0840
  • DOI: 10.5897/AJPAC
  • Start Year: 2007
  • Published Articles: 357

Full Length Research Paper

A high yield synthesis of phenytoin and related compounds using microwave activation

Fernand A. Gbaguidi1,2*, Salomé S. D. KPOVIESSI1, Coco N. Kapanda2, Giulio G. Muccioli2, Didier M. Lambert2, Géorges C. Accrombessi1, Moudachirou Mansourou1 and Jacques H. Poupaert2
1Organic and Physical Chemistry laboratory, Faculté des Sciences et Techniques, (FAST) Université d’Abomey-Calavi (UAC) BP 526, Cotonou. 2School of Pharmacy, Université Catholique de Louvain, Avenue Emmanuel Mounier 73, B-1200 Brussels, Belgium.
Email: [email protected]

  •  Accepted: 16 May 2011
  •  Published: 31 July 2011

Abstract

A reaction system is described to synthesize phenytoin, a major antiepileptic drug, and structurally related compounds using a two-step approach. The first step involves the treatment of a benzil derivative by thiourea in dimethylsulfoxide (DMSO) in aqueous KOH under microwave activation. The resulting 2-thiohydantoin was then oxidized to the corresponding hydantoin using perhydrol in dimethylformamide (DMF) in acetic acid.  Both steps proceeded in high yield. For example, with this method, phenytoin was obtained in 80% yield while by the conventional Biltz’s method, the yield rarely exceeded 50%. The first step can be advantageously performed using microwave activation. Our process is based on a mechanistic approach supported by theoretical PM3 calculations.

 

Key words: Phenytoin, antiepileptic drug, 2-thiohydantoin, Biltz’s method.