Synthesis of benzoin under supramolecular catalysis involving cyclodextrins in water: application for the preparation of the antiepileptic drug phenytoin.

Abstract

Among the cyclodextrins screened for the synthesis of 2-hydroxy-1,2-diphenylethanone (benzoin) in water, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) exhibited the highest yield in the benzoin condensation reactions, and HP-β-CD can be recycled several times with little loss of activity through the addition of fresh VB1. As an example of supramolecular catalysis, the methodology was applied to the “green” synthesis of the antiepileptic drug phenytoin through benzoin condensation, oxidation, and cyclization reactions in the presence of HP-β-CD, without the use of any harmful organic solvent. Moreover, the complexation behaviors of HP-β-CD with benzaldehyde and intermediates were studied by UV-vis and 2D-ROESY NMR spectroscopies to reveal the plausible mechanisms of the reactions, and HP-β-CD did not act as a simple phase transfer agent.