video tutorial Synthesis of phenytoin; an anti-seizure drug

Name: video tutorial - Synthesis of phenytoin; an anti-seizure drug
Uploaded: 2025-12-11T09:03:44.054Z
Duration: 11 min 25 s
Description: In this video, we're going to perform another experiment with Benz-Yl....We prepared this using the procedure we covered in a previous video.

Goal: synthesize phenytoin (a hydantoin) via a benzyl-derived reaction with urea under basic ethanol reflux.
Starting materials and amounts: benzyl crystals, 5 g; urea (burya) crystals, 2.9 g (2× molar excess relative to benzyl); sodium hydroxide, 3.8 g (4× molar excess) dissolved in 10 mL water.
Solvent: absolute ethanol (40 mL; 95% ethanol also acceptable).
Procedure: dissolve benzyl and urea in warm ethanol; prepare NaOH solution separately; add to reaction to form a dark slurry; reflux with a condenser for about 1 h; color changes from dark brown to lighter brown/orange/yellow; observe formation of a white precipitate and later a thick slurry upon addition of NaOH; continue heating to reflux; after ~1 h, allow to react and then cool; the mixture eventually changes and a salt intermediate forms.
Workup and mechanism: benzyl contains two ketones; hydroxide deprotonates urea, enabling urea nitrogen to attack the ketone carbonyls forming an intermediate; rearrangement yields a five-membered ring; the product initially forms as a sodium salt and is protonated to yield phenytoin upon acidification.
Reaction termination and isolation: cool, dilute with water, filter off inorganic/by-products; acidify the filtrate dropwise with concentrated HCl to precipitate phenytoin; after acidification, additional hydrolysis of urea may occur, producing ammonia and smoke; allow crystallization by cooling for several hours; filter and wash the crystals; dry thoroughly.
Product and yield: crude phenytoin, 4.3 g, 72% yield based on starting benzyl; can be recrystallized from hot ethanol for higher purity, though this procedure used the crude product.
Notes: phenytoin was historically used as an anti-epileptic drug but is not considered safe or effective by modern standards; the synthesis demonstrates formation of a new heterocyclic ring containing three carbons and two nitrogens, illustrating important ring-forming strategies in organic synthesis.