4. Phenytoin
Systematic name: 5,5-diphenylimidazolidine-2,4-dione; 5,5-diphenylhydantoine
Chemicals:
benzil (1,2-diphenyl-1,2-dione) 2.3g (0.011 mol)
urea 1 g (0.017 mol)
sodium 0.7 g (0.03 mol)
propan-2-ol 50 ml
Scheme of preparation:
Procedure:
Sodium (is supplied by the laboratory technician cut into small pieces) is gradually added into
propan-2-ol placed in a well dried round-bottom flask equipped with a condenser with a humidityabsorbing
closure. After its dissolution by the stirring on a magnetic stirrer (forming of alcoholate),
urea is added and finally 2.3 g benzil (well dried). The reaction mixture is then refluxed under
stirring on a magnetic stirrer for 30 minutes. Once a precipitate begins to form water is added until
the precipitate is dissolved (8 – 16 ml). Then approx. 25 ml of the solvent is distilled off on a rotary
vacuum evaporator. The mixture is then poured into 170 ml of cold water and let stand. The formed
precipitate of the side product is then filtered off. The filtrate which contains sodium salt of
phenytoin is carefully acidulated with concentrated hydrochloric acid to the pH ~3. The microcrystalline
precipitate of phenytoin is then formed. It is isolated by suction, washed with water on
the filter and dried. It can be recrystallized from boiling water with usage of active carbon. Its
purity, especially the absence of starting benzil, is then tested by TLC with benzil as the comparison
compound. The identity is then confirmed by 1
H- and 13
C-nuclear magnetic resonance (NMR)
spectroscopy: place approx. 20 mg of the dried substance into a plastic tube with a lid and consult
your lecturer.
Yield 65-70% of theory.
Properties:
Phenytoin is a colourless micro-crystalline compound of m.p. 293-296o
C, insoluble in water,
benzene and chloroform. (The side reaction product 1,5-diphenyl-2,4,6,8tetraazabicyclo[3,3,0]octan-3,7-dione
or 3a,6a-diphenyltetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione
has m.p. 390 – 394°C. Both melting temperatures are, unfortunately, not measurable
O O
+ NH2 NH2
O
N
N
O
O
H
H
NN
N N
O
O
HH
H H
[210,23] [60,06]
[252,27]
i-C3H7ONa
on a common capillary melting point apparatus.) Phenytoin dissolves in alkaline hydroxides
solutions forming salts. It was first prepared by Biltz and Rimpel as early as in 1908. It is still used
as an antiepileptic (Epilan D Gerot®
).