Originator
Paradione,Abbott, US ,1949
Uses
Paramethadione acts as an antiepileptic and anticonvulsant agent.
Uses
Paramethadione is also used in minor forms of epilepsy.
Definition
ChEBI: Paramethadione is an oxazolidinone.
Manufacturing Process
About 143.1 grams (one mol) of 5-methyl-5-ethyloxazolidine-2,4-dione is dissolved in 300 cc of methanol containing 23 grams of sodium. To the above mixture is added 126 grams of dimethyl sulfate in 10 cc portions while the temperature is maintained at about 50°C by external cooling. The mixture is then heated briefly to boiling, cooled, diluted with about 500 cc of water and extracted with two 250 cc portions of benzene. The benzene extract is separated, washed once with sodium bicarbonate solution and once with water. The benzene is removed by evaporation on a steam bath and the residue is fractionally distilled. The material boiling at 112° to 116°C at 25 mm pressure is taken; nD25=1.4495. Upon further fractionation, a very pure specimen boils at 101°-102°C at 11 mm.
The 5-methyl-5-ethyloxazolidine-2,4-dionemay be prepared by reacting methyl ethyl ketone with sodium cyanide and with ammonium thiocyanate followed by desulfurization. This intermediate may also be prepared by condensing α-hydroxy-α-methylbutyramide with ethyl chlorocarbonate or by condensing ethyl α-hydroxy-α-methylbutyrate with urea. Another method described (Traube and Aschar, Ber., 46, 2077-1913) consists in the condensation of ethyl α-hydroxy-α-methylbutyrate with guanidine followed by hydrolysis.
Brand name
Paradione (Abbott).
Therapeutic Function
Anticonvulsant
Safety Profile
Moderately toxic by ingestion and intraperitoneal routes. Experimental teratogenic effects. Other experimental reproductive effects. Whenheated to decomposition it emits toxic fumes of NOx.
Synthesis
Paramethadione, 5-ethyl-3,5-dimethyloxazolidine-2,4-dione (9.8.3),
differs from trimethadione only in the substitution of one methyl group with an ethyl
group. It is synthesized in a completely analogous manner, except that it comes from
2-hydroxy-2-methylbutyric acid instead of 2-hydroxyisobutyric acid [29].
