5, 5-Dimethyl-2, 4-oxazolidinedione

TABLE 6.12. IMIDAZOLONES FROM 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE AND 2//-AZIRINES ... 

Trimethadione is rapidly absorbed, with peak levels reached within an hour after drug administration. It is distributed to all perfused tissues, with a volume of distribution that approximates that of total body water. It is not bound to plasma proteins. Trimethadione is completely metabolized in the liver by demethylation to 5,5-dimethyl-2,4-oxazolidinedione (dimethadione), which may exert the major antiseizure activity. The clearance of dimethadione is 0.08 L/kg/d this metabolite has an extremely long half-life (240 hours). 

SYNS AC 1198 BAX 1400Z DIMETHADIONE DIMETHYLOXAZOLIDINEDIONE 5,5-DIMETHYL-OXAZOLIDINE-2,4-DIONE 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE DMO EUPRACTONE NSC-30152... 

Acetone cyanohydrin is obtained from the interaction of acetone and hydrocyanic acid, which on subsequent hydrolysis followed by esterification with ethanol yields ethyldimethylglycolate. This is condensed with urea in the presence of sodium ethoxide to yield 5, 5-dimethyl-oxazolidinedione-2, 4-dione. Trimethadione is finally obtained by treating the resulting product with dimethyl sulphate in the presence of sodium hydroxide. 

Unsubstituted oxazolidinediones are prepared directly from the unsubstituted C-3 amides. Treatment of 4-deacetylvinblastine amide (59) with sodium hydride in tetrahydrofuran followed by the addition of dimethyl carbonate gives 4-deacetyl-3-oxazolidinedione (101) in 40% yield. 

A logical construction of the 2,4-oxazolidinedione system is by condensation of an a-hydroxyacylamide with ethyl chloroformate or dimethyl carbonate under basic conditions (equation 183). Two other general syntheses are by the action of isocyanates on a-hydroxy acids in the presence of sodium (equation 184) and by treatment of esters of a-hydroxy acids with urea and sodium ethoxide (equation 185). 

Sodium derivative of 5-ethyl-5-methyl-2, 4-oxazolidinedione is obtained by refluxing urea and ethyl-a-hydroxy-a-methylbutyrate for 24 horns in the presence of sodium methoxide, due to eondensation followed by cyclization. N-methylation is carried out by treatment with dimethyl sulphate. 

Therapeutic Function Anticonvulsant Chemical Name 5-ethyl-3,5-dimethyl-2,4-oxazolidinedione Common Name Isoethadione Structural Formula h.c,. 

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