3,5,5-TRIMETHYLOXAZOLIDINE-2,4-DIONE Property

Melting point:

45-46°C

Boiling point:

78-80°C 5mm

Density 

1.3075 (rough estimate)

refractive index 

1.4290 (estimate)

Flash point:

78-80°C/5mm

storage temp. 

Inert atmosphere,Room Temperature

solubility 

Soluble in water, very soluble in ethanol (96 per cent).

pka

-2.18±0.40(Predicted)

form 

Solid

color 

White to Off-White

Water Solubility 

Soluble in water 50 g/L.

Merck 

14,9706

BRN 

121627

CAS DataBase Reference

127-48-0(CAS DataBase Reference)

EPA Substance Registry System

Trimethadione (127-48-0)

Safety

Hazard Codes 

T

Risk Statements 

61-20/21/22

Safety Statements 

53-22-36/37/39-45

WGK Germany 

3

RTECS 

RQ2100000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H360May damage fertility or the unborn child

Precautionary statements

P201Obtain special instructions before use.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P308+P313IF exposed or concerned: Get medical advice/attention.

3,5,5-TRIMETHYLOXAZOLIDINE-2,4-DIONE Chemical Properties,Usage,Production

Chemical Properties

White, granular, crystalline substance; camphor-like odor. Soluble in water; freely soluble in alcohol, chloroform, and ether; pH 6.0 (5% solution).

Originator

Tridione,Abbott,US,1946

Uses

antifungal

Uses

Trimethadione is used in minor forms of epilepsy that does not respond to treatment of other drugs.

Uses

3,5,5-Trimethyloxazolidine-2,4-dione is used in the control of absence (petit mal) seizures that are refractory to treatment with other medications. It is used in the treatment of epilepsy.

Definition

ChEBI: Trimethadione is an oxazolidinone that is 1,3-oxazolidine-2,4-dione substituted by methyl groups at positions 3, 5 and 5. It is an antiepileptic agent. It has a role as a geroprotector and an anticonvulsant.

Manufacturing Process

To a cooled solution of 23 parts of sodium in 400 parts of dry ethanol are added 60 parts of dry urea and 132 parts of ethyl α-hydroxy-isobutyrate. The mixture is heated on a steam bath under reflux for about 16 hours and the liberated ammonia is removed from the solution by drawing a current of dry air through it at the boiling point. The solution of the sodium salt of 5,5- dimethyloxazolidine-2,4-dione so obtained is cooled and treated with 284 parts of methyl iodide. The mixture is allowed to stand at room temperature for 3 days, excess methyl iodide and ethanol are then removed by distillation under reduced pressure.
The residue is dissolved in ether and the solution is washed with sodium chloride solution and then with a little sodium thiosulfate solution. The ethereal solution is dried over sodium sulfate and ether removed by distillation. A yield of 108 parts of 3,5,5-trimethyloxazolidine-2,4-dione is obtained having a melting point of 45° to 46°C with slight softening at 43°C. This represents a 75% theory yield on the ethyl α-hydroxy-iso-butyrate taken. The product may be further purified by dissolving the minimum quantity of dry ether and cooling to -10°C. The product so obtained melts sharply at 45.5° to 46.5°C according to US Patent 2,559,011.

brand name

Absentol (Nourypharma), Epidione (Bellon), Ptimal (EGIS), Tridione/Trimedone (Abbott).

Therapeutic Function

Anticonvulsant

Synthesis Reference(s)

Tetrahedron, 51, p. 5891, 1995 DOI: 10.1016/0040-4020(95)00257-9

Hazard

May have adverse side effects; toxic in overdose.

Clinical Use

Trimethadione is indicated only for control of absence seizures refractory to treatment with other AEDs. It is ineffective against other seizure types. Trimethadione is a pro-drug and is metabolized by N-demethylation to dimethadione, which is effective in the pentylenetetrazole test, which acts by decreasing T-type calcium currents. Trimethadione is rapidly absorbed, is not protein bound, and has a half-life of 16 to 24 hours. The half-life of dimethadione, however, is substantially longer (i.e., 6–13 days), and dimethadione accumulates to concentrations greater than the parent drug. Because of its potentially fatal side effects. including aplastic anemia, nephrosis, idiosyncratic rashes, and exfoliative dermatitis, trimethadione rarely is used today.

Synthesis

Trimethadione, 3,5,5-trimethyloxazolidine-2,4-dione (9.8.2), is synthesized by methylating 5,5-trimethyloxazolidine-2,4-dione (9.8.1) with dimethylsulfate.Starting 5,5-trimethyloxazolidine-2,4-dione (9.8.1) is in turn synthesized by the cyclocondensation of the ester of 2-hydroxyisobutyric acid with urea [26¨C28].