50-12-4

Basic information

• Product Name: (S)-MEPHENYTOIN
• Synonyms: (S)-(+)-5-ETHYL-3-METHYL-5-PHENYL-2,4-IMIDAZOLIDINEDIONE;(S)-(+)-5-ETHYL-3-METHYL-5-PHENYLHYDANTOIN;(S)-5-ETHYL-3-METHYL-5-PHENYLHYDANTOIN;(S)-(+)-MEPHENYTOIN;(S)-MEPHENYTOIN;(+/-)-5-ETHYL-3-METHYL-5-PHENYL-2,4-IMIDAZOLIDINEDIONE;(+/-)-5-ETHYL-3-METHYL-5-PHENYLHYDANTOIN;(+/-)-MEPHENYTOIN
• CAS NO: 50-12-4
• Molecular Formula: C₁₂H₁₄N₂O₂
• Molecular Weight: 218.25
• EINECS: 200-012-8
• Mol File: 50-12-4.mol

Chemical Properties

• Melting Point: 135-138 °C
• Boiling Point: 358.94°C (rough estimate)
• Flash Point: °C
• Appearance: off-white/solid
• Density: 1.154±0.06 g/cm3 (20 ºC 760 Torr)
• Refractive Index: 1.6660 (estimate)
• Storage Temp.: 2-8°C
• PKA: pKa 8.1 (Uncertain)
• CAS DataBase Reference: (S)-MEPHENYTOIN(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-MEPHENYTOIN(50-12-4)
• EPA Substance Registry System: (S)-MEPHENYTOIN(50-12-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• Hazardous Substances Data: 50-12-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-Mephenytoin is used as an anticonvulsant agent for the treatment of focal and Jacksonian seizures in patients who are refractory to less toxic AEDs. It is particularly useful in cases where safer drugs have failed to provide the desired therapeutic effects. However, its use is limited due to the potential for severe toxicities, such as severe rash, agranulocytosis, and hepatitis.
Used in Research and Development:
(S)-Mephenytoin can be utilized in research and development for the study of its pharmacological properties, mechanisms of action, and potential applications in the treatment of various neurological disorders. This may include investigations into its interactions with other drugs, its metabolism, and the development of novel drug delivery systems to improve its efficacy and safety profile.

Originator

Mesantoin,Sandoz

Manufacturing Process

23 parts sodium was dissolved in 300 parts of ethanol and added to 160 parts of 5-phenylcyanacetamide in 750 parts of ethanol. A mixture was cooled straight away and a sodium salt of amide precipitated as a white powder. 200 parts of ethyl iodide was added to this mixture and heated for 1.5 hours. The ethanol was distilled off, water was added to the residue and rapidly hardened oil precipitated. After recrystallization from ethanol, 5-ethyl-5- phenylacetamide afforded; MP: 116°C.100 parts of sodium hydroxide was solved in 500 parts of water and added to 83 parts of bromine by cooling. 5-Ethyl-5-phenylacetamide was added to above prepared mixture. It dissolved quickly, whereupon all mass was heated some time, cooled and stood at room temperature some hours. Then a solution of sodium bisulfite was added before the formed precipitate dissolved. The reaction mixture was filtered, the filtrate was acidified to give rapidly hardened oil. After recrystallization from ethanol 5-ethyl-3-methyl-5-phenylhydantoin was yielded as the bright needles; MP: 201°-202°C.

Therapeutic Function

Anticonvulsant, Antiepileptic

Biological Activity

CYP2C19 substrate. Anticonvulsant.

Biochem/physiol Actions

CYP2B6 and CYP2C19 substrate; anticonvulsive, antiepileptic.

Safety Profile

Poison by ingestion and intraperitoneal routes. Human systemic effects by ingestion: somnolence, hemorrhage, changes in teeth and supporting structures. Human mutation data reported. An experimental teratogen. An FDA proprietary drug used as an anticonvulsant. When heated to decomposition it emits toxic fumes of NOx.

InChI:InChI=1/C12H14N2O2/c1-3-12(9-7-5-4-6-8-9)10(15)14(2)11(16)13-12/h4-8H,3H2,1-2H3,(H,13,16)

Upstream product

• 2216-93-5 5-ethyl-5-phenyl-imidazolidine-2,4-dione 
• 38605-67-3 2-Ethyl-5-methyl-2-phenylhydantoinsaeure 
• 115-38-8 mephobarbital 
• 75356-45-5 1-(1-Cyano-1-phenyl-propyl)-3-methyl-urea 
• 75356-45-5 1-(1-Cyano-1-phenyl-propyl)-3-methyl-urea 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 74-89-5 methylamine 
• 75356-38-6 racem-α-Aethyl-α-cyan-benzylisocyanat 
• 33875-36-4 2-Isocyanato-2-phenyl-butyronitrile 
• 1462367-24-3 methyl 2-{[(4-methoxyphenyl)methyl][methyl(phenyl)carbamoyl]amino}butanoate 
• 1462367-26-5 2-{[(4-methoxyphenyl)methyl][methyl(phenyl)carbamoyl]amino}butanoic acid 
• 1462367-31-2 5-ethyl-1-[(4-methoxyphenyl)methyl]-3-methyl-5-phenylimidazolidine-2,4-dione 
• 74-88-4 methyl iodide 

Downstream Products

• 38605-67-3 2-Ethyl-5-methyl-2-phenylhydantoinsaeure 
• 50-12-4 (-)-Mephenytoin 

Relevant articles and documents

Palladium Catalyzed C-Arylation of Amino Acid Derived Hydantoins

Palladium(II) trifluoroacetate (5 mol %) catalyzes the C-arylation of N,N-disubstituted hydantoins by aryl iodides in good yield. The reaction proceeds through base-promoted enolization of the amino acid derived hydantoins, and the resulting 5,5-disubstituted hydantoins may be deprotected at one or both N atoms to yield biologically active structures or alternatively hydrolyzed to the parent α-aryl α-amino acids. The reaction is successful with a variety of parent amino acids and a range of electron-rich and electron-poor aryl iodides.

Pseudoephedrine-Directed Asymmetric α-Arylation of α-Amino Acid Derivatives

Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N′-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N′-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character.

Intramolecular arylation of amino acid enolates

Dianionic enolates formed from N′-aryl urea derivatives of amino acids undergo intramolecular C-arylation by attack of the enolate anion on the N′-aryl ring, leading to a hydantoin derivative of a quaternary amino acid. In situ IR studies allow identification of four intermediates on the reaction pathway.

Chromatographic Resolutions of Racemates, XI. Comparison of Optically Active Polyamides and Cellulose Triacetate

On optically active polyacrylic and polymethacrylic amides (1a-e) as well as on microcrystalline cellulose triacetate (2), numerous racemates including drugs are separated at least partially, the amide 4f completely on cellulose triacetate.By repeated chromatography on the polyamide 1a, (+)- and (-)-mandelic acid (4a) and (+)-hexobarbital (9d) also were obtained optically pure.

Racemic and Optically Active Hydantoins from Disubstituted Cyanoacetic Acids

Starting from the chiral disubstituted cyanoacetic acids 1 the racemates and some enantiomers of the 5,5-disubstituted hydantoins 6 and of the 3-methylhydantoins 7 are synthesized via the isocyanates 3.Their absolute configurations are determined.