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Ethosuximide

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Name

Ethosuximide

EINECS 201-048-7
CAS No. 77-67-8 Density 1.1522 (rough estimate)
PSA 46.17000 LogP 0.77800
Solubility ethanol: 100 mg/mL Melting Point 51 °C
Formula C7H11 N O2 Boiling Point 265.3 °C at 760 mmHg
Molecular Weight 141.17 Flash Point 123.8 °C
Transport Information N/A Appearance N/A
Safety 36 Risk Codes 22
Molecular Structure Molecular Structure of 77-67-8 (ETHOSUXIMIDE) Hazard Symbols HarmfulXn
Synonyms

Succinimide,2-ethyl-2-methyl- (6CI,7CI,8CI); (?à)-Ethosuximide; 2-Ethyl-2-methylsuccinimide; 2-Methyl-2-ethylsuccinimide;3-Ethyl-3-methylpyrrolidine-2,5-dione; 3-Ethyl-3-methylsuccinimide;3-Methyl-3-ethylpyrrolidine-2,5-dione; 3-Methyl-3-ethylsuccinimide; Atysmal;C.I. 366; CN 10395; Capitus; Emeside; Epileo Petitmal; Ethosuxide;Ethosuximide; Ethymal; Etosuximid; H 940; Mesentol; NSC 64013; PM 671; Pemal;Peptinimid; Petinimid; Petnidan; Piknolepsin; Pyknolepsinum; Ronton; Simatin;Succimal; Succimitin; Suxilep; Suximal; Suxinutin; Zarodan; Zarondan;Zarondan-Saft; Zarontin; a-Ethyl-a-methylsuccinimide;a-Methyl-a-ethylsuccinimide

Article Data 12

Ethosuximide Synthetic route

C14H17NO3

77-67-8

ethosuximide

Conditions
ConditionsYield
Stage #1: C14H17NO3 With palladium on activated charcoal; hydrogen
Stage #2: With triethylamine; α-bromoacetophenone
83%
166324-36-3

4-ethyl-1-(4-methoxybenzyl)-4-methylpyrrolidine-2,5-dione

77-67-8

ethosuximide

Conditions
ConditionsYield
With ammonium cerium(IV) nitrate In water; acetonitrile for 1h; Ambient temperature;47%
631-31-2

2-ethyl-2-methylsuccinic acid

77-67-8

ethosuximide

Conditions
ConditionsYield
With ammonia
With ammonium hydroxide at 200℃;
With ammonium hydroxide In water at 190℃; for 1.5h;
ammonium salt of/the/ α-methyl-α-ethyl-succinic acid

ammonium salt of/the/ α-methyl-α-ethyl-succinic acid

77-67-8

ethosuximide

Conditions
ConditionsYield
durch Destillation;
96-17-3, 57456-98-1

2-Methylbutyraldehyde

Ag2O

Ag2O

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 1.) MgSO4, 2.) N,N-diethylaniline / 1.) Et2O, 2 h, RT, 2.) toluene, -78 deg C to RT, 24 h
2: N-chlorosuccinimide / 40 deg C, 2 h; 80 deg C, 1 h
3: SiO2, H2O / 1.) 35 deg C, overnight then 60 deg C, 30 min, 2.) benzene, 1 h
4: 58 percent / Raney nickel (W-2) / ethanol / 3 h / Heating
5: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
6: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature
View Scheme
166324-35-2

4-ethyl-5-hydroxy-1-(4-methoxybenzyl)-4-methylpyrrolidin-2-one

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
2: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature
View Scheme
166324-34-1

4-ethyl-5-hydroxy-1-(4-methoxybenzyl)-4-methyl-3-(methylthio)pyrrolidin-2-one

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 58 percent / Raney nickel (W-2) / ethanol / 3 h / Heating
2: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
3: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature
View Scheme

N-(2-methylbut-1-enyl)-N-(4-methoxybenzyl)-α-(methylthio)acetamide

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: N-chlorosuccinimide / 40 deg C, 2 h; 80 deg C, 1 h
2: SiO2, H2O / 1.) 35 deg C, overnight then 60 deg C, 30 min, 2.) benzene, 1 h
3: 58 percent / Raney nickel (W-2) / ethanol / 3 h / Heating
4: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
5: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature
View Scheme
1027595-29-4

2-Chloro-N-(4-methoxy-benzyl)-N-((E)-2-methyl-but-1-enyl)-2-methylsulfanyl-acetamide

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: SiO2, H2O / 1.) 35 deg C, overnight then 60 deg C, 30 min, 2.) benzene, 1 h
2: 58 percent / Raney nickel (W-2) / ethanol / 3 h / Heating
3: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
4: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature
View Scheme

C15H21NO2

77-67-8

ethosuximide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: copper (I) acetate; Bathocuproine; oxygen / toluene / 80 °C / 760.05 Torr
2: hydrogen; palladium on activated charcoal
View Scheme

Ethosuximide Chemical Properties

Molecular Structure of Ethosuximide (CAS NO.77-67-8):

EINECS: 201-048-7
IUPAC Name: 3-Ethyl-3-methylpyrrolidine-2,5-dione 
Molecular Formula: C7H11NO2
Molecular Weight: 141.167740 g/mol
XLogP3: 0.4
H-Bond Donor: 1
H-Bond Acceptor: 2
Canonical SMILES: CCC1(CC(=O)NC1=O)C
InChI: InChI=1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
InChIKey: HAPOVYFOVVWLRS-UHFFFAOYSA-N
Index of Refraction: 1.608
Molar Refractivity: 35.06 cm3
Molar Volume: 101.3 cm3
Surface Tension: 56.1 dyne/cm
Density: 1.274 g/cm3
Flash Point: 77.9 °C
Melting Point: 51 °C
Enthalpy of Vaporization: 44.14 kJ/mol
Boiling Point: 205.2 °C at 760 mmHg
Vapour Pressure: 0.254 mmHg at 25 °C
Water Solubility: 5.51e+004 mg/L at 25 °C
BRN: 0117054

Ethosuximide Toxicity Data With Reference

1.    

cyt-hmn:lyms 30 mg/L

    MUREAV    Mutation Research. 204 (1988),623.
2.    

orl-rat TDLo:66,600 µg/kg (6-14D preg):REP

    40YJAX    Evaluation of Embryotoxicity, Mutagenicity and Carcinogenicity Risks In New Drugs Benesova, O., et al., eds.,Prague, Czechoslovakia.: Univerzita Karlova,1970,59.
3.    

orl-mus LD50:1530 mg/kg

    EPILAK    Epilepsia. 4 (4)(1963),66.
4.    

ipr-mus LD50:1752 mg/kg

    EPILAK    Epilepsia. 29 (1988),198.
5.    

scu-mus LD50:1810 mg/kg

    NIIRDN    “Drugs in Japan. Ethical Drugs, 6th Edition 1982“ Edited by Japan Pharmaceutical Information Center. 6 (1982),117.
6.    

ivn-mus LD50:780 mg/kg

    NEPHBW    Neuropharmacology. 24 (1985),427.

Ethosuximide Safety Profile

Safety Information of Ethosuximide (CAS NO.77-67-8):
Hazard Codes: Xn Harmful
Risk Statements: 22
R22:Harmful if swallowed
Safety Statements: 36
S36:Wear suitable protective clothing
WGK Germany: 3
RTECS: WN2800000
Moderately toxic by ingestion, intravenous, subcutaneous, and intraperitoneal routes. Experimental teratogenic and reproductive effects. Mutation data reported. An anticonvulsant. When heated to decomposition it emits toxic fumes of NOx.

Ethosuximide Specification

  Ethosuximide with CAS registry number of 77-67-8 is also known as Ethosuximide [USAN:INN:BAN:JAN] ; (+-)-2-Ethyl-2-methylsuccinimide ; 2,5-Pyrrolidinedione, 3-ethyl-3-methyl- ; 2,5-Pyrrolidinedione, 3-ethyl-3-methyl-, (+-)- ; 2-Ethyl-2-methylsuccinimide ; 2-Methyl-2-ethylsuccinimide ; 3-Ethyl-3-methylpyrrolidine-2,5-dione ; 3-Ethyl-3-methylsuccinimide ; 3-Methyl-3-ethylpyrrolidine-2,5-dione ; 3-Methyl-3-ethylsuccinimide ; 5-21-09-00595 (Beilstein Handbook Reference) ; Aethosuccimidum ; Aethosuximide ; Aethosuximide [German] ; Asamid ; Atysmal ; C.I. 366 ; CI 366 ; CN-10,395 ; Capitus ; Emeside ; Epileo Petit MAL ; Ethosuccimide ; Ethosuccinimide ; Ethosuxide ; Ethosuximide ; Ethosuximidum ; Ethosuximidum [INN-Latin] ; Ethymal ; Etomal ; Etosuccimide ; Etosuccimide [DCIT] ; Etosuximid ; Etosuximida ; Etosuximida [INN-Spanish] ; Etosuximide ; H 940 ; H-490 ; HSDB 1119 ; Mesentol ; N-Ethyl methylsuccinimide ; NSC 64013 ; PM 671 ; Pemal ; Pemalin ; Pentinimid ; Peptinimid ; Petinimid ; Petnidan ; Piknolepsin ; Pyknolepsinum ; Ronton ; Simatin ; Simatin(E) ; Succimal ; Succimitin ; Succinimide, 2-ethyl-2-methyl- ; Suxilep ; Suximal ; Suxin ; Suxinutin ; Thetamid ; Thilopemal ; UNII-5SEH9X1D1D ; Zaraondan ; Zarodan ; Zarondan ; Zarondan-saft ; Zarontin ; Zartalin ; alpha-Ethyl-alpha-methylsuccinimide ; alpha-Methyl-alpha-ethylsuccinimide ; gamma-Methyl-gamma-ethyl-succinimide . It is a drug for treating absence seizures under the trade names Emeside and Zarontin due to the mechanism of action which is ethosuximide is a T-type calcium channel blocker with an IC50 of 12 ± 2 mmol/L. Emeside capsules were discontinued by their manufacturer, Laboratories for Applied Biology, in 2005. Zarontin capsules were discontinued by Pfizer in 2007. Syrup preparations of both brands are still available.

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