695-53-4

Basic information

• Product Name: 5,5-Dimethyloxazolidine-2,4-dione
• Synonyms: propazone;5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE;5,5'-DIMETHYLOXAZOLIDIN-2,4-DIONE;5,5'-DIMETHYLOXAZOLIDINE-2,4-DIONE;5,5-DIMETHYLOXAZOLIDINE-2,4-DIONE;DIMETHADIONE;2,4-Oxazolidinedione, 5,5-dimethyl-;5,5-Dimethyl-1,3-oxazolidine-2,4-dione
• CAS NO: 695-53-4
• Molecular Formula: C₅H₇NO₃
• Molecular Weight: 129.11
• EINECS: 211-781-4
• Product Categories: Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks;Oxazolines/Oxazolidines;Heterocycles;Oxazole&Isoxazole
• Mol File: 695-53-4.mol
• Article Data: 10

Chemical Properties

• Melting Point: 77-80 °C(lit.)
• Boiling Point: 137 °C / 6mmHg
• Flash Point: 44.2oC
• Appearance: White/Crystalline Powder
• Density: 1.3816 (rough estimate)
• Vapor Pressure: 4.01mmHg at 25°C
• Refractive Index: 1.4220 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform, Ethyl Acetate
• PKA: 6.13(at 37℃)
• Merck: 14,3213
• BRN: 113541
• CAS DataBase Reference: 5,5-Dimethyloxazolidine-2,4-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 5,5-Dimethyloxazolidine-2,4-dione(695-53-4)
• EPA Substance Registry System: 5,5-Dimethyloxazolidine-2,4-dione(695-53-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-40-33-36/37/38
• Safety Statements: 22-36-24/25-23-36/37-26
• WGK Germany: 3
• RTECS: RP9100000
• TSCA: Yes
• Hazardous Substances Data: 695-53-4(Hazardous Substances Data)

Usage

Description

5,5-Dimethyloxazolidine-2,4-dione is an organic compound that features a five-membered oxazolidine ring with two ketone groups at the 2 and 4 positions, and two methyl groups at the 5 position. It is known for its potential applications in various fields, including pharmaceuticals and chemical synthesis.

Uses

Used in Pharmaceutical Industry:
5,5-Dimethyloxazolidine-2,4-dione is used as a reactant in the synthesis of nickel benzoannulated or naphthoannulated β-oxatetraazachlorin complexes, which have potential applications in medicinal chemistry.
Used in Pharmacological Research:
5,5-Dimethyloxazolidine-2,4-dione is used as a molecule involved in pharmacological studies, including the identification of bioequivalent generic substitutes for antiepileptic drugs, screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis, and dissolving protein plugs in patients with choledochal cyst or pancreaticobiliary maljunctions.
Used in Anticonvulsant Applications:
5,5-Dimethyloxazolidine-2,4-dione is used as an anticonvulsant agent, which may help in the treatment of epilepsy and other seizure disorders.
Used in Intracellular pH Measurement:
5,5-Dimethyloxazolidine-2,4-dione is used as an in vivo measurement of intracellular pH, which can be useful in studying cellular processes and monitoring the effects of various treatments on cell physiology.

Safety Profile

Moderately toxic by intraperitoneal and intravenous routes. Experimental teratogenic and reproductive effects. When heated to decomposition it emits toxic fumes of NOx. Used as an anticonvulsant.

InChI:InChI=1/C5H7NO3/c1-3-4(7)6(2)5(8)9-3/h3H,1-2H3

Synthetic route

ethyl 2-hydroxy-2,2-dimethylethanoate (80-55-7) + Trichloroacetyl isocyanate (3019-71-4) → dimethadione (695-53-4)

Conditions	Yield
Stage #1: ethyl 2-hydroxy-2,2-dimethylethanoate; Trichloroacetyl isocyanate In dichloromethane at 0 - 20℃; Stage #2: With triethylamine In ethanol Reflux;	72%

5,5-dimethyl-2-thioxo-4-oxazolidinone (6453-39-0) + diethyl sulphite (623-81-4) → dimethadione (695-53-4) + 3-ethyl-5,5-dimethyl-2-thioxo-oxazolidin-4-one (17994-46-6)

Conditions	Yield
With potassium carbonate; acetone

5,5-dimethyl-2-thioxo-4-oxazolidinone (6453-39-0) → dimethadione (695-53-4)

Conditions	Yield
With water; lead acetate
With water; bromine; potassium bromide

sodium ethanolate (141-52-6) + urea (57-13-6) + ethyl 2-hydroxy-2,2-dimethylethanoate (80-55-7) → dimethadione (695-53-4)

urea (57-13-6) + ethyl 2-hydroxy-2,2-dimethylethanoate (80-55-7) → dimethadione (695-53-4)

Conditions	Yield
With sodium ethanolate

5,5-dimethyl-4-p-tolylimino-oxazolidin-2-one (26212-62-4) → dimethadione (695-53-4)

Conditions	Yield
With hydrogenchloride In ethanol for 10h; Heating;

trimethadione (127-48-0) → dimethadione (695-53-4)

Conditions	Yield
metabolism study in epileptic fowl;
With human liver microsomes In various solvent(s) at 37℃; for 0.333333h; Enzyme kinetics; N-demethylation; Enzymatic reaction;

4-(tert-Butylimino)-5,5-dimethyloxazolidin-2-on (77626-29-0) → dimethadione (695-53-4)

Conditions	Yield
With oxonium

isocyanate de chlorosulfonyle (1189-71-5) + 2-hydroxy-2-methylpropanenitrile (75-86-5) → dimethadione (695-53-4)

Conditions	Yield
With hydrogenchloride; triethylamine 1a) benzene, r.t., 1 h, 1b) reflux, 3 h, 2) EtOH, reflux, 6 h; Yield given. Multistep reaction;
Product distribution; multistep reaction; other cyanohydrins;

acetonylsulfocarbaminate → dimethadione (695-53-4)

Conditions	Yield
With silver nitrate
With lead(IV) tetraacetate

(α-bromo-isobutyryl)-carbamic acid ethyl ester (77609-28-0) → dimethadione (695-53-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) PCl5 2: petroleum ether; CHCl3 / Heating 3: H3O(1+) View Scheme

[2-Bromo-1-tert-butylamino-2-methyl-prop-(E)-ylidene]-carbamic acid ethyl ester (77609-26-8) → dimethadione (695-53-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: petroleum ether; CHCl3 / Heating 2: H3O(1+) View Scheme

(2-ethoxy-5,5-dimethyl-oxazol-4-ylidene)-p-tolyl-amine (26212-60-2) → dimethadione (695-53-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: AcOH / acetone / 3 h / Ambient temperature 2: aq. HCl / ethanol / 10 h / Heating View Scheme

methyl 2-hydroxy-2-methylpropionate (2110-78-3) + urea (57-13-6) → dimethadione (695-53-4)

Conditions	Yield
With sodium methylate In methanol

dimethadione (695-53-4) + benzylacrylate (2495-35-4) → benzyl 3-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)propanoate (1076230-05-1)

Conditions	Yield
With pyridine In water at 20℃; for 22h; Heating / reflux;	100%

dimethadione (695-53-4) + 2-(3,4-dimethoxyphenyl)ethyl alcohol (7417-21-2) → 3-<2-(3,4-dimethoxyphenyl)ethyl>-5,5-dimethyloxazolidine-2,4-dione (86970-73-2)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃;	99%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 14h; Ambient temperature;	70%

dimethadione (695-53-4) + 2-nitrobenzyl chloride (612-23-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 5,5-dimethyl-3-(2-nitrobenzyl)oxazolidine-2,4-dione (907994-44-9)

Conditions	Yield
With potassium carbonate In hexane; water	93%

dimethadione (695-53-4) + 2-nitrobenzyl chloride (612-23-7) → 5,5-dimethyl-3-(2-nitrobenzyl)oxazolidine-2,4-dione (907994-44-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h;	93%

dimethadione (695-53-4) + 3'-(Dimethylamino)spiroazirin> (108805-12-5) → 4-(Dimethylamino)-1-(2-hydroxy-2-methylpropanoyl)-1,3-diazaspiro<4.4>non-3-en-2-on (131842-37-0)

Conditions	Yield
In acetonitrile for 120h; Ambient temperature;	88%

dimethadione (695-53-4) + 3-dimethylamino-2,2-dimethyl-2H-azirine (54856-83-6) → 5-(Dimethylamino)-3,4-dihydro-3-(2'-hydroxy-2'-methylpropionyl)-4,4-dimethyl-2H-imidazol-2-on (117460-19-2)

Conditions	Yield
In acetonitrile for 120h; Mechanism; Ambient temperature; 15N labelling experiments;	83%
In acetonitrile for 120h; Ambient temperature;	83%

dimethadione (695-53-4) + benzoyl chloride (98-88-4) → 3-Benzoyl-5,5-dimethyl-oxazolidine-2,4-dione (74529-69-4)

Conditions	Yield
With pyridine; aluminium trichloride In acetonitrile for 3h; Ambient temperature;	73%

dimethadione (695-53-4) + p-toluenesulfonyl chloride (98-59-9) → 5,5-dimethyl-N-[(4-methylphenyl)sulfonyl]oxazolidine-2,4-dione (74529-55-8)

Conditions	Yield
With pyridine; aluminium trichloride In acetonitrile for 3h; Ambient temperature;	73%
With sodium In tetrahydrofuran for 3h; Reflux;	22%

dimethadione (695-53-4) + 3-(Dimethylamino)-2-methyl-2-(1-methylethyl)-2H-azirin (107267-45-8) → 5-(Dimethylamino)-3,4-dihydro-4-isopropyl-4-methyl-3-(2-hydroxy-2-methylpropanoyl)-2H-imidazol-2-on (131842-36-9)

Conditions	Yield
In acetonitrile for 120h; Mechanism; Ambient temperature;	72%
In acetonitrile for 120h; Ambient temperature;	72%

2-thiophenethanol (5402-55-1) + dimethadione (695-53-4) → 5,5-Dimethyl-3-(2-thiophen-2-yl-ethyl)-oxazolidine-2,4-dione (86970-75-4)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 14h; Ambient temperature;	68%

2-(2-methyl-[3]thienyl)-ethanol (89500-82-3) + dimethadione (695-53-4) → 5,5-Dimethyl-3-[2-(2-methyl-thiophen-3-yl)-ethyl]-oxazolidine-2,4-dione (89500-85-6)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 14h; Ambient temperature;	68%

dimethadione (695-53-4) + 2-(3,4-dihydronaphthalen-1-yl)ethan-1-ol (4725-34-2) → N-<2-(3,4-dihydro-1-naphtyl)ethyl>-5,5-dimethyl-2,4-oxazolidinedione

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 14h; Ambient temperature;	65%

dimethadione (695-53-4) + 2-(2-hydroxypropyl)-5-methylthiophene (86970-96-9) → 5,5-Dimethyl-3-[1-methyl-2-(5-methyl-thiophen-2-yl)-ethyl]-oxazolidine-2,4-dione (86970-77-6)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 14h; Ambient temperature;	65%

dimethadione (695-53-4) + 1-cyclohexyl-N-(2-hydroxyethyl)-3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide → 1-Cyclohexyl-N-[2-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)-ethyl]-3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 2h;	65%

dimethadione (695-53-4) + 4-methoxy-benzoyl chloride (100-07-2) → 5,5-dimethyl-N-(4-methoxybenzoyl)oxazolidine-2,4-dione (1381863-04-2)

Conditions	Yield
Stage #1: 4-methoxy-benzoyl chloride With triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: dimethadione In tetrahydrofuran Reflux;	41%

methyl 3,4,5,7-tetra-O-benzoyl-α-D-gluco-hept-2-ulopyranosonate + dimethadione (695-53-4) → 5,5-dimethyl-3-[methyl (3,4,5,7-tetra-O-benzoyl-β-D-gluco-hept-2-ulopyranosyl)onate]oxazolidin-2,4-dione

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 24h; Mitsunobu Displacement; stereoselective reaction;	33%

dimethadione (695-53-4) + 4-fluoro-3-(trifluoromethyl)phenylboronic acid → 3-[4-fluoro-3-(trifluoromethyl)phenyl]-5,5-dimethyloxazolidine-2,4-dione

Conditions	Yield
With oxygen; copper diacetate In methanol at 70℃; for 12h;	29%

dimethadione (695-53-4) + 1,2-dicyanonaphthalene (19291-76-0) → 2,2-dimethyl-3-oxa-tri(1,2-naphtho)tetraazachlorin, nickel complex

Conditions	Yield
With ammonium molybdate; urea; nickel dichloride In quinoline at 250℃; for 0.5h; Inert atmosphere;	8%

dimethadione (695-53-4) + 2,3-Naphthalenedicarboxylic anhydride (716-39-2) → 2,2-dimethyl-3-oxa-tri(2,3-naphtho)tetraazachlorin, nickel complex (1310681-92-5)

Conditions	Yield
With ammonium molybdate; urea; nickel dichloride In sulfolane for 1h; Inert atmosphere; Reflux;	6.4%

dimethadione (695-53-4) + phthalimide (136918-14-4) → 2,2-dimethyl-3-oxa-tribenzo-tetraazachlorin, nickel complex (1310681-91-4)

Conditions	Yield
With ammonium molybdate; urea; nickel dichloride In quinoline at 250℃; for 0.166667h; Inert atmosphere;	5.6%

dimethadione (695-53-4) + phthalonitrile (91-15-6) → 2,2-dimethyl-3-oxa-tribenzo-tetraazachlorin, nickel complex (1310681-91-4)

Conditions	Yield
With ammonium molybdate; urea; nickel dichloride In quinoline at 250℃; for 0.5h; Inert atmosphere;	4.2%

diazomethane (186581-53-3, 908094-01-9) + dimethadione (695-53-4) → trimethadione (127-48-0)

2-vinylpyridine (100-69-6) + dimethadione (695-53-4) → 5,5-dimethyl-3-(2-pyridin-2-yl-ethyl)-oxazolidine-2,4-dione (104509-14-0)

1-bromo-butane (109-65-9) + dimethadione (695-53-4) → 3-butyl-5,5-dimethyl-oxazolidine-2,4-dione (99063-24-8)

Conditions	Yield
With potassium carbonate; acetone

dimethadione (695-53-4) + diethyl sulfate (64-67-5) → 3-ethyl-5,5-dimethyl-oxazolidine-2,4-dione (520-77-4)

Conditions	Yield
With potassium carbonate; acetone
With potassium ethoxide
With potassium carbonate; acetone

dimethadione (695-53-4) + tert-butylamine (75-64-9) → α-(N'-tert-butyl-ureido)-isobutyric acid (118979-45-6)

dimethadione (695-53-4) + 2-(diethylamino)ethyl chloride (100-35-6) → 3-(2-diethylamino-ethyl)-5,5-dimethyl-oxazolidine-2,4-dione

Conditions	Yield
With sodium ethanolate

dimethadione (695-53-4) + dimethyl sulfate (77-78-1) → trimethadione (127-48-0)

dimethadione (695-53-4) + methyl iodide (74-88-4) → trimethadione (127-48-0)

Conditions	Yield
With methanol; potassium hydroxide

Upstream product

• 141-52-6 sodium ethanolate 
• 57-13-6 urea 
• 80-55-7 ethyl 2-hydroxy-2,2-dimethylethanoate 
• 26212-62-4 5,5-dimethyl-4-p-tolylimino-oxazolidin-2-one 
• 26212-60-2 (2-ethoxy-5,5-dimethyl-oxazol-4-ylidene)-p-tolyl-amine 
• 2110-78-3 methyl 2-hydroxy-2-methylpropionate 
• 3019-71-4 Trichloroacetyl isocyanate 
• 77609-26-8 [2-Bromo-1-tert-butylamino-2-methyl-prop-(E)-ylidene]-carbamic acid ethyl ester 
• 77609-28-0 (α-bromo-isobutyryl)-carbamic acid ethyl ester 
• 1189-71-5 isocyanate de chlorosulfonyle 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 77626-29-0 4-(tert-Butylimino)-5,5-dimethyloxazolidin-2-on 
• 127-48-0 trimethadione 
• 6453-39-0 5,5-dimethyl-2-thioxo-4-oxazolidinone 

Downstream Products

• 520-77-4 3-ethyl-5,5-dimethyl-oxazolidine-2,4-dione 
• 127-48-0 trimethadione 
• 74529-69-4 3-Benzoyl-5,5-dimethyl-oxazolidine-2,4-dione 
• 74529-55-8 5,5-dimethyl-N-[(4-methylphenyl)sulfonyl]oxazolidine-2,4-dione 
• 1381863-04-2 5,5-dimethyl-N-(4-methoxybenzoyl)oxazolidine-2,4-dione 
• 473724-01-5 C₄₄H₅₃N₅O₉ 
• 1076230-05-1 benzyl 3-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)propanoate 
• 259827-47-9 2-[3-(1-adamantyl)-2-(5,5-dimethyl-2,4-dioxooxazolidinyl)-3-oxopropanamido]-4-nitroanisole 
• 907994-44-9 5,5-dimethyl-3-(2-nitrobenzyl)oxazolidine-2,4-dione 
• 86970-90-3 (5R,9bS)-1,1,5,8-Tetramethyl-1,5,6,9b-tetrahydro-oxazolo[3,4-a]thieno[3,2-c]pyridin-3-one 
• 86970-88-9 1,5,6,10b-Tetrahydro-8,9-dimethoxy-1,1-dimethyl-3H-oxazolo<4,3-a>isoquinolin-3-one 
• 89500-95-8 1,1,7-Trimethyl-1,5,6,9b-tetrahydro-oxazolo[3,4-a]thieno[3,4-c]pyridin-3-one 
• 182553-19-1 4-n-butyl-3-[2-(3,4-dimethoxyphenyl)ethyl]-4-hydroxy-5,5-dimethyloxazolidin-2-one 
• 594-61-6 2-methyllactic acid 

Relevant articles and documents

Trimethadione metabolism by human liver cytochrome P450: Evidence for the involvement of CYP2E1

1. Caucasian liver samples were used in this study. N-demethylation of trimethadione (TMO) to dimethadione (DMO) was monitored in the presence of chemical inhibitors of CYPs, such as fluconazole, quinidine, dimethyl-nitrosamine, acetaminophen, phenacetin, chlorzoxazone and mephenytoin. Trimethadione N-demethylation was selectively inhibited by dimethylnitrosamine and chlorzoxazone (> 50%) and weakly inhibited by tolbutamide (12%) and fluconazole (22%), whereas other inhibitors showed no effect. This result suggested that TMO metabolism to DMO is mainly mediated by CYP2E1 and marginally by CYP2C and CYP3A4. 2. Fifteen human livers were screened and interindividual variability of TMO N-demethylation activity was 3-fold. Chlorzoxazone 6-hydroxylation activity was also measured and both activities were significantly correlated (r = 0.735, p 0.01). 3. DMO production by human cDNA expressed CYP enzymes was observed mainly for CYP2E1 (10.8 nmol/tube), marginally for CYP2C8 (0.22 nmol/tube) and not detectable for other CYP enzymes. 4. These results indicate that TMO metabolism is primarily catalysed by CYP2E1 and that trimethadione would be a suitable selective probe drug for the estimation of human CYP2E1 activity in vivo.

A facile one-pot synthesis of 3-unsubstituted-2,4-oxazolidinediones via in situ generation of carbamates from α-hydroxyesters using trichloroacetyl isocyanate

A convenient, high yield one-pot methodology for the synthesis of pharmaceutically interesting 3-unsubstituted-2,4-oxazolidinediones from α-hydroxyesters is described. A primary carbamate was generated in situ from the corresponding α-hydroxyester and tri

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