Chlordiazepoxide

Chlordiazepoxide Basic information
Product Name:Chlordiazepoxide
Synonyms:7-Cloro-2-metilamino-5-fenil-3H-1,4-benzodiazepina 4-ossido;7-cloro-2-metilamino-5-fenil-3h-1,4-benzodiazepina4-ossido;Abboxide;Chloradiazepoxide;Chloridazepoxide;Chloridiazepide;Chloridiazepoxide;Chlozepid
CAS:58-25-3
MF:C16H14ClN3O
MW:299.75
EINECS:200-371-0
Product Categories:Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
Mol File:58-25-3.mol
Chlordiazepoxide Structure
Chlordiazepoxide Chemical Properties
Melting point 230-232°C
Boiling point 549.0±60.0 °C(Predicted)
density 1.2967 (rough estimate)
refractive index 1.6490 (estimate)
Fp 9℃
storage temp. Controlled Substance, -20°C Freezer, Under Inert Atmosphere
solubility Practically insoluble in water, sparingly soluble in ethanol (96 per cent)
pka4.8(at 25℃)
form A crystalline solid
Water Solubility 2g/L(room temperature)
CAS DataBase Reference58-25-3(CAS DataBase Reference)
NIST Chemistry ReferenceBenzodiazepine-4-oxide, 7-chloro-2-methylamino-5-phenyl-3h-1,4-(58-25-3)
EPA Substance Registry SystemChlordiazepoxide (58-25-3)
Safety Information
Hazard Codes F,T
Risk Statements 11-23/24/25-39/23/24/25
Safety Statements 7-16-36/37-45
RIDADR 3249
WGK Germany 1
HazardClass 6.1(b)
PackingGroup III
HS Code 2933910000
Hazardous Substances Data58-25-3(Hazardous Substances Data)
ToxicityLD50 oral in rabbit: 590mg/kg
MSDS Information
Chlordiazepoxide Usage And Synthesis
Chemical PropertiesPale Yellow Solid
OriginatorLibrium,Roche,W. Germany,1960
UsesControlled substance (depressant). Anxiolytic. Prototype of the benzodiazepine anxiolytics
DefinitionChEBI: A benzodiazepine that is 3H-1,4-benzodiazepine 4-oxide substituted by a chloro group at position 7, a phenyl group at position 5 and a methylamino group at position 2.
Manufacturing ProcessA mixture of 202 g 2-amino-5-chlorobenzophenone, 190 g hydroxylamine hydrochloride, 500 cc pyridine and 1,200 cc alcohol was refluxed for 16 hours, then concentrated in vacuo to dryness. The residue was treated with a mixture of ether and water. The water was separated, the ether layer containing a considerable amount of precipitated reaction product was washed with some water and diluted with petroleum ether. The crystalline reaction product, 2-amino-5-chlorobenzophenone-alpha-oxime, was filtered off. The product was recrystallized from a mixture of ether and petroleum ether forming colorless prisms, MP 164 to 167°C.
To a warm solution (50°C) of 172.5 g (0.7 mol) of 2-amino-5- chlorobenzophenone-alpha-oxime in one liter glacial acetic acid were added 110 cc (1.47 mols) chloroacetyl chloride. The mixture was heated for 10 minutes at 50°C and then stirred at room temperature for 15 hours. The precipitated yellow prisms, 2-chloromethyl-4-phenyl-6-chloroquinazoline 3- oxide hydrochloride, were filtered off, melting range 128° to 150°C with dec.
The acetic acid mother liquor, containing the rest of the reaction product, was concentrated in vacuo. The residue was dissolved in methylene chloride and washed with ice cold sodium carbonate solution. The organic solution was dried, concentrated in vacuo to a small volume and diluted with ether and petroleum ether. Fine yellow needles of 2-chloromethyl-4-phenyl-6- chloroquinazoline 3-oxide precipitated. The pure base was recrystallized from a mixture of methylene chloride, ether and petroleum ether, MP 133° to 134°C.
Ninety-eight grams of 6-chloro-2-chloromethyl-4-phenylquinazoline 3-oxide hydrochloride were introduced into 600 cc of ice cold 25% methanolic methylamine. The mixture was initially cooled to about 30°C and then stirred at room temperature. After 15 hours the reaction product which precipitated was filtered off. The mother liquor was concentrated in vacuo to dryness. The residue was dissolved in methylene chloride, washed with water and dried with sodium sulfate. The methylene chloride solution was concentrated in vacuo and the crystalline residue was boiled with a small amount of acetone to dissolve the more soluble impurities. The mixture was then cooled at 5°C for 10 hours and filtered. The crystalline product, 7-chloro-2-methylamino-5- phenyl-3H-1,4-benzodiazepine 4-oxide, was recrystallized from ethanol forming light yellow plates, MP 236° to 236.5°C.
A solution of 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide in an equivalent amount of methanolic hydrochloric acid was diluted with ether and petroleum ether.
The precipitated hydrochloride was filtered off and recrystallized from methanol, MP 213°C.
Brand nameLibrium (Valeant).
Therapeutic FunctionTranquilizer
Synthesis Reference(s)The Journal of Organic Chemistry, 26, p. 1111, 1961 DOI: 10.1021/jo01063a034
HazardAnticonvulsant, sedative, and amnesic properties.
MetabolismChlordiazepoxide is well absorbed after oral administration, and peak blood concentration usually is reached in approximately 4 hours. Intramuscular absorption of chlordiazepoxide, however, is slower and erratic. The half-life of chlordiazepoxide is variable but usually quite long (6–30 hours). The initial N-demethylation product, N-desmethylchloridiazepoxide, undergoes deamination to form the demoxepam, which is extensively metabolized, and less than 1% of a dose of chlordiazepoxide is excreted as demoxepam. Demoxepam can undergo four different metabolic fates. Removal of the N-oxide moiety yields the active metabolite, N-desmethyldiazepam (desoxydemoxepam). This product is a metabolite of both chlordiazepoxide and diazepam and can be hydroxylated to yield oxazepam, another active metabolite that is rapidly glucuronidated and excreted in the urine. Another possibility for metabolism of demoxepam is hydrolysis to the “opened lactam,” which is inactive. The two other metabolites of demoxepam are the products of ring A hydroxylation (9-hydroxydemoxepam) or ring C hydroxylation (4′-hydroxydemoxepam), both of which are inactive.
Chlordiazepoxide Preparation Products And Raw materials
Raw materials2-Amino-5-chlorobenzophenone-->2-AMINO-5-CHLOROBENZOPHENONE OXIME-->Methylamine-->Hydrochloric acid-->HYDROXYLAMINE-->Chloroacetyl chloride
Methylparaben Methyl Bensulfuron methyl ETHYLENE OXIDE Methotrexate USP25 (Diethoxymethyl)diphenylphosphine oxide Iron oxide Difluorochloromethane NITRIC OXIDE Kresoxim-methyl DBU NITROUS OXIDE Methyl acrylate Metallic oxides Methyl bromide CHLOROPHOSPHONAZO III Diazapam Phenylacetic acid

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