CHLORDIAZEPOXIDE HYDROCHLORIDE Chemical Properties

Melting point:

213°

solubility 

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

Stability:

Stable. Incompatible with strong oxidizing agents.

CAS DataBase Reference

438-41-5(CAS DataBase Reference)

EPA Substance Registry System

Chlordiazepoxide hydrochloride (438-41-5)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-62-63-68

Safety Statements 

22-36/37

WGK Germany 

3

RTECS 

DE9450000

HS Code 

2933910000

Toxicity

LD50 oral in rabbit: 590mg/kg

MSDS

• Language:English Provider:SigmaAldrich

CHLORDIAZEPOXIDE HYDROCHLORIDE Usage And Synthesis

Chemical Properties

white crystalline powder

Originator

Librium,Roche,W. Germany,1960

Uses

Sedative-hypnotic.

Manufacturing Process

A 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 name

Librium (Valeant).

Therapeutic Function

Tranquilizer

General Description

Chlordiazepoxide hydrochloride, 7-chloro-2-(methylamino)-5-phenyl-3H-1,4-benzodiazepine4-oxide monohydrochloride (Librium), is well absorbedafter oral administration. Peak plasma levels are reachedin 2 to 4 hours. The half-life of chlordiazepoxide is 6 to30 hours. N-demethylation and hydrolysis of the condensedamidino group are rapid and extensive, producing demoxepamas a major metabolite. Demoxepam can undergo fourdifferent metabolic fates. It is converted principally to itsactive metabolite nordazepam, which is also a major activemetabolite of diazepam, clorazepate, and prazepam.Nordazepam, in turn, is converted principally to active oxazepam(marketed separately), which conjugated to the excretedglucuronide. Because of the long half-life of parentdrug and its active metabolites, this drug is long acting andself-tapering. As with diazepam (vide infra), repeated administrationof chlordiazepoxide can result in accumulationof parent drug and its active metabolites, and thus cause excessivesedation.

General Description

Crystals or off-white powder.

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

Acidic salt of an amine. Materials in this group are generally soluble in water. The resulting solutions contain moderate concentrations of hydrogen ions and have pH's of less than 7.0. They react as acids to neutralize bases. These neutralizations generate heat, but less or far less than is generated by neutralization of inorganic acids, inorganic oxoacids, and carboxylic acid. They usually do not react as either oxidizing agents or reducing agents but such behavior is not impossible.

Hazard

CNS depressant. Manufacture and dosage controlled by law.

Fire Hazard

Flash point data for CHLORDIAZEPOXIDE HYDROCHLORIDE are not available. CHLORDIAZEPOXIDE HYDROCHLORIDE is probably combustible.

Safety Profile

Poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion and subcutaneous routes. An experimental teratogen. Experimental reproductive effects. Human systemic effects: ataxia, dlstorted perceptions, hallucinations, somnolence, and surface EEG changes. Mutation data reported. A minor tranquhzer. When heated to decomposition it emits very toxic fumes of HCl and NOx.

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: metabolism possibly increased by rifampicin.
Antipsychotics: enhanced sedative effects; serious adverse events reported with clozapine and benzodiazepines.
Antivirals: concentration possibly increased by ritonavir.
Sodium oxybate: enhanced effects of sodium oxybate - avoid.
Ulcer-healing drugs: metabolism inhibited by cimetidine.

Metabolism

Chlordiazepoxide is extensively metabolised in the liver. The elimination half-life of chlordiazepoxide ranges from about 6-30 hours, but its main active metabolite desmethyldiazepam (nordazepam) has a half-life of several days. Other pharmacologically active metabolites of chlordiazepoxide include desmethylchlordiazepoxide, demoxepam, and oxazepam.
Unchanged drug and metabolites are excreted in the urine, mainly as conjugated metabolites.

CHLORDIAZEPOXIDE HYDROCHLORIDE(438-41-5)Related Product Information

• Ziprasidone mesilate
• CHLORDIAZEPOXIDE HYDROCHLORIDE
• Acetophenone oxime
• Benzophenone oxime
• Benzophenone imine
• Chlordiazepoxide
• 2-AMINO-5-CHLOROBENZOPHENONE OXIME
• 4-CHLORO-O-TOLUIDINE HYDROCHLORIDE
• demethylchlordimeform
• 3-CHLOROBENZENECARBALDEHYDE OXIME
• (2-AMINOPHENYL)(PHENYL)METHANONE OXIME
• NORCHLORDIAZEPOXIDE
• CHLORDIAZEPOXIDE HYDROCHLORIDE - * PSY
• CHLORDIAZEPOXIDE HYDROCHLORIDE IMP. A (EP): 7-CHLORO-5-PHENYL-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE 4-OXIDE(DEMOXEPAM)
• CHLORDIAZEPOXIDE HYDROCHLORIDE IMP. C (EP): (2-AMINO-5-CHLOROPHENYL)PHENYL-METHANONE (AMINOCHLOROBENZOPHENONE)
• CHLORDIAZEPOXIDE HYDROCHLORIDE IMP. B (EP): 6-CHLORO-2-(CHLOROMETHYL)-4-PHENYLQUINAZOLINE 3-OXIDE
• N,N-didemethylchlordimeform
• Chlordiazepoxide Hcl