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)

Flash point:

9℃

storage temp. 

Controlled Substance, -20°C Freezer, Under Inert Atmosphere

solubility 

Practically insoluble in water, sparingly soluble in ethanol (96 per cent)

pka

4.8(at 25℃)

form 

A crystalline solid

Water Solubility 

2g/L(room temperature)

CAS DataBase Reference

58-25-3(CAS DataBase Reference)

NIST Chemistry Reference

Benzodiazepine-4-oxide, 7-chloro-2-methylamino-5-phenyl-3h-1,4-(58-25-3)

EPA Substance Registry System

Chlordiazepoxide (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 Data

58-25-3(Hazardous Substances Data)

Toxicity

LD50 oral in rabbit: 590mg/kg

Chlordiazepoxide Usage And Synthesis

Chemical Properties

Pale Yellow Solid

Originator

Librium,Roche,W. Germany,1960

Uses

Controlled substance (depressant). Anxiolytic. Prototype of the benzodiazepine anxiolytics

Definition

ChEBI: 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 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

Synthesis Reference(s)

The Journal of Organic Chemistry, 26, p. 1111, 1961 DOI: 10.1021/jo01063a034

Hazard

Anticonvulsant, sedative, and amnesic properties.

Metabolism

Chlordiazepoxide 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(58-25-3)Related Product Information

• NITRIC OXIDE
• CHLOROPHOSPHONAZO III
• Bensulfuron methyl
• ETHYLENE OXIDE
• Methyl acrylate
• Iron oxide
• DBU
• Methylparaben
• superoxide dismutase
• Kresoxim-methyl
• Tranexamic Acid
• Methotrexate
• PHENYL VALERATE
• (Diethoxymethyl)diphenylphosphine oxide
• Methyl
• Methotrexate USP25
• NITROUS OXIDE
• Methyl bromide