Bromazepam Chemical Properties

Melting point:

237-238.5oC (dec.)

Boiling point:

490.7±45.0 °C(Predicted)

Density 

1.5573 (rough estimate)

refractive index 

1.6520 (estimate)

Flash point:

11 °C

storage temp. 

2-8°C

solubility 

Practically insoluble in water, slightly soluble or sparingly soluble in ethanol (96 per cent) and in methylene chloride.

pka

pKa 2.5(spectro, polarographic) (Uncertain);5.2(spectro, polarographic) (Uncertain);11.8(spectro, polarographic) (Uncertain)

form 

A crystalline solid

CAS DataBase Reference

1812-30-2(CAS DataBase Reference)

NIST Chemistry Reference

Bromazepam(1812-30-2)

Safety Information

Hazard Codes 

Xn,T,F

Risk Statements 

22-36/37/38-39/23/24/25-23/24/25-11

Safety Statements 

26-36-45-36/37-16-7

RIDADR 

3249

WGK Germany 

3

RTECS 

DE9800000

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2933330000

Toxicity

LD50 orally in rats: 3050 ±405 mg/kg (Goldenthal)

MSDS

• Language:English Provider:SigmaAldrich

Bromazepam Usage And Synthesis

Description

Bromazepam is a psychoactive benzodiazepine derivative and prescription drug that is commonly abused and often used in ‘drug-facilitated crimes’. This product is intended for forensic and research applications.

Chemical Properties

Crystalline Solid

Originator

Lexotan,Roche,Italy,1975

Uses

Controlled substance (depressant). Anxiolytic.

Definition

ChEBI: Bromazepam is an organic molecular entity.

Manufacturing Process

Example: 32.8 grams of 2-(2-aminobenzoyl)-pyridine and 200 cc of acetic anhydride were stirred at room temperature for 3 hours and then permitted to stand overnight. Evaporation to dryness and digestion of the residue with 200 cc of water containing a little sodium bicarbonate to make the pH slightly alkaline gave 2-(2-acetamidobenzoyl)-pyridine as a light tan powder, which upon crystallization from methanol formed colorless crystals melting at 151°- 153°C.
A solution of 8.6 cc of bromine in 100 cc of acetic acid was added slowly over a 3.5 hour period to a stirred solution of 38.5 grams of 2-(2- acetamidobenzoyl)-pyridinein 250 cc of acetic acid. The dark solution was stirred for another 3 hours, permitted to stand over night, stirred for 1 hour with N2 sweeping, and evaporated at diminished pressure in the hood. The gummy residue (75 grams) was treated with water and ether, made alkaline with dilute sodium bicarbonate solution, and separated. Both phases contained undissolved product which was filtered off. Additional crops were obtained by further extraction of the aqueous phase with ether and evaporation of the resulting ether solutions. All these materials were recrystallized from methanol (decolorizing carbon added) yielding 2-(2-acetamido-5-bromobenzoyl)- pyridineas yellow crystals melting at 131.5°-133°C.
20.85 grams of 2-(2-acetamido-5-bromobenzoyl)-pyridinein 250 cc of 20% hydrochloric acid in ethanol were heated to reflux for 2 hours. 100 cc of alcohol were added after one hour to maintain fluidity. The mixture stood overnight, was chilled and filtered to give 20.5 grams of colorless crystalline 2-(2-amino-5-bromobenzoyl)-pyridinehydrochloride. Digestion of this hydrochloride with 0.5liter hot water hydrolyzed this product to the free base, 2-(2-amino-5-bromobenzoyl)-pyridine which formed yellow crystals, melting at 98°-100°C. Evaporation of the alcoholic mother liquor, water digestion of the residue, and alkalization of the water digests afforded additional crops of 2-(2-amino-5-bromobenzoyl)pyridine.
0.145 kg of 2-(2-amino-5-bromobenzoyl)-pyridine, was dissolved in 2.0 liters of glacial acetic acid. The resultant solution was placed in a 3 liter, 3-necked, round bottom flask fitted with a stirrer, thermometer and dropping funnel. The system was protected by a drying tube filled with anhydrous calcium chloride. To the solution, with stirring at room temperature, were carefully added 46.7 ml of bromoacetyl bromide. After the addition was completed, the stirring was continued for two hours. The mixture was then warmed to 40°C, stirred at that temperature for 1.5 hours, chilled and filtered. The residue, after being washed with glacial acetic acid, was dried in vacuo over flake potassium hydroxide to give 2-(2-bromoacetamido-5-bromobenzoyl)- pyridinehydrobromide orange crystals, MP 205°-206°C, dec.
The hydrobromide was hydrolyzed to the free base as follows: 0.119 kg of 2- (2-bromoacetamido-5-bromobenzoyl)-pyridine hydrobromide was stirred with 1.2 liters of cold water for 3.5 hours. The mixture was chilled and filtered, and the residue washed with cold water and dried to give 2-(2-bromoacetamido-5- bromobenzoyl)-pyridine, MP 101°C (sinters), 103°-106°C, dec.
93.0 grams of 2-(2-bromoacetamido-5-bromobenzoyl)-pyridinewas carefully added to 0.5 liter of anhydrous ammonia in a 1 liter, 3-necked, round bottom flask equipped with stirrer and reflux condenser and cooled by a Dry Iceacetone bath. The system was protected from moisture by a drying tube containing anhydrous calcium chloride. After stirring for 2 hours, the cooling bath was removed. The mixture was then stirred for 6 hours, during which time the ammonia gradually boiled off. 0.4 liter of water was added to the solid residue and stirrind was resumed for about 2 hours. The solid was then filtered off, washed with water and dried in vacuo over potassium hydroxide flakes. The residue was dissolved on a steam bath in 1.4 liters of ethyl alcohol-acetonitrile (1:1) (decolorizing charcoal added). The solution was filtered hot and the filtrate chilled overnight. The crystalline deposit was filtered off, washed with cold ethyl alcohol and dried in vacuo over flake potassium hydroxide to give 54.2 grams. 7-Bromo-1,3-dihydro-5-(2-pyridyl)- 2H-1,4-benzodiazepin-2-one, MP 238°C (sinters), 239°-240.5°, dec. Further processing of the mother liquor yielded additional product.

brand name

Lectopam (Roche, Puerto Rico).

Therapeutic Function

Tranquilizer

Enzyme inhibitor

This lipophilic valium-like benzodiazepine (FW = 316.20 g/mol; CAS 1812- 30-2; IUPAC Name: 7-bromo-5-(pyridin-2-yl)-1H-benzo[e][1,4]diazepin- 2(3H)-one), is a long-lasting anxiolytic agent used to treat anxiety or panic states. Like diazepam, bromazepam is a positive allosteric modulator of GABAA receptors, promoting GABA binding, which in turn increases the total conduction of chloride ions across the neuronal cell membrane. Like other benzodiazepines, bromazepam also inhibits the acetylcholine receptoroperated potassium current. Bromazepam is mainly metabolized by oxidative pathways within the liver.

Bromazepam(1812-30-2)Related Product Information

• Sulfasalazine
• Chromium picolinate
• 3-METHYLADENINE
• DBU
• 4-Methylpyridine
• Diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
• BROMAZEPAM - * PSY
• Bromine
• 4'-Bromoacetanilide
• 4-BROMO-2-ETHYLACETANILIDE
• Bromazepam
• 4-BROMO-2-ETHYLANILINE
• 4-BROMO-N,2-DIETHYLANILINE
• CHEMBRDG-BB 5668895
• 2-ACETAMIDO-5-BROMOTOLUENE
• BROMAZEPAM [CONTROLLED SUBSTANCE]
• BROMAZEPAM FOR SYSTEM SUITABILITY - * PSY
• BROMAZEPAM IMP. A (EP): (2-AMINO-5-BROMOPHENYL)(PYRIDIN-2-YL)METHANONE