Alprazolam Chemical Properties

Melting point:

228-228.50C

Boiling point:

463.51°C (rough estimate)

Density 

1.2000 (rough estimate)

refractive index 

1.6110 (estimate)

Flash point:

11 °C

storage temp. 

2-8°C

solubility 

H₂O: insoluble

pka

2.37±0.40(Predicted)

Water Solubility 

70mg/L(ambient temperature)

BCS Class

1

CAS DataBase Reference

28981-97-7(CAS DataBase Reference)

NIST Chemistry Reference

Alprazolam(28981-97-7)

EPA Substance Registry System

Alprazolam (28981-97-7)

Safety Information

Hazard Codes 

Xn,T,F

Risk Statements 

22-39/23/24/25-23/24/25-11

Safety Statements 

36-45-36/37-16-7

RIDADR 

3249

WGK Germany 

3

RTECS 

XZ5473000

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2933910000

Hazardous Substances Data

28981-97-7(Hazardous Substances Data)

Toxicity

LD50 in mice, rats (mg/kg): 1020, >2000 orally; 540, 610 i.p. (Nakajima)

DEA Controlled Substances

CSCN: 2882
CAS SCH: Ⅳ
NARC: N

MSDS

• Language:English Provider:Alprazolam
• Language:English Provider:SigmaAldrich

Alprazolam Usage And Synthesis

Description

Alprazolam (Item No. 14255) is an analytical reference material categorized as a benzodiazepine. Alprazolam is regulated as a Schedule IV compound in the United States. This product is intended for research and forensic applications.

Chemical Properties

White Crystalline Solid

Originator

Xanax ,Upjohn ,US ,1981

Uses

Controlled substance (depressant). Anxiolytic

Uses

Atorvastatin metabolite

Definition

ChEBI: A member of the class of triazolobenzodiazepines that is 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine carrying methyl, phenyl and chloro substituents at positions 1, 6 and 8 respectively. Alprazolam is only found in individu ls that have taken this drug.

Manufacturing Process

6-Chloro-2-hydrazino-4-phenylquinoline: A stirred mixture of 2,6-dichloro-4- phenylquinoline (2.7 g, 0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuum. The residue was suspended in warm water, and the solid was collected by filtration, dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g (67% yield) of 6-chloro-2-hydrazino-4-phenylquinoline of melting point 156.5-157°C. 7-Chloro-1-methyl-5-phenyl-s-trizolo[4,3-a]quinoline: A stirred mixture of 6- chloro-2-hydrazino-4-phenylquinoline (1.4 g, 0.0052 mol), triethylorthoacetate (0.925 g, 0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short, glass helix-packed column. The mixture was concentrated to dryness in vacuum and the residue was crystallized from methanol-ethyl acetate to give: 1.28 g of 7-chloro-1- methyl-5-phenyl-s-triazolo[4,3-a]quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride:methanol and had a melting point 252.5-253.5°C.
5-Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone (Oxidation of 7- chloro-1-methyl-5-phenyl-s-trizolo[4,3-a]quinoline): A stirred suspension of 7- chloro-1-methyl-5-phenyl-s-triazolo[4,3-a] quinoline (2,94 g, 0.01 mol) in acetone (110 ml) was cooled in an ice-bath and treated slowly with a solution prepared by adding sodium periodate (2 g) to a stirred suspension of ruthenium dioxide (200 mg) in water (35 ml). The mixture became dark. Additional sodium periodate (8 g) was added during the next 15 minutes. The ice-bath was removed and the mixture was stirred for 45 minutes. Additional sodium periodate (4 g) was added and the mixture was stirred at ambient temperature for 18 hours and filtered. The solid was washed with acetone and the combined filtrate was concentrated in vacuum. The residue was suspended in water and extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate and concentrated. The residue was chromatographed on silica gel (100 g) with 10% methanol and 90% ethyl acetate; 50 ml fractions were collected. The product was eluted in fractions 10-20 and was crystallized from ethyl acetate to give: 0.405 g of melting point 168-169.5°C and 0.291 g of melting point 167.5-169°C (23.4% yield) of 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone. The analytical sample had a melting point of 168°C.
5-Chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]benzophenone: A stirred mixture of 5-chloro-2-(3-methyl-4H-1,2,4-triazolo-4- yl)benzophenone, (2.98 g, 0.01 mol) paraformaldehyde (3 g) and xylene (100 ml) was warmed under nitrogen, in a bath maintained at 125°C for 7 hours. The mixture was then concentrated in vacuum. The residue was chromatographed on silica gel (150 g) with 3% methanol-97% chloroform. Fifty ml fractions were collected. The product was eluted in fractions 20-44. The fractions were concentrated and the residue was crystallized from ethanol-ethyl acetate to give: 1.64 g of melting point 138-142°C; 0.316 g of melting point 138.5-141°C; 0.431 g of melting point 139-141°C (72.8% yield) of 5-chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4- yl]benzophenone. The analytical sample had a melting point of 138-139°C. 5-Chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-benzophenone: A solution of 5-chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]- benzophenone (328 mg, 0.001 mol) in dry, hydrocarbon-stabilized chloroform (5 ml) was cooled in an ice-bath and treated with phosphorus tribromide (0.1 ml). The colorless solution was kept in the ice-bath for 55 minutes, at ambient temperature (22-24°C), for 5 hours. The resulting yellow solution was poured into a mixture of ice and dilute sodium bicarbonate. This mixture was extracted with chloroform. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated. The residue was crystallized from methylene chloride-ethyl acetate to give: 0.285 g of melting point 200- 240°C (decomposition) and 0.030 g of melting point 200-220°C (decomposition) of 5-chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4- yl]benzophenone. The analytical sample had a melting point of 200-240°C.
8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine: A stirred suspension of 5-chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol- 4-yl]-benzophenone (391 mg, 0.001 mol) in tetrahydrofuran (15 ml) was cooled in an ice-bath and treated with a saturated solution of ammonia in methanol (12.5 ml). The resulting solution was allowed to warm to ambient temperature and stand for 24 hours. It was then concentrated in vacuum. The residue was suspended in water, treated with a little sodium bicarbonate and extracted with methylene chloride. The extract was washed with brine, dried with anhydrous potassium carbonate and concentrated. The residue was crystallized from methylene chloride-ethyl acetate to give 0.220 g of crude product of melting point 227-228.5°C. Recrystallization of this material from ethyl acetate gave 0.142 g of melting point 228-229.5°C of 8-chloro-1- methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.

brand name

Niravam (Schwarz Pharma); Xanax (Pharmacia & Upjohn).

Therapeutic Function

Tranquilizer

General Description

Alprazolam, 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine (Xanax), israpidly absorbed from the GI tract. Protein binding is lower(～70%) than with most benzodiazepines because of itslower lipophilicity.α-Hydroxylation of the methyl group tothe methyl alcohol (a reaction analogous to benzylic hydroxylation)followed by conjugation is rapid; consequently,the duration of action is short. The drug is a highlypotent anxiolytic on a milligram basis.

Alprazolam(28981-97-7)Related Product Information

• Kresoxim-methyl
• Methylparaben
• PHENYL VALERATE
• 1H-Benzotriazole
• Basic Violet 1
• 1-CHLOROMETHYL-1H-1,2,4-TRIAZOLE
• Methanol
• Acetonitrile
• 5-Methyl-1H-benzotriazole
• Dichloromethylphenylsilane
• Methyl acrylate
• Trimethylphenylammonium chloride
• Methyltriphenylphosphonium bromide
• 1,2,4-Triazole
• Methyl
• Alprazolam
• Difluorochloromethane
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• Alprazolam Xanax