Disclaimer : I dont encourage anyone to do this as the chemicals used in this are extremely volatile and this is also highly illegal so this is for educational purposes only
Synthesis of Alprazolam
WARNING:
This synthesis is highly complex and takes several hours to complete. It involves handling volatile and toxic chemicals and should only be attempted by a professional. Proceed with extreme caution.
Raw Materials:
[] 2,6-Dichloro-4-phenylquinoline
[] Hydrazine Hydrate
[] Triethyl Orthoacetate
[] Sodium Periodate
[] Paraformaldehyde
[] Phosphorus Tribromide
[*] Ammonia
Step-by-Step Synthesis:
Step 1: Preparation of 6-Chloro-2-hydrazino-4-phenylquinoline
[] Mixing the Reactants: Combine 2,6-dichloro-4-phenylquinoline (2.7 g, 0.01 mol) and hydrazine hydrate (6.8 g) in a stirred mixture.
[] Refluxing: Reflux the mixture under nitrogen for 1 hour.
[] Concentration: Concentrate the mixture in vacuo.
[] Filtration: Suspend the residue in warm water and collect the solid by filtration.
[*] Drying and Recrystallization: Dry the solid and recrystallize it from ethyl acetate and Skelly B hexanes to obtain 1.81 g (67% yield) of 6-chloro-2-hydrazino-4-phenylquinoline with a melting point of 156.5°-157°C.
Step 2: Preparation of 7-Chloro-1-methyl-6-phenyl-s-triazolo[4,3-a]quinoline
[] Mixing the Reactants: Combine 6-chloro-2-hydrazino-4-phenylquinoline (1.4 g, 0.0052 mol), triethyl orthoacetate (0.925 g, 0.0057 mol), and xylene (100 ml) in a stirred mixture.
[] Refluxing: Reflux the mixture under nitrogen for 2 hours and 40 minutes, removing the ethanol formed by distillation.
[] Concentration: Concentrate the mixture to dryness in vacuo.
[] Crystallization: Crystallize the residue from methanol and ethyl acetate to obtain 1.28 g (83.9% yield) of 7-chloro-1-methyl-6-phenyl-s-triazolo[4,3-a]quinoline with a melting point of 252.5°C-253.5°C.
Step 3: Oxidation to 5-Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone
Synthesis of Alprazolam
WARNING:
This synthesis is highly complex and takes several hours to complete. It involves handling volatile and toxic chemicals and should only be attempted by a professional. Proceed with extreme caution.
Raw Materials:
[] 2,6-Dichloro-4-phenylquinoline
[] Hydrazine Hydrate
[] Triethyl Orthoacetate
[] Sodium Periodate
[] Paraformaldehyde
[] Phosphorus Tribromide
[*] Ammonia
Step-by-Step Synthesis:
Step 1: Preparation of 6-Chloro-2-hydrazino-4-phenylquinoline
[] Mixing the Reactants: Combine 2,6-dichloro-4-phenylquinoline (2.7 g, 0.01 mol) and hydrazine hydrate (6.8 g) in a stirred mixture.
[] Refluxing: Reflux the mixture under nitrogen for 1 hour.
[] Concentration: Concentrate the mixture in vacuo.
[] Filtration: Suspend the residue in warm water and collect the solid by filtration.
[*] Drying and Recrystallization: Dry the solid and recrystallize it from ethyl acetate and Skelly B hexanes to obtain 1.81 g (67% yield) of 6-chloro-2-hydrazino-4-phenylquinoline with a melting point of 156.5°-157°C.
Step 2: Preparation of 7-Chloro-1-methyl-6-phenyl-s-triazolo[4,3-a]quinoline
[] Mixing the Reactants: Combine 6-chloro-2-hydrazino-4-phenylquinoline (1.4 g, 0.0052 mol), triethyl orthoacetate (0.925 g, 0.0057 mol), and xylene (100 ml) in a stirred mixture.
[] Refluxing: Reflux the mixture under nitrogen for 2 hours and 40 minutes, removing the ethanol formed by distillation.
[] Concentration: Concentrate the mixture to dryness in vacuo.
[] Crystallization: Crystallize the residue from methanol and ethyl acetate to obtain 1.28 g (83.9% yield) of 7-chloro-1-methyl-6-phenyl-s-triazolo[4,3-a]quinoline with a melting point of 252.5°C-253.5°C.
Step 3: Oxidation to 5-Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone
[] Preparation of the Suspension: Suspend 7-chloro-1-methyl-6-phenyl-s-triazolo[4,3-a]quinoline (2.94 g, 0.01 mol) in acetone (110 ml) and cool in an ice bath.
[] Adding Sodium Periodate: Slowly add a solution of sodium periodate (2 g) and ruthenium dioxide (200 mg) in water (35 ml) to the suspension.
[] Stirring: Stir the mixture for 45 minutes, add additional sodium periodate (8 g), and stir for another 18 hours at ambient temperature.
[] Filtration and Concentration: Filter the mixture, wash the solid with acetone, and concentrate the filtrate in vacuo.
[] Extraction and Chromatography: Suspend the residue in water, extract with methylene chloride, dry over anhydrous potassium carbonate, and concentrate. Chromatograph the residue on silica gel with 10% methanol and 90% ethyl acetate to obtain 0.405 g and 0.291 g (23.4% yield) of 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone with melting points of 168°C-169.5
Last edited: