Desomorphine Synthesis from Codeine
Step 1: Conversion of Codeine to α-Chlorocodide
Reagents and Materials:
50 g Codeine
55 g Thionyl chloride (SOCl₂)
Reflux setup with magnetic stirrer
Saturated brine (NaCl solution)
Procedure:
Place 50 g of codeine in a round-bottom flask.
While stirring, slowly add 55 g of thionyl chloride dropwise to the flask.
Reflux the mixture at 85 °C for 3 hours under constant stirring.
After completion, wash the reaction mixture three times with saturated salt water (brine) to remove acidic residues.
Separate the organic layer to obtain α-Chlorocodide.
Yield: Approximately 65%.
Step 2: Reduction to Desocodeine
Reagents and Materials:
Hydrogen gas + Palladium on carbon (Pd-C) or a mixture of 37% hydrochloric acid and ZnCl₂
Oil bath
Argon gas (inert atmosphere recommended)
Sodium carbonate solution (Na₂CO₃)
Procedure:
Add the crude α-Chlorocodide to a reaction flask.
Under an argon atmosphere, add hydrogen gas and Pd-C catalyst to the flask.
Alternatively, a solution of HCl (37%) and zinc chloride may be used as a reducing system.
Heat the reaction mixture in an oil bath under reflux for 2 hours.
Upon completion, cool the mixture and wash with a sodium carbonate solution to neutralize acids.
Extract and isolate the product, Desocodeine.
Yield: Approximately 60% or higher.
Step 3: Demethylation to Desomorphine (Krokodil)
Reagents and Materials:
Hydrogen bromide (HBr)
50% Hydrogen peroxide (H₂O₂)
Sodium carbonate solution (Na₂CO₃)
Procedure:
Prepare a 2:1 mixture of hydrogen bromide and 50% hydrogen peroxide.
Add the Desocodeine solution dropwise into this oxidizing mixture over 30 minutes with constant stirring.
Heat the reaction to 70–80 °C and reflux until a reddish solution forms.
After completion, wash the reaction mixture with saturated sodium carbonate to remove excess acid and peroxide.
Isolate and purify the final product: Desomorphine (commonly known as Krokodil).
Overall Yield: Approximately 60%.
Step 1: Conversion of Codeine to α-Chlorocodide
Reagents and Materials:
50 g Codeine
55 g Thionyl chloride (SOCl₂)
Reflux setup with magnetic stirrer
Saturated brine (NaCl solution)
Procedure:
Place 50 g of codeine in a round-bottom flask.
While stirring, slowly add 55 g of thionyl chloride dropwise to the flask.
Reflux the mixture at 85 °C for 3 hours under constant stirring.
After completion, wash the reaction mixture three times with saturated salt water (brine) to remove acidic residues.
Separate the organic layer to obtain α-Chlorocodide.
Yield: Approximately 65%.
Step 2: Reduction to Desocodeine
Reagents and Materials:
Hydrogen gas + Palladium on carbon (Pd-C) or a mixture of 37% hydrochloric acid and ZnCl₂
Oil bath
Argon gas (inert atmosphere recommended)
Sodium carbonate solution (Na₂CO₃)
Procedure:
Add the crude α-Chlorocodide to a reaction flask.
Under an argon atmosphere, add hydrogen gas and Pd-C catalyst to the flask.
Alternatively, a solution of HCl (37%) and zinc chloride may be used as a reducing system.
Heat the reaction mixture in an oil bath under reflux for 2 hours.
Upon completion, cool the mixture and wash with a sodium carbonate solution to neutralize acids.
Extract and isolate the product, Desocodeine.
Yield: Approximately 60% or higher.
Step 3: Demethylation to Desomorphine (Krokodil)
Reagents and Materials:
Hydrogen bromide (HBr)
50% Hydrogen peroxide (H₂O₂)
Sodium carbonate solution (Na₂CO₃)
Procedure:
Prepare a 2:1 mixture of hydrogen bromide and 50% hydrogen peroxide.
Add the Desocodeine solution dropwise into this oxidizing mixture over 30 minutes with constant stirring.
Heat the reaction to 70–80 °C and reflux until a reddish solution forms.
After completion, wash the reaction mixture with saturated sodium carbonate to remove excess acid and peroxide.
Isolate and purify the final product: Desomorphine (commonly known as Krokodil).
Overall Yield: Approximately 60%.