Hydrogen Bromide → Codeine

Participants

Reaction Conditions

Reaction Steps

Thebaine (2.0 g) was dissolved in warm glacial acetic acid (10 ml) then chilled in an ice/water bath. A 45% w/v solution of anhydrous hydrogen bromide in glacial acetic acid (6 ml, 2.7 g HBr) was added dropwise with stirring over 9 minutes. Stirring was continued for 20 minutes during which time a fine precipitate separated. Methanol (75 ml) was added to a solution of sodium hydroxide (12.72 g) in water (75 ml). This solution was chilled (10° C.) and sodium borohydride (247 mg) added. The above slurry of 8-bromodihydrocodeinone hydrobromide in acetic acid was added portionwise to the sodium hydroxide-sodium borohydride mixture with vigorous stirring over 34 minutes keeping the temperature below 10° C. by means of an ice bath. After the addition, the mixture was allowed to stir for 30 minutes. Chloroform (50 ml) was added, the mixture stirred vigorously, allowed to settle and the layers separated. The aqueous phase was extracted with fresh chloroform (2 × 20 ml). The combined chloroform extracts were washed with brine (3 × 50 ml), dried (Na2SO4) and evaporated under reduced pressure. Final traces of solvent were removed under high vacuum. The fluffy off-white solid (1.85 g) displayed one major spot on TLC and one major peak on GLC, both of which corresponded to codeine. Codeinone was absent, and only minor amounts of other alkaloidal substances were present.

Provenance & Evidence