The Birch Reaction: Methamphetamine from (pseudo)ephedrine


All chemicals were reagent grade, with no special treatment of the tetrahydrofuran (THF), and the atmosphere above the condensed ammonia was not flushed with nitrogen gas. A three-neck flask was cooled in a dry ice/acetone bath. A condenser was fitted in the center neck, an additional funnel containing l-ephedrine base in THF was fitted into one side neck, and a rubber stopper fitted with a glass tube extending to the bottom of the flask was fitted in the third neck. Anhydrous ammonia gas was condensed and collected in the flask. Small pieces of lithium metal were rinsed in petroleum ether, patted dry, and added to the condensed ammonia. A deep royal blue color was noted as the lithium metal dissolved in the condensed ammonia. The l-ephedrine was added dropwise to the lithium ammonia solution over a period of approximately 10 min. with stirring. When all of the l-ephedrine had been added, ammonium chloride was added slowly to the solution. The flask was removed from the cooling bath, and the cooled ammonia was allowed to warm to room temperature and evaporate from the flask through the side necks. When most of the ammonia had evaporated, water was added to the remaining solution until it cleared and any remaining lithium metal was decomposed. The remaining solution was removed from the flask to a separatory funnel, where the aqueous layer was discarded. The THF layer was dried with magnesium sulfate, and the hydrochloride salt of the methamphetamine was made by bubbling hydrogen chloride through the THF.

The time required for the reaction to proceed from the condensing of the ammonia gas in the reaction flask until the excess lithium was decomposed was approximately 1 h. The majority of the time was spent waiting for the condensed ammonia to evaporate from the reaction flask. The reaction was found to reduce l-ephedrine to d-methamphetamine quickly and easily. Furthermore, it was found that the reaction converted phenylpropanolamine to amphetamine and methylephedrine to dimethylamphetamine. It was also found [in a second synthesis] that the ephedrine would reduce to methamphetamine without the addition of ammonium chloride as a quenching agent.

Reference: From Ely & McGarth J Forensic Sci 35, 720-3 (1990)