Synthesis Of Methamphetamine

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Methamphetamine synthesis via reductive alkylation hydrogenolysis of phenyl-2-propanone with N-benzylmethylamine


Methamphetamine was synthesized by reductive alkylation hydrogenolysis of phenyl-2-propanone with N-benzylmethylamine. The expected product N-benzylmethamphetamine, once formed, undergoes hydrogenolysis to methamphetamine and toluene. The progress of the reaction, the intermediates formed during the reaction, and the products were analyzed by gas chromatography and mass spectrometry.

Standard Synthesis

In the original variation, (S)-pseudoephedrine is extracted from decongestant. This involves the use of different organic solvents at various stages. It is key that the pure isomer (S)-pseudoephedrine, the diastereomer of (R)-ephedrine, is extracted. This is further converted by reduction (e.g. by the traditional way involving iodine and red phosphorus, as shown in Breaking Bad) into (S)-N-methylamphetamine. 

Blue-Meth Synthesis

A possible alternative route is based on phenyl acetic acid and acetic acid, e.g., acetic acid anhydride, and leads initially to phenyl acetone through reduction with supported thorium oxide, from thorium nitrate, as catalyst in a tube furnace [11]. This synthesis route is probably that followed by Walter and Jesse and is very demanding, not least due to the preparation of radioactive thorium.

There then follows the reaction of phenyl acetone with methylamine and the subsequent reduction of the resulting N-methylimine. These two steps can take place as a multistep or one-pot reaction. Mercury aluminium amalgam can be used as catalyst for the reduction, as discussed by Walter and Jesse. Episode (IV-1), however, only shows how aluminium granulate is added to the reactor. Sodium amalgam or lithium aluminium hydride would also be possible catalysts [3].

As the reaction is not stereospecific, it yields the racemate (S)/(R)-N-methyl methamphetamine (Note: This synthesis step could also be carried out stereospecifically with the aid of stereoselective catalysts or, alternatively, a stereospecific separation of the product could take place before or after crystallization. Unfortunately, there is no indication of the method given in Breaking Bad). The resulting product is then separated from any remaining starting materials or by-products by steam distillation. This produces the clouds of steam that are often seen in the series. Finally, the oil obtained from the distillation has to be crystallized from an organic solvent, e.g. toluene. So it is all quite simple – maybe too simple?


[3] N. Stojanovska, S. Fu, M. Tahtouh, T. Kelly, A. Beavis, K. P. Kirkbride, Forensic Sci. Int. 2013, 224, 8–26. DOI: 10.1016/j.forsciint.2012.10.040 .

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