Breaking Good: how to synthesize Pseudoephedrine (Sudafed) From N-Methylamphetamine (crystal meth)

Photo: Chris Howey / Shutterstock

Genius scientific paper* of the day: "A Simple and Convenient Synthesis of Pseudoephedrine From N-Methylamphetamine, by O. Hai and I. B. Hakkenshit." (PDF).

A response by annoyed Sudafed users to the onerous demands by pharmacies for ID and tracking, due to the fact that this helpful and common over-the-counter drug can be used to manufacture crystal meth.

Snip from the paper:

A novel and straightforward synthesis of pseudoephidrine from readily available N-methylamphetamine is presented. This practical synthesis is expected to be a disruptive technology replacing the need to find an open pharmacy.

Pseudoephedrine, active ingredient of Sudafed®, has long been the most popular nasal decongestant in the United States due to its effectiveness and relatively mild side effects [1]. In recent years it has become increasingly difficult to obtain psuedoephedine in many states because of its use as a precursor for the illegal drug N-methylamphetamine (also known under various names including crystal meth, meth, ice, etc.)[1,2]. While in the past many stores were able to sell pseudoephedrine, new laws in the United States have restricted sales to pharmacies, with the medicine kept behind the counter. The pharmacies require signatures and examination of government issued ID in order to purchase pseudoephedrine. Because the hours of availability of such pharmacies are often limited, it would be of great interest to have a simple synthesis of pseudoephedrine from reagents which can be more readily procured.

A quick search of several neighborhoods of the United States revealed that while pseudoephedrine is difficult to obtain, N-methylamphetamine can be procured at almost any time on short notice and in quantities sufficient for synthesis of useful amounts of the desired material. Moreover, according to government maintained statistics, Nmethylmphetamine is becoming an increasingly attractive starting material for pseudoephedrine, as the availability of Nmethylmphetamine has remained high while prices have dropped and purity has increased [2]. We present here a convenient series of transformations using reagents which can be found in most well stocked organic chemistry laboratories to produce psuedoephedrine from N-methylamphetamine.

(via @ioerror. Images, via Shutterstock: At top, a type of glass pipe commonly used to smoke crystal meth. Inset, N-Methylamphetamine. Below, a LOL, referencing an episode in the first season of meth-themed TV show Breaking Bad, via @yesthatkarim.)

* Note the name of the authors, and that of the journal. It's parody, folks.


      1.  Thanks, figured it was a parody, but it’s hard to tell at a glance.  The subject matters a bit of a give away though, isn’t it?

    1. The affiliation from Miskatonic University is part of the Cthulhu mythos; the institute of theoretical experiments and the author I.B. Hakkenshit are also clues.

  1. Brilliant. I live in BFE and it’s 45 minutes to the pharmacy which often has a 45 minute line. I’m sure I could find meth a few minutes away outside with no lines, and  I wouldn’t even have to sign the idiotic wavers.

    Now if I could only make it into Polar Pur too (another product I can’t buy due to the bullshit War on Some Drugs).

  2. Polar Pur is easy.  Purchase either sodium or potassium iodide.  Dissolve in sulphuric acid and water, dry,  Now heat the resulting mess while covered with a bowl containing ice.  the iodine will sublimate and condense as crystals on the bowl. 

    Scrape into pill bottles.  Instant polar pur.  

  3. “How to turn $1 million in Real Estate into $25 in cash” — Steve Martin’s (fictitious) book title.

  4. Could you wind up with ephedrine, instead? Wasn’t that the OTC decongestant before being banned as too easy to make into meth, and replaced by psudoephedrine? 

    1. I would be suspicious of this.  With that lithium amide present I would expect it to react with the oxidant (step 3 -> 4) competitively with the carbon.  This would probably end up with a huge mess.  It looks like the authors just took the reaction in the referenced J. Chem. Soc. paper (which is legit and is almost the same reaction, just with an extra methyl group on the nitrogen) and substituted in their substrate.  Maybe if they had protected the amine with some sort of silyl group first, with deprotection at the end, it might work.  Although I wouldn’t be surprised if these guys weren’t real chemists at all.
      I also wouldn’t recommend eating anything which was one step away from a chromium reagent or HMPA without some much more serious clean up than what they mention in the paper.

      1. That sounds right. I think it’s pretty hard to get a dilithium organometallic. Harder than just chucking in twice as much BuLi anyway.Still, it’s not complete bullshit and is pretty damn impressive for a ‘joke’ paper.You could probably make it work by protecting the N-hydrogen with something, though it might screw up the stereoselectivity (I have no idea how the reaction with MoOPH works, but a protective group could sterically hinder any complexes).

    2. Derek Lowe, over at “In the Pipeline”, has blogged about this here.

      He says:

      Their route, based on a 1985 paper in J. Chem. Soc. Chem. Comm., is not exactly trailer-park chemistry, though. (I note that they have the reference a bit wrong as well; there was no plainJ. Chem. Soc. in 1985). It involves a chromium carbonyl complex of the aryl ring, formation of a chiral lithium dianion, and oxidation of that with MoOPH, which would give you pseudephedrine after decomplexation. There’s no way to tell if these reactions have actually been run, of course. Based on the literature precedent, it might work, although I’d be worried about maintaining the chirality of the dianion. (For what it’s worth, the authors are also aware of this problem, and claim that the selectivity was unaffected).

  5. I found out about this via a tweet, the wording of which I enjoyed:

    “US Crackdown on crystal meth means Sudafed is hard to buy.  But meth is easy to buy; here’s how to make Sudafed from it.”. @ciphergoth:disqus

    The War on Drugs™

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