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By James Ashenhurst

Class exercise: Come up with a synthesis for this illegal drug

Last updated: March 27th, 2019

A while ago I got the following letter from a concerned parent (lightly edited for length).

I was shocked when my daughter came home from organic chemistry lecture the other day and lamented that her organic chemistry instructor had on a quiz, the following question:

Synthesize methamphetamine from pseudoephedrine in six steps.

I understand that all sorts of compounds, good and deleterious, can be synthesized from a starting material. I understand the decongestant and the stimulant have carbon rings (benzene) and nitrogen (amine). The decongestant has the R-OH group. The meth maker must remove the –OH and replace it with H. I understand all of that intuitively, but what I don’t understand is why is an organic chemistry instructor at college asking this of his 18, and 19 year old students? Where are the ethics involved in chemistry? I have a 4-year chemistry (baccalaureate) and it is very old (nearing 30 years), so my memory of organic chemistry is foggy, however, I do not recall ever being asked to show my expertise  – the steps in how to synthesize an illegal drug.

What are your opinions of this question, coming from the vantage point of a chemistry professor? Am I reading too much into it, by being offended by it? Why couldn’t the instructor ask students about how to create a hand-held sniffer that could sample air in a “potential” meth lab and determine the fingerprints (chemical signature) associated with the meth chemical…something positive. Or, maybe I am missing the point, the student needs to know how to synthesize the “bad” to help sleuth it out in real-life (e.g., advise an equipment manufacturer in how to design and implement a hand-held sniffer)?

My first thought was “Six steps! That’s woefully inefficient!” Anyhow, I wrote back the following:

I think the intent of the instructor was to try to get the class to work on a real-world example of a chemical synthesis problem. The choice of amphetamine as a target was probably chosen due to the instructor surmising that the illicit nature of the drug would engage the attention of the class. True, he could probably just have easily had them work on the synthesis of a life-saving drug, but I don’t feel it is my place to offer an opinion on the instructor’s judgment in this matter. This question does not ask the students to actually carry out the synthesis, but instead apply their knowledge of chemical reactions and chemical transformations toward a plan for the synthesis. Everything is done “on paper”. At no point are students expected to actually carry this out in the laboratory.

In my opinion, it is a little bit like taking a screenwriting course and having an assignment from the teacher to write a script about a murder. One might quarrel with the judgment of an instructor giving out such an assignment, but I think you would agree with me that there is a tremendous divide between writing a story about a crime and actually carrying it out. Furthermore, the syntheses planned by the students bear no resemblance to how methamphetamine is actually illegally synthesized from pseudoephedrine, and the reagents required for the syntheses are all heavily restricted and monitored by the government.

I would close in saying that 18 and 19 year olds are adults, and with adulthood comes responsibility. Our knowledge gives us the power to both create and destroy, and it is my hope that students who embark on learning about the art of organic synthesis choose to use their knowledge wisely. For good or for ill, we must trust that the youth of today will use their best judgment in making decisions, because it is to them that we will eventually hand the reins of society.

I hope this has addressed some of your concerns.

Yours truly, James Ashenhurst

Back when I was an undergrad I spent a fair amount of time looking into organic chemistry’s Dark Arts: explosives and drugs. It was the old-school Anarchist’s Cookbook and PIKHAL where I was first introduced to detailed accounts of working up a LiAlH4 reaction, reductive amination, nitro group reduction and a host of other procedures. And I’m not the only one.  My curiosity was stoked: what’s a Soxhlet extractor? How does aluminum amalgam work? What’s behind the choice of various solvents for extraction, recrystallization, and so on? I was driven to understand these weird terms and procedures.  If not for this curiosity, I’m not sure I would have gone down the path of being an organic chemist.

Some of the first syntheses I ever sketched out were on molecules of dubious legality. It was fun applying the knowledge I’d learned towards something practical – and forbidden. I don’t have those notes anymore but if I did I’d probably just heave a sigh of embarassment at how amateurish,  inefficient and impractical my synthetic plan was.

The irony was that several years later when I was a ruthlessly efficient synthesis machine working in a fully equipped chemistry lab, there was never any thought of doing something dumb like making MDMA – even though we had a big bottle of of piperonal and a boss on sabbatical in California.  “Take a day or two off to screw around? Risk getting arrested? That’s gonna delay my Ph.D.! ”

So if students want to dabble in the dark arts – on paper, of course – I’d say it’s no more dangerous (and a hell of a lot more productive) than playing a game of Grand Theft Auto and doing some carjackings. You’ll probably learn something and be engaged in the process.


PS Here are some excellent examples of how the pros do it:

Prof. Willstatter’s synthesis of cocaine (1923) – (Wiley subscription – and German – required)

Prof. R.B. Woodward’s synthesis of lysergic acid – a classic – (1956) ACS subscription required)

Prof. Gilbert Stork’s synthesis of morphine (ACS subscription required)

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Comment section

21 thoughts on “Class exercise: Come up with a synthesis for this illegal drug

  1. I asked my students to synthesize methamphetamine starting with benzene – thus disconnecting it from “how illegal drug makers actually do it.” Yes, it engaged interest, and no, no one actually considered actually doing it.

  2. This parent is very naive if they think this information isn’t readily available on the internet.

    I have given this sort of question in class to link paper chemistry to what goes on in the real world.

    Like you, I believe that parents should be trying to encourage their offspring to engage in critical thinking rather than trying to “protect” them from reality.

  3. This is very interesting! Sorry if my english is not good. As an org. chemistry student, I have been many times very interested in the processes involved in the synthesis of ilegal drugs and explosives. This is only natural if you think that chemistry knowledge can be powerful and dangerous. I agree with Christine, the parent is naive, young students will always feel curious about these things, and actually I think curiosity is a good thing. I can be curious about serial killers and their behaviour, it doesn’t mean I will become one!!!

  4. Look,

    Im a university chemistry student, every chemistry major will wonder how its made. Its not super complicated, and its quite interesting. It by no means shows that anyone has the intent to make it. I also agree with a comment above, its no secret how to make meth. its all readily avaliable online.

    stick to worrying about adderal

    1. I by no means am a chemist,but im an avid fan of the science!!!your last comment has been a fascination of mine for many yeairs!!!I can see the basic chemistry,but am frustr ated past there!!!the synthesis should be simple,but Im dumbfounded!!!HELP-before I wear out my brain!!!!!!!

  5. Looks like the poster of this ‘question’ just wants to show off his expertise on the synthesis of meth… Anyone can do it, whether it be drugies or chemists, so it doesn’t matter if a professor is challenging his/her students with a fun scenario. If your child goes home and starts making meth, congrats you’re special…

  6. The war on Drugs is a sham.. Consenting adults can synthesize or ingest any substance they choose.. regardless of what a certain group of people write down on paper and claim is against an imaginary rule called “law” If these things were freely available with proper quality control, there would be no need for clandestine labs and impure synthesis with toxic byproducts not removed ect.. sure an 18 or 19 year old probably shouldn’t be making methamphetamines.. but if your of age, have the knowledge of it and proper safety precautions. you should be allowed to synthesize and ingest whatever it is you wish. period!

    1. I happen to agree. I dont think prohibition works. Ever. We should know that by now. But I also know that society would never accept a world were people are free to take anything they like. Also, that is a topic for another thread my friend.

    2. Good point here. I must say, in the 1920’s when alcohol was prohibited crime skyrocketed as a direct result. In our times, when the government sought to subdue meth in the streets by limiting psudo and other precursors, it opened the doors in the south for the cartels to import from their super labs. Meth use has stayed the same. It pushed the “labs” further underground exactly the same way the old “bootleggers” did it with moonshine. It was politics, nothing more. If the people in power truly cared about crime involving meth, and the health of Americans in relation to any drugs, then they would allow all of them (drugs) to be legal and controlled/taxed like cigarettes. In fact I would bet my life that the only reason the government does not do this is because each person in power on the rise is too afraid of public opinion, and stigma regarding such matters. Again, politics. Make them all legal, basically affordable, and clean/controlled just like alcohol/tobacco, and prescription drugs. Oh wait, I almost forgot… They already do have them all as prescriptions… This way they can be outrageously expensive, and basically off limits for most. How stupid. Our government is so caught up in being greedy and corrupt… I feel that for the most part, they don’t give a damn about any of us. They want to keep our youth dumb, and the ever widening divide between the affluent, and the poor. They know that if we get too wise, in our numbers, they would soon be out of power. Oh no not that… Anything but a world in which it is truly “For the people, by the people, and of the people.” No no no… Its for the haves… Its not for the have nots! There was a statement made by a man in power long ago which stated that “the people of america are too ignorant to think rightly for themselves. We need to be controlled, and subdued.” Eisenhower warned about the Military Industrial Complex, Truman warned about leaving the Gold Standard. As soon as we handed the american dollar over to the “Federal Reserve” we were owned by a cartel of a handful of men. It is they who call the real shots. Hmm… Or maybe Im just another stupid ignorant american who cant read or think for myself. Wow… I don’t get it. Why is everyone so asleep. Ignorance is that blissful I guess. By the way… 9/11/01 was an inside job. Do the research. Read the constitution, assemble in large numbers, and take our country back. There just might be time to save the world. However, I truly doubt it.

  7. I think this knowledge is completely applicable, some pharmaceutical drugs for the treatment of ADD are nothing more than methamphetamine or a closely related derivative.

    I love this kind of stuff, and I think it has definitely driven my fascination and interest in chemistry. I read a book a while back call “total synthesis” which dealt with making MDMA and methamphetamine and other “research chemicals” at home, I have also read some of Tikal and Phikal, and I have also had many great conversations with professors at school about grey area topics, like morphine and heroin and the history of such analgesics, including the role Bayer played in synthesizing and selling heroin over the counter. This IS chemistry. You have to take the good with the bad. I dont see anything wrong with it, as long as you know where to draw the line.

    Just for the hell of it, and because now I am curious, how would you remove the hydroxyl group? Clemmensen reduction?

    1. ADD is a mix of amphetamine salts and Meth Amphetamine is available as Desoxyn, a schedule II medication.

      Voice of Reason and Sam, I agree, however people need to also take full responsible for the consequences of their action. Meaning, if someone does synth and ingest they are still fully liable for their behavior and as a tax payer I should bare no financial responsibility for their rehab.. freedom and responsibility have to go hand in hand..

  8. Dr Ashenhurst,

    So nice to hear that you as well as others had their fascination stoked by reading Shulgins works along with literature of similar “dark” interest, its always nice to know you’re not alone. I never considered actually being a chemist or going into academics until my mid forties unfortunately, but curiosity won and now I’m taking a class or two at a time as life affords and doing undergrad research with dreams of entering a pHd program, hopefully before I hit 50. Id like to stay in academics or research, I’m more interested in science than trying to make a lot of money and normally leave research ready for more (-:.. I thank you for your honesty in this matter, it helps validate my own source of interest.

  9. Amphetamine and methamphetamine are not the same molecule
    One is cooked by domestic drug lords and sold under the prescription name “Adderall”
    The other is cooked by foreign drug lords and sold on the street under the name “crystal meth”

  10. This parent is clearly not educated in chemistry (or is incapable of seeing the bigger picture here). This synthesis problem is very common as my undergraduate organic professor included a very similar synthesis and mechanism problem on our “amines” test. It’s a quintessential example of amine chemistry. I do agree, however, that the starting material should have been something simpler (I.e. Benzene or the like), but that’s completely at the discretion of the instructor. Ignorant non-Chem people should think before they speak.

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