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)