To Synthesize or to Buy? That is the question.

And you should too!

Einstein probably synthesized his own compounds. (Flickr user hernandezmariacristina)

Happy summer, everyone!  Sorry for the cheesy title.  Because I’m still an undergrad, I get the chance to take some pretty cool classes that have a little to nothing to do with chemistry.  This can either be a nice break (i.e: Shakespeare, see title) or an unwelcome distraction (…Spanish).  I’m soaking in as much diverse education as I can before I start specializing in my PhD.  This is all besides the point.

Anyway, I wanted to pose a question.  When you’re running a synthesis, an assay, or whatever else it is you do in your lab, and you require a reagent that is expensive and difficult to synthesize, do you spend days synthesizing it yourself, or buy it at ridiculous price from a manufacturer?  From what I can gather, there are two camps.  Tell me if I’m wrong.  PIs/Professors are more likely to encourage grad students to synthesize everything from scratch, and the graduate students vice versa.  Whether their opinion is born from distrust of the manufacturers, a desire to teach you (the student) some more synthesis, or plain sadism is up to debate.  The advantage is that you get to gain some more experience in what is probably a very classic synthesis, helping you gain some ‘lab chops.’  The disadvantage, of course, that that you have to stop watching Futurama to synthesize this molecule that you could just buy.

I’ve recently had an interesting experience.  I had bought a reagent from a manufacturer, expecting to use it as a positive control.  For whatever reason, it wasn’t working.  After around two weeks of frustrated testing, I found that the molar mass of my positive control didn’t match to mass it was supposed to be (by MALDI).  So therefore, we got sent a faulty reagent.  Kind of a bummer, right?

After this debacle, I resolved myself to synthesize it myself, spurning the multimillion dollar industry for my own two hands.  After a week of synthesis and purification, I am a proud owner of a compound which has a molar mass that is too large for the compound I would’ve wanted to synthesize.  I still haven’t run enough tests to see how far I’ve gone wrong, but as of now it seems possible that I’ve somehow messed up, which puts me at a unique crosscroads.

Do I synthesize my positive control again?  It only took me a week, and is much less expensive than buying it from a manufacturer.  Also, I can make gobs at a time (technical term), and I can only buy a small quantity.   On the other hand, I could just buy it again and hope for this best.  Sure, it’s much more expensive, but it’d be so easy!  Plus, I could finish this episode of futurama.

So, my chemist friends, if you were in my place, what would you do?  Synthesize or buy?

Author: Sidechain Bob

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  1. It depends. If you can buy 100 mg and that will be all you need for the foreseeable future, I would buy it. A lot of people look at the high cost of a reagent and figure they can make it more cheaply, but more often than not, they can’t once they figure in their own time.

    For an intermediate that I need in a synthesis, I would make it if I needed more than was going to be available commercially. For an assay standard, it is usually an easy choice (and then if it isn’t the right stuff, you have someone you can complain to as well).

  2. Not knowing what you’re doing or what kind of positive control you need… I’d spend another half day on SciFinder and find a different positive control.

    For me in a synthesis lab, I’d find another reaction to perform the desired transformation. God knows there’s dozens of ways to oxidize an alcohol. And it’s probably something the lab down the hall already has in stock 🙂

  3. As you value your time more and more, your willingness to spend other people’s money to synthesize starting materials and reagents will go up and up.

  4. uh, synthesize s/b purchase.

  5. The standard answer in industry is buy if you can, make if you have to. Especially if the chemistry is nasty in some way (nitrations, for example.) You will often come out better buying your bonds instead of making them. That said, as a student your labor is cheap and if the cost of materials to make the target is less than the cost to purchase, you should expect to be making compounds. There’s only one way to learn bench chemistry and that’s to get into the lab and do it.

    And Futurama’s all on Netflix Instant. Get into the lab now and stream Futurama later when you should be studying for one of those diversity requirement classes.

  6. “The advantage is that you get to gain some more experience in what is probably a very classic synthesis, helping you gain some ‘lab chops.’”

    The true advantage is that you start to learn what you should buy and what you should synthesize.

  7. If you got a bad reagent directly from the supplier then you need to call them up and let them know. They should send you a new bottle for free. It’s happened several times before in my lab.

    • I’m planning on calling them and faxing over the MALDI in question – thanks for the suggestion!

  8. 1) Is the purchased material definitely the wrong stuff. Why MALDI? What’s the expected and actual masses? is the result an artefact of the ionisation technique?
    2) Some things work really well and others don’t. You don’t really know until you’ve tried. The best thing to do is to convince the supervisor that the reason why something doesn’t work is due to no omission on your part. The way to do this is to exude a level of competence which you either get by being actually competent or learning to look competent. Anyway once the supervisor feels that you are basically thorough, They will be more willing to simply accept that synthetic strategies sometimes just don’t work and that it is simply not worth the time to work out why or one that does.
    3) You could find a better way of making the stuff.

  9. I work in a total synthesis lab, and my response to this question is: buy a little bit the first time. Then, if the reaction works, consider making it yourself thereafter.

    You don’t want to spend a lot of time making something that you will use once and never need again. Nor do you want the quality of your reagent to be a question mark in whether the reaction works. (Typically, purchased reagents are more reliable.) And, if that’s not enough of a reason to buy, remember that you never want to be in a position to have to explain to your PI why you can’t make some ridiculously simple-looking molecule that is commercially available; it just looks bad.

  10. This reminds me of a story.

    As a third or fourth year grad student (sadly they all blur together in one depressed blob), I saw we didn’t have a reagent in our inventory, so I go about making it b/c it was a one-stepper and we had all the precursors.

    Making it involves bubbling chlorine gas through the SM. So I set up all the proper precautions – ring stand for the lecture bottle of Cl2, bubble into a KOH solution to make bleach w/ the excess Cl2, etc… I get everything set up, take a few pictures for posterity, and open the lecture bottle. … Nothing happens. Either the old old lecture bottle was rusted shut or the cylinder of Cl2 was empty. I decided to let the waste management people figure out which.

    I’m recounting this story to a friend who proceeds to inform me we have a few bottles of the stuff cataloged under an alternative name! Blasted IUPAC names AND common names!

  11. It’s my personal experience that being told to purchase or synthesize material has to do with the state of funding in the lab more than it does the learning experience. As a grad student we ran lean (ie; we didn’t have money) and I learned to make a lot of the stuff I needed. When I came into my postdoc suggesting simple gram-scale routes to my starting materials my PI told me not to waste my time and just buy what I needed.

    I agree with Stewie, call the company and get a replacement or refund. That happened to us with Aldrich and they didn’t even require proof, they just took us at our word and sent a new bottle!

  12. I am from the big pharmaceutical industry prior to joining the academia. I see immense differences the way these two behemoth operates. The big companies have lot of resources and in a World where time is money, where possible we brought them from commercial vendors. Those analogs that were not available, we preferred to synthesize the same. Care must be taken to make sure that the synthesis is only 5 to 6 steps long, otherwise you could be spending several weeks for nothing. In academia, I do not see that happening. The known compounds are synthesized (instead must be brought) and understand that we need only few mg for initial HTS. The thumb rule is simple in drug discovery….be it in industry or academia and that is do not re-discover the wheel. Time is literally money in drug discovery.