Wednesday, November 13, 2013

11 things to say about a paper that didn't work

You see a reaction that might help you out, you run it on your substrate and it doesn't work. What to do next?
  1. "%$#%$#^%$^%^^%!!!!!"
  2. "72 hours to run a reaction -- nice long vacation they took..."
  3. "Oh, that guy. Never mind." 
  4. "That's what you get when you follow a paper from [prestigious university X]"
  5. "Look at this table -- have they never heard of a heterocycle?" 
  6. "Potassium carbonate for this -- what an arbitrary choice." 
  7. "*&&&**(**!!!!"
  8. "I knew I should have never trusted a journal with an impact factor below 10!"
  9. "That's what you get when you follow a paper from East Pudknocker U."
  10. "Look at this typo in the SI!"
  11. "Well, maybe we should read the paper again...." 

20 comments:

  1. "Units! What are the g*d D*mned units! g or kg!!!!!!! "

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  2. "Surely they would have said something if they used a fresh bottle of catalyst...."

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  3. That wasn't isolated yield, it was just by NMR. Pffft

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    1. NMR yield is the best way to report yield (with proper internal standard). It tells you how the reaction 'really' went. Isolated yields depend on your skillz.

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    2. Depends what you want - as an assay of how good the reaction is relative to alternatives, NMR yields would make sense. I assume, though, that most people just want to know how much stuff they can expect to get out at the end, and isolated yields tell them that much more effectively than NMR yields. While isolated yields depend significantly on experimenter skill, they probably also depend on how much gorp is in the reaction and how hard it is to separate from desired material.

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    3. If there's gorp in the reaction, people shouldn't be eating in the lab.

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    4. If I can't get clean product at the end, what good is a reaction? I'm always concerned when people report yield by NMR or GC or worse yet just percent conversion. Why couldn't they isolate their products?

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    5. The reaction didn't work without granola. Remind me to put that in the SI.

      Oh, and it also fails if you get a blue M+M in there, too. Oops.

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    6. What I'm thinking of, is that typically in an academic lab you work on small scale to save precious catalyst if you're developing a method. It's easy for the product to get lost on the walls of the separatory funnel, column, or whatever. If you were working on a large scale, the yield would be much higher, but you can't afford it. Then you're reporting small isolated yields that in theory should work much better. I think this happens much more often than isolation problems. I often don't believe the 99% isolated yields from methods development labs, but I would be willing to believe them more if they were NMR yields.

      For anonymous, the reason that product is not isolated, is because you do it for the first few, but when you're running 40 different substrates and developing a catalytic method, and you know that isolated yields are not reliable numbers, and you demonstrated the isolability in those first few, then there is no point.

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    7. I understand that, but with lots of compounds (alkaloids as cited lots by T. Hudlicky in his book, for example) high NMR yields aren't that relevant, because the products are hard to get from the reaction mixtures - they oxidize and condense and do lots of other things that make them hard to get out. NMR yields would give you a relative assessment of the method relative to others for the same compound, but it doesn't tell you what you will actually get if you use it.

      People interested in method development are probably interested in a relative assessment of method quality, but other people will want the method to help them make the compounds, and the NMR yields may not be helpful in telling them what they'll get out. If yields are supposed to assess method quality, it would probably be more honest to directly compare methods.

      Unless they're on large scale, 99% isolated yields are probably bunk, but if they're willing to report those, well, then why wouldn't they report questionable yields by NMR?

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    8. "Unless they're on large scale, 99% isolated yields are probably bunk, but if they're willing to report those, well, then why wouldn't they report questionable yields by NMR?"

      Yes, that is true...

      I still disagree with you on the other point however. NMR is the one true method that will tell you how well the reaction went. A reaction on a sensitive substrate could be worked up in a glove box, theoretically, by industry types who have a lot of money. Otherwise isolated yields on difficult substrates are a good substitute for telling how little money your lab has. Of course, I do have isolated yields for new, air-sensitive (and other non air sensitive) compounds that I made in my papers, but I often know that I probably could have done a lot better if I really wanted to, especially when I check the NMR scale reaction. Still with all the academic limitations, it's better for someone reading your paper to be pleasantly surprised (or to think of you as having bad technique) then by them getting angry at you for not being able to repeat a high yield. Recently I've been putting down both yields for some challenging compounds (isolated and NMR).

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  4. "That's it! Time to start a witch hunt on Bracher's blog." ;-)

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    1. Or, in a similar vein "I better take a real good look at that baseline noise in the SI".

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  5. 11, then 11, then 11 again. If it still does not work alternate 1 and 7 for a number of times, the start again modifying all that seems less likely to actually work.....

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  6. After 11 :"These NMRs are unwatchable. How they publish higher than me?"

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  7. Still looking for the experimental section... it's gotta be around here somewhere...

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  8. conversion = 'NMR yield'
    yield = weighted isolated material

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    1. Conversion of starting definitely does not equal NMR yield. You can get more than one product. Especially with some reactions that I do.

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  9. Conversion doesn't equal yield - just because starting material's gone doesn't mean it went to product. NMR yield means you actually (well, probably) know what your product is; if you have an appropriate standard, it also tells you how much of your product is there.

    Conversion yield = "well, it's gone, but I don't know where it went". Really not helpful.

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