Monday, January 7, 2013

Escalation: Authors Respond

Regular readers know I sent out an inquiry to the Fe-S authors a few days back:

Dear Prof. Nguyen:

Good afternoon. My name is See Arr Oh (a pseudonym), and I write a chemistry blog called Just Like Cooking. I've posted about one of your recent publications in JACS ASAP:

Another chemist at Princeton graciously offered to repeat one of your reactions (Table 2, entry 2), and could not duplicate your group's yield or purity. Further discussion can be found in the comments section of the second post. Additionally several other members of the chemistry community have expressed an interest in running it themselves, with the intention of aggregating data under the Twitter hashtag #RealTimeChem.

Please share some more information - do you have any hints or tips for successful duplication? 

Thank you in advance,
See Arr Oh

Unfortunately, my spam filter ate the (prompt) response, and thus I'm posting it a few days later than when I received it back on 1/2/13:

Dear See Arr Oh,

Thank you for your mail. First, you should carry out the reaction in the same scale as described, otherwise, sulfur is comsumed by reacting with methylhetarene before combining with iron. Second, a vigorous stirring is necessary to disperse iron powder into the reaction mixture. At this temperature, the reaction mixture is homogeneous except iron powder. Third, the reaction should be carried out under Ar atmosphere because oxygen is not an innocent impurity. Oxygen in the reaction tube is best removed in vacuo (10 mmHg is ok) then the tube is filled with Ar. This cycle is repeated twice. Before running an NMR spectrum of the crude mixture, paramagnetic iron residue should be removed by syringe filtration to avoid any magnetic pertubation. In most cases, the products were formed as black solid. The prduct is fluorescent with UV lamp.



Interesting tidbits: vigorous stirring, as opposed to a debate in the comments over whether we should stir the reaction at all, scalability issues, and recommendations for NMR analysis - Fe junk really does mess that up!

Methinks this advice might come too late* for anyone trying the reaction today; sorry, B.R.S.M.!

*Addendum - That's a lot of "insider info" in that email, and I'd argue a lot of the online discussion we've had on this reaction could have been avoided by a more complete Supporting Information file. None of that info was available either there or in the paper, nearest I can tell. Readers?


  1. The response is useful but still somewhat puzzling. It doesn't make sense to me that the scale should be so important, since the ratio of sulfur:substrate will be the same regardless. Also, are they saying the reaction must be run on exactly the same scale as in the paper? If so, it seems not particularly useful.
    I am still suspect about the stirring. All of the iron was stuck to my stirbar at the conclusion of the reaction; it seems like the stir bar would therefore *not* "disperse iron powder."
    It is good to know that the reaction is very sensitive to oxygen. I imagine this was the main factor responsible for its failure in my hands. Still, more information about the type of vessel they actually used would be helpful.

  2. Actually, I made some lucky guesses! I've just put the reaction on, using 2-nitroaniline and 4-picoline in a small Schlenk tube. I chose the same scale as the authors, just to be sure. Because the tube's quite small, the reaction can be stirred efficiently and rapidly, so there's no worry about that. I excluded air as best I could using a good pump/Schlenk line to evacuate and back-fill the flask with argon. It's heating up as we speak.

    Regarding the authors' feedback, I'm surprised that scale is so important, but it can be. I've doubled working reactions before, only to have them completely fail. No-one seems to know what a 'pressure equalising tube' is, but that might be a language thing. I figured a Schlenk tube under argon (but obviously, with a bubbler) would kinda fit that description. Might be a language barrier thing. The SI for that paper was not good, and I'm surprised that no further information about the iron was given. I used a new bottle of 'reduced grade' iron which I opened just before Christmas. That stuff's nice and fine, and has worked well in a few other tricky reductions. It's quite pokey. I'm excited to see what tomorrow brings!

  3. Re: vigorous stirring. Might an overhead stirrer be what they used? That wouldn't stick to anything.

    1. You know in your heart it's a graduate student, standing there all night, shaking it every 30 seconds...

    2. (There's a link in my last post; it's hard to see.)

    3. No worries, I totally caught it! : )