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Derek Lowe The 2002 Model

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Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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September 20, 2010

Sodium Hydride As Oxidant, Again?

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Posted by Derek

Many readers will remember the "sodium hydride as an oxidizing reagent" story from last year. (For the non-chemists in the audience, the problem here is that sodium hydride is most certainly not what you'd think of as an oxidizing reagent, quite the opposite, in fact. Seeing the paper's title was, for an organic chemist, a bit like reading about a new way to sweeten drinks with vinegar).

This was famously live-blogged over at Totally Synthetic and picked up on around the chemical blog world. The current thinking, though, is that adventitious oxygen is really doing the work here. If you run the reaction under strict inert atmosphere conditions, you get no more oxidation. (And it still doesn't appear that any note has been added to the original JACS paper). Update - make that no note added to the abstract page. The paper itself is still accessible, although it does have notes that it was withdrawn.

Well, now we have another one. This paper in press in Tetrahedron Letters claims oxidation of benzoins to benzils with good ol' sodium hydride. In this case, anyway, the authors (from Korea) did try running the reaction under inert atmosphere, and saw their yield go down. Their proposed mechanism involves molecular oxygen, in fact, and is quite plausible. (I've seen anion-oxygen chemistry myself - if you deprotonate Strecker amines of benzaldehydes, you'll convert them into amides via oxygen in your solvent, that is, if you don't saturate things with inert gas first). Still, I'd rather that they titled this paper differently, since it's not sodium hydride that's doing the oxidation here. You could probably get this to happen with NaHMDS, t-butoxide, or the base of your choice.

And, weirdly, the authors (as far as I can see by going over the PDF) manage not to cite the original JACS NaH oxidation paper at all. You'd never think that anyone had tried this before, especially not in one of the most high-profile chemical journals in the world, just last year, with plenty of added press coverage. What does it take a get a paper cited? Update: given the withdrawn-but-still-available status of the original, this becomes a trickier question. The earlier paper seems to have clearly gone through the same sort of chemistry, but the mechanism - and thus the point of the whole paper - was misassigned. Do you cite it, or not?

Comments (14) + TrackBacks (0) | Category: Chemical News | The Scientific Literature


1. chemist4hire on September 20, 2010 12:31 PM writes...

Well the original JACS paper was retracted.

If you were the author of the paper, would you cite a retracted paper? I have never been in that situation, so do not know what the proper protocol is for such a situation. I thought you treated retracted papers as if they never existed in the literature to begin with.

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2. student on September 20, 2010 12:38 PM writes...

It's in tet lett. so it probably never even got peer reviewed.

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3. strayxray on September 20, 2010 1:18 PM writes...

Would the editors of Tetrahedron Letters allow a paper to cite a retracted paper?

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4. watcher on September 20, 2010 2:15 PM writes...

There is no reason to cite a withdrawn paper. The removal is an acknoledgement that the work was not suitable to be published, so that also means it should not be cited, as the reason for citation assumes an element of previous authority.

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5. Henning Makholm on September 20, 2010 3:00 PM writes...

This all depends on what the purpose of citations is supposed to be. To tell the reader where he can read more about such-and-such topic? To document where the authors got their ideas? To back an assertion that the current paper does not have the room to make an independent case for? To prove that the authors are familiar with the relevant literature? To allocate academic brownie points to the authors of the cited paper?

Some of these goals are invalidated by the prior paper being retracted. Some remain as relevant as they ever were.

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6. Dr. Smalls on September 20, 2010 3:29 PM writes...

I like using O2 and NaOH to convert fluorene to fluorenone. This is an easy demonstration of O2 oxidation.

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7. eugene on September 20, 2010 6:41 PM writes...

Well, if I let a lot of my pyridine derivatives sit around on the shelf and some oxygen gets in under the cap, eventually they'll become oxidized with no base needed at all! Well... I suppose pyridine.

I vote for not citing the original. After all, it's been retracted.

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8. syregnask on September 21, 2010 1:50 AM writes...

Not only is the title of that Tetrahedron Lett. paper misleading, but the graphical abstract does nothing to make up for it.

As for citing last year's story, maybe it could be done by citing the RSC piece about it (well, if that had itself been published in a different form that might have been easier).

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9. p on September 21, 2010 5:53 AM writes...

Just to add my 2 cents to everyone else's, base and O2 isn't exactly a new-fangled oxidation protocol. I've used it dozens of times, with various bases. As Dr. Smalls says, you could just as easily use NaOH or TEA.

Also, providing an "inert" atmosphere can be tricky. We do chemistry that is sensitive to O2 and simply blowing some argon or N2 in doesn't cut it. It takes work to get rid of O2. So, if they tried to omit O2 and see the yield go down, I'd feel safe saying they simply cut the concentration of O2.

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10. ddddddd on September 21, 2010 7:46 AM writes...

You should cite it for sure. Even if it was retracted, just highlight it's dubious nature in the text and cite it anyway. It's helpful to a potential reader and the two are way too similar to not merit a citation imo.

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11. Ed on September 21, 2010 8:07 AM writes...

I suspect your inorganic chemistry readership are giggling at their "degassing" procedures

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12. Zoltan on September 21, 2010 11:23 AM writes...


Giggling indeed!

I haven't found the "degassing procedures" in the paper, are there any? What's the source of the NaH (in mineral oil) and THF (peroxides in an old flask?). Schlenk line or glove-box?

Mentioning "oxygen-free THF" just doesn't cut it.

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13. European Chemist on September 21, 2010 12:12 PM writes...

I was just wondering that letting that NaH oxidation paper into JACS actually got the journal and the authors a lot of media coverage. Even if for the bad reasons. After all this time still can't quite figure out how that stuff got past 3 referees.

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14. startup on October 15, 2010 9:58 AM writes...

re: vinegar. You are aware that lead acetate is quite sweet, right?

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