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| Sorry, JACS, we exaggerated a little |
Chemist Matt Katcher of Princeton has been kind enough to re-run one of the examples from the paper (Table 2, example 2). He's skeptical, based on TLC, NMR, and LCMS, that even trace product has formed; the authors claim 83%.
What's missing here?
Looks like there's some 'splainin to do! Anybody else have a few minutes today? Maybe, with enough groundswell, we could have another NaH oxidation fight on our hands.
Who's in?
For those interested and not following on Twitter, I still think the reaction might work, but it may not be a simple "dump and stir". If I did it again, I would run it in a Schlenk tube to minimize exposure to air. Admittedly, the iron that I used was from an old bottle, so that could have been a factor. I did run it on one-fifth the scale they report (1 mmol vs. 5 mmol), but I doubt that matters too much. Finally, I did notice that the stir bar got stuck a few times, and that may be problematic if the reaction is heterogeneous. Hope this helps anyone else who tries!
ReplyDelete- Matt Katcher
Yeah, you probably need to use fresh iron and purge with Argon. It could be that if you have O2 in there in any way it will inhibit the reaction by oxidizing the iron or the transient FeS species. The authors run the reaction under Argon.
DeleteActually, if you want to test this, run two same reactions side by side, and just keep one away from O2, and run the other in air.
Another test would be order of addition of reagents.
Also, the reaction is definitely heterogeneous in terms of generating FeS from solid iron, so you will need finely divided iron (they used 100 mesh from sigma aldrich).
DeleteIts not clear if the authors stirred their reactions. They use a "pressure equalization tube". Googling around does not give any clue about what the heck that is. Maybe they meant high pressure reactor, like a Parr reactor? Maybe email the authors to ask what their appartus was?
(this is the same anonymous that posted at 4:07)
I did realize later that using a stir bar with iron might not have been the best idea (looks like the iron was stuck to the stir bar at the end of the reaction). Paper says they used 100 mesh FeS powder but I didn't see anything about what kind of Fe they used...
DeleteIron-sulfur cluster are instantly oxidized upon exposure to air. It's a good idea to run the reaction under strictly anaerobic conditions reaction.
DeleteI am not impressed - it does not address any synthetic methodology need. Normally as a process chemist if you need benzoxazoles or benzimidazoles you mix aromatic aldehyde with o-benzenediamine or o-aminophenol, add bisulfite and reflux the mix in water under air, you get high yield, the functional group tolerance is very good.
ReplyDeleteThe only reason this is in JACS is the proposed catalytic Fe-S cluster/ pre-biotic chemistry angle. Otherwise it is a Tet Let grade stuff.
What greatly annoys me is that the reaction conditions closely parallel more than century old classical Willgerodt chemistry (ammonium polysulfide in water, 150C, 1-2 days heating in a sealed tube) and obviously activated (=relatively acidic C-H) methyls on heterocycles will readily produce an aldehyde equivalent under these conditions, by Methyl group thiolation + oxidation with polysulfide species. At the same time, sulfides and polysulfides at elevated temperature are excellent agents for reducting nitroaromatics to anilines, they have been also used for more than century for the purpose. So perhaps they just coupled two facile polysulfide-based redox processes together and the real reason why pre-formed FeS performs poorly is that it must to disproportionate to polysulfide species which is not really favored thermodynamically. I would be more conviced about their iron sulfide cluster catalysis proposal if they tested and excluded Aldrich-available potassium and ammonium polysulfide as a catalyst
"if you need benzoxazoles or benzimidazoles you mix aromatic aldehyde with o-benzenediamine or o-aminophenol"
Deletewhile aromatic aldehydes'starting materials are aromatic alcohol or methylarenes, while o-benzenediamine or o-aminophenol are prepared by reduction of nitro compounds.
"Otherwise it is a Tet Let grade stuff." It should be at least Org. Lett. because of its unprecedented simplicity.
"What greatly annoys me is that the reaction conditions closely parallel more than century old classical Willgerodt chemistry"
This reaction cannot be considered as a Willgerodt extension because sulfur is used in only catalytic amounts.
"150C, 1-2 days heating" The mild conditions are the conditions which can afford the desired products without hampering other functional groups present in the molecules. Do you think O° C with n-BuLi, NaOH or NaH in the presence of ArX, ArNH2 or ArNO2 is better than 150 °C with S or Fe or FeS ?
"obviously activated (=relatively acidic C-H) methyls on heterocycles will readily produce an aldehyde equivalent under these conditions, by Methyl group thiolation + oxidation with polysulfide species. At the same time, sulfides and polysulfides at elevated temperature are excellent agents for reducting nitroaromatics to anilines, they have been also used"
easier said than done.
"they have been also used for more than century for the purpose" In 100 years, A chemical reactions will be carried out with molecules.
"So perhaps they just coupled two facile polysulfide-based redox processes together and the real reason why pre-formed FeS performs poorly is that it must to disproportionate to polysulfide species which is not really favored thermodynamically." This is the nature of any catalytic system for reaction A + B ---> P. A catalyst Cat. will reacts with A to yield intermediate A-Cat. which can be attacked by B to afford the final product P and release Cat.
"I would be more conviced about their iron sulfide cluster catalysis proposal if they tested and excluded Aldrich-available potassium and ammonium polysulfide as a catalyst" I think they did run these experiments but sometimes, for clarity reasons, some results are not described in paper.
You wouldn't happen to be one of the authors, would you? (hopeful...)
Deletewhen you put a new twist on a century old heterocyclic chemistry and the resulting methodology is ho-hum in its scope and usefulness, it has to have some other redeeming quality to get into a high profile journal. In this case the aspect that makes it JACS-worthy is the Fe-S cluster catalysis. But the authors did not gather supporting evidence for this mechanism - they also did not bother to disprove or even discuss the most obvious alternatives to their favorite proposal. (And if they did try poloysulfides - then why its not in the goddamned experimental conditions table??) Maybe the authors were afraid to look into the alternative mechanism so that they could be more "honest" in their sales pitch. Because they realized they could not get a polysulfide-catalyzed paper into JACS. (OR, even more sad possibility is that perhaps no alternative mechanisms occurred to the authors)
DeleteSo while it is still a marginally less sloppy paper than the "NaH-catalyzed oxidation" it provides yet another proof that the JACS editors are sleeping on the job
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ReplyDelete