Sciencemadness Discussion Board

Mg/HCOONH4 oxime reduction...

kmno4 - 8-4-2007 at 02:26

From Rhodium's archive:

http://www.erowid.org/archive/rhodium/chemistry/oxime2amine....

I have tried this recently, with benzophenone oxime, but almost all oxime was recovered unchanged :mad:

Did anybody have successful effects with any oxime and this procedure ?

Nicodem - 8-4-2007 at 03:20

It did not work for me either.

PainKilla - 8-4-2007 at 11:48

That is interesting, as the procedure seems to have been existent for a while, and that is not the only journal reporting it... (1) ((look at Scheme 87, p 1282)) has a few references reporting this reaction.

There are a few other relatively simple (ie, no hydrides etc) methods to reduce oximes, including (2) Zn/NH4OOCH or NH4Cl, (3) various CTH reductions, and (4)Zn/CH3COOH (for which I have no access to references) but I haven't seen any reports of them being used practically by amateurs. An interesting and relatively easy route is through U-Ni-B (3a), though I don't believe there is much testing with atmospheric pressure (as far as yields and reaction times go, though apparently it does work) - the yields may likely suffer but it should still be doable.

A bit off topic but:
It's also very easy to convert aldoximes to nitriles, for which there are many, though most too difficult for the amateur, methods of reduction. Urushibara may come to the rescue again for this (5). There are also plenty of easy ways to convert aldehydes straight to nitriles, (6), (7) ((almost straight from aldehyde :)), though these are, I suppose of limited use (aldoximes). I have included most of the mentioned lit. and some other fairly relevant journal articles in the attached .rar.

1 - Magnesium in Methanol (Mg/MeOH) in Organic Syntheses - Current Organic Chemistry, 2004, 8, 1263-1287
2 - J. Chem. Res. (S) 6, 332-334 (2003) http://www.erowid.org/archive/rhodium/chemistry/oxime2amine....
3 - Just look at the references section for any of the above journals (concerning oxime reduction), pretty much all they reference is the CTH methods :(.
3a - New Hydrogenating Catalysts, Kazuo Hata, p. 192-196
4 - ?
5 - New Hydrogenating Catalysts, Kazuo Hata, p. 186-192
6 - One-pot synthesis of nitriles from aldehydes using hydroxylamine NaHCO3 and MW irradiation. ARKIVOC 2006 (ii) 41-44
7 - Synthesis of Nitriles from Aldoximes Using Silica Gel as Catalyst Under Microwave Irradiation. SYNTHETIC COMMUNICATIONS Vol. 33, No. 17, pp. 3085–3088, 2003

Does the Mg/HCOONH4 reduction work on aldoximes?

[Edited on 8-4-2007 by PainKilla]

Attachment: oximenitrilealdoxime reductions etc.rar (1.9MB)
This file has been downloaded 844 times

Nicodem - 8-4-2007 at 12:32

PainKilla, thanks for the compilation and the papers.
Quote:
Originally posted by PainKilla
That is interesting, as the procedure seems to have been existent for a while, and that is not the only journal reporting it... (1) ((look at Scheme 87, p 1282)) has a few references reporting this reaction.

Well, let's be honest. How many can reproduce any of the numerous Indian methods from the crappy 'letters' journals (the most famous for irreproducibility certainly being Tetrahedron Lett., but I don't think Synth. Comm. is lagging far behind)? I would estimate 60-80% are irreproducible while the rest give yields completely different than the publicized ones. I would expect no less from authors giving a title like "Magnesium-Catalyzed Proficient Reduction of Oximes to Amines Using Ammonium Formate" when they provide no proof of catalysis at all while it is obvious that Mg is the actual reducent and gets consumed during the putative reaction. Where the hell are the peer reviewers when you need them!:mad:

PainKilla - 8-4-2007 at 12:50

No problem, it's the least I can do.

As far as journals go, I am still in high-school so I haven't had the chance yet to test how irreproducible the (mostly Indian, now that I actually take note of it) procedures are but, I see your point.

These scientists have an excellent approach to the scientific method. I especially liked this, in reference to your comment: A control experiment was carried out using oximes with ammonium formate, but without magnesium powder does not yield any reduced product and the starting material is recovered in 100%. This confirms the role of magnesium as catalyst.

I hope the procedure does work (at least a little bit), as I will be testing it on 4-hydroxy-3-methoxy benzaldoxime. If it doesn't work, then Zn/Formate (probably doesn't work either), Zn/CH3COOH, and then U-Ni-B... I just find it annoying to make the nickel catalysts, even though it takes not even the whole of 30 minutes.

I like peer-review too, old journals always seem to be fairly reliable.

Sandmeyer - 8-4-2007 at 15:00

They should include an additional filter in scifinder for indian papers, I usually skip them as experience has shown that much of what they publish is fantasy. Anyways this review, that has been discussed in another thread, might be of some help:

https://sciencemadness.org/talk/viewthread.php?action=attach...
Quote:
These scientists have an excellent approach to the scientific method. I especially liked this, in reference to your comment: A control experiment was carried out using oximes with ammonium formate, but without magnesium powder does not yield any reduced product and the starting material is recovered in 100%. This confirms the role of magnesium as catalyst.


No it does not, just because a reaction doesn't work unless a component is present doesn't make this component a catalyst. That statement could have been made by authors to boost the credibility of their bullshit method; "Look, now it works, now it dosen't..." when in fact it doesn't work at all.

[Edited on 8-4-2007 by Sandmeyer]

PainKilla - 8-4-2007 at 15:18

Sorry, I should have been more clear. That was supposed to be somewhat (read: completely) sarcastic :D.

PS: That review and a few other nice tidbits are in the attached .rar.

Nicodem - 9-4-2007 at 00:20

I understood the sarcasm but the issue is pretty sad, not to say upsetting. Just note their claim in the abstract:
Quote:
Various aldoximes and ketoximes were selectively reduced to the corresponding amines by catalytic transfer hydrogenation employing low cost magnesium powder and ammonium formate at room temperature.

They claim Mg as a catalyst for transfer hydrogenation! The bloody Mg does not even have d orbitals! It can't possibly catalyze any hydrogenation at all. Good damn peer reviewers that are incapable to even read the periodic system chart!

The same authors in their other, practically identical paper, with the only difference of using zinc, claimed the same bullshit about catalytic transfer hydrogenation all over the paper. Their "proof" was the same:
Quote:
A control experiment was carried out using oximes with ammonium formate or ammonium chloride, but without zinc dust, and the starting material was recovered in almost quantitatively. This clearly indicates that zinc catalyses the reaction. In anticipating metal/alcohol reduction, experiments were performed in absence of hydrogen donor by refluxing substrate with methanol and zinc dust for 4-5 hours. Even after a longer period the starting material was isolated in quantitative yield, which clearly indicates the requirement of ammonium formate or ammonium chloride for the reduction. Here methanol serves as a solvent.

Is it surprising that a zinc dissolving reaction does not proceed without acid and that the acid itself can not reduce the substrate in the absence of the reducent? And they call this a clear indication for zinc acting as a catalyst!

These things just piss me off…:mad:

kmno4 - 9-4-2007 at 03:19

In the case of Zn/HCOONH4/EtOH(95%) I was able successfuly to reduce acetophenone oxime to amine (in good yield). Now I have just made some (Ph)2C=N-OH and decided to try Mg procedure with methanol as solvent.
Besides, I do not belive in used amount of solvent: 20 mmol - it is enough for substrates only to be wet and unable to sir. Original paper also gives "mmol". Propably this is an error and should be "cm3".

Nicodem - 9-4-2007 at 04:30

If you have the time, try also with using only HCOOH instead of HCOONH4. The reduction with NH4Cl/MeOH/Zn at room temperature is a standard procedure to reduce oximes only up to the N-hydroxyamine stage and I don't trust the characterization of the products as claimed by the authors. Some oximes might efficiently reduce to amines like in your case, but other might stop at the N-hydroxy stage. I do not exclude that the ammonia formed by the consumption of HCOONH4 and NH4Cl actually helps the reduction by complexing Zn2+ and thus additionally raising the redox potential of Zn metal, but I would still like to see a comparison with using HCOOH as proton source. After all nitroalkanes get reduced to amines by the HCOOH/MeOH/Zn system and the oxime/nitroso is supposed to be an intermediate.

The procedure in the paper uses the theoretical minimum of Zn needed to reduce the oxime (10mmol per 5mmol substrate) which is unpractical as the zinc powder never completely dissolves (especially if containing Pb contamination it tends to get "poisoned" at the end). And even if it does completely dissolve, it is a bit too optimistic that all would get used for the reduction and absolutely no H2 would evolve. I would recommend at least 15-20mmol zinc per 5mol substrate to get optimal yields.

PS: Reductions with aluminium amalgam are certainly more reliable even though more messy. The only oximes that I was unable to reduce with aluminium amalgam are the ones having a methoxy or phenoxy group alpha to oxime group (they can actually be recovered unchanged!). Simple oximes were however always efficiently reduced.