Oxime reduction with magnesium/nh4cooh

sony · Tue Mar 22, 2005 8:32 pm

On http://rhodium.moppy.net/www.rhodium.ws/chemistry/oxime2amine.mg-af.html there is a procedure described for the reduction of oximes. Before they use the Magnesium they clean it up :

Magnesium powder was purchased from SISCO Research Laboratories Pvt. Ltd., Bombay (India) and was treated with 0.01 N hydrochloric acid for about 2 min. It was filtered through a sintered glass funnel and washed with water, dry methanol and dry ether. Thus obtained magnesium was vacuum dried and stored.

Does anybody see a problem with using Magnesium Oxide here ?

64bandil · Busy Bee

Instead of magnesium?

It will most definately not work with magnesium oxide instead. Magnesium reduces the oxime to the amine, and while doing so it gets oxidized to magensium oxide. If it's allready oxidized, then it will unable to reduce anything. The only reason they treat it with dilute acid is to remove any oxide layer present...

So go fetch some real magnesium Smile

Regards
Bandil

IndoleAmine · Dreamreader Deluxe

Please also note that it HAS to be the Mg from SISCO Research Laboratories Pvt. Ltd., Bombay (India), other brands most surely won't work. Laughing

(just like with Reynolds foil!!!!)

No, serious: I have never heard of a successful reduction of a USEFUL oxime to an amine using Mg/NH4COOH, the paper talks only about certain aromatic oximes AFAIK - so it would be very interesting to hear about the outcome of this xperiment!

i_A

Vitriodor · Fri Mar 25, 2005 12:17 am

This reaction seem to work for compounds which have an oxime group next to the phenyl ring (alpha position), as is shown in the article mentioned by Sony. But are there reasons why it wouldn´t work for reduction of beta oximes, the type of molecules we are interested in ?

anime · Thu Apr 14, 2005 9:32 pm

IndoleAmine · Dreamreader Deluxe

Can we have a writeup please? Although the yields aren't high, you're still the first one to report the successful use of Mg for reducing oximes AFAIK - so it would be nice to hear a few details... Wink

i_a

anime · Sat Apr 16, 2005 5:02 am

The reaction was performed a long time ago, recently swim has not been so keen on producing hcl salts because of hydrochloric gas, but swim will re-run the reaction and post the results. One thing is for sure is that an amine product is produced and the product is enjoyable active. (Often a pinkish color product is obtained via this method).

The yield for first time production were ok, 10g for 20g of oxime, following yields were lower ~2-5g / 20g oxime. (probably due to impure oxime and other factors). The magnesium needs to be activated, zinc works too.

anime · Tue Apr 19, 2005 6:24 am

I had a strange dream this afternoon, I was taking a brief nap and accently slept too long...In the dream I walked into my kitchen and there was an elf performing some chemistry. I sat there watching as he performed the following reaction:

9g. (46mmole) of crude (1) MDP2P-oxime is added to a solution of 80ml of IPA (99.9%) and 30ml of 95% Formic acid(3). 9g of magnesium powder (2) is added to the solution, the solution quickly becomes warm to touch. The entire solution is stirred at room temperature for 2 hours.

A 50% solution of NaOH is added and a violent reaction takes place. The 150ml beaker used could not contain the boiling IPA and the contents were quickly tranferrered into a mason jar (1 quart)(The first empty thing the elves could see). It was noted that two layers formed, a orange color IPA layer and a clear aqueous layer. The IPA layer is seperated, and extracted with 150ml of toluene. The aqueous layer is extracted with 50ml of toluene. The extracts are combined, washed with a brine solution and dried over MgSO4. The toluene is gassed with dry HCl.

Total yield 3.2g of white powder.
The molar yield is 31.7%.

He told me the following things after the reaction was perfomed.

(1) From his experience, recrystallized MDP2P-oxime gives higher yields.
(2). Amount of magnesium is an overkill, 3-4g should be fine.
(3). Formic acid was used instead of ammonium formate. Reaction seems to run the same, although when basifying there is no nasty release of ammonia gas.

IndoleAmine · Dreamreader Deluxe

At least its faster than a leuckart... Very Happy

And completely OTC too...

Makes me wonder if zinc/HCOOH can reduce oximes too.. Question

(and just to remember: sodium/alcohol reduces oximes too, in >90% yield if done properly... Wink

)

(BTW formic acid is no good hydrogen donor compared to ammonium formate)

i_a

anime · Tue Apr 19, 2005 11:26 am

The Zinc/Ammonium chloride reduction works too, yields are similar. As stated, pure recrystallized oxime yields higher, the trick to the zinc is the activation it via the dilute hcl. The magnesium is easier to stir than the zinc, its not as dense.

Formic acid was used because NO2 reductions using Amm. formate worked with formic acid as the donor. I know potassium formate is suppose to be a good hydrogen donor.

I'm sure this procedure can be optimized the biggest problem is getting the oxime to dissolve in the solvent, MeOH and IPA were tried, the MDP2P oxime seems more soluble in IPA.

joe_aldehyde · huxleys associate

how do you guys avoid precipitating a lot of Mg(OH)2 or Zn(OH)2 in that kind of reductions? not only do Zn/HCOOH nitro reductions have low yields but the workup is also horrible, having to handle huge amounts of unfilterable precipitate.

anime · Fri Sep 16, 2005 3:13 am

Joe, instead of basifying the mixture one could go ahead and evaporate the IPA layer after filtration of the Mg(0). Basification at any point will result in a very ugly emulsion layer that makes you tear hair out of your head and want to give up chemistry.

My last attempt at reduction via Mg/Formate salt resulted in horrible non existent yields, I think the trick is to limit the amount of Mg used in this reaction to a min. (since the rxn is supposedly catalytic). I think more formate salt and longer reaction times could give better yields, reaction for 1hr -2hr was found to have a large quantity of unreacted oxime.

Another (better IMO) option would be going to some Urushibara, Urushibara can reduce nitrogroups at atmospheric pressure hydrogen gas, I'm sure would play very well with formate salts at reducing the =NOH -NO2 to the corresponding amines via CTH. Raney Nickel works well here too.

Urushibara as you know is easy to make. If you have Pd/C you can use it too.

joe_aldehyde · huxleys associate

just evaporating the IPA layer? well, what do you end up with, then? the Zn salts need to go somewhere. or do you separate the IPA layer? how do you find out where your amine resides? i have a hard time measuring the pH of my post rxn mixture, which seems to be mostly neutral (quite some amine ought to be in the water layer at that pH). i have been tearing my hair out and seriously - i cursed all synthetic approaches. are there no high yielding, easy reductions? fuck NaBH4, fuck Al/Hg (toxic shit, never gonna touch that again, yields are low), fuck Zn and certainly fuck CTH that unreliable bitch.

yes i have pd/c, but as posted earlier it SUCKS big time, no idea why - once i get low yields, next time i get nothing. any ideas? i need to think long and hard about LAH or red-al...i guess LAH might be the last word about reductions. quite dangerous, though...too dangerous.

anime · Fri Sep 16, 2005 4:13 am

generally when u remove the IPA u'll end up with some oil, if you were infact using a base for the reduction ie HCOOK/NH4 intead of HCOOH, the amine can be sucked up with some non-polar solvent.

Mind you even with this method the yields are pretty pathetic.

joe_aldehyde · huxleys associate

i guess the biggest problems are oxime and subsequently ketone formation which condense with the amine to the imine and get reduced...ending up in the precipitate after an a/b. really sucks...
i wonder which reduction method would circumvent these kinds of reaction mechanisms. what stages do nitroalkanes undergo when being reduced? i guess an intermediate oxime is always unfavorable when working in aqueous environment. acidic environments could trigger a nef reaction which yields a ketone, same problem...