Reduction of oximes to corresponding amines

Hello

At first i wanna say that i tried reductive amination to prepare primary amines with of course 25% NH3 and yield was pathetic , so i started search something more "yield" and i think that's reduction of oximes , i found in some paper (references at the end) extremely easy preparation for example : acetoxime (withouth extraction , heating etc) look at this:


"Hydroxylamine hydrochloride (69g) was dissolved in 140 ml water and 140 ml 20% NaOH was added. Acetone (140 ml ) was added and the mixture was vigorously stirred for 10 minutes. The reaction mixture was allowed to stand for one day and the crystals were collected by suction. Weight: 45 g or 62% yield."

Now we have our oxime so i wanna my amine in these case isopropylamine , they write the best for reduction is sodium and anhydrous ethanol (s....t hell no ! too expensive) so i want to try Al/Hg reduction , i have make some changed recipe for that and i wanna know if that will works :

"We mix 125 ml methanol and 25 ml water and add to that in reaction flask 5 g al foil balls and 0,1 g HgCl2, we wait 20 minutes to finish amalgamation , so we prepare second solution 11 g acetoxime in 50 ml methanol (should easily dissolve i searched and they write very soulible in alcohol), after 20 minutes we add our solution oxime to reaction flask and put reflux condenser , ater the reaction stops we chill to room temperature our solution and now i don't know what to do :

1) extract with 2x50 ml toluene and gas with HCl

2) filtrate the solution and evaporate amine ?????

3) is that nessesary to add NaOH solution to dissolve remain Al foil ?

and most imporant question : did someone try reduction of oxime and how about yield ???? beacuse if is shitty , i give up

thnaks for any help

References :

C-13 Nuclear Magnetic Resonance Spectra of Amines by Cheng-Hsia Wang

Quote: Originally posted by arsphenamine

Consider running a Beckmann rearr. on the ketoxime to yield N-methyl acetamide ... which does NOT stink.

Quote: Originally posted by mario840

1) extract with 2x50 ml toluene and gas with HCl 2) filtrate the solution and evaporate amine ????? 3) is that nessesary to add NaOH solution to dissolve remain Al foil ?

Quote: Originally posted by mario840

so the step when i add NaOH to liberate amine MUST BE DONE ? or can i right after when reaction is over extract with toluene ?

Quote:

K. Abiraj and D. Channe Gowda J. Chem. Res. (S) 6, 332-334 (2003) Reduction of oximes to amines, general procedure: To a solution of the substrate (5 mmole) in methanol (10 ml) was added ammonium formate (10-20 mmole) [or ammonium chloride (10-20 mmol)] and zinc dust (10 mmol). The mixture was stirred under reflux. After the completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite. The filtrate was evaporated under vacuum and the residue was taken into chloroform or ether, washed twice with 80% saturated brine solution and finally with water. The organic layer was dried over anhydrous sodium sulphate and evaporation of the organic layer was followed by purification either by preparative TLC, or by column chromatography, to yield the desired product.

I don't agree with that , why? look at in rhodium for reductiuon of oximes with al-hg , I want al-hg (i don't have acess to ammonium formate, magnesium etc.):

"JACS 111, 6228 (1989) To a solution of the oxime (24.6 mg, 0.521 mmol) in 10% H2O-THF (30ml) were added aluminum amalgam, which was prepared from 0.25g of granular aluminum and 2% HgCl2 (0.1ml) in 10% H2O-THF (0.5ml). The reaction mixture was stirred for 3h at room temperature. 3ml conc NaHCO3 was added, and the reaction mixture was filtered and the filter cake washed with ethyl acetate. The filtrate was diluted with water and extracted with ethyl acetate. The extracts was washed with brine, dried over MgSO4 and concentrated in vacuo to give 20.34 mg (85%) of the desired amine as an oil."

As you know to amalagmation start there need to be water, so here it is 10% H2O-THF , and there is no mention to H+ donor like acetic acid or formic (in other examples also don't add any of acid like formic or acetic) , sure there is NaOH in these case NaHCO3 witch is base, there only extract, wash with brine and evaporate in vacuo and look at the yield ---> 85%
I think instead MeOH better will be to use Isopropanol wich form nice 2 layer after reduction, bottom - unreacted al and top aimne + some isopropanol, add NaOH and extract with toluene or ether or etc.

By the way thx for reply , i wanna know if someone reduce oximes (not exactly these one) what yield he got

Quote: Originally posted by mario840

Quote: A problem in your procedure is a missing H+ donor. You have to add some formic- or acetic acid to get the reaction working I think. I don't agree with that , why? look at in rhodium for reductiuon of oximes with al-hg , I want al-hg (i don't have acess to ammonium formate, magnesium etc.): "JACS 111, 6228 (1989) To a solution of the oxime (24.6 mg, 0.521 mmol) in 10% H2O-THF (30ml) were added aluminum amalgam, which was prepared from 0.25g of granular aluminum and 2% HgCl2 (0.1ml) in 10% H2O-THF (0.5ml). The reaction mixture was stirred for 3h at room temperature. 3ml conc NaHCO3 was added, and the reaction mixture was filtered and the filter cake washed with ethyl acetate. The filtrate was diluted with water and extracted with ethyl acetate. The extracts was washed with brine, dried over MgSO4 and concentrated in vacuo to give 20.34 mg (85%) of the desired amine as an oil." As you know to amalagmation start there need to be water, so here it is 10% H2O-THF , and there is no mention to H+ donor like acetic acid or formic (in other examples also don't add any of acid like formic or acetic) , sure there is NaOH in these case NaHCO3 witch is base, there only extract, wash with brine and evaporate in vacuo and look at the yield ---> 85% I think instead MeOH better will be to use Isopropanol wich form nice 2 layer after reduction, bottom - unreacted al and top aimne + some isopropanol, add NaOH and extract with toluene or ether or etc. By the way thx for reply , i wanna know if someone reduce oximes (not exactly these one) what yield he got

Aaah, H2O is the H-donor in that reaction I think.
Some hydrogen is absolutely neccessary! See picture!
H2O is a much better H-donor than MeOH and any acid should be a much better donor than water. But you can try it with water.



[Edited on 1-10-2010 by Methansaeuretier]

Quote: Originally posted by Methansaeuretier

Quote: K. Abiraj and D. Channe Gowda J. Chem. Res. (S) 6, 332-334 (2003) Reduction of oximes to amines, general procedure: To a solution of the substrate (5 mmole) in methanol (10 ml) was added ammonium formate (10-20 mmole) [or ammonium chloride (10-20 mmol)] and zinc dust (10 mmol). The mixture was stirred under reflux. After the completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite. The filtrate was evaporated under vacuum and the residue was taken into chloroform or ether, washed twice with 80% saturated brine solution and finally with water. The organic layer was dried over anhydrous sodium sulphate and evaporation of the organic layer was followed by purification either by preparative TLC, or by column chromatography, to yield the desired product. In this case formic or acetic acid may work even better. [Edited on 29-9-2010 by Methansaeuretier]

@scrambles - this appears to be a typical catalytic metal reduction, using Zn as the catalytic surface and ammonium formate or ammonium chloride as the hydrogen source. If you look up zinc ammonium formate on google scholar, you will find a lot of reductions of nitrogen in almost any oxidation state down to the amine. Nitro, nitroso, oxime, imine, etc.

A very useful reaction and one of the reasons I keep a bottle of zinc dust under my lab bench!

Quote: Originally posted by fledarmus

this appears to be a typical catalytic metal reduction, using Zn as the catalytic surface and ammonium formate or ammonium chloride as the hydrogen source. If you look up zinc ammonium formate on google scholar, you will find a lot of reductions of nitrogen in almost any oxidation state down to the amine. Nitro, nitroso, oxime, imine, etc.