[electic]

Hi everyone
I would like to ask a couple of questions if i may.

I have recently been studying the reduction of oximes to >hydroxylamine>amine ,but i have read a lot of misleading information claiming that the reduction with formates and metal will yield amines ,but from what i understand is a reduction of oximes in a neutral or basic medium will yield hydroxylamines where as in acid medium would yield amines,my question is why would the formate reductions with dissolving metals follow any different rules.
And further more will a strong acid like hcl and metal reduce oximes to amines or would it be likely to stop a the hydroxylamine.if a dissolving metal reduction of oximes can proceed to amines could someone please provide me the mechanism.


many thanks electric

[Archer]

It is very difficult to stop the reduction of an oxime at the hydroxylamine, N-O bonds are easily cleaved under many reduction conditions. Any time that I reduce oximes they end up as amines with the exception of NaBH₃CN reduction.

Formic acid is a different to the other organic acids in that it is capable of reducing C=N bonds as in the Leukart-Wallach reaction. It delivers H₂ and decomposes to CO₂.

[electic]

Thanks archer for your fast response that clears things up .
Is it possible to reduce oximes to amines with zinc and hydrochloric acid or acetic acid,or is a more stronger metal hydride needed.


thanks electic

[Archer]

Thanks archer for your fast response that clears things up .
Is it possible to reduce oximes to amines with zinc and hydrochloric acid or acetic acid,or is a more stronger metal hydride needed.

Could you provide a little more detail on your application? i.e. what the molecule is that you are trying to reduce.

[electic]

Hi Archer

Because of the availability of chemicals i am using acetone and ammonium hydroxide to form the ketoxime and reducing it to isopropyl amine.
But i am unable to find any protocol for the reduction using zinc and acid only expensive hydride reducing agents or catylitic hydrogenation,i could not see why the zinc reduction would not work but i thought i would ask someone with more knowledge in this area than me.


thanks heaps for the replies 

[clarkstill]

If you want to make the oxime you need to be using hydroxylamine, not ammonium hydroxide!

[Archer]

Because of the availability of chemicals i am using acetone and ammonium hydroxide to form the ketoxime and reducing it to isopropyl amine.

This won't form a ketoxime from this reaction, ammonium hydroxide will give you a very unstable imine which will hydrolyse in the presence of hydrochloric acid.

But i am unable to find any protocol for the reduction using zinc and acid only expensive hydride reducing agents or catylitic hydrogenation,i could not see why the zinc reduction would not work but i thought i would ask someone with more knowledge in this area than me.

I sympathise with your situation, I have tried to make low MW amines because I needed one quickly for a reference material. The issue comes from the work up. Isopropylamine is very soluble in water making it difficult to purify so your yields will be small for a great deal of effort.
 

Considering that isopropylamine is about £25 or $40 a litre you should investigate more into a supplier rather than trying to make it.

[electic]

well i must be wrong i thought the reaction of a hydroxyl amine and a ketone formed an oxime , and the reaction of a primary amine and a ketone formed an imine or at least thats what i thought.
As for the purification process is isopropyl amine free base slightly soluble in water making an a/b extraction difficult

regards electic

[Archer]

well i must be wrong i thought the reaction of a hydroxyl amine and a ketone formed an oxime , and the reaction of a primary amine and a ketone formed an imine or at least thats what i thought.

You are right,

Ketone + hydroxylamine  oxime + water
Ketone + Ammonia  imine + water
Ketone + primary amine  N-substituted imine + water

You put this:

i am using acetone and ammonium hydroxide to form the ketoxime and reducing it to isopropyl amine.

Ammonium hydroxide is not the same as hydroxylamine.

As for the purification process is isopropyl amine free base slightly soluble in water making an a/b extraction difficult

It is freely soluble in water, making a/b extraction challenging if you want to prepare a useful quanitity.

[electic]

sorry archer

my bad i meant hydroxyl amine NH20H
i will try salting out water layer in the a/b see if that helps

thanks electic

[electic]

Hi Archer

! Quote
You are right,

Ketone + hydroxylamine   oxime + water
Ketone + Ammonia   imine + water
Ketone + primary amine   N-substituted imine + water

The reason i asked was i have forgot a lot of chemistry that i learnt earlier in my life ,but being right means i haven't forgot everything thank god.
Getting back to the reduction of my low molecular weight oxime i have effectively reduced this compound to the amine with a metal hydride ,and i thought i would try the reduction with zinc and acid ,i no there is preparative methods for the reduction of oxime with zinc and acid but i haven't seen any patents or abstracts to support that claim.
This is why i asked if you have any credible information to say that this reduction works,or if you have succeeded your  self with this method ,it would be nice to no if this is posable before i do it.
Or i suppose i will just give it a go.


regards electic

[electic]

well surely there is someone that can help me with this not just archer.
Or is this to simple of chemistry for anyone to bother replying, i mean to say there are a lot of lookers but no replies
or did i ask a stupid question.


thanks electic

[Archer]

I have a method but it makes the acetamide which needs acid hydrolysis to yeild the amine.

To a solution of oxime (13 mmol) in a mixture of acetic acid (10 mL) and acetic anhydride (4ml) under Argon at 0-5 °C, zinc dust *CARE* (see note) (3.4 g, 52 mmol) is added portionwise over 90 minutes while the temperature is kept about 40 °C and stirred. Once the reaction is complete by TLC, (a total of two hours is normally sifficient) the solids are removed by filtration *CARE* . The filtrate is evaporated under vacuum. The residue is dissolved in a mixture of diethylether (30 mL) and
water (20 mL). After separation of the phases, the organic layer is washed with NaHCO₃, dried (Na₂SO₄) and evaporated. The
residue can be used in the hydrolysis step without further purification.

Note that powdered metals are extremely flamable and zinc is no exception.

Also consider that this will make about 1 gram of your product if you are lucky, scale up is risky as the potential for fire becomes greater.

[electic]

Thanks Archer

I haven't done a Beckmann rearrangement before but i should give it a go , only problem is you are not allowed to have that particular anhydride where i am from but i thought it was not required for this reaction to proceed my understanding is it is done with conc h2s04 but maybe i am wrong.
I suppose the question i asked about the reduction of oximes to amines with zinc and hydrochloric acid, now i think about it the oxime will maybe undergo hydrolysis to the parent ketone and is why reductions to amines cannot be done in a strong acid medium ? is this correct


regards electic

[electic]

Hi everyone can someone tell me why there is over 500 views on my post more than any other post in the organic forum but no one wants to reply strange to me ,but maybe it is to simple of a topic and maybe should have been posted it in beginnings forum.
There appears that there is very few replies to anyones posts in all forums ,i would of thought this contradicts what this forum stands for.
The first thing you read when you sign up is feel free to post questions and we will get back a reply as soon as possible

? cant work it out

regards electic