Sciencemadness Discussion Board

Amine synthesis

Random - 12-5-2011 at 14:52

I was thinking about synthesis of amines from ketones (and aldehydes can also be used) and I found this webpage:

http://www.drugs-forum.com/chemistry/chemistry/methylamine.html

In this, aldehyde is reacting in acidic medium with ammonium chloride to form imine and then imine reacts with with water and aldehyde to make carboxylic acid and amine.

Now, if ketone is used, for example 2-butanone, 2-butylimine should be formed. But this is not aldehyde to reduce imine to amine, so I would need to reduce it with something.

But, I read on many places that imines are unstable. What is formed when they decompose?

From wikipedia:
Quote:

The most important reactions of imines are their hydrolysis to the corresponding amine and carbonyl compound. Otherwise this functional group participates in many other reactions, many of which are analogous to the reactions of aldehydes and ketones.


So, imine should be hydrolised with maybe HCl(aq) to amine and a carbonyl compound (in this, 2-butanone should be formed along with amine).

So, would 2-butylamine synthesis work like that? I would react MEK (2-butanone) with NH4Cl to make 2-butylimine. Then it would be hydrolysed with formed HCl(aq) to make 2-butylamine?

Though, when I think, ammonia could act as the simplest amine and it would be formed instead of 2-butylamine.

Then, I should actually use reductive amination. What can be used for reductive amination of ketones? Maybe NH4OH(aq) + Sodium metabisulfite or dithionite would work? I don't have access to hydrides.

Sedit - 12-5-2011 at 17:45

Im not sure exactly where your at here but when it suggest hydrolysis you will not get the amine of butanone you will just recover your starting products with the amine in the form of the hydrochloride salt.

IE: you made an amine with Butanone and ammonia. After hydrolysis you yeild nothing but Butanone and Ammonium Chloride...

Reductive amination does not techincally work on a ketone. What you are reducing is the Imine. Reduction of the ketone yeilds an alcohol.

A good method albeit toxic yet well studied in the amature community is the use of Hg/Al to reduce the Imine to the Amine. There are alternative means of activating the aluminum being explored which use Copper sulfate and Sodium chloride so perhaps for experimental reasons it would be worth a go.

DJF90 - 12-5-2011 at 18:08

Quote:
Reductive amination does not techincally work on a ketone. What you are reducing is the Imine.


Reductive amination *does* work on a ketone. The "amination" part suggests introduction of nitrogen (as an amine). Reductive amination of an imine does not exist - that is purely a reduction (to the amine). Similarly, you can't call the reduction of a nitro group a "reductive amination" - it is not, and I'm sure you'll agree with this (and hopefully see the analogy).

The imine is an intermediate in the reductive amination of a ketone or aldehyde with an amine or ammonia. When formaldehyde is used, this is capable of reducing the imine to the methylamine, itself being oxidised to formate. Formate is also capable of reducing imines (c.f. Leuckart reaction). Hydride species will also do it, and what generally varies is the conditions required to effect the reduction. For example, Sodium cyanoborohydride is a sufficiently weak hydride reagent to not reduce ketones or imines at neutral pH, and in fact requires a pH of about 5 to work efficiently; this occurs because the imine becomes protonated to the iminium cation, which is orders of magnitude more nucleophilic. Sodium triacetoxyborohydride works on a similar principle.

(Please note that the above example is not strictly true - NaCNBH3 *will* reduce ketones and imines at neutral pH, but the reaction is very slow in comparison to that with the iminium species. Reduction of the ketone does not occur to any appreciable extent even at pH5 as this species still exists in its unprotonated form.)

[Edited on 13-5-2011 by DJF90]

Sedit - 12-5-2011 at 18:14

I agree DJF90, my wording was put that way because I wanted to make it clear that the carbonyl was not magically becomming an amine. I wanted to stress what exactly was being reduced in the amination process. His words about the hydrolysis made me very confused so I wanted him to be sure he understood that the Imine is where the reduction takes place when amination is performed.