The Hive > Novel Discourse

Imines to amines with Zn/5% aq NaOH

(1/3) > >>

I have no idea if this method will work on any useful ketimines. But since NaBH4 probably will become quite difficult to obtain in a not too distant future, it can be beneficial to have a few options.

Tet. Lett. vol 39 (1988), 8873-8876.

Water has many advantages as a solvent for organic reactions from the aspects of cost, safety, simple operation and environmental concerns as compared with use of an organic solvent, and many organic reactions such as the Diels-Alder reaction, pinacol coupling, the aldol reaction and so on have been reported. We have been continuously investigating reductive dehalogenation of halogenated compounds and reductive coupling reaction of carbonyl compounds with metals in aqueous media. We report here our significant finding that in 5% aq NaOH solution without any organic solvents, zinc powder is effective for the reduction of imines to give the corresponding amines under mild conditions with a simple procedure.

When imines (1a-q) were treated with zinc powder in 5% aq NaOH solution at room temperature, reduction proceeded and the corresponding amines (2a-q) were obtained in 53-88% yields. Further we have found that no traces of amines  and carbonyl compounds formed by hydrolysis of imines were obtained in our method though imines tend to be hydrolyzed in acidic or basic solution.

In the case of aldimines having a substituent group on the aromatic ring, reaction is shortened, but the reason for the effect of the substituent group is now clear yet. Our method is not limited to aldimines and works as well with aliphatic imine and ketimines.

General procedure

To a stirred mixture 5 mmol imine  and 20 ml  5% aq NaOH at room temperature was gradually added 5g zinc powder during 10 minutes. When addition is complete the mixture is stirred for the appropriate time (1-7 hours, TLC). The insoluble materials were removed by filtration and the filtrate extracted with EtOAc. The extract is then washed with water, dried over MgSO4 and evaporated in vacuo to give a crude amine which can be distilled or crystallised as it is.

Benzaldehyde oxime gave benzylamine in 63% yield after 22 hours, with no trace of N-benzyl hydroxylamine.

Benzylidene-phenyl-amine gave benzyl-phenyl-amine in 82% yield after 7.2 hours.

(4-F-Benzylidene)-phenyl-amine gave (4-F-benzyl-phenyl)-amine in 85% yield after 0.7 hours.

Benzylidene-methyl-amine gave N-benzyl-N-methylamine in 53% yield after 0.2 hours. 

I will try the following when I have the time.

To some appropriate P2P dissolved in MeOH or EtOH, 30-40% aq methylamine is added. Zn powder and aq NaOH is added and the mixture stirred for a few hours. If the imine is reduced by the Zn/NaOH system the equlibrium should be shifted towards amine even if the imine formation conditions aren´t optional. The yields can´t be any worse than with Al(Hg), and the world should benefit from the lack of Hg in the reaction.

...what the Zn/ammonium formate or Zn/formic acid system would do to a poor ketimine? The formic acid would for sure give the corrects conditions for imine formation. A P2P, amine, alcohol/water, Zn and formic acid....Hmm!

Well let´s try it.

Since it seems that you were talking to yourself (I know that feeling), I 'll give some feedback  :) .

Did the examples in the Tetrahedron article mention aliphatic amines or only aromatic amines?  I ask this question because I have an article where they get excellent yields for the reductive amination of ketones with primary aromatic amines using activated Zn / AcOH, but they state that the reaction doesn't work for aliphatic amines.  See Post 343078 (missing) (Cyrax: "Thx Rhodium, I didn't have that article in my ...", General Discourse).  OK, the procedure is not the same as yours, but I am somewhat sceptical.  However, don't let this discourage you.  If the Zn reduction of methylimines works, that would be great.

Here is the link to the full text article  :)
this seems to work.

Got democracy?


[0] Message Index

[#] Next page

Go to full version