Imines to amines with Zn/5% aq NaOH

[Barium]

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. 

[Barium]

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.

[Barium]

...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.

[Cyrax]

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.

[ChemisTris]

Here is the link to the full text article  
edit:

http://chemistris2.tripod.com/tl.pdf

this seems to work.

Got democracy?

http://www.dhushara.com/book/multinet/democ/wed.htm

[GC_MS]

Gives me an error msg when i want to read the first page, chemistris
WOMAN.ZIP: Great Shareware, but be careful of viruses...

[Cyrax]

There was no error when I viewed it, GC_MS (with acrobat reader V5.0).

In example 1h, they condense benzaldehyde with methylamine, the yield is only 53 %   .

I hope an optimized procedure can be found for P2P ...

[GC_MS]

SWiM dls with opera and the pdf is fux0red; he dls with IE and it is fine. wtf?
Cyrax: yields look low indeed   ... Deriving from 1a-1c, single substituents don't seem to have that much of an effect.
WOMAN.ZIP: Great Shareware, but be careful of viruses...

[thewire]

Hydrogenation Reactions of ketimines and aldimines

2. Reduction using metals
4. Sodium borohydride
Harada, K.; Patai, S. The Chemistry of the Carbon Nitrogen Double Bond; John Wiley and Sons,
Inc.: New York, 1970;pp. 276-298

A mixture of methylamine and m-methoxybenzylmethyl ketone yields the corresponding N-methylamine by reduction with aluminium and water (equation 110) ref. 118

118. G. Hildebrandt, U.S.Pat. 2,344,356 (1944);Chem. Altstr., 38, 3421 (1944).
------------------
Organic Reaction in Water. Part 1. A Convenient Method for Reduction of
lmines Using Zinc Powder

Tetrahedron Letters 39 (1998) 8873-8876
---------------
A simple and efficient method for the preparation of secondary N-alkylarylamines via reductive amination of ketones with primary aromatic amines using activated zinc/acetic acid is described. It requires only equimolar amounts of the starting compounds and affords good yields of the corresponding amines (50-90%). It is not applicable to aldehydes nor aliphatic amines

Synthesis, 1991, 11, pp. 1043-1045
-----------------
Reductive Amination with Metallic Magnesium
J. Chem. Soc. Perkin Trans. 1, 265-269 (1995)

https://www.erowid.org/archive/rhodium/chemistry/redamin.magnesium.html
---------

[thewire]

121. H. Schonenberger, H. Thies and A. Rapp, Arch. Pharm., 298, 635 (1965)
Der Einfluß von Lösungsmitteln auf den Verlauf der Reduktion Schiffscher Basen mit aktiviertem Aluminium (pages 635–638)

When benzylidenealkylamines (41) and ethanol are treated with activated aluminium, a
mixture of benzylalkylamines (42) and NN'-dialkyl-a-a'-diphenylethylenediamines (43) is obtained (equation 112) ref 121.

-----------------
Cp2TiCl2 catalyzed reduction of imines by isopropyl magnesium bromide

Abstract  Refluxing RCH:NR1 (R = Ph, 4-ClC6H4, 4-MeOC6H4, 4-Me2NC6H4; R1 = Ph, 4-ClC6H4, 4-BrC6H4, Bu, cyclohexyl) with Me2CHMgBr in the presence of dicyclopentadienyltitanium dichloride in Et2O gave 66-93% RCH2NHR1.

http://sioc-journal.cn/Jwk_hxxb/EN/abstract/abstract335004.shtml#
------------
A new synthetic method for the reduction of imines by samarium-induced reaction

IJC-B Vol.40B(11) [November 2001] p1134
------------------

[thewire]

YAKUGAKU ZASSHI
Vol. 75 (1955) No. 9 P 1161-1162

The Reduction of Schiff Bases with Sodium Borohydride

Zen-ichi Horii, Tatsuo Sakai, Takeshi Inoi
Released: February 19, 2010

Reduction of Schiff bases with sodium borohydride yielded the corresponding secondary amines, the yield of which was much better than that by reduction with lithium aluminum hydride.
----------------
Reduction of Schiff Bases with Sodium Borohydride
J. H. Billman and A. C. Diesing, J. Org. Chem., 23, 1068 (1957).

[lullu]

A few interesting papers regarding the original topic of reductive amination via zinc/NaOH or KOH can be found here:
https://www.sciencemadness.org/talk/viewthread.php?tid=24752