03-02-03 14:53
No 413177
      Reduction of ketoximes with Zn/NH3
(Rated as: excellent)

Reduction of oximes with Zn/NH3 - A mini review

The UTFSE was used and no article was found on Rhodium's page, too. Lego hopes that this is new to the Hive.

Abstract: Various oximes are reduced with Zn in aqueous saturated NH3 with or without the addition of EtOH or ammonium acetate in moderate to good yields.

Keywords: Reduction, Oximes, Amines, Zn, NH3, zinc, ammonia, OTC

The following articles are collected from various references:

Entry; Educt; n (Educt) [mole]; n Zinc [mole]; Solvent [ml][NH3/EtOH]; n NH4OAc [mole]; Reaction conditions; Yield [%]
1; Fluorenonoxime1; 0.56; 2.30; 2500:500; 0; Reflux, 2.5 h; 80
2; Naphtylphenlyketoxime1; 0.27; 1.38; 2500:125; 0.39; Reflux, 3h; 80
3; b-Naphtyl-methyl-ketoxime1; 0.27; 1.15; 1000:500; 0.32; 60C, 6h; 60
4; Acetophenoneoxime1; 0.89; 3.82; 1200:1200; 1.56; 50C, 5h; 53
5; pyruvic acid oxime1; 0.29; 0.91; 750:0; 0; 60C, 10h; 60
6; 2-Amino-5-chlor-benzophenoneoxime2; 0.1; 0.75; 900:150; 0.065; Reflux, 3h; 94.6
7; (3-Methyl-2-pyridyl)-phenyl-ketoneoxime3; 0.126; 0.573; 375+250 ml H2O; 0.13; Reflux, 3h; 85
8; 2-Methylthiobenzophenoneoxime4; 0.023; 0.069; 80+15; 0; 50C, 18h; 90
9; (2-amino-6-phenylpyridin-3-yl)(phenyl)methanone oxime5; 0.0146; 0.84; 120+40; 0.01; Reflux, 12h; 76.3
10; Di(2-pyridyl) ketone oxime6; 0.025; 0.113; 75+85+50 ml H2O; 0.0428; Reflux, 4.5 h; 91

All molar weight were calculated either with ACD/ChemSketch Freeware 5.11, adopted from the original references or from reference books.


Molecule: a1 ("c\21ccccc1c3c(C/2=N/O)cccc3")

The oxime 1 (prepared from 100 g of the corresponding ketone) is suspended in 2.5 l of concentrated ammonia and 500 ml EtOH. 150 g zinc dust and 1 ml octanole are added. Reflux for 2.5 h. Filtrate, wash properly with Et2O, the filtrate is extracted 5 times each with 600 ml Et2O. [] Yield: 80%1
120 g 4 are stirred in 1200 ml of concentrated NH3 and 1200 ml EtOH with 120 g ammonium acetate and 250 g zinc dust for 5 h at 50C. [workup]. Yield: 53%1


Molecule: a2 ("c13ccccc3cccc1/C(c2ccccc2)=N/O")

The oxime 2 (prepared from 61.8 g of the corresponding ketone) is dissolved in a solution of 30 g ammonium acetate in 1.25 l of concentrated ammonia and 125 ml EtOH. 30 g of zinc dust are added and the mixture is heated to reflux. After 20 minutes and 3 h 30 g of zinc dust are added each. After refluxing a yellow has precipitated. The reaction mixture is filtered, the zinc is residued boiled with benzene and the filtrated is extracted 3 times with benzene. The pooled extracts are washed with water, dried und concentrated in vacuo. Yield: 80%1


Molecule: a3 ("c12ccccc2ccc(c1)/C(C)=N/O")

50 g of 3 were stirred with 50 g zinc dust and 25 g ammonium acetate in 500 ml of concentrated NH3 and 500 ml EtOH for 4 h at 60C. 25 g zinc dust are added and 500 ml of concentrated NH3 and stirs for another 2 h at 60C. After cooling to RT the mixture is filtrated and washed with benzene. [workup] Yield: 60%1


Molecule: a4 ("c1(ccccc1)/C(C)=N/O")

120 g 4 are stirred in 1200 ml of concentrated NH3 and 1200 ml EtOH with 120 g ammonium acetate and 250 g zinc dust for 5 h at 50C. [workup]. Yield: 53%1


Molecule: a5 ("C/C(C(O)=O)=N/O")

30 g 5 are stirred with 30 g of zinc dust in 450 ml of concentrated ammonia for 2 h at 60C. 15 g zinc dust and 150 ml of concentrated NH3 are added and stirred for 4 h at 60C. The same amount of zinc and ammonia is added and stirred for another 4 h at 70C. Afterwards the mixture is filtrated, wash with warm water und H2S bubbled in the solution. ZnS is seperated by centrifugation, boiled with water and centrifugated. [] Yield: 60%1


Molecule: a6 ("c1(cc(ccc1N)Cl)/C(c2ccccc2)=N/O")

A mixture of 24.7 g (0.1 mole) 6, 35 g (0.6 mol) zinc dust, 900 ml of concentrated ammonia, 5 g (0.065 mole) ammonium acetate und 150 ml EtOH are refluxed for 3 h. After 1 h another 10 g (0.15 mole) of zinc dust are added. [] Yield: 94.6%2


Molecule: a7 ("c1(ncccc1C)/C(c2ccccc2)=N/O")

26.7 g of 7 and 10 g ammonium acetate are dissolved in 375 ml of concentrated aqueous ammonia and 250 ml H2O. To this solution 37.5 g zinc dust are added in small portions over a period of 2 h at RT. The mixture is refluxed for 3h. []. Yield: 85%3


Molecule: a8 ("c1(c(cccc1)SC)/C(c2ccccc2)=N/O ")

Ammonia gas was bubbled for 20 minutes into a ice-cooled mixture of ethanol (15 ml) and concentrated ammonia (80 ml). To this, oxime 8 (5 g, 0.023 mole) and zinc dust 325 mesh (4.5, 0.069 g-atom) were successively added. After 18 hours of stirring to 50 all the starting material disappeared (tlc) and the hot solution was rapidly filtered. The pH of the resulting filtrate was adjusted to 9 by cautious addition of hydrochloric acid at 0. The solution was then concentrated to 3/4 of the initial volume and extracted with ethyl acetate. Removal of the solvent gave an oil which was chromatographed (ethyl acetate:light petroleum, 3:10) to yield pure amine 10 (4.2g, 90%).4


Molecule: a9 ("c1(c(nc(cc1)c2ccccc2)N)/C(=N/O)c3ccccc3")

4.0 g (14.6 mmol, according to ChemSketch 13.9 mmol) 9, 5.5 g zinc-dust and 0.8 g ammonium acetate were refluxed in 120 ml concentrated ammonia and 40 ml EtOH were refluxed for 12 h under continous stirring. After cooling the mixture is filtrated, the zinc dust washed with CHCl3, the aqueous solution extracted with CHCl3 and the pooled CHCl3 extracts concentrad under vacuo. [] Yield: 76.3%5


Molecule: a10 ("c1(ncccc1)/C(c2ccccn2)=N/O")

In a mixture of 85 ml EtOH, 50 ml H2OP and 75 ml 23% aqueous NH3 solution, 5.00 g (25.0 mmol) 10 and 3.30 g (42.8 mmol) ammonium acetate werde dissolved and heated to 80C. Over a period of 30 min, 7.36 g (113 mmol) zinc dust werde added. After heating to reflux for 4.5 h, the solids were removed by filtration and the filtrated concentrated at the rotoevaporator (60C, 30 Torr). The resulting aqueous solution (ca. 10 ml) was basified with 10 N NaOH solution and extracted with CH2Cl2 (5 x 15 ml). The combined organic phases werde washed with 10 ml brine and dried with MgSO4. After evaporation of the solvent 4.21 g (22.7 mol, 91%) of the amine were obtained as colorless oil. No further purification was necessary.6

The reduction only proceeds smoothly if the ketoxime has at least one aryl group. Diarylketoxime react easily to the corresponding amines with zinc in concentrated ammonia in the presence of ethanol and ammonium acetate. Aryl-alkyl-ketoximes are harder to reduce but still in satisfying yields if the amine is high boling and does not tend towards entering complexes with zinc1.

Comment from Lego: All ketoximes (except 5) have an aryl group in alpha-position, so this method mighty fail for substituted phenyl acetone oximes or substituted phenylacetaldehyde oximes.


[1] Monatshefte fuer Chemie 94(4) 677-80 1963
[2] Journal fuer Praktische Chemie 324(5)  832-40 1982
[3] Synthesis 9 593-5 1976
[4] Tetrahedron 52(22) 7745-7754 1996
[5] Archiv der Pharmazie, 318(9), 777-81, 1985
[6] European Journal of Organic Chemistry, 1271-1273, 1998

Lego is not responsible for any translating errors nor for any damages caused by this errors. In case of doubt ask him for the original articles.
(Hive Bee)
03-13-03 12:41
No 416665
      This post is great. Thanks Lego.  Bookmark   

This post is great.  Thanks Lego.  Wow, this beats sure as hell Na / EtOH
(Chief Bee)
10-15-04 05:47
No 535958
      Reference #1 from the above review     

Reduktion von Ketoximen mit Zinkstaub in ammoniakalkalischer Lsung
Johannes C. Jochims
Monatshefte fuer Chemie 94(4) 677-80 1963 (../rhodium/djvu /ketoxime2amine.zn-nh3.djvu)

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