Reductive amination with Zn/iPrOH and molecular sievesEur. J. Org. Chem. 1998, 1271-1273Abstract: A ketone is treated with a primary amine to form an imine in iPrOH in the presence of molecular sieves and HOAc. This amine is reduced to the amine with Zn in good yield.
Keywords: Reductive amination, zinc, acetic acid, isopropylalcohol, isopropanol, IPA, molecular sieves, imine, ketone, primary amine
The abstract of this article has been posted at the Hive before, but not the exact method. See
Post 164964 (not existing) and
Post 108765
(dormouse: "Red. Amin. with molecular sieves and Zn/IPA -Feck", Novel Discourse).
The authors tried to synthesize
III from
I and
II via reductive amination. Common methods like NaBH
3CN, NaBH(OAc)
3, LAH failed for this target compound.
Experimental: 1.00 g (5.43 mmol) ketone
I and 1.00 g(5.40 mmol) amine
II were dissolved in 10 ml of absolute isopropanol and dried with molecular sieves 3 Å for 1 h at RT. 1.00 ml (17.5 mmol) glacial acetic acid were added unter N
2 atmosphere and the reaction mixture refluxed for 6 h. The oil bath was then removed and 870 mg (13.3 mmol) Zn dust was added in portions over a period of 5 min. After 5 min the reaction mixture became solid. It was partly dissolved with 15 of isopropanol. The solids were removed by filtration and washed with methanol until the filtrate was colorless. The solvent was evaporated (50°C, 30 Torr) and the residue dissolved in 20 ml 2 M NaOH solution and 10 ml CH
2Cl
2. The phases were separated and the aqueous one extracted with 10 ml CH
2Cl
2. The combined organic phases were washed with 5 ml of brine, dried with MgSO
4 and the solvent evaporated (40°C, 30 Torr.). The crude oil was dissolved in 0.5 ml of CH
2Cl
2 and 20 ml of
tert-butyl methyl ether and washed with 2 M NaOH solution (15 x 5 ml). The organic phase was washed with brine and dried with MgSO4. After evaporation of the solvent and drying the residue under oil-pump vacuum, 1.35 g (3.82 mmol, 70%) BDMPA
III were obtained as pale-yellow viscous oil.
I
Molecule:
a1 ("O=C(c1ccccn1)c2ncccc2")
II
Molecule:
a2 ("NC(c1ccccn1)c2ncccc2")
III
Molecule:
a3 ("N(C(c1ccccn1)c2ncccc2)C(c3ncccc3)c4ccccn4")
Comments by Lego: iPrOH was purchased from a standard chemical supplier and was not dried further.
Maybe the amount of acetic acid may be reduced if primary amines like methylamine are used because the authors assume pyridyl groups to act as a 'proton sponge' inhibiting the protonation of the intermediate carbinol amine.
The authors did not use any other high boiling alcohol, may be 1-butanol may also work or even better. The amine
II was prepared from the corresponding oxime with Zn/NH
3, see
Post 413177
(Lego: "Reduction of ketoximes with Zn/NH3", Novel Discourse)
