Direct reductive amination of carbonyl compounds using sodium..., H. ALINEZHAD, et al.,
N -(p-cyanobenzyl)-N-Phenylamine. (entry 2) IR: 3330, 2940, 2850, 2210, 1610, 1530 cm−1 1 H-
;
NMR (500 MHz, CDCl3): δ 7.60 (d, 2H, phenyl), 7.46 (d, 2H, phenyl), 7.15 (m, 2H, phenyl), 6.72 (t, 1H,
phenyl), 6.56 (t, 2H, phenyl), 4.41 (s, 2H, CH2), 4.20 (br, 1H, NH).
N -(p-methoxybenzyl)-N-Phenylamine. (entry 4) 1 H-NMR (500 MHz, CDCl3): δ 7.24 (d, 2H,
phenyl), 7.16 (t, 2H, phenyl), 6.88 (d, 2H, phenyl), 6.66 (m, 3H, phenyl), 4.25 (s, 2H, CH2), 3.99 (br, 1H, NH),
3.79 (s, 3H, OMe).
N -Phenyl-N-(3-phenyl-2-propenyl)aniline. (entry 12) IR: 3315, 3057, 3025, 2930, 2817, 1597,
1494, 1447, 967, 779, 692 cm−1
;
1 H-NMR (500 MHz, CDCl3): δ 7.17-7.38 (m, 5H), 6.73-6.61 (m, 7H), 3.94
(dd, 2H), 3.92 (br s, 1H).
N -methyl-N-phenyl benzylamine. (entry 8) IR: 3411, 3055, 2926, 1602, 1503 cm−1
(500 MHz, CDCl3): δ 7.19-7.31 (m, 7H), 6.70-6.75 (m, 3H), 4.52 (s, 2H), 3.00 (s, 3H).
;
1 H-NMR
Results and discussion
The reductive amination of a wide variety of aldehydes and ketones with primary and secondary amines in the
presence of NaBH4 –silica chloride under neutral conditions was successful and gave the desired products in good
to excellent yields (89%-97%) as summarized in the Table. Under such a condition, carbonyl compounds were
not reduced in the reaction mixture, whereas the imine intermediates were converted easily to the corresponding
amines. This reagent is suitable for use of chemoselective reduction of imines having nitro and cyano groups,
since this reagent cannot reduce the nitro and cyano groups (entries 2, 3, and 6). 4-Nitroaniline under similar
reaction conditions with 0.5 mmol excess of NaBH4 afforded 97% of N -benzyl-4-nitroaniline within 20 min
(entry 6). We found that 4-choloroanilines under optimal conditions efficiently react with benzaldehyde to
produce the corresponding amine within 12 min (entry 7). In the case of α, β-unsaturated aldehydes and
amines such as cinnamaldehyde and allyl amine, the reductive amination was successfully achieved without
reduction of the C=C bond (entries 12, 13, and 16). Aliphatic aldehydes such as butanal underwent reductive
amination successfully to give corresponding amines (entry 14). Reductive amination of cyclic and acyclic
aliphatic ketones such as cyclohexanone and 2-heptanone with different aromatic and aliphatic amines such
as aniline, allylamine, pipyridine, morpholine, and pyrrolidine also gave excellent yields of the corresponding
amines (entries 15-20).
Conclusion
We described an efficient and chemoselective method for the synthesis of amines by reductive amination of
carbonyl compounds with various amines in the presence of sodium borohydride and silica chloride. The scope
of the reaction was demonstrated with aliphatic, aromatic, cyclic, and acyclic carbonyl compounds with primary
and secondary amines. This method afforded amines as the only isolated products at room temperature. The
neutral non-aqueous reaction conditions, simple workup, isolation of pure products, high yields, very short
reaction time, and the use of safe and inexpensive reagent with no special handling technique are the notable
advantages of the present method.
309