Synthetic communications reviews: Synthesis of primary amines by one-pot reductive amination of aldehydes

Article abstract of DOI:10.1080/00397911.2012.714830

We report here a novel, one-pot, two-step reductive amination of aldehydes for the atom-economical synthesis of primary amines. The amination step has been carried out with hydroxylammonium chloride and does not require the use of a base. In the subsequent reduction step, a metal zinc/hydrochloride acid system has been used. This method is applicable to both aliphatic and aromatic aldehydes. The operational simplicity, the short reaction times, and the mild reaction conditions add to the value of this method as a practical alternative to the reductive amination of aldehydes. Copyright

Full text of DOI:10.1080/00397911.2012.714830

SYNTHESIS OF PRIMARY AMINES BY ONE-POT REDUCTIVE
AMINATION OF ALDEHYDES
Mohamed Ali Ayedi,1,2 Yves Le Bigot,1 Houcine Ammar,2 Souhir Abid,2 Rachid El Gharbi2 and Michel
Delmas1
1
Université de Toulouse, INP-ENSIACET, Laboratoire de Génie Chimique (LGC), 4, allée Emile Monso. BP :
44362, 31030, Toulouse Cedex 4, France; Tel: +33 6 89 84 92 46;
2
Laboratoire de Chimie Appliquée, Faculté des Sciences de Sfax, Université de Sfax, BP 1170, 3000 Sfax,
Tunisie.
Supplementary Material
Table of Contents
I. Analytical data of amines...................................................................................................S - 2
II. Copies of 1H and 13C NMR spectra..................................................................................S – 7
III. Elemental microanalyses.............................................................................................S - 15
S ‐ 1/15

I. Analytical data of amines
Furfurylamine (1c)
O
NH2
General procedure applied on 49 mmol of Furfural (1a) afforded furfurylamine (1c)
(4.709 g, 99%).
IR: 3379 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 1.30 (s, 2H; NH2), 3.62 (s, 2H; CH2), 5.95 (m, 1H;
CH), 6.13 (m, 1H; CH), 7.17 (m, 1H; CH) ppm;
13C NMR (75 MHz, CDCl3): δ= 39.2, 104.8, 110.0, 141.3, 156.8 ppm.
Elemental microanalyses: Calculated for C5H7NO: C, 61.84; H, 7.27; N, 14.42. Found:
C, 61.83; H, 7.25; N, 14.45.
Benzylamine (2c)
NH2
General procedure applied on 49 mmol of benzaldehyd (2a) afforded Benzylamine
(2c) (5.195 g, 99%).
IR: 3369 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 1.50 (s, 2H; NH2), 3.82 (s, 2H; CH2), 7.38 (m, 5H; Ar)
ppm;
13C NMR (75 MHz, CDCl3): δ= 46.5, 126.7, 127.1, 128.5, 143.4 ppm.
S ‐ 2/15

Elemental microanalyses: Calculated for C7H9N: C, 78.46; H, 8.47; N, 13.07. Found:
C, 78.44; H, 8.46; N, 13.09.
4-Methylbenzylamine (3c)
NH2
General procedure applied on 49 mmol of 4-tolualdehyde (3a) afforded 4-
Methylbenzylamine (3c) (5.875 g, 99%).
IR: 3300 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 1.45 (s, 2H; NH2), 2.36 (s, 3H; CH3), 3.38 (s, 2H;
CH2), 7.19 (m, 4H, Ar) ppm;
13C NMR (75 MHz, CDCl3): δ= 21.1, 46.3, 127.1, 129.2, 136.2, 140.5ppm.
Elemental microanalyses: Calculated for C8H11N: C, 79.29; H, 9.15; N, 11.56. Found:
C, 79.26; H, 9.13; N, 11.59.
3-Methylbenzylamine (4c)
NH2
General procedure applied on 49 mmol of 3-tolualdehyde (4a) afforded 3-
Methylbenzylamine (4c) (5.871 g, 99%).
IR: 3313 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 1.44 (s, 2H, NH2), 2.33 (s, 3H, CH3), 3.75 (s, 2H,
CH2), 7.04 (m, 3H, Ar), 7.20 (m, 1H, Ar) ppm;
S ‐ 3/15

13C NMR (75 MHz, CDCl3): δ= 20.8, 45.8, 123.5, 126.8, 127.2, 127.7, 137.3, 142.8
ppm.
Elemental microanalyses: Calculated for C8H11N: C, 79.29; H, 9.15; N, 11.56. Found:
C, 79.25; H, 9.13; N, 11.58.
4-methoxybenzylamine (5c)
O
NH2
General procedure applied on 49 mmol of 4-anysaldehyde (5a) afforded 4-
methoxybenzylamine (5c) (6.254 g, 93%).
IR: 3365 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 1.30 (s, 2H, NH2), 3.62 (s, 3H, CH3), 3.64 (s, 2H,
CH2), 6.43 (m, 2H, Ar), 7.78 (m, 2H, Ar) ppm;
13C NMR (75 MHz, CDCl3): δ= 45.2, 54.3, 113.2, 127.6, 135.0, 157.8 ppm. Elemental
microanalyses: Calculated for C8H11NO: C, 70.04; H, 8.08; N, 10.21. Found: C, 70.02;
H, 8.05; N, 10.24
3-methoxybenzylamine (6c)
O
NH2
General procedure applied on 49 mmol of 3-anysaldehyde (6a) afforded 3-
methoxybenzylamine (6c) (6.384 g, 95%).
IR: 3362 cm-1 (N-H);
S ‐ 4/15

1H NMR (300MHz, CDCl3): δ= 1.44 (s, 2H, NH2), 3.71 (s, 3H, CH3), 3.75 (s, 2H,
CH2), 6.71 (m, 1H, Ar), 6.81(m, 2H, Ar), 7.18 (m, 1H, Ar) ppm;
13C NMR (75 MHz, CDCl3): δ= 45.9, 54.6, 111.7, 112.1, 118.8, 129.0, 144.7, 159.4
ppm.
Elemental microanalyses: Calculated for C8H11NO: C, 70.04; H, 8.08; N, 10.21.
Found: C, 70.02; H, 8.05; N, 10.23.
2-ethylhexan-1-amine (7c)
NH2
General procedure applied on 49 mmol of 2-ethylhexanal (7a) afforded 2-ethylhexan-
1-amine (7c) (5.513 g, 87%).
IR: 3376 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 0.67 (m, 6H, 2CH3), 1.06 (m, 11H, 4CH2, NH2 and
CH), 2.39 (d, 2H, CH2) ppm;
13C NMR (75 MHz, CDCl3): δ= 10.5, 13.6, 22.7, 23.4, 28.6, 30.4, 41.9, 44.3 ppm.
Elemental microanalyses: Calculated for C8H19N: C, 74.34; H, 14.82; N, 10.84. Found:
C, 74.30; H, 14.79; N, 10.86.
Octan-1-amine (8c)
NH2
General procedure applied on 49 mmol of octanal (8a) afforded Octan-1-amine (8c)
(5.069 g, 80%).
S ‐ 5/15

IR: 3384 cm-1 (N-H);
1H NMR (300MHz, CDCl3): δ= 0.68 (m, 3H, CH3), 0.88 (s, 2H, NH2), 1.09 (m, 10H,
5CH2), 1.23 (m, 2H, CH2), 2.48 (m, 2H, CH2) ppm;
13C NMR (75 MHz, CDCl3): δ= 13.9, 22.5, 26.8, 29.2, 29.4, 31.7, 33.8, 42.2 ppm.
Elemental microanalyses: Calculated for C8H19N: C, 74.34; H, 14.82; N, 10.84. Found:
C, 74.31; H, 14.81; N, 10.85.
S ‐ 6/15

III. Copies of 1H and 13C NMR spectra
Furfurylamine (1c)
O
NH2
S ‐ 7/15

Benzylamine (2c)
NH2
S ‐ 8/15

4-Methylbenzylamine (3c)
NH2
S ‐ 9/15

3-Methylbenzylamine (4c)
NH2
S ‐ 10/15

4-methoxybenzylamine (5c)
O
NH2
S ‐ 11/15

3-methoxybenzylamine (6c)
O
NH2
S ‐ 12/15

2-ethylhexan-1-amine (7c)
NH2
S ‐ 13/15

Octan-1-amine (8c)
NH2
S ‐ 14/15

IV. Elemental microanalyses
Furfurylamine (1c) (C5H7NO)
Eléments
% théorique
Résultats
% Exp.
1er essai
62,24
7,31
% Exp.
2ème essai
60,93
% Exp.
3èmeessai
62,32
C
H
N
S
61.84
7.27
C
H
N
S
7,29
7,15
14.42
13,97
15,24
14,14
Benzylamine (2c)(C7H9N)
Eléments
% théorique
Résultats
% Exp.
1er essai
77,74
8,35
% Exp.
2ème essai
79,59
% Exp.
3ème essai
77,99
C
H
N
S
78,46
8,47
C
H
N
S
8,58
8,45
13,07
13,87
12,26
13,14
4-Methylbenzylamine (3c) (C8H11N)
Eléments
% théorique
Résultats
% Exp.
1er essai
80,15
9,01
% Exp.
2ème essai
79,52
% Exp.
3ème essai
78,11
C
H
N
S
79,29
9,15
C
H
N
S
9,28
9,10
11,56
12,02
11,29
11,46
S ‐ 15/15

3-Methylbenzylamine (4c) (C8H11N)
Eléments
% théorique
Résultats
% Exp.
1er essai
79,54
8,97
% Exp.
2ème essai
78,92
% Exp.
3ème essai
79,29
C
H
N
S
79,29
9,15
C
H
N
S
9,28
9,14
11,56
11,68
11,47
11,59
4-methoxybenzylamine (5c) (C8H11NO)
Eléments
% théorique
Résultats
% Exp.
1er essai
69,34
8,12
% Exp.
2ème essai
72,04
7,96
% Exp.
3ème essai
68,68
C
H
N
S
70,04
8,08
C
H
N
S
8,07
10,21
11,16
9,26
10,30
3-methoxybenzylamine (6c) (C8H11NO)
Eléments
% théorique
Résultats
% Exp.
1er essai
70,35
8,11
% Exp.
% Exp.
2
ème essai
3
ème essai
C
H
N
S
70,04
8,08
C
H
N
S
69,27
7,86
9,58
70,44
8,18
10,21
10,36
10,75
S ‐ 16/15

2-ethylhexan-1-amine (7c)(C8H19N)
Eléments
% théorique
Résultats
% Exp.
1er essai
73,58
% Exp.
2ème essai
73,98
% Exp.
3ème essai
75,34
C
H
N
S
74,34
14,82
10,84
C
H
N
S
14,55
14,97
14,85
10,95
11,36
10,27
Octan-1-amine (8c)(C8H19N)
Eléments
% théorique
Résultats
% Exp.
1er essai
75,26
% Exp.
2ème essai
74,09
% Exp.
3ème essai
73,58
C
H
N
S
74,34
14,82
10,84
C
H
N
S
14,90
14,89
14,64
10,37
10,12
12,06
S ‐ 17/15