Convenient and clean synthesis of imines from primary benzylamines

Article abstract of DOI:10.1039/c0ob00043d

The current syntheses of imines from benzylamines are often performed in organic solvents or under harsh reaction conditions. Clean oxidation of primary benzylamines to imines has been successfully achieved using H₂O ₂ in water at room temperature catalyzed by V₂O ₅. Among the 10 imine products, 5 of them precipitated from the reaction and led pure products after simple filtration. No organic solvents are needed in the whole process. The yields are good to quantitative. This represents an efficient and green procedure of the synthesis of imines. A similar green oxidation of benzylamines to aromatic aldehydes is also reported. A benzylic anion-involved mechanism is proposed based on the experiments.

Full text of DOI:10.1039/c0ob00043d

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Convenient and clean synthesis of imines from primary benzylamines†
Guobiao Chu and Chunbao Li*
Received 26th April 2010, Accepted 30th June 2010
DOI: 10.1039/c0ob00043d
The current syntheses of imines from benzylamines are often performed in organic solvents or under
harsh reaction conditions. Clean oxidation of primary benzylamines to imines has been successfully
achieved using H2O2 in water at room temperature catalyzed by V2O5. Among the 10 imine products, 5
of them precipitated from the reaction and led pure products after simple filtration. No organic solvents
are needed in the whole process. The yields are good to quantitative. This represents an efficient and
green procedure of the synthesis of imines. A similar green oxidation of benzylamines to aromatic
aldehydes is also reported. A benzylic anion-involved mechanism is proposed based on the experiments.
Table 1 Optimization for the oxidation of p-chlorobenzylamine.a
Introduction
As imines are important intermediates in the synthesis of biolog-
ically active nitrogen-containing compounds,1 their preparation
attracts extensive attention. Considerable progress has been made
in recent years in developing catalytic oxidation of secondary
amines into imines.2 However, comparatively little attention has
been devoted to the oxidation of primary amines, probably because
the corresponding imines usually constitute intermediate products
that are rapidly dehydrogenated to nitriles3 due to a second a-
amino hydrogen. The oxidation of primary amines with IBX leads
to the corresponding carbonyl species, even with the application
of short reaction times, following hydrolysis of the initially formed
imine product in situ.4 As a result, extended efforts have been
made to develop catalytic systems that utilize green oxidants for
the synthesis of imines from primary amines; notable examples
include 10% PVMo/C,5 a series of uracil-annulated heteroazulene
derivatives,6 bulk gold powder and supported gold,7 and tyrosine-
derived quinone.8 Most of the methods suffer from prolonged
reaction times, or higher reaction temperatures. Furthermore,
they all have to suffer from unfriendly organic solvents. Landge
et al. have reported9 the microwave-assisted oxidative coupling
of amines to imines with a solid catalyst without the use of any
solvent. However, the transformation is performed at 150 ◦C. We
aim to find a green oxidation of amines under mild conditions.
Water as a reaction medium has attracted both academic
and industrial interests because of its special properties such as
safety, nontoxicity, inflammability, cheapness and environmental
friendliness. Hydrogen peroxide along with oxygen is regarded as a
green oxidant. We intend to develop an oxidation procedure using
H2O2 in water catalyzed by V2O5. V2O5 is an inexpensive and stable
chemical and has successfully catalyzed various oxidations.10
Entry
H2O2 (equiv.)
V2O5 (equiv.)
Time/h
Yield (%)b
1c
2
3
4
5
6
7
8
—
1
3
5
3
3
3
3
0.01
0.1
0.1
0.1
—
0.05
0.08
0.15
6
6
n.d
54
91
90
trace
63
3.5
3.5
6
3.5
3.5
3.5
90
89
a Reaction conditions: 1a (200 mg, 1 equiv.), H2O (5 mL), rt. b Isolated
yields. c n.d = not detected.
by V2O5 in water, at room temperature. Initially, the oxidation
of 4-chlorobenzylamine (1a) was chosen as a model reaction
and the reaction was carried out in water at room temperature.
Control experiments (Table 1, entries 1 and 5) revealed that
hydrogen peroxide and vanadium pentoxide are all required for
this reaction. Without H2O2 no imine was detected (Table 1, entry
1). Without V2O5 very little of 4-chlorobenzaldehyde was obtained
(Table 1, entry 5). We obtained the optimized reaction conditions,
viz. 3 equiv. of H2O2 (30% solution in water) as an oxidant and
0.08 equiv. of V2O5 as a catalyst at room temperature (Table 1,
entry 7).
Building upon this result, we treated a variety of substituted
benzylamines with hydrogen peroxide in the presence of vanadium
pentoxide at room temperature. The system gave the correspond-
ing imines in good to quantitative yields and Table 2 summarizes
the results. As some imines are solid and insoluble in water,
5 among 10 imine products (Table 2, entries 1, 4, 7, 8, 10)
precipitated directly from the reaction mixtures. Products purer
than 97% were collected by simple filtrations. No purification
step was needed for any of the imine products. The yield of
the oxidation of 2,3-dichlorobenzylamine into the corresponding
imine was quantitative (Table 2, entry 7). However, in the literature,
organic solvents were necessary either during the oxidation of the
amines or in the work-up step. This represents an efficient and
Results and discussion
In the present paper, we report our results relating to the oxidation
of benzylamines to the corresponding imines using H2O2 catalyzed
Department of Chemistry, Tianjin University, Tianjin, 300072, China.
E-mail: lichunbao@tju.edu.cn; Fax: +862227403475
† Electronic supplementary information (ESI) available: Experimental
1
procedures, H NMR, 13C NMR and MS spectral data for compounds.
See DOI: 10.1039/c0ob00043d
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Table 2 Oxidation of variously substituted benzylamines to imines.a
Entry
1
Substrate
Product
Time/h
2.5
Yield (%)b
91
2a
2
3
2b
2c
10
10
64
75
4
5
2d
2e
4.5
6
80
76
6
7
2f
6
1
87
2g
>99
8
2h
2i
2j
4
83
66
78c
9
8
10
12
a Reaction conditions: substituted benzylamine (200 mg, 1 equiv.), H2O2 (30% solution in water) (3 equiv.), V2O5 (0.08 equiv), H2O (5 mL), rt. All the
conversions were 100% except for entry 10 (50%). b Isolated yields. c 50% of starting material was recovered.
green procedure for the synthesis of imines starting from primary
benzylamines.
However, when benzylamines of Table 3 were treated with H2O2
and V2O5 at rt, no imines were obtained. When the systems
were heated to 50 ◦C, they gave aromatic aldehydes in high
yields (Table 3). In contrast to the benzylamines bearing electron-
withdrawing groups in Table 2, the benzylamines in Table 3 bear
electron-donating groups.
It has been reported10a,11 that benzyl alcohols can be oxidated
into aromatic aldehydes in water. However, in the literature12 the
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Table 3 Oxidation of benzylamines to aromatic aldehydes.a
Entry
1
Substrate
Product
Time/h
10
Yield (%)b
76
3k
3l
2
3
11
12
78
66
3m
4
3n
12
70c
a Reaction conditions: substituted benzylamine (200 mg, 1 equiv.), H2O2 (30% solution in water) (3 equiv.), V2O5 (0.08 equiv) H2O (5 mL), 50 ◦C. All the
conversions were 100% except for entry 4 (70%). b Isolated yields. c 30% of starting material was recovered.
transformation of benzylamines into aromatic aldehydes often
needs organic solvents. Only catalyzed by expensive enzymes13
can the oxidations be performed in water. Our oxidation provides
a greener synthesis of aromatic aldehydes from benzylamines in
water catalyzed by inexpensive and stable catalyst (V2O5).
On the basis of the above experiments and previous researches,10
a plausible mechanism is proposed (Scheme 1). After ioniza-
tion V2O5 is oxidized by H2O2 into a yellow species HOV(O2)2.
This is supported by the facts that the reaction solution is yellow
and 3 equiv of H2O2 are needed for the completion of the reaction
(Table 1). Acid HOV(O2)2 forms a salt (I) with benzylamine.
One of the oxygens deprotonates the benzylic hydrogen leading
to benzylic anion II. Electron-withdrawing groups on aromatic
ring stabilize anion II; while electron-donating groups hamper the
formation of benzylic anion II. Therefore, benzylamines of Table 2
were oxidized to the corresponding imines at room temperature
and those of Table 3 had to be oxidized to aromatic aldehydes
at elevated temperature (50 ◦C). Presumably, imines were also
formed in the later process. However, they were hydrolyzed at
higher temperature and the amines were then oxidized into the
Scheme 1 A plausible mechanism for the oxidation of benzylamine
aromatic aldehydes.
Conclusions
Experimental
In conclusion, the methodology reported herein is expected to
be a quite general route for oxidation a wide range of primary
benzylamines in water, leading to imines or aromatic aldehydes.
Its advantages are obvious from the perspective of green chemistry.
Apart from being an environmentally benign reaction, the method
benefits from the use of inexpensive and safe starting materials and
produces imines or aromatic aldehydes in good to quantitative
yields.
General procedure for the preparation of imines in water
In a round bottom flask, benzylamine (200 mg, 1 equiv.), V2O5
(0.08 equiv) was suspended in water (5 ml) with vigorous stirring.
Then, H2O2 (30% solution in water) (3 equiv.) was added to the
reaction mixture. The reaction was slightly yellow. The solid imine
was filtered to afford pure product when the reaction completed
(monitored by TLC). The oily product was extracted with EtOAc
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(2 ¥ 5 mL). The extract was washed with water (2 ¥ 3 mL), dried
over anhydrous Na2SO4. The solvent was concentrated in vacuum
to give pure imine without further purification.
Notes and references
1 (a) S. I. Murahashi, Angew. Chem., Int. Ed. Engl., 1995, 34, 2443; (b) S. I.
Murahashi and Y. Imada, in Transition Metals for Organic Synthesis,
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2 G. Jiang, J. Chen, J. S. Huang and C. M. Che, Org. Lett., 2009, 11,
4568, and references cited therein.
N-(2-Chlorobenzyl) 2-chlorobenzaldimine (2d)
1H NMR (CDCl3, 400 MHz) d 8.89 (s, 1H), 8.14 (d, J = 9.2 Hz,
1H), 7.46–7.23 (m, 7H), 4.97 (s, 2H); 13C NMR (CDCl3, 100 MHz):
d 159.8, 136.8, 135.3, 133.4, 133.1, 131.7, 129.8, 129.7, 129.4, 128.5,
128.3, 127.0, 126.9, 62.2; MS (ESI): m/z (%) [M + H]+ = 264 (100),
265 (18), 266 (60); Anal. Calcd. For C14H11Cl2N: C, 63.66; H, 4.20;
N, 5.30 Found: C, 63.74; H, 4.10; N, 5.22.
3 (a) K. Yamaguchi and N. Mizuno, Angew. Chem., Int. Ed., 2003, 42,
1480; (b) K. Mori, K. Yamaguchi, T. Mizugaki, K. Ebitani and K.
Kaneda, Chem. Commun., 2001, 461; (c) Y. Maeda, T. Nishimura and
S. Uemura, Bull. Chem. Soc. Jpn., 2003, 76, 2399; (d) K. Yamaguchi
and N. Mizuno, Chem.–Eur. J., 2003, 9, 4353; (e) S. Kamiguchi, A.
Nakamura, A. Suzuki, M. Kodomari, M. Nomura, Y. Iwasawa and T.
Chihara, J. Catal., 2005, 230, 204, and references cited therein.
4 (a) K. C. Nicolaou, C. J. N. Mathison and T. Montagnon, Angew.
Chem., Int. Ed., 2003, 42, 4077; (b) K. C. Nicolaou, C. J. N. Mathison
and T. Montagnon, J. Am. Chem. Soc., 2004, 126, 5192.
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Nakayama, M. Hamamoto, Y. Nishiyama and Y. Ishii, Chem. Lett.,
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Naya and M. Nitta, Tetrahedron, 2004, 60, 9139; (c) M. Nitta, D.
Ohtsuki, Y. Mitsumoto and S. I. Naya, Tetrahedron, 2005, 61, 6073;
(d) S. I. Naya, Y. Yamaguchi and M. Nitta, Tetrahedron, 2005, 61,
7384.
7 (a) B. Zhu, M. Lazar, B. G. Trewyn and R. J. Angelici, J. Catal., 2008,
260, 1; (b) A. Grirrane, A. Corma and H. Garcia, J. Catal., 2009, 264,
138.
N-(2,3-Dichlorobenzyl) 2,3-dichlorobenzaldimine (2g)
1H NMR (CDCl3, 400 MHz) d 8.91 (s, 1H), 8.05 (d, J = 7.6 Hz,
1H), 7.56 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.37 (d, J =
7.2 Hz, 1H), 7.30–7.21 (m, 2H), 4.99 (s, 2H); 13C NMR (CDCl3,
100 MHz): d 159.9, 139.0, 135.1, 133.5, 133.4, 133.1, 132.4, 131.6,
129.1, 127.6, 127.4, 127.3, 126.7, 62.7; MS (ESI): m/z (%) [M +
H]+ = 332 (78), 334 (100), 336 (47); Anal. Calcd. For C14H9Cl4N:
C, 50.49; H, 2.72; N, 4.21 Found: C, 50.61; H, 2.67; N, 4.30.
8 M. Mure, Acc. Chem. Res., 2004, 37, 131, and references therein.
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Lett., 2007, 48, 5161.
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water
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4239.
In a round bottom flask, benzylamine (200 mg, 1 equiv.), V2O5
(0.08 equiv) was suspended in water (5 ml) with vigorous stirring.
H2O2 (30% solution in water) (3 equiv.) was added to the reaction
mixture. The system was heated to 50 ◦C and monitored by TLC to
completion. The reaction mixture was extracted with EtOAc (2 ¥
5 mL). The extract was washed with water (2 ¥ 3 mL), dried over
anhydrous Na2SO4. The solvent was concentrated in a vacuum to
give crude product, which was then filtered through a silica gel
pad with petroleum ether to afford aromatic aldehyde.
13 (a) A. Yoshida, Y. Takenaka, H. Tamaki, I. Frebort, O. Adachi and
H. Kumagai, J. Ferment. Bioeng., 1997, 84, 603; (b) R. H. H. van den
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Acknowledgements
We thank NSFC for financial support.
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The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 4716–4719 | 4719
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