Direct conversion of benzylamines to imines via atmospheric oxidation in the presence of VO(Hhpic)2 catalyst

Article abstract of DOI:10.1016/j.tetlet.2010.02.150

Oxovanadium complex bearing 3-hydroxypicolinic acid (H₂hpic), that is, VO(Hhpic)₂, successfully catalyzes a highly selective oxidation of benzylamines to the corresponding N-(benzylidene)benzylamines under atmospheric molecular oxygen. In addition, the use of imidazolium-type ionic liquids as solvent makes it possible to attain recycling of the catalyst.

Full text of DOI:10.1016/j.tetlet.2010.02.150

Tetrahedron Letters 51 (2010) 2450–2452
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Tetrahedron Letters
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Direct conversion of benzylamines to imines via atmospheric oxidation
in the presence of VO(Hhpic)2 catalyst
a
b
Shintaro Kodama a, Jun Yoshida a, Akihiro Nomoto a, , Yukihiro Ueta , Shigenobu Yano ,
*
Michio Ueshima a, Akiya Ogawa a,
*
a Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
b Endowed Research Section, Photomedical Science, Innovative Collaboration Center, Kyoto University, Kyoto 615-8250, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Oxovanadium complex bearing 3-hydroxypicolinic acid (H2hpic), that is, VO(Hhpic)2, successfully cata-
lyzes a highly selective oxidation of benzylamines to the corresponding N-(benzylidene)benzylamines
under atmospheric molecular oxygen. In addition, the use of imidazolium-type ionic liquids as solvent
makes it possible to attain recycling of the catalyst.
Received 28 December 2009
Revised 20 February 2010
Accepted 25 February 2010
Available online 3 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Oxidation reaction
Vanadium catalyst
Amines
Atmospheric oxygen
Catalytic oxidation reactions of organic compounds with the aid
of molecular oxygen as the primary oxidant have attracted much
attention from a green chemical viewpoint in recent years.1 In par-
ticular, considerable efforts have been devoted to accomplish the
oxidation of alcohols to carbonyl compounds. By contrast, the cor-
responding amine to imine conversion by oxidation has remained
largely undeveloped, despite great utility of imines in the synthesis
of industrial materials and biologically active compounds, such as
amides, chiral amines, oxazolidines, hydroxyamines, and nitrones.2
Since the oxidation of primary amines generally leads to other
nitrogen containing compounds, such as nitriles,3 it is of great
importance to develop the catalytic oxidation of the primary
amines to the corresponding imines using molecular oxygen.4 Di-
rect synthesis of imines from the primary amines by oxidation of-
fers an alternative synthetic route to the condensation of an amine
with a carbonyl compound.
Herein, we wish to report the selective oxidation of benzylam-
ines to produce directly the corresponding N-(benzylidene)benzyl-
amine derivatives catalyzed by an oxovanadium complex bearing
3-hydroxypicolinic acid (H2hpic), that is, VO(Hhpic)2 (Fig. 1), under
the atmosphere of molecular oxygen.5,6
We first examined reactions of benzylamine 1a with vanadium
catalysts under the atmosphere of molecular oxygen in acetonitrile
(Table 1).7 Among the catalysts employed, VO(Hhpic)2 was found
to be the most effective catalyst for converting benzylamine 1a
to N-(benzylidene)benzylamine 2a (entry 1). General vanadium
Table 1
Oxidation of benzylamine with vanadium catalystsa
V Catalyst
O
2 (0.1 MPa)
NH2
N
CH3CN, 120 oC, 18 h
1a
2a
O
O
Entry
V Catalyst
Mol %
Yieldb (%) 2a
Recoveryb (%) 1a
H
N
HO
O
O
1
2
3
4
5
VO(Hhpic)2
VO(acac)2
V2O5
VOSO4
None
2
2
1
2
86
34
30
30
Trace
45
52
V
O
N
H O
O
2
43
No reaction
Figure 1. Structure of VO(Hhpic)2.
a
Reactions were carried out on 1.5 mmol scale in a stainless autoclave with
stirring under oxygen (0.1 MPa).
* Corresponding authors. Tel./fax: +81 72 254 9290 (A.O.).
E-mail address: ogawa@chem.osakafu-u.ac.jp (A. Ogawa).
b
Determined by 1H NMR.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.150

S. Kodama et al. / Tetrahedron Letters 51 (2010) 2450–2452
2451
Table 2
Oxidation of amine derivativesa
Entry
Substrate
Product
Time (h)
Yieldb (%)
Ar
NH
2
Ar
N
N
N
Ar
1
2
3
4
Ar=C6H5
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
1a
1b
1c
1d
2a
2b
2c
2d
18
24
18
24
86c
70
72c
71
Ph
N
H
Ph
Ph
Ph
Ph
5
6
1e
1f
2e
2f
42
18
37c,d
NH
N
78
Ph
Ph
N
Ph
7
1g
2g
24
75
Ph
a
Reactions were carried out using 1.5 mmol of substrate, 10.3 mg (0.03 mmol) of VO(Hhpic)2, and 6 mL of acetonitrile in a stainless autoclave with stirring at 120 °C under
0.1 MPa of oxygen for appropriate times.
b
Isolated yield.
c
Determined by 1H NMR.
d
The starting material (58%) was recovered.
catalysts in oxidation reactions such as VO(acac)2 and V2O5 had
less catalytic activity (entries 2 and 3). In the case of VOSO4, which
is the starting material of VO(Hhpic)2, 2a was formed in a low yield
under the same condition (entry 4).
Table 4
Recycling study of VO(Hhpic)2 in ionic liquida
VO(Hhpic)2 (2 mol%)
O2 (0.1 MPa)
NH2
N
Results of the oxidation of various benzylamine derivatives
using VO(Hhpic)2 are shown in Table 2. Oxidations of p-substituted
benzylamine derivatives 1aÀd proceeded successfully to afford the
corresponding imines 2aÀd (entries 1À4). As to the oxidation of
the secondary amines (entries 5 and 6), dibenzylamine 1e was oxi-
dized to the corresponding imine 2e in a moderate yield (entry 5).
On the other hand, 1,2,3,4-tetrahydroisoquinoline 1f was selec-
tively dehydrogenated to 3,4-dihydroisoquinoline 2f (entry 6).
Interestingly, the oxidation of tertiary amine 1g proceeded to af-
ford N-(benzylidene)aniline 2g in a good yield via the elimination
of a benzyl group (benzaldehyde (75%, 1H NMR yield) was formed
as a byproduct) (entry 7).8
[hmim]PF6
120 oC, 6 h
1a
2a
Run
1st
69
2nd
70
3rd
64
4th
67
5th
68
6th
66
7th
56
8th
58
9th
Yieldb,c (%)
68 (67)d
a
The reaction was carried out with benzylamine (1.5 mmol), and VO(Hhpic)2
(0.3 mmol) dissolved in [hmim]PF6 (2 mL) in a 30 mL two-necked round-bottomed
flask with stirring under atmospheric oxygen (for 1st). After extraction with Et2O,
benzylamine was then added to the resulting ionic liquid phase containing the
catalyst (for the other runs).
b
The starting benzylamine still remained, but no byproduct was detected.
Determined by 1H NMR.
c
d
Isolated yield.
Based on our interest in green chemistry, we next examined the
present oxidation of amines to imines using ionic liquid (IL) as an
eco-friendly solvent. IL has a nature of reasonable thermal and
chemical stability, negligible vapor pressure, non-flammability,
and high capacity to dissolve various organic and inorganic com-
pounds.9–11
Table 3
Oxidation of benzylamines in ionic liquidsa
The results of the oxidation using ILs in a glass vessel are sum-
marized in Table 3.12 We first conducted the oxidation of 1a using
1-hexyl-3-methylimidazolium hexafluorophosphate, [hmim]PF6,
as a solvent. As a result, the oxidation product 2a was obtained
in 75% yield (entry 1). On the other hand, other ILs bearing differ-
ent alkyl chain or counter anion were less effective, resulting mod-
erate to low yields of 2a (entries 2À4).13,14 When we conducted the
oxidation of 1b using [hmim]PF6, the product 2b was formed in
73% yield.
Next, recycling feature of the catalyst in [hmim]PF6 was demon-
strated, as shown in Table 4. After extraction with diethyl ether to
separate the products from the IL, the IL containing the catalyst
was dried in vacuo for 6 h, and the resulting ionic liquid layer
was used for the oxidation reaction. The result shows that
[hmim]PF6 containing VO(Hhpic)2 was successfully reused for fur-
ther eight runs without any detectable loss in catalytic activity.
In summary, we have found that VO(Hhpic)2 is a highly effec-
tive catalyst for selective oxidation of benzylamines to the corre-
sponding imines by molecular oxygen in acetonitrile. In addition,
VO(Hhpic)2 in ionic liquids could be employed as a reusable cata-
lyst for the oxidation of benzylamines to imines. Further studies of
the oxidation using ionic liquids are in progress. Results will be re-
ported in due course.
VO(Hhpic)2 (2 mol%)
O
2 (0.1 MPa)
Ar
NH2
Ar
N
Ar
Ionic Liquid
120 oC, 6 h
1
2
Entry
1
Substrate
NH2
Ionic liquid
Yieldb (%)
Me
nHex
PF6
nBu
N
N
N
N
N
75
46
43
18
+
+
-
Me
Me
Me
N
2
3
4
-
PF6
nBu
1a
1b
N
+
+
-
BF4
Et
BF4
N
-
nHex
NH2
Me
N
N
+
-
5
73
PF6
Cl
a
All reactions were carried out in 1.5 mmol scale using a glass vessel filled with
Determined by 1H NMR.
O2.
b

2452
S. Kodama et al. / Tetrahedron Letters 51 (2010) 2450–2452
Ohshiro, Y.; Ikeda, I. Chem. Lett. 1993, 1889; (i) Neumann, R.; Levin, M. J. Org.
Acknowledgments
Chem. 1991, 56, 5707.
5. Nakai, M.; Obata, M.; Sekiguchi, F.; Kato, M.; Shiro, M.; Ichimura, A.; Kinoshita,
I.; Mikuriya, M.; Inohara, T.; Kawabe, K.; Sakurai, H.; Orvig, C.; Yano, S. J. Inorg.
Biochem. 2004, 98, 105.
6. We have reported that VO(Hhpic)2 has a catalytic activity for the oxidation of
benzyl alcohols with molecular oxygen: Kodama, S.; Ueta, Y.; Yoshida, J.;
Nomoto, A.; Yano, S.; Ueshima, M.; Ogawa, A. Dalton Trans. 2009, 9708.
7. General procedure for the oxidation of benzylamines using an autoclave or sealed
tube (Table 1): The vanadium complex (0.03 mmol, 10.3 mg), amine
This research was supported by JST Research Seeds Quest Pro-
gram (Lower Carbon Society), from the Ministry of Education, Cul-
ture, Sports, Science and Technology, Japan, and Kansai Research
Foundation for Technology Promotion (KRF). S.K. acknowledges Re-
search Fellowships of the Japan Society for the Promotion of Sci-
ence (JSPS) for Young Scientists.
(1.5 mmol), and acetonitrile (6 mL) were placed in
a 50 mL autoclave in
sequence, and then oxygen was introduced (0.1 MPa). This autoclave was then
put into an oil bath (120 °C) under magnetic stirring for the desired reaction
time. The resulting mixture was filtered through a Celite pad. After evaporation
of the solvent, the product was purified by column chromatography on silica
gel using ethyl acetate and hexane as eluent to afford the analytically pure
imines.
Supplementary data
Experimental procedures, compound characterization, and se-
lected 1H and 13C NMR spectral data are available. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.tetlet.2010.02.150.
8. Similar conditions could not employed with simple aliphatic amines such as
aminomethylcyclohexane and di-n-hexylamine, and further detailed
optimization of the conditions is required for the oxidation of them.
9. (a) For reviews concerning catalytic reactions using ionic liquids, see:
Wasserscheid, P.; Schulz, P. In Ionic Liquids in Synthesis; 2nd ed.;
Wasserscheid, P., Welton, T., Eds., Wiley-VCH: Weinheim, 2008; pp 369–463.
Chapter 5.3; (b) Muzart, J. Adv. Synth. Catal. 2006, 348, 275; (c) Fei, Z.; Geldbach,
T. J.; Zhao, D.; Dyson, P. J. Chem. Eur. J. 2006, 12, 2122; (d) Miao, W.; Chan, T. H.
Acc. Chem. Res. 2006, 39, 897; (e) Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S.
M. S. Tetrahedron 2005, 61, 1015; (f) Baudequin, C.; Brégeon, D.; Levillain, J.;
Guillen, F.; Plaquevent, J.-C.; Gaumont, A.-C. Tetrahedron: Asymmetry 2005, 16,
3921; (g) Welton, T. Coord. Chem. Rev. 2004, 248, 2459; (h) Sheldon, R. Chem.
Commun. 2001, 2399; (i) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev.
2002, 102, 3667.
10. Catalytic oxidation of alcohols in ILs: (a) Chhikara, B. S.; Chandra, R.; Tandon, V.
J. Catal. 2005, 230, 436; (b) Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507; (c)
Wolfson, A.; Wuyts, S.; De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A.
Tetrahedron Lett. 2002, 43, 8107.
11. Ragauskas and co-workers reported selective aerobic oxidation of alcohols
using vanadium catalysts in IL: Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2007,
48, 273.
12. General procedure for the oxidation of benzylamines in [hmim]PF6 (Table 3): In a
30 mL two-necked round-bottomed flask with a stirring bar under atmosphere
of oxygen, VO(Hhpic)2 (0.03 mmol, 10.3 mg), amine (1.5 mmol), and
[hmim]PF6 (2 mL) were placed, and then the mixture was heated at 120 °C
for the appropriate time with magnetic stirring. The resulting mixture was
extracted with diethyl ether. The extracts were concentrated in vacuo. The
product was confirmed by 1H NMR spectroscopy. Purification of the product by
column chromatography on silica gel using ethyl acetate and hexane as eluent
afforded the analytically pure imines.
13. Although other ionic liquids, such as [hmim]Cl, [bmim]Tf2N, and [edmim]Tf2N
(Tf2N: bis(trifluoromehanesulfonyl)imide), were employed for this reaction,
the separation of the product from these ionic liquids was relatively difficult,
compared with the oxidation in [hmim]PF6.
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