Mimicking the environment of living organisms to achieve the oxidative coupling of amines to imines catalyzed by water-soluble metalloporphyrins

Article abstract of DOI:10.1016/j.tetlet.2012.04.096

Highly efficient procedure for preparing imines from the oxidative coupling of amines catalyzed by metalloporphyrins using water as the only solvent has been developed. Manganese porphyrin showed an excellent activity for the oxidative coupling of a wide

Full text of DOI:10.1016/j.tetlet.2012.04.096

Tetrahedron Letters 53 (2012) 3369–3373
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Tetrahedron Letters
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Mimicking the environment of living organisms to achieve the oxidative
coupling of amines to imines catalyzed by water-soluble metalloporphyrins
⇑
Xian-Tai Zhou, Qing-Gang Ren, Hong-Bing Ji
School of Chemistry and Chemical Engineering, Key Laboratory of Low-Carbon Chemistry & Energy Conservation of Guangdong Province, Sun Yat-sen University,
Guangzhou 510275, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 January 2012
Revised 3 April 2012
Accepted 20 April 2012
Available online 27 April 2012
Highly efficient procedure for preparing imines from the oxidative coupling of amines catalyzed by
metalloporphyrins using water as the only solvent has been developed. Manganese porphyrin showed
an excellent activity for the oxidative coupling of a wide range of amines under mild conditions. Further
investigations of the oxidative coupling reaction led to the elucidation of the possible mechanism.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Water-soluble metalloporphyrin
Oxidative coupling
Amine
Water
Introduction
synthesis of imines, herein we report the first example on the oxi-
dative coupling of amines to imines catalyzed by metalloporphy-
1
Imines are useful intermediates for reduction, nucleophilic
addition, condensations, and cycloadditions.3 The synthetic
procedures of imines involve the oxidation of primary/secondary
rins in water medium (Scheme 1). The catalytic system has
proved to be effective for the oxidative coupling of amines to imi-
nes, in which various amines were readily reacted to afford the cor-
responding imines under mild conditions. The process also
provides a possible way for mimicking the aqueous oxidations of
the numerous nitrogenous organic compounds in living organisms.
2
4
5
amines, condensation of amine and carbonyl compound. Most
of the catalytic reactions are conducted with metal oxidants such
as dichromate ions, permanganate ions, manganese dioxide, silver
6
oxide, and lead tetraacetate in organic solvents. From environmen-
tal and economic viewpoints, chemical reactions using water as
Results and discussion
solvent have received considerable attention.7
Metalloporphyrins as chemical models of cytochrome P450 and
related monooxygenases have been used to carry out the oxidation
reactions of various organic compounds.8 As to the oxidation of
amines, most of the metalloporphyrin-mediated oxidations were
conducted in organic solvents. Bailey and James ever reported
the aerobic dehydrogenation of amines to nitriles or the corre-
sponding carbonyl compounds with ruthenium(II) porphyrin in
Aerobic oxidative coupling of benzylamine
For the initial studies on the catalytic activity of different water-
soluble metalloporphyrins in the oxidative coupling of amines to
imines in water medium, benzylamine was selected as a model
substrate to assess their catalytic properties in this reaction. The
oxidative coupling of benzylamine catalyzed by these catalysts
produced N-benzylbenzaldimine as the main product. A small
amount of benzaldehyde, the direct oxidation product of benzyl-
amine were detected in the oxidative coupling reactions. The re-
sults are summarized in Table 1.
9
benzene. Kim and Thakur reported the oxidative coupling of
amines to imines catalyzed by manganese porphyrins in acetoni-
1
0
trile. We ever reported the efficient oxidative coupling reactions
1
1
of amines to imines by MnTPPCl with toluene as solvent. There-
fore, the oxidations catalyzed by metalloporphyrins with water as
solvent will be of great significance, which is closer to simulate the
environments of the enzyme-mediated process because nitro-con-
taining organic compounds, cytochrome P450, and dioxygen were
related to the life origin. To obtain greener procedures for the
The reaction was first examined for the blank experiment with
2
mmol of t-BuOOH at 60 °C for 3 h. Under such conditions, as
shown in Table 1, only 13% of benzylamine was converted, indicat-
ing that the oxidative coupling reaction could hardly be initiated
only with an oxidant (entry 1); while a catalytic amount of
water-soluble metalloporphyrins catalyst could remarkably
promote the reaction. The catalytic activities of water-soluble
metalloporphyrins for the oxidative coupling reaction of
⇑
Corresponding author. Tel.: +86 20 84113658; fax: +86 20 84113654.
E-mail address: jihb@mail.sysu.edu.cn (H.-B. Ji).
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.096

3
370
X.-T. Zhou et al. / Tetrahedron Letters 53 (2012) 3369–3373
t-BuOOH, H O, 60°C
2
NH2
N
2
R
N
MnTE4PyP: R=C H , M=Mn
2
5
CoTE4PyP: R=C H , M=Co
2
5
5
CuTE4PyP: R=C
MnTM4PyP: R=CH , M=Mn
2
H
, M=Cu
N
N
N
N
3
M
N
R
R
N
CoTM4PyP: R=CH , M=Co
3
CuTM4PyP: R=CH , M=Cu
3
N
R
Scheme 1. The oxidative coupling reaction of benzylamine catalyzed by water-soluble metalloporphyrins in water.
benzylamine appeared to be dependent on the nature of central
ions (entries 2–7).
Table 1
Oxidative coupling of benzylamine catalyzed by various water-soluble
metalloporphyrinsa
The present results clearly show that manganese porphyrins are
considerably more active than copper and cobalt porphyrin cata-
lysts for the oxidative coupling reaction. Usually, cobalt porphyrins
are efficient for aerobic hydroxylation of alkane and olefins, but the
water-soluble cobalt porphyrins presented extremely low activity
for the reaction (entries 4 and 7). It indicates that the mechanism
of the oxidative coupling of amine to imine is different from that
of C–H hydroxylation. Although, copper porphyrins with different
substituents were more favorable for the conversion of benzyl-
amine, the selectivity of imine was only 60% and 62%, respectively
Selectivityb (%)
Yieldc (%)
Entry
Catalyst
Conv. (%)
1
2
3
4
5
6
7
None
13
86
97
30
86
95
28
78
69
88
60
63
78
62
64
54
8
76
58
19
67
59
18
42
MnTE4PyP
CuTE4PyP
CoTE4PyP
MnTM4PyP
CuTM4PyP
CoTM4PyP
d
8
MnSO
4
a
Benzylamine (1 mmol), catalyst (5 Â 10À4 mmol), t-BuOOH (2 mmol), water
(
entries 3 and 6). In addition, the catalytic activity and selectivity of
(
5 mL), 60 °C, 3 h.
b
different water-soluble metalloporphyrins are possibly influenced
by the stability of different valences of metal atoms.
The substituents (ethyl and methyl) on the porphyrins ring had
little effect on the activity for the oxidative coupling reaction.
The other products are benzaldehyde and benzonitrile.
Isolated yields.
Catalyst (5 Â 10 mmol).
c
d
À3
Table 2
Oxidative coupling of amines to imines in water catalyzed by MnTE4PyPa
Entry
Substrate
Product
T (h)
Conv. (%)
86
Selectivity (%)
88
Yieldb (%)
76
NH2
N
1
3
NH2
N
2
3
2
2
97
98
82
84
80
82
NH2
N
O
F
O
F
O
NH2
N
4
5
3
4
99
98
83
86
82
84
F
NH2
N
Cl
Cl
Cl
Cl
Cl
Cl
Cl
6
NH2
N
4
75
88
66
Cl
Cl
NH2
N
N
7
8
3
5
81
75
85
67
69
50
NH2
Cl
Cl Cl
a
À4
Amine (1 mmol), MnTEPyP (5 Â 10 mmol), t-BuOOH (2 mmol), water (5 mL), 60 °C.
b
Isolated yields.

X.-T. Zhou et al. / Tetrahedron Letters 53 (2012) 3369–3373
3371
benzylamine due to the poor selectivity of N-benzylbenzaldimine
even by enhancing the amount of catalyst (entry 8).
4
63
1
1
0
0
.5
.0
.5
.0
Oxidative coupling of various amines in water catalyzed by
MnTE4PyP
4
51
In order to explore the generality of the catalytic system, vari-
ous amines were evaluated by performing the reaction with water
as solvent and the results are summarized in Table 2.
4
31
a
b
c
As shown in Table 2, most substrates were smoothly converted
into the corresponding imines with high efficiency under mild con-
ditions. The aromatic substitutes at the p-position promoted the
efficiency of benzylamine conversion no matter the electronic nat-
ure of substitutes, but a slight decreased selectivity of coupling
products was observed (entries 2–5). Compared with electronic
properties of substrates, it seemed that the efficiency of oxidative
coupling reaction is more dependent on the steric structure (en-
tries 6–8). The electronic nature of aromatic substitutes at the o-
position also affected the efficiency, in which the electron-with-
drawing groups (entry 8) retarded the oxidative coupling so that
longer reaction times are required.
4
00
500
Wavelength/nm
600
Figure 1. In situ UV–vis spectra of MnTE4PyP in the oxidative coupling reaction of
benzylamine, (a) initial, (b) after adding benzylamine, (c) after adding t-BuOOH.
4
63
1
1
0
0
.5
.0
.5
.0
a
b
c
d
Plausible mechanism for the oxidative coupling reaction in
water
In the aqueous oxidative coupling of benzylamine catalyzed by
water-soluble manganese porphyrins, benzaldehyde, and benzoni-
trile could be determined (total selectivity is about 10%). From Ta-
ble 1, the blank experiment clearly suggested that MnTE4PyP is
crucial for the oxidative coupling reaction. The presence of high-va-
lent manganese porphyrin was confirmed by in situ UV–vis spectra
in the catalytic system. As shown in Figure 1, the initial character-
4
00
500
Wavelength/nm
600
12
istic absorption peaks of MnTE4PyP were at 463 and 562 nm. By
adding benzylamine into the solution, the Soret band of MnTE4PyP
was shifted to 451 nm immediately. It could be attributed to the
coordination of Mn ion and benzylamine, in which benzylamine
acted as an axial ligand. While after adding the oxidant t-BuOOH
into the mixture solution, in situ UV–vis spectrum determination
revealed the disappearance of peak at 451 nm and a new absorption
peak formation at 431 nm, which suggested the generation of high-
valent oxidant active species oxo-Mn(IV). GC analysis revealed
the formation of the coupling product, which is also indicative of
the presence of an active species.
Figure 2. In situ UV–vis spectrum of MnTE4PyP in the oxidative coupling reaction
of benzylamine, (a) reaction conducted for 30 min, (b) reaction conducted for 2 h,
(
c) reaction conducted for 3 h, (d) the initial curve of MnTE4PyP.
4
Manganese(II) compound such as MnSO also presented high activ-
ity for the oxidation of benzylamine, which could further demon-
strate that the reaction was closely related to the nature of
central ions. Compared with manganese porphyrins, manganese
salt was unfavorable for the oxidative coupling reaction of
1
3
O
PorMnIV
PorMnII
OH
t-BuOOH
PorMnII
PhCH=NH
a)
PhC
N
(
H O
2
3
OH
Ph
Ph
C
H
NH2
H
O
MnIV
O
Ph
C
H
N
H
NH3
PorMnIV
O
1
OH
PhCH NH2
2
PhCH NH
2
2
Ph
N
H
Ph
(
b)
Ph
N
Ph
2
Scheme 2. A plausible mechanism for the oxidative coupling of amine to imine catalyzed by MnTE4PyP in water.

3
372
X.-T. Zhou et al. / Tetrahedron Letters 53 (2012) 3369–3373
NH
2
N
N
MnTE4PyP(5x10-4mmol)
NH
1mmol)
Conv.: <1%
2
t-BuOOH(2mmol), H O(5mL)
2
(
Yield: <1%
Scheme 3. Oxidative coupling of n-butylamine and cyclohexanemethylamine.
Figure 3. The optimized molecular structures of n-butylamine (a), cyclohexanemethylamine (b), and benzylamine (c).
The reaction was initiated with the addition of an oxidant in the
Conclusion
In conclusion, an environmentally-friendly protocol has been
mixture with a new absorption peak formation at 431 nm, as de-
scribed above and followed by the catalytic process of oxidative
coupling that was monitored by an in situ UV–vis spectrophotom-
eter as shown inFigure 2. The curves of a, b, and c showed the spec-
tra of the point after the reaction for 0.5, 2, and 3 h, respectively.
Increment at 463 and 570 nm in the catalytic process was observed
with some loss of intensity. It indicated that active species oxo-
Mn(IV) was converted into initial manganese(II) porphyrin in the
oxidative coupling reaction of benzylamine.
developed for oxidative coupling of amines to give imines using
water as the solvent. The MnTE4PyP-based catalytic system has
proved to be effective in the oxidative coupling reaction of amines
with t-BuOOH as a terminal oxidant. The oxidative coupling of ben-
zylamine by MnTE4PyP in water gave product in up to 76% isolated
yield. Various amines could be successfully converted. The oxida-
tive coupling was through the formation of high-valent oxo-man-
ganese species.
1
1
On the basis of above observations and previous works,
a
plausible reaction mechanism for the oxidative coupling of benzyl-
amine with water-soluble manganese porphyrin as catalyst has
been proposed as showed in Scheme 2. Through the reaction with
benzylamine, the role of high valence manganese intermediate in
the present system is to produce a Schiff-base imine intermediate
Acknowledgments
The authors thank the National Natural Science Foundation of
China (Nos. 21036009, 21176267 and 20976203), Higher-level tal-
ent project for the Guangdong provincial Universities and the Fun-
damental Research Funds for the Central Universities for providing
financial support to this project.
(a). Then, benzaldehyde (1) was generated from the hydrolysis of
Schiff-base imine intermediate with the elimination of a molecule
1
1
of ammonia. Coupled imine product (2) was generated by the re-
moval of a water molecule from the intermediate (b). In addition,
benzonitrile (3) was generated by the dehydrogenation of Schiff-
base imine intermediate (a) in the presence of high valence manga-
nese intermediate.
References and notes
1.
(a) Casey, C. P.; Bikzhanova, G. A.; Guzei, I. A. J. Am. Chem. Soc. 2006, 128, 2286;
b) Li, B. Y.; Yao, Y. M.; Wang, Y. R.; Zhang, Y.; Shen, Q. Inorg. Chem. Commun.
008, 11, 349; (c) Nugent, T. C.; El-Shazly, M. Adv. Synth. Catal. 2011, 353, Cp6.
(
2
In the mechanism, Schiff-base imine intermediate is generated
through the electrophilic attack of benzylamine by oxo-Mn species.
Therefore, the electronic atmosphere of N atom could affect the
reactivity for the different amines. The assumption was confirmed
from the extremely different results that aliphatic amine was used
as substrate. No product could be obtained in the oxidation of n-
butylamine and cyclohexanemethylamine under the same reaction
conditions (Scheme 3).
2. (a) Harried, S. S.; Croghan, M. D.; Kaller, M. R.; Lopez, P.; Zhong, W. G.; Hungate,
R.; Reider, P. J. J. Org. Chem. 2009, 74, 5975; (b) Kobayashi, S.; Gustafsson, T.;
Shimizu, Y.; Kiyohara, H.; Matsubara, R. Org. Lett. 2006, 8, 4923; (c) Reddy, L. R.;
Prashad, M. Chem. Commun. 2010, 46, 222.
3. (a) Fang, Y. Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 5660; (b) Gan, Y.;
Harwood, L. M.; Richards, S. C.; Smith, I. E. D.; Vinader, V. Tetrahedron:
Asymmetry 2009, 20, 723; (c) Ioannou, E.; Hirsch, A.; Elemes, Y. Tetrahedron
2007, 63, 7070.
4
5
.
.
(a) Aschwanden, L.; Mallat, T.; Krumeich, F.; Baiker, A. J. Mol. Catal. A 2009, 309,
57; (b) Christian, G. J.; Llobet, A.; Maseras, F. Inorg. Chem. 2010, 49, 5977; (c) D
Jiang, D. M.; Mallat, T.; Krumeich, F.; Baiker, A. Catal. Commun. 2011, 12, 602.
(a) Miecznikowski, J. R.; Crabtree, R. H. Polyhedron 2004, 23, 2857; (b) Newman,
C. A.; Antilla, J. C.; Chen, P.; Predeus, A. V.; Fielding, L.; Wulff, W. D. J. Am. Chem.
Soc. 2007, 129, 7216; (c) Zhang, Y.; Lu, Z. J.; Desai, A.; Wulff, W. D. Org. Lett.
To get a better understanding, calculations were performed
with the Gaussian03W package using the density functional theory
1
4
(
DFT). Full geometry optimizations of different substrates were
performed employing Becke’s three parameter Lee–Yang–Parr cor-
relation functions (B3LYP) combined with 6–31 + G(d,p) basis set.
The optimized structures for n-butylamine, cyclohexanemethyl-
amine, and benzylamine are presented in Figure 3.
According to the calculated results, the NBO (Natural Bond
Orbital) charges of N atom for the three substrates are À0.2826,
À0.3014, and À0.7017 eV, respectively. The aliphatic amines have
a larger charge for the N atom. The more positive charges could re-
tard the electrophilic attack of high-valent metal intermediate to N
atom, which resulted in the poor reactivity under the same
reactions.
2
008, 10, 5429.
(a) Murahashi, S. I.; Komiya, N.; Terai, H.; Nakae, T. J. Am. Chem. Soc. 2003, 125,
5312; (b) Wang, J. R.; Fu, Y.; Zhang, B. B.; Cui, X.; Liu, L.; Guo, Q. X. Tetrahedron
Lett. 2006, 47, 8293; (c) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc.
002, 124, 766; (d) Steinhoff, B. A.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348.
6.
1
2
7
.
.
(a) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563; (b) Lipshutz, B. H.;
Ghorai, S.; Aguinaldo, G. T. Adv. Synth. Catal. 2008, 350, 953; (c) Firouzabadi, H.;
Iranpoor, N.; Gholinejad, M. Tetrahedron 2009, 65, 7079.
(a) Yamanishi, K.; Miyazawa, M.; Yairi, T.; Sakai, S.; Nishina, N.; Kobori, Y.;
Kondo, M.; Uchida, F. Angew. Chem., Int. Ed. 2011, 50, 6583; (b) Che, C. M.; Lo, V.
K. Y.; Zhou, C. Y.; Huang, J. S. Chem. Soc. Rev. 1950, 2011, 40; (c) Ji, H. B.; Zhou, X.
T. Biomimetics, Learning from Nature; In-Tech publishing: Vienna, 2010; (d)
Meunier, B.; de Visser, S. P.; Shaik, S. Chem. Rev. 2004, 104, 3947.
8

X.-T. Zhou et al. / Tetrahedron Letters 53 (2012) 3369–3373
3373
9
.
Bailey, A. J.; James, B. R. Chem. Commun. 1996, 2343.
13. (a) Nam, W.; Kim, I.; Lim, M. H.; Choi, H. J.; Lee, J. S.; Jang, H. G. Chem. Eur. J.
2002, 8, 20671; (b) Groves, J. T.; Lee, J. B.; Marla, S. S. J. Am. Chem. Soc. 1997, 119,
6269.
1
1
1
0. Kim, S. S.; Thakur, S. S. Bull. Korean Chem. Soc. 2005, 26, 1600.
1. Yuan, Q. L.; Zhou, X. T.; Ji, H. B. Catal. Commun. 2010, 12, 202.
2. Groves, J. T.; Watanabe, Y.; McMurry, T. J. J. Am. Chem. Soc. 1983, 105, 4489.
14. Frisch, M. J. Gaussian W03, Revision D. 01; Gaussian, Inc.: Wallingford, CT, 2004.