Aerobic oxidative coupling of amines by carbon nitride photocatalysis with visible light

Article abstract of DOI:10.1002/anie.201004365

Coupling on sunshine: A simple and efficient synthesis of benzoxazoles, benzimidazoles, and benzothiazoles is realized through a one-pot preparation driven by a photocatalytic cascade reaction. Carbon nitride and visible light are employed to achieve this metal-free aerobic oxidation of amines to imines (see scheme; mpg-C₃N₄=mesoporous graphite carbon nitride). Copyright

Full text of DOI:10.1002/anie.201004365

DOI: 10.1002/anie.201004365
Photocatalysis
Aerobic Oxidative Coupling of Amines by Carbon Nitride
Photocatalysis with Visible Light**
Fangzheng Su, Smitha C. Mathew, Lennart Mꢀhlmann, Markus Antonietti, Xinchen Wang,* and
Siegfried Blechert*
The use of sunlight as a driving force for chemical reactions
shows great promise in synthetic chemistry.[1] As most organic
molecules are transparent in the visible spectrum, light
sensitizers are often employed to trigger organic transforma-
tions through electron transfer mediated by quenching
reagents.[2] Metal–organic dyes have been used as such
sensitizers because of the long lifetime of their excited
states; however, there is a concern about the stability of dyes
during long-term operations.[3] The inclusion of precious
metals such as ruthenium in the dyes also restricts their
practical applications.
Recently, our research group has introduced graphitic
carbon nitride (g-C3N4) as a metal-free photocatalyst for
hydrogen evolution using visible light.[4] Electrochemical and
optical analyses have been therefore performed to reveal the
top of the valance band and the bottom of the conduction
band of g-C3N4. These bands were detected at 1.4 V and
À1.3 V versus the normal hydrogen electrode, respectively.[5]
Light-induced electrons with large reduction potential can
easily activate molecular oxygen to mediate energy and
electron transfer while the moderate oxidation potential of
the holes prevents the synthesized organic compounds from
being oxidized in an uncontrollable manner. This feature
suggested that g-C3N4 can act as a gentle photocatalyst for
promoting organic redox synthesis in a broader fashion.
Indeed, when our work was extended to selective alcohol
oxidation, it was found that light-excited g-C3N4 can activate
O2 for oxidation of alcohols to aldehydes/ketones with high
selectivity.[6]
Herein, we advance carbon nitride photocatalysis medi-
ated by carbon nitride species for the oxidation of amines into
imines, which are regarded as important electrophilic inter-
mediates in organic synthesis.[7] Although selective oxidation
of secondary amines into imines can be achieved by employ-
ing stoichimetric amounts of reagents[8] with the noteworthy
case of o-iodoxybenzoic acid,[9] effort has been devoted to
developing catalytic systems using simple oxygen/air as the
terminal oxidant. Recently, several transition-metal based
catalysts[10] have been developed for this purpose, but they
oxidize only a limited range of amines into imines at relatively
high temperature (mostly > 1108C). We report the aerobic
oxidation of amines into imines in excellent yields using a
mesoporous graphite carbon nitride (mpg-C3N4) photocata-
lyst. We also integrate this oxidative coupling approach into a
one-pot synthesis of benzoxazoles, benzimidazoles, and
benzothiazoles, which are interesting and important com-
pounds that occur widely as biologically active natural
products, as well as marketed drugs or drug candidates.[11]
Results of control experiments and optimization of
reaction conditions for the oxidation of benzylamine are
listed in Table 1. No oxidation occurred in the absence of light
or mpg-C3N4, even with high pressure O2 (Table 1, entries 1
and 2). With mpg-C3N4, light, and O2, the conversion reached
Table 1: Transformation of benzylamine catalyzed by mpg-C3N4.[a]
[*] F. Su, Prof. Dr. M. Antonietti, Prof. Dr. X. Wang
Department of Colloid Chemistry, Max-Planck Institute of Colloids
and Interfaces
Research Campus Golm, 14476 Potsdam (Germany)
E-mail: xinchen.wang@mpikg.mpg.de
Entry
Solvent
T [8C]
Conv. [%]
Sel. [%]
1[b]
2[c]
3
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
methanol
60
60
60
60
60
80
80
80
30
80
80
80
–
–
–
–
Dr. S. C. Mathew, L. Mꢀhlmann, Prof. Dr. S. Blechert
Institute of Chemistry, Technical University Berlin
Strasse des 17. Juni 135, 10623 Berlin (Germany)
E-mail: blechert@mailbox.tu-berlin.de
34
34
36
60
61
16
13
52
31
35
99
99
99
99
98
99
99
99
99
99
4[d]
5[e]
6
Prof. Dr. X. Wang
Research Institute of Photocatalysis, State Key Laboratory Breeding
Base of Photocatalysis, Fuzhou University
Fuzhou 350002 (PR China)
7[f]
8[g]
9
10
11
12
[**] Supported by the Cluster of Excellence “Unifying Concepts in
Catalysis” coordinated by the TU Berlin and funded by the DFG, the
973 Program (2007CB613306), the ENERCHEM project of the Max
Planck Society, the NSF of China (21033003), and the Program for
New Century Excellent Talents in University of China (NCET-07-
0192). S.C.M thanks the Alexander von Humboldt Foundation for a
postdoctoral fellowship.
toluene
trifluorotoluene
[a] Reaction conditions: benzylamine (1 mmol), mpg-C3N4 catalyst
(50 mg), solvent (10 mL), O2 (0.5 MPa), l>420 nm, 2 h. [b] Without
using the catalyst. [c] Without using light. [d] 0.2 MPa. [e] 0.8 MPa.
[f] 5 mol% of radical scavenger 2,6-di-tert-butyl-4-methylphenol was
added. [g] Under an atmosphere of Ar.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004365.
Angew. Chem. Int. Ed. 2011, 50, 657 –660
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
657

Communications
34 and 60% at 60 and 808C, respectively, with high selectivity
corresponding imines with high yields; however, the oxidation
of the former (Table 2, entries 5 and 6) proceeded much more
efficiently than those of the latter (Table 2 entries 7 and 8).
Moreover, higher reaction rates for para-substituted benzyl-
amines relative to the meta and ortho isomers reveal the
presence of a steric effect (Table 2, entries 6, 9, and 10).
Heterocyclic amines containing nitrogen and sulfur atoms,
which usually poison most metal catalysts, could also be
converted into the corresponding imines in excellent yields
(Table 2, entries 11 and 12). Note that the oxidation of both
pyridyl- and thiophene-methylamine appeared much more
efficient than that of their phenyl counterparts. The oxidation
of amines lacking a hydrogen atom at the a-carbon position,
such as aniline, did not proceed under the chosen reaction
conditions, and only a trace amount of azo compound was
detected (Table 2, entry 13). Secondary amines also afforded
the imines in moderate to excellent yields by oxidative
dehydrogenation photocatalyzed by mpg-C3N4. But in the
case of dibenzylamine, a comparably low selectivity (80%)
for the imine was observed (Table 2, entry 15), with the main
(99%) to give N-benzylidene benzylamine (Table 1,
entries 3–6). The yield remained unchanged (Table 1,
entry 7) when a radical scavenger (2,6-di-tert-butyl-4-methyl-
phenol) was added, thus excluding the possibility of an
autooxidation process through a radical chain pathway.
Acetonitrile was found to be the best medium among the
solvents examined (Table 1, entries 8–12).
Thus, under optimized conditions (Table 1, entry 7),
complete conversion of benzylamine into N-benzylidene
benzylamine was obtained in 3.5 hours (Table 2, entries 1–
4).The oxidation of various amines was therefore examined
under these reaction conditions, and the results are also listed
in Table 2. Benzylamines substituted with electron-donating
groups (CH3 and OCH3) and electron-withdraw groups (Cl
and CF3) could also undergo oxidative coupling to the
Table 2: Oxidation of various amines using mpg-C3N4.[a] The general
reaction is applicable to entries 1–10.
by-product being benzaldehyde; the formation of which was
[12]
À
ascribed to the oxidative cleavage of the C N bond. The
same phenomenon also occurred in the case of N-benzylani-
line (Table 2, entry 16), with by-products of benzaldehyde and
aniline being formed. The oxidation of 1,2,3,4-tetrahydroiso-
quinoline proceeded quite smoothly with complete conver-
sion and high selectivity in 2 hours (Table 2, entry 14).
However, the reaction took place at a much lower rate for
1,2,3,4-tetrahydroquinoline, where a higher temperature and
longer reaction time were necessary for the high conversion of
the substrate (Table 2, entry 17). Regioselective oxidations
were observed when unsymmetrical secondary amines were
employed: the reaction proceeded to yield the conjugated N-
benzylidene products in remarkably high selectivity rather
than those generated from oxidation on the less activated site
(Table 2, entries 14–18). Indole and an imidazole derivative
were synthesized in high yields by the oxidation of the
corresponding indoline and imidazoline (Table 2, entries 18
and 19). After the reaction, some products were isolated by
distillation (Table 2, entries 1, 5–7, and 12).
The relationship between the activity and the wavelength
of incident light was investigated. The results showed that the
activity of mpg-C3N4 corresponded well with its optical
absorption spectrum (Figure S1 in the Supporting Informa-
tion). After the reaction, mpg-C3N4 could be easily separated
and reused. There was no loss in terms of the catalytic activity
during three consecutive runs (Table 2, entries 2–4). The
recycled catalyst showed no significant differences with the
fresh one in terms of local structure (as confirmed by X-ray
diffraction analysis, see the Supporting Information).
Entry Substrate
Product
t [h] Conv. [%] Sel. [%]
1
2
3
4
5
6
7
8
9
10
R=H
reuse 1
reuse 2
reuse 3
R=p-Me
R=p-OMe
R=p-Cl
R=p-CF3
R=o-OMe
R=m-OMe
R=H
3.5
3.5
3.5
3.5
2.5
2
4
5
2
2
99 90[b]
99
99
99
99
99
99
98
98
90
96
99
99
99
R=p-Me
R=p-OMe
R=p-Cl
R=p-CF3
R=o-OMe
R=m-OMe
95 89[b]
95 91[b]
91 79[b]
95
69
72
11
12
13
14
15
1
2
2
2
2
95
96
98
–
99 82[b]
1
99
70
91
80
16
3
46
92
17[c]
18
4.5
5
90
46
88
91
98
97
To get more insight into the mechanism of the present
catalytic reaction, the relative rates of oxidative coupling of
para-substituted benzylamines (MeO, Me, H, Cl, and CF3
groups) were examined. A reasonable linearity between the
log(kx/kh) values and the Brown–Okamoto constant (s+)
parameters for the oxidation of para-substituted benzyl-
amines was obtained, thereby suggesting that the reaction
proceeds via the intermediacy of a carbocationic species
(Figure 1).[13] The kinetic isotopic effect (KIE) was inves-
19
4.5
20
3
82
87
[a] Reaction conditions: substrate (1 mmol), mpg-C3N4 catalyst (50 mg),
CH3CN (10 mL), 808C, O2 (0.5 MPa). [b] Isolated by distillation.
[c] 0.6 mmol of substrate, 1008C.
658
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loses an electron, thus producing the carbocationic-radical-
type intermediate. The superoxide radical anion then
abstracts a proton and a hydrogen atom to form the
corresponding imine, and seems to be the rate-determining
step for the oxidation reaction as demonstrated by the kH/
kD value of intramolecular deuterium isotope effects. As we
never observe molecular H2O2, we assume the existence of a
second, similar two-electron cycle on mpg-C3N4 that leads to
the formation of water and an imine.[6] The positively charged
hole can coordinate to the imine and thereby make it more
prone to nucleophilic attack by the amine to form the aminal.
The aminal group will then undergo hole-assisted elimination
of ammonia to afford the final coupled product.
A one-pot synthesis of benzoxazoles, benzimidazoles, and
benzothiazoles was also explored, in which the initial imines
generated from the oxidative coupling reaction underwent
intramolecular cycloaddition and subsequent oxidation to the
target compounds, as depicted in Table 3. As classical
methods for the synthesis of benzoxazoles, benzimidazoles,
and benzothiazoles usually need rigorous conditions (i.e. high
temperature) or hazardous oxidants,[15] the proposed process
would represent an interesting and economically efficient
catalytic strategy. Indeed, the use of 2-aminophenol, 2-
aminothiophenol, and o-phenylenediamine as starting mate-
rials, respectively, gave the corresponding cascade products in
moderate to high conversions (Table 3, entries 1–3). The
presence of intermediate imine (detected and confirmed by
GC-MS analysis) during the reaction procedures,[16] regard-
less of the different starting substrates, also provides strong
proof for the proposed mechanism. Unfortunately, relatively
low selectivities (ca. 70%) were obtained in the synthesis of
benzoxazoles, with the main side product being benzalde-
hydes (Table 3, entries 1–4). In contrast, high conversions
Figure 1. Hammett plots for the oxidation of substituted benzylamines
with oxygen using mpg-C3N4 catalyst. Hammett plots were obtained
from a ratio of conversion with reaction time of 30 min.
tigated by the oxidation of a-deutero benzylamine and a
moderate kH/kD value of 2.3 was obtained (Scheme 1).
Scheme 1. Kinetic isotope effect on the oxidative coupling of a-deutero
benzylamine.
On the basis of the above results, the proposed reaction
mechanism is presented in Scheme 2. Similar to inorganic
photocatalysts that promote organic photosynthesis,[14] the
reaction is initiated by electron (eÀ) and hole (h+) pairs
photogenerated by the irradiation of mpg-C3N4. The photo-
generated electron reduces molecular oxygen to produce
CO2À, as already confirmed by electron spin resonance analysis
in a previous report.[6] The oxidative coupling of amines then
proceeds through several steps. Initially, the amine probably
Table 3: One-pot aerobic coupling synthesis of benzoxazoles, benzimid-
azoles, and benzothiazoles.[a]
Entry
R
X
t [h]
Conv. [%][b]
Sel. [%][b]
1
2
CH3
H
H
Cl
CH3
H
Cl
OCH3
H
O
O
O
O
NCH3
NCH3
NCH3
S
S
S
5
5
5
5
4
5
5.5
4
5
99
99
99
70
97
99
98
96
91
97
69
75
24
74
92
98
91
97
92
93
3[d]
4
5
6
7
8
9
10
Cl
5.5
[a] Reaction conditions: substituted benzylamine (1 mmol), mpg-C3N4
catalyst (50 mg), 2-aminophenol (2-aminothiophenol or o-phenylenedi-
amine) (3 mmol), CH3CN (10 mL), 1008C, O2 (0.5 MPa. [b] Conversion
and selectivity were based on benzylamines. [d] 808C; using the main
product of 2-hydroxybenzoimine.
Scheme 2. Proposed mechanism for aerobic oxidative coupling of
amines.
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Communications
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were observed in the synthesis of benzimidazoles and
benzothiazoles using substituted benzylamines (OCH3, CH3,
H. and Cl; Table 3, entries 5–10).
To conclude, we have developed a metal-free, heteroge-
neous catalysis protocol for the aerobic oxidation of amines
into imines using carbon nitride and visible light. This
photocatalytic process avoided the employment of any
metal derivative or organic oxidizing agents, and the catalyst
was found to be stable and reusable. Specifically, a simple and
efficient synthesis of benzoxazoles, benzimidazoles, and
benzothiazoles could be realized through a one-pot synthesis
by this photocatalytic cascade reaction with notably high
yields. The clean and mild synthetic method described here is
expected to be extended to a variety of compounds possessing
these core structures.
Received: July 16, 2010
Revised: October 7, 2010
Published online: December 8, 2010
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Keywords: aerobic oxidative coupling · amines · carbon nitride ·
photochemistry · visible light
.
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660
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