Facile aerobic photooxidation of methyl group in the aromatic nucleus in the presence of an organocatalyst under VIS irradiation

Article abstract of DOI:10.1039/c1gc15154a

We report a useful method for a facile synthesis of carboxylic acids from methyl aromatics by aerobic photooxidation using VIS irradiation and easily handled 2-chloroanthraquinone as organic catalysts under mild conditions such as an air atmosphere and ambient pressure and temperature. This is a more environmentally benign oxidation than previous methods, which require drastic reaction conditions.

Full text of DOI:10.1039/c1gc15154a

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Green Chemistry
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COMMUNICATION
Facile aerobic photooxidation of methyl group in the aromatic nucleus in the
presence of an organocatalyst under VIS irradiation†
Norihiro Tada, Kasumi Hattori, Tomoya Nobuta, Tsuyoshi Miura and Akichika Itoh*
Received 9th February 2011, Accepted 12th April 2011
DOI: 10.1039/c1gc15154a
Table 1 Study of reaction conditions
We report a useful method for a facile synthesis of
carboxylic acids from methyl aromatics by aerobic pho-
tooxidation using VIS irradiation and easily handled 2-
chloroanthraquinone as organic catalysts under mild con-
ditions such as an air atmosphere and ambient pressure
and temperature. This is a more environmentally benign
oxidation than previous methods, which require drastic
reaction conditions.
Yield (%)a
Entry
Catalyst
Solvent
2a
3a
2a + 3a
1
2
3
4
5
6
7
8
9
AQN
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
acetone
MeCN
MeOH
PhH
31
28
32
39
40
29
38
0
45
36
35
60
50
42
34
0
76
64
67
99
90
71
72
0
Oxidation is the most fundamental and important transforma-
tion in organic synthesis. Many methods and reagents have
been developed to date; however, these reactions typically
involve the use of large quantities of heavy metals and complex
organic compounds, generate large amounts of waste, and
are not environmentally benign.1 On the other hand, many
researchers have recently reported catalytic oxidation processes
with hydrogen peroxide or molecular oxygen2 that generate
little waste. Molecular oxygen in particular has received much
attention as an ultimate oxidant, since it is photosynthesized by
plants, produces little waste, is inexpensive, and has a larger
atom efficiency than other oxidants. However, the methods
usually involve the use of heavy metals, high pressure, or high
temperature. Hence, we have attempted photooxidation with
molecular oxygen. Some properties of light make it a clean
reagent because it has neither shape nor weight to be emitted
as residue. Thus, it has become a key method for developing
environmentally benign processes. In fact, effective use of light,
which is abundantly available, is an exciting research topic in
many fields including energy-related disciplines. We reported
previously that alcohols and methyl groups in an aromatic
nucleus were oxidized directly to the corresponding carboxylic
acids in the presence of catalytic halogen sources in an oxygen
atmosphere under UV or VIS irradiation.3 In particular, metal-
free direct oxidation of a methyl group in the aromatic nucleus
to the corresponding carboxylic acid is generally very difficult;
however, with our method, we could accomplish it under mild
2-Me-AQN
2-tBu-AQN
AQN-2-CO2H
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
13
0
18
5
31
5
10
hexane
a Yields were determined by 1H-NMR.
conditions. This new oxidation reaction is appealing in terms of
green chemistry4 because it does not use heavy metals, reduces
waste, and uses molecular oxygen and inexpensive reagents.
However, the use of halogen sources and a high concentration
of oxygen remain as obstacles to a more environmentally benign
green method. This motivates the project described here, in
which we have been able to determine that a photosensitizer
might be used as a catalyst. Here, we report our detailed study
of oxidation from methyl group in the aromatic nucleus to the
corresponding carboxylic acids under VIS irradiation in the
presence of a catalytic photosensitizer in an air atmosphere.
To explore this approach, we selected 4-tert-butyltoluene (1a)
as a test substrate to optimize the reaction conditions (Table
1). Although we examined the reaction conditions with various
photosensitizers, the yields of 2a + 3a were unsatisfactory, except
for anthraquinone derivatives. An excellent yield was obtained
using 2-chloroanthraquinone (2-Cl-AQN) or anthraquinone 2-
carboxylic acid (AQN-2-CO2H) in EtOAc for 10 h (entries 4 and
5); however, they produced both 2a and 3a as a mixture.
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196,
Japan. E-mail: itoha@gifu-pu.ac.jp; Fax: (+81) 58-230-8108;
Tel: (+81) 58-230-8108
† Electronic supplementary information (ESI) available: Experimental
procedures, characterization of the compounds, NMR and MS spectra.
See DOI: 10.1039/c1gc15154a
To increase the yield of 2a and decrease that of 3a, we
examined suitable additives. The addition of a catalytic amount
of acid or base was found to be effective (Table 2).5 In particular,
only 2a was given in high yield, and 3a could not be detected
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of oxygen is below the lower limit of explosion (entry 4).7 To
the best of our knowledge, this is the first successful report of
aerobic oxidation with such a low concentration of molecular
oxygen.
Table 2 Study of additives
Table 3 shows the scope and limitations of this oxidation with
methyl aromatics under the optimized conditions. All products
were obtained in excellent to good yields in an air atmosphere
and VIS irradiation from fluorescent lamps. Reactions are
generally achieved in a shorter time when catalytic amounts
of K2CO3 or TFA are used as additives. An electron-donating
group in the aromatic nucleus accelerates the reaction, and
an electron-withdrawing group retards it. Xylene (1b, 1c 1d),
which possesses two methyl groups in the aromatic nucleus,
produced mainly methyl benzoic acid (2b, 2c, 2d) because of the
electron-withdrawing property of the carboxylic group that was
formed. 4,4¢-Oxybis-benzoic acid (2k), which is the monomer
for a functional polymer, is also obtained in good yield under
similar reaction conditions.
Yield (%)a
Time (h) 2a
2-Cl-AQN
Entry (equiv.)
Additive (equiv)
3a
1
2
3
4
5
6
7
8
0.1
0.1
K2CO3 (0.05)
K2CO3 (0.05)
K2CO3 (0.05)
K2CO3 (0.05)
K2CO3 (0.01)
K2CO3 (0.05)
10
12
12
24
12
12
78
0
0
0
0
0
0
7
0
0
0
0
85
0.08
0.08
0.08
0.05
0.1
0.08
0.08
0.08
0.08
100 (97)b
99 (95)b,c
89
88
70
TFA (0.4)/H2O (75 mL) 24
TFA (0.4)/H2O (75 mL) 24
TFA (0.3)/H2O (75 mL) 24
TFA (0.2)/H2O (75 mL) 24
TFA (0.3)/H2O (50 mL) 24
93
9
10
11
100 (99)b
79
86
a Yields were determined by H-NMR. b Isolated yields. c The reaction
1
We found that our aerobic photooxidative esterification
involved a path through dimethyl acetal from aldehyde under
CBr4-MeOH.8 To clarify the reaction mechanism, we studied
its time course and found that adding a catalytic amount of
acid or base accelerates the decomposition of the peracid to
the corresponding carboxylic acid.9 With TFA, the peracid was
detected even after 20 h; however, with K2CO3 no peracid was
detected. These results suggest that the decomposition of peracid
to the corresponding acid is slower in the presence of an acid
than in the presence of a base. In addition, the fact that peracids
remain when other bases such as Na2CO3 and CaCO3 are added
suggests that both the reactions proceed through the same
reaction path regardless of the addition of an acid or a base.
Furthermore, the concentration of peroxide was measured by
iodometry; the results show that peroxide, which is not derived
was carried out under a 5% concentration of O2 for 24 h.
when K2CO3 or trifluoroacetic acid (TFA) was used as an
additive.6 Moreover, the addition of water was found to increase
the yield of 2a when TFA was used. Surprisingly, a similar
reaction rate was obtained when using air instead of pure oxygen
under the optimized reaction conditions mentioned above. This
contrasts with our previous oxidative reaction, in which the
yields of products under pure oxygen and an air atmosphere
differed considerably. Furthermore, this oxidation proceeds
smoothly even under a 5% oxygen concentration, which is one-
fourth the concentration in air (entry 4). Thus, this reaction is
much safer than previous methods, since a 5% concentration
Table 3 Scope and limitations of aerobic photooxidation
A: 97% (12 h)
B: 99% (24 h)
A: 75% (12 h)
B: 83% (24 h)
A: 68% (18 h)
B: 61% (24 h)
A: 60% (18 h)
B: 63% (24 h)
A: 86% (18 h)
B: 87% (30 h)
A: 70% (24 h)
B: 78% (30 h)
A: 68% (36 h)
B: 56% (48 h)
A: 58% (24 h)
B: 68% (30 h)
A: 70% (30 h)
B: 56% (48 h)
A: 52% (72 h)
B: 39% (72 h)b
A: 60% (48 h)c,d
B: 70% (72 h)c,e
Isolated yields.a Method A: K2CO3 (0.05 equiv); Method B: TFA (0.3 equiv)/H2O (75 mL). b TFA (0.6 equiv) was used. c 2-Cl-AQN (0.16 equiv) and
EtOAc (2 mL) were used. d K2CO3 (0.1 equiv) was used. e TFA (0.6 equiv) and H2O (100 mL) were used.
1670 | Green Chem., 2011, 13, 1669–1671
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from the substrate, is generated in situ. This result suggests that
hydrogen peroxide is formed in the course of this reaction.10 In
light of all the information above, we assumed the following
mechanism (Scheme 1). Excited anthraquinone, which absorbs
light,11 abstracts the hydrogen radical at the benzylic position
to produce benzyl radical 4, which traps molecular oxygen.
Aldehyde 7 forms through peroxyradical 5 and hydroperoxide
6.12 Hydrate 8, which is formed by the addition of water to 7,
is transformed to benzyl radical 9 through the elimination of
the hydrogen radical by excited anthraquinone.13 Furthermore,
hydroperoxide 11 is produced through peroxyradical 10 by
trapping molecular oxygen. Next, in the presence of a catalytic
amount of acid or base, carboxylic acid 2 is produced through
peracid 3 under the release of hydrogen peroxide. Water is
thought to have two important roles: accelerating the final step,
from 3 to 2, in the case of acids and increasing its solubility to
the reaction mixture in the case of bases. An optimal pH of the
acids is thought to be required for this final step.6,14
and high temperature. It is interesting in terms of not only
synthetic organic chemistry but also environmental chemistry.
Notes and references
1 Comprehensive Organic Transformations: A Guide to Functional
Group Preparations, ed. R. C. Larock, Wiley-VCH, New York,
1999.
2 For recent examples of oxidation of alcohols to the corresponding
carboxylic acids with molecular oxygen, see: P. J. Figiel, J. M. Sobczak
and J. J. Ziolkowski, Chem. Commun., 2004, 244; K. Ebitani, H.-B.
Ji, T. Mizugaki and K. Kaneda, J. Mol. Catal. A: Chem., 2004, 212,
161; X. Baucherel, L. Gonsalvi and I. W. C. E. Arends, Adv. Synth.
Catal., 2004, 346, 286; S. Ellwood, R. A. Sheldon, Y. Matsumura, Y.
Yamamoto, N. Moriyama, S. Furukubo, F. Iwasaki and O. Onomura,
Tetrahedron Lett., 2003, 45, 8221; Y. Uozumi and R. Nakao, Angew.
Chem., Int. Ed., 2003, 42, 194.
3 A. Itoh, S. Hashimoto, T. Kodama and Y. Masaki, Synlett, 2005,
2107; A. Itoh, S. Hashimoto and Y. Masaki, Synlett, 2005, 2639;
S. Hirashima and A. Itoh, Synthesis, 2006, 1757; K. Kuwabara
and A. Itoh, Synthesis, 2006, 1949; S. Hirashima, S. Hashimoto,
Y. Masaki and A. Itoh, Tetrahedron, 2006, 62, 7887; T. Sugai and
A. Itoh, Tetrahedron Lett., 2007, 48, 9096; S. Hirashima and A.
Itoh, Photochem. Photobiol. Sci., 2007, 6, 521; T. Sugai and A. Itoh,
Tetrahedron Lett., 2007, 48, 2931; S. Hirashima and A. Itoh, Green
Chem., 2007, 9, 318; S. Hirashima and A. Itoh, J. Synth. Org. Chem.
Jpn., 2008, 66, 748; N. Tada and A. Itoh, Kokagaku, 2009, 40, 148.
4 P. T. Anastas, J. C. Warner, Green Chemistry, Theory and Practice,
Oxford University Press, 1998.
5 The yield of the product decreases when going down in AQN
concentration. In our examination, 8 mol% of the catalyst was found
to produce the product in high yield constantly.
6 See Tables S1–S4 in the ESI†.
7 See Table S5 in the ESI†.
8 S. Hirashima, T. Nobuta, N. Tada, T. Miura and A. Itoh, Org. Lett.,
2010, 12, 3645.
9 See Fig. 1–3 in the ESI†.
10 We also detected the formation of molecular oxygen when the
reaction mixture made contact with catalase. See the ESI† regarding
the measurement of peroxide by iodometry.
11 2-Chloroanthraquinone absorbs light with wavelengths shorter than
450 nm, and the fluorescent lamp radiates visible light with wave-
lengths longer than 400 nm. Thus, 2-chloroanthraquinone absorbs
light between 400 and 450 nm.
12 The aldehyde 7 is also thought to be formed through Russell
termination path from peroxyradical 5. Russell termination leads to
a mixture of aldehyde and alcohol. And the alcohol will be oxidized
in the system rapidly.
13 We have never examined the stability of organo photocatalyst. There
is a possibility that peroxide adducts of AQN exist in solution since
we detected the compound derived from AQN by NMR; however,
we could not determine the detailed structure.
14 Acetone and acetonitrile easily form the solvent-HOOH adducts, and
produce benzoylperoxide; however, we do not think this is applicable
to our protocol with EtOAc as solvent.
Scheme 1 Plausible path.
In conclusion, we report a useful method for a facile syn-
thesis of carboxylic acids from methyl group in the aromatic
nucleus by aerobic photooxidation using VIS irradiation and
easily handled 2-chloroanthraquinone as an organic catalyst
under mild conditions such as an air atmosphere and ambient
pressure and temperature. This is a more environmentally benign
oxidation than previous methods, which require drastic reaction
conditions, e.g., large amounts of heavy metals, high pressure,
This journal is
The Royal Society of Chemistry 2011
Green Chem., 2011, 13, 1669–1671 | 1671
©