Facile aerobic photooxidation of alcohols using 2-chloroanthraquinone under visible light irradiation

Article abstract of DOI:10.1055/s-0033-1338420

A facile photooxidation of alcohols to obtain carboxylic acids and ketones using easily handled 2-chloroanthraquinone as an organocatalyst under visible light irradiation in an air atmosphere is reported. The reaction conditions are mild, such as an air atmosphere and ambient pressure and temperature. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1338420

2684▌
SPECIAL TOPIC
special topic
Facile Aerobic Photooxidation of Alcohols Using 2-Chloroanthraquinone
under Visible Light Irradiation
Aerobic Photooxidation
Yoshiko Shimada, Kasumi Hattori, Norihiro Tada, Tsuyoshi Miura, Akichika Itoh*
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan
Fax +81(58)2308108; E-mail: itoha@gifu-pu.ac.jp
Received: 08.03.2013; Accepted after revision: 20.03.2013
alytic amount of potassium carbonate under visible light
Abstract: A facile photooxidation of alcohols to obtain carboxylic
irradiation in an air atmosphere. Use of 2-chloroanthra-
acids and ketones using easily handled 2-chloroanthraquinone as an
quinone (2-Cl-AQN) in EtOAc (Table 1, entry 5) afforded
organocatalyst under visible light irradiation in an air atmosphere is
good yield of benzoic acid (2a). Note that in the absence
of potassium carbonate, the yield of benzoic acid (2a) de-
creased and perbenzoic acid (3a) was obtained as a major
product (entry 11).
reported. The reaction conditions are mild, such as an air atmo-
sphere and ambient pressure and temperature.
Key words: alcohols, carboxylic acids, 2-chloroanthraquinone,
photooxidation, visible light
air, fluorescent lamp (VIS)
O
2-Cl-AQN (cat.)
Oxidation of alcohols to carboxylic acids is an important
transformation in organic synthesis because carboxylic
acids have always attracted considerable interest as versa-
tile compounds or intermediates. Thus, many methods
and reagents have been reported until now; however,
these reactions basically involve the use of large quanti-
ties of heavy metals and complex organic compounds,
generate large amount of waste, and are not environmen-
tally benign.1 Moreover, recently, many researchers have
reported catalytic oxidation processes with molecular ox-
ygen.2 Molecular oxygen has received much attention as
an ultimate oxidant because it is photosynthesized by
plants, produces little waste, is inexpensive, and has larger
atom efficiency than other oxidants. However, the meth-
ods require drastic reaction conditions such as the use of
heavy metals, high pressure, or high temperature. On the
basis of this background, we have studied catalytic photo-
oxidation with molecular oxygen as a terminal oxidant.3
Recently, we reported that methyl groups in an aromatic
nucleus were oxidized directly to the corresponding car-
boxylic acids in the presence of 2-chloroanthraquinone as
an organocatalyst in an air atmosphere under visible light
irradiation.4 In the course of our further study of this pho-
tooxidation, we found that alcohols could also be directly
oxidized to the corresponding carboxylic acids. This oxi-
dation reaction is appealing in terms of green chemistry5
because it does not use heavy metals, reduces waste, and
uses inexpensive organocatalysts, and molecular oxygen
in air. Here we report our detailed study of oxidation from
alcohols to the corresponding carboxylic acids under vis-
ible light irradiation in the presence of a catalytic photo-
sensitizer in an air atmosphere (Scheme 1).
R
OH
R
OH
Scheme 1 Aerobic photooxidation of alcohols
Table 1 Study of Reaction Conditions
air, fluorescent lamp (VIS)
catalyst (0.1 equiv)
CO2H
CO3H
K2CO3 (0.05 equiv)
OH
+
solvent (1 mL), 15 h
1a (0.3 mmol)
2a
3a
Entry
Catalyst
Solvent
Yield (%)a
2a
3a
1
2
AQN
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
acetone
MeCN
MeOH
benzene
hexane
EtOAc
69
74
74
19
89
80
30
0
0
0
2-Me-AQN
2-t-Bu-AQN
AQN-2-CO2H
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
2-Cl-AQN
3
trace
0
4
5
0
6
0
7
0
8
0
9
56
0
21
0
10
11b
33
57
a Yields were determined by 1H NMR spectroscopy.
b The reaction was carried out without K2CO3.
To optimize the reaction conditions, benzyl alcohol (1a)
was used as a test substrate (Table 1). Various photosen-
sitizers and solvents were examined in the presence of cat-
To increase the yield of benzoic acid (2a), a detailed study
was conducted on additives (Table 2). The result revealed
that the addition of a catalytic amount of K2CO3 or trifluo-
roacetic acid and water was effective for the conversion of
perbenzoic acid to benzoic acid. Benzoic acid (2a) was
obtained in high yields using 0.05 equivalents of K2CO3
SYNTHESIS 2013, 45, 2684–2688
Advanced online publication: 16.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338420; Art ID: SS2013-C0164-ST
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Aerobic Photooxidation
2685
tron-donating group in aromatic nucleus gave the corre-
sponding carboxylic acids 2a–e in good yields in an air
atmosphere and using visible light irradiation from fluo-
rescent lamps in the presence of K2CO3 (Method A) or
TFA–H2O (Method B); however, the substrate with a
strong electron-withdrawing group gave only a trace of
the carboxylic acid 2f. An aliphatic alcohol was also ex-
amined, which gave the corresponding carboxylic acid 2g
in low yield. Furthermore, secondary alcohols reacted ef-
ficiently to give the corresponding aromatic and aliphatic
ketones in good to high yields under similar conditions in
the absence of additives (Scheme 3).
Table 2 Study of Additives
air, fluorescent lamp (VIS)
CO2H
CO3H
2-Cl-AQN, additive
OH
+
EtOAc (1 mL)
1a (0.3 mmol)
2a
3a
Entry 2-Cl-AQN Additive
Time Yield
(h)
(equiv)
(equiv)
(%)a
2a
3a
1
2
3
4
0.1
K2CO3 (0.05)
K2CO3 (0.05)
K2CO3 (0.01)
K2CO3 (0.05)
K2CO3 (0.05)
K2CO3 (0.05)
15
12
12
15
24
12
89
92
88
98
89
73
91
100
77
38
78
0
0.08
0.08
0.08
0
5
air, fluorecent lamp (VIS)
OH
R2
O
0
2-Cl-AQN (0.08 equiv)
R1
EtOAc (1 mL)
R1
R2
5b 0.08
0
1 (0.3 mmol)
2
6
7
0.05
0.1
0
O
O
O
O
TFA (0.4)–H2O (100 μL) 24
TFA (0.4)–H2O (100 μL) 24
TFA (0.3)–H2O (100 μL) 24
TFA (0.4)–H2O (100 μL) 24
TFA (0.4)–H2O (100 μL) 24
0
8
0.08
0.08
0.08
0.05
0
9
2h: 76% (10 h) 2ia: 78% (12 h) 2jb: 93% (15 h) 2ka: 83% (20 h)
9
13
22
15
Scheme 3 Scope and limitations of secondary alcohols. Reagents
10
11
a
b
and conditions: AQN-2-CO2H (0.08 equiv) was used. AQN-2-
CO2H (0.1 equiv) was used. Isolated yields are shown. For 2k, the
yield was determined by 1H NMR spectroscopy.
a Yields were determined by 1H NMR spectroscopy.
b The reaction was carried out under a 5% concentration of O2.
To clarify the reaction mechanism, the time course of aer-
obic photooxidation of the alcohol was studied in the pres-
ence of K2CO3 (Scheme 4) and TFA–H2O (Scheme 5)
with 1a as a test substrate. It was revealed that benzalde-
hyde (4a) was detected by 1H NMR in both cases, and that
it serves as an intermediate. Furthermore, in the presence
of TFA–H2O, perbenzoic acid (3a) was also detected. On
the contrary, no perbenzoic acid (3a) was detected in the
presence of K2CO3, which suggests that perbenzoic acid
(3a) can be more easily converted to benzoic acid in the
presence of K2CO3 than TFA–H2O.
or 0.4 equivalents of TFA and 100 μL of H2O (Table 2, en-
tries 4 and 8). Surprisingly, this oxidation proceeds
smoothly even under a 5% oxygen concentration, which is
one-fourth the concentration in air, and shows much safer
progress than the conventional methods (entry 5).
Scheme 2 shows the scope and limitations of this reaction
with primary alcohols under the optimized conditions.
Both substrates with an electron-withdrawing and elec-
The reaction mechanism shown in Scheme 6 is proposed
to explain the results. Excited anthraquinone, which ab-
sorbs light,6 abstracts the hydrogen radical at the benzylic
position of 1 to produce benzyl radical 5, which traps mo-
lecular oxygen. Aldehyde 4 is formed through peroxy rad-
ical 6 and hydroperoxide 7. Hydrate 8, which is formed by
the addition of water to 4, is transformed to benzyl radical
9 through the abstraction of the hydrogen radical by excit-
ed anthraquinone. Moreover, hydroperoxide 11 is pro-
duced through peroxy radical 10. Then, carboxylic acid 2
is produced through per acid 3 in the presence of a catalyt-
ic amount of K2CO3 or TFA–H2O.
air, fluorescent lamp (VIS)
2-Cl-AQN (0.08 equiv)
O
additive
R
OH
R
OH
EtOAc (1 mL)
CO2H
1 (0.3 mmol)
2
CO2H
CO2H
CO2H
t-Bu
MeO
Cl
2a
2b
2c
2d
A: 96% (15 h) A: 87% (12 h)
B: 99% (24 h) B: 90% (24 h)
A: 82% (18 h)
B: 87% (24 h)
A: 91% (15 h)
B: 85% (24 h)
CO2H
CO2H
In conclusion, we have reported a useful method for a fac-
ile synthesis of carboxylic acids from alcohols by aerobic
photooxidation using visible light irradiation and easily
handled 2-chloroanthraquinone as an organocatalyst un-
der mild conditions such as an air atmosphere and ambient
pressure and temperature.
CO2H
10
O2N
Br
2e
2f
A: trace
B: trace
2g
A: 87% (15 h)
B: 83% (24 h)
A: 36% (12 h)
B: 32% (36 h)
Scheme 2 Scope and limitations of aerobic photooxidation. Re-
agents and conditions: Method A: K2CO3 (0.05 equiv); Method B:
TFA (0.4 equiv), H2O (100 μL). Isolated yields are shown.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2684–2688

2686
Y. Shimada et al.
SPECIAL TOPIC
air, fluorescent lamp (VIS)
2-Cl-AQN (0.08 equiv)
K2CO3 (0.05 equiv)
R
OH
EtOAc (1 mL)
1a (0.3 mmol)
2a: R = CO2H
3a: R = CO3H
4a: R = CHO
Time (h)
Scheme 4 Time course of aerobic photooxidaiton with K2CO3
air, fluorescent lamp (VIS)
2-Cl-AQN (0.08 equiv)
TFA (0.4 equiv), H2O (100 mL)
R
OH
EtOAc (1 mL)
1a (0.3 mmol)
2a: R = CO2H
3a: R = CO3H
4a: R = CHO
Time (h)
Scheme 5 Time course of aerobic photooxidaiton with TFA
All anhyd solvents were obtained from Kanto Kagaku Co., Ltd.
Other chemicals used were of reagent grade and were obtained from
Aldrich Chemical Co., Tokyo Kasei Kogyo Co., Ltd., and Wako
Pure Chemical Industries, Ltd. 1H NMR and 13C NMR spectra were
recorded on a JEOL AL 400 spectrometer (400 MHz for 1H NMR
and 100 MHz for 13C NMR) or JEOL ECA-500 spectrometer (500
MHz for 1H NMR and 125 MHz for 13C NMR). The Chemical shifts
(δ) are reported in parts per million (ppm) downfield from internal
Me4Si. Mass spectra (MS) were recorded on a JEOL JMS-SX102A
instrument. Preparative TLC was carried out on precoated plates of
silica gel (MERCK, silica gel F-254).
Aerobic Photooxidation; Benzoic Acid (2a); Typical Procedure
for Method A
A solution of benzyl alcohol (1a; 32 mg, 0.3 mmol), 2-Cl-AQN (5.8
mg, 0.024 mmol), and K2CO3 (2.1 mg, 0.015 mmol, 0.05 equiv) in
anhyd EtOAc (1 mL) in a Pyrex test tube under an air atmosphere
was stirred and irradiated externally with four 22 W fluorescent
lamps for 15 h. The reaction mixture was extracted with 10% aq
NaHCO3 (30 mL), acidified with aq 2 N HCl, and extracted with
Et2O (3 × 20 mL). Evaporation of the solvent from the combined or-
ganic layers provided benzoic acid (2a) as a colorless solid; yield:
35.3 mg (96%); Method B, 36.1 mg (99%); colorless solid; mp 121–
123 °C. CAS Registry Number: 65-85-0.
Synthesis 2013, 45, 2684–2688
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Aerobic Photooxidation
2687
OO•
OH
AQN*
AQH• AQN
AQH•
•
O2
OH
OH
1
5
4
6
8
OOH
O
OH
OH
AQH•
AQN*
H2O
OH
H
H2O2
7
9
OH
HO
OO•
HO
OOH
OH
AQH• AQN
•
O2
OH
OH
H2O
10
11
O
O
H2O H2O2
acid or base
OH
OOH
2
3
Scheme 6 Plausible path for the aerobic photooxidation
1H NMR (500 MHz, CDCl3): δ = 8.13 (d, J = 7.4 Hz, 2 H), 7.62 (t,
J = 7.4 Hz, 1 H), 7.48 (t, J = 7.4 Hz, 2 H).
p-Bromobenzoic Acid (2e)
CAS Registry Number: 586-76-5
13C NMR (125 MHz, acetone-d6): δ = 172.6, 133.9, 130.3, 129.4,
128.6.
Yield: Method A, 51.9 mg (87%); Method B, 50.1 mg (83%); col-
orless solid; mp 250–252 °C.
1H NMR (500 MHz, acetone-d6): δ = 7.93 (d, J = 8.6 Hz, 2 H), 7.67
(d, J = 8.6 Hz, 2 H).
13C NMR (100 MHz, acetone-d6): δ = 166.9, 132.6, 132.3, 130.7,
MS: m/z = 122 (M+), 105, 77.
The synthesized compounds 2a–e have been reported in the litera-
ture and were characterized by comparing the corresponding spec-
troscopic data.4 The products 2f–k were identified by comparison of
their analytical data with those of authentic samples.
128.1.
MS: m/z = 200 (M+), 183, 155.
1-Dodecanoic Acid (2g)
4-tert-Butylbenzoic Acid (2b)
CAS Registry Number: 98-73-7
CAS Registry Number: 143-07-7
Yield: Method A, 46.4 mg (87%); Method B, 48.2 mg (90%); col-
orless solid; mp 163–164 °C.
1H NMR (500 MHz, CDCl3): δ = 8.06 (d, J = 8.7 Hz, 2 H), 7.49 (d,
J = 8.7 Hz, 2 H), 1.35 (s, 9 H).
13C NMR (125 MHz, CDCl3): δ = 172.6, 157.7, 130.2, 126.7, 125.6,
35.3, 31.2.
Yield: Method A, 21.4 mg (36%); Method B, 19.5 mg (32%); col-
orless solid; mp 43–44 °C.
1H NMR (500 MHz, CDCl3): δ = 2.35 (t, J = 7.4 Hz, 2 H), 1.66–1.60
(m, 2 H), 1.35–1.26 (m, 16 H), 0.88 (t, J = 6.9 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 180.2, 34.2, 32.0, 29.7, 29.5, 29.4,
29.3, 29.1, 24.8, 22.8, 14.2.
MS: m/z = 178 (M+), 163, 135, 91.
MS: m/z = 200 (M+), 129, 73.
p-Methoxybenzoic Acid (2c)
CAS Registry Number: 100-09-4
Acetophenone (2h)
CAS Registry Number: 98-86-2
Yield: Method A, 37.6 mg (82%); Method B, 39.7 mg (87%); col-
orless solid; mp 181–183 °C.
1H NMR (400 MHz, acetone-d6): δ = 7.96 (d, J = 9.2 Hz, 2 H), 7.0
(d, J = 9.2 Hz, 2 H), 3.85 (s, 3 H).
13C NMR (100 MHz, acetone-d6): δ = 167.5, 164.4, 132.5, 123.7,
114.5, 55.8.
Yield: 27.5 mg (76%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.57 (t,
J = 8.0 Hz, 1 H), 7.47 (t, J = 8.0 Hz, 2 H), 2.61 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 198.3, 137.2, 133.2, 128.7, 128.4,
26.7.
MS: m/z = 120 (M+), 105, 77.
MS: m/z = 152 (M+), 135, 107.
Indanone (2i)
p-Chlorobenzoic Acid (2d)
CAS Registry Number: 83-33-0
CAS Registry Number: 74-11-3
Yield: 31.0 mg (78%); colorless solid; mp 38–40 °C.
Yield: Method A, 42.6 mg (91%); Method B, 39.7 mg (85%); col-
orless solid; mp 236–237 °C.
1H NMR (500 MHz, acetone-d6): δ = 8.01 (d, J = 8.6 Hz, 2 H), 7.53
(d, J = 8.6 Hz, 2 H).
13C NMR (100 MHz, acetone-d6): δ = 166.7, 139.5, 132.1, 130.3,
129.5.
1H NMR (500 MHz, CDCl3): δ = 7.77 (d, J = 8.1 Hz, 1 H), 7.61–
7.57 (m, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.39–7.36 (m, 1 H), 3.16–
3.14 (m, 2 H), 2.71–2.68 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 207.2, 155.3, 137.2, 134.7, 127.4,
126.8, 123.8, 36.3, 25.9.
MS: m/z = 132 (M+), 104, 78.
MS: m/z = 156 (M+), 139, 111.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2684–2688

2688
Y. Shimada et al.
SPECIAL TOPIC
(2) For recent examples of oxidation of alcohols to the
Benzophenone (2j)
CAS Registry Number: 119-61-9
corresponding carboxylic acids with molecular oxygen, see:
(a) Figiel, P. J.; Sobczak, J. M.; Ziólkowski, J. J. Chem.
Commun. 2004, 244. (b) Ebitani, K.; Ji, H.-B.; Mizugaki, T.;
Kaneda, K. J. Mol. Catal. A: Chem. 2004, 212, 161.
(c) Baucherel, X.; Gonsalvi, L.; Arends, I. W. C. E.;
Ellwood, S.; Sheldon, R. A. Adv. Synth. Catal. 2004, 346,
286. (d) Matsumura, Y.; Yamamoto, Y.; Moriyama, N.;
Furukubo, S.; Iwasaki, F.; Onomura, O. Tetrahedron Lett.
2003, 45, 8221. (e) Uozumi, Y.; Nakao, R. Angew. Chem.
Int. Ed. 2003, 42, 194.
Yield: 50.7 mg (93%); colorless solid; mp 46–48 °C.
1H NMR (500 MHz, CDCl3): δ = 7.79 (d, J = 8.0 Hz, 4 H), 7.58 (t,
J = 8.0 Hz, 2 H), 7.47 (t, J = 8.0 Hz, 4 H).
13C NMR (125 MHz, CDCl3): δ = 196.9, 137.7, 132.5, 130.2, 128.4.
MS: m/z = 182 (M+), 105, 77.
Dodecane-2-one (2k)
CAS Registry Number: 6175-49-1
(3) (a) Itoh, A.; Hashimoto, S.; Kodama, T.; Masaki, Y. Synlett
2005, 2107. (b) Itoh, A.; Hashimoto, S.; Masaki, Y. Synlett
2005, 2639. (c) Hirashima, S.; Itoh, A. Synthesis 2006, 1757.
(d) Kuwabara, K.; Itoh, A. Synthesis 2006, 1949.
Yield: 83% (by 1H NMR); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 2.42 (t, J = 7.4 Hz, 2 H), 2.13 (s,
3 H), 1.58–1.55 (m, 2 H), 1.31–1.26 (m, 14 H), 0.88 (t, J = 6.9 Hz,
3 H).
13C NMR (125 MHz, CDCl3): δ = 209.5, 43.9, 32.0, 29.9, 29.6, 29.5,
29.5, 29.4, 29.3, 23.9, 22.8, 14.2.
(e) Hirashima, S.; Hashimoto, S.; Masaki, Y.; Itoh, A.
Tetrahedron 2006, 62, 7887. (f) Sugai, T.; Itoh, A.
Tetrahedron Lett. 2007, 48, 9096. (g) Hirashima, S.; Itoh, A.
Photochem. Photobiol. Sci. 2007, 6, 521. (h) Sugai, T.; Itoh,
A. Tetrahedron Lett. 2007, 48, 2931. (i) Hirashima, S.; Itoh,
A. Green Chem. 2007, 9, 318.
MS: m/z = 184 (M+), 126, 71, 58.
(4) Tada, N.; Hattori, K.; Nobuta, T.; Miura, T.; Itoh, A. Green
Chem. 2011, 13, 1669.
Acknowledgment
This work was supported by Grant-in-Aid for Young Scientists
(B)(No. 24790015) from the Japan Society for the Promotion of
Science (JSPS).
(5) Anastas, P. T.; Warner, J. C. Green Chemistry, Theory and
Practice; Oxford University Press: Oxford, 1998.
(6) 2-Chloroanthraquinone absorbs light with wavelengths
shorter than 450 nm, and the fluorescent lamp radiates
visible light with wavelengths longer than 400 nm. Thus, 2-
chloroanthraquinone absorbs light between 400 and 450 nm.
References
(1) Larock, R. C. Comprehensive Organic Transformations,
2nd ed.; Wiley-VCH: Weinheim, 1999.
Synthesis 2013, 45, 2684–2688
© Georg Thieme Verlag Stuttgart · New York