Aerobic photooxidative cleavage of 1,3-diketones to carboxylic acids using 2-chloroanthraquinone

Article abstract of DOI:10.1016/j.tetlet.2013.09.015

We developed direct aerobic photooxidation of 1,3-diketones to corresponding carboxylic acids in the presence of a catalytic amount of 2-chloroanthraquinone under visible light irradiation from fluorescent lamps.

Full text of DOI:10.1016/j.tetlet.2013.09.015

Tetrahedron Letters 54 (2013) 6218–6221
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Tetrahedron Letters
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Aerobic photooxidative cleavage of 1,3-diketones to carboxylic acids
using 2-chloroanthraquinone
Yuma Tachikawa a, Lei Cui a, Yoko Matsusaki a, Norihiro Tada a, Tsuyoshi Miura b, Akichika Itoh a,
⇑
a Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
b Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2013
Revised 29 August 2013
Accepted 4 September 2013
Available online 10 September 2013
We developed direct aerobic photooxidation of 1,3-diketones to corresponding carboxylic acids in the
presence of a catalytic amount of 2-chloroanthraquinone under visible light irradiation from fluorescent
lamps.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Aerobic
Carboxylic acid
2-Chloroanthraquinone
1,3-Diketone
Photooxidation
Carboxylic acids and their derivatives are widely used as indus-
trial sources of various organic substances, such as liquid crystal
polymers, cosmetics, pharmaceuticals, agrochemicals, and food
additives. Thus, many useful methods have been developed for
the preparation of carboxylic acids, such as (i) oxidation of alkyl
benzenes, primary alcohols, and aldehydes; (ii) reaction of organo-
metallic reagents with carbon dioxide; (iii) oxidative cleavage of
alkenes, alkynes, and vicinal diols; and (iv) haloform-type reac-
tions.1 The oxidative conversion of 1,3-diketones, which are easily
prepared via Claisen condensation, to carboxylic acids is a supple-
mentary reaction for the preparation of carboxylic acids. There are
several reports on the synthesis of carboxylic acids from 1,3-dike-
tones;2 however, these methods require large quantities of
reagents, such as CAN,2c oxone,2d PIDA,2h and SnCl4;2i heavy metal
Considering this, we have developed an aerobic photooxidative
reaction using visible light irradiation and organophotocatalysts;4
thus, we examined metal- and halogen-free aerobic photooxidative
conditions for the cleavage of 1,3-diketone and successfully found
that using a catalytic amount of 2-chloroanthraquinone (2-Cl-
AQN) in the presence of cesium carbonate (Cs2CO3) allowed us to
perform the direct oxidative conversion of 1,3-diketone to carbox-
ylic acids under visible light irradiation from a general-purpose
fluorescent lamp (Scheme 1). Herein, we describe details of this
reaction.
Table 1 shows the results of our study of aerobic oxidation con-
ducted with 1-phenyl-1,3-butanedione (1a). Reactions were per-
formed in a Pyrex glass test tube fitted with an O2 balloon under
photoirradiation with four 22 W fluorescent lamps. Among the cat-
alysts and solvents examined, 2-Cl-AQN and acetone were found to
be the most efficient for the reaction, albeit in low yields (entries
1–11). Next, we investigated the effect of the additives (entries
12–16) and found that Cs2CO3 promoted the reaction most effi-
ciently (entry 16). It is noted that Na2CO3 and CaCO3 have little ef-
fect probably because of their low solubility (entries 12 and 13).
The fact that benzoic acid (2a) was not obtained or was obtained
only in low yield without 2-Cl-AQN, photoirradiation, or molecular
2b
catalysts, such as In(OTf)3 and CH3ReO3;2f high-temperature
aqueous solutions;2a and electrochemically oxidative conditions.2e,g
Recently, we have reported an oxidative cleavage of 1,3-diketones
to carboxylic acids by aerobic photooxidation using catalytic
amounts of iodine under light irradiation with a 400 W high-pres-
sure mercury lamp.3 Although this reaction is a metal-free reaction
of 1,3-diketone to carboxylic acids and uses molecular oxygen as the
terminal oxidant, which is inexpensive and highly atom efficient, it
requires a halogen source and a high-pressure mercury lamp. Thus,
a more environmentally benign protocol for the conversion of 1,3-
diketones to carboxylic acids is highly desirable.
O2, h
ν (VIS)
O
O
O
O
cat. 2-Cl-AQN, Cs2CO3
R1
R2
R1
OH HO
R2
⇑
Corresponding author.
E-mail address: itoha@gifu-pu.ac.jp (A. Itoh).
Scheme 1. Aerobic oxidative cleavage of 1,3-diketones to carboxylic acids.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.015

Y. Tachikawa et al. / Tetrahedron Letters 54 (2013) 6218–6221
6219
Table 1
Table 2
Study of reaction conditionsa
Scope and limitationsa
O2, hν (VIS)
O2, hν (VIS)
2-Cl-AQN (0.1 equiv)
Cs2CO3 (0.5 equiv)
O
O
O
catalyst (equiv)
additive (equiv)
OH
substrate
product
2
solvent, 20 h
acetone
1
1a
2a
Entry Substrate
Time
(h)
Product
Yieldb
(%)
Entry
Catalyst (equiv)
Additive (equiv)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Methylene blue (0.1)
9,10-DCA (0.1)
Benzophenone (0.1)
2-tBu-AQN (0.1)
AQN (0.1)
—
—
—
—
—
—
—
—
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
CH2Cl2
AcOEt
MeCN
Hexane
i-PrOH
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Trace
0
0
O
O
O
OH
1
20
20
20
72
89
72
12
12
22
20
19
17
15
15
14
19
41
67
74
57
63
57
67
0
1a
2a
O
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
2-Cl-AQN (0.05)
2-Cl-AQN (0.15)
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
—
O
O
OH
2
9
—
—
—
Cl
Cl
1b
O
2b
10
11
12
13
14
15
16
17
18
19
20
21
22c
23d
O
O
Cs2CO3 (0.5)
Na2CO3 (0.5)
NaOH (0.5)
Ca(OH)2 (0.5)
Cs2CO3 (0.5)
Cs2CO3 (0.5)
Cs2CO3 (0.5)
Cs2CO3 (0.25)
Cs2CO3 (0.75)
Cs2CO3 (0.5)
Cs2CO3 (0.5)
Cs2CQ3 (0.5)
OH
3
Me
Me
MeO
1c
O
2c
O
O
OH
2d
4
20
20
20
77
72
70
MeO
1d
O
O
O
OH
2e
5
2-Cl-AQN (0.1)
2-Cl-AQN (0.1)
0
6
1e
O
O
O
a
A
solution of 1-phenyl-1,3-butanedione (1a, 0.3 mmol),
a
catalyst, and an
OH
6
additive in a dry solvent (5 mL) purged with an O2 balloon was stirred and irradi-
ated externally with four 22 W fluorescent lamp for 20 h.
S
1f
O
S
2f
Yields were determined by 1H NMR spectroscopy with an internal standard
b
O
O
O
(1,1,2,2-tetrachloroethane).
c
The reaction was carried out in the dark.
The reaction was carried out under argon.
OH
70c
d
7
48
1g
2a
O
O
OEt
OH
8
48
20
20
49
28
24
1h
2a
oxygen shows the necessity of these ingredients for this reaction
(entries 21–23).
O
O
O
O
Table 2 shows the scope and limitations of this reaction with
various 1,3-diketones under the optimal reaction conditions.5
When benzoylacetones were used as substrates, the corresponding
carboxylic acids were obtained in good-to-high yields, regardless
of the presence of an electron-donating or electron-withdrawing
group on the benzene ring (entries 1–4). Furthermore, 2-naphthoic
acid (2e) and 3-thiophenecarboxylic acid (2f) were obtained from
1e and 1f in good yields (entries 5 and 6). Dibenzoylmethane
(1g) was also oxidized to 2a in good yield (entry 7). Furthermore,
1,3-oxoester (1h) was converted to 2a in moderate yield (entry
8). In addition, 1,3-cyclohexanedione (1i) and 2-hydroxyacetophe-
none (1j) were oxidized to corresponding carboxylic acids (2i and
2a) albeit in low yields, respectively (entries 9 and 10). Under these
conditions, acetophenone (1k) functioned as a poor substrate (en-
try 11).
9
HO
OH
2i
1i
O
O
O
OH
OH
10
2a
1j
O
11
20
0
Me
OH
1k
2a
a
A
solution of substrate (1, 0.3 mmol), 2-Cl-AQN (0.1 equiv), and Cs2CO3
(0.5 equiv) in dry acetone (5 mL) purged with an O2 balloon was stirred and irra-
diated externally with four 22 W fluorescent lamp.
b
Isolated yields.
0.42 mmol of 2a was obtained.
c
To clarify the reaction mechanism, we studied the time course
of the aerobic photooxidative cleavage of 1,3-diketone (1g) under
optimized reaction conditions (Fig. 1), and 1,2,3-triketone (3g)
(including its monohydrate 3g0) and 1,2-diketone (4g) were de-
tected by 1H NMR. Thus, 3g and 4g were used as substrates under
various conditions. When 3g was used as a substrate under the
optimal conditions, 2a was obtained in good yield (Table 3, entry
1). Although the reaction proceeded in the absence of 2-Cl-AQN,
no reaction proceeded in the absence of Cs2CO3, suggesting that
Cs2CO3 is essential for this step (entries 2 and 3). Furthermore, in
the absence of light irradiation, the yield of 2a was low (entry
5).6 Although 4g followed the same tendency, 2a was obtained in
modest yield in the absence of Cs2CO3 (Table 4, entries 3 and 4).
Scheme 2 shows a plausible path for this reaction, which is pos-
tulated by considering the requirement of continuous irradiation, a
catalytic amount of anthraquinone, molecular oxygen, base, and
the time course study of the oxidative cleavage of 1g. The
compound 1,3-diketone 1 was initially oxidized to triketone 3 by
an excited anthraquinone in the presence of molecular oxygen.7
Next, in the presence of a base, a hydrate of triketone 3 (30) was
formed, and 30 was converted to 1,2-diketone 4 through benzilic

6220
Y. Tachikawa et al. / Tetrahedron Letters 54 (2013) 6218–6221
O
O
Table 4
Study of reaction intermediatea
O
3g
O
O
conditions
O2, hν (VIS)
O
O
O
OH
2-Cl-AQN (0.1 equiv)
Cs2CO3 (0.5 equiv)
acetone, 48 h
O
2a
4g
acetone
O
Entry
Conditions
Yieldb (%)
1g
4g
O
2a
4g
OH
1
2
3
4
5
O2, hv (VIS), 2-Cl-AQN, Cs2CO3
O2, hv (VIS), Cs2CO3
O2, hv (VIS), 2-Cl-AQN
O2, hv (VIS)
87
70
29
44
0
0
Trace
20
19
2a
O2, dark, 2-Cl-AQN, Cs2CO3
2
a
A solution of diphenylethanedione (4g, 0.3 mmol), 2-Cl-AQN (0.1 equiv), and
Cs2CO3 (0.5 equiv) in dry acetone (5 mL) purged with an O2 balloon was stirred and
irradiated externally with four 22 W fluorescent lamp for 48 h.
b
Yields were determined by 1H NMR spectroscopy with an internal standard
(1,1,2,2-tetrachloroethane).
h
ν
AQN
1)
2)
AQN*
AQH
O
O
AQN*
O
O
O
O
O2
Figure 1. Time course of aerobic photooxidative cleavage of 1,3-diketone.
R
R
R
R
R
R
OO
1
5
6
Table 3
Study of reaction intermediatea
O
R
O
R
O
O
AQH
AQN
H2O
R
R
base
O
O
O
OOH
O
H2O
R
3
conditions
7
OH
HO
OH
acetone, 48 h
O
AQH
O
O
AQN*
O
3g'
Conditions
2a
base
O
R
R
Entry
Yieldb (%)
R
R
R
HO COOH
HO
OH
HO COO
8
3'
9
2a
3g00
1
2
3
4
5
O2, hv (VIS), 2-Cl-AQN, Cs2CO3
O2, hv (VIS), Cs2CO3
O2, hv (VIS), 2-Cl-AQN
O2, hv (VIS)
79
67
0
0
11
0
2
93
93
42
O
O2
R
R
R
R
+H
HO
OOH
OH
H2O2
CO2
O2, dark, 2-Cl-AQN, Cs2CQ3
10
11
a
A solution of 2,2-dihydroxy-1,3-diphenyl-1,3-propanedione (3g0, 0.3 mmol), 2-
hν
O2
O
O
+
O
Cl-AQN (0.1 equiv), and Cs2CO3 (0.5 equiv) in dry acetone (5 mL) purged with an O2
balloon was stirred and irradiated externally with four 22 W fluorescent lamp for
48 h.
R
O
R
R
R
OO
13
12
b
Yields were determined by 1H NMR spectroscopy with an internal standard
4
(1,1,2,2-tetrachloroethane).
O
R
OH
acid rearrangement,8 decarboxylation, and oxidation.9 Finally, 1,2-
diketone 4 was converted to carboxylic acid 2 via acyl radical 12
and acylperoxy radical 13.10
2
Scheme 2. Plausible reaction meachanism.
In conclusion, we have found a useful method for the direct aer-
obic photooxidation of 1,3-diketones to form the corresponding
carboxylic acid in the presence of a catalytic amount of 2-Cl-AQN
and Cs2CO3 under visible light irradiation from fluorescent lamps.
This reaction is interesting from the viewpoint of green chemistry
because of the absence of heavy metals and halogens, waste reduc-
tion, and the use of visible light and molecular oxygen.
References and notes
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Acknowledgments
This work was supported by Grant-in-Aid for Young Scientists
(B)(No. 24790015) from the Japan Society for the Promotion of Sci-
ence (JSPS).

Y. Tachikawa et al. / Tetrahedron Letters 54 (2013) 6218–6221
6221
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5. General procedure: A solution of 1-phenyl-1,3-butanedione (1a, 0.3 mmol), 2-
chloroanthraquinone (0.03 mmol), and Cs2CO3 (0.15 mmol) in dry acetone
(5 mL) in a Pyrex test tube, purged with an O2 balloon, was stirred and
irradiated externally with four 22 W fluorescent lamp for 20 h. The aqueous
solution was washed with EtOAc, and then acidified with 2 M aq HCl solution,
which was extracted with EtOAc. The organic layer was washed with brine and
dried over MgSO4, and concentrated in vacuo. The pure product 2a was
obtained by acid-base extraction with Et2O. All synthesized compounds (2a–
2f) have been reported in the literature3 and were characterized by comparing
the corresponding spectroscopic data.
8. Benzilic acid rearrangement of triketone to benzil, see: (a) Gurumurthy, R.;
Narasimhan, K. Ind. J. Chem. 1979, 18B, 4–5; (b) Roberts, J. D.; Smith, D. R.; Lee,
C. C. J. Am. Chem. Soc. 1951, 73, 618–625.
9. Oxidation of b-dicarbonyl compounds to
M.; Nakayama, H.; Miura, T.; Itoh, A. Synlett 2010, 1979–1983.
10. Photooxidation of -diketones to carboxylic acids, see: (a) Sawaki, Y.
a-diketones, see: Tada, N.; Shomura,
a
Tetrahedron 1985, 41, 2199–2205; (b) Sawaki, Y.; Foote, C. J. Org. Chem. 1983,
48, 4934–4940; (c) Sawaki, Y. Bull. Chem. Soc. Jpn. 1983, 56, 3464–3470; (d)
Biro, C. W. Chem. Commun. 1968, 1537.
6. Low yield of 2a was perhaps obtained via retro-Claisen reaction of 30 in the
presence of base and absence of photo-irradiation.