Facile aerobic photo-oxidation of aldehydes in the presence of catalytic lithium bromide

Article abstract of DOI:10.1248/cpb.54.1457

Aldehydes were found to be oxidized to the corresponding carboxylic acid in the presence of catalytic lithium bromide under photo-irradiation.

Full text of DOI:10.1248/cpb.54.1457

October 2006
Notes
Chem. Pharm. Bull. 54(10) 1457—1458 (2006)
1457
Facile Aerobic Photo-Oxidation of Aldehydes in the Presence of Catalytic
Lithium Bromide
Shin-ichi HIRASHIMA and Akichika ITOH*
Gifu Pharmaceutical University; Mitahora-higashi, Gifu 502–8585, Japan.
Received May 25, 2006; accepted July 18, 2006
Aldehydes were found to be oxidized to the corresponding carboxylic acid in the presence of catalytic
lithium bromide under photo-irradiation.
Key words aerobic photo-oxidation; aldehyde; carboxylic acid; catalytic lithium bromide
Oxidation reactions are the foundation of synthetic chem- effective, all of the reactions were carried out under O2-bal-
istry; however, most of the oxidants, which have been investi- loon (entry 5). Although addition of H2O did not affect the
gated so far, involve heavy metals and complex organic com- yield of 2, we exclusively used anhydrous solvents for this
pounds and go against the notion of Green Chemistry.1) On study since the solvents are purer than other grade of general
the other hand, molecular oxygen, which is photosynthesized solvents (entry 6). That no oxidation proceeded without irra-
by plants, is considered to be an infinite resource and is an diation of UV and that the decrease in chemical yield of 2
effective oxidant of larger atom efficiency than that of other without lithium bromide even after 24-h irradiation show the
oxidants, and has recently received much attention. In the necessity of both for this reaction (entries 7, 8). Furthermore,
course of our study of photo-oxidation with molecular oxy- from the fact that the target substance was not detected when
gen, we have found that a methyl group at an aromatic nu- conducting the reaction in an argon atmosphere, we can as-
cleus and alcohols were oxidized directly to the correspond- sume that the actual oxidant in this reaction is molecular
ing carboxylic acid, respectively, in the presence of catalytic oxygen (entry 9).
lithium bromide under irradiation by a high-pressure mer-
Table 2 shows the generality of this oxidation reaction
cury lamp.2,3) We further observed through experiments to using a variety of aldehydes. Aromatic aldehydes, in general,
expand application of this reaction that an oxidation reaction afford the corresponding benzoic acids in good yields (en-
also proceeds using 4-tert-butylbenzaldehyde (1) as the test tries 1—4). Aliphatic aldehydes, in general, were less reac-
substrate, affording 4-tert-butylbenzoic acid (2) (Chart 1). In tive than aromatic aldehydes, and afforded the corresponding
this letter we report in detail our investigation of the general- carboxylic acids in high to modest yield (entries 5—7) under
ity of this reaction.4—6)
the conditions of 5-h external irradiation by 400 W high-
pressure mercury lamp. Although we also carried out the re-
Results and Discussion
Table 1. Study of Reaction Conditions of Aerobic Photo-Oxidation
Table 1 shows the results of a study of reaction conditions
conducted with 1 as test substrate under the conditions of ex-
ternal irradiation by a 400 W high-pressure mercury lamp in
an oxygen atmosphere. We do not have any direct evidence;
however, we believe an effective wavelength of the light is
365 nm, which is an emission line of the strongest and
longest wave length in an ultraviolet region irradiated from a
high-pressure mercury lamp, since passing through water, a
test tube and a cooling jacket, which are made from Pyrex
glass, and air is necessary for the light to effect this reaction.
Among the alkali metal halides7) and solvents examined,
lithium bromide8) and ethyl acetate were found to afford the
corresponding carboxylic acid 2 most efficiently, and typical
alkali metal halides other than lithium bromide were found to
be little reactive for this oxidation in similar to the previous
reaction we examined.2,3) Although the best result from our
tests was obtained when using 0.4 eq of lithium bromide, the
difference in the yield when using 0.2 or 0.3 eq of lithium
bromide was hardly discernible (entries 1, 2, 4). Since bub-
bling of O2 through the reaction mixture was found to be not
Time
(h)
Yield of 2
Entry
MX
(eq)
Solvent
(%)a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
—
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiCl
NaBr
KBr
0.2
0.3
0.4
0.4
0.4
0.4
0.4
—
0.4
0.4
0.5
1.0
0.4
0.4
0.4
0.4
0.4
0.4
5
5
3
5
5
5
5
24
5
10
5
5
5
5
5
5
5
5
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
acetone
hexane
MeCN
EtOAc
EtOAc
EtOAc
88
91
72
93
94b)
92c)
0d)
54
0e)
83
89
62
59
79
57
68
60
64
a) All yields are for pure, isolated products. b) The reaction was carried out under
the bubbling of O2. c) The reaction was carried out in the presence of 1 eq of H2O.
d) The reaction was carried out in the dark. e) The reaction was carried out in an Ar
atmosphere.
Chart 1
∗ To whom correspondence should be addressed. e-mail: itoha@gifu-pu.ac.jp
© 2006 Pharmaceutical Society of Japan

1458
Vol. 54, No. 10
Table 2. Aerobic Photo-Oxidation for Various Aldehyde Substrates
tinuous aerobic photo-oxidation of the bromo anion from
lithium bromide (Eqs. 1, 2).10) Bromine, then, was formed by
aerobic photo-oxidation of hydrogen bromide, which is gen-
erated in equation 2 (Eq. 3). Radical species 15 was trans-
formed to acyl bromide 16, and the carboxylic acid was
formed by reaction with water (Eqs. 4, 5).11—15)
LiBr (0.4 eq), hn (400 W)
O2-balloon
Substrate
(50 mg)
Product
→
EtOAc (5 ml), 5 h
Entry
1
Substrate
Product (yield %)a)
Conclusion
This new form of oxidation reaction is interesting in keep-
ing with the notion of Green Chemistry due to non-use of
heavy metals, waste reduction, use of molecular oxygen, in-
expensive acquisition of reagents, and possible solvent recov-
ery.
(93)
2
3
(89)
(95)
Experimental
All of dry 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 In-
dustries, Ltd. All reactions were carried out in a Pyrex test tube equipped
with an O2-balloon, which was set up from the center of 400-W high pres-
sure mercury lamp to the distance of 37.5 mm. All of the products are
known compounds and were identified by comparison of their NMR spectra
with those of authentic samples.
Typical Procedure A solution (5 ml) of the substrate (50 mg) and LiBr
(0.4 eq) in dry ethyl acetate was stirred and irradiated at room temperature
with a 400-W high-pressure mercury lamp externally for the indicated time.
The reaction mixture was concentrated under reduced pressure, and 10%
NaOH aqueous solution was added. The aqueous solution was washed with
diethyl ether, and then acidified with 2 N HCl aqueous solution, which was
extracted with diethyl ether. The organic layer was washed with brine and
dried over Na2SO4, and concentrated under reduced pressure. The product
was pure without further purification.
4
5
6
(97)
(85)
(62)
7
(45)
References and Notes
a) All yields are for pure, isolated products.
1) “Comprehensive Organic Transformations: A Guide to Functional
Group Preparations,” ed. by Larock R. C., Wiley-VCH, New York,
1999.
2) Itoh A., Hashimoto S., Kodama T., Masaki Y., Synlett, 2005, 2107—
2109 (2005).
3) Itoh A., Hashimoto S., Masaki Y., Synlett, 2005, 2639—2640 (2005).
4) Chen H., An T., Fang Y., Yu T., Indian J. Chem. Sec. B, 38B, 805—
809 (1999).
5) Kharat A. N., Pendleton P., Badalyan A., Abedini M., Amini M. M., J.
Mol. Catal. A: Chem., 175, 277—283 (2001).
6) Partenheimer W., Grushin V. V., Adv. Synth. Catal., 343, 102—111
(2001).
7) We have examined only alkali metal halides since they are inexpen-
sive, easy to handle, and more environmentally benign than other
metal halides.
8) Among our examined, lithium bromide of at least 1.72 g (20 mmol) is
dissolved in 5 ml of ethyl acetate.
Chart 2. Possible Path of the Aerobic Photo-oxidation of Aldehyde
9) The yields of 10 and 14 were 80% and 47% respectively.
10) Minisci F., Porta O., Recupero F., Punta C., Gambarotti C., Pierini M.,
Galimberti L., Synlett, 2004, 2203—2205 (2004).
11) Hamamoto M., Nakayama K., Nishiyama Y., Ishii Y., J. Org. Chem.,
58, 6421—6425 (1993).
12) Mastrorilli P., Nobile F., Tetrahedron Lett., 35, 4193—4196 (1994).
13) Yamada T., Takai T., Rhode O., Mukaiyama T., Chem. Lett., 1991, 1—
4 (1991).
14) Yamada T., Takai T., Rhode O., Mukaiyama T., Bull. Chem. Soc. Jpn.,
64, 2109—2117 (1991).
15) Takai T., Hata E., Yamada T., Mukaiyama T., Bull. Chem. Soc. Jpn.,
64, 2513—2518 (1991).
actions with 9 and 13 under bubbling of O2, increase of the
yields of 10 and 14 could not be observed.9)
Reaction Mechanism We present in Chart 2 what we
believe is a path of this oxidation, which is postulated by
considering all the necessity of the catalytic amount of
lithium bromide, molecular oxygen and continuous photo-ir-
radiation to complete this reaction. We believe that the radi-
cal species 15 is generated by abstraction of a hydrogen radi-
cal from an aldehyde with a bromo radical, formed by con-