Photo-oxidation of aldehydes with molecular oxygen in the presence of catalytic bromine or hydrobromic acid

Article abstract of DOI:10.1248/cpb.55.156

Aldehydes were found to be oxidized with molecular oxygen to the corresponding carboxylic acid in the presence of catalytic hydrobromic acid or bromine under photo-irradiation.

Full text of DOI:10.1248/cpb.55.156

156
Notes
Chem. Pharm. Bull. 55(1) 156—158 (2007)
Vol. 55, No. 1
Photo-Oxidation of Aldehydes with Molecular Oxygen in the Presence of
Catalytic Bromine or Hydrobromic Acid
Shin-ichi HIRASHIMA and Akichika ITOH*
Gifu Pharmaceutical University; Mitahora-higashi, Gifu 502–8585, Japan.
Received September 22, 2006; accepted October 26, 2006
Aldehydes were found to be oxidized with molecular oxygen to the corresponding carboxylic acid in the
presence of catalytic hydrobromic acid or bromine under photo-irradiation.
Key words aldehyde; bromine; hydrobromic acid; molecular oxygen; photo-oxidation
The notion of green chemistry is becoming well estab- (entry 14). That no oxidation proceeded without irradiation
lished, and the development of environmentally benign of UV or use of bromine shows the necessity of both for this
processes is the goal of various research projects.1) The reaction (entries 6, 10). Since 2 was not detected when con-
method using molecular oxygen is one way consistent with ducting the reaction in an argon atmosphere, molecular oxy-
this notion due to its high atomic effect or E-factor as an oxi- gen is thought to be the terminal oxidant (entry 7).
dant. With this background in mind, we have been engaged
Table 2 shows the generality of this oxidation reaction
in aerobic photo-oxidation of alcohols and a methyl group at using a variety of aldehydes. Aromatic aldehydes, 1, 3 and 5,
the aromatic nucleus with several bromo sources.2—8) In the afforded the corresponding benzoic acids in high yields (en-
course of our further study for expanding application of this tries 1—3). On the other hand, 7 gave 45% of 8 and 28% of
reaction, aldehydes were found to be oxidized to the corre- anhydride of 8, and 9 gave 31% of 10 and several by-prod-
sponding carboxylic acids in the presence of catalytic lithium ucts, which were oxidized at the aromatic methyl group, were
bromide.9) Although lithium bromide is undoubtedly an inex- detected. Aliphatic aldehydes, 11 and 13, also afforded the
pensive and safe reagent, it is not necessarily easy to handle corresponding carboxylic acid in good yield in the presence
due to its hygroscopic property and the promoting effect of of 0.14 eq of bromine24); however, 15 was found to be less re-
lithium bromide is presumed to be lower than that of other active than other aldehydes examined, and the starting mate-
bromo sources, bromine or hydrobromic acid, by our previ- rial seemed to be remained when the reaction stopped (en-
ous experiments.3—7) Herein, we report in detail our study on tries 6—8).25)
the generality and limitation of this aerobic photo-oxidation
As mentioned above, bromine was found to be more effec-
of aldehydes to the carboxylic acids10—22) in the presence of a tive than lithium bromide since the amount of bromine re-
catalytic bromine or hydrobromic acid, which are inexpen- quired for carrying out this reaction smoothly is much
sive, safe and easily separable from the reaction mixture by smaller than that of lithium bromide.5,6) On the other hand, it
extraction.
is difficult to say that bromine is a good reagent because of
its intractable and toxic properties. Compared with this, hy-
drobromic acid (48% aqueous solution of hydrogen bromide)
Results and Discussion
Table 1 shows the results of a study of reaction conditions
conducted with 1 as test substrate and catalytic bromine as
promoter under irradiation with a 400 W high-pressure mer-
cury lamp externally in an oxygen atmosphere. Since passing
through water, a test tube and a cooling jacket, which are
made of Pyrex glass, and air is necessary for light to effect
this reaction, 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. Among the solvents exam-
ined,23) acetonitrile was found to afford the corresponding
carboxylic acid 2 most efficiently against the result with
lithium bromide.5,6) Although the best result from our tests
was obtained when using 0.07 eq of bromine for 5 h, 2 was
obtained in good yield when using 0.07 eq of bromine for 1 h
or 0.0175 eq of bromine for 5 h (entries 5, 8, 11). Since dull
red of bromine was thought to inhibit transmission of light,
the yield of 2 decreased when using 0.35 eq of bromine
Table 1. Study of Reaction Conditions of Aerobic Photo-Oxidation with
Br2
Entry
Br2 (eq)
Time (h)
Solvent
Yield of 2 (%)a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
—
5
5
5
5
5
5
5
1
3
5
5
5
5
5
EtOAc
Acetone
iPr2O
72
73
66
63
100
0b)
0c)
92
98
42
77
78
99
73
Hexane
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
0.0175
0.035
0.14
0.35
a) All yields are for pure, isolated products. b) The reaction was carried out in the
dark. c) The reaction was carried out in an Ar atmosphere.
Chart 1
∗ To whom correspondence should be addressed. e-mail: itoha@gifu-pu.ac.jp
© 2007 Pharmaceutical Society of Japan

January 2007
157
Table 2. Aerobic Photo-Oxidation with Br2
Table 4. Aerobic Photo-Oxidation with HBr aq.
Entry
Substrate
Br2 (eq)
0.07
Product
Yield (%)a)
(100)
Entry
Substrate
HBr (eq)
0.2
Product
Yield (%)a)
1
2
1
2
(90)
0.07
(94)
0.2
(100)
3
0.07
(97)
3
0.2
(100)
4
5
0.07
0.07
(45)b)
(31)
4
5
0.2
0.2
(100)
(22)b)
6
0.14
(88)
6
0.1
(71)
7
8
0.14
0.14
(71)
(47)
7
8
0.1
0.1
(37)
(45)
a) All yields are for pure, isolated products. b) 28% of 4-chlorobenzoic anhydride
a) All yields are for pure, isolated products. b) 20% of 3-hydroxy-1(3H)-isoben-
was also obtained.
zofuranone was also obtained.
Table 3. Study of Reaction Conditions of Aerobic Photo-Oxidation with
HBr aq.
Entry
HBr (eq)
Time (h)
Solvent
Yield of 2 (%)a)
1
2
3
4
5
6
7
8
9
0.2
0.2
0.2
0.2
0.2
0.2
0.2
—
5
5
5
5
5
5
3
5
5
5
EtOAc
Acetone
Hexane
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
67
64
69
100
0b)
0c)
74
72
95
100
Chart 2. Possible Path of the Aerobic Photo-Oxidation of Aldehyde
0.1
0.3
10
of the product is low without a bromo source as shown in
Table 1; however, 3 showed high reactivity under the oxida-
tion condition in the absence of a bromo source, and afforded
4 in 72% yield (entry 8).
a) All yields are for pure, isolated products. b) The reaction was carried out in the
dark. c) The reaction was carried out in an Ar atmosphere.
is superior in the point of easy treatment. Table 3 shows the
Table 4 shows the generality and limitation of this reaction
results of a study of reaction conditions with hydrobromic using a variety of aldehydes. In general, aromatic aldehydes
acid under the irradiation of UV. As shown in Table 1, among afforded the corresponding carboxylic acids in high yield
the solvents examined, acetonitrile was found to be the most with 0.2 eq of hydrobromic acid; however, 10 was obtained in
suitable in a similar manner with bromine. Although the best low yield due to production of 20% of 3-hydroxy-1-(3H)-
result was obtained when using 0.2 eq of hydrobromic acid26) isobenzofuranone, which was oxidized at the aromatic
for 5 h, 4 was also obtained in high yield even when using methyl group, when using 9 as substrate. On the other hand,
0.1 eq of hydrobromic acid (entries 4, 9). In general, the yield aliphatic aldehydes gave the products in moderate yield with

158
Vol. 55, No. 1
0.1 eq of hydrobromic acid27) as well as the case using
bromine as shown in Table 2.
References and Notes
1) Sheldon R. A., Chemtech, 24, 38—47 (1994).
2) Kuwabara K., Itoh A., Synthesis, 2006, 1949—1952 (2006).
3) Hirashima S., Hashimoto S., Masaki Y., Itoh A., Tetrahedron, 62,
7887—7891 (2006).
4) Hirashima S., Itoh A., Synthesis, 2006, 1757—1759 (2006).
5) Itoh A., Hashimoto S., Kodama T., Masaki Y., Synlett, 2005, 2107—
2109 (2005).
6) Itoh A., Hashimoto S., Masaki Y., Synlett, 2005, 2639—2640 (2005).
7) Itoh A., Hashimoto S., Kuwabara K., Kodama T., Masaki Y., Green
Chemistry, 7, 830—832 (2005).
8) Itoh A., Kodama T., Hashimoto S., Masaki Y., Synthesis, 2003, 2289—
2291 (2003).
9) Hirashima S., Itoh A., Chem. Pharm. Bull., 54, 1457—1458 (2006).
10) Corma A., Domine M. E., Chem. Commun., 2005, 4042—4044
(2005).
11) Kholdeeva O. A., Vanina M. P., Timofeeva M. N., Maksimovskaya R.
I., Trubistina T. A., Melgunov M. S., Burgina E. B., Mrowiec-Bialon
J., Jarzebski A. B., Hill C. L., J. Catal., 226, 363—371 (2004).
12) Ji H. B., He D. G., Song J., Qian Y., Chin. Chem. Lett., 15, 1241—
1244 (2004).
Reaction Mechanism Chart 2 shows a plausible path of
this oxidation due to the necessity of a catalytic amount of
bromine or hydrobromic acid, molecular oxygen and contin-
uous photo-irradiation to complete this reaction. We believe
that the radical species 17 is generated by abstraction of a hy-
drogen radical from an aldehyde with a bromo radical,
formed by continuous aerobic photo-oxidation of the bromo
anion from hydrogen bromide or bromine (Eqs. 1, 1ꢀ and
2).28) Bromine, then, was formed by aerobic photo-oxidation
of hydrogen bromide, which is generated in Eq. 2 (Eq. 3).
Radical species 17 was transformed to acyl bromide 18, and
the carboxylic acid was formed by reaction with water (Eqs.
4 and 5). We do not have any direct evidence for generation
of 18; however, we believe a considerable amount of car-
boxylic anhydride was formed through 18 (entry 4 in Table
2).
13) Kharat A. N., Pendleton P., Badalyan A., Abedini M., Amini M. M., J.
Mol. Catal. A: Chem., 175, 277—283 (2001).
14) Chen H., An T., Fang Y., Yu T., Indian J. Chem. Sec. B, 38B, 805—
809 (1999).
15) Mastrorilli P., Nobile C. F., Tetrahedron Lett., 35, 4193—4196 (1994).
16) Punniyamurthy T., Kalra S. J. S., Iqbal J., Tetrahedron Lett., 35,
2959—2960 (1994).
Conclusion
As mentioned above, photo-oxidation with molecular oxy-
gen of aldehydes in the presence of a catalytic amount of
bromine, and hydrogen bromide, was studied, and the corre-
sponding carboxylic acid was obtained in moderate to high 17) Hamamoto M., Nakayama K., Nishiyama Y., Ishii Y., J. Org. Chem.,
58, 6421—6425 (1993).
18) Bhatia B., Iqbal J., Tetrahedron Lett., 33, 7961—7964 (1992).
19) Abad A., Arno M., Cunat A. C., Marin M. L., Zaragoza R. J., J. Org.
Chem., 57, 6861—6869 (1992).
20) Yamada T., Rhode O., Takai T., Mukaiyama T., Chem. Lett., 1991, 5—
8 (1991).
21) Riley D. P., Getman D. P., Beck G. R., Heintz R. M., J. Org. Chem., 52,
287—290 (1987).
22) Garratt P. J., Doecke C. W., Weber J. C., Paquette L. A., J. Org. Chem.,
51, 449—452 (1986).
23) We exclusively used anhydrous solvents for this study since the sol-
vents are purer than other grades of general solvents.
24) The corresponding carboxylic acids were obtained in moderate yields
when using 0.07 eq of bromine.
25) Since the boiling point of 15 is not so high, remained 15 in the crude
product was thought to be evaporated under reduced pressure with a
vacuum pump.
26) The equivalent indicates the amount of hydrogen bromide in the hy-
drobromic acid.
27) Since the reaction mixture was tarry and the product 12 was obtained
only in 33% yield when using 11 and 0.2 eq of hydrobromic acid,
0.1 eq of hydrobromic acid was exclusively used for aliphatic aldehy-
des.
yield. Especially, hydrobromic acid is inexpensive, safe, and
easy to handle due to its non-hygroscopic property, and thus,
this new form of oxidation reaction is interesting in keeping
with the notion of Green Chemistry.
Experimental
All dry solvents were obtained from Kanto Kagaku Co., Ltd. Other chem-
icals used were of reagent grade and were obtained from Aldrich Chemical
Co., Tokyo Kasei Kogyo Co., Ltd. and Wako Pure Chemical Industries, Ltd.
Acetonitrile solution of bromine was previously prepared for easy treatment.
HBr was added as 48% hydrobromic acid. All reactions were carried out in a
Pyrex test tube equipped with an O2-balloon, which was set up from the cen-
ter of 400-W high pressure 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 Br2
(0.07 eq) in dry acetonitrile was stirred and irradiated at room temperature
with a 400-W high-pressure mercury lamp externally for 5 h. 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.
28) Minisci F., Porta O., Recupero F., Punta C., Gambarotti C., Pierini M.,
Galimberti L., Synlett, 2004, 2203—2205 (2004).