SHORT PAPER
1757
Synthesis of Benzoic Acids by Aerobic Photooxidation with Hydrobromic Acid
Synthesis of
B
h
e
nzoic Acids
i
by Ae
n
r
obic Photoo
-
xidation
i
with H
c
ydrobromi
h
c
A
cid i Hirashima, Akichika Itoh*
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
E-mail: itoha@gifu-pu.ac.jp
Received 8 December 2005; revised 18 January 2006
Table 1 Study of Reaction Conditions of Aerobic Photooxidation
Abstract: A methyl group at an aromatic nucleus is oxidized direct-
ly to the corresponding carboxylic acid in the presence of molecular
oxygen and catalytic hydrobromic acid under photoirradiation.
hν (400 W)
aq HBr
CO2H
O2-balloon
tBu
tBu
1 (50 mg)
Key words: aerobic, benzoic acid, hydrobromic acid, methyl
group, photooxidation
solvent, 10 h
2
Entry
aq HBr (equiv) Solvent
Yield of 2 (%)a
Oxidation, especially introduction of oxygen-containing
functional groups to hydrocarbon, is a fundamental and
most important reaction in the synthesis of a large number
of chemicals from fossil fuel. However, most of them in-
volve the use of large quantities of heavy metals which re-
sults in the discharge of considerable amounts of
contaminants, and are not at all environmentally benign.1
With this background in mind, we discovered in the
course of our study of photooxidation that 4-tert-butyltol-
uene (1) is oxidized directly to 4-tert-butyl benzoic acid
(2) in ethyl acetate in an oxygen atmosphere in the pres-
ence of LiBr.2 The mechanism of this reaction has not yet
been determined; however, we believe that HBr is formed
in situ from a bromo radical, which is formed under irra-
diation from LiBr, and a hydrogen radical, which is ab-
stracted from the benzylic position. If addition of
hydrobromic acid, which is an inexpensive and easily
handled reagent as an aqueous solution of HBr, is enough
to effect the oxidation, this reaction is expected to be a
useful and convenient oxidation method in view of the use
of molecular oxygen as the terminal oxidant and the non-
requirement of environmentally detrimental heavy metals
and halogenated solvents.3 In this letter we report in detail
our investigation of the generality of this aerobic photoox-
idation of a methyl group at the aromatic nucleus with hy-
drobromic acid.
1
2
0.14
0.14
0.14
0.14
0.14
0.10
0.20
0.30
0.40
0.50
Hexane
Acetone
MeCN
i-Pr2O
49
51
51
0
3
4
5
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
93
65
98
96
91
100
6
7
8
9
10
a All yields are for pure and isolated products.
radiation of UV or the addition of hydrobromic acid
shows the necessity of both for this reaction.
Table 2 shows the results for the oxidation of several sub-
strates under the reaction conditions outlined above. Al-
though an electron-donating group, such as a tert-butyl
group or a methoxy group at an aromatic nucleus, in gen-
eral, enhanced the reaction rate, an electron-withdrawing
group, such as a cyano or a chloro group, retarded the re-
action rate, and gave the corresponding benzoic acid in
modest yield (entries 1–6). Especially when 4-nitrotolu-
ene (13) was used, no product 14 was obtained after ten
hours; however, a 87% yield of 14 was obtained after 36
hours (entry 7). p-Xylene (15) a polymethylbenzene, was
oxidized to terephthalic acid (16) in 52% yield in the pres-
ence of 0.4 equivalents of HBr. 1-Methylnaphthalene and
2-methylnaphthalene (17 and 19) afforded the naphthoic
acids 18 and 20, respectively in high yields. Furthermore,
2-methylthiophene (21), a heterocyclic compound, af-
forded the corresponding carboxylic acid 22 in modest
yield. However, a trace amount of 24 was detected when
2-picoline (23) was used as the substrate.
Table 1 shows our initial study of the reaction conditions
of the aerobic photooxidation, which was carried out us-
ing 4-tert-butyltoluene (1, 50 mg, 0.269 mmol) as a test
substrate with hydrobromic acid in various solvents. We
do not know the reason, however, ethyl acetate was found
to be the most suitable solvent for this reaction among the
typical solvents examined. Since the yield of 2 was almost
quantitative when more than 0.2 equivalents of hydrobro-
mic acid with reference to 1 were used, we usually used
this amount of hydrobromic acid for the subsequent ex-
periments. That no oxidation proceeded without either ir-
SYNTHESIS 2006, No. 11, pp 1757–1759
x
x.
x
x
.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-942356; Art ID: F20805SS
© Georg Thieme Verlag Stuttgart · New York
We believe that the benzyl radical species 25 is generated
by abstraction of a hydrogen radical with a bromo radical,