SHORT PAPER
2289
Oxidation of the Methyl Group at the Aromatic Nucleus with Molecular
Oxygen in the Presence of N-Bromosuccinimide under Photoirradiation
Oxidation of the
M
k
ethyl
G
roup
i
at the
c
A
romatic
N
h
ucleus ika Itoh,* Tomohiro Kodama, Shouei Hashimoto, Yukio Masaki
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
E-mail: itoha@gifu-pu.ac.jp
Received 25 April 2003; revised 15 July 2003
alent) in several solvents using 400-W high-pressure mer-
cury lamps under aerobic atmosphere at room temperature
for 12 hours. Among the solvents examined, ethyl acetate
was found to be suitable for the reaction to afford 2 in 85%
Abstract: A methyl group at the aromatic nucleus can be oxidized
to the corresponding carboxylic acid directly in the presence of N-
bromosuccinimide (NBS) under photoirradiation. By considering
both the promoting effect of oxygen and a catalytic amount of NBS,
aerobic oxidation via hydroperoxide, which is thought to be gener- yield (entries 1, 10–13). The result that without either ir-
ated by abstraction of a hydrogen with a bromo radical from NBS,
proceeded.
radiation, oxygen, or NBS, 2 was not obtained or was ob-
tained only in low yield shows the necessity of all of the
Key words: oxidations, methyl group, N-bromosuccinimide, pho-
toirradiation, molecular oxygen
foregoing conditions for this reaction (entries 2–4). The
oxidation yielding 2 was surprisingly promoted even by a
catalytic amount of NBS, although a longer reaction time
was required (entries 5 and 6). On the other hand, an ex-
The oxidation reaction using molecular oxygen is impor- cess amount of NBS retarded the reaction (entries 7–9).
tant from synthetic and industrial points of view, and
Table 1 Study of Reaction Conditions for the Oxidation of 4-tert-
Butyltoluene (1) with NBS
many workers are engaged in the development of new
strategies for aerobic oxidation.1,2 On the other hand, N-
CO2H
bromosuccinimide (NBS) is also used for oxidation at al-
lylic and benzylic positions, which is thought to be an aer-
NBS, hν
solvent (5 mL)
tBu
tBu
obic oxidation via a brominated intermediate; however,
there are few reports about them,3 and, to our knowledge,
there is only one study that was directed toward oxidation
at the benzylic position with NBS in which the yield of the
products was very low.4 In executing our ongoing project
involving oxidation reactions at the benzylic position un-
der photoirradiation we noticed that arylmethyl halides
were easily oxidized to the corresponding carboxylic ac-
ids in the presence of mesoporous silicas under photoirra-
diation.5 The results suggest that the oxidation of methyl
groups at the aromatic nucleus to the corresponding car-
boxylic acid proceeds under the condition where haloge-
nation at the methyl group occurs in situ, and we found
that 4-tert-butyltoluene (1) was oxidized directly to 4-tert-
butylbenzoic acid (2) in the presence of NBS under pho-
toirradiation (Scheme 1). Now we report our study on the
generality of this oxidation with NBS under photoirradia-
tion.
1 (100 mg)
2
Entry
1
Solvent
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
Me2CO
CH2Cl2
i-Pr2O
THF
NBS (equiv) Time (h) Yield of 2 (%)
1.0
1.0
1.0
–
12
12a
12b
12
12
24
12
12
12
12
12
12
12
85
0c
2
3
0d
9
4
5
0.3
0.3
1.2
1.5
2.0
1.0
1.0
1.0
1.0
69
6
78
83
78
56
56
54
19
6
7
8
9
10
11
12
13
Table 1 shows the results of the transformation of 4-tert-
butyltoluene (1, 100 mg) in the presence of NBS (1 equiv-
a The reaction was carried out in the dark.
b The reaction was carried out under an argon atmosphere.
c 4-tert-Butylbenzaldehyde (2%), 4-tert-butylbenzyl bromide (56%),
and 4-tert-butylbenzal bromide (15%) were obtained.
d 4% of 4-tert-butylbenzaldehhyde was obtained, and 43% of 1 was
recovered.
Scheme 1
SYNTHESIS 2003, No. 15, pp 2289–2291
x
x.
x
x
.
2
0
0
3
Advanced online publication: 23.09.2003
DOI: 10.1055/s-2003-41077; Art ID: F03803SS.pdf
© Georg Thieme Verlag Stuttgart · New York