Oxidation of nitrotoluenes with air using N-hydroxyphthalimide analogues as key catalysts

Article abstract of DOI:10.1016/S0040-4039(03)00212-0

Nitrotoluenes are efficiently oxidized with air to the corresponding nitrobenzoic acids by the use of N-acetoxyphthalimide (NAPI) as a key catalyst. Thus, p- and m-nitrotoluenes under 10 atm of air in the presence of NAPI combined with Co(OAc)₂ (0.5 mol%) and Mn(OAc)₂ (0.05 mol%) at 130°C afforded p- and m-nitrobenzoic acids in 81 and 92% yields, respectively. o-Nitrotoluene was oxidized to o-nitrobenzoic acid in 51% yield by the aid of NO₂.

Full text of DOI:10.1016/S0040-4039(03)00212-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2053–2056
Oxidation of nitrotoluenes with air using N-hydroxyphthalimide
analogues as key catalysts
Naoko Sawatari, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry & High Technology Research Center, Faculty of Engineering, Kansai University, Suita,
Osaka 564-8680, Japan
Received 12 December 2002; revised 14 January 2003; accepted 17 January 2003
Abstract—Nitrotoluenes are efficiently oxidized with air to the corresponding nitrobenzoic acids by the use of N-acetoxyphthalimide
(NAPI) as a key catalyst. Thus, p- and m-nitrotoluenes under 10 atm of air in the presence of NAPI combined with Co(OAc)2
(0.5 mol%) and Mn(OAc)2 (0.05 mol%) at 130°C afforded p- and m-nitrobenzoic acids in 81 and 92% yields, respectively.
o-Nitrotoluene was oxidized to o-nitrobenzoic acid in 51% yield by the aid of NO2. © 2003 Elsevier Science Ltd. All rights reserved.
Aerobic oxidations of alkylbenzenes are very important
industrial processes for the production of primary and
speciality chemicals and monomer materials like tereph-
thalic acid. Nowadays, they are practised in large scale
in chemical industry worldwide.1 These aerobic oxida-
tions are usually carried out under the influence of
cobalt salt, manganese salt and bromide ion using
acetic acid as a solvent.
nately, we have recently developed an innovative cata-
lytic method for the aerobic oxidation of hydrocarbons
using N-hydroxy-phthalimide (NHPI) which serves as a
carbon radical-producing catalyst (CRPC) from
alkanes.4
In continuation of our study on the aerobic oxidation
of hydrocarbons by this catalytic system, we would like
to report the aerobic oxidation of nitrotoluenes, which
are very difficult to be oxidized by the conventional
autoxidations, by NHPI analogues such as N-acetoxy-
phthalimide (NAPI) and N,N-dihydroxypyromellit-
imide (NDHPI) as key catalysts (Eq. (1)).
However, the aerobic oxidation of nitrotoluenes involv-
ing
a strong electron-withdrawing substituent to
nitrobenzoic acids is very difficult to carry out using
this catalytic system even under high pressure of air and
higher reaction temperature (around 175°C).2 Under
these conditions, the oxidation is accompanied by
undesired side-reactions like decarboxylation of the
resulting nitrobenzoic acids and degradation of acetic
acid used as a solvent. Other drawbacks of this catalytic
system are the use of high corrosive bromide ion and
the formation of brominated by-products. To overcome
these problems, it is necessary to develop a bromide-
free catalytic system for the aerobic oxidations.
Although Neuman et al. have reported the Ru-cata-
lyzed liquid-phase oxidation of deactivated toluenes like
cyanotoluenes and nitrotoluenes with aqueous sodium
hypochloride under phase-transfer conditions,3 the aer-
obic oxidation of nitrotoluenes has been little studied
by a catalytic system not involving bromide ion. There-
fore, the development of an efficient bromide-free cata-
lytic system for the aerobic oxidation of nitrotoluenes is
desired for a long time in industrial chemistry. Fortu-
(1)
The oxidation of p-nitrotoluene (1a) with air was exam-
ined by the use of several NHPI analogues in acetic
acid under various reaction conditions (Table 1).
* Corresponding author. Tel.: +81-6368-0793; fax: +81-6339-4026;
e-mail: ishii@ipcku.kansai-u.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00212-0

2054
N. Sawatari et al. / Tetrahedron Letters 44 (2003) 2053–2056
Table 1. Aerobic oxidation of p-nitrotoluene (1a) by
Table 2. Aerobic oxidation of m-nitrotoluene (1b) by
NHPI analoguesa
NHPI analoguesa
Run Catalyst
Temp. (°C)
Conv. (%)
Yield (%)
Run Catalyst
Temp. (°C)
Conv. (%)
Yield (%)
2a
3a
2b
3b
1
2
3
4
NHPI
NHPI
NHPI
–
NHPI
NHPI
NAPI
NDHPI
100
110
130
130
130
130
130
130
51
76
85
10
74
33
91
91
43
65
78
nd
65
21
81
80
2
7
6
nd
6
2
7
5
1
NHPI
NAPI
NDHPI
NHPI
130
130
130
100
91
\99
90
82
92
80
62
6
5
5
5
2
3b
4
70
5b
6c
7
a 1b (2 mmol) was reacted under the same conditions as Table 1.
b NDHPI (5 mol%) was used.
8d
(3b) (6%) (Table 2, run 1). When NAPI was employed
in place of NHPI under these conditions, 1b was com-
pletely converted to form 2b (92%) and 3b (5%) (run 2).
The oxidation results using 5 mol% of NDHPI were
almost the same as those using 10 mol% of NHPI (run
3). The reactivity of 1b for the aerobic oxidation by
NHPI at 100°C was compared with that of 1a (run 4).
It was found that 1b was oxidized more easily than 1a
to give 2b in relatively good yield (60%). These results
indicate that 1b is more reactive than 1a. From the
consideration of Hammett constants of 1a (|=0.78)
and 1b (|=0.70), the reactivity of 1a and 1b for the
present oxidation seems to be reasonable.
a 1a (2 mmol) was reacted under 10 atm of air in the presence of
NHPI analogue (10 mol%), Co(OAc)2 (0.5 mol%) and Mn(OAc)2
(0.05 mol%) in acetic acid (5 mL) for 14 h.
b In the absence of Mn(OAc)2.
c In the absence of Co(OAc)2.
d NDHPI (5 mol%) was used.
The oxidation of 1a under air (10 atm) in the presence
of NHPI (10 mol%), Co(OAc)2 (0.5 mol%) and
Mn(OAc)2 (0.05 mol%) at 100°C afforded p-nitrobenz-
oic acid (2a) (43%) along with a small amount of
p-nitrobenzaldehyde (3a) (2%) (run 1). The yield of 2a
increased with raising the reaction temperature, and 2a
was obtained in satisfactory yield (78%) at 130°C (run
3). Needless to say, the reaction in the absence of the
NHPI under these conditions afforded no nitrobenzoic
acid (run 4). Effects of Co(OAc)2 and Mn(OAc)2 on the
oxidation of 1a were examined (runs 5 and 6). The
oxidation was markedly retarded without Co(OAc)2,
while 1a was oxidized in relatively good yield (65%)
even in the absence of Mn(OAc)2. NHPI analogues,
NAPI and NDHPI were also effective for the present
oxidation (runs 7 and 8).
o-Nitrotoluene (1c) is known to be reluctant substrate
for the aerobic oxidation due to the steric hindrance of
the adjacent bulky NO2 and the electronic effect of NO2
having the strong electron withdrawing property which
deactivates the reactivity of the methyl group. There-
fore, it is desired to develop a new efficient method for
the oxidation of 1c through a catalytic process.
Thus, the oxidation of 1c by CRPC was performed
under various reaction conditions (Table 3).
In a previous paper, we showed that NAPI, which
corresponds to the NHPI protected by the acetyl group,
is more stable than the NHPI and that it is gradually
hydrolyzed to the NHPI with water containing in acetic
acid used as a solvent.5 In the present oxidation, there-
fore, the NAPI served as the CRPC to catalyze the
oxidation of 1a. It is interesting to note that NDHPI,
involving two hydroxyimide moieties, was efficiently
catalyzed the oxidation even in the presence of a half
amount (5 mol%) of NHPI which corresponds to 10
mol% of NHPI based on the hydroxyimide unit. This
fact indicates that the catalytic activity of hydroxyimide
moiety of the NDHPI was comparable to that of the
NHPI.
In contrast to the oxidation of 1a and 1b by NDHPI
and NAPI catalysts which show higher catalytic activi-
ties at 130°C, 1c was difficult to be oxidized by both
catalysts at this temperature (runs 1 and 2). By the use
of 10 mol% of NDHPI under these conditions, a small
amount of o-nitrobenzoic acid (2.4%) (2c) was formed
along with 4% yield of o-nitrobenzaldehyde (3c) (run
3). These results suggest that the hydrogen abstraction
from the methyl group of 1c is difficult to occur up to
130°C. Thus, the oxidation of 1c by NHPI assisted by
a radical initiator, AIBN, was examined (run 4). It was
found that 1c was oxidized to some extent under the
influence of AIBN to give 2c in 15% yield. Even at
higher temperature (150°C), 1c was difficult to be oxi-
dized by NHPI and NAPI, while NDHPI promoted
slightly the oxidation to form 2c in 16% yield (runs
5–7).
We next examined the oxidation of m-nitrotoluene (1b)
under several conditions in which the 1a was smoothly
oxidized (Table 2).
In a previous paper, we reported that the oxidation of
methylquinolines by NHPI is markedly accelerated by
the addition of a catalytic amount of nitrogen dioxide
(NO2).6 Thus, the oxidation of 1c by NHPI/Co(OAc)2/
Mn(OAc)2 was run by the addition of NO2 (20 mol%)
The reaction of 1b by NHPI (10 mol%) combined with
Co(OAc)2 (0.5 mol%) and Mn(OAc)2 (0.05 mol%)
under 10 atm of air at 130°C gave m-nitrobenzoic acid
(2b) in 82% yield together with m-nitrobenzaldehyde

N. Sawatari et al. / Tetrahedron Letters 44 (2003) 2053–2056
Table 3. Aerobic oxidation of o-nitrotoluene (1c) by NHPI analoguesa
2055
Run
Catalyst
Additive (mol%)
Temp. (°C)
Conv. (%)
Yield (%)
2c
3c
1
NHPI
NAPI
DNHPI
NHPI
NHPI
NAPI
NDHPI
NHPI
NHPI
NAPI
130
130
130
130
150
150
150
150
150
150
150
3
8
nd
nd
2.4
nd
nd
4
3
2
1
3
4
2
2
3b
4
17
19
20
18
23
52
25
35
58
AIBN (1)
15
11
10
16
46
11
29
51
5
6
7
8
9
10
11
NO2 (20)
AIBN (1)
NO2 (20)
NO2 (20)
3
4
NDHPI
a 1c (2 mmol) was reacted under the same conditions as Table 1.
b NDHPI (5 mol%) was used.
Scheme 1.
at 150°C (run 8). As expected, 1c was fairly oxidized to
give 2c in 46% yield and 3c in 4% yield. The same
oxidation by adding AIBN instead of NO2 under these
conditions gave 2c in 11% yield (run 9). However, the
yield was not improved by the addition of NO2 to
NAPI for the oxidation of 1c, probably because of the
difficulty of the reaction of the NAPI protected by
acetyl group with NO2 (run 10). In contrast, the yield
of 2c was improved to 51% by adding NO2 to the
NDHPI (run 11).
nitrobenzyl radical which is trapped by O2 to give
benzylperoxy radical followed by 2c through the redox
decomposition of the corresponding hydroperoxide by
metal ions (Scheme 1).
The resulting HNO2 is known to convert into HNO3
and NO which is readily oxidized to NO2 under the
present conditions.7 In addition, we show that HNO3
reacts with the hydroxyimide in the NHPI to form
PINO.8
Similarly, the oxidations of 1a and 1b were also acceler-
ated by adding a small amount of NO2. For example,
when the oxidation of 1b was carried out in the pres-
ence of 10 mol% of NO2 under the reaction conditions
as shown in Table 2 run 4, the yield of 2b increased to
70% at 79% conversion.
In conclusion, the present oxidation of nitrotoluenes
with air by the use of CRPC provides an alternative
practical green route to nitrobenzoic acids.
Acknowledgements
It was thought that NO2, which possesses stronger
oxidizing ability than O2, would smoothly abstract the
hydrogen atom from NHPI to form phthalimide N-
oxyl radical (PINO). The resulting PINO abstracts the
hydrogen atom of methyl group of 1c to form o-
This work was partially support by a Grant-Aid for
Scientific Research (KAKENHI) (S) (No. 13853008)
from Japan Society for the Promotion of Science
(JSPS).

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N. Sawatari et al. / Tetrahedron Letters 44 (2003) 2053–2056
4. (a) Ishii, Y.; Nakayama, K.; Takeno, M.; Sakaguchi, S.;
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