Nitration of alkanes with nitric acid catalyzed by N-hydroxyphthalimide

Article abstract of DOI:10.1039/b102374h

Catalytic nitration of alkanes with nitric acid was first successfully achieved by the use of N-hydroxyphthalimide (NHPI) under mild conditions; the key to the present nitration was found to be the in situ generation of NO₂ and phthalimide N-ox

Full text of DOI:10.1039/b102374h

Nitration of alkanes with nitric acid catalyzed by
N-hydroxyphthalimide
Shinji Isozaki, Yoshiki Nishiwaki, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering and High Technology Research Center,
Kansai University, Suita, Osaka 564-8680, Japan. E-mail: ishii@ipcku.kansai-u.ac.jp
Received (in Cambridge, UK) 13th March 2001, Accepted 11th June 2001
First published as an Advance Article on the web 5th July 2001
Catalytic nitration of alkanes with nitric acid was first
2
nitric acid was easily converted into NO in the presence of
successfully achieved by the use of N-hydroxyphthalimide
(
NHPI) under mild conditions; the key to the present
2
nitration was found to be the in situ generation of NO and
phthalimide N-oxyl radical by the reaction of NHPI with
nitric acid.
(2)
Nitration of saturated hydrocarbons using nitric acid is usually
NHPI under relatively mild conditions, although it is known that
carried out at fairly high temperature (250–400 °C) because of
the nitration of alkane with HNO must be carried out at high
temperature because of the difficulty in decomposing HNO to
From EPR measurements, it was found that the
phthalimide N-oxyl radical (PINO) was formed with the
evolution of NO by the reaction of the NHPI with nitric acid.‡
NHPI is known to be easily oxidized with Pb(OAc) to the
PINO. In the present reaction, nitric acid serves as a good
oxidizing agent of the NHPI to form the PINO and NO [eqn.
2)].
In order to obtain further insight into the present nitration, 1
3
1
difficulty in generating NO
2
from HNO
3
. The nitration under
3
such severe conditions resulted in not only the homolysis of C–
H bonds but also the cleavage of the C–C bonds of hydro-
carbons. As a consequence, the reaction is messy and often
difficult to control, and exhibits poor product selectivity. To
carry out the nitration selectively, in situ generations of alkyl
1c
2
NO .
2
4
3
2 3
radicals from alkanes and NO from HNO must be achieved
2
under mild conditions. Recently, we have developed a novel
catalytic method for the nitration of aliphatic hydrocarbons with
(
2
NO
now find that alkanes can be nitrated with nitric acid through the
in situ generation of NO and alkyl radicals by the use of NHPI
2
using NHPI as the catalyst under mild conditions. We
was allowed to react with nitric acid in the presence of copper
in place of NHPI, since it is known that nitric acid reacts with
2
4
copper metal, generating NO
2
according to eqn. (3). However,
as a catalyst under mild conditions.
The nitration of adamantane (1) was chosen as a model
reaction and carried out in the presence of nitric acid and a
catalytic amount of NHPI in trifluorotoluene, affording 1-
nitroadamantane (2) (64%) and 1,3-dinitroadamantane (3) (3%)
along with oxygenated products, adamantan-1-ol (4) (9%) and
adamantan-2-one (5) (5%) [eqn. (1), Table 1 entry 1]. In a
(
3)
4)
(
previous paper, we showed that the nitration of 1 with NO
2
as
a nitrating reagent affords 2 in 66% yield. The nitration of 1
with HNO which is easier to handle than NO was found to be
almost same as that with NO
2
3
2
no nitration took place, although the generation of NO
observed [eqn. (4)].
2
was
2
.
Table 2 summarizes the representative results for the nitration
of various saturated hydrocarbons and their derivatives with
nitric acid under the influence of the NHPI in trifluorotoluene at
6
0 °C for 15 h.
,3-Dimethyladamantane (6) reacted with nitric acid under
these conditions to give 1-nitro-3,5-dimethyladamantane (7) in
7% selectivity at 77% conversion (entry 1). When the NHPI
1
6
used was increased from 0.1 mmol to 0.2 mmol, 7 was obtained
in higher conversion and selectivity (entry 2). The nitration
3
Table 1 Nitration of adamantane (1) with HNO by NHPI under various
conditionsa
(1)
Table 1 shows the catalytic nitration of 1 with nitric acid by
the NHPI under several reaction conditions.† Among the
solvents examined, trifluorotoluene and acetic acid were found
to be good solvents. Acetonitrile and ethyl acetate considerably
retarded the nitration (entries 3 and 4). No reaction took place in
the absence of NHPI (entry 5). The present nitration under air
afforded oxygenated products, 4 and 5, rather than nitro
compounds (entry 6).
Select. (%)
Entry
Solvent Conv. (%)
2
3
4
5
1
2
3
4
PhCF
AcOH
CH CN
AcOEt
AcOH
3
87
93
55
34
> 2
40
64
62
38
24
n.d.
n.d.
3
9
6
9
21
n.d.
33
5
4
4
3
n.d.
13
n.d.
n.d.
n.d.
n.d.
n.d.
3
b
5
Upon treatment of NHPI with nitric acid at 60 °C, we found
c
6
PhCF
3
the evolution of brown gas attributed to NO
suggests that the nitric acid reacts easily with the NHPI to
generate NO in the reaction system [eqn. (2)]. Importantly,
2
. This finding
a
1
3
(1 mmol) was reacted with HNO (1.5 mmol) in the presence of NHPI
0.1 mmol) at 60 °C for 15 h. In the absence of NHPI. Under air.
b
c
(
2
1352
Chem. Commun., 2001, 1352–1353
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102374h

View Online
Table 2 Nitration of various substrates with HNO
3
by NHPIa
Conv.
(%)
Select.
(%)
Entry
1
Substrate
Product
77
67
6
7
b
2
6
6
89
50
7
7
81
95
c
d
3
Scheme 1 A possible nitration path of alkanes with nitric acid by NHPI.
4
89
57
(47)
jected to the nitration under these reacion conditions. Thus,
(74)
1
-chloroadamantane, 1-nitroadamantane, and ethyl 1-adaman-
8
9
tanecarboxylate were nitrated to the corresponding nitro
compounds in fair to good selectivities (entries 9–11).
On the basis of these results, a possible reaction path for the
present catalytic nitration of alkanes with nitric acid by the
NHPI is shown in Scheme 1.
5
75
56e
The nitration is initiated by the in situ generation of PINO and
6f
32dg
NO
2
from NHPI and nitric acid, respectively. The resulting
—
PINO abstracts the hydrogen atom from alkanes to give NHPI
and alkyl radicals which are readily trapped by NO
2
to form
nitroalkanes.
In conclusion, the present alkane nitration with nitric acid
provides a facile method for the preparation of nitroalkanes, by
the use of cheap and easily available nitric acid compared with
7f
8
—
60dh
65
2
NO .
80
This work was partially supported by the Research for the
Future program, JSPS and DAICEL Chemical Industries, Ltd.
9
59
73
32
61
79
91
Notes and references
†
A typical reaction was carried out as follows: economic grade
concentrated nitric acid (60% over) was used without any treatment. The
reaction was carried out as follows: to a two necked flask was added
adamantane (1) (1 mmol), NHPI (0.1 mmol) and nitric acid (1.5 mmol) in
trifluorotoluene (3 mL), and the mixture was reacted under argon at 60 °C
for 15 h. After evaporation of the solvent under reduced pressure, the
reaction mixture was extracted with diisopropyl ether and the extracts were
1
0
3
washed with aq. NaHCO . After separation of the organic phase, the
1
1
mixture was subjected to silica gel chromatograph, giving 1-nitroada-
mantane (2) (57%), 1,3-dinitroadamantane (3) (3%) together with oxy-
genated products, adamantan-1-ol (4) (8%) and adamantan-2-one (5) (4%)
(Table 1, entry 1).
‡ Electron paramagnetic resonance (EPR) measurements were carried out
under selected conditions. To a two necked flask was added NHPI (0.1
mmol) and nitric acid (1.5 mmol) in trifluorotoluene (10 mL), and the
mixture was reacted under argon at 60 °C for 1 h. The EPR spectrum
attributed to PINO was clearly observed as a triplet signal based on
a
Reaction is shown in text. Parentheses show the conversion and selectivity
in the nitration using NO instead of HNO . NHPI (0.2 mmol) was used.
2 3
Substrate (3.0 mmol) was used. Based on HNO
trocyclooctane (14%) and cyclooctanone (10%) were obtained. Substrate
5 mL) was used. Adipic acid (5%) was obtained. Benzyl alcohol (21%)
and benzaldehyde (19%) were obtained.
b
c
d
e
3
used. Dini-
f
g
h
(
hyperfine splitting (hfs) by the nitrogen atom (g = 2.0074, a
The g-value and hfs constant observed for PINO were consistent with those
g = 2.0073, a
= 0.423 mT) reported by Mackor et al.3b
N
= 0.46 mT).
using excess 6 with respect to nitric acid resulted in 7 in
(
N
excellent yield (95%). The nitration of endo-tricyclo-
5.2.1.02 ]decane (8) occurred selectively at the fused tertiary
,6
[
1
(a) F. L. Albright, Chem. Eng., 1966, 73, 149, and references therein; (b)
C–H bond to give the corresponding nitro compound 9 (57%).
On the other hand, the nitration of 8 with NO instead of HNO
resulted in 9 in low yield (47% selectivity, 74% conversion).
Consequently, 8 was found to be nitrated with HNO in higher
selectivity. Cyclooctane was also nitrated to form nitro-
cyclooctane (56%) and a regioisomeric mixture of dinitro-
cyclooctane (14%) as well as a small amount of cyclooctanone
G. B. Bachman, J. Org. Chem., 1952, 17, 906; (c) L. F. Albright, in Kirk-
Othmer Encyclopedia of Chemical Technology, Vol 17, eds. J. I.
Kroschwite and M. Howe-Grant, Wiley, New York, 1995, 68; (d) H. B.
Hass, E. B. Hodge and B. M. Vanderbilt, Ind. Eng. Chem., 1936, 339.
S. Sakaguchi, Y. Nishiwaki, T. Kitamura and Y. Ishii, Angew. Chem. Int.
Ed., 2001, 40, 222.
2
3
3
2
3
(a) A. Calder, A. R. Forrester and R. H. Thomson, J. Chem. Soc. (C),
1
969, 567; (b) A. Mackor, A. J. Wajar and J. de Boer, Tetrahedron, 1968,
(
10%) at 75% conversion. Cyclohexane was difficult to nitrate
2
4, 1623.
5
selectively because of the formation of adipic acid (5%).
Aliphatic hydrocarbon like 2-methylhexane was nitrated at the
tertiary position to lead to 2-methyl-2-nitrohexane in relatively
good selectivity. Several substituted adamantanes were sub-
4
R. Lee and F. L. Albright, Ind. Eng. Chem. Proc. Des. Dev., 1965, 4,
41.
4
5 V. Anantharaj, J. Bhonsle, T. Canteenwala and L. W. Chiang, J. Chem.
Soc., Perkin Trans. 1, 1999, 31.
Chem. Commun., 2001, 1352–1353
1353