Mendeleev Commun., 2012, 22, 67–69
– 67 –
© 2012 Mendeleev Communications. All rights reserved.
Mendeleev
Communications
Nitric acid esters are used as components of high-energetic mate-
rials
1
and active ingredients of pharmaceuticals.
2
They are con ven-
tionally produced by O-nitra tion of alcohols with nitric acid,
3
nitric/
sulfuric acid mix tures,
1(a),4
acetyl nitrate,
4(c),5
nitronium salts,
4(e),6
nitrogen oxides
7
and some other nitrating agents
8
in organic
solvents or under neat condi tions. Being performed in a large
scale, these reactions are associated with safety and/or waste
disposal problems caused by intensive heat evolution and by the
presence of considerable amounts of organic nitrates in the acidic
wastes and aqueous washings.
9
A promising approach to address these issues is based on
carrying out the nitration in an N
2
O
5
/CO
2
liquid system. Dinitrogen
pentoxide is an extremely active and versatile nitrating agent
which can be easily prepared in laboratory and industry by oxida-
tion of available N
2
O
4
with ozone.
10
According to the equation
of this reaction (Scheme 1) nitric acid is formed as byproduct
and it is recoverable for reuse.
7(g)
Inexpensive, non-toxic, incom-
bustible and thermally stable com pressed CO
2
is a suitable medium
for various reactions of organic compounds.
11
The idea to combine
N
2
O
5
and CO
2
in nitration reactions affording high-energetic
materials is not new.
12–14
This approach has been applied to the
synthesis of some promising high-energetic nitric esters such as
3-methyl-3-oxetanemethyl nitrate and cyclodextrin nitrate. We
expanded the area of using the N
2
O
5
/CO
2
liquid system to the
synthesis of wider range of nitric esters, some of them having
pharmaceutical application.
At first, we examined the nitration of 1-hexanol 1c feeding
it to a solution of N
2
O
5
in liquid CO
2
(55–75 bar) at 0 °C (pro-
cedure A)
†
(Table 1).The nitrate 2c was generated in a yield of
90% when a 10 mol% excess of N
2
O
5
was used and the reaction
was carried out for 30 min (entry 2). Increasing of the nitrating
agent amount (entry 3) or the reaction duration (entry 5) did not
increase the yield.
This procedure appeared to be applicable to the nitration of
various alcohols 1a–d and polyols 1f and 1j. In all cases the cor-
responding nitric esters 2a–d, 2f and 2j were obtained in yields
Synthesis of nitric acid esters from alcohols in
a dinitrogen pentoxide/carbon dioxide liquid system
Ilya V. Kuchurov, Igor V. Fomenkov, Sergei G. Zlotin* and Vladimir A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: zlotin@ioc.ac.ru
03.004DOI: 10.1016/j.mencom.2012.
Organic nitric acid esters have been prepared in 89–98% yield by the nitration of the corresponding alcohols and polyols with N
2
O
5
in liquid CO
2
.
R(OH)
n
+ 1.1n
N
2
O
5
liquid CO
2
R(ONO
2
)
n
+ HNO
3
1a–l2a–l
Scheme 1 For the certain compounds, see Table 2.
†
Dinitrogen pentoxide was synthesized according to the published
procedure.
15
Alcohols were provided by Acros Organics. Carbon dioxide
(99.995%) was supplied by the Linde Gas (Russia). IR spectra were
obtained on a Specord M-80 spectrometer in thin film on NaCl plates
or in KBr pellets.
1
H and
13
C NMR spectra were recorded on a Bruker
AM-300 spectrometer (300 and 75 MHz for
1
H and
13
C, respectively)
using TMS as the internal standard.
n-Hexyl nitrate 2c. Procedure A. A steel autoclave (25 cm
3
) containing
N
2
O
5
(0.95 g, 8.8 mmol) was filled with liquid CO
2
(65 bar) and cooled
to 0 °C. Then 1-hexanol 1c (1 cm
3
, 0.82 g, 8.0 mmol) was added by a
syringe pump with a flow rate of 0.05 cm
3
min
–1
. After the addition,
reactor pressure was 75 bar. The reaction mixture was stirred for 30 min,
CO
2
was then removed, and the residue was poured into ice water (50 ml).
The product was extracted with CH
2
Cl
2
(4 × 10 ml), the combined organic
extracts were washed successively with saturated aqueous NaHCO
3
(2 × 20 ml), water (25 ml) and dried over Na
2
SO
4
. Evaporation of the
solvent afforded 1.06 g (90%) of compound 2c. Nitric esters 2a,b,d,f,j
were synthesized similarly using 1.1 equiv. N
2
O
5
per each hydroxy group
of corresponding alcohol 1 (see Table 2). The physicochemical and spectral
data of obtained nitro esters are below and identical to reported ones.
Procedure B. A steel autoclave (25 cm
3
) containing 1-hexanol 1c (1 cm
3
,
0.82 g, 8 mmol) was filled with liquid CO
2
to a pressure of 60 bar and
cooled to 0 °C. Then N
2
O
5
(0.95 g, 8.8 mmol) dissolved in liquid CO
2
(~ 3.5 g) was added in ten portions. The pressure after the addition was
80 bar. The reaction mixture was stirred for 30 min, CO
2
was then removed,
and the residue was poured into ice water (50 ml). n-Hexyl nitrate 2c was
isolated as described above. The yield of 2c was 1.15 g (97%). Nitrate
esters 2a,b,d–l were synthesized similarly using 1.1 equiv. N
2
O
5
per
hydroxy group of alcohol 1 (see Table 2).
n-Butyl nitrate 2a: bp 134 °C (lit.,
8(e)
130–133 °C), n
D
20
1.4063. IR (NaCl,
n/cm
–1
): 1626 (NO
2
as
), 1270 (NO
2
s
).
1
H NMR (CDCl
3
) d: 4.45 (t, 2 H,
CH
2
ONO
2
, J 6.7 Hz), 1.75–1.66 (m, 2 H, CH
2
), 1.50–1.40 (m, 2 H, CH
2
),
0.96 (t, 3 H, Me, J 7.3 Hz).
13
C NMR (CDCl
3
) d: 73.17, 28.71, 18.89, 13.52.
2-Butyl nitrate 2b: bp 123 °C (lit.,
8(e)
120–122 °C), n
D
20
1.4018. IR (NaCl,
n/cm
–1
) 1625 (NO
2
as
), 1260 (NO
2
s
).
1
H NMR (CDCl
3
) d: 5.01 (q, 1H,
CHONO
2
, J 6.3 Hz), 1.77–1.59 (m, 2 H, CH
2
), 1.33 (d, 2 H, CH
2
, J 6.2 Hz),
0.97 (t, 3 H, Me, J 7.5 Hz).
13
C NMR (CDCl
3
) d: 82.44, 27.03, 17.75,
9.33.
n-Hexyl nitrate 2c: bp 54–55 °C / 4 Torr (lit.,
8(d)
51–53 °C / 4 Torr), n
D
20
1.4191. IR (NaCl, n/cm
–1
): 1630 (NO
2
as
), 1270 (NO
2
s
).
1
H NMR (CDCl
3
)
d: 4.44 (t, 2 H, CH
2
ONO
2
, J 6.6 Hz), 1.76–1.67 (m, 2 H, CH
2
), 1.42–1.31
[m, 6 H, (CH
2
)
3
], 0.90 (t, 3 H, Me, J 6.7 Hz).
13
C NMR (CDCl
3
) d: 73.54,
31.34, 26.79, 27.37, 22.49, 13.94.
Nitration of model compound Table 1 1c in the N
2
O
5
/CO
2
liquid system.
a
Entry N
2
O
5
(equiv.) Time/min Isolated yield of 2c (%)
1 1.0 30 75
2 1.1 30 90
3 1.5 30 89
4 1.1 15 87
5 1.1 60 90
a
The reactions were carried out using 1-hexanol 1c (8 mmol) and N
2
O
5
(8–12 mmol)
at 55–75 bar and 0 °C.