Safe and Convenient Synthesis of Primary N -Nitramines in the Freon Media

Article abstract of DOI:10.1055/s-0036-1588616

A convenient one-pot synthesis of primary aliphatic N-nitramines, which includes the nitration of available N,N′-dialkyloxalamides or N-alkylcarbamates with dinitrogen pentoxide in the 1,1,1,2-tetrafluoroethane media followed by ammonolysis of intermediate N-nitroamides in the same solvent has been developed. The method is environmentally safe, and affords target N-nitramines in up to 94% overall yield.

Full text of DOI:10.1055/s-0036-1588616

SYNTHESIS
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X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
paper
A
M. N. Zharkov et al.
Paper
Synthesis
Safe and Convenient Synthesis of Primary N-Nitramines in the
Freon Media
Mikhail N. Zharkova
Ilya V. Kuchurova
Igor V. Fomenkova
Vladimir A. Tartakovskya
Ivan V. Fedyaninb
O
H
R
N
N
H
R
R
NO2
1. N2O5
2. liquid NH3
N
H
O
or
53–94%
liquid CF3CH2F
6–8 bar, one-pot
H
N
(11 examples)
EtO2C
R
Sergei G. Zlotin*a
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy
of Sciences, 47, Leninsky prosp., 119991 Moscow,
Russian Federation
b A. N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, 28 Vavilova St., 119991 Moscow,
Russian Federation
zlotin@ioc.ac.ru
Received: 27.07.2016
Accepted after revision: 10.09.2016
Published online: 12.10.2016
is not suitable as the medium for subsequent basic hydroly-
sis or ammonolysis reactions because it readily generates
metal carbonates or ammonium carbamate, respectively,
with corresponding reagents.17,18
DOI: 10.1055/s-0036-1588616; Art ID: ss-2016-t0532-op
Abstract A convenient one-pot synthesis of primary aliphatic N-nitra-
mines, which includes the nitration of available N,N′-dialkyloxalamides
or N-alkylcarbamates with dinitrogen pentoxide in the 1,1,1,2-tetraflu-
oroethane media followed by ammonolysis of intermediate N-nitroam-
ides in the same solvent has been developed. The method is environ-
mentally safe, and affords target N-nitramines in up to 94% overall yield.
Herein, we report the first one-pot synthesis of primary
N-nitramines from the corresponding N-alkylamides or N-
alkylcarbamates by a sequence of nitration and ammonoly-
sis reactions performed in the same vessel with the use of
liquid 1,1,1,2-tetrafluoroethane (TFE) as a reaction medi-
um.
Key words nitration, dinitrogen pentoxide, nitramides, nitramines,
TFE is an available compound, which is commercially
used as a freon in freezing units. It is chemically resistant to
both DNP and ammonia, and can be readily liquefied due to
its remarkably low equilibrium vapor pressure (5.7 bar at
20 °C vs 57.3 bar for carbon dioxide).19 Finally, it is, like car-
bon dioxide, practically nontoxic for humans.20,21 Volatile
freons have never been used as media for the synthesis of
N-nitramines.
We have found that N,N′-dialkyloxalamides 1a–d and N-
alkylcarbamates 2a–c react with 10% molar-excess of DNP
under mild conditions in TFE to afford the corresponding
N,N′-dinitrooxalamides 3a–d or N-nitrourethanes 4a–c in
high yields (Table 1). Among alternative starting com-
pounds 1d and 2b, which contain bulky cyclohexyl group,
urethane 2b appeared a more active substrate producing N-
nitrourethane 4b in nearly quantitative yield (Table 1, entry
4 vs 6). Bis-N-alkylcarbamates 6a–c underwent nitration
with DNP (2.2 equiv) in the studied conditions to give the
corresponding bis-N-nitrourethanes 7a–c in 90–98% yield
(entries 8–10). Intermediate nitro compounds 3, 4, and 7
were readily isolated after decompression by standard
methods and fully characterized by NMR/IR spectra and (for
novel compounds 3c and 7b) by microanalysis data.
Taking advantage of the remarkable chemical resistance
of TFE towards electrophilic (DNP) and nucleophilic (NH3)
reagents, we succeeded in attaining a one-pot nitra-
1,1,1,2-tetrafluoroethane
Primary N-nitramines are versatile building blocks for
combinatorial synthesis of various N-nitramino com-
pounds, which are used as components of rocket propel-
lants and plasticizers, or other components of high energy
compositions.1–6 The classic two-step synthesis of primary
N-nitramines is based on the nitration of N-alkylamides (N-
alkylcarbamates) with nitric acid,7 mixed acids (HNO3–
H2SO4),8 or HNO3–Ac2O nitrating system9 followed by basic
hydrolysis7 (ammonolysis)10–13 of corresponding N-nitra-
mides or N-nitrourethanes. However, a highly excessive
amount of the nitrating agents is needed at the nitration
step. As a result, large volumes of wasted acids demanding
utilization are formed.3 Furthermore, the necessity for
shock- and friction-sensitive intermediate N-nitramides
(N-nitrourethanes) to be isolated makes the procedure risky
with respect to the potential for explosion.
Recently, the significantly less harmful for the environ-
ment synthesis of N-nitramides (N-nitrourethanes) by the
nitration of corresponding amides (urethanes) with nearly
equimolar amount of dinitrogen pentoxide (DNP) in liquid
or supercritical carbon dioxide medium has been devel-
oped.14–16 Yet, an expensive high-pressure (up to 150 bar)
equipment is needed in this case. Moreover, carbon dioxide
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
M. N. Zharkov et al.
Paper
Synthesis
Table 1 Synthesis of N,N′-Dinitrooxalamides 3, N-Nitrourethanes 4 and 7, and Their One-Pot Transformation to N-Nitroamines 5 and 8 in TFE Mediuma
O
O
NO2
N
H
N
R
R
N
H
R
N
R
O
NO2
or
O
1
3
R
NO2
N
H
or
N2O5
(2.2 equiv for 1, 5,
1.1 equiv for 2)
NH3
NO2
N
H
(10 equiv for 3, 6
5 equiv for 4)
5
N
EtO2C
R
EtO2C
R
2
4
TFE, 6 bar
5–20 °C
TFE, 8 bar
5–20 °C, 20 min
CO2Et
X
CO2Et
NO2
HN
HN
O2N
O2N
N
N
X
X
NH4NO3,
[C(O)NH2]2 or
EtOC(O)NH2
HN
HN
CO2Et
NO2
CO2Et
6
7
8
Entry
Substrate
R in 1–5
X in 6–8
Nitration time (h)
3, 4, and 7 Yield (%)b 5 and 8 Yield (%)b,c
1
2
1a
1b
1c
1d
2a
2b
2c
6a
6b
6c
Me
–
–
–
–
–
–
–
2.0
2.0
2.0
4.0
0.5
2.0
2.0
2.0
2.0
2.0
3a, 95
3b, 93
3c, 93
3d, 63
4a, 95
4b, 93
4c, 95
7a, 98
7b, 91
7c, 90
5a, 80
5b, 91
5c, 86
5d, 53
5e, 93
5d, 76
5f, 17d
8a, 93
8b, 86
8c, 87
n-Pr
3
n-C5H9
4
c-C6H11
5
Et
6
c-C6H11
7
t-Bu
–
8
-(CH2)2-
-(CH2)3-
9
–
10
–
trans-cyclohexane-1,2-diyl
a The reactions were carried out with 1 or 6 (5 mmol) or 2 (10 mmol), and DNP (11 mmol).
b Isolated yield.
c Yield in the one-pot reaction.
d 1H NMR data.
tion/ammonolysis reaction sequence in TFE medium with-
out isolation of intermediates 3, 4, and 7 (Table 1). Once the
nitrations were complete, the reactor was cooled to 5 °C
and gradually filled with ammonia by means of a syringe
pump. After 20 minutes, TFE and ammonia excess were re-
moved by decompression and the resulting nitramines 5a–f
and 8a–c were isolated from residual ammonium salts by
careful protonation with ethanol or hydrochloric acid (in
case of nitramines 8a–c) (see the experimental section).
The yields of compounds 5 and 8 in the one-pot reaction
were commonly higher (76–93%) than those reported in the
literture.7,13,22–27 The only exception was tert-butylnitra-
mine (5f), which we managed to synthesize in only 17%
yield (1H NMR data). The poor yield may be attributed in
this case to unfavorable steric impact of the bulky tert-butyl
group.
clic N-nitrourethane 1016 in the same TFE medium afforded
(2-nitramino)ethyl carbamate (11) in 94% overall yield
(Scheme 1).
O
O
N2O5
(1.1 equiv)
NH3
(5 equiv)
O2N
O2N
O
NH2
N
H
HN
N
O
O
CF3CH2F, 8 bar
5–20 °C, 1 h
CF3CH2F, 6 bar
5–20 °C, 2 h
O
9
10
11 (94%)
Scheme 1 One-pot synthesis of (2-nitramino)ethyl carbamate (11)
Synthesized nitramines 5, 8, and 11 were characterized
by 1H NMR and IR data. The signals of the NH protons of pri-
mary N-nitramine (δ = 12.10) and amide (δ = 6.54) groups
in the 1H NMR spectrum of compound 11 testify to the ring
cleavage in compound 10. The structure of compound 11 is
also in accordance with the 13C NMR and 14N NMR spectra,
which contained signals of CH2 and C=O carbon atoms (δ =
44.6, 59.6, and 156.4) and the nitrogen atom of the nitro
group (δ = 25.9), respectively. The crystal structure of com-
pound 8с was established by a single-crystal X-ray diffrac-
tion study (Figure 1).28
Functionalized nitramines can also be synthesized un-
der the proposed conditions. Indeed, the nitration of oxazo-
lidine-2-one 9 followed by the one-pot ammonolysis of cy-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
M. N. Zharkov et al.
Paper
Synthesis
quired on a Bruker Alfa spectrophotometer. X-ray diffraction data for
8c were collected on a Bruker APEX DUO diffractometer [λ(MoKα) =
0.71073 Å, ω-scans with 0.55° step and 10 s per frame exposure,
2θ <60°]. Fluid CF3CH2F was obtained from Linde Gas Russia. Starting
34
compounds 1,30 2, 6,31,32 933 and N2O5 were prepared according to
reported methods.
Nitro Compounds 3, 4, and 7; General Procedure
A steel autoclave-reactor containing substrate 1 or 6 (5 mmol or 10
mmol for 2) was filled with liquid TFE at r.t. by one third of volume
and cooled to 5 °С. DNP (1.19 g, 11 mmol) was placed into an auxilia-
ry dosing vessel, which was then closed and filled with the same fluid
TFE by half. The obtained DNP solution was slowly added to the reac-
tor (temperature increase of more than 5 °С is to be avoided during re-
agent addition!). The dosing vessel was twice washed with TFE (one
third of volume) to transfer residual DNP into the reactor. The reac-
tion mixture was stirred at 6 bar at r.t. for the time given in Table 1.
Then H2O (2 mL) was added to the reactor to decompose the excess of
the nitrating agent. The fluid was removed by decompression. The au-
toclave was opened and ice water (20 mL) was added to the residue.
The resulting mixture was neutralized with aq NaHCO3 and extracted
with EtOAc (3 × 20 mL). The combined organic extracts were dried
(anhyd MgSO4) and the solvent was evaporated under reduced pres-
sure (50 Torr) to afford the desired nitro compound 3, 4, or 7 (Table 1).
Figure 1 General view of molecule 8c in crystal. Anisotropic displace-
ment parameters are drawn at 50% probability.
The ORTEP representation of the molecular structure
for compound 8c, as determined by X-ray diffraction, shows
that the cyclohexane ring adopts a chair conformation, and
both nitramine substituents are in equatorial positions. The
N1–N2 and N3–N4 bond lengths are equal to 1.3274(13)
and 1.3303(12) Å, respectively; these values are slightly
higher than 1.318(2) Å reported for N-methylnitramine,29
but are comparable with other aliphatic nitramines. Both
hydrogen atoms of nitramine groups are in weak intermo-
lecular hydrogen bonds with oxygen atoms of nitro groups
[N···O 2.9043(13) and 2.9313(12) Å].
The developed one-pot procedure is environment-
friendly as the only by-products are ammonium nitrate and
ethyl carbamate or oxamide that may have further chemical
or agricultural application (e.g., as fertilizers). The TFE fluid
can be readily re-compressed (as it is in freezing units) and
recycled in the reaction. The recycling would not bring
about any excessive energy expenditure taking into account
the low equilibrium vapor pressure of this compound. From
a practical viewpoint, the method provides an industrially
applicable pathway to produce nitramine-derived high en-
ergy materials.
N,N′-Dimethyl-N,N′-dinitrooxalamide (3a)
Colorless solid; yield: 1.03 g (95%); mp 123–124 °С (EtOAc) (Lit.16 mp
124 °C).
IR (KBr): 1732 and 1706 (C=O), 1572 (NO2), 1345 cm–1 (NO2).
1H NMR (300.13 MHz, DMSO-d6): δ = 3.65 (s, 6 H, CH3).
13C NMR (75.47 MHz, DMSO-d6): δ = 158.6, 32.5.
N,N′-Dinitro-N,N′-di(propyl)oxalamide (3b)
Colorless solid; yield: 1.22 g (93%); mp 41–42 °С (EtOAc) (Lit.35 mp
44 °C).
IR (KBr): 1729 and 1706 (C=O), 1576 (NO2), 1297 cm–1 (NO2).
1H NMR (300.13 MHz, CDCl3): δ = 4.23–4.02 (m, 4 H, 2 × NCH2), 1.77
(sext, J = 7.4 Hz, 4 H, 2 × CH2CH2CH3), 1.00 (t, J = 7.4 Hz, 6 H, 2 × CH3).
13C NMR (75.47 MHz, CDCl3): δ = 159.0, 47.5, 19.8, 10.8.
14N NMR (21.69 MHz, CDCl3): δ = –44.8 (NO2).
In summary, an efficient, safe, and applicable to indus-
try one-pot synthesis of aliphatic N-nitramines from avail-
able N,N′-dialkyloxalamides or N-alkylcarbamates via the
nitration/ammonolysis reaction sequence in 1,1,1,2-tetra-
fluoroethane medium has been developed. A series of novel
(3c, 7b, and 11) and previously reported N-nitramines have
been effectively prepared in up to 94% yields by the devel-
oped procedure.
N,N′-Dinitro-N,N′-di(pentyl)oxalamide (3c)
Light-yellow liquid; yield: 1.48 g (93%); bp 124–126 °С/0.65 Torr.
IR (film): 1707 (C=O), 1577 (NO2), 1303 and 1254 cm–1 (NO2).
1H NMR (300.13 MHz, CDCl3): δ = 3.15 (dt, J = 7.7, 7,4 Hz, 4 H, 2 ×
NCH2), 1.73 (quint, J = 7.1 Hz, 4 H, 2 × NCH2CH2), 1.44–1.24 (m, 8 H, 2
× CH2CH2CH3), 0.91 (t, J = 6.6 Hz, 6 H, 2 × CH3).
13C NMR (75.47 MHz, CDCl3): δ = 158.9, 46.13, 28.5, 25.9, 22.2, 13.9.
14N NMR (21.69 MHz, CDCl3): δ = –44.7 (NO2).
Anal. Calcd for C12H22N4O6: C, 45.3; H, 7.0; N, 17.6. Found: C, 45.1; H,
7.3; N, 17.3.
The reactions were carried out in 22 cm3 steel autoclave equipped
with sapphire windows, magnetic stirrer, and pressure and tempera-
ture sensors. An auxiliary 13 cm3 steel dosing vessel with magnetic
stirrer was used for the preparation of nitrating agent solutions. Melt-
ing points were obtained on Stuart®, SMP40 apparatus. 1H, 13C, and
14N NMR spectra were recorded on a Bruker AM-300 spectrometer
(300.13, 75.47, and 21.69 MHz, respectively). IR spectra were ac-
N,N′-Dicyclohexyl-N,N′-dinitrooxalamide (3d)
Colorless solid; yield: 1.08 g (63%); mp 128 °С (EtOAc) (Lit.25 mp
130 °C).
IR (KBr): 1728 and 1703 (C=O), 1563 (NO2), 1297 cm–1 (NO2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

D
M. N. Zharkov et al.
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Synthesis
1H NMR (300.13 MHz, CDCl3): δ = 4.66 (tt, J = 12.2, 3.6 Hz, 2 H, 2 × CH),
Anal. Calcd for C9H16N4O8: С, 35.1; H, 5.2; N, 18.2. Found: С, 35.4; H,
2.25–1.16 [m, 20 H, 2 × (CH2)5].
5.45; N, 18.2.
13C NMR (75.47 MHz, CDCl3): δ = 159.3, 59.7, 27.9, 26.1, 24.9.
14N NMR (21.69 MHz, CDCl3): δ = –39.1 (NO2).
Diethyl Cyclohexane-1,2-diylbis(nitrocarbamate) (7c)
Yellow liquid; yield: 1.56 (90%); bp 94–95 °С/0.65 Torr; nD20 1.4837.
Anal. Calcd for C24H22N4O6: C, 49.1; H, 6.5; N, 16.4. Found: C, 49.05; H,
6.6; N, 16.3.
IR (film): 1769 (C=O), 1586 (NO2), 1335 and 1310 (NO2), 1234 and
1200 cm–1 (C–O).
1H NMR (300.13 MHz, CDCl3): δ = 5.10–4.98 (m, 2 H, 2 × CH), 4.33 (q,
J = 7.1 Hz, 4 H, 2 × OCH2CH3), 2.16–1.78 (m, 8 H, 2 × CHCH2CH2), 1.34
(t, J = 7.2 Hz, 6 H, 2 × OCH2CH3).
13C NMR (75.47 MHz, CDCl3): δ = 150.9, 65.1, 61.2, 29.3, 24.9, 14.0.
14N NMR (21.69 MHz, CDCl3): δ = –42.8 (NO2).
Ethyl N-Ethyl-N-nitrocarbamate (4a)
Light-yellow liquid; yield: 1.54 g (95%).
IR (film): 1772 (C=O), 1576 (NO2), 1310 (NO2), 1222 cm–1 (C–O).
1H NMR (300.13 MHz, DMSO-d6): δ = 4.32 (q, J = 7.1 Hz, 2 H,
NCH2CH3), 4.05 (q, J = 7.0 Hz, 2 H, OCH2CH3), 1.29 (t, J = 7.1 Hz, 3 H,
NCH2CH3), 1.21 (t, J = 7.0 Hz, 3 H, OCH2CH3).
Anal. Calcd for C12H20N4O8: С, 41.4; H, 5.8; N, 16.1. Found: С, 41.3; H,
5.8; N, 16.25.
Ethyl N-Cyclohexyl-N-nitrocarbamate (4b)
One-Pot Synthesis of N-Nitramines 5, 8, and 11; General Procedure
Colorless liquid; yield: 2.01
g (93%); bp 93–95 °С/0.6 Torr;
nD20 1.4650.
A steel autoclave-reactor containing substrate 1 or 6 (5 mmol or 10
mmol for 2 or 9) was filled with liquid TFE at r.t. by one third of vol-
ume and cooled to 5 °С. DNP (1.19 g, 11 mmol) was placed into an
auxiliary dosing vessel, which was then closed and filled with the
same fluid TFE by half. The obtained DNP solution was slowly added
to the reactor (temperature increase of more than 5 °С is to be avoided
during reagent addition!). The dosing vessel was twice washed with
the fluid TFE (one third of volume) to transfer residual DNP into the
reactor. The reaction mixture was stirred at r.t. at 6 bar for the time
given in Table 1. Once the nitration was completed, the autoclave was
cooled to 5 °С and liquid ammonia (1.3 mL, 50 mmol) was gradually
added with intensive stirring by a syringe pump at a flow-rate of 0.1–
0.2 mL/min (temperature increase of more than 10 °С is to be avoided
during reagent addition!). The reaction mass was stirred at r.t. for 20
min. Then the fluid and the excess of ammonia were removed via de-
compression and the autoclave was opened.
IR (film): 1769 (C=O), 1580 (NO2), 1304 (NO2), 1217 cm–1 (C–O).
1H NMR (300.13 MHz, CDCl3): δ = 4.34 (q, J = 7.1 Hz, 2 H, OCH2CH3),
1.95–1.06 [m, 10 H, (CH2)5], 1.35 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75.47 MHz, CDCl3): δ = 151.3, 64.6, 61.2, 29.5, 25.9, 25.1,
14.0.
14N NMR (21.69 MHz, CDCl3): δ = –40.5 (NO2).
Anal. Calcd for C9H16N2O4: C, 50.0; H, 7.5; N, 13.0. Found: C, 50.3; H,
7.4; N, 12.9.
Ethyl N-tert-Butyl-N-nitrocarbamate (4c)
Yellow liquid; yield: 1.82 g (95%); bp 49 °С/0.8 Torr (Lit.36 bp 49–
51 °C/0.4 Torr); nD20 1.4335.
IR (film): 1769 and 1745 (C=O), 1557 (NO2), 1328 (NO2), 1270 cm–1
(C-O).
Isolation of Nitramines 5a–d; General Procedure
1H NMR (300.13 MHz, CDCl3): δ = 4.32 (q, J = 7.1 Hz, 2 H, OCH2CH3),
1.50 (s, 9 H, t-C4H9), 1.33 (t, J = 7.2 Hz, 3 H, OCH2CH3).
13C NMR (75.47 MHz, CDCl3): δ = 151.6, 64.7, 62.2, 27.2, 13.9.
14N NMR (21.69 MHz, CDCl3): δ = –37.3 (NO2).
After decompression, 96% EtOH (40 mL) was added to the residue and
the mixture was stirred at 50 °С for 10 min. The solvent was evaporat-
ed under reduced pressure (30 Torr). Et2O (40 mL) was added to the
residue and the resulting suspension was vigorously stirred for 5–10
min. The solid (oxamide and NH4NO3) was filtered off and washed
with Et2O (2 × 15 mL). The combined Et2O layers were evaporated to
afford the corresponding nitramine 5a–d (Table 1).
Diethyl Ethane-1,2-diylbis(nitrocarbamate) (7a)
Colorless solid; yield: 1.44 g (98%); mp 81–82 °С (EtOAc) (Lit.16 mp
80–82 °C).
IR (KBr): 1735 (C=O), 1586 (NO2), 1280 (NO2), 1241 cm–1 (C–O).
N-Methylnitramine (5а)
Colorless solid; yield: 0.61 g (80%); mp 36 °С (Et2O); bp 82 °C/12 Torr
1H NMR (300.13 MHz, DMSO-d6): δ = 4.39 (s, 4 H, 2 × CH2NNO2), 4.25
(q, J = 7.1 Hz, 4 H, 2 × OCH2CH3), 1.24 (t, J = 7.1 Hz, 6 H, 2 × OCH2CH3).
(Lit.12 bp 80–85 °C/10 Torr).
IR (KBr): 3432 and 3387 (NH), 1572 (NO2), 1342 cm–1 (NO2).
1H NMR (300.13 MHz, CDCl3): δ = 9.01 (br s, 1 H, NH), 3.18 (s, 3 H,
Diethyl Propane-1,3-diylbis(nitrocarbamate) (7b)
CH3).
Yellow liquid; yield: 1.40 g (91%); bp 131–135 °С/0.7 Torr;
nD20 1.4789.
13C NMR (75.47 MHz, CDCl3): δ = 32.6.
IR (film): 1773 and 1741 (C=O), 1577 (NO2), 1314 (NO2), 1235 cm–1
(C–O).
1H NMR (300.13 MHz, CDCl3): δ = 4.36 (q, J = 7.1 Hz, 4 H, 2 ×
OCH2CH3), 4.13 (t, J = 7.1 Hz, 4 H, 2 × NCH2), 2.10 (quint, J = 7.1 Hz, 2 H,
CH2CH2CH2), 1.36 (t, J = 7.2 Hz, 6 H, 2 × OCH2CH3).
13C NMR (75.47 MHz, CDCl3): δ = 150.4, 65.0, 46.6, 25.6, 14.1.
14N NMR (21.69 MHz, CDCl3): δ = –43.9 (NO2).
14N NMR (21.69 MHz, CDCl3): δ = –25.6 (NO2).
Anal. Calcd for CH4N2O2: С, 15.8; H, 5.3; N, 36.8. Found: C, 15.8; H, 5.2;
N, 36.7.
N-(Propyl)nitramine (5b)
Colorless liquid; yield: 0.95 g (91%); bp 62–62 °С/0.8 Torr (Lit.24 bp
47–48 °C/0.3 Torr); nD20 1.4582.
IR (film): 3299br (NH), 1572 (NO2), 1322 cm–1 (NO2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

E
M. N. Zharkov et al.
Paper
Synthesis
1H NMR (300.13 MHz, CDCl3): δ = 8.61 (br s, 1 H, NH), 3.61–3.48 (m, 2
H, NHCH2), 1.65 (sext, J = 7.3 Hz, 2 H, CH2CH2CH3), 0.98 (t, J = 7.4 Hz, 3
H, CH3).
Isolation of Nitramines 8a–c and 11; General Procedure
After decompression, the residue was extracted with Et2O (4 × 15 mL)
(for 8a–c) to afford ethyl carbamate as by-product (0.85 g, 98%). Cold
H2O (10 mL) was added to the residue and the mixture was acidified
by aq 10 N HCl (2 mL) with vigorous stirring. The precipitate was fil-
tered, washed with H2O (2 × 15 mL), and dried at r.t. (70 Torr) to af-
ford the corresponding nitramines 8a and 8c. Alternatively, the aque-
ous mixture was extracted with EtOAc (4 × 15 mL). The combined or-
ganic extracts were dried (anhyd MgSO4) and the solvent was
evaporated under reduced pressure (50 Torr) to afford the corre-
sponding nitramine 8b or 11.
N-(Pentyl)nitramine (5c)
Colorless liquid; yield: 1.14 g (86%); bp 86 °С/0.8 Torr (Lit.13 mp 60–
62 °C/0.02 Torr); nD20 1.4595.
IR (film): 3287 and 3139 (NH), 1577 (NO2), 1331 cm–1 (NO2).
1H NMR (300.13 MHz, CDCl3): δ = 8.80 (br s, 1 H, NH), 3.62–3.48 (m, 2
H, NHCH2), 1.60 (quint, J = 6.8 Hz, 2 H, NHCH2CH2), 1.39–1.27 (m, 4 H,
CH2CH2CH3), 0.89 (t, J = 6.2 Hz, 3 H, CH3).
13C NMR (75.47 MHz, CDCl3): δ = 46.4, 28.8, 26.5, 22.2, 13.9.
14N NMR (21.69 MHz, CDCl3): δ = –22.6 (NO2).
1,2-Ethylenedinitramine (8а)
Colorless solid; yield: 0.70 g (93%); mp 177 °С (H2O) (Lit.4 mp 180 °C).
Anal. Calcd for C5H12N2O2: С, 45.4; H, 9.15; N, 21.2. Found: C, 45.7; H,
IR (KBr): 3236 and 3117 (NH), 1594 (NO2), 1351 cm–1 (NO2).
9.0, N, 21.25.
1H NMR (300.13 MHz, DMSO-d6): δ = 12.08 (br s, 2 H, NH), 3.59 (s, 4
H, CH2CH2).
N-Cyclohexylnitramine (5d)
14N NMR (21.69 MHz, DMSO-d6): δ = –26.0 (NO2).
From 1d; Yellow viscous liquid; yield: 0.60 g (53%); bp 98 °С/0.7 Torr
(Lit.11 bp 121–122 °C/3 Torr; nD20 1.5000.
IR (film): 3278 and 3137 (NH), 1576 (NO2), 1339 cm–1 (NO2).
1H NMR (300.13 MHz, CDCl3): δ = 8.75 (br s, 1 H, NH), 4.02–3.88 (m, 1
H, CH), 2.07–1.15 [m, 10 H, (CH2)5].
13C NMR (75.47 MHz, CDCl3): δ = 55.5, 30.3, 25.3, 24.3.
14N NMR (21.69 MHz, CDCl3): δ = –28.8 (NO2).
1,3-Propylenedinitramine (8b)
Colorless solid; 0.71 g (86%); mp 66–67 °С (EtOAc) (Lit.22 mp 67 °C).
IR (KBr): 3320 and 3099 (NH), 1579 (NO2), 1314 cm–1 (NO2).
1H NMR (300.13 MHz, DMSO-d6): δ = 12.00 (br s, 2 H, NH), 3.45 (t, J =
7.0 Hz, 4 H, 2 × NHCH2), 1.76 (quint, J = 6.9 Hz, 2 H, CH2CH2CH2).
14N NMR (21.69 MHz, DMSO-d6): δ = –25.6 (NO2).
Anal. Calcd for C6H12N2O2: C, 50.0; H, 8.4; N, 19.4. Found: C, 50.0; H,
8.4, N, 19.5.
1,2-Cyclohexanediyldinitramine (8с)
Colorless solid; yield: 0.89 g (87%); mp 150 °С (H2O) (Lit.27 mp 163
°C).
Isolation of Nitramines 5d–f; General Procedure
After decompression, the residue was extracted with Et2O (4 × 15
mL). The combined organic extracts were evaporated to afford ethyl
carbamate (quant). EtOH (96%, 40 mL) was added to the solid residue
(a mixture of NH4NO3 and N-alkylnitramine 5 ammonium salt) and
the mixture was stirred at 55 °С for 10 min. The solvent was removed
under reduced pressure (30 Torr). Et2O (40 mL) was added to the resi-
due and the resulting suspension was vigorously stirred for 5–10 min.
The solid (NH4NO3) was filtered off, and washed with Et2O (2 × 15
mL). The combined organic phases were evaporated to afford the cor-
responding nitramines 5d–f (Table 1).
IR (KBr): 3315 and 3223 (NH), 1587 and 1557 (NO2), 1297 cm–1 (NO2).
1H NMR (300.13 MHz, DMSO-d6): δ = 12.13 (br s, 2 H, NH), 4.02–3.81
(m, 2 H, 2 × CH), 2.14–1.89 (m, 2 H, 2 × CHCHBCH2), 1.79–1.55 (m, 2 H,
2 × CHCHACH2), 1.4–1.11 (m, 4 H, 2 × CHCH2CH2).
13C NMR (75.47 MHz, DMSO-d6): δ = 55.7, 29.5, 23.5.
14N NMR (21.69 MHz, DMSO-d6): δ = –27.3 (NO2).
Anal. Calcd for C6H12N4O4: С, 35.3; H, 5.9; N, 27.4. Found: C, 35.6; H,
6.0; N, 27.4.
(2-Nitramino)ethyl Carbamate (11)
N-Cyclohexylnitramine (5d)
Colorless solid; yield: 1.10 g (94%); mp 84 °С (EtOAc).
From 2b: Yellow viscous liquid; yield: 0.87 g (76%).
IR (KBr): 3490 (NH2), 3367 and 3306 (NH), 3189 and 3110 (NH2),
1710 (C=O), 1576 (NO2), 1317 (NO2), 1238 cm–1 (C–O).
1H NMR (300.13 MHz, DMSO-d6): δ = 12.10 (br s, 1 H, NH), 6.54 (br s,
2 H, NH2), 4.04 (t, J = 5.3 Hz, 2 H, OCH2), 3.61 (q, J = 4.8 Hz, 2 H,
NHCH2).
13C NMR (75.47 MHz, DMSO-d6): δ = 156.4, 59.6, 44.6.
14N NMR (21.69 MHz, DMSO-d6): δ = –25.9 (NO2).
Characteristics of the product were similar to those for compound 5d
obtained from 1d.
N-Ethylnitramine (5e)
Colorless liquid; yield: 0.84 g (93%); bp 82–83 °С/8 Torr (Lit.37 bp 98
°C/15 Torr); nD20 1.4545.
IR (film): 3281br (NH), 1574 (NO2), 1322 cm–1 (NO2).
Anal. Calcd for C3H7N3O4: C, 24.2; H, 4.7; N, 28.2. Found: C, 24.2; H,
4.8; N, 28.05.
1H NMR (300.13 MHz, CDCl3): δ = 9.14 (br s, 1 H, NH), 3.59 (dq, J = 7.0,
1.9 Hz, 2 H, CH2), 1.22 (t, J = 7.2 Hz, 3 H, CH3).
N-tert-Butylnitramine (5f)
1H NMR (300.13 MHz, CDCl3): δ = 8.60 (br s, 1 H, NH), 1.39 (s, 9 H, t-
Acknowledgment
C4H9).
The work was financially supported by the Russian Foundation of Ba-
sic Research (projects 13-03-12223 and 16-29-01042).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
M. N. Zharkov et al.
Paper
Synthesis
Supporting Information
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Supporting information for this article is available online at
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F