Synthesis of 3-(2-azidoethyl)-1,5-dinitro-1,3,5-triazacycloheptane

Full text of DOI:10.1134/S1070428007100363

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 10, pp. 1581−1583. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © A. S. Medvedeva, L. P. Safronova, M. M. Demina, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 10,
pp. 1582−1584.
SHORT
COMMUNICATIONS
Synthesis of 3-(2-Azidoethyl)-1,5-dinitro-1,3,5-triazacycloheptane
A. S. Medvedeva, L. P. Safronova, and M. M. Demina
Faworsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, Irkutsk, 664033 Russia
e-mail: amedved@irioch.irk.ru
Received May 3, 2007
DOI: 10.1134/S1070428007100363
Cyclic nitroamines are known as important energy-
rich compounds [1] and biologically active nucleosides
[2, 3]. Owing to the easily departing nitro group hetero-
cyclic N-nitroamines are used as mild N- [4] and C-
nitrating agents [2, 5].
The information on cyclic azidonitroamines [13] is
very limited for they are inaccessible and instable.
Organic azides are sensitive to mechanical actions [6]
that limits their application. The presence of a seven-
membered heterocycle should favor increased stability
of azidonitroamines. Aiming at preparation of azido-
nitroamines stable under common conditions we carried
out a synthesis of previously unknown 3-(2-azidoethyl)-
1,5-dinitro-1,3,5-triazacycloheptane.
Introduction of functional groups into the side chain
of the cyclic nitroamines extends the synthetic potential
of these compounds. In particular, the presence of
an azido group not only increases the energy-content of
nitroamines but also opens new opportunities to apply
them as energy-rich precursors in preparation of a wide
range of new derivatives [6, 7]. One of the widely spread
and swiftly developing methods of synthetic application
of azides is the 1,3-dipolar cycloaddition of these com-
pounds to acetylene systems for preparation of versatile
1,2,3-triazoles interesting for medicine [8], nanoparticles
generation [9, 10], producing functionalized oligo-
saccharides [11] and dendrimers [9].
In the published description of the synthesis of 3-(2-
hydroxyethyl)-1,5-dinitro-1,3,5-triazacycloheptane (I)
obtained by Mannich reaction through condensation of
N,N'-ethylenedinitroamine with formaldehyde and
monoethanolamine [14] no spectral characteristics of the
compound were given. For subsequent introduction of
an azido group into the side chain of heterocyclic nitro-
amine I we investigated the electrophilic substitution of
the hydroxy group by chlorine and tosyl group.
The reactivity of functionalized nitroamines may be
governed both by the character of the functional groups
and/or by the relatively weak chemical bond N−NO2
sensitive to the action of bases [12] and acids [2]. The
lability of the bond requires special mild conditions for
chemical transformations in the side chain of cyclic
nitroamines.
The chlorination of heterocyclic alcohol I with thionyl
chloride in a mixture of dichloromethane and pyridine
at 42–70°C within 6 h occurred with the formation of
intermediate themally unstable chlorosulfite II. After
recrystallization compound II from chloroform we
isolated previously unknown 1,5-dinitro-3-(2-chloro-
ethyl)-1,3,5-triazacycloheptane (III) in 30% yield, mp
Scheme 1.
O2N
O2N
O2N
N
N
N
SOCl2
Py
N CH2CH2OH
N CH2CH2OSOCl
N CH2CH2Cl
_ SO2
N
N
N
O2N
O2N
O2N
I
II
III
1581

MEDVEDEVA et al.
1582
198–199°C (Scheme 1). The structure and composition
of compound II are confirmed by H NMR spectrum
ized by the signals of the methylene protons of the ring
and the side chain.
1
and elemental analysis. The 1H NMR spectrum alongside
the singlets of methylene protons belonging to the seven-
membered heterocycle (4.17 and 5.12 ppm) and a triplet
at 2.90 ppm (NCH2, side chain) contains a triplet of CH2O
at 4.02 ppm.
3-(2-Hydroxyethyl)-1,5-dinitro-1,3,5-triaza-
cycloheptane (I). Yield 71%, mp 105–106°C (104–
105°C [14]). IR spectrum, ν, cm–1: 720, 750, 798, 880,
930, 950, 1005, 1015, 1050, 1070, 1130, 1160, 1195,
1240, 1260, 1295, 1300, 1340, 1400, 1500, 1505, 2850,
2890, 2940, 3060, 3400 br. 1H NMR spectrum (DMSO-d6),
δ, ppm: 2.56 t (2H, NCH2, side chain, 3J 6.1 Hz), 3.52 t
(2H, CH2O, 3J 6.1 Hz), 4.19 C (4H, NCH2CH2N), 4.62
C (1H, OH), 5.14 C (4H, NCH2N).
The IR spectrum of compound III contains absorption
bands of the stretching vibrations of the nitro group in
the region 1340, 1500 cm-1. 1H NMR spectrum is char-
acterized by the signals of the methylene protons of the
ring and the side chain. In the 13C NMR spectrum signals
are observed from the fragments NCH2N, NCH2CH2N,
CH2Cl, and NCH2 (side chain).
1,5-Dinitro-3-(2-chloroethyl)-1,3,5-triaza-
cycloheptane (III). To a mixture of 2.0 g (8.5 mmol) of
alcohol I, 0.7 ml (8.5 mmol) of pyridine, and 7 ml of
dichloromethane at cooling with ice a solution was added
of 0.7 ml (9.5 mmol) of thionyl chloride in 6 ml of
dichloromethane. The reaction mixture was stirred for
4 h at 40°C, the solvent was distilled off, 6 ml of pyridine
was added, and the stirring was continued for 2 h at 70°C.
On cooling the mixture was poured on ice, the oily layer
was separated, diluted with 5 ml of dichloromethane,
the separated precipitate was filtered off and dried in a
vacuum. We isolated 0.97 g of powdery chlorosulfite
II. 1H NMR spectrum (DMSO-d6), δ, ppm: 2.90 t (2H,
By reaction of alcohol I with p-toluenesulfonyl
chloride in pyridine we obtained a previously unknown
1,5-dinitro-3-(2-tosylethyl)-1,3,5-triazacycloheptane
(IV) in 73% yield (Scheme 2). In the IR spectrum of
tosylate IV the stretching vibrations bands are present
1
from the nitro group and the phenyl ring. H NMR
spectrum contains the signals from the methylene protons
of the aza ring NCH2CH2N and NCH2N, and also of the
side chain NCH2, CH2O, the resonances of phenyl and
methyl groups.
3
NCH2, side chain, J 5.1 Hz), 4.02 t (2H, CH2O,
The synthesis of the target azidonitroamine was
performed by replacing with azide ion the tosyl group
of compound IV obtained in a preparative yield. It is
known that 1-(bromomethyl)-3,5,7-trinitro-1,3,5,7-tetra-
azacyclooctane is inert to the treatment with sodium
azide, and the bromine is readily substituted at the use
of generated in situ acyl azide [13].
3J 5.1 Hz), 4.17 s (4H, NCH2CH2N), 5.12 s (4H, NCH2N).
Found, %: C 23.51; H 4.23; Cl 10.30; N 21.20; S 11.16.
C6H12ClN5O6S. Calculated, %: C 22.67; H 3.78;
Cl 11.18; N 22.04; S 10.07. On recrystallization of
compound II from chloroform we isolated 0.64 (30%)
of colorless crystals of compound III, mp 198–199°C.
IR spectrum, ν, cm–1: 700, 750, 785, 800, 880, 905, 935,
945, 960, 1000, 1020, 1070, 1100, 1130, 1150, 1180,
1220, 1240, 1260, 1290, 1305, 1340 [νs(NO2)], 1370,
1395, 1430, 1450, 1490, 1500 [νas(NO2)], 1605 sh. 1H NMR
spectrum (DMSO-d6), δ, ppm: 2.97 t (2H, NCH2, side
chain, 3J 6.8 Hz), 3.73 t (2H, CH2Cl, 3J 6.8 Hz), 4.21 s
(4H, NCH2CH2N), 5.16 s (4H, NCH2N). 13C NMR
spectrum (DMSO-d6), δ, ppm: 67.45 (NCH2N), 50.77
(NCH2CH2N), 46.35 (CH2Cl), 41.73 (NCH2, side chain).
By reaction of tosylate IV with sodium azide in DMF
within 15 h at 95–100°C we obtained previously
unknown 3-(2-azidoethyl)-1,5-dinitro-1,3,5-triazacyclo-
heptane (V) in 54% yield. The IR spectrum of azido-
nitroamine V contains the absorption bands of the
stretching vibrations of the nitro group and a strong band
corresponding to the stretching vibrations of the azido
group. 1H NMR spectrum of compound V is character-
Scheme 2.
O2N
O2N
N
N
NaN3
DMF
TsCl
Py
I
N CH2CH2OTs
N CH2CH2N3
N
N
O2N
O2N
IV
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 10 2007

SYNTHESIS OF 3-(2-AZIDOETHYL)-1,5-DINITRO-1,3,5-TRIAZACYCLOHEPTANE
1583
Found, %: C 28.20; H 5.13; Cl 14.13; N 27.20.
REFERENCES
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1,5-Dinitro-3-(2-tosylethyl)-1,3,5-triazacyclo-
heptane (IV). To a solution of 1.18 g (5 mmol) of alcohol
I in 10 ml of anhydrous pyridine at –2...–4°C was added
by portions 1.4 g (7 mmol) of p-toluenesulfonyl chloride
within 30 min. The reaction mixture was stirred at room
temperature for 4 h, the solution was poured into a mix-
ture of 30 g of ice and 4 ml of concn. HCl. The precipitat-
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1.52 g (73%), mp 113–115°C (chloroform–hexane). IR
spectrum, ν, cm–1: 700, 720, 745, 790, 810, 880, 885,
945, 1010, 1055, 1070, 1080, 1140, 1170, 1180, 1220, 1260,
1265, 1295, 1345 [νs(NO2)], 1490, 1510 [νas(NO2)], 1595
(Ph). 1H NMR spectrum (CDCl3), δ, ppm: 2.44 C (3H,
3
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(2H, CH2O, 3J 5.1 Hz), 4.18 s (4H, NCH2CH2N), 5.02 s
(4H, NCH2N), 7.34 d (2H, Ph), 7.79 d (2H, Ph). Found,
%: C 40.01; H 5.02; N 17.90; S 7.95. C13H19N5O7S.
Calculated, %: C 40.09; H 4.91; N 17.98; S 8.23.
3-(2-Azidoethyl)-1,5-dinitro-1,3,5-triaza-
cycloheptane (V). A mixture of 1.0 g (2.5 mmol) of
tosylate IV, 0.2 g (3.0 mmol) of sodium azide, and 15 ml
of anhydrous DMF was stirred for 15 h at 95–100°C.
The reaction mixture was cooled to 10°C and poured
into 20 ml of ice water. The crystalline precipitate was
filtered off, washed with water and ether, and dried under
a reduced pressure. Yield 0.35 g (54%), mp 115–117°C
(chloroform–hexane). IR spectrum, ν, cm–1: 700, 750,
795, 800, 850, 895, 945, 980, 1020, 1050, 1070, 1130,
1170, 1230, 1235, 1260, 1290, 1305, 1340 [νs(NO2)],
1
1505 [νas(NO2)], 2100 C (N3). H NMR spectrum
(CDCl3), δ, ppm: 2.96 t (2H, NCH2, side chain, 3J 6.8 Hz),
3.46 t (2H, CH2N3, 3J 6.8 Hz), 4.22 s (4H, NCH2CH2N),
5.12 s (4H, NCH2N). Found, %: C 27.68; H 4.85; N 43.50.
C6H12N8O4. Calculated, %: C 27.69; H 4.65; N 43.06.
IR spectra were recorded on a spectrophotometer
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and 100.62 MHz respectively), internal reference HMDS.
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[15].
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 10 2007