Facile preparation of 7,11-di(4-nitrobenzenesulfonyl)-diaza-1,4-dioxa-7,11- spiro[4,7]dodecan-9-one

Article abstract of DOI:10.1002/jhet.5570430242

Compound 1 as a key intermediate for the synthesis of 3,3,7,7-tetrakis- (difluoroamino)octahydro-1,5-dinitro-1,5-diazocine (HNFX) and 3,3-bis(difluoroamino)octahydro-1,5,7,7-tetranitro-1,5-diazocine (TNFX) is described. Cycloalkylation of 3 with 1,3-dibro

Full text of DOI:10.1002/jhet.5570430242

Mar-Apr 2006
519
Facile Preparation of 7,11-Di(4-nitrobenzenesulfonyl)-diaza-1,4-
dioxa-7,11-spiro[4,7]dodecan-9-one
Young-Dae Park, Su-Dong Cho, Jeum-Jong Kim, Ho-Kyun Kim,
Deok-Heon Kweon, Sang-Gyeong Lee, and Yong-Jin Yoon *
Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University,
Chinju 660-701, Korea.
yjyoon@nongae.gsnu.ac.kr
Received July 29, 2005
Br Br
O
NsHN
NHNs
NH2 NH2
OH
O
OH
NNs
3 steps
NsN
2 steps
O
Compound 1 as a key intermediate for the synthesis of 3,3,7,7-tetrakis-(difluoroamino)octahydro-1,5-
dinitro-1,5-diazocine (HNFX) and 3,3-bis(difluoroamino)octahydro-1,5,7,7-tetranitro-1,5-diazocine
(TNFX) is described. Cycloalkylation of 3 with 1,3-dibromopropan-2-ol (4) afforded 1,5-protected-1,5-
diazocine 2, followed by chromic acid oxidation to ketone 1 in good yield.
J. Heterocyclic Chem., 43, 519 (2006).
Scheme 1
NNs
Gem-Bis(difluoroamino)-substituted heterocyclic nitra-
mines have independently been proposed by Zheng et al. [1]
and Chapman, et al. [2] as potentially superior explosives or
solid propellant oxidizers. For instance, 3,3,7,7-tetrakis-
(difluoroamino)octahydro-1,5-dinitro-1,5-diazocine (HNFX)
[3] and 3,3-bis(difluoroamino)octahydro-1,5,7,7-tetranitro-
1,5-diazocine (TNFX) [4] have received much attention.
Recently, some new synthetic methods have been reported
for this intermediate [4-6]. The key intermediates for the
synthesis of HNFX and TNFX are 1,5-bis(4-nitro-
benzenesulfonyl or acyl)-1,5-diazocin-3,7(2H,6H)-dione
[5,6] and 1,5-bis(4-nitrobenzenesulfonyl)-[1,3]dioxolan-2-yl-
1,5-diazacin-3(2H)-one [4]. Despite the importance of 3-
halo-2-(halomethyl)-1-propenes as a key material for the
construction of 1,5-diazacycloocatan-3,7(2H,6H)-one ring,
their use is impeded by high cost and, relatively inefficient
preparative procedures [7-9]. The method for the
construction of 1,5-diazocine also suffers from one or more
limitations including the multistage process, the use of
ozone, and the low yield.
This paper reports on a convenient synthesis of 7,11-di(4-
nitrobenzenesulfonyl)-1,4-dioxa-7,11-diaza-spiro[4,7]do-
decan-9-one (1) as a key intermediate for HNFX and TNFX.
The retrosynthesis of compound 1 is shown in Scheme
1, where 1,3-dibromopropan-2-ol (4) is a useful moiety
for the construction of the 1,5-diazocine ring from
compound 3. Therefore, we selected commercially
available compound 4 as a key source of a three carbon
synthon.
O
O
O
O
NHNs
NsHN
Br
Br
NNs
+
NsN
NsN
O
O
OH
OH
O
1
2
3
4
1,3-diaminopropan-2-ol (5) was N-protected by p-
nitrobenzenesulfonyl groups, followed by chromic acid
oxidation to ketone 7, and the latter carbonyl function was
protected through reaction with ethylene glycol to form its
1,3-dioxolane derivative 3 in 84% yield. Cycloalkylation
of 3 with 1,3-dibromopropan-2-ol (4) instead of 3-halo-2-
(halomethyl)-1-propene
afforded
1,5-protected-1,5-
diazocine 2 in 81% yield. Oxidation of 2 with chromic
acid gave the corresponding ketone 1 in 85% yield.
The structures of synthetic compounds were established
by the IR, NMR and elemental analyses. The proton
magnetic resonance spectrum of 2 showed proton signals
of six CH2, one CH and one OH involving the proton
signals of two phenyl rings. The infrared spectrum of 1
showed the absorption peak of carbonyl group at 1750
cm-1 instead of the absorption peak of hydroxyl group.
The proton magnetic resonance spectrum of 1 also
showed the proton signals of six CH2 involving the proton
signals of two phenyl rings.
In conclusion, our preparation procedures demonstrated
that 7,11-di(4-nitrobenzenesulfonyl)-1,4-dioxa-7,11-diaza-
spiro[4,7]dodecan-9-one (1) was successfully synthesized
In our strategy for the synthesis of compound 1 outlined
in Scheme 2, the commercially available starting material,

520
Y.-D. Park, S.-D. Cho, J.-J. Kim, H.-K. Kim, D.-H. Kweon,
S.-G. Lee, and Y.-J. Yoon
Vol 43
Scheme 2
NHNs
NH2 NH2
NsHN
NHNs
NsHN
p-NsCl, K2CO3
CrO3, H2SO4
H2O, THF
(90%)
H2O, acetone
(85%)
OH
OH
O
5
6
7
ethylene glycol
TsOH, toulene
(84%)
O
O
O
O
i) NaOMe
MeOH
NHNs
Br
Br
NsHN
NNs
NNs
CrO3, H2SO4
NsN
NsN
+
H2O, acetone
(85%)
ii) EtOH
O
O
OH
O
OH
1
3
2
4
mixture was stirred for 12 hours at room temperature. After
pouring the mixture into ice water (200 mL) with stirring, the
resulting residue was filtered and washed with excess water to
give an 85% yield of 7 as white crystals (THF/n-hexane = 1:2,
v/v), mp. 202-204 °C; IR (KBr) 3300, 2900, 1750, 1620, 1540,
from compound 5 and 1,1-dibromopropen-2-ol (4) as a
C3- synthon.
EXPEREMENRAL
1
1360, 1160 cm-1; H NMR (acetone-d6): ꢀ 4,13 (s, 4H), 7.12 (s,
2H), 8.11 (d, J = 8.7, 4H), 8.40 ppm (d, 4H, J = 8.7 Hz); 13C
NMR (acetone-d6): ꢀ 49.1, 124.3, 127.9, 146.1, 149.4, 199.9
ppm.
Melting points were determined with a capillary apparatus
1
and uncorrected. H and 13C NMR spectra were recorded on a
Varian Inova 500 spectrometer with chemical shifts values
Anal. Calcd for C15H14N4O9S2: C, 39.30; H, 3.08; N, 12.22; S,
13.99. Found: C, 39.38; H, 3.11; N, 12.31; S, 14.02.
reported in ꢀ units (ppm) relative to an internal standard (TMS).
IR spectra were obtained on
a
Hitachi 270-50 IR
spectrophotometer. Elemental analyses were performed with a
Perkin Elmer 240C. Open-bed chromatography was carried out
on silica gel (70 ~ 230 mesh, Merck) using gravity flow. The
column was packed as slurries with the elution solvent.
2-Ethylenedioxy-1,3-di(4-nitrobenzenesulfonamido)propane (3).
A mixture of 7 (6 g, 26 mmol), ethylene glycol (3 g, 48
mmol), p-toluene sulfonic acid monohydrate (0.25 g) and
toluene (100 mL) was refluxed for 3 days in a two necked flask
equipped with a Dean-Stark tube. After cooling to room
temperature, the mixture was filtered and washed with
methylene chloride to give an 84% yield of 3, White crystals
(THF), mp 224-226 °C; IR (KBr) 3300, 3150, 2900, 1620, 1540,
1370, 1180, 1060 cm-1; 1H NMR (DMSO-d6): ꢀ 2.96 (d, 4H, J =
6.4 Hz), 3.59 (s, 4H), 7.99 (d, 4H, J = 9.1 Hz), 8.13 (s, 2H), 8.37
ppm (d, 4H, J = 8.84 Hz); 13C NMR (DMSO-d6): ꢀ 45.9, 65.0,
106.7, 124.2, 127.8, 146.7, 149.3 ppm.
1,3-Di(4-nitrobenzenesulfonamido)propanol (6).
Compound 5 (1 g, 11.7 mmol) and potassium carbonate (4.3
g, 31 mmol) were dissolved in water (20 mL). The
tetrahydrofuran solution of 4-nitrobenzenesulfonyl chloride (5.8
g, 26.4 mmol, of sulfonyl chloride dissolved in 15 mL of THF)
was slowly added to this solution. The reaction mixture was
stirred for 12 hours. After evaporating tetrahydrofuran under
reduced pressure, the residue was filtered. This residue was
washed with excess water, and then methylene chloride (100
mL). The resulting residue was applied to the top of an open-bed
silica gel column (3 x 7 cm). The column was eluted with ethyl
acetate/n-hexane (1:1, v/v). Fractions containing the product
were combined, evaporated under reduced pressure and dried in
air to give compound 6 in 90% yield as white crystals (ethyl
acetate/n-hexane = 1:1, v/v), mp 205-207 °C; IR (KBr) 3550,
3300, 2900, 1620, 1530, 1350, 1160 cm-1; 1H NMR (acetone-d6):
ꢀ 2.96 (m, 2H), 3.11 (m, 2H), 3.78 (m, 1H, D2O exchangeable),
4.40 (d, 1H, J = 5.5 Hz, D2O exchangeable), 6.89 (m, 2H), 8.11
(d, 4H, J = 9.15 Hz), 8.42 ppm (d, 4H, J = 9.15 Hz); 13C NMR
(acetone-d6): ꢀ 47.4, 69.8, 125.2, 129.2, 147.5, 151.0 ppm.
Anal. Calcd for C15H16N4O9S2: C, 39.13; H, 3.50; N, 12.17; S,
13.93. Found: C, 39.21; H, 3.55; N, 12.22; S, 13.98
Anal. Calcd for C17H18N4O10S2: C, 40.64; H, 3.61; N, 11.15; S,
12.76. Found: C, 40.71; H, 3.70; N, 11.21; S, 12.81.
7,11-Di(4-nitrobenzenesulfonyl)-1,4-dioxa-7,11-diaza-
spiro[4,7]dodecan-9-ol (2).
To a methanolic solution of 3 (3 g, 7.2 mmol in 200 mL of
dry methanol), methanolic sodium methoxide (NaOMe, 0.5 g,
21 mmol in 50 mL of dry methanol) was added slowly with
stirring. The mixture was refluxed for 1 hour. After evaporating
methanol under reduced pressure, the resulting residue was
dissolved in ethanol (200 mL). A solution of 4 (2.3 g, 10.8 mmol
in 50 mL of ethanol) was added slowly to the above ethanol
solution with stirring. The reaction mixture was refluxed for 24
hours. After cooling to room temperature, the mixture was
poured into ice water (300 mL). The solution was adjusted to pH
10 using conc-HCl. The resulting precipitate was filtered and
washed with excess water. The residue was applied to the top of
an open-bed silica gel column (3 x 7 cm). The column was
eluted with ethyl acetate/methylene chloride (0.5:9.5, v/v). The
1,3-Di(4-nitrobenzenesulfonamido)propan-2-one (7).
To the solution of 6 (5 g, 11.17 mmol in acetone 150 mL),
chromium (VI)oxide solution (2.9 g of CrO3 and 3 mL of H2SO4
in 8 mL of water) was added slowly stirring at 20 °C. The

Mar-Apr 2006
Facile Preparation of 7,11-Di(4-nitrobenzenesulfonyl)-diaza-1,4-
dioxa-7,11-spiro[4,7]dodecan-9-one
521
fraction containing the product were combined and evaporated
under reduced pressure to give an 81% yield of 2, Pale yellow
crystals (THF/n-hexane = 1:2, v/v), mp. 249-251 °C; IR (KBr)
3500, 3110, 2900, 1620, 1530, 1360, 1100 cm-1; 1H NMR
(DMSO-d6): ꢀ 3.11 (m, 2H), 3.25 (d, 2H, J = 14.1 Hz), 3.43 (m,
2H), 3.63 (d, 2H, J = 14.1 Hz), 3.83 (m, 1H), 3.92 (s, 4H), 5.27
(bs, 1H, deuterium oxide-exchangeable), 8.12 (d, 4H, J = 8.4
Hz), 8.41 ppm (d, 4H, J = 8.4 Hz); 13C NMR (DMSO-d6): ꢀ
53.87, 54.94, 64.61, 67.87, 105.65, 124.57, 128.82, 143.71,
149.83ppm.
8.6 Hz), 8.41 ppm (d, 4H, J = 8.6 Hz); 13C NMR (DMSO-d6):
ꢀ 55.15, 64.85, 66.94, 106.54, 124.77, 128.77, 142.94, 150.10,
202.42 ppm.
Anal. Calcd. for C20H20N4O11S2: C, 43.16; H, 3.62; N, 10.07;
S, 11.52. Found: C, 43.22; H, 3.70; N, 10.13; S, 11.59.
REFERENCES AND NOTES
[1] Y. Zheng, T. Huang, M. Zhang, X. Wang, International
Beijing,
Synposium on Pyrotechnics and Explosives [Proceedings],
China, Oct 1987; China Academic Publishers: Beijing, 1987; pp 234-
240).
Anal. Calcd for C20H22N4O11S2: C, 43.01; H, 3.97; N, 10.03;
S, 11.48. Found: C, 43.09; H, 4.04; N, 10.21; S, 11.53.
[2] R. D. Chapman, T. G. Archibald, K. Baum, Research in
Energetic Compounds, Report ONR-7-1 (Interim); Fluorochem Inc.:
Azusa, CA, Oct 1989.
7,11-Di(4-nitrobenzenesulfonyl)-1,4-dioxa-7,11-diaza-spiro[4,7]-
dodecan-9-one (1).
[3] R. S. Miller, Mater. Res. Soc. Sym. Proc., 418, 3 (1996).
[4] T. Axenrod, X. –P. Guan, J. Sun, L. Qi, R. D. Chapman, R.
D. Gilardi, Tetrahedron Lett., 42, 2621 (2001).
[5] R. D. Chapman, M. F. Welker, C. B. Kreutzberger, J. Org.
Chem., 63, 1566 (1998).
[6] P. R. Dave, F. Forohar, J. Org. Chem., 61, 8897 (1996).
[7] T. Axenrod, K. K. Das, H. Yazdekhasti, Org. Orep. Proced.
Int., 29, 358 (1997).
To a solution of 2 (1 g, 1.8 mmol in acetone 50 mL),
chrominium (VI) oxide solution (0.54 g of CrO3 and 1 mL of
H2SO4 in 8 mL of water) was added slowly stirring at 20 °C. The
mixture was stirred for 12 hours at room temperature. After
pouring the mixture into ice water (100 mL) with stirring, the
resulting residue was collected by filtration and washed with
excess water to give an 82% yield of 1 as beige crystals (THF/n-
hexane = 1:1, v/v), mp. 240-242 °C; IR (KBr) 3150, 1750, 1620,
1540, 1360, 1160, 1100, 1000, 860, 800 cm-1; 1H NMR (DMSO-
d6): ꢀ 3.60 (s, 4H), 3.94 (s, 4H), 3.96 (s, 4H), 8.20 (d, 4H, J =
[8] K. M. Lynch, W. P. Dailey, J. Org. Chem., 61, 8897 (1995).
[9] A. Mooradian, J. B. Cloke, J. Am. Chem. Soc., 67, 942
(1945).