Synthesis of nitropyrazolidines

Article abstract of DOI:10.1002/jhet.5570440141

(Chemical Equation Presented) Synthesis of 1, 2-diacetyl-4, 4-dinitropyrazolidine 1 and results of further nitration of the 1,2-diacetyl-4,4-dinitropyrazolidine are described.

Full text of DOI:10.1002/jhet.5570440141

Jan-Feb 2007
241
Synthesis of Nitropyrazolidines
Reddy Damavarapua, Rao Surapanenia, Raja Duddub, Farhad Farhorb,
Paritosh Daveb and Damon Parrishc
a. U.S. Army ARDEC, Bldg 3028 Picatinny Arsenal, New Jersey 07806
b. SAIC at ARDEC, Bldg 3028 Picatinny Arsenal, New Jersey 07806
c.Naval Research Laboratory, Code 6030, Washington, D.C. 20375
Email: rdamava@pica.army.mil
Received March 28, 2006
CH2
O2N
NO2
N
N
N
N
Ac
Ac
Ac
Ac
1
Synthesis of 1, 2-diacetyl-4, 4-dinitropyrazolidine 1 and results of further nitration of the 1,2-diacetyl-
4,4-dinitropyrazolidine are described.
J. Heterocyclic Chem., 44, 241 (2007).
INTRODUCTION
The starting material 4-methylidene-1,2-diacetyl
pyrazolidine 2 was prepared using literature reported
procedure with modification (Scheme 2) [7]. Thus
reaction of the di-potassium salt of a 1,2-diacetyl-
hydrazine with methallyl dichloride in anhydrous DMF
under reflux conditions afforded 2. Ozonolysis of 2 in
dichloromethane at -78° C followed by quenching of the
reaction mixture with dimethyl sulfide resulted in the
formation of the desired pyrazolidinone 3. The structure
of the ketone 3 was confirmed by spectral data as well as
single crystal X-ray crystallography. The reaction of 3
with hydroxylamine hydrochloride in aqueous methanol
afforded the corresponding oxime 4 as a white solid.
In modern ordnance there is a strong requirement for
explosives having good thermal stability, impact
insensitivity and explosive performance [1-3]. However,
these requirements are somewhat mutually exclusive.
Those explosives having good thermal stability and
impact insensitivity exhibit poorer explosive perfor-
mances and vice versa. With this background, in the past
we have synthesized several gem-dinitro and polynitro
energetic compounds [4,5]. In a continuation of the
program that is aimed at the development of new,
insensitive and yet more powerful energetic formulations
and ingredients, we needed to synthesize a gem-dinitro-
pyrazolidine [6] compound bearing electron withdrawing
groups such as acetyl, nitro on the nitrogen atoms of the
ring. It is in this context that we have chosen 1,2-diacetyl-
4,4-dinitropyrazolidine as our target compound and
undertaken its synthesis. Herein we describe the results of
our synthesis of the target compound 1 and our attempts
to further nitrate 1 to the corresponding tetranitro
compound 8.
Scheme 2
CH2
CH2
N
H
H
K+EtO-
N
N
+
Ac
N
Cl
Ac
DMF, reflux
Cl
Ac
Ac
2
NOH
O
RESULTS AND DISCUSSION
O3 /CH2Cl2
-78o
NH2OH.HCl
A retro-synthetic analysis of 1 indicated that synthesis
of 1,2-diacetylpyrazolidine-4-oxime and its subsequent
nitration are the key steps in accomplishing the synthesis
of 4,4-dinitropyrazolidine (Scheme 1).
N
N
Ac
4
N
N
NaOAc
C
Ac
Ac
Ac
3
The compound 4 (Scheme 3) was subsequently reacted
with 100% nitric acid in refluxing dichloromethane,
followed by careful quenching of the reaction mixture at
0°C with 90% H2O2, to obtain the target product diacetyl-
dinitropyrazolidine 1. The structure of the diacetylpyrazo-
lidine was established unambiguously via single crystal
X-ray crystallography.
Scheme 1
NOH
CH2
N
O2N
N
NO2
Ac
N
N
N
N
Ac
Ac
Ac
Ac
Ac
1
2

242
R. Damavarapu, R. Surapaneni, R. Duddu, F. Farhor, P. Daveand D. Parrish
Vol 44
Scheme 3
Furthermore, cyclic nitramines with 4 and 6 membered
rings [5,8] containing gem-dinitro groups at the ꢀ-position
with respect to the nitramino group are well known.
However, the corresponding cyclic nitramines with 5
membered ring are not known to the best of our
knowledge. Hence, after successful synthesis of the target
compound and in further extension of our work, we made
attempts to convert the diacetyl groups of 1 to the
corresponding dinitro groups. Our efforts on further
nitration to convert the 1,2-diacetyl functionality of 1 to
corresponding nitro groups under a variety of conditions
(H2SO4/HNO3, 100% HNO3, (CF3CO)2O/100% HNO3,
Nafion-HNO3, NO2BF4 and N2O4) did not result in the
NOH
O2N
N
ON
NO2
Ac
NO2
Ac
100% HNO3
90% H2O2
N
N
N
N
N
Ac
Ac
Ac
Ac
4
1
Theoretical calculations by scientists in our labs
predicted that 1,2,4,4-tetranitropyrazolidine (8), another
interesting gem-dinitropyrazolidine with electron with-
drawing nitro groups on the ring nitrogen atoms would be
a high density and high performance energetic material.
Scheme 4
O2N
N
O2N
N
O2N
H
NO2
Ac
NO2
NO2
Ac
O2N
O2N
NO2
Ac
Nitration
N
N
N
N
N
N
Ac
O2N
Ac
4b
1
4a
5
O2N
O2N
O2N
O2N
O2N
N
NO2
NO2
NO2
H
NO2
NO2
N
N
N
N
N
O2N
7
6
8
An ORTEP view and X-ray crystal structure [10] data for 3 and 1.
3
1
Chemical Formula:
MW
C7H10N2O3
170.17
C7H10N4O6
246.19
Appearance:
Clear colorless prism
Clear colorless prism
Crystal size(mm):
Crystal System:
Temperature:
Detector Distance (cm):
Frame Time:
0.31x0.25x0.20
Monoclinic
-180° C
5
10
0.34x0.24x0.16
Orthorhombic
-180° C
5
10
Space Group:
C2/C
Pca21
Unit cell dimensions:
a: 12.72(3)
b: 8.076(19)
c: 9.41(2)
4
ꢁ: 90
ꢀ: 123.54(4)
ꢂ: 90
a: 11.1081(5)
b: 7.4047(14)
c: 15.4195(15)
4
ꢁ: 90
ꢀ: 90
ꢂ: 90
Z:
3
Volume (Å )
806 (3)
1034.81(9)

Jan-Feb 2007
Synthesis of Nitropyrazolidines
243
Density (Mg/m3):
μ (μμꢀ1):
Goof:
1.402 at -180° C, 1.401 at 21° C
1.580 at -180° C, 1.534 at 21° C 1.492
0.111
1.058
0.966
0.978
0.0374
0.0451
0.1169
0.0552
0.1227
2707
0.139
1.112
0.954
0.978
0.0276
0.0324
0.0913
0.0332
0.0924
4547
Tmin
:
Tmax
Rint:
:
R1 (I>2ꢁ):
wR2 (I>2ꢁ):
R1 (all data):
wR2 (all data):
Reflections Collected:
Unique Reflections:
Max Resolution Å:
% Completeness:
946
0.75
94.4
1933
0.75
95.1
mmol) was added, drop-wise, over a period of 15 min and
heating under reflux was continued for another 5 hr. The cooled
reaction mixture was filtered and the filtrate was evaporated
under reduced pressure. The residual oil was distilled under
vacuum- fractionated in a bulb-to-bulb apparatus (170 to 185°) -
formation of desired product. Instead, an unstable pale
yellow liquid was isolated. The NMR characteristics of
this compound are consistent with argued structure 3,4,4-
trinitro-1-acetylpyrazolidene 5 (Scheme 4). However, due
to apparent instability of 5, it could not be sufficiently
purified and thoroughly characterized to establish the
structure unambiguously.
1
to obtain 2.33 grams of pure product. H (CDCl3): 2.16 (s, 6H),
3.64 (br s, 2H), 4.82 (br s, 2H), 5.13 (s, 2H). Anal. Calcd. for
C8H12O2N2: C, 57.13; H, 7.19; N, 16.65. Found: C, 57.10; H,
7.18; N, 16.64.
Further nitration of 5 was carried out in an attempt to
synthesize tetranitropyrazolidine. A pale yellow unstable
liquid, always containing trace amounts of impurities
detected by NMR analysis was isolated from the reaction
mixture. Our efforts to purify this crude compound were not
successful. The proton NMR of this liquid showed a singlet
at 5.26 ppm along with another signal at 7.55 ppm (since the
integrations do not correspond to each other, this clearly
indicates the mixture of two compounds). The appearance of
a signal in the aromatic region and isolation of N-acetyl-
3,4,4-trinitropyrazoline 5 suggests that the first step in the
nitration of 1,2-diacetyl-4,4-dinitropyrazolidine 1 is the
formation of 1-acetyl-2,4,4-trinitropyrazolidine 4a, which
readily undergoes a HONO elimination to yield N-acetyl-
4,4-dinitropyrazoline 4b which undergoes further nitration
[9] to form 1-acetyl-3, 4, 4-trinitropyrazoline 5. The
unstable compound 5 again undergoes nitration leading to
the formation of 1,3,4,4-tetranitropyrazolidene 6 which
further transforms to 7 again by HONO elimination.
1-2-Diacetyl pyrazolidine-4-one (3). A solution of 4-methyli-
dine-1,2-diacetyl pyrazolidine (500 mg, 2.97 mmol) in anhydrous
CH2Cl2 (25 mL) was cooled to -78°C using a dry ice-acetone bath.
Ozone gas was bubbled into this cold solution until the blue color
persisted. The reaction mixture was then purged with N2 gas to
remove excess of ozone and quenched with dimethylsulfide (1.5
mL). The reaction mixture was allowed to warm gradually to
room temperature and stirred for another 2 hr. The resulting turbid
solution was then evaporated under reduced pressure to yield a
white solid. This solid was triturated with CH2Cl2 and filtered to
obtain pure product as a white solid in 79% (400 mg) yield. m.p:
179-181°; ir (potassium bromide): 3017 (m), 2932 (w), 1778 (s),
1677 (s), 1417 (s), 1381 (s), 1272 (m), 1217 9m), 1192 (m), 1152
(m), 1033 (m) cm-1; 1H-nmr (CDCl3): 2.25 (s, 6H, 2xCH3), 3.48 (d,
ABq, J= 17.88Hz, 2H), 4.62 (d, ABq, J=17.88Hz, 2H); 13C-nmr
(CDCl3): 20.45, 51,94, 175.13; 205.88. Anal. Calcd. for
C7H10O3N2: C, 49.41; H, 5.92; N, 16.46. Found: C, 49.41; H,
5.91; N, 16.44
1-2-Diacetylpyrazolidine-4-one-oxime (4). To a suspension
of ketone 3 (380 mg, 2.23 mmol) in water (1 mL) was added
sodium acetate (478 mg, 3.52 mmol) and hydroxylamine
hydrochloride (242 mg, 3.52 mmol) sequentially. The reaction
mixture was heated in a pre-heated oil bath at 60°C for 45 min.
The solid that formed was collected by filtration and washed
with a few drops of ice-cold water. The resulting solid was air
dried to give the pure product 4 in 55% (220 mg) yield. m.p 197-
198°; ir (potassium bromide): 3431 (br, s), 1678 (s), 1442 (s),
In summary we have synthesized and characterized 1,2-
diacetyl-4,4-dinitropyrazolidine by NMR spectra and X-
ray analysis. Our attempts of further nitration of 5 led to
the formation of unstable polynitropyrazolidine products.
1
1376 (s), 1224 (s), 1045 (m) cm-1; H-nmr (acetone-d6): 2.15 (s,
EXPERIMENTAL
6H, 2xCH3), 3.85 (br S, 2H), 4.78 (dd, J=60.1, 20.1 Hz, 2H);
13C-nmr (acetone-d6): 20.7, 46.1, 47.1, 157.2, 175.6.
Calcd. for C7H11O3N3: C, 45.40; H, 5.99; N, 22.69. Found: C,
45.41; H, 5.97; N, 22.67
1,2-Diacetyl 4,4-dinitropyrazolidine (1). To a suspension of
the oxime 4 (200 mg, 1.08 mmol) in anhydrous CH2Cl2 under
reflux was added drop-wise 99% HNO3 (1.5 mL). The resulting
blue reaction mixture was refluxed for 20 min, gradually
allowed to cool to room temperature and then cooled to 0°C in
an ice-salt bath. To this cooled reaction mixture was added
Anal.
4-Methylidene-1,2-diacetylpyrazolidine (2). To a solution
of elemental potassium (4.2g, 107mmol) in anhydrous ethanol
(60 mL) was added diacetylhydrazine (97%, 6.00 g, 50.1 mmol)
in warm anhydrous ethanol (60 mL). The resulting mixture was
refluxed for 1 hr. The reaction mixture was evaporated to
dryness on a rotary evaporator under vacuum. Anhydrous
dimethylformamide (85 mL) was added to the residual
translucent solid and the reaction mixture was heated at 155 °C
for l hr. 3-Chloro-2-chloromethyl-1-propene (96%, 6.56g, 50.4

244
R. Damavarapu, R. Surapaneni, R. Duddu, F. Farhor, P. Daveand D. Parrish
Vol 44
[2] E. Osawa and O. Yonimitsu, Carbocyclic cage compounds:
Chemistry and Applications; VCH Publishers, Inc., New York, USA,
1992.
[3] L. F. Albright, R. V. C. Carr, R. J Schmitt, Recent Laboratory
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Meeting of the American Chemical Society, Anaheim, CA, April 2-7,
1995; American Chemical Society, Washington DC, 1996
carefully and drop-wise 90% H2O2 (1.5 mL). The resulting
heterogeneous mixture was stirred for 45 min. The reaction
mixture was diluted with water (5 mL) and extracted with
CH2Cl2 (3x5 mL). The organic layers were combined, washed
with water (1x10 mL), brine (1x10 mL), dried (Na2SO4) and
evaporated under reduced pressure to yield the crude product as
pale yellow syrup. This crude product was subjected to column
purification (Si-gel, 15 % EtOAc-Hexanes) to give the pure
product in 11% yield (31 mg). m.p 123-125°; ir (potassium
bromide): 3133(s), 1731 (m), 1505 (s), 1410 (s), 1359 (s), 1288
(s), 1190 (m), 1160 (m), 1028 (m), 997 (s) cm-1; 1H-nmr
(CDCl3): 2.23 (s, 6H, 2xCH3), 4.06 (d, J = 14.5 Hz, 2H), 5.38 (d,
J = 14.5 Hz, 2H); 13C-nmr (CDCl3): 20.1, 53.8, 120.6, 174.4.
Anal. Calcd. for C7H10O6N4: C, 34.15 ; H, 4.09; N, 22.76. Found:
C, 34.15; H, 4.10; N, 22.74
[4a] R. Duddu, P. R. Dave, R. Damavarapu, R. Surapaneni, R.
Gilardi, Syn. Comm., 35, 2709 (2005); [b] Dave, R. Duddu, K. Yang, R.
Damavarpu, N. Gelber, R. Surpaneni, R. Gilardi, Tetrahedron Lett., 45,
2159 (2004); [c] T. Axenrod, C. Watnick, H. Yazdekhasti, P. R. Dave,
Tetrahedron Lett., 34, 6677 (1993); [d] T. Axenrod, C. Watnick, H.
Yazdekhasti, P. R. Dave, J. Org. Chem., 60, 1959 (1995); [e] A. P.
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60, 4943 (1995).
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Phys. Chem., 99, 5009 (1995).
Nitration of 1,2-diacetyl-4,4-dinitropyrazolidine. To a
refluxing solution of diacetyl dinitropyrazolidine 1 (25 mg) in
dichloromethane (5 mL) under nitrogen was added drop wise a
mixture of sulphuric acid and nitric acid (15:85, 0.5 mL) via an
addition funnel. The reaction mixture was refluxed for 1 h and then
cooled to room temperature, poured over crushed ice (10 g) and
extracted with dichloromethane (3x5 mL). The combined organic
layer was washed with water (1x10 mL), and brine (1x10 mL) and
dried (Na2SO4). The solvent was evaporated to yield a pale yellow
syrup (8 mg) which was then subjected to preparative TLC (25 %
EtOAc: Hexanes as eluent). The products isolated were found to
be unstable and the NMR spectra of the isolated products
tentatively indicated the formation of products 5, and 6. However,
the instability of the products did not allow for a complete and
thorough characterization to prove tentatively assigned structures
unambiguously.
[6] J. H. Boyer, Organic Nitrochemisty, Series 1. Nitro azoles.
The C-Nitrodereivatives of Five membered N and N, O heterocycles,
VHC, 1986
[7a] E. Endo, T. Uchida, K. Yamaguchi, Heterocycles, 53,
151(2000); [b] S. Caccamese, P. Finocchiaro, P. Maraviga, G.
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Frankel., J. Org. Chem., 26, 4709 (1961); [c] M. D. Cliff, Heterocycles,
48, 657 (1998); [d] D. A. Levins, C. D. Bedford, S. J. Staats,
Propellnets, Explosives, Pyrotechnics, 8, 74 (1983).
Acknowledgement. The authors wish to express their thanks
to Drs. Jin Rai Cho and Soo Gyeong Cho of Agency for Defense
Development (ADD), Republic of Korea (ROK) for their helpful
cooperation in performing theoretical calculations.
[9a] P. Bouchet, J. Elguero, R. Jacquier, Bull. Soc. Chim. Fr.,
4716 (1967); [b] O. B. KremLeva, F. A. Gabitov, A. L. Fridman, Khim.
Geterotsikl. Soedin., 703 (1977)
[10] Complete crystallographic information files for 1, and 3 have
been deposited with the Cambridge Crystallographic Data Center as
supplementary publications CCDC 600980 & 600981 Copies of this data
can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ (UK); Tel.: (+44) 1223-336-408, Fax: (+44) 1223-
336-033, or E-mail: deposit@ccdc.cam.ac.uk.
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