Selective nitrosation of guanazine: preparation of azidoaminotriazole and nitrosoguanazine anion-Cu(II) complexes

Article abstract of DOI:10.1016/j.tetlet.2006.06.177

Guanazine (3,4,5-triamino-1,2,4-triazole) is selectively nitrosated on C-NH₂ to produce nitrosoguanazine (3-nitrosamino-4,5-diamino-1,2,4-triazole). The nitrosoguanazine is used to prepare 5-azido-3-amino-1,2,4-triazole and nitrosoguanazine anion-Cu(II) complexes.

Full text of DOI:10.1016/j.tetlet.2006.06.177

Tetrahedron Letters 47 (2006) 6663–6666
Selective nitrosation of guanazine: preparation of
azidoaminotriazole and nitrosoguanazine anion–Cu(II) complexes
a
b
c,
d
Magdy Bichay, John W. Fronabarger, Richard Gilardi, Ray J. Butcher,
b
a,
b
*
William B. Sanborn, Michael E. Sitzmann and Michael D. Williams
a
Indian Head Division, Naval Surface Warfare Center, Indian Head, MD 20640, USA
b
Pacific Scientific Energetic Materials Co., Chandler, AZ 85226, USA
Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC 20375, USA
c
d
Department of Chemistry, Howard University, Washington, DC 20059, USA
Received 24 March 2006; revised 26 June 2006; accepted 30 June 2006
Available online 27 July 2006
2
Abstract—Guanazine (3,4,5-triamino-1,2,4-triazole) is selectively nitrosated on C–NH to produce nitrosoguanazine (3-nitros-
amino-4,5-diamino-1,2,4-triazole). The nitrosoguanazine is used to prepare 5-azido-3-amino-1,2,4-triazole and nitrosoguanazine
anion–Cu(II) complexes.
Published by Elsevier Ltd.
1
1
. Introduction and discussion
aryl-5-alkyl-1,2,4-triazoles and 3-nitrosamino-5-amino-
2
,3
1,2,4-triazole.
Reports of isolation of primary nitrosamino compounds
are rare, due, at least in part, to the fact that these
compounds readily convert to diazonium salts under
normal reaction conditions. Among these reported
nitrosamino compounds, we found 3-nitrosamino-4-
We have prepared a primary nitrosamino-triazole com-
pound for use as an intermediate to other materials.
Thus, we report here (Scheme 1): (a) The selective nitro-
sation of guanazine (1) (3,4,5-triamino-1,2,4-triazole) to
N
N
N
HN
N
N
i
H2N
ii
H2N
H2N
N
N
NHNO
N
v
NH2
N3
1
2
3
H2N
H2N
iii
iv
N
N
copper (II) complex
2 anion)3 (Cu2+)3 (OH ) (NO3 )2 (H2O)2
acid salts
6, HNO salt
H2N
-
-
(
3
7
, HCl salt
N
5
NNO
M
H2N
4
a; M = Na
b; M = K
4
8
Scheme 1. Reagents and conditions: (i) 1 equiv HOAc, 1 equiv NaNO
2
, H
2
O, 0–25 ꢀC/20 h (product 2 is possibly dimer); (ii) H
(6) or dilute HCl (7).
2
O, 75 ꢀC/45 min;
(
iii) NaOH (4a) or KOH (4b), H O; (iv) Cu(II)(NO (2.5H O), H O; (v) dilute HNO
2
3
)
2
2
2
3
Keywords: Nitrosoguanazine; Azidoaminotriazole; Nitrosoguanazine anion–Cu(II) complexes.
*
Corresponding author. Tel.: +1 301 744 4735; fax: +1 301 744 4445; e-mail addresses: rgilardi@epix.net; michael.sitzmann@navy.mil
Present Address: 5 Overlook Rd., Clarks Summit, PA 18411, USA.
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.06.177

6664
M. Bichay et al. / Tetrahedron Letters 47 (2006) 6663–6666
produce nitrosoguanazine (2) (3-nitrosamino-4,5-diami-
no-1,2,4-triazole); (b) The conversion of 2 to 5-azido-3-
amino-1,2,4-triazole (3); and (c) The conversion of salts
4
a,b to nitrosoguanazine anion–Cu(II) complex 5.
This work began with an interest in the preparation of
4
,5
3
as a versatile intermediate to new energetic materi-
als. Our initial approach to 3, involving selective diazo-
tization of 1, gave a low yield of impure 3; thus, the
approach was changed to the preparation and use of 2
6
as an intermediate to 3. The latter approach, involving
7
,8
selective nitrosation of 1, produces high-purity 2 that
can be easily converted to 3 by heating in H O or H O/
2
2
9
HOAc.
Nitrosoguanazine 2 was treated with NaOH or KOH in
1
0
water to give the respective salts, 4a and 4b. Crystal
1
1
11
structure analyses of 4a (Fig. 1) and b show that
nitrosation of 1 has occurred on C–NH rather than
2
Figure 2. The crystal structure of the complex Cu(II) salt, 5; as
mentioned above, there are also two nitrate anions and two water
molecules in the asymmetric unit that are not shown here because they
occur above and below this roughly planar cluster and would obscure
the view. The central oxygen is part of a hydroxyl ion; its proton lies
above the plane and is not shown.
on N–NH . Apparently, the C–NH , being the more ba-
2
2
+
sic amine, is more susceptible to NO attack. Salt 4a is a
hydrate, while 4b is free of water. The salts have high
thermal stability as determined by DSC.
1
0
Salts 4a and 4b, when treated with copper(II) nitrate
in water, form nitrosoguanazine anion–Cu(II) complex
1
2
5
.
Crystal structure analysis of 5 (Fig. 2) shows that
the complex contains three nitrosoguanazine anions,
2
+
three Cu , and hydroxide, along with two nitrate
1
1
ions and two water molecules. The complex is very
similar in structure to those recently reported for
3
5
-acetylamino-1,2,4-triazole anion and 3-acetylamino-
-amino-1,2,4-triazole anion.
1
3,14
Azidoaminotriazole 3 is sufficiently basic that it readily
forms acid salts, for example, HNO salt 6 and HCl salt
3
1
5
Figure 3. The crystal structure of 6, a nitrate salt of 3, as revealed by
X-ray analysis; atoms are represented by ‘50% probability’ displace-
ment ellipsoids.
hydrate 7. Crystal structure analyses were performed
1
1
11
on 6 (Fig. 3) and 7, as well as on the free amine
1
1
3
.
The IR spectra of 3 and its salts 6 and 7 show very
significant differences in the region of azide group
absorption: compound 3 has a single very strong peak
at 2147 cm ; 7 has a single peak (2151) of medium
intensity; 6 shows two absorptions (2202 and 2165)
and they are of weak intensity.
ꢀ1
We anticipate that azidoaminotriazole and nitrosoguan-
azine, possessing multiple functionality including reac-
tive amine groups, will be of interest as intermediates
toward other new materials. In addition, it may be pos-
sible to produce new complexes similar to 5 by expand-
ing to other types of heterocyclic anions.
2. Crystal structures
There are two separate ion pairs and two water mole-
cules linked together in a cluster in the 4a crystal. The
anions are chemically identical, but differ in their ion–
ion and hydrogen-bonding packing interactions, shown
by the dashed lines in Figure 1. There are also two sep-
arate ion pairs in the asymmetric unit of 6 (Fig. 3), form-
ing a cluster which appears to be symmetric, but it
contains neither 2-fold nor inversion symmetry. The
two anions differ because of different packing interac-
tions, but not significantly.
Figure 1. The crystal structure of 4a, a hydrated sodium salt of 2, as
revealed by X-ray analysis; atoms are represented by displacement
ellipsoids containing 50% of the probability density.

M. Bichay et al. / Tetrahedron Letters 47 (2006) 6663–6666
6665
The crystal structure of 5 (Fig. 2) should be considered
to be low-precision, because its data come from a
twinned crystal which compromised the overall quality
of the collected crystal data. Two components were
found from the diffraction pattern; both components
were used to fit the unit cell and data from both compo-
nents were used to refine. However, the structure refines
to a high R value of 8.7% for the observed reflections, so
there may be other unrecognized components affecting
the data. Hydrogen atoms could not reliably be located,
but considerations of the shape of the multi-atom ions,
the relative weights of the nonhydrogen atoms and the
overall charge balance led us uniquely to the reported
structure.
NaNO (3.36 g, 48.7 mmol) was added, followed by
HOAc (2.92 g, 48.7 mmol) in water (54 mL) dropwise
over 10 min. The flask was stoppered and held at 0 ꢀC for
2
1
h before being warmed to 23 ꢀC over 2 h. After an
additional 1 h, the mixture was allowed to stand overnight
17 h) before the precipitate was removed by filtration and
washed with water to give 2 (4.87 g, 72%), mp 143 ꢀC dec.
(
1
H NMR (DMSO-d
broad); IR (ATR): 3301, 3171, 1680 (strong), 1636, 1564,
1504, 1256 (strong), 1146, 1067, 980, 901, 800, 752,
6
): 5.68 (s, 2H), 6.28 (s, 2H) 13.8
(
ꢀ1
720 cm . Calcd for C H N O : C, 16.79; H, 3.52; N,
4
10 14
2
68.51. Found: C, 16.69; H, 3.63; N, 68.29; DSC (20 ꢀC/
min): onset: 152; peak: 154.
8
. Possibly
2
is
a
nitroso dimer of the form
RNH(O)N@N(O)NHR. This possibility is supported by
the IR spectrum which shows a strong absorption at
ꢀ1
1
256 cm . Very little data are available for primary
nitrosamines but the N@O stretching absorption for
secondary nitrosamine dimers is in the 1300 region
compared to 1430–1530 for the monomers: (Rao, C. N.
R.; Bhaskar, K. R. In The Chemistry of the Nitro and
Nitroso Group, Part 1; Feuer, H., Ed. Spectroscopy of the
Nitroso Group; John Wiley: New York, 1969; p 144, see
also Zahradnik, R.; Svatek, E.; Chvapil, M. Chemicke
Listy pro Vedu a Prumysl, 1957, 51, 2232–2242.) A dimer is
also suggested by the very low solubility of 2 in water
compared to 1. Compound 2 was not sufficiently soluble
3
. Analytical methods
Differential scanning calorimetry (DSC) experiments for
energetic complexes 5 should be performed using amounts
of 0.2 mg or less: The IR spectra were recorded via atten-
uated total reflectance (ATR) on a ThermoNicolet Ava-
tar 370 FT-IR Spectrometer. NMR spectra were
recorded using either Varian 300 MHz Mercury Plus
system or a Varian Inova system equipped with a
in DMSO for
Laboratories).
a molecular wt analysis (Galbraith
5
mm triple resonance triaxial PFG probe at 500 MHz
1
13
for H and 125 MHz for C (referenced to residual sol-
vent signals). Elemental analyses were performed by
Galbraith Laboratories, Inc., Knoxville, TN. In general,
for high-nitrogen heterocyclic compounds, we have
experienced difficulty in obtaining consistent analytical
values for N. The values found for N are often low, even
though values for other elements (C, H, etc.) are accept-
able. The analytical purity is further established using
other techniques (NMR, IR, DSC, mp).
9
. Preparation of azidoaminotriazole 3: Compound 2 (0.86 g,
mmol) was stirred in water (7 mL), HOAc (0.09 g,
3
1.5 mmol) in water (2 mL) was added, and the mixture was
heated to 78–80 ꢀC over 15 min and then held at approx
75–77 ꢀC for 45 min (Note: For a similar reaction in water
alone without added HOAc, the yield of 3 was approx-
imately 5% less). The warm mixture was filtered to remove
a small amount of dark material and the filtrate was
evaporated under reduced pressure. The residue was
washed with 3 · 1.5 mL water to give 3 (0.56 g, 75%) as
1
brownish yellow crystals, mp 175 ꢀC, dec. H NMR
1
3
(
DMSO-d
6
): 6.31 (s, 2H), 11.91 (s, 1H); C NMR
): 154.4, 157.3; IR (ATR): 3420, 3398, 3161,
Acknowledgement
(DMSO-d
6
2
1
1
1
147 (N
3
, very strong), 1670, 1601, 1544 (strong), 1461,
ꢀ
1
410, 1361, 1225, 1107, 718 cm . Calcd for C H N : C,
9.20; H, 2.42; N, 78.38. Found (crystals from water): C,
8.90; H, 2.42; N, 77.65. Found (crystals from methanol):
Support for this work was received from the Indian
Head Division, Naval Surface Warfare Center,
Research and Technology Department (Core Program).
2
3
7
C, 18.97; H, 2.41; N, 77.55; DSC (20 ꢀC/min): onset: 174;
peak: 184.
1
0. Preparation of nitrosoguanazine salts 4a and 4b: Com-
pound 2 (0.92 g, 6.4 mmol) was stirred in water (15 mL) at
References and notes
2
3 ꢀC while slowly adding NaOH (0.27 g, 6.7 mmol) in
1
. Gehlen, von H.; Dost, J. Leibigs Ann. Chem. 1963, 665,
44–149.
water (9 mL) dropwise. Additional dilute NaOH was
added as necessary to give complete solution. The water
1
2
3
. Hauser, M. US Patent 3,431,251, 1969.
. Namestnikov, V. I.; Kofman, T. P.; Pevzner, M. S. USSR
SU 1,027,159, 1983.
. Kofman, T. P.; Kartseva, G. Yu.; Namestnikov, V. I.;
Paketina, E. A. Russ. J. Org. Chem. 1998, 34, 1032–1039,
Translated from Zh. Org. Khim., 1998 34, 1084–1090.
. Kofman, T. P. Russ. J. Org. Chem. 2001, 37, 1158–1168,
Translated from Zh. Org. Khim., 2001, 37, 1217–1227.
was evaporated and the residue was stirred with CH
(5 mL) to give insoluble yellow-orange salt 4a (0.77 g).
CH Cl (10 mL) added to the filtrate gave an additional
0.30 g; total yield of 4a (1.07 g, 91%). C NMR (D
3
OH
2
2
1
3
4
2
O):
154.7, 155.0; IR (ATR): 3310, 3109, 1660 (strong), 1620,
1580, 1560, 1499, 1330, 1282, 1239 (strong), 1143, 983,
ꢀ
1
5
944, 904, 890, 748, 720, 696 cm . DSC (20 ꢀC/min):
endotherm: 131; onset: 259; peak: 265. Calcd for
(
Refs. 4 and 5 report the use of 3 but do not provide
C H N NaO : C, 13.12; H, 3.30; N, 53.55; Na, 12.56.
2 6 7 2
synthesis/characterization data for this compound).
Found: C, 12.92; H, 3.66; N, 51.44, Na, 12.64.
6
7
. Fronabarger, J. W.; Sitzmann, M. E.; Williams, M. D.
Compound 4b was prepared similarly using KOH. The
reaction residue (from removal of water), stirred with
‘
Azidoaminotriazole, Nitrosoguanazine, and Azidonitr-
1
3
amine Compounds, Intermediates and Salts, and Pro-
cesses Thereof’, US Patent Application, 31 October 2005.
. Preparation of nitrosoguanazine 2: A solution of 1 (5.4 g,
CH OH, gave 4b (1.04 g, 91%). C NMR (D O): 154.9,
3 2
155.0; IR (ATR): 3319, 3131, 1657, 1631, 1574, 1518, 1491,
ꢀ
1
1276, 1244, 1143, 1038, 956, 889, 723, 701 cm . DSC
4
7.3 mmol) in 90 mL water was stirred in an ice bath,
(20 ꢀC/min): onset: 228; peak: 247.

6666
M. Bichay et al. / Tetrahedron Letters 47 (2006) 6663–6666
11. Crystallographic data have been deposited with the Cam-
(ATR): 3335, 1665 (strong), 1557, 1505, 1388, 1357, 1080
ꢀ
ꢀ1
bridge Crystallographic Data Centre as supplementary
publications CCDC-601041 for 3, CCDC-601042 for 4a,
CCDC-601043 for 4b, CCDC-601044 for 5, CCDC-601045
for 6, and CCDC-601046 for 7. Copies of the data can be
obtained freely on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ (UK); Tel.: +44 1223 336
(very strong) ðClO Þ, 921, 726 cm
.
4
Use of CuSO (5H O) with 4b gave a green sulfate complex.
4
2
IR (ATR): 3321, 1657, 1626, 1549, 1504, 1386, 1324, 1100–
ꢀ
2
ꢀ1
1040 (very strong) ðSO4 Þ, 972, 920, 746, 724 cm
.
13. Ferrer, S.; Haasnoot, J. G.; Reedijk, J.; Muller, E.; Biagini
Cingi, M.; Mannoti Lanfranchi, M.; Lanfredi, A. M.;
Ribas, J. Inorg. Chem. 2000, 39, 1859–1867.
408, fax: +44 1223 336 033, and e-mail: deposit@ccdc.cam.
ac.uk.
14. Ferrer, S.; Lloret, F.; Bertomeu, I.; Alzuet, G.; Borras, J.;
Garcia-Granda, S.; Liu-Gonzalez, M.; Haasnoot, J. G.
Inorg. Chem. 2002, 41, 5821–5830.
1
2. Preparation of complex 5: Caution! Compound 5 is an
energetic material and can deflagrate (see below). To a
solution of 4b (0.24 g, 1.3 mmol) in water (3 mL) at 22 ꢀC
was added dropwise copper(II) nitrate hemipentahydrate
15. Preparation of acid salts 6 and 7: Compound 3 (50 mg) in
5 mL of water was acidified with dilute HNO
3
and the
1
(
0.30 g, 1.3 mmol) in water (2 mL). The initial brown
solution was evaporated to give crystals of 6 (60 mg). H
1
3
precipitate turns to green by the end of the addition. The
mixture was stirred for 15 min before it was filtered to give
NMR (DMSO-d
6 6
): 9.21 (br s); C NMR (DMSO-d ):
149.6, 153.7; IR (ATR): 3430, 3338, 2738, (2202, 2165, N
3
,
5
as a green solid (0.27 g, 79%). IR (ATR): 3312, 1661
weak), 1714 (medium strong), 1590, 1530, 1434, 1301
(strong), 1183, 1048, 1034, 1002, 843, 815, 803, 727,
707 cm . DSC (20 ꢀC/min): onset: 172; peak: 174. Calcd
2 4 8 3
for C H N O : C, 12.77; H, 2.14; N, 59.57. Found: C,
(
strong), 1623, 1544, 1503, 1390–1318 (very strong), 1166,
ꢀ1
ꢀ1
1138, 1080, 1070, 1046, 918, 820, 747, 726 cm . When
heated, the product deflagrates (with a burst of flame) in
the vicinity of 230 ꢀC; DSC (20 ꢀC/min): onset: 218; peak:
12.92; H, 2.31; N, 59.15.
Salt 7 was prepared similarly using dilute HCl. IR (ATR):
2
31. Calcd for C H Cu N O : C, 9.08; H, 2.16; N,
6
17
3
23 12
4
0.57. Found: C, 9.00; H, 2.42; N, 39.41.
(6H O) gave a green perchlo-
3383, 3256, 3096, 2951, 2719, 2151 (N
3
, medium strong),
Similarly, 4b with Cu(ClO
rate complex. Caution! This product is a sensitive powerful
4
)
2
2
1685 (strong), 1593, 1522, 1358, 1201, 1049, 1009, 873,
ꢀ
801, 757, 718 cm . Calcd for C H ClN O: C, 13.38; H,
2 6 7
1
explosive; when heated, it explodes in the vicinity of
3.37; Cl, 19.74, N, 54.60. Found: C, 13.85; H, 3.33; Cl,
19.88, N, 55.43.
230 ꢀC; DSC (20 ꢀC/min): onset: 206; peak: 232. IR