Synthesis of 7-Azidofurazano[3,4-b]tetrazolopyrazine and isomer's structure in different polarity solvents

Article abstract of DOI:10.14233/ajchem.2013.14164

7-Azidofurazano[3,4-b]tetrazolopyrazine (FSZPA) was synthesized via methoxylation, nitration hydrazinolysis and azidation, using 2,6- dichloropyrazine as a starting material. The structures of 7-azidofurazano[3,4- b]tetrazolopyrazine and intermediates were identified by FTIR, NMR and elemental analysis. ¹⁵N and ¹³C NMR spectra showed three isomer forms resulting from the reversible opening and closing between asido and tetrazole depending on polarity of the solvents.

Full text of DOI:10.14233/ajchem.2013.14164

Asian Journal of Chemistry; Vol. 25, No. 9 (2013), 4979-4982
http://dx.doi.org/10.14233/ajchem.2013.14164
Synthesis of 7-Azidofurazano[3,4-b]tetrazolopyrazine and
Isomer's Structure in Different Polarity Solvents
*
TAO GUO, MIN LIU, JUN JIANG, SHAO-JUN QIU and ZHONG-XUE GE
Xi'an Modern Chemistry Research Institute, Xi'an 710065, P.R. China
*Corresponding author: Fax: +86 29 88220423; Tel: +86 29 88294436; E-mail: shaojqiu@yahoo.com
(Received: 6 June 2012; Accepted: 13 March 2013)
AJC-13117
7-Azidofurazano[3,4-b]tetrazolopyrazine (FSZPA) was synthesized via methoxylation, nitration hydrazinolysis and azidation, using 2,6-
dichloropyrazine as a starting material. The structures of 7-azidofurazano[3,4-b]tetrazolopyrazine and intermediates were identified by
FTIR, NMR and elemental analysis. 15N and 13C NMR spectra showed three isomer forms resulting from the reversible opening and
closing between asido and tetrazole depending on polarity of the solvents.
Key Words: Furoxan, Furazan, Pyrazine, Nucleophilic.
between the structure of FSZPA isomers and solvents polarity
was also investigated by 15N and 13C NMR spectroscopy.
INTRODUCTION
In recent years, nitrogen heterocyclic compounds with
high nitrogen and less hydrogen and even without hydrogen,
showing high generation enthalpy and high density, are
developed to use as a new type of energetic materials. A series
of studies on five- or six-membered nitrogen containing
heterocyclic compounds and their derivatives have been
carried out. DNBF and CL-14 are the typical examples1-3. As
we known, the increase of energy density is observed when
introducing furazan or tetrzole substituent into aromatic rings.
Furoxans and tetrazoles was tried to introduce into pyrazine
ring by Guillou and co-workers to synthesize 7-nitrofuraxan-
[3,4-b]tetrazolopyrazine (FTZPN) (Scheme-I), but eventually
the final product was 7-azidofurazano[3,4-b]tetrazolopyrazine
(FSZPA)4,5 (Scheme-II).
OMe
NO2
Cl
OMe
MeO
O2N
MeO
N
N
Cl
N
N
N
N
2
1
N3
H2N NH
HN NH2
NO2
N
N
N
N
N
O
N
N
N
H2N N
H
N
4
5
FSZPA
Scheme-II
O
NO2
EXPERIMENTAL
2,6-Dimethoxypyrazine (1): To the stirred sodium
N
N
N
O
N
N
methylate solution (115.7 g, 0.6 mol) was added 2,6-
dichloropyrazine (29.8 g, 0.2 mol) in batches at 80 ºC. After
refluxing for 18 h, the reaction was cooled. The mixture was
poured into ice water and extracted with ether, dried over
Na2SO4 and concentrated to give compound 1 (27.2 g, 97 %)
N
N
FTZPN
Scheme-I
In this work, we synthesized 7-azidofurazano[3,4-
b]tetrazolopyrazine and discussed the mechanism of
methoxylation, nitration, nucleophilic substitution, denitrifi-
cation and cyclization. Furthermore, we examined that FSZPA
had not less than three isomers. The dependency relationship
1
as white crystals. m.p. 36-38 ºC (Lit. 38-39 ºC6); H NMR
[(CD3)2CO, 500 MHz] δ: 4.05 (s, 6H, -OCH3), 7.85 (s, 2H,
CH); 13C NMR [(CD3)2CO, 125 MHz] δ: 52.9 (-OCH3), 124.5
(-COMe), 159.2 (-CN). Anal. calcd. for C6H6N2O6: C, 31.31;
H, 2.63; N, 24.34. Found: C, 31.03; H, 2.62; N, 24.02.

4980 Guo et al.
Asian J. Chem.
2,6-Dimethoxy-3,5-dinitropyrazine (2): 20 % oleum
1H NMR, 13C NMR and 15N NMR spectra (NMR) analysis
were recorded on a BrukerAV500 nuclear magnetic resonance
spectrometer. Room-temperature Fourier transform infrared
(FTIR) spectra were recorded in the range 400-4000 cm-1 on a
Thermo Nicolet NEXUS870 spectrometer using the KBr pellet
technique. Elemental analysis was obtained by using an
Elementar VARI-EL-3 Vario elemental analyzer.
(300 mL) and fuming nitric acid (200 mL) were chilled in an
ice bath and compound 1 (1.5 g, 0.1 mol) was added slowly.
The solution was stirred at 0-2 ºC for 0.5 h and then heated to
room temperature for 3 h. The reaction mixture was poured
into cold water. The precipitate was filtered off, washed with
water and dried in air to yield compound 2 (14.8, 65 %) as a
1
yellow powder. m.p. 155-157 ºC (Lit. 154 ºC7); H NMR
RESULTS AND DISCUSSION
(CDCl3, 500 MHz) δ: 4.33 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ : 57.6 (-OCH3), 131.6 (-C-OMe), 156.1 (-C-NO2); IR
(KBr, νmax, cm-1): 3033, 3058, 1581, 1542, 1273 cm-1; Anal.
calcd for C6H8N2O2: C, 51.43; H, 5.71; N 20.0. Found: C, 51.38;
H, 5.66; N, 19.84.
Nucleophilic substitution and nitration on pyrazine
ring: Methoxylation gave 73 % compound 1 by using the
concentration of sodium methoxide less than 20 %, while the
yield of compound 1 was obviously increased with the
concentration more than 28 %. Interestingly, using methanolic
sodium methoxide (2 equiv) at reflux for 3.5 h, this resulted
in compound 1 along with small amounts of the mono-
metoxylated byproduct. Moreover, the separation was difficult
by recrystallization or column chromatography. Therefore,
97 % yield of compound 1 was obtained by employing the
methanolic sodium methoxide (3 equiv) at reflux temperature
for 18 h. As we known, electronegativity of nitrogen was larger
than that of carbon, which results in the lower electron density
of carbon atom and imbalance of electron density in nitrogen
heterocyclic ring like pyrazines and pyridines. Thus, the
nitration reaction of electron-deficient heterocycles did not
undergo electrophilic substitution under normal conditions
unless substituted with electron-donating substituents. The
electron density of carbon atom was even much lower due to
2,6-dichloropyrazine containing two electron-withdrawing
chlorine atoms, which led to the nitration reaction hardly to
occur even in high temperature conditions. In contrast, nitration
of compound 2, 6-dimethoxypyrazine by forming far more
electron-rich pyrazine ring system, which was obtained from
the substitutions of methoxy groups in 2,6-dichloropyrazine
rings, gave the dinitrated compound 2 easily in nitric-sulfuric
acid at room temperature.
2,6-Diamino-3,5-dinitropyrazine (3): A solution of
aqueous ammonia (28 %, 10 mL) was added to compound 2
(5.0 g, 21.7 mmol) in acetonitrile (85 mL). The solution was
refluxed for 2 h. After cooling, the precipitated solid was
filtered off, washed with diethyl ether and dried in air to give
compound 3 (3.9 g, 90 %) as orange powder. m.p. 327-330 ºC
[Lit. > 300 ºC (dec.)]8; 1H NMR (CDCl3, 500 MHz) δ: 8.21 (s,
2H); 13C NMR (CDCl3, 125 MHz) δ: 126.1 (-C-OMe), 156.1
(-C-NO2). Anal. calcd. for C4H4N6O4: C 24.01, H 2.01, N,
42.00. Found: C, 24.37; H, 1.93; N, 41.48.
2,3,6-Trihydrazino-5-nitropyrazine (4): Hydrazine
hydrate was dropwise added to the mixture of compound 2
(2.0 g, 9.5 mmol) in absolute ethanol (80 mL) at -78 ºC in 20
min. The solution was stirred at -78 ºC for 2 h. The precipitate
was filtered off, washed with ethanol and dried in air to give
compound 4 (1.4 g, 97 %) as a brown solid. m.p. 201-204 ºC;
IR (KBr, νmax, cm-1): 3368, 3322, 3280, 1478. Anal. calcd. for
C4H9N9O2: C, 22.33; H, 4.22; N, 61.50. Found: C, 21.60; H,
4.70; N, 59.48.
7-Azidofurazano[3,4-b]tetrazolopyrazine (5): Method
1: A mixture of compound 4 (0.6 g, 2.8 mmol) in dry aceto-
nitrile (20 mL) was chilled at -40 ºC and the solution of NO2BF4
(2.4 g) in acetonitrile (20 mL) was added slowly.After stirring
for 30 min, the solution was poured into cold water. The
aqueous phase was extracted with diethyl ether (30 mL × 2)
and organic fraction was dried over MgSO4 and concentrated
to give compound 5 (0.12 g, 24 %) as a white crystals. m.p.
79-81 ºC.
Influence of different nucleopilic reagent: In order to
introduce the furoxan and tetrazole rings in 7-nitrofuraxan[3,4-
b]tetrazolopyrazine, this meant to the synthesis of the precur-
sor 2,6-diazido-3,5-dinitropyrazine (Scheme-III), in which the
furoxan ring could be obtained by nitrogen removal of
intramolecular between the azido and ortho nitro group. 2,6-
Diazido-3,5-dinitropyrazine could be prepared by the direct
nucleophilic substitution of a methoxy group or by the
replacement of a diazonium moiety by the N3– ions. In later
case, that implied the preparation of a diamino or of a dihydrazino
compound like, respectively, compounds 3 and 4. Therefore,
our attention was turned to investigate the nucleophilic substi-
tution reactions with compound 2.
Method 2: The compound 4 was dissolved in acetic acid
and the temperature was then chilled to -5 ºC. A solution of
NaNO2 (1.7 mol/L,15 mL) was added dropwise with vigorous
stirring while maintaining the temperature below 3 ºC for 2 h
and then poured into ice water. The aqueous phase was extracted
with diethyl ether (30 mL × 2) and organic phase was dried
over MgSO4 and concentrated to dryness to give compound 5
(0.11 g, 20 %) as a white crystals. m.p. 79-81 ºC.
The direct displacement of methoxy group by N3- ions
gave no reaction in compound 2. On the other hand, compound
3 was successfully achieved using aqueous ammonia in aceto-
nitrile at atmospheric pressure. However, treatment of compound
3 with sodium nitrite followed by sodium azide was found to
be ineffective to form the diazido precursor 2,6-diazido-3,5-
dinitropyrazine. The reason may be that electron-withdrawing
effect of nitro group greatly reduced both the reactivity of the
amino group and the stability of the diazonium salts. Using
13C NMR (CDCl3, 125 MHz) δ: 149.2 (C1-5AA), 150.9
(C5-5AA); 13C NMR [(CD3)2CO, 125 MHz] δ: 138.8 (C7-
5AT), 140.7 (C5-5AT), 150.1 (C1-5AT), 151.5 (C8-5AT); 13C
NMR (DMSO-d6, 125 MHz) δ: 139.1 (C8-5TT), 141.2 (C1-
5TT); 15N NMR (CDCl3, 36 MHz) δ: 249.4 (N12-5AA); 15N
NMR [(CD3)2CO, 36 MHz] δ : 252.1 (N15-5AT), 361.3 (N12-
5AT); 15N NMR (DMSO-d6, 36 MHz) δ: 360.8 (N12-5TT).
Anal. calcd for C4N10O: C, 23.54; N, 68.62. Found: C, 24.08;
N, 68.94.

Vol. 25, No. 9 (2013)
Synthesis of 7-Azidofurazano[3,4-b]tetrazolopyrazine 4981
other nucleophiles only either led to extensive decomposition
of compound 2, or gave no reaction. Eventually, compound 4
as a brown solid was given in yield 97 % by employing
hydrazine hydrate in ethanol at -78 ºC for 2 h.
Effect of solvent polarity on structure of isomers: In
nitrogen heteroaromatic ring the tetrazole ring nitrogen atom
could be easily formed between nitrogen atom and its adjacent
azido in polarity solvents. As reported in literature, the azido
of 3,6-diazidotetrazine along with its adjacent nitrogen atom
gradually transformed into tetrazole ring with increasing
polarity of solvents13. (Scheme-V)
NH
H N
2
2
N
N
O N
2
NO
2
3
N N
.
NH H O
3
2
N3
N3
N N
DAT
OMe
N
N
N
N
3
MeO
3
N
-
N
H N-HN
NH-NH
N H . H O
2
N
2
3
2
4
2
X
O N
2
NO
2
N
O N
2
NO
2
N
N N
N N
H N-HN
2
NO
2
N
Increasing polarity
Decreasing polarity
4
2
N
N
N
N
N
N
N
N
N
Scheme-III
N
N3
N
N
Cyclization reactions of furazan and tetrazole: Based
upon the reasearch of the transformation of hydrazines into
azides using dinitrogen tetroxide and clay supported ferric
nitrate9,10, we undertook a nitrosation reaction for compound
4 with two kinds of nitrosating reagents i.e., nitrosonium
tetrafluoroborate and sodium nitrite in acetic acid. Both of
nitrosating regents gave compound 5 as white crystals in about
20 % yield. Compound 5 contained a tetrazole ring along with
an azido substituent and a quite unexpected furazan ring
instead of the expected furoxan.
Scheme-V
In this work, we investigated the relations between diffe-
rent isomers of compound 5 and polarity of solvents. Based
on significant difference of 15N NMR chemical shifts featured
by tetrazole ring and azido, the 13C and 15N NMR in different
polarity solvents showed that compound 5 would have three
isomeric forms in solution (Table-1). The 13C NMR spectrum
displayed two sets of signals of different chemical shifts. The
15N NMR signals at 250 ppm and 360 ppm were generally
attributed to the azide function displacement and tetrazole
rings, respectively. In deuterated chloroform, 15N NMR signal
at 249.4 ppm along with 13C NMR signals at 149.2 ppm and
150.9 ppm would belong to an open diazido 5AA. On the
other hand, the 15N NMR signals at 252.3 ppm and 362.9 ppm
as well as 13C NMR signals at 138.2 ppm, 149.6 ppm and
151.7 ppm would be assigned to the monotetrazole 5AT.
(Scheme-VI)
The compound 2 was treated with hydrazine hydrate to
lead to compound 4 rather than gave the 2,6-dihydrazino-3,5-
dinitropyrazine, which involved a nucleophilic aromatic
substitution of one of the nitro group adjacent to intracyclic
nitrogen by a hydrazine group in compound 2.11 Compound 4
underwent nitrosation reaction to form intermediate 6 with
three azidos and then led to intermediate 7 with a furoxan and
tetrazole side ring by eliminating N2 in heating, which might
be followed by a remarkable reduction of the furoxan into a
furazan side ring eventurally, akin to dismutation. This reduction
process has actually been reported in the past for some
functionalized furoxans upon treatment with hydrogen peroxide
in trifluoroacetic acid12, which would explain the lower yield
of compound 5 obtained (Scheme-IV).
12
11
N
N
4
6
10
N
4
N
N
6
5
N N N
10
N
7
N
5
1
7
12 11
O
3
3
O
14
N N N
15
13
8
1
N
15 14 13
N N N
N
8
N
N
9
2
2
N
N
5AT
5AA
N
H2NHN
H2NHN
N
N
NHNH2
NO2
N
N
12
N
1 1
10
N
O
2
4
N
N
N
6
N
5
1
N
N3
7
3
O
5
4
13
N
N
8
N9
2
[O]
N15
N
14
5TT
Scheme-VI
N
N
N3
N3
N
N
N3
N
Even more interesting, another phenomenon was observed
in deuterated acetone. The 15N NMR signal at 252.1 ppm and
361.3 ppm along with 13C signals at 138.8, 140.7, 150.1 and
151.5 ppm corresponded to the 5AT form. On the other hand,
the 15N NMR signals at 360.2 ppm along with 13C NMR signals
at 138.7 and 140.4 ppm would only come from a tetracyclic
form 5TT featuring two tetrazole rings in its structure.
N
N
O
O
NO2
N
N
N3
7
6
Scheme-IV

4982 Guo et al.
Asian J. Chem.
Furthermore, a similar pattern was observed in deuterated
dimethylsulfoxide. The 15N NMR signals at 139.1 ppm as well
as 13C NMR signals at 141.2 ppm were attributed to the
tetrazole rings.
Conclusion
In conclusion, 7-azidofurazano[3,4-b]tetrazolopyrazine
has been synthesized by a nucleophilic aromatic substitution
of a nitro group adjacent to nitrogen atom using hydrazine
hydrate, nitrosation reaction and cyclization. An unexpected
dismutation involving the transformation between furoxan and
furazan has been described. Furthermore, our studies based
on 13C and 15N NMR data have shown that in different solvents
compound 5 exists in equilibrium between three isomeric
forms 5AA, 5AT and 5TT relaying on the polarity of solvents.
TABLE-1
13C AND 15N NMR CHEMICAL SHIFTS FOR THE
AZIDE (A) AND TETRAZOLE (T) IN CHLOROFORM,
ACETONE AND DMSO OF COMPOUND 5
Atom
C1
Solvent
CDCl3
5AA
5AT
149.6
150.1
5TT
149.2
Acetone-d6
DMSO-d6
CDCl3
140.4
141.2
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C5
C7
149.2
150.9
150.9
249.4
249.4
140.3
140.7
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151.7
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