Oxodiazonium ion generation 5. 3-(N-Nitroamino)-4-phenylfuroxan: Synthesis and reactivity

Article abstract of DOI:10.1007/s11172-012-0048-z

3-(N-Nitroamino)-4-phenylfuroxan, the first representative of the furoxan series that contains the N-nitroamino group in position 3 of the furoxan ring, was obtained. This compound is not very stable; its structure was confirmed by chemical transformation

Full text of DOI:10.1007/s11172-012-0048-z

Russian Chemical Bulletin, International Edition, Vol. 61, No. 2, pp. 351—354, February, 2012
351
Oxodiazonium ion generation
5.* 3ꢀ(NꢀNitroamino)ꢀ4ꢀphenylfuroxan: synthesis and reactivity
V. P. Zelenov, A. A. Voronin, A. M. Churakov, M. S. Klenov, Yu. A. Strelenko, and V. A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: churakov@ioc.ac.ru
3ꢀ(NꢀNitroamino)ꢀ4ꢀphenylfuroxan, the first representative of the furoxan series that conꢀ
tains the Nꢀnitroamino group in position 3 of the furoxan ring, was obtained. This compound is
not very stable; its structure was confirmed by chemical transformations into an ammonium salt
and Nꢀ and Oꢀmethyl derivatives. Under standard conditions for oxodiazonium ion generation
from nitramine, 3ꢀ(Nꢀnitroamino)ꢀ4ꢀphenylfuroxan underwent a transformation into the corꢀ
responding azofuroxan, viz., 3,3´ꢀdiazenediylbis(4ꢀphenylꢀ1,2,5ꢀoxadiazole 2ꢀoxide), while the
Oꢀmethyl derivative of 3ꢀ(Nꢀnitroamino)ꢀ4ꢀphenylfuroxan yielded 2ꢀhydroxyiminoꢀ2ꢀphenylꢀ
acetonitrile. The changed reactivity of the oxodiazonium ion was explained by its intramolecular
interaction with the exocyclic O atom of the furoxan system.
Key words: nitramines, furoxans, oxodiazonium ion, nitration, 1H, 13C, and 14N NMR
spectroscopy.
Previously,2 we have transformed amine 1 into comꢀ
pound 2, a first representative of (Nꢀnitroamino)furoxans,
and its Oꢀmethyl derivative 3. A reaction of nitramine 2
with the system H2SO4/Ac2O, as well as a reaction of
compound 3 with H2SO4, gives [1,2,5]oxadiazolo[3,4ꢀc]ꢀ
cinnoline 1,5ꢀdioxide (4). Supposedly, these reactions inꢀ
volve the formation of oxodiazonium ion A undergoing
intramolecular cyclization with the phenyl ring (Scheme 1).
In the present work, our task was to study the reactivity
of ion B containing the exocyclic O atom of the furoxan
system in the vicinity of the oxodiazonium ion, in contrast to
ion A. The precursors of ion B were nitramine 5 (prepared
from amine 6) and its Oꢀmethyl derivative 7 (Scheme 2).
Synthesis of the starting materials. Nitramine 5 was
obtained by nitration of aminofuroxan 6 with the system
HNO3/NH4NO3/H2O employed previously2 for the synꢀ
thesis of nitramine 2. Nitramine 5 was isolated as white
crystals. Since this compound is unstable, the crystals were
immediately dissolved in cooled Et2O and used in a reacꢀ
tion with diazomethane or (NH4)2CO3 (see Scheme 2).
The ratio of the resulting Oꢀ and Nꢀmethyl derivatives
7 and 8 is 6 : 5 (1H NMR). The structures of these prodꢀ
Scheme 1
* For Part 4, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 349—352, February, 2012.
1066ꢀ5285/12/6102ꢀ351 © 2012 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Zelenov et al.
Scheme 2
oxan 1 in Ac2O immediately followed by addition of a soꢀ
lution of two equivalents of 93% H2SO4 in Ac2O results in
the rapid formation of nitramine 2 gradually transformed
into cinnoline 4 (see Scheme 1). The reaction at 5—10 C
is completed in 10 min.
A similar reaction with aminofuroxan 6 (Scheme 3)
also gives a nitramine (TLC, AcOEt—light petroleum
(1 : 3)); however, its subsequent transformation produces
azo compound 11 (31% yield) rather than the expected
cinnoline 10. This azo compound was also obtained indeꢀ
pendently by oxidation of amine 6 with dibromoisocyanꢀ
uric acid (DBI) (Scheme 3) according to a previously deꢀ
veloped method.4
Scheme 3
i. HNO3/NH4NO3/H2O = 75 : 18 : 7 (wt/wt), –5 to 0 C, 3 h;
ii. CH2N2/Et2O; iii. (NH4)2CO3/MeOH.
1
ucts were confirmed by H, 13C, and 14N NMR spectroꢀ
scopy. The signals in the 13C NMR spectra were comꢀ
pletely assigned using 2D correlation experiments (13C—1H
HMBC and HSQC). According to 1H and 13C NMR data,
Oꢀmethyl derivative 7 is a virtually individual stereoisomer
with the Eꢀconfiguration of the azoxy fragment (by analoꢀ
gy with Oꢀmethylated nitramine 3, see Ref. 3).
i. HNO3 (1 equiv.)/Ac2O, 93% H2SO4 (2 equiv.)/Ac2O, 5—10 C,
10 min.
Note that 3ꢀ(Nꢀnitroamino)ꢀ4ꢀphenylfuroxan (5) is
a first representative of the furoxan series that contains the
nitramine substituent in position 3 of the furoxan ring.
Treatment of a cold solution of nitramine 5 in methaꢀ
nol with ammonium carbonate produces relatively stable
ammonium salt 9.
Generation of the oxodiazonium ion from nitramine 5.
Earlier,2 we have found that addition of an equivalent of
conc. HNO3 (d = 1.5 g cm–3) to a solution of aminofurꢀ
Since the formation of azo compound 11 from nitrꢀ
amine 5 occurs under the conditions used to generate oxoꢀ
diazonium ion A from nitramine 2 (see Scheme 1), one
can assume that the corresponding cation B is generated
from nitramine 5 as well. The marked distinction between
the reactivities of these cations can be attributed to the
existence of the conformation B´ (Scheme 4) stabilized by
an intramolecular ionic interaction. This conformation
Scheme 4

Oxodiazonium ion generation
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
353
have negative values). IR spectra were recorded on a Specord
Mꢀ80 spectrometer. Mass spectra were measured on a Kratos
MSꢀ300 instrument (EI, 70 eV). The course of the reactions was
monitored by TLC on 60 F254 plates (Merck). Chemapol 40/60
silica gel was used for column chromatography. A solution of
diazomethane in diethyl ether5 and 3ꢀaminoꢀ4ꢀphenylfuroxan
(6)6 were prepared according to known procedures.
3ꢀ(NꢀNitroamino)ꢀ4ꢀphenylfuroxan (5). 3ꢀAminoꢀ4ꢀphenylꢀ
furoxan (6) (1.77 g, 10 mmol) was added at –5 C to a stirred
nitrating mixture (18 g) of HNO3 (13.5 g, 214 mmol), NH4NO3
(3.2 g, 40 mmol), and water (1.3 g). The reaction mixture was
stirred at –2 to –8 C for 3 h and poured onto crushed ice (50 g)
in cold (0 C) 20% aqueous NH4NO3 (30 mL). The precipitate
of nitramine 5 that formed was promptly filtered off, washed on
a Schott filter funnel with cold 20% aqueous NH4NO3
(3×15 mL), dried on the same funnel for 1—2 min, and immediꢀ
ately used in subsequent reactions.
precludes the cyclization into cinnoline, yet allowing interꢀ
molecular reactions.
According to quantum chemical computations
(B3LYP/6ꢀ31++G(d,2p)), the distance between the exoꢀ
cyclic O atom of the furoxan system and the central N
atom of the fragment [—N=N=O]+ in ion B´ is 2.86 Å
which suggests the formation of an intramolecular bond.
A possible pathway leading to azo compound 11 inꢀ
volves an attack of the Nꢀnitroamino group on the oxodiaꢀ
zonium ion (see Scheme 4).
To prevent the intermolecular interaction of the oxoꢀ
diazonium ion with nitramine, cation B´ was generated
from Oꢀmethyl derivative 7 (Scheme 5) under the condiꢀ
tions used for the generation of cation A from compound 3
(see Scheme 1).
However, a reaction of furoxan 7 with H2SO4 (25 C,
10 min) gave 2ꢀhydroxyiminoꢀ2ꢀphenylacetonitrile (12)
in 64% yield rather than the expected cinnoline 10. The
same product was obtained in 65% yield by a reaction of
furoxan 7 with CF3COOH in the presence of (CF3CO)2O
(25 C, 72 h). The mechanism of the formation of oxime 12
still remains unclear.
Reaction of 3ꢀ(Nꢀnitroamino)ꢀ4ꢀphenylfuroxan (5) with diazoꢀ
methane. Freshly prepared nitramine 5 was dissolved at 0 C
in Et2O (80 mL) and a solution of diazomethane was added at
0—5 C with stirring until nitramine 5 was completely consumed
(monitoring by TLC). Then the solvent was removed in vacuo.
The final mixture contained Oꢀ and Nꢀmethyl derivatives 7 and
8 (1.67 g) and an impurity of aminofuroxan 6 (TLC). The mixꢀ
ture was separated by column chromatography on silica gel with
light petroleum—CHCl3 (20 : 1) as an eluent.
3ꢀ[(E)ꢀ(MethoxyꢀONNꢀazoxy)ꢀ4ꢀphenyl]ꢀ1,2,5ꢀoxadiazole
2ꢀoxide (7). Yield 0.72 g (31%), Rf 0.36 (CHCl3), m.p. 79—81 C.
Found (%): C, 45.52; H, 3.33; N, 23.95. C9H8N4O4. Calculatꢀ
ed (%): C, 45.77; H, 3.41; N, 23.72. 1H NMR (CDCl3), : 4.18
(s, 3 H, OMe); 7.44—7.50 (m, 3 H, H(3´), H(4´), H(5´)); 7.82
(dd, 2 H, H(2´), H(6´), J = 7.8 Hz, J = 1.4 Hz). 13C NMR
(CDCl3), : 59.2 (OMe); 118.6 (C(3)); 125.5 (C(1´)); 127.0
(C(2´), C(6´)); 129.2 (C(3´), C(5´)); 131.6 (C(4´)); 151.7 (C(4)).
The signals in the 13C NMR spectrum were assigned using an
Scheme 5
HMBC experiment. 14N NMR (CDCl3), : –54 (NO, 
=
1/2
= 170 Hz).
3ꢀ(NꢀMethylꢀNꢀnitro)aminoꢀ4ꢀphenylꢀ1,2,5ꢀoxadiazole
2ꢀoxide (8). Yield 0.07 g (3%), Rf 0.44 (CHCl3), m.p.
137.5—139.5 C (from CDCl3). Found (%): C, 45.59; H, 3.29;
N, 23.70. C9H8N4O4. Calculated (%): C, 45.77; H, 3.41;
N, 23.72. 1H NMR (CDCl3), : 3.66 (s, 3 H, Me); 7.53 (t, 2 H,
H(3´), H(5´), J = 7.5 Hz); 7.58 (t, 2 H, H(4´), J = 7.5 Hz); 7.69
(d, 2 H, H(2´), H(6´), J = 7.6 Hz). 13C NMR (CDCl3), : 38.2
(Me); 116.5 (C(3)); 124.8 (C(1´)); 126.6 (C(2´), C(6´)); 129.6
(C(3´), C(5´)); 132.1 (C(4´)); 154.0 (C(4)). The signals in the
13C NMR spectrum were assigned using HMBC and HSQC
experiments. 14N NMR (CDCl3), : –36 (N—NO2, 1/2 = 35 Hz).
3ꢀ(NꢀNitroamino)ꢀ4ꢀphenylfuroxan, ammonium salt (9). The
crystals of nitramine 5 freshly prepared from aminofuroxan 6
(0.354 g, 2 mmol) as described above were dissolved at 0 C in
MeOH (10 mL). Then (NH4)2CO3 (1 g, 10 mmol) was added at
0 C with vigorous stirring. The excess of ammonium carbonate
was filtered off and the solvent was removed in vacuo. The resiꢀ
due was washed with light petroleum—AcOEt (1 : 1, 20 mL).
The resulting crystals were dissolved in AcOEt (35 mL) at 40 C.
The solution was filtered to separate an insoluble impurity of
(NH4)2CO3 and concentrated in vacuo. The resulting ammoniꢀ
um salt 9 (0.161 g) was crystallized from MeOH—AcOEt—light
petroleum (1 : 5 : 6). The yield of compound 9 was 62 mg (21%),
white crystals, m.p. 123—127 C (decomp.). Found (%): C, 39.78;
i. 93% H2SO4, 25 C, 10 min; ii. CF3COOH/(CF3CO)2O, 25 C,
72 h.
To sum up, oxodiazonium ion B´ generated under stanꢀ
dard conditions from nitramine 5 or Oꢀmethylated nitrꢀ
amine 7 is not involved in intramolecular cyclization with
the phenyl ring, yet participating in other reactions. Such
a changed reactivity compared to the oxodiazonium ion A
generated from nitramine 2 or Oꢀmethylated nitramine 3
is probably due to an intramolecular interaction of the
oxodiazonium ion with the exocyclic (Nꢀoxide) O atom of
the furoxan system.
Experimental
1
H, 13C, and 14N NMR spectra were recorded on a Bruker
DRXꢀ500 instrument (500.13, 125.76, and 36.14 MHz, respecꢀ
tively). Chemical shifts are referenced to SiMe4 (1H, 13C) or
MeNO2 (
14N, external standard; the highꢀfield chemical shifts

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Zelenov et al.
H, 3.75; N, 29.39. C8H9N5O4. Calculated (%): C, 40.17; H, 3.79;
N, 29.28. 1H NMR (acetoneꢀd6), : 7.48—7.51 (m, 3 H, H(3´),
H(4´), H(5´)); 7.92 (d, 2 H, H(2´), H(6´), J = 5.8 Hz). 13C NMR
(acetoneꢀd6), : 122.3 (C(3)); 127.6 (C(2´), C(6´)); 128.7 (C(1´));
130.0 (C(3´), C(5´)); 131.8 (C(4´)); 154.9 (C(4)). The signals in
the 13C NMR spectrum were assigned using an HSQC experiꢀ
ment. 14N NMR (acetoneꢀd6), : –13 (N—NO2, 1/2 = 60 Hz);
–362 (NH4+, 1/2 = 20 Hz).
2ꢀHydroxyiminoꢀ2ꢀphenylacetonitrile (12). The Na salt of
2ꢀhydroxyiminoꢀ2ꢀphenylacetonitrile (67 mg, 0.4 mmol) preꢀ
pared according to a known procedure7 was dissolved in a mixꢀ
ture of CH2Cl2 (2 mL) and AcOEt (1 mL). Then 93% H2SO4
(0.042 mL, 0.78 mmol) was added at 20 C with vigorous stirring.
The reaction mixture was stirred for 5 min and passed through
a short column of silica gel with CH2Cl2 as an eluent. The eluate
was concentrated to give 2ꢀhydroxyiminoꢀ2ꢀphenylacetonitrile
(12). Yield 58 mg (100%), m.p. 130—131 C (cf. Ref. 7: 129 C).
1H NMR (acetoneꢀd6), : 7.52—7.54 (m, 3 H, H(3´), H(4´),
H(5´)); 7.79—7.81 (m, 2 H, H(2´), H(6´)); 12.69 (br.s, 1 H,
OH). 13C NMR (acetoneꢀd6), : 110.8 (CN), 127.1 (C(2´),
C(6´)), 130.5 (C(3´), C(5´)), 131.2 (C(1´)), 132.3 (C(4´)), 133.7
(C=NOH).
Reaction of 3ꢀ(methoxyꢀONNꢀazoxy)ꢀ4ꢀphenylꢀ1,2,5ꢀoxadiꢀ
azole 2ꢀoxide (7) with H2SO4. OꢀMethylated derivative 7 (81 mg,
0.34 mmol) was added to 93% H2SO4 (0.71 mL) at 20 C with
vigorous stirring. The reaction mixture was stirred at 20 C for
10 min. Then crushed ice (3.5 g) was added in one portion. The
precipitate that formed was filtered off; organic material was
extracted from the aqueous solution with CHCl3 (3×5 mL). The
precipitate and the extracts were combined, dried with MgSO4,
and concentrated in vacuo. The product was purified by column
chromatography on silica gel with CHCl3 as an eluent. The yield
of 2ꢀhydroxyiminoꢀ2ꢀphenylacetonitrile (12) was 32 mg (64%),
m.p. 127—129.5 C. The 1H and 13C NMR and mass spectra
of this product are identical with those of compound 12 deꢀ
scribed above.
(from light petroleum—AcOEt) (cf. Ref. 8: 196—197 C). The
1H NMR, IR, and mass spectra of compound 11 agree with the
literature data.8
Reaction of 3ꢀaminoꢀ4ꢀphenylfuroxan (6) with the system
HNO3/H2SO4/Ac2O. A solution of HNO3 (d = 1.5 g cm–3
,
36 mg, 0.57 mmol) in Ac2O (0.5 mL) and then 93% H2SO4
(113 mg, 1.15 mmol) in Ac2O (0.5 mL) were added at 3 C to
a stirred solution of 3ꢀaminoꢀ4ꢀphenylfuroxan (6) (102 mg,
0.58 mmol) in Ac2O (2 mL). The reaction mixture was stirred at
5—8 C for 40 min, poured into a water—ice mixture (30 mL),
and stirred for an additional 30 min. The precipitate that formed
was filtered off and dissolved in CHCl3 (10 mL). The resulting
solution was dried with MgSO4 and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
with CHCl3 as an eluent. The crude product was suspended in
benzene (1 mL), the undissolved impurity was filtered off, and
the mother liquor was concentrated in vacuo. The yield of comꢀ
pound 11 was 31 mg (31%), m.p. 193—198 C (decomp.). The
1H NMR, IR, and mass spectra of compound 11 agree with the
literature data.8
We are grateful to V. N. Solkan for his assistance in
quantum chemical computations.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00752)
and the Ministry of Education and Science (State Conꢀ
tract No. 02.740.11.0258).
References
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Reaction of 3ꢀ(methoxyꢀONNꢀazoxy)ꢀ4ꢀphenylꢀ1,2,5ꢀoxadiꢀ
azole 2ꢀoxide (7) with a mixture of CF3COOH and (CF3CO)2O.
Compound 7 (30 mg, 0.13 mmol) was added at 25 C to a mixꢀ
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tion mixture was stirred for 72 h until the starting compound was
completely consumed. The solvent was removed in vacuo and
the residue was purified by column chromatography on silica gel
with CHCl3 as an eluent. The yield of 2ꢀhydroxyiminoꢀ2ꢀphenylꢀ
acetonitrile (12) was 12 mg (65%), m.p. 125 C. The 1H and 13
C
5. F. Arndt, in Organic Syntheses, Vol. 15, Wiley, New York,
1935, pp. 3—4.
NMR and mass spectra of this product are identical with those of
compound 12 described above.
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3,3´ꢀDiazenediylbis(4ꢀphenylꢀ1,2,5ꢀoxadiazole 2ꢀoxide) (11).
Dibromoisocyanuric acid (163 mg, 1.2 mmol) was added at 25 C
to a stirred suspension of 3ꢀaminoꢀ4ꢀphenylfuroxan (6) (100 mg,
0.6 mmol) in CH2Cl2 (8 mL). The reaction mixture was stirred
for 2.5 h. The precipitate that formed was filtered off and
washed with CH2Cl2 (3×5 mL). The combined filtrate was passed
through a short column of silica gel with CH2Cl2 (30 mL) as an
eluent. The solvent was removed in vacuo. The yield of azoꢀ
furoxan 11 was 94 mg (95%), orangeꢀred crystals, m.p. 194—196 C
Received July 26, 2011