Dinitrogen trioxide-mediated domino process for the regioselective construction of 4-nitrofuroxans from acrylic acids

Article abstract of DOI:10.1002/hc.21166

4-Nitrofuroxans (4-nitro-1,2,5-oxadiazole 2-oxides) were prepared by a dinitrogen trioxide-mediated domino reaction of acrylic acids under the action of NaNO₂ excess in AcOH at room temperature. The reaction proceeds completely regioselectively and presents a new, simple, general, and safe method for the preparation of both 3-aryl- and 3-alkyl-4-nitrofuroxans available with difficulty before. A mechanism for the furoxan ring construction through a four-step one-pot protocol is proposed. The synthesized nitrofuroxans have been characterized by multinuclear NMR spectroscopy and X-ray powder diffraction.

Full text of DOI:10.1002/hc.21166

Heteroatom Chemistry
Volume 25, Number 4, 2014
Dinitrogen Trioxide–Mediated Domino
Process for the Regioselective Construction of
4-Nitrofuroxans from Acrylic Acids
Leonid L. Fershtat,1 Marina I. Struchkova,1
Alexander S. Goloveshkin,2 Ivan S. Bushmarinov,2
and Nina N. Makhova1
1N. D. Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, Moscow, Russia
2A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences,
Moscow, Russia
Received 23 December 2013; revised 14 March 2014
late 19th century when pioneering methods of the
ABSTRACT:
4-Nitrofuroxans
(4-nitro-1,2,5-
furoxan ring formation such as oxidation of vici-
nal glyoximes [1a], cyclodimerization of nitrile ox-
ides [1b], and dehydration of α-nitrooximes [1c]
were described. Furoxan chemistry has been vigor-
ously evolving for the past 100-year period due to
its unique properties that distinguish it from other
azoles [2]. First of all, furoxan is used as a build-
ing block containing a “hidden” nitro group or two
nitroso groups. In the course of its chemical trans-
formation, the nitro group can be released in such
reactions as the Boulton–Katritzky rearrangement
of benzo- and monocyclic furoxans [3] and, in other
cases, a reaction, primarily under action of nucle-
ophiles, may involve nitroso groups (e.g., the Beirut
reaction of benzofuroxans [4] and aminofuroxans re-
arrangement to triazol-1-oxides [5]). Another unique
property of furoxans is their susceptibility to thermal
isomerization in which the exocyclic oxygen atom
transfers from one nitrogen atom to the other [6].
The reaction can be described as a direct opening
of the furoxan ring, resulting in a dinitrosoethylene
intermediate to be followed by direct cyclization to
another isomer without involving any other parti-
cles and without generating any additional inter-
mediate complexes—so-called “no mechanism reac-
tion.” Equal reaction rates in different solvents are
used as the evidence [6b]. The preference in generat-
ing a particular isomer depends on the electronic
oxadiazole 2-oxides) were prepared by a dinitrogen
trioxide–mediated domino reaction of acrylic acids
under the action of NaNO2 excess in AcOH at
room temperature. The reaction proceeds completely
regioselectively and presents a new, simple, gen-
eral, and safe method for the preparation of both
3-aryl- and 3-alkyl-4-nitrofuroxans available with
difficulty before. A mechanism for the furoxan ring
construction through a four-step one-pot protocol is
proposed. The synthesized nitrofuroxans have been
characterized by multinuclear NMR spectroscopy and
ꢀC
X-ray powder diffraction. 2014 Wiley Periodicals,
Inc. Heteroatom Chem. 25:226–237, 2014; View
this article online at wileyonlinelibrary.com. DOI
10.1002/hc.21166
INTRODUCTION
A synthesis of the first representatives of furox-
ans (1,2,5-oxadiazole 2-oxides) dates back to the
Correspondence to: Nina Makhova; e-mail: mnn@ioc.ac.ru.
Contract grant sponsor: Russian Academy of Sciences (the pro-
gram OKhNM-04).
Contract grant sponsor: Russian Foundation for Basic Re-
search.
Contract grant numbers: 12-03-12012 OFNM and 12-03-31560.
2014 Wiley Periodicals, Inc.
ꢀC
226

Dinitrogen Trioxide–Mediated Domino Process for the Regioselective Construction of 4-Nitrofuroxans 227
effects of substituents at С(3) and С(4) atoms of
the furoxan ring. Furoxans chemical behavior dif-
fers from N-oxides of other nitrogen heterocycles:
In spite of their capability of reduction to corre-
sponding furazans under the action of various agents
such as PCl3, phosphines, phosphites, SnCl2, or Zn
in АсОН [7], attempts to prepare furoxans by oxi-
dation of furazans have failed. Symmetrically sub-
stituted furoxans can dissociate under heating into
two nitrile oxides as a result of cycloreversion. In
the reaction conditions, the latter can either be cap-
tured as cycloadducts by means of an interaction
with various dipolarophiles or isomerize to respec-
tive isocyanates [8].
SCHEME 1 Known synthetic routes to nitrofuroxans.
Continuous investigations revealed key poten-
tial applications of furoxans. It has been found that
furoxan derivatives have a broad range of biological
activity [9]—they act as nitric oxide (NO) donors [10]
and as neuroprotective and procognitive agents [11]
as well as delay cytotoxic [12], antihelmintic [13a],
antibacterial [13b], and fungicidal [13c] activities.
In addition, the furoxan ring is of interest as a struc-
tural unit for designing energetic compounds ow-
ing to positive enthalpy of formation and the pres-
ence of two active oxygen atoms inside the ring [14].
This makes nitrofuroxans especially attractive since
the nitro group adds two active oxygen atoms to
the molecule. Some nitrofuroxan derivatives (e.g.,
4,4ꢁ-dinitro-3,3ꢁ-diazenofuroxan) have high explo-
sive performance [15]. In addition, nitrofuroxans are
efficient NO donors [16]. Furthermore, they are very
useful as sources of polyfunctional derivatives pre-
pared by nucleophilic substitution of the nitro group
under the action of N-, O-, S-nucleophiles or hydride
ion, by reductive condensation to azo- and azoxy-
derivatives, etc. [2a].
Several representatives both of 3-nitrofuroxans
1 and of 4-nitrofuroxans 2 prepared by different
synthetic routes are described. Most of them have
been developed in past few years. In particular, our
research team developed a method for the synthe-
sis of 3-nitro-4-R-furoxans 1 (R = Ar, СОМе, СО2Et)
based on nitrosation of dipotassium salts of 2-R-2-
hydroximino-1,1-dinitroethanes 3 [17]. By refluxing
in toluene, 3-nitroisomers 1 isomerize quantitatively
to thermodynamically preferable 4-nitroisomers 2.
4-Nitrofuroxans 2 can also be prepared by oxida-
tive cyclization of the amphi-form of corresponding
nitroglyoximes 4 [18], as well as by means of the
amino group oxidation in 4-aminofuroxans [19] 5
and of the β-nitrostyrenes interaction with NaNO2
in AcOH [20] 6 ( Scheme 1).
ans 5 is restricted because of an insufficient set
of starting compounds. Moreover, to oxidize the
latter rather strong oxidative mixtures are needed.
Low yields of 4-nitrofuroxans 2 are typical for
their synthesis from β-nitrostyrenes 6 and nitro-
sation of dipotassium salts of 2-R-2-hydroximino-
1,1-dinitroethanes 3 runs successfully exclusively
with aromatic or electron-withdrawing substituents.
In addition, dipotassium salts per se and their
precursors—dinitromethane sodium or potassium
salt—are high explosives. In regard to isomeric alkyl-
nitrofuroxans, methods of their synthesis actually
have not been developed and just their individual
representatives have been described so far. There-
fore, a search for a new general as well as simpler
and safer approach to the synthesis of nitrofuroxans
remains relevant.
In search for such approach, we paid our
attention to furoxan ring formation methods based
on the interaction of unsaturated compounds with
nitrosating agents having been in focus of many
investigations for a long time. The first synthesis of
4-aryl-3-methylfuroxans involving the treatment of
arylmethylethylene with NaNO2 in АсОН medium
was published by Angeli back in 1892 [1c]. Later on,
other authors replicated this reaction and examined
the action of the same nitrosating system on some
other disubstituted ethylenes, including structures
with functional substituents, such as cinnamic
alcohol [21a] or methylformylethylene [21b]. It
was established that the first reaction step was the
N2O3 addition to the double bond of starting olefin
that gave pseudonitrosite 7. Its nitroso fragment
isomerizes to the oxime fragment at heating, and
only after that the furoxan ring forms through
dehydration of α-nitrooxime 8. To effectively
transform pseudonitrosite 7, which forms nitroso
dimer 9, to α-nitrooxime 8 heating in polar aprotic
solvents (dimethylformamide, dimethyl sulfoxide,
hexamethylphosphoramide) is required and, for
Unfortunately, all the methods have serious dis-
advantages. The preparation of 4-nitrofuroxans 2
by oxidation of nitroglyoximes 4 or aminofurox-
Heteroatom Chemistry DOI 10.1002/hc

228 Fershtat et al.
SCHEME 2 Mechanism for the formation of the furoxan ring by means of the α-nitrooxime dehydration.
SCHEME 3 Known examples for the synthesis of nitrofuroxans from acrylic acids.
dehydration, most effective appeared to be heating
of α-nitrooxime 8 in sulfuric or polyphosphoric acid
[21c] (Scheme 2). For dialkylpseudonitrosites, the
proposed synthetic method was based on passing
of the NO and О2 gaseous mixture through an ether
solution of disubstituted ethylenes [21c].
nitrofuroxans were prepared in low yields and in
most cases as a mixture of 3- and 4-nitroisomers
(Scheme 3).
RESULTS AND DISCUSSION
Recently [22], the preparation of a mixture
of isomeric 3(4)-R-4(3)-arylfuroxans from the β-R-
substituted styrenes under the action of NOBF4 un-
der basic or even almost neutral reaction conditions
has been reported. Since the reaction yields a mix-
ture of the isomers, the authors suppose that the in-
termediate product is a dinitrosoethylene derivative
rather than α-nitrooxime.
Since both 2-alkyl- and 2-arylsubstituted acrylic
acids are readily available compounds, we decided
to study in detail their behavior under the action
of different nitrosating systems. To do that, we
presynthesized a representative set of 2-alkyl- and
2-arylacrylic acids 10b–g and 11a–d by known meth-
ods [26]. 2,9-Dimethylenedecanedioic acid (10h) un-
known before was prepared from malonic ester and
α,ω-dibromohexane in a similar manner.
At first, we investigated a possibility of using the
conditions described in [20, 25] (NaNO2 in a two-
phase system: 60% H2SO4–DCE, 50оС) to prepare
nitrofuroxans 1 and 2 with different substituents.
We managed to synthesize 3-methyl-4-nitrofuroxan
2a in the proposed conditions [25] even in higher
yield—36%. Furthermore, we found this approach
to be general for the synthesis of other alkylnitro-
furoxans from 2-alkylacrylic acids 10c–h, which re-
acted irrespective of the alkyl substituent structure
(Method A). However, the actually inseparable mix-
ture of 3- and 4-nitrofuroxans 1c–e,g,h and 2c–e,g,h
(Table 1) in most cases (with the exception of en-
tries 1 and 5) was obtained in moderate yields. The
method also proved to be suitable for the synthe-
sis of nitrophenylfuroxan from 1-phenylacrylic acid
11а, yet still as a mixture of two isomers 1i and 2i.
The ratio of isomers 1 and 2 was estimated on
the basis of the integral intensity ratio of proton
signals in the 1Н NMR spectra and signals from NO2
Few efforts of using a reaction between un-
saturated compounds and nitrosating agents with
the view of preparing nitrofuroxans have been
described. A successful synthesis of 4-nitro-3-
phenylfuroxan from styrene has been reported; how-
ever, authors failed to introduce substituted styrenes
into the reaction [23]. As mentioned above (Scheme
1), we succeeded in preparing 3-aryl-4-nitrofuroxans
2 from β-nitrostyrenes in low yields [20]. An in-
separable mixture of isomeric 4(3)-methyl-3(4)-
nitrofuroxans 1а and 2а (ratio 1:13) was isolated in
a minor yield (3.3%) after 2-methylmaleic acid ni-
1
tration and characterized by H, 13С, and 14N NMR
spectroscopy [24].
A principal possibility to synthesize 3-methyl-
4-nitrofuroxan 2a in 24% yield by an interaction
between methacrylic acid 10a and NaNO2 in a two-
phase system 60% H2SO4–dichloroethane (DCE)
at low heating (50°C) was for the first time shown
in [25]. Later on, we extended this approach to
some other 2-alkylacrylic acids [20]. Corresponding
Heteroatom Chemistry DOI 10.1002/hc

Dinitrogen Trioxide–Mediated Domino Process for the Regioselective Construction of 4-Nitrofuroxans 229
TABLE 1 Synthesis of 3-R-4-Nitrofuroxans 2 by Means of Method A
Chemical Shift of the NO2
Group in 14N NMR (ppm)
Entry
R
1
2
Ratio a 2/1
Yield b 2 (%)
1
2
3
4
5
6
Me (10a)
nPr (10c)
iPr (10d)
nBu (10e)
Cy (10f)
–
–34.89
–34.73
–34.19
–34.76
–34.11
–35.42
99:1
9:1
10:1
12:1
99:1
11:1
2a (36)
2c (39)
2d (34)
2e (39)
2f (39)
2g (12)
–38.25
–38.16
–38.25
–
–38.95
–38.25
Bn (10g)
7
(10h)
–32.60
5:1
2hc (28)
8
Ph (11a)
–39.88
–35.32
11:1
2i (24)
aDetermined by the integral intensity ratio of proton signals in the 1Н NMR spectra.
bIsolated yield.
c
groups in the 14N NMR spectra since positions of
the substituents in nitrofuroxans derivatives can be
teristics of the isolated isomers were completely in
agreement with the literature [17b]. In addition, 3-
nitroisomer 1i was isomerized to 4-nitroisomer 2i
by refluxing of the mixture in toluene in the same
conditions (Table 1).
To increase the yields of the final products,
we have performed a wide search of reaction con-
ditions by the example of methacrylic acid 10a
varying a nitrosating reagent (NaNO2, N2O4), its
amount (3–9 mol for 1 mol of initial acrylic
acid), reaction medium (H2SO4–DCE, ionic liq-
uid 1-ethyl-3-methylimidazolium hydrogen sulfate
([emim]HSO4), AcOH), temperature (0–100°C), and
reaction time (0.5–120 h) (Table 2).
According to the data from Table 2, conditions
for the synthesis of 3-methyl-4-nitrofuroxan 2a in
Method B (entry 5) proved to be the best. Those were
extended to the other 2-substituted acrylic acids.
It appeared that the reaction of all synthesized 2-
alkylacrylic acids 10b–h as well as 2-arylacrylic acids
11a–d with the NaNO2 excess in AcOH at room tem-
perature proceeded completely regioselectively and
resulted in only 3-R-4-nitrofuroxans 2a–l in moder-
ate and high yields (Table 3). Important advantages
of the developed method include easy isolation of
synthesized 4-nitrofuroxans and the absence of im-
purities. To isolate the final products, it is just needed
to pour the reaction mixture in water and either filter
them or extract with CH2Cl2 followed by evaporation
of the solvent.
1
unambiguously determined on the basis of the H,
14N, and 13C NMR spectra (Table 1).
As shown in [20,24], chemical shifts of protons of
СН2 fragments at C(3) carbon atoms in the 1Н NMR
spectra of 3-alkyl-4-nitrofuroxans 2 are located more
upfield as compared to the analogous group of sig-
nals at the С(4) carbon atom of the furoxan ring in
4-alkyl-3-nitrofuroxans 1 (ꢀδ = ꢀ0.2 ppm). The ni-
tro group position at the furoxan ring referring to the
N-oxide fragment can also be determined using 14N
NMR spectra data for isomeric arylnitrofuroxans
[17a,b]—the signal of the 3-nitro group moved up-
field by 3.7–4.7 ppm relative to the 4-nitro group
signal. A close difference in chemical shifts of the
signals from the nitro groups (ꢀδ = 3.3 ppm) is
also observed in isomeric methylnitrofuroxans 1a
and 2a. The signals of C(3) and C(4) carbon atoms
in the 13C NMR spectra of isomeric arylnitrofurox-
ans are varied in a similar manner [17a,b]: The
chemical shift of the С(3) carbon atom in 4-aryl-3-
nitrofuroxans occurs upfield by ꢀ20–25 ppm in com-
parison with that of the C(4) carbon atom in 3-aryl-4-
nitrofuroxans. Synthesized 4-alkyl-3-nitrofuroxans
1c–e,g,h were not isolated and were isomerized to
3-alkyl-4-nitrofuroxans 2c–e,g,h by refluxing of the
prepared mixtures of isomers in toluene for 3 h. Iso-
meric nitrophenylfuroxans 1i and 2i were separated
by column chromatography on SiO2. The charac-
Heteroatom Chemistry DOI 10.1002/hc

230 Fershtat et al.
TABLE 2 Optimization of the Reaction Conditions for the Synthesis of 3-Methyl-4-nitrofuroxan 2a
Entry
Nitrosation Reagent (mol)
Reaction Medium
Temperature (оС)
Time (h)
Yield 2a (%)
1
2
3
4
5
6
NaNO2 (3.5)
NaNO2 (3)
NaNO2 (3)
N2O4 (5)
NaNO2 (9)
NaNO2 (9)
60% H2SO4–DCE
[emim][HSO4]
[emim][HSO4]
Et2O
AcOH
CF3COOH
50
20
100
0
20
20
0.5
120
120
3
72
72
36
0
0
10
51
8
TABLE 3 Synthesis of 3-R-4-Nitrofuroxans 2 by Means of
sults in the pseudonitrosite 12 formation by addition
of N2O3 generated from NaNO2 in AcOH, to the dou-
ble bond of acrylic acids 10 or 11. Furthermore, the
methylene group of intermediate 12 is nitrosated un-
der the action of N2O3 resulting in a dinitroso deriva-
tive 13. The latter undergoes decarboxylation with
simultaneous isomerization of both nitroso groups
to the oxime ones to give amphi-glyoximes 14, which
are oxidized to 4-nitrofuroxans 2 under the action
of the same nitrogen oxides. The appearance of the
mixture of isomeric nitrofuroxans by Method А may
be explained by the formation of the mixture of iso-
meric amphi-glyoximes at heating in the presence of
H2SO4.
Method B
Entry
R
Time (h)
Yield a 2 (%)
1
2
3
4
5
6
7
Me (10a)
72
72
72
72
72
72
72
2a (51)
2b (32)
2c (52)
2d (55)
2e (54)
2f (57)
2g (41)
MeOCH2CH2 (10b)
nPr (10c)
iPr (10d)
nBu (10e)
Cy (10f)
Bn (10g)
The structure of the synthesized compounds was
established by a totality of elemental and spectral
analysis data (1H, 13C, 14N NMR spectroscopy, mass
spectrometry, and IR), and the structure of com-
pound 2h was additionally supported by powder X-
ray diffraction data.
The powder diffraction pattern (see the Exper-
imental section) of 2h was indexed using TOPAS
4.2 software [27] in the orthorhombic crystal sys-
tem, with the Pbca space group judged from the cell
volume (expected Zꢁ = 0.5) and the systematic ab-
sences. The lattice parameters (after Rietveld refine-
8
(10h)
120
2hb (70)
9
Ph (11a)
Naphthalen-1-yl (11b)
p-MeC6H4 (11c)
72
72
72
72
2i (36)
2j (71)
2k (35)
2l (33)
10
11
12
p-ClC6H4 (11d)
aIsolated yield.
b
To explain the regioselective formation of 3-R-4-
nitrofuroxans 2 from acrylic acids 10a–h and 11a–
d and the NaNO2 excess in AcOH, we proposed a
hypothetic Scheme 4, which differs from Scheme 2
for the formation of furoxan ring by means of the
α-nitrooxime dehydration. Most likely, this reaction
represents the dinitrogen trioxide–mediated domino
process and involves four sequential steps. The first
step is similar to the first step of Scheme 2 and re-
˚
˚
ment) are a = 13.86225(22) A, b = 10.20307(14) A,
3
˚
˚
c = 10.33897 (14) A, and V = 1462.32(4) A .
The crude molecular geometry for the struc-
ture solution was obtained using the MM approach
as implemented in Marvin (Marvin 5.8.1, 2012;
ChemAxon, http://www.chemaxon.com). Since we
expected Zꢁ = 0.5, half of the molecule (see Fig. 3)
was used as a model for structure solution in direct
SCHEME 4 Proposed mechanism for the formation of 3-R-4-nitrofuroxans 2 from 1-R-acrylic acids 10 and 11.
Heteroatom Chemistry DOI 10.1002/hc

Dinitrogen Trioxide–Mediated Domino Process for the Regioselective Construction of 4-Nitrofuroxans 231
8.274/1.653 with Rexp/Rꢁexp values of 0.681/1.729,
2
˚
χ = 4.786, and rms ꢀd of 0.015 A.
Synthesized alkylnitrofuroxans are either low-
melting compounds (2a,f,g,i–l) or stable distillable
liquids (2c–e). They incorporate four active oxygen
atoms in the molecule and are challenging as promis-
ing ingredients (e.g., plasticizers) for energetic for-
mulations. The density of the liquids 2c, 2d, and
2e was measured with a pycnometer and found
to be 1.266, 1.300, and 1.180 g cm−3, respectively.
The heat of formation (࢞fHo) is very important pa-
rameter in evaluating the performance of energetic
materials. This characteristic can be calculated for
furoxan derivatives by various quantum chemical
methods [33]. However, recently it has been shown
that for furoxans a simple prediction of ࢞fH can be
performed with good accuracy by using the addi-
tive method based on the values of the group contri-
FIGURE 1 Box-and-whisker plots for bond length deviation
bution and the intramolecular interaction [34]. The
calculated values for 4-nitro-3-propyl- and isopropy-
lfuroxans 2c,d and 3-butyl-4-nitrofuroxan 2e are –
8.57 and –15.44 kcal mol−1, respectively.
(ꢀd) distributions in Rietveld refinements of 2h at varied val-
ues of global penalty function weighting (K1).
space using the Parallel Tempering method as imple-
mented in FOX [28]. Indeed, in the solution found
the molecule lies around the inversion center.
CONCLUSIONS
Further Rietveld refinement was performed
using breakable restraints based on previously
published the “Morse” restraint model [29] and was
applied during the Rietveld refinement in TOPAS
(see the Experimental section). The analysis of
the deviations of refined bond lengths from the
defined values within this restraint model has
been shown to validate Rietveld refined structures:
The structures containing no outliers in bond ꢀd
distribution are considered correct. The restraints
for the refinement initially were prepared basing
on a PBE/L2 [30] calculation of 2h using PRIRODA
software [31]. However, the calculated geometry of
the furoxan ring in this model has been problematic,
In summary, our investigations have resulted in
a development of simple, general, efficient, and
safe method for the synthesis of 3-alkyl- and 3-
aryl-4-nitrofuroxans. This method is based on the
N2O3-mediated domino reaction of corresponding
acrylic acids with NaNO2 excess in AcOH at room
temperature. A four-step one-pot route of the re-
action is described. The target nitrofuroxans are
formed completely regioselectively with moderate
and good yields. It is especially important that the de-
veloped method allows preparing earlier hardly ac-
cessible 3-alkyl-4-nitrofuroxans. Synthesized alkyl-
nitrofuroxans are either low-melting compounds
or stable distillable liquids with sufficiently high
density and enthalpy of formation. They incorporate
four active oxygen atoms in the molecule and show
promise as ingredients of energetic formulations.
˚
with O2–N2 distance of 1.7 A and model showed
outliers in the refinement. We assume that such
discrepancy is caused by the incorrect description of
polar bonds by PBE functional: The ring geometry
in the calculated model deviated significantly from
the published crystal structure of 2a [32]. Thus, the
restraints for the final refinement were prepared on
the basis of the structure of 2a for the furoxan ring
and a PBE/L2 for the alkyl chain.
EXPERIMENTAL
General
All reactions were carried out in well-cleaned glass-
ware with magnetic stirring. All starting materials
were purchased from commercial sources. Melting
points were measured on a Gallenkamp Sanyo ap-
paratus and are not corrected. Elemental analyses
were performed on the CHN analyzer Perkin–Elmer
2400. The IR spectra (ν, cm−1) were measured using
a Bruker “Alpha” spectrometer. Mass spectra were
After 150 refinements in TOPAS with the de-
creasing penalty function weight (K1; see the Ex-
perimental section), there were not outliers in
the bond length deviation (ꢀd) distribution (see
Fig. 1), supporting the correctness of the refined
structure. At K1 = 3, the refinement converged to
ꢁ
Rp/RP /RWP/RWPꢁ/RBragg values of 2.269/9.703/3.259/
Heteroatom Chemistry DOI 10.1002/hc

232 Fershtat et al.
FIGURE 2 Experimental and calculated powder patterns for 2h at K1 = 3 and their difference.
measured using a Finnigan MAT INCOS-50 instru-
ment. The NMR spectra of all compounds were mea-
sured using a Bruker AC200-31 spectrometer at 200
MHz for 1H and 50.3 MHz for 13C spectra and a
Bruker AM-300 spectrometer at 300 MHz for 1H,
75.5 MHz for 13C spectra and 21.5 MHz for 14N spec-
tra in CDCl3 or [D6]DMSO. 1H and 13C spectra were
recorded using TMS as an internal standard. 14N
spectra were measured using CH3NO2 (δ14N = 0.0
ppm) as an external standard. Analytical thin-layer
chromatography (TLC) was carried out on Merck
25 TLC silica gel 60 F254 aluminum sheets. The X-
ray powder diffraction (XRD) of 2h was measured
on a Bruker D8 Advance Vario diffractometer with
a LynxEye detector and Ge (111) monochromator,
˚
λ(Cu Kα1) = 1.54060 A, ꢁ/2ꢁ scan from 7° to 120°,
stepsize 0.018338° (see Fig. 2). The measurement
was performed in the transmission mode, with 2h
deposited between two Kapton films.
FIGURE 3 Molecular structure of 2h in crystal. Atoms are
represented by spheres indicating their isotropic thermal dis-
placements (ρ = 50%). Only symmetry independent atoms
are labeled.
The penalty function in the breakable restrained
refinement is defined as follows:
ꢀ
i
i
i
P = K1
κi[1 − e−a |D −d | 2
]
i
with stirring for 3 h. After cooling down to room
temperature, water (20 mL) was added and the
resulting mixture was acidified with 3 N aqueous
HCl until pH 1. An organic layer was separated,
washed twice with water and with brine, dried over
MgSO4. The solution was filtered, and the solvent
was evaporated under reduced pressure to give the
desired product as a white solid. Yield 5.75 g (72%);
mp 135–136°C; IR (KBr): ν = 1627, 1692, 2877,
where P is a penalty function, K1 is a global penalty
function weighting, κi is the weighting of the individ-
ual bond penalty, ai is a coefficient corresponding to
the bond force constant, Di is the defined length of a
given bond, and di is its refined length at the current
minimization step. It is a modification of “Morse”
restraint model, which does not suffer from asym-
metry of the bond potential.
1
2904, 2922 cm−1; H NMR (300 MHz, [D6]DMSO):
2,9-Dimethylenedecanedioic acid (10h). Diethy-
lamine (70.8 mmol) and paraformaldehyde (106
mmol) were added to a solution of octane-1,1,8,8-
tetracarboxylic acid [26a] (35.4 mmol) in EtOAc
(80 mL) at 5–10°C, and the mixture was refluxed
δ = 1.22–1.26 (m, 4H, CH2CH2CH2CH2CH2CH2),
1.37 (t, J = 6.2 Hz, 4H, CH2CH2CH2CH2CH2CH2),
2.17 (t, J = 7.8 Hz, 4H, CH2CH2CH2CH2CH2CH2),
5.40 (s, 2H, 2CH), 6.01 (s, 2H, 2CH), 8.9–10.1
(br s, 2H,
2
COOH); 13C NMR (75.5 MHz,
Heteroatom Chemistry DOI 10.1002/hc

Dinitrogen Trioxide–Mediated Domino Process for the Regioselective Construction of 4-Nitrofuroxans 233
[D6]DMSO): δ = 27.91 (s, CH2CH2CH2CH2CH2CH2),
an diacrylic acid 10h (10 mmol, 2.26 g) in a mix-
ture of acetic acid (110 mL) and water (11 mL),
NaNO2 (60 mmol, 4.14 g) was added at room tem-
perature. Stirring was continued at room tempera-
ture overnight. The residual amount of NaNO2 (120
mmol, 8.28 g) was divided into 10 equal portions;
each portion was added to a reaction medium ev-
ery 10 h. Then water (400 mL) was added. The solid
formed was filtered, washed with water, and dried
in air.
28.37 (s, CH2CH2CH2CH2CH2CH2), 31.27 (s,
CH2CH2CH2CH2CH2CH2), 123.96 (s, 2 × C CH2),
141.19 (s, 2 × C CH2), 168.09 (s, 2 × COOH); MS (70
eV): m/z (%): 226 (12) [M]+, 181 (29) [M – COOH]+,
136 (41) [M – 2COOH]+; elemental analysis calcd for
C12H18O4: C 63.70; H 8.02; found: C 63.66; H 7.99.
Method A: 4-Nitrofuroxans 2a,c–i from 2-Acrylic
Acids and NaNO2 in a Two-Phase System H2SO4–
dichloroethane (DCE).
3-Methyl-4-nitrofuroxan (2a) [24]. Pale yellow
solid; yield 1.04 g (36%)—method A; 0.74 g (51%)—
method B; mp 68–69°C; Rf = 0.43 (CCl4/CHCl3 2:1);
IR (KBr): ν = 644, 829, 1057, 1126, 1359, 1385, 1499,
1569, 1628, 2904 cm−1; 1H NMR (200 MHz, CDCl3):
δ = 2.51 (s, 3H, CH3); 13C NMR (50.3 MHz, CDCl3):
δ = 9.01 (s, CH3), 107.62 (s, C(3) furoxan), 158.93
(s, C(4) furoxan); 14N NMR (21.5 MHz, CDCl3): δ =
–34.89 (s, NO2); MS (70 eV): m/z (%): 145 (36) [M]+,
115 (33) [M – NO]+, 99 (16) [M – NO2]+, 85 (100) [M –
2NO]+, 69 (44) [M – NO – NO2]+; elemental analysis
calcd for C3H3N3O4: C 24.84; H 2.08; N 28.96; found:
C 24.90; H 2.10; N 28.90.
General Procedure. NaNO2 (70 mmol, 4.83 g)
was added portionwise to a mixture of 6 mL of 60%
H2SO4 and a solution of appropriate acrylic acid (20
mmol) in 20 mL DCE at 50°C for 30 min, and the mix-
ture was vigorously stirred at this temperature for
additional 30 min. Then the organic layer was sepa-
rated and washed with 3% Na2CO3 aqueous solution
until the organic phase was completely became col-
orless, washed with water, and dried over MgSO4.
The solution was filtered, and the solvent was evap-
orated under reduced pressure to give the product
as a mixture of 3- and 4-nitroisomers, which were
analyzed by multinuclear NMR spectroscopy. All ob-
tained mixtures were dissolved in toluene (3 mL) and
refluxed for 3 h. Then the solvent was evaporated un-
der reduced pressure to give quantitatively the cor-
responding 4-nitrofuroxans. In addition, isomers 1i
and 2i were separated by column chromatography
(eluent: CCl4–CHCl3, 3:1).
3-(2-Methoxyethyl)-4-nitrofuroxan (2b) [20].
Yellow oil; yield 0.60 g (32%); Rf = 0.34 (CCl4/CHCl3
2:1); IR (KBr): ν = 835, 1058, 1105, 1192, 1360,
1
1433, 1575, 1632, 1642, 2873, 2946, 2970 cm−1; H
NMR (300 MHz, CDCl3): δ = 3.14 (t, J = 5.9 Hz,
2H, CH3OCH2CH2), 3.28 (s, 3H, CH3OCH2CH2),
3.63–3.69 (m, 2H, CH3OCH2CH2); 13C NMR (75.5
MHz, CDCl3): δ = 23.41 (s, CH3OCH2CH2), 58.34 (s,
CH3OCH2CH2), 66.54 (s, CH3OCH2CH2), 108.27 (s,
C(3) furoxan), 158.91 (s, C(4) furoxan); 14N NMR
(21.5 MHz, CDCl3): δ = –34.68 (s, NO2); MS (70 eV):
m/z (%): 189 (36) [M]+, 159 (24) [M – NO]+, 143
(11) [M – NO2]+, 129 (31) [M – 2NO]+, 113 (30) [M
– NO – NO2]+, 83 (100) [M – 2NO – NO2]+, 59 (61)
[MeOCH2CH2]+, 45 (26) [MeOCH2]+; elemental
analysis calcd for C5H7N3O5: C 31.75; H 3.73; N
22.22; found: C 31.79; H 3.79; N 22.17.
Method B: 4-Nitrofuroxans 2a–g,i–l from 2-
Acrylic Acids and NaNO2 in Acetic Acid.
General Procedure. To a stirred solution of an
appropriate acrylic acid (10 mmol) in a mixture of
acetic acid (50 mL) and water (5 mL), NaNO2 (30
mmol, 2.07 g) was added at room temperature. Stir-
ring was continued at room temperature overnight.
The residual amount of NaNO2 (60 mmol, 4.14 g)
was divided into six equal portions; each portion
was added to a reaction medium every 10 h. Then
water (300 mL) was added. If the solid formed, it
was filtered, washed with water, and dried in air.
If the solid was not formed, the solution was ex-
tracted with CH2Cl2 (4×30 mL). Combined organic
layers were washed with saturated NaHCO3 solution
(2×60 mL), then with water and dried over MgSO4.
Organic solution was filtered, and the solvent was
evaporated under reduced pressure to afford a pure
furoxan compound.
4-Nitro-3-propylfuroxan (2c). Yellow oil; yield
1.35 g (39%) as a mixture of regioisomers—method
A; 0.90 g (52%)—method B; bp 67–68°C (0.6 mmHg);
Rf = 0.64 (CCl4/CHCl3 2:1); IR (KBr): ν = 828, 1030,
1059, 1133, 1225, 1274, 1358, 1431, 1462, 1502, 1571,
1
1631, 2879, 2939, 2971 cm−1; H NMR (300 MHz,
CDCl3): δ = 1.03 (t, J = 7.4 Hz, 3H, CH3CH2CH2),
1.68–1.86 (m, 2H, CH3CH2CH2), 2.87 (t, J = 7.3 Hz,
2H, CH3CH2CH2); 13C NMR (75.5 MHz, CDCl3): δ =
13.30 (s, CH3CH2CH2), 19.14 (s, CH3CH2CH2), 24.84
(s, CH3CH2CH2), 110.62 (s, C(3) furoxan), 158.71
(s, C(4) furoxan); 14N NMR (21.5 MHz, CDCl3):
Method B: Furoxan 2h from Diacrylic Acid 10h
and NaNO2 in Acetic Acid. To a stirred solution of
Heteroatom Chemistry DOI 10.1002/hc

234 Fershtat et al.
187 (27) [M]+, 157 (19) [M – NO]+, 141 (15) [M –
NO2]+, 127 (51) [M – 2NO]+, 111 (12) [M – NO –
NO2]+, 81 (20) [M – 2NO – NO2]+, 57 (100) [Bu]+;
elemental analysis calcd for C6H9N3O4: C 38.51; H
4.85; N 22.45; found: C 38.56; H 4.89; N 22.41.
δ = –34.73 (s, NO2); MS (70 eV): m/z (%): 173 (27)
[M]+, 143 (19) [M – NO]+, 127 (14) [M+ – NO2]+, 113
(41) [M+ – 2NO]+, 97 (29) [M – NO – NO2]+, 67 (38)
[M – 2NO – NO2]+, 43 (100) [Pr]+. elemental analysis
calcd for C5H7N3O4: C 34.69; H 4.08; N 24.27; found:
C 34.72; H 4.05; N 24.31.
4-Butyl-3-nitrofuroxan (1e). 1H NMR (200
MHz, CDCl3): δ (distinguishable peaks) = 2.32-
2.40 (m, 2H, CH3CH2CH2CH2), 2.98–3.09 (m,
2H, CH3CH2CH2CH2); 13C NMR (50.3 MHz,
CDCl3): δ (distinguishable peaks) = 13.87 (s,
CH3CH2CH2CH2), 22.36 (s, CH3CH2CH2CH2), 26.42
(s, CH3CH2CH2CH2), 29.51 (s, CH3CH2CH2CH2);
14N NMR (21.5 MHz, CDCl3): δ (distinguishable
peak) = –38.25 (s, NO2).
3-Nitro-4-propylfuroxan (1c). 1H NMR (300
MHz, CDCl3): δ (distinguishable peaks) = 1.83–
1.88 (m, 2H, CH3CH2CH2), 3.01–3.06 (m, 2H,
CH3CH2CH2); 13C NMR (75.5 MHz, CDCl3): δ (dis-
tinguishable peaks) = 17.34 (s, CH3CH2CH2), 19.65
(s, CH3CH2CH2), 28.75 (s, CH3CH2CH2), 127.09 (s,
C(3) furoxan); 14N NMR (21.5 MHz, CDCl3): δ (dis-
tinguishable peak) = –38.25 (s, NO2).
3-Isopropyl-4-nitrofuroxan (2d). Yellow oil;
yield 1.17 g (34%) as a mixture of regioisomers—
method A; 0.95 g (55%)—method B; bp 66–67°C
(0.6 mmHg); Rf = 0.57 (CCl4/CHCl3 2:1); IR (KBr):
ν = 1037, 1281, 1319, 1357, 1391, 1460, 1499, 1568,
3-Cyclohexyl-4-nitrofuroxan (2f). Yellow solid;
yield 1.65 g (39%)—method A; 1.21 g (57%)—method
B; mp 80–81°C; Rf = 0.66 (CCl4/CHCl3 2:1); IR (KBr):
ν = 761, 792, 833, 875, 999, 1074, 1142, 1238, 1282,
1353, 1450, 1496, 1563, 1620, 1736, 2858, 2926, 2941
1
1626, 2839, 2882, 2964 cm−1; H NMR (300 MHz,
cm−1
;
1H NMR (200 MHz, CDCl3): δ = 1.27–2.18
CDCl3): δ = 1.37 (d, J = 7.1 Hz, 6H, (CH3)2CH),
3.52–3.61 (m, 1H, CH); 13C NMR (75.5 MHz, CDCl3):
δ = 16.80 (s, 2 × CH3), 24.09 (s, (CH3)2CH), 113.19
(s, C(3) furoxan), 157.91 (s, C(4) furoxan); 14N NMR
(21.5 MHz, CDCl3): δ = –34.19 (s, NO2); MS (70 eV):
m/z (%): 173 (32) [M]+, 143 (24) [M – NO]+, 127 (23)
[M – NO2]+, 113 (49) [M – 2NO]+, 97 (11) [M – NO
– NO2]+, 67 (26) [M – 2NO – NO2]+, 43 (100) [iPr]+;
elemental analysis calcd for C5H7N3O4: C 34.69; H
4.08; N 24.27; found: C 34.73; H 4.11; N 24.30.
(m, 10H, 5CH2), 3.14–3.26 (m, 1H, CH); 13C NMR
(75.5 MHz, CDCl3): δ = 25.07, 25.69, 26.28, 33.34
(all s, C6H11), 112.42 (s, C(3) furoxan), 158.61 (s, C(4)
furoxan); 14N NMR (21.5 MHz, CDCl3): δ = –34.11
(s, NO2); MS (70 eV): m/z (%): 213 (11) [M]+, 183
(10) [M – NO]+, 167 (7) [M – NO2]+, 153 (30) [M –
2NO]+, 137 (14) [M – NO – NO2]+, 107 (9) [M – 2NO
– NO2]+, 83 (100) [Cy]+; elemental analysis calcd for
C8H11N3O4: C 45.07; H 5.20; N 19.71; found: C 45.03;
H 5.24; N 19.75.
4-Isopropyl-3-nitrofuroxan (1d). 1H NMR (300
MHz, CDCl3): δ (distinguishable peak) = 1.45 (d, J =
6.9 Hz, 6 H, (CH3)2CH); 13C NMR (75.5 MHz, CDCl3):
δ (distinguishable peaks) = 19.80 (s, 2 × CH3), 27.67
(s, (CH3)2CH); 14N NMR (21.5 MHz, CDCl3): δ (dis-
tinguishable peak) = –38.16 (s, NO2).
3-Benzyl-4-nitrofuroxan (2g). Yellow solid;
yield 0.53 g (12%) as a mixture of regioisomers—
method A; 0.91 g (41%)—method B; mp 82–84°C;
Rf = 0.50 (CCl4/CHCl3 2:1); IR (KBr): ν = 715, 770,
832, 1047, 1084, 1189, 1357, 1421, 1456, 1501, 1563,
1
1631, 2913 cm−1; H NMR (300 MHz, CDCl3): δ =
4.22 (s, 2H, C6H5CH2), 7.34 (s, 5H, C6H5CH2); 13C
NMR (75.5 MHz, CDCl3): δ = 28.80 (s, C6H5CH2),
108.78 (s, C(3) furoxan), 128.28, 128.68, 129.18,
132.73 (all s, C6H5), 157.12 (s, C(4) furoxan); 14N
NMR (21.5 MHz, CDCl3): δ = –35.42 (s, NO2); MS
(70 eV): m/z (%): 221 (41) [M]+, 191 (18) [M – NO]+,
175 (16) [M – NO2]+, 161 (32) [M – 2NO]+, 145 (21)
[M – NO – NO2]+, 115 (29) [M – 2NO – NO2]+, 91
(100) [Bn]+; elemental analysis calcd for C9H7N3O4:
C 48.87; H 3.19; N 19.00; found: C 48.90; H 3.14; N
18.96.
3-Butyl-4-nitrofuroxan (2e). Yellow oil; yield
1.46 g (39%) as a mixture of regioisomers—method
A; 1.01 g (54%)—method B; bp 73–74°C (0.6 mmHg);
Rf = 0.60 (CCl4/CHCl3 2:1); IR (KBr): ν = 830,
1052, 1357, 1430, 1466, 1501, 1570, 1629, 2875,
2935, 2963 cm−1 1H NMR (300 MHz, CDCl3):
;
δ = 0.97 (t, J = 7.4 Hz, 3H, CH3CH2CH2CH2),
1.36–1.48 (m, 2H, CH3CH2CH2CH2), 1.58–1.75
(m, 2H, CH3CH2CH2CH2), 2.88 (t,
J
=
7.4
Hz, 2H, CH3CH2CH2CH2); 13C NMR (50.3 MHz,
CDCl3): δ = 13.52 (s, CH3CH2CH2CH2), 22.22
(s, CH3CH2CH2CH2), 23.00 (s, CH3CH2CH2CH2),
27.69 (s, CH3CH2CH2CH2), 110.74 (s, C(3) furoxan),
159.04 (s, C(4) furoxan); 14N NMR (21.5 MHz,
CDCl3): δ = –34.76 (s, NO2); MS (70 eV): m/z (%):
4-Benzyl-3-nitrofuroxan (1g). 1H NMR (300
MHz, CDCl3): δ (distinguishable peaks) = 4.43 (s, 2H,
C6H5CH2), 7.57–7.62 (m, 5H, C6H5CH2); 13C NMR
(75.5 MHz, CDCl3): δ (distinguishable peaks) = 36.48
Heteroatom Chemistry DOI 10.1002/hc

Dinitrogen Trioxide–Mediated Domino Process for the Regioselective Construction of 4-Nitrofuroxans 235
(s, PhCH2), 127.36, 128.51, 128.91, 129.19, 133.74
Rf = 0.70 (CCl4/CHCl3 2:1); IR (KBr): ν = 693, 767,
853, 1008, 1273, 1299, 1356, 1417, 1463, 1481, 1525,
1545, 1617, 1656 cm−1; 1H NMR (300 MHz, CDCl3):
δ = 7.59–7.73 (m, 5H, Ph); 13C NMR (75.5 MHz,
CDCl3): δ = 123.98 (s, C(3) furoxan), 129.04, 129.14,
132.27 (all s, C6H5), 151.35 (s, C(4) furoxan); 14N
NMR (21.5 MHz, CDCl3): δ = –39.88 (s, NO2); MS
(all s, C6H5); 14N NMR (21.5 MHz, CDCl3): δ (distin-
guishable peak) = –38.95 (s, NO2).
3,3ꢁ-(Hexane-1,6-diyl)bis(4-nitrofuroxan) (2h).
Pale yellow solid; yield 1.93 g (28%) as a mixture
of regioisomers—method A; 2.41 g (70%)—method
B; mp 124–125°C; Rf = 0.37 (CCl4/CHCl3 2:1); IR
(KBr): ν = 814, 919, 1042, 1059, 1148, 1197, 1356,
(70 eV): m/z (%): 207 (24) [M]+, 177 (32) [M – NO]+
,
161 (19) [M – NO2]+, 147 (31) [M – 2NO]+, 131 (44)
[M – NO – NO2]+, 101 (53) [M – 2NO – NO2]+, 77
(100) [Ph]+; elemental analysis calcd for C8H5N3O4:
C 46.39; H 2.43; N 20.29; found: C 46.41; H 2.45; N
20.27.
1432, 1497, 1567, 1624, 2868, 2937, 2951 cm−1
;
1H NMR (200 MHz, [D6]DMSO): δ = 1.38 (br
s, 4H, CH2CH2CH2CH2CH2CH2), 1.64 (br s, 4H,
CH2CH2CH2CH2CH2CH2), 2.78 (t, J = 7.0 Hz, 4H,
CH2CH2CH2CH2CH2CH2); 13C NMR (75.5 MHz,
DMSO-d6): δ = 22.75 (s, CH2CH2CH2CH2CH2CH2),
24.52 (s, CH2CH2CH2CH2CH2CH2), 27.85 (s,
CH2CH2CH2CH2CH2CH2), 111.26 (s, C(3) furoxan),
159.20 (s, C(4) furoxan); 14N NMR (21.5 MHz,
[D6]DMSO): δ = –32.60 (s, NO2); MS (70 eV): m/z
(%): 344 (6) [M]+, 314 (7) [M – NO]+, 298 (11) [M
– NO2]+, 284 (25) [M – 2NO]+, 268 (21) [M – NO –
NO2]+, 254 (17) [M – 3NO]+, 252 (13) [M – 2NO2]+,
238 (9) [M – 2NO – NO2]+, 224 (100) [M – 4NO]+,
162 (10) [M – 3NO – 2NO2]+, 132 (39) [M – 4NO –
2NO2]+; elemental analysis calcd for C10H12N6O8:
C 34.89; H 3.51; N 24.41; found: C 34.93; H 3.57; N
24.38.
3-(Naphthalen-1-yl)-4-nitrofuroxan (2j). Yellow
solid; yield 1.83 g (71%); mp 95–96°C; Rf = 0.48
(CCl4/CHCl3 2:1); IR (KBr): ν = 776, 806, 832,
955, 1044, 1075, 1256, 1285, 1357, 1497, 1514,
1568, 1619 cm−1 1H NMR (200 MHz, CDCl3): δ
;
= 7.42–7.44 (m, 1H, Ar-H), 7.56–7.65 (m, 4 H, Ar-
H), 7.97–8.02 (m, 1 H, Ar-H), 8.10–8.14 (m, 1H,
Ar-H); 13C NMR (75.5 MHz, CDCl3): δ = 108.83
(s, C(3) furoxan), 116.86, 123.26, 125.21, 127.12,
128.29, 129.43, 129.94, 130.13, 133.02, 133.89 (all
s, C10H7), 158.73 (s, C(4) furoxan); 14N NMR (21.5
MHz, CDCl3): δ = –36.17 (s, NO2); MS (70 eV):
m/z (%): 257 (18) [M]+, 227 (15) [M – NO]+, 211
(21) [M – NO2]+, 197 (35) [M – 2NO]+, 181 (9)
[M – NO – NO2]+, 151 (26) [M – 2NO – NO2]+,
127 (100) [Naphthyl]+; elemental analysis calcd for
C12H7N3O4: C 56.04; H 2.74; N 16.34; found: C 55.99;
H 2.78; N 16.31.
4,4ꢁ-(Hexane-1,6-diyl)bis(3-nitrofuroxan) (1h).
1H NMR (200 MHz, CDCl3): δ (distinguishable peak)
= 3.02–3.05 (m, 4H, CH2CH2CH2CH2CH2CH2);
13C NMR (75.5 MHz, CDCl3): δ (distinguishable
peaks)
=
23.32 (s, CH2CH2CH2CH2CH2CH2),
25.19 (s, CH2CH2CH2CH2CH2CH2), 29.73 (s,
CH2CH2CH2CH2CH2CH2); 14N NMR (21.5 MHz,
CDCl3): δ (distinguishable peak) = –38.25 (s, NO2).
4-Nitro-3-(p-tolyl)furoxan (2k). Yellow solid;
yield 0.77 g (35%); mp 88–89°C; Rf = 0.59
(CCl4/CHCl3 2:1); IR (KBr): ν = 779, 821, 990, 1074,
1121, 1273, 1288, 1364, 1480, 1523, 1561, 1609, 2922
1
4-Nitro-3-phenylfuroxan (2i) [17b]. Pale yellow
solid; yield 0.77 g (19%)—method A; 0.74 g (36%)—
method B; mp 96–97oC; Rf = 0.49 (CCl4/CHCl3 2:1);
IR (KBr): ν = 693, 759, 1284, 1292, 1375, 1469, 1496,
1532, 1576, 1619 cm−1; 1H NMR (300 MHz, CDCl3):
δ = 7.60 (s, 5H, Ph); 13C NMR (75.5 MHz, CDCl3):
δ = 109.15 (s, C(3) furoxan), 119.51, 128.83, 129.32,
131.98 (all s, C6H5), 158.11 (s, C(4) furoxan); 14N
NMR (21.5 MHz, CDCl3): δ = –35.32 (s, NO2); MS
cm−1; H NMR (200 MHz, CDCl3): δ = 2.46 (s, 3H,
CH3), 7.37 (d, J = 7.9 Hz, 2H, Ar-H), 7.50 (d, J =
7.9 Hz, 2H, Ar-H); 13C NMR (50.3 MHz, CDCl3):
δ = 21.68 (s, CH3), 111.98 (s, C(3) furoxan), 116.33,
128.63, 130.03, 142.74 (all s, C6H4), 159.44 (s, C(4)
furoxan); 14N NMR (21.5 MHz, CDCl3): δ = –35.03
(s, NO2); MS (70 eV): m/z (%): 221 (33) [M]+, 191
(17) [M – NO]+, 175 (12) [M – NO2]+, 161 (29) [M
– 2NO]+, 145 (23) [M – NO – NO2]+, 115 (43) [M –
2NO – NO2]+, 91 (56) [MeC6H4]+, 76 (100) [C6H4]+.
elemental analysis calcd for C9H7N3O4: C 48.87; H
3.19; N 19.00; found: C 48.82; H 3.22; N 19.04.
(70 eV): m/z (%): 207 (27) [M]+, 177 (25) [M – NO]+
,
161 (8) [M – NO2]+, 147 (35) [M – 2NO]+, 131 (37)
[M – NO – NO2]+, 101 (37) [M – 2NO – NO2]+, 77
(100) [Ph]+; elemental analysis calcd for C8H5N3O4:
C 46.39; H 2.43; N 20.29; found: C 46.43; H 2.39; N
20.24.
3-(4-Chlorophenyl)-4-nitrofuroxan (2l). Yellow
oil; yield 0.80 g (33%); Rf = 0.57 (CCl4/CHCl3 2:1);
IR (KBr): ν = 785, 844, 997, 1091, 1146, 1291,
1
3-Nitro-4-phenylfuroxan (1i) [17b]. Pale yellow
1379, 1480, 1526, 1567, 1615 cm−1; H NMR (300
solid; yield 0.07 g (2%)—method A; mp 109–110oC;
MHz, CDCl3): δ = 7.57 (br s, 4H, Ar-H); 13C NMR
Heteroatom Chemistry DOI 10.1002/hc

236 Fershtat et al.
(g) Stevens, J.; Schweizer, M.; Rauhut, G. J Am Chem
Soc 2001, 123, 7326.
(50.3 MHz, CDCl3): δ = 108.83 (s, C(3) furoxan),
117.88, 129.73, 130.25, 138.45 (all s, C6H4), 157.65
(s, C(4) furoxan); 14N NMR (21.5 MHz, CDCl3): δ =
–35.81 (s, NO2); MS (70 eV): m/z (%): 243 (6) [M +
2]+, 241 (16) [M]+, 213 (5) [M – NO + 2]+, 211 (15)
[M – NO]+, 197 (4) [M – NO2 + 2]+, 195 (9) [M+
– NO2]+, 183 (11) [M – 2NO + 2]+, 181 (32) [M –
2NO]+, 167 (10) [M – NO – NO2 + 2]+, 165 (26) [M
– NO – NO2]+, 137 (13) [M – 2NO – NO2 + 2]+, 135
(40) [M – 2NO – NO2]+, 113 (21) [ClC6H4 + 2]+, 111
(59) [ClC6H4]+, 76 (100) [C6H4]+; elemental analysis
calcd for C8H4ClN3O4: C 39.77; H 1.67; N 17.39; Cl
14.67; found: C 39.81; H 1.63; N 17.34; Cl 14.70.
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