Reactions of 5,7-dichloro-4,6-dinitrobenzofuroxane and -furazane with triphenylphosphine

Article abstract of DOI:10.1134/S1070428012050156

Reactions of 5,7-dichloro-4,6-dinitrobenzofuroxane and 5,7-dichloro-4,6- dinitrobenzofurazane with triphenylphosphine proceed through a nucleophilic aromatic substitution of chlorine and nitro groups in the six-membered ring of the heterocycles. The structure of the phosphorylation products was established from the IR, ³¹P NMR, and mass spectra and from XRD and elemental analysis. Schemes of the routes of the phosphorylation are discussed.

Full text of DOI:10.1134/S1070428012050156

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 5, pp. 721−727. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © I.V. Galkina, E.V. Tudrii, E.A. Berdnikov, L.M. Yusupova, F.S. Levinson, D.B. Krivolapov, I.A. Litvinov, R.A. Cherkasov, V.I. Galkin,
2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 5, pp. 722−727.
Reactions of 5,7-Dichloro-4,6-dinitrobenzofuroxane
and -furazane with Triphenylphosphine
I. V. Galkinaa, E. V. Tudriia, E. A. Berdnikova, L. M. Yusupovab, F. S. Levinsonb,
D. B. Krivolapovc, I. A. Litvinovc, R. A. Cherkasova, and V. I. Galkina
aKazan(Volga Region) Federal University, Kazan, 420008 Russia
e-mail: vig54@mail.ru
bKazan State Engineering University, Kazan, Russia
cArbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center,
Russian Academy of Sciences, Kazan, Russia
Received April 25, 2011
Abstract—Reactions of 5,7-dichloro-4,6-dinitrobenzofuroxane and 5,7-dichloro-4,6-dinitrobenzofurazane with
triphenylphosphine proceed through a nucleophilic aromatic substitution of chlorine and nitro groups in the six-
membered ring of the heterocycles. The structure of the phosphorylation products was established from the IR,
31P NMR, and mass spectra and from XRD and elemental analysis. Schemes of the routes of the phosphorylation
are discussed.
DOI: 10.1134/S1070428012050156
Although the chemistry of chloronitro-substituted
benzofuroxanes and benzofurazanes, substances
possessing a pronounced and versatile biological action,
is now well understood [1–7], no publications describe
the introduction into their molecules of potentially
pharmacophoric organophosphorus substituents. Yet we
presume that combining in the same molecule so powerful
pharmacophores like oxadiazole and phosphorus-
containing fragments is evidently interesting both
from the view of synthetic and theoretical chemistry of
phosphorus and nitrogen and also as the possibility to
search for new substances exhibiting potential biological
activity.
The reaction of 5,7-dichloro-4,6-dinitrobenzofuroxane
(I) with triphenylphosphine in the ratio 1:2 is accompa-
nied with the intensive change in the color of the reac-
tion mixture from yellow to dark-red apparently due to
the evolution of nitrosyl chloride. On completion of the
process dark-red crystals precipitated.
We established formerly [8] that the phosphorylation
with triphenylphosphine of chloronitrobenzofuroxanes
involved the reaction sites of the heterocycle linked both to
chloro- and nitro-substituents. However the reaction does
not stop at the formation of 5,7-bis(triphenylphosphonio)-
4,6-dinitrobenzofuroxanyl dichloride A (Scheme 2), but
proceeds on: chloride-ions of diphosphonium salt III
formed in the first stage in attempt at further stabilization
of the system attack its other electrophilic sites.
In this research we investigated the reaction of 5,7-di-
chloro-4,6-dinitrobenzofuroxane (I) and its structural
analog, 5,7-dichloro-4,6-dinitrobenzofurazane (II) with
triphenylphosphine.The reactions proceed under mild
conditions in alcohol-ether solution at room temperature,
with heat evolution leading to the formation of uncommon
products of di- and monosubstitution. In the reaction with
benzofuroxane I regardless the reagents ratio a product
of diphosphorylation III was isolated, but the synthetic
result of benzofurazane II phosphorylation depended
on the ratio of the initial reagents are afforded different
phosphorylation products IV–VII (Scheme 1).
As a result of the relatively synchronic processes of
the nucleophilic attack of chloride-anions on the nitro-
gen atom and of the oxygen from the nitro group on the
carbon atom of the C–NO2 bond the electron density in
the system is redistributed to form diphosphabetain di-
phenoate III and unstable molecules of nitrosyl chloride
Cl–N=O. The latter suffer the disproportionation to give
molecular chlorine and nitrogen oxide. Therewith the
structure of the final product III may be described by
a series of mesomeric structures from diphosphabetain
721

GALKINA et al.
722
Scheme 1.
Ph3P+
Cl
_ O
Ph3P
O2N
Cl
N
N
N
N
2 PPh3
_NOCl
O
O
NO2
I
O
III
O
O
PPh3] +
[Ph3P
N
_ O
Cl
O2N
Cl
O2N
Cl
N
N
N
O
N
2 PPh3
_Ph3PO
+
+
O
O
Cl
_Cl
+PPh3
V
O _
NO2
IV
O_
O2N
Cl
N
N
O
O2N
Cl
Cl
Cl
N
O
N
N
N
NO2
II
4 PPh3
_4Ph3PO, _N2,
_ [Ph3P
_
PPh3] +
N
Cl
+PPh3
+PPh3
VII
VI
Scheme 2.
_
_
Cl
O Ph3P+
Cl
N
N
N
+
O2N
O
N
O
2Ph3P +
O
+
Ph3P
N
Cl
N+
_O
O
NO2
I
O
O
Cl_
А
+
+
Ph3P
Ph3P
_O
_O
N
N
N
O
O
+
N
Ph3P
Ph3P
O _
IIIa
O
IIIb
O
O
2Cl
N O
+
Ph3P
Ph3P
2NO
Cl2
O
O
N
N
N
N
O
O
+
Ph3P
Ph3P
O _
IIIc
O
IIId
O
O
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

REACTIONS OF 5,7-DICHLORO-4,6-DINITROBENZOFUROXANE
723
diphenoate IIIa to phosphorus diketodiyl IIId [8]. The
composition and structure of compound III was proved
b the elemental analysis and a number of physical and
physicochemical methods. The final structure of the
product was established by XRD study [8].
The facts supporting the above shown Scheme 2 we
obtained at the study of the reaction mixture by means
of ESR [9]. Just in the first minutes of the reaction
a clear signal of te nitroxyl radical appeared in the ESR
spectrum of the reaction mixture (Fig. 1). The intensity
of the signal grew with time, passed through a maximum
and later decreased. These findings unambiguously show
the formation of NO in the course of the reaction. It is
also necessary to stress the importance of the visual
observations in the course of the process.
The phosphorylation of chlorine-substituted
benzofurazane II with triphenylphosphine in the
ratio 1:2 resulted in a mixture of phosphonium
derivatives: diphosphonium iminium salt IV and
aryltriphenylphosphonium chloride V (Scheme 1). The
structure of compound IV was proved by XRD analysis
B0, Gs
Fig. 1. Variation in time of ESR spectra of the reaction mixture.
by XRD method but also of phosphonium salt V which
was detected in the reaction mixture by 31P NMR spec-
troscopy (δ 23.68 ppm) (Scheme 3).
The analogous phosphorylation of benzofuroxane II
under the condition of a large excess of triphenylphos-
phine (1 : 4) in order to maximally bind the intermedi-
ately formed NOCl in triphenylphosphazophosphonium
chloride fundamentally changed the reaction direction
(Scheme 1).
(Fig. 2).
In keeping with the assumed reaction scheme the
phosphorus nucleophile attacks the atom C4 with the
initial replacement of a nitro group. Two molecules of
benzofurazane II are brought into the reaction simultane-
ously taking part not only in the formation of compound
IV (δP 18.17 ppm) whose crystal structure was established
A product resulted corresponding to two monophos-
phorylated benzofurazanes VI, VII crystallized together
Scheme 3.
Cl
Cl
Cl
O2N
Cl
O2N
Cl
O2N
Cl
N
N
N
N
N
N
PPh3
O
2
O
+
O
+PPh3 O N O_
O _
NO2
NO2
Cl
Cl N O
+ 3Ph3P
O2N
O2N
N
N
O
N
_
PPh3]+
[Ph3P
.
N
Ph PO
+
Cl
O
+
Cl N O
3
N
Cl
Cl
Cl
+PPh3
PPh3]+
NO2
[Ph3P
O2N
N
O _
O _
Cl
O2N
Cl
O2N
O2N
+
N
N
N
N
N
N
N
N
_
PPh ]+
.
O
O
[Ph P
N
O
O +
Ph3PO
+
Cl
3
3
Cl
Cl
Cl
Cl _
+PPh3
+PPh3
NO2
NO2
IV
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

GALKINA et al.
724
Thus we have shown for the first time the possibil-
ity of the introduction of potentially pharmacophoric
phosphorus-containing groups into the molecules of
chloronitro-substituted benzofuroxanes and benzofura-
zanes. It was also established that the direction and the
synthetic result of the phosphorylation depended on the
ratio of the initial reagents, and primarily on the reactiv-
ity of the heterocycle, since in contrast to benzofuroxane
the reaction of the corresponding benzofurazane with
triphenylphosphine did not provide the diphosphoryla-
tion product even at the four-fold excess of phosphine
apparently due to the higher electrophilicity of the ben-
zofuroxane ring having an additional oxygen atom in the
five-membered ring of the heterocycle.
Fig. 2. Spatial arrangement in the crystal of N-triphe-
nylphosphoranilidenetriphenylphosphoraniminium-6-chloro-
5,7-dinitro-2,1,3-benzoxadiazol-4-olate (IV).
EXPERIMENTAL
in one crystal in the ratio 1 : 1. The combined crystalliza-
tion product gave rise to two signals in the 31PNMR spec-
trum: 26.2 (VI) and 27.2 ppm (VII). The remaining two
signals belong to triphenylphosphine oxide (δP 32 ppm)
and to the expected triphenylphosphazophosphonium
chloride (δP 16.33 ppm).
31P NMR spectra were registered on a spectrometer
Bruker Avance-400. Chemical shifts were determined
with respect to external reference, 85% H3PO4. ESR
spectra were recorded on spectrometers Varian E-12 and
Bruker Elexys 680. The superhigh frequency 9.7 GHz.
IR spectra were taken on a spectrophotometer Specord
25IR in the range 400–3700 cm–1 from mulls in mineral
oil between KBr plates. Mass spectra of matrix-activated
laser desorption/ionization (MALDI) were obtained on a
time-of-flight mass spectrometer Dynamo MALDI TOF
Thermo Bioanalysis Finnigan, USA. The laser desorption
was performed with a UV laser with the wavelength of
337 nm. By repeated selection as matrix inert substances
The final structure of compounds VI, VII was
established by XRD study (Figs. 3, 4).
As follows from the reaction scheme we assumed
(Scheme 4), the attack of triphenylphosphine in this case
occurs at the carbon atom linked to the nitro group and
not to the chlorine atom. The subsequent transformations
are governed by the thermodynamic factors and totally
correspond to those described above.
Fig. 3. Spatial arrangement in the crystal of 6-chloro-5-nitro-7-(triphenylphosphonio)-2,1,3-benzoxadiazol-4-olate (VI) and 5,6-dichloro-
7-(triphenylphosphonio)-2,1,3-benzoxadiazol-4-olate (VII).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

REACTIONS OF 5,7-DICHLORO-4,6-DINITROBENZOFUROXANE
725
Scheme 4.
Cl
O N O
N
Cl
Cl_
O2N
Cl
O2N
Cl
O2N
Cl
O2N
Cl
N
N
N
N
N
N
PPh3
O
O
O
O
+
N
Cl
O N O_
+PPh3 _O N O
O N O_
+PPh3
+PPh3
NO2
II
Cl_
Cl_
O2N
O_
O N O
O N O
N
O N O
N
Cl
Cl
O2N
N
N
O2N
Route 2
N
N
Route 1
_NOCl
O
O
O
O
N
Cl
N
Cl
Cl
+PPh3
+PPh3
Cl
+PPh3
+PPh3
O_
N
N
+
O
N2O3
Cl
_
+ Cl
PPh3]
+PPh3
[Ph3P
Cl N O + 3 Ph3P
N
_Ph3PO
VII
N2O3 + 3 Ph3P
3 Ph P
N
2
+
3
were chosen. The sample was prepared by the “dried
drop” procedure: the mixture of a matrix solution in
methanol (0.1 wt%) and of an analyzed substance in
methanol (1 wt%) were placed on sublayer and dried at
40°C.
522, 441 (C–P–C). 31P NMR spectrum : δ 18.17 ppm.
Mass spectrum: m/z 797.5 [M + H]+. Found, %: C 63.75;
H 3.39; N 8.75. C42H30ClN5O6P2. Calculated, %: C 63.20;
H 3.76; N 8.78.
Compound V was detected in the reaction mixture by
31P NMR spectrum (δ 23.68 ppm).
7-Oxo-4-(triphenylphosphonio)-6-(triphenylphos-
phoranilidene)-6,7-dihydro-2,1,3-benzoxadiazol
-
5-olate 1-oxide (III). The procedure of the synthesis is
described in [8]. Yield 0.17 g (75%). 13P NMR spectrum
(DMSO): δ 27.1 ppm. Mass spectrum: m/z 689 [M + H]
+ for C42H31N2O4P2. Found, %: C 71.33; H 4.27; N 4.11;
P 9.06. C42H30N2O4P2·H2O. Calculated, %: C 71.39;
H 4.53; N 3.97; P 8.78. The structure was proved by
XRD analysis [8].
N-Triphenylphosphoranilidenetriphenylphospho-
raniminium-6-chloro-5,7-dinitro-2,1,3-benzoxadiazol-
4-olate (IV). To a solution of 0.188 g (0.72 mmol) of
triphenylphosphine in 10 ml of a mixture of ethanol
with ethyl ether, 1:3, was added dropwise at stirring
0.1 g (0.36 mmol) of dichlorodinitrobenzofurazane
II in 10 ml of the same solvent. On completion of the
reaction the solvent was evaporated, the precipitated red-
orange crystals were purified with ether. Yield 0.062 g
(46%), mp 242.4°C. IR spectrum, ν, cm–1: 1624 (C=N),
1590 (O–C=C), 1523 (NO2), 1520 (C=C), 1492 (C–N),
1362, 1261 (C–O), 1102, 830 (=C–P), 828 (C–Cl), 552,
Fig. 4. Geometry of the molecule of crystal VIII, solid solution
of compounds VI, VII.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

GALKINA et al.
726
Table
6-Chloro-5-nitro-7-(triphenylphosphonio)-2,1,3-
benzoxadiazol-4-olate (VI) and 5,6-dichloro-7-(tri-
phenylphosphonio)-2,1,3-benzoxadiazol-4-olate (VII).
To a solution of 0.47 g (1.79 mmol) of triphenylphosphine
in 10 ml of the mixture C2H5OH–(C2H5)2O, 1:3, was add-
ed dropwise at stirring a solution of 0.13 g (0.45 mmol)
of dichlorodinitrobenzofurazane II in 10 ml of the same
solvent. On completion of the reaction the solvent was
evaporated, the precipitated dark red crystals were puri-
fied with ether. Overall yield 0.12 g (67%), mp 223.7°C.
IR spectrum, ν, cm–1: 1627 (C=N), 1592 (O–C=C), 1523,
1362 (NO2), 1520 (C=C), 1492 (C–N), 1107 (=C–P), 832,
830 (C–Cl), 554, 527, 446 (C–P–C). 31P NMR spec-
trum (C6H5CH3): 26.2 (VI), 27.2 (VII) ppm. Found, %:
C 63.75; H 3.39; N 8.75. C42H30ClN5O6P2. Calculated,
%: C 63.20; H 3.76; N 8.78.
Parameter
IV
VIII
Color, appear- Orange, prismatic
ance
Orange, prismatic
Empirical
formula
C36H30NP2·C6ClN4O6 1/2(C24H15N3O4PCl) +
1/2(C24H15N2O2PCl2)
Crystal system
Space group
Z
Triclinic
Rhombic
P212121
4
P-1
2
a, Å
b, Å
c, Å
α, deg
β, deg
γ, deg
V, Å 3
10.7204(5)
13.8141(7)
14.7448(7)
62.4390(10)
82.7510(10)
82.0290(10)
1912.31(16)
9.0875(15)
13.731(2)
17.129(3)
2137.4(6)
941.06
XRD analysis of crystals of compound IV and solid
solution VIII of compounds VI, VII was carried out
at 20°C on an automatic diffractometer Bruker Smart
APEX2 (λMoKα, graphite monochromator, ω-scanning).
The structures were solved by the direct method using
SIR program [10] and refined first in the isotropic, then
in anisotropic approximation along SHELXL-97 soft-
ware[11]. The hydrogen atoms coordinates were found
from the difference Fourier series and were refined
isotropically. All calculations were carried out applying
programs WinGX [12] andAPEX2 [13]. The figures were
drawn using PLATON program [14]. In crystal VIII the
substituents at the atom C6 of furoxane were disordered
(Cl and NO2, 1:1), i.e., crystal VIII was a solid solution
of compounds VI, VII. In this crystals the molecules by
turns are located in the same place.
Molecular
weight
798.10
1.386
2.40
Density
(calc.), g cm–3
1.462
3.48
Extinction
factor, μMO,
cm–1
F(000)
824
964
Range of θ
1.92 ≤ θ ≤ 27.00
0.0191
1.90 ≤ θ ≤ 27.00
0.0475
Rint
Range of
–13 ≤ h ≤ 13,
–17 ≤ k ≤ 17,
–18 ≤ l ≤ 18
20882/8262
–11 ≤ h ≤ 11,
–17 ≤ k ≤ 17,
–21 ≤ l ≤ 21
16773/4649
measuring
reflections
Reflections
measured/in-
dependent
Number of
measured re-
flections with
The main crystallographic data and the refinement
parameters of structures IV, VIII are given in the table.
6820
3163
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REACTIONS OF 5,7-DICHLORO-4,6-DINITROBENZOFUROXANE
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