Synthesis of new functionalized 5,5-dimethyl-1-pyrroline 1-oxides and their investigation as spin traps

Article abstract of DOI:10.1007/s11172-010-0358-y

The reactions of 5,5-dimethyl-3-oxo-1-pyrroline 1-oxide (3-oxo-DMPO, 1) with NH₂OH and N₂H₄ afforded oxime (2a) and hydrazone (2b), respectively. The reaction products were studied as spin traps for the short-lived radicals HO^?, Ph^?, PhCO ₂ ^?, NC(Me₂)C^?, and NC(Me₂)CO^?. The nitroxides generated in the reactions of the above-mentioned short-lived radicals with nitrones 1 and 2a,b were characterized by ESR spectroscopy. Of these nitrones, oxime 2a is the most effective radical trap.

Full text of DOI:10.1007/s11172-010-0358-y

Russian Chemical Bulletin, International Edition, Vol. 59, No. 11, pp. 2081—2085, November, 2010
2081
Synthesis of new functionalized 5,5ꢀdimethylꢀ1ꢀpyrroline 1ꢀoxides
and their investigation as spin traps
V. A. Golubev, G. V. Shilov, and V. D. Sen´
Institute of Problems of Chemical Physics, Russian Academy of Sciences,
1
42432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 522 3507. Eꢀmail: senvd@icp.ac.ru
The reactions of 5,5ꢀdimethylꢀ3ꢀoxoꢀ1ꢀpyrroline 1ꢀoxide (3ꢀoxoꢀDMPO, 1) with NH OH
2
and N H afforded oxime (2a) and hydrazone (2b), respectively. The reaction products were
2
4
•
•
•
•
studied as spin traps for the shortꢀlived radicals HO , Ph , PhCO , NC(Me )C , and
NC(Me )CO . The nitroxides generated in the reactions of the aboveꢀmentioned shortꢀlived
2
2
•
2
radicals with nitrones 1 and 2a,b were characterized by ESR spectroscopy. Of these nitrones,
oxime 2a is the most effective radical trap.
Key words: nitrones, spin traps, nitroxides, ESR spectroscopy, 5,5ꢀdimethylꢀ1ꢀpyrroline
1
ꢀoxide.
Spin traps, most of which are either heterocyclic or
acyclic nitrones, are widely used for the detection of shortꢀ
trones are antioxidants, they are of interest as biologically
active compounds (see, for example, Ref. 8).
1
,2
lived radicals in chemical and biological systems. The
spin trapping method is based on the addition of active
radicals to nitrones to form nitroxides quite stable in soluꢀ
tion and the detection of the latter by ESR spectroscopy.
An advantage of cyclic nitrones, such as 5,5ꢀdimethylꢀ1ꢀ
pyrroline 1ꢀoxide (DMPO) and its analogs, is that the
ESR spectra of the nitroxides generated from these niꢀ
trones essentially depend on the nature of the added active
radicals and, as a consequence, the ESR spectra are more
informative.3 Almost all known analogs of DMPO are
oils, due to which they are difficult to purify and use.
Recently, we have developed the new method for the
synthesis of 5,5ꢀdimethylꢀ3ꢀoxoꢀ1ꢀpyrroline 1ꢀoxide (1),
whose carbonyl group can be used for the preparation of
derivatives. In the present study, we synthesized crystalꢀ
line derivatives of nitrone 1, viz., oxime (2a) and hydraꢀ
zone (2b) (Scheme 1), which can easily be purified. These
compounds were studied as spin traps. Since these niꢀ
Oxime 2a was obtained in ~90% yield by the reaction
of nitrone 1 with hydroxylamine. According to the HPLC
data, oxime 2 exists as a mixture of E and Z isomers
(67 : 33). Oxime Eꢀ2a with m.p. 149—150 °C was isolated
by the triple crystallization from benzene. Oxime Zꢀ2a
was obtained by the preparative chromatography on silica
gel and has m.p. 183—184 °C after the recrystallization
from benzene. The structure of oxime Eꢀ2a was deterꢀ
mined by Xꢀray diffraction and confirmed by IR, UV, and
NMR spectroscopy and mass spectrometry. The structure
of oxime Zꢀ2a was determined by IR and UV spectroscopy
and mass spectrometry and confirmed by the isomerizaꢀ
tion to oxime Eꢀ2a.
—5
6
,7
The structure of oxime Eꢀ2a is shown in Fig. 1. The
bond lengths and bond angles in Eꢀ2a are given in Tables 1
and 2, respectively. The pyrroline ring of oxime Eꢀ2a
is almost planar. The C(1) atom deviates from the
C(2)C(3)N(1)C(4) plane toward the C(5) atom by only
–
0.051(2) Å. The oxygen atom O(1) of the nitrone group
(–0.027(2) Å) is also almost in the plane of the ring, whereꢀ
Scheme 1
as the N(2) and O(2) atoms of the oxime group deviate
from this plane by +0.171(2) and +0.194(2) Å, respecꢀ
tively. The N(1)—C(3) and N(1)—O(1) bond lengths are
1
.309(4) and 1.285(3) Å, respectively, and are in the range
9
typical of cyclic nitrones. The C(2)—C(3) bond (1.429(4)
Å) is shortened due to the conjugation of the oxime group
with the nitrone moiety. The oxygen atom O(2) of the
oxime group is in the trans position with respect to the
C(3) atom of the pyrroline ring. Consequently, according
to the E/Z nomenclature of oximes, the isomer with m.p.
R = OH (a), NH2 (b)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2028—2032, November, 2010.
066ꢀ5285/10/5911ꢀ2081 © 2010 Springer Science+Business Media, Inc.
1

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Golubev et al.
The UV spectrum of oxime Eꢀ2a substantially differs
from the spectrum of Zꢀ2a. The spectrum of the E isomer
in water shows one intense band at λ
= 272 nm
max
O(2)
–1
–1
(
ε = 21000 L mol cm ) assigned to the absorption of
the nitrone group. The conjugation of the nitrone group
with the oxime moiety results in the shift of the absorption
maximum to longer wavelengths by 38 nm and an increase
in its intensity by a factor of ~3 compared to the absorpꢀ
N(2)
1
0
tion band of DMPO. In the spectrum of the Z isomer,
the maximum of this absorption band is observed at 282 nm
–
1
–1
(
ε = 13900 L mol cm ).
C(2)
In an alkaline medium, the UV spectra of oximes Eꢀ
C(1)
and Zꢀ2a differ from the aboveꢀdescribed spectra due to
–
–1
the ionization of the oxime group. At [OH ] ≥ 0.9 mol L
,
C(3)
the equilibrium is completely shifted to anions Eꢀ and
Zꢀ2a (Scheme 2).
–
C(4)
Scheme 2
C(6)
N(1)
C(5)
O(1)
Fig. 1. Molecular structure of oxime Eꢀ2a.
1
49—150 °C is the E isomer. In the crystal structure, molꢀ
ecules Eꢀ2a are linked by the short O(2)—H...O(1) hydroꢀ
gen bonds to form infinite chains. The O(2)—H(2)
and H(2)—O(1) bond lengths are 0.82 and 1.84 Å, resꢀ
pectively.
Table 1. Bond lengths (d) in oxime Eꢀ2a
Bond
d/Å
Bond
d/Å
O(1)—N(1)
O(2)—N(2)
N(1)—C(3)
N(1)—C(4)
N(2)—C(2)
1.285(3)
1.406(3)
1.309(4)
1.517(4)
1.283(4)
C(2)—C(3)
C(2)—C(1)
C(4)—C(6)
C(4)—C(5)
C(4)—C(1)
1.429(4)
1.491(4)
1.507(5)
1.520(5)
1.538(4)
–
The UV spectrum of anion Eꢀ2a shows two bands at
–
1
–1
λmax = 303 (ε = 22600 L mol cm ) and 250 nm
Table 2. Bond angles (ω) in oxime Eꢀ2a
Angle ω/deg Angle
ε = 3300 L mol–1 cm ). The UV spectrum of anion Zꢀ2a
also has two bands at λmax = 326 (ε = 11600 L mol cm–1)
and 251 nm (ε = 8300 L mol cm ). The UV spectrum
of anion Zꢀ2a is gradually transformed into the spectrum
–1
–
(
–
1
ω/deg
–1
–1
–
O(1)—N(1)—C(3) 126.4(2)
O(1)—N(1)—C(4) 119.8(2)
C(3)—N(1)—C(4) 113.6(2)
C(2)—N(2)—O(2) 109.1(2)
N(2)—C(2)—C(3) 123.3(3)
N(2)—C(2)—C(1) 127.7(3)
C(3)—C(2)—C(1) 109.0(2)
C(2)—C(1)—C(4) 105.1(2)
N(1)—C(3)—C(2) 109.9(3)
C(6)—C(4)—N(1) 107.3(3)
–
of anion Eꢀ2a with a halfꢀlife of 3.7 days at 20 °C.
C(6)—C(4)—C(5)
N(1)—C(4)—C(5) 109.6(2)
C(6)—C(4)—C(1) 113.0(3)
N(1)—C(4)—C(1) 101.7(2)
C(5)—C(4)—C(1) 112.9(3)
111.7(3)
Hydrazone 2b was formed in ~90% yield by the reacꢀ
tion of hydrazine with nitrone 1. It is characterized by the
distinct m.p. 144—145 °C and is one of the possible E/Z
isomers. The structure of 2b was confirmed by IR, UV,
and NMR spectroscopy and mass spectrometry. The UV
spectrum of hydrazone 2b in water consists of one intense

5
,5ꢀDimethylꢀ1ꢀpyrroline 1ꢀoxide derivatives
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2083
band at λmax = 295 nm (ε = 17000 L mol–1 cm–1). The IR
spectrum of hydrazone 2b shows absorption bands of the
Scheme 3
–
1
–1
nitrone (1545 cm ) and methine (3060 cm ) groups,
whose frequencies are similar to those of the correspondꢀ
ing bands of nitrones 1 and 2a. In addition, the spectrum
–
1
of hydrazone 2b has stretching (3330 and 3355 cm ) and
–
1
bending (1613 cm ) bands of the NH group and a band
2
–
1
at 1673 cm (assigned to the C=NNH double bond).
The H NMR spectrum of hydrazone 2b has singlets at δ
2
1
1
.34, 2.68, 7.27, and 6.45 of the methyl, methylene, meꢀ
thine, and amino groups, respectively.
We studied nitrones 1 and 2a,b as traps for the HO•
radical and the radicals generated by the thermal decomꢀ
position of benzoyl peroxide (BzO Bz) and azoisobutyꢀ
2
ronitrile (AIBN). The relative efficiencies of nitrones 1
and 2a,b and DMPO as spin traps were estimated based
on their reactions with the HO radical. The intensities of
Benzoyl peroxide is thermally decomposed to benzoylꢀ
oxyl and phenyl radicals, which can add to oxime 2a to
•
the ESR signals of the resulting adducts indicate that oxime
form two nitroxides. The heating of a solution of BzO Bz
a and DMPO are the most effective traps for the HO•
2
2
and oxime 2a in benzene at 70 °C over a short period of
time affords one nitroxide as the major product, whose
ESR spectrum consists of six lines with the splitting conꢀ
stants aN = 1.43 and aH = 1.80 mT. The spectrum with
these constants is similar to the spectrum of the adduct of
DMPO with the phenyl radical, where aN = 1.378 and
radical.
•
The HO radicals generated in the reaction of H O
2
2
with FeSO add to oxime 2a to form nitroxide 3. The ESR
4
spectrum of the latter consists of four lines with the splitꢀ
ting constants a = 1.54 and a = 1.40 mT (Fig. 2).
N
H
The spectrum of radical 3 is similar to the spectrum of
aH = 1.921 mT, and differs from the spectrum of the adꢀ
•
the adduct of DMPO with the HO radical, where a
=
N
duct of DMPO with benzoyloxyl radical, where a = 1.224
3
N
=
a = 1.501 mT. The intensity of the spectrum of radical 3
H
12
and a = 0.963 mT. Consequently, the sextet spectrum
H
rapidly decreases due to the decay of 3 with a halfꢀlife of
3 min. Presumably, radical 3 is transformed into disproꢀ
belongs to radical 5.
~
At 20 °C, radical 5 decays with a halfꢀlife of ~6 min,
apparently, as a result of the disproportionation to hydrꢀ
oxypyrrolidine 6 and nitrone 7 (Scheme 4).
portionation products, viz., cyclic hydroxamic acid 4 and
the starting oxime 2a (Scheme 3). The formation of acid 4
is evidenced by the lilac color of the reaction solution
1
1
characteristic of complexes of hydroxamic acids with
3
+
•
Fe ions. The reaction of oxime 2a with HO affords
radical 3 along with the secondary nitroxide characterized by
Scheme 4
the triplet ESR spectrum and a = 1.67 mT (see Fig. 2).
N
The heating of a solution of BzO Bz and oxime 2a over
2
a long period of time (>5 min) affords radical 5 along with
two other nitroxides, whose triplet spectra have the splitꢀ
ting constants aN = 1.59 and 1.39 mT. Based on the aN
values, these can be radicals 8 and 9 generated as a result
of the addition of the phenyl and benzoyloxyl radicals,
respectively, to nitrone 7 (Scheme 5).
3
24
326
328
330
332 B/mT
Fig. 2. ESR spectrum of the nitroxides, which were formed in
the reaction of nitrone 2a with the HO• radicals generated by
the reaction of FeSO with H O in a phosphate buffer (pH 6.8)
The thermal decomposition of AIBN under argon gives
•
the cyanoisopropyl radicals NC(Me) C , which react with
2
4
–
2
2
1
–3
–1
oxime 2a to form the corresponding nitroxide at a very low
concentration. This makes it impossible to reliably charꢀ
acterize the latter by ESR spectroscopy. Oxime 2a is a more
effective trap for radicals generated by the thermal deꢀ
at [2a] = 0.05 mol L , [H O ] = 1•10 mol L , [FeSO ] =
2
2
4
–
3
–1
=
1•10 mol L , and 25 °C (solid line), and the simulation of
the spectrum of nitroxide 6 with aN = 1.54 mT and aH = 1.40 mT
dashed line).
(

2084
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010
Golubev et al.
Scheme 5
Experimental
,5ꢀDimethylꢀ3ꢀoxoꢀ1ꢀpyrroline 1ꢀoxide (1) was synthesized
5
from 2,2,6,6ꢀtetramethylꢀ4ꢀoxopiperidineꢀ1ꢀoxyl according to
6
a procedure described previously. Hydroxylamine hydrochlorꢀ
ide was recrystallized from methanol; DMPO and hydrazine
hydrate (Aldrich) were used without additional purification.
The IR spectra were recorded on a Specord 75ꢀIR spectroꢀ
meter, the UV spectra were measured on a Specord UV—Vis
1
spectrometer, and the H NMR spectra were recorded on a
DRXꢀ500 spectrometer (500 MHz). The mass spectra were obtained
on a Clarusꢀ500 spectrometer with the ionization energy of 70 eV.
The ESR spectra were measured at ~20 °C on a SE/X 2544
instrument at 2 mW microwave power and a modulation ampliꢀ
tude of 0.32 mT. The spectra of the nitroxides generated by the
reactions of nitrones with active radicals were simulated with the
use of the WINEPRꢀSimFonia program. The chromatographic
analysis was carried out on a Milikhrom liquid chromatograph
equipped with a 2×64 mm column packed with Separon C18 or
Silasorbꢀ600. The preparative separation was carried out on an
HPPꢀ5001 chromatograph equipped with a 10×250 mm column
packed with Silasorbꢀ600 (7 μm). The GLC analysis was perꢀ
formed on a Clarusꢀ500 GLCꢀmass spectrometer equipped with
a 30 m capillary column using diphenylpolysiloxane/dimethylꢀ
polysiloxane (1 : 19). The melting points were measured on
a PHMK meltingꢀpoint apparatus.
Single crystals of oxime Eꢀ2a were grown by the crystallizaꢀ
tion from benzene. The Xꢀray diffraction data were collected on
a Pꢀ4 automated fourꢀcircle diffractometer (Bruker) (graphite
monochromator, λ(MoꢀKα) = 0.71073 Å, 293 K, θ/2θꢀscanning
technique) from a single crystal with dimensions 0.4×0.3×0.15 mm.
The unit cell parameters were determined and refined based on
35 reflections in the angle range θ = 10—15°. The experimental
data were measured in the angle range θ = 2.46—24.99°. The
total number of independent reflections was 1103; the number of
reflections with I > 2σ(I) was 757.
composition of AIBN in air. In this case, the nitroxides
characterized by sextet and triplet ESR spectra are formed.
The sextet with the splitting constants aN = 1.26 mT and
aH = 1.00 mT corresponds to radical 10, which is
•
the addition product of the NC(Me) CO radical to
2
oxime 2a. The characteristics of this addition product are
similar to those of the analogous adduct of DMPO (a =
N
3
,12
=
1.266 mT and a = 0.837 mT).
H
Radical 10 is transformed into diamagnetic products
according to the secondꢀorder law with a halfꢀlife of
.7 min at 20 °C. Apparently, the triplet spectrum with
3
aN = 1.47 mT belongs to acyclic nitroxide 11 (Scheme 6),
which is formed as a result of the rearrangement postulꢀ
ated previously12 for the analogous adduct of DMPO.
Scheme 6
Principal crystallographic parameters are a = 5.970(1) Å,
b = 7.872(1) Å, c = 8.012(3) Å, α = 77.020(10)°, β = 77.300(10)°,
3
–3
γ = 88.29(2)°, V = 357.86(15) Å , Z = 2, d
= 1.319 g cm ,
calc
space group Pꢀ1, triclinic centrosymmetric. The structure was
solved by direct methods. The atomic positions and thermal paꢀ
rameters of nonhydrogen atoms were refined isotropically and
then with anisotropic displacement parameters by the fullꢀmaꢀ
trix leastꢀsquares method. The hydrogen atoms were located in
difference Fourier maps and refined using the riding model. All
calculations were carried out with the use of the SHELXTL
The product of the reaction of oxime 2a with the perꢀ
•
oxyl radical NC(Me) CO , like the analogous adduct of
2
2
13
program package. The final R factors were as follows: R =
1
DMPO, was not detected. This product is unstable and,
=
0.0551 based on 757 reflections with I > 2σ(I) and R = 0.0915
1
apparently, decomposes to hydroxamic acid 4 and the
based on all 1103 reflections; GOOF = 1.001.
•
NC(Me) CO radical, which is trapped by oxime 2a to
3ꢀHydroxyiminoꢀ5,5ꢀdimethylꢀ1ꢀpyrroline 1ꢀoxide (2a). Soꢀ
dium carbonate (509 mg, 4.8 mmol) was slowly added with stirꢀ
ring to a solution of pyrroline oxide 1 (763 mg, 6 mmol) and
hydroxylamine hydrochloride (625 mg, 9 mmol) in water (6 mL).
Then the reaction mixture was heated at 80 °C for ~1 h until
nitrone 1 was completely consumed. After cooling, the reaction
mixture was extracted with ethyl acetate (4×5 mL). The extract
was dried with Na SO and concentrated in vacuo. Oxime 2a
2
3
,12
form nitroxide 10.
Therefore, we synthesized nitrones 1 and 2a,b and
found that oxime 2a is a new promising spin trap. The
ability of nitrone 2a to trap active radicals and the ESR
characteristics of the resulting adducts are similar to those
of DMPO. In addition, oxime 2a is a crystalline comꢀ
pound, which can easily be purified by the recrystallizaꢀ
tion. The functional carbonyl, oxime, and hydrazone
groups of nitrones 1 and 2a,b can be used for the synthesis
of new traps (analogs of DMPO).
2
4
was obtained in a yield of 759 mg (89%) as a mixture of isomers
Eꢀ2a (67%) and Zꢀ2a (33%) (HPLC and TLC data). The triple
recrystallization of the mixture of oximes 2a from benzene afꢀ
forded isomer Eꢀ2a, m.p. 149—150 °C. Found (%): C, 50.51;

5
,5ꢀDimethylꢀ1ꢀpyrroline 1ꢀoxide derivatives
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2085
H, 7.16; N, 19.90. C H N O . Calculated (%): C, 50.69;
carried out in thinꢀwalled glass tubes 4.0—4.5 mm in diameter.
Solutions of nitrone and benzoyl peroxide (~0.02 mmol each) in
benzene (0.4 mL) were placed in a tube and twice degassed at
10 Torr. The tube was sealed at 10 Torr, heated at 70 °C
during a specified time, and rapidly cooled. The ESR spectra of
the resulting nitroxides were immediately recorded.
6
10
2
2
H, 7.09; N, 19.71. M = 142.16. MS (EI, 70 eV), m/z (I (%)):
rel
+
+
+
1
[
42 [M] (65), 127 [M – Me] (16), 126 [M – O] (3), 111
M – HNO] (11), 94 (24), 84 (12), 80 (13), 59 (100). H NMR
+
1
–2
–2
(
DMSOꢀd ), δ: 1.34 (s, 6 H, 2 Me); 2.85 (s, 2 H, CH ); 7.45 (s, 1 H,
6
2
–1
–1
–1
CH); 11.34 (s, 1 H, OH). IR (CHCl ), ν/cm (ε/L mol cm ):
3
9
3
70 (190) [N—OH]; 1545 (560) [C=N—O]; 1635 (4) [C=NOH];
Reactions of nitrones 1 and 2 with radicals generated by the
thermal decomposition of azoisobutyronitrile (AIBN). The reacꢀ
tions were carried out in the absence of oxygen analogously to
that described above. To trap the radicals, which were generated
by the thermal decomposition of AIBN in air, the tube was heatꢀ
ed at 60 or 70 °C for 1—2 min. Then the tube was rapidly cooled,
and the ESR spectra of the nitroxides were recorded with purgꢀ
ing of the solutions with argon.
116 [=C—H]; 3206 [O—H bound]; 3566 [O—H free]. UV,
λmax/nm (ε/L mol–1 cm ) in MeCN: 277 (22600); in H O: 272
–1
2
(
21000); in 0.88 M NaOH: 303 (22600), 250 (3300).
Oxime Zꢀ2a was isolated by preparative chromatography of
a mixture of the isomers of oxime 2a on a 10×250 mm Silasorbꢀ
00 column using the Et O—MeOH system (97 : 3) as the eluꢀ
6
2
ent. The retention volumes for Zꢀ2a and Eꢀ2a were 33 and 42 mL,
respectively. Oxime Zꢀ2a was crystallized from benzene as colꢀ
orless plates, m.p. 183—184 °C. MS (EI, 70 eV), m/z (I (%)):
rel
References
+
+
+
1
42 [M] (73), 127 [M – Me] (22), 126 [M – O] (5), 111
+
[
M – HNO] (14), 94 (38), 84 (15), 80 (20), 59 (100). IR (CHCl ),
3
–
1
–1
–1
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Method], Izdꢀvo MGU, Moscow, 1984, 186 pp. (in Russian).
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ν/cm (ε/L mol cm ): 953 (170) [N—OH]; 1540 (760)
[
C=N—O]; 1650 (5) [C=NOH]; 3131 [=C—H]; 3256 [O—H
bound]; 3576 [O—H free]. UV, λmax/nm (ε/L mol– cm ) in
1
–1
2
004, 6, 619.
MeCN: 286 (14300), 260 sh (8900); in H O: 282 (13900), 260 sh
2
3
4
. D. L. Haire, U. M. Oehler, P. H. Krygsman, E. G. Janzen,
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(
10300); in 0.88 M NaOH: 326 (11600), 251 (8300).
ꢀHydrazonoꢀ5,5ꢀdimethylꢀ1ꢀpyrroline 1ꢀoxide (2b). Nitroꢀ
3
ne 1 (127 mg, 1 mmol) and acetic acid (4 mg) were added to
a solution of hydrazine hydrate (60 mg, 1.2 mmol) in a 2 : 1
ethanol—chloroform mixture (9 mL). The reaction solution was
kept at 25—30 °C for 5 days. Then the mixture was refluxed for
2
003, 68, 7811.
5
. F. A. Villamena, S. Xia, J. K. Merle, R. Lauricella, B. Tucꢀ
cio, C. M. Hadad, J. L. Zweier, J. Am. Chem. Soc., 2007,
4
h under argon. The solution was concentrated in vacuo, the
1
29, 8177.
. V. A. Golubev, V. D. Sen´, Zh. Org. Khim., 2010, 46, 1050
Russ. J. Org. Chem. (Engl. Transl.), 2010, 46, 1049].
. V. A. Golubev, V. D. Sen´, Izv. Akad. Nauk, Ser. Khim.,
009, 1767 [Russ. Chem. Bull., Int. Ed., 2009, 58, 1824].
residue was triturated with diethyl ether, and the solid product
was filtered off, washed with diethyl ether, and dried. The yield
of hydrazone 2b was 127 mg (90%), colorless needles (from
benzene), m.p. 144—145 °C. Found (%): C, 51.17; H, 7.67;
N, 29.63. C H N O. Calculated (%): C, 51.05; H, 7.85; N, 29.77.
6
7
[
2
6
11
3
+
8. R. A. Floyd, R. D. Kopke, C.ꢀH. Choi, S. B. Foster,
S. Doblas, R. A. Towner, Free Radic. Biol. Med., 2008,
M = 141.17. MS (EI, 70 eV), m/z (I (%)): 141 [M] (39),
26 [M – Me] (2), 110 [M – HNO] (2), 108 [M – NH OH] (2),
5 (3), 83 (3), 82 (7), 81 (12), 80 (12), 68 (13), 58 (28), 56 (15),
5 (100). H NMR (DMSOꢀd ), δ: 1.34 (s, 6 H, 2 Me); 2.68
rel
+
+
+
1
8
5
2
4
5, 1361.
1
9. F. A. Villamena, A. Rockenbauer, J. Galluci, M. Velayutham,
C. M. Hadad, J. L. Zweier, J. Org. Chem., 2004, 69, 7994.
10. E. Bonnet, R. F. C. Brown, V. M. Clark, I. O. Sutherland,
A. Todd, J. Chem. Soc., 1959, 2094.
11. A. T. Pilipenko, O. S. Zul´figarov, Gidroksamovye kisloty
Hydroxamic Acids], Nauka, Moscow, 1989, p. 25 (in Russian).
2. E. G. Janzen, P. H. Krygsman, D. A. Lindsay, D. L. Haire,
6
(
s, 2 H, CH ); 6.45 (s, 2 H, NH ); 7.23 (s, 1 H, CH). IR (Nujol
2 2
–
1
mulls), ν/cm : 1545 (C=N—O); 1613 (NH ); 1673 (C=N);
3
cm ) in H O: 295 (17000); in ethanol: 305 (17500).
2
060 (=C—H); 3330, 3355 (NH ). UV, λ /nm (ε/L mol–
1
2 max
–
1
2
[
Reactions of nitrones 1 and 2 with Fenton's reagent. The reꢀ
1
actions were carried out with the use of solutions with the folꢀ
lowing concentrations (mol L–1): (a) [FeSO •7H O] = 2•10
–3
J. Am. Chem. Soc., 1990, 112, 8279.
4
2
–
3
13. G. M. Sheldrick (8/06/2000), SHELXTL v. 6.14, Strucꢀ
ture Determination Software Suite, Bruker AXS, Madison,
WI, USA.
in water, (b) [nitrone] = 0.1 and [H O ] = 2•10 in a phosꢀ
2
2
phate buffer (pH 7). Aliquots of the solutions were mixed, the
reaction solution was rapidly transferred to a quartz tube with an
inner diameter of 1 mm, and the ESR spectra of the nitroxides
that formed were immediately recorded.
Reactions of nitrones 1 and 2 with radicals generated by the
thermal decomposition of benzoyl peroxide. The reactions were
Received December 4, 2009;
in revised form July 16, 2010