Cascade reactions of Me3Si-substituted imidazolidine-1,3-diols with PbO2, including oxidation of the corresponding diol and subsequent elimination of the trimethylsilyl fragment

Article abstract of DOI:10.1002/ejoc.200700113

It was found that reactions of 2-Me₃Si-R-substituted (Si-C _sp or Si-C_sp2) imidazolidine-1,3-diols with PbO ₂ in MeOH are cascade reactions, which involve the oxidation of imidazolidine-1,3-diols into nitronyl ni

Full text of DOI:10.1002/ejoc.200700113

FULL PAPER
DOI: 10.1002/ejoc.200700113
Cascade Reactions of Me3Si-Substituted Imidazolidine-1,3-Diols with PbO2,
Including Oxidation of the Corresponding Diol and Subsequent Elimination of
the Trimethylsilyl Fragment
Eugene Tretyakov,[a] Galina Romanenko,[a] Vladimir Ikorskii,[a] Dmitry Stass,[b]
Vladimir Vasiliev,[c] Maria Demina,[d] Alexander Mareev,[d] Alevtina Medvedeva,[d]
Elena Gorelik,[a] and Victor Ovcharenko*[a]
Keywords: Nitrogen oxides / Cleavage reactions / Oxidation / Protecting groups / Alkynes
It was found that reactions of 2-Me3Si-R-substituted (Si–Csp
or Si–Csp2) imidazolidine-1,3-diols with PbO2 in MeOH are
cascade reactions, which involve the oxidation of imidazolid-
ine-1,3-diols into nitronyl nitroxide (NN–R–SiMe3) and fur-
ther elimination of the Me3Si group to give NN–R–H. The
efficiency of a one-pot approach in the synthesis of nitronyl
nitroxides is demonstrated by reference to syntheses of
2-ethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-
oxide-1-oxyl (2), 2-(4-ethynylphenyl)-4,4,5,5-tetramethyl-
4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (8), (E)-4,4,5,5-tet-
ramethyl-2-[2-(pyrrolidin-1-yl)vinyl]-4,5-dihydro-1H-imid-
azole-3-oxide-1-oxyl (3a), (E)-2-[2-(diisopropylamino)vinyl]-
4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-
oxyl (3b), and 4,4,5,5-tetramethyl-2-(1H-1,2,3-triazol-5-yl)-
4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (H11). Interaction
of 2 with secondary amines formed only trans isomers 3a and
3b. X-ray investigation of 3a and 3b confirmed that the reac-
tion is regiospecific. Static magnetochemical measurements
detected weak exchange interactions between the odd elec-
trons of the paramagnetic centers in the solid nitronyl ni-
troxide products, including H11 whose crystals consist of hel-
ices formed by numerous intermolecular H bonds. The ESR
spectra of 3a, 3b, and H11 show substantial delocalization of
spin density to the substituent. Modeling reproducibly gave
equal hyperfine coupling constants (HFC) for the imidazoline
nitrogen atoms of 3b and different HFC for the nitrogen
atoms of 3a and H11, indicating that rotation of the two cyclic
substituents is hindered.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
cedures for the synthesis of key nitroxides, leading to vari-
ous polyfunctional spin-labeled derivatives.
Introduction
Nitronyl (NN–R) and imino nitroxides (IN–R) have at-
tracted increased interest as paramagnetic organic compo-
nents in the design of molecule-based magnets because of
their potential for varying the spatial and electronic struc-
ture allows selective variation of the sign and magnitude of
the exchange interaction energy inside heterospin exchange
clusters.[1] This calls for the development of effective pro-
An example of these nitroxides is NN–CϵC–H (2),
which was recently synthesized by oxidation of 2-[2-(tri-
methylsilyl)ethynyl]-4,4,5,5-tetramethylimidazolidine-1,3-
diol (1) with NaIO4 in NN–CϵC–SiMe3 with further re-
moval of the Me3Si group.[2]
[a] International Tomography Center, Siberian Branch, Russian
Academy of Sciences
Institutskaya Street, 3a, 630090 Novosibirsk, Russian Federa-
tion
Fax: +7-383-3333455
E-mail: Victor.Ovcharenko@tomo.nsc.ru
Our efforts to improve the synthetic procedure of 2 re-
[b] Institute of Chemical Kinetics and Combustion, Siberian vealed a nontrivial fact. If oxidation of 1 is carried out in a
Branch of the Russian Academy of Sciences
PbO2/MeOH (or EtOH) system, it is accompanied by elimi-
Institutskaya Street, 3, 630090 Novosibirsk, Russian Federation
nation of the Me3Si group. In this process, which is actually
a variation of the one-pot synthesis of 2, this compound
may be obtained in high yield (≈ 70%). The present investi-
gation was stimulated by this result and showed that the
suggested synthetic approach, namely, a cascade of two suc-
cessive reactions is useful for syntheses of various NN–R,
including unknown ones.
[c] N. N. Vorozhtsov Institute of Organic Chemistry, Siberian
Branch of Russian Academy of Sciences
Academician Lavrent’ev Avenue, 9, 630090 Novosibirsk, Rus-
sian Federation
[d] A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences
Favorsky Street, 1, 664033 Irkutsk, Russian Federation
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2007, 3639–3647
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V. Ovcharenko et al.
FULL PAPER
1.73Ϯ0.01 B.M. (see Supporting Information). This indi-
cates that in solids 3a and 3b, the intermolecular exchange
interactions between the odd electrons of the paramagnetic
centers are weak.
Results and Discussion
When PbO2 was added to a MeOH or EtOH solution
of 1, the reaction mixture quickly became blue–violet, and
compound 2 was the sole reaction product (Scheme 1). TLC
monitoring of the oxidation of 1 in PbO2/MeOH did not
reveal the formation of nitroxide NN–CϵC–SiMe3, which
indicates that the C–Si bond is quickly split in intermediate
NN–CϵC–SiMe3. Elimination of the SiMe3 group in the
course of the oxidation of 1 in alcohols made it possible to
avoid isolation of NN–CϵC–SiMe3, which was previously
mentioned[2] to be a rather labile compound, in pure form
or in solution and significantly increased the yield of 2
(from 20 to 70%). The effective one-pot synthesis of poly-
functional nitronyl nitroxides naturally evolved as an elabo-
ration of the given procedure for the transformation of 1
into 2. Thus, the addition of pyrrolidine to the reaction
mixture formed by the oxidation of 1 led to spin-labeled
enamine 3a, which formed within a few minutes as a sole
product with ca. 90% yield based on 1 (Scheme 1). The re-
action with (iPr)2NH proceeded in a similar way, but was a
little more sluggish (≈3.5 h) and led to 3b as a sole product
with ≈75% yield based on 1. The above examples demon-
strate that the one-pot synthesis of 2 is possible and that
this compound may be further subjected to one-pot func-
tionalization by using reagents unreactive with PbO2.
Figure 1. Molecular structure of 3a.
Returning to the discussion of the transformation of 1
into 2 in PbO2/MeOH, we note that Si–Csp bond splitting
requires the presence of a base in the reaction mixture.[4]
Evidently, PbO2 in itself cannot perform this function. Nev-
ertheless, we carried out a special experiment to prove this.
For this, authentic nitroxide, NN–CϵC–SiMe3, was added
to the PbO2/MeOH system and remained unchanged in it.
In contrast, the addition of Pb(OH)2 suspended in tiny
amount of water to a NN–CϵC–SiMe3 solution in meth-
anol followed with agitation for 5 h resulted in full transfor-
mation of NN–CϵC–SiMe3 into 2. This gave us grounds
to assume that in the course of the transformation of 1 into
2, Si–Csp bond splitting had a provoking effect on Pb-
(OH)2 that was formed in the reaction. Thus, in the PbO2/
MeOH system, compound 1 actually enters a cascade of
transformations with NN–CϵC–SiMe3 and Pb(OH)2
formed at the first stage and with Me3Si further removed
from NN–CϵC–SiMe3 under the action of Pb(OH)2 that
accumulates in the system.
Scheme 1.
Nitronyl nitroxides were grown as X-ray quality single
crystals by slowly evaporating the CH2Cl2/n-heptane solu-
tions of 3a and 3b. Analysis of 3a and 3b indicated that
the addition of secondary amines to the triple bond occurs
regiospecifically and forms trans isomers. The structure of
To prove the efficiency of this approach we synthesized
3b was described previously.[3] Crystals 3a contain two crys- nitroxide NN–C6H4–CϵC–H (8). Previously, 8 was pre-
tallographically independent and structurally related ni- pared by a reaction of OHC–C6H4–CϵC–H with bis(hy-
tronyl nitroxide molecules (Figure 1). In one of these mole- droxylamine) 5 with further oxidation of the imidazolidine-
cules, the pyrrolidine cycle has a gosh conformation with 1,3-diol.[5] For the synthesis of OHC–C6H4–CϵC–H, the
C11A and C12A atoms deviating by –0.19 and 0.25 Å, starting compound was OHC–C6H4–CϵC–SiMe3 (4), and
respectively, from the plane; in the other molecule, the cycle the sequence of stages was altered. At first, a reaction was
has an envelope conformation, in which the C atom is sim- performed between 4 and 5 to synthesize 6, and then 6 was
ilar to the one designated by C11A in Figure 1 departs from oxidized in the PbO2/MeOH system. As a result, target
the plane by 0.24 Å. The angle between the planes through compound 8 was isolated in 90–95% yield (Scheme 2). Note
the CN2 fragment of the imidazoline ring and the NC2 frag- that specially synthesized nitroxide 7, as well as NN–CϵC–
ment of the pyrrolidine ring is 12.8(3) and 16.6(3)°. In the SiMe3, remained unchanged in the PbO2/MeOH system,
imidazoline ring, the deviation of atoms from the plane is but transformed into 8 after the addition of a MeOH solu-
up to 0.02 Å. The N–O bond lengths are typical for ni- tion of NH3. As in case of 1, TLC monitoring of the oxi-
troxides: 1.284(3)–1.295(3) Å. The intermolecular distances dation of 6 in PbO2/MeOH did not reveal the formation of
between the O atoms exceed 5.3 Å; that is, in the solid state, nitroxide 7, which indicates that the C–Si bond is quickly
the paramagnetic centers are widely separated. For this split in intermediate 7. Thus 6, as well as 1, undergoes a
reason, in the range 25–300 K the effective magnetic mo- cascade transformation (oxidation–desilylation) in the
ment of 3a and 3b remains almost unchanged: PbO2/MeOH system, forming nitroxide 8.
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Cascade Reactions of Me3Si-Substituted Imidazolidine-1,3-diols with PbO2
FULL PAPER
Scheme 2.
The oxidation–desilylation method proved to be highly
effective for the synthesis of 1,2,3-triazolyl-substituted ni-
tronyl nitroxide H11. To demonstrate the advantages of this
method, let us first describe the products formed during
classical synthesis of H11.
The reaction of aldehyde 9[6] with bis(hydroxylamine) 5
in MeOH (Scheme 3) did not lead to the formation of ex-
pected imidazolidine-1,3-diol 10. This was attributed to the
fact that under these conditions, 10 is spontaneously dehy-
drated into 4,4,5,5-tetramethyl-2-(1H-1,2,3-triazol-5-yl)-
4,5-dihydro-1H-imidazol-1-ol (12) (Scheme 3). Structural
analysis of the methanol solvate of this compound,
12·MeOH, indicated that in the solid state the compound
exists as zwitterions (Figure 2a) linked via numerous H
bonds into layers (Figure 2b).[7] The MeOH solvate mole-
cules lie between layers.
Figure 2. Structure of the zwitterion (a) and layer motif in the
structure of 12·MeOH (b).
not form H11 either. We could only observe red coloring of
the reaction mixture; isolation of any individual compound
from this mixture again led to crystallization of zwitterion
12. However, oxidation of the crude product with PbO2 in
MeOH led to the isolation of a dark blue amorphous prod-
uct, which corresponded to the molecular formula
Pb3O2(11)2, where 11 is deprotonated nitroxide H11 (ele-
ment analysis and LC–MSD data). Previously, we described
the formation of lead complexes of this kind when we inves-
tigated the products of oxidation of pyrazolyl-substituted
imidazolidine-1,3-diols with lead dioxide.[8] When a solu-
tion of Pb3O2(11)2 was kept for a few days in a MeOH/
H2O mixture in an open flask, we observed the formation
of a gray finely divided precipitate and a solution of H11.
Scheme 3.
When condensation of 9 was carried out with sulfate To achieve faster decomposition of Pb3O2(11)2 to isolate
5·H2SO4·H2O, but not with compound 5 itself, and the re- H11, we added an excess amount of AcOH to its solution
action was conducted in water, but not in MeOH, a crude in CHCl3.
product was isolated, which contained imidazolidine-1,3-
The above-described difficulties may be avoided if H11 is
diol 10. The product, however, could not be purified by synthesized from trimethylsilyl derivative 13, but not from
recrystallization because the dehydrated derivative of 10 Ϫ 9 itself, and if an oxidation–desilylation cascade process is
compound 12 Ϫ was the only solid isolated from the employed (Scheme 4). Interaction of 13 and 5 in MeOH
mother solution. Oxidation of a suspension of the crude led to a voluminous precipitate of colorless thin needles of
product with NaIO4 in a mixture of CHCl3 and H2O did imidazolidine-1,3-diol 14 isolated from the solution. Unlike
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V. Ovcharenko et al.
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10, compound 14 is not liable to dehydration on heating or
prolonged storage in solution. Due to this property, it may
be recrystallized and used in further transformations.
Scheme 4.
When 14 was oxidized in PbO2/MeOH, we isolated a
navy blue powder that contained Pb3O2(11)2 as the major
product (LC–MSD data). The intense signal (m/z = 223.1)
of ion 11 corresponded to the fundamental chromato-
graphic peak in the LC–MSD. Signals with m/z = 295 and
m/z = 207.1 from chromatographic peaks with small areas
were also recorded and corresponded to insignificant
amounts of ions 15 and 16 (see Supporting Information).
Our numerous attempts to crystallize the dark blue finely
disperse powder failed to give a crystal suitable for X-ray
study. However, element analysis of the product of
recrystallization indicated that the compound had a molec-
ular formula Pb3O2(11)2. Dissolution of this complex in
CHCl3 containing AcOH led to gradual decomposition of
the complex and to isolation of free nitroxide H11 as a solu-
tion, which may be further isolated with ca. 45% yield.
Figure 3. Molecular structure (a) and helix formation in H11 (b).
Figure 4 shows the experimental and simulated ESR
Although H11 crystallized as a conglomerate of crystals, spectra of 3a, 3b, and H11 in toluene. The overall spectra
single crystal fragments could be separated, which allowed are very similar and rather typical for 2-imidazoline radi-
us to determine the structure of nitronyl nitroxide. In mole- cals, showing the dominant quintet from two nitrogen
cule H11, (Figure 3a) the angle between the planes of the atoms of the imidazoline cycle.
triazole ring and the CN2 fragment of the imidazoline ring
All spectra show substantial delocalization of spin den-
is 12.6(4)°. The N–O distances are 1.263(5) and 1.273(5) Å. sity into the substituent, as is evident from the better of
In the solid state, the molecules that are arranged around less-resolved substructures of the lines. The latter conclu-
the 41 axis are H-bonded into helices (Figure 3b).[9] How- sion is in good agreement with the spin density distribution
ever, although solid H11 contains H-bonds that involve N– from DFT calculations. The spin delocalization pattern
O groups, exchange interactions between the odd electrons could be clearly seen on the spin density plots from PBE0/
of the paramagnetic centers of the individual molecules are EPR-II calculations shown in Figure 5.
weak. This is indicated by the effective magnetic moment
The DFT estimations of hyperfine coupling constants
of the compound (1.73Ϯ0.01 B.M.), which remains almost were made to provide a clear correlation between the vari-
invariable within a wide range of temperatures, 25–300 K ous structural elements and the electronic structure. In the
(see Supporting Information).
present case, the DFT calculations are essential for the as-
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Cascade Reactions of Me3Si-Substituted Imidazolidine-1,3-diols with PbO2
FULL PAPER
Figure 4. ESR spectra of 3b (a, aЈ), 3a (b, bЈ), and H11 (c, cЈ) in toluene. Left column gives full spectra, and blowups of the corresponding
central line are shown in the right column. The bottom trace of each pair gives the experimental spectrum, and the top trace shows the
results of its simulation.
signment of the signals providing important guidelines for
spectral simulations of the EPR spectra. In general, a rea-
sonably good agreement was obtained between the experi-
mental and calculated 14N hyperfine interactions of the
imidazoline nitrogen atoms (Table 1). The slight undere-
stimation of the Nim HFC by DFT calculations is in agree-
ment with previous studies[10] and does not have any signifi-
cant effect on the spin density distribution and other HFCs.
For the nitrogen atoms in substituents and for the protons
the DFT calculations give good predictions for the hyper-
fine couplings. These, in turn, were rather useful for EPR
signal assignments and served as constraints on the simula-
tion parameters.
Modeling of experimental spectra reproducibly gave
equal hyperfine coupling constants (HFC) for the imid-
azoline nitrogen atoms of 3b and different HFC for the ni-
trogen atoms of 3a and H11, indicating that rotation of the
two cyclic substituents is hindered (Table 1). This is also a
possible reason for poorer resolution of the spectral sub-
structure of these two radicals. Only Nim HFC could be
determined for H11 because of the unresolved structure.
However, the lines of the nitrogen quintet are inhomoge-
neously broadened; to reproduce the broadening, according
to the DFT calculations it is necessary to introduce not
only HFC of 0.02 mT with 12 protons of the methyl groups
typical for these radicals, but also additional couplings with
the nuclei of the triazole substituent. The estimated accu-
Figure 5. Spin density plots for 3a (a), 3b (b), and H11 (c) from
PBE0/EPR-II calculations.
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V. Ovcharenko et al.
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Table 1. Experimental[a] and calculated[b] values of isotropic HFC C–Si bond cleavage, and the formation of a lead complex,
(a in mT) of 3a, 3b, and H11.
from which the target nitroxide was isolated at the last
stage. Thus, one can state that the suggested cascade reac-
tion can serve as a convenient synthetic approach for the
syntheses of other nitroxides.
3a
3b
H11
PBE0 Exp
PBE0
Exp
PBE0
Exp
N1im
N2im
Him
H8a
H9a
N3a
0.677 0.801
0.653 0.742
–0.026 0.02
–0.156 0.056 –0.136
0.243 0.096 0.226
–0.076 0.067 –0.084
0.686
0.675
–0.027
0.775
0.775
0.677 0.751
0.557 0.728
0.028 –0.023
0.074
[c]
0.122
0.051
Experimental Section
H10a, H10b, H13a, H13b –0.162 0.040
General Methods: 4,4,5,5-Tetramethyl-2-[2-(trimethylsilyl)ethynyl]-
imidazolidine-1,3-diol[2] (1), 4-[(trimethylsilyl)ethynyl]benzalde-
hyde[4] (4), 1H-1,2,3-triazole-5-carbaldehyde[6] (9), N,NЈ-(2,3-di-
methylbutane-2,3-diyl)bis(hydroxylamine)[11,12] (7), and 4-(trimeth-
ylsilyl)-1H-1,2,3-triazole-5-carbaldehyde[6] (13) were prepared ac-
cording to the published procedures. All the solvents used were
reagent quality. All of them were removed under reduced pressure,
and all commercial reagents were used without additional purifica-
tion. The reactions were monitored by TLC using silica gel 60 F254
aluminum sheets from Merck. The yields are given for pure sub-
stances obtained after recrystallization. IR spectra were obtained
from KBr pellets with a Bruker VECTOR 22 infrared spectrometer.
Melting points were obtained with a Boetius melting point appara-
tus. Microanalyses were performed with a Carlo Erba 1106 ana-
lyzer. Mass spectra were recorded with a Finnigan MAT-8200 in-
strument using the electron impact ionization technique (70 eV).
X-band CW ESR spectra were recorded with a Bruker EMX spec-
trometer for dilute degassed toluene solutions at room temperature
and modeled with the Winsim v.0.96 free package as described ear-
lier.[13] LC–MSD analysis was performed with an Agilent 1100
Series LC–MSD instrument. The system included a binary pump,
vacuum degasser, autosampler, thermostatted column compart-
ment, diode array detector, and mass-selective detector in electro-
spray ionization (ESI) mode. Flow injection analysis was done for
optimization of MS parameters. MS conditions: ionization mode –
negative scan in the range m/z = 200–1300; Vcap 4000 V; nebulizer
50 psig; drying gas flow 10 L/min; drying gas temperature 340 °C;
fragmentor 40 V. Chromatographic conditions: Zorbax Rx-C18
column (4.6ϫ150 mm, 5 µm particles, 30 °C); water/MeOH mobile
phase; gradient 50 to 90% MeOH from 5th to 10th min; flow rate
0.5 mL/min; injection volume 5 µL; diode-array detector: signal
N3
N4
N5
H10
H5
–0.038
0.007
0.009
0.180
0.019
[a] EPR experiment does not provide information on signs of HFCs
and gives the absolute values only. Analysis of experimental spectra
gave giso = 2.0067 for 3a, giso = 2.0065 for 3b, giso = 2.0065 for
H11. [b] Average a values which are greater than 0.005 mT. [c]
Numbering of atoms corresponds to the numbering scheme in Fig-
ures 1 and 3a.
racy in determining the HFC constants and the g values is
0.005 mT and 0.0001, respectively.
The final comment on modeling of the given spectra is
that although reproduction of the finer substructure of
well-resolved lines is consistent and reliable with the given
sets of parameters, their uniqueness cannot be guaranteed
because the spectra are overcrowded and the couplings are
too small and close-lying. The dominant nitrogen HFC val-
ues, as well as the g values and the conclusion about spin
density delocalization to the substituent, are quite reliable,
but the actual values of HFC for the nuclei of substituents
should probably be adopted with certain caution.
Conclusions
Thus, our study established that the interaction between 254/16 nm, 600/80 nm, reference 850/50 nm. The magnetochemical
experiment was followed with an MPMS-5S (“Quantum Design”)
SQUID magnetometer at temperatures from 2 to 300 K in a homo-
geneous external magnetic field of up to 49.5 kOe. The molar mag-
netic susceptibility χ was calculated using Pascal’s additive scheme
including diamagnetic corrections.
Me3Si-Csp and Me3Si-Csp2 bearing imidazolidine-1,3-diols
with PbO2 in MeOH occurs as a cascade of reactions, in-
volving oxidation of imidazolidine-1,3-diol into nitronyl ni-
troxide and further removal of the Me3Si group under the
action of Pb(OH)2 formed in the course of the reaction.
This approach permitted us to accomplish effective synthe-
ses of NN–CϵC–H and NN–C6H4–CϵC–H, avoiding the
stage of formation of the corresponding Me3Si-substituted
spin-labeled acetylenes. The resulting monosubstituted
spin-labeled acetylene NN–CϵC–H may be introduced in
further transformations without isolating it from the reac-
tion mixture, which was demonstrated by the one-pot syn-
thesis of enamine-substituted nitronyl nitroxides. We also
succeeded in developing a synthetic procedure for 1,2,3-tri-
2-Ethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-
oxyl (2): PbO2 (500 mg, 2.1 mmol) was added at room temperature
to a stirred solution of 4,4,5,5-tetramethyl-2-[2-(trimethylsilyl)eth-
ynyl]imidazolidine-1,3-diol (1) (100 mg, 0.39 mmol) in MeOH
(4 mL). The reaction mixture was stirred for 30 min and filtered.
The solution was concentrated to a volume of ca. 2 mL. Then it
was diluted with benzene (10 mL) and placed onto a column [silica
gel Merck (0.063–0.100 mm for column chromatography),
15ϫ1.5 cm, wetted with benzene]. The column was eluted with
ethyl acetate, and a bluish violet fraction was collected; the fraction
azolyl-substituted nitronyl nitroxide; in the course of syn- was evaporated. The solvent was distilled off, the residue ground
with hexane, and the solvent decanted. Yield 50 mg (70%). Spectral
thesis, a Me3Si group was deliberately introduced at an
early stage to ensure stability of the imidazolidine-1,3-diol
intermediate against dehydration. The Me3Si group was
then eliminated in the course of the cascade reaction; this
data for nitroxide 2 are identical to those obtained earlier.[2]
(E)-4,4,5,5-Tetramethyl-2-[2-(pyrrolidin-1-yl)vinyl]-4,5-dihydro-1H-
imidazole-3-oxide-1-oxyl (3a): PbO2 (500 mg, 2.1 mmol) was added
reaction involved the oxidation of imidazolidine-1,3-diol, at room temperature to a stirred solution of 1 (100 mg, 0.39 mmol)
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Cascade Reactions of Me3Si-Substituted Imidazolidine-1,3-diols with PbO2
FULL PAPER
in MeOH (5 mL). After 30 min, pyrrolidine (50 µL) was added. The
reaction mixture was stirred for 30 min and filtered. The mother
solution was concentrated to a volume of ca. 2 mL. Then it was
diluted with benzene (10 mL) and placed onto a column [silica gel
Merck (0.063–0.100 mm for column chromatography), 5ϫ1.5 cm,
wetted with benzene]. The column was eluted with ethyl acetate,
and a bluish violet fraction was collected; the fraction was evapo-
rated. The solvent was distilled off, the residue ground with hexane,
and the solvent decanted. Yield 90 mg (90%). M.p. 149–151 °C.
minutes and then filtered. The filtrate was evaporated, and the yel-
lowish brown crystalline residue was ground with ethyl acetate and
filtered off. The yield of crude product 10 was from 25 to 50%.
The product was used without additional purification. Storage of
a solution of imidazolidine-1,3-diol 10 in MeOH for a few days led
to the formation of 4,5-dihydro-1H-imidazol-1-ol 12.
4,4,5,5-Tetramethyl-2-(1H-1,2,3-triazol-5-yl)-4,5-dihydro-1H-imid-
azol-1-ol (12): N,NЈ-(2,3-dimethylbutane-2,3-diyl)bis(hydroxyl-
amine) 5 (270 mg, 1.82 mmol) was added at room temperature to
a stirred solution of 1H-1,2,3-triazole-5-carbaldehyde (9) (175 mg,
1.80 mmol) in MeOH (5 mL). The reaction mixture was stirred for
2 h at room temperature until a yellow solution formed. Then the
solution was kept at ca. 5 °C for 100 h. The solvent was evaporated.
The viscous yellowish brown residue was ground with ethyl acetate,
which caused fast crystallization of the residue. The resulting pale
yellow powder was filtered off, washed with cool ethyl acetate on
the filter, and dried in vacuo. Yield: 300 mg (80%). M.p. Ͼ300 °C.
Compound 12·MeOH solvate crystals suitable for an X-ray analy-
sis were grown by slowly evaporating the solution of the product
IR: ν = 542, 617, 642, 772, 867, 881, 947, 966, 1131, 1192, 1206,
˜
1266, 1298, 1323, 1357, 1428, 1453, 1484, 1615, 2853, 2964, 3044,
3076 cm–1. C13H22N3O2 (252.33): calcd. C 61.9, H 8.8, N 16.7;
found C 62.4, H 8.8, N 16.7. Perfect crystals were grown by slowly
evaporating a CH2Cl2/n-heptane solution of nitroxide 3a at ca.
5 °C.
(E)-2-[2-(Diisopropylamino)vinyl]-4,4,5,5-tetramethyl-4,5-dihydro-
1H-imidazole-3-oxide-1-oxyl (3b): The compound was synthesized
from 1 similarly to 3a with 75% yield. Spectral data of nitroxide
3b are identical to the data obtained earlier.[3]
in MeOH/ethyl acetate (1:1) at room temperature. IR: ν = 444, 462,
˜
4,4,5,5-Tetramethyl-2-{4-[(trimethylsilyl)ethynyl]phenyl}imid-
azolidine-1,3-diol (6): 4-[(Trimethylsilyl)ethynyl]benzaldehyde (4)
(200 mg, 1 mmol) and N,NЈ-(2,3-dimethylbutane-2,3-diyl)bis-
(hydroxylamine) 5 (150 mg, 1 mmol) were dissolved in MeOH
(10 mL). The solution was maintained at room temperature for 2 h,
and then at ca. 5 °C for 48 h. Yield 80 mg (60%). M.p. 186–195 °C
522, 592, 641, 705, 729, 772, 855, 885, 962, 1062, 1125, 1148, 1184,
1210, 1247, 1326, 1377, 1450, 1617, 2399 (very broad band), 2937,
2982, 3123 cm–1. C9H15N5O·MeOH (241.29): calcd. C 49.8, H 7.9,
N 29.0; found C 50.0, H 7.6, N 29.3.
4,4,5,5-Tetramethyl-2-[4-(trimethylsilyl)-1H-1,2,3-triazol-5-yl]imid-
azolidine-1,3-diol (14): N,NЈ-(2,3-dimethylbutane-2,3-diyl)bis(hyd-
roxylamine) 5 (236 mg, 1.59 mmol) was added at room temperature
to a stirred solution of 4-(trimethylsilyl)-1H-1,2,3-triazole-5-carbal-
dehyde (13) (270 mg, 1.60 mmol) in MeOH (10 mL). The reaction
mixture was stirred for 10 h, within which bulk precipitate of color-
less thin needles gradually formed. The precipitate was filtered off
and washed with ethyl acetate on a filter. Yield: 340 mg (70%).
For element analysis, a small amount of 14 was recrystallized from
(dec.). IR: ν = 547, 650, 702, 760, 803, 825, 841, 873, 914, 994,
˜
1018, 1086, 1144, 1218, 1250, 1301, 1379, 1464, 1508, 2161, 2921,
2958, 2993, 3283 (very broad band) cm–1. C18H28N2O2Si (332.51):
calcd. C 65.0, H 8.5, N 8.4; found C 64.8, H 8.4, N 8.1.
2-{4-[(Trimethylsilyl)ethynyl]phenyl}-4,4,5,5-tetramethyl-4,5-di-
hydro-1H-imidazole-3-oxide-1-oxyl (7): NaIO4 (250 mg, 1.17 mmol)
was added for 30 min in portions to a mixture of imidazolidine-
1,3-diol 6 (260 mg, 0.78 mmol), CH2Cl2 (12 mL), and H2O (6 mL),
which was stirred at 10 °C. Then the reaction mixture was stirred
for 3 h and filtered. The organic layer was separated, and the aque-
ous layer extracted with CH2Cl2 (2ϫ10 mL). The consolidated or-
ganic extracts were dried with Na2SO4, and then filtered and the
solvents evaporated. The residue was dissolved in a minimal
amount of ethyl acetate, and the resulting solution was placed into
a SiO2 (2ϫ5 cm) column. Ethyl acetate was used as an eluent. The
dark blue fraction was diluted with heptane (30 mL) and concen-
trated at a pressure of 100 Torr until the volume reached ca. 10 mL.
Nitroxide 7, which precipitated as thin needles, was filtered off.
MeOH. M.p. 233–235 °C. IR: ν = 700, 765, 845, 870, 916, 996,
˜
1019, 1159, 1189, 1256, 1321, 1377, 1456, 2954, 3239 cm–1
.
C12H25N5O2Si (299.45): calcd. C 48.1, H 8.4, N 23.4; found C 47.6,
H 8.4, N 23.3.
4,4,5,5-Tetramethyl-2-(1H-1,2,3-triazol-5-yl)-4,5-dihydro-1H-imid-
azole-3-oxide-1-oxyl (H11): Procedure A: PbO2 (500 mg, 2.1 mmol)
was added at room temperature to a stirred solution of imidazolid-
ine-1,3-diol 14 (150 mg, 0.50 mmol) in MeOH (5 mL). The reaction
mixture was stirred for 24 h and filtered. The filtrate was evapo-
rated; the navy blue residue was ground with a mixture of hexane
with ethyl acetate, which led to crystallization of the residue. The
precipitate was filtered off, washed with hexane, dried in air, and
analyzed by HPLC–MSD (see Supporting Information). After
recrystallization of the reaction product from DMF/Et2O or
CHCl3/toluene, Pb3O2(11)2 (11 is deprotonated H11) precipitated
as amorphous dark blue powder. Yield: 290 mg (55%). The product
is slowly hydrolyzed by water; it is sparingly soluble in toluene and
Et2O, but well-soluble in DMF, CH2Cl2, acetone, MeOH, and
Yield: 183 mg (70%). M.p. 174–175 °C. IR: ν = 547, 616, 653, 757,
˜
836, 867, 1018, 1102, 1132, 1166, 1220, 1251, 1300, 1363, 1388,
1423, 1452, 2159, 2954 cm–1. C18H25N2O2Si (329.49): calcd. C 65.6,
H 7.7, N 8.5; found C 65.9, H 7.7, N 8.7.
2-(4-Ethynylphenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-
3-oxide-1-oxyl (8): The compound was synthesized from 4,4,5,5-
tetramethyl-2-{4-[(trimethylsilyl)ethynyl]phenyl}imidazolidine-1,3-
diol (6) similarly to 2 with 94% yield. Spectral data and the m.p.
of nitroxide 8 are identical to those obtained earlier.[5]
EtOH. IR: ν = 470, 542, 635, 691, 755, 845, 868, 975, 1043, 1088,
˜
1137, 1169, 1215, 1244, 1334, 1372, 1412, 1453, 1577, 2984, 3418
(very broad band) cm– 1 . LC–MS: m/z (%) = 223 [11]– .
C18H26N10O6Pb3 (1100.06): calcd. C 19.7, H 2.4, N 12.7; found C
18.2, H 2.4, N 10.2.
4,4,5,5-Tetramethyl-2-(1H-1,2,3-triazol-5-yl)imidazolidine-1,3-diol
(10): Sulfate hydrate N,NЈ-(2,3-dimethylbutane-2,3-diyl)bis(hydrox-
ylamine) (7·H2SO4·H2O) (350 mg, 1.33 mmol) was added at room
temperature to a stirred solution of 1H-1,2,3-triazole-5-carbal-
dehyde (9) (130 mg, 1.34 mmol) in H2O (5 mL). The reaction mix-
ture was stirred for 24 h at room temperature until yellow suspen-
sion formed. The mixture was neutralized with NaHCO3 (300 mg);
the organic layer was filtered off, washed with cold H2O (5 mL),
and dried in air. The resulting product was suspended in MeOH
(15 mL); the mixture was kept in an ultrasound bath for a few
Pb3O2(11)2 (190 mg) was dissolved in CHCl3 (15 mL), which con-
tained AcOH (0.5 mL). The resulting solution was stirred for 24 h
at room temperature, and then filtered. The filtrate was evaporated,
and the viscous navy blue residue was dissolved in CHCl3. The
resulting solution was placed onto a column [silica gel Merck
(0.063–0.100 mm for column chromatography), 10ϫ1.5 cm, wetted
Eur. J. Org. Chem. 2007, 3639–3647
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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V. Ovcharenko et al.
FULL PAPER
with ethyl acetate]. The column was eluted with ethyl acetate/
1688 unique, Rint = 0.1248; 166 parameters; Goof = 1.047; R indices
MeOH (5:1), which allowed the separation of the byproducts. After for IϾ2σ R1 = 0.0894, wR2 = 0.2389; R indices (all data) R1
=
the eluate became colorless, MeOH/AcOH (10:1) was passed
through the column. The blue fraction was collected and the sol-
vents evaporated. The resulting navy blue oily residue was ground
with ethyl acetate, which caused crystallization of the residue. The
precipitate was filtered off and recrystallized from a mixture of
MeOH with toluene using hot filtration. The filtrate was concen-
trated until a precipitate started to form, whereupon it was stored
at ca. 5 °C for 10 h. The single crystal residue was filtered off,
washed with hexane, and dried in vacuo. Yields were about 30 mg
(80%). H11 is well-soluble in MeOH and EtOH, not readily soluble
in CH2Cl2, and insoluble in ethyl acetate and benzene. Heating of
crystals H11 to 180–190 °C formed a green liquid, which became
0.1137, wR2 = 0.2571.
CCDC-627770 (for H11), -627771 (for 3a), and -628480 (for 12)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Computational Details: All calculations were done with the ORCA
electronic structure package version 2.5.20.[14] Geometry optimiza-
tions were performed at the UPBE/6-31G(d) level, and the isotropic
hyperfine coupling constants were obtained for the optimized
structures at UPBE0/EPR-II level.[15] The calculated HFC values
were then averaged over the fast internal molecular motions. The
spin density plots were made by the Molekel program.[16]
orange after heating to 200 °C. IR: ν = 541, 602, 665, 822, 867,
˜
965, 1057, 1136, 1171, 1214, 1234, 1315, 1374, 1410, 1451, 1508,
2868, 2982, 3052, 3177 cm–1. C9H14N5O2 (224.24): calcd. C 48.2,
H 6.3, N 31.2; found C 48.7, H 6.3, N 31.5. Crystals H11 were
grown by slowly evaporating a MeOH/toluene (3:1) solution of this
compound at ca. 5 °C. Single crystal fragments suitable for an X-
ray analysis were separated from the resulting navy blue crystals.
Supporting Information (see footnote on the first page of this arti-
cle): Temperature dependencies of the effective magnetic moments
for nitroxides, LC–MSD analysis of the reaction product prepared
by the oxidation of 4,4,5,5-tetramethyl-2-[4-(trimethylsilyl)-1H-
1,2,3-triazol-5-yl]imidazolidine-1,3-diol (14) with PbO2 in MeOH,
and cartesian coordinates of optimized structures 3a, 3b and H11.
Procedure B: PbO2 (350 mg, 1.46 mmol) was added at room tem-
perature to a stirred solution of crude imidazolidine-1,3-diol 10
(70 mg, 0.31 mmol) in MeOH (5 mL). The reaction mixture was
stirred for 14 h and filtered. The product (290 mg, dark blue
amorphous powder) was separated from the filtrate as per Pro-
Acknowledgments
cedure A. IR: ν = 468, 542, 611, 691, 753, 818, 868, 976, 1038,
˜
We are grateful to RFBR (grants 06–03–32157, 05–03–32305, 06–
03–32742, and 07–03–00824), to the RAS (grants 5.7.2, NSh-
4821.2006.3, and MK-4362.2006.3), SB RAS (grants 9 and 25), and
to the Bruker Company for financial support. The authors thank
Dr. A. I. Kruppa for his help in modeling ESR spectra.
1083, 1137, 1171, 1216, 1334, 1372, 1414, 1453, 1580, 2987, 3441
(very broad band) cm–1 [the IR spectrum of the product is identical
to the spectrum of Pb3O2(11)2]. C9H14N5O2 (224.24): calcd. C 48.2,
H 6.3, N 31.2; found C 18.0, H 2.0, N 8.7. Pb3O2(11)2 was trans-
formed into H11 by Procedure A with 45 mg (65%) yield.
X-ray Crystal Structure Determination of 3a, 12, and H11: Data for
crystals of compounds were collected at room temperature with a
Smart APEX CCD diffractometer using graphite-monochromated
Mo-Kα (λ = 0.71073 Å), operating at 50 kV and 40 mA. In all cases,
data were collected in a hemisphere of reciprocal space using a
combination of five exposure sets. The cell parameters were deter-
mined and refined by least-squares fits of all reflections. The first
50 frames were recollected to monitor crystal decay at the end of
data collection, and no appreciable decay was observed. The struc-
tures were solved by direct methods and refined by least-squares
procedures on F2. All non-hydrogen atoms were refined anisotropi-
cally. All hydrogen atoms were included in their calculated posi-
tions and refined as riding on the respective carbon-bonded atoms.
All structure solution and refinement calculations were performed
with Bruker SHELXTL version 6.12.
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Medvedeva, Russ. J. Org. Chem. 2004, 40, 1804–1809.
[7] Structural data for O1–H1···N3Ј fragments: O1–H1 1.07(6);
H1···N3Ј 1.54(6); O1···N3Ј 2.601(4) Å, ЄO–H–N 170(5)°; for
N2–H2···N5ЈЈ fragments: N2–H2 0.87(4), H2···N5ЈЈ 2.14(4),
N2···N5ЈЈ 2.960(4) Å, ЄN–H–N 158(4)°.
[8] E. V. Tretyakov, S. E. Tolstikov, G. V. Romanenko, Yu. G.
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[9] Structural data for N5–H5···N3Ј fragments: N5–H5 0.98(6),
H5···N3Ј 1.93(6), N5···N3Ј 2.789(5) Å, ЄN5–H5–N3Ј 146(5)°;
for N5–H5···O2Ј fragments: H5···O2Ј 2.32(6), N5···O2Ј
2.988(5) Å, ЄN5–H5–O2Ј 125(4)°.
Compound 3a: C13H22N3O2; FW = 252.34; orthorhombic, P212121;
a = 10.903(2), b = 14.211(3), c = 17.769(3) Å, V = 2753.3(8) Å3; Z
= 8, Dcalcd. = 1.217 g/cm3; µ = 0.083 mm–1; 2.19ϽθϽ23.31°; 19145
collected, 3958 unique, Rint = 0.0901; 502 parameters; Goof =
0.927; R indices for IϾ2σ R1 = 0.0504, wR2 = 0.1068; R indices
(all data) R1 = 0.0676, wR2 = 0.1148.
Compound 12: C10H19N5O2; FW = 241.30; monoclinic, P21/c; a =
10.460(4), b = 10.994(4), c = 11.056(4) Å; β = 102.988(8)°; V =
1238.9(9) Å3; Z = 4; Dcalcd. = 1.294 g/cm3; µ = 0.094 mm–1;
2.65ϽθϽ23.22°; 6634 collected, 1773 unique, Rint = 0.0598; 231
parameters; Goof = 1.106; R indices for IϾ2σ R1 = 0.0683, wR2 =
0.1799; R indices (all data) R1 = 0.0910, wR2 = 0.1929.
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Compound H11: C9H14N5O2; FW = 224.25; tetragonal, I41/a; a =
20.743(3), c = 10.880(2) Å; V = 4681.3(12) Å3; Z = 16; DC
=
1.273 g/cm3; µ = 0.094 mm–1; 1.96ϽθϽ23.29°; 17693 collected,
3646
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Cascade Reactions of Me3Si-Substituted Imidazolidine-1,3-diols with PbO2
FULL PAPER
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Received: February 9, 2007
Published Online: June 18, 2007
Eur. J. Org. Chem. 2007, 3639–3647
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3647